Ebook Proceedings DY09

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Filodiritto Editore – Proceedings
PROCEEDINGS
OF THE BIENNIAL MEETING OF THE ROMANIAN
SOCIETY OF NEUROGASTROENTEROLOGY
NeurogastRO
2019
(07-09 November 2019, Iași)
Editors
Vasile Drug & Dan L. Dumitrașcu
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INDEX
Foreword 6
Doctor-Patient Relationship, the Keystone of Clinical Outcomes

in Quality Healthcare of Gastroesophageal Reflux Disease 7
ANTON Carmen, DIMACHE Mihaela, ONOFREI Roxana, HARJA Alina,
DRUG Vasile, BARBOI Oana, GOLOGAN Elena, OANA Timofte,
ANTON Emil
Gut Microbiota and Quality of Life 13

BABIN Alexandru, DAVID Liliana, NEDELCU Laurentiu,
TZANEVA Valentina, DUMITRASCU Dan Lucian
Psychogastroenterology in Neurogastroenterologyopathy:
A Pragmatic Clinical Approach 17
BEREZOVSCAIA Elena, LUPAȘCO Iulianna,
DUMBRAVA Vlada-Tatiana, VENGHER Ina
Diverticulosis and Irritable Bowel Syndrome – Simple Association

or Causal Relationship? 23
DIMACHE Mihaela, ANTON Carmen, TIMOFTE Oana,
CIORCILĂ Ciprian, ONOFREI Roxana, DUDUMAN Sandina
Optical Diagnosis of Barrett Oesophagus in 2019 27

DOBRU Daniela E.
Faecal Transplant in Irritable Bowel Syndrome: Moving Forward? 33

DRANGA Mihaela, MIHAI Cătălina, GAVRILESCU Otilia,
ANDRONIC Andrei, OTEA Andreea, LEUSTEAN Alina,
BARBOI Oana-Bogdana, DRUG Vasile,
CIJEVSCHI PRELIPCEAN Cristina, FLORIA Mariana
How to Produce a Good Paper on Neurogastroenterology?

Why are some Papers Rejected? 39
DUMITRASCU Dan-Lucian
The Relationship Between Depression and Inflammatory Bowel Disease 42

FADGYAS STANCULETE Mihaela, CAPATINA Octavia,
DUMITRASCU Dan Lucian, POJOGA Cristina
Gastroesophageal Reflux Disease and Esophagitis after Paroxysmal

Atrial Fibrillation Ablation 46
FLORIA Mariana, MIHAI Catalina, RADU Smaranda, BĂRBOI Oana,
TĂNASE Maria Daniela, GRECU Mihaela,
CIJEVSCHI-PRELIPCEAN Cristina, DRUG Vasile Liviu
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Gastroparesis and Atrial Fibrillation: What is the Relationship? 53

RADU Smaranda, MIHAI Catalina, DRANGA Mihaela, OUATU Anca,
TANASE Daniela Maria, CIJEVSCHI-PRELIPCEAN Cristina,
FLORIA Mariana
The Role of Diet on the Symptoms of Gastroesophageal Reflux Disease

in Patients with Non-Alcoholic Steatohepatitis 59
GOLOGAN Elena, GOLOGAN Andrei Nicolae, ANTON Sorana,
ANTON Carmen, TIMOFTE Oana
Gerd After Surgery for Oesophageal Atresia 65

GAVRILESCU Simona, APRODU Gabriel, DRUG Vasile, BĂRBOI Oana,
LĂPTOIU Alma, TETIA Teodora Tetia, HANGANU Elena
Phytotherapy in Some Digestive Disorders 70

LUNGOCI Constantin, BĂRBOI Oana-Bogdana, ROBU Teodor
High Resolution Manometry in Oradea ‒ First Years’ Experience 77

MUNTEANU Mihai, BRISC Cristina, DEMIAN Luiza, BRISC Ciprian
The Distribution and Features of Colonic Diverticula Complicated

with Acute Diverticulitis ‒ Single Tertiary Center Experience 81
MUZÎCA Cristina-Maria, STANCIU Carol, HUIBAN Laura, PETREA Oana,
FRUNZUC Georgiana, SÎNGEAP Ana-Maria, TRIFAN Anca
The Age and Level of Studies in the Treatment Decision

for Irritable Bowel Syndrome 87
PALAMARU Andreea-Luiza, TOADER Elena, MUSTEAȚĂ Mădalina-Anca,
ROTARU Tudor-Ștefan
Genetic Aspects of Hirschsprung’s Disease 91

PÂNZARU Monica-Cristina, BUTNARIU Lăcrămioara-Ionela, CABA Lavinia,
POPESCU Roxana, GAVRIL Eva, POPA Setalia, RESMERIŢĂ Irina,
GORDUZA Eusebiu Vlad, RUSU Cristina
Complete Mucosal Recovery: A 2019 Perspective on Intestinal Health

and Celiac Disease 96
PLEȘA Alina, SFRIJAN Cristina, GORINCIOI Cristina, MAZILU Bogdan,
APETREI-CORDUNEANU Otilia, GHEORGHE Liliana, GÎRLEANU Irina,
TRIFAN Anca, NEMȚEANU Roxana
Rational-Emotive Behavioural Psychotherapy in Psychosomatic Diseases 101

POJOGA Cristina, FADGYAS STANCULETE Mihaela
Rumination Syndrome: A Treatment Update 105

POPA Stefan-Lucian, CHIARIONI Giuseppe, DAVID Liliana
Oesophageal Motility Disorders in Children ‒ A 5 Years’ Experience 109

POP Daniela, POP Radu Samuel, PÎRVAN Alexandru, FARCĂU Dorin
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Between the Symptoms’ Debut and the Beginning of Treatment:

Age Groups in Irritable Bowel Syndrome 115
ROTARU Tudor-Ștefan, PALAMARU Andreea Luiza,
MUSTEAȚĂ Mădălina Anca, TOADER Elena
Diagnotic Role of H2-Breath Tests in Neurogastroenterology 120

SURDEA-BLAGA Teodora, DUMITRASCU Dan-Lucian,
ABENAVOLI Ludovico
Suffering caused by Symptoms of Irritable Bowel Syndrome:

Self-reported Level by Various Age Groups 123
TOADER Elena, PALAMARU Andreea Luiza,
MUSTEAȚĂ Mădălina Anca, ROTARU Tudor-Ștefan
Minimal Endoscopical Lesions and Diagnosis of Dyspepsia 128

TOCIA Cristina, DUMITRU Andrei, DUMITRU Eugen
Correlations of the Quality of Life with the Negative Emotions

and Automatic Thoughts in Preuniversity Education 134
TRIFF Dorin-Gheorghe, TRIFF Zorica
Irritable Bowel Syndrome and Fibromyalgia: Prevalence,

Clinical Characteristics and Psychological Impact 139
ZUGRAVU (POP) Dalina-Diana, RUSU Flaviu, DUMITRASCU Dan Lucian
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FOREWORD
Dear readers,
Please find in this volume the proceedings of the NeurogastRO Meeting held in Iași between
7-9 November 2019.
NeurogastRO is a series of biennial meetings of neurogastroenterology organized by the
Romanian Society of Neurogastroenterology founded in 2005. These meetings had always a
strong international participation and in recent years it became a forum on functional and
motility gastrointestinal disorders in Central and Eastern Europe. In this most recent edition,
we brought lecturers from this part of Europe but also key opinion leaders from the European
Society of Neurogastroenterology and Motility.
Here is a selected number of papers based on the presentations in Iasi: original research,
reviews, mainly from oral but also from some poster presentations.
As you see, one can find inside a little bit from every subdomain of neurogastroenterology.
The papers are conceived by specialists from all established medical centres of this country
but also from Albania, Bulgaria, Italy and Republic of Moldova.
Editors
Prof. Vasile Drug
Prof. Dan L. Dumitrașcu
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Doctor-Patient Relationship, the Keystone of Clinical Outcomes in

Quality Healthcare of Gastroesophageal Reflux Disease
ANTON Carmen1, DIMACHE Mihaela2, ONOFREI Roxana3, HARJA Alina4,

DRUG Vasile5, BARBOI Oana6, GOLOGAN Elena7, OANA Timofte8,
ANTON Emil9
University of Medicine and Pharmacy “Grigore T. Popa” Iași, (ROMANIA)

1,2,5,6,7,8,9
Institute of Gastroenterology and Hepatology, Hospital “St. Spiridon”, Iași, (ROMANIA)

1,2,3,4,5,6,7,8
Emails: carmen_ro2008@yahoo.com, mimidimache@yahoo.com, onofrei.roxana92@yahoo.com, alina2harja@gmail.com,

vasidrug@email.com, oany_leo@yahoo.com, elenagologan2007@yahoo.com, oanatimofte@yahoo.com,
emil.anton@yahoo.com
Abstract
Gastroesophageal reflux disease (GERD) affects 33% of the general population and the
prevalence in the developed world is constantly rising. GERD presents with a host of
oesophageal and extra-oesophageal symptoms, contributing to wide variations in clinical
practice in both, the diagnosis and treatment of GERD. The brain-gut axis is helpful in
explaining why symptoms persist despite treatment. The accurate diagnosis of GERD relies on
the careful questioning of the patient by the doctor. Patient-reported outcomes (PRO) tools can
help advance physician-patient communication and the GERD Impact Scale (GIS) is a
commonly used PRO. The shared decision making(SDM) approach increases patient
satisfaction and treatment adherence especially in chronic conditions. Psychological factors,
such as stress, influence gut functioning which may impact clinical outcomes in GERD. pH-
impedance testing is useful in the PPI-refractory symptoms. The most reliable method of
diagnosis remains endoscopy of the upper GI tract, including biopsy in mucosal damage. The
positive response to PPI therapy is used as a confirmation of initial GERD diagnosis.
Keywords: Gastroesophageal reflux disease, patient-physician communication, patient-reported outcomes,
shared decision making
General Stats. Definition
Gastroesophageal reflux disease (GERD) is a common digestive disorder worldwide with an

estimated prevalence of 18.1-27.8% in North America [1]. There is a trend for higher
prevalence in North America compared to Europe and also in Northern over Southern Europe
[2]. Significant improvement in quality of life (QOL), including decreased physical pain,
increased vitality, physical and social function, emotional wellbeing has been associated with
the successful treatment of GERD symptoms [3].
GERD is defined as symptoms or mucosal damage produced by the abnormal reflux of
gastric contents into the oesophagus or beyond, into the oral cavity (including larynx) or lung
[4, 5].
Diagnosis of GERD
The diagnosis of GERD is made typically by a combination of clinical symptoms, as well as

objective testing with oesophageal pH monitoring and upper endoscopy [6], which may be
normal in patients with GERD, or there may be evidence of esophagitis of varying degrees,
7
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peptic strictures, Barrett’s metaplasia, and oesophageal adenocarcinoma [7]. During pregnancy,
GERD is symptomatic mostly in the third trimester, with increasing uterine volume and
progesterone hormone level, being reversible after delivery [8].
An oesophageal manometry should be performed in patients with suspected GERD with
chest pain and/or dysphagia and a normal upper endoscopy, to exclude an oesophageal motility
disorder [9]. To confirm the diagnosis of GERD in those with persistent symptoms (whether
typical or atypical, particularly if a trial of twice-daily PPI has failed) or to monitor the adequacy
of treatment in those with continued symptoms the ambulatory pH monitoring is also used [10,
11].
Therapeutic Options
GERD is a chronic disease that typically requires long term management in the form of
lifestyle modification, medical therapy and, for a subset of patients, surgical therapy. Lifestyle
and diet have included traditionally weight loss, avoidance of night-time meals, head of bed
elevation and elimination of trigger foods such as chocolate, caffeine and alcohol [12]. The
mainstay of treatment of GERD is acid suppression which can be achieved with several classes
of medications including antacids, proton-pump inhibitors (PPIs) or histamine-receptor
antagonists (H2RAs). If symptoms are refractory to proper medical therapy, an alternate PPI
can be used or the dosing can be increased [13]. Another approach in the PPI-refractory patient
involves the addition to bid PPI of night-time H2RAs for persistent symptoms [14]. A well-
studied medication is the GABAb agonist baclofen which has been shown to reduce
postprandial reflux events and acid exposure in normal individuals and in patients with GERD
by inhibiting transient lower oesophageal sphincter relaxations, thought to be the primary cause
of reflux events [15]. Unfortunately, side effects often preclude continued use of this medication
and include drowsiness (up to 63%), dizziness (5%-15%), weakness (5%-15%), and fatigue
(2%-4%) [16]. A long-term therapy option in patients with GERD is surgical treatment, which
typically include laparoscopic fundoplication or bariatric surgery. In view of the invasiveness
of surgery, several endoscopic therapies for GERD have been attempted, the latest endoscopic
techniques for treatment of GERD being trans-oral incisionless fundoplication [17].
Psychosocial Factors in the Patient Outcome
Understanding the factors of PPI nonresponse may help to identify resistance process and
optimize patient’s treatment. Almost 40% of patients presents persistent GERD symptoms on
standard dose PPI [18]. Possible factors may be related to persistent acid reflux, noncompliance
to treatment, esophagitis of another aetiology (eosinophilic esophagitis, pill or infectious
esophagitis), functional heartburn or hypersensitivity [19]. Functional digestive disorders
(dyspepsia, constipation, irritable bowel syndrome), low body mass index, hiatus hernia and
hypotensive esophago-gastric junction were more frequently implicated in PPI non-responders
[20].
Taken from another perspective, a bio-psycho-social model integrates the physical and
psychosocial factors that contribute to the patient’s illness and offers an effective approach for
the diagnosis and a multidisciplinary management of GERD. During time, an increased number
of studies have been performed in order to establish potential relations between the symptoms
and causal factors of GERD on the one side, and psycho-physiological, as well as other
psychologically relevant aspects on the other. The role of brain-gut bidirectional
communication cannot be overstated. The normal gastrointestinal functioning and the
modulation of disease activity are controlled by the central nervous system through neural,
immunological and hormonal bidirectional communication with the gut. Psychological factors,
8
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such as stress, may impact clinical outcomes in GERD by affecting gut functioning and
perception of peripheral gut nerve input to the central nervous system. There is a continuous
feedback loop between the brain and the gut which can explain why symptoms can persist
despite a standard treatment. Hypervigilance to gut input represents a combination of increased
gut sensory sensitivity with exaggerated threat perception surrounding gut symptoms. Kahrilas
defined it as the “cognitive-affective process that stems from hyperawareness of discomfort” in
patients with refractory reflux symptoms [21]. In other words, some patients feel discomfort at
levels where other people may not be bothered by it (visceral hypersensitivity) and they become
caught in a negative feedback loop of discomfort, pain and anxiety. In one study, hypervigilance
accounted for 50% of patient-reported symptom severity while psychological distress
(depression, somatization, anxiety) was found to be within normal limits in the treatment
refractory group [22]. Physicians must provide education about the origin of the symptoms,
about the brain-gut axis and how hypersensitive gut nerves can be responsible for some
symptoms. More testing, more PPI, or more surgery is not the answer. Behavioural
interventions which are focusing on increasing their coping skills and target hypersensitivity
proved to be quite successful [23].
Patient-centred Communication
Medical, ethical and socioeconomic issues can influence an effective physician-patient

communication. A physician should be able to identify pitfalls and learn how to deal with those
circumstances in order to provide optimal patient care. Epstein and Street defined patient-
centred communication as: “(1) Understanding the patient within his or her own psychological
and social context; (2) eliciting, understanding and validating the patient’s perspective; (3)
reaching a shared understanding of the patient's problem and its treatment and (4) helping a
patient share power by offering him or her meaningful involvement in choices relating to his or
her health [24]. A number of studies showed that some verbal behaviours like psychosocial talk,
empathy, information sharing, time spend in health education, courtesy, humour and
clarification have a positive effect on health outcomes. A couple of nonverbal behaviours like
head nodding, leaning forward, arms and legs uncrossed proved to be quite beneficial too. In
the context of GERD, there are limited research regarding physician-patient communication,
GERD management and its impact on patient outcome. In a study about how patient education
improves GERD management, only 66% of patients thought they had a comprehensive
discussion with their physician and they were more knowledgeable about how and when to take
their medication [25].
Patient-reported outcomes (PRO) tools can improve physician-patient communication by
capturing patient’s perceptions of GERD management and by measuring the impact of GERD
from patient’s perspectives. The GERD Impact Scale (GIS) is a commonly used PRO. This
validated questionnaire was designed to aid physicians in the identification of an appropriate
treatment and to evaluate the patient’s response to treatment. The GIS was developed from an
initial systematic literature review, followed by patient focus groups, primary care physician
and patient cognitive interviews. The GIS has demonstrated good psychometric properties in
newly diagnosed GERD patients and those already receiving treatment, being a valid and
reliable tool for use in clinical practice to identify instances of need for more effective therapy
in subjects with a confirmed diagnosis of GERD. The GIS is composed of nine questions and
uses a four-graded Likert scale for answers: i.e., daily, often, sometimes, and never. The
questions cover three dimensions upper GI symptoms, other acid-related GI symptoms and the
impact of the symptoms on the patient’s daily lives [26].
Other PRO tools include Health-related QOL scale for GERD (GERD-HRQL), QOL
questionnaire for GERD (GERD-QOL), and Quality of reflux questionnaire (Reflux-Qual) The
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GERD-HRQL was developed to survey symptomatic outcomes and therapeutic effects in

patients with GERD. The scale has 11 items, which focus on heartburn symptoms, dysphagia,
medication effects and the patient’s present health condition. Each item is scored from 0 to 5,
with a higher score indicating a better QOL. The GERD-QOL scale consisted of 16 items
clustered into the four subscales: daily activity, treatment effect, diet and psychological well-
being. The final score can range from 0 to 100, with a higher score indicating a better QOL.
Reflux-Qual questionnaire consists of eight items, including daily life, well-being,
psychological impact and sleeping/eating, with a score ranging from 0 to 100 [27]. Employing
validated PRO tools at diagnosis and during ongoing pharmacotherapy demonstrates physician
concern and care for the GERD patient.
Shared decision making in the management of GERD

In order to combat the lack of patient-physician communication, experts have proposed
shared decision making (SDM) as a new model for clinical practice. SDM was designed to
create a partnership between patient and clinician which is based on a discussion of patient
values and preferences, treatment options, sharing opinions and a mutual decision which
include follow-up plans [28]. The concept of SDM is strongly based on the caring conversation
and respectful relationship of the physician and patient. Physicians can provide patient-centred
care and can improve patient satisfaction by using the SDM approach to every step in GERD
management-diagnosis, medication trials and adjustments, further solutions for refractory
symptoms. The SDM approach help patients to include their experience as a central part of care
decision and to share their concerns.
The best way for physicians to gather important information is to use the PROs discussed
above. Using PRO tools, as part of SDM model, may help improve the use of PPI therapy in
several ways. In patients with good initial response to PPIs the best choice is to maintain the
lowest dose necessary for the control of the symptoms. PROs can also be useful for the cases
with treatment failure, in which cases the physician must check the adherence and proper dosing
30 min prior to eating or the need for dose-escalation. Limiting unnecessary PPI exposure
should be a target because long-term PPI therapy can lead to community acquired pneumonia,
enteric infections, increased risk of vertebral and hip fractures (increased absorbition of
calcium), rebound acid hypersecretion and secondary hypergastrinemia [29]. On the other hand,
the lifestyle modifications represent a major recommendation in the treatment of GERD.
Weight loss, avoiding trigger foods, decreased alcohol use, smoking cessation, avoiding late
night meals and elevating the head of the bed reduced GERD symptoms and improved QOL.
Conclusions
Physician-patient communication improvement and SDM in GERD are two approaches that
could optimize patient-reported outcomes.
The brain-gut connection and hypervigilance have an important role in symptom resolution
and treatment success, explaining non-PPI responders.
pH-impedance testing showed that the PPI-refractory symptoms are related to continued
episodes of reflux.
The upper GI endoscopy is usually reserved for evaluation of GERD-associated
complications.
SDM with the incorporation of PROs includes the patients in the treatment, promoting their
adherence and satisfaction, ultimately impacting the health-related QOL.
Doctor-patient relationship can help clinicians optimize treatment, but may also help the
patient understand, accept and manage persisting symptoms, potentially avoiding unnecessary
invasive testing and expense.
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Gut Microbiota and Quality of Life
BABIN Alexandru1, DAVID Liliana2, NEDELCU Laurentiu3,

TZANEVA Valentina4, DUMITRASCU Dan Lucian1
1
Nicolae Testemitanu State University of Medicine and Pharmacy Chisinau (MOLDOVA)
2
Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca (ROMANIA)
3
Transilvania University Brasov (ROMANIA)
4
Trakia University Stara Zagora (BULGARIA)
Emails: alexababin@rambler.ru, lilidavid2007@yahoo.com, laurnedelcu@yahoo.com, vtzaneva@gmail.com,
ddumitrascu@umfcluj.ro
Abstract
This is a review on the microbiota and quality of life. The authors undertook a thorough
literature search and synthesized the information in this proceedings paper. We review first the
definition and the assessment methods of quality of life (QoL), i.e., of health-related quality of
life (HRQoL). In continuation we look for the effect of gut health and pathology induced by
alterations of microbiota. This pathology is involving a large spectrum of conditions from
irritable bowel syndrome (IBS) to digestive cancers and metabolic diseases. In conclusion,
microbiota is an essential factor for health and for the maintenance of high scores for quality of
life. Probiotic supplementation is indicated.
Keywords: biopsychosocial medicine, gut microbiota, quality of life, psychosomatic
Introduction
In the medical practice, the health care providers look for outcomes. One of the most modern
outcomes is represented by the quality of life (QoL). The part of QoL reflected by the health
status of each individual is called health-related quality of life (HR-QoL) [1, 2].
Definition of the Quality of Life
HR-QoL is defined as the objective and subjective evaluation of the health being state:
physical, material, social and emotional, of the personal development and of the target oriented
activities, according to the set of personal values [1]. There are some features of the HR-QoL:
QoL is not a concept specific to medicine, but a concept applied also to many other fields:
ecological, economic, cultural, physical, social, psychological; QoL is associated to the health
state is the object of (psychosomatic) medicine (health-related quality of life). There are several
fields of QoL. It is considered that the HR-QoL is a concept reflecting physical and emotional
state, individual and social behaviour, compared to the previous health condition. We assess by
QoL the perspective of the patient on the own disease or health; we also assessment of the
evolution of the disease. HR-QoL refers to physical, psychological, social aspects of the health;
QoL is subjective and multidimensional [2].
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Associated Concepts
There are several concepts that should not be confounded with HR-QoL. The main factors
are the following:
Satisfaction: This is a concept defining the degree of satisfaction of the patient in respect to
the contact with the medical doctor, investigations, therapy. Indeed, with the development of
techniques, we observe changes in the relationship between patient and physician. Therefore,
hi-tech medicine has the risk to impair the satisfaction of the patients. One should add to this
the lack of time of the doctor, which causes frustration and in satisfaction. Satisfaction is
enhanced by psychosomatic approach.
Wellbeing: The patients are concerned by own symptoms and the cognitions made about the
symptoms. Well-being produces satisfaction while lack of satisfaction leads to anxiety and
hostility.
Adjustment to illness: This is a surrogate for QoL. This is a parameter investigated with the
scale of Derogatis (PAIS) looking for: satisfaction, physical functionability, vocation, familial
state, social environment, sexual life. This questionnaire offers information on the QoL.
Measurement of QoL
In the medical practice there is a need to assess HR-QoL. The steps needed to assess this
parameter are presented in table 1 [2].
Table 1. Steps in the measurement of HR-QoL

Evaluation of patients
Clinical examinations plus lab tests
Identification of patients’ needs
Identification of psycho-social behaviours
Follow-up
Therapy of choice
Final aims
Negative emotions may cause somatic symptoms and alters QoL. This is explained either by
the: disability hypothesis: negative emotions are the consequence of health problems, i.e., in
hemochromatosis or by: psychosomatic hypothesis: negative emotions may generate health
problems, i.e., in viral hepatitis [3].
To assess the QoL we need specific questionnaires. These are general or specific for a
specific disease only (table 2 [2]):
Table 2. Characteristics required for a tool to assess QoL

Reproducibility
Validity
Fiability
Easy to understand
Responsitivity to change
Results easy to interpreted
Types of Questionnaires
To measure QoL, there are different questionnaires. These are presented in table 3 [2].
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Table 3. Types of questionnaires for QoL

Simple questionnaires
(single score) Multidisciplinary questionnaires
ARA, Karnofski General: SF-36, EuroQoL
APACHE II, APACHE III Specific: APQLQ ‒ Angina Pectoris Quality of Life Questionnaire; MacNew Heart
Disease Health-related Quality of Life Questionnaire; SAQ ‒ Seattle Angina Questionnaire; Hepatitis Quality
of Life Questionnaire, IBS-QoL, IBD-QoL
The Role of Microbiota
Microbiota is very important for the health of the gut. It has been suggested that
environmental cancer risk is determined by the interaction between diet and microbes.
Microbiota is important for the metabolic syndrome regulation as well for the organic (IBD,
colorectal cancer (CRC)) of functional gastrointestinal disorders. It has been found that a higher
prevalence of Fusobacterium nucleatum and of Enterobacteriaceae is encountered in CRC than
in healthy subjects [4]. Differences in microbial and archaeal species detected in biopsies of
mucosa were observed between healthy controls and patients presenting precancerous
conditions like tubular adenomas or even CCR [4].
Actually, the bacteria in the gut interact with inflammation, diet, and genetically
characteristics of the host in order to dictate the evolution toward CRC [5]. In order to prevent
the progress to medical conditions able to deteriorate the QoL, several attempts have been
proposed. The main objective is to manipulate the gut microbiota in order to prevent as primary
or secondary prevention following conditions: metabolic syndrome, IBD, CRC or even IBS
Main possibility is the use of probiotics [6, 7]. Other possibility to change microflora is to
change the diet, being well-known that microbiota depends also o diet or fasting [6, 8]. At the
level of hypothesis remains the faecal material transplantation, but this method is not yet entered
in guidelines for this indication [9, 10]. Other study showed that the eicosapentaenoic acid-free
fatty acid (EPA-FFA) is able to prevent the occurrence of colorectal polyps or even to decrease
its growth speed in a FAP model [11]. This EPA diet has also a simultaneous effect on
microbiota. Indeed, it was shown that it can increase the prevalence of Lactobacilli species in
gut [11, 12]. Beside the experimental demonstration of CRC preventive potential, if used by
humans, they offer a feeling of well-being a self-estime based on the conscience that the
subjects leave and eat healthy.
Conclusions
The assessment of QoL is very important for patients and for the health care system.
Microbiota changes are associated with health impairment and thus with QoL deterioration.
Use of probiotics are therefore highly recommended in an attempt to restore the QoL by
preventing chronic gastrointestinal conditions like IBD, CRC, IBS or the metabolic syndrome.
REFERENCES
1. Dumitrascu DL: Heath related quality of life. Proceedings Humboldt Kolleg Timisoara, Techn Univ
Timisoara Publ. 2011.
2. Dumitrascu DL: Curs de psihosomatica, Ed. Med Univ. I Hatieganu Cluj 2007.
3. Pojoga C, Dumitrascu DL. Quality of life in functional gastrointestinal disorders: assessment and
management. Rom. J Intern Med. 2006; 44(3): pp. 229-39.
4. Mira-Pascual L, Cabrera-Rubio R, Ocon S, Costales P, Parra A, Suarez A, Moris F, Rodrigo L, Mira A,
Collado MC. Microbial mucosal colonic shifts associated with the development of colorectal cancer
reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol. J Gastroenterol. 2015;
50(2): pp. 167-79.
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5. Irrazábal T, Belcheva A, Girardin SE, Martin A, Philpott DJ. The multifaceted role of the intestinal
microbiota in colon cancer. Mol Cell 2014; 24; 54(2): pp. 309-20.
6. Walsh CJ, Guinane CM, O’Toole PW, Cotter PD. Beneficial modulation of the gut microbiota. FEBS
Lett. 2014. doi: 10.1016/j.febslet.2014.03.035.
7. Kobyliak N, Abenavoli L, Mykhalchyshyn G, Kononenko L, Boccuto L, Kyriienko D, Dynnyk O.A
Multi-Strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD
Patients: Evidence from a Randomized Clinical Trial. J Gastrointestin Liver Dis. 2018 Mar; 27(1): pp.
41-49. Tarkan
8. Cammarota G, Ianiro G, Tilg H, Rajilić-Stojanović M, Kump P, Satokari R, Sokol H, Arkkila, Pintus C,
Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link
A, de Groot P, de Vos WM5, Högenauer C, Malfertheiner P, Mattila E, Milosavljević T, Nieuwdorp M,
Sanguinetti M, Simren M, Gasbarrini A; European FMT Working Group. European consensus conference
on faecal microbiota transplantation in clinical practice. Gut. 2017; 66(4): pp. 569-580. doi:
10.1136/gutjnl-2016-313017.
9. Filip M, Tzaneva V, Dumitrascu DL. Fecal transplantation: digestive and extra digestive clinical
applications. Clujul Med. 2018 Jul; 91(3): pp. 259-265. doi: 10.15386/cjmed-946
10. Piazzi G, D’Argenio G, Prossomariti A, Lembo V, Mazzone G, Candela M, Biagi E, Brigidi P, Vitaglione
P, Fogliano V, D’Angelo L, Fazio C, Munarini A, Belluzzi A, Ceccarelli C, Chieco P, Balbi T, Loadman
PM, Hull MA, Romano M, Bazzoli F, Ricciardiello L. Eicosapentaenoic acid free fatty acid prevents and
suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signalling and gut
microbiota. Int. J Cancer. 2014; doi: 10.1002/ijc.28853.
11. Hagland HR, Soreide K. Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut
microbiome and metabolic pathways. Cancer Lett. 2014. pii: S0304-3835(14) pp. 00133-5. doi:
10.1016/j.canlet.2014.02.026.
12. Karakan T. Intermittent fasting and gut microbiota. Turk J Gastroenterol. 2019 Dec; 30(12): p. 1008. doi:
10.5152/tjg.2019.101219.
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Psychogastroenterology in Neurogastroenterologyopathy: A
Pragmatic Clinical Approach
BEREZOVSCAIA Elena1, LUPAȘCO Iulianna1, DUMBRAVA Vlada-Tatiana1,

VENGHER Ina1
1
Laboratory of Gastroenterology, State University of Medicine and Pharmacy “Nicolae Testemitanu”,
(REPUBLIC OF MOLDOVA)
Email: elenaberezovskaia69@gmail.com
Abstract
Psychogastroenterology is a quite new field of neurogastroenterology putting emphasis on

the mind-body relationship. From this point of view, it interferes with psychosomatic medicine
or biopsychosocial medicine. Neurogastroenterology is focused on the gastrointestinal tract
while psychosomatic medicine is focusing on all the human body and mind. Liver is not an
object for neurogastroenterology but interferes with it by the psychosomatic approach of some
chronic liver diseases. Psychological changes may occur both in the gastrointestinal disorders
(like the FGID or DGBI) and in chronic liver disease. Both types of clinical pathology are
chronic conditions involving the emotional response to daily suffering and hassles. And both
of them have impact on the health-related quality of life.
The purpose of this study was to evaluate the anxiety in patients with chronic hepatopathy,
factors well known impaired in FGID mainly studied in IBS.
In order to determine anxiety, we used The Self Rating Anxiety Scale Zung. There were
evaluated 57 patients with an established diagnosis of chronic liver disease. Patients were
divided into 3 groups: the first group (I) were patients with chronic HBV (n=20), the second
(II), with chronic HCV infection (n=10), the third (III), with non-alcoholic liver steatosis
(n=27). We used a control group consisting of 21 age and sex matched healthy individuals.
According to the data received, the anxiety was significantly increased in patients with
chronic HСV infection, presenting 52.753.69 (p<0.01). Patients with chronic HBV infection
had the anxiety level slightly lower, amounted to 48.312.29 (p<0.01), while the lowest rates
were found in individuals with liver steatosis ‒ 42.961.64 (p<0.05). In the same time, the
important thing is that in all groups the level of anxiety was significantly higher in comparison
to practically healthy individuals, in whom it was 39.051.88.
The data obtained demonstrate that the anxiety was increased in all chronic liver disease, but
more pronounced in patients with liver pathology caused by chronic HCV infection, which
could be explained by social and psychological factors and direct neurotoxic effects of HCV.
In this way we prove that chronic suffering leads to psychological changes.
Keywords: Anxiety, Chronic liver disease, Neurogastroenterology, Psychogastroenterology
Introduction
Psychogastroenterology is a quite new field of neurogastroenterology putting emphasis on

the mind-body relationship. From this point of view, it interferes with psychosomatic medicine
or biopsychosocial medicine. Neurogastroenterology is focused on the gastrointestinal tract
while psychosomatic medicine is focusing on all the human body and mind. Liver is not an
object for neurogastroenterology but interferes with it by the psychosomatic approach of some
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chronic liver diseases. Psychological changes may occur both in the gastrointestinal disorders
(like the FGID or DGBI) and in chronic liver disease. Both types of clinical pathology are
chronic conditions involving the emotional response to daily suffering and hassles. And both
of them have impact on the health-related quality of life.
Chronic diffuse liver diseases remain one of the most acute problems in many countries of
the world. According to international statistical reports, there is a continuous increase in the
prevalence of hepatopathies. In world rankings, chronic diffuse liver disease is one of the main
causes of premature death, killing more than a million people every year. According to WHO
data, in 2017, the Republic of Moldova ranked first in Europe in terms of mortality from liver
disease and entered the top five countries in the world in terms of this indicator. [15, 16].
Over the past decades, chronic hepatopathies have been considered the regional pathology
of the country; they constantly occupy leading places in the ratings of prevalence and temporary
disability. The other main issue is that chronic hepatopathies evolving into cirrhosis of the liver,
in the natural course of disease evolution, contribute to an increase in disability and mortality
in people of young working age, which in turn leads to significant economic losses [9, 11]. At
the same time, chronic hepatopathies are accompanied by a wide range of somatic and
psychological problems that have a significant impact on the life of these patients.
Formation of anxiety in patients with chronic somatic diseases is a well-known actual
problem of modern medicine, regarding to health practitioners as well as to the inner circle of
the patient and the community as a whole.
The purpose of this study was to evaluate the anxiety in patients with chronic hepatopathy.
Methods
Patients of both genders, with chronic diffuse liver diseases, over the age of 18 years, who
underwent an outpatient private gastroenterologist consulting at the Chisinau Private Medical
Center, from May 2017 to December 2018, were invited to participate in the study.
Patients with liver cirrhosis (before and after liver transplantation), with HBV-HCV co-
infection, those who received antiviral therapy in the last 6 months, patients with other chronic
diseases in the exacerbation phase, with malignant neoplasms were excluded from the study, as
well as excessive drinkers and persons with mental disorders or people who unable to
communicate, or refused to participate in the study. The control group invited men and women
who denied having any acute or chronic diseases in the acute stage for the past 6 months, over
the age of 18 years, who regularly underwent medical examination at the place of work (study)
or residence.
The diagnosis of chronic viral hepatitis B or chronic HBV infection was based on existing
clinical recommendations and guides [3, 17]: on the identification of positive markers of
hepatitis B virus (ELISA test) more than six months; with or without detection of HBV DNA
(polymerase chain reaction); determining serum levels of ALT and other liver enzymes, etc.
The diagnosis of chronic hepatitis C or chronic HCV infection was based on clinical
recommendations and guides [4, 18]: on the determination of HCV antibodies or HCV RNA
(>15 IU/ml) in the presence of clinical signs of chronic hepatitis, or an increase in serum ALT.
The diagnosis of liver steatosis was based on data obtained from a clinical examination (body
mass index, etc.), ultrasound examination, determination of serum activity levels of ALT, AST,
GGTP, cholesterol, triglycerides, Ritis coefficient (AST/ALT) <1, HOMA-IR index >2.5 and
in the absence of markers of viral liver alteration [5, 9].
Thus, 57 patients with an established diagnosis of chronic liver disease (with chronic HBV
or HCV infection and patients with liver steatosis) were selected to participate in the study.
Patients were divided into 3 groups:
(I) patients with chronic HBV infection (HBV) ‒ 20 people,
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(II) patients with chronic HCV infection (HCV) ‒ 10 people,

(III) patients with liver steatosis (LS) ‒ 27 people.
The control group (CG) consisted of 21 healthy individuals.
To determine the level of anxiety, we used The Self Rating Anxiety Scale Zung (SAS),
adapted in Romanian and Russian [10, 21]. SAS present a norm-referenced scale, being a 20
item Likert scale, in which items tap psychological and physiological symptoms and are rated
by participants according to how each applied to them within the past week, using an existing
4-point scale, ranging from 1 (none, or a little of the time) to 4 (most, or all of the time). Raw
scores (ranges 20-80) were converted into index scores by dividing the sum of the raw scores
by 80, and multiplying by 100. The recommended SAS cut-of level is 45 indexed points. Thus,
results exceeding 45 points serve the basis for determining anxiety disorder [2]. In the study,
patients independently filled out questionnaire forms during their visit to the outpatient
consulting.
To process the data, we used the data analysis package for statistical processing of Excel
2010. The data are presented in the form M ± m, where M is the arithmetic mean and m is the
standard error of the mean. The significance of differences (P) between groups was determined
using the nonparametric Mann-Whitney U-test. The significance threshold was fixed at p<0.05.
Results and Discussion
At the first stage of the study, we carried out a comparative analysis of the average values of
anxiety indicators in 57 patients with chronic hepatopathies in comparison with practically
healthy people. The obtained data are presented in fig. 1. It should be noted that the indicator
of the level of anxiety in patients is significantly higher than in the control group and is
46.561.36 vs 39.051.88 (p<0.01) in the CG.
Fig. 1. Anxiety indicators in patients with chronic hepatopathy (CHP) and in healthy individuals (CG)
Subsequently, we conducted an analysis of three groups of patients, formed taking into

account the etiological principle. As a result, it was found that the level of manifestation of
anxiety in all experimental groups was significantly higher than in the control group (fig. 2). It
should be noted that the most pronounced changes were observed in patients with chronic
hepatitis of HCV aetiology, where the average anxiety level was 52.753.69 (p<0.01) vs
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39.051.88 in the group of practically healthy individuals. In patients with chronic HBV
infection, this indicator was slightly lower – 48.312.29 (p<0.01) and the lowest average values
were found in individuals with liver steatosis – 42.961.64 (p<0.05).
Results reveal that patients with liver pathology of chronic HCV infection presented more
anxiety comparing with those suffering from chronic HBV infection, Liver Steatosis and
healthy individuals.
Albeit most investigations have focused on one type of viral hepatitis, especially chronic
HCV infection, identifying anxiety in 41%, as it was highlighted in Australian outpatients with
chronic hepatitis C [14].
In the study conducted by Alavian S. M. (2007) it was demonstrated the higher prevalence
of anxiety in patients with chronic viral hepatitis C in comparison to chronic viral hepatitis B
and normal controls [1]. In the study published by Sing (1997), hepatitis C patients showed to
have more anxiety in comparison with other liver diseases [13].
Fig. 2. Anxiety indicators in patients with chronic HBV and HCV infection, liver steatosis (LS)
and in the control group
Various hypotheses have been elaborated for explanation of the presence of more anxiety
manifestations in patients suffering of chronic HCV and HBV infection in comparison with
those who have other liver diseases. Some of these associate the higher probability of
psychiatric disorders in HCV positive patients to the following:
1) direct effect of viruses;
2) effects of manifestations of stigma regarding patients with chronic infection HBV and
HCV;
3) coincidence of psychiatric disorders with some risk factors of these viruses and other.
In favour of the first hypothesis Hilsabeck (2002) mentioned that the occurrence of cognitive
disorders has been reported after being infected with hepatitis HCV [7], however there are no
such reports for hepatitis HBV.
A number of studies [12, 20] report that a diagnosis of HCV or HBV infection affects the
social functioning of a person, stigma is observed on the part of relatives, the employer and
society as a whole, which contributes to the formation of anxiety in patients with viral hepatitis,
what can be considered in support of the second hypothesis.
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Reports demonstrating that patients suffering from anxiety show higher risk behaviours,
which impose them to acquire hepatitis viruses, are in line with the third hypothesis [6, 19].
Given the identified trend, and the multiplicity of possible causes of increased anxiety in
patients with hepatopathies, we need to conclude that there is a need for a more detailed analysis
of this problem on a larger number of examined persons.
This pragmatically model is comparable to that from FGID (22). Like in FGID, chronic
symptomatology creates anxiety. This is a pleading for the application of psychosomatic
medicine i.e., psychogastroenterology in neurogastroenterology.
Conclusion
Both FGID and chronic liver diseases are chronic conditions where the biopsychosocial
model applies. Therefore, these both conditions have anxiety scores higher than healthy
subjects. The highest level of anxiety was observed in patients with chronic HCV infection,
which could be explained as social and psychological factors, on one hand and the direct
neurotoxic effect of HCV, on the other.
REFERENCES
1. Alavian S. M., Tavallaii S. A., Farahani M. A. et al., (2007). Infectious Diseases and Tropical Medicine
Research Center Evaluation of the severity of depression and anxiety in hepatitis B and hepatitis C
patients: a case control study. Iranian Journal of Clinical Infectious Diseases 2(3), pp. 113-119.
2. Dunstan D. A., Scott N., Todd A. K. (2017). Screening for anxiety and depression: reassessing the utility
of the Zung scales. BMC Psychiatry 17, art. nr. 329.
3. EASL (2017). Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of
Hepatology 67, pp. 370-398.
4. EASL (2018). Recommendations on Treatment of Hepatitis C. Journal of Hepatology 69(2), pp. 461-
511.
5. EASL-EASD-EASO (2016). Clinical Practice Guidelines for the management of non-alcoholic fatty liver
disease. Journal of Hepatology 64, pp. 1388-1402.
6. El-Serag H. B., Kunik M., Rabeneck L. (2002). Psychiatric disorders among veterans with hepatitis C
infection. J. Gastroenterology 123, pp. 476-482.
7. Hilsabeck RC, Perry W, Hassanein TI. (2002). Neuropsychological impairment in patients with chronic
hepatitis C. Hepatology 35(2), pp. 440-446.
8. Lupașco Iu. (2014). Hepatitele cronice și alte forme ale bolilor cronice difuze ale ficatului. Chișinău, p.
328.
9. Lupaşco Iu. (2017). Hepatitele cronice virale B și C la adulți (factori de risc, particularitățile clinic-
evalutive, hormonal-metabolice, imunologice și optimizarea metodelor de tratament). Teză de doctor
habilitat în ştiinţe medicale. Chișinău, p. 302.
10. PCN-278 (2017). Tulburările de anxietate. Chișinău, p. 77.
11. Prisacari V., Paraschiv A., Spînu C. et al., (2013). Hepatitele virale parenterale și ciroze hepatice –
epidemiologia, clinica, diagnosticul, tratamentul, prevenirea și controlul. Ghid. Chișinău, p. 160.
12. Rafique I., Saqib M.A.N., Siddiqui S. et al., (2015) Experiences of stigma among hepatitis B and C
patients in Rawalpindi and Islamabad, Pakistan. East Mediterr. Health J., 20(12) 2, pp. 796-803.
13. Singh N., Gayowski T., Wagener M. M. et al., (1997). Vulnerability to psychological distress and
depression in patients with end-stage liver disease due to hepatitis C virus. Clin. Transplantation 11, pp.
406-411.
14. Stewart B., Mikocka-Walus A., Morgan J. et al., (2007). Anxiety and depression in Australian chronic
hepatitis C outpatients: prevalence and predictors. B. Australas Psychiatry 20(6), pp. 496-500.
15. WHO (2016). Global health sector strategy on viral hepatitis 2016-2021. Geneva: WHO. Available at:
http:www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/
16. WHO (2017). https:www.worldlifeexpectancy.com/cause-of-death/liver-disease/by-country.
17. WHO (2017). Guidelines on hepatitis B and C testing. Geneva: WHO, p. 204.
18. WHO (2018). Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus
infection. WHO.
19. Yovtcheva S. P., Rifai M. A., Moles J. K., et al., (2001). Psychiatric comorbidity among hepatitis C-
positive patients. Psychosomatics 42, pp. 411-415.
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20. Zacks S., Beavers K., Theodore D. et al., (2006). Social stigmatization and hepatitis C virus infection. J.
Clin. Gastroenterol. 40(3), pp. 220-224.
21. Ерилин Е. А. Анисимова Е. Н., Анисимова Н. Ю. (2016) Методы оценки психоэмоционального
состояния пациентов в условиях амбулаторного стоматологического приёма. Вестник новых
медицинских технологий (Электронное издание), Издательство: Тульский государственный
университет (Тула) 2, cc. 124-130.
22. Vitellio P, Chira A, De Angelis M, Dumitrascu DL, Portincasa P. Probiotics in Psychosocial Stress and
Anxiety. A Systematic Review. J Gastrointestin Liver Dis DOI: 10.15403/jgld-352
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Diverticulosis and Irritable Bowel Syndrome – Simple Association

or Causal Relationship?
DIMACHE Mihaela1, ANTON Carmen2, TIMOFTE Oana3,

CIORCILĂ Ciprian4, ONOFREI Roxana5, DUDUMAN Sandina6
UMF “Gr. T. Popa” Iași; IGH, Sp. “Sf. Spiridon” Iași; (ROMÂNIA)
1,2,3
IGH, Sp. “Sf. Spiridon” Iași; (ROMÂNIA)

4,5,6
Emails: mimidimache@yahoo.com, carmen_ro2008@yahoo.com, oanatimo@yahoo.com, ciprian_ciorcila@yahoo.com,

onofrei.roxana92@yahoo.com, sandinabistriceanu@gmail.com
Abstract
The association between diverticular disease and irritable bowel syndrome (IBS) is not very
well defined. Many elderly patients have diverticulosis, mostly without any symptom.
Nevertheless, some of them present symptomatology suggesting IBS (“IBS-like
symptoms”). Is the association of the two entities a simple coincidence or the presence of
diverticulosis leads to some abnormalities of the colon that cause the symptoms? We try to
summarize some new scientific data in order to answer this difficult question.
Keywords: Diverticulosis, irritable bowel syndrome, symptomatology
The Central Issue
Many elderly patients (approximately 40-50% of aged people between 60 and 70 years old)
have diverticulosis, mostly without symptoms. Yet, some of them present recurrent abdominal
pain and disturbed bowel habit, symptoms suggesting IBS and which are therefore called “IBS-
like symptoms”.
The question that arises is: “Do these patients have IBS and coincidentally diverticulosis or
the presence of diverticulosis leads to some specific abnormalities of the colon that cause the
symptoms” [1]?
How to Answer the Question?
How to answer this question has troubled clinicians all over the world for many years? New
data from recent studies come and try to clarify this debate.
The results of a Japanese study published in 2014 in American Journal of Gastroenterology
add new data to this controversy [2].
It shows that in a cohort of Japanese patients situated between 60 and 70 years old and
undergoing colonoscopy, around 40% have diverticulosis and 7.5% have symptoms compatible
with IBS. The percentage of patients with diverticulosis is similar to that in the western studies.
The location of diverticuli is predominant on the right colon, a feature different from the
western patients: 21.6% on the right colon, 6.6% on the left colon and 12.0% bilateral.
In this Asian group of patients, the study shows that those with left-sided diverticulosis were
3 times more likely to have IBS symptoms than those with right-sided diverticulosis [2].
The conclusion of the study is that the link between diverticulosis and IBS depends on the
site of the diverticula. In the group of aged patients with diverticulosis, those with left-sided
diverticula are predisposed to IBS – like symptoms.
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The relation between the left-sided diverticula and the IBS symptoms may be explained
through the differences of behaviour between the right-sided diverticula and the left-sided
diverticula. To explain this relation, we must look first on the anatomo-functional differences
between the right colon and the left colon. The right colon has a larger diameter (around 2.5
cm), a thinner wall and a mean length of 10 cm [3], while the left colon has a smaller diameter
(approximately 1.8 cm), a thicker wall with better represented muscles and a mean length of 16
cm [4]. The right colon contains low-viscosity fluid and has a lower motor activity [3], while
the left colon shows a higher motor activity, designed to propel the viscous/hard material
distally [4].
As a result, the right colon has less frequent diverticula, with less frequent complications
(especially bleeding) [5]. The left colon has more frequent diverticula, which may cause severe
complications, like perforation, fistulation or abscess formation [6].
The increased motility index together with the higher intraluminal pressures especially after
meals explain the different behaviour between right diverticula and left diverticula. In the group
of patients with diverticular disease, those with left-sided diverticula are more frequently
symptomatic and are predisposed to more frequent and severe complications than those patients
with right-sided diverticula, who are usually asymptomatic [7].
How Many Patients with Diverticulosis Have Symptomatology?

