Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression.

Bile acid (BA) homeostasis is regulated by the extensive cross-talk between liver and intestine. Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders. In this study we investigated the regulatory mechanisms of BA in the intestine. We showed that the BA levels in the gallbladder and faeces were significantly increased, whereas serum BA levels decreased in systemic Krüppel-like factor 9 (Klf9) deficiency (Klf9-/-) mice. These phenotypes were also observed in the intestine-specific Klf9-deleted (Klf9vil-/-) mice. In contrast, BA levels in the gallbladder and faeces were reduced, whereas BA levels in the serum were increased in intestinal Klf9 transgenic (Klf9Rosa26+/+) mice. By using a combination of biochemical, molecular and functional assays, we revealed that Klf9 promoted the expression of apical sodium-dependent bile acid transporter (Asbt) in the terminal ileum to enhance BA absorption in the intestine. Reabsorbed BA affected liver BA synthetic enzymes by regulating Fgf15 expression. This study has identified a previously neglected transcriptional pathway that regulates BA homeostasis.

Utilizing bifurcated allogeneic vein grafts: a novel approach for preventing sinistral portal hypertension following Pancreaticoduodenectomy. a 10-year before and after study.

BACKGROUND: Sinistral portal hypertension (SPH) may occurs in patients with pancreatic carcinoma after pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) cofluence resection. This study aimed to evaluate outcomes with the bifurcated allogeneic vein replacement in the prevention of SPH in pancreatic carcinoma patients. MATERIALS AND METHODS: A total of 81 patients were included. We retrospectively collected clinicopathological data from 66 patients underwent PD with S-M-P confluence resection in our hospital from Jan. 2011 to Dec. 2021, compared the correlation between different venous reconstruction methods using log-rank tests and clinical outcomes through univariate and multivariate analyses. Secondly, we prospectively collected clinical data and outcomes of 15 patients who underwent splenic vein reconstruction from Jan. 2021 to Jan. 2023. RESULTS: In the retrospective study, 43 cases received reconstruction by bifurcated allogeneic vein (Reconstruction group) and 23 cases received simply SV ligation (Ligation group). The preoperative platelet counts and spleen volume were similar between two groups (P>0.05). Nevertheless, at 1 month, 3 months and 6 months after operation, the related indexes of SPH such as platelet count, spleen volume, spleen volume ratio and esophagogastric varices (EGV) grade in Reconstruction group were better than those in Ligation group (P<0.05). 6 months after surgery, the incidence of SPH in Ligation group was significantly higher than in Reconstruction group (36.4% vs. 8.1%, respectively). In the prospective study, the incidence of SPH in patients undergoing SV reconstruction was 6.7% (1/15). CONCLUSION: Without compromising surgical outcomes, reconstruction of the S-M-P confluence by bifurcated allogeneic vein is a better method to avoid SPH in patients with advanced pancreatic carcinoma.

Prognostic Value for Perioperative Serum Total Cholesterol Level on Postoperative Long-Term Prognosis of Pancreatic Cancer: A Retrospective Clinical Study.

Cholesterol correlates with occurrence and progression of pancreatic cancer and has predictive value for postoperative prognosis in various cancers. Our study intended to reveal the relationship between perioperative serum total cholesterol (TC) level and postoperative prognosis of pancreatic cancer. We retrospectively analyzed the data of pancreatic cancer patients who underwent surgical treatment at our hospital from January 2015 to December 2021. ROC curves between serum TC level at each time point and 1-year survival rate were drawn, from which study object and optimal cutoff value was determined. Patients were divided into low and high-TC groups, and perioperative data and prognosis were compared. Risk factors for poor postoperative prognosis were identified by univariate and multivariate analysis. Overall survival rates at postoperative 1, 2 and 3 years in the low and high-TC groups were 52.9%, 29.4%, and 15.6% and 80.4%, 47.2%, and 33.8% (p = 0.005), respectively. Multivariate analysis confirmed tumor differentiation degree (RR = 2.054, 95% CI: 1.396-3.025), pTNM stage (RR = 1.595, 95% CI: 1.020-2.494), lymph node metastasis (RR = 1.693, 95% CI: 1.127-2.544), and postoperative 4-week serum TC level (RR = 0.663, 95% CI: 0.466-0.944) as independent risk factors for prognosis of pancreatic cancer. We conclude that postoperative 4-week serum TC level has certain predictive value for long-term postoperative prognosis of pancreatic cancer.

Effect of the preoperative prognostic nutritional index on the long-term prognosis in patients with borderline resectable pancreatic cancer after pancreaticoduodenectomy.

