Improvement in aged liver regeneration using cell transplantation with chemically induced liver progenitors.

BACKGROUND: A decrease in the regenerative capacity of age-damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age-damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes. METHODS: Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans-splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated. RESULTS: At 7 days post-hepatectomy, LW/BW ratios were significantly better in CLiP-treated old mice than in untreated old mice (p = .02). By contrast, no effect of CLiP transplantation was observed in young mice (p = .62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67-positive cells (p < .01). Flow cytometry analysis of green fluorescent protein-labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver. CONCLUSIONS: CLiP transplantation appears to ameliorate the age-related decline in liver regeneration in mice.

Analysis of the Clinical Course in a Population of Patients with Biliary Tract Cancer Diagnosed as Unresectable After Portal Vein Embolization: A Case Series.

Portal vein embolization (PVE) is recommended as a preoperative procedure for patients with biliary tract cancer scheduled to undergo hepatic resection of more than 50%-60% of the liver. However, details and/or information regarding the follow-up of unresectable cases are often lacking, and the clinical course of unresectable cases is not well analyzed and reported. This study aimed to clarify the clinical prognosis of patients with unresectable biliary tract cancer after PVE. We retrospectively analyzed the clinical backgrounds of patients with biliary tract cancer who underwent PVE without subsequent resection between January 2011 and October 2022. Of the 21 patients with biliary tract cancer who underwent PVE during the study period, eight (38%) cases were unsuitable for resection after PVE for the following reasons: intraoperatively detected dissemination (n=2), para-aortic lymph node metastasis (n=1), liver metastasis (n=1), decreased liver function (n=2), development of liver metastasis while waiting (n=1), and insufficient residual liver volume (n=1). All patients received subsequent chemotherapy, including gemcitabine plus S-1 therapy in three cases, gemcitabine plus cisplatin plus S-1 in three cases, and gemcitabine plus cisplatin or S-1+cisplatin in one case each. As there is currently no curative treatment for biliary tract cancer other than surgery, multidisciplinary management and treatment of patient factors, including tumor factors and liver function, are essential to reducing the number of unresectable cases after PVE.

Feasibility of Organ Transportation by a Drone: An Experimental Study Using a Rat Model.

BACKGROUND: Recently, the successful delivery of organs for transplantation using drones was reported. We investigated the influence of transportation by drones on the quality of liver grafts using a rat model. METHODS: Livers of 12 rats (8 and 32 weeks old) were divided into 2 groups of six. Livers were split into 2 parts and allocated to the drone or control groups (both n = 12). The drone experiment was conducted between islands in Nagasaki Prefecture, Japan. The distance between the islands was 12 km. Livers of the drone group were transported by a multicopter at a speed of 30 km-40 km/h over 60 m above sea level. Transported liver quality was analyzed by histology, and biochemistry data were compared between groups. RESULTS: Cold ischemia time did not differ between groups (902 min and 909 min, respectively). There were no differences in macroscopic findings regarding coloration and damage between groups. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in preservation fluid were graft weight-corrected and compared, and no significant differences were found between groups: AST/g (4.61 vs 4.81 IU/L), ALT/g (2.78 vs 2.92 IU/L), and ALP/g (39.1 vs 37.0 IU/L). Immunochemical staining showed no significant difference between groups for terminal deoxynucleotidyl transferase dUTP nick and labeling staining (141 vs 113 cells), CD163 (818 vs 870 cells), and TNF-α (1.25 vs 1.41 scores). CONCLUSIONS: The simulation experiment of organ transport for transplantation by drones was successfully conducted. There were no differences in the quality of livers transported by drones or other means. Further studies including large-animal experiments could lead to future clinical applications.

Preliminary Observations of An Ex Vivo Normothermic Whole Blood Machine Perfusion in An Experimental Liver Transplant Porcine Model.

BACKGROUND: Even though transplantation is an essential treatment with no viable alternatives, a significant worldwide donor shortage persists. In this study, we assessed the metabolism of livers that underwent extended periods of circulatory death and subsequently conducted functional validation through transplantation to explore the feasibility of using livers from an uncontrolled donor after circulatory death (u-DCD). METHODS: A donor model simulating u-DCD was constructed using pigs. The prolonged warm ischemia time (WIT) was set to 60, 120, and 180 minutes, and the liver function was evaluated after 24 hours of perfusion using an originally developed normothermic perfusion system. Based on the results, functional confirmation by transplantation was performed on the 2 groups with prolonged WIT of 60 and 180 minutes. RESULTS: Based on the 24-hour perfusion of the liver alone, we evaluated the function by transplanting the WI 60-minute model and 180-minute model (N = 3 each). Warm ischemia was 73.5 ± 3.7 minutes and 188 ± 3 minutes in the 60-minute model and 180-minute model, respectively. In the model with 60 minutes of WI, one case survived until the endpoint, and 2 cases survived between 8 and 12 hours, whereas, in the model with 180 minutes of WI, they died within 6 hours. CONCLUSION: We constructed a completely uncontrolled circulatory arrest model without anticoagulation and showed the possibility of using u-DCD livers by ex vivo machine perfusion and transplantation.

Percutaneous Direct Puncture of Retropancreatic Splenic Vein and Portal Thrombectomy in a Patient With Liver Transplantation and Simultaneous Splenectomy.

Portal vein thrombosis following liver transplantation is generally managed by endovascular treatment. Although several techniques are available for portal venous access, trans-splenic access is of interest because it avoids damage to the liver graft. However, the spleen cannot be punctured to access the portal vein after splenectomy. We herein report a case of portal vein thrombosis following living donor liver transplantation with simultaneous splenectomy successfully treated by percutaneous intervention with direct puncture of the retropancreatic splenic vein. The splenic vein was punctured under computed tomography guidance in the prone position. Portal venography revealed a contrast defect due to a thrombus in the extrahepatic to intrahepatic portal vein. The portal vein was reopened after thrombectomy, and the portal vein thrombosis did not recur for 2 y. The technique and advantages of our approach are described.

Hepatic sclerosing haemangioma showing restricted diffusion: A case report with histopathologic correlation.

Hepatic sclerosing haemangiomas are rare benign tumours that are often difficult to distinguish from malignant tumours because these tumours do not show the typical imaging features of cavernous haemangiomas. We report a case of a sclerosing haemangioma that showed restricted diffusion and was difficult to differentiate from a malignancy. A 60-year-old female was referred to our hospital for evaluation of a hepatic mass that was incidentally diagnosed after a CT scan for right lower quadrant abdominal pain. Contrast-enhanced dynamic CT showed hepatic capsular retraction, with a small peripheral enhancement of the mass. The lesion appeared homogeneously hypointense on T1W images, heterogeneously hyperintense on T2W images, hyperintense on diffusion-weighted images, and hypointense on apparent diffusion coefficient (ADC) map. The lesion was suspected to be a cholangiocellular carcinoma and was surgically resected, but a final diagnosis of hepatic sclerosing haemangioma was made. Hepatic sclerosing/sclerosed haemangiomas are usually considered to show an increased ADC, which is useful for distinguishing them from malignant tumours. However, in this particular case, most of the lesion contained many obliterated or narrowed vascular channels, which might have acted as septa restricting the diffusion of water molecules in the intervening fibrous and/or hyalinised tissue. Hepatic sclerosing haemangiomas in the process of becoming completely fibrotic may show restricted diffusion, similar to malignant tumours.