A comparison of treatment and outcomes of perihilar cholangiocarcinoma between Eastern and Western centers.

BACKGROUND: Perihilar cholangiocarcinoma (PHC) often requires extensive surgery which is associated with substantial morbidity and mortality. This study aimed to compare an Eastern and Western PHC cohort in terms of patient characteristics, treatment strategies and outcomes including a propensity score matched analysis. METHODS: All consecutive patients who underwent combined biliary and liver resection for PHC between 2005 and 2016 at two Western and one Eastern center were included. The overall perioperative and long-term outcomes of the cohorts were compared and a propensity score matched analysis was performed to compare perioperative outcomes. RESULTS: A total of 210 Western patients were compared to 164 Eastern patients. Western patients had inferior survival compared to the East (hazard-ratio 1.72 (1-23-2.40) P < 0.001) corrected for age, ASA score, tumor stage and margin status. After propensity score matching, liver failure rate, morbidity, and mortality were similar. There was more biliary leakage (38% versus 13%, p = 0.015) in the West. CONCLUSION: There were major differences in patient characteristics, treatment strategies, perioperative outcomes and survival between Eastern and Western PHC cohorts. Future studies should focus whether these findings are due to the differences in the treatment or the disease itself.

A preoperative prognostic model to predict surgical success in patients with perihilar cholangiocarcinoma.

BACKGROUND: Patients with resectable perihilar cholangiocarcinoma (PHC) on imaging have a substantial risk of metastatic or locally advanced disease, incomplete (R1) resection, and 90-day mortality. Our aim was to develop a preoperative prognostic model to predict surgical success, defined as a complete (R0) resection without 90-day mortality, in patients with resectable PHC on imaging. STUDY DESIGN: Patients with PHC who underwent exploratory laparotomy in three tertiary referral centers were identified. Multivariable logistic regression was performed to identify preoperatively available prognostic factors. A prognostic model was developed using data from two European centers and validated in one American center. RESULTS: In total, 671 patients with PHC underwent exploratory laparotomy. In the derivation cohort, surgical success was achieved in 102 of 331 patients (30.8%). No resection was performed in 176 patients (53.2%) because of metastatic or locally advanced disease. Of the 155 patients (46.8%) who underwent a resection, 38 (24.5%) had an R1-resection. Of the remaining 117 (35.3%), 15 (12.8%) had 90-day mortality. Independent poor prognostic factors for surgical success were identified, and a preoperative prognostic model was developed with a concordance index of 0.71. External validation showed good concordance (0.70). CONCLUSION: Surgical success was achieved in only 30% of patients with PHC undergoing exploratory laparotomy and could be predicted by age, cholangitis, hepatic artery involvement, lymph node metastases, and Blumgart stage.

Atorvastatin does not protect against ischemia-reperfusion damage in cholestatic rat livers.

BACKGROUND: Extrahepatic cholestasis sensitizes the liver to ischemia/reperfusion (I/R) injury during surgery for perihilar cholangiocarcinoma. It is associated with pre-existent sterile inflammation, microvascular perfusion defects, and impaired energy status. Statins have been shown to protect against I/R injury in normal and steatotic mouse livers. Therefore, the hepatoprotective properties of atorvastatin were evaluated in a rat model of cholestatic I/R injury. METHODS: Male Wistar rats were subjected to 70% hepatic ischemia (during 30 min) at 7 days after bile duct ligation. Rats were randomized to atorvastatin treatment or vehicle-control in three test arms: (1) oral treatment with 5 mg/kg during 7 days after bile duct ligation; (2) intravenous treatment with 2.5, 5, or 7.5 mg/kg at 24 h before ischemia; and (3) intravenous treatment with 5 mg/kg at 30 min before ischemia. Hepatocellular damage was assessed by plasma alanine aminotransferase (ALT) and histological necrosis. RESULTS: I/R induced severe hepatocellular injury in the cholestatic rat livers (~10-fold increase in ALT at 6 h after I/R and ~30% necrotic areas at 24 h after I/R). Both oral and intravenous atorvastatin treatment decreased ALT levels before ischemia. Intravenous atorvastatin treatment at 5 mg/kg at 24 h before ischemia was the only regimen that reduced ALT levels at 6 h after reperfusion, but not at 24 h after reperfusion. None of the tested regimens were able to reduce histological necrosis at 24 h after reperfusion. CONCLUSION: Pre-treatment with atorvastatin did not protect cholestatic livers from hepatocellular damage after I/R. Clinical studies investigating the role of statins in the protection against hepatic I/R injury should not include cholestatic patients with perihilar cholangiocarcinoma. These patients require (pharmacological) interventions that specifically target the cholestasis-associated hepatopathology.

