Development and validation of a novel preoperative clinical model for predicting lymph node metastasis in perihilar cholangiocarcinoma.

BACKGROUD: We aimed to develop a novel preoperative nomogram to predict lymph node metastasis (LNM) in perihilar cholangiocarcinoma (pCCA) patients. METHODS: 160 pCCA patients were enrolled at Lihuili Hospital from July 2006 to May 2022. A novel nomogram model was established to predict LNM in pCCA patients based on the independent predictive factors selected by the multivariate logistic regression model. The precision of the nomogram model was evaluated through internal and external validation with calibration curve statistics and the concordance index (C-index). Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate and determine the clinical utility of the nomogram. RESULTS: Multivariate logistic regression demonstrated that age (OR = 0.963, 95% CI: 0.930-0.996, P = 0.030), CA19-9 level (> 559.8 U/mL vs. ≤559.8 U/mL: OR = 3.162, 95% CI: 1.519-6.582, P = 0.002) and tumour diameter (OR = 1.388, 95% CI: 1.083-1.778, P = 0.010) were independent predictive factors of LNM in pCCA patients. The C-index was 0.763 (95% CI: 0.667-0.860) and 0.677 (95% CI: 0.580-0.773) in training cohort and validation cohort, respectively. ROC curve analysis indicated the comparative stability and adequate discriminative ability of nomogram. The sensitivity and specificity were 0.820 and 0.652 in training cohort and 0.704 and 0.649 in validation cohort, respectively. DCA revealed that the nomogram model could augment net benefits in the prediction of LNM in pCCA patients. CONCLUSIONS: The novel prediction model is useful for predicting LNM in pCCA patients and showed adequate discriminative ability and high predictive accuracy.

Impact of insomnia upon inflammatory digestive diseases and biomarkers: a two-sample mendelian randomization research on Europeans.

BACKGROUND: A number of observational studies indicate that insomnia is linked to inflammatory digestive diseases (IDDs). However, the definite relationship between insomnia and IDDs remains unclear. METHODS: We obtained the publicly available data from genome-wide association studies (GWAS) to conduct two-sample Mendelian randomization (MR) for association assessment. Five MR analysis methods were used to calculate the odds ratio (OR) and effect estimate, and the heterogeneity and pleiotropy tests were performed to evaluate the robustness of the variable instruments (IVs). RESULTS: One exposure and twenty outcome datasets based on European populations were included in this study. Using the inverse variance weighted method, we found insomnia was closely correlated with esophageal ulcer (OR = 1.011, 95%CI = 1.004-1.017, p = 0.001) and abdominal pain (effect estimate = 1.016, 95%CI = 1.005-1.026, p = 0.003). Suggestive evidence of a positively association was observed between insomnia and duodenal ulcer (OR = 1.006, 95%CI = 1.002-1.011, p = 0.009), gastric ulcer (OR = 1.008, 95%CI = 1.001-1.014, p = 0.013), rectal polyp (OR = 1.005, 95%CI = 1.000-1.010, p = 0.034), haemorrhoidal disease (OR = 1.242, 95%CI = 1.004-1.535, p = 0.045) and monocyte percentage (effect estimate = 1.151, 95%CI = 1.028-1.288, p = 0.014). No correlations were observed among other IDDs, phenotypes and biomarkers. CONCLUSIONS: Our MR study assessed the relationship between insomnia and IDDs/phenotypes/biomarkers in depth and revealed potential associations between insomnia and ulcers of the esophagus and abdominal pain.

A Comparative Study of Laparoscopic and Open Approaches for Right Hemihepatectomy in Hepatocellular Carcinoma Patients: Safety and Short-Term Outcomes.

BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, with China reporting over half of global cases. While traditional open liver resection is effective, it often results in large incisions and significant complications. Laparoscopic hepatectomy, particularly for right hemi-hepatectomy, features smaller incisions and quicker recovery, but its widespread adoption is hindered by its procedural complexity and a steep learning curve. This study compares the safety and efficacy of laparoscopic versus open right hemi-hepatectomy with an anterior approach in 57 patients with HCC. MATERIAL AND METHODS The data of patients with HCC who underwent treatment at our center from January 2016 to December 2020 were retrospectively analyzed. RESULTS We included a total of 57 patients with histopathologically-confirmed HCC - 23 in the laparoscopic group and 34 in the open group. Operation time was significantly shorter in the open group than in the laparoscopic group (234.5±66.9 vs 297.0±74.9, P=0.002). Intraoperative bleeding was significantly less in the laparoscopic group (P=0.042). There were no statistically significant differences in postoperative complications between the 2 groups. Postoperative hospital stay was significantly shorter in the laparoscopic group (12 days vs 15 days, P=0.044). There was no significant difference in postoperative overall survival (OS) and disease-free survival (DFS) between the 2 groups (P>0.05). CONCLUSIONS In patients with hepatocellular carcinoma, the laparoscopic right hemi-hepatectomy with the anterior approach technique has the same safety and comparable short-term outcomes as open surgery.

