Interdisciplinary Discussion

Viszeralmedizin 2015;31:200–203 Published online: June 15, 2015

DOI: 10.1159/000434663

Acute and Chronic Inflammation of the Biliary System

Chair: Tim Lankisch a

Participants: Hüseyin Bektas b Alexander Dechêne c Hanno Ehlken d Gabriele I. Kirchner e

Hauke Lang f Christoph Schramm d
a
Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Hanover,
Germany,
b
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hanover, Germany,
c
Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Germany,
d
I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany,
e
Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, Regensburg, Germany,
f
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsmedizin Mainz, Mainz, Germany

Question 1: What is your diagnostic approach to a Kirchner: In my opinion, the medical history of the patient is
patient with biliary strictures of unknown origin? important. Total serum IgG, serum IgG4, and pANCA should be
determined. If cholestatic parameters are increased, ERC is indi-
Dechêne: In patients with jaundice, ultrasound gives an over- cated to search for significant and treatable biliary strictures. In
view of the presence and location of biliary obstruction, whereas addition, brush cytology and biopsy is recommended in patients
magnetic resonance imaging (MRI) is much more accurate. As with a suspect biliary stricture or positive serum IgG4. In case of
treatment is mainly guided by the distinction between benign and intraluminal material like biliary casts, a removal of this material
malignant origin of the stricture, tissue retrieval is an important is mandatory, and bile collection for microbiological analysis is
issue in stricture management. I use endoscopic retrograde cholan- needed. In some cases the performance of a liver biopsy is
giography (ERC) to characterize stricture location and extention of helpful.
the stricture. Regarding imaging-guided tissue sampling, cholangi-
oscopy offers the best results. Histological workup shows typical
features of autoimmune diseases as well, and immunohistological Question 2: Secondary sclerosing cholangitis (SSC)
staining of biliary samples can reveal immunoglobulin (Ig) G4- in critically ill patients is an underdiagnosed
associated disease. emerging disease. What do you think is the best
way to diagnose SSC in critically ill patients?
Ehlken/Schramm: In case of a clinical suspicion for a new biliary
stricture, firstly we take a careful history including information on Dechêne: The typical history of pre-existing critical illness and/
previous imaging studies that helps establishing a reference for or previous severe disease including polytrauma as well as cardio-
comparison. Secondly, we recommend imaging studies with ab- vascular and infectious events guides the presumptive diagnosis in
dominal ultrasound as well as liver MRI plus magnetic resonance patients with clinical and serological signs of cholestasis. Septic
cholangiopancreatography (MRCP) to detect a mass lesion and to cholestasis can be excluded in most cases by the typical patterns of
specify where the stricture is localized. Our approach to verify ma- the laboratory results. Transcutaneous ultrasound often does not
lignancy would then be an endoscopic retrograde cholangiopan- show major pathology, given the rarefication of the biliary tract,
creatography (ERCP) with brush cytology and, if needed, biopsy – and MRI is precluded by the critical state the patients are in. We
also repeatedly and in conjunction with cholangioscopy. In pa- found that ERCP offers a sensitivity towards SSC but is invasive
tients with primary sclerosing cholangitis (PSC), additional fluo- and requires a considerable number of resources and staff to care
rescence in situ hybridization (FISH) of biliary brushings could for the critically ill patient.
enhance the sensitivity of brush cytology by around 20%.