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.

Development of a Risk Score to Predict Detection of Metastasized or Locally Advanced Perihilar Cholangiocarcinoma at Staging Laparoscopy.

BACKGROUND: Nearly half of patients with perihilar cholangiocarcinoma (PHC) have incurable tumors at laparotomy. Staging laparoscopy (SL) potentially detects metastases or locally advanced disease, thereby avoiding unnecessary laparotomy. However, the diagnostic yield of SL has decreased with improved imaging in recent years. OBJECTIVE: The aim of this study was to identify predictors for detecting metastasized or locally advanced PHC at SL and to develop a risk score to select patients who may benefit most from this procedure. METHODS: Data of patients with potentially resectable PHC who underwent SL between 2000 and 2015 in our center were retrospectively analyzed. Multivariable logistic regression analysis was used to identify independent predictors and to develop a preoperative risk score. RESULTS: Unresectable PHC was detected in 41 of 273 patients undergoing SL (yield 15 %). Overall sensitivity of SL was 30 %, with highest sensitivity for detecting peritoneal metastases (73 %). Preoperative imaging factors that were independently associated with unresectability at SL were tumor size ≥4.5 cm, bilateral portal vein involvement, suspected lymph node metastases, and suspected (extra)hepatic metastases on imaging without the possibility of diagnosis by percutaneous- or endoscopic ultrasound-guided biopsy. The derived preoperative risk score showed good discrimination to predict unresectability (area under the curve 0.77, 95 % confidence interval 0.68-0.86) and identified three subgroups with a predicted low-risk of 7 % (N = 203 patients), intermediate-risk of 21 % (N = 39), and high-risk of 58 % (N = 31). CONCLUSIONS: A selective approach for SL in PHC is recommended since the overall yield is low. The proposed preoperative risk score is useful in selecting patients for SL.

External biliary drainage following major liver resection for perihilar cholangiocarcinoma: impact on development of liver failure and biliary leakage.

BACKGROUND: Preoperative biliary drainage is considered essential in perihilar cholangiocarcinoma (PHC) requiring major hepatectomy with biliary-enteric reconstruction. However, evidence for postoperative biliary drainage as to protect the anastomosis is currently lacking. This study investigated the impact of postoperative external biliary drainage on the development of post-hepatectomy biliary leakage and liver failure (PHLF). METHODS: All patients who underwent major liver resection for suspected PHC between 2000 and 2015 were retrospectively analyzed. Biliary leakage and PHLF was defined as grade B or higher according to the International Study Group of Liver Surgery (ISGLS) criteria. RESULTS: Eighty-nine out of 125 (71%) patients had postoperative external biliary drainage. PHLF was more prevalent in the drain group (29% versus 6%; P = 0.004). There was no difference in the incidence of biliary leakage (32% versus 36%). On multivariable analysis, postoperative external biliary drainage was identified as an independent risk factor for PHLF (Odds-ratio 10.3, 95% confidence interval 2.1-50.4; P = 0.004). CONCLUSIONS: External biliary drainage following major hepatectomy for PHC was associated with an increased incidence of PHLF. It is therefore not recommended to routinely use postoperative external biliary drainage, especially as there is no evidence that this decreases the risk of biliary anastomotic leakage.