Evaluation of Large Language Model Performance and Reliability for Citations and References in Scholarly Writing: Cross-Disciplinary Study.

BACKGROUND: Large language models (LLMs) have gained prominence since the release of ChatGPT in late 2022. OBJECTIVE: The aim of this study was to assess the accuracy of citations and references generated by ChatGPT (GPT-3.5) in two distinct academic domains: the natural sciences and humanities. METHODS: Two researchers independently prompted ChatGPT to write an introduction section for a manuscript and include citations; they then evaluated the accuracy of the citations and Digital Object Identifiers (DOIs). Results were compared between the two disciplines. RESULTS: Ten topics were included, including 5 in the natural sciences and 5 in the humanities. A total of 102 citations were generated, with 55 in the natural sciences and 47 in the humanities. Among these, 40 citations (72.7%) in the natural sciences and 36 citations (76.6%) in the humanities were confirmed to exist (P=.42). There were significant disparities found in DOI presence in the natural sciences (39/55, 70.9%) and the humanities (18/47, 38.3%), along with significant differences in accuracy between the two disciplines (18/55, 32.7% vs 4/47, 8.5%). DOI hallucination was more prevalent in the humanities (42/55, 89.4%). The Levenshtein distance was significantly higher in the humanities than in the natural sciences, reflecting the lower DOI accuracy. CONCLUSIONS: ChatGPT's performance in generating citations and references varies across disciplines. Differences in DOI standards and disciplinary nuances contribute to performance variations. Researchers should consider the strengths and limitations of artificial intelligence writing tools with respect to citation accuracy. The use of domain-specific models may enhance accuracy.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Lactobacillus rhamnosus GG combined with inosine ameliorates alcohol-induced liver injury through regulation of intestinal barrier and Treg/Th1 cells.

BACKGROUND: Intestinal epithelial barrier disruption and bacterial translocation exacerbates the progression of alcoholic liver disease. Lactobacillus rhamnosus GG (LGG), a probiotic, has been shown benefits in chronic liver disease and in regulating gut dysbiosis. Previous studies showed the protective roles of LGG in ethanol-disrupted gut barrier functions and liver injury. Inosine, a metabolite produced by intestinal bacteria, has the anti-inflammatory and immunregulatory functions. In this study, the synergistic effect of LGG and inosine was investigated in a mouse model of alcohol-induced liver disease (ALD). METHODS: Male C57BL/6 mice were fed with a Lieber-DeCarli diet containing 5% alcohol for four weeks to establish a model of alcohol-induced liver injury. LGG or a combination of LGG and inosine were administrated orally to explore a new therapeutic method for alcohol-induced liver disease and to investigate the underlying mechanisms. Liver damage was evaluated by transaminases and pathological changes. Tight junction proteins, composition of the gut microbiome, cytokines, lipopolysaccharides (LPS), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), F4/80+ macrophages, as well as p38, Jun N-terminal kinase (JNK), were determined by qRT-PCR, RNAseq, ELISA, IHC and western blot. Regulatory T (Treg) cells were characterized by positive staining of CD4, CD25 and Foxp3 using flow cytometry. IFN-γ-producing CD4+ T (Th1) cells were examined by intracellular cytokine staining. RESULTS: Alcohol consumption induced elevated liver enzymes, steatosis and inflammation, while LGG combined with inosine treatment was more significant to ameliorate these symptoms compared with LGG alone. When LGG combined with inosine were administered to ALD mice, intestinal microecology significantly improved reflected by intestinal villi and tight junction proteins recovery and the restoration of intestinal flora. Combined therapy inhibited phosphorylation of p38 and JNK to alleviate hepatic inflammation. Moreover, flow cytometry analysis showed that long-term excessive alcohol consumption reduced Tregs population while increased Th1 population, which was restored by a combination of LGG and inosine treatment. CONCLUSIONS: The findings from the study indicate that the combined LGG and inosine treatment ameliorates ALD by improving the gut ecosystem, intestinal barrier function, immune homeostasis and liver injury.

