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Background: Whether standard lymphadenectomy or extended lymphadenectomy should be performed is still under debate during pancreaticoduodenectomy (PD). We aimed to compare their morbidity and mortality rates among patients with pancreatic head cancer (PHC). Material and methods: In this retrospective study, a total of 322 patients were enrolled. According to the scope of intraoperative lymph node dissection, patients were divided into extended lymphadenectomy group (n=120) and standard lymphadenectomy group (n=202). Based on the resectability of the tumor, there were 198 cases of resectable PHC and 124 cases of boardline resectable PHC, respectively, in which further stratified analysis was carried out according to the extent of lymph node dissection.Results: All patients completed the operation successfully, with a perioperative morbidity rate of 27.9% and mortality rate of 0.9%. As for the overall patients, patients in the extended lymphadenectomy group had higher NLR, longer operation time, more intraoperative blood loss, lymph node dissection and patients with BRPHC. (PConclusions: Patients with BRPHC tended to have vast lymph node metastasis. Extended lymphadenectomy can improve their long-term survival.

BACKGROUND Distal cholangiocarcinoma (DCC) presents as one of the relatively rare malignant tumors in the digestive system and has a poor long-term prognosis. Curative resection is currently the most appropriate therapy for patients with DCC because of the lack of effective adjuvant therapies. Therefore, it is important to accurately predict the prognosis for formulating a reasonable treatment plan and avoiding unnecessary surgical trauma. AIM To minimize the interference of obstructive jaundice on carbohydrate antigen 19-9 (CA19-9) level by adapting CA19-9 to γ-glutamyltransferase (GGT) as an indicator, to determine the strong associations between CA19-9/GGT and postoperative neoplasm recurrence and long-term outcome of DCC. METHODS We enrolled 186 patients who were diagnosed with DCC between January 2010 and December 2019 and performed radical excision with strict criteria as follows in our hospital. Receiver operating characteristic curves were drawn according to preoperative CA19-9/GGT and 1-year survival. Based on this, patients were divided into two groups (group 1, low-ratio, n = 81; group 2, high-ratio, n = 105). Afterwards, by the way of univariate and multivariate analysis, the risk factors influencing postoperative tumor recrudesce and long-term prognosis of patients with DCC were screened out. RESULTS Optimum cut-off value of CA19-9/GGT was 0.12. Patients in group 2 represented higher CA19-9 and lymphatic metastasis rate accompanied by lower GGT, when compared with group 1 (P < 0.05). The 1-, 3- and 5-year overall survival rates of patients in groups 1 and 2 were 88.3%, 59.2% and 48.1%, and 61.0%, 13.6% and 13.6%, respectively (P = 0.000). Multivariate analysis indicated that CA19-9/GGT, lymphatic metastasis and tumor differentiation were independent risk factors for tumor recurrence and long-term prognosis of DCC. CONCLUSION Elevation of CA19-9/GGT performed better as a biomarker of aggressive carcinoma and predictor of poor clinical outcomes by reducing the effect of obstruction of biliary tract on CA19-9 concentration in patients with DCC.

Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.

Aim: Desmoid tumor (DT) is a rare, locally aggressive benign neoplasm with a high recurrence rate. The majority of sporadic DTs are associated with mutations in CTNNB1, but whether CTNNB1 mutations are associated with the risk of DT recurrence remains unclear. The goal of this meta-analysis was to evaluate the association between CTNNB1 mutation and recurrence in surgically treated DT patients. Methods: PubMed, Embase and Cochrane library were systematically searched. The outcome of interest was the risk of recurrence. The number of patients with CTNNB1 mutation and the number of recurrences they developed were recorded and compared. The quality of these studies was assessed using the Newcastle–Ottawa Quality Assessment Scale. Odds ratios and variances were calculated and pooled. Results: A total of eight studies were identified including 637 patients. S45F-mutated DTs were more likely to recur compared with wild type, T41A and other mutated DTs. However, there were no statistically significant differences in the rate of recurrence between wild type and T41A mutation or other mutation. Conclusions: Among CTNNB1 mutations, the mutation S45F is a high-risk factor for recurrence of DT and may be a predictive marker for the recurrence of sporadic DT.

