Tsuyoshi Kobayashi

Background/Purpose: Optimal perioperative antithrombotic therapy (ATT) management during emergency cholecystectomy for acute cholecystitis remains controversial. We examined whether continuing single‐agent ATT is associated with hemorrhagic risk compared with no ATT. Methods: This retrospective cohort study included 1018 patients (826 without ATT, 192 continued on single‐agent ATT) at seven institutions (2020–2023). Propensity score overlap weighting balanced 12 baseline covariates. The primary outcome was intraoperative blood loss > 100 mL; risk ratios and 95% confidence intervals were estimated via modified Poisson regression, with upper confidence bound compared against a pre‐specified risk ratio (1.5). Results: The primary outcome occurred in 27.3% and 25.4% of the non‐ATT and continued‐ATT groups, respectively (risk ratio: 0.93, 95% confidence interval: 0.69–1.26). The upper bound of the confidence interval was within the pre‐specified margin. No significant differences were observed in perioperative bleeding complications or hospital stay. Secondary outcomes, sensitivity analyses, and drug‐specific subgroup analyses (including direct oral anticoagulants) yielded consistent results. Conclusions: Continuing single‐agent ATT was comparable to no ATT regarding bleeding during cholecystectomy for acute cholecystitis. These findings suggest that emergency cholecystectomy can be performed without meaningful increases in hemorrhagic risk in patients for whom adequate preoperative ATT washout is not feasible.

Introduction and importance: Eosinophilic granuloma is a histopathological condition characterized by eosinophil-rich granulomatous inflammation and is considered a manifestation of allergic reactions. Hepatic eosinophilic granuloma (HEG) is an extremely rare entity and is most commonly associated with parasitic infections. We report a case of HEG without peripheral eosinophilia or a confirmed parasitic infection, with a difficult preoperative diagnosis, treated by laparoscopic liver resection. Case presentation: A 67-year-old woman was referred for further evaluation of a liver tumor in segment 3 detected by computed tomography performed for unexplained abdominal pain. Tumor markers were not elevated, and although further imaging studies did not exclude hepatic malignancy, an inflammatory pseudotumor or intrahepatic cholangiocarcinoma was suspected. Laparoscopic sub-segmentectomy of segment 3, and lymph node dissection around the common hepatic artery, were performed for diagnostic and therapeutic purposes, respectively. Histopathological examination revealed a granuloma with marked eosinophilic infiltration and central coagulative necrosis. Tests for mycobacterial infection were negative, and neither parasitic organisms nor serological evidence of parasitic infection was identified. Clinical discussion: Preoperative diagnosis of HEG remains challenging because its radiological findings often resemble those of hepatic malignancies, particularly in the absence of peripheral eosinophilia or evidence of parasitic infection. Conclusion: HEG is most frequently associated with parasitic infections. However, precise preoperative diagnosis of nonparasitic HEG remains challenging. Laparoscopic resection enabled a definitive diagnosis. Therefore, HEG should be considered in the differential diagnosis of primary hepatic tumors, even in the absence of confirmed parasitic infections or peripheral eosinophilia. Minimally invasive surgery is a reasonable option from both therapeutic and diagnostic perspectives.

Introduction: Hydrogen therapy has been reported to exert antioxidative and anti-inflammatory effects and has attracted increasing clinical interest across various medical fields. In cancer treatment, a waiting period often exists between the treatment decision and surgery; however, structured and evidence-based preoperative interventions during this interval remain limited. Home-based hydrogen gas inhalation, which enables long-duration, repeated administration, may represent a feasible and practical strategy for preoperative optimization. This study aims to evaluate the safety and feasibility of a standardized home-based hydrogen gas inhalation protocol in patients scheduled for liver resection. Methods: This is a prospective, single-center, single-arm, open-label exploratory clinical trial with a planned enrollment of eight participants. Eligible patients scheduled for liver resection will undergo home-based hydrogen gas inhalation during sleep and, additionally, for approximately 1 hour each morning and evening for 14 consecutive days in the preoperative waiting period. The primary endpoint is feasibility, defined as protocol adherence based on predefined inhalation duration criteria. Safety will be assessed by the incidence of adverse events. Secondary and exploratory assessments include changes in inflammation-related, immune-related, and nutrition-related indices, oxidative stress markers, body composition parameters, questionnaire-based quality of life, and tumor markers. This study is registered in the Japan Registry of Clinical Trials (jRCT: jRCTs062250073). Conclusion: This study protocol is designed to evaluate the feasibility and safety of preoperative home-based hydrogen gas inhalation and to generate preliminary data to inform the design of subsequent clinical trials investigating its potential role in perioperative care for liver surgery.

Background and Aim: Epithelial‐myoepithelial carcinoma (EMC), a malignant tumor with biphasic epithelial and myoepithelial differentiation, is typically a salivary gland neoplasm. Contrastingly, myoepithelial carcinoma (MEC) predominantly comprises myoepithelial cells. In salivary gland pathology, biphasic ductal tumors are classified as EMC, even with a predominant myoepithelial component. Primary hepatic tumors showing myoepithelial and epithelial–myoepithelial differentiation are rare, with uncertain definition and clinical behavior owing to limited reported hepatic carcinoma with MEC/EMC spectrum cases. Here, we report a unique case with intrahepatic recurrence that was successfully managed with repeat hepatectomies. Case: A 66‐year‐old woman presented with pain in the right hypochondrium. Imaging revealed a 13 cm tumor in the right hepatic lobe, and biopsy suggested squamous cell carcinoma. After portal vein embolization, right trisectionectomy was performed. Histopathology revealed a biphasic structure with duct‐forming epithelial cells surrounded by myoepithelial cells, confirming hepatic carcinoma with epithelial–myoepithelial differentiation. After 2 years, multiple intrahepatic recurrences without extrahepatic disease were detected and repeat hepatectomies were performed. The patient remains recurrence‐free 1 year post‐reoperation. Conclusions: Hepatic carcinoma with epithelial–myoepithelial differentiation is rare, with uncertain definition and clinical behavior. Careful exclusion of extrahepatic primaries, detailed immunophenotyping, and long‐term surveillance are essential. Repeat hepatectomies may be a curative option for intrahepatic recurrence in selected patients.