© 2015 S. Karger GmbH, Freiburg Prof. Dr. med. Tim Lankisch

1662–6664/15/0313–0200$39.50/0 Klinik für Gastroenterologie, Hepatologie und Endokrinologie
Fax +49 761 4 52 07 14 Zentrum Innere Medizin, Medizinische Hochschule Hannover
Information@Karger.com Accessible online at: Carl-Neuberg-Straße 1, 30625 Hannover, Germany
www.karger.com www.karger.com/vim Lankisch.Tim@mh-hannover.de
 Ehlken/Schramm: Due to the absence of early markers, suspi- Question 4: Cancer surveillance is critical and
cion for SSC usually arises when the critically ill patient develops difficult in patients with PSC. What is your
strongly elevated cholestasis parameters; thus, especially serum AP surveillance strategy?
levels and SSC should always be on the list of differentials when the
patient becomes jaundiced after around 10–14 days in the absence Dechêne: I encourage every patient to find a specialized gastro-
of overt sepsis. To ascertain the diagnosis of SSC of the critically ill enterologist and see her or him at least twice a year. In PSC pa-
patient, MRCP and ERCP are the most sensitive modalities. ERCP tients with dominant biliary strictures and/or cholangitis, sampling
might have a better sensitivity to detect early changes of the biliary of suspicious strictured biliary segments either by brush cytology
tree, and it offers the possibility to remove biliary casts and to ob- or, if possible, by forceps biopsy is possible during ERC performed
tain bile fluid for microbiology. for decompression. A recently introduced digital cholangioscopy
system enables differentiation of vascular patterns in inflammatory
Kirchner: The best way to diagnose sclerosing cholangitis in versus malignant biliary lesions and shows promising first results
critically ill patients (SC-CIP) is an ERC. If ERC is not possible, towards image-guided tissue sampling. Patients without indica-
liver biopsy is the second best diagnostic tool, as reported in the tions for endoscopy will be sent for MRCP every 12 months. It is
literature. In patients with SCC the sensitivity and specificity of important to keep in mind that most PSC patients suffer from
MRCP or ultrasound is low. chronic inflammatory bowel disease (IBD) and should therefore
undergo colon cancer screening at least as often as IBD patients
without PSC.
Question 3: The optimal therapy of SSC in critical
patients remains unknown. How do you treat such Ehlken/Schramm: Unfortunately, we still lack prospective data
patients? on this important problem. Concerning cholangiocarcinoma and
gallbladder cancer, we would counsel the patient to undergo ab-
Dechêne: To be honest, treatment options are sparse – partly be- dominal ultrasound in 6-monthly intervals. Additionally, we
cause the triggering event has happened weeks or months before would argue for liver MRI plus MRCP every year. Given the in-
the onset of symptoms and cannot be controlled any more. The creased risk of colon cancer that comes with PSC-associated coli-
aim is therefore to prevent or slow down progressive biliary de- tis, our patients are advised to have colonoscopy with mapping
struction. Repeated ERCs enable the removal of biliary casts and biopsies every 1 (–2) years. The PSC patient without clinical or
the dilatation of strictures in a proportion of patients but carries histological signs of colitis would be counseled to undergo colo-
the risk of inducing infectious cholangitis. As mortality in SSC noscopy every 5 years.
arises mainly from septic complications, antibiotic treatment is fre-
quently necessary, and endoscopic bile sampling can help to iden- Kirchner: Cholangiocarcinoma often occurs within the first year
tify biliary bacterial flora. of PSC diagnosis. In patients with dominant biliary strictures, ERC
One of the most important treatment measures that should be with biliary brush cytology, biopsy, and cholangioscopy should be
offered to patients with progressive disease is orthotopic liver performed. Intraductal sonography may also be helpful, if availa-
transplantation (OLT). However, many patients are suffering from ble. In patients with dominant bile duct strictures and increased
severe comorbidities and are not eligible for OLT. cholestatic parameters, ERC should be repeated every 3–6 months.
FISH analyses for detection of chromosome abnormalities could
Ehlken/Schramm: In the critically ill patient with SSC, we would give additional hints regarding cholangiocarcinoma. In patients
recommend an ERCP for collection of bile for microbiology testing with mild PSC, MRCP should be performed once a year.
and subsequent antibiotic treatment, sphincterotomy, and removal
of biliary casts. The use of ursodeoxycholic acid seems a reasonable
option, although there are no controlled studies to recommend its Question 5: According to your experience, what is
use. Most importantly, however, depending on the dynamics and you approach to diagnose IgG4 cholangiopathy in
prognosis of the underlying disease, SSC of the critically ill pro- patients with biliary strictures of unknown origin?
gresses to end-stage liver disease in a large proportion of patients,
and liver transplantation is an option for some of these patients. Dechêne: The initial workup of biliary strictures potentially aris-
ing from autoimmunity in our center includes cross-sectional im-
Kirchner: In patients with SSC, ERC with removal of biliary aging (where pancreatic lesions typical for IgG4-related disease
casts and bile collection for microbiological investigation is needed. would be found), tissue sampling of biliary strictures and the major
Resistogram-based antibiotic therapy should be performed for 14 papilla (with immunohistological staining for IgG4), and measure-
days. Due to the poor outcome of SSC, patients should be evalu- ment of IgG4 levels in aspirated bile samples as well as in serum.
ated early for liver transplantation. In a number of patients with equivocal results and no evidence
of malignant disease, I use a 4-week course of steroid treatment be-
fore re-evaluation of treatment response as a diagnostic criterion.