Perioperative blood transfusion is not associated with overall survival or time to recurrence after resection of perihilar cholangiocarcinoma.

BACKGROUND: Perioperative blood transfusions have been associated with worse oncological outcome in several types of cancer. The objective of this study was to assess the effect of perioperative blood transfusions on time to recurrence and overall survival (OS) in patients who underwent curative-intent resection of perihilar cholangiocarcinoma (PHC). METHODS: This retrospective cohort study included consecutive patients with resected PHC between 1992 and 2013 in a specialized center. Patients with 90-day mortality after surgery were excluded. Patients who did and did not receive perioperative blood transfusions were compared using univariable Kaplan-Meier analysis and multivariable Cox regression. RESULTS: Of 145 included patients, 80 (55.2%) received perioperative blood transfusions. The median OS was 49 months for patients without and 41 months for patients with blood transfusions (P = 0.46). In risk-adjusted multivariable Cox regression analysis, blood transfusion was not associated with OS (HR 1.00, 95% CI 0.59-1.68, P = 0.99) or time to recurrence (HR 1.00, 95% CI 0.57-1.78, P = 0.99). In addition, no differences in effect were found between different types of blood products transfused. CONCLUSION: Blood transfusion was not associated with survival or time to recurrence after curative resection of PHC in this series. The alleged association is presumably related to the circumstances necessitating blood transfusions.

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 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.

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].

Preoperative computed tomography assessment of skeletal muscle mass is valuable in predicting outcomes following hepatectomy for perihilar cholangiocarcinoma.

BACKGROUND: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with high rates of morbidity and mortality. OBJECTIVES: This study investigated the impact of low skeletal muscle mass on short- and longterm outcomes following hepatectomy for PHC. METHODS: Patients included underwent liver surgery for PHC between 1998 and 2013. Total skeletal muscle mass was measured at the level of the third lumbar vertebra using available preoperative computed tomography images. Sex-specific cut-offs for low skeletal muscle mass were determined by optimal stratification. RESULTS: In 100 patients, low skeletal muscle mass was present in 42 (42.0%) subjects. The rate of postoperative complications (Clavien-Dindo Grade III and higher) was greater in patients with low skeletal muscle mass (66.7% versus 48.3%; multivariable adjusted P = 0.070). Incidences of sepsis (28.6% versus 5.2%) and liver failure (35.7% versus 15.5%) were increased in patients with low skeletal muscle mass. In addition, 90-day mortality was associated with low skeletal muscle mass in univariate analysis (28.6% versus 8.6%; P = 0.009). Median overall survival was shorter in patients with low muscle mass (22.8 months versus 47.5 months; P = 0.014). On multivariable analysis, low skeletal muscle mass remained a significant prognostic factor (hazard ratio 2.02; P = 0.020). CONCLUSIONS: Low skeletal muscle mass has a negative impact on postoperative mortality and overall survival following resection of PHC and should therefore be considered in preoperative risk assessment.

Comparison of techniques for volumetric analysis of the future liver remnant: implications for major hepatic resections.

OBJECTIVE: The purpose of this work was to compare measured and estimated volumetry prior to liver resection. METHODS: Data for consecutive patients submitted to major liver resection for colorectal liver metastases at two centres during 2004-2012 were reviewed. All patients underwent volumetric analysis to define the measured total liver volume (mTLV) and measured future liver remnant ratio (mR(FLR)). The estimated total liver volume (eTLV) standardized to body surface area and estimated future liver remnant ratio (eR(FLR)) were calculated. Descriptive statistics were generated and compared. A difference between mR(FLR) and eR(FLR) of ±5% was considered clinically relevant. RESULTS: Data for a total of 116 patients were included. All patients underwent major resection and 51% underwent portal vein embolization. The mean difference between mTLV and eTLV was 157 ml (P < 0.0001), whereas the mean difference between mR(FLR) and eR(FLR) was -1.7% (P = 0.013). By linear regression, eTLV was only moderately predictive of mTLV (R(2) = 0.35). The distribution of differences between mR(FLR) and eR(FLR) demonstrated that the formula over- or underestimated mR(FLR) by ≥5% in 31.9% of patients. CONCLUSIONS: Measured and estimated volumetry yielded differences in the FLR of ≥5% in almost one-third of patients, potentially affecting clinical decision making. Estimated volumetry should be used cautiously and cannot be recommended for general use.