The purpose was aimed to establish a simple computational model to predict tumor prognosis by combining neutrophil to lymphocyte Ratio (NLR) and biomarkers of oncological characteristics in patients undergoing vascular reconstructive radical resection of PDAC. The enrolled patients was divided into high or low NLR group with the cutoff value determined by the receiver operator characteristic (ROC) curve. Different vascular anastomoses were selected according to the Chaoyang classification of PDAC. Survival rates were calculated using the Kaplan-Meier and evaluated with the log-rank test. Cox risk regression model was used to analyze the independent risk factors for prognostic survival. The optimal cut-off value of NRL was correlated with the differentiation, tumor size, TNM stage and distant metastasis of advanced PDAC. A curative resection with vascular reconstructive of advanced PDAC according to Chaoyang classification can obviously improve the survival benefits. Cox proportional hazards demonstrated higher evaluated NLR, incisal margin R1 and lymphatic metastasis were the independent risk predictor for prognosis with the HR > 2, meanwhile, age beyond 55, TNM stage of III-IV or Tumor size > 4cm were also the obvious independent risk predictor for prognosis with the HR ≤ 2. The advanced PADC patients marked of RS group (3 < RS ≤ 6) showed no more than 24 months of survival time according to RS model based on the six independent risk predictors. Vascular reconstruction in radical resection of advanced PDAC improved survival, higher elevated NLR (>2.90) was a negative predictor of DFS and OS in those patients accompanying portal system invasion.

Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model.Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 μg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study.Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1β) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-β1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats’ bile duct wall and less local scar formation at anastomotic stoma compared to the control group.Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure.

Background: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic cancer (PC). The purpose of this study was to identify predictors of PC in CP patients. Methods: Electronic medical records (EMRs) of CP patients from two cohorts were collected, and a logistic regression analysis was performed to investigate the risk factors for PC. Subsequently, we validated the value of the risk prediction model with the EMRs of a third cohort. Results: The derivation cohort consisted of 2,545 CP patients, and among them, 14 patients developed PC 7 years after CP diagnosis. Cyst of the pancreas [COP; odds ratio (OR): 4.37, 95% confidence interval (CI): 1.11 to 18.40, P=0.033], loss of weight (LW; OR: 3.21, 95% CI: 0.76 to 12.91, P=0.096) and high platelet (PLT) count (OR: 1.01 per 1 increment, 95% CI: 1.00 to 1.01, P=0.042) were independent risk factors for PC among CP patients. A risk prediction equation was constructed as follows: ln[p/(1–p)] = –6.68 + 1.55COP + 1.23LW + 0.0046PLT. The areas under the receiver operating characteristic (ROC) curve of our risk score were 0.83 and 0.72 in the derivation and validation cohorts, respectively. A score >0.0128 and >0.0122 had the best balance between sensitivity and specificity in the derivation and validation cohorts, respectively. Conclusions: In CP patients, LW, COP and high PLT count were identified as novel predictors of PC. A risk prediction model based on these factors exhibited moderate predictive value for CP patients.

