Percutaneous Preoperative Biliary Drainage for Resectable Perihilar Cholangiocarcinoma: No Association with Survival and No Increase in Seeding Metastases

Background: Endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) are both used to resolve jaundice before surgery for perihilar cholangiocarcinoma (PHC). PTBD has been associated with seeding metastases. The aim of this study was to compare overall survival (OS) and the incidence of initial seeding metastases that potentially influence survival in patients with preoperative PTBD versus EBD. Methods: Between 1991 and 2012, a total of 278 patients underwent preoperative biliary drainage and resection of PHC at 2 institutions in the Netherlands and the United States. Of these, 33 patients were excluded for postoperative mortality. Among the 245 included patients, 88 patients who underwent preoperative PTBD (with or without previous EBD) were compared to 157 patients who underwent EBD only. Survival analysis was done with Kaplan–Meier and Cox regression with propensity score adjustment. Results: Unadjusted median OS was comparable between the PTBD group (35 months) and EBD-only group (41 months; P = 0.26). After adjustment for propensity score, OS between the PTBD group and EBD-only group was similar (hazard ratio, 1.05; 95 % confidence interval, 0.74–1.49; P = 0.80). Seeding metastases in the laparotomy scar occurred as initial recurrence in 7 patients, including 3 patients (3.4 %) in the PTBD group and 4 patients (2.7 %) in the EBD-only group (P = 0.71). No patient had an initial recurrence in percutaneous catheter tracts. Conclusions: The present study found no effect of PTBD on survival compared to patients with EBD and no increase in seeding metastases that developed as initial recurrence. These data suggest that PTBD can safely be used in preoperative management of PHC

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 [, 11 October 2013]

Recurrence Rate and Pattern of Perihilar Cholangiocarcinoma after Curative Intent Resection Presented at the 11th Congress of the European-African Hepato-Pancreato-Biliary Association, Manchester, UK, April 2015.

Background The aim of this study was to investigate the rate and pattern of recurrence after curative intent resection of perihilar cholangiocarcinoma (PHC). Study Design Patients were included from 2 prospectively maintained databases. Recurrences were categorized by site. Time to recurrence and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method. Cox proportional hazards modeling was used to identify independent poor prognostic factors. Results Between 1991 and 2012, 306 consecutive patients met inclusion criteria. Median overall survival was 40 months. A recurrence was diagnosed in 177 patients (58%). An initial local recurrence was found in 26% of patients: liver hilum (11%), hepaticojejunostomy (8%), liver resection margin (8%), or distal bile duct remnant (2%). An initial distant recurrence was observed in 40% of patients: retroperitoneal lymph nodes (14%), intrahepatic away from the resection margin (13%), peritoneum (12%), and lungs (8%). Only 18% of patients had an isolated initial local recurrence. The estimated overall recurrence rate was 76% at 8 years. After a recurrence-free period of 5 years, 28% of patients developed a recurrence in the next 3 years. Median RFS was 26 months. Independent prognostic factors for RFS were resection margin, lymph node status, and tumor differentiation. Only node-positive PHC precluded RFS beyond 7 years. Conclusions Perihilar cholangiocarcinoma will recur in most patients (76%) after resection, emphasizing the need for better adjuvant strategies. The high recurrence rate of up to 8 years justifies prolonged surveillance. Only patients with an isolated initial local recurrence (18%) may have benefited from a more extensive resection or liver transplantation. Node-positive PHC appears incurable

High mortality after ALPPS for perihilar cholangiocarcinoma: Case-control analysis including the first series from the international ALPPS registry

Introduction: Resection of perihilar cholangiocarcinoma (PHC) entails high-risk surgery with postoperative mortality reported up to 18%, even in specialized centers. The aim of this study was to compare outcomes of PHC patients who underwent associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) to patients who underwent resection without ALPPS. Methods: All patients who underwent ALPPS for PHC were identified from the international ALPPS registry and matched controls were selected from a standard resection cohort from two centers based on future remnant liver size. Outcomes included morbidity, mortality, and overall survival. Results: ALPPS for PHC was associated with 48% (14/29) 90-day mortality. 90-day mortality was 13% in 257 patients who underwent major liver resection for PHC without ALPPS. The 29 ALPPS patients were matched to 29 patients resected without ALPPS, with similar future liver remnant volume (P = 0.480). Mortality in the matched control group was 24% (P = 0.100) and median OS was 27 months, comparted to 6 months after ALPPS (P = 0.064). Discussion: Outcomes of ALPPS for PHC appear inferior compared to standard extended resections in high-risk patients. Therefore, portal vein embolization should remain the preferred method to increase future remnant liver volume in patients with PHC. ALPPS is not recommended for PHC

Survival after resection of perihilar cholangiocarcinoma-Development and external validation of a prognostic nomogram

Background: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). Patients and methods: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. Results: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. Conclusions: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials

Postoperative Mortality after Liver Resection for Perihilar Cholangiocarcinoma: Development of a Risk Score and Importance of Biliary Drainage of the Future Liver Remnant

Background: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). Study Design: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. Results: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume 50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). Conclusions: The mortality risk score for p