Percutaneous-endoscopic rendezvous procedure for the management of bile duct injuries after cholecystectomy: short- and long-term outcomes.

BACKGROUND: Bile duct injury (BDI) remains a daunting complication of laparoscopic cholecystectomy. In patients with complex BDI, a percutaneous-endoscopic rendezvous procedure may be required to establish bile duct continuity. The aim of this study was to assess short- and long-term outcomes of the rendezvous procedure. METHODS: All consecutive patients with BDI referred to our tertiary referral center between 1995 and 2016 were analyzed. A rendezvous procedure was performed when endoscopic or radiologic intervention failed, and when deemed feasible by a dedicated multidisciplinary team including hepatopancreaticobiliary surgeons, gastrointestinal endoscopists, and interventional radiologists. Classification of BDI, technical success of the rendezvous procedure, procedure-related adverse events, and outcomes were assessed. RESULTS: Among a total of 812 patients, rendezvous was performed in 47 (6 %), 31 (66 %) of whom were diagnosed with complete transection of the bile duct (Amsterdam type D/Strasberg type E injury). The primary success rate of rendezvous was 94 % (44 /47 patients). Overall morbidity was 18 % (10 /55 procedures). No life-threatening adverse events or 90-day mortality occurred. After a median follow-up of 40 months (interquartile range 23 - 54 months), rendezvous was the final successful treatment in 26 /47 patients (55 %). In 14 /47 patients (30 %), rendezvous acted as a bridge to surgery, with hepaticojejunostomy being chosen either primarily or secondarily to treat refractory or relapsing stenosis. CONCLUSIONS: In experienced hands, rendezvous was a safe procedure, with a long-term success rate of 55 %. When endoscopic or transhepatic interventions fail to restore bile duct continuity in patients with BDI, rendezvous should be considered, either as definitive treatment or as a bridge to elective surgery.

Temoporfin improves efficacy of photodynamic therapy in advanced biliary tract carcinoma: A multicenter prospective phase II study.

UNLABELLED: Photodynamic therapy using porfimer (P-PDT) improves palliation and survival in nonresectable hilar bile duct cancer. Tumoricidal penetration depth of temoporfin-PDT (T-PDT) is twice that of P-PDT. In a single-arm phase II study we investigated the safety, efficacy, survival time, and adverse events of T-PDT compared with previous data on P-PDT. Twenty-nine patients (median 71 [range 47-88] years) with nonresectable hilar bile duct cancer were treated with T-PDT (median 1 [range 1-4] sessions) plus stenting and followed up every 3 months. The PDT was well tolerated. In patients with occluded segments at baseline (n=28) a reopening of a median of 3 (range 1-7) segments could be achieved: n=16 local response and n=11 stable local disease, one progressive disease. Cholestasis and performance significantly improved when impaired at baseline. Time to local tumor progression was a median of 6.5 (2.7-41.0) months. Overall survival time was a median of 15.4 (range 4.4-62.4) months. Patients died from tumor progression (55%), cholangitis (18%), pneumonia (7%), hemobilia (7%), esophagus variceal hemorrhage (3%), and vascular diseases (10%). Adverse events were cholangitis (n=4), liver abscess (n=2), cholecystitis (n=2), phototoxic skin (n=5), and injection site reactions (n=7). Compared to previous P-PDT, T-PDT shows prolonged time to local tumor progression (median 6.5 versus 4.3 months, P<0.01), fewer PDT treatments needed (median 1 versus 3, P<0.01), a higher 6-month survival rate (83% versus 70%, P<0.01), and a trend for longer overall median survival (15.4 versus 9.3 months, P=0.72) yet not significantly different. The risk of adverse events is not increased except for (avoidable) subcutaneous phototoxicity at the injection site. CONCLUSION: Temoporfin-PDT can safely be delivered to hilar bile duct cancer patients and results in prolonged patency of hilar bile ducts, a trend for longer survival time, and similar palliation as with P-PDT.