The differentiation of human mesenchymal stem cells (hMSCs) into hepatocyte-like cells in vitro provides a promising candidate for cell therapy of liver diseases, and cell aggregates have been proposed to improve the efficiency of expansion and differentiation. Previously, we engineered multicellular aggregates incorporating human E-cadherin fusion protein (hE-cad-Fc)-coated poly(lactic-co-glycolic acid) (PLGA) microparticles (hE-cad-PLGAs), and a significant improvement was obtained in both cellular proliferation of and cytokine secretion by hMSCs. In this study, hepatic differentiation of hMSCs was induced by a biomimetic microenvironment consisting of these engineered aggregates and a cocktail of specific cytokines. The ratio of hE-cad-PLGAs to hMSCs in engineered hMSCs aggregates was optimized to 1:3 for hepatic differentiation. The expressions of hepatic-specific markers were significantly promoted, and cell polarity and activated drug metabolism enzymes were established in MSC/hE-cad-PLGA aggregates compared with MSC and MSC/PLGA aggregates. Moreover, the expressions of stemness and definitive endoderm markers confirmed effectively induced endoderm differentiation in MSC/hE-cad-PLGA aggregates, which was consistent with the pattern of embryonic development. After pre-differentiation for 1 week, the MSC/hE-cad-PLGA aggregates continuously progressed the hepatic phenotype expression in healthy rat peritoneum. Therefore, the biomimetic microenvironment constructed by hE-cad-PLGAs in engineered multicellular aggregates was able to promote the process of endoderm differentiation and the subsequent hepatic differentiation of hMSCs. It would be appropriate for applied research in hepatotoxic drug screening and cell-based treatment of liver diseases. By optimizing with other cytokine cocktail, the engineered multicellular aggregates can be applied to the construction of other endoderm-derived organs. Statement of significance The differentiation of mesenchymal stem cells (MSCs) into hepatocyte-like cells in vitro provides a promising for cell therapy for liver diseases, and cell aggregates have been proposed to improve the expansion and differentiation efficiency. Here, engineered multicellular aggregates were constructed by E-cadherin modified microparticles (hE-cad-PLGAs) construct a biomimetic microenvironment to promote the process of endoderm differentiation and the subsequent hepatic differentiation of hMSCs. Furthermore, after pre-differentiation for 1 week, the MSC/hE-cad-PLGA aggregates continuously progressed the hepatic phenotype expression in healthy rat peritoneum. Therefore, engineered multicellular aggregates with hE-cad-PLGAs would be appropriate for applied research in hepatotoxic drug screening and cell-based treatment of liver diseases, and provide a promising method in the construction of other endoderm-derived organs.

To evaluate the effect of preoperative serum alpha-fetoprotein(AFP) level to total tumor volume (TTV) ratio as a prognostic marker on predicting the tumor recurrence and overall survival time of patients with hepatocellular carcinoma (HCC) after liver transplantation. One-hundred eight patients with HCC who underwent liver transplantation in Beijing Chaoyang Hospital from April 2013 to October 2017 were studied. Divided into AFP/TTV≤2 group and AFP/TTV>2 group by the best cut-off score calculated by receiver operation characteristic curve, the clinical and pathological data of the patients in two groups were compared to explore the relationship between AFP/TTV and tumor recurrence together with the prognosis of HCC patients after liver transplantation. Risk factors of early tumor recurrence and poor prognosis of HCC in patients after liver transplantation were studied by multivariate regression analysis. Kaplan-Meier survival analysis was used to compare the tumor-free survival and overall survival between the two groups of patients. In 108 patients, 47 patients have AFP/TTV≤2 while 61 patients have AFP/TTV>2. Patients in AFP/TTV≤2 group have longer tumor-free survival time and overall survival time compared with patients in AFP/TTV>2 group. The age, total bilirubin level, serum AFP level, TTV, portal vein tumor thrombus and AFP/TTV (all P 2 (HR = 4.624, P 2 (HR = 4.257, P 2 is an independent risk factor for both early tumor recurrence and poor prognosis of patients with HCC after liver transplantation.