Another question is how many patients with diverticulosis have symptoms.
Studies have shown that only a subgroup of patients with diverticulosis has symptoms,
representing 20-33%, but the percentage varies upon the study. The diverticula are diagnosed
only after a colonic investigation (most frequently, colonoscopy), usually recommended for
symptomatology [8].
Some studies suggest that up to third of the patients with diverticulosis have chronic
abdominal pain, more likely if they have a history of an episode of prolonged severe pain
suggestive of diverticulitis. It seems that a higher proportion of the patients with diverticulosis
report pain after a hospitalization for acute diverticulitis [8].
The results of an interesting study published in 2013 in Clinical Gastroenterology
Hepatology support the relation between acute diverticulitis and irritable bowel syndrome [9].
The study confirms this association, by showing that the patients admitted for acute
diverticulitis have a 4.7-fold increased risk for developing IBS over the next 6 years after
hospitalization. These patients present chronic abdominal pain with disturbed bowel transit
(loose or hard stools), symptoms which occur for the first time after an episode of acute
diverticulitis.
The conclusion of the study is that the IBS-like symptomatology in a patient with
diverticulosis may be triggered by an episode of acute diverticulitis. This clinical entity is called
post-diverticulitis IBS [9].
Someone may ask why post-diverticulitis IBS is possible to occur. Studies have shown
potentially shared pathophysiologic mechanisms between IBS and symptomatic diverticular
disease:
1) Some IBS patients present low-grade colonic inflammation, without macroscopic colitis,
the inflammation may modify intestinal reflexes and amplify visceral sensitivity, which
consequently will alter intestinal motility in IBS [10]. Likewise, some studies have
shown chronic microscopic inflammation present in biopsies taken from diverticular
region in patients with symptomatic diverticular disease [11].
2) Similar to IBS, patients with symptomatic diverticular disease show a hypersensitivity
to distension, due either to peripheral changes induced by episodes of diverticulitis, or to
altered central processing of painful stimuli.
24
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3) In patients with diverticulosis, an episode of acute inflammation (acute diverticulitis)

may induce important peripheral changes, like increased enteric response to chemical
stimuli. This peripheral response may cause the occurrence of hypersensitivity to
distension [12].
4) Other patients with diverticulosis may have visceral hypersensitivity due to altered
central processing of painful stimuli. Their symptoms could have appeared after severe
prolonged pain associated with an episode of diverticulitis or after recent psychological
trauma such as bereavement [13].
5) Other studies have shown that symptomatic (uncomplicated) diverticular disease (DD)
is associated with enhanced perception of distension, not only in the diverticular region
(usually sigmoid), but also in the unaffected colon. In symptomatic diverticulosis, it is a
generalized hyperperception of intestinal stimuli which resembles IBS; these features are
not present in asymptomatic DD [14].
6) Other data support a potential association between the intestinal microbiota and
symptomatic diverticular disease.
Gut-directed antibiotics may reduce episodes of recurrent diverticulitis and treat abdominal
symptoms in symptomatic diverticular disease. Evidence also show modest benefits of
antibiotics in IBS [15].
7) Low dietary fiber intake, a risk factor for both diverticular disease and IBS with
constipation, is associated with alterations in gut microbiota; these changes may
determine bacterial overgrowth, which will lead to episodes of acute diverticulitis.
Intestinal bacterial overgrowth may also occur in many patients with IBS [15, 16].
The importance of the history of the disease and of the psychological typology of the patient
Studies have shown that the history of the disease and the psychological typology of the
patient are very important in establishing the model of relationship between IBS and
diverticulosis:
1) A first model is the patient who has had IBS for many years and who is discovered in
the 6th decade of life with diverticulosis (usually by colonoscopy). He has psychological
features or comorbidities that predispose to IBS (anxiety, depression, poor quality of
life).
In this case, the presence of IBS and diverticulosis represent a simple association, and the
therapy must be medical (antispasmodics and low-dose tricyclic antidepressants for pain,
soluble fibre for constipation or loperamide for diarrhoea) [17].
2) A second model is the patient who has not developed IBS in early adulthood, has neither
anxiety nor depression, and who develops a symptomatology suggestive of IBS after an
episode of acute diverticulitis. The occurrence of IBS-like symptoms is probably due to
peripheral changes induced by the episode of acute colonic inflammation.
In this case, the patient may have “IBS-like diverticular disease”, which represents a causal
relationship between the two entities. If the medical treatment is not successful, the patient may
respond to subtotal colectomy [18].
Conclusions
Patients with right-sided diverticulosis are usually asymptomatic, while patients with left-
sided diverticula are more frequently predisposed to IBS-like symptoms.
In those patients without history of IBS, or psychological features characteristic to IBS, who
develop recurrent abdominal pain and disturbed bowel habit after an episode of acute
diverticulitis, IBS-like symptoms match the model of “post-diverticulitis IBS”.
25
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Patients with a long history of IBS, with antecedents of anxiety or depression, who are
discovered with diverticulosis in their 6th-7th decade of life, have most probably a simple
association of the two diseases.
In a person with diverticulosis, without history of IBS, without an episode of prolonged
abdominal pain suggesting diverticulitis, who begin to have IBS-like symptoms after a severe
psychological stress, there is possible a connection with an altered central processing of painful
stimuli.
Prospective studies in which patients with diverticulosis are assessed for IBS-like symptoms
and psychological factors and followed over time are necessary to define the complex
correlation between the two conditions and the optimal therapeutic approach.
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J Gastroenterol 2014; 109: pp. 1906-1908.
2. Yamada E, Inamori M, Uchida E, et al., Association between the location of diverticular disease and the
irritable bowel syndrome: a multicentre study in Japan. Am J Gastroenterol. 2014; 109: pp. 1900-5.
3. Marciani L, Pritchard SE, et al., Delayed gastric emptying and reduced postprandial small bowel water
content of equicaloric whole meal bread versus rice meals in healthy subjects: novel MRI insights. Eur.
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6. Law WL, Lo CY, et al., Emergency surgery for colonic diverticulitis: differences between right-sided
and left-sided lesions. Int. J Colorectal Dis 2011; 16: pp. 280-4.
7. Bassotti G, Battaglia E, et al., Alterations in colonic motility and relationship to pain in colonic
diverticulosis. Clin. Gastroenterol. Hepatol. 2005; 3: pp. 248-53.
8. Simpson J, Neal KR, et al., Patterns of pain in diverticular disease and the influence of acute
diverticulitis. Eur. J Gastroenterol Hepatol 2003; 15: pp. 1005-10.
9. Cohen E, Fuller G, Bolus R, et al., Increased risk for irritable bowel syndrome after acute diverticulitis.
Clin Gastroenterol Hepatol 2013; 11(12): pp. 1614-1619.
10. Kozak LJ, DeFrances CJ, et al., National hospital discharge survey: 2004 annual summary with detailed
diagnosis and procedure data. Vital Health Stat 2006; 13: pp. 1-209.
11. Horgan AF, McConnel EJ, et al., Atypical diverticular disease: surgical results. Dis Colon Rectum 2001;
44: pp. 1315-18.
12. Simpson J, Sundler F, et al., Postinflammatory damage to the enteric nervous system in diverticular
disease and its relationship to symptoms. Neurogastroenterol Motil 2009; 21: pp. 847-58.
13. Smith J, Marciani L, et al., Cortical brain activation in response to somatic pain in symptomatic
diverticular disease. Neurogastroenterol Motil 2012; 24: p. 188.
14. Clemens CHM, Samsom M, Roelafs J, et al., Colorectal visceral perception in diverticular disease. Gut
2004; 53: pp. 717-722.
15. Tursi A, Brandimarte G, et al., Assessment of small intestinal bacterial overgrowth in uncomplicated
acute diverticulitis of the colon. World J Gastroenterol 2005; 11: pp. 2773-76.
16. Brandimarte G, Tursi A. Rifaximin plus mesalazine followed by mesalazine alone is highly effective in
obtaining remission of symptomatic uncomplicated diverticular disease. Med Sci Monit 2004; 10: p.
150.
17. Koloski NA, Jones M, et al., The brain-gut pathway in functional gastrointestinal disorders is
bidirectional: a 12-years prospective population-based study. Gut 2012; 61: pp. 1284-90.
18. Spiller RC. Irritable bowel syndrome: gender, infection, lifestyle or what else? Dig Dis 2011; 29: pp.
215-21.
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Optical Diagnosis of Barrett Oesophagus in 2019
DOBRU Daniela E.1

1
University of Medicine, Pharmacy, Science and Technology Targu Mures, Gastroenterology Department, (ROMANIA)
Email: danidobru@gmail.com
Abstract
Barrett oesophagus (BE) is a well-defined risk factor for the development of oesophageal
adenocarcinoma (EAP). For the diagnosis of BE two criteria has to be met: endoscopical criteria
which has to show squamocolumnar junction (Z line) displaced at least 1 cm or more proximal
to the esophagogastric junction and pathology criteria which shows specialised intestinal
metaplasia detected by biopsy.
Current strategies focus on identifying the high risk patients for developing Barrett’s relating
cancer at an early stage, which are potentially curable stages. Screening of high risk patients
and surveillance of BE patients are current recommendations of the national and international
guidelines. Optical diagnosis of Barret oesophagus is mandatory for surveillance in order to
find dysplasia or Barrett’s relating adenocarcinoma. Advanced endoscopic imaging
technologies and chromo-endoscopy may improve detection of dysplastic Barrett by mucosal
visualisation and enhancement of fine structural and microvascular details and may guide
targeted biopsies for the detection of dysplasia during surveillance of patients with previously
non-dysplastic BE.
Keywords: Barrett oesophagus, oesophageal adenocarcinoma, optical diagnosis
Introduction
Optical diagnosis of Barrett oesophagus (BE) is one of the biggest challenge for any
endoscopist. The pressure comes from its potential progress to oesophageal adenocarcinoma
which still remains the 8th most common cancer worldwide with an estimated of 456000 new
cases/year. Oesophageal adenocarcinoma has a very poor survival rate with the highest
mortality rates occurring in Eastern Asia (14.1 per 100,000) Southern Africa (12.8 per 100,000)
[1].
The survival data by stage shows a huge difference between the 5 year-survival rate in early
stages (stage 0 and stage 1) compared with the advanced stages which have a very low survival
rate. (Fig. 1).
All these data suggest that in order to find early stages of Barett’s related cancer with very
good prognosis, a precise optical diagnosis is mandatory.
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Fig. 1. Survival rate in oesophageal cancer according to the stage
The Rationale for the Optical Diagnosis in Barrett Oesophagus
Cancer risk in BE
There are different reports on cancer incidence ranging between 0.2%~1.9%. A meta-
analysis from 57 studies resulted in 0.33% incidence in all BE patients and 0.19% incidence in
short-segment BE, if non-dysplastric Barrett oesophagus was found at index endoscopy. So, the
cancer risk in non-dysplastic BE was low [2]. A more recent study conducted in Netherland,
Ireland and Denmark on unselected patients with Barrett oesophagus shows similar data on
incidence of BE related adenocarcinoma (0,12-0,14% per year) [3], [4].
The appearance of dysplasia of the Barrett epithelium change the cancer risk as it was
demonstrated in recent studies. A meta-analysis of 24 studies with more than 2500 patients with
low grade dysplasia, with 2 years of endoscopic surveillance showed an annual progression rate
to cancer of 5.4 (3.2-7.6) per 1000 years, and progression to high-grade dysplasia or cancer
combined of 17.3 (9.9-24.7) per 1000 patient-years [5]. Patients with high grade dysplasia have
the highest progression rates to cancer. The progression rates are confounded by a few factors:
HGD patients routinely undergo intervention such as endoscopic resection so they are not
followed up more than 6 months and the co-existence of HGD lesions with invasive
adenocarcinoma lesions. Data on this issue comes from small size studies and are not consistent.
Rastolgi at al showed in a systematic review of 4 original studies, a progression rate to cancer
in these patients with high-grade dysplasia of 6.58 (4.97-8.19) per 100 years [5].
Optical Diagnosis in Barrett Oesophagus
Pre-adoption requirements for optical diagnosis in Barrett

Optical diagnosis of BE requires high quality endoscopy according to the key performance
measures for upper gastrointestinal endoscopy recommended by ESGE and United European
Gastroenterology. [6] ESGE suggests that HD endoscopy, dye or virtual chromo endoscopy, as
well as add-on devices can be used in surveillance of patients with BE.
The following pre-adoption technical requirements are mandatory for optical diagnosis in
BE: HD endoscopy equipment, optimal equipment for the process of acquiring and storing
images and/or video capture, appropriate video processor, large HD monitor, suitable cables for
transporting the HD digital signal and HD (video) capture to save the (video) images,
appropriate photo documentation.
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Optical diagnosis steps

A high quality endoscopy begins with thorough preparation of the patient; conscious
sedation or deep sedation will give physician more confidence and patient more compliance.
Second, excess mucus should be removed using a mucolytic solution delivered by water jet
through the endoscope. Typically, a 2% solution of simethicone or N-acetylcysteine is used to
remove mucous and bubble formation.
The process of an optical diagnosis of Barrett epithelium has three steps: detection of any
suspicious area, characterisation and delineation.
Frequently the detection task of suspicious areas is the most difficult one, in particular in
patients with flat Barrett epithelium. Moreover, studies have also demonstrated that the majority
of high-grade intraepithelial neoplasia or early oesophageal cancer is non-polypoid and even
Barrett experts, achieved a mean sensitivity of 80,4% and a mean specificity of 88,4% in
prediction of high-grade dysplasia.
An important step of the improvement of the detection of dysplastic Barrett is the inspection
time. ESGE recommend a upper go endoscopy time of ≥7 minutes and inspection time of ≥1
minute/cm of the circumferential extent of the Barrett’s epithelium [6].
Identifying the endoscopic landmarks in BE is essential to ensure that patients have BE and
not intestinal metaplasia of the cardia. The top of the visible gastric folds is the anatomic
landmark of the gastro-oesophageal junction, the position from which measurements of visible
columnar tissue should begin [7].
The Prague classification is widely recommending to be used in order to standardize the
reporting of endoscopic and histologic findings in patients with BE. Prague classification
identify the location of the top of the gastric folds, the proximal extent of both the
circumferential BE segment (C) as well as the maximal extent of any tongues (M) or islands.
Fig. 2 [8].
Fig. 2. Prague classification measurements from the get junction: A. extent of circumferential BE(C) BE A,
Extent of circumferential BE. B, maximal (M) extent of BE segment including tongues
The characterization of the epithelium Barrett, another important task, requires the
endoscopies to spend at least 1 minute inspecting each centimetre of BE mucosa. A particular
focus is necessary on the right wall and proximal segment of Barrett epithelium as dysplasia is
more commonly seen at these sites [9-12].
The endoscopies have to be aware that dysplastic or early neoplastic lesions may be missed
as these are tiny, subtle or flat lesions.
The following features may predict dysplastic or early neoplastic lesions on BE:
- disordered mucosal pit patterns,
- modified vascular pattern/vascular abnormalities,
29
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- depressions, or nodularity with associated dilation and formation of aberrant vessels,

- areas with colour changes of the mucosa.
All these modification of mucosal and vascular pattern should be recorded based on Paris
classification. [13] Fig. 3. Based on the type of the lesion the endoscopist may predict the
appropriate endoscopic therapy.
Fig. 3. The Paris classification of early and/or superficial tumours in the GI tract
Virtual chromo endoscopy (narrow band imaging NBI, i-Scan imaging system and blue light
imaging BLI) is considered nowadays a useful tool in characterization of Barrett epithelium.
These new technologies are able to enhance mucosal and vascular patterns seen at
endoscopic assessment and all typically stratify lesions as dysplastic or non-dysplastic based
on mucosal or vascular patterns. Validated classification systems should be applied when using
these virtual chromo-endoscopy modalities patterns (BING classification for NBI, BLINC
classification for BLI [14, 15], Fig. 4, Fig. 5.
Fig. 4. The BLINC classification
30
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Likely Diagnosis Non-dysplastic Barrett Dysplastic Barrett
Mucosal pattern Regular Irregular

= Circular, ridge/villous or = Absent or irregular
tubular patterns
Vascular Pattern Regular Irregular

= Blood vessels regular along = Focally or diffusely
or between mucosal ridges distributed vessels not
and/or those showing normal, following normal architecture
long, branching patterns of the mucosa
Fig. 5. The BING classification
The topical application of dyes may improve the characterization of Barrett epithelium as
well as delineation of the lesion. Data shows that acetic acid spray applied to the oesophageal
mucosa during endoscopy is a very effective, cheap, universal and goes with all endoscopic
platforms. After the application of a dilute (1.5%-3.0%) acetic acid solution, clinicians should
observe the mucosa, which under normal circumstances turns white within seconds. This colour
change highlights mucosal patterns more clearly, facilitating a more sensitive and specific
identification of potentially neoplastic areas. The premature loss of aceto-whitening is also
associated with the presence of early neoplasia [16, 17].
Conclusions
Optical diagnosis of Barrett oesophagus may be challenging and the differentiation between
non-dysplastic Barrett and dysplastic Barrett is the key. There are steps to be followed in order
to find those tiny lesions which might be dysplastic or cancer lesions. Thorough preparation of
the patient, prolonged inspection time of the mucosa, the use of classical or virtual HD chromo-
endoscopy and the validated classifications bring us closer to a more precise diagnosis.
And never the less, the endoscopists should be properly trained to perform a high quality
optical diagnosis and recognize subtle visible abnormalities associated with early neoplasia.
REFERENCES
1. GLOBOCAN 2012 (IARC) (20.04.2016)

2. Desai TK, Krishnan K, Samala N, Singh J, Cluley J, Perla S, Howden CW. The incidence of
oesophageal adenocarcinoma in non-dysplastic Barrett oesophagus: a meta analyses. GUT 2012 Jul;
61(7), pp. 970-6.
3. Bhat S, Coleman HG, Yousef F, et al., Risk of malignant progression in Barrett’s oesophagus
patients: results from a large population-based study. J Natl Cancer Inst. 2011; 103: pp. 1049-1057.
4. De Jonge PJF, van Blankenstein M, Looman CWN, et al., Risk of malignant progression in patients
with Barrett’s oesophagus: A Dutch nationwide cohort study. Gut. 2010; 59: pp. 1030-1036.
5. Singh S, Manickam P, Amin AV, et al., Incidence of oesophageal adenocarcinoma in Barrett’s
oesophagus with low-grade dysplasia: a systematic review and meta-analysis. Gastrointest. Endosc.
2014; 79: pp. 897.e4-909.e4.
6. Bisschops R, Areia M, Coron E et al., Performance measures for upper gastrointestinal endoscopy:
A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.
Endoscopy 2016; 48: pp. 843-864
7. Spechler SJ, Zeroogian JM, Antonioli DA, et al., Prevalence of metaplasia at the gastro-oesophageal
junction. Lancet 2017; 344: pp. 1533-1536.
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8. Sharma P, Dent J, Armstrong D, et al., The development and validation of an endoscopic grading
system for Barrett’s oesophagus: The Prague C & M criteria. Gastroenterology 2006; 131: pp. 1392-
1399.
9. Edebo A, Vieth M, Tam W, et al., Circumferential and axial distribution of oesophageal mucosal
damage in reflux disease. Dis Oesophagus 2007; 20: pp. 232-238.
10. Pech O, Gossner L, Manner H, et al., Prospective evaluation of the macroscopic types and location
of early Barrett’s neoplasia in 380 lesions. Endoscopy 2007; 39: pp. 588-593.
11. Enestvedt BK, Lugo R, Guarner-Argente C, et al., Location, location, location: does early cancer in
Barrett’s oesophagus have a preference? Gastrointest Endosc 2013; 78: pp. 462-467.
12. Cotton CC, Duits LC, Wolf WA, et al., Spatial predisposition of dysplasia in Barrett’s oesophagus
segments: a pooled analysis of the SURF and AIM – Dysplasia Trials. Am J Gastroenterol 2015;
110: pp. 1412-1419.
13. Endoscopic Classification Review Group. Update on the Paris classification of superficial neoplastic
lesions in the digestive tract. Endoscopy 2005; 37: pp. 570-578.
14. Sharma P, Bergman JJ, Goda K, et al., Development and validation of a classification system to
identify high-grade dysplasia and oesophageal adenocarcinoma in Barrett’s oesophagus using
narrow-band imaging. Gastroenterology 2016; 150: pp. 591-598.
15. Kandiah K, Chedgy FJQ, Subramanian S, et al., International development and validation of a
classification system for the identification of Barrett’s neoplasia using acetic acid chromo-
endoscopy: The Portsmouth acetic acid classification (PREDICT). Gut 2017.
16. Sharma P, Savides TJ, Canto MI, et al., The American Society for Gastrointestinal Endoscopy PIVI
(Preservation and Incorporation of Valuable Endoscopic Innovations) on imaging in Barrett’s
Esophagus. Gastrointest. Endosc. 2012; 76: pp. 252-254.
17. Sharma P, Bergman JJ, Goda K, et al., Development and validation of a classification system to
identify high-grade dysplasia and oesophageal adenocarcinoma in Barrett’s oesophagus using
narrow-band imaging. Gastroenterology 2016; 150: pp. 591-598.
18. Kandiah K, Chedgy FJQ, Subramaniam S, et al., International development and validation of a
classification system for the identification of Barrett’s neoplasia using acetic acid chromo-
endoscopy: The Portsmouth acetic acid classification (PREDICT). Gut 2017.
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Faecal Transplant in Irritable Bowel Syndrome: Moving

Forward?
DRANGA Mihaela1,2, MIHAI Cătălina1,2*, GAVRILESCU Otilia1,2,

ANDRONIC Andrei2, OTEA Andreea2, LEUSTEAN Alina2,
BARBOI Oana-Bogdana1,2, DRUG Vasile1,2,
CIJEVSCHI PRELIPCEAN Cristina2, FLORIA Mariana1,3
1
“Grigore T. Popa” University of Medicine and Pharmacy, Iaşi (ROMÂNIA)
2
“St. Spiridon” Hospital, Hepatology and Gastroenterology Institute, Iaşi (ROMÂNIA)
3
Emergency Military Clinical Hospital, Iaşi (ROMÂNIA)
*
Corresponding author: MIHAI Cătălina
Emails: mihaela_dra@yahoo.com, catalinamihai@yahoo.com, otilianedelciuc@yahoo.com, andrei2020.am@gmail.com,
andreea.otea@yahoo.com, alina_mihaela1811@yahoo.com, oany_leo@yahoo.com, vasidrug@email.com,
cristinacijevschi@yahoo.com, floria_mariana@yahoo.com
Abstract
Irritable bowel syndrome (IBS) is the most common gastrointestinal disease. The effect of
the available therapies is limited. It includes psychological support, dietary interventions, and
drugs, depending on the individual symptom characteristics. Recent evidences suggest an
important role of alterations in the gastrointestinal flora. The gut microbiota has recently been
shown to be involved not only in gastrointestinal diseases, but also in a variety of systemic
inflammatory and metabolic diseases. Studies have been shown that dysbiosis plays an
important role in the pathogenesis of IBS. Starting from these findings, some authors proposed
modulation of gut microbiota with faecal microbiota transplantation as treatment option for
IBS.
There are several administration methods: retention enema, colonoscopy, nasogastric/naso-
duodenal tube, endoscopy or oral. There is no standardization in the preparation and
administration of the faecal suspension. Small studies showed some positive effect in IBS
patients but they are a few and on a small number of patients. The meta-analysis does not
support this treatment for IBS patients. Further studies on larger population are necessary to
validate this therapy for IBS patients and to include it into guidelines.
Keywords: faecal transplant, microbiota, irritable bowel syndrome
Irritable bowel syndrome (IBS) is the most common gastrointestinal disease being found in
5.8-17.5% of the adult population [1]. That is associated with significant morbidity and great
costs due to the expensive investigations to exclude other pathology. IBS is a long-lasting
condition, more than 6 months, most of the patients are having symptoms for decades [2]. IBS
is defined as recurrent abdominal pain on average at least 1 day/week in the last 3 months,
associated with two or more of the following criteria: a) related to defecation, b) associated with
a change in the frequency of stool, c) associated with a change in the form (appearance) of stool
[3]. IBS can be classified into one of four subtypes (diarrhoea predominant, constipation-
predominant, mixed or un-subtyped) based on predominant stool form and frequency [4].
The effect of the available therapies is limited. It includes psychological support, dietary
interventions, and drugs, depending on the individual symptom characteristics (diarrhoea or
constipation dominated IBS) [5].
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The cause of IBS still remains unknown. IBS is a disorder of gut-brain axes with multiple
etiologist. Factors involved in physiopathology: intestinal dysmotility, visceral
hypersensitivity, immunological, psychosocial factors, do not completely explain the symptoms
[6]. Recent evidences suggest an important role of alterations in the gastrointestinal flora; this
fact has led to an increasing interest in probiotic and antibiotic as therapy in IBS [7].
The gut microbiota (500-1,000 different bacterial species, viruses, protozoal communities
and fungi), has recently been shown to be involved not only in gastrointestinal diseases, but
also in a variety of systemic inflammatory and metabolic diseases [8]. The microbiome is
characterized by resilience, stability and complexity. A healthy microbioma protects against
pathogens, trains the immune system, and contributes to digestion of food in order to supply
energy and nutrients. These characteristics are influenced from the time of birth into old age by
the route of birth, genetic factors, geographic factors, diet, medication. Some of these factors
can introduce perturbations, potentially introducing microbial dysbiosis [9].
Studies have been shown that dysbiosis plays an important role in the pathogenesis of IBS
[10]. Starting from these findings, some authors propose modulation of gut microbiota with
agents such as probiotics, prebiotics, symbiotics, luminal antibiotics, and faecal microbiota
transplantation (FMT) as treatment options for IBS. FMT is defined as the transfer of
gastrointestinal (GI) microbiota from a healthy donor into the GI tract of a patient with a certain
disease. The rationalization behind this is that a perturbed imbalance in our intestinal microbiota
(dysbiosis) is associated with or causes disease; it can be corrected with introduction of donor
faces [11].
The faecal transplant is used from the ancient times. The first documentation is from fourth
century when a Chinese physician, Ge Hong advised patients suffering from severe diarrhoea
to consume fresh stool from a healthy neighbour as a form of treatment of what he called
“yellow soup” [12]. In the 17th century veterinarians also use stool as a therapeutic modality,
given by oral or rectal means [13]. During World War II, German soldier used camel stool to
treat bacterial dysentery [14].
In 1958 was published the first article using this technique. Eiseman et al., reports the
treatment of patients with antibiotic-associated diarrhoea with FMT via retention enema. The
patients recovered promptly from the diarrhoea [15]. Since 1991 FMT is administrated via naso-
gastric tube [16] and since 2000 via colonoscopy [17].
The question that appeared was that the FMT was durable. In a study from 2010, the authors
stated that stability in composition over a 24-week period, has a prolonged cure rate of 91-94%
and determined an immediate and complete resolution of symptoms in patients with
refractory/recurrent Clostridium difficile infection [18].
There is no standardization in the preparation and administration of the faecal suspension.
Every hospital prepared their own protocol. The donor must be a healthy relative or friend,
ideally not sharing living quarters, with normal, daily stools, no recent antibiotics in the last six
months. The donor must be checked to exclude: hepatitis A, B, C, HIV-1, HIV-2, syphilis. Also
we must perform stool cultures, stool for ova and parasite and specific analyse to exclude C.
difficile infection in order to rule out asymptomatic carriage [19]. The recipient also must be
tested anterior to FMT for HIV and hepatitis markers to avoid future question about the
transmission [19].
There are several administration methods: retention enema, colonoscopy, nasogastric/naso-
duodenal tube, endoscopy or oral.
Retention enema
It is the first method use. There are numerous studies with the efficacy of FMT via retention
enema in patients with refractory/recurrent Clostridium difficile infection, with very good
results. There are also kits for home administration. This procedure was used in 2010: stool
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infusate (~250 mL) was self-administered or administered by a family member with a 94% cure
rate [20]. We did not found any study with this procedure in patients with IBS.
Colonoscopy
This method seems to be superior to the prior method. It offers a greater area of
recolonization proximal to the splenic flexure and also delivers the microbiota to the distal small
bowel. The preparation method consists in: 200-300 g of donor stool is suspended in 200-300
mL of normal saline, homogenized briefly (2 min) in kitchen blender to a liquid consistency
and give via enema within 10 minutes or filter then infuse via colonoscopy into intestinal tract.
It must be retaining for at least 6 hours (loperamide pre-treatment) and then follow a high
fiber diet. The process can be repeated daily for five days, but this is not practical [18].
There are several studies using this method but they were made on a small group of patients
with IBS. In 2015, Cruz et al., administered FMT in 9 patients with IBS. The follow up period
was of 3 months. The authors observed that FMT was beneficial in reducing symptoms.
Moreover, they observed that there was a profound change in microbiome in predominant
diarrhoea IBS patients [21].
In another study, performed in Koreea, Hong et al., studied the effect of FMT via
colonoscopy in 10 patients with IBS. The follow up periods were 12 and 26 weeks. They noticed
symptoms improvement after FMT in 80% of patients. However, those who showed significant
improvement in IBS severity scores during the first month returned to their pre-FMT state after
3 months [22].
Syzenko et al., analysed the benefits of FMT via colonoscopy on 12 patients with IBS. The
follow up period was not reported. The authors observed significant rate of clinical
improvement in refractory IBS symptoms after FMT (p<0.01) [23].
Mizuno et al., followed the effect of FMT via colonoscopy on 12 patients and observed that
FMT improved stool form and depressed mood. Bifidobacterium-rich donor faeces were related
to successful FMT. When the authors compared the microbiota of the patients receiving FMT
from effective donors (responsive patients) with ineffective donors (nonresponsive patients)
they have noticed that the FMT of the effective donors had a significant higher concentration
of the phylum Actinobacteria which is part of Biffidobacterium genus (p=0.02) [24].
Nasogastric/naso-duodenal tube (NG/NJ tube)

Patient and stool preparation is similar. In the evening before, and morning of the instillation,
we must administrate proton pump inhibitors (omeprazole 20 mg) to decrease gastric acid. NG
or NJ tube is placed.
The positioning is confirmed by X-ray and Gastrografin follow-through. A single instillation
of 25 to 30 g of stool diluted in 50 mL of saline is administered. Through this method we can
deliver the bacteria to the distal small bowel and throughout the colon [25].
In a recent study, Holvoet et al., analysed 64 patients with IBS with bloating. The participants
were split into two groups: 42 patients received FMT and 22 placebos. The follow up period
was 3 months. At the end of the follow up period a significant larger number of patient that
received FMT 20/41 (49%) had a release of the symptoms compare to the placebo group 6/21
(29%) (p=0,004) [26].
Endoscopy
Pinn and colab. studied the IBS patients with refractory symptoms. They administered a
faecal suspension ‒ 50-100 ml in distal duodenum or proximal jejunum via endoscopy. The
study observed the length of symptom-free intervals, abdominal pain, bloating, flatus,
dyspepsia, frequency of bowel movements, and overall well-being before and after procedure.
35
©
The study was performed on a small number of 13 patients. The results were very good: 70%
of the patients experienced resolution or improvement of symptoms after FMT, in 72% the
abdominal pain reduced, 67% have a resolution of dyspepsia, 50% of bloating and 45% of
flatus.
The improvement of overall well-being was obtained in almost half of the patients (46%)
[27].
In a recent study on a much larger number of participants (90) Johnsen et al., compared FMT
with placebo in patients with IBS. There were three study groups: 30 participants were enrolled
in the placebo group, 30 patients with IBS received fresh FMT and 30 patients frozen FMT.
The study had as the end point the reduction with 75 points of IBS-SSS (severity scoring
system). The follow up periods were at 3 months and 12 months. The authors observed that at
3 months the end point was achieved by a significant more patients in FMT group than in
placebo group (36 (65%) of 55 FMT vs 12 (43%) of 28 placebos (0.049)). Although this effect
did not maintain at 12 months (31 (56%) of 55 FMT vs 10 (36%) of 28 placebos (p=0.075)).
The authors also noticed that in the first months the FMT with froze faeces had better results
than with fresh stool, but in time the results are similar [28].
Oral administration
The protocol consists in making a faecal suspension in normal saline using a commercial
blender. After that it is concentrated by centrifugation and re-suspended in saline at one-tenth
the volume. The solution obtained is pipetted into size 0 capsules (650 µL), closed and then
sealed in size 00 capsules. Acid resistant capsules were stored frozen at -80 °C (-112 °F). 1-2
hours prior to administration, they were transferred to -20 °C, then transported on dry ice. 30
capsules contained sieved, concentrated material derived from a mean of 48 g of faeces [29].
Halkjaer SI et al., studied 51 patients with IBS divided into two groups: 25 patients received
FMT, 26 patients were in the control group and received placebo. The patients were sub
classified in three different IBS subtypes: constipation-predominant (IBS-C), diarrhoea-
predominant (IBS-D) or alternating periods of constipation and diarrhoea (IBS-M). All of the
patients received 25 capsules/day in the morning with water, in three days. FMT and placebo
capsules were identical in appearance: form, colour and size. Placebo capsules where made
from saline, glycerol and food colouring E150. It was a double blind study and the identity of
the capsules was unknown to participants, researchers and primary investigators. The authors
studied IBS-SSS and the quality of life (QoL) of the participants of the study at a follow up
periods of three and six months. There were no significant differences between the IBS-SSS at
the 3 months and 6 months follow up periods between the two groups, although the authors
noticed that the difference between the final score at 3 and 6 months and the score at the
beginning was significant. The QoL also improved significant in FMT group comparing to
placebo group starting with the first months [30].
Although the studies seem promising, a meta-analysis made last year showed that the
benefits of the FMT were observed only in single arm clinical trials were 59,9% of patients had
an improvement of IBS symptoms. This effect does not appear when the authors analysed the
randomized clinical trials so they conclude that the current systematic review and meta-analysis
do not support FMT as a successful treatment strategy in IBS [31].
Conclusions
Although the studies showed some positive effect of FMT in IBS patients, there are few and
on a limited number of patients. The meta-analysis does not support this treatment for IBS
patients. Further studies on larger population are necessary to validate this therapy for IBS
patients and to include it into guidelines.
36
©
REFERENCES
1. Sperber, A.D. (2017). The global prevalence of IBS in adults remains elusive due to the heterogeneity of
studies. A Rome foundation working team literature review. Gut 66, pp. 1075-82.
2. Soares, R.L. (2014) Irritable bowel syndrome: a clinical review. World J Gastroenterol. 20, pp. 12144-
60.
3. Schmulson, M.J (2017). What Is New in Rome IV.J Neurogastroenterol Motil. 23(2), pp. 151-163.
4. Drossman, D.A. (2016). Rome IV ‒ functional GI disorders: disorders of gut-brain interaction.
Gastroenterology 150, pp. 1257-61.
5. Berg, L.K. (2016). Effect of fructose-reduced diet in patients with irritable bowel syndrome, and its
correlation to a standard fructose breath test. Scand. J Gastroenterol 48, pp. 936-43.
6. Drossman, D.A. (2016). Functional gastrointestinal disorders: history, pathophysiology, clinical features
and Rome IV. Gastroenterology 150, pp. 1262-1279.
7. Ford, A.C. (2014). Efficacy of prebiotics, probiotics, and symbiotic in irritable bowel syndrome and
chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 109, pp. 1547-
1561.
8. Lee, K.N. (2014) Intestinal microbiota in pathophysiology and management of irritable bowel syndrome.
World J Gastroenterol 20, pp. 8886-97.
9. Kostic, A.D. (2014). The Microbiome in Inflammatory Bowel Diseases: Current Status and the Future
Ahead. Gastroenterology 146(6), pp. 1489-1499.
10. Hong, S.N. (2014). Unravelling the ties between irritable bowel syndrome and intestinal microbiota. WJG
20, pp. 2470-2481.
11. Schmulson, M. (2018). Faecal microbiota transfers for bowel disorders: efficacy or hype? Curr. Opin.
Pharmacol. 43, pp. 72-80.
12. Halkjær, S.I. (2017). Can faecal microbiota transplantation cure irritable bowel syndrome? WJG 23(22),
pp. 4112-4120.
13. Borody, T.J. (2004). Bacterio-therapy using faecal flora: toying with human motions. J Clin
Gastroenterol.38, pp. 475-483.
14. Smits, L.P. (2013). Therapeutic potential of faecal microbiota transplantation. Gastroenterology. 145, pp.
946-953.
15. Eiseman, B. (1958). Faecal enema as an adjunct in the treatment of pseudomembranous enterocolitis.
Surgery. 44(5), pp. 854-9.
16. Aas, J. (2003). Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor
stool administered via a nasogastric tube. Clin. Infect. Dis. 36(5), pp. 580-585.
17. Persky, S.E. (2000). Treatment of recurrent Clostridium difficile – associated diarrhoea by administration
of donated stool directly through a colonoscopy. Am J Gastroenterol. 95(11), pp. 3283-3285.
18. Yoon, S.S. (2010). Treatment of refractory/recurrent C. difficile-associated disease by donated stool
transplanted via colonoscopy: a case series of 12 patients. J Clin. Gastroenterol. 44(8), pp. 562-6.
19. Surawicz, C.M. (2013). Guidelines for diagnosis, treatment, and prevention of Clostridium difficile
infections. Am J Gastroenterol. 108(4), pp. 478-98.
20. Silverman, M.S. (2010). Success of self-administered home fecal transplantation for chronic Clostridium
difficile infection. Clin. Gastroenterol. Hepatol. 8(5), pp. 471-3.
21. Cruz-Aguilar, R. (2015). Faecal microbiota transplantation as a novel therapy for irritable bowel
syndrome with predominant diarrhoea. Neurogastroenterol Motil 27, p. 110.
22. Hong, J. (2016). Treatment of irritable bowel syndrome with faecal microbiota transplantation: a case
series of 10 patients. United European Gastroenterol J 17, p. 4.
23. Syzenko, G. (2016). Efficiency of FMT in cases of “treatment-resistant” IBS. United European
Gastroenterol J; 4, p. A294.
24. Mizuno, S. (2017). Bifidobacterium-rich faecal donor may be a positive predictor for successful faecal
microbiota transplantation inpatients with irritable bowel syndrome. Digestion 96, pp. 29-38.
25. vanNood, E. (2013). Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl. J
Med 368, pp. 407-415.
26. Holvoet, T. (2017). Assessment of faecal microbial transfer in irritable bowel syndrome with severe
bloating. Gut. 66(5), pp. 980-982.
27. Pinn, D.M. (2014). Is Faecal Microbiota Transplantation the Answer for Irritable Bowel Syndrome? A
Single-Center Experience. Am J Gastroenetrol. 109 (11), pp. 1831-1832.
28. Johnsen, P.H. (2018). Faecal microbiota transplantation versus placebo for moderate-to-severe irritable
bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial.
Lancet Gastroenterol Hepatol. 3(1), pp. 17-24.
37
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29. Youngster, I. (2014). Oral, capsulized, frozen faecal microbiota transplantation for relapsing Clostridium
difficile infection. JAMA.312(17), pp. 1772-1778.
30. Halkjær, S.I. (2018). Faecal microbiota transplantation alters gut microbiota in patients with irritable
bowel syndrome: results from a randomised, double-blind placebo-controlled study. Gut 0, pp. 1-9.
31. Myneedu K. (2019). Faecal microbiota transplantation in irritable bowel syndrome: A systematic review
andmeta-analysis. United European Gastroenterology Journal7(8), pp. 1033-1041.
38
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How to Produce a Good Paper on Neurogastroenterology? Why

are some Papers Rejected?
DUMITRASCU Dan-Lucian1
1
Author Affiliation Iuliu Hatieganu University of Medicine and Pharmacy ì Cluj-Napoca, 2nd Medical Dept. (ROMANIA)
Email: ddumitrascu@umfcluj.ro
Abstract
We speak now on “to publish or to perish”. The pressure to publish is therefore increasing.
The number of papers in different biomedical fields is also increasing. Concurrence is high.
Speed of publication may make the difference. Being successful means having less failures,
thus less rejected papers. This paper is a cook book on how publish successfully.
Keywords: Neurogastroenterology, Medical journals, Publishing
Introduction
This is a “how to” paper on successful publishing in biomedical journals. The writing of this
text evolved from the necessity to share our experience of author of several medical papers, of
peer reviewers for many journals, of board members of several medical periodicals and editor
in chief of two medical journals (one indexed in Pubmed, the other on Clarivate. We considered
a kind of duty to present a lecture on this topic during the NeurogastRO 2019 meeting in Iasi
for young investigators motivated to publish in the field of neurogastroenterology.
Background
Neurogastroenterology is a quite recent field of gastroenterology and is dedicated to the

research and clinical management of pathological conditions in relation with the functional
gastrointestinal disorders (called also disorders of the gut-brain interaction) [1] and of the
motility disorders. This subspecialty is including very hot topics like gut microbiota [2] and
emerging therapies [3]. In order to keep pace with the accumulation of new scientific data,
many manuscripts are submitted putting pressure on the limited space of the medical journals,
even in the period of flourishing of biomedical journals. Young scientists need advice on how
to select journals where to submit in order to avoid rejection of their work.
Where are We Now
There are now over 1000 full papers of diseases representing the focus of
neurogastroenterology indexed on Pubmed. As another example, on IBS there are over 14000.
On functional dyspepsia there are 1800. On GERD there are over 34,000. On achalasia there
are. We should mention that two main journals publish exclusively neurogastroenterology
papers: Neurogastroenterology & Motility, the journal of ESNM, with IF off and the Journal of
Neurogastroenterology and Motility published in Korea and mainly addressed to Asian authors
but not only. There are also regional journals like the one for Latin American countries and
some others. But every journal of gastroenterology is eligible for submission of manuscripts on
39
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neurogastroenterological topics. Unfortunately, many published manuscripts do not have great

impact because they have low translational properties or are not applicable for clinical practice.
Many are duplicating well know data or represent local initiatives for guidelines with local
necessity only. No wonder that John Ioannidis expressed in his manuscript which is considered
to be the most cited paper that most of the scientific products published in medical journals are
not useful [4].
Apart this paradox, young investigators have to take care in order to create good manuscripts
which once published, would be useful to the scientific world and to humanity and not only to
own academic careers.
The competition between journals is also very strong and most editors prefer high level
manuscripts. Best journals retain for publication (almost always after revisions requests) even
less than 10% of submitted manuscripts. Less important journals may reject fewer manuscripts,
i.e., 50%, or 20-30% depending on how many manuscripts they receive. Predator journals
receive for publications almost everything with the condition to receive the publication fees.
How the Publish Successfully Without Getting Many Manuscripts Rejected?
- Do not submit rubbish; please take care of your prestige and if at the beginning of the
career, of your future.
- Respect the ethical requirements in respect to multiple publication, salami publication,
conferring authorship, fraudulent processing of data, plagiarism etc. [5, 6]. Most
journals verify text overlapping as first action after receiving your manuscripts.
- If you are happy with your manuscript, send it to an appropriate journal. If it is a very
valuable work, you should try a very reputed journal. If your work is less innovative,
your target should not be too high. If you are aware that this is an educational
manuscript, address it to a scholastic or ocal journal to be accessed by local interested
people.
- Do not send articles with data duplicating previous knowledge or observational data of
local interest to a global journal or to a journal focussing on the pathology of other
continents.
- If your methodology is not of top level, do not submit to a neurogastroenterology
journals (where quality of methodology is carefully checked) but rather to a journal of
general gastroenterology or even of internal medicine, where your manuscript might
find a higher interest.
- Try to cite references from the journals where you submit, this will always make
pleasure to the editors.
- Respect the technical conditions required by the journal: length, illustrations, format,
citation style etc.
- If the manuscript is returned for revision, try to revise it clearly, politely and fast, not
forgetting to thank to reviewers and editor. You may have big chances to have the
manuscript accepted.
- Rebuttal of editor’s decision is almost always not useful.
- If your manuscript is rejected, do not mind. Use the advice of the peer reviewers and
submit the new version to another journal, usually with a lower IF. Resubmitting to the
same journal a manuscript once rejected is almost never successful.
- Remember the advice: publish your research in those journals where you would have
liked to read it!
- Having an outstanding well-known scientist behind, as senior author, is a strong asset.
40
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Conclusions
In this contemporary competitive era, the concurrence between authors to reach good
journals is impressive. The pressure to publish is high because of academic requirements and
of the need to study new pathogenic pathways, new diagnostic methods and new therapies for
the disorders of the gastrointestinal gut-brain axis. In order to avoid failures and to be
successful, young investigators in the field of neurogastroenterology should be aware of the
value of their own work, on the limited availability of publication space in good or very good
journals and of the methods to improve chances to have their manuscripts accepted for
publication.
REFERENCES
1. Drossman DA Functional gastrointestinal disorders: what’s new for Rome IV? Lancet Gastroenterol
Hepatol. 2016 Sep; 1(1): pp. 6-8. doi: 10.1016/S2468-1253(16)30022-X. 2016.
2. Mayer EA, Tillisch K, Gupta A J. Gut/brain axis and the microbiota. J Clin. Invest. 2015, 2; 125(3): pp.
926-38. doi: 10.1172/JCI76304.
3. Dumitraşcu DL, Nedelcu L, Pop S, Blaga-Surdea T, Dadu RT, Costin S, Popescu M, Picos A, David L
The use of complementary and alternative therapies and of psychotherapy by Romanian patients with
irritable bowel syndrome. Rom J Intern Med. 2013; 51(3-4): pp. 148-51.
4. Ioannidis JP. How to make more published research true. PLoS Med. 2014 Oct 21; 11(10): p. e1001747.
doi: 10.1371/journal.pmed.1001747
5. Dumitrascu D, Dumitrascu DL. Trepte spre stiinta. Introducer in metodologia cercetarii. Ed. 2-a. Ed.
Med. Univ. Iuliu Hatiganu 2006.
6. Moore N. How to Do Research: A Practical Guide to Designing and Managing Research Projects Facet,
2006.
41
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The Relationship Between Depression and Inflammatory Bowel