Background: The preoperative prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in cancer patients. This study aims to reflect the correlation between the preoperative PNI and prognosis in patients with borderline resectable pancreatic cancer (BRPC) after pancreaticoduodenectomy (PD). Methods: Medical records of patients with BRPC after PD between Jan 2011 and Dec 2021 in our hospital were retrospectively analyzed. The preoperative PNI was calculated, and the receiver operating characteristic curve was obtained based on the preoperative PNI and the 1-year survival rate. Patients were divided into two groups (High-PNI and Low-PNI) following the best cut-off value of the preoperative PNI, and demographic and pathologic findings were compared between the two groups. Univariate and multivariate analysis were performed to identify risk factors in recurrence and long-term survival. Results: The best cut-off value for the preoperative PNI was 44.6 (sensitivity: 62.46%; specificity: 83.33%; area under the curve: 0.724). Patients in the low-PNI group had significantly shorter recurrence-free survival (P=0.008) and overall survival (P=0.009). The preoperative PNI (P=0.009) and lymph node metastasis (P=0.04) were independent risk factors for tumor recurrence. The preoperative PNI (P=0.001), lymph node metastasis (P=0.04), neoadjuvant chemotherapy (P=0.04) were independent risk factors for long-term survival in patients. Conclusion: The preoperative PNI, lymph node metastasis, neoadjuvant chemotherapy were independent risk factors for recurrence and long-term survival in patients with BRPC. The preoperative PNI might be an indicator that can predict BRPC patients' recurrence and survival. Patients with high-PNI would benefit from neoadjuvant chemotherapy.

Application of cholecystic duct plasty in the prevention of biliary complications following orthotopic liver transplantation.

Background: The purpose was aimed to evaluate the safety and effectiveness of cholecystic duct plasty (CDP) and biliary reconstruction techniques preventing biliary complications following orthotopic liver transplantation (OLT) first proposed by our center. Methods: 127 enrolled patients who underwent LT in our center from January 2015 to December 2019 were analyzed retrospectively. According to the mode of biliary tract reconstruction, patients were divided into CDP group (Group 1, n = 53) and control group (Group 2, n = 74). The differences of perioperative general data, biliary complications and long-term prognosis between two groups were compared and analyzed. Results: All patients completed the operation successfully, the incidence of perioperative complications was 22.8%. There was no significant difference in perioperative general data and complications between the two groups. Follow-up ended in June 2020, with a median follow-up period of 31 months. During the follow-up period, biliary complications occurred in 26 patients, with an overall incidence of 20.5%. The overall incidence of biliary complications and anastomotic stenosis in Group 1 was lower than that in Group 2 (P < 0.05). There was no significant difference in overall prognosis between the two groups (P = 0.274), however, the cumulative incidence of biliary complications in Group 1 was lower than that in Group 2 (P = 0.035). Conclusion: Reconstruction of common bile duct by CDP represents considerable safety and practicability, particularly for patients with small diameter of common bile duct or wide discrepancy of bile duct size between donor and recipient.

Corrigendum: Application of cholecystic duct plasty in the prevention of biliary complications following orthotopic liver transplantation.

[This corrects the article DOI: 10.3389/fsurg.2023.1087327.].

Clinical Value of Mean Platelet Volume to Platelet Ratio (MPR) in Distinguishing Mass-Forming Chronic Pancreatitis and Pancreatic Cancer.

BACKGROUND: Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC. METHODS: We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC (n = 383) and MFCP groups (n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings. RESULTS: The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively (p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively (p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively. CONCLUSION: MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.

Development and validation of machine learning models for predicting prognosis and guiding individualized postoperative chemotherapy: A real-world study of distal cholangiocarcinoma.

Background: Distal cholangiocarcinoma (dCCA), originating from the common bile duct, is greatly associated with a dismal prognosis. A series of different studies based on cancer classification have been developed, aimed to optimize therapy and predict and improve prognosis. In this study, we explored and compared several novel machine learning models that might lead to an improvement in prediction accuracy and treatment options for patients with dCCA. Methods: In this study, 169 patients with dCCA were recruited and randomly divided into the training cohort (n = 118) and the validation cohort (n = 51), and their medical records were reviewed, including survival outcomes, laboratory values, treatment strategies, pathological results, and demographic information. Variables identified as independently associated with the primary outcome by least absolute shrinkage and selection operator (LASSO) regression, the random survival forest (RSF) algorithm, and univariate and multivariate Cox regression analyses were introduced to establish the following different machine learning models and canonical regression model: support vector machine (SVM), SurvivalTree, Coxboost, RSF, DeepSurv, and Cox proportional hazards (CoxPH). We measured and compared the performance of models using the receiver operating characteristic (ROC) curve, integrated Brier score (IBS), and concordance index (C-index) following cross-validation. The machine learning model with the best performance was screened out and compared with the TNM Classification using ROC, IBS, and C-index. Finally, patients were stratified based on the model with the best performance to assess whether they benefited from postoperative chemotherapy through the log-rank test. Results: Among medical features, five variables, including tumor differentiation, T-stage, lymph node metastasis (LNM), albumin-to-fibrinogen ratio (AFR), and carbohydrate antigen 19-9 (CA19-9), were used to develop machine learning models. In the training cohort and the validation cohort, C-index achieved 0.763 vs. 0.686 (SVM), 0.749 vs. 0.692 (SurvivalTree), 0.747 vs. 0.690 (Coxboost), 0.745 vs. 0.690 (RSF), 0.746 vs. 0.711 (DeepSurv), and 0.724 vs. 0.701 (CoxPH), respectively. The DeepSurv model (0.823 vs. 0.754) had the highest mean area under the ROC curve (AUC) than other models, including SVM (0.819 vs. 0.736), SurvivalTree (0.814 vs. 0.737), Coxboost (0.816 vs. 0.734), RSF (0.813 vs. 0.730), and CoxPH (0.788 vs. 0.753). The IBS of the DeepSurv model (0.132 vs. 0.147) was lower than that of SurvivalTree (0.135 vs. 0.236), Coxboost (0.141 vs. 0.207), RSF (0.140 vs. 0.225), and CoxPH (0.145 vs. 0.196). Results of the calibration chart and decision curve analysis (DCA) also demonstrated that DeepSurv had a satisfactory predictive performance. In addition, the performance of the DeepSurv model was better than that of the TNM Classification in C-index, mean AUC, and IBS (0.746 vs. 0.598, 0.823 vs. 0.613, and 0.132 vs. 0.186, respectively) in the training cohort. Patients were stratified and divided into high- and low-risk groups based on the DeepSurv model. In the training cohort, patients in the high-risk group would not benefit from postoperative chemotherapy (p = 0.519). In the low-risk group, patients receiving postoperative chemotherapy might have a better prognosis (p = 0.035). Conclusions: In this study, the DeepSurv model was good at predicting prognosis and risk stratification to guide treatment options. AFR level might be a potential prognostic factor for dCCA. For the low-risk group in the DeepSurv model, patients might benefit from postoperative chemotherapy.

