Biliary complications after liver transplantation: old problems and new challenges.

Due to a vulnerable blood supply of the bile ducts, biliary complications are a major source of morbidity after liver transplantation (LT). Manifestation is either seen at the anastomotic region or at multiple locations of the donor biliary system, termed as nonanastomotic biliary strictures. Major risk factors include old donor age, marginal grafts and prolonged ischemia time. Moreover, partial LT or living donor liver transplantation (LDLT) and donation after cardiac death (DCD) bear a markedly higher risk of biliary complications. Especially accumulation of several risk factors is critical and should be avoided. Prophylaxis is still a major issue; however no gold standard is established so far, since many risk factors cannot be influenced directly. The diagnostic workup is mostly started with noninvasive imaging studies namely MRI and MRCP, but direct cholangiography still remains the gold standard. Especially nonanastomotic strictures require a multidisciplinary treatment approach. The primary management of anastomotic strictures is mainly interventional. However, surgical revision is finally indicated in a significant number of cases. Using adequate treatment algorithms, a very high success rate can be achieved in anastomotic complications, but in nonanastomotic strictures a relevant number of graft failures are still inevitable.

Tumor necrosis factor alpha inhibitors as immunomodulatory antirejection agents after intestinal transplantation.

We reported the successful administration of infliximab for late-onset OKT3-resistant rejection in two patients, who presented persistent ulcerative inflammation of the ileal graft after intestinal transplantation (ITX). Based on this experience, the present study demonstrated our long-term experience with infliximab for different types of rejection-related and inflammatory allograft alterations. Infliximab administration (5 mg/kg body weight (BW)) was initiated at a mean of 18.2 ± 14.1 months after transplantation. The number of administrations per patient averaged 8.4 ± 6.7. Repeat dosing was timed according to clinical signs and graft histology in addition to serum-levels of tumor necrosis factor alpha (TNFα), lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP). Infliximab was successful in the following patients: patients with late-onset OKT3- and steroid-refractory rejection who presented persistent ulcerative alterations of the ileal graft (n = 5), patients with ulcerative ileitis/anastomositis, who did not show typical histological rejection signs (n = 2), and one patient with early-onset OKT3-resistant rejection. Infliximab was not successful in one patient with early-onset OKT3-resistant rejection that was accompanied by treatment-refractory humoral rejection. In conclusion, infliximab can expand therapeutic options for late-onset OKT3- and steroid-refractory rejection and chronic inflammatory graft alterations in intestinal allograft recipients.

Management and outcomes of haemorrhage after pancreatogastrostomy versus pancreatojejunostomy.

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a major cause of morbidity and mortality after pancreaticoduodenectomy (PD). It remains unclear whether performance of a pancreatogastrostomy (PG) instead of a pancreatojejunostomy (PJ) improves outcomes owing to better endoscopic accessibility. METHODS: A large retrospective analysis was undertaken to compare outcomes of PPH, depending on whether a PG or PJ was performed. The primary outcome was the rate of successful endoscopy. A secondary outcome was the therapeutic success after adding surgery. RESULTS: Of 944 patients who had a PD, 8·4 per cent developed PPH. Endoscopy was the primary intervention in 21 (81 per cent) of 26 patients with a PG and 34 (64 per cent) of 53 with a PJ; it identified the bleeding site in 35 and 25 per cent respectively (P = 0·347). Successful endoscopic treatment was more common in the PG group (31 versus 9 per cent; P = 0·026). Surgery was performed for PPH in 15 patients (58 per cent) with a PG and 35 (66 per cent) with a PJ (P = 0·470). The majority of haemorrhages that required surgery were non-anastomotic intra-abdominal haemorrhages (12 of 15 versus 21 of 35; P = 0·171). Endoscopic or conservative treatment for PPH was successful in 42 per cent of patients with a PG and 32 per cent with a PJ (P = 0·520). The success rate increased to 85 and 91 per cent respectively when surgery was included in the algorithm (P = 0·467). CONCLUSION: The type of pancreatic anastomosis and its inherent effect on endoscopic accessibility had very little impact on the outcome of PPH. This was because haemorrhage frequently occurred from intra-abdominal or non-anastomotic intraluminal lesions.

