佐田 尚宏

Portal cavernoma cholangiopathy (PCC) is a complex condition associated with portal hypertension, particularly in patients with extrahepatic portal vein obstruction (EHPVO). Herein, we present a case of liver failure with PCC in a 55-year-old male successfully treated with living-donor liver transplantation (LDLT). The patient had a history of gastrointestinal bleeding and recurrence of cholangitis. Imaging studies confirmed cavernous transformation and pericholedochal varices. Preoperative angiography verified hepatopetal flow in the pericholedochal varix, which facilitated successful anastomosis with the donor's portal vein during LDLT. Histological examination of the explanted liver confirmed vanishing bile duct syndrome (VBDS) and secondary bile stasis was considered to have caused liver failure. No postoperative complications were observed within 13 months of LDLT. We report the first case of VBDS in the PCC resulting from EHPVO that was successfully managed with LDLT. Careful management of similar cases should involve angiography and long-term postoperative monitoring of portal vein complications.

BACKGROUND: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis. METHODS: Male Lewis rats were fed with a methionine and choline-deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV). RESULTS: The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division. CONCLUSIONS: MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx.

A 50-year-old man was diagnosed with type 1 autoimmune pancreatitis (AIP) following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and a histopathological examination. After six months of untreated follow-up, the serum IgG4 level decreased, and the diffuse pancreatic enlargement improved; however, a pancreatic head mass became apparent. EUS-FNA of this mass revealed pancreatic ductal adenocarcinoma (PDAC) with IgG4-positive plasma cells. In addition, the resected specimen revealed PDAC, without any features of AIP. After pancreatoduodenectomy, AIP did not recur. The development of AIP in this case could be related to paraneoplastic syndrome.

This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.