Disease
FADGYAS STANCULETE Mihaela1, CAPATINA Octavia1,

DUMITRASCU Dan Lucian2, POJOGA Cristina3,4
1
Department of Neuroscience, University of Medicine and Pharmacy Iuliu Hațieganu Cluj Napoca (ROMANIA)
2
Department of Internal Medicine, University of Medicine and Pharmacy Iuliu Hațieganu Cluj Napoca (ROMANIA)
3
International Institute for the Advanced Studies of Psychotherapy and Applied Mental Health, Babes Bolyai University,
Cluj Napoca (ROMANIA)
4
Regional Institute of Gastroenterology and Hepatology O Fodor, Cluj-Napoca (ROMANIA)
Email: mihaelastanculete@yahoo.com
Abstract
Introduction
Chronic conditions often have psychiatric comorbidities, especially anxiety and depression.
The new conceptualizations of the gut-brain axis have brought into question the existence of
a bidirectional relationship between depression and inflammatory bowel diseases, multiple
mechanisms being involved. Psychiatric comorbidities seem to correlate with the severity of
inflammatory bowel diseases and influence their clinical evolution and prognosis.
Material and Method

We performed an analysis of the literature on the bidirectional relationship between
depression and inflammatory bowel disease. The articles were identified by keyword search in
electronic databases (Pubmed, Medline, and PsychINFO).
Results
Data from the literature support the existence of a two-way relationship between depression
and inflammatory bowel disease.
Conclusions
The approach of patients with inflammatory bowel disease should be made within the
biopsychosocial model. An evaluation algorithm of these patients should be established in order
to detect the presence of comorbid depression so that adequate management of these cases can
be achieved.
Keywords: inflammatory bowel disease, depression, bi-directionality, biopsychosocial model
The Bidirectional Link Between Depression and IBD
This review considers recent evidence on the link between depression and inflammatory
bowel diseases (IBD). Ulcerative colitis and Chron’s disease represent chronic conditions.
Depression is associated with worsened disease activity and increased frequency of flares.
Moreover, depression has a considerable impact on the quality of life and is related to sexual
dysfunction, work absenteeism, and increased risk of suicide (1). Depression has also been
shown to be a risk factor for poor medication adherence, which is another way by which
depression may increase a patient’s risk for worsening IBD (2).
42
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In some studies, depression was unrelated to disease activity, preceded the onset, or was
correlated with the disease activity. Table 1 present the results of different studies.
Table 1. Association between depression and IBD

Study population Scale Result Authors
Seventy-nine consecutive Zung self-rating - depression was Addolorato et al., (1997)
patients, 43 with Crohn’s Depression Scale significantly associated (3)
disease (CD) and 36 with with physical morbidity
ulcerative colitis (UC) and correlated with
malnutrition in CD and
UC patients.
- depression was
unrelated to disease
activity
26 patients with Crohn’s Diagnostic Interview psychiatric disturbance Tarter et al., (1988) (4)
Disease (CD), 27 subjects Schedule (DIS) precedes the onset of CD
with ulcerative colitis
(UC), and 28 normal
controls.
18 CD patients Beck Depression levels of depressive Mardini et al., (2004) (5)
Inventory (BDI), Beck symptoms are positively
Hopelessness Scale associated with future
(BHS) changes in Crohn’s
Disease activity
2007 patients, 1122 CD, Hospital Anxiety and -significant association Mikocka-Walus et al.,
885 UC Depression Scale between symptoms of (2016) (6)
(HADS) depression or anxiety and
clinical recurrence.
-the link between
depressive symptoms and
clinical recurrence
stronger in participants
with CD
Poor coping and IBD

IBD symptoms could determine a reduction in patient’s ability to engage in pleasant
activities due to either disease activity or significant changes in one’s lifestyle (various
restrictions on travel, dietary restriction, periods of hospitalization or nutrition support, surgical
interventions).
Coping mechanisms associated with the development of depression in CD are a great use of
denial, low utilization rates of planning, and positive reframing (7). Studies showed that
depression impacts health-promoting behaviours such as diet, sleep hygiene, quitting smoking,
practicing exercise, and maintaining a good social support network (8).
Cytokine targets in the brain: neurotransmitters

The interplay between inflammatory pathways and synthesis of neurotransmitters, and
complex neurocircuitry can lead to depression and may impair the responsiveness to current
antidepressant therapies. Moreover, the opposite is also true, treatment-resistant patients exhibit
increased inflammatory markers.
The inflammatory response in IBD can affect both metabolic and molecular pathways
influencing neurotransmitter systems. It is observed an alteration in neurocircuits that regulate
various behaviours, especially behaviours relevant to decreased motivation, and avoidance. The
major mechanisms involved in the decrease of monoamine availability are presented in Table
1.
43
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Table 2. The link between inflammatory cytokines and decrease availability of monoamines
Cytokines Effect on monoamines Authors
IL-1β and TNF induction of p. 38 increase the expression and Zhu, C. B. et al., (2010) (9)
mitogen-activated function of the reuptake pumps for
protein kinase (MAPK) serotonin
Increased CSF levels of IL-6 generation of reactive Felger, J. C. et al., (2013) (10)
oxygen and nitrogen species
decrease the availability of
tetrahydrobiopterin (BH4)
Activation of the enzyme decreased production of serotonin Raison, C. L. et al., (2010). (11)
indoleamine 2,3-dioxygenase (activation of kynurenine pathway)
(IDO)
Unfortunately, until now, studies show that anti-inflammatory agents may demonstrate
significant antidepressant activity only in subgroups of patients characterized by increased
peripheral inflammation (12).
The influence of antidepressant therapy on the immune system

Studies have demonstrated that the induction of depression can reactivate inflammation of
the colonic mucosa (13). Anti-inflammatory properties of antidepressants, including
imipramine, amitriptyline and clomipramine, have been investigated in many studies (14, 15).
The anti-inflammatory effects are mediated by decreasing the production of nitric oxide
(NO) and TNF-α in microglia and astrocyte cultures at mRNA levels and also due to the effects
on the inhibitory cytokine IL-10 (16).
Conclusions
The studies of patients with CD or UC found evidence for bi-directional effects of IBD
activity and psychiatric disorders, especially depression. Patients with IBD should be monitored
for psychological well-being and treated accordingly (antidepressant therapy and
psychotherapy) because the interventions can be extremely effective.
REFERENCES
1. Bennebroek Evertsz, F., Thijssens, N. A. M., Stokkers, P. C. F., Grootenhuis, M. A., Bockting, C. L. H.,
Nieuwkerk, P. T., & Sprangers, M. A. G. (2012). Do inflammatory bowel disease patients with anxiety
and depressive symptoms receive the care they need? Journal of Crohn’s and Colitis, 6(1), pp. 68-76.
2. Keefer, L. (2019). The Time Has Come to Integrate Behavioural Health Services into IBD Centres.
Journal of Crohn’s and Colitis,13 (7), pp. 817-818.
3. Addolorato, G., Capristo, E., Stefanini, G. F., & Gasbarrini, G. (1997). Inflammatory bowel disease: a
study of the association between anxiety and depression, physical morbidity, and nutritional status.
Scandinavian journal of gastroenterology, 32(10), pp. 1013-1021.
4. Tarter, R. E., Switala, J., Carra, J., Edwards, K. L., & Van Thiel, D. H. (1988). Inflammatory bowel
disease: psychiatric status of patients before and after disease onset. The International Journal of
Psychiatry in Medicine, 17(2), pp. 173-181.
5. Mardini, H. E., Kip, K. E., & Wilson, J. W. (2004). Crohn’s disease: a two-year prospective study of the
association between psychological distress and disease activity. Digestive diseases and sciences, 49(3),
pp. 492-497.
6. Mikocka-Walus, A., Pittet, V., Rossel, J. B., von Känel, R., Anderegg, C., Bauerfeind, P., ... &
Biedermann, L. (2016). Symptoms of depression and anxiety are independently associated with clinical
recurrence of inflammatory bowel disease. Clinical gastroenterology and hepatology, 14(6), pp. 829-835.
7. Viganò, C., Calzolari, R., Marinaccio, P. M., Bezzio, C., Furfaro, F., Ba, G., & Maconi, G. (2016).
Unrevealed depression involves dysfunctional coping strategies in Crohn’s disease patients in clinical
remission. Gastroenterology research and practice, 7803262.
8. Trivedi, M. H., Lin, E. H., & Katon, W. J. (2007). Consensus recommendations for improving adherence,
self-management, and outcomes in patients with depression. CNS Spectr, 12(8 Suppl. 13), pp. 1-27.
44
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9. Zhu, C. B., Lindler, K. M., Owens, A. W., Daws, L. C., Blakely, R. D., & Hewlett, W. A. (2010).
Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioural despair linked to
MAPK regulation of CNS serotonin transporters. Neuropsychopharmacology, 35(13), pp. 2510-2520.
10. Felger, J. C., Li, L., Marvar, P. J., Woolwine, B. J., Harrison, D. G., Raison, C. L., & Miller, A. H. (2013).
Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine
concentrations. Brain, behaviour, and immunity, 31, pp. 153-160.
11. Raison, C. L., Dantzer, R., Kelley, K. W., Lawson, M. A., Woolwine, B. J., Vogt, G., ... & Miller, A. H.
(2010). CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-α:
relationship to CNS immune responses and depression. Molecular psychiatry, 15(4), pp. 393-403.
12. Miller, A. H., & Raison, C. L. (2015). Are anti-inflammatory therapies viable treatments for psychiatric
disorders? where the rubber meets the road. JAMA psychiatry, 72(6), pp. 527-528.
13. Ghia, J. E., Blennerhassett, P., & Collins, S. M. (2008). Impaired parasympathetic function increases
susceptibility to inflammatory bowel disease in a mouse model of depression. The Journal of clinical
investigation, 118(6), pp. 2209-2218.
14. Abdel-Salam, O. M., Nofal, S. M., & El-Shenawy, S. M. (2003). Evaluation of the anti-inflammatory and
anti-nociceptive effects of different antidepressants in the rat. Pharmacological research, 48(2), pp. 157-
165.
15. Rahimi, H. R., Shiri, M., & Razmi, A. (2012). Antidepressants can treat inflammatory bowel disease
through regulation of the nuclear factor-κB/nitric oxide pathway and inhibition of cytokine production:
A hypothesis. World journal of gastrointestinal pharmacology and therapeutics, 3(6), pp. 83-85.
16. Guaiana, G., Barbui, C., & Hotopf, M. (2007). Amitriptyline for depression. Cochrane Database of
Systematic Reviews, (3). 18: CD004186.
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Gastroesophageal Reflux Disease and Esophagitis after

Paroxysmal Atrial Fibrillation Ablation
FLORIA Mariana1,2, MIHAI Catalina1,3*, RADU Smaranda1, BĂRBOI Oana1,3,

TĂNASE Maria Daniela1, GRECU Mihaela4,
CIJEVSCHI-PRELIPCEAN Cristina1,3, DRUG Vasile Liviu1,3
1
Grigore T. Popa University of Medicine and Pharmacy, Iași (ROMANIA)
2
Emergency Military Clinical Hospital, Iasi (ROMANIA)
3
Hepatology and Gastroenterology Institute, Iasi (ROMANIA)
4
Cardiovascular Disease Institute and CCTIFA Department, Iaşi (ROMANIA)
*
Corresponding author: MIHAI Catalina
Emails: floria_mariana@yahoo.com, catalinamihai@yahoo.com, radu.smaranda@gmail.com, oany_leo@yahoo.com,
tanasedm@gmail.com, mihaelagrecu@yahoo.com, cristinacijevschi@yahoo.com, vasidrug@email.com
Abstract
Due to the close positioning of the oesophagus and the atria, patients undergoing catheter
ablation of paroxysmal atrial fibrillation (AF) might have an increasing risk to develop
oesophageal wall injury and gastroesophageal reflux disease (GERD). We prospectively
studied the presence of gastroesophageal reflux disease and esophagitis after ablation of
paroxysmal AF. All patients were prospectively included by a joint team consisting of
gastroenterologist and cardiologist based on patient’s complaints. Gastroesophageal reflux
disease diagnosis was clinically assessed by gastroenterologist before and at 3 months after
endocardial radiofrequency catheter AF ablation. All patients underwent also upper
gastrointestinal endoscopy, transthoracic echocardiography and 24 hour ECG Holter
monitoring. Seventy-five patients were included in 2 groups: 46 patients with AF ablation
(study group) and 29 patients without AF ablation (control group). Patients with AF ablation
were younger (57.76±7.66 years’ vs 67.81±8.52 years; P=0.001), predominantly men (62.2%
vs 33.3%; P=0.030) and with higher body mass index (28.96±3.12 kg/m2 vs 26.81±5.19 kg/m2;
P=0.046). In study and control group were 88.9% respectively 57.1% patients with sinus rhythm
(P=0.009). No differences in terms of sinus rhythm in patients with versus without GERD
(89.5% vs 88.5%; P=0.709). Esophagitis (55.0% vs 43.8%; p=0.049) and not GERD (42.2% vs
61.9%; P=0.220) was more significantly frequent in the study group. Although symptomatic
GERD is not more frequently, patients undergoing catheter ablation of paroxysmal AF seems
to have an increasing risk to develop esophagitis 3 months after this procedure.
Keywords: Gastroesophageal reflux disease, esophagitis, atrial fibrillation, ablation
Introduction
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, and its incidence
has risen in countries with rapidly aging populations [1]. Gastroesophageal reflux disease
(GERD), one of the most frequent benign disorders of the upper gastrointestinal tract, is defined
as a condition that develops when the reflux of gastric content causes troublesome symptoms
or complications [2]. Due to the close positioning of the oesophagus and the atria, patients
undergoing AF ablation seem to have an increasing risk to develop oesophageal wall injury and
GERD [3-7]. These patients could develop oesophageal injury by direct thermal injury ranging
from erythema and esophagitis, necrosis and ulcer, to a very severe complication, atrio-
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esophageal fistula. The latter is a rare but frequently fatal complication of AF ablation that
occurs in 0.1% to 0.25% of procedures [8]. However, it seems that oesophagus damage after
AF ablation is a tip of the iceberg, the endo-sonography showing a high prevalence of
mediastinal changing [9]. Therefore, we aimed to study prospectively the presence of
symptomatic GERD and esophagitis in naïve patients who underwent paroxysmal AF ablation.
Materials and Methods
We aimed to study prospectively the presence of symptomatic GERD and esophagitis at 3

months after radiofrequency catheter ablation of paroxysmal AF. We followed the methods of
Mariana Floria et al., 2017 [10].
Inclusion criteria: patients older than 18 years, with documented refractory paroxysmal AF
referred for endocardial catheter ablation (according with the guidelines recommendations [1]:
younger, healthy persons with symptomatic paroxysmal AF refractory to 1 or more
antiarrhythmic medications and taking into account patient preference for this technique),
without any prior gastroenterological evaluation or treatment (naïve patients), with symptoms
suggesting GERD.
Exclusion criteria: patients <18 years, with chronic gastrointestinal diseases like
inflammatory bowel disease and coeliac disease or under treatment with proton pomp
inhibitors; patients with any valvular disease more than mild, thyroid disorders, previous
myocardial infarction, transient ischemic attack or stroke; patients who refused to be included;
patients with a pacemaker/defibrillator, inflammatory disorders or immunosuppressive therapy,
active neoplasm, dementia or other neurological or psychiatric invaliding pathology; all patients
with nonsteroidal anti-inflammatory drugs (including acetylsalicylic acid at a dose greater than
100 mg/day) at enrolment and during the preceding 30 days [10].
Non-valvular AF [1] and GERD [2] diagnosis was defined according with current guidelines.
Therefore, non-valvular AF was referred to patients without mitral stenosis or artificial heart
valves [1]. Symptomatic GERD was diagnosed by gastroenterologist clinically. Symptomatic
GERD was defined as mild symptoms of heartburn and/or regurgitation at least 2 times per
week or moderate/severe symptoms occurring more than 1 day a week, perceived as
“troublesome” by patients (according with Montreal definition) [2]. All patients underwent
gastroenterological and cardiologic assessment: upper gastrointestinal endoscopy (even if they
were asymptomatic), 24 hours holter ECG monitoring and bi-dimensional transthoracic
echocardiography [10].
During the upper gastrointestinal endoscopy, the presence of hiatus hernia (as favouring
condition of GERD), esophagitis (by Los Angeles classification) and Barrett’s oesophagus were
noted. Among biological parameters, pro-BNP, as marker of left atrium structural remodelling,
was assessed in these two groups.
Paroxysmal AF was defined as AF that terminates spontaneously or with intervention within
7 days of onset [11]. The catheter AF ablation procedure consisted of endocardial ostial
isolation of each pulmonary vein antrum by radiofrequency energy using a Lasso ™ catheter
(Biosense Webster, CA, USA) and an irrigated tip Celsius™ Thermo Cool (Biosense Webster,
CA, USA), as currently recommended [12]. Antrum pulmonary vein isolation was obtained at
35W (by radiofrequency energy). In patients with paroxysmal AF longer than 24 hours the
ablation procedure was completed by complex fractionated atrial electrogram and cavo-
tricuspid isthmus ablation (if common atrial flutter was confirmed before or during procedure).
The procedure was done using local anaesthesia by femoral access and deep sedation with
morphine fractionated intravenous during energy application.
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This study has been performed in compliance with the ethical principles of the Hospital and
University Ethics Committee. Informed consent was obtained from each patient before the
inclusion in the study. This study conforms to the Declaration of Helsinki.
Statistical analysis
Categorical data are presented as frequencies and percentages; continuous variables are
expressed as mean ± standard deviation. Categorical, ordinal and numerical variables were
compared between groups using χ2, Cochran and Wilcoxon rank sum tests, Kruskal-Wallis and
Anova test respectively. All statistical tests were two-tailed and performed with SPSS 15.0
(SPSS Inc., Chicago, IL, USA). A P-value<0.05 was set as statistical significance.
Results and Discussion
Seventy-five patients were included in 2 groups: 46 patients with AF ablation (study group)
and 29 patients without AF ablation (control group). Baseline data (before ablation procedure)
of both groups are represented in table 1. Patients with AF ablation were younger (P=0.001),
predominantly men (p=0.030) and with higher body mass index (P=0.046). In ablation versus
control group, symptomatic GERD and esophagitis was not significantly more frequent.
Despite of no differences between left atrium area in these groups, pro-BNP was
significantly higher in patients without AF ablation (344±180 vs 760±253 pg/ml, P=0.001).
Table 1. Patient characteristics

PARAMETER STUDY GROUP (N=46) CONTROL GROUP (N=29) P value
Age (years) 57.76±7.66 67.81±8.52 0.001

Men (%) 28 (62.2) 7 (33.3) 0.030
BMI (kg/m )
† 2
28.96±3.12 26.81±5.19 0.046
Smoking (%) 18 (39.1) 10 (34.4) 0.07
Dyslipidaemia (%) 31 (68.8) 14 (66.6) 0.918
Hypertension (%) 29 (64.4) 19 (90.5) 0.028
Diabetes mellitus (%) 8 (17.7) 4 (19.0) 0.827
GERD ‡ (%) 19 (42.2) 13 (61.9) 0.220
Esophagitis (%) 12 (26.7) 8 (38.1) 0.513
Hiatal hernia (%) 12 (26.7) 5 (23.8) 0.956
Left atrium area (cm )
2
26.51±5.31 26.47±5.33 0.766
Pro-BNP§ (pg/mL) 344±180 760±253 0.001
Data are frequency counts (percentage of total) or mean ± standard deviation.
†
BMI=body mass index; §BNP=brain natrium peptide; ‡GERD = gastroesophageal reflux disease
In the study and control group, under antiarrhythmic drugs, were 88.9% respectively 57.1%
patients with sinus rhythm (P=0.009). Comparative data of echocardiographic and
gastroenterological parameters in patients with versus without AF ablation are showed in table
2.
Table 2. Echocardiographic and gastroenterological parameters at 3 months after atrial fibrillation ablation
PARAMETER STUDY GROUP CONTROL GROUP P-value
With GERD§ Without With GERD§ Without

N=20 GERD§ N=19 GERD§
N=26 N=10
ECHOCARDIOGRAPHY
E/A ratio† 1.27±0.43 1.53±0.68 0.89±0.48 1.89±0.49 0.046
E/Em ratio‡ 7.90±1.47 8.41±3.43 9.61±2.77 8.88±5.14 0.475
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E wave deceleration time 219.17±41.04 203.75±41.13 239.58±62.28 192.86±54.53 0.222

(ms)
Left atrium area (cm2) 25.34±5.06 27.26±5.21 26.31±5.13 27.30±5.06 0.625
Left ventricle ejection 59.52±6.87 58.36±7.79 53.06±8.17 54.50±7.62 0.048
fraction (%)
GASTROENTEROLOGY
Esophagitis (%) 55.0 6.9 43.8 10.0 0.001*
Hiatal hernia (%) 15.0 17.2 25.0 10.0 0.775*
* Kruskal-Wallis Test
†
E/A ratio=E wave velocity/A wave velocity ratio; ‡E/Em ratio=E wave velocity/Em velocity ratio;
§
GERD=gastroesophageal reflux disease.
In terms of echocardiographic parameters, left ventricular ejection fraction was significantly

lower in patients without AF ablation; left ventricular diastolic function in these patients was
also modified (as revealed by E/A ratio). Esophagitis was more frequently in patients with
symptomatic GERD (irrespective of AF ablation procedure; P=0.001), in the absence of more
frequently hiatal hernia. The presence of Barrett’s oesophagus or more than Los Angeles grade
A esophagitis (one or more mucosal breaks confined to the mucosal folds, each not more than
5 mm in maximum length) were not objected in both groups.
In AF ablation group, there were not differences in terms of sinus rhythm in patients with
versus without symptomatic GERD (89.5% vs 88.5%; P=0.709), at 3 months after procedure.
In terms of echocardiographic parameters (table 3), when we analysed only the patients with
symptomatic GERD, left ventricular ejection fraction was remained statistically significantly
lower in patients with AF ablation; left ventricular diastolic function in these patients has
retained its significance (as revealed by E/A and E/Em ratio). Esophagitis remained statistically
significantly present in patients with symptomatic GERD and AF ablation procedure (P=0.049),
also in the absence of more frequently hiatal hernia.
Table 3. Echocardiographic and gastroenterological parameters in patients with symptomatic GERD at 3 months
after atrial fibrillation ablation
SYMPTOMATIC GERD¶
PARAMETER P-value
With AF† Ablation (N=20) Without AF† Ablation (N=19)
ECHOCARDIOGRAPHY
E/A ratio‡ 1.27±0.43 0.89±0.48 0.036
E/Em ratio §
7.90±1.47 9.61±2.77 0.034
E wave deceleration time (ms) 219.17±41.04 239.58±62.28 0.480
Left atrium area (cm2) 25.34±5.06 26.31±5.33 0.585
Left ventricle ejection fraction 59.52±6.87 53.06±8.17 0.016
(%)
GASTROENTEROLOGY
Esophagitis (%) 55.0 43.8 0.049*
Hiatal hernia (%) 15.0 25.0 0.458*
*Kruskal-Wallis Test. Data are frequency counts (percentage of total) or mean ± standard deviation.
†
AF=atrial fibrillation; ‡E/A ratio=E wave velocity/A wave velocity ratio; §E/Em ratio=E wave velocity/Em
velocity ratio; ¶GERD=gastroesophageal reflux disease
Discussion
Since AF ablation was defined as a new technique with intended curative visa of this
arrhythmia, the cardiologist point of view about the relationship between AF and GERD was
more complex expressed in the literature [13-17]. First of all, the presence of GERD in patients
with AF was studied as a possible trigger of this arrhythmia [16]. On the other side, the impact
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of radiofrequency catheter ablation of left atrium can provoke oesophageal lesion and vagal
nerve damage [17], due to thermal injury in up to 47% of patients following pulmonary vein
isolation [9]. For example, oesophageal ulcerations, a possible precursor of a dramatic life-
threatening condition like atrio-esophageal fistula, or oesophageal motility as Jackhammer
oesophagus are some of described entities due to the impact of radiofrequency catheter ablation
of left atrium [15].
Esophagitis may be found in patients with GERD but without symptoms. In this study we
did not find more frequently symptomatic GERD 3 months after the ablation procedure, but
esophagitis (no more severe than Los Angeles A grade) was more frequently in these patients.
However, it seems that fewer than 50% of patients with typical GERD symptoms have
endoscopically recognizable mucosal lesions [18]. Nearly all of the guidelines on the diagnosis
and treatment of GERD recommend that reflux esophagitis should be classified endoscopically
and the Los Angeles classification should be used [2].
It is in debate if oesophageal acid levels increase after pulmonary vein antrum isolation. A
small study infirmed already this hypothesis [19]. A significant number of patients undergoing
radiofrequency catheter ablation of AF develop pathologic acid reflux 24 hours after ablation
diagnosed by leadless pH-metry capsules and esophagoscopy [4]. However, complete recovery
of oesophageal lesions was shown by esophagoscopy 2-4 weeks post ablation [6].
Early recognition and active management of these oesophageal injuries may lead to better
outcomes. Although oesophageal temperature monitoring can be useful, multiple factors such
as patient characteristics and specific strategies for radiofrequency energy delivery also merit
consideration [20]. For example, it is very important the assessment of the oesophagus position
in the pre-procedural CT/MRI scan and reduction of power during energy application at the
posterior left-atrial wall in close proximity to the oesophagus [21].
Nowadays the electrophysiologists are more attentive during AF ablation when they made
the applications on left atrial posterior wall because of a sever complication like atrio-
esophageal fistula. They are also more attentive in patient selection. Therefore, the risk of
developing oesophageal wall injury and consequently GERD or esophagitis is much lower.
However, symptomatic GERD seems to not affect the outcome of AF ablation group in the
short term (at 3 months after procedure), taking into account that in this group, there were not
differences in terms of sinus rhythm in patients with versus without symptomatic GERD.
There are some differences in basic characteristics of patients included in this study (table
1). These factors might influence the results. In the study group, mean BMI and the percentage
of men were higher. It seems that prevalence of AF is higher at all ages in men than in women
[22]. In addition, women tend to be referred for AF ablation less and later than are men [23]. It
is well known that men with AF are more symptomatic than women, therefore they ask more
frequently for AF ablation, considered as curative procedure of this arrhythmia. Mean age (a
factor that favours GERD or esophagitis) in the study group was lower comparing with the
control group. According with AF guidelines the ablation procedure is recommended to the
younger, healthy persons with symptomatic paroxysmal AF refractory to 1 or more
antiarrhythmic medications, which preferred this technique [1]. These could explain the
differences in basic characteristics of patients included in this study.
This study is important because early diagnosis of GERD or esophagitis may lead to better
outcomes after AF ablation. For example, although still debatable, it seems that a short term
with proton pomp inhibitors treatment the first 3 months after ablation procedure might prevent
esophagitis related complications [20, 21, 24].
Study limitations
The patients did not undergo high-resolution manometry and impedance-pH to rule out
asymptomatic and non-erosive GERD or oesophageal dysmotility. However, according to our
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knowledge, non-erosive GERD was not describing in patients with AF ablation. The two groups
included in the study were not quite similar in basic characteristics, because the ablation
technique must be preferred by the patient (according with AF guidelines), and is addressed to
the younger patients [1].
Conclusions
Although symptomatic GERD is not more frequently, patients undergoing catheter ablation
of paroxysmal AF seems to have an increasing risk to develop esophagitis 3 months after this
procedure.
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Gastroparesis and Atrial Fibrillation: What is the Relationship?
RADU Smaranda1, MIHAI Catalina1,2*, DRANGA Mihaela1,2, OUATU Anca1,3,

TANASE Daniela Maria1,3, CIJEVSCHI-PRELIPCEAN Cristina1,2,
FLORIA Mariana1,4
1
Grigore T. Popa University of Medicine and Pharmacy, Iași (ROMANIA)
2
Hepatology and Gastroenterology Institute, Iasi (ROMANIA)
3 rd
3 Medical Clinic of Emergency Hospital, Iasi (ROMANIA)
4
Emergency Military Clinical Hospital, Iasi (ROMANIA)
*
Corresponding author: MIHAI Catalina
Emails: radu.smaranda@gmail.com, catalinamihai@yahoo.com, mihaela_dra@yahoo.com, ank_mihailescu@yahoo.com,
tanasedm@gmail.com, cristinacijevschi@yahoo.com, floria_mariana@yahoo.com
Abstract
Gastroparesis is an abnormal gastric motility defined by delayed gastric emptying in the

absence of mechanical obstruction. It can manifest through early feeling of fullness, nausea,
vomiting, pain in the upper abdomen or heartburn. The gold standard diagnostic method is solid
meal gastric scintigraphy and the two most frequent etiologist are diabetes mellitus and post-
surgical. A rarer aetiology is gastroparesis as a complication of atrial fibrillation (AF) ablation,
either by radiofrequency or cryoablation. Major gastrointestinal complications of AF ablation
procedures have been reported, such as atrioesophageal fistula, transient phrenic nerve palsy
and gastroparesis (frequently seen following cryoablation). These two complications are linked
to oesophageal thermical injury occurring in the context of the left atrium’s anatomical
proximity when applying the ablation energy (either radiofrequency or cryoablation).
Interestingly, same-day late-gadolinium enhancement cardiac magnetic resonance scans
seem to identify immediate post-ablation oesophageal injuries. In general, gastroparesis
symptoms are self-resolving and usually do not persist beyond six months after the ablation
procedure. The management is conservative and consists of prokinetic agents and antiemetic’s.
More severe cases might require injecting botulinum toxin in the pyloric sphincter. In
clinical practice, in the presence of symptoms suggestive of post-AF ablation gastrointestinal
complications, we propose an approach based on 7 steps for diagnosis and treatment. Taking
into consideration the increasing incidence of both AF and AF-related procedures, especially
catheter ablations, gastroenterologists must be aware of this rare complication, to facilitate early
initial diagnosis and management.
Keywords: Gastroparesis, vagus nerve, atrial fibrillation, ablation
Introduction
Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia, recognized on
the electrocardiogram by irregularly irregular RR intervals with a duration >30s. This
arrhythmia increase fivefold thromboembolic events, therefore 25% of strokes are in the context
of AF [1]. Also, it decreases quality of life, being associated with heart failure and cognitive
dysfunction irrespective of optimal oral anticoagulation therapy [1]. Catheter ablation (by either
radiofrequency or cryoablation) is recommended to restore sinus rhythm in symptomatic
patient’s refractory to drug therapy. Although the initial success rate is relatively high, various
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complications like thromboembolic events, tamponade, severe pulmonary vein stenosis,

femoral pseudo-aneurysm, atrioesophageal fistula and or gastroparesis have been reported [1].
Data on vagus nerve injury due to radiofrequency ablation energy was also published.
Gastroparesis is an abnormal gastric motility defined by delayed gastric emptying in the
absence of mechanical obstruction [2]; it could manifest through an early feeling of fullness,
nausea, vomiting, pain in the upper abdomen or heartburn [3]. The diagnosis of gastroparesis
can be made by solid meal gastric scintigraphy, which seems to be the gold standard method.
The most frequently aetiology is diabetes mellitus or post-surgical. However, a new
aetiology of this disease is related to AF ablation, being a complication of this procedure.
Prevalence of Gastroparesis after Atrial Fibrillation Ablation
The estimated prevalence of gastroparesis after radiofrequency ablation and cryoablation AF

procedures is 10% and 6%, respectively [4]. Cryoballoon ablation induces gastroparesis by
determining reversible damage to the vagus nerve resulting from transient coagulation. This
mechanism by which cryoablation is associated with this complication could explain a smaller
prevalence. Probably a number of patients might be not clinically symptomatic and even the
condition might be underdiagnosed.
Pathophysiology of Gastroparesis after Atrial Fibrillation Ablation
The most frequent aetiology of gastroparesis is diabetes mellitus or post-surgical. For

diabetes mellitus the pathophysiology seems to be related to atrial natriuretic peptide (ANP)
secretion and upregulation of receptor natriuretic peptide receptor type A (NPR-A) [5]. Atrial
myocytes are the main source of ANP. Besides the heart, the ANP family is also distributed in
other organs, including the gastrointestinal tract [6]. ANP and its NPR-A have been detected in
the gastric antrum [7]. ANP seems to have an inhibitory effect on the regulation of
gastrointestinal motility [5]. Natriuretic peptides relax gastric circular and longitudinal smooth
muscles [5]. Some drugs such as anticholinergics, opioids, levodopa, tricyclic antidepressants,
and phenothiazine’s were also incriminated as possible factors which could induce
gastroparesis [8]. It is known that the vagus nerve innervates the stomach and pyloric sphincter
but also left atrium and inferior pulmonary veins. Therefore, periesophageal vagal thermical
nerve injury might explains this complication after AF ablation [9]. Transmural thermal injury,
such as oesophageal erosion/ulcer and perioesophageal nerve injury leading to gastric hypo-
motility is an important complication associated with pulmonary vein isolation [10], the main
technique of AF ablation. However, unknown factors could be implicated in the pathogenesis
of gastroparesis in some patients. In addition, an earlier onset of symptoms seems to correlate
with significant residual gastric motor dysfunction [11].
Diagnosis of Gastroparesis after Atrial Fibrillation Ablation
Gastroparesis diagnosing is based on patient symptoms like nausea, vomiting, painful

abdominal distention, 2-24 hours after AF catheter ablation [12]. Differential diagnosis should
include other post ablation complications, such as oesophageal ulceration/perforation/fistula;
diabetic gastroparesis or bowel obstruction. Exploring gastroparesis in the context of AF
ablation means plain abdominal radiography, upper gastroesophageal endoscopy and
sometimes computer-tomography. However, solid meal gastric scintigraphy is the gold
standard of gastroparesis diagnosis [9]. A blood test is mandatory to exclude electrolyte
abnormality, diabetes, and dysfunction of the thyroid gland.
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Recently, authors explored the use of late-gadolinium enhancement cardiac magnetic

resonance (LGE-CMR) in diagnosing AF ablation-related gastrointestinal complications,
including atrio-esophageal fistula and oesophageal erosions [13-16]. It seems that anterior
oesophageal enhancement is present in nearly 30% of the patients and this correlates with
oesophageal erosions [13, 14]. Given the risks of performing an upper gastrointestinal
endoscopy in the case of atrio-esophageal fistula, as well as the reported 80% mortality of the
latter, the authors proposed CMR scans as a screening method that would prompt clinicians into
further investigations in case of both symptoms and abnormal findings [16].
There is a syndrome named AF gut syndrome that was defined as symptoms of decreased
gastrointestinal motility that occur after radiofrequency catheter ablation treatment [17]. It
seems that this syndrome is self-reversible. Its occurrence is based on treatment site and time,
redo procedures, energy intensity, and vagus nerve tract anatomical characteristics [17].
Table I summarizes the three main gastrointestinal complications of AF catheter ablation.
Either the most frequent or the most severe complications were considered.
Table I. Main gastrointestinal complications following atrial fibrillation catheter ablation
AF: atrial fibrillation; CT: computer tomography; LA: left atrium; LGE-CMR: late-gadolinium enhancement cardiac magnetic resonance;
UGD: upper gastroesophageal endoscopy
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Management of Gastroparesis after Atrial Fibrillation Ablation
Usually this complication after AF catheter ablation is self-resolving and it takes up to 3-6
months for gastric motility to recover [12]. A complete bowel rest during hospital stay could
be important, as well as the consumption of small frequent meals that are low fat and fiber has
been shown to improve symptoms [3]. Sometimes it requires mechanical decompression and
oral/intravenous prokinetic agents (i.e., metoclopramide, erythromycin, domperidone, or 5-
hydroxytryptamine receptor agonists) and antiemetic’s [2]. Rarely, the management of severe
gastroparesis associated with AF ablation can include botulinum toxin injection in the pyloric
sphincter or esophago-jejunal anastomosis [10].
In clinical practice, in the presence of symptom of an ablation AF gut disease, we propose
an approach based on the following 7 steps:
1. Appropriate history taking with physical examination (systemic disease must be
excluded) followed by a simple abdomen X-ray is essential for the diagnosis.
2. An L tube insertion associated with the restoration of fluid and electrolyte (if necessary)
is the first step of the treatment. Diet could be also very important.
3. An anatomic study (endoscopic exam with new device and emptying food material) is
the next step, following by a gastrointestinal study, if necessary.
4. A gastrointestinal motility drug (prescribed at low doses) could follow a gastrointestinal
motility study, based on gastric emptying scan.
5. If symptoms are persistent, the patient must continue the exercise and motility drug.
6. Other more invasive treatment options could be taken into consideration, in patients
with symptoms lasting longer than 4 weeks (endoscopy followed by balloon dilation or
by local injection of Botulinum toxin).
7. Follow up with simple abdomen X-ray and gastric emptying scan is recommended.
However, most patients recover within 4-6 weeks with conservative treatment if rapid
diagnosis and proper treatment and rehabilitation are made [16].
Prevention of Gastroparesis after Atrial Fibrillation Ablation
The are some methods to prevent this complication after AF ablation. The majority of these
are related to AF ablation technique [10]. The first is to use irrigated tip-catheters to diminished
transmural thermic injury of the oesophagus. The operator should reduce radiofrequency power
output (approx. 30 W) and radiofrequency energy application time (<30s). Also, it must avoid
LA posterior wall applications and may consider monitoring oesophageal temperature and
STOP if >42 ºC. However, always take into consideration that lowering the temperature and
output may influence ablation outcomes in terms of sinus rhythm restoration. Smaller left atrial
diameter could be a predictor of symptomatic gastroparesis following cryoablation [9]. A
preventive soft diet trial for 7 days in high risk patient (long time of RFCA, recurrent RFCA,
multifocal site, the habit of rapid consumption, high RFCA energy) is advisable [17]. The use
of this treatment procedure in AF patients increased in the last years. This is very important,
especially since the inpatient admissions for diabetes mellitus-associated gastroparesis have
already increased, with a subsequently increase in costs over the last 16 years [18].
Table II summarizes studies reporting post-atrial fibrillation ablation gastroparesis/gastric
hypo-motility.
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Table II. Studies focusing on post-atrial fibrillation ablation gastroparesis/gastric hypo-motility