Background Left‐sided portal hypertension is usually found in patients undergoing pancreaticoduodenectomy (PD) with spleno‐mesenterico‐portal (S‐M‐P) confluence resection. This study is to explore the outcomes of S‐M‐P confluence reconstruction after resection by using bifurcated allogeneic vein. Methods Clinicopathologic data of patients who underwent extensive PD with S‐M‐P confluence resection for carcinoma of pancreatic head/uncinate process in our hospital between December 2011 and August 2018 were retrospectively reviewed and clinical outcomes of vein reconstruction after resection were analyzed. Results Of the 37 patients enrolled, S‐M‐P reconstruction by bifurcated allogeneic vein was performed in 24 cases (group 1) and simply splenic vein ligation in 13 cases (group 2). Items including pathological results, blood loss, and complications were comparable between the two groups, operation time was longer in group 1 (573.8 vs. 479.2 min, p = 0.018). Significantly decreased platelet count (205.9 vs. 133.1 × 109/L, p = 0.001) and increased splenic volume (270.9 vs. 452.2 ml, p

Shao-Cheng Lyu,* Jing Wang,* Mengxiu Huang,* Han-Xuan Wang, Lin Zhou, Qiang He, Ren Lang Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ren LangDepartment of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, No. 8 Gongtinan Road, Chaoyang District, Beijing, 100020, People’s Republic of ChinaTel +86-10-85231504Fax +86-10-85231503Email dr_langren@126.comBackground: The aim of this study was to reduce the influence of biliary obstruction on carbohydrate antigen 19-9 level (CA19-9) by introducing the CA19-9 level to serum γ-glutamyltransferase (GGT) ratio as an indicator, and ultimately to reveal the correlation between CA19-9/GGT and the prognosis of patients with pancreatic head carcinoma (PHC).Methods: A total of 339 enrolled patients who underwent pancreatoduodenectomy for PHC in Beijing ChaoYang Hospital from January 2010 to December 2019 were analyzed retrospectively. The optimal cut-off value, according to which patients were divided into a low-ratio group (Group 1, n=179) and a high-ratio group (Group 2, n=160), was determined by the ROC curve obtained from preoperative CA19-9/GGT and 1-year survival. Through univariate and multivariate analyses, risk factors for postoperative tumor recurrence and long-term survival were screened out among PHC patients.Results: The best cut-off value of CA19-9/GGT was 2.07 (area under the curve=0.567, 95% CI 0.498– 0.636). Compared with Group 2, Group 1 had lower CA19-9, and higher GGT, total bilirubin (TB) and lymph-node metastasis rate (P< 0.05). The 1-, 2- and 3-year disease-free survival rates of patients in Groups 1 and 2 were 68.2%, 42.5% and 28.2%, and 42.2%, 19.3% and 18.3%, respectively (P=0.000), and the 1-, 2- and 3-year overall survival rates were 79.1%, 50.7% and 29.1%, and 56.7%, 22.2% and 17.2%, respectively (P=0.000). Multivariate analysis showed that CA19-9/GGT, portal system invasion and lymph-node metastasis were independent risk factors for postoperative tumor recurrence and long-term survival among patients with PHC.Conclusion: Compared with CA19-9 level alone, CA19-9/GGT plays a more precise role in the evaluation of postoperative tumor recurrence and the long-term prognosis of PHC patients. The lower the ratio, the better the long-term prognosis. The CA19-9/GGT ratio may prove to be a useful biomarker for identifying PHC patients at high risk of early recurrence and unfavorable prognosis.Keywords: pancreatic head carcinoma, pancreatoduodenectomy, carbohydrate antigen 19-9, γ-glutamyltransferase, prognosis

BACKGROUND: The present study aimed to analyze the scar formation mechanism following Roux-en-Y choledochojejunostomy (CJS) in a novel rat model of obstructive jaundice. METHODS: The biliary obstruction model of Sprague-Dawley (SD) rats was established in advance, and 24 rats were randomly divided into 4 groups (control group, 1-day ligation group, 3-day ligation group, and 5-day ligation group). Changes in postoperative weight, common bile duct diameter, and laboratory indexes were analyzed to determine the best operation time. Roux-en-Y CJS in rats was studied based on the model, and the rats were randomly divided into 4 groups [control group, 3-day choledochojejunostomy (CJS) group, 7-day CJS group, and 30-day CJS group]. The same indexes were analyzed, and the characteristics of scar formation were evaluated by histopathology and polymerase chain reaction examination. RESULTS: The third day after common bile duct ligation is the best time for a Roux-en-Y CJS. The common bile duct diameter expands to 4.2 mm on average, and these physiological characteristics are consistent with current standard clinical findings. After completing CJS, the rats’ weight returned to normal levels, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), and C-reactive protein (CRP) indexes gradually decreased (P