Development of nomogram models of inflammatory markers based on clinical database to predict prognosis for hepatocellular carcinoma after surgical resection.

BACKGROUND: Inflammation plays a significant role in tumour development, progression, and metastasis. In this study, we focused on comparing the predictive potential of inflammatory markers for overall survival (OS), recurrence-free survival (RFS), and 1- and 2-year RFS in hepatocellular carcinoma (HCC) patients. METHODS: A total of 360 HCC patients were included in this study. A LASSO regression analysis model was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors for HCC prognosis. Nomogram prediction models were established and decision curve analysis (DCA) was conducted to determine the clinical utility of the nomogram model. RESULTS: Multivariate Cox regression analysis indicated that the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS, and aspartate aminotransferase-to-platelet ratio (APRI) was a common independent prognostic factor among RFS, 1-year RFS, and 2-year RFS. The systemic inflammation response index (SIRI) was an independent prognostic factor for 1-year RFS in HCC patients after curative resection. Nomograms established and achieved a better concordance index of 0.772(95% CI: 0.730-0.814), 0.774(95% CI: 0.734-0.815), 0.809(95% CI: 0.766-0.852), and 0.756(95% CI: 0.696-0.816) in predicting OS, RFS, 1-year RFS, and 2-year RFS respectively. The risk scores calculated by nomogram models divided HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram models could augment net benefits and exhibited a wider range of threshold probabilities in the prediction of HCC prognosis. CONCLUSIONS: The nomograms showed high predictive accuracy for OS, RFS, 1-year RFS, and 2-year RFS in HCC patients after surgical resection. The nomograms could be useful clinical tools to guide a rational and personalized treatment approach and prognosis judgement.

IGF-1 contributes to liver cancer development in diabetes patients by promoting autophagy.

INTRODUCTION AND OBJECTIVES: Type 2 diabetes mellitus (T2DM) increases the occurrence and mortality of liver cancer. Insulin growth factor (IGF) plays a crucial role in the development of diabetes and liver cancer, and specifically, IGF-1 may be involved in the development of liver cancer with preexisting T2DM. Autophagy contributes to cancer cell survival and apoptosis. However, the relationship between IGF-1 and autophagy has rarely been evaluated. The purpose of this study was to investigate whether IGF-1 promotes the development of liver cancer in T2DM patients by promoting autophagy. MATERIALS AND METHODS: Thirty-three hepatocellular carcinoma (HCC) patients with T2DM and 33 age-matched patients with HCC without T2DM were included in this study. We analyzed the expression of IGF-1 and autophagy-related LC3 and p62 mRNA and the prognosis of two groups. In vitro, we stimulated HepG2 cells with IGF-1 and then detected changes in autophagy and cell proliferation, apoptosis, and migration in the presence/absence of wortmannin, an autophagy inhibitor. RESULTS: IGF-1 promoted autophagy, resulting in inhibition of apoptosis and induction of growth and migration of HepG2 cells. Inhibition of autophagy by wortmannin impaired IGF-1 function. Higher expression of IGF-1 was detected in HCC patients with T2DM. IGF-1 expression was higher in liver cancer tissue compared to paracancerous tissue. Elevated IGF-1 was associated with a poor prognosis in patients with HCC. CONCLUSIONS: IGF-1 participates in the development of liver cancer by inducing autophagy. Elevated IGF-1 was a prognostic factor for patients with HCC, especially when accompanied by T2DM.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Options for the treatment of intrahepatic recurrent hepatocellular carcinoma: Salvage liver transplantation or rehepatectomy?

