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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]

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]

Background: Cholangiocarcinoma is characterized by significant cellular heterogeneity and complex intercellular communication, which contribute to its progression and therapeutic resistance. Therefore, unraveling this complexity is essential for the development of effective treatments. Methods: We employed single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and intercellular communication in cholangiocarcinoma and adjacent normal tissues from two patients. Distinct cell types were identified, and gene ontology analyses were conducted to determine enriched pathways. Moreover, cell-cell communications were analyzed using CellChat, a computational framework. Additionally, we performed sub-clustering analysis of T cells and fibroblasts. Results: The scRNA-seq analysis revealed distinct cell clusters and diverse cellular compositions of cholangiocarcinoma. CellChat analysis underscored an amplified outgoing signal from fibroblasts within the tumor, suggesting their pivotal role in the tumor microenvironment. Furthermore, T cell sub-clustering analysis revealed an active immune response within the tumor and new tumor-specific T cell clonotypes, suggesting scope for targeted immunotherapies. Moreover, fibroblast sub-clustering analysis indicated distinct functional states and highlighted the role of activated fibroblasts in shaping intercellular communication, particularly via CD99 and FN1 signaling. Conclusion: Our findings reveal the intricate cellular heterogeneity and dynamic intercellular communication in cholangiocarcinoma, providing valuable insights into disease progression and potential therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Zhang, Xu, Tang, Chen, Guan and Zhang.)

Background: Nodal status is a vital prognostic factor for ampullary adenocarcinoma. This study was designed to evaluate the clinical significance of the positive nodes in this disease., Methods: Data from 110 patients who underwent curative pancreatoduodenectomy for ampullary adenocarcinoma between January 2007 and December 2018 were retrospectively collected and analyzed., Results: The median number of lymph nodes per patient was 32 (20-46). Metastatic lymph nodes were found in 84 (76.4%) patients. In patients with positive nodules, the most commonly involved nodes were the #13 (80.1%) and #17 (78.6%) nodes, followed by #12 (69.0%) and #8 nodes (57.1%). Patients with 3-4 positive nodes among #13, #17, #12, and #8 had lower survival rates than those with 0 or 1-2 nodes., Conclusion: Ampullary adenocarcinoma commonly spreads to #13, #17, #12, and #8 lymph nodes. These nodes affected the patients' survival rates dramatically., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Zhang, Guan, Wang, Hao and Zhou.)

Objective: Tumor recurrence remains the main dilemma after surgical treatment of ampulla of Vater carcinoma. This study was designed to identify the prognostic factors and evaluate the recurrence patterns of ampulla of Vater cancer., Methods: A total of 286 patients who underwent surgical resection of ampulla of Vater cancer in two medical centers from January 2000 to October 2016 were collected. Data on clinicopathologic factors, survival rate, and recurrence patterns were retrospectively analyzed., Results: A total of 158 patients (55.2%) survived without evidence of recurrence (non-recurrence), whereas 65 (22.7%) and 63 patients (22.1%) suffered from recurrence of the disease within 12 months (early recurrence) and after 12 months (late recurrence), respectively. Early-recurrence patients exhibited a more advanced disease (advanced tumor stage, lymph node involvement, pancreas invasion, and late TNM stage) than late-recurrence patients. The first or primary location of cancer recurrence in 33 patients (25.8%) was locoregional. Metastasis developed in the liver in 30 patients (23.4%), peritoneum in 13 patients (10.2%), lungs in 10 patients (7.8%), and para-aortic or superior mesenteric artery lymph node in 10 patients (7.8%). Multiple metastases were observed in 26 patients (20.3%)., Conclusion: The most common patterns of postoperative recurrence are locoregional and recurrent liver metastasis. The recurrence patterns with the worst prognosis are peritoneal and multiple metastases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Liu, Hao and Zhou.)

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is one of the most common cancers in HBV-endemic regions, with irreversible progression and poor prognosis. HBV-related HCC patients lack effective antiviral/antitumor B cell antibody responses. We hypothesize that dysregulation of PD-1-expressing follicular helper T (Tfh) cell, induced by intrahepatic/intratumoral PD-L1 expression in HCC, could contribute to the defects in B cell immunity. The Tfh responses in healthy control (HC) subjects, chronic hepatitis B (HepB) patients, and HBV-related HCC patients were examined. Compared to HC and HepB individuals, HCC patients showed reduced ICOS expression, IL-10 and IL-21 secretion, and proliferation in Tfh cells. Tfh cells from stage III patients demonstrated increased impairment than those from stage I and stage II patients. Compared to Tfh cells from HC and HepB subjects, those from stage III HCC patients were significantly less effective at inducing the differentiation of naive B cells toward plasmablasts. HCC is known to upregulate hepatic PD-L1 expression, which could suppress Tfh responses. Blocking PD-1 partially rescued the Tfh functions in stage I and stage II HCC subjects but not in stage III HCC patients, while treatment with recombinant PD-L1 strongly suppressed Tfh functions in all HCC stages. Moreover, the level of IL-10 and IL-21 expression by Tfh cells was inversely correlated with the intensity of PD-L1 expression in resected tumors. Together, our results demonstrated an HCC-specific Tfh exhaustion, which might have resulted from elevated PD-1 and PD-L1 signaling.

Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9<466 U/ml were more responsive to chemotherapeutic agents than those with CA19-9≥571 U/ml (88.9% vs 0%, P<0.001). We conclude that the combination of GEM plus S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733)., Competing Interests: The authors declare that they have no conflicts of interest.

Background: Studies investigating the association between hepatitis C virus (HCV) infections and the occurrence of cholangiocarcinoma (CCA), especially intrahepatic cholangiocarcinoma (ICC), have shown inconsistent findings. Although previous meta-analyses referred to HCV and CCA, they mainly focused on ICC rather than CCA or extrahepatic cholangiocarcinoma (ECC). Since then, relevant new studies have been published on the association between HCV and ICC. Since the different anatomic locations of CCA have distinct epidemiologic features and different risk factors, it is necessary to evaluate the relationship between HCV infection and ICC, ECC, and CCA., Methods: Relevant studies were identified by searching PUBMED, EMBASE, and MEDLINE databases prior to 1 August 2013. Pooled risk estimates were calculated with random-effects models using STATA 11.0., Results: A total of 16 case-control studies were included in the final analysis. Pooled risk estimates showed a statistically significant increasing risk of CCA (odds ratio (OR) = 5.44, 95% CI, 2.72 to 10.89). The pooled risk estimate of ICC (OR = 3.38, 95% CI, 2.72 to 4.21) was higher than that of ECC (OR = 1.75, 95% CI, 1.00 to 3.05). In a subgroup analysis, the pooled risk estimate of ICC in studies from North America was obviously higher than in Asia (6.48 versus 2.01). The Begg funnel plot and Egger test showed no evidence of publication bias., Conclusions: HCV infection is associated with the increasing risk of CCA, especially ICC.

Objectives: We hypothesized that the combination of APACHE II and Model for End-Stage Liver Disease systems would work satisfactorily in patients admitted to intensive care unit after living-donor liver transplant., Materials and Methods: Data were retrospectively collected from the database of our surgical team. The study included 38 patients (hepatitis B virus cirrhosis, 47.4%; hepatocellular carcinoma, 28.9%; other diseases, 23.7%). Laboratory values were obtained. Vital signs, Glasgow Coma scale scores, and urine output were abstracted. Variables included age, sex, acute physiology score, APACHE II score, APACHE II-predicted intensive care unit and hospital mortality, predicted length of intensive care unit, and hospital stay. Patients' actual length of intensive care unit and hospital stays, intensive care unit and hospital discharge status, and discharge location were recorded. Standardized mortality ratios were calculated. Discrimination and calibration of APACHE II were assessed. All patients were divided into 3 groups: Model for End-Stage Liver Disease score: >25, 18 to 25, and <18. Predicted hospital mortality was calculated and compared., Results: Mean APACHE II scores of survivors and non-survivors were 13.03 and 23.67. Mean risk of death was 7.05% and 25.07%. APACHE II scores and risk of death between survivors and non-survivors was significantly different (P <.001). The cutoff value of APACHE II score and Model for End-Stage Liver Disease score in the receiving operating characteristic curve was 20 and 25. Patients with APACHE II scores greater than 20 or Model for End-Stage Liver Disease scores greater than 25 had higher predicted hospital mortality after living-donor liver transplant., Conclusions: The modified APACHE II model provides an accurate prognosis of patients receiving a living-donor liver transplant. The combined application of Model for End-Stage Liver Disease score and APACHE II score can improve the predictive accuracy.

Background: Severe acute pancreatitis (SAP) as a common acute abdomen due to complicated causes is characterized by lots of morbidities, difficult treatment, and high mortality. This study was designed to investigate the role of individually staged nutritional support (ISNS) in the treatment of SAP., Methods: One hundred patients with SAP admitted to our hospital from January 1997 to October 2002 were randomly divided into total parenteral nutrition group (TPN group, 50 patients) and individually staged nutrition group (individualized group, 50 patients), between which the therapeutic outcome and the incidence of complications were carefully analyzed., Results: Compared with the TPN group, the individualized group had less complications (62 vs 94 patients) including incubation related complications (2% vs 16%), superinfections (8% vs 30%), hepatic functional insufficiency (4% vs 24%) and intra-peritoneal infections (4% vs 12%), in addition to a sooner restoring of oral nutrition (18.5 vs 24.8 days, P<0.05), a shorter hospital stay (24.5 vs 30.2 days) and a lower hospital cost (4.1 vs 5.8 10,000 yuan, P<0.05)., Conclusion: ISNS, which provides SAP patients with sufficient energy and nutrients according to their true pathological status, is an ideal nutrition planning with lowered incidence of complications, shortened hospital stay and lightened financial burden.