Long-term follow-up of a randomized trial of biliary drainage in perihilar cholangiocarcinoma.

BACKGROUND AND AIMS: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes. METHODS: Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions. RESULTS: A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54-70). The median OS was 13 months (95% CI 7.9-18.1) in the EBD and 7 months (95% CI 0.0-17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2-4) for the EBD group and 2 (1-3) for the PTBD group (P = 0.77). DISCUSSION: Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers.

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial.

Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function. Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes. Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018. Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed. Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality. Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach. Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings. Trial Registration: ISRCTN Identifier: ISRCTN45877994.

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.

No Superiority of Stents vs Balloon Dilatation for Dominant Strictures in Patients With Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Dominant strictures occur in approximately 50% of patients with primary sclerosing cholangitis (PSC). Short-term stents have been reported to produce longer resolution of dominant strictures than single-balloon dilatation. We performed a prospective study to compare the efficacy and safety of balloon dilatation vs short-term stents in patients with non-end-stage PSC. METHODS: We performed an open-label trial of patients with PSC undergoing therapeutic endoscopic retrograde cholangiopancreatography (ERCP) at 9 tertiary-care centers in Europe, from July 2011 through April 2016. Patients found to have a dominant stricture during ERCP were randomly assigned to groups that underwent balloon dilatation (n = 31) or stent placement for a maximum of 2 weeks (n = 34); patients were followed for 24 months. The primary outcome was the cumulative recurrence-free patency of the primary dominant strictures. RESULTS: Study recruitment was terminated after a planned interim analysis because of futility and differences in treatment-related serious adverse events (SAEs) between groups. The cumulative recurrence-free rate did not differ significantly between groups (0.34 for the stent group and 0.30 for the balloon dilatation group at 24 months; P = 1.0). Most patients in both groups had reductions in symptoms at 3 months after the procedure. There were 17 treatment-related SAEs: post-ERCP pancreatitis in 9 patients and bacterial cholangitis in 4 patients. SAEs occurred in 15 patients in the stent group (45%) and in only 2 patients in the balloon dilatation group (6.7%) (odds ratio, 11.7; 95% confidence interval, 2.4-57.2; P = .001). CONCLUSIONS: In a multicenter randomized trial of patients with PSC and a dominant stricture, short-term stents were not superior to balloon dilatation and were associated with a significantly higher occurrence of treatment-related SAEs. Balloon dilatation should be the initial treatment of choice for dominant strictures in patients with PSC. This may be particularly relevant to patients with an intact papilla. ClinicalTrials.gov no. NCT01398917.

Long-term follow-up and risk factors for strictures after hepaticojejunostomy for bile duct injury: An analysis of surgical and percutaneous treatment in a tertiary center.

BACKGROUND: Hepaticojejunostomy is commonly indicated for major bile duct injury after cholecystectomy. The debate about the timing of hepaticojejunostomy for bile duct injury persists since data on postoperative outcomes, including postoperative strictures, are lacking. The aim of this study was to analyze short- and long-term outcomes of hepaticojejunostomy for bile duct injury, including risk factors for strictures. METHOD: Analysis of outcome of hepaticojejunostomy in bile duct injury patients referred to a multidisciplinary team. RESULTS: Between the years1991 and 2016, 281 patients underwent hepaticojejunostomy for bile duct injury. Clavien-Dindo grade III complications occurred in 31 patients (11%) and 90-day mortality occurred in 2 patients (0.7%). After a median follow-up of 10.5 years (interquartile range 6.7-14.8 years), clinically relevant strictures were found in 37 patients (13.2%). Strictures were treated with percutaneous dilatation in 33 patients (89.2%), and 4 patients (1.4%) were reoperated. The stricture rate in patients undergoing hepaticojejunostomy <14 days, between 14-90 days, and >90 days after bile duct injury was 15.8%, 18.7%, and 9.9%, respectively. The stricture rate for early versus intermediate and late repair did not differ (P = 0.766 and 0.431, respectively). The stricture rate for repair after 14-90 days, however, was higher compared with repair >90 days after bile duct injury (P = 0.045). In multivariable analysis male gender was the only independent variable associated with stricture formation (OR 6.7, 95% CI 1.8-25.4, P = 0.005). CONCLUSION: Hepaticojejunostomy is a relatively safe treatment of bile duct injury. Timing of surgery and intermediate repair affect long-term stricture rate; most anastomotic strictures can be treated successfully with percutaneous dilation.

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.