[Stenosis and iatrogenic perforation as complication following long-term stenting of the oesophagus]. / Narbige Stenose und iatrogene Perforation als -Komplikation nach Langzeitstenting des Ösophagus.

Anastomotic leaks after oesophagojejunostomy usually are treated by endoluminal stenting with self-expandable metal or plastic stents. Here we present a patient with more than 4 years of oesophageal stenting for anastomotic leakage after gastrectomy. During the attempted removal of the stent he experienced a perforation of the jejunum. Emergency surgery with complete resection of the stent and transhiatal oesophagojejunostomy was performed. Generally, early removal of oesophageal stents 4-6 weeks after implantation is recommended, as later attempts often fail and may lead to extensive surgery.

Feasibility of hepatic radiofrequency ablation in patients with bilioenteric anastomoses.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) in the liver is contraindicated in the presence of bilioenteric anastomoses, because it predisposes to occasionally devastating infectious complications. The purpose of this single-center experience is to demonstrate the technical feasibility of such procedures. METHODOLOGY: Patients with bilioenteric anastomoses were offered ultrasound-guided RFA, if an interdisciplinary tumor board endorsed this decision, or an intraoperative opportunity to achieve a tumor-free situation emerged. All procedures were carried out under general anesthesia in a surgical operation theatre. RFA was performed percutaneously (n=3) and open surgically (n=3) with two different types of monopolar devices. All patients received antibiotic prophylaxis with various different agents. RESULTS: Six patients with seven tumor nodules were treated. The average age of the patients was 59 +/- 7 years. Mean size of the tumors was 20 +/- 7 mm. Median follow up was 15 months. No infectious complication including intrahepatic abscess occurred. No local recurrence was detected. CONCLUSIONS: The presented data indicates the feasibility of RFA in patients with bilioenteric anastomoses, and infectious problems, namely intrahepatic abscess formation, do not inevitably occur. The role of antimicrobial prophylaxis remains unclear. The importance of ensuring an unobstructed and uninhibited biliary flow distally in the bilioenteric track is stressed.

[Clinical and pathological prognostic factors for cancers of the esophagogastric junction]. / Klinisch-pathologische Prognosefaktoren des Adenokarzinoms des gastroösophagealen Ubergangs.

INTRODUCTION: Adenocarcinoma of the esophagogastric junction (AEG) is a particular tumour entity because two substantially different surgical procedures are required according to the location. There is no difference in long-term prognosis between the tumour types in spite of the different surgical procedures. We were interested to evaluate the clinical and pathological prognostic factors of the AEGs which were operated in our department. PATIENTS AND METHODS: 108 patients were operated for AEG between 1.1.2000 and 1.4.2006 in our institution. 32 (29.6 %) patients with distal esophageal cancer (type I according to Siewert) underwent a transthoracic esophagectomy with gastric pull-up and two-field lymphadenectomy. 57 (52.8 %) patients with type II and 19 (17.6 %) patients with type III cancers received an extended gastrectomy with D2 lymphadenectomy. The retrospective analysis was focused on clinical and pathological parameters. Possible differences between the tumour types were also evaluated. Median follow-up was 11.4 months (range: 1-57 months). RESULTS: Follow-up data were complete for 107 patients. A median survival of 17.4 +/- 3.25 months and a cumulative survival of 30 % were independent of the tumour location and the surgical procedure. Overall hospital mortality was 3.7 %. The univariate analysis showed that survival was significantly associated with the T category, lymph node status, lymphangio- and angioinvasion and tumour grading. In the multivariate analysis, only lymph node status was identified as an independent prognosis factor for survival. Where-as the R status was not a prognostic factor per se, how-ever, patients with an R0 situation without lymphangio- and angioinvasion had a significantly better survival compared to all other patients (p = 0.001). An increased angioinvasion rate was observed in type III tumours (52.6 %) in comparison to type I (21.9 %) and type II (21.1 %) tumours. CONCLUSION: The prognostic factors of our patients determined substantially the prognosis of the patients. Patients with lymph- or haemangioinvasion should regarded as high-risk patients independent of the R status. Close oncological follow-up including potential adjuvant treatment in these patients is recommended.

