Background: s/Aims: Patients with hepatocellular carcinoma (HCC) and histologically confirmed F4 cirrhosis often have limited hepatic reserve, making major hepatectomy difficult. Although laparoscopic liver resection is increasingly performed, its perioperative safety in this setting remains unclear. This study compared laparoscopic and open partial hepatectomy in these patients using propensity score matching (PSM). Methods: Among 298 patients who underwent hepatectomy for HCC between 2006 and 2023, 112 with histologically confirmed F4 cirrhosis who underwent partial hepatectomy were included (laparoscopic, n = 60; open, n = 52). PSM was performed using previous liver resection, difficulty score, tumor size, tumor number, and platelet count, yielding 32 matched pairs. Outcomes included operative time, blood loss, transfusion requirements, complications, hospital stay, posthepatectomy liver failure (PHLF), R0 resection rate, and 30-day mortality. Results: After matching, intraoperative blood loss was significantly lower in the laparoscopic group than in the open group (50 mL vs. 295 mL, p < 0.001). Operative time, transfusion rate, complication rate, R0 resection rate, and 30-day mortality were comparable between groups. Hospital stay was significantly shorter in the laparoscopic group (13 vs. 22 days, p < 0.001). Grade A PHLF occurred in one patient in the open group, with no significant between-group difference. Conclusions In patients with HCC and histologically confirmed F4 cirrhosis, laparoscopic partial hepatectomy was associated with less blood loss and shorter hospital stay than open surgery, without increasing perioperative morbidity. It may be a safe option in carefully selected patients undergoing limited liver resection.

Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

BACKGROUND/AIMS: Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. METHODS: CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed. RESULTS: Mγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients. CONCLUSIONS: These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.
Blotting, Western ; Candida albicans* ; Candida* ; Crohn Disease* ; Cytokines* ; Flow Cytometry ; Fungi ; Healthy Volunteers ; Humans ; In Vitro Techniques ; Inflammation ; Interleukin-6 ; Macrophage Colony-Stimulating Factor ; Macrophages* ; Microbiota ; Monocytes ; Mucous Membrane* ; Necrosis ; Tumor Necrosis Factor-alpha