Objectives: Preoperative chemotherapy increases resectability in patients with resectable colorectal liver metastasis who undergo curative hepatectomy; however, there is no consensus regarding patient selection. The aim of this study was to identify high-risk patients with synchronous colorectal liver metastasis and compare the outcomes of preoperative chemotherapy with those of upfront surgery.Methods: This multi-institutional, retrospective study enrolled patients who underwent their first liver resection for synchronous colorectal liver metastasis from January 2010 to July 2019. We retrospectively studied the clinicopathological features and prognoses of synchronous colorectal liver metastasis subjected to curative liver resection. Surgical outcomes were compared between the preoperative chemotherapy and upfront surgery groups.Results: We analyzed 215 patients categorized into the preoperative chemotherapy (n=111) and upfront surgery (n=104) groups. The distribution of primary colorectal cancer locations significantly differed, and the preoperative chemotherapy group had more and larger tumors than did the upfront surgery group. There were no significant between-group differences in recurrence-free survival and overall survival. Primary lymph node metastasis ≥N2, tumor burden score >5, positive carbohydrate antigen 19-9 on treatment, and the Kirsten rat sarcoma viral oncogene homolog mutation were independent risk factors for recurrence-free survival. The recurrence-free survival rate was significantly higher in the preoperative chemotheapy group than in the upfront surgery group for patients with ≥2 risk factors.Conclusions: Our study suggests new criteria for identifying high-risk patients with synchronous colorectal liver metastasis and shows that preoperative chemotherapy may be an effective option for high-risk patients with ≥2 risk factors.

Introduction: Metabolic dysfunction associated steatotic liver disease promotes intrahepatic metastasis of liver cancer, although not uniformly. However, the mechanisms underlying steatosis-induced progression of liver cancer are not well understood. Antitumor properties of thrombomodulin (TM) are unknown. We aimed to investigate whether TM contributes to the suppression of hepatocellular carcinoma (HCC) progression in the steatotic livers of mice. Methods: Mice were fed a normal or choline-deficient diet (CDD) for 4 weeks, followed by splenic injection of mouse Hepa1-6 cells. Hepatic tumors were analyzed 3 weeks after the injection. Results: CDD induced hepatic steatosis, which resulted in a hypoxic state and the downregulation of TM in the liver. CDD-induced hepatic steatosis promoted HCC progression and increased serum levels of high motility group box 1 (HMGB-1), which were suppressed by recombinant TM (rTM). However, HCC progression was not promoted in non-steatotic livers. In TM^+/- mice with hepatic steatosis, of which endogenous TM was severely down-regulated, ischemia-reperfusion significantly enhanced HCC progression compared to that in wild-type mice with steatotic livers, both of which were also ameliorated by rTM. In vitro, hypoxia promoted Hepa1-6 cell motility and secretion of HMGB-1 from the Hepa1-6 cells, and the addition of HMGB-1 also enhanced the motility of the Hepa1-6 cells in the non-hypoxic state, which was suppressed by rTM and anti-HMGB-1 antibodies. Discussion: These findings suggest that hepatic steatosis has a prometastatic effect through the downregulation of TM. TM has a tumor-suppressive function via the inhibition of HMGB-1 activity. Plain Language Summary: Steatotic liver reduces the expression of TM and accelerated the progression of HCC by decreasing the capacity of TM to absorb HMGB-1. rTM may be a useful modality to prevent HCC progression in steatotic livers during hepatic surgery.

Aim: Bile acids accumulation in hepatocytes causes liver damage and contributes to the development of hepatocellular carcinoma. However, the association between serum bile acid levels and postoperative intrahepatic recurrence in hepatocellular carcinoma remains unclear. We investigated the effect of preoperative serum bile acid levels on intrahepatic recurrence in patients with hepatocellular carcinoma following initial curative hepatectomy. Methods: This retrospective study included 249 patients with hepatocellular carcinoma who had preoperative serum bile acid levels measured and underwent initial curative hepatectomy between April 2010 and December 2018. We investigated the associations among serum bile acid levels, liver fibrosis, and postoperative outcomes in these patients. Results: Patients with high serum bile acid levels had a high prevalence of hepatitis C virus‐positive, a high proportion of preoperative ursodeoxycholic acid use, and poor liver reserve function. These patients had more severe pathological liver fibrosis and necro‐inflammatory reaction and blood‐based markers for liver fibrosis were higher than those in patients with low serum bile acid levels. Compared with blood‐based markers for liver fibrosis, serum bile acids were more accurate prognostic indicators of intrahepatic recurrence. High serum bile acid levels were associated with poor overall survival and high intrahepatic recurrence rates in patients with hepatocellular carcinoma following initial curative hepatectomy. High serum bile acid levels represented an independent risk factor for postoperative intrahepatic recurrence. Conclusions: Serum bile acid levels reflect both the degree of liver fibrosis and necro‐inflammatory reaction and are associated with postoperative intrahepatic recurrence in patients with hepatocellular carcinoma following initial curative hepatectomy.