A prospective randomised study on narrow-band imaging versus conventional colonoscopy for adenoma detection: does narrow-band imaging induce a learning effect?

BACKGROUND AND AIMS: Colonoscopy is an established method of colorectal cancer screening, but has an adenoma miss rate of 10-20%. Detection rates are expected to improve with optimised visualisation methods. This prospective randomised study evaluated narrow-band imaging (NBI), a new technique that may enhance image contrast in colon adenoma detection. METHODS: Eligible patients presenting for diagnostic colonoscopy were randomly assigned to undergo wide-angle colonoscopy using either conventional high-resolution imaging or NBI during instrument withdrawal. The primary outcome parameter was the difference in the adenoma detection rate between the two techniques. RESULTS: A total of 401 patients were included (mean age 59.4 years, 52.6% men). Adenomas were detected more frequently in the NBI group (23%) than in the control group (17%) with a number of 17 colonoscopies needed to find one additional adenoma patient; however, the difference was not statistically significant (p = 0.129). When the two techniques were compared in consecutive subgroups of 100 study patients, adenoma rates in the NBI group remained fairly stable, whereas these rates steadily increased in the control group (8%, 15%, 17%, and 26.5%, respectively). Significant differences in the first 100 cases (26.5% versus 8%; p = 0.02) could not be maintained in the last 100 cases (25.5% versus 26.5%, p = 0.91). CONCLUSIONS: The increased adenoma detection rate means of NBI colonoscopy were statistically not significant. It remains speculative as to whether the increasing adenoma rate in the conventional group may have been caused by a training effect of better polyp recognition on NBI.

[Therapy of chronic persisting biloma after liver resection by enteral drainage]. / Therapie chronisch persistierender Biliome nach Leberresektion durch enterale Drainage.

Postoperative bile leaks represent a typical complication in liver surgery with a frequency ranging from 5 % to 12 % in large series. The treatment of choice is usually conservative. Using sufficient transcutaneous drainage with flushing of the biloma cavity and endoscopic retrograde cholangiography (ERC) with sphincterotomy and possibly stenting, the cure rate of bile leaks is approximately 95 %. In very rare cases all of these measures remain unsuccessful especially in cases of leakage from separated liver segments without connection to the main bile duct system. In relevantly separated liver segments this can lead to a chronically secreting bile fistula.We report a series of seven patients after complex liver resections, in which a chronic bile cavity was definitively treated with a jejunum loop as internal drainage. The prior conservative therapy included cavity suction drainage and optionally an additional ERC with or without stent insertion. After several weeks of bile leak persistence and radiological confirmation of suturable bile wall the operative treatment was carried out. The biloma cavity was careful dissected, opened and anastomosed with a jejunal loop. The further postoperative course was uncomplicated in all patients.It is possible to treat chronic persistent bile leaks safely and effectively by internal drainage through the jejunal loop after formation of a suturable biloma cavity membrane.

[Impact of the body mass index on the prognosis and complication rate after surgical resection of cancers at the oesophagogastric junction]. / Einfluss des Body-Mass-Index auf die Prognose und Komplikationsrate nach Resektion beim Kardiakarzinom.

