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The differences between Bismuth IIIa and IIIb types of hilar cholangiocarcinoma are unclear. Thus, this study aimed to compare the clinical characteristics of the Bismuth IIIa and IIIb types of hilar cholangiocarcinoma. A case series analysis was designed to explore the clinical and pathological findings and survival of 144 patients with hilar cholangiocarcinoma who underwent curative hepatectomy between 2007 and 2018. The patients in the IIIa group received portal vein embolization and transfusion more frequently than those in the IIIb group (18.3% vs. 0.0%, P < 0.05 and 36.6% vs. 25.0%, P < 0.05). The incidence of posthepatectomy liver failure and serious surgical complications (≥ grade B) was significantly higher in the IIIa group than in the IIIb group (12.2% vs. 4.5%, P < 0.01 and 32.9% vs. 9.1%, P < 0.01). Tumors of the patients in the IIIa group had more advanced T and N stages than those of the patients in the IIIb group (P < 0.01). The patients in the IIIa group had poorer disease-free and overall survival rates than those in the IIIb group (P = 0.014 and P = 0.048). N stage and lymphovascular invasion were independently correlated with disease-free survival, whereas T and N stages were independently correlated with overall survival in the IIIb group. Meanwhile, T stage, N stage, and lymphovascular invasion were independently correlated with disease-free survival, whereas posthepatectomy liver failure, complication, and T stage were independently correlated with overall survival in the IIIa group. Hepatic and portal vessel metastasis occurred more frequently in the IIIa group than in the IIIb group (7.3% vs. 0.0%, P < 0.05). In our centers, patients with Bismuth IIIb hilar cholangiocarcinoma exhibited better disease-free and overall survival rates with more favorable clinicopathological characteristics than those with IIIa hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease with unknown causes. The initiation of PBC is associated with bacterial infections and abnormal immune correlates, such as the presence of self-reactive anti-mitochondrial antibodies and shifted balance of T cell subsets. In particular, the CD4 + CXCR5 + follicular helper T (Tfh) cells are highly activated in PBC patients and are significantly associated with PBC severity, but the underlying reasons are unknown. In this study, we found that the circulating CD4 + CXCR5 + T cells were enriched with the interferon (IFN)-γ-secreting Th1-subtype and the interleukin (IL)-17-secreting Th17-subtype, but not the IL-4-secreting Th2 subtype. We further demonstrated that a host of microbial motifs, including Pam3CSK4, poly(I:C), LPS, imiquimod, and CpG, could significantly stimulate IFN-γ, IL-17, and/or IL-21 from circulating CD4 + CXCR5 + T cells in PBC patients, especially in the presence of monocytes and B cells. Whole bacterial cells of Escherichia coli , Novosphingobium aromaticivorans , and Mycobacterium gordonae , could also potently stimulate IFN-γ, IL-17, and/or IL-21 production from circulating CD4 + CXCR5 + T cells. But interestingly, while the whole cell could potently stimulate circulating CD4 + CXCR5 + T cells from both healthy controls and PBC patients, the cell protein lysate could only potently stimulate circulating CD4 + CXCR5 + T cells from PBC patients, but not those from healthy controls, suggesting that circulating CD4 + CXCR5 + T cells in PBC patients had distinctive antigen-specificity from those in healthy individuals. Together, these data demonstrated that bacterial antigen stimulation is a potential source of aberrant Tfh cell activation in PBC patients. [ABSTRACT FROM AUTHOR]

Background Treatment options for patients with portal vein ( PV) stenosis or occlusion after surgery are limited. The purpose of this study was to investigate the efficacy and safety of PV stent placement in patients with portal vein occlusion or stenosis after radical operation for hepatobiliary pancreatic malignant tumour. Methods We retrospectively reviewed the records of 59 patients who underwent portal venous stent placement at the Asan Medical Center, Seoul, Korea, for PV stenosis or occlusion between February 2008 and February 2012. Results Stents were placed in the portal venous system across stenotic ( n = 47) and occlusive ( n = 12) lesions after percutaneous transhepatic portography. Reasons for stent placement were tumour recurrence ( n = 30), portal vein resection and anastomosis ( n = 18) and post-operative inflammatory changes ( n = 11). Pressure gradients (superior mesenteric vein, main PV) decreased immediately after stent placement, from 10.5 mm Hg ± 4.4 (standard deviation) to 2.5 mm Hg ± 2.6 ( P < 0.0001). Liver function was improved post-stenting ( P < 0.05). The median time between the original surgery and stent placement was 16 (1-137) days in the vascular-orientated group and 306 (13-3703) days in the tumour recurrence group ( P < 0.0001). Transient fever developed in 11 patients, but resolved in 2-5 days. Stents were occluded in 15 of the 59 patients (25.4%). Conclusion PV stent placement is a safe choice, has an acceptable success rate and provides marked relief from portal hypertension due to portal vein occlusion or stenosis after hepatobiliary pancreatic surgery. Liver function data are also improved after portal venous stent placement. [ABSTRACT FROM AUTHOR]

Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM. [ABSTRACT FROM AUTHOR]

Autoimmune pancreatitis (AIP) is a fibro‐inflammatory disease characterized by inflammation and fibrosis of the pancreas. It is a systemic disease that can affect multiple organs, including the bile ducts, kidneys, lungs, and other organs. However, due to its complex presentation, AIP is often challenging to diagnose, and misdiagnosis with pancreatic tumors can occur. In our study, we reviewed three cases of atypical AIP where patients had normal serum IgG4 levels, leading to initial misdiagnosis with pancreatic tumors. Delayed diagnosis resulted in irreversible pathologies such as retroperitoneal fibrosis. All three patients had bile duct involvement, and imaging findings were similar to those of tumors, further complicating the diagnosis. The correct diagnosis was confirmed only after diagnostic therapy. Our study aims to raise awareness of atypical AIP and improve diagnostic efficiency by analyzing the clinical characteristics of these patients. [ABSTRACT FROM AUTHOR]

Background: The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients. Methods: We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018. Results: The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30–40 (P = 0.047). Conclusions: AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer with one of the worst survival rate of all malignancies. Recent studies have identified that immunosuppressive B cells could employ the PD‐1/PD‐L1 pathway to suppress antitumour T cell responses; hence, we examined the expression and function of PD‐L1 in B cells. We found that the PD‐L1 expression was significantly enriched in tumour‐infiltrating (TI) B cells than in peripheral blood (PB) B cells from the same patients. Additionally, the PB B cells from stage III and stage IV PDAC patients presented significantly higher PD‐L1 than the PB B cells from healthy controls. High PD‐L1 expression in PB B cells could be achieved by stimulation via CpG and less effectively via anti‐BCR plus CD40L, but not by coculture with pancreatic cancer cell lines in vitro. Also, STAT1 and STAT3 inhibition significantly suppressed PD‐L1 upregulation in stimulated B cells. CpG‐stimulated PB B cells could inhibit the IFN‐γ expression and proliferation of CD8 T cells in a PD‐L1‐dependent manner. Also, TI CD8 T cells incubated with whole TI B cells presented significantly lower IFN‐γ expression and lower proliferation, than TI CD8 T cells incubated with PD‐L1+ cell‐depleted TI B cells, suggesting that PD‐L1+ B cells could also suppress CD8 T cells in the tumour. Overall, this study identified that B cells could suppress CD8 T cells via PD‐L1 expression, indicating a novel pathway of immuno‐regulation in pancreatic cancer. [ABSTRACT FROM AUTHOR]

F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Heme oxygenase-1 has been identified to protect allograft from ischemia/reperfusion and immunologic rejection. Activity of heme oxygenase-1 is regulated by a guanine-thymine dinucleotide length polymorphism in the heme oxygenase-1 gene promoter. In this study, we aimed to explore the impact of the heme oxygenase-1 gene promoter polymorphism of donors and recipients on the orthotopic liver graft function after transplantation. Sixty recipients and their accompanying donors of orthotopic liver allografts were included retrospectively in this study. Heme oxygenase-1 gene promoter polymorphism was assessed using genomic DNA isolated from cryopreserved splenocytes or peripheral blood mononuclear cells and analyzed by genetic analyzer. Small allele of the donor heme oxygenase-1 gene polymorphism significantly prolonged the graft survival ( p = 0.017). Recipients of allografts from a class of small-allele carrier had significantly lower serum total bilirubin compared with recipients of a nonclass small-allele donor liver ( p < 0.01). Additionally, in recipients of small-carrier allografts, cold ischemia time (<10 h or ≥10 h) did not affect the total bilirubin significantly. Our study suggested a protective function of donor-derived heme oxygenase-1 gene promoter polymorphism on orthotopic liver allograft function after transplantation. [ABSTRACT FROM AUTHOR]