Successful Interventional Treatment for Arterioportal Fistula Caused by Radiofrequency Ablation for Hepatocellular Carcinoma

Radiofrequency ablation (RFA) is commonly used as a treatment for small hepatocellular carcinoma (HCC). Although several complications such as intraperitoneal bleeding are often observed after RFA, hepatic arterioportal fistula (APF) is a less frequently occurring complication. In this study, we describe two cases of APF caused by RFA, which was successfully occluded by an interventional approach. Case 1 involved a 68-year-old man with solitary HCC in segment VIII of the liver. Both contrast-enhanced computed tomography and color Doppler sonography indicated an APF between the anterosuperior branch of the right hepatic artery (A8) and the portal branch (P8). Concordant with these findings, digital subtraction angiography (DSA) revealed an APF in segment VIII of the liver. Subsequently, the APF was successfully occluded by transarterial embolization (TAE) using gelatin sponge particles. Case 2 involved a 67-year-old man with solitary HCC in segment VII of the liver. Although he developed obstructive jaundice because of hemobilia after RFA, it was improved by endoscopic nasobiliary drainage and the systemic administration of antibiotics. In addition, color Doppler sonography revealed a disturbed flow of the right branch of the portal vein. Similar to case 1, DSA showed an APF between A8 and P8. The APF was successfully embolized by TAE using microcoils. In conclusion, it appears that the formation of APF should be checked after RFA. It is preferable to treat RFA-induced APF promptly by an interventional approach to avoid secondary complications such as portal hypertension and liver dysfunction

Fatal Diaphragmatic Hernia following Radiofrequency Ablation for Hepatocellular Carcinoma: A Case Report and Literature Review

An 81-year-old man was admitted to our hospital because of right quadrant abdominal pain. On admission, his liver function was Child-Pugh grade C (10 points). Computed tomography (CT) revealed a diaphragmatic herniation of bowel loops into the right thoracic cavity, accompanied by pleural effusion. Although diaphragmatic hernia was successfully repaired by emergency surgery, he died of liver failure 23 days after the surgery. A retrospective reading of CT images revealed the presence of diaphragmatic injury after radiofrequency ablation (RFA) which had been conducted 33 months before the development of diaphragmatic hernia. Of importance, the lesion of the diaphragmatic injury was located on the estimated needle track of RFA for hepatocellular carcinomas in segment 5 and segment 5/8, but not adjacent to their ablation areas. Subsequently, diaphragmatic perforation had been observed 24 months before admission. This suggests that diaphragmatic hernia caused by RFA is not necessarily due to thermal damage of ablation and is possibly life-threatening, at least in some patients with an impaired liver function

Acute Liver Failure Occurring during the First Trimester of Pregnancy Successfully Treated with Living Donor Liver Transplantation

Acute liver failure (ALF) during pregnancy remains difficult to treat, and despite advances in treatment, liver transplantation must be selected as treatment option in certain cases. We report a 30-year-old woman with ALF of unknown etiology, occurring during the first trimester of pregnancy. Her condition was complicated by consciousness disturbance and coagulopathy due to ALF, but she was successfully treated with living donor liver transplantation 7 days after dilatation and curettage. At 9-month followup, she was in good medical condition. Liver transplantation has been reported as one of the treatment options for ALF during pregnancy with the prognosis varying depending on the trimester, from living donor or deceased donor liver transplantation. Of importance is that clinicians always think of emergent liver transplantation as a therapeutic option in ALF even in the first trimester of pregnancy

Phase Ib trial of durvalumab plus tremelimumab in combination with particle radiotherapy in advanced hepatocellular carcinoma patients with macrovascular invasion: DEPARTURE trial

