Normal values for esophageal manometry in the sitting position

Gastrointestinal Endoscopy, 2006

Background: Chromoscopy either as a vital or contrast stain has been shown to be useful to detect specialized intestinal metaplasia (SIM) and dysplasia in Barrett's esophagus (BE). Narrow Band Imaging (NBI) is a novel imaging technique that uses optical filters to enhance the mucosal contrast, revealing the superficial structural and microvascular patterns. The aim of our study was to study the utility of high resolution magnification endoscopy (HRME) with NBI in patients with BE. Methods: Consecutive patients with known BE undergoing surveillance endoscopy were enrolled in the study. Conventional white light endoscopy was followed by HRME with NBI using a high resolution magnification endoscope (Olympus GIF-Q240Z, 115Â) and an NBI light source. Structural and microvascular patterns within the Barrett's segment were identified and biopsies taken that were read by pathologists blinded to NBI findings. Results: Thirty patients with BE were evaluated (mean age 63 yrs, 24 males). Mean length of Barrett's segment was 3.6 cm (range 1-10 cm). With NBI, striking contrast was observed between squamous and columnar mucosa. Three distinct mucosal pit patterns (tubular/villous/linear, circular, distorted) and two microvascular patterns (regular lace-like network, and irregular-dilated-tortuous) were seen. A total of 183 biopsies were taken. The yield of SIM on targeted biopsies according to the pit patterns was as follows: tubular/ linear/villous structural pattern with regular microvessels 83/87 (95.4%), circular 0/9 (0%), and regular microvascular pattern (RMVP) with no structural pattern 52/53 (98.1%). Sensitivity, specificity, and positive predictive values of the combination of tubular/villous/linear pattern with regular microvessels and/or RMVP with no structural pattern for detecting SIM were 100%, 69%, and 97.5%, respectively. The sensitivity and specificity of the above patterns in patients with long segment BE and short segment BE were 100%, 75%, and 100%, 67% respectively. High grade dysplasia (HGD) was diagnosed in 5 cases. Sensitivity, specificity, and positive predictive values of the irregular microvascular pattern for the detection of HGD were 100%. In all cases with HGD we could visualise a demarcation line between the neoplastic and non-neoplastic tissue. Conclusion: Using HRME with NBI we described the non-dysplastic and dysplastic features in BE. It provides detailed images of capillaries and mucosal pit patterns without the need for chromoscopy. Further studies are required to prove the efficacy of this technique in routine clinical practice for BE surveillance.

Human Pathology, 2001

Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis of treatment. We rigorously tested modified 1988 criteria, assessing intraobserver and interobserver reproducibility. Participants submitted slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two hundred fifty slides were divided into 2 groups. The first 125 slides were reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12 gastrointestinal pathologists without prior discussion of criteria. Results were analyzed by statistics, which correct for agreement by chance. A consensus meeting was then held, establishing, by group review of the index 125 slides, the criteria outlined herein. The second 125-slide set was then reviewed twice by each of the same 12 pathologists, and follow-up statistics were calculated. When statistical analysis was performed using 2 broad diagnostic categories (BE, IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both before and after the consensus meeting (mean ‫؍‬ 0.82 and 0.80). Interobserver agreement was substantial ( ‫؍‬ 0.66) and improved after the consensus meeting ( ‫؍‬ 0.70; P ‫؍‬ .02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean intraobserver improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver improved from 0.43 to 0.46 (both moderate agreement). When statistical analysis was performed using 4 diagnostic categories that required distinction between LGD and IND (BE; IND; LGD; HGD and carcinoma), the pre-consensus meeting mean intraobserver was 0.60 (substantial agreement), improving to 0.65 after the meeting (P < .05). Interobserver agreement was poorer, with premeeting and postmeeting mean values unchanged ( ‫؍‬ 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma ( ‫؍‬ 0.65), moderate to substantial for BE ( ‫؍‬ 0.58), fair for LGD ( ‫؍‬ 0.32), and slight for IND ( ‫؍‬ 0.15). The intraobserver reproducibility for the diagnosis of dysplasia in BE was substantial. Interobserver reproducibility was substantial at the ends of the spectrum (BE and HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation improved overall after the application of a modified grading system developed at a consensus conference but not in separation of BE, IND, and LGD. The criteria used by the group are presented. HUM PATHOL 32:368-378. Copyright

Gastrointestinal Endoscopy

Clinical Gastroenterology and Hepatology, 2013

BACKGROUND & AIMS: It is not clear whether length of Barrett's esophagus (BE) is a risk factor for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with nondysplastic BE. We studied the risk of progression to HGD or EAC in patients with nondysplastic BE, based on segment length. We analyzed data from a large cohort of patients participating in the BE Study-a multicenter outcomes project comprising 5 US tertiary care referral centers. Histologic changes were graded as low-grade dysplasia, HGD, or EAC. The study included patients with BE of documented length without dysplasia and at least 1 year of follow-up evaluation (n [ 1175; 88% male), and excluded patients who developed HGD or EAC within 1 year of their BE diagnosis. The mean follow-up period was 5.5 y (6463 patient-years). The annual risk of HGD and EAC was plotted in 3-cm increments (£3 cm, 4-6 cm, 7-9 cm, 10-12 cm, and ‡13 cm). We calculated the association between time to progression and length of BE. The mean BE length was 3.6 cm; 44 patients developed HGD or EAC, with an annual incidence rate of 0.67%/y. Compared with nonprogressors, patients who developed HGD or EAC had longer BE segments (6.1 vs 3.5 cm; P < .001). Logistic regression analysis showed a 28% increase in risk of HGD or EAC for every 1-cm increase in BE length (P [ .01). Patients with BE segment lengths of 3 cm or shorter took longer to develop HGD or EAC than those with lengths longer than 4 cm (6 vs 4 y; P [ nonsignificant).