Background Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and acute liver failure. However, in-hospital death cannot be avoided. We designed this study to analyze patients' in-hospital mortality rate after LT and the factors correlated with in-hospital death. Methods The data of patients who received LT in our hospital between January 11, 2015, and November 19, 2019, were obtained from the China Liver Transplant Registry and medical records. The in-hospital mortality rate was calculated, and factors related to mortality, cause of death, and factors related to cause of death were analyzed by reviewing patients' data. Results A total of 529 patients who underwent cadaveric LT were enrolled in this study. Modified piggyback orthotopic LT was performed for all patients. Seventy patients died in the hospital after LT, and the in-hospital mortality rate was 13.2%. Factors including model for end-stage liver disease (MELD) score, Child-Pugh grading, intraoperative blood loss, and anhepatic phase were correlated with in-hospital death. MELD score and intraoperative blood loss were determined as the two independent risk factors of in-hospital death. The first two causes of death were infection (34.3%) and primary non-function (15.7%). Pulmonary fungal infection was the main cause of infectious death. MELD score was the independent risk factor for infectious death, and both body mass index of donors and cold ischemic time were independent risk factors of primary non-function. Conclusions In-hospital death poses a threat to certain patients undergoing LT. Our study suggests that the main cause of in-hospital death is an infection, followed by primary non-function.

Background To analyze the related factors affecting the prognosis of pancreatic carcinoma with portal system invasion. Methods We retrospectively analyzed the clinical data of 118 patients with portal venous system invasion in Beijing Chaoyang Hospital between January 2011 and December 2018. Only patients with borderline resectable pancreatic cancer were included in this study. Borderline pancreatic cancer was defined according to NCCN (The National Comprehensive Cancer Network) guidelines. All patients underwent surgical treatment combined with vascular resection and reconstruction. The prognosis was evaluated according to the follow-up results, and the related risk factors for prognosis were analyzed. The survival curve was drawn by Kaplan-Meier method, and the survival rate was compared by log-rank test. Multivariate Cox regression was used to analyze the prognostic factors. Results In our research, all of 126 patients were successfully completed the operations. Complications occurred in 29.7% of patients and perioperative death in 4.0%. A total of 118 patients were followed up and the followed-up rate was 97.5% (118/121). The overall 1-year, 2-year and 3-year survival rates were 49.2%, 27.1% and 19.8%, And the median survival time was 20 months. Multivariate analysis showed that preoperative CA19-9 (RR 1.449, 95% CI: 1.053-1.994), N status (RR 2.533, 95% CI: 1.337-4.798), degree of tumor differentiation (RR 1.592, 95% CI: 1.064-2.381) and venous invasion depth (RR 2.03, 95% CI: 1.504-2.758) were independent risk factors for the prognosis. Conclusions The long-term prognosis of pancreatic carcinoma patients with portal system invasion is poor. The venous invasion depth is an independent risk factor for the prognosis of pancreatic carcinoma with portal system invasion, the deeper of venous invasion, the worse the prognosis, and poorly differentiated tumors have the worst prognosis. Other independent risk factors included N status and the preoperative CA19-9. Those may help with patients' selection for different treatment protocols.

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.

