A Hepatocellular Cancer Patient-derived Organoid Xenograft Model to Investigate Impact of Liver Regeneration on Tumor Growth.

Recurrence poses a notable challenge after hepatocellular carcinoma (HCC) treatment, impacting more than 70% of patients who undergo surgical resection. Recurrence stems from undetected micro-metastasis or de novo cancer, potentially triggered by postsurgical liver regeneration. Prior research employed HCC cell lines in orthotopic models to study the impact of liver regeneration, but their limited validity prompted the need for a more representative model. Here, we introduce a novel approach utilizing patient-derived HCC organoids to investigate the influence of liver regeneration on HCC. Patient tumor tissues are processed to create tumor organoids, embedded in a three-dimensional basement membrane matrix, and cultured in a liver-specific medium. One million organoids are injected into the right superior lobe (RSL) of immunodeficient mice, confirming macroscopic tumor growth through sonography. The intervention group undergoes resection of the left lateral lobe (LLL) (30% of total liver volume) or additionally, the middle lobe (ML) (65% of total liver volume) to induce liver regeneration within the tumor site. The control group experiences re-laparotomy without liver tissue resection. After 2 weeks, both groups undergo tumor and normal tissue explantation. In conclusion, this patient-derived HCC organoid model offers a robust platform to investigate the impact of liver regeneration post-cancer resection. Its multi-cellular composition, genetic diversity, and prolonged culture capabilities make it an invaluable tool for studying HCC recurrence mechanisms and potential interventions.

The short- and long-term outcome after the surgical management of common bile duct stones in a tertiary referral hospital.

BACKGROUND: The removal of common bile duct stones by endoscopic retrograde cholangiopancreatography (ERCP) shows excellent results with low complication rates and is therefore considered a gold standard. However, in case of stones non-removable by ERCP, surgical extraction is needed. The surgical approach is still controversial and clinical guidelines are missing. This study aims to analyze the outcomes of patients treated with choledochotomy or hepaticojejunostomy for common bile duct stones. METHODS: All patients who underwent choledochotomy or hepaticojejunostomy for common bile duct stones at a tertiary referral hospital over 11 years were included. The analyzed data contains basic demographics, diagnostics, surgical parameters, length of hospitalization, and morbidity and mortality. RESULTS: Over the study period, 4375 patients underwent cholecystectomy, and 655 received an ERCP with stone extraction, with 48 of these patients receiving subsequent surgical treatment. ERCP was attempted in 23/30 (77%) of the choledochotomy patients pre/intraoperatively and 11/18 (56%) in hepaticojejunostomy patients. The 30-day major complication rate (Clavien-Dindo > II) was 1/30 (3%) in the choledochotomy group and 2/18 (11%) in the hepaticojejunostomy group. Complications after 30 days occurred in 3/30 (10%) patients and 2/18 (11%), respectively, and no mortality occurred. CONCLUSION: ERCP should still be considered the gold standard, although due to low short- and long-term morbidity rates, choledochotomy and hepaticojejunostomy represent effective surgical solutions for common bile duct stones.

Persistent acute cholecystitis after cholecystostomy - increased mortality due to treatment approach?

BACKGROUND: Percutaneous cholecystostomy (PC) is a treatment option for acute cholecystitis (AC) in cases where cholecystectomy (CCY) is not feasible due to limited health conditions. The use of PC remains questionable. The aim was to retrospectively analyse the outcome of patients after PC. METHODS: All patients who underwent PC for AC at a tertiary referral hospital over 10 years were included. Descriptive statistics, analysed mortality with and without CCY after PC, and a multivariable logistic regression for potential confounder and a landmark sensitivity analysis for immortal time bias were used. RESULTS: Of 158 patients, 79 were treated with PC alone and 79 had PC with subsequent CCY. Without CCY, 48% (38 patients) died compared to 9% with CCY. In the multivariable analysis CCY was associated with 85% lower risk of mortality. The landmark analysis was compatible with the main analyses. Direct PC-complications occurred in 17% patients. Histologically, 22/75 (29%) specimens showed chronic cholecystitis, and 76% AC. CONCLUSION: Due to the high mortality rate of PC alone, performing up-front CCY is proposed. PC represents no definitive treatment for AC and should remain a short-term solution because of the persistent inflammatory focus. According to these findings, almost all specimens showed persistent inflammation.