Prognostic biomarkers in patients with resected cholangiocarcinoma: a systematic review and meta-analysis.

PURPOSE: Biomarkers for patients with resected cholangiocarcinoma (CC) can improve staging and may ultimately result in personalized medicine. Studies evaluating these biomarkers often have shown inconsistent results. We performed a systematic review and meta-analysis to investigate the prognostic value of all immunohistochemistry-based markers that have been evaluated in patients with resected CC. METHODS: In July 2013, we searched the two main medical literature databases: MEDLINE and EMBASE. We extracted hazard ratios (HRs) and associated 95% confidence intervals (CIs) from the identified studies and performed random-effects model meta-analyses on overall survival (OS) in accordance with preferred reporting items for systematic reviews and meta-analyses statement and reporting recommendations for tumor marker prognostic studies (REMARK) guidelines. RESULTS: A total of 73 studies, including 4,126 patients studying 77 individual biomarkers, met the inclusion criteria. Fourteen studies were graded with a low risk of bias. Biomarkers prognostic of OS in pooled analysis included fascin (HR 2.58; 95% CI 1.19-5.58), EGFR (HR 1.79; 95% CI 1.14-2.8), MUC1 (HR 2.52; 95% CI 1.49-4.26), MUC4 (HR 2.45; 95% CI 1.56-3.86), and p27 (HR 0.29; 95% CI 0.14-0.6). Other markers showed promising results in single studies, including HSP27, Akt, HDGF, MUC6, p16, p-4EBP1, S100A4, α-SMA, Keratin 903, and TROP2. CONCLUSIONS: Meta-analysis demonstrated that the biomarkers fascin, EGFR, MUC1, MUC4, and p27 are associated with survival in patients with resected CC. Future studies should validate these, and other promising biomarkers, and adhere to the REMARK guidelines.

Differences in immunohistochemical biomarkers between intra- and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIM: Cholangiocarcinomas of different locations differ in growth patterns, symptoms, treatment response, and survival. Still, they are regarded in many studies as a uniform malignancy. Because intra- (iCCA) and extrahepatic (eCCA) cholangiocarcinoma display such differences, we performed a systematic review and meta-analysis to analyze differences in the immunohistochemical profile of these tumors. METHODS: In February 2014, we searched the two main medical literature databases MEDLINE and EMBASE. We extracted risk ratios and 95% confidence intervals from the identified studies and performed random-effects model meta-analyses in accordance with PRISMA and REMARK guidelines. RESULTS: A total of 54 cohort studies, including 4458 patients and studying 102 individual markers met the inclusion criteria. Of the 57 markers that were evaluated in more than 30 iCCA and eCCA patients, 18 showed a statistically significant difference in expression between iCCA and eCCA. Biomarkers expressed differently between iCCA and eCCA included potential targets of therapy: EGFR, c-erbB-2 and VEGF-A. Several markers showed no statistical difference but large 95% confidence intervals, suggesting insufficient sample size. CONCLUSIONS: This systematic review shows differences in marker expression between iCCA and eCCA. Consequently, patients with iCCA and eCCA may benefit from different treatment strategies.

Injury complexity factors predict heterotopic ossification restricting motion after elbow trauma.

