Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching.

BACKGROUND: Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS: Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. RESULTS: During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. CONCLUSION: Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.

Endoscopic versus percutaneous intervention for palliation in malignant hilar bile duct obstruction - A comparative cohort study.

BACKGROUND: Biliary drainage in patients managed palliatively for malignant hilar obstruction can be achieved by endoscopic transpapillary stenting using endoscopic retrograde cholangiography (ERC) or percutaneous transhepatic stent or catheter placement using percutaneous transhepatic cholangiography (PTC). This study compares ERC and PTC drainage for malignant hilar bile duct obstruction. METHODS: A retrospective study of drainage procedures at two academic hospitals was conducted from 2015 to 2020. Procedural success (divided into access-, bridging-, and technical success), therapeutic success, duration of therapeutic success and complications were analysed for different Bismuth-Corlette stricture types. RESULTS: A total of 293 patients were included, 153 (52.2%) in the ERC group and 140 (47.8%) in the PTC group. Access and bridging success in the ERC and PTC groups were 83.5% vs. 97.2% (p < 0.001) and 90.2% vs. 84.5% (p = 0.119), respectively. Technical and therapeutic success were equivalent between the two groups (98.3% vs. 99.3%, p = 0.854 and 81.7% vs. 73.3%, p = 0.242). Duration of therapeutic success was longer after ERC drainage compared to PTC drainage (p = 0.009) with a 3-month gain in duration of therapeutic success after ERC drainage (p = 0.006, 95% CI [26-160]). Cholangitis rates were equivalent (21.4% vs. 24.7%, p = 0.530), pancreatitis was more common in the ERC group (9.4% vs. 0%, p < 0.001) and procedure-related deaths more common in the PTC group (6.0% vs. 15.8%, p < 0.001). CONCLUSION: Although ERC and PTC drainage of malignant hilar obstruction were similar regarding technical and therapeutic success, ERC drainage was more durable. Outcome differences for B-C stricture types should be explored in future studies.

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: Report of an international multicenter cohort study with propensity score matching.

BACKGROUND: Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence. METHODS: Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described. RESULTS: During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P = .0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01-109] P = .049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23-154] P = .033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04-91.4] P < .001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15-14.4] P = .030) as predictors of recurrence. CONCLUSION: The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data.

Serum lipase should be the laboratory test of choice for suspected acute pancreatitis.

Background. Serum lipase and amylase are biochemical analyses used to establish the diagnosis of acute pancreatitis (AP). Despite lipase having been shown internationally to be a more sensitive and specific test, amylase remains a popular first-line test.Objective. To provide a local basis for the recommendation of the best first-line laboratory test, an assessment of their performance in our local setting was undertaken.Methods. From a prospective dataset on patients with acute abdominal pain and raised serum lipase and/or amylase values, the sensitivity and specificity of serum lipase, amylase and the two in combination was calculated for the diagnosis of AP, as defined by the Atlanta criteria.Results. During the study period, 476 patients presented with acute upper or generalised abdominal pain and raised serum amylase and/or lipase values. The median age of the patients was 43 years (range 14 - 85), and 58% were men and 42% women. Of the patients, 322 (68%) presented with abdominal conditions other than AP, and 154 (32%) had AP. Ethanol abuse and gallstones accounted for 55% and 23% of cases of AP, respectively. Lipase displayed a sensitivity of 91% for AP, against 62% for amylase. Specificity was 92% for lipase and 93% for amylase. Dual testing with lipase and amylase had a sensitivity of 93%.Conclusions. Lipase is a more sensitive test than amylase when utilising cut-off levels to diagnose AP. Lipase should replace amylase as the first-line laboratory investigation for suspected AP.

Endoscopic management of bile leaks after laparoscopic cholecystectomy.

BACKGROUND: A bile leak is an infrequent but potentially serious complication after biliary tract surgery. Endoscopic intervention is widely accepted as the treatment of choice. This study assessed the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy and biliary stenting in the management of postoperative bile leaks. METHODS: An ERCP database in a tertiary referral centre was reviewed retrospectively to identify all patients with bile leaks after laparoscopic cholecystectomy. Patient records and endoscopy reports were reviewed. RESULTS: One hundred and thirteen patients (92 women, 21 men; median age 47 years, range 22 - 82 years) with a bile leak were referred for initial endoscopic management at a median of 12 days (range 2 - 104 days) after surgery. Presenting features included intra-abdominal collections with pain in 58 cases (51.3%), abnormal liver function tests (LFTs) in 22 (19.5%), bile leak in 25 (22.1%), and sepsis in 8 (7.1%). Twenty-nine patients (25.7%) were found to have either major bile duct injuries without duct continuity, vascular injuries or other endoscopic findings requiring surgical or radiological intervention. Of 84 patients managed endoscopically, 44 had a cystic duct (CD) leak, 26 a CD leak and common bile duct (CBD) stones, and 14 a CBD injury amenable to endoscopic stenting. Of the 70 patients with CD leaks (group A), 24 underwent sphincterotomy only (including 8 stone extractions), 43 had a sphincterotomy with stent placement (including 18 stone extractions) and 1 had only a stent placed, while 2 patients with previous sphincterotomies required no further intervention. The average number of ERCPs in group A was 2.3 (range 1 - 7). Of the 14 patients with bile duct injuries treated endoscopically (group B), 7 had a class D, 5 an E5 and 2 a class B injury; 13 patients underwent sphincterotomy and stenting, and 1 had a sphincterotomy only. Group B required an average of 3.6 ERCPs (range 2 - 5). The 113 patients underwent a total of 269 ERCPs (mean 2.4, range 1 - 7). Seven patients had one or more complications related to the ERCP: 3 acute pancreatitis, 2 cholangitis, 2 sphincterotomy bleeds, 1 duodenal perforation and 1 impacted Dormia basket, the latter 2 requiring operative intervention. CONCLUSIONS: Three-quarters of bile leaks after laparoscopic cholecystectomy were due to CD leaks (with or without retained stones) or lesser bile duct injuries and were amenable to definitive endoscopic therapy. Nineteen patients (16.8%) had major injuries that required operative intervention.