Seminars in thoracic and cardiovascular surgery, 2005

The incidence of esophageal cancer has increased dramatically in the Western population in the last 2 decades. In 1975, about three fourths of the esophageal neoplasms were squamous cell carcinomas and the remainder were adenocarcinomas. During the last 2 to 3 decades, this pattern has changed dramatically and the incidence of squamous cell carcinomas has declined while the incidence of adenocarcinomas has increased. The reason for this dramatic increase is not clear, but gastro esophageal reflux disease, obesity and Barrett&#39;s esophagus have been identified as risk factors. High grade dysplasia in Barrett&#39;s esophagus is a premalignant condition which can progress to invasive adenocarcinoma. In this article, we discuss the natural history of high grade dysplasia (HGD), difficulties in the diagnosis, the incidence of adenocarcinoma in resected specimens and the surgical aspects in the treatment of HGD, including minimally invasive esophagectomy.

Gastrointestinal Endoscopy, 2014

Background: Combined endoscopic therapy (CET) using endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) is widely accepted as a credible alternative to surgery for patients with early esophageal cancer (EAC) and high grade dysplasia (HGD) within Barrett's esophagus (BE). Identification and removal of subtle lesions that may harbour neoplasia is a critical step in the assessment and staging of dysplastic BE (DBE). It is imperative that intramucosal cancer (IMC) is removed and submucosal cancer (SMC) excluded before commencing RFA treatment. Aims: To compare detection rates of visible mucosal abnormalities (VMAs) and EAC in patients with DBE in the community setting vs. a specialised Barrett's unit (SBU). To assess the impact of EMR on staging of disease and impact on subsequent management. Methods: From 2008 to August 2011, consecutive patients referred to a tertiary centre SBU for management of DBE underwent assessment using high definition white light endoscopy (HD-WLE) and narrow band imaging (NBI). Biopsies were taken according to Seattle protocol in addition to targeted biopsies of VMAs seen on HD-WLE/NBI. VMAs thought to harbour advanced dysplasia/neoplasia based on Paris Classification, mucosal pattern or after biopsy confirmation were removed with EMR. Comprehensive referral endoscopy details on this cohort were retrospectively collected. Referral histology was retrospectively collected and reviewed by an expert GI pathologist. The reviewed results were used as the baseline histology to compare subsequent results. Results: 69 patients (88% male; median age 69 years) were referred. At referral endoscopy, the use of HD-WLE and NBI was 57% and 14%. Adherence to Seattle protocol was 20%. VMAs were described at referral endoscopy in 42% cases compared with 94% of cases at SBU assessment (p!0.001). EMR was performed in 47 cases (68%) at SBU. At referral endoscopy, 18 cases of cancer (all IMCs) were detected. SBU assessment confirmed EAC in all 18 cases and identified an additional 10 EAC cases (56% increase cancer detection, pZ0.036). Of these 10 cases, 3 had VMAs identified at referral; all 10 had VMAs at SBU. EMR of these VMAs at SBU found SMC (nZ4) and IMC (nZ6), resulting in esophagectomy (nZ4), chemoradiotherapy (nZ1) and CET (nZ5). VMAs that were detected at assessment but not referral ranged from very subtle flat lesions (Paris 02B) with irregular mucosal patterns seen on NBI, to small, subtly raised areas of nodularity (Paris 02A) to larger, more obvious nodules (Paris 01S). Conclusion: Assessment of patients with DBE at a SBU resulted in improved detection of VMAs and EAC. EMR of early EACs was critical in determining a patient's appropriateness for ongoing CET versus referral for surgery or chemoradiotherapy. These data suggest patients with DBE should be assessed at a SBU prior to embarking on definitive management.

