Revival of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma: An international multicenter study with promising outcomes.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma has been considered to be contraindicated due to the initial poor results. Given the recent reports of improved outcomes, we aimed to collect the recent experiences of different centers performing associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma to analyze factors related to improved outcomes. METHODS: This proof-of-concept study collected contemporary cases of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma and analyzed for morbidity, short and long-term survival, and factors associated with outcomes. RESULTS: In total, 39 patients from 8 centers underwent associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma from 2010 to 2020. The median preoperative future liver remnant volume was 323 mL (155-460 mL). The median future liver remnant increase was 58.7% (8.9% -264.5%) with a median interstage interval of 13 days (6-60 days). Post-stage 1 and post-stage 2 biliary leaks occurred in 2 (7.7%) and 4 (15%) patients. Six patients (23%) after stage 1 and 6 (23%) after stage 2 experienced grade 3 or higher complications. Two patients (7.7%) died within 90 days after stage 2. The 1-, 3-, and 5-year survival was 92%, 69%, and 55%, respectively. A subgroup analysis revealed poor survival for patients undergoing additional vascular resection and lymph node positivity. Lymph node-negative patients showed excellent survival demonstrated by 1-, 3-, and 5-year survival of 86%, 86%, and 86%. CONCLUSION: This study highlights that the critical attitude toward associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma needs to be revised. In selected patients with perihilar cholangiocarcinoma, associating liver partition and portal vein ligation for staged hepatectomy can achieve favorable survival that compares to the outcome of established surgical treatment strategies reported in benchmark studies for perihilar cholangiocarcinoma including 1-stage hepatectomy and liver transplantation.

Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation.

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p < 0.001). Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Current management of portal vein thrombosis in liver transplantation.

Nontumoral portal vein thrombosis (PVT) is present at liver transplantation (LT) in 5-26% of cirrhotic patients, and is known to affect post LT outcomes. Up to 31% of patients who are found to have PVT at the time of LT, would have had PVT at the time of initial listing, but others develop PVT during the waiting period. Adequate screening and treatment of the PVT on the waiting list for LT is thus essential so that a portoportal anastomoses can be performed at the time of LT. Early PVT (Yerdel Grade I/II) can be usually managed by thrombectomy, whereas Grade III PVT may require a jump graft from the superior mesenteric vein to the graft PV. Complete portomesenteric thrombosis is a huge challenge, and sometimes a cause for denying a LT in these patients, with multivisceral transplant being the only alternative. The presence of spontaneous, or previously surgically created portosytemic shunts like the leinorenal shunt, may serve as a good inflow option (renoportal anastomosis) in these patients to establish a physiological reconstruction. Although challenging, good outcomes are possible in patients with complex PVT if the appropriate surgical technique is chosen to ensure portal inflow and resolution of PHT post LT.

Organ dysfunction in cirrhosis: a mechanism involving the microcirculation.

INTRODUCTION: Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. PATIENTS AND METHODS: We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan-Meier analysis was carried out. RESULTS: Fifty-four patients and 18 controls were included. Inflammatory and endothelial markers increased in advanced disease. FCD was reduced and RBCA was progressively lower according to disease severity. RBCA correlated inversely with inflammatory and endothelial biomarkers, and directly with renal function. The presence of hepatic encephalopathy correlated inversely with RBCA and directly with IL-6 and endothelin-1. In multivariate analysis, RBCA was an independent factor for organ dysfunction. The area under the receiver operating chartacteristic curve for IL-6 for survival was 0.74 (0.59-0.89), P=0.05. Transplant-free survival was 97.5% for values under 5.78 ng/ml (IL-6 best cutoff) and 83.9% above 5.78 ng/ml, log-rank=0.018. Eleven patients underwent transplantation, with an overall improvement in microcirculatory function. CONCLUSION: Our results suggest a mechanism of organ damage in cirrhosis, where microcirculatory dysfunction could be correlated to inflammatory and endothelial biomarkers, and loss of multiorgan function. IL-6 seems to be an important survival marker of inflammation. Liver transplantation improved microcirculatory dysfunction, corroborating this hypothesis.