Number of patients with
Type of energy Number of
Author, year gastroparesis/gastric Reference
used (RF/CB) patients
hypo-motility
Shigeta T. et al.,
CB 101 16 [19]
2019
Miyazaki S. et al.,
CB 104 18 [20]
2017
Aksu T. et al.,
CB/RF 58/46 6/1 [21]
2015
Lakkireddy D. et
RF 27 9 [22]
al., 2015
Tsuboi I. et al.,
RF 257 3 [23]
2014
Knopp H. et al.,
RF 425 72 [24]
2014
Miyazaki S. et al.,
RF 525 13 [25]
2014
Guiot A. et al.,
CB 66 6 [26]
2012
CB: cryo-baloon; RF: radiofrequency
Conclusion
Gastroparesis is a rare, however still underdiagnosed and underreported complication

following AF catheter ablation. Patients usually complain of abdominal painful distention,
nausea and vomiting after a minim of 2 hours post catheter ablation. The diagnostic should
exclude life-threatening complications, such as atrio-oesophageal fistula. Most patients recover
within 4-6 weeks with conservative treatment if rapid diagnosis and proper treatment and
rehabilitation are made. This rare complication is usually self-resolving, the management
including complete bowel rest, mechanical decompression and prokinetic agents. Very rarely,
in case of symptoms persistence, botulinum toxin A injection or surgical diversions may be
taken into consideration. Because this interventional treatment of AF increased in the last years,
gastroenterologists must be aware of this rare complication, to facilitate early initial diagnosis
and management.
REFERENCES
1. Calkins, H., Hindricks, G., Cappato, R., et al., (2017). 2017 HRS/EHRA/ECAS/APHRS/SOLAECE
expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary. J
Arrhythm 33, pp. 369-409.
2. Aksu, T., Golcuk, S., Guler, T.E., et al., (2015). Gastroparesis as a complication of atrial fibrillation
ablation. Am J Cardiol 116, pp. 92-7.
3. Aksu, T., Güler, T.E., Bozyel, S., Ebru Gölcük, Ş., Erden, I. (2015). An underestimated complication of
atrial fibrillation ablation: gastroparesis. Pacing Clin Electrophysiol 38(5), pp. 653-4.
4. Draganov, P.V. (2009). Gastroparesis: Current diagnostic challenges and management considerations.
World J Gastroenterol 15(1), pp. 25-37.
5. Qiu, Z.X., Mei, B., Wu, Y.S., Huang, X., Wang, Z.Y., Han Y.F., et al., (2010). Atrial natriuretic peptide
signal pathway upregulated in stomach of streptozotocin-induced diabetic mice. World J Gastroenterol
16(1), pp. 48-55.
6. Gonzalez Bosc, L.V., Majowicz, M.P., Vidal, N.A. (2000). Effects of atrial natriuretic peptide in the gut.
Peptides 21, pp. 875-887.
7. Guo, H.S., Cai, Z.X., Wu, T.H., Xu, J., Qiu, Y., Xu, W.X. (2007). Inhibitory effect of dendroaspis
natriuretic peptide on spontaneous contraction in gastric antral circular smooth muscles of guinea pigs.
Acta Pharmacol. Sin 28, pp. 1797-1802.
8. Sunata Y., Mori H., Hirai Y., et al., (2018). A Case of Gastroparesis after Cryo-balloon Ablation followed
by Medication-Induced Recovery within 6 Months. Case Rep Gastroenterol. 12(2), pp. 473-478.
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9. Zipursky, J.S., Shadowitz, S. (2017). Severe gastroparesis after catheter ablation for atrial fibrillation
CMAJ 189(9), p. E368.
10. Kaneshiro, T., Matsumoto, Y., Nodera, M., et al., (2018). Anatomical predisposing factors of transmural
thermal injury after pulmonary vein isolation. Europace 20(7), pp. 1122-1128.
11. McLellan, A.J., Kistler, P.M. (2013). Periesophageal vagal nerve injury post-AF ablation: the oesophagus
a vulnerable neighbour? J Cardiovasc. Electrophysiol 24(8), pp. 852-854.
12. Camilleri, M., Parkman, H.P. Shafi, M.A., et al., (2013). Clinical guideline: management of gastroparesis.
Am J Gastroenterol 108, pp. 18-37.
13. Meng, J., Peters, D.C., Hsing, J.M., et al., (2010). Late gadolinium enhancement of the esophagus is
common on cardiac MR several months after pulmonary vein isolation: preliminary observations. Pacing
Clin. Electrophysiol 33(6), pp. 661-666.
14. Baher, A., Kheirkhahan, M., Rechenmacher, S.J., et al., (2018). High-Power Radiofrequency Catheter
Ablation of Atrial Fibrillation: Using Late Gadolinium Enhancement Magnetic Resonance Imaging as a
Novel Index of Oesophageal Injury. JACC Clin. Electrophysiol. 4(12), pp. 1583-1594.
15. Navaravong, L., Marrouche, N. (2019). CMR Guidance of RFA to Atrial Arrhythmias. In: Kwong RY,
Jerosch-Herold M, Heydari B, editors. Cardiovascular Magnetic Resonance Imaging. New York, NY:
Springer New York, pp. 407-18.
16. Lee, D.S., Lee, S.J. (2014). Severe Gastroparesis following Radiofrequency Catheter Ablation for Atrial
Fibrillation: Suggestion for Diagnosis, Treatment, and Device for Gastroparesis after RFCA. Case Rep
Gastrointest Med 2014: 923637. doi: 10.1155/2014/923637.
17. Long, M.T., Ko, D., Arnold, L.M., et al., (2019). Gastrointestinal and liver diseases and atrial fibrillation:
a review of the literature. Therap. Adv. Gastroenterol 12:1756284819832237. doi:
10.1177/1756284819832237.
18. Wadhwa, V., Mehta, D., Jobanputra, Y., Lopez, R., Thota, P.N., Sanaka, M.R. (2017). Healthcare
utilization and costs associated with gastroparesis. J Gastroenterol. 23(24), pp. 4428-4436.
19. Shigeta, T., Okishige, K., Aoyagi, H., et al., (2019). Clinical investigation of oesophageal injury from
cryo-balloon ablation of persistent atrial fibrillation. PACE 42(2), pp. 230-237.
20. Miyazaki, S., Nakamura, H., Taniguchi, H., et al., (2017). Gastric hypo-motility after second-generation
cryo-balloon Ablation-Unrecognized silent nerve injury after cryo-balloon ablation. Heart rhythm 14(5),
pp. 670-677.
21. Aksu, T., Golcuk, S., Guler, T.E., et al., (2015). Gastroparesis as a Complication of Atrial Fibrillation
Ablation. Am J Cardiol 116(1), pp. 92-97.
22. Lakkireddy, D., Reddy, Y.M., Atkins, D., et al., (2015). Effect of atrial fibrillation ablation on gastric
motility: the atrial fibrillation gut study. Circ. Arrhythm. Electrophysiol 8(3), pp. 531-536.
23. Tsuboi, I., Hayashi, M., Miyauchi, Y., et al., (2014). Anatomical factors associated with periesophageal
vagus nerve injury after catheter ablation of atrial fibrillation. J Nippon Med Sch. 81(4), pp. 248-257.
24. Knopp, H., Halm, U., Lamberts, R., et al., (2014). Incidental and ablation-induced findings during upper
gastrointestinal endoscopy in patients after ablation of atrial fibrillation: a retrospective study of 425
patients. Heart rhythm 11(4), pp. 574-578.
25. Miyazaki, S., Taniguchi, H., Kusa, S., et al., (2014). Factors associated with periesophageal vagal nerve
injury after pulmonary vein antrum isolation. J Am Heart Assoc. 3(5), e001209.
26. Guiot, A., Savouré, A., Godin, B., et al., (2012). Collateral nervous damages after cryo-balloon
pulmonary vein isolation. J Cardiovasc Electrophysiol 23(4), pp. 346-351.
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The Role of Diet on the Symptoms of Gastroesophageal Reflux

Disease in Patients with Non-Alcoholic Steatohepatitis
GOLOGAN Elena1, GOLOGAN Andrei Nicolae1, ANTON Sorana1,

ANTON Carmen1, TIMOFTE Oana1
1
University of Medicine and Pharmacy “Grigore T Popa”, Iasi, (ROMANIA)
Emails: elenagologan2007@yahoo.com, oanatimo@yahoo.com
Abstract
This is a prospective observational study, regarding the evolution of gastroesophageal reflux

disease (GERD) symptoms in a lot of 50 obese patients with non-alcoholic steatohepatitis
(NASH) who consent to a restrictive diet and sport. A lot of 50 obese patients with NASH and
GERD typical symptoms, mean BMI=33.1, 25 women and 25 men, mean age 47.8 years, were
studied mainly for liver function and GERD symptoms before and after one year of
Mediterranean diet recommended in order to reduce with more than 10% weight and 1 hour per
day moderate physical activity. No initial gastroscopy needed. No medication to reduce gastric
acidity. Initially the patients had mean values of: ALT 151.5 IU/l, AST 175.7 IU/l, serum
albumin 3.9 g/dl, serum bilirubin 1.9 mg/dl, fasting glucose level 149 mg/dl, triglycerides 470
mg/dl and a mean value of arterial pressure 165/96 mmHg. The patients were treated only by
Mediterranean diet in order to achieve a slow weight loss and 7 hours per week moderate
physical activity. After one year the mean values of BMI decreased at 25.1, ALT at 41.7 IU/l,
AST at 46.3 IU/l, serum albumin 4.7 g/dl, serum bilirubin 1.1 mg/dl, fasting glucose level 109
mg/dl, triglycerides 197 mg/dl and a mean value of arterial pressure 135/83 mmHg. Regarding
GERD, after 1 year, the 2 typical GERD symptoms were both present only in 1 patient, 2
patients had only pyrosis, no regurgitations, in 5 patients the symptoms of GERD diminished
and 42 patients were symptom-free. In conclusion, the role of diet and sport in NASH in order
to decrease the BMI is also essential for the improvement of GERD symptoms in patients with
both diseases.
Keywords: GERD, NASH, Mediterranean diet
Background
Gastroesophageal reflux disease (GERD) is a frequent disease defined on clinical basis, with
ambulatory treatment and requiring clinical surveillance for the efficacy of treatment. Non-
alcoholic steatohepatitis (NASH) is also a frequent disease defined on laboratory and ultrasound
findings and requiring surveillance on the same criteria. In clinical practice in the ambulatory
of gastroenterology and hepatology department, one of the most frequent diseases for initial
consultation and surveillance is steatohepatitis. Usually when we are looking for this disease,
we are interested in alcohol consumption, but sometimes, not rarely, this disease is not
correlated to alcoholism, but with metabolic disturbances; we expect some unanimously
recognised correlations with type 2 diabetes mellitus, arterial hypertension, dyslipidaemia and
obesity. But many patients with steatohepatitis are claiming for typical symptoms of GERD.
Whether for the alcoholic patients this combination of steatohepatitis and GERD is expected
due to the direct effect of alcohol on liver and gastroesophageal motor and gastric secretory
function, for NASH this correlation is less expected. In obese NASH patients, we may expect
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a good improvement of the liver function in patients who follow a restrictive diet. But this diet
often improves also the GERD symptoms in these patients reducing the need for acid inhibitor
drugs. In this observational study, we tried to find if the diet only may reduce GERD symptoms
in NASH patients, considering a step-up approach in treating these patients.
Material and Method
The study was performed in a group of 50 overweight or obese patients with NASH who
presented also typical symptoms of GERD: pyrosis and regurgitations. The patients were
consulted in an outpatient department.
The interval of surveillance was 1 year for each patient; the study was conducted between
January 2017 and September 2018.
In addition to the association of the two mentioned diseases with overweight or obesity, the
main including criteria was the informed consent of the patients to a one-year program that
includes changes in their lifestyle: a monitored diet and daily physical activity. The diet was
designed by a nutritionist for each patient and was based mostly on a Mediterranean type: lot
of vegetables, fruits, beans, whole grains, some fish and less red meat. The patients were
advised to drink alkaline water, at least half of their daily liquid intake.
There were excluded the patients with: alcoholic steatohepatitis, viral hepatitis, patients
under 18 years old, patients with difficulties of understanding the importance of recommended
lifestyle changes and normal weight patients with NASH.
The investigated parameters in evolution were: the symptoms of GERD (by questionnaire),
the liver function (by laboratory tests), liver fibrosis (by fibromax) and liver morphology (by
ultrasound examination); also, an anthropological study of body mass index was performed for
each patient. In addition, the blood pressure was measured at the beginning and at the end of
the study though the hypertensive patients were surveyed more often by their cardiologists.
Results
There were studied 50 adult patients, 25 women and 25 men, mean age 47.8 years. They
were observed by gastroenterologist at the beginning, after one month, and then after six and
twelve months (from the start) equivalent for one-year period for every patient.
The initial body mass index (BMI) of the group was 33.1 kg/m2. The nutritional condition
was surveyed by the nutritionist each month.
The examination for liver function included: serum transaminases (aspartate
aminotransferase-ASAT, alanine aminotransferase-ALAT, gamma-glutamyl trans peptidase-
GGT), cholestasis syndrome (serum bilirubin and alkaline phosphatase), metabolic syndrome
(serum glucose, uric acid, cholesterol and triglycerides, serum albumin), coagulation (INR,
prothrombin index). The examination for the liver structure included an ultrasound abdominal
examination with details on: liver size, liver echo-structure and data regarding a possible portal
hypertension (portal vein size, spleen size, splenic vein size, gallbladder wall, peritoneum) in
order to exclude focal liver lesions.
These laboratory tests were performed initially, after six months and after one year.
A Fibromax test was performed at start and after one year.
For GERD symptoms we used a simple clinical questionnaire based on semiology of the
disease with questions regarding:
 the presence of typical GERD symptoms (inclusion criteria): regurgitations and pyrosis
 the absence of exclusion or alarm symptoms: anaemia, dysphagia, weight loss
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 additional extra-digestive symptoms: chronic cough, dysphonia, recurrent upper

respiratory tract infections, non-cardiac chest pain, non-allergic asthma and nocturnal
dyspnoea.
This questionnaire was performed at the beginning and repeated after one month, after six
months from the beginning and after one year.
The patient went to nutritionist in order to receive a nutritional plan that includes a
Mediterranean diet adjusted individually and designed in order to achieve a weight loss at least
10% reported to the initial weight.
Considering the approach of the treatment for GERD in step-up manner, additionally the
patients were advised to some of the classical hygiene-dietetic measures, though nowadays
disputed: avoidance of sweet food, small quantity meals, the last meal of the day ‒ the smallest
and not too close to the bedtime hour and a two pillow sleep. Alkaline water was recommended
for about half of the daily liquid intake.
Every patient was counselled for one-hour moderate physical activity but every patient chose
the manner of his activity (sport or walking) according with his physical condition, pleasure
and time availability.
The body mass index decreased from 33.1 to 25.1 after one year (Fig. 1).
Regarding NASH, the final results compared to the initial point showed:
 a decrease in medium ALAT level from 151 IU/ml to 41 IU/ml
 a decrease in medium ASAT level from 175 IU/ml to 46 IU/ml
 a decrease in medium alkaline phosphatase level from 132 IU/ml to 120 IU/ml
 a decrease in medium GGT level from 97 IU/ml to 32 IU/ml
 a decrease in medium serum glucose level from 149 mg/dl to 109 mg/dl
 a decrease in medium triglycerides level from 470 mg/dl to 194 mg/dl
 a decrease in medium total cholesterol level from 290 mg/dl to 265 mg/dl (Fig. 2a)
 an increase in medium albumin level from 3.9 mg/dl to 4.7 mg/dl
 a decrease in medium bilirubin level from 1.9 mg/dl to 1.1 mg/dl
 a decrease in medium INR level from 1.2 to 1.1 (Fig. 2b).
The symptoms of GERD had a spectacular evolution.
After one year only one of the patients had persistent GERD both typical symptoms: pyrosis
and regurgitation; moreover, because after one month the symptoms were similar as at start we
started a treatment with proton pump inhibitor and even so the symptoms persisted. There was
done an upper digestive endoscopy after two months revealing a giant hiatal hernia. This case
was considered with lack of response.
After one year two other patients (4%) had persistent pyrosis but no regurgitations.
In other five patients (10%) the symptoms were sporadic present but significant more
diminished then at the beginning.
From the extra-digestive symptoms, there was a good resolution of dysphonia, non-allergic
asthma and dyspnoea, but with less spectacular results on chronic cough (in 2 patients was
persistent).
A high percentage of 84% (42 patients) were GERD symptom free after one year.
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40 BMI
33,1
30 25,1
20
10
0
initial final
Fig. 1. Evolution of body-mass index (BMI)
500 470
450
400
350
290
300 265
250
197
200 175
151 149
150 132120
97 109
100
41 46
50 32
0
ALAT ASAT ALP GGT glycemia triglycerides
initial final
Fig. 2a. Evolution of liver tests
5 4,7
4,5
3,9
4
3,5
3
2,5
1,9
2
1,5 1,1 1,2 1,1
1
0,5
0
albuminemia bilirubine INR
initial final
Fig. 2b. Evolution of liver tests
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60
50 50
50
40
30
20
12
9
10 4 5
3 2 2 2 3
1 0 0 1 0
0
pyrosis regurgitation dysphonia cough asthma URT infections toracic pain dyspnea
initial final
Fig. 3. GERD symptoms evolution
Discussions
The role of the Mediterranean diet is recognized as beneficial in NASH. Numerous studies
show that a diet rich in fruits, vegetables, beans, whole grains, fish and small amount of red
meat and on the other part a diet poor in sweets, processed foods, fast food and red meat greatly
reduce liver steatosis [1], [2].
If the patients in the studied group had the diet indication anyway, we considered it useful
to study its effect also on GERD, preferring a less “aggressive drug” approach, moreover as the
efficacy of the drugs in NASH is questionable and in GERD the step-up approach can be used
without medications but only with diet at the beginning.
In 2017, a study by Zalvan and colleagues demonstrated the effect of the Mediterranean diet
and the consumption of alkaline water on laryngopharyngeal reflux and the benefit of this
combination compared to the use of proton pump inhibitors [3]. But this type of reflux is not
possible in the absence of gastroesophageal reflux, which is why we considered this study as a
starting point in the use of the step-up treatment of the symptoms of gastroesophageal reflux in
patients with associated NASH and GERD in which the Mediterranean diet was anyway
recommended.
Mone and colleagues in another study show a direct positive correlation between the
Mediterranean diet and GERD [4].
In a recent study by Newberry and co-workers, physio-pathological explanations for
gastroesophageal reflux symptoms and how they are influenced by diet are being attempted [5].
Starting from the current diagnosis of GERD [6] and considering the mechanisms of the
disease, the most used current treatments we must recognize that they do not interfere with the
cause of the disease but only with its consequences, which is why new methods of management
of GERD are currently being sought [7] through the prism of pathophysiology but also from
the prism of one of the intrinsic principles of medicine “primum non nocere”; that is why
approaching GERD through diet as a first step, obviously with the follow-up of patients from
the perspective of the evolution of symptoms is a variant to consider.
In the group studied the effects of the diet were significant also on GERD, in the majority of
patients not finding the medication useful.
Of course, there are limitations of the study: small number of patients, lack of a witness
group, plain questionnaire, but further studies are needed to detail the actual findings.
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Conclusions
The role of diet and moderate physical activity in overweight or obese NASH patients (in
order to decrease the body weight) who presented also GERD symptoms was essential for the
reduction of these GERD symptoms. This clinical ascertainment may be possible due to: the
diaphragmatic detention secondary to weight loss that induces a lower intra-abdominal
pressure, due to increased contraction strength secondary to physical activity and due to the
limitation of hyper-glucidic food that simultaneously stimulates acidity.
Regarding these, we may try as first intention the treatment of a functional disease as GERD
with the old-fashioned method of step-up with good results in many (but selected) patients.
For good results the patient’s compliance is essential, based on the understanding of the
disease as the doctor explains to each patient.
REFERENCES
1. Della Corte C, Mosca A, Vania A, Alterio A, Iasevoli S, Nobili V. (2017). Good adherence to the
Mediterranean diet reduces the risk for NASH and diabetes in paediatric patients with obesity: The results
of an Italian Study. Nutrition, 39-40, pp. 8-14.
2. McCarthy EM, Rinella ME. (2012). The Role of Diet and Nutrient Composition in Non-alcoholic Fatty
Liver Disease. Journal of the Academy of Nutrition and Dietetics 112(3), pp. 401-409.
3. Zalvan C, Hu S, Greengerg B, et al., (2017). A Comparison of Alkaline Water and Mediterranean Diet
Vs Proton Pump Inhibition for treatment of Laryngopharyngeal Reflux. JAMA Otolaringol Head Surg.
143(10), pp. 1023-1029.
4. Mone I, Kraja B, Bregu A, Duraj V, Sadiku E, Burazeri G, Hyska J. (2016). Adherence to a predominantly
Mediterranean diet decreases the risk of gastroesophageal reflux disease: a cross-sectional study in a
South Eastern European Population. Dis Esophagus 29(7), pp. 794-800.
5. Newberry C, Lynch K. (2019). The role of diet in the development and management of gastroesophageal
reflux disease: why we feel the burn. J Thorac Dis. 11(Suppl. 12), pp. S1594-S1601.
6. Gywali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout A, Vaezi M, Sifrim D, Fox MR, Vela MF,
Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S. (2018). Modern Diagnosis of GERD: The
Lyon Consensus. Gut 67(7), pp. 1351-1362.
7. Gyawali CP, Fass R. (2018). Management of Gastroesophageal Reflux Disease. Gastroenterology; 154:
pp. 302-18.
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Gerd After Surgery for Oesophageal Atresia
GAVRILESCU Simona1,2, APRODU Gabriel1,2, DRUG Vasile3,

BĂRBOI Oana3, LĂPTOIU Alma2, TETIA Teodora Tetia2, HANGANU Elena1,2
1
Discipline of Pediatric Surgery-University of Medicine and Pharmacy “Grigore T. Popa” Iasi (ROMANIA)
2
Clinic of Paediatric Surgery and Orthopaedics of the St. Mary Children’s Emergency Clinical Hospital, Iasi (ROMANIA)
3
Discipline of Gastroenterology ‒ University of Medicine and Pharmacy “Grigore T. Popa” Iasi (ROMANIA)
Abstract
Oesophageal atresia is the most common congenital malformation of the oesophagus

requiring surgical treatment in the neonatal period. There are few studies in the literature
regarding the occurrence of gastrointestinal, nutritional and respiratory manifestations in the
medium and long term follow-up of patients operated for oesophageal atresia by primary
anastomosis or cervico-stomy/gastrostomy respectively esophagoplasty.
Purpose
The purpose of this paper is to identify the distant occurrence of gastroesophageal
manifestations, respectively respiteurs and the incidence of digestive and extra digestive
manifestations of gastroesophageal reflux in a tertiary centre for the treatment and follow-up of
patients with oesophageal atresia.
Method
We present the results of a descriptive retrospective study over a period of 10 years that used
the database of the Emergency Clinical Hospital for Children “Sf. Maria”. We identified a
number of 48 patients with oesophageal atresia operated between 2008-2018 who could be
contacted for the follow-up protocol. Patient evaluation was performed using a questionnaire
addressed by telephone regarding respiratory and digestive symptoms.
Results
Gastrointestinal reflux events were reported by 28 patients (63%) and solid dysphagia was
reported by 18 patients (49%). No patient was hospitalized for gastric fundoplication at follow-
up. Respiratory symptoms were reported by 23% of patients with the most common conditions
being coughing, wheezing (52%), bronchitis (8,7%), repeated pneumonia (80%) and asthma
(10%).
Conclusions
There is a hidden morbidity marked in patients with oesophageal atresia operated during the
neonatal period. They require a multidisciplinary approach for long-term follow-up of
gastrointestinal manifestations of gastroesophageal reflux and respiratory disorders.
Keywords: oesophageal atresia, reflux, follow-up
Introduction
Since the first oesophageal atresia operated in Romania in 1962, by Professor Doctor
Vereanu, have been over 57 years [1]. The infant mortality in this condition reached almost
90% in our country until 20 years ago. Today, the healing reaches over 80% internationally [2].,
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and every case we can save represents a big leap in the last years of paediatric surgery in
Romania.
General Information’s
Oesophageal atresia is the congenital discontinuity of the oesophagus, with or without

communication with the respiratory tract through a fistula. Oesophageal atresia has an incidence
of 1 in 3000 to 1 in 5000 new-borns alive [3]. It is considered that there is a higher prevalence
in men, but this is not perfectly proven and is not valid for all variants of atresia. Family cases
have rarely been reported.
The fact that it is frequently associated with other malformations, suggests a disorder in
embryogenesis. In week 3 of intrauterine life, the oesophagus is delimited within the anterior
intestine. In the next 2 weeks, the lower respiratory tract will develop through a proximal
expansion of the ventral wall of the intestine, with enlargement of the oesophagus in length.
The two structures will be separated by a sept consisting of the para-axial mesenchyme.
Disruption of the mechanism of separation and mesenchymal migration leads to its abnormal
communication with the airways [4].
A cyclical variation of the incidence was observed, without a seasonal link. It was suggested
that the anomaly might be caused by an infectious agent, or that thalidomide might be involved,
as well as progesterone alone or associated with estrogenic. Experimental studies have shown
oesophageal atresia without fistula in offspring of mice with riboflavin deficiencies, but the
resounding in human pathology is unclear.
Oesophageal atresia presents many forms and multiple classification systems have been
designed. According to the Ladd classification, the most used in our clinic and in Romania,
there are 4 types of oesophageal atresia. Type I in which the two segments are separated,
without communication with the trachea, and the upper segment ends near the vertebra D2-D3.
Type II which implies the existence of a small fistula between the upper segment of the
oesophagus and the trachea, in which case the lower segment exceeds the diaphragm. Type III,
the most common, encountered in 85-90% of cases, in which the upper segment descends to
level D2-D3, where it ends blindly in the glove finger and opens as a fistula on the dorsal face
of the trachea. It is subdivided, depending on the distance between the ends, in two
subcategories. Type IV is defined by the communication of both ends of the oesophagus
malformed with the trachea, through two fistulas.
Almost half of the cases of atresia are associated with major anomalies of other structures.
The most common cause of mortality or difficult postoperative evolution is multiple
congenital anomalies. All these defects can be isolated, but the patent is grouped into
malformative associations, known under various acronyms (CHARGE, VACTER,
VACTERL).
The diagnosis of oesophageal atresia can be made in several stages of the patient’s life;
antenatal by the ultrasound of the pregnant uterus, when the atresia is suspected by the presence
of polyhydramnios (but not specific) or the absence of the stomach shadow (the stomach is
filled with amniotic fluid from the trachea through the esotracheal fistula or is occupied by
gastric secretions). Any new-born must be checked for permeability of the digestive tract in the
birth ward. An ordinary catheter, with a thickness of 6-8 Ch., passes through the nostril to the
stomach. It is known that the probe reached the stomach after a journey of 15-20 cm and gastric
secretions can be aspirated. If the probe stops at 8-10 cm from the nostril or the gingival arch,
it is most likely atresia.
The treatment is exclusively surgical. Currently, most surgeons are supporters of primary
anastomosis. This can be achieved both by direct approach, by right lateral thoracotomy in the
IV intercostal space, as well as minimally invasive, thoracoscopic. The fistula will be ligated
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and sectioned and the oesophageal ends will be anastomosed. The greater the distance between
the ends, the greater the number of postoperative complications. If the distance exceeds 4
vertebrae, it will be considered for fistula ligation and a preliminary feeding gastrostomy,
followed by esophagoplasty. If oesophageal replacement is the procedure of choice, cervical
oesophagostomy is necessary.
Personal Contributions
We present the results of a descriptive-retrospective study over a period of 10 years that used
the database of the Emergency Clinical Hospital for Children “Sf. Maria”, Iași.
We performed, through a questionnaire (Fig. 1) addressed to the families of these patients
by telephone, an up-to-date analysis of the gastroesophageal and respiratory manifestations and
the presence of gastroesophageal reflux in the patients operated by oesophageal atresia during
2008-2018.
The questionnaire (Fig. 1) included a total of thirteen questions and was adapted from a study
conducted by Schier and colleagues in 2001, at the Jena University Medical Center, Germany
[6].
Fig. 1.
117 patients were included in the present study, of which 4 cases were not identified in the
database as having oesophageal atresia, and 10 patients could not be contacted. The mortality
rate was around 48.76%, with a decrease in recent years. There has been a predominance of
pathology in males.
There were no references to the antenatal diagnosis, from what parents remember. In one
case the suspicion of the existence of oesophageal atresia after the ultrasound diagnosis of
pohydramnios was raised. In 88% of cases the diagnosis was established early, in the first 12
hours of life and only in 1% late, after the first 24 hours of life.
In the present study 30 patients from the 44 respondents had associated malformations. The
most common were heart malformations, without being other than those found in the general
population, namely: persistence of the arterial duct, atrial septal defect or permeable oval
foramen. It should be noted that the most common cause of mortality of these patients is
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multiple congenital anomalies. Detection of congenital heart disease in association with

oesophageal atresia is an indication for genetic testing and careful screening for other foetal
abnormalities. Congenital heart disease is associated with a higher mortality in oesophageal
atresia but it is not the cause of it.
From the point of view of treatment, 84% of patients had primary anastomosis by direct
approach and only 14% of cervico and gastrostomy.
At 20.45%, due to anastomosis disruption in the postoperative period, iterative thoracotomy
was required, with cervical and gastrostomy. If this option was preferred, esophagoplasia was
subsequently performed using colonic tube in 77.8% of cases and only in 22% was performed
pull-gastric. We mention that this was done in clinics abroad.
In 20.45% of cases, stenosis appeared at the site of anastomosis. No patient required surgery,
such as enlargement or narrowing of the anastomosis area, oesophageal dilatations with Savary-
Gilliard dilator with progressive gauge were enough.
If mortality is related to the associated malformations in the treatment of atresia, the long-
term evolution is related to the persistence of a gastroesophageal reflux. The most common
digestive clinical signs mentioned by the interviewed parents were retrosternal discomfort, food
impactation, dysphagia for solids, dysphagia for liquids, odynophagia. Most parents report their
occurrence more often than once a week. Even in the absence of clinical signs a patient with
operated atresia should be evaluated clinically and radiologically periodically, at 6 months, up
to the age of 4-5 years. The symptoms in the respiratory sphere related by the patients were
recurrent coughing and wheezing. 91.3% of patients had repeated respiratory infections. 70.3%
of them need hospitalization. Aspiration pneumonia occurred in 80% of patients. Most parents
consider that the frequency of symptoms has decreased with the growth of the child, even if no
treatment is applied.
The investigation of the presence of reflux after oesophageal anastomosis should be done
systematically. It exposes the child to chronic respiratory disease, to an esophagitis which in
turn can be complicated by stenosis and a high risk of malignancy. 63.6% of the patients in the
study were diagnosed with reflux. Of these, 20 benefited from primary anastomosis and 8 from
cervical and gastrostomy. It should be noted that no patient was hospitalized for gastric
fundoplication during the follow-up period. Only 35% required drug therapy to control the
symptoms The most commonly used drugs were histamine H2 antagonists and proton pump
inhibitors. Early diagnosis and management of gastroesophageal reflux may help to minimize
subsequent lower airways disease and restrictive lung disease.
The literature cites multiple causes of gastroesophageal reflux in patients with oesophageal
atresia. There is talk of a congenital anomaly of innervation of the oesophagus, a decrease of
the neural tissue at the distal oesophageal level, the presence of gastrostomy as a favouring
factor, the intraoperative damage of the vagal nerves and the excessive tension at the place of
the anastomosis, which can ascend the lower end of the oesophagus, modifying the competency
of cardia. Curious is that there are cases of gastroesophageal reflux in children whose
anastomosis was not under tension.
Conclusions
Early diagnosis of GERD is important in children and young adults with history of
oesophageal atresia not only for the caused discomfort but for the respiratory complications that
may be associated and the increased risk of malignancy. Multiple factors seem to be
contributing to the aetiology of GERD in patients with repaired oesophageal atresia.
In most cases the evolution of reflux will be favourable with proper treatment. The patient
with oesophageal atresia should be closely monitored and controlled by a team of paediatric
gastroenterologists and paediatric surgeons and taken to adulthood by a gastroenterologist.
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REFERENCES
1. Pesamosca, A., Vereanu, D. ‒ Atrezia de esofag și fistulele esotraheale. În “Chirurgie Infantilã si

Ortopedie – Urgente” Editura Medicalã (Bucuresti) 1973, pp. 116-122.
2. Pinheiro, Paulo Fernando Martins, Ana Cristina Simões e Silva, and Regina Maria Pereira. “Current
knowledge on esophageal atresia.” World journal of gastroenterology: WJG 18.28 (2012): p. 3662.
3. Helardot, P. ‒ Atresie de l’oesophage. “Chirurgie digestif de l’enfant” Ed. Doin Editeur (Paris) 1990, pp.
83-102.
4. Ioannides, Adonis S., and Andrew J. Copp. “Embryology of oesophageal atresia.” Seminars in paediatric
surgery. Vol. 18. No. 1. WB Saunders, 2009.
5. Little, Danny C., et al., “Long-term analysis of children with oesophageal atresia and tracheoesophageal
fistula”. Journal of paediatric surgery 38.6 (2003): pp. 852-856.
6. Schier F, Korn S, Michel E. Experiences of a parent support group with the long-term consequences of
oesophageal atresia. J Pediatr. Surg. 2001; 36 (4): pp. 605-10.
7. Mirra, Virginia, et al., “Longitudinal follow-up of chronic pulmonary manifestations in oesophageal
atresia: a clinical algorithm and review of the literature.” Paediatrics & Neonatology 58.1 (2017): pp. 8-
15.
8. Mahoney, Lisa, and Rachel Rosen. “Feeding problems and their underlying mechanisms in the
oesophageal atresia – tracheoesophageal fistula patient.” Frontiers in paediatrics 5 (2017): p. 127.
9. Gibreel, Waleed, et al., “Swallowing dysfunction and quality of life in adults with surgically corrected
oesophageal atresia/tracheoesophageal fistula as infants: forty years of follow-up.” Annals of surgery
266.2 (2017): pp. 305-310.
10. Aprodu G., Botez C., Munteanu V., Gotia D.G. “Patologia chirurgicală a esofagului la copil”. Ed. Gr. T.
Popa, Iași (2003).
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Phototherapy in Some Digestive Disorders
LUNGOCI Constantin1, BĂRBOI Oana-Bogdana2, ROBU Teodor1

1
Faculty of Agriculture, “Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Iasi,
(ROMANIA)
2
Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115, Iași,
(ROMANIA)
Email: teorobu@uaiasi.ro
Abstract
The expanded matching feature that some species of plants have had over time as treatment
for conditions of various types, including those of the digestive tract, leads us to believe that
there is no person who, during life, because of experiencing a gastric or intestinal disorder, has
never resorted to an herbal remedy. Regarding this, we can take as example the common
infusions of peppermint, chamomile, Saint John’s worth etc.
Numerous disorders of the digestive tract are caused by the fact that daily, through food, the
digestive tract is in permanent contact with food, but also with some non-food substances.
In this study, two digestive disorders are going to be referred to. They are nowadays
frequently encountered, and the phyto-therapeutic medication responds successfully to them:
the timpanists and the irritable colon.
The floristic composition of the greened area in Romania as well as in Moldova, offers a
wide range of spontaneous and cultivated plants, which, under various forms of preparation,
fall into the composition of herbal products. The paper will present some of these local species
and their uses, synthesizing some agronomic, biochemical and phyto-therapheutic results for
the diseases studied.
Keywords: tympanites, irritable colon, carminative, phytoncides, Apiaceae, Lamiaceae
Introduction
Generally speaking, tympanites can be defined as an accumulation of gases in the intestine

that leads to an increase in the volume of the abdomen. Symptomatically, it is manifested by
abdominal bloating and flatulence. The causes may vary: aerophagia, intestinal fermentation or
other conditions (enterocolitis, hypoacetic gastritis, pancreatic and cholecystic disorders) etc.
[4]. The plants used in the treatment of tympanites are known by the generic name of
carminatives. They possess some active ingredients that stop the development of the pathogenic
flora. These active ingredients are also called phytonic substances. Another specific action of
these plants is relaxing the smooth muscles in the intestine, favouring the evacuation of
intestinal gases. Most phytotherapeutic medicine formulations contain ‒ as main components ‒
plants from the family of Apiaceae. Furthermore, the results of these plants are increased by a
synergism and a stimulation of the carminative effect, in the case of some species of the
Lamiaceae family being also parts in the mixture [3, 4].
The irritable colon is characterized by the lack of balance between the motor activity of the
intestine and the secretory activity of the mucous membranes. Studies show that the disease
comes from the high load of metabolic residues, but also toxic deposits. The formation of the
mucoid plate is due to the action of some internal or external factors: excessive consumption of
meat, foods contaminated with pesticides, drug abuse. As internal factors, worth mentioning
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for are intestinal parasites, bacteria or stomach acidity. Thus, the lumen of the colon narrows,
the transit is deficient, and the colon becomes a reservoir of toxins that, in the first phase, moves
to the neighbouring organs. In the herbal treatment, the emphasis is on the use of plants with
carminative, antiseptic, antispasmodic and sedative effect [5]. Herbal products try to offer
efficacy through the multiple actions: both on the psychic factor (with the help of sedative,
soothing medication) as well as on the symptoms with the help of the carminative plants,
regulating the intestinal transit and antispasmodic.
Methodology
The herbs presented in this paper are grown and studied at USAMV’s Iasi crop fields named
“The collection of medicinal and aromatic herbs”. Also the growth technique was correlated
speciality’s literature, the agronomic one as well as the medical one.
These were backed up by the results from the field, especially for the three species of the
Apiaceae family.
Results
1. Anise ‒ (Pimpinella annisum L.) ‒ native to the eastern Mediterranean area, in our country
it is cultivated in the southern counties Constanta, Brăila, Ialomița, Timiș, Teleorman,
preferring sunny and wind-free lands [6]. The maturation of the seeds is done stepwise and
shakes very easily. Therefore, harvesting begins when 50% of the umbels become brown and
the plants begin to yellow.
From this plant the fruits are used ‒ Anisi Fructus with a content of 1.5-6% volatile oil, fatty
oil and protein substances [4]. The main components are trans-anetole 85-95% volatile oil and
estragol (1-2%). Fatty oil has a participation rate in seeds of 10-30%. In meteorism and other
digestive disorders a dose of 1 gr is recommended. daily in children over 12 years. The
administration period should not exceed 2 weeks. It is usually given as an infusion, decoction
or tincture [7]. Other uses: food industry, taste and odor correction, animal feed, soap making,
honey plant [6].
2. Cumin ‒ (Carum carvi L.) ‒ originating in South Asia and Turkey [5], improved forms
are cultivated in the country in the Western Plain, Hațegului Country, Bârsei Country,
Transylvania Plateau [6]. It is used for both fruit (Carvi fructus) harvesting when 60-75% of
the umbels have been browned and by mowing 20 cm from the soil level for the whole plant
(Carvi herba) [5].
The species is of interest for the content in volatile oil 3-7%, which has as main components
carvona (50-60%), limonene (30-40%), but also for the content in fatty oil, proteins and mineral
substances. Considered the plant with the best carminative properties, the medicinal forms act
on the level of the smooth muscle and have a selective bacterial potential (only on the
pathogenic flora). It is given in a dose of 1-6 grams/day. It is not given to children under 10
years of age [7].
The forms of preparation and administration are various: infusion, decoction, tincture, syrup,
volatile oil and powder. In table 1 and figure 1 we have presented some of our studies regarding
the loss of seed weight, but also of the volatile oil content of the species Carum carvi L.
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Table 1. The weight loss dynamic and the volatile oil of the species Carum carvi L.
Time Quantity of % gr. seed % U.V.
% U.V.
(months) seeds (gr.) loss loss
0 1000 100 7,1 100
6 0,964 96,4 6,6 93,0
12 0,950 95,0 6,0 84,5
18 0,941 94,1 5,5 77,5
24 0,936 93,6 5,1 71,8
Fig. 1. The weight loss dynamic and the volatile oil of the species Carum carvi L.
3. Coriander ‒ (Coriandrum sativum L.) ‒ native to the Near East and Southern Europe, we
have a large area of cultivation in our country. Sandra and Omagiu varieties rich in linalool are
grown [5]. It is grown for fruit (Coriandri fructus) which is harvested when 60-70% of the fruits
have been ripe. The species has a volatile oil content of 0.5-0.9%, main components linalool
(80-85%), and 15% fatty oil [6]. It enters into the composition of medicinal forms that have in-
between derivatives (e.g., Sennae folium) to prevent the appearance of intestinal colic.
Aqueous, hydro alcoholic and alcoholic extracts are obtained [7]. In table 2 and figure 2 we
presented some of our studies regarding the loss of seed weight, but also of the volatile oil
content of the species Coriandrum sativum L.
In table 2 and figure 2 we have presented some of our studies regarding the loss of seed
weight, but also of the volatile oil content of the Foeniculum vulgare Mill species:
Table 2. The weight loss dynamic and the volatile oil of the species Coriandrum sativum L.
Time Quantity of % gr. seed % U.V.
% U.V.
(months) seeds (gr.) loss loss
0 1000 100 0,88 100
6 0,970 97 0,78 88,6
12 0,955 95,5 0,65 73,9
18 0,945 94,5 0,58 65,9
24 0,938 93,8 0,54 61,3
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% 100
80
60
40
20
0
0 6 12 18 24
Timpul (luni)
% Pierdere g. semin]e % Pierdere U.V.
Fig. 2. The weight loss dynamic and the volatile oil of the species Coriandrum sativum L.
4. Fennel ‒ (Foeniculum vulgare Mill.) ‒ native to southern Europe and the Near East, it is
cultivated frequently in the country in the Plain of Oltenia, Dobrogea, Bărăganan, Burnaz,
Timiș, etc. [7]. It is used both the whole plant (Foeniculi herba), but more often the fruits
(Foeniculi fructus). Harvesting is recommended when 50% of the umbels have browned, as
they shake very easily [7]. Plants are rich in volatile oil 2-4% in grass and 3-7% in fruit.
Anethole 50-80%, fenchone 10-30% predominate in the chemical composition, the other
components having very small percentages [6]. Fennel is commonly used in the fight against
meteorism and flatulence, but it is also recommended as an adjuvant with laxatives, it reduces
gastrointestinal spasms. In the form of infusion is used an amount of 10-15 grams/day, 5-7
grams’ tincture and 10-20 grams’/day syrup. It is not given to patients with duodenal ulcer and
nervous system disorders ‒ epileptiform seizures [8].
In table 3 and figure 3 we have presented some of our studies regarding the loss of seed
weight, but also of the volatile oil content of the Foeniculum vulgare Mill species:
Table 3. The weight loss dynamic and the volatile oil of the species Foeniculum vulgare Mill
Time Quantity of % gr. % U.V.
% U.V.
(months) seeds (gr.) seed loss loss
0 1000 100 1,92 100
6 0,966 96,6 1,80 93,8
12 0,955 95,5 1,65 85,9
18 0,943 94,3 1,58 82,3
24 0,937 93,7 1,52 79,2
Fig. 3. The weight loss dynamic and the volatile oil of the species Foeniculum vulgare Mill.
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5. Mint ‒ (Mentha sp.) ‒ used since ancient times, remnants found in the Egyptian pyramids
have spread to England, where most varieties come from today. In Romania, it is cultivated
mainly in the country of Bârsei, the south of Oltenia and Muntenia and the Timiș field. The raw
material is represented by the aerial part (Folium et Herba Menthe) [7]. Harvesting is done at
full flowering through mowing. In the chemical composition, 0.5-4% volatile oil, 6-12%
tannins, flavonoids etc. predominate. The major components of volatile oil are menthol 30-
55%, menton 14-32%, isomentone 1.5-10%, methyl acetate 2.8-10%, mentofuran etc. The
volatile oil has an effect on the smooth muscles, relaxing it. At the level of the digestive tract,
the amplitude of the contractions diminishes. It also has a specific action on the stomach
sphincters, but it also acts on the intestinal bacteria, which leads to the reduction of volatile
sulphur compounds. For digestive disorders it is used as an infusion in variable doses from 3-5
grams’ day in children, up to 1.5-3 grams/day in adults three times a day.
Mint oil is also used in the case of irritable colon in the form of gastro resistant capsules, in
doses of 0.2-0.4 ml/capsule 3 times a day [8].
6. Lavender ‒ (Lavandula sp. L.) ‒ originating in the Mediterranean area, until the beginning
of the First World War it was harvested from spontaneous flora, but the growing demand
necessitated its introduction into culture [6]. In our country it is cultivated in most areas, both
as a culture plant, but also for the ornamental role in parks and gardens [7]. The raw material is
inflorescences (Lavandule angustifoliae flos, Flores Spicae, Lavandule flos).
Harvesting is done in full bloom [6]. The main commercialized product is 0.7-1.4% volatile
oil in green inflorescences. The biochemical composition is extremely diverse. The main
components of the oil are 50-60% lineally acetate, geraniol, linalool etc. [4]. The combined
spasmolytic, sedative and coagulative-carminative action recommends the plant product as a
treatment for stomach disorders [8]. It is usually used as an infusion [7].
Among the plants used in ameliorating or treating the irritable colon, there can be mentioned:
1. Flax ‒ (Linum usitatissimum L.) ‒ originating in South-East Asia, it is cultivated on large
areas in the country and it is compatible for fields around the most regions of the country. The
raw material used in herbal medicine is seed (Lini semen), flax oil (Oleum linea) obtained by
cold pressing [6]. The seeds have a content of 3-10% mucilage being made up of three
poloholosidic fractions, in which two of them are acidic and one neutral located at the level of
the seminal tegument. All of them, by the means of acid hydrolysis, determines the appearance
of mucilaginous compounds [8]. Also, the fatty oil located in the cotyledons is rich in linoleic
acid 52%, linoleic 17%, oleic 20%, palmitic 6% and stearic 4%. It influences the intestinal
transit, especially the colon, by increasing the volume of the bowel and stimulates its
evacuation. This effect is due to the swelling of carbohydrate polymers in the presence of water
[3]. It is used in the form of ground seeds, mucilaginous extracts, alcoholic extracts, etc. In the
case of digestive disorders that require softening of the stool and easy defecation, the dose of
administration is 10-15 grams/day with 150 ml of water in 2-3 halves [8].
2. Saint John’s wort ‒ (Hypericum perforatum L) – The provenience can be traced in Europe
and West Asia, as in Romania, it can be found on hills and plains. The main raw material is the
aerial terminal part of the plant, not more than 2 mm thick (Hyperici herba) [6]. Contains 0.4-
0.6% ethereal oil in flowers, flavonic glycosides, hypericin etc. Due to the bioactive
components, it is well suited to combat gastric disorders. The using methods may vary, but,
mainly, it is used as infusion, but also in the form of tincture, macerate or soothing oil. It is also
used in veterinary medicine as a digestive and antidiarrheal medicine [7].
3. Valerian ‒ Valeriana officinalis L. ‒ Frequently it can be found in the spontaneous flora
of the Caucasus Mountains, southern Siberia, while in Europe it is mostly encountered in the
Alps. In Romania, the valerian is spread across forests, depressions, shady and humid areas.
The raw material is represented by roots and rhizomes (Valerianae rhizoma cum radicibus).
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The difference in the chemical composition is given by the presence of 0.3-1% volatile oil,
valepotrias and lignin derivatives [7]. It is used in the medicine form of treatment for cases of
irritable colon, due to its antispasmodic role. The form of administration is infusion, maceration,
tincture or powder.
4. Field bindweed ‒ Convolvulus arvensis L. – This plant is commonly spread around plains
as well as hills. The necessary raw material is represented by its stems with leaves and flowers
(Convolvuli herba). It is harvested by tearing as the plants begin to bloom. The difference in
the chemical composition is given by the presence of flavonoids, tannins and resins
(convolvulin, jalapine) [6]. The field bindweed is used as an infusion due to its purgative
potential. No adverse effects are known because of the consumption of the products obtained
from this plant [1].
5. Sweet flag (or, more commonly named ‒ calamus) ‒ Acorus calamus L. – The origins can
be found in East Asia and it was brought inland by migrant peoples. The rhizomes of this species
were used to maintain potable water, preventing the development of microorganisms (antiseptic
role). In Romania, the farmers are cultivating sweet flag on marshy land (especially in the
Danube meadow) or in the fields that can be irrigated by the surface runoff. The raw material
is rhizomes (Calami rhizoma), which is harvested in the fall of the second culture year.
The chemical composition is given by the volatile oil rich in azarone, azarilic aldehyde,
camphor, eugenol, but also by other components such as: resins, mineral salts, sugars etc. [6].
From a pharmacodynamics’ point of view, it acts on gastric secretion and peristalsis, due to
the bitter aromatic components [8]. It is used mainly as a decoction of 1-1.5 gr. of the well-
chopped vegetable product. It is advisable to use caution for short periods of time as well,
because, when used for a long time, it is considered that some metabolites possess carcinogenic
potential.
Conclusions
1. The occurrence of digestive disorders is increasing worldwide as well as nationally;