BACKGROUND: An elevated body mass index (BMI) is associated with an increased incidence of cancer at the gastro-oesophageal junction. Less is known about the postoperative complication rate and prognosis in relation to the BMI. PATIENTS AND METHODS: We investigated 108 patients with cancer of the cardia and a BMI below (group 1, n = 56) or above (group 2, n = 52) 25 kg / m (2), who were operated from 2000 to 2006 in our department. According to the Siewert classification, the tumours were subdivided into 3 types. Patients with type I cancers (n = 26) received a transthoracic oesophageal resection with gastric pull up. Patients with type II (n = 61) or type III (n = 21) cancers underwent an extended gastrectomy. The complication rates and survival were analysed. RESULTS: The complications were pulmonary (respiratory insufficiency n = 12, pneumonia n = 12, bronchitis n = 7, pulmonary embolism n = 2), surgical (anastomotic leakage n = 7, abscesses n = 8, bleeding n = 2, chylus fistula n = 1), or functional (dysphagia n = 5, nausea n = 5, heart burn n = 4, delayed enteral passage n = 6, vomiting n = 9). Patients of group 2 showed more delayed enteral passages (5 vs. 1) and more vomiting (7 vs. 2) than those of group 1. The median stay in the intensive care unit was shorter in group 1 than in group 2 (3 vs. 5 days) (p = 0.021). Overall hospitalisation was 14 days in the mean in both groups. We found no significant difference in the postoperative mortality of 6.5 % (n = 7) between the two groups. Overall survival after a follow-up of 42 months was 34 % (group 1) and 25 % (group 2). The difference did not reach statistical significance (p = 0.961). Patients with an elevated BMI show slightly more complications than those with a lower BMI. CONCLUSIONS: Our data show that patients with elevated BMI have slightly more complications and an identical long term survival as patients with normal body weight.

[Acute pancreatitis and duodenobiliary fistula--a rare complication of Crohn's disease]. / Akute Pankreatitis und choledochobulbäre Fistel--eine seltene Komplikation bei Morbus Crohn.

HISTORY: A 53-year-old man with long-standing Crohn's disease presented with recurrent abdominal pain and vomiting; lipase levels were elevated. INVESTIGATIONS AND DIAGNOSIS: At admission ultrasound demonstrated a swollen head of the pancreas, dilated pancreatic and intrahepatic bile ducts and peripancreatic fluid. At upper gastrointestinal endoscopy a 10 mm bleeding ulcer was identified, which histologically proved to be epitheloid cell-containing granulomas. A fistula connecting to the hepatocholedochal duct was identified at the floor of the ulcer. Helicobacter pylori was not demonstrated. TREATMENT AND COURSE: After sphincterotomy of the papilla of Vater concrements were extracted and a stent was implanted into the common bile duct. Ultimately a total of five stents were consecutively implanted via the major papilla, closing the fistula. After three years all stents were removed and pancreatitis did not recur. CONCLUSION: The differential diagnosis of abdominal pain in patients with Crohn's disease is often difficult and should include fistulas of the upper gastrointestinal tract which may be treated endoscopically.

[Endoscopic therapy of acute and chronic pancreatitis]. / Endoskopische Therapie bei akuter und chronischer Pankreatitis.

Endoscopic therapy is valuable for both acute and chronic pancreatitis. Early endoscopic papillotomy appears, in the case of a severe course of acute biliary pancreatitis, to be advantageous. Endoscopic drainage can be considered in cases of acute fluid retention and necrosis as well as subacute, non-healing pancreatitis or cyst development. By acute chronic pancreatitis with strictures or bile duct stones, papillotomy, dilation and stent insertion can lead to an improvement in pain symptoms. An improvement in endo- or exocrine function, however, is not expected. Studies on the endoscopic therapy of pancreatitis are still very limited, and recommendations can usually only be made based on retrospective case series.

[Clinical results of intestinal and multivisceral transplantation at the Charité, Berlin. A case series]. / Klinische Ergebnisse der Dünndarm- und Multiviszeraltransplantation an der Berliner Charité - Eine Fallserie -