Prospective evaluation of ERCP performance: results of a nationwide quality registry.

BACKGROUND AND STUDY AIMS: Despite significant interest from health care authorities, patient organizations, and insurance companies, data on procedural outcome and quality of endoscopic retrograde cholangiopancreatography (ERCP) in general and academic practice are sparse. The aims of this study were to assess procedural outcome of ERCP within a large prospective registry in The Netherlands, and to evaluate associations between endoscopist-related factors and procedural outcome. METHODS: All endoscopists performing ERCP in The Netherlands were invited to register their ERCPs over a 1-year period using the Rotterdam Assessment Form for ERCP (RAF-E). The primary outcome measure was procedural success. A priori difficulty level of the procedure was classified according to Schutz. Baseline characteristics of the endoscopist (e. g. previous experience) were recorded at study entry. Regression analysis was performed to identify predictors of procedural outcome. RESULTS: A total of 8575 ERCPs were registered by 171 endoscopists from 61 centers, constituting about 50 % of all ERCPs performed nationally during the study period. Overall procedural success was 85.8 %. Intact papillary anatomy was present in 5106 patients (59.5 %): procedural success in this subgroup of patients was 83.4 % vs. 89.4 % after sphincterotomy (P < 0.001). Multivariate logistic regression identified "degree of difficulty," "intact papillary anatomy," and "previous ERCP failure" to be independently associated with procedural failure. "Yearly volume of ERCPs" and "trainee involvement" were independently associated with success. CONCLUSIONS: The nationwide prospective RAF-E registry proved to be a valuable tool to gain insight into procedural outcome of ERCPs.

Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial.

BACKGROUND: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. METHODS/DESIGN: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. DISCUSSION: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma. TRIAL REGISTRATION: Netherlands Trial Register [ NTR4243 , 11 October 2013].

Competence development in ERCP: the learning curve of novice trainees.

BACKGROUND AND STUDY AIM: Measures for competence in endoscopic retrograde cholangiopancreatography (ERCP) during training are poorly defined. Currently, various training and accreditation programs base verification of competence on performance of a minimum number of procedures. There is a general awareness that procedural competence certification should be based on objective performance criteria. Continuous self-assessment using a Rotterdam Assessment Form for ERCP (RAF-E) can provide insight into trainee performance. The study aim was to express development in ERCP competence as a learning curve. METHODS: ERCP trainees at a tertiary referral center in the Netherlands were invited to participate. Performed procedures were appraised using RAF-E. Indication for each ERCP and presence of a virgin papilla were documented. Complexity was graded on a 3-point scale. The primary outcome parameter was common bile duct (CBD) cannulation success rate. Success of the intended therapeutic interventions was additionally expressed as a learning curve. RESULTS: 15 trainees were included. 1541 ERCPs (624 procedures in native papillary anatomy) were assessed through RAF-E. Unassisted CBD cannulation success rate improved from 36 % at baseline to 85 % after 200 procedures (P < 0.001), and in 624 patients with a virgin papilla from 22 % at baseline to 68 % after 180 procedures (P < 0.001). Learning curves for therapeutic interventions showed significant improvements for successful sphincterotomy (P = 0.01) and stent placement (P < 0.001). CONCLUSIONS: Learning curves are a valuable means for assessing competence in ERCP. Differences in learning curves can be shown with RAF-E. Verification of competence should be based on actual performance, instead of minimum numbers.

Preoperative biliary drainage for cancer of the head of the pancreas.