BACKGROUND: Heterotopic ossification (HO) is a common extrinsic cause of elbow stiffness after trauma. However, factors associated with the development of HO are incompletely understood. QUESTIONS/PURPOSES: We retrospectively identified (1) patient-related demographic factors, (2) injury-related factors, and (3) treatment-related factors associated with the development of HO severe enough to restrict motion after surgery for elbow trauma. We also determined what percentage of the variation in HO restricting motion was explained by the variables studied. METHODS: Between 2001 and 2007, we performed surgery on 417 adult patients for elbow fractures; of these, 284 (68%) were available for radiographs at a minimum of 4 months and clinical review at a minimum of 6 months after surgery (mean, 7.9 months; range, 6­31 months). HO was classified according to the Hastings and Graham system. Patients with HO restricting motion (defined as a Hastings and Graham Class II or III) were compared with patients without HO restricting motion in terms of demographics, fracture location, elbow dislocation, open wound, mechanism of injury, ipsilateral fracture, head trauma, time from injury to surgery, number of surgeries within 4 weeks, total number of surgeries, bone graft, and infection, using bivariate and multivariable analyses. A total of 96 patients had radiographic HO, and in 27 (10% of those available for followup), it restricted motion. RESULTS: There were no patient-related demographic factors that predicted the formation of symptomatic HO. Ulnohumeral dislocation in addition to fracture (odds ratio, 2.38; 95% CI, 1.01­5.64; p = 0.048) but not fracture location was associated with HO. Longer time from injury to definitive surgery and number of surgical procedures in the first 4 weeks were also independent predictors of HO (p = 0.01 and 0.004, respectively). These factors explained 20% of the variance in risk for HO restricting motion. CONCLUSIONS: HO restricting motion after operative elbow fracture treatment associates with factors that seem related to injury complexity, in particular, ulnohumeral dislocation, delay, and number of early surgeries; however, a substantial portion of the variation among patients with elbow fracture who develop restrictive HO remains unexplained. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Patterns of recurrence after resection of gallbladder cancer without routine extrahepatic bile duct resection.

OBJECTIVE: Routine extrahepatic bile duct (EBD) resection in non-jaundiced patients with gallbladder cancer (GBC) is controversial. The aim of this study was to retrospectively analyse patterns of recurrence in patients who underwent resection of GBC without routine EBD resection. METHODS: This analysis referred to 58 patients who had undergone explorative laparotomy for GBC during 2000-2012 at a single, tertiary referral centre. Overall survival, time to recurrence, and patterns of recurrence were assessed in patients who underwent conventional negative-margin (R0) resection without routine EBD resection. RESULTS: Of 58 patients submitted to explorative laparotomy for GBC, 26 (45%) patients underwent R0 resection without EBD resection (tumour stage T1b in five patients, T2 in 17, T3 in three, and T4 in one). The 3-year survival rate among these patients was 78% at a median follow-up of 33 months (range: 13-127 months). Seven patients developed recurrent disease at a median of 9 months (range: 2-25 months) after resection. No patients developed isolated recurrent disease at the EBD. CONCLUSIONS: Of 26 patients resected for GBC, none developed isolated recurrent disease at the EBD after conventional resection of GBC without EBD resection. This finding suggests that routine EBD resection is of no additional value.

American Joint Committee on Cancer staging for resected perihilar cholangiocarcinoma: a comparison of the 6th and 7th editions.

OBJECTIVES: This study was conducted to evaluate the prognostic value of, respectively, the 6th and 7th editions of the American Joint Committee on Cancer (AJCC) staging system for patients with resected perihilar cholangiocarcinoma (PHC). METHODS: Patients who underwent resection of PHC between 1991 and 2012 were identified from prospective databases at two centres. Overall survival was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index and Brier score were used to compare the prognostic accuracy of the staging systems. RESULTS: Data for a total of 306 patients were analysed. Staging according to the 7th edition upstaged 63% of patients in comparison with staging by the 6th edition. The log-rank P-value for both staging systems was highly statistically significant (P < 0.001). Staging according to the 6th edition categorized 93% of patients as having stage I or II disease, whereas staging according to the 7th edition distributed patients more equally across stages. Prognostic accuracy was similar between the staging systems: the concordance index was 0.59 and the Brier score 0.17 for both the 6th and 7th editions. The same prognostic accuracy was achieved using an alternative tumour-node-metastasis (TNM) stage grouping simplified to four rather than six stage groups. CONCLUSIONS: The 6th and 7th editions of the AJCC staging system for PHC have similar prognostic accuracy. Other prognostic factors can potentially improve individual patient prognostication.