2. Among digestive disorders, the most commonly encountered ones are tympanites and
the irritable colon disorder;
3. The range of species used to ameliorate or treating the two disorders belongs to a
diversified flora (crop plants, herbs in agricultural crops or plants existing in a
spontaneous flora), which is most often not exploited to its true potential;
4. The valuable content within the active ingredients and the ecological environment in
which they live, proves them as being some valuable sources of exploitation, together
with their use as raw materials in obtaining many types of herbal products;
5. The percentage of active ingredients differs depending on the organ of the plant but also
on the disposition of the organ on the plant;
6. The concentration of the active substances is influenced by the phenophase, by the
moment the diurnal moment of the harvest, altitude, the exposure of the slope etc.
Acknowledgments
This work was supported by a grant of the Romanian Minister of Research and Innovation,
CCCDI-UEFISCDI, project number PN-III-P1-1.2-PCCDI-2017-0850/ contract 14 PCCDI
/2018, within PNCDI III.
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7. ROBU Teodor, MILICĂ Constantin (2004). Plante medicinale autohtone, Editura Institutul European,
Iași, pp. 64, 85, 104, 128, 148, 191, 176.
8. STĂNESCU Ursula and col. (2014). Plante medicinale de la A la Z, Editura POLIROM, Iași, pp. 132,
201, 272, 324, 349, 360, 390, 611.
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High Resolution Manometry in Oradea ‒ First Year’S Experience
MUNTEANU Mihai1, BRISC Cristina1, DEMIAN Luiza1, BRISC Ciprian1

1
Oradea University, Faculty of Medicine and Pharmacy, County Clinical Hospital of Emergency, Oradea (ROMANIA)
Email: mihaimunteanual@yahoo.com
Abstract
High resolution manometry (HRM) is performed to record the mechanically relevant aspects
of the swallow in order to gain insight into oesophageal (patho)physiology and to correlate
patient symptoms with the observed manometric patterns, in order to improve the accuracy of
diagnosis. Our aim was to underline the variety of cases and the challenges that a physiology
unit faces in the beginning of the activity. We investigated patients from Oradea County
Emergency Hospital. All patients underwent upper endoscopy before the procedure. Inclusion
criteria: dysphagia, chest pain, heartburn, regurgitation, belching. The protocol that we used
was 10 wet swallows, 5ml each, then 5 rapid swallows, then 200ml free drinking test. The
procedure took place in the morning, with the patient being fasting, in the semi-upright position.
Solid food test we only performed if clinical scenario asked for it. The device that we used
was produced by Diversatek Healthcare (Sandhill Scientific) and the software that we used for
data analysis was Zvu® Advanced Diagnostic GI Software. The probe was a 32channel
pressure, 16 impedances from UniSensor (regular value for IRPm was 28mmHg). Chicago
Classification v3 was used to interpretate the findings. Exclusion criteria were intolerance to
the procedure and findings in upper endoscopy non-compatible with the HRM procedure. We
investigated 36 patients (pts) from Gastroenterology, Diabetology and ENT department. All
tolerated the investigation. No patient refused the procedure and nobody asked for the
interruption of the procedure. 18 cases (50%) were women and 18 cases were men (50%). Mean
age was 64 years old, median 65 years old, minimum 39 years old and maximum 89 years old.
Mean age in women was 65,75 and in men 62,25. We found achalasia and EGJ outflow
obstruction: type 1 achalasia (2 pt.), type 2 achalasia (2 pt.), EGJ outflow obstruction (4 pts).
We found major disorders of peristalsis: absent contractility (6pts), Jackhammer oesophagus
(2 pt.). We also found minor disorders of peristalsis: ineffective oesophageal motility (10 pts)
and fragmented peristalsis (6 pts). 4 patients had normal oesophageal motility. Hiatal hernia
was diagnosed in 9 patients. In 1 case we encountered a problem: “butterfly” pattern because
of a big hiatal hernia. We encountered many challenges during our first year but we passed
them all. By performing HRM we managed to improve our diagnostic accuracy and the patients
were able to receive the best therapeutic option tailored on their needs.
Keywords: High resolution manometry (HRM), high resolution impedance manometry (HRiM),
oesophageal motility disorders, peristalsis disorders, achalasia
Introduction
High resolution manometry (HRM) started from conventional manometry. HRM is

performed to record the mechanically relevant aspects of the swallow in order to gain insight
into oesophageal (patho)physiology and to correlate patient symptoms with the observed
manometric patterns, resulting in improved accuracy of the diagnosis [1]. In contrast to
conventional manometry, HRM records intraluminal oesophageal pressure at closely spaced
intervals (high spatial resolution) from the length of the oesophagus [1]. Minor progress, in
77
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addition to improved spatial resolution, have also been improvements in the frequency and
accuracy with which pressure signals can be recorded (temporal resolution) and the accuracy
of pressure measurement (pressure resolution) [2]. Two basic verities of manometric catheter
are available to record pressures within the oesophagus lumen, solid state and water perfused,
with significant differences regarding their properties [1]. HRM involves computerized
acquisition of oesophageal pressure data, and display as pressure topography such that distance
along the oesophagus, amplitude of peristalsis and time are apparent in the generated colour
image [3]. These findings offer significant gain in the assessment of lower oesophageal
sphincter (LES) and the oesophageal body contraction segments. The current, state-of-the-art
combined high-resolution impedance manometry (HRiM) systems provides a powerful tool to
assess oesophageal motility and function with the ability to evaluate the efficiency of
oesophageal motility and bolus transit through the oesophagus [1]. Combined HRiM recordings
are of value in clarifying the mechanisms of gastro-oesophageal reflux episodes and symptoms
in GERD patients as well as patients with suspected behavioural disorders such as rumination
and belching [4].
Methods
Our aim was to underline the variety of cases and the challenges that a physiology unit faces
in the beginning of the activity. We investigated patients from Oradea County Emergency
Hospital. All patients underwent upper gastrointestinal endoscopy before the HRM procedure.
Our inclusion criteria were: dysphagia, non-cardiac chest pain, heartburn, regurgitation,
belching, or any other symptom for which HRM was necessary for establishing the diagnosis.
The exclusion criteria were: any endoscopic findings that explain the symptoms of the
patient and for which the HRM procedure was no longer necessary, intolerance of the procedure
or the refusal of performing the procedure.
All patients were fasting at the time of the procedure, in order to protect the patient for
aspirating intra-gastric or intra-oesophageal contents. If the patient was on drugs that could alter
the oesophageal motility, those were stopped 3 days before (calcium channel blockers, nitrates,
prokinetics, loperamide, opiate agonists or antagonists, anticholinergics, beta-adrenergic
antagonists, tricyclic antidepressants).
The position of the patient was semi-upright.
The protocol that we used consisted of a 30 second baseline recording after the placement
of the catheter, then 10 wet swallows, 5ml each, then 5 rapid swallows, then 200ml free drinking
test. The delay between 2 swallows was at least 30 seconds. Solid food test was only performed
if the clinical scenario asked for it.
The device that we used was produced by Diversatek Healthcare (Sandhill Scientific) and
the software that we used for data analysis was Zvu ® Advanced Diagnostic GI Software. The
probe that we used was a solid state catheter, 32channel pressure (spaced 1 cm), 16 impedances
from UniSensor (regular value for IRPm was 28mmHg).
For normal values Chicago Classification v3 was used to interpretate the findings, along
with the recommendation of the manufacturer [5].
Results
We investigated 36 patients from Oradea County Emergency Hospital, departments of

Gastroenterology, Diabetology and ENT.
All patients tolerated the investigation. No patient refused the procedure and nobody asked
for the interruption of the procedure.
All studies were evaluable.
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18 cases (50%) were women and 18 cases were men (50%). Mean age was 64 years old,
median 65 years old, minimum 39 years old and maximum 89 years old. Mean age in women
was 65,75 years old and in men 62,25 years old.
We found achalasia and EGJ outflow obstruction (8 patients, 22% of the patients): type 1
achalasia (2 patients), type 2 achlasia (2 patients), EGJ outflow obstruction (4 patients).
We also found major disorders of peristalsis (8 patients, 22%): absent contractility (6
patients), Jackhammer oesophagus (2 patients).
We also found minor disorders of peristalsis (16 patients, 44%): ineffective oesophageal
motility (10 patients) and fragmented peristalsis (6 patients).
Only 4 patients (11%) had normal oesophageal motility.
Hiatal hernia was diagnosed in 9 patients. Fig 1-4 illustrates some of our studies.
In 1 patient we encountered a problem: the “butterfly” pattern because of a big hiatal hernia.
Fig. 1. Type 2 Fig. 2. Fig. 3. Absentent Fig. 4. Butterfly

Achalasia Jackhammer contractility Effect
Discussion
Before starting performing HRM, we needed to prepare with both theoretical and practical
knowledge. In order to start the activity of our physiology unit, one did attend two courses,
theoretical and practical courses (Netherlands and Romania) and participating in a 2 weeks’
fellowship offered by the United European Gastroenterology in a European Centre where HRM
is performed.
During our first year of activity as a physiology unit, we managed to investigate 36 patients,
which is about 0,69 patients/week and if we include the leave (4 weeks in Romania), we
investigated 0,75 patients/week. Those are small numbers comparing with other European
centers, but we cannot offer any data regarding other centers in our country, considering that
HRM is performed in only a couple of medical centres.
Our rate of evaluable studies was 100%, which is about the same like in the literature ‒ 99%
[6].
Our gender balance was completely equal between males and females, although most of the
studies are male-predominant [1].
Age distribution was the same as in other studies [6].
Achalasia and EGJ outflow obstruction was found in 22% of the studies performed, numbers
which are slightly lower than in other studies (18.4% achalasia + 11.1% EGJ outflow
obstruction) [6].
Major findings encountered for 22% in our studies, slightly higher than in other studies [6].
Minor findings occurred for the majority of the results, 44%, slightly higher than in the
literature [1].
Normal oesophageal motility based on exclusion criteria was found in 11% of the patients,
lower than in other studies [6].
The small number of patients that we managed to enrol so far are probably responsible for
these results, which slightly different than what we have seen in the literature so far.
Geographical population characteristics might also be responsible for these results.
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Conclusions
We managed to perform HRM studies in a reasonable number of patients with results that
are comparable to what we have seen in other studies performed so far.
We encountered many challenges during our first year but we passed them all and these
could be an imbols for one who wants to start a physiology unit.
Performing HRM was of great advantage because we managed to improve our diagnostic
accuracy and our patients were able to receive the best therapeutic option tailored on their needs.
REFERENCES
1. Fox M, Kahrilas P, Pandolfino J, Zerbib F. Manual of High Resolution Oesophageal Manometry. 1st
Edition. Bremen, Uni-med, 2014.
2. Bredenoord AJ, Hebbard GS. Technical aspects of clinical high-resolution manometry studies.
Neurogastroenterol Motil 2012; 24: pp. 5-10.
3. Clouse RE, Staiano A. Topography of the oesophageal peristaltic pressure wave. Am J Physiol 1991;
261: pp. G677-84.
4. Pandolfino JE, Shi G, Zhang Q et al., Measuring EGJ opening patterns using high resolution intraluminal
impedance. Neurogastroenterol Motil 2005; 17: pp. 200-6.
5. Bredenoord AJ, Fox M, Kahrilas PJ et al., Chicago classification criteria of oesophageal motility
disorders defined in high resolution oesophageal pressure topography (EPT). Neurogastroenterol Motil
2012; 24 Suppl. 1: pp. 57-65.
6. Pandolfino JE, Ghosh SK, Rice J et al., Classifying oesophageal motility by pressure topography
characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol2008; 103: pp. 27-37.
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The Distribution and Features of Colonic Diverticula Complicated

with Acute Diverticulitis ‒ Single Tertiary Center Experience
MUZÎCA Cristina-Maria1,2, STANCIU Carol1, HUIBAN Laura1,2,

PETREA Oana1,2, FRUNZUC Georgiana1, SÎNGEAP Ana-Maria1,2,
TRIFAN Anca1,2
1
Institute of Gastroenterology and Hepatology, Iasi, (ROMANIA)
2
“Grigore T. Popa” University of Medicine and Pharmacy, Iași (ROMANIA)
Emails: lungu.christina@yahoo.com, stanciucarol@yahoo.com, huiban.laura@yahoo.com,
stoica_oanacristina@yahoo.com, frunzuc.georgiana@yahoo.com, anamaria.singeap@yahoo.com, ancatrifan@yahoo.com
Abstract
Introduction
The colonic diverticular disease is common in industrial countries and has significant impact
on patient health as well as health care cost. Recent studies have shown a rise in diverticular
disease-associated hospital admissions and also an increasing prevalence among younger
patients in developing countries which have adopted western diets.
Aim
We aimed to evaluate the incidence of colonic diverticulosis and acute diverticulitis in the
adult population referred to a gastroenterology medical center from North Eastern Romania.
Methods
We analysed 5000 colonoscopies performed between January 1st 2016 and December 31st
2017 in the Institute of Gastroenterology and Hepatology, Iasi.
Results
Our cohort included 5000 patients investigated by colonoscopy during the mentioned period.
Eight hundred and six (16.1%) patients were diagnosed with colonic diverticula, with the
following demographic features: 411 (51%) were females and 395 (49%) males, mean age 67
years, 545 (68%) from urban area and 261 (32%) from rural area. The diverticula localization
was predominantly in the sigmoid colon (221-28%) followed by the left colon (192-24%) and
the entire colon (176-22%). The other locations were: descending colon (89-11%), transverse
and left colon (51-6.3%), ascending colon (31-3.8%), transverse colon (22-2.7%), cecum (9-
1.1%), ascending and sigmoid (4-0.5%), right colon (3-0.4%), ascending and descending colon
(3-0.4%), ascending and transverse (2-0.2%), sigmoid and cecum (2-0.2%) and left colon and
cecum (1-0.1%). Diverticulitis specific signs were found in 20 (2.5%) patients, of which 15
(75%) associated peridiverticular inflammation.
Conclusion
Recent studies show that the incidence of diverticular disease is increasing in developing
countries and affects younger patients, which implies an increased risk of life-threatening
complications. Our study shows a high incidence of diverticula in patients evaluated by
colonoscopy, with a worrying percentage of patients with acute diverticulitis.
Keywords: diverticulosis, acute diverticulitis
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Introduction
The colonic diverticular disease (CDD) includes all clinical manifestations of colonic
diverticula, causing considerable acute and chronic suffering. The CDD is common in industrial
countries and has significant impact on patient health as well as health care cost. Although this
condition is specific for the elderly patients, recent studies have shown a rise in diverticular
disease-associated hospital admissions and also an increasing prevalence among younger
patients in developing countries which have adopted western diets.
Colonic diverticula (CD) are in fact out-pouching’s of colonic mucosa and submucosa that
emerge through the muscularis propria, most frequently at the points where the blood vessels
supplying the submucosa and mucosa penetrates the wall, which means these structures are
pseudodiverticulas [1]. The real diverticula of the colon contain all layers of the colonic wall
and are rarely seen in white population, rather are specific for the Asian patients [2]. The
structural alterations of the colonic wall such as elastosis of the taenia coli or muscular layer
thickening are often present [3-5]. CD can be complicated by a spectrum of diseases including
diverticulitis and diverticular bleeding [4].
Whilst considered more common among elderly patients, recent studies show a continuous
rise of the incidence of CD in the younger population. Hence, the diagnostic methods, the
indications for surgery as well as treatment modalities have been evolving, resulting in more
options in the therapy for CD.
Due to the fact that diverticula are, by definition, asymptomatic, there is scarce data
regarding the distribution and characteristics of diverticulosis. Most studies which assessed the
incidence of CD may have considerable selection bias (e.g., autopsy, imaging, colonoscopy)
therefore it is difficult to determine the real incidence of CD [5]. Also there is no conclusive
data for the global incidence of CD, the standardized incidence rate of hospitalization for acute
diverticulitis being available only in countries like the U.S., rising from 59 to 71/100,000 from
1998 to 2005 (data from a sample consisting of 20% of the U.S. population) [6]. The incidence
of CD is increasing in the Western population and apparently remains very rare in rural Africa
and Asia [7]. As countries become urbanized, the incidence of the disease appears to be in
continuous rising, supposedly due to the adoption of Western diet characterized by low dietary
fiber intake.
Epidemiology of CD in Romania is poorly known due to limited data. However, a recent
retrospective study conducted in Romania has yielded results which show an increasing
frequency of diverticulosis from 1.29% in 2002 to 2.5% in 2005, among admitted patients [8].
Also, the maximum incidence of CD reported by another study is observed in elderly
patients, aged 60 and above [9]. Regarding the gender distribution of the disease, the current
literature does not offer any conclusive data. The prevalence and pattern of CD differ among
ethnic groups and lifestyles with left-sided disease being most common in Western and
developed countries, while right-sided diverticulosis is more prevalent in Asian and developing
countries [10-12].
Painter and Burkitt reported in their study published in 1971 a strong association between
low-fiber diets and CD [13]. Also, data provided by prospective observational studies show that
both physical activity and a high-fiber diet are associated with a lower risk of developing
diverticular disease [14].
In Romania, there is limited data regarding the epidemiology and characteristics of CD. The
widespread utilization of screening colonoscopy offers an unprecedented opportunity to learn
more about this condition. In our study we aimed to describe the incidence, distribution and
characteristics of CD enumerating them by number, location in the colon and association with
inflammation signs in the adult population referred to a tertiary gastroenterology medical
center.
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Methodology
We analysed 5000 colonoscopies performed between January 1 st 2016 and December 31st
2017 in the Institute of Gastroenterology and Hepatology, Iasi. We included patients 18 years
and older, which had a satisfactorily preparation for colonoscopy, and a complete exam to the
cecum. Diverticula were evaluated by the gastroenterologist counted in each segment of the
colon (cecum, ascending, transverse, descending, and sigmoid colon). Inflammation was
assessed as any sign of redness or ulceration near a diverticulum.
Statistical Analysis
Descriptive statistics are provided as mean ± standard deviation (SD) for continuous
variables. Student’s two-tailed t test for paired samples was performed to evaluate differences
in diverticula prevalence and distribution related to patient gender and age. Statistical analysis
was carried out using SPSS (version 21.0; SPSS, Chicago, IL, USA), and a p values of less than
0.05 were considered statistically significant.
Results
Our cohort included 5000 patients investigated by colonoscopy between January 1 st 2016
and December 31st 2017. Mean age was 56.13±14.9 years, 2705 (54%) were females and 2295
(46%) were males, predominantly from urban area (3350-67%).
Eight hundred and six (16.1%) patients were diagnosed with colonic diverticula, with the
following demographic features: 411 (51%) were females and 395 (49%) males, mean age 67
years, 545 (68%) from urban area and 261 (32%) from rural area.
The main localization for diverticula was predominantly in the sigmoid colon (221-28%)
followed by the left colon (192-24%) and the entire colon (176-22%) (Figure 1).
250
200
150
100
50
0
Sigmoid colon Left colon Entire colon
Fig. 1. The main locations for diverticula
The other locations were: descending colon (89-11%), transverse and left colon (51-6.3%),
ascending colon (31-3.8%), transverse colon (22-2.7%), cecum (9-1.1%), ascending and
sigmoid (4-0.5%), right colon (3-0.4%), ascending and descending colon (3-0.4%), ascending
and transverse (2-0.2%), sigmoid and cecum (2-0.2%) and left colon and cecum (1-0.1%)
(Figure 2).
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Left colon+cecum
Sigmoid+cecum
Ascending+transverse colon
Ascending+descending colon
Right colon
Transverse colon
Cecum
Ascending colon
Transverse+left colon
Descending colon
Ascending + sigmoid colon
0 20 40 60 80 100
Fig. 2. Other locations of diverticula
Diverticulitis specific signs were found in 20 (2.5%) patients, of which 15 (75%) associated
peridiverticular inflammation. We found a significant association of the prevalence of
diverticulitis and age above 65 years (p=0.003).
No significant difference in diverticula prevalence and distribution was observed related to
patient gender (p>0.05).
Disease extension increased with age in all colonic segments, especially in the sigmoid
colon, ranging from 16.5% for patients under 40 years of age to 68% for those older than 65
years.
Discussion
We found that the incidence of CD in our study is comparable with that of similar studies
performed in European countries and Asian communities who have adopted a Western life
style, supporting the idea that diverticula prevalence in developing countries is increasing,
likely attributed to population aging and dietary changes. Likewise, the mean age of patients
with diverticula in our study was 67 years, demonstrating a steady increment of the disease
prevalence with increased age.
Lee et al., detected diverticulosis in 19 per cent of 1,000 autopsy examinations in Singapore,
more often in males than females aged under 60 years [15]. Also, Chia et al., reported a similar
frequency of diverticulosis (20%) in the barium enemas performed over an 18 – month period
(1987-1988) in a Singapore hospital [16]. The incidence of diverticulosis increased with age
and was similar among males and females. The results of these studies showed almost an equal
prevalence rate of diverticulosis compared to Western countries. Authors suggest that the
frequency is influenced by dietary and other environmental factors and the location depends on
genetic factors. This observation was confirmed by an increase in the diverticulosis prevalence
in Asian countries adopting a Western life style with a remaining anatomic pattern specific for
Asia [17, 18]. In our study, the disease incidence increased with age, and gender does not seem
to be related to diverticula incidence and distribution. These data are consistent with previous
studies demonstrating no difference in gender distribution between age classes in patients with
diverticular disease [19, 20]. In our study, the most commonly encountered was the left-sided
diverticulosis, with the highest frequency of the disease in the sigmoid colon, which is specific
for non-Asian communities. This data is consistent with the available studies. Beuran et al.,
showed in their retrospective study that 90% of diverticula were located in the left colon [9].
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We found a relatively low incidence of acute uncomplicated diverticulitis (AUD) among the
study group. Similarly, Tursi et al., found an incidence of 2% of AUD in a population of which
12% of patients were diagnosed with diverticula [22]. However, a nationwide in-patient sample
survey, performed in US, found that the incidence of patients admitted with acute diverticulitis
raised from 120 500 in 1998 to 151 900 in 2005 (a 26% increase) [6].
Conclusion
Diverticular disease of the colon is a significant problem in elderly patients, affecting equally
both females and males, with the most common occurrence in sigmoid and descending colon.
Recent studies show that the incidence of CD is increasing in developing countries and
affects younger patients, which implies an increased risk of life-threatening complications. Our
study shows a high incidence of diverticula in patients evaluated by colonoscopy, with a
percentage of patients with acute diverticulitis consistent with available data.
REFERENCES
1. Burkitt, D.P., Walker, A.R.P., Painter, N.S. (1979) Effect of dietary fibre on stools and transit-times and
its role in the causation of disease. Lancet. 1979; ii: pp. 1408-1411.
2. Brian West A (2006). The pathology of diverticulosis: classical concepts and mucosal changes in
diverticula. J Clin. Gastroenterol. 2006 Aug;40 Suppl. 3: pp. S126-31. Review. PubMed PMID:
16885695.
3. Maykel, J.A., Opelka, F.G. (2004). Colonic diverticulosis and diverticular haemorrhage. Clin Colon
Rectal Surg. 2004; 17: pp. 195-204.
4. Cohen, E., Fuller, G, Bolus R, et al., (2013). Increased risk for irritable bowel syndrome after acute
diverticulitis. Clinical gastroenterology and hepatology: the official clinical practice journal of the
American Gastroenterological Association. 2013; 11(12): pp. 1614-9. Epub. 2013/03/26. [PubMed:
23524129].
5. Barroso, A.O., Quigley, E.M. (2015). Diverticula and Diverticulitis: Time for a Reappraisal.
Gastroenterol Hepatol. (N Y). 2015 Oct; 11(10): pp. 680-8. PubMed PMID: 27330495; PubMed Central
PMCID: PMC4849520.
6. Etzioni, D. A., Mack, T. M., Beart, R.W., and Kaiser, A. M. (2009) “Diverticulitis in the United States:
1998-2005: changing patterns of disease and treatment” Ann. Surg., vol. 249, no. 2, pp. 210-7, Feb. 2009.
7. Tănase, I., Păun, S., Stoica, B., et al., (2015) Epidemiology of diverticular disease ‒ systematic review of
the literature. Chirurgia (Bucur). 2015; 110(1): pp. 9-14.
8. Miron, A., Ardelean, M., Bogdan, M., and Giulea, C. “[Surgical management of colonic diverticular
disease].” Chirurgia (Bucur)., vol. 102, no. 1, pp. 37-42.
9. Beuran, M., Iordache, F., Chiotoroiu, A. L., Teleanu, et al., “Complicated diverticular disease ‒ our recent
experience,” Chirurgia (Bucur)., vol. 104, no. 1, pp. 25-9.
10. Kang, J.Y., Melville, D., Maxwell, J.D. (2004) Epidemiology and management of diverticular disease of
the colon. Drugs Aging. 2004; 21: pp. 211-228.
11. Jun, S., Stollman, N. (2002) Epidemiology of diverticular disease. Best Pract. Res Clin Gastroenterol.
2002; 16: pp. 529-542.
12. Stollman, N., Raskin, J.B. (2004) Diverticular disease of the colon. Lancet. 2004; 363: pp. 631-639.
13. Painter, N.S., Burkitt, D.P. (1971) Diverticular disease of the colon: a deficiency disease of Western
civilization. Br Med J. 1971; 2: pp. 450-4.
14. Humes, D., Simpson, J., & Spiller, R. C. (2007). Colonic diverticular disease. BMJ clinical evidence,
2007, 0405.
15. Lee, Y.S. (1986) Diverticular disease of the large bowel in Singapore. An autopsy survey. Dis Colon
Rectum 1986; 29: pp. 330-335.
16. Chia, J.G., Wilde, C.C., Ngoi, S.S., et al., (1991) Trends of diverticular disease of the large bowel in a
newly developed country. Dis Colon Rectum 1991; 34: pp. 498-501.
17. Vajrabukka, T., Saksornchai, H., Jimakorn, P. (1980) Diverticular disease of the colon in a far-eastern
community. Dis Colon Rectum 1980; 23: pp. 151-154.
18. Sugihara, H., Muto, T., Morioka, Y., et al., (1984) Diverticular disease of the colon in Japan. A review
of 615 cases. Dis Colon Rectum 1984; 27: pp. 531-537.
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19. Jung, H.K., Choung, R.S., Locke, G.R. 3rd, et al., (2010) Diarrhoea-predominant irritable bowel syndrome
is associated with diverticular disease: a population-based study. Am J Gastroenterol 105: pp. 652-66131.
20. Parra-Blanco, A. (2010) Colonic diverticular disease: pathophysiology and clinical picture. Digestion
73(Suppl. 1): pp. 47-57.
21. Hughes, L.E. (1969) Post-mortem survey of diverticular disease of the colon. I. Diverticulosis and
diverticulitis. Gut 1969; 10: pp. 336-344.
22. Tursi, A., Elisei, W., Giorgetti, G.M., et al., (2011) Inflammatory manifestations at colonoscopy in
patients with colonic diverticular disease. Aliment Pharmacol Ther. 2011 Feb; 33(3): pp. 358-65.
doi:10.1111/j.1365-2036.2010.04530. x. Epub. 2010 Dec 7. PubMed PMID: 21133960.
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The Age and Level of Studies in the Treatment Decision for

Irritable Bowel Syndrome
PALAMARU Andreea-Luiza1,2, TOADER Elena1,2,

MUSTEAȚĂ Mădalina-Anca1, ROTARU Tudor-Ștefan1,2
1
Institute of Gastroenterology and Hepatology, St. Spiridon Emergency County Hospital, Iasi (ROMANIA)
2
“Gr. T. Popa” University of Medicine and Pharmacy Iasi (ROMANIA)
Emails: luiza.palamaru@yahoo.com, toader.elena@yahoo.com, anca.mada13@gmail.com, t_rotaru@yahoo.com
Abstract
Irritable bowel syndrome is the most common functional type gastrointestinal disorder with
a negative impact on the quality of life of patients. The negative impact of the investigations
and/or treatment on the quality of life of patients depends on variables such as the age of the
patient but also on the level of studies they have. The objective of the study is to analyse how
the age and the level of education of the patients influences the compliance with investigations
and treatment. A group of patients diagnosed with irritable bowel syndrome (N=42. 22 women
and 20 men) and committed in the Institute of Gastroenterology and Hepatology in “St. Spiridon
Hospital” in Iași, Romania, answered to six-point Likert-scale questions regarding psycho-
social aspects of the irritable bowel. Patients reported the age and other socio-demographic
variables, as well as data on the debut of symptoms and the debut of treatment. Spearman’s ρ
non-parametric correlations were calculated between the number of months from the debut of
symptoms to the debut of treatment and investigations and the age of the patient, respectively
the level of studies. There is a significant positive, mean correlation, between the age of the
patient and the number of months passed from the beginning of symptoms to investigations
and/or treatment (Spearman ρ(40)=0,45; p<0,01). There is a significant negative, mean
correlation, between the level of studies and the number of months passed from the beginning
of the symptoms to investigations and/or treatment (Spearman ρ(40)=-0,38; p<0,01). The longer
time between the debut of symptoms and conducting investigations among elderly patients, can
be explained by the existence of many other conditions in their medical history. The level of
studies of the patients influences the degree of awareness of the symptomatology and the
potential alarm signal on a more serious condition.
Keywords: irritable bowel syndrome, age, studies, treatment
Introduction
Irritable bowel syndrome is a functional gastrointestinal disease characterized by recurrent

abdominal pain, discomfort and altered bowel habits which do not present with identifiable
organic lesions. The diagnosis of irritable bowel syndrome- according to the Rome IV criteria-
requires that patients have had recurrent abdominal pain (at least 1 day/week in the last 3
months) that is related to defecation, an associated change in stool frequency, and/or an
associated change in stool form.
Irritable bowel syndrome is a common gastrointestinal disorder with an estimated global
prevalence of around 10%. Its high prevalence and chronic nature decrease patients’ quality of
life and place a significant economic burden on healthcare systems in both western and eastern
countries.
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There is a growing body of evidence suggesting a possible role for the gut microbiota in
irritable bowel syndrome pathogenesis. Irritable bowel syndrome has been significantly
associated with small intestinal bacterial overgrowth (SIBO) (4% to 78%) and prior
gastrointestinal infection (5% to 32%), suggesting that enteric dysbiosis) is a potential
pathogenic mechanism of irritable bowel syndrome [1]. SIBO is characterized by an increase
in the number and/or presence of atypical bacteria in the upper gut, which in turn affects
intestinal motility and metabolism differently, depending on whether hydrogen gas or methane
is produced [2]. Next-generation sequencing has revealed that irritable bowel syndrome
patients, compared with healthy controls, show significantly lower abundance in enteric
Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii [1].
As the Rome III criteria indicate, the key features are abdominal pain or discomfort that is
clearly linked to bowel function, either being relieved by defecation or associated with a change
in stool form or consistency. These symptoms are not explained by biochemical or structural
abnormalities. Symptoms should be present for at least 6 months to clearly distinguish those
from other conditions such as infections, which often pass quickly, or progressive diseases such
as bowel cancer that are usually diagnosed within 6 months of symptom onset.
Irritable bowel syndrome is the most common functional type gastrointestinal disorder with
a negative impact on the quality of life of patients. Is considered a painful condition and those
with painless bowel dysfunction are labelled as having “functional constipation” or “functional
diarrhoea”.
The complications of are decreased quality of life, time off from work and school, personal
expenses of medications and physician visits, and psychological problems such as depression
and anxiety [3]. The negative impact of the investigations and/or treatment on the quality of life
of patients depends on variables such as the age of the patient but also on the level of studies
they have.
The objective of the study is to analyse how the age and the level of education of the patients
influences the compliance with investigations and treatment.
Material and Method
A group of patients diagnosed with irritable bowel syndrome (N=42. 22 women and 20 men)
and committed in the Institute of Gastroenterology and Hepatology in “St. Spiridon Hospital”
in Iași, Romania, between August 2019 and October 2019, answered to six-point Likert-scale
questions regarding psycho-social aspects of the irritable bowel.
Patients were considered eligible for inclusion if they were over than 30 years of age, had
irritable bowel syndrome symptoms (assessed according to the Rome III diagnostic criteria) at
the time of visit.
Irritable bowel syndrome was defined as recurrent abdominal pain or discomfort (at least 3
days per month in the last 3 months) with an onset at least 6 months before the diagnosis
associated with 2 or more of the following: improvement with defecation, onset associated with
a change in the frequency of stools and onset associated with a change in the form of the stools.
The irritable bowel syndrome subgroups were classified as constipation-predominant
irritable bowel syndrome, diarrhoea-predominant irritable bowel syndrome, and mixed type
(both constipation and diarrhoea irritable bowel syndrome).
A total of 64 patients were eligible for the study. The questionnaire distributed to patients
included both socio-demographic aspects and qualitative information related to both forms of
irritable bowel syndrome. The results were anonymous only the research team having access to
patients’ answers. Some questions referred to various symptoms and social problems and
referred to less pleasant experiences. A section on psycho-social problems was also included:
interaction with relatives, husband or wife, children or work activity.
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This study contributed to a better understanding of how patients with irritable bowel
syndrome live with their condition. Such scientific conclusions can help physicians and the
scientific society to provide better care to patients suffering from irritable bowel syndrome, and
better access to evidence-based medicine.
The patient’s participation in the study was limited to a single stage.
Patients were selected according to the rural or urban areas. Regarding the level of education,
patients were invited to choose between options such as primary education, secondary
education, high school, university or post-university studies.
Patients were asked to indicate the year of onset of symptoms associated with irritable bowel
syndrome and how long after this time they were diagnosed. Symptom management options
were related to information on the Internet, consultation with a general practitioner or self-
medication with medicines or herbal remedies.
For the processing of the results was used a nonparametric measure of rank correlation
(statistical dependence between the rankings of two variables), Spearman’s rank correlation
coefficient.
Results
There is a significant positive, mean correlation, between the age of the patient and the
number of months passed from the beginning of symptoms to investigations and/or treatment
(Spearman ρ(40)=0,45; p<0,01) (Fig. 1). There is a significant negative, mean correlation,
between the level of studies and the number of months passed from the beginning of the
symptoms to investigations and/or treatment (Spearman ρ(40)=-0,38; p<0,01) (Fig. 2).
A
g
e
The number of months passed from the beginning of symptoms to

investigations and/or treatment
Fig. 1. Correlation between the age of the patient and number of months passed from the beginning of symptoms
to investigations and/or treatment
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Level
of
studies
The number of months passed from the

beginning of symptoms to investigations and/or
treatment
Fig. 2. Correlation between the level of studies and the number of months passed from the beginning of the
symptoms to investigations and/or treatment
Conclusions
The longer time between the debut of symptoms and conducting investigations among
elderly patients, can be explained by the existence of many other conditions in their medical
history. Usually, elderly patients have many comorbidities, the most commonly encountered in
daily medical practice being cardio-vascular, neurological and diabetes. The existence of these
associated pathologies leads to the iatrogenesis associated with the elderly, which has to follow
which must follow several treatment schemes concurrently.
Symptoms associated with irritable bowel syndrome may be sub-classified by other life-
threatening conditions of the patient.
The level of studies of the patients influences the degree of awareness of the
symptomatology and the potential alarm signal on a more serious condition. Patients with an
advanced educational level showed a higher degree of awareness of the need for investigations
and treatment of irritable bowel syndrome compared to patients with secondary education. Also,
the patients with university studies presented a high therapeutic compliance, this being
generated by the fear of the existence of a digestive pathology superimposed on the irritable
bowel syndrome.
REFERENCES
1. Herndon CC, Wang YP, Lu CL. Targeting the gut microbiota for the treatment of irritable bowel
syndrome: Review article. Kaohsiung J Med Sci., 2019; pp. 1-11.
2. Lee SH, Cho DY, Joo NS et al., Effect of eradicating hydrogen-forming small intestinal bacterial
overgrowth with rifaximin on body weight change: Observational Study. Medicine, 2019; pp. 98-51.
3. Greenberger, N.J, Blumberg R.S, Burakoff R. (2017). Current Diagnosis &Treatment: Gastroenterology,
Hepatology, & Endoscopy. McGraw-Hill Medical, pp. 231-232.
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Genetic Aspects of Hirschsprung’s Disease
PÂNZARU Monica-Cristina1, BUTNARIU Lăcrămioara-Ionela1,

CABA Lavinia1, POPESCU Roxana1, GAVRIL Eva1, POPA Setalia1,
RESMERIŢĂ Irina1, GORDUZA Eusebiu Vlad1, RUSU Cristina1
1
“Grigore T. Popa” University of Medicine and Pharmacy, Medical Genetics Department, Iasi, (ROMANIA)
Email: monica.panzaru@yahoo.com
Abstract
Hirschsprung’s disease (HD) is a congenital disorder, characterized by complete absence of

neuronal ganglion cells in a portion of the intestinal tract, due to a disruption of normal neural
crest cell migration, proliferation, differentiation and/or apoptosis. HD may occur as an isolated
finding or as part of a multisystem disorder. The most common associated anomalies include:
heart defects (septal, patent ductus arteriosus, Fallot tetralogy), gastrointestinal malformations
(Meckel diverticulum, malrotation, and imperforate anus), central nervous system (Dandy-
Walker malformation), and genitourinary abnormalities (cryptorchidism, hypospadias, and
renal malformations). HD has a complex genetic aetiology with several genes being described
as associated with either isolated or syndromic forms. A large number of chromosomal
anomalies have been described in HD: trisomy 21, del13q22, del10q11.2, del10q23.1, del2q22,
del 4p12 and del 17q21/dup 17q21-q23. Monogenic syndromes frequently associated with HD
include: Waardenburg-Shah, Mowat-Willson, Goldberg-Shprintzen, multiple endocrine
neoplasia type 2, intestinal neuronal dysplasia type B, congenital central hypoventilation,
Bardet-Biedl, Cartilage hair hypoplasia and Smith-Lemli-Opitz. Non-syndromic HD has been
associated with pathogenic variants in a number of genes: RET, GDNF, NRTN, EDNRB, EDN3,
ECE1, NRG1, NRG 3, SEMA3C, SEMA3, SOX10. The inheritance of non-syndromic HD is
complex and characterized by variable penetrance. The recognition of syndromic HD is
essential for disease prognosis and accurate genetic counselling. This emphasises the
importance of detailed family history, careful clinical examination and genetic testing of new-
borns diagnosed with HD.
Keywords: Hirschsprung’s disease, genetics
Hirschsprung disease (HD) is a congenital intestinal motility disorder, characterized by signs

of intestinal obstruction due to complete absence of neuronal ganglion cells from a portion of
the intestinal tract [1]. Harald Hirschsprung, described in 1888 two cases who died from chronic
severe constipation with abdominal distension resulting in congenital mega-colon [2]. In 1948,
the absence of intramural ganglion cells of the myenteric and submucosal plexuses downstream
of the dilated part of the intestine was discovered as the cause of the disease [3].
The aganglionic fragment includes the distal rectum and a portion of contiguous proximal
intestine. In 80% of cases, aganglionosis is limited to the rectosigmoid; in 15%-20%, extends
proximal to the sigmoid; in about 5%, affects the entire colon. Rarely, the aganglionosis extends
to the entire bowel [4]. The most accepted theory of the cause of HD is that there is a defect in
the craniocaudally migration of neuroblasts originating from the neural crest. Defects in the
survival, migration, proliferation, and differentiation of these progenitor cells within the
gastrointestinal tract may contribute to the disorder [5, 6]. HD has an incidence of around
1:5,000 live births, with a 4:1 male: female gender bias [7, 8].
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HD may occur as an isolated finding (70% of cases) or as part of a multisystem disorder.

Associated anomalies have been detected in between 5% and 57% of HD patients according
to literature [9-11]. The most common associated anomalies are:
 heart defects (atrial or ventricular septal defects, patent ductus arteriosus, Fallot
tetralogy, dilatation of aortic root)
 gastrointestinal (Meckel diverticulum, malrotation, and imperforate anus, sacral-rectal
fistula)
 central nervous system (Dandy-Walker malformation, corpus calossum agenesis,
microcephaly)
 genitourinary abnormalities (cryptorchidism, inguinal hernia, hypospadias, kidney
malformations, urethral fistula)
 ophthalmologic abnormalities (astigmatism, myopia, strabismus, amblyopia, papilla
abnormalities) [11-13].
HD has a complex genetic aetiology. A large number of chromosomal anomalies have been
described in HD patients (Table 1); Down syndrome is the most frequent, involving 2-10% of
cases [9, 14-21].
Table I. Chromosomal anomalies associated with HD

Chromosomal anomalies Features
Intellectual disability (ID), hypotonia, sleep apnoea,
Deletion 10q11
cleft or high palate, epilepsy, long segment HD
Deletion 10q23.1 Mostly isolated HD
ID, growth failure, craniofacial features, heart defect,
Deletion 13q
short segment HD
ID, microcephaly, craniofacial features, seizures,
Deletion 2q22
short stature
Deletion 4p12-p13 ID, short stature, craniofacial features
Deletions/duplications 17q21 ID, multiple anomalies
Tri 22pter-q11 Pre-auricular anomalies, anal atresia, iris coloboma,
craniofacial features
Monogenic syndromes frequently associated with HD are numerous: Waardenburg-Shah,

Mowat-Willson, Goldberg-Shprintzen, multiple endocrine neoplasia type 2, familial
dysautonomia, congenital central hypoventilation, Bardet-Biedl.
Waardenburg-Shah syndrome (WSS), also known as Waardenburg syndrome type 4 is
characterized by the association of sensorineural hearing loss, pigmentary abnormalities
(including white forelock, eyebrows and eyelashes, heterochromia of the irides, possibly retinal
pigment abnormalities and/or hypo-pigmented patches on the skin) and HD. WSS is a neuro-
cristopathy genetically heterogeneous, caused by mutations in EDNRB, EDN3 and SOX10 [22].
Congenital central hypoventilation syndrome (CCHS) is a rare, life-threatening condition,
characterized by apparent hypoventilation with monotonous respiratory rates and shallow
breathing due to autonomic nervous system dysregulation and, in some cases, altered
development of neural crest-derived structures (HD and/or tumours-neuroblastoma,
ganglioneuroma). CCHS is associated with pathogenic variants in PHOX2B [23].
Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma
(FMTC) are cancer predisposition syndromes with an autosomal dominant inheritance. MEN
2A is defined by predisposition to MTC, pheochromocytoma, or parathyroid
adenoma/hyperplasia. In addition to MTC and pheochromocytoma, MEN 2B present with oral
neuromas, modulated corneal nerve fibers and marfanoid habitus. FMTC and MEN 2 can be
associated with HD. Germline pathogenic variants of the RET gene have been identified in
MEN 2 and FMTC [24, 25].
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Familial dysautonomia (FD) is characterized by progressive degeneration of sensory,

sympathetic, and parasympathetic neurons. Affected individuals have gastrointestinal
dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain and temperature,
abnormal sweat, tear, saliva production and cardiovascular instability. FD is caused by
pathogenic biallelic variants in ELP1 [26].
The main features of Mowat-Wilson syndrome (MWS), also known as Hirschsprung Disease
‒ Intellectual Disability Syndrome, are: distinctive facial appearance in association with
variable moderate-to-severe ID, epilepsy, HD, growth restriction with microcephaly, and
multiple congenital anomalies, including genital anomalies (in particular hypospadias),
congenital heart disease (particularly abnormalities of the pulmonary arteries and/or valves),
and eye defects. MWS is caused by deleterious de novo heterozygous variations in the ZEB2
gene [27].
Goldberg-Shprintzen syndrome (GOSHS) is an autosomal recessive disorder of ID,
microcephaly, specific facial dysmorphism and HD. Phenotypic overlap exists between
GOSHS and MWS, but GOSHS cases may also have cleft palate and coloboma. GOSHS is
caused by mutations in the KIAA1279 (also known as K1F1BP) gene, and appears to be
inherited in an autosomal recessive pattern [28].
Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous, autosomal
recessive, ciliopathy disorder. BBS is characterized by progressive retinal dystrophy, truncal
obesity, postaxial polydactyly, renal abnormalities, hypogonadism and variable but generally
mild ID. HD has been documented in 2-10% of BBS cases. At least 19 genes are associated
with BBS [29, 30].
The Cartilage Hair Hypoplasia (CHH) combines skeletal dysplasia with joint
hypermobility, fine silky hair, immunodeficiency, anaemia, increased risk for malignancy,
gastrointestinal dysfunction, and impaired spermatogenesis. HD is observed in 7-8% of cases.
CHH is associated with biallelic pathogenic variants in RMRP gene [31].
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol
biosynthesis. The classic phenotype of SLOS include: microcephaly, congenital heart disease,
growth and developmental delays, distinctive facial features, underdeveloped external genitalia
with hypospadias in males, and characteristically, syndactyly of toes two or three. HD has been
described in a significant number of SLOS patients. SLOS is caused by pathogenic variants in
DHCR7, the gene encoding enzyme 7-dehydrocholesterol reductase [32, 33].
The classic phenotype of Fryns syndrome (FS) includes: hypoplasia of the distal digits,
coarse facial features, variable diaphragmatic hernia, and a variety of other anomalies of the
cardiac, gastrointestinal, genitourinary, and central nervous systems. Six cases with HD in
addition FS were reported, suggesting that FS represent a neuro-cristopathy [34, 35].
Non-syndromic HD has been associated with pathogenic variants in a number of genes from
four major groups: RET and its ligands GDNF and NRTN; EDNRB and the related genes EDN3
and ECE1; the NRG signalling pathway (NRG1 and NRG3); and the SEMA signalling pathway
(SEMA3C and SEMA3D). The inheritance of non-syndromic HD is complex and characterized
by variable penetrance [4, 9].
RET and its ligands GDNF and NRTN.
The RET proto-oncogene, is one of the receptor tyrosine kinases, cell-surface molecules that
transduce signals for cell growth and differentiation and plays a critical role in normal enteric
nervous system (ENS proliferation). Mutations in RET account for up to 35% of sporadic HD
and 50% of familial cases. The proteins glial-derived neurotrophic factor (GDNF) and NRTN
(or NTN; neurturin) are 2 RET ligands, and GDNF family receptor α1 (GFRα1) is a RET co-
receptor, which together play key roles in the control of ENS differentiation. Mutations in these
ligands and/or co-receptor can be found in a small minority of HD cases and can occur in
association with a RET mutation [36-38].
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EDNRB and the related genes EDN3 and ECE1.