OBJECTIVE: To explore prognostic factors by comparing the efficacy of salvage liver transplantation (sLT) and rehepatectomy (RH) for the treatment of recurrent hepatocellular carcinoma after hepatectomy. METHODS: Clinical data were collected for 124 patients treated at our center from January 2012 to August 2018. The median follow-up time for the patients was 39 months. By analyzing the clinical data between the sLT group (46 cases) and RH group (78 cases), the factors affecting the prognosis of patients were compared. RESULTS: The proportion of alpha-fetoprotein (AFP) ≥ 100 µg/L in the recurrence group was significantly higher than that in the recurrence-free group (70.0% vs 22.2%, P = .014). The postoperative overall survival (OS) and recurrence-free survival (RFS) were better in the sLT group than in the RH group (81.2% vs 36.9%, P < .01; 77.1% vs 55.6%, P = .019). In the sLT group, the OS and RFS in the AFP < 100 µg/L group were superior to those in the AFP ≥ 100 µg/L group (P = .046 and P = .002). CONCLUSION: The sLT group had achieved better efficacy than RH group, but when AFP ≥ 100 µg/L, sLT did not achieve better efficacy than RH.

DNA damage-induced activation of ATM promotes ß-TRCP-mediated ARID1A ubiquitination and destruction in gastric cancer cells.

BACKGROUND: AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor suppressor protein. The loss of ARID1A been observed in several types of human cancers and associated with poor patient prognosis. Previously, we have reported that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer cells during DNA damage response. However, the ubiquitin e3 ligase that mediated this process remains unclear. MATERIALS AND METHODS: The interaction between ARID1A and ß-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin RNAs (shRNAs) were used to knockdown (KD) gene expression. RESULTS: Here we show that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the ubiquitin E3 ligase complex SCFß-TRCP. ß-TRCP recognizes ARID1A through a canonical degron site (DSGXXS) after its phosphorylation in response to DNA damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase impaired DNA damage-induced ARID1A destruction. CONCLUSIONS: Our studies provide a novel molecular mechanism for the negative regulation of ARID1A by ß-TRCP and ATM in DNA damaged gastric cancer cells.

A novel technique of inserting pancreaticogastrostomy with duct-to-mucosa anastomosis can potentially reduce postoperative pancreatic fistula.

BACKGROUND: We describe our novel technique of inserting pancreaticogastrostomy (IPG) after pancreaticoduodenectomy. In our technique, the seromuscular and mucosal layers of the posterior gastric wall are separated to create a mucosal pouch. A duct-to-mucosa anastomosis is performed through a small incision in the mucosal layer. An inner suture at the seromuscular-mucosal margin incorporating the pancreatic parenchyma and an outer suture on the exterior margin of the seromuscular layer to wrap the pouch around the pancreas are placed to complete the IPG. MATERIALS AND METHODS: We examined the clinicopathological features and outcomes of 259 patients who underwent pancreaticoduodenectomy between January 2010 and April 2014. RESULTS: One hundred forty-three (55.2%) patients underwent IPG, while 116 (44.8%) had conventional pancreaticojejunostomy. Most preoperative and intraoperative parameters were comparable. Overall morbidity in the IPG group was 28.7%. The rate of grade A postoperative pancreatic fistula (POPF) was 7.0%, and the rates of grade B and C POPF were 0.7% and 0.0%, respectively. The corresponding rates of grade A, B, and C fistulae were 5.2%, 8.6%, and 5.2%, respectively. CONCLUSIONS: In selected patients, our novel technique can be performed safely and may reduce the rates of POPF.

[Value and safety of the surgery with vascular resection and reconstruction for pancreatic cancer].

OBJECTIVE: To investigate the value and safety of the surgery with vascular resection and reconstruction during pancreatectomy for pancreatic cancer. METHODS: The clinical data of 206 patients with pancreatic cancer who underwent radical resection were retrospectively analyzed from January 2009 to March 2014 in Lihuili Hospital, Medical center of Ningbo.All cases were divided into non-vascular resection group(132 cases), the combined vein resection group(66 cases) and the combined arterial resection group(8 cases). The peri-operation data, the incidence of postoperative complications and the survival were compared in pairs among three groups.All patients were followed up till September 2014. RESULTS: There were no statistical differences for the preoperative data among three groups.The operation time and the blood loss (M(QR)) were (347±96)minutes and (500(400)) ml in non-vascular resection group, (425±91)minutes and (800(500))ml in combined vein resection group, (508±120)minutes and (1 750(2 075))ml in combined arterial resection group, with significant differences among three groups(all P<0.01). The incidence of postoperative complication was 16.7%(22/132) in non-vascular resection group, 28.8%(19/66) in combined vein resection group, and 6 cases in combined arterial resection group, respectively.There were significant differences between non-vascular resection group and combined vein resection group(P<0.05), non-vascular resection group and combined arterial resection group(P<0.05), as well as between combined vein resection group and combined arterial resection group(P<0.05). The median survival time was 15 months for non-vascular resection group, 15 months for combined vein resection group, and 12 months for combined arterial resection group.No significant difference was found among three groups(all P>0.05). The postoperative mortality was nil for all of groups. CONCLUSIONS: Compared with non-vascular resection, combined vein resection can be performed safely with a similar prognosis. The surgery of combined arterial resection could only be justified when R0 resection for pancreatic cancer could be achieved for highly selected patients.