BACKGROUND: The benefits of preoperative biliary drainage, which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head, are unclear. METHODS: In this multicenter, randomized trial, we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head. Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter (2.3 to 14.6 mg per deciliter) were randomly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks, followed by surgery, or surgery alone within 1 week after diagnosis. Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retrograde cholangiopancreatography. The primary outcome was the rate of serious complications within 120 days after randomization. RESULTS: We enrolled 202 patients; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage; 6 patients were excluded from the analysis. The rates of serious complications were 39% (37 patients) in the early-surgery group and 74% (75 patients) in the biliary-drainage group (relative risk in the early-surgery group, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). Preoperative biliary drainage was successful in 96 patients (94%) after one or more attempts, with complications in 47 patients (46%). Surgery-related complications occurred in 35 patients (37%) in the early-surgery group and in 48 patients (47%) in the biliary-drainage group (relative risk, 0.79; 95% CI, 0.57 to 1.11; P=0.14). Mortality and the length of hospital stay did not differ significantly between the two groups. CONCLUSIONS: Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications. (Current Controlled Trials number, ISRCTN31939699.)

Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis.

BACKGROUND & AIMS: A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. METHODS: Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. RESULTS: During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. CONCLUSIONS: In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.

Surgical treatment of gastrinomas: a single-centre experience.

BACKGROUND: Gastrinomas are rare neuroendocrine tumours, and responsible for Zollinger-Ellison syndrome (ZES). Surgery is the only treatment that can cure gastrinomas. The success of surgical treatment of gastrinomas in a single centre was evaluated. METHODS: A retrospective review of all patients who underwent resection for a gastrinoma between 1992 and 2011 at a single institution was performed. Presentation, diagnostics, operative management and outcome were analysed. RESULTS: Eleven patients with a median age of 46 years were included. All patients had fasting hypergastrinaemia and a primary tumour was localized using imaging studies in all patients. A pylorus-preserving pancreaticoduodenectomy was performed in three patients: two patients underwent duodenectomy and one patient central pancreatectomy. The remaining five patients underwent enucleation. A primary tumour was removed in nine patients: five tumours were situated in the pancreas, three in the duodenum and one patient was considered to have a primary lymph node gastrinoma. The median follow-up was 3 years (range 1-15) after which 7 patients were disease-free and 3 patients had (suspected) metastatic disease. One patient died 13 years after initial surgery. CONCLUSION: The success of surgical treatment of a gastrinoma in this series was 7/11 with a median follow-up of 3 years; comparable to recent published studies.

Extent of liver resection for hilar cholangiocarcinoma (Klatskin tumor): how much is enough?

BACKGROUND: Hilar resection in combination with extended liver resections has resulted in a higher rate of R0 resections and increased survival in patients with hilar cholangiocarcinoma (HCCA). This aggressive surgical approach is, however, associated with high rates of operative morbidity and mortality, largely due to postresectional liver failure. We previously reported a series after resection of HCCA in which R0 resection rate was 59% with a mortality rate of 10%. In this study, we assessed mortality of extended liver resections after optimizing liver functional reserve and application of parenchyma-sparing techniques. METHODS: From 2008 until June 2010, 41 consecutive patients underwent resection on the suspicion of HCCA. Preoperative workup included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. Modified right and left extended hemihepatectomies were performed preserving parts of segments 4 and 8, respectively, while pursuing complete excision of the tumor. Outcomes of resection were evaluated. RESULTS: The majority of resections (78%) were performed for Bismuth type III-IV tumors. Preoperative biliary drainage was undertaken in 37 (90%) patients. Hilar resection in combination with liver resection was performed in 35 (85%) patients. Of these resections, 61% were modified extended resections including central liver resections. The R0 resection rate was 92%. Postoperative morbidity and mortality rates were 54 and 7%, respectively. CONCLUSION: Strategies to optimize liver function and to reduce removal of functional liver parenchyma were associated with a decrease in mortality (7%) while undertaking extended resection for HCCA with an R0 resection rate of 92%.

Therapeutic delay and survival after surgery for cancer of the pancreatic head with or without preoperative biliary drainage.