Long-term Impact of Bile Duct Injury on Morbidity, Mortality, Quality of Life, and Work Related Limitations.

OBJECTIVE: Assessment of long-term comprehensive outcome of multimodality treatment of bile duct injury (BDI) in terms of morbidity, mortality, quality of life (QoL), survival, and work related limitations. BACKGROUND: The impact of BDI on work ability is scarcely investigated. METHODS: BDI patients referred to a tertiary center after BDI were included (n = 800). QoL and work related limitations (HLQ) were compared with 175 control patients after uncomplicated laparoscopic cholecystectomy. RESULTS: The mean survival after BDI was 17.6 years (95% confidence interval, CI, 17.2-18.0 years). BDI related mortality was 3.5% (28/800). Corrected for sex, ASA classification, treatment and type of injury, survival is worse in male patients (hazard ratio, HR 1.50, 95% CI 1.01-2.33) and progressively worse with higher ASA classification (ASA2: 5.25 (2.94-9.37), ASA3: 18.1 (9.79-33.3). Patients treated surgically had a significantly better survival (HR: 0.45 (95% CI: 0.25-0.80). BDI patients reported a significantly worse physical QoL compared with the control group and worse disease specific QoL. Loss of productivity of work was significantly higher among BDI patients. There also was a significant hindrance in unpaid work. A higher number of bile duct injury patients were receiving disability benefits after long-term follow-up (34.9% vs 19.6%, P = 0.004). CONCLUSIONS: Reconstructive surgery in BDI patients is associated with improved survival. Although the clinical outcome of multidisciplinary treatment of bile duct injury is good, it is associated with a significant decrease in QoL, loss of productivity in both paid and unpaid work and high rates of disability benefits use.

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.

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.

Operative Versus Nonoperative Management of Blunt Pancreatic Trauma in Children: A Systematic Review.

The aim of this study was to compare operative versus nonoperative management of blunt pancreatic trauma in children. A systematic literature search was performed. Studies including children with blunt pancreatic injuries classified according to the American Association for the Surgery of Trauma classification were included. The primary outcome was pseudocyst formation. After screening 526 studies, 23 studies with 928 patients were included. Sufficient data were available for 674 patients (73%). Of 309 patients with grade I or II injuries, 258 (83%) were initially managed nonoperatively with a 96% success rate. Of 365 patients with grade III, IV, or V injuries, nonoperative management was initially chosen for 167 patients (46%) with an 89% success rate. Pseudocysts occurred in 18% of patients managed nonoperatively versus 4% of patients managed operatively (P < 0.01), of whom 65% were treated nonoperatively. Hospitalization was 20.5 days after nonoperative versus 15.1 days after operative management (nonparametric t test, P = 0.41). Blunt pancreatic trauma in children can be managed nonoperatively in the majority of patients with grade I or II injuries and in about half of the patients with grade III to V injuries. Although pseudocysts are more common after nonoperative management, two thirds can be managed nonoperatively.

Comparing 3 guidelines on the management of surgically removed pancreatic cysts with regard to pathological outcome.

BACKGROUND AND AIMS: Currently, 3 guidelines are available for the management of pancreatic cysts. These guidelines vary in their indication for resection of high-risk cysts. We retrospectively compared the final pathologic outcome of surgically removed pancreatic cysts with the indications for resection according to 3 different guidelines. METHODS: Patients who underwent pancreatic resection were extracted from our prospective pancreatic cyst database (2006-present). The final histopathologic diagnosis was compared with the initial indication for surgery stated by the guidelines of the International Association of Pancreatology (IAP), European Study Group on Cystic tumors of the Pancreas and American Gastroenterological Association (AGA). We considered surgery in retrospect justified for malignancy, high-grade dysplasia, solid pseudopapillary neoplasms, neuroendocrine tumors or symptom improvement. Furthermore, we evaluated the patients with suspected intraductal papillary mucinous neoplasm (IPMN) separately. RESULTS: Overall, 115 patients underwent pancreatic resection. The preoperative diagnosis was correct in 83 of 115 patients (72%) and differentiation between benign and premalignant in 99 of 115 patients (86%). In retrospect, surgery was justified according to the aforementioned criteria in 52 of 115 patients (45%). For patients with suspected IPMN (n = 75) resection was justified in 36 of 67 (54%), 36 of 68 (53%), and 32 of 54 (59%) of patients who would have had surgery based on the IAP, European, or AGA guidelines, respectively. The AGA guideline would have avoided resection in 21 of 75 (28%) patients, versus 8 of 75 (11%) and 7 of 75 (9%) when the IAP or European guideline would have been applied strictly. Nevertheless, 4 of 33 patients (12%) with high-grade dysplasia or malignancy would have been missed with the AGA guidelines, compared with none with the IAP or European guidelines. CONCLUSION: Although fewer patients undergo unnecessary surgery based on the AGA guidelines, the risk of missing malignancy or high-grade dysplasia with this guideline seems considerably high.