Prognostic Value of Neoadjuvant Chemotherapy in Patients with Borderline Resectable Pancreatic Carcinoma Followed by Pancreatectomy with Portal Vein Resection and Reconstruction with Venous Allograft.

BACKGROUND: Neo-adjuvant chemotherapy (NAC) represents one of the current research hotspots in the field of pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate the prognostic value of NAC in patients with borderline resectable pancreatic cancer (BRPC) followed by pancreatectomy with portal vein (PV) resection and reconstruction with venous allograft (VAG). METHODS: Medical records of patients with BPRC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG between April 2013 and March 2021 were analyzed retrospectively. Outcomes of patients with and without NAC (NAC, Group 1 vs. non-NAC, Group 2) were compared with focus on R0 resection rates, morbidity, and survival. RESULTS: Of the 77 patients with pancreatectomy, PV resection and reconstruction with VAG were identified. Overall survival (OS) rates of 0.5-, 1-, and 2-year were 80.5%, 59.7%, and 31.2%, respectively (median survival time, MST, 14 months). Of these, 24 patients (Group 1) underwent operation following received NAC, and the remaining 53 patients did not (Group 2). The R0 resection rate of vascular margin was 100% vs. 84.9% (p = 0.04), respectively. Morbidity of post-operative pancreatic fistula (POPF) was 0% vs. 17.8% (p = 0.07), respectively. The OS of 0.5-, 1- and 2-year and MST of 2 groups were 83.3%, 66.7%, 41.7%, 16 months, and 79.2%, 55.6%, 26.4%, 13 months, respectively. Multivariate analysis revealed that carbohydrate antigen 19-9 (CA19-9) serum level and postoperative chemotherapy were independent prognostic factors in patients with BRPC after surgery. CONCLUSION: NAC might improve the R0 resection rate and POPF in patients with BRPC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG. Survival benefit exists in patients with BRPC who received NAC before pancreatectomy. Postoperative chemotherapy also had a favorable effect on OS of BRPC patients. Elevated CA 19-9 serum level is associated with poor prognosis, even after NAC-combining operation.

Clinical value of extended lymphadenectomy in radical surgery for pancreatic head carcinoma at different T stages.

BACKGROUND: As the lymph-node metastasis rate and sites vary among pancreatic head carcinomas (PHCs) of different T stages, selective extended lymphadenectomy (ELD) performance may improve the prognosis of patients with PHC. AIM: To investigate the effect of ELD on the long-term prognosis of patients with PHC of different T stages. METHODS: We analyzed data from 216 patients with PHC who underwent surgery at our hospital between January 2011 and December 2021. The patients were divided into extended and standard lymphadenectomy (SLD) groups according to extent of lymphadenectomy and into T1, T2, and T3 groups according to the 8th edition of the American Joint Committee on Cancer's staging system. Perioperative data and prognoses were compared among groups. Risk factors associated with prognoses were identified through univariate and multivariate analyses. RESULTS: The 1-, 2- and 3-year overall survival (OS) rates in the extended and SLD groups were 69.0%, 39.5%, and 26.8% and 55.1%, 32.6%, and 22.1%, respectively (P = 0.073). The 1-, 2- and 3-year disease-free survival rates in the extended and SLD groups of patients with stage-T3 PHC were 50.3%, 25.1%, and 15.1% and 22.1%, 1.7%, and 0%, respectively (P = 0.025); the corresponding OS rates were 65.3%, 38.1%, and 21.8% and 36.1%, 7.5%, and 0%, respectively (P = 0.073). Multivariate analysis indicated that portal vein invasion and lymphadenectomy extent were risk factors for prognosis in patients with stage-T3 PHC. CONCLUSION: ELD may improve the prognosis of patients with stage-T3 PHC and may be of benefit if performed selectively.