Positive association between lymphotoxin-alpha variation rs909253 and cancer risk: a meta-analysis based on 36 case-control studies.

Lymphotoxin-alpha (LTA) polymorphism rs909253 has been reported to be a risk factor for cancers, but some results are inconsistent. To establish a more conclusive association, we performed a meta-analysis of this variant with cancers. A systematic search was performed for informative case-control studies of rs909253 with cancers among literature databases, including PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Chinese Periodical Database. After a comprehensive filtration procedure, 36 publications involved with 35,677 participants were selected for the current meta-analysis. Stratified factors, such as cancer type, populations, and source of control, were used for a better interpretation of this variant. Minimal heterogeneity was shown in the current meta-analysis (I (2) = 0.0%, P = 0.48). Our results show a significant association of rs909253 and cancer risk (odds ratio (OR) = 1.12, P (z) < 0.001). In the subgroup analysis, significant association of rs909253 was found in adenocarcinoma (OR = 1.16, P (z) < 0.001) and hematological malignancy (OR = 1.10, P (z) < 0.001). Our meta-analyses established a significant association of rs909253 with cancer risk among multiple populations including North Americans, Asians, and Europeans.

A CDAHFD-induced mouse model mimicking human NASH in the metabolism of hepatic phosphatidylcholines and acyl carnitines.

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a cluster of conditions associated with lipid metabolism disorders. Ideal animal models mimicking the human NASH need to be explored to better understand the pathogenesis. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has recently been used to induce the NASH model, but the advantages are not established. NASH models were induced using the well-known traditional methionine- and choline-deficient (MCD) diet for 5 weeks and the recently used CDAHFD for 3 weeks. Liver phenotypes were analyzed to evaluate the differences in markers related to NASH. Lipidomics and metabolism analyses were used to investigate the effects of dietary regimens on the lipidome of the liver. The CDAHFD induced stronger NASH responses than the MCD, including lipid deposition, liver injury, inflammation, bile acid overload and hepatocyte proliferation. A significant difference in the hepatic lipidome was revealed between the CDAHFD and MCD-induced NASH models. In particular, the CDAHFD reduced the hepatic levels of phosphatidylcholines (PCs) and acylcarnitines (ACs), which was supported by the metabolism analysis and in line with the tendency of human NASH. Pathologically, the CDAHFD could effectively induce a more human-like NASH model over the traditional MCD. The hepatic PCs, ACs and their metabolism in CDAHFD-treated mice were down-regulated, similar to those in human NASH.

Sarcomatoid carcinoma of the pancreas (Review).

Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of undifferentiated pancreatic ductal adenocarcinoma, with a generally poor prognosis and only sporadic cases reported worldwide. Histologically, the most notable feature of SCP is the presence of abundant of mesenchymatoid spindle tumor cells in the tumor, which lack glandular differentiation. Immunohistochemically, SCP is characterized by the expression of both mesenchymal and epithelial markers. With only a few reported cases, there is limited knowledge about its molecular and clinicopathological characteristics. Therefore, the present study performed a literature search to identify all relevant published studies. The present review provides an overview of the histogenesis, diagnosis, genetic features, prognosis and treatment of SCP, specifically focusing on the molecular alterations. Furthermore, a single-center experience is reported, which adds to the limited evidence available in the literature.

Extended Left Hemihapatectomy with Right Hepatic Artery Reconstruction for Primary Hepatic Neuroendocrine Neoplasm: A Brief Report.