Right hepatectomy due to hepatolithiasis caused by endoclip migration after laparoscopic cholecystectomy: a case report.

Complications related to cholecystectomy occur in <3% of patients. Endoclip migration after laparoscopic cholecystectomy with hepatolithiasis is an extremely rare complication. We report a case of hepatolithiasis secondary to endoclip migration after laparoscopic cholecystectomy treated successfully via right hepatectomy. A 35-year-old female presented with upper abdominal pain, fever and vomiting 9 years after laparoscopic cholecystectomy for chronic calculus cholecystitis. Laboratory investigation revealed gamma-glutamyl transpeptidase of 550 U/L and alkaline phosphatase of 350 U/L. Magnetic resonance cholangiopancreatography revealed a dilated intrahepatic bile duct in segment 6 filled with stones. After preoperative evaluation, a right hepatectomy was performed using the intermittent Pringle maneuver. The postoperative recovery was uneventful and the patient was well after 4 months of follow-up. Although rare, endoclip migration should be considered in patients presenting with intrahepatic lithiasis even many years after laparoscopic cholecystectomy. Liver resection may be necessary in cases of failure of endoscopic extraction.

Risk factors for long-term mortality in a large cohort of patients wait-listed for liver transplantation in Brazil.

Liver donor shortage and long waiting times are observed in many liver transplant programs worldwide. The aim of this study was to evaluate the wait list in a developing country, before and after the introduction of the MELD scoring system. In addition, the MELD score ability to predict mortality in this setting was assessed. A single-center retrospective study of patients wait-listed for liver transplantation between 1997 and 2010 was undertaken. There were 1339 and 762 patients on the list in pre-MELD and MELD era, respectively. A competitive risk analysis was performed to assess age, gender, disease diagnosis, serum sodium, MELD, Child-Pugh, ABO type, and body mass index. Also, MELD score predictive ability at 3, 6, 12, and 24 months after list enrollment was evaluated. The overall mortality rates on waiting list were 31.0% and 28.1% (P = 0.16), and the median waiting times were 412 and 952 days (P < 0.001), in pre and MELD eras, respectively. The competitive risk analysis yielded the following significant P values for both eras: HCC (0.03 and <0.001), MELD (<0.001 and 0.002), sodium level (0.002 and <0.001), and Child-Pugh (0.02 and <0.001). The MELD mortality predictions at 3, 6, 12, and 24 months were similar. In conclusion, in a liver transplant program with long waiting times, the MELD system introduction did not improve mortality rate. In either pre and MELD eras, HCC diagnosis, serum sodium, Child-Pugh, and MELD were significant predictors of prognosis. Short- and long-term MELD based mortality predictions were similarly accurate. Strategies for increasing the liver donor pool should be implemented to improve mortality.

Extrahepatic right hepatic duct diverticulum: a rare entity.

BACKGROUND: Douglas described choledochal cysts in 1852 and Todani proposed an anatomy-based classification in 1977. The classification is the most extensively used, but does not include some rare variations. We present a case of hepatic duct diverticulum, one of the variations, and discuss its diagnosis and treatment. METHODS: A 57-year-old woman presented with upper abdominal pain and discomfort associated with nausea and vomiting. She was finally diagnosed with cholelithiasis and right hepatic duct diverticulum. RESULT: The patient underwent resection of the hepatic duct diverticulum and cholecystectomy, and was asymptomatic 26 months after surgery. CONCLUSIONS: Hepatic duct diverticulum is a rare form of choledochal cyst, not included in Todani's classification. Todani's classification including this and other uncommon variations of choledochal cysts must be reviewed. The best diagnostic imaging methods and treatment for choledochal cysts must be defined.