Predictors of diagnosis of ulnar neuropathy after surgically treated distal humerus fractures.

PURPOSE: Ulnar nerve dysfunction is a common sequela of surgical treatment of distal humerus fractures. This study addresses the null hypothesis that different types of distal humerus injuries have comparable rates of diagnosis of ulnar neuropathy. METHODS: We assessed diagnosis of ulnar neuropathy in 107 consecutive adults who had a surgically treated fracture of the distal humerus followed up at least 6 months after injury. Diagnosis of ulnar neuropathy was defined as documentation of sensory and motor dysfunction of the ulnar nerve in the medical record. Fractures were categorized as either columnar fractures or fractures of the capitellum and trochlea. The explanatory (independent) variables included age, sex, fracture type, AO type, associated wound, associated elbow dislocation, mechanism of trauma, ipsilateral skeletal injury, olecranon osteotomy, implant over or below the medial epicondyle, infection, time from injury to surgery, the number of surgeries within 4 weeks and 6 months of injury, the total number of surgeries, and whether the nerve was transposed. RESULTS: Postoperative ulnar neuropathy was diagnosed in 17 of 107 patients (16%), including 16 of 59 columnar fractures (21%). The only risk factor for ulnar neuropathy was columnar fracture. CONCLUSIONS: Patients with columnar fractures might be at higher risk for the development of postoperative ulnar neuropathy than patients with capitellum and trochlea fractures, regardless of whether the ulnar nerve was transposed. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Validation study of postoperative liver failure and mortality risk scores after liver resection for perihilar cholangiocarcinoma.

Background: Surgery for perihilar cholangiocarcinoma (PHCC) remains a challenging procedure with high morbidity and mortality. The Academic Medical Center (Amsterdam UMC) and Memorial Sloan Kettering Cancer Center proposed a postoperative mortality risk score (POMRS) and post-hepatectomy liver failure score (PHLFS) to predict patient outcomes. This study aimed to validate the POMRS and PHLFS for PHCC patients at Hokkaido University. Methods: Medical records of 260 consecutive PHCC patients who had undergone major hepatectomy with extrahepatic bile duct resection without pancreaticoduodenectomy at Hokkaido University between March 2001 and November 2018 were evaluated to validate the PHLFS and POMRS. Results: The observed risks for PHLF were 13.7%, 24.5%, and 39.8% for the low-risk, intermediate-risk, and high-risk groups, respectively, in the study cohort. A receiver-operator characteristic (ROC) analysis revealed that the PHLFS had moderate predictive value, with an analysis under the curve (AUC) value of 0.62. Mortality rates based on the POMRS were 1.7%, 5%, and 5.1% for the low-risk, intermediate-risk, and high-risk groups, respectively. The ROC analysis demonstrated an AUC value of 0.58. Conclusions: This external validation study showed that for PHLFS the threshold for discrimination in an Eastern cohort was reached (AUC >0.6), but it would require optimization of the model before use in clinical practice is acceptable. The POMRS were not applicable in the eastern cohort. Further external validation is recommended.

Osteonecrosis after open reduction and internal fixation of a bicolumnar fracture of the distal humerus: a report of four cases.

Four cases with osteonecrosis of the trochlea after open reduction and internal fixation of a fracture involving both the medial and lateral columns of the distal humerus above the base of the olecranon fossa (a bicolumnar fracture of the distal humerus) are reported to bring attention to this complication.