Acute and Chronic Inflammation of the Biliary Viszeralmedizin 2015;31:200–203 201

System
 Ehlken/Schramm: Many if not most cases of IgG4 cholangiopa- Question 7: Preoperative staging in patients with
thy come along with autoimmune pancreatitis. If autoimmune bile duct cancer is of great importance prior to
pancreatitis is already proven, biliary strictures on MRCP should surgical resection. In some patients, however, the
raise a high level of suspicion for the diagnosis of IgG4 cholangio- diagnosis and staging remains inconclusive. When
pathy. For a definitive diagnosis, compatible findings on imaging do you perform explorative surgery?
studies should be complemented by increased levels of serum IgG4
and plasma cell infiltrates upon bile duct histology. However, it is Bektas: If there are no contraindications, we always recommend
difficult and sometimes impossible to differentiate IgG4-associated an exploratory laparotomy because in most cases this is the only
strictures from PSC and sometimes cholangiocarcinoma (CCA); way of assessing the operability.
therefore, a trial of steroids is warranted in many patients which
may not have a significant impact on the patient’s course with a Ehlken/Schramm: In any case of doubt regarding the suitability
final diagnosis of CCA or PSC. for surgical resection, we would recommend laparoscopy to ex-
clude peritoneal seeding or intrahepatic spread of CCA. Cross-sec-
Kirchner: In patients with biliary strictures of unknown origin, tional imaging cannot detect small intrahepatic lesions and early
detection of serum IgG4 and histology of the distal biliary duct and peritoneal carcinosis. At our center, we prefer mini-laparoscopy
the papilla Vateri is recommended. which is minimally invasive and can be performed even on an out-
patient basis.

Question 6: In acute cholecystitis the timing of Lang: We perform explorative laparotomy in all patients in
surgery is crucial. What is the maximal time interval whom preoperative diagnostic tools do not show a contraindica-
you allow between the onset of symptoms and tion for resection. Contraindications are:
surgery? And why? – distant metastases;
– extensive bilateral tumor growth far into both liver lobes; this
Bektas: The timing of surgery in acute cholecystitis is crucial. means ‘extended’ Bismuth type IV (early type IV is often resect-
According to the current data, acute cholecystitis should be treated able);
just like an acute appendicitis. If you want to operate in an interval, – ipsilateral extended biliary tumor growth and contralateral liv-
however, an interval of about 4–5 weeks after acute cholecystitis er atrophy, usually due to vascular invasion (typically in Bis-
should be adhered to. muth type IIIA and contralateral portal vein infiltration);
– ipsilateral extended tumor growth and contralateral vascular
Ehlken/Schramm: Early cholecystectomy is the treatment of invasion which cannot be managed by resection and recon-
choice. There are data and theoretical considerations on the grade struction of vessels.
of inflammation suggesting that surgery within 72 h after the onset
of symptoms or also within the first 7 days comes with a benefit for
the patient since hospitalization time was shorter, risk of bile duct Participants
injury was found to be lower, and conversion from laparoscopy to
open surgery was also less frequent. Prof. Dr. med. Hüseyin Bektas
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
In a patient with worsening symptoms despite adequate medical
Medizinische Hochschule Hannover
treatment and signs or symptoms of sepsis, such as hemodynamic Carl-Neuberg-Straße 1, 30625 Hannover, Germany
instability, emergency cholecystectomy must be evaluated irrespec- Bektas.Hueseyin @ mh-hannover.de
   

tive of the above considerations.

Dr. med. Alexander Dechêne
Klinik für Gastroenterologie und Hepatologie
Lang: In acute cholecystitis we try to perform surgery early, usu-
Universitätsklinikum Essen
ally laparoscopic cholecystectomy. Hufelandstraße 55, 45122 Essen, Germany
We aim to perform surgery within 24 h after the onset of symp- alexander.dechene @ uk-essen.de
   

toms; however, this is not a fixed rule. Depending on signs of in-

flammations (laboratory data as well as clinical signs), we usually Dr. med. Hanno Ehlken
I. Medizinische Klinik und Poliklinik
also accept 48 h or sometimes even longer. The decision for opera-
Universitätsklinikum Hamburg-Eppendorf
tion is always made on an individual basis. In cases with longer Martinistraße 52, 20246 Hamburg, Germany
onset of symptoms and danger for critical, serious condition, we h.ehlken @ uke.de
   

prefer conservative treatment and cholecystectomy in the later

period.

202 Viszeralmedizin 2015;31:200–203 Lankisch/Bektas/Dechêne/Ehlken/Kirchner/

Lang/Schramm
Prof. Dr. Gabriele I. Kirchner Prof. Dr. med. Christoph Schramm
Klinik und Poliklinik für Innere Medizin I I. Medizinische Klinik und Poliklinik
Universitätsklinikum Regensburg Universitätsklinikum Hamburg-Eppendorf
93042 Regensburg, Germany Martinistraße 52, 20246 Hamburg, Germany
Gabriele.Kirchner @ klinik.uni-regensburg.de
    c.schramm @ uke.de
   

Prof. Dr. med. Hauke Lang

Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
Universitätsmedizin Mainz
Langenbeckstraße 1, 55131 Mainz, Germany
hauke.lang @ unimedizin-mainz.de