PubMed, 2023

Squamous dysplasia is the histological precursor of esophageal squamous cell carcinoma (ESCC). The optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. We aimed to assess the ESCC risk in patients with esophageal squamous dysplasia in a Western country. This nationwide cohort study included all patients with esophageal squamous dysplasia, diagnosed between 1991 and 2020 in the Dutch nationwide pathology databank (Palga). Squamous dysplasia was divided in mild-to-moderate dysplasia (mild, low-grade, and moderate dysplasia) and higher-grade dysplasia (high-grade dysplasia, severe dysplasia, carcinoma in situ). ESCC were identified in Palga and the Netherlands Cancer Registry. The primary endpoint was diagnosis of prevalent (≤6 months) and incident (>6 months after squamous dysplasia) ESCC. In total, 873 patients (55% male, aged 68 years SD ± 13.2) were diagnosed with esophageal squamous dysplasia, comprising mild-to-moderate dysplasia (n = 456), higher-grade dysplasia (n = 393), and dysplasia not otherwise specified (n = 24). ESCC was diagnosed in 77 (17%) patients with mild-to-moderate dysplasia (49 prevalent, 28 incident ESCC) and in 162 (41%) patients with higher-grade dysplasia (128 prevalent, 34 incident ESCC). After excluding prevalent ESCC, the annual risk of ESCC was 4.0% (95% CI: 2.7-5.7%) in patients with mild-to-moderate dysplasia and 8.5% (95% CI: 5.9-11.7%) in patients with higher-grade dysplasia. All patients with squamous dysplasia, including those with mild-to-moderate dysplasia, have a substantial risk of developing ESCC. Consequently, endoscopic surveillance of the esophageal mucosa or endoscopic resection of dysplasia should be considered for patients with mild-to-moderate dysplasia in Western countries. KEY MESSAGES What is already known on this topic? Squamous dysplasia is the histological precursor of ESCC and is divided in distinct grades, based on the proportion of the squamous epithelium with histopathological abnormalities. In Western countries, the optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. What this study adds The ESCC risk of patients with squamous dysplasia was increased for all patients with squamous dysplasia in a Western country; 2.1% for patients with mild dysplasia, 5.1% for low-grade dysplasia, and 5.2% for moderate dysplasia. Increasing grades of squamous dysplasia were associated with an increased ESCC risk. How this study might affect research, practice, or policy We recommend that endoscopic follow-up or treatment should be considered in all patients with esophageal squamous dysplasia in Western countries: 1) for patients with mild, low-grade, and moderate dysplasia, endoscopic surveillance with careful inspection with narrow band imaging or dye-based chromoendoscopy of the esophageal mucosa is indicated; and 2) for patients with high-grade dysplasia, severe dysplasia and carcinoma in situ adequate endoscopic staging and in case of suspected neoplasia endoscopic treatment should be performed.

Histopathology, 2007

Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation between general and gastrointestinal pathologists Aims: To determine interobserver variation in grading of dysplasia in Barrett's oesophagus (BO) between nonexpert general pathologists and expert gastrointestinal pathologists on the one hand and between expert pathologists on the other hand. Methods and results: In this prospective multicentre study, non-expert and expert pathologists graded biopsy specimens of 920 patients with endoscopic BO, which were blindly reviewed by one member of a panel of expert pathologists (panel experts) and by a second panel expert in case of disagreement on dysplasia grade. Agreement between two of three pathologists was established as the final diagnosis. Analysis was performed by j statistics. Due to absence of intestinal metaplasia, 127 ⁄ 920 (14%) patients were excluded. The interobserver agreement for dysplasia [no dysplasia (ND) versus indefinite for dysplasia ⁄ low-grade dysplasia (IND ⁄ LGD) versus high-grade dysplasia (HGD) ⁄ adenocarcinoma (AC)] between non-experts and first panel experts and between initial experts and first panel experts was fair (j ¼ 0.24 and j ¼ 0.27, respectively), and substantial for differentiation of HGD ⁄ AC from ND ⁄ IND ⁄ LGD (j ¼ 0.62 and j ¼ 0.58, respectively). Conclusions: There was considerable interobserver variability in the interpretation of ND or IND ⁄ LGD in BO between non-experts and experts, but also between expert pathologists. This suggests that less subjective markers are needed to determine the risk of developing AC in BO.

FERNÁNDEZ-GÖTZ, M. and Roymans, N. (2024): Archaeology of the Roman Conquest: Tracing the Legions, Reclaiming the Conquered. Cambridge University Press, New York. https://doi.org/10.1017/9781009182003

This Element volume provides an up-to-date synthesis of the archaeology of the Roman conquest, combining new theoretical and methodological approaches with the latest fieldwork results. Recent advances in conflict archaeology research are revolutionising our knowledge of Rome's military campaigns in Western and Central Europe, allowing scholars to reassess the impact of the conquest on the indigenous populations. The volume explores different types of material evidence for the Roman wars of conquest, including temporary camps, battlefields, coinage production, and regional settlement patterns. These and other topics are examined using four case studies: Caesar's Gallic Wars, the Cantabrian and Asturian Wars, the Germanic Wars of Augustus, and the Roman conquest of Britain. By focusing on the 'dark sides' of the Roman expansion and reclaiming the memory of the conquered, the Element aims to contribute to a more holistic understanding of the processes of incorporation and integration into the Roman Empire. REVIEWS: "Archaeology of the Roman Conquest is an entirely convincing reevaluation of the violent actions undertaken by Roman commanders as they conquered substantial areas of Western Europe and of the variable responses of local communities to these invasions. It will become required reading for anyone interested in the assimilation of these peoples into the Roman Empire". Prof. Richard Hingley - Durham University "The Roman conquest of Western Europe is well-studied by generations of scholars. The authors nevertheless succeed in providing new insights into a history that is still highly topical today". Dr. Stefan Burmeister - Museum und Park Kalkriese