The endothelin receptor B gene (EDNRB) codes for a G-protein receptor that binds
endothelin’s, small proteins with potent vasoactive effects. EDNRB interacts with the ligand,
endothelin-3 (EDN3), which is activated through posttranslational modification by endothelin-
converting enzyme 1 (encoded by ECE1). Mutations in EDNRB and the ligand EDN3 account
for approximately 10% of HD [4, 36].
NRG signalling pathway.
Neuregulins include a large family of EGF-like signalling proteins that have been implicated
in cell-cell communication during development. Studies indicated that NRG1 played a critical
role in the development of the enteric neurons as well as vagus nerve. Copy number variants in
NRG3 (a paralog of NRG1) have been implicated in HD pathogenesis [4, 16, 39, 40].
SEMA signalling pathway.
These proteins are involved in neuronal migration, proliferation, survival, and/or axonal
guidance. The 4 class 3 Semaphoring are expressed in gut tissues during development, and
SEMA3C and SEMA3D are both expressed in the ENS in several animal models [4, 41].
The recognition of syndromic HD is essential for disease prognosis and accurate genetic
counselling. The family history and physical examination are important for the establishment
of a clinical diagnosis, which is then used for the selection of relevant genetic tests.
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anomalies in Hirschsprung’s disease. Orphanet J Rare Dis 8, p. 184.
12. Sarioglu A, Tanyel FC, Buyukpamukcu N, Hicsonmez A. (1997). Hirschsprung-associated congenital
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Pediatr. 2014; 2: p. 99.
14. Fewtrell MS, Tam PK, Thomson AH et al., (1994). Hirschsprung’s disease associated with a deletion of
chromosome 10 (q11.2q21.2): a further link with the neuro-cristopathies? J Med Genet 31, pp. 325-7.
15. Stankiewicz P, Kulkarni S, Dharmadhikari AV, et al., (2012). Recurrent deletions and reciprocal
duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-
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41. Jiang Q, Arnold S, Heanue T et al., (2015). Functional loss of semaphoring 3C and/or semaphoring 3D
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Complete Mucosal Recovery: A 2019 Perspective on Intestinal

Health and Celiac Disease
PLEȘA Alina1,2, SFRIJAN Cristina2, GORINCIOI Cristina2, MAZILU Bogdan2,

APETREI-CORDUNEANU Otilia1, GHEORGHE Liliana1,3,
GÎRLEANU Irina1,2, TRIFAN Anca1,2, NEMȚEANU Roxana1,2
1
University of Medicine and Pharmacy “Grigore T. Popa”, Faculty of Medicine, Iasi, (ROMANIA)
2
“St. Spiridon” Hospital, Institute of Gastroenterology and Hepatology, Iasi, (ROMANIA)
3
Department of Radiology, “St. Spiridon” Hospital, Iasi, (ROMANIA)
Emails: alinaplesaro@yahoo.com, cryss_c25@yahoo.com, zuico.cristina@gmail.com, mazilu_bogdanbt@yahoo.com,
otiliaapetrei@gmail.com, moisiil@yahoo.com, gilda_25@yahoo.com, ancatrifan@yahoo.com, maxim_roxxana@yahoo.com
Abstract
The diagnosis of celiac disease (CD) is defined by the presence of symptoms, HLA-
DQ2/DQ8, specific antibodies in serum, and duodenal histology. The aim of the present study
is to assess the clinical, histological and serological response to gluten free diet (GFD) and also
whether serum TG2-IgA antibody tests are useful biomarkers of VA in patients with CD treated
with a GFD. The study included the cohort of patients age ≥18 years old, with biopsy proven
CD. A total of 102 patients were enrolled, predominately female (n=80, 78.4%), median age at
diagnosis 40 years. At baseline, TG2-IgA levels were good predictors for identifying severe
mucosal injury with a statistically significant difference when comparing patients with mild
enteropathy versus those with VA, 35.10±61.53U vs 132.82±108.85U, p=0.002. Marsh 3c was
observed in 34 (33.3%), subtotal VA (Marsh 3b) in 18 (17.6%) cases, partial VA (Marsh3a) in
27 (26.5%) cases, while the reminder had mild enteropathy (Marsh I, II) in 23 (22.5%) cases.
Negative TG2 levels and different degrees of VA were documented in 12, 11.7% cases. At
follow-up, the overall mean antibody titter was 28.14±60.19U, and serological response was
documented in 79 (76.7%) cases. Further prospective studies are needed to assess the outcome
of intestinal histological recovery during GFD among patients with CD, and also finding the
best non-invasive easy to use tools to assess adherence to the GFD and mucosal healing.
Keywords: celiac disease, mucosal healing, celiac serology
Introduction
There is increasing concern and awareness of the multifaceted symptomatology and systemic
effects of celiac disease (CD). The diagnosis of CD is variable defined by four components: the
presence of symptoms, HLA-DQ2/DQ8, specific antibodies in serum, and duodenal histology
([1], [2]).
There is general agreement concerning regular follow-up of CD patients, however the
follow-up modalities are not currently standardized. Re-biopsy may be undertaken to prove
mucosal healing, however, its invasiveness, discomfort, costs and possible complications limit
its use in routine follow-up. Therefore, reliable non-invasive surrogate markers of mucosal
healing are highly desirable, as the current ones have been disappointing. Consequently,
serological tests such as anti-tissue transglutaminase antibodies (TG2) and/or anti-endomysial
(EMA) IgA tests are commonly used to monitor patients and are often interpreted clinically as
reflecting mucosal damage on a gluten-free diet (GFD). These so-called “celiac antibody tests”
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were initially developed and validated for screening for CD among untreated persons
consuming a gluten-containing diet and they perform well in this context. ([3], [4])
In CD, similar to other chronic intestinal conditions, such as inflammatory bowel disease,
meaningful monitoring requires tools that reliably reflect mucosal health. Histologic recovery
of small intestinal mucosa is assumed to occur within 6 to 24 months after initiating the GFD
([4], [5]). A good clinical response is observed in most patients after a few weeks of GFD.
However, mucosal healing does not occur in all patients with CD in whom complete clinical
response is achieved ([5], [6]). Also, severe mucosal damage can be detected among
asymptomatic patients. Persistent VA is often present among patients with normalized
serology’s, but is more commonly present in those whose adherence to the GFD is poor ([6],
[7], [8]).
The aim of the present study is to assess the clinical, histological and serological response
to GFD and also whether serum TG2-IgA antibody tests are useful biomarkers of VA in patients
with CD treated with a GFD.
Statistical and Power Analysis

Statistical analysis was performed using SPSS 18 software (SPSS Chicago Inc., IL, USA).
Data were summarized by descriptive statistics, including percentages and counts for
categorical date and medians and ranges for continuous parameters. Pearsons chi-square test or
Fisher’s exact test (as appropriate) was used to measure and compare the proportions of
categorical variables, and the t-Test for continuous variables. A P-value <0.05 was considered
statistically significant.
Ethics
The study was approved by the ethical committee and all participants were informed about
the study according to the study protocol and gave their written informed consent.
Material and Methods
The study cohort included patients age ≥18 years old, with biopsy proven CD evaluated in
the Institute of Gastroenterology and Hepatology, a tertiary referral centre. Patients who did not
have the biopsy report, serological assessment at baseline and follow-up, prior history of
tuberculosis or malignancy were excluded from the study. Electronic or paper patient records
were collected and information about presenting symptoms, serology, laboratory parameters,
and histological assessment of biopsy samples were obtained manually and stored into one data
base. The data were assessed at the time of diagnosis (baseline) and at follow-up.
All patients had duodenal biopsies at diagnosis and at least one follow-up intestinal biopsy
to assess mucosal recovery after at least 6 months after diagnosis and initiation of GFD. For
patients with more than one follow-up biopsy, the earliest follow-up biopsy within the time
period of 6 months to five years was included. Clinical response was defined as “complete” in
the absence of diarrhoea or any evidence of the presenting symptoms and “partial” when some
clinical improvement was documented after treatment with a GFD but without return to
normality. Serological response was defined as a negative tTG2 result at follow-up
(seroconversion or simply a negative serologic test at follow-up). Histological improvement
was arbitrarily defined by an increase of villous to crypt ratio ≥2.0 points in the follow-up
biopsy with respect to the baseline. Mucosal healing was defined by a Marsh 0 at follow-up
biopsy. Intestinal neoplasia was excluded using MRI or CT scans in selected cases.
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Results
A total of 186 adults with CD admitted in the Institute of Gastroenterology and Hepatology
were considered for inclusion. Among them, 102 patients with both diagnostic and follow-up
biopsy data available were enrolled. The cohort was predominately female (n=80, 78.4%) with
a median (range) age at diagnosis 40 years (20-73). Clinical presentation was classical in the
majority of patients (n=81, 79.4%) and atypical in the remaining 21 cases. Weight loss was also
a common symptom identified in 60 (58.8%) patients. One third, 35 (34.31%) had iron
deficiency anaemia and diarrhoea as reasons for referral. Serology results at the time of CD
diagnosis was available for all included subjects, with a mean TG2-IgA value of
115.92±103.94U/ml, range 2.22-379.89U/ml, and anti-gliadine antibodies (AGA) with a mean
value of 63.65±69.84U/ml, range 1.02-292.50U/ml. At baseline, TG2-IgA levels were good
predictors for identifying severe mucosal injury (Fig. 1, 2). There was a statistically significant
difference when comparing patients with mild enteropathy versus those with different degrees
of VA 35.10±61.53U vs 132.82±108.85U, p=0.002. Among the 102 patients with a diagnostic
biopsy prior to GFD, Marsh 3c was observed in 34 (33.3%), subtotal VA (Marsh 3b) in 18
(17.6%) cases, partial VA (Marsh3a) in 27 (26.5%) cases, while the reminder had mild
enteropathy (Marsh I, II) in 23 (22.5%) cases. Negative TG2 levels and different degrees of VA
were documented in 12, 11.7% cases.
Fig. I. Correlation between antibody levels and severity of mucosal injury

Fig. II. Sensitivity and specificity of celiac antibodies at baseline
At follow-up, 73 (71.5%) patients had a complete clinical response after gluten withdrawal
(in the absence of any of the presenting symptoms), and 29 (28.5%) had some clinical
improvement but without complete return to normality. Clinical presentation at diagnosis of
CD was not associated with mucosal recovery at the time of first follow-up biopsy after GFD
(p=0.79). The overall mean antibody titer at follow-up was 28.14±60.19U, and serological
response was documented in 79 (77.4%) cases.
After implementation of GFD, 68 cases (66.6%) had one follow-up biopsy after diagnosis,
and the remaining had more than one biopsy. Histological improvement and mucosal recovery
were identified in 74 (72.5%) cases, whilst 27 (27.5%) had some degree of intestinal VA (Marsh
type 3). Total VA was confirmed in 6 (5.9%) of patients. Mucosal healing was confirmed in
only one case, Marsh 0 at a single follow-up biopsy. Patients with partial VA on the initial
diagnostic biopsy were less likely to have persistent VA on follow-up biopsy (66.6%) than
those who originally had total/subtotal VA (50.9%, p=0.003).
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Discussions
There is considerable heterogeneity across studies concerning complete mucosal recovery

ratios achieved by a GFD in CD. Intact mucosa has yet remained a desirable goal of the therapy.
The duodenal biopsy is still regarded as the reference standard for the diagnosis and
monitoring of CD patients, but there is a lack of sampling quality of duodenal biopsy
interpretation. Description of biopsy specimens including positioning, Marsh classification,
villous-crypt ratio, counting of lymphocytes (more than 25 per high power field) to define
lymphocytosis is recommended. CD3 staining for T cells, as well as anti-transglutaminase
(TG2) IgA deposits may be included ([8], [9]). Using the Marsh-Oberhuber classification,
complete mucosal healing is the equivalent of the histological Marsh 0 grade (normal mucosa),
while mucosal recovery can be attributed to histological improvement of villous architecture,
with downgrading from total VA to partial atrophy or even Marsh 1-2 ([9], [10]).
The intestinal biopsies from an upper endoscopy are an important tool in the follow-up of
CD. Histological evaluation is in essence an evaluation of mucosal healing. If damage equating
to at least Marsh 2 changes are still present, another biopsy is required, after 12 months ([7],
[8]). However, the correlation between symptoms, mucosal healing, and later outcome of CD
is not clear ([8]).
The degree of mucosal damage has been shown to correlate with the presence and titers of
both anti-TG2 and EMA (anti-endomysial). Studies have shown that EMA-seropositivity
correlates well with more severe VA, but not with the presence of gastrointestinal symptoms or
the clinical mode of disease presentation ([7], [8]). Other studies have shown that anti-TG2
levels of 100 units or grater occur almost exclusively in adults and children manifesting some
degrees of VA ([11]). In one study in adults, Pekki et al., assessed the factors predicting
incomplete mucosal recovery: malabsorption (55% vs 41%, P¼ .003), high EMA (46% vs 25%,
P<.001), and severe mucosal damage (total atrophy 32% vs 19%, P<.001) at diagnosis ([12]).
In our study, we reported a good correlation between antibody levels at diagnosis and
severity of mucosal damage at baseline in the diagnosis of CD, with good sensitivity and
specificity in detecting VA among patients with CD.
The role of serology as a useful tool in follow-up of CD patients is still a matter of debate.
Vecsei et al., in a recent paper reported the usefulness of serology, specifically for EMA in
the paediatric population with a median time for mucosal healing of 2.2 years ([13]). In a recent
meta-analysis, Silvester et al., observed that the positive predictive value and sensitivity of
persistently positive TG2-IgA determination was fairly low with a sensitivity at 0.38 for adults.
The negative predictive value of serology in adult patients on a GFD for 1 year or more was
higher, with a specificity of 0.80 for adults, and 0.87 for children, concluding that the usefulness
of serology at follow-up is limited for adults ([14]). A refinement of the TG2 IgA determination
utilizing the detectable levels below the upper normal limit may add in the identification of
patients with CD with mucosal healing ([15]).
In this study, we have addressed an important question using simultaneous clinical,
histological and serological assessment. Our paper has shown that the antibody levels do not
correlate with the severity of mucosal damage at follow-up. Antibody levels decrease
substantially after the first weeks of GFD, while intestinal healing occurs in months/years
irrespective of antibody levels. However, these antibodies often decrease and/or disappear
regardless of histological healing and GFD adherence, whereas the initial symptoms may
improve right after the beginning of the GFD, even if the histological resolution is slower.
Therefore, antibody negativity and the disappearance of initial symptoms are not always
reliable markers for assessing adherence and the histological response to diet. In adult patients
on GFD, no agreement currently exists as to the necessity of gastroscopic/histological control
during follow‐up or regarding the appropriate timing ([16]).
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Conclusion
Currently, the existing bodies of evidence contrast one another due to the retrospective
nature of most relevant studies concerning the need and timing of follow-up biopsy, and the
long-term outcome of obtaining mucosal healing. Further prospective studies are needed to
assess the outcome of intestinal histological recovery during GFD among patients with CD, and
also finding the best non-invasive easy to use tools to assess adherence to the GFD and mucosal
healing.
REFERENCES
1. Rubio-Tapia A, Hill ID, Kelly CP, et al., (2013). ACG clinical guidelines: diagnosis and management of
celiac disease. Am J Gastroenterol;108, pp. 656-676.
2. Hill ID, Dirks MH, Liptak GS, et al., (2005). Guideline for the diagnosis and treatment of celiac disease
in children: recommendations of the North American Society for Paediatric Gastroenterology,
Hepatology and Nutrition. J Pediatr. Gastroenterol. Nutr.; 40, pp. 1-19.
3. Husby S, Koletzko S, Korponay-Szabo IR, et al., (2012). European Society for Paediatric
Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr.
Gastroenterol. Nutr. 2012; 54, pp. 136-160.
4. Rubio-Tapia A, Rahim MW, See JA, et al., (2010). Mucosal recovery and mortality in adults with celiac
disease after treatment with a gluten-free diet. Am J Gastroenterol; 105, pp. 1412-1420.
5. Werkstetter KJ, Korponay-Szabo IR, Popp A, et al., (2017) Accuracy in diagnosis of celiac disease
without biopsies in clinical practice. Gastroenterology; 153, pp. 924-935.
6. Vermeersch P, Geboes K, Marien G, et al., (2013). Defining thresholds of antibody levels improves
diagnosis of celiac disease. Clin. Gastroenterol. Hepatol; 11, pp. 398-403.
7. Nachman F, del Campo MP, Gonzalez A, et al., (2010). Long-term deterioration of quality of life in adult
patients with celiac disease is associated with treatment noncompliance. Dig Liver Dis 42, pp. 685-691.
8. Taavela Taavela J, Kurppa K, Collin P, et al., (2013). Degree of damage to the small bowel and serum
antibody titers correlate with clinical presentation of patients with celiac disease. Clin. Gastroenterol
Hepatol. 1, pp. 166-171.
9. Oberhuber G, Granditsch G, Vogelsang H (1999).The histopathology of coeliac disease: time for a
standardized report scheme for pathologists. Eur. J Gastroenterol. Hepatol 11(10), pp. 1185-1194.
10. Rostami K, Marsh MN, Johnson MW, et al., (2017). ROC-king onwards: intraepithelial lymphocyte
counts, distribution& role in coeliac disease mucosal interpretation. Gut; 66, pp. 2080-2086.
11. Al-Toma, A., Volta, U., Auricchio, R., Castillejo, G., et al., (2019). European Society for the Study of
Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United
European Gastroenterol J, 7(5), pp. 583-613.
12. Pekki H, Kurppa K, Maki M, et al., (2017). Performing routine follow-up biopsy 1 year after diagnosis
does not affect long-term outcomes in coeliac disease. Aliment Pharmacol. Ther.; 45, pp. 1459-1468.
13. Vecsei E, Steinwendner S, Kogler H, et al., (2014). Follow-up of paediatric celiac disease: value of
antibodies in predicting mucosal healing, a prospective cohort study. BMC Gastroenterol.; 14, pp. 28-33.
14. Silvester JA, Kurada S, Szwajcer A, et al., (2017). Tests for serum transglutaminase and endomysial
antibodies do not detect most patients with celiac disease and persistent villous atrophy on gluten-free
diets: a meta-analysis. Gastroenterology;153, pp. 689-701.
15. Fang H, King KS, Larson JJ, et al., (2017). Undetectable negative tissue transglutaminase IgA antibodies
predict mucosal healing in treated coeliac disease patients. Aliment Pharmacol. Ther 46, pp. 681-687.
16. Hill PG, Holmes GK (2008). Coeliac disease: a biopsy is not always necessary for diagnosis. Aliment
Pharmacol. Ther. 27, pp. 572-577.
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Rational-Emotive Behavioural Psychotherapy in Psychosomatic

Diseases
POJOGA Cristina1,2, FADGYAS STANCULETE Mihaela3

1
Babes-Bolyai University, Department of Clinical Psychology and Psychotherapy, International Institute for Advanced Study
of Psychotherapy and Applied Mental Health (ROMANIA)
2
Regional Institute of Gastroenterology and Hepatology O Fodor, Cluj-Napoca (ROMANIA)
3
Department of Neurosciences, University of Medicine and Pharmacy Iuliu Hațieganu, Cluj Napoca, (ROMANIA)
Email: cristinapojoga@yahoo.com
Abstract
Introduction
Digestive psychosomatic pathology is represented by diseases whose symptoms are
triggered/exacerbated/maintained by psychological factors.
There is a bidirectional correlation between the central nervous system and the digestive
system, each of them having an important influence on the other, these correlation representing
the brain-gut axis. The nervous system influences the digestive functions through motility,
enzyme secretion, microbial balance, and the digestive system influences (mainly through
microbiota) the neurotransmitters, stress/anxiety level, mood and behaviour.
There are many mechanisms involved in the onset of functional gastrointestinal diseases:
systemic and mucosal inflammation, chronic infections, altered intestinal permeability,
imbalance of serotonin metabolism, genetic factors.
Material and Method

We performed an analysis of the literature on the relationship between psychosomatic
diseases and the presence of psychiatric comorbidities, and the efficacy of psychotherapy in
this kind of pathology. The articles were identified by keyword search in electronic databases
(Pubmed, Medline, and PsychINFO).
Results
There are studies that show that in healthy population there is an association between the
presence of irrational beliefs and serological inflammatory markers (Papageorgiou C, 2006). In
functional diseases (irritable bowel syndrome) there is a correlation between production of
cytokines and level of depression and anxiety (YanboZhen, 2015).
A meta-analysis published in 2016 shows the efficacy of psychotherapy on short and long-
terms in patients with irritable bowel syndrome (Laird, 2016).
Conclusions
Psychotherapy is indicated in patients who are open to the idea that psychological factors
play a role in the onset and maintenance of the symptoms and is useful in reducing anxiety and
depression, implementing lifestyle changes, increasing patient compliance, reducing symptoms
intensity.
Keywords: psychosomatic diseases, psychotherapy, functional disorder
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Introduction
Psychosomatic disorders are conditions caused/exacerbated/perpetuated (fully/partially) by

psychological factors. The medical specialists tend to use for these illnesses the term “functional
diseases.” They refer to the presence of physical symptoms in the absence of structural or
biochemical abnormalities. This concept is now considered to be outdated because if
appropriate tests are applied, structural or biochemical abnormalities that explain or cause the
symptoms may be found in many patients.
In the case of functional gastrointestinal functional diseases, there are multiple mechanisms
involved in brain-gut dysfunction (1): systemic and mucosal inflammation, chronic infections,
altered intestinal permeability, abnormalities in the serotonin metabolism, and genetic factors.
The brain influences the functions of the gut, influencing the motility, secretion, nutrient
delivery, and microbial balance. The gut influences the brain, having an effect on
neurotransmitters, stress/anxiety, mood, and behaviour. Microbiota also plays a central role in
this inter-correlation (2). It is now demonstrated that there are significant changes in the gut
microbiota (GM) of humans with depression and animal models of depression and chronic
stress (3).
Material and Method
We performed an analysis of the literature on the relationship between psychosomatic

diseases and the presence of psychiatric comorbidities, and the efficacy of psychotherapy in
this kind of pathology. The articles were identified by keyword search in electronic databases
(Pubmed, Medline, and PsychINFO).
Results
There are studies that show that there is an association between plasma inflammatory
markers and irrational beliefs. Papageorgiou, in 2006 (4), took into study 853 healthy subjects:
453 men and 400 women and measured their serum levels of CRP, IL 6, amyloid A, TNF alpha
and also administered to the subject the validated food frequency questionnaire and the
irrational beliefs inventory (IBI). He found positive correlations between the scores at the IBI
and: CRP (rho=0.14, p=0. 02), IL6 (rho=0.11, p=0.02), TNF⍺ (rho=0.21, p=0.014), White
blood cells count (rho=0.14, p=0.02). In conclusion, we can say that irrational beliefs are
associated with increased inflammation process, among apparently healthy individuals.
There are also reports about the production of cytokine in peripheral blood in patients with
functional gastrointestinal disorders. Yanbo Zhen administered to patients with irritable bowel
syndrome with diarrhoea the self-rating anxiety scale (SAS) and self-rating depression scale
(SDS) and measured their level of TNF-α (pg/ml), IL-8 (pg/ml) and IL-10 (pg/ml) and the
results showed there is an association of cytokine production in peripheral blood mononuclear
cells in pts with IBS-D with anxiety and depression scores (5).
The imbalance of tumour necrosis factor-α, interleukin-8, and interleukin-10 production
evokes barrier dysfunction, severe abdominal symptoms and psychological disorders in patients
with irritable bowel syndrome-associated diarrhoea.
There is an activation of the immune system in patients with IBS, reflected by increased
levels of cytokines in the colonic mucosa, as well as an increase in the release of pro-
inflammatory cytokines. High levels of these cytokines are associated with anxiety and
depression, linking the gut with altered brain function (6).
The conceptual model in functional gastrointestinal disorders is based on multiple factors
that are intercorrelated and, by their intercorrelation, result in the symptoms of the disease and
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also the illness behaviour (1). These factors are predisposition (genetics, environment, early life
events), psychological factors (stress, irrational beliefs, coping styles, social support, comorbid
psychiatric disorders), and physiologic factors (motility, visceral sensations, inflammation).
The intercorrelation of these factors is mediated via central nervous system and enteric
nervous system. We cannot influence predispositions, but we are able to influence physiologic
factors through medication and psychological factors through psychotherapeutic interventions
(including rational emotive behavioural therapy).
Traditionally, the burden of disease is assessed by measurement of laboratory indices and
impact on life expectancy, but these traditional markers often do not parallel a patient’s feelings
or perceptions about the disease. But nowadays, physicians realized it is important to measure
how patients perceive their illness and to quantify its impact on their lives. Psychosomatic
disorders are conditions with no impact on life expectancy, but with high impact on the quality
of life.
Considering that the cause of functional gastrointestinal disorders is not clearly identified,
the possibility of an effective cure is also limited. There are no universally accepted
management guidelines, but it is largely established that we need an interdisciplinary approach
to treat these functional conditions effectively (7).
The treatment strategy in this kind of pathology is to reassure the patient that it is not a severe
disease, to explain the mechanisms behind the symptoms, to implement lifestyle modifications,
and to make use of pharmacotherapy and psychotherapy.
Because our aim is also to educate the patient about functional gastrointestinal disorders, we
need to explain the disorder in a way that meets the patient’s needs and in a way that fits with
our treatment plan depending on the main pathophysiologic mechanism that is behind the
symptoms.
When deciding on therapy, we need to assess which are the predominant symptoms, which
are the stressors that can be addressed, whether the patients have a specific bias towards or
against any type of treatment, what are his/her irrational beliefs, and the emotional, behavioural
consequences. We also need to seek the existence of any psychiatric comorbidities.
The problem with pharmacotherapy in functional gastrointestinal disorders is that, although
there are a lot of drugs of various classes of action, they have only limited efficacy, and a lot of
drugs are in the experimental phase or not well documented in clinical trials.
Psychotherapeutic interventions are indicated in patients open to the idea that psychological
factors play a role in the development and maintenance of symptomatology. They reduce
anxiety/depression level, help to implement lifestyle changes, enhance patient’s compliance,
and alleviate the intensity of symptoms. Concomitant treatment of diagnosed depression or
anxiety disorders in such patients through psychotherapy and pharmacological treatment often
helps to alleviate specific IBS symptoms (8).
Among the etiopathogenic mechanisms in psychosomatic disorders, the interpretation of the
symptoms by the patient has a crucial role in generating the illness behaviour, so this is the
target that psychotherapeutic interventions need to aim. In addition, gastrointestinal symptoms
can be the consequence of inadequate coping strategies and a cause of individually perceived
stress at the same time, forming a vicious circle of symptoms (9).
A meta-analysis published in 2016 analysed 41 trials related to the use of psychological
therapies in irritable bowel syndrome. In total, there were 2290 individuals (1183 assigned to
psychotherapy and 1107 assigned to a control condition). Therapeutic modalities were
cognitive and cognitive-behavioural therapies (20 trials), relaxation (6 trials) hypnosis (5 trials).
The subjects were evaluated as follows: immediate/short-term follow-up (1-6 months after
treatment) /long-term follow-up (6-12 months after treatment). In conclusion, psychological
therapies had a medium effect on gastrointestinal symptom severity (d=0.69) immediately after
treatment. Individuals who received psychotherapy had a greater reduction in gastrointestinal
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symptoms after treatment than 75% of individuals assigned to a control condition. After short-
term follow-up periods and long-term follow-up periods, this effect remained significant and
medium in magnitude (d=0.76 and d=0.73, respectively) (10).
Conclusions
Even if functional disorders are conditions without any impact on the life expectancy of the
patients, they are an essential burden of health-related quality of life, and their treatment
represents a real challenge for the medical team. Psychotherapy is an important tool in
managing the symptoms of this kind of pathology. Some studies show an important
improvement of symptomatology and quality of life when psychological therapeutic options
are used (cognitive behavioural therapy, rational emotive behavioural therapy, hypnotherapy,
relaxation techniques).
REFERENCES
1. Drossmann DA. (2016). Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical

Features and Rome IV. Gastroenterology. Feb 19. pii: S0016-5085(16) pp. 00223-7. doi:
10.1053/j.gastro.2016.02.032. [Epub ahead of print]
2. De Palma G, Collins SM, Bercik P. (2014). The microbiota-gut-brain axis in functional gastrointestinal
disorders. Gut Microbes. May-Jun;5(3):419-29. doi: 10.4161/gmic.29417. Epub 2014 Jun 12.
3. Li N. Wang Q, Wang Y, Sun A, Lin Y, Jin Y, Li X. (2019). Faecal microbiota transplantation from
chronic unpredictable mild stress mice donors affects anxiety-like and depression-like behaviour in
recipient mice via the gut microbiota-inflammation-brain axis. Stress. Sep; 22(5): pp. 592-602. doi:
10.1080/10253890.2019.1617267. Epub 2019 May 24.
4. Papageorgiou C, Panagiotakos DB, Pitsavos C, Tsetsekou E, Kontoangelos K, Stefanadis C, Soldatos C.
(2006). Association between plasma inflammatory markers and irrational beliefs; the ATTICA
epidemiological study. Prog. Neuropsychopharmacol Biol. Psychiatry. Dec 30; 30(8): pp. 1496-503.
Epub 2006 Jul 17.
5. Zhen Y, Chu C, Zhou S,Qi M, Shu R. (2015). Imbalance of tumour necrosis factor-α, interleukin-8 and
interleukin-10 production evokes barrier dysfunction, severe abdominal symptoms and psychological
disorders in patients with irritable bowel syndrome-associated diarrhoea. Mol Med Rep. Oct; 12(4): pp.
5239-45. doi: 10.3892/mmr.2015.4079. Epub 2015 Jul 15.
6. Lee STH. (2020). Inflammation, depression, and anxiety disorder: A population-based study examining
the association between Interleukin-6 and the experiencing of depressive and anxiety symptoms.
Psychiatry Res. Jan 25; 285: p. 112809. doi: 10.1016/j.psychres.2020.112809. [Epub ahead of print]
7. Nelkowska DD. (2020). Treating irritable bowel syndrome through an interdisciplinary approach. Ann
Gastroenterol. Jan-Feb; 33(1): pp. 1-8.
8. Ford AC, Talley NJ, Schoenfeld PS. (2009). Efficacy of antidepressants and psychological therapies in
irritable bowel syndrome: systematic review and meta-analysis. Gut; 58: pp. 367-78.
9. Mukhtar K, Nawaz H, Abid S. (2019). Functional gastrointestinal disorders and gut-brain axis: What does
the future hold? World J Gastroenterol. Feb 7; 25(5): pp. 552-566. doi: 10.3748/wjg. v25.i5.552.
10. Laird KT, Tanner-Smith EE, Russell AC, Hollon SD, Walker LS. (2016). Short-term and Long-term
Efficacy of Psychological Therapies for Irritable Bowel Syndrome: A Systematic Review and Meta-
analysis. Clin. Gastroenterol Hepatol. Jul; 14(7): pp. 937-947. e4. doi: 10.1016/j.cgh.2015.11.020. Epub
2015 Dec 22. Review.
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Rumination Syndrome: A Treatment Update
POPA Stefan-Lucian1, CHIARIONI Giuseppe2, DAVID Liliana1

1
2nd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, (ROMANIA)
2
Division of Gastroenterology of the University of Verona, AOUI Verona, Italy and Division of Gastroenterology and
Hepatology & Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill,
NC, (USA)
Emails: popa.stefan@umfcluj.ro, chiarioni@alice.it, lilidavid2007@yahoo.com
Abstract
Rumination syndrome is a rare a functional gastrointestinal disorder, defined as repetitive

regurgitation of the food that was recently ingested, which will lead to re-swallowing or spitting
it out and it is not preceded by nausea. This behaviour can be observed during the meal or right
afterwards. Usually it is misdiagnosed with gastroesophageal reflux disease or bulimia, because
the patients complain of reflux or emesis. Easy to use and frequently applied by clinicians are
the Rome IV clinical criteria for the diagnosis of rumination syndrome. The treatment consists
in biofeedback, relaxation techniques, patient education and diaphragmatic breathing and after
a long period of time will restore the gastroesophageal pressure and stop the regurgitation.
Caution is recommended when choosing surgery or medications to treat rumination
syndrome, because limited research is available consisting primarily of uncontrolled case
reports. An extensive study of underlying pathogenesis is the main step for developing an
efficient treatment. Diaphragmatic breathing is the most efficient type of treatment.
Keywords: Rumination Syndrome, Functional Gastrointestinal Disorders, FGID, Disorders of gut‐brain interaction, DGBI
Introduction
Rumination syndrome is a rare a functional gastrointestinal disorder, defined as repetitive

regurgitation of the food that was recently ingested, which will lead to re-swallowing or spitting
it out [1]. Usually it is not preceded by nausea which represents the main difference from
vomiting, and it can be distinguished from reflux because it is not acidic and contains the food
that just got ingested.
This behaviour can be observed during the meal or right afterwards. It was more often
described in children with mental retardation, but nowadays it can be present at adolescents and
adults with normal IQ [2]. Usually it is misdiagnosed with gastroesophageal reflux disease or
bulimia, because the patients complain of reflux or emesis. There are several symptoms that
may be present in the rumination syndrome such as: nausea, pyrosis, dyspepsia and weight loss.
Up to 30% of the patients with rumination syndrome have a psychiatric disorder.
Diagnosis
The diagnosis of this pathology is clinical, however, manometry is the most frequently used
para-clinical exploration [1-3]. Easy to use and frequently applied by clinicians are the Rome
IV clinical criteria for the diagnosis of rumination syndrome (Table 1).
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Rome IV criteria for Rumination Syndrome

Persistent or recurrent regurgitation of recently ingested food into the mouth with subsequent spitting or re-mastication and
swallowing
Regurgitation is not preceded by retching
 Supportive criteria
 Effortless regurgitation events usually are not preceded by nausea
 Regurgitate contains recognizable food that might have a pleasant taste
 The process tends to cease when the regurgitated material becomes acidic
Criteria fulfilled for the past 3 months with symptom onset at least 6 months before diagnosis
Table 1. Rome IV criteria for diagnosis of Rumination Syndrome
In DSM-5 the following criteria used for the diagnosis: (1) repeated regurgitation of food
over a period of at least 1 month, regurgitated food may be re-chewed, re-swallowed or spit
out; (2) the repeated regurgitation is not attributable to an associated gastrointestinal or other
medical pathology; (3) the eating disturbance does not occur exclusively during the course of
anorexia nervosa, bulimia nervosa, binge-eating disorder or avoidant/restrictive food intake
disorder; (4) if the behaviour occurs within the context of another mental disorder (generalized
anxiety disorder, depressive disorder) or neurodevelopmental disorder (cognitive impairment,
intellectual disability), it must be sufficiently severe to warrant independent clinical attention
[3].
Differential diagnoses include a wide variety of diseases: anorexia nervosa, esophagitis,
gastroesophageal reflux disease, hypercalcemia, Addison disease, bulimia, paediatric
hypertrophic pyloric stenosis, peptic ulcer disease, Sandifer syndrome, small-bowel obstruction
imaging and type 1 diabetes mellitus, oesophageal disorders (oesophageal, achalasia, hiatal
hernia), gastric disorders (gastroparesis, gastric carcinoma, peptic ulcer disease), small bowel
disorders (pseudo-obstruction), pregnancy, tumours, organic lesions, basal meningitis, drugs
that effect swallowing and oesophageal functioning (digitalis, chemotherapeutic agents,
benzodiazepines, neuroleptics), functional disorders (functional dyspepsia, psychogenic
vomiting, oral-motor dysfunction, anatomic defects, H-type tracheoesophageal fistula) and
food allergies [1-5].
The most frequent complications include: halitosis, malnutrition, weight loss, growth failure,
choking, aspiration pneumonia, electrolyte imbalance, dehydration and dental pathology,
particularly dental caries [1-6].
A study performed by Halland et al., analysed 20 patients with rumination syndrome, 20
patients who had gastroesophageal reflux disease (GERD) and 40 healthy controls.
Baseline impedance measured during high-resolution impedance manometry (HRIM) was
chosen because it can distinguish patients with upper gastrointestinal disorder from controls,
due to differences in oesophageal acid exposure. Furthermore, baseline impedance was
measured over 15 seconds during the landmark period of HRIM in all 18 impedance sensors
[7]. The result was that baseline impedance measured during HRIM in patients with rumination
syndrome is significantly lower than controls and similar in patients with GERD suggesting
that the postprandial regurgitation in rumination syndrome alters both the distal and proximal
oesophageal mucosal barrier [7].
Treatment
The treatment consists in biofeedback, relaxation techniques, patient education and

diaphragmatic breathing and after a long period of time will restore the gastroesophageal
pressure and stop the regurgitation [8-12]. Caution is recommended when choosing surgery or
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medications to treat rumination syndrome, because limited research is available consisting

primarily of uncontrolled case reports.
A difficult part of the management of rumination syndrome is a complete explanation of the
disorder and the pathogenetic roots responsible for the clinical symptomatology.
The first element that should be introduced and explained to the patients is the way the
abdominal wall muscles activate the intra-abdominal content by contractions of the muscles of
the anterior wall, the diaphragm, and the accessory thoracic musculature.
The pathogenetic stages include 3 main components: thoracic suction, abdominal thrust and
hiatal opening, with the result of regurgitation and afterwards the rumination. In relation with
the pathogenetic elements, diaphragmatic breathing can be applied easily by putting a hand on
the chest and on the abdomen during respiration, and only allowing the hand on the abdomen
to move out with inspiration, while the chest remains in position [9].
Patients are instructed to take profound breaths by protruding the abdomen while keeping
the chest as stationary as possible [9-14]. The present guidelines recommend 6 to 8 respirations
per minute with a slow and complete inhalation or exhalation.
Diaphragmatic breathing is recommended for 15 minutes after each meal, or longer if the
sensation of rumination remains [8-12]. Some authors recommend patients to use the technique
also in the absence of meals.
Pharmaceutical agents aim to influence the gastric accommodation, emptying, or lower
oesophageal sphincter function in order to obtain clinical remission in rumination syndrome [9-
13]. The antipsychotic levosulpiride, a selective dopamine D 2-receptor antagonist with
prokinetic activity, was examined in a study on 21 adults with rumination syndrome over an 8-
month period in combination with supportive psychotherapy and 38% of the treated patients
reported an improvement in symptoms, 48% reported no change and 14% reported the
worsening of symptoms [9].
One of the most frequently used pharmacological agents is baclofen, at a dose of 10 mg 3
times daily. Baclofen was initially approved by the FDA in 1992 and is a gamma-aminobutyric
acid (GABA) agonist used as a skeletal muscle relaxant [14]. It was initially used for the relief
of painful and uncomfortable muscle spasms caused by spinal cord injury and multiple
sclerosis. Rome Foundation working team recently made recommendations for tricyclic
antidepressants to treat disorders of gut‐brain interaction, that were entitled functional
gastrointestinal disorders in the past, but no evidence shows the reduction of regurgitations in
this approach [4].
Available non-aversive behavioural strategies include the following: diaphragmatic
breathing, hypnotherapy for functional gastrointestinal disorders (FGID), self-hypnosis with
relaxation, small bites of normal amounts of food over an extended eating time, if self-
stimulation is identified, reinforcement of incompatible behaviours, reinforcement of other
behaviours, special feeding techniques, contingent exercise, defined as physical activity
required upon ruminating, habit reversal with relaxation, biofeedback with abdominal
relaxation, complete chewing, weight reduction, anxiety and psychological stress management,
throat clearing, sipping water between bites, interdiction for caffeine and alcohol [8-14].
In severe cases, in which the pharmacological treatment is inefficient, surgical procedures
have been described. The most frequently used surgical technique is gastroesophageal
fundoplication. It is considered an anti-reflux surgical intervention in cases with a clear
physiological aetiology and when the rumination has not responded to less invasive
interventions [4-7]. Little is known about the short-term and long-term evolution of individuals
with rumination syndrome. It has been described that rumination may persist for months to
years and the disorder remits without treatment in infants more often than in adults.
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Other therapeutically options were suggested by various case reports and chart reviews
including alternative behavioural strategies, general relaxation, aversion training and distraction
(e.g., gum chewing) but no current evidence showed results superior to placebo [9, 10].
Other medications have been tried to reduce regurgitations and all the other bothering
symptoms including H2 blockers, PPIs, prokinetics, and antiemetic’s. However, no effect on
regurgitations frequency and amplitude was found and patients experienced no change
regarding the quality of life [14-18].
Conclusion
Rumination syndrome is complex yet understudied disorder and often the patients are
misdiagnosed. An extensive study of underlying pathogenesis is the main step for developing
an efficient treatment. Diaphragmatic breathing is the most efficient type of treatment. Further
studies on the long term effects of available pharmacological agents are needed.
REFERENCES
1. Talley N. Rumination syndrome. Gastroenterology & hepatology. 2011; Nov. 7(2), pp. 117-8.
2. Cooper, C. J., Otoukesh, S., Mojtahedzadeh, M., Galvis, J. M., & McCallum, R. W. (2014). Subtotal
Gastrectomy as “Last Resort” Consideration in the Management of Refractory Rumination Syndrome.
Gastroenterology research, 7(3-4), pp. 98-101.
3. American Psychiatric Association. Rumination. Diagnostic and Statistical Manual of Mental Disorders
(5th Ed.). 2013. Pp. 332-333.
4. Drossman D, Chang L, Chey WD, et al., (eds). ROME IV: Functional Gastrointestinal Disorders ‒
Disorders of Gut-Brain Interaction, 4 ed. Rome Foundation: Raleigh, NC, 2016.
5. Kessing BF, Govaert F, Masclee AA, Conchillo JM. Impedance measurements and high-resolution
manometry help to better define rumination episodes. Scand. J Gastroenterol. 2011 Nov. 46(11): pp.
1310-5.
6. Ellis CR, Parr TS, Singh NN. Rumination Prevention and Treatment of Severe Behaviour Problems:
Models and Methods. Dev. 1997. Pp 237-52.
7. Halland M, Ravi K, Nelson HA, Katzka DA, Talley NJ, Crowell MD. Baseline Impedance Measured
During High-resolution Oesophageal Impedance Manometry in Patients with Rumination Syndrome is
as Abnormal as in Patients with GERD. J Clin. Gastroenterol. 2018 Dec 19.
8. Halland M, Pandolfino J, Barba E. Diagnosis and Treatment of Rumination Syndrome. Clin Gastroenterol
Hepatol. 2018; 16(10): pp. 1549-1555.
9. Murray HB, Juarascio AS, Di Lorenzo C, Drossman DA, Thomas JJ. Diagnosis and Treatment of
Rumination Syndrome: A Critical Review. Am J Gastroenterol. 2019 Apr; 114(4): pp. 562-578.
10. Kessing BF, Smout AJ, Bredenoord AJ. Current diagnosis and management of the rumination syndrome.
J Clin Gastroenterol. 2014; 48(6): pp. 478-483.
11. Absah I, Rishi A, Talley NJ, Katzka D, Halland M. Rumination syndrome: pathophysiology, diagnosis,
and treatment. Neurogastroenterol Motil. 2017; 29(4): 10.1111/nmo.12954.
12. Chial HJ, Camilleri M, Williams DE, et al., Rumination syndrome in children and adolescents: Diagnosis,
treatment, and prognosis. Paediatrics 2003; 111: pp. 158-62.
13. Barba E, Accarino A, Soldevilla A, et al., Randomized, placebo-controlled trial of biofeedback for the
treatment of rumination. Am J Gastroenterol 2016; 111: pp. 1007-13.
14. Ertzgaard P, Campo C, Calabrese A. Efficacy and safety of oral baclofen in the management of spasticity:
A rationale for intrathecal baclofen. J Rehabil. Med. 2017; 49(3): pp. 193-203.
15. Kanodia AK, Kim I, Sturmberg JP. A personalized systems medicine approach to refractory rumination.
J Eval. Clin. Pract. 2011; 17: pp. 515-9.
16. Lang R, Mulloy A, Giesbers S, et al., Behavioural interventions for rumination and operant vomiting in
individuals with intellectual disabilities: A systematic review. Res Dev Disabil. 2011; 32: pp. 2193-205.
17. Hyuk, L., Poong-Lyul, R., Eun-Ha, P. Clinical outcome of rumination syndrome in adults without
psychiatric illness: a prospective study. J Gastroenterol. Hepatol. 2007; 22: pp. 1741-1747.
18. Hussain ZH, Henderson EE, Maradey-Romerao C, George N, Fass R, Lacy BE. The Proton Pump
Inhibitor Non-Responder: A Clinical Conundrum [published correction appears in Clin. Transl.
Gastroenterol. 2015 Oct 08;6: e115. Clin. Transl. Gastroenterol. 2015; 6(8): e106. Published 2015 Aug
13. doi:10.1038/ctg.2015.32.
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Oesophageal Motility Disorders in Children ‒ A 5 Years’