BACKGROUND rimary hepatic neuroendocrine neoplasms (PHNEN) are exceedingly rare tumors with atypical clinical manifestations, accounting for less than 0.5% of all neuroendocrine tumors. Currently, there is a lack of consensus on their management, and guidelines do not recommend postoperative chemotherapy for patients with stage G1/G2 disease after curative resection. We present a case report of PHNEN, outlining its diagnostic challenges, treatment strategy, and clinical outcomes. CASE REPORT A 31-year-old man presented with jaundice and was initially diagnosed with suspected IgG4-related disease, which initially appeared to respond to steroid therapy, but manifested worsening jaundice 4 months after initial treatment. Subsequent evaluation revealed a PHNEN NET G2 with lymph node metastasis and invasion of the right hepatic artery; and involvement of the hepatic duct at the hepatic hilum, primarily the left hepatic duct. The patient underwent extended left hemi-hepatectomy with caudate lobe resection, bile duct resection, and lymphadenectomy, followed by reconstruction of the right hepatic artery. Postoperatively, the patient received adjuvant chemotherapy consisting of capecitabine (1000 mg bid D1-14) and temozolomide (200 mg qn D10-14) for 6 cycles. Currently, the patient remains disease free 43 months after treatment. CONCLUSIONS PHNEN presents diagnostic challenges due to its rarity and lack of specific markers. Surgical resection remains the cornerstone of treatment, with chemotherapy being considered in select cases with high-risk features. Further research is needed to refine treatment approaches and improve outcomes for patients with PHNEN.

Comparison of laparoscopic versus open pancreaticoduodenectomy combined with portal vein/superior mesenteric vein resection and reconstruction for pancreatic cancer: a propensity score matching analysis.

Background: Open surgery is gradually replaced by minimally invasive surgery, but few studies have reported the feasibility of laparoscopic pancreaticoduodenectomy (LPD) combined with vascular resection and reconstruction. The present study compared the efficacy of LPD with open pancreaticoduodenectomy (OPD) combined with portal vein/superior mesenteric vein (PV/SMV) resection and reconstruction for pancreatic cancer. Methods: The clinical data of patients who underwent PD combined with PV/SMV resection and reconstruction from March 2016 to August 2022 at our institution were retrospectively analyzed. The perioperative outcomes and survival outcomes were compared after propensity score matching (PSM). Results: The original cohort included 64 patients. Sixteen pairs of patients were obtained by 1:1 PSM. The intraoperative blood loss was greater in the OPD group than in the LPD group (550 vs. 200 mL, P=0.04), and the PV clamp time was longer in the LPD group than in the OPD group (29.4 vs. 18.8 min, P<0.001). There was no significant difference in the incidence of postoperative complications. The median overall survival and progression-free survival were comparable between the two groups (P>0.05). Conclusions: LPD combined with PV/SMV resection and reconstruction is safe and feasible in selected patients and results in similar perioperative outcomes and prognosis as open surgery.

Prognostic and Immune Infiltration Analysis of Transaldolase 1 (TALDO1) in Hepatocellular Carcinoma.

Background: Transaldolase 1 (TALDO1) deficiency was associated with hepatocellular carcinoma (HCC), but the association between TALDO1 and prognosis in HCC remains unclear. Material and Methods: RNA-seq and clinical data of HCC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. CCK8 and EdU assays were utilized to examine the effect of TALDO1 on HCC proliferation. Transwell assay was used to explore the effect of TALDO1 on HCC migration. Western Blot was applied to detected the expression levels of pathway-related proteins. Results: TALDO1 mRNA level was higher in HCC tissues than in control normal tissues in TCGA and GEO databases (P<0.001, P<0.001). Expression of TALDO1 mRNA was associated with histologic grade (P=0.021). Multivariate regression analysis revealed that high TALDO1 mRNA expression was an independent risk factor for prognosis (P<0.001). High expression of TALDO1 had poor overall survival (OS) (P=0.046). Additionally, Nomogram prognostic model of TALDO1 and clinicopathological parameters could predict the prognostic OS of HCC patients. Functional enrichment and immune infiltration analysis revealed that TALDO1 negatively regulates immune response. Furthermore, knockdown TALDO1 expression suppressed the proliferation and migration ability of HCC cells. Mechanistically, TALDO1 leaded to activation of the mitogen-activated protein kinase (MAPK) pathway and enhancement of epithelial-mesenchymal transition (EMT). Conclusion: Our findings demonstrated that TALDO1 could serve as a promising novel biomarker for HCC patients, which might modulate the immune microenvironment resulting in a poor prognosis.

Risk factors for acute rejection in liver transplantation and its impact on the outcomes of recipients.

OBJECTIVE: To determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients. METHODS: Clinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection. RESULTS: 244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group. CONCLUSION: Acute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients. SUMMARY: Clinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.