OBJECTIVE: To evaluate the relation between delay in surgery because of preoperative biliary drainage (PBD) and survival in patients scheduled for surgery for pancreatic head cancer. BACKGROUND: Patients with obstructive jaundice due to pancreatic head cancer can undergo PBD. The associated delay of surgery can lead to more advanced cancer stages at surgical exploration, affecting resection rate and survival. METHODS: We conducted a multicenter, randomized controlled clinical trial to compare PBD with early surgery (ES) for pancreatic head cancer for complications. We obtained Kaplan-Meier estimates of overall survival for patients with pathology-proven malignancy and compared survival functions of ES and PBD groups using log-rank test statistics. Multivariable Cox regression analyses were performed to evaluate the prognostic role of time to surgery for overall survival. RESULTS: Mean times from randomization to surgery were 1.2 (0.9-1.5) and 5.1 (4.8-5.5) weeks in the ES and PBD groups, respectively (P < 0.001). In the ES group, 60 (67%) of 89 patients underwent resection, versus 53 (58%) of 91 patients in the PBD group (P = 0.20). Median survival after randomization was 12.2 (9.1-15.4) months in the ES group versus 12.7 (8.9-16.6) months in the PBD group (P = 0.91). A longer time to surgery was significantly associated with slightly lower mortality rate after surgery (hazard ratio = 0.90, 95% CI, 0.83-0.97), when taking into account resection, bilirubin, complications, pancreatic adenocarcinoma, tumor-positive lymph nodes, and microscopically residual disease. CONCLUSIONS: In patients with pancreatic head cancer, the delay in surgery associated with PBD does not impair or benefit survival rate.

Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis.

BACKGROUND: For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS: All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS: Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS: Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-trials.com].).

Immunoglobulin G4-associated cholangitis: one variant of immunoglobulin G4-related systemic disease.

IgG4-associated cholangitis (IAC) is a recently defined disease entity which shares a number of clinical, biochemical, and radiological features with primary sclerosing cholangitis (PSC). In contrast to PSC, IAC responds to immunosuppressive treatment, is not associated with inflammatory bowel disease, and mainly affects elderly men above the age of 60 years. Today, IAC is regarded as one variant of IgG4-related systemic disease (ISD) of which autoimmune pancreatitis (AIP) is the best studied organ manifestation. The diagnosis of IAC is based on biochemical, radiological and histologic features, among which elevated serum levels of IgG4, extra- and intrahepatic biliary strictures as visualized by cholangiography, multifocal IgG4-rich lymphoplasmacytic sclerosing infiltrations in liver and bile duct tissue, and association with AIP are of key importance. This review aims at summarizing clinical features, diagnostic criteria, therapeutic strategies and most recent insights in the pathophysiology of IAC and other organ manifestations of ISD.

Intrabiliary Migrated Clips and Coils as a Nidus for Biliary Stone Formation: A Rare Complication following Laparoscopic Cholecystectomy.

Clips inserted during laparoscopic cholecystectomy (LC) may migrate into the biliary system and function as a nidus for the formation of gallstones. Here, we present a series of 4 patients who presented with this rare complication 5-17 years after LC. All 4 patients presented with symptomatic choledocholithiasis with biochemical and radiological signs of biliary obstruction. Three patients also had fever and infectious parameters, compatible with concurrent cholangitis. All patients successfully underwent endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy and stone extraction. Patients with cholangitis also had antibiotic treatment. In 3 patients, obstruction of the common bile duct was caused by a single, relatively large stone that had formed around a clip (supposedly the cystic duct clip). In 1 patient, multiple stones had formed around an intrabiliary migrated cluster of coils that had been used for arterial embolization of a pseudo-aneurysm of the right hepatic artery. In conclusion, surgical clips and coils can migrate into the biliary tract and serve as a nidus for the formation of bile duct stones. Although rare, this complication should caution surgeons not to place clips "at random" during cholecystectomy. Patients with this rare complication are best managed by ERCP in combination with sphincterotomy and stone extraction.

Endoscopic versus percutaneous biliary drainage in patients with resectable perihilar cholangiocarcinoma: a multicentre, randomised controlled trial.