Experience
POP Daniela1, POP Radu Samuel2, PÎRVAN Alexandru1,3, FARCĂU Dorin1,2

1
“Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, (ROMANIA)
2
3rd Paediatric Clinic, Emergency Hospital for Children, Cluj-Napoca, (ROMANIA)
3 nd
2 Paediatric Clinic, Emergency Hospital for Children, Cluj-Napoca, (ROMANIA)
Emails: daniellapop@yahoo.com, radusamuelpop@gmail.com, alexandru.pirvan@umfcluj.ro, dorinfarcau@yahoo.com
Abstract
Oesophageal manometry has been used for the characterization of oesophageal motility
disorders. The objective of this study was to retrospectively evaluate the oesophageal
manometry tracings recorded in children with suspicion of oesophageal motility disorders.
Material and Method

We retrospectively analysed the oesophageal manometry tracings of 17 children investigated
in our department over 5 years, mean age ± standard deviation (SD)=8±5.4 years.
Results
The main indication for performing this investigation in our patients was dysphagia (13/17
children). Four children were diagnosed with achalasia (3 boys). The mean value of the basal
pressure of the lower oesophageal sphincter (LES)±SD was in them 38±18 mmHg. The mean
value ± SD of the values of the amplitude of the oesophageal peristaltic waves was 34.5±20
mmHg and of the pressure of the upper oesophageal sphincter (UES) was 93.3±20 mmHg in
our patients with achalasia. Oesophageal manometry was used for the evaluation of two patients
with scleroderma. The recorded parameters were normal in their cases.
Conclusions
Achalasia is the most frequent motility disorder diagnosed with oesophageal manometry in
our hospital.
Keywords: oesophageal manometry, achalasia, children
Introduction
The aboral movement of the gastrointestinal content is the result of the complex interaction
between the gastrointestinal muscle layer, enteral, peripheric, and central nervous system. Each
part of the digestive tract has a characteristic pattern of the motor function, which allows
fulfilling its specific roles. The evaluation of the gastrointestinal motility is accomplished with
manometry studies, meant to identify and describe changes of the intraluminal pressure [1].
Some of the indications for performing oesophageal manometry are the diagnosis of primary
and secondary oesophageal motility disorders, the evaluation of the oesophageal motor function
in children with dysphagia, odynophagia and non-cardiac thoracic pain [2].
Achalasia is an oesophageal motility disorder with the following manometric features:
incomplete relaxation of the lower oesophageal sphincter (LES), absence of peristalsis in the
esophageal body, high pressure of the LES and high intraluminal oesophageal pressure,
compared with the intra-gastric pressure [1].
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The objective of this study was to evaluate the oesophageal manometry tracings performed
in children with suspicion of oesophageal motility disorders.
Material and Method
Between October 2012 and January 2018 in the 3rd Paediatric Clinic in Cluj-Napoca, 17
children, (age range 7 months-17 years, mean age ± standard deviation (SD)=8±5.4 years) were
evaluated using oesophageal manometry. This was a descriptive study, in which we
retrospectively analysed the oesophageal manometry tracings of these patients. The indication
for performing the investigation was: dysphagia in 13 patients, thoracic pain and failure to
thrive in one patient respectively and food refusal in 2 children.
The patients were investigated using conventional oesophageal manometry. The equipment
that we used is made of a water perfusion pump that pumps water through the 4 channels of a
catheter. The manometry tracings are shown on the computer screen in real-time. The procedure
was performed without sedating the patients. The four channels of the catheter open with holes
placed at 3-5 cm apart. The catheter for oesophageal manometry is introduced through the nose
in the stomach, and after that, it is pulled until the holes of the channels reach the high-pressure
zone corresponding to the LES, then the oesophageal body and the upper oesophageal sphincter
(UES). The oesophageal parameters that we measured were: the basal pressure of the LES, the
relaxation after wet and dry swallows, the amplitude, speed and duration of the peristaltic waves
of the oesophageal body and the pressure of the UES. In each patient, we evaluated the
relaxation of the LES after 15-20 wet swallows.
Regarding the statistical analysis, the values were expressed as mean ± SD.
Results
There were analysed 14 tracings of oesophageal manometry. In 3 patients, the results were
not interpretable because the patients did not cooperate, and the tracings had a lot of artefacts.
Four patients (3 boys, mean age ± SD=11±4 years) were diagnosed with achalasia. The
youngest patient diagnosed with achalasia was 4 years 6 months old. In two of these patients,
we found incomplete relaxation of the LES after wet swallows. In one of the patients, the
pressure of the LES and the relaxation after wet or dry swallows were not evaluated because of
the lack of compliance. The patient was re-evaluated using oesophageal manometry after the
treatment of the achalasia, and we found incomplete relaxations of the LES. In one of the
patients, (a 12 years old boy), we found incomplete relaxations after some swallows, but
complete after others. This patient also had low amplitude peristaltic waves of the oesophageal
body.
In Fig. 1. is shown the incomplete relaxation of the LES in one of the patients. The mean
value ± SD of the basal pressure of the LES in patients with achalasia was 38±18 mmHg.
Fig. 1. On channel 2 the pressure and the incomplete relaxations of the LES
in a patient with achalasia are recorded
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In 3 patients diagnosed with achalasia we found low values of the amplitude of the peristaltic
waves (Fig. 2.). The mean value ± SD of the amplitude of the peristaltic waves of the
oesophageal body was 34.5±20 mmHg, and of the pressure of the UES of 93.3±20 mmHg, in
patients with achalasia. The values of the oesophageal manometry parameters are shown in
table 1.
Fig. 2. On channels 2, 3, 4 we recorded low amplitude waves in a patient with achalasia
Table 1. Values of the oesophageal manometry parameters measured in patients with achalasia
Patients Age Sex The basal Amplitude of the peristaltic waves Basal pressure of the UES
diagnosed (years) pressure of the ‒ mean value (value maximum) ‒ mean value (maximum
with achalasia LES ‒ mean (mmHg) value) (mmHg)
value (value
maximum)
(mmHg)
1. 12 B 53 (60) 20 (30) 100 (120)
2. 15 B 43 (45) 25 (35) 110 (140)
3. 11 G 18 (20) 65 (70) Not determined
4. 4 B Was not evaluated 28 (39) 70 (90)
23 (25) (after the
surgical
intervention)
Among the evaluated patients, there were two patients diagnosed with scleroderma (2 girls,
aged 6 and 14 years respectively, the 6 years old diagnosed with localized scleroderma) and
referred to us because of the dysphagia they presented. There were no pathological changes in
the oesophageal motility parameters (Fig. 3).
Fig. 3. Normal amplitude, speed, and duration of the peristaltic waves on all the channels
in a patient with scleroderma
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One patient previously diagnosed with neurofibromatosis was evaluated for feeding refusal.
He had high values of the pressure of the LES (mean value 60 mmHg, maximum value=70
mmHg), but with complete relaxations after wet swallows. The rest of the evaluated features
were normal.
One patient, a girl, aged 8 years and 7 months had high values of the pressure of the LES
(40-45 mmHg), with complete relaxation and low amplitude waves of the oesophageal body
(20-22 mmHg).
The patients (n=6) who did not associate chronic disease, which can be related to motility
disorders of the oesophagus, had mean values of the basal pressure of the LES±SD=25.6±4.1
mmHg. The mean values ± SD of the amplitudes of the peristaltic waves was 66±14.5 mmHg,
and of the mean pressures ± SD of the UES of 55.8±11.2 mmHg. The oesophageal manometry
features recorded in each patient are shown in table 2.
Table 2. Values of the oesophageal manometry features recorded in patients without chronic diseases
and with normal tracings
Patients with Age Sex Basal Amplitude of the peristaltic waves in Basal pressure of the
normal (years) pressure of the oesophageal body ‒ mean value UES – mean value
oesophageal the LES – (maximum value) (mmHg) (maximum value)
manometry mean value (mmHg)
tracings (maximum
value)
(mmHg)
1. 1 B 28 (33) 40 (50) 42 (44)
2. 12 G 23 (25) 75 (90) 47 (52)
3. 3 B 19 (22) 66 (70) Not determined
4. 4 B 31 (35) 60 (70) 55 (60)
5. 5 B 26 (28) 78 (80) 45 (50)
6. 17 G 27 (30) 77 (80) 70 (75)
Discussions
The oesophagus has three zones from a functional point of view: UES, oesophageal body,
and LES [1].
Achalasia is an oesophageal motility disorder, rare in children (incidence is 0.11/100000
children annually, with less than 5% of the cases having symptoms under the age of 15 years)
[3]. The aetiology of this disease is not known, but the physio-pathological mechanism is the
degenerscence of the neurons of the myenteric plexus that innervates the LES leading to an
imbalance between excitatory and inhibitory neurons. The consequence is the incomplete
relaxation of the LES, absence of peristalsis in the oesophageal body and increased basal
pressure of the LES. The most frequent symptoms are vomiting, dysphagia, regurgitations, and
weight loss. Patients might also have atypical signs and symptoms like nocturnal cough,
dysphonia, aspiration pneumonia, feeding disorders, especially in young children and infants.
The diagnosis is suggested by the characteristic aspect of the radiologic examination of the
oesophagus with contrast substance and confirmed by oesophageal manometry [4, 5]. The
patients diagnosed with achalasia had as main symptom dysphagia, not explained by other
diseases that obstruct the oesophagus.
Morera and Norko [6] retrospectively evaluate the oesophageal manometry tracings of 29
patients aged under 18 years, diagnosed with achalasia. The authors bring arguments which
contradict previous observations which state that the absence of the relaxation of the LES is
mandatory for the diagnosis of achalasia. They notice relaxations of the LES after some
swallows, but they describe these relaxations as being abnormal. Recognizing the heterogeneity
of the functioning of the LES would allow an earlier diagnosis of achalasia [6]. Of the patients
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diagnosed by us with achalasia, two had classic manometric criteria. In one of the patients with
achalasia, the basal pressure of the LES was not determined at the first evaluation. It was only
determined after the therapeutic procedure (peroral endoscopic myotomy-POEM) when we
recorded the incomplete relaxation of the LES and normal basal pressure. In another patient,
we recorded both complete and incomplete relaxations of the LES after wet swallows.
One of the patients investigated for dysphagia, 8 years 7 months old girl, had high values of
the LES pressure and low amplitude peristaltic waves, but the relaxation of the LES after wet
swallows was complete. Also, a six years and 4 months old boy, diagnosed with
neurofibromatosis had high values of the pressure of the LES, but complete relaxations of the
LES and normal peristalsis of the oesophageal body. The motility disorders in these patients
were not classified in a specific entity.
From a clinical point of view, the oesophageal manometry (conventional or high-resolution)
tracings can be useful in demonstrating a correlation between abnormal contraction patterns
and symptoms, but there are numerous controversies regarding the interpretation of some
oesophageal motility disorders less well described [7]. These controversies arise all the more in
paediatric pathology, where we apply classifications based on studies in adult patients, like the
Chicago classification of oesophageal motility disorders [8]. Normal and pathological values
taken from adults don’t take into account the patients’ age, length/height, length of the
oesophagus, the diameter of the esogastric junction or other characteristics that could change
the results in children [9]. On the other hand, the symptoms are reported, especially in small
children, by the parents or caretakers, losing accuracy and making difficult their correlation
with the changes in the manometry tracings [7].
There are few studies regarding the normal values of the oesophageal manometry parameters
in children and most of the times they are investigating a small number of children. In table 3
there are some normal values of the parameters measured with oesophageal manometry [10],
values that are comparable with the ones determined by us in the patients with normal tracings.
Table 3. Normal values of the oesophageal manometry features (values expressed as mean ± SD)
Hillemeier et al., Cucchiara et al., [12] Moroz et al., Chitkara et al., [14]
[11] [13]
Mean age (range) 7.9 months 11 months (2-36 (2 weeks-12 12.4±1,5 years
months) years)
Number of children 15 16 62 11
(n)
Basal pressure of 22.4±4.7 15±2 30.6±2,3 24±2
the LES (mmHg) (>1 year)
Amplitude of the 50.2±3,2 59±20 - 60.7±9.5 (upper
peristaltic waves oesophagus)
(mmHg) 94±3.3 (lower
oesophagus)
Oesophageal manometry allows the diagnosis of the oesophageal motility disorders that can
accompany diseases of the connective tissue, like scleroderma. The changes that can be found
are low pressure of the LES, absent of inefficient peristalsis in the distal oesophagus. Data from
studies in adult’s state that changes in the motility of the oesophagus were found in 75-80% of
the patients with scleroderma, with high-resolution manometry; 55% of them had classical
changes [15, 16]. In children, there are very few data. In the patients evaluated by us, there were
no manometrical changes. Studies performed in adults suggest that the impairment of the
oesophageal motility is correlated with the extension of the skin injury and not with the duration
of the disease [17].
The limits of this study are represented by the small number of cases that did not allow a
proper statistical analysis and its retrospective character. We still use conventional manometry
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and not high-resolution manometry. High-resolution manometry allows a topographic

description of the changes in the pressures of the oesophagus, classification of the types of
achalasia, allowing the choice of the best therapeutic option. The main difference is represented
by the high number of sensors used in high-resolution manometry, situated at less than 1 cm
apart (not at 3-5 cm like in the catheters used in conventional manometry). Another advantage
is the fact that the catheters are not water perfused, and the measurements can be done in a
longer period of time. Also, it is not necessary to withdraw the catheter, given the high number
of sensors, the whole oesophageal peristalsis being evaluated at a certain moment.
Conclusions
Achalasia is the most frequent oesophageal motility disorder that was diagnosed in our
hospital, by conventional manometry. Some cases of achalasia might remain undiagnosed if we
only take into consideration the classic criteria.
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15. Denaxas K, Ladas SD, Karamanolis GP. Evaluation and management of oesophageal manifestations in
systemic sclerosis. Annals of Gastroenterology 2018; 31: pp. 165-70.
16. Savariono E, Mei F, Parodi A, et al., Gastrointestinal motility disorder assessment in systemic sclerosis.
Rheumatology (Oxford) 2013; 52: pp. 1095-100.
17. Kimmel JN, Carlson DA, Hinchcliff M, et al., The association between systemic sclerosis disease
manifestations and oesophageal high-resolution manometry parameters. Neurogastroenterol Motil 2016;
28 (8): pp. 1157-65.
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Between the Symptoms’ Debut and the Beginning of Treatment:

Age Groups in Irritable Bowel Syndrome
ROTARU Tudor-Ștefan1, PALAMARU Andreea Luiza1,2,

MUSTEAȚĂ Mădălina Anca1,2, TOADER Elena1,2
1
University of Medicine and Pharmacy “Gr. T. Popa”, Iași (ROMANIA)
2
Institute of Gastroenterology and Hepatology “St. Spiridon” Hospital, Iași (ROMANIA)
Emails: tudor.rotaru@umfiasi.ro, luiza.palamaru@yahoo.com, ancamadalina.musteata@gmail.com,
elena.toader@umfiasi.ro
Abstract
There are several variables that influence the way patients with irritable bowel syndrome
(IBS) manage symptoms and enact illness-related behaviours. There is evidence of differences
among age groups with respect to some IBS symptoms. There is also evidence that behaviours
like use of the Internet, use of herbal medicine and late consultation with a general-practitioner
are found in samples of IBS patients. On a small sample of IBS patients (N=42), we analysed
the possible differences among age groups with respect to: consulting a general practitioner,
Internet use, self-medication or intake of herbal products. We found that Internet use between
the debut of symptoms and the moment of diagnosis was significantly more frequent in the 30-
40 age group when compared with all other age groups. We explain this because of particular
challenges of this life period combined with less free time and easier access to the Internet. This
result also matches other findings in literature concerning age-relevant behaviours and patterns.
More refined measures are needed to further explore age-related differences in both
symptoms and behaviours in IBS patients.
Keywords: Irritable bowel syndrome, age groups, self-medication, Internet use
Introduction
The way in which a patient deal with irritable bowel syndrome (IBS) depends on age,
education but also on the information sources the patient has about their disease [1], [2], [3].
Cognitive processes like dispositional optimism [4] or adult attachment styles [5][6] may
play a role in developing disease-related psychopathology triggered by stressors like a
functional disease [7]. Since the Internet can also genuinely be used for web-based trans-
diagnostic programs [8], it is likely that its use by irritable bowel patients vary between justified
information [9] and compulsive behaviours meant to soothe anxiety [10]. For IBS, the Internet
seems a primary source of health information [11]. There are age-relevant behaviours and
symptoms in IBS patients, some of them connected to an overexposure to confusing information
and anxiety [12]. In some samples, the expression rate of some IBS symptoms is higher among
females and those aged 20-49 years than males and those aged 50-79 years, respectively [13].
In some other samples, IBS was shown to increase with age and to be slightly higher in
women than in men [14]. Some scholars consider the general practitioner as a first line of
defines against unnecessary investigation [15]. Other researchers have shown a preference of
some IBS patients trying to treat themselves with herbal medicine [16]. At least in some
samples, patients who fulfil the criteria for irritable bowel syndrome have a significantly higher
tendency to self-treat their gastrointestinal symptoms [17], [18]. We want to analyse if there are
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differences among age groups with respect to: consulting the general practitioner, Internet use,
self-medication or intake of herbal products.
Method
We performed a questionnaire-based survey on a group of patients diagnosed with irritable

bowel syndrome (N=42 of which 22 are women and 20 are men). The age mean was 43,98,
with a minim of 25 and a maximum of 78. The patients were admitted in the Institute of
Gastroenterology and Hepatology “St. Spiridon” Hospital, Iași, Romania. The participants
answered to one-item dichotomic measures. The questions referred to symptoms and psycho-
social aspects of irritable bowel syndrome. In Table 1, the questions and variables collected
from the patients can be observed as well as the dichotomic nature of the majority of items. The
patients reported age as well and other socio-demographic variables. The data was split by age
decades: 20-30, 30-40, 40-50 and patients over 50 years old. The significance between the
observed and the expected difference in each of the variables was calculated.
Variable modalities (possible answers)

Gender male/female
Age in years to be filled in
Level of graduated studies a) no studies
(check the appropriate box) b) primary studies
c) secondary studies
d) high-school
e) University
f) Post-university studies
Provenance a) Rural
b) Urban
Between the debut of the symptoms and the a) I consulted with my GP
receipt of the diagnosis, what did you do? b) I read over the Internet
(check all that apply) c) I treated myself with medication
d) I treated myself with naturist products
e) something else (please write): _____________
Table 1. The questions included in the survey of Irritable Bowel Syndrome
Results
There are statistically significant differences between age decades with respect to Internet
use in the period comprised between symptom’s debut and the moment of diagnosis receipt
χ[3]=24,16; p<0,01. In Figure 1 the clustered bar graph representing the Internet use across all
four age groups can be observed. The effect size is strong as shown by the indicator Cramer’s
Phi=0,76. The Internet use between the debut of symptoms and the moment of diagnosis was
significantly more frequent in the 30-40 age group when compared with all the other age groups
put together χ[1]=21,9; p<0,01. The effect size is strong as shown by the indicator Cramer’s
Phi=0,74. In Figure 2 the clustered bar graph representing the Internet use across the two
recoded age groups can be observed. The Internet use between the debut of symptoms and the
moment of diagnosis was significantly less frequent with patients older than 50 when compared
with all other age groups put together: χ[1]=7,47; p<0,01. The effect size is moderate as shown
by the indicator Cramer’s Phi=0,42. Other statistical computations between observed and
expected frequency did not reach the statistical significance threshold. This was the case for
having consulted the GP before the receipt of the diagnosis (χ[3]=0,96; p>0,05), self-medication
(χ[3]=2,81; p>0,05) and use of herbal products (χ[3]=3,21; p>0,05).
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Fig. 2. Clustered-bar graph illustrating the comparison among all four age groups with respect to Internet use
Fig. 3. Clustered-bar graph illustrating the comparison between the 30-40 age decade and all other subjects with
respect to Internet use
Fig. 4. Clustered-bar graph illustrating the comparison between the patients over 50 years old and all other
patients with respect to Internet use
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Discussion
The use of the Internet is more frequent in the age group 30-40 in our sample. This could be
explained by a set of psychosocial variables. People in this group might experience the
challenges of a maximum emphasis on their professional life. This might translate into less time
to take the appropriate steps for accurate information and more temptation to use the Internet
for answers related to their symptoms and uncertainties. This finding fits the observations about
the Internet as a primary source of health information [11]. It is also a relative match to the
narratives of patients building a trust relationship with either their general practitioner or their
gastroenterologist (19). Trust in the doctor and reliance on the Internet seem to go against each
other when it comes to irritable bowel syndrome, at least in some samples [9]. Since searching
the Internet can be a compulsion in itself in the case of IBS patients with hypochondriac
tendencies [10], this behaviour can self-enhance and multiply. All the aforementioned
information cannot fully explain the big difference we found in Internet use between the 30-40
age group and the rest of the age groups. A sudden raise in illness-awareness and illness-anxiety
could also be higher in this age range, since younger people might show more optimistic bias
towards the future [4], and older people might already be used to illness-related problems. Our
result is, somehow, a match to other age-related findings about symptoms of irritable-bowel
syndrome [13].
All the other statistical computations did not reach statistical significance. This might be due
to the small sample size, which allows for small numbers of observations in the Chi-Square
cross tabulations. The results with no statistical significance might also mean that differences
among the age groups in IBS concern only a limited set of behaviours. Moderating and
mediating variables might play a role, in this they can only be investigated with measures
beyond the dichotomy approach we used in this study.
Conclusion
Age-related differences in IBS patients are an important variable to be considered when

dealing with symptoms and behaviours. In our sample, people aged 30-40 used the Internet far
more frequently than any of the other age groups. This might be explained by the professional
challenges of this period. More refined measures are needed in other to investigate other age-
related differences and their possible role in the management of irritable-bowel syndrome.
REFERENCES
1. Rotaru T-S, Drug V-L. Responsibility of patients towards the management of their Irritable Bowel
Syndrome (IBS): A qualitative study. Neurogastroenterol Motil. Aug. 2017; 29(2, SI): p. 36.
2. Rotaru T-S. Trust in Doctor Patient Relationship in the Context of IBS. В: Drug, V and Dumitrascu, DL,
red. Neurogastro 2017 – Meeting of the Romanian Society of Neurogastroenterology with Rome IV
Regional Central East European Meeting. Filodiritto Editore publisher; pp. 105-9.
3. Rotaru TS, Drug V, Oprea L. Mutual trust between doctors and Irritable Bowel patients: a qualitative
study. Eur J Clin Invest. 2015; 45(2, SI): p. 39.
4. Gherasim LR, Măirean C, Rusu A. Dispositional Optimism and Judgments of Future Life Events:
Affective States as Moderators. J Happiness Stud. 2016; 17(3): pp. 1015-31. Available at:
https://doi.org/10.1007/s10902-015-9629-5
5. Rotaru T-Ş, Dafinoiu I. Attachment and Suggestion-Related Phenomena. Int. J Clin. Exp. Hypn. 2014;
62(2): pp. 195-214. Available at: http://www.tandfonline.com/doi/abs/10.1080/00207144.2014.869134
6. Rotaru T-Ş, Rusu A. Psychometric Properties of the Romanian Version of Experiences in Close
Relationships-revised Questionnaire (ECR-R). Procedia ‒ Soc. Behav. Sci. 2013; 78(0): pp. 51-5.
Available at: http://www.sciencedirect.com/science/article/pii/S1877042813008185
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7. Fond G, Loundou A, Hamdani N, Boukouaci W, Dargel A, Oliveira J, et al., Anxiety and depression
comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis. Eur. Arch
Psychiatry Clin. Neurosci. Dec. 2014; 264(8): pp. 651-60.
8. Tulbure BT, Rusu A, Sava FA, Salagean N, Farchione TJ. A Web-Based Trans diagnostic Intervention
for Affective and Mood Disorders: Randomized Controlled Trial. JMIR Ment. Heal. Мay 2018; 5(2): p.
e36.
9. Rotaru T-S, Anton C, Barboi O, Mihai C, Stefanescu G, Drug V. Trust in the gastroenterologist and trust
in the internet: Do they go against each other in irritable bowel patients? Neurogastroenterol Motil. Aug.
2019; 31(4, SI).
10. Rotaru T-S, Drug V. A trust-based model for the interaction with anxious patients suffering from Irritable
Bowel Syndrome (IBS). Neurogastroenterol Motil. Aug. 2018; 30 (1, SI).
11. Alfaro-Cruz L, Kaul I, Zhang Y, Shulman RJ, Chumpitazi BP. Assessment of Quality and Readability of
Internet Dietary Information on Irritable Bowel Syndrome. Clin. Gastroenterol Hepatol. Feb. 2019; 17(3):
pp. 566-7.
12. Rotaru T-S, Drug V, Oprea L. How doctor-patient mutual trust is built in the context of irritable bowel
syndrome: A qualitative study. Rev Cercet si Interv Soc. 2016; 55.
13. Kosako M, Akiho H, Miwa H, Kanazawa M, Fukudo S. Impact of symptoms by gender and age in
Japanese subjects with irritable bowel syndrome with constipation (IBS-C): a large population-based
internet survey. Biopsychosoc Med. 2018; 12: p. 12.
14. Pan C-H, Chang C-C, Su C-T, Tsai P-S. Trends in Irritable Bowel Syndrome Incidence among Taiwanese
Adults during 2003-2013: A Population-Based Study of Sex and Age Differences. PLoS One. 2016;
11(11): p. e0166922.
15. Whorwell PJ. Editorial: preventing unnecessary investigation and surgery in the irritable bowel
syndrome-the critical role of the general practitioner. Том 47, Alimentary pharmacology & therapeutics.
England; 2018. Pp. 1558-9.
16. Bahrami HR, Hamedi S, Salari R, Noras M. Herbal Medicines for the Management of Irritable Bowel
Syndrome: A Systematic Review. Electron physician. Aug. 2016; 8(8): pp. 2719-25.
17. Kua C-H, Ng S-T, Lhode R, Kowalski S, Gwee K-A. Irritable bowel syndrome and other gastrointestinal
disorders: evaluating self-medication in an Asian community setting. Int. J Clin. Pharm. Aug. 2012;
34(4): pp. 561-8.
18. Niknam R, Mousavi S, Safarpour A, Mahmoudi L, Mahmoudi P. Self-medication of irritable bowel
syndrome and dyspepsia: How appropriate is it? J Res Pharm Pract. 2016; 5(2): pp. 121-5.
syndrome: A qualitative study. Rev Cercet si Interv Soc. 2016; p. 55.
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Diagnostic Role of H2-Breath Tests in Neurogastroenterology
SURDEA-BLAGA Teodora1, DUMITRASCU Dan-Lucian1,

ABENAVOLI Ludovico2
1
2nd Dept. Of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca (ROMANIA)
2
Università Catanzaro (ITALY)
Emails: dora_blaga@yahoo.com, ddumitrascu@umfcluj.ro, l.abnavoli@unicz.it
Abstract
Breath tests are not respiratory tests but tests designed to evaluated the gastrointestinal tract.
The most common breath tests are those using as marker H2 or C13. We will present a
review including original data showing the importance of these tests in the assessment of the
Small bacterial intestinal overgrowth (SIBO) and of the malabsorption syndrome caused by
disaccharidase deficiency (lactose and fructose malabsoprtion). Despite the controversies about
their diagnostic value developed in recent years, we continue to consider these tests as useful
and not expensive tools for rapid examinations of patients with diarrhoea or bloating.
Keywords: Breath test, Disaccharides, Malabsorption, Small intestinal bacterial overgrowth
Introduction
The hydrogen breath tests are tests based on the measurement of the H2 concentration in the
expired air after the ingestion of a certain substrate [1]. The most commonly used substrates for
the H2-breath tests are displayed in table 1 [1]. There is also other hydrogen based breath tests
which did not gain clinical use.
Table 1. Commonly used H2-breath tests

Substrate Indication Name
Glucose Small intestinal bacterial Glucose H2-breath test
overgrowth (SIBO)
Lactulose SIBO
Orocecal transit time Lactulose H2-breath test
Lactose Lactase deficiency Lactose H2-breath test
Fructose Fructose deficiency Fructose H2-breath test
The most frequent use of H2-breath test is the small bowel intestinal overgrowth (SIBO).
Definition of SIBO
SIBO is defined as the presence of bacteria in the small bowel in a higher concentration than
normal [2]. Normal values mean that in the upper small bowel one can find less than 100 colony
forming units (CFU)/ml. The largest majority of these bacteria are G+ positive aerobic
microbes. Therefore, one can define SIBO as the condition differing from this value above.
SIBO is also defined as the presence of G- aerobic bacteria and/or of anaerobes. In severe
cases, SIBO may result in nutrient malabsorption and intestinal inflammation [3]. Symptoms
related to bacterial overgrowth in the small intestine are diarrhoea, anaemia, weight loss and
malabsorption [1, 3].
SIBO may also be diagnosed by the lactulose H2-breath test, but this test is less reliable.
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Indeed, the lactulose test is measuring rather the oro-cecal transit time than SIBO. Indeed,
the lactulose test is measuring rather the oro-cecal transit time than SIBO.
A Clinical Application
We present in continuation data from one of our studies on SIBO. We tested with glucose
H2-breath test a group of 72 consecutive patients with IBS for SIBO [4, 5].
Exclusion criteria were: antibiotics ingested 4 weeks before the breath test; colonoscopy one
month before the breath test; H2 fasting level over 10 ppm [1, 4, 5].
All patients were investigated using the glucose H2-breath test. In order to undergo this test,
patients were given dietary restrictions starting from the lunch of the day before. They were not
allowed fermentable products, including potatoes, beans, broccoli, bread or other similar
products, milk and other dairy products. They were allowed to eat proteins, with meat, chicken
or fish fasting and were not allowed to chew gum, smoke and exercising 2 hours before and
during the (hyperventilation can cause changes in breath H2 content). Vitamins and laxatives
were forbidden at least in the 24 hrs before the GHBT. Just before the test, subjects were asked
to brush their teeth and mouth was disinfected with chlorhexidine [5].
The investigation was carried out with 50 g of glucose dissolved in 250 ml water. After a
baseline sample of expired air, patients drink the substrate and start collecting breath at 15-min
interval up to 120 min. The test is considered positive if there is a clear H2 peak, exceeding 20
ppm before the 120 minutes have elapsed. Eight out of 72 initial patients (11.1%) had evidence
of SIBO. They were 6 females (75%) and 2 males (25%). There is a non-statistical significant
differences concerning age and gender between SIBO positive and negative patients (p>0.05)
[4]. All positive patients for SIBO have been treated with Rifaximin 1200 mg (400mgx3/day)
for 14 days. One week after the end of treatment 7 out of 8 SIBO patients have been retested to
reassess the efficacy of the treatment (negative glucose H2-breath test and improvement of
symptoms). Only one patient (patients with IBS-D) still was positive for SIBO, and showed a
negative glucose H2-breath test after another 14 days’ cure of antibiotic therapy. Improvement
of IBS symptom after the end of treatment was evaluated using the Likert scale, 4 (57.1%) of
patients out of 7 that were retested showed an almost complete improvement in symptoms, 2
partial improvements (28.5%) and 1 patient with little improvement (14.2%) [5].
In another study we observed that those IBS patients who express positive low-degree
intestinal inflammation measured by faecal calprotectin are those who present SIBO [6].
What Equipment’s for H2 Testing?
There are several equipment’s for the H2 breath testing. Some are for individual use; it means
that they can be used with the help of an instructed nurse or resident for patients one by one.
Other equipment’s can be used simultaneously by several patients in the lab. Important is
that the patient should be fasting, restrained from smoking, with the disinfected mouth by a
mouth wash. In non H2 producers, one recommends the methane test, more frequently used in
USA but less in Europe.
Conclusions
The H2 breath tests are still very useful for the assessment of SIBO and of lactose and
fructose malabsorption. A need for guidelines is obvious and a working group financed by UED
will soon present its conclusions.
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REFERENCES
1. Dumitrascu DL, Bor S, Tutuian R, Chiarioni G, Drug V, Surdea-Blaga T: Syllabus of the UEG HRM
Hands-on Course Cluj-Napoca 2019.
2. Saad RJ, Chey WD. Breath tests for gastrointestinal disease: the real deal or just a lot of hot air.
Gastroenterology. 2007; 133: pp. 1763-1766.
3. Simon G L, Gorbach S L. Intestinal flora in health and disease. Gastroenterology 1984. Pp. 86174-193.
4. Ghoshal UC. How to interpret hydrogen breath tests? J Neurogastroenterol Motil. 2011, 17(3): pp. 312-
7.
5. Moraru IG, Moraru AG, Andrei M, Iordache T, Drug V, Diculescu M, Portincasa P, Dumitrascu DL.
Small intestinal bacterial overgrowth is associated to symptoms in irritable bowel syndrome. Evidence
from a multicentre study in Romania. Rom J Intern Med. 2014; 52(3): pp. 143-50.
6. David L, Babin A, Picos A, Dumitrascu DL Small Intestinal Bacterial Overgrowth is Associated with
Intestinal Inflammation in the Irritable Bowel Syndrome. Clujul Med. 2014; 87(3): pp. 163-5.
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Suffering caused by Symptoms of Irritable Bowel Syndrome: Self-

reported Level by Various Age Groups
TOADER Elena1,2, PALAMARU Andreea Luiza1,2,

MUSTEAȚĂ Mădălina Anca1,2, ROTARU Tudor-Ștefan1
1
University of Medicine and Pharmacy “Gr. T. Popa”, Iași (ROMANIA)
2
Institute of Gastroenterology and Hepatology “St. Spiridon” Hospital, Iași (ROMANIA)
Emails: elena.toader@umfiasi.ro, luiza.palamaru@yahoo.com, ancamadalina.musteata@gmail.com,
tudor.rotaru@umfiasi.ro
Abstract
There are only several studies concerning age and irritable bowel syndrome with respect to
psycho-social impairment. These belong to different cultures and different methodologies.
Their findings are various and not easy to summarize. We aim to analyse possible differences
among age groups, in a Romanian sample (N=42), with respect to self-reported distress by
patients with irritable bowel syndrome in a psychosocial context. Most of results did not reach
a statistical difference. In our small sample, we found that patients under 30 years-old reported
less anxiety about “a more serious disease which could manifest” because of their intestinal
problems. We provided several possible explanations for this result, in contact with the current
literature. More complex mediating-moderating models might succeed in revealing the role of
age in the way people cope with psycho-social impairments.
Keywords: age groups, irritable bowel syndrome, psycho-social impairment, illness-related anxiety
Introduction
Studies in the field do not usually report an age specific profile for the psychosocial
impairment due to irritable bowel syndrome (IBS). However, researchers have identified some
differences considering age and sex, with respect to symptoms and symptom management. For
instance, in a Japanese sample, the expression rate of some IBS constipation-type symptoms
was higher among females and those aged 20-49 years than males and those aged 50-79 years,
respectively [1]. In another sample of Turkish IBS patients, the results suggested that sleep
quality worsened with age [2]. In a Columbian children’s sample, scholars found out that IBS
prevalence was generally higher in younger children compared with adolescents, regardless of
sex [3]. In a large American sample, anxiety was higher among patients with several
comorbidities, but this effect was more pronounced for younger adults. Depression was also
predicted by the interaction between age and comorbidities and showed the same pattern as
anxiety [4]. A set of compulsive behaviours meant to soothe anxiety was theorized in our
previous findings [5]. This is consistent with other results in the field that show a connection
between coping with IBS and other psychosocial variables. The way in which a patient cope
with irritable bowel syndrome (IBS) depends on age, education, information sources the patient
has about their disease [6], [7], [8], psychosocial traits like dispositional optimism [9] or adult
attachment styles [10], [11]. In general, the use of the Internet by the irritable bowel patients
vary between justified information or diagnosis programs [12] and anxiety or confusion-
triggered behaviours [13], [14]. This study aims to analyse possible differences among age
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groups, in a Romanian sample, with respect to self-reported distress by patients with irritable
bowel syndrome in a psychosocial context: family, friends, work and subjective fears.
Method
A group of patients, (N=42) diagnosed with Irritable Bowel Syndrome, answered questions
on Likert-type scales in six points. The questions pertained to psycho-social issues of irritable
bowel syndrome. They were built as a single-item measure and not as a multiple-item
psychometric scale. The self-report had the following instruction: “Think about your daily life
in society. Include here the interaction with your relatives, spouse, your children or work
activity. Please evaluate, on the scale below, how distressing you find these unpleasant aspects
of your social life”. The ordinal six-level scale was coded as follows: 6 ‒ I find it completely
distressing; 5 ‒ I find it very distressing; 4 ‒ I find it distressing enough; 3 ‒ It bothers me quite
a bit; 2 ‒ I find it a little bothering; 1 ‒ It doesn’t bother me at all. The specific items that were
used in this inquiry can be observed in Table 2.
Item Single item self-report measure

no.
1 The pain connected with my irritable bowel.
2 The frequent visits to the restroom for number two.
3 Flatulence (gas).
4 The fact that I have to refuse some dishes, when they are offered to me.
5 The fact that I have to take drugs in certain moments.
6 The noises my intestines make in certain moments.
7 The fact that I get scared by a more serious disease which could manifest because of my intestinal
problems.
8 The fact I don’t seem to find a doctor who truly understands me concerning my Irritable Bowel
Syndrome.
Table 2. Single-item self-report measures used in the study
The patients also reported age and other socio-demographical variables as well as data about
the onset of the symptoms and the start of treatment. The data was split on age decades, and the
statistical significance of the difference between the mean of each age group was calculated.
Results
The difference between the means computed with the Kruskall-Wallis non-parametric test
did not reach any statistical significance. The false-negative tendency in non-parametric tests
is, however, to be noted. In a single case, the nonparametric Kruskall-Wallis H test got close to
the significance threshold, with respect to the differences among the age groups regarding their
fear of a more serious disease Kruskall Wallis χ2[3]=6,54; p=0,08. In Fig. 5 this difference can
be observed.
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Fig. 5. Differences among age groups because of their fear of a more serious disease (means)
After recoding a dichotomy variable, the patients in the youngest age group seem to have a
significantly lower fear of disease than the others (Mann-Whithney U=19, Z=-2,55, p<0,01).
The comparison can be observed in Fig. 6.
Fig. 6. Comparison between two (recoded) age groups
Discussion
The non-significant results might be due to quite small sample sizes which in turn, demand
nonparametric statistical tests and have less power to detect differences. It is noteworthy to
admit that the group of patients aged less than 30 years-old amounted to only four members.
Statistically, this small number of observations should be successfully countered by the use
of non-parametric tests which take the computed ranks into consideration. The significant result
might be explained by less worries the young patients have about their health: the absence of
other illnesses that are more frequent in older patients might make patients more optimistic
about their general state of health. However, this does not seem to match other findings in the
literature which show that the effect of comorbidities was more pronounced in younger adults.
However, in that particular American sample, age was considered a moderating factor and
not a plain independent measure for comparison [4]. In our study, statistics did not allow for
any analysis of moderating or mediating effects. The result also goes against some insights that
we gained through qualitative studies, pertaining to the anxieties younger people might have
about any other serious illness [14]. Another possible explanation is that younger patients have
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lived less with this functional disease, so the effect on their quality of life might not be perceived
as serious.
The big number of non-significant results might also be in line with the general trend of the
findings of other research teams. In the PubMed database, only thirteen results come up when
searching “age” and “irritable bowel” for the document title. It is possible that the lack of
differences among age groups has gone unreported in the scholar literature. It is also possible
that effects, like mediation or moderation of variables can better explain both types of previous
findings: on the one hand, younger patients seem more comfortable and less scared about a
more serious disease that might impair them as a consequence of their intestinal problems, like
the findings in this present study. On the other hand, the same younger people seem to have
more anxieties and more compulsive behaviours [5], [13], [14], including the amount of time
they spend on the Internet. Mediating and moderating variables could explain both, as some
studies suggest [4]. It is likely that further research, on a wider range of samples and the use of
more complex statistical computations could unravel the role of age.
Conclusion
Psycho-social and symptom-related issues of irritable bowel syndrome do not show cogent
differences among age-groups in our sample. Only one result is consistent with some previous
findings but not with others. This refers to the lower level of anxiety patients under thirty years-
old report about another serious illness that might impair them in the future. We have provided
some common-sense hypothesis but also some literature findings to explain this result. Further
research and more complex mediation-moderation models might explain the role age has when
it comes to these types of psychosocial aspects related to IBS.
REFERENCES
1. Kosako M, Akiho H, Miwa H, Kanazawa M, Fukudo S. Impact of symptoms by gender and age in
Japanese subjects with irritable bowel syndrome with constipation (IBS-C): a large population-based
internet survey. Biopsychosoc Med. 2018; 12: p. 12.
2. Acay A, Bal A, Oruc S, Ozkececi T, Sariaydin M, Demirbas H, et. al. Does frequency of restless legs
syndrome and poor sleep quality increase with age in irritable bowel syndrome? Wien Klin Wochenschr.
Dec. 2016; 128(Suppl. 8): pp. 604-9.
3. Lu PL, Velasco-Benitez CA, Saps M. Sex, Age, and Prevalence of Paediatric Irritable Bowel Syndrome
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Minimal Endoscopically Lesions and Diagnosis of Dyspepsia
TOCIA Cristina1,2, DUMITRU Andrei1, DUMITRU Eugen1,2

1
Ovidius University of Constanta, Faculty of Medicine, (ROMANIA)
2
Gastroenterology Department of Constanta County Clinical Emergency Hospital, (ROMANIA)
Emails: cristina.tocia@yahoo.com, dr.andreidumitru@gmail.com, eugen.dumitru@yahoo.com
Abstract
Dyspepsia is a very common gastrointestinal complaint and it is estimated that occurs in at

least 20% of the population. Endoscopy plays an important role in the classification of
dyspepsia as organic or functional and is the most accurate investigation recommended in the
work up of dyspepsia. More than half of the patients are diagnosed with functional dyspepsia
and up to 20%-30% are found to have organic causes. Innovative endoscopic technology for
improving mucosal visualization have revolutionized endoscopy; recent advanced endoscopic
imaging is very useful for detection of minimal endoscopic lesions, but despite these improved
endoscopic technologies, the relationship between mild or equivocal minimal endoscopic
findings and dyspepsia symptomatology is confusing because treating and healing the organic
cause does not always lead to the symptoms resolution. The relationship between mucosal
abnormalities or minimal endoscopic findings and dyspeptic symptoms will remain difficult to
establish as long as etiopathogeny of dyspepsia remains incompletely elucidated and future
research in this area is needed.
Keywords: dyspepsia, endoscopy, NBI
Introduction
Dyspepsia, which involves a broad spectrum of symptoms, is a very common gastrointestinal

complaint in the outpatient and inpatient settings. The exact worldwide prevalence of dyspepsia
is not known, but it is estimated that occurs in at least 20% of the population [1]. Endoscopy is
the most accurate investigation recommended in the work up of dyspepsia to exclude organic
causes [2]. More than half of the patients are diagnosed with functional dyspepsia and up to
20%-30% are found to have organic causes [3, 4]. Nowadays, recent advanced endoscopic
imaging is very useful for detection of minimal endoscopic lesions, but despite these improved
endoscopic technologies, the relationship between mild or equivocal minimal endoscopic
findings and dyspepsia symptomatology is confusing because treating and healing the organic
cause does not always lead to the symptoms resolution. Moreover, dyspepsia has an important
financial burden to patients and to the healthcare system, and also a negative impact on patient’s
health-related quality of life and on work productivity [5, 6, 7].
Definition and Classification of Dyspepsia
Dyspepsia is defined by a variety of upper gastrointestinal symptoms including epigastric

pain or burning, bloating, early satiety, postprandial fullness or nausea [8]. According to the
recently published Roma IV consensus [3], functional dyspepsia is defined by any combination
of these four symptoms: bothersome postprandial fullness, bothersome early satiation, or
bothersome epigastric pain or burning which occur at least 3 days per week over the last 3
months with an onset of at least 6 months prior to diagnosis; also, symptoms have no possible
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organic cause on endoscopy, are not relieved only by defecation and are not associated with
stool irregularities. Criteria related to bowel habit was introduced to rule out irritable bowel
syndrome as a cause of the symptoms, although these two conditions can coexist [9].
Furthermore, functional dyspepsia is classified into two subtypes according to the
predominant symptoms: epigastric pain syndrome (EPS) and postprandial distress syndrome
(PDS) [3]. EPS is defined by intermittent epigastric pain or burning which occur at least once
time per week related or not to food ingestion; PDS is defined by bothersome postprandial
fullness or early satiety in relationship with normal-sized meals which occurs at least several
times per week [10]. Bloating, nausea, belching can also be present, but are not specific to
dyspepsia. Rome IV classification involves also the overlap of the two subtypes in up to one-
third of patients with functional dyspepsia [11], especially in the hospital setting [12]. Alarm
features in patients with dyspepsia are: age >55 years with new onset dyspepsia (ACG/CAG
guidelines [13] recommend the age threshold >60 years), unintentional weight loss, progressive
dysphagia or odynophagia, vomiting, upper digestive haemorrhage, evidence of iron deficiency
anaemia, palpable abdominal or epigastric mass and family history of upper digestive cancer
[14].
Approach to a Patient with Dyspepsia
The approach to a patient with dyspepsia depends on the clinical presentation, patient age,
presence or absence of alarm features and of Helicobacter pylori infection.
According to AGA/CAG guidelines [13], after a detailed history and careful physical
examination, patients <60 years who don’t present alarm features are diagnosed with un-
investigated dyspepsia and a test and treat strategy for Helicobacter Pylori is recommended; if
the test is negative or in the case of persistent symptoms, empiric therapy is recommended. The
presence of >1 alarm feature or persistent dyspepsia represent indications for upper digestive
endoscopy in such patients. Patients >60 years should undergo an upper digestive endoscopy
[13]. Finally, patients irrespective of age who further undergo investigations and no organic
cause is identified are diagnosed with functional dyspepsia and treated accordingly. Therefore,
it is important to distinguish un-investigated dyspepsia from functional dyspepsia.
Role of Endoscopy in Dyspepsia
Endoscopy plays an important role in the classification of dyspepsia as organic or functional.