Long-term follow-up of neoplastic pancreatic cysts without high-risk stigmata: how often do we change treatment strategy because of malignant transformation?

UNLABELLED: * OBJECTIVE: Patients with potentially premalignant neoplastic pancreatic cysts without high-risk stigmata usually enter a surveillance program. Data on outcomes of such surveillance programs are scarce. We aimed to evaluate the resection rate and malignancy rate during follow-up. MATERIAL AND METHODS: From our prospective database (2006-2015) of patients with pancreatic cysts, we analyzed patients with pancreatic cysts without high-risk stigmata with at least six months follow-up. RESULTS: In total, 146 patients were followed for a median of 29 months (IQR 13.5-50 months). In 124 patients (84.9%), no changes in clinical or imaging characteristics occurred during follow-up. Thirteen patients (8.9%) developed an indication for surgery after a median follow-up of 25 months (IQR 12-42 months). Two patients did not undergo surgery because of comorbidity, 11 patients (7.5%) underwent resection. Indications for surgery were symptoms (n = 2), development of a pancreatic mass (n = 1), a new nodule (n = 2), thickened cyst wall (n = 1), pancreatic duct dilation (n = 3), and/or suspicion of mucinous cystic neoplasm (MCN) (n = 3). Postoperative histology showed one pancreatic malignancy not originating from the cyst, three mixed type-intraductal papillary mucinous neoplasm (IPMN), one side branch-IPMN, two MCN, one neuroendocrine tumor, one serous cystadenoma, one inflammatory cyst, and one lymphangioma. The highest grade of cyst dysplasia was borderline dysplasia. CONCLUSIONS: Most neoplastic pancreatic cysts without high-risk stigmata at initial presentation show no substantial change during 1-4-year follow-up. Only 7.5% of patients underwent surgery and less than 1% of patients developed pancreatic malignancy. This indicates that additional markers are needed to tailor treatment of pancreatic cysts.

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.

Clinical outcomes and prevalence of cancer in patients with possible groove pancreatitis.

BACKGROUND AND AIM: Data on non-surgical treatment of groove pancreatitis (GP) and the risk of cancer are lacking. We aimed to determine the prevalence and predictors of cancer in patients in whom the diagnosis GP was considered, and to evaluate symptom improvement after treatment. STUDY: Patients referred with possible GP (2001-2014) were retrospectively included. An experienced radiologist reassessed imaging. GP patients received questionnaires evaluating their symptoms. RESULTS: From the 38 possible GP patients, 10 had cancer (26%) and 28 GP (74%). Compared with cancer patients, GP patients more frequently had cysts (2/10 vs. 18/28, P = 0.03), less often jaundice (6/10 vs 3/27, P < 0.01), an abrupt caliber change of the CBD (5/10 vs. 2/28, P < 0.01) or suspicious cytology (5/9 vs 2/20, P = 0.02). Of the 28 GP patients, 14 patients were treated conservatively of whom 12 reported symptom improvement after a median follow-up of 45 months (range 7-127 months). All 6 patients treated endoscopically and 7/8 patients treated surgically reported symptom improvement. Surgery, performed because of treatment failure (3/8) or inability to exclude malignancy (5/8), caused mortality in 1/8 patients. CONCLUSIONS: Suspicion of pancreatic cancer should be high in patients presenting with possible GP. Conservative, endoscopic and surgical treatment can all lead to symptom improvement, suggesting a 'step-up approach' to GP once cancer is excluded.

Self-expandable metal stents for malignant gastric outlet obstruction: A pooled analysis of prospective literature.