BACKGROUND: In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma. METHODS: We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 µmol/L [2·9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243. FINDINGS: From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3·67, 95% CI 1·15-11·69; p=0·03). Three of the 11 deaths among patients in the percutaneous transhepatic biliary drainage group occurred before surgery. The proportion of patients with severe preoperative drainage-related complications was similar between the groups (17 [63%] patients in the percutaneous transhepatic biliary drainage group vs 18 [67%] in the endoscopic biliary drainage group; relative risk 0·94, 95% CI 0·64-1·40). 16 (59%) patients in the percutaneous transhepatic biliary drainage group and ten (37%) patients in the endoscopic biliary drainage group developed preoperative cholangitis (p=0·1). 15 (56%) patients required additional percutaneous transhepatic biliary drainage after endoscopic biliary drainage, whereas only one (4%) patient required endoscopic biliary drainage after percutaneous transhepatic biliary drainage. INTERPRETATION: The study was prematurely stopped because of higher all-cause mortality in the percutaneous transhepatic biliary drainage group. Post-drainage complications were similar between groups, but the data should be interpreted with caution because of the small sample size. The results call for further prospective studies and reconsideration of indications and strategy towards biliary drainage in this complex disease. FUNDING: Dutch Cancer Foundation.

Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial).

BACKGROUND: Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. METHODS/DESIGN: Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). DISCUSSION: The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor.

Stent patency in patients with distal malignant biliary obstruction receiving chemo(radio)therapy.

BACKGROUND AND STUDY AIMS: Recent literature suggests that chemo(radio)therapy might reduce the patency of plastic stents in patients with malignant biliary obstruction. Whether this might also be valid for other types of stents is unknown. The aim of this study was to determine the influence of chemo(radio)therapy on the patency of fully-covered self-expandable metal stents (FCSEMSs) and plastic stents. PATIENTS AND METHODS: We retrospectively reviewed the electronic medical records of patients with distal malignant biliary obstruction who underwent biliary stent placement between April 2001 and July 2015. Primary outcome was duration of stent patency. Secondary outcome was stent patency at 3 and 6 months. We used Kaplan-Meier survival analyses to compare stent patency rates between patients who received chemo(radio)therapy and patients who did not. RESULTS: A total of 291 biliary stents (151 metal and 140 plastic) were identified. The median cumulative stent patency of FCSEMSs did not differ between patients receiving chemo(radio)therapy (n = 51) and those (n = 100) who did not ( P  = 0.70, log-rank test). The estimated cumulative stent patency of plastic stents was also comparable in 99 patients without and 41 patients with chemo(radio)therapy ( P  = 0.73, log-rank test). At 3 and 6 months, FCSEMS patency rates were 87 % and 83 % in patients without chemo(radio)therapy and 96 % and 83 % in patients with therapy, respectively. Plastic patency rates were 69 % and 55 % in patients without and 85 % and 39 % in patients with therapy, respectively. After 1 year, 78 % of the FCSEMSs were still patent in patients without chemo(radio)therapy and 69 % of the FCSEMSs were still patent in patients with therapy. CONCLUSION: Our data indicate that chemo(radio)therapy does not reduce the patency of biliary fully-covered metal and plastic stents.

Ablation with irreversible electroporation in patients with advanced perihilar cholangiocarcinoma (ALPACA): a multicentre phase I/II feasibility study protocol.