Background: Advanced hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) has the worst prognosis among all HCC cases, due to its uniqueness of disease condition. Development of revolutionary therapeutic approaches to improve prognosis in these patients is an essential medical issue. A phase I/II trial demonstrated that treatment with durvalumab, an anti-programmed death-ligand 1 antibody, alone or in combination with tremelimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody, exhibited potential efficacy in patients with advanced HCC. Conversely, particle radiotherapy, including carbon-ion radiotherapy, has been shown to achieve unique dose distribution by delivering high-dose radiation to the target tumor while reducing the radiation dose to normal tissues due to its physical characteristics. Studies demonstrated that particle radiotherapy could achieve good local control in patients with HCC, including those with MVI. Additionally, particle radiotherapy as well as photon irradiation not only mediate localized tumor killing but also modify the tumor microenvironment, thereby potentiating the efficacy of immune checkpoint inhibitors. The DEPARTURE trial aims to evaluate whether treatment with durvalumab, alone or in combination with tremelimumab, plus particle radiotherapy is a safe and synergistically effective treatment in patients with advanced HCC and MVI.Methods: This is a phase Ib, multi-center, open-label, single-arm, investigator-initiated clinical trial to assess the safety of durvalumab monotherapy in combination with particle radiotherapy (Cohort A) and that of durvalumab plus tremelimumab in combination with particle radiotherapy (Cohort B) in advanced HCC patients with MVI who are ineligible for standard systemic therapy and Child–Pugh A liver disease. Cohort A will receive 1500 mg durvalumab every four weeks in principle. Cohort B will receive 1500 mg durvalumab every four weeks in principle and 300 mg tremelimumab only on day 1 of the first cycle. Carbon-ion radiotherapy will be administered after day 8 of the first cycle, following the first dose of either durvalumab or durvalumab plus tremelimumab on day 1. Dose prescription and fractionations are 60 Gy (RBE) in four fractions/1 week. Intrahepatic nodule with MVI is the target lesion for carbon-ion radiotherapy. Primary study endpoints are rates of all and severe adverse events including DLTs. Secondary endpoints include rates of overall survival, 6-month survival, objective response, and 6-month progression-free survival as well as time to progression

Potential of circulating receptor-interacting protein kinase 3 levels as a marker of acute liver injury

Abstract The pathogenesis of acute liver failure (ALF) involves cell death. Necroptosis is a newly suggested programmed cell death, and receptor-interacting protein kinase 3 (RIPK3) has been reported as a marker for necroptosis. However, there are few reports on necroptosis in ALF. Therefore, we evaluated the role of cell death markers such as cytokeratin (CK) 18, cleaved CK (cCK) 18, and RIPK3 in ALF, as well as cytokines and hepatocyte growth factor (HGF). Seventy-one hospitalized patients with acute liver injury (38 nonsevere hepatitis [non-SH]/22 severe hepatitis [SH]/11 ALF) were studied. No significant difference was found for cytokines, but a substantial increase in HGF levels was found following the severity of hepatitis. The non-SH group had lower levels of CK18 and cCK18 than the SH/ALF group. RIPK3 was significantly lower in the non-SH/SH group than in the ALF group. HGF, RIPK3, and albumin levels were found to be important predictive variables. The present study suggests that cCK18, CK18, and RIPK3 are associated with the severity of hepatitis. RIPK3 and other markers related cell death may be useful for understanding the pathogenesis of ALF and as a prognostic marker of acute liver injury

Cholangiocarcinoma Derived from Remnant Intrapancreatic Bile Duct Arising 32 Years after Congenital Choledochal Cyst Excision: A Case Report

We report a rare case of a 46-year-old woman with cholangiocarcinoma derived from remnant intrapancreatic bile duct arising 32 years after the excision of a congenital choledochal cyst. She had undergone anastomosis of the choledochal cyst and duodenum at birth, excision of the choledochal cyst and hepaticoduodenostomy with jejunal interposition at 14 years of age as well as the excision of an infectious cyst around the anastomosis site at 21 years of age. At 29 years of age, she was diagnosed with a chronic hepatitis C virus (HCV) infection and was referred to our hospital for treatment. She did not consent to interferon-based therapy against the HCV infection. At 46 years of age, she experienced epigastric discomfort. A dynamic CT revealed multiple tumors in the liver, a tumor in the head of the pancreas as well as lymph node metastases in the mediastinum and abdominal cavity. A liver tumor biopsy revealed adenocarcinoma, and she was clinically diagnosed with cholangiocarcinoma derived from remnant intrapancreatic bile duct with multiple metastasis in the liver and lymph node metastasis. She requested palliative therapy and eventually died during the treatment course. The autopsy specimen revealed a tumor in the head of the pancreas, and on the basis of local existence and the pattern of metastasis, it was confirmed as cholangiocarcinoma derived from remnant intrapancreatic bile duct. A microscopic examination revealed a poorly differentiated adenocarcinoma. This report provides information on a case of cholangiocarcinoma derived from remnant intrapancreatic bile duct arising after the excision of congenital choledochal cyst that was assessed pathologically