BACKGROUND AND OBJECTIVE: Intestinal transplantation (ITx) is the only causal therapy of short bowel syndrome (SBS). Long-term survival after ITx has been improved significantly during the last years. The experience with ITx at the Charite, Campus Virchow Klinikum, are described and discussed. PATIENTS AND METHODS: Twelve isolated ITx and one multivisceral transplantation (including stomach, pancreatodudenal complex, small intestine, liver, ascending colon, right kidney, and adrenal gland) were performed. Mean recipient age was 37.7+/-10.6 yrs (median: 35 yrs; range: 27 - 58 yrs; M:F = 8:5). All patients had irreversible SBS (0 - 30 cm residual bowel length; mean: 11.8+/-11.4 cm; median: 13 cm). RESULTS: 6-months and 1-year patient and graft survival were 85 % (11/13) and 77 % (10/13), respectively. Reasons for graft loss and patient death were necrotizing enterocolitis, severe, muromonab-resistent, acute rejection, and graft ischemia due to complex coagulopathy. All other patients had good long-term outcome. They received enteral nutrition at six hours after operation and were persistently off total parenteral nutrition (TPN) by week two after ITx. CONCLUSION: ITx as established in our centre, with 1-year-patient and graft survival rates of 77 %, reflects current international standard. ITx is complementary to conservative and other operative methods of treating SBS. Referral and indication criteria need wider dissemination to prevent life-threatening complications of TPN.

Magnetic resonance cholangiopancreatography-guided unilateral endoscopic stent placement for Klatskin tumors.

BACKGROUND: Advanced and incurable Klatskin tumors of Bismuth-type III and IV cause obstructive jaundice. Palliation of patients with Klatskin tumors is usually carried out by bilateral endoscopic stent placement. Endoscopic retrograde cholangiography (ERC) in such patients is associated with a comparatively high morbidity and mortality mainly due to postprocedure bacterial cholangitis. To reduce ERC-related complications the outcome of replacing ERC with magnetic resonance cholangiopancreatography (MRCP) was investigated. Subsequently, unilateral contrast injection and stent placement were performed, thus avoiding bilateral contrast injection and stent insertion. METHODS: Patients thought to have a Klatskin tumor underwent clinical evaluation, laboratory, and noninvasive imaging studies before ERC. Patients were enrolled in this feasibility study if investigators agreed with the clinical diagnosis of an advanced and incurable Klatskin tumor. MRCP images were used to determine the predominate ductal drainage for the liver segments thus directing stent placement. Based on these findings, unilateral ERC and subsequent unilateral stent placement were performed. Antibiotics were not given before ERC. Amsterdam-type stents (10F) were placed and replaced routinely at 2 months. In cases of earlier occlusion, the stents were replaced immediately. RESULTS: Thirty-five patients underwent MRCP, ERC, and unilateral stent deployment. Two further patients enrolled after MRCP were withdrawn because ERC could not be carried out. In 35 patients with unilateral stents bilirubin levels decreased (18.9 +/- 6.3 mg/dL to 3.2 +/- 2.3 mg/dL) and jaundice resolved in 86%. After first stent deployment, post-ERC bacterial cholangitis occurred in 6% (2 of 35) of patients. CONCLUSIONS: This new method of MRCP-guided endoscopic unilateral stent placement could reduce ERC-related complications caused by initial stent deployment. The results of this study justify a randomized prospective comparative trial.

Complete bile duct sequestration after liver transplantation, caused by ischemic-type biliary lesions.

Ischemic-type biliary lesions (ITBLs) are the most frequent cause of nonanastomotic biliary strictures in liver grafts, affecting about 2-19 % of patients after liver transplantation. ITBL is characterized by bile duct destruction, subsequent stricture formation, and sequestration. We report here the case of a patient affected by extremely severe ITBL, with sequestration and disintegration of the entire bile duct system, in which it was possible to extract the complete biliary tree endoscopically in a single piece. Histological examination revealed that all cells of the bile duct wall had been destroyed within 3 months after liver transplantation and replaced by connective tissue. Subsequently, biliary stricture formation occurred at the hepatic hilum, as well as the adjacent large bile ducts. It may be hypothesized that cellular rejection of small bile ducts leads to the vanishing bile duct syndrome, whereas cellular rejection of large bile ducts results in ITBL. The strictures were repeatedly dilated by endoscopic means, allowing successful control of stricture formation, as well as maintenance of liver function. At the time of writing, the grafted organ and the patient had survived for more than 3 years in good health. This is the first detailed report on a sequestration of the entire bile duct system caused by ITBL, successfully treated for several years by endoscopic means.