AIM: To provide an overview of the clinical outcomes of self-expandable metal stent (SEMS) placement for malignant gastric outlet obstruction (MGOO). METHODS: A systematic literature search was performed in PubMed of the literature published between January 2009 and March 2015. Only prospective studies that reported on the clinical success of stent placement for MGOO were included. The primary endpoint was clinical success, defined according to the definition used in the original article. Data were pooled and analyzed using descriptive statistics. Subgroup analyses were performed for partially covered SEMSs (PCSEMSs) and uncovered SEMSs (UCSEMSs) using Fisher's exact test. RESULTS: A total of 19 studies, including 1281 patients, were included in the final analysis. Gastric (42%) and pancreatic (37%) cancer were the main causes of MGOO. UCSEMSs were used in 76% of patients and PCSEMSs in 24%. The overall pooled technical success rate was 97.3% and the clinical success rate was 85.7%. Stent dysfunction occurred in 19.6% of patients, mainly caused by re-obstruction (12.6%) and stent migration (4.3%), and was comparable between PCSEMSs and UCSEMSs (21.2% vs 19.1%, respectively, P = 0.412). Re-obstruction was more common with UCSEMSs (14.9% vs 5.1%, P < 0.001) and stent migration was more frequent after PCSEMS placement (10.9% vs 2.2%, P < 0.001). The overall perforation rate was 1.2%. Bleeding was reported in 4.1% of patients, including major bleeding in 0.8%. The median stent patency ranged from 68 to 307 d in five studies. The median overall survival ranged from 49 to 183 d in 13 studies. CONCLUSION: The clinical outcomes in this large population showed that enteral stent placement was feasible, effective and safe. Therefore, stent placement is a valid treatment option for the palliation of MGOO.

The Long-Term Impact of Autoimmune Pancreatitis on Pancreatic Function, Quality of Life, and Life Expectancy.

OBJECTIVE: To evaluate the long-term outcome of autoimmune pancreatitis. METHODS: Patients with at least 2 years of follow-up were included. Information was collected regarding disease characteristics, treatment outcome, diagnosed malignancies, and mortality. In addition, pancreatic function and quality of life were assessed prospectively. RESULTS: 107 patients were included (87% men, 90% with type 1), with a median follow-up of 74 (interquartile range, 49-108) months. One third was operated for suspected pancreatic cancer (32%). Most patients were (successfully) treated with steroids (83%), but relapses were common (52%), for which no risk factors could be identified. Pancreatic carcinoma was not observed.Prospective data were obtained from 64%, as 17% had died, 7% were lost to follow-up, and 13% refused to participate. After a median of 75 (interquartile range, 50-106) months, 46% still used active treatment. Exocrine and endocrine insufficiencies were highly prevalent (82% and 57%, respectively). Quality of life and survival were not impaired, as compared with a reference population. CONCLUSIONS: Despite an excellent initial treatment response, relapses are common, even in type 2, and almost half of the patients require maintenance therapy. Pancreatic insufficiency is highly prevalent, which calls for active screening. Pancreatic cancer was not observed, and quality of life and survival are not impaired.

Preoperative biliary drainage in perihilar cholangiocarcinoma: identifying patients who require percutaneous drainage after failed endoscopic drainage.

BACKGROUND AND STUDY AIMS: Preoperative biliary drainage is often initiated with endoscopic retrograde cholangiopancreatography (ERCP) in patients with potentially resectable perihilar cholangiocarcinoma (PHC), but additional percutaneous transhepatic catheter (PTC) drainage is frequently required. This study aimed to develop and validate a prediction model to identify patients with a high risk of inadequate ERCP drainage. PATIENTS AND METHODS: Patients with potentially resectable PHC and (attempted) preoperative ERCP drainage were included from two specialty center cohorts between 2001 and 2013. Indications for additional PTC drainage were failure to place an endoscopic stent, failure to relieve jaundice, cholangitis, or insufficient drainage of the future liver remnant. A prediction model was derived from the European cohort and externally validated in the USA cohort. RESULTS: Of the 288 patients, 108 (38%) required additional preoperative PTC drainage after inadequate ERCP drainage. Independent risk factors for additional PTC drainage were proximal biliary obstruction on preoperative imaging (Bismuth 3 or 4) and predrainage total bilirubin level. The prediction model identified three subgroups: patients with low risk (7%), moderate risk (40%), and high risk (62%). The high-risk group consisted of patients with a total bilirubin level above 150 µmol/L and Bismuth 3a or 4 tumors, who typically require preoperative drainage of the angulated left bile ducts. The prediction model had good discrimination (area under the curve 0.74) and adequate calibration in the external validation cohort. CONCLUSIONS: Selected patients with potentially resectable PHC have a high risk (62%) of inadequate preoperative ERCP drainage requiring additional PTC drainage. These patients might do better with initial PTC drainage instead of ERCP.