INTRODUCTION: The majority of patients with perihilar cholangiocarcinoma (PHC) has locally advanced disease or distant lymph node metastases on presentation or exploratory laparotomy, which makes them not eligible for resection. As the prognosis of patients with locally advanced PHC or lymph node metastases in the palliative setting is significantly better compared with patients with organ metastases, ablative therapies may be beneficial. Unfortunately, current ablative options are limited. Photodynamic therapy causes skin phototoxicity and thermal ablative methods, such as stereotactic body radiation therapy and radiofrequency ablation, which are affected by a heat/cold-sink effect when tumours are located close to vascular structures, such as the liver hilum. These limitations may be overcome by irreversible electroporation (IRE), a relatively new ablative method that is currently being studied in several other soft tissue tumours, such as hepatic and pancreatic tumours. METHODS AND ANALYSIS: In this multicentre phase I/II safety and feasibility study, 20 patients with unresectable PHC due to vascular or distant lymph node involvement will undergo IRE. Ten patients who present with unresectable PHC will undergo CT-guided percutaneous IRE, whereas ultrasound-guided IRE will be performed in 10 patients with unresectable tumours detected at exploratory laparotomy. The primary outcome is the total number of clinically relevant complications (Common Terminology Criteria for Adverse Events, score of≥3) within 90 days. Secondary outcomes include quality of life, tumour response, metal stent patency and survival. Follow-up will be 2 years. ETHICS AND DISSEMINATION: The protocol has been approved by the local ethics committees. Data and results will be submitted to a peer-reviewed journal. CONCLUSION: The Ablation with irreversible eLectroportation in Patients with Advanced perihilar CholangiocarcinomA (ALPACA) study is designed to assess the feasibility of IRE for advanced PHC. The main purpose is to inform whether a follow-up trial to evaluate safety and effectiveness in a larger cohort would be feasible.

Obstructive jaundice due to hepatobiliary cystadenoma or cystadenocarcinoma.

Hepatobiliary cystadenomas (HBC) and cystadenocarcinomas are rare cystic lesions. Most patients with these lesions are asymptomatic, but presentation with obstructive jaundice may occur. The first patient presented with intermittent colicky pain and recurrent obstructive jaundice. Imaging studies revealed a polypoid lesion in the left hepatic duct. The second patient had recurrent jaundice and cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) showed a cystic lesion at the confluence of the hepatic duct. In the third patient with intermittent jaundice and cholangitis, cholangioscopy revealed a papillomatous structure protruding into the left bile duct system. In the fourth patient with obstructive jaundice, CT-scan showed slight dilatation of the intrahepatic bile ducts and dilatation of the common bile duct of 3 cm. ERCP showed filling of a cystic lesion. All patients underwent partial liver resection, revealing HBC in the specimen. In the fifth patient presenting with obstructive jaundice, ultrasound examination showed a hyperechogenic cystic lesion centrally in the liver. The resection specimen revealed a hepatobiliary cystadenocarcinoma. HBC and cystadenocarcinoma may give rise to obstructive jaundice. Evaluation with cross-sectional imaging techniques is useful. ERCP is a useful tool to differentiate extraductal from intraductal obstruction.

Genetic Abnormalities in Biliary Brush Samples for Distinguishing Cholangiocarcinoma from Benign Strictures in Primary Sclerosing Cholangitis.

Background. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and is strongly associated with cholangiocarcinoma (CCA). The lack of efficient diagnostic methods for CCA is a major problem. Testing for genetic abnormalities may increase the diagnostic value of cytology. Methods. We assessed genetic abnormalities for CDKN2A, TP53, ERBB2, 20q, MYC, and chromosomes 7 and 17 and measures of genetic clonal diversity in brush samples from 29 PSC patients with benign biliary strictures and 12 patients with sporadic CCA or PSC-associated CCA. Diagnostic performance of cytology alone and in combination with genetic markers was evaluated by sensitivity, specificity, and area under the curve analysis. Results. The presence of MYC gain and CDKN2A loss as well as a higher clonal diversity was significantly associated with malignancy. MYC gain increased the sensitivity of cytology from 50% to 83%. However, the specificity decreased from 97% to 76%. The diagnostic accuracy of the best performing measures of clonal diversity was similar to the combination of cytology and MYC. Adding CDKN2A loss to the panel had no additional benefit. Conclusion. Evaluation of MYC abnormalities and measures of clonal diversity in brush cytology specimens may be of clinical value in distinguishing CCA from benign biliary strictures in PSC.