As a general observation, it is recommended that patients should undergo endoscopy during
a symptomatic phase of the disease and in the absence of any medication, particularly acid
suppressants for an accurate examination and diagnosis. Many patients with dyspepsia are
referred for endoscopy and the appropriate role of endoscopy in such patients is of interest for
both gastroenterologists and healthcare costs.
The past, present and future of image-enhanced endoscopy (IEE)

Innovative endoscopic technology for improving mucosal visualization have revolutionized
endoscopy. These technologies help the endoscopes to view mucosal details or abnormalities
and adjacent structures like vasculature.
First flexible endoscope with fiberoptic technology used for visualization of gastrointestinal
tract was pioneered in 1957 by Hirchowitz et al., [15]. Then, in the 1990s, fiberoptic technology
was replaced with video endoscopy (standard definition endoscopes) and the resolution of
images was between 100.000-400.000 pixels; of note, current endoscopes (high definition (HD)
endoscopes) have a pixel density of more than 1 million and have the advantage of a better
visualization of mucosal surface details [16]. Additionally, HD endoscopes allows the
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visualisation of lesions at a 30 to 35 ‒ fold magnification; magnifying endoscopes can optically

magnify or zoom the images up to 150 fold and obtain a closer image of the mucosa [17]. The
need for improving image acquisition in endoscopy in order to characterize better subtle lesions
or to recognise early cancer has fuelled research to the implementation of novel types of
endoscopy systems based on new optical technologies. Recent advances in image-enhanced
endoscopy using dye, optical, and/or electronic methods provides easier assessment by
providing high-contrast images details of mucosal microstructure and microvasculature. There
are two types of IEE: dye-based chromo-endoscopy (CE) and virtual CE like NBI (narrow band
imaging), i-SCAN, FICE and BLI which use software-driven post-image processing [18].
These innovating technologies have the ability to clarify the dividing line between functional
and organic dyspepsia which largely depends on endoscopic findings.
The main role of CE is in the screening of malignant and premalignant lesion in order to
enhance diagnostic accuracy by clearly delineating the lesion and guiding biopsies [19]. Despite
these advantages (simple technique, harmless to the human body, cost-effective method), the
application of chromo-endoscopy in the screening programs is limited.
The future of endoscopy imaging is reserved for confocal laser endomicroscopy and auto
fluorescence endoscopy which are currently used under research protocols.
Technology in endoscopy has revolutionized the field of gastroenterology. Using these
improved technologies in image acquisition (image-enhanced endoscopy) it is expected that the
prevalence of functional dyspepsia will decrease and the prevalence of organic dyspepsia will
increase in the future.
Overuse of endoscopy?
Many endoscopies worldwide (56% of upper gastrointestinal endoscopies) are performed
for inappropriate indications [20, 21] and dyspepsia is one of the most common indication [34].
Despite current available guidelines on dyspepsia, studies still report overuse of endoscopy
in this field [22]. Overuse of endoscopy results from both patient perspective and doctor
perspective: unfiltered open-access referrals, low adherence to guidelines or maybe fear of
missing a cancer behind dyspeptic symptoms or therapy failure.
Looking at data from literature regarding low prevalence of organic dyspepsia,
approximately 25% of patients having an underlying organic cause [4], implementation of
strategies to reduce the overuse of upper gastrointestinal endoscopy is needed.
Endoscopic findings in dyspepsia: incidental or of uncertain significance?

A systematic review and meta-analysis showed that more than 70% had normal endoscopy,
20% erosive esophagitis, less than 10% had peptic ulcer disease and less than 1% upper
gastrointestinal cancer [4]. Without doubt, peptic ulcer disease, esophagitis or malignancy clear
relate to dyspeptic symptoms, but the association between peptic ulcer Helicobacter pylori
positive and disappearance of dyspeptic symptoms after eradication therapy is uncertain or
debatable: complete resolution of the symptomatology after Helicobacter pylori eradication was
seen in 55% of peptic ulcer patients [23]. Helicobacter pylori-associated dyspepsia as a
functional or organic dyspepsia is a controversial topic in literature, other studies showing that
10% of the treated patients remain symptom-free in the long term [24]. Debatable is also the
association between gastroduodenal erosions and dyspeptic symptoms, some considering a few
erosions in the stomach to be clinically irrelevant, others considering to be part of the spectrum
of duodenal ulcer disease [25]. More confusing is the relationship between dyspeptic symptoms
and non-erosive gastritis or duodenitis), the correlation between them being poor or non-
existent and many doctors consider such minor abnormalities clinically irrelevant [25]. Studies
that compared endoscopic findings in patients with dyspepsia with those in controls, with the
exception of peptic ulcer disease, showed no clinically relevant association between causes
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identified at endoscopy and dyspeptic symptoms [26]. A further debatable idea is the
relationship between Helicobacter pylori infection and gastric mucosal inflammation and if it
is sufficient evidence to support the hypothesis that this infection should be considered an
organic cause of dyspepsia; usually, the mucosal abnormalities associated with HP, if present,
are nonspecific; this point of view is based on the lack of regression of symptomatology that is
commonly observed after eradication therapy [25]. A study conducted in Switzerland found
that 46% of consecutive endoscopies were inappropriate although a clinically significant lesion
was almost likely to be present in the non-appropriate group as in the appropriate group; of
note, 16% had peptic ulcer in the appropriate group and 13% in the non-appropriate group [27].
Similar results were also observed in a study performed in UK [28]. A systematic review
and meta-analysis demonstrated that the prevalence of dyspepsia in individuals with
gastroesophageal reflux disease is almost 7-fold that of subjects without GERD, and that there
is overlap between the 2 conditions in up to one-quarter of individuals [29]. Another unresolved
problem regarding causes of dyspeptic symptoms is the acceptance by some of minor or
equivocal mucosal abnormalities in the distal oesophagus or cardia as evidence of reflux
induced inflammation whereas others admit only evidence of mucosal breaks as a minimum;
some practitioners are willing to accept a limited number of erosions compatible with functional
dyspepsia [30] and some would consider organic causes only tissue destruction or gross
mucosal alteration [25]. Maybe this practice comes from lessons learnt in the past that dyspeptic
symptoms are recurrent or persistent despite identification and treatment of subtle changes in
the mucosa. More research is required to understands the pathophysiology of symptoms in these
patients and the role of medication and other therapies.
Role of Biopsies in Dyspepsia
The need for routine biopsies in the absence of obvious endoscopic abnormalities is
controversial. The decision to perform biopsies is clear when lesions are present, but the
dilemma appears when the endoscopy is normal. Classically, the definition of the normal-
appearing mucosa rests on the assumption that standard WLE was used, all published literature
in this topic being based on this instrument [31], but advances in IEE showed improvement in
detection of minimal mucosal changes otherwise considered “normal” with WLE alone.
Routine use of NBI allows targeted biopsies instead of random biopsy samples which are
costly and time consuming [32].
High-quality endoscopy is a prerequisite for a proper diagnosis and assessment of upper
gastrointestinal preneoplastic changes as the most concerning cause of dyspepsia is malignancy.
Some important ESGE key performance measures [33] include minim 7-minute procedure
time, photo documentation of anatomical landmarks and abnormal findings and validated
biopsy protocol to detect gastric intestinal metaplasia. According to MAPS II guideline [34],
virtual CE can be used for guiding biopsies in order to stage atrophic and metaplastic changes
and can be used for targeting neoplastic lesions; MAPS II recommend to take biopsies from at
least two topographic sites (antrum and corpus, at the lesser and greater curvature of each) and
labelled in two separate vials and to take additional biopsies of visible suspicious lesions.
Conclusions
Endoscopy is, and will remain, the gold standard investigation for dyspepsia which is one of
the most common encountered gastrointestinal complaint in practice. Technology of image-
enhanced endoscopy has revolutionized the field of endoscopy. With the widespread of these
advances in image acquisition technologies it is expected that the prevalence of functional
dyspepsia will decrease and the prevalence of organic dyspepsia will increase in the future.
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Despite this, the relationship between mucosal abnormalities or minimal endoscopic

findings and dyspeptic symptoms will remain difficult to establish as long as etiopathogeny of
dyspepsia remains incompletely elucidated and future research in this area is needed.
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Correlations of the Quality of Life with the Negative Emotions

and Automatic Thoughts in Pre-University Education
TRIFF Dorin-Gheorghe1, TRIFF Zorica2

1
Emergency Hospital County Baia Mare (ROMANIA)
2
Technical University of Cluj-Napoca, North University Center of Baia Mare (ROMANIA)
Emails: triffdorin@gmail.com, ztriff@yahoo.com
Abstract
Automatic thoughts as general vulnerability factors along with negative emotions and
occupational stressors may be associated with the employees’ decreased quality of life. The
occupational and individual context are important in cognitive behavioural psychotherapy.
During the periodic medical check-up, the employees from 2 secondary schools and a high
school voluntarily completed and returned 180 questionnaires. The questionnaires focused on
the employees’ individual characteristics, 14 occupational stressors, the presence of automatic
thoughts (the Automated Thinking Questionnaire-ATQ), the quality of life (SF 36), and
presence of functional and dysfunctional negative emotions (Profile of Affective Distress-
PAD). There are no significant differences between schools regarding age, level of education
or income, perceived self-efficacy, ATQ scores, PAD scores and SF36 subscales. In high
school, the length of experience as an employee in the unit is higher (p=0.0044) as well as the
stressors represented by the difficult collaboration with the pupils’ parents (p=0.0144), and the
salary level (p=0.0069). Concordant, significant results were obtained in all 3 school units:
- the ATQ score correlates significantly with the scores of the energy and pain subscales
(SF36), with the score of the functional negative emotions (PAD) and within it, with the
worry-anxiety component;
- the total distress score correlates significantly, negatively (p<0.05) with the dimensions
of mental health, energy, general health status;
- the dysfunctional negative emotions are significantly negatively correlated with the
dimensions of mental health and energy and positively with the negative functional
emotions. The negative functional emotions are negatively correlated with the mental
health.
- the quality of life is negatively correlated through the dimensions of mental health,
energy and general health status with negative emotions and through the energy and
pain subscales with the ATQ score.
Keywords: quality of life, negative emotions, automatic thoughts, education
Introduction
The notion of “quality of life” is a general one, including and summarizing the perceived
quality, in accordance with the individual and sociocultural knowledge, beliefs, and values, in
different fields of life: interpersonal relations, valorisation, and social integration (elements
synthesized in the concept of social performance), physical and emotional performance. In an
individual, the perception of the “quality of life” depends on his/her cognitive structures in
relation to the environment and to the situational or long-lasting context that generates his/her
feeling of control over this environment. The general cognitive structures belong to the
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personality structure of the individual, being trans-situational or associated with activating

events or with life situations, generating in this last case local cognitions or automatic thoughts.
In their turn, automatic thoughts produce affective emotional, psychophysiological, and
behavioural responses (Fig. 1) [1]. These mechanisms may be either dysfunctional leading to
inadequate responses or disease, or they may be functional or normal. Environmental stressors,
by their amplitude or especially by their persistence can lead to negative emotions that change
the perception of one’s own quality of life. Cognitive behavioural therapy aims at restructuring
dysfunctional cognitions and acquiring new, efficient functional ones that will change the
perception of “activating events” as well as their consequences.
ACTIVATING EVENTS BELIEFS

-external situation (life events) the mode of perception and
-internal situation representation of the activating
(psychophysiological aspects, event
emotions, behaviour)
CONSEQUENCES
responses (affective,
subjective, behavioral)
EFFECTIVE
assimilation of effective
functional and/or rational
cognitions DISPUTING
restructuring of dysfunctional and/or
irrational cognitions
Fig. 1. The ABC cognitive model
In response to environmental stressors, especially in situations where the individual

repeatedly comes into contact with them, such as the occupational and family environment,
self-efficacy can modulate and diminish the negative reaction of stressors on the body.
Material and Method
During the periodic medical check-up, the employees from 2 secondary schools and a high
school voluntarily completed and returned 180 questionnaires. The questionnaires focused on
the employees’ individual characteristics, 14 occupational stressors, the presence of automatic
thoughts (the Automated Thinking Questionnaire-ATQ), the quality of life (SF 36), and
presence of functional and dysfunctional negative emotions (Profile of Affective Distress-PAD)
[2], [3]. Perceived self-efficacy was evaluated through “General self-efficacy” questionnaire
(Baban, A., Schwarzer, R., Jerusalem, M., 1996) [4]. Occupational stressors evaluated by
frequency (4 points Likert scale) are presented in the following table.
Table 1. Stressors in school workplace

No. stressors
1 unable to change unpleasant aspects
2 increased responsibility
3 communications with superiors
4 communications with other employees
5 wage levels
6 work schedule
7 workloads
8 daily completion of documents
9 difficulties in collaboration with pupils
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10 difficulties in collaboration with parents

11 the need for additional work
12 risks of disease
13 risks of injury
14 others
Individual characteristics of workers were as follows: sex, type of residence, age, length of
employment in education and in the school unit. For data analysis (software) we used Epi Info
v. 3.5.3, SPSS v 16.0. Statistical tests used: Kruskal-Wallis test, Mann-Whitney test (U test),
ANOVA, Kruskal-Wallis test and Spearman correlation coefficient for correlations between
questionnaire variables (ρ), correlation is significant at the 0.05 level.
Results and Discussions
There are no significant differences between schools regarding age, level of education or
income, perceived self-efficacy, ATQ scores, PAD scores and SF36 subscales. In high school,
the length of experience as an employee in the unit is higher (p=0.0044) as well as the stressors
represented by the difficult collaboration with the pupils’ parents (p=0.0144), and the salary
level (p=0.0069). The characteristics of the populations represented by the studied school units
by age, length of work in the unit, length of work in education, gende and type of residence are
shown in the following tables (Table 2 and table 3).
Table 2. The characteristics of the studied samples by age and length of work
Age (years) length of work in the unit length of work in education
School unit mean minimum maximum mean minimum maximum mean minimum maximum
secondary school no 1 43.88 27 62 8.16 0.2 42 17.08 1 42
secondary school no 2 41.06 26 62 8 1 39 17.36 4 42
high school 46.22 22 70 14.17 0.2 42 20.06 1 51
Table 3. The characteristics of the studied samples by gender and type of residence
School unit Gender(no.) Type of residence (no.)
men women rural urban
secondary school no 1 10 45 5 50
secondary school no 2 9 20 2 27
high school 23 53 41 36
The significant correlations of the scores obtained in the ATQ and PAD questionnaires with
the quality of life dimensions from the SF36 questionnaire, in the 4 school units are as follows:
- ATQ correlates negatively with the following: energy (p=0.027 in school no. 1; p=0.031
in school no. 2; p=0.027 in high school) and bodily pain (p=0.016 in school no. 1;
p=0.02 in school no. 2; p=0.016 in high school) and positive with “negative functional
emotions” (p=0.021 in school no. 1; p=0.032 in school no. 2; p=0.021 in high school);
- “negative dysfunctional emotions” correlates negatively with the following:
 “vitality” (energy) (p=0.029 in school no. 1; p=0.003 in school no. 2; p=0.029 in high
school) and “mental health” (p=0.007 in school no. 1; p=0.001 in school no. 2; p=0.007
in high school);
 and positive with “negative functional emotions” (p<0.001 in all three school units) and
“total distress score” (p<0.001 in all three school units);
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- “negative functional emotions” correlates negatively with “mental health” only in

school no 1 and in school no 2 (p<0.001 in school no. 1; p=0.002 in school no. 2;) and
positive with “negative dysfunctional emotions” (as it was mentioned) and “total
distress score” (p<0.001 in in all three school units);
- “total distress score” correlates negatively with the following:
 “vitality” (energy) (p=0.021 in school no. 1; p=0.001 in school no. 2; p=0.021 in high
school), “mental health” (p<0.001 in school no. 1, in school no.2 and in high school),
 “general health perceptions” (p=0.028 in school no. 1; p=0.032 in school no. 2; p=0.028
in high school).
The scores in the perceived self-efficacy questionnaire has no significant correlations in all
three school units with the occupational stressors.
The significant correlations of the scores obtained in the ATQ, PAD and quality of life
dimensions from the SF36 questionnaire with the occupational stressors in the 3 school units
are as follows:
- ATQ correlates positively with: “increased responsibility” (p=0.002 in school no.1;
p<0,001 in school no. 2; p=0 .008 in high school), “daily completion of documents”
(p=0.001 in school no. 1; p=0.001 in school no. 2; p=0.019 in high school), “the need
for additional work” (p=0.002 in school no. 1; p<0,001 in school no. 2; p=0.012 in high
school);
- “vitality” has negative correlation only with “risks of disease” (p=0.034 in school no. 1;
p<0,001 in school no. 2; p=0 .012 in high school);
- “social role functioning” negative with “risks of disease” (p=0.030 in school no. 1;
p<0,001 in school no. 2; p<0,001 in high school) “risks of injury” (p=0.003 in school
no. 1; p<0,001 in school no. 2; p=0.040 in high school);
- “mental health” correlates negatively with “communication with superiors” (p=0.015 in
school no. 1; p=0.001 in school no. 2; p=0.044 in high school) and “increased
responsibility” (p=0.001 in school no. 1; p<0,001 in school no. 2; p=0.003 in high
school);
- “bodily pain” correlates negatively with the “risks of disease” (p=0.036 in school no. 1;
p<0,001 in school no. 2; p=0.001 in high school);
- “general health perceptions” correlates negatively with “communication with superiors”
(p=0.033 in school no. 1; p=0.001 in school no. 2; p=0.036 in high school) and “risks
of disease” (p=0.013 in school no. 1; p<0,001 in school no. 2; p<0,001 in high school);
- “negative functional emotions” correlate positively with the following: “increased
responsibility” (p=0.005 in school no. 1; p<0,001 in school no. 2; p=0.021 in high
school), “risks of injury” (p=0.005 in school no. 1; p<0,001 in school no. 2; p=0.018 in
high school), “communication with other employees” (p=0.038 in school no. 1; p=0.014
in school no. 2; p=0.019 in high school);
- “negative dysfunctional emotions” correlates, positively, with the following:
“communication with superiors” (p=0.017 in school no. 1; p=0 .008 in school no. 2;
p=0.039 in high school), “increased responsibility” (p=0.003 in school no. 1; p<0,001
in school no. 2; p=0.033 in high school), “risks of injury” (p=0.002 in school no. 1;
p<0,001 in school no. 2; p=0.031 in high school);
- “total distress score” correlates positively with the following “communication with
superiors” (p=0.016 in school no. 1; p=0.023 in school no. 2; p=0.042 in high school),
“increased responsibility” (p<0,001 in school no. 1; p<0,001 in school no. 2; p=0.012
in high school), “communication with other employees” (p=0.007 in school no. 1;
p=0.002 in school no. 2; p=0.002 in high school).
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Conclusions
The employees’ perceived self-efficacy are associated differently with the dimensions of the
quality of life, depending on the school unit.
It all three school units, the quality of the low life is associated with the increase of the
frequency of the following occupational stressors: increased responsibility, communication
with superiors, communication with other employees, risks of disease, risks of injury, daily
completion of documents, the need for additional work. Surprisingly, the perception of
diminished quality of life of employees is not associated with the increase in the frequency of
occupational stressors represented by wage levels, work schedule and workloads.
Concordant, significant results were obtained in all 3 school units:
- the ATQ score correlates significantly with the scores of the energy and pain subscales (SF36),
with the score of the functional negative emotions (PAD) and within it, with the worry-anxiety
component;
- the total distress score correlates significantly, negatively (p<0.05) with the dimensions
of mental health, energy, general health status;
- the dysfunctional negative emotions are significantly negatively correlated with the
dimensions of mental health and energy and positively with the negative functional
emotions. The negative functional emotions are negatively correlated with the mental
health.
- the quality of life is negatively correlated through the dimensions of mental health,
energy and general health status with negative emotions and through the energy and
pain subscales with the ATQ score.
The data presented show a constant association in the occupational environment of
educational units of some dimensions of the quality of life with negative emotion and negative
automatic thoughts, as long as the association between negative emotion and negative automatic
thoughts in these school units does not always appear. These data indicate the predominant
association of negative emotion or negative automatic thoughts with the perception of quality
of life compared with the association of automatic thoughts with negative emotions.
REFERENCES
1. David D. (2012). Tractate of cognitive and behavioural psychotherapies. Second Ed. Polirom, Iasi, pp.
69-73
2. Hollon, S., Kendall, P. (2007). Automatic Thoughts Questionnaire (adapt at de Moldovan, R.). În D.
David (coordonator0, Sistem De Evaluare Clinică. Editura RTS, Cluj-Napoca.
3. Opris, D, Macavei, B. (2007). The profile of emotional distress; Norms for the Romanian population.
Journal of Cognitive and Behavioural Psychotherapies 2007; 7: pp. 139-152.
4. Baban A, Schwarzer R & Jerusalem M. (1996). General Self-Efficacy Scale. Retrieved at 08.05.2019
from: http://userpage.fu-erlin.de/~health/rumania.htm
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Irritable Bowel Syndrome and Fibromyalgia: Prevalence, Clinical

Characteristics and Psychological Impact
ZUGRAVU (POP) Dalina-Diana1, RUSU Flaviu1, DUMITRASCU Dan Lucian1

1
2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, (ROMANIA)
Emails: Dianadalina1@gmail.com, flaviurusu@yahoo.com, dan_dumitrascu@yahoo.de
Abstract
Introduction
There is a well-established association between Irritable Bowel Syndrome (IBS) and
Fibromyalgia (FM). The global prevalence of IBS is up to 11% in the general population, FM
has a prevalence of 2-8% in the general population. IBS and FM have some common symptoms
and comorbidities, and almost half of the patients with IBS experience symptoms of FM.
Aims
The aims of our research were to characterize the demographic data about IBS, FM and, IBS
and FM, to identify the common symptomatology of patients with IBS, FM and, IBS and FM,
and to study the prevalence of the common symptoms between the three groups.
Methods
We conducted a study on a period of 30 months. We recruited three groups of patients IBS,
FM and IBS+FM and we selected our data from our Medical Database. For patients with FM
we have taken into consideration only the diagnosis of the patients that accused widespread
pain for more than three months, and we selected only the patients with IBS diagnosis using
Rome IV criteria. We compared the three groups of patients analysing demographic data,
symptomatology and comorbidities.
Results
We included a total of 292 patients. From this total, 162 patients were only with IBS, 67
were only with FM and 63 of them were both with IBS and FM. In all the three groups, most
of the patients were from urban area. In all three groups female gender were more affected, 110
of IBS patients, 46 of FM patients and 34 of IBS+FM patients were female. The mean age of
patients included in study was 44.9±17.3 years. The men mean age was 41±16.69, and women
mean age was 45.87±17.42 (p=0.021). In IBS patients, men mean age was 37.88±16.59, and
women mean age was 44.37±19.48 (p=0.033). Regarding symptomatology, difficulty
concentrating was present in 139 of the patients with IBS, 61 of the patients with FM and 45 of
the patients with IBS+FM, fatigue for no reason was present in 34 of the patients with IBS, 45
of the patients with FM and 24 of the patients with IBS+FM, bloating was present in 149 of the
patients with IBS, 51 of the patients with FM and 45. Most frequent comorbidities present in
all the three groups were anxiety and depression. Anxiety was present in 16 of the patients with
IBS, in 19 of the patients with FM and in 29 of the patients with IBS+FM. Depression was
present in 42 of the patients with IBS, in 39 of the patients with FM and in 40 of the patients
with IBS+FM.
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Conclusions
IBS and FM are frequent in the general population, separated or overlapping. Women are
most affected in all the three groups and the mean age of women is higher than the mean age
of men. Urban area is the most affected in our study. There were significant differences between
symptoms like bloating, fatigue for no reason and difficulty concentrating between all the three
groups. There were also significant differences between prevalence anxiety and depressio n
among the patients in our groups. Patients with FM, IBS and especially those with IBS+FM are
a major problem of the heath system because there are using a lot of resources for diagnosis
and treatment.
Keywords: Irritable bowel syndrome, fibromyalgia, comorbidities, symptoms
Introduction
Irritable Bowel Syndrome (IBS) is defined as a chronic functional disorder that affects the
lower gastrointestinal tract, without any structural or biochemical alteration. (1) The main
symptom is abdominal pain, or discomfort followed by altered bowel habit like diarrhoea or
constipation or association between them; and/or abdominal bloating (1), (2).
The global prevalence of IBS is among 8.8% (3)-11% (4) of the general population, being a
very common disorder. (3) Worldwide the lowest prevalence of IBS is registered in France,
about 1.1% (5)-3.3% (3), and the highest prevalence worldwide is registered in Mexico up to
35.5% (6). The global incidence of IBS is about 1%-2% per year. (7)
In the present the diagnosis of IBS is based on Rome IV criteria: recurrent abdominal pain
one or more days per week in the last 3 months associated with at least two of following
symptoms: related with defecation, change in frequency of stool, change in form of stool. (8)
Rome IV describes four subtypes of IBS: IBS-C (at least 25% of stool with Type 1-2 of Bristol
Stool Scale, but no more than 25% of stool Type 6-7 of Bristol Stool Scale), IBS-D (at least
25% of stool with Type 6-7 of Bristol Stool Scale, but no more than 25% of stool Type 1-2 of
Bristol Stool Scale), IBS-M (at least 25% of stool with Type 1-2 of Bristol Stool Scale, and at
least 25% of stool Type 6-7 of Bristol Stool Scale) and IBS-U (Patients who fulfil IBS
diagnostic criteria, but cannot be included in any other of the three subtypes). (8), (9).
Fibromyalgia (FM) is a rheumatic disorder that affects between 2% (10) and 8% of the
general population. Is considered to be the most common rheumatic disorder, after
osteoarthritis. (11) The diagnosis of FM is characterized by chronic widespread pain, associated
with sleep or mood disturbance, memory problems, increased fatigue and hypersensitivity
which is described as an amplification of the central nervous system pain. (12) FM is in the
most of the cases linked to several medical disorders including depression, anxiety (13), GERD
and functional dyspepsia, IBS. The most commonly gastrointestinal disorder associated with
FM is IBS. (14)
Patients with FM and IBS have some common comorbidities. The most frequently described
up to now are anxiety, depression, higher rates of sleep problems, chronic fatigue and other
mental health issues. (15), (16).
The aims of our research were to characterize the demographic data about IBS, FM and, IBS
and FM, to identify the common symptomatology of patients with IBS, FM and, IBS and FM,
and to study the prevalence of the common symptoms between the three groups.
Methods
Protocol
We conducted a retrospective longitudinal study conducted in a single tertiary center, based
on the survey of the patient’s records, using data from our Medical Database, 2nd Medical
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Department, Cluj-Napoca. The data were collected from medical records of the patients
admitted in a period of 30 months between 01.01.2017-30.06.2019. We selected only the
patients with IBS diagnosis using Rome IV criteria mentioned in their file. For patients with
FM we have taken into consideration only the diagnosis of the patients that accused widespread
pain for more than three months without underlying any medical condition that could cause the
pain. We selected two groups of patients with IBS and FM. We decided to add a new group to
our research with patients who had both IBS and FM, noted below as IBS+FM. So, in the final
our study was performed on three groups: patients with IBS, patients with FM and patient who
had both IBS+FM. We compared the three groups of patients analysing demographic data (age,
gender, geographical distribution), symptomatology (walking up still feeling tired, bloating,
difficulty concentrating, memory problems, abdominal pain daily/weekly, constipation
daily/weekly, diarrhoea daily/weekly, fatigue) and comorbidities (depression and anxiety). For
the diagnosis of depression and anxiety we selected only the patients with psychiatric
confirmation.
Inclusion criteria: we selected only adult individuals (aged >18 years old), new diagnosed
patients with IBS and/or FM, patients with IBS diagnosed using Rome IV criteria, patients
admitted to our medical department who were included in our medical database.
Exclusion criteria: pregnant women, oncological patients. We excluded the patients that
could perceive IBS-like or FM-like symptoms.
Statistical analysis
We described the three groups IBS, FM and IBS+FM, and compared demographic data,
symptomatology and comorbidities between the three groups.
The results were analysed using Medcalc v19.1 and Microsoft Excel 2017. We used mean ±
SD for age, and we applied the t test for independent samples to compare the age of both genders
in every single group calculating p value. We applied Pearson’s chi-squared test to calculate
the p value for all the symptoms and comorbidities described before, in addition to see if we
have a statistically significant difference between the three groups. We considered both t test
and Pearson’s chi-squared test statistically significant at a p value of <0.05.
Results
We identified 297 patients that fulfil the inclusion criteria from which we excluded 5 patients
(4 oncological patients and 1 pregnant woman). After exclusion criteria was applied, we
included a total of 292 patients. From this total, 162 patients were only with IBS, 67 were only
with FM and 63 of them were both with IBS and FM.
In all the three groups, most of the patients were from urban area. Regarding geographical
distribution, 109 (67.2%) of IBS patients, 46 (68.65) of FM patients and 47 (74.6%) of IBS+FM
patients were from urban area. There was no statistically significant difference between
geographical area in the three groups (chi square 1.15, p=0.56). Regarding gender distribution,
in our study we had 190 (65%) women and 102 (34.9%) men. In all three groups female gender
were more affected, 110 (67.9%) of IBS patients, 46 (68.6%) of FM patients and 34 (53.9%) of
IBS+FM patients were female. There was no statistically significant difference between
genders in the three groups (chi square 4.36, p=0.11). (Fig. 1)
The mean age of patients included in study was 44.9±17.3 years, with the lowest age at 18
years and the highest age at 83 years. There were 93 (31.8%) of patients between 18-30 years,
152 (52%) of patients between 31 and 55 years and 47 (16.1%) of patients older than 56 years.
(Fig. 1) The men mean age was 41±16.69, and women mean age was 45.87±17.42, being
statistically significant difference between genders in this group (p=0.021).
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IBS No % FM No % IBS+FM No %
Gender 162 100 Gender 67 100 Gender 63 100
Male 52 32.1 Male 21 31.3 Male 29 46
Female 110 67.9 Female 46 68.6 Female 34 53.9
Rural 53 32.7 Rural 21 31.3 Rural 16 25.3
Male 16 30.1 Male 6 28.5 Male 7 43.7
Urban 109 67.2 Urban 46 68.6 Urban 47 74.6
Male 36 33 Male 15 32.6 Male 22 46.8
Age 162 100 Age 67 100 Age 63 100
18-30 71 43.8 18-30 10 14.9 18-30 12 19
31-55 76 46.9 31-55 41 61.1 31-55 35 55.5
56-83 15 9.2 56-83 16 23.8 56-83 16 25.4

Fig. 1. Demographic data (gender, geographical distribution, age) of patients with Irritable Bowel Syndrome,
Fibromyalgia and Irritable Bowel Syndrome with Fibromyalgia
The mean age in the three groups was 42.4±18.8 years for patients with IBS, 46.7±15.2 years
for patients with FM and 45.5±14.7 years for patients with IBS+FM. We compared the
differences of age between genders in all the three groups. In IBS patients, men mean age was
37.88±16.59, and women mean age was 44.37±19.48, being statistically significant difference
between genders in this group (p=0.033). In FM patients, men mean age was 44.07±17.32, and
women mean age was 48.8±13.37, there was no statistically significant difference between
genders in this group (p=0.22). In IBS+FM patients, men mean age was 43±15.88, and women
mean age was 47.59±13.48, there was no statistically significant difference between genders in
this group (p=0.23).
Regarding symptomatology, 152 (93.8%) of the patients with IBS, 65 (96.15%) of the
patients with FM and 60 (95.2%) of the patients with IBS+FM accused symptoms like wake up
still feeling tired. There were no statistically significant differences between all the three groups
(chi-square: 1.01, p=0.60). Memory problems were present in 131 (80.1%) of the patients with
IBS, 60 (84.6%) of the patients with FM and 50 (79.4%) of the patients with IBS+FM, but there
were no statistically significant differences between all the three groups (chi-square: 3.04,
p=0.22). Symptoms like difficulty concentrating were present in 139 (85.8%) of the patients
with IBS, 61 (91%) of the patients with FM and 45 (71.4%) of the patients with IBS+FM, there
was a statistically significant difference between the three groups (chi-square: 10.222,
p=0.006). Fatigue for no reason was present in 34 (20.9%) of the patients with IBS, 45 (67.1%)
of the patients with FM and 24 (38.1%) of the patients with IBS+FM, there was a statistically
significant difference between the three groups (chi-square: 44.545, p<0.001). Bloating was
present in 149 (91.9%) of the patients with IBS, 51 (76.1%) of the patients with FM and 45
(71.4%) of the patients with IBS+FM, there was a statistically significant difference between
the three groups (chi-square: 18.081, p<0.001). Symptoms like abdominal pain, constipation
and diarrhoea were included in diagnosis criteria so we did not compare them between the
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groups. At patients with IBS, abdominal pain was present daily at 56 (34.5%) patients and
weekly at 106 (65.4%) patients; constipation was present in at least two episodes per week at
14 (8.6%) patients and in only one episode per week at 71 (43.8%) patients; and diarrhoea was
present daily at 25 (15.4%) patients and weekly at 64 (39.5%) patients. At patients with
IBS+FM, abdominal pain was present daily at 20 (31.7%) patients and weekly at 43 (68.8%)
patients; constipation was present in at least two episodes per week at 9 (14.3%) patients and
in only one episode per week at 32 (50.8%) patients; and diarrhoea was present daily at 12
(19%) patients and weekly at 30 (47.6%) patients.
Most frequent comorbidities present in all the three groups were anxiety and depression.
Anxiety was present in 16 (9.8%) of the patients with IBS, in 19 (28.3%) of the patients with
FM and in 29 (46%) of the patients with IBS+FM, being a statistically significant difference
between the three groups (chi-square: 36.754, p<0.001). Depression was present in 42 (25.9%)
of the patients with IBS, in 39 (58.2%) of the patients with FM and in 40 (63.4%) of the patients
with IBS+FM, being a statistically significant difference between the three groups (chi-square:
36.456, p<0.001).
Discussions
IBS and FM are very common conditions. Patients with FM have a risk of 1.54-fold higher
to develop IBS comparing with patients without FM (17). The overlap between them is very
intensively studied in literature, being present in 75% of patients with IBS-D and 85.5% of
patients with IBS-C (18). Although we did not split IBS in the four subgroups, because we did
not have enough medical data from patients, in our study only 24.7% of the patients with IBS
had been diagnosed with FM. One of the explanations could be that FM is underdiagnosed in
our region. IBS affects both men and women, but when we speak about frequency in a gender,
women seem to be more affected than men by IBS (19). Another study showed that women
with IBS are affected up to 1.5-3-fold higher than men are affected (4). A study conducted by
Queiroz showed that women with FM are 3 times more affected than men with FM are (20). A
study conducted by Akkus showed that women with FM are 5 times more affected than men
with FM are (21). Our study showed a higher prevalence of functional disease at female gender,
our results being related with the ones found in literature.
Some studies showed that the mean age in IBS is 40 (22)-47 (18) years, while another study
states that 50% of the patients have their first IBS symptoms before 35 years (4). A study
conducted by Katz showed that mean age for the onset of symptoms of FM is 35.3 years. In this
study is also mentioned that 10% of FM cases can appear before 18 years or after 50 years old,
but most of the cases are found between 30 and 50 years (23). According to another study, mean
age of the patients that presented both IBS and FM is 51.5±16.3 years. (17) Some of our results
regarding mean age of the patients with IBS or FM are comparable with the ones found in
literature, with the mention that our patients were only adults (aged >18 years), while in our
study the mean age of patients with IBS+FM is lower.
Due to some studies published in the literature, in urban area the prevalence of FM is higher
than in rural area (24), results comparing with those we found in our study. In the literature
different results can be found about geographical prevalence of IBS, compared to those
presented in our study and, in a study performed on European and north American population
(25), (26). A study conducted on Palestinian population showed that patients from rural area
are more affected of IBS than patients from urban area. (27)
According to a study conducted by Lubrano, it has been observed that the presence of FM
in patients with IBS may be associated with more severe symptoms (28), another study showed
that almost 40% of patients with FM and IBS are experiencing severe symptoms (17), especially
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pain. Similar results had been obtained by Przekop in his study (29). The results were
comparable with our results.
Due to a study, 94% of the patients with IBS experience also anxiety, depression or
somatoform disorder. (30) Regarding FM, 19% of the patients experience depressive
symptoms, and 62-86% experience a major depressive disorder, 40% of the patients have a risk
of depression at any moment after FM onset (31). In IBS+FM, there is an OR=3.5 (95% CI 2.8
– 4.5) for depression to appear, comparing to general population (30). Our results are
comparable with those found in the literature.
Conclusions
IBS and FM are frequent disorders found in the general population, and very common is also
the overlap between the two disorders. Women are the most affected in all our three groups
IBS, FM and IBS+FM. We observed that the mean age of women is significantly higher in IBS
than the mean age of men. We also observed that there is a higher affectation of patients in the
urban area. There was a significantly difference between symptoms like fatigue for no reason,
difficulty concentrating and bloating between the three groups. Memory problems and waking
up still feeling tired were quite common in all the three groups, but without any significant
differences between them. We noticed a significant difference between the prevalence of
comorbidities like anxiety and depression among the patients in our groups. Patients with FM,
IBS and especially those with IBS+FM are a major problem of the heath system because there
are using a lot of resources for diagnosis and treatment.
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Filodiritto Editore – Proceedings

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First Edition April 2020

© Copyright 2020 Filodiritto Publisher

Doctor-Patient Relationship, the Keystone of Clinical Outcomes

Gut Microbiota and Quality of Life 13

Diverticulosis and Irritable Bowel Syndrome – Simple Association

Optical Diagnosis of Barrett Oesophagus in 2019 27

Faecal Transplant in Irritable Bowel Syndrome: Moving Forward? 33

How to Produce a Good Paper on Neurogastroenterology?

The Relationship Between Depression and Inflammatory Bowel Disease 42

Gastroesophageal Reflux Disease and Esophagitis after Paroxysmal

Gastroparesis and Atrial Fibrillation: What is the Relationship? 53

The Role of Diet on the Symptoms of Gastroesophageal Reflux Disease

Gerd After Surgery for Oesophageal Atresia 65

Phytotherapy in Some Digestive Disorders 70

High Resolution Manometry in Oradea ‒ First Years’ Experience 77

The Distribution and Features of Colonic Diverticula Complicated

The Age and Level of Studies in the Treatment Decision

Genetic Aspects of Hirschsprung’s Disease 91

Complete Mucosal Recovery: A 2019 Perspective on Intestinal Health

Rational-Emotive Behavioural Psychotherapy in Psychosomatic Diseases 101

Rumination Syndrome: A Treatment Update 105

Oesophageal Motility Disorders in Children ‒ A 5 Years’ Experience 109

Between the Symptoms’ Debut and the Beginning of Treatment:

Diagnotic Role of H2-Breath Tests in Neurogastroenterology 120

Suffering caused by Symptoms of Irritable Bowel Syndrome:

Minimal Endoscopical Lesions and Diagnosis of Dyspepsia 128

Correlations of the Quality of Life with the Negative Emotions

Irritable Bowel Syndrome and Fibromyalgia: Prevalence,

Doctor-Patient Relationship, the Keystone of Clinical Outcomes in

ANTON Carmen1, DIMACHE Mihaela2, ONOFREI Roxana3, HARJA Alina4,

University of Medicine and Pharmacy “Grigore T. Popa” Iași, (ROMANIA)

Institute of Gastroenterology and Hepatology, Hospital “St. Spiridon”, Iași, (ROMANIA)

Emails: carmen_ro2008@yahoo.com, mimidimache@yahoo.com, onofrei.roxana92@yahoo.com, alina2harja@gmail.com,

General Stats. Definition

Gastroesophageal reflux disease (GERD) is a common digestive disorder worldwide with an

The diagnosis of GERD is made typically by a combination of clinical symptoms, as well as

Psychosocial Factors in the Patient Outcome

Medical, ethical and socioeconomic issues can influence an effective physician-patient

GERD-HRQL was developed to survey symptomatic outcomes and therapeutic effects in

Shared decision making in the management of GERD

Gut Microbiota and Quality of Life

BABIN Alexandru1, DAVID Liliana2, NEDELCU Laurentiu3,

Definition of the Quality of Life

Table 1. Steps in the measurement of HR-QoL

Table 2. Characteristics required for a tool to assess QoL

Table 3. Types of questionnaires for QoL

The Role of Microbiota

BEREZOVSCAIA Elena1, LUPAȘCO Iulianna1, DUMBRAVA Vlada-Tatiana1,

Psychogastroenterology is a quite new field of neurogastroenterology putting emphasis on

Psychogastroenterology is a quite new field of neurogastroenterology putting emphasis on

(II) patients with chronic HCV infection (HCV) ‒ 10 people,

Results and Discussion

Subsequently, we conducted an analysis of three groups of patients, formed taking into

Diverticulosis and Irritable Bowel Syndrome – Simple Association

DIMACHE Mihaela1, ANTON Carmen2, TIMOFTE Oana3,

IGH, Sp. “Sf. Spiridon” Iași; (ROMÂNIA)