Background: Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC).Methods: GEO database (GSE31568, GSE41372, and GSE32688) and the PC cohort of The Cancer Genome Atlas were applied to discover the expression and prognostic role of miR-1301-3p. In the validation cohort, qRT-PCR was performed in 72 paired PC tissue samples. CCK-8, wound healing, and transwell migration assays were used to detect miR-1301-3p function on PC cells. Luciferase reporter assays and western blotting were performed to discover the potential target of miR-1301-3p on EMT.Results: Our study revealed that miR-1301-3p was downregulated in PC tissues compared with normal samples. A low level of miR-1301-3p was associated with malignant pathological differentiation, lymphatic metastasis, tumor residual, and unsatisfactory overall survival. Gene Ontology analyses indicated that miR-1301-3p possibly regulated cell cycle and adheren junction. In vitro assays showed that miR-1301-3p suppressed proliferation, migration, and invasion ability of PC cells. Mechanically, miR-1301-3p inhibits RhoA expression, and knockdown of RhoA upregulated E-cadherin; however, downregulated N-cadherin and vimentin level.Conclusions: MiR-1301-3p acts as a prognostic biomarker for PC and inhibits PC progression by targeting RhoA induced EMT process.

An increased level of microbial translocation has been observed in HIV-infected individuals. The host response to microbial translocation is compromised in HIV-infected progressors but remains unknown in HIV-infected long-term nonprogressors (LTNPs). To evaluate microbial translocation in HIV, we assessed lipopolysaccharide (LPS) immunohistochemistry staining in lymph nodes. We found enriched bacterial LPS immunohistochemistry staining in the germinal center of a lymph node from an HIV-infected LTNP, evenly distributed from three progressors with impaired germinal center structures and rarely detected from two HIV-negative individuals. The impaired germinal center structures were consistent with collagen deposition in lymph nodes using immunohistochemistry staining. These results suggest greater immune responses against bacterial LPS translocation in LTNPs, which may reveal an important mechanism in controlling microbial translocation and disease progression in HIV LTNPs.

Patients with pancreatic head cancer involving the superior mesenteric-portal vein can benefit from vascular resection and reconstruction. We aimed to propose our vascular classification and assess its effect in this study.Data of consecutive patients, who were diagnosed with pancreatic head cancer, and underwent radical pancreaticoduodenectomy combined with superior mesenteric-portal vein resection and reconstruction at our institute between October 2013 and August 2016, were retrospectively collected. On a scale of one to four, our classification was proposed. Perioperative parameters were then analyzed among the four types.There were a total of 52 patients with 11 in type Ⅰ, 15 in type Ⅱ, 18 in type Ⅲ, 8 in type Ⅳ. The respective operative time and estimated blood loss of types Ⅲ (425-990 min, 265-1820 mL) and Ⅳ (480-1036 min, 330-1690 mL) were greater than those of types Ⅰ (300-824 min, 200-1255 mL) and Ⅱ (369-875 min, 305-1400 mL) (p 0.05). Type Ⅳ had larger tumors (4-7 cm) than type Ⅰ (1.5-4 cm) (p 0.05). Percentage of tunica intima involvement and the median survival time of type Ⅰ (9.1%, 22 months) were lower and longer than those of types Ⅱ (46.7%, 17 months) and Ⅲ (44.4%, 16 months; p 0.05), and even lower and longer than those of type Ⅳ (87.5%, 10 months; p 0.01), respectively.Our classification can provide a system to grade patients with venous invasion in order of surgical difficulty and survival.

Acute-on-chronic liver failure (ACLF) is characterized by organ failure mediated by acute decompensation of cirrhosis. Recent studies have highlighted the importance of the gut-liver axis (GLS) and its association with ACLF pathogenesis. In this review, we discuss the mechanisms related to the alteration of the GLA and their involvement in ACLF pathogenesis and suggest some possible therapeutic options that could modulate the GLA dysfunction. This knowledge may provide information useful for the design of therapeutic strategies for gut dysbiosis and its complications in ACLF.

Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

Background: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC). Methods: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan−Meier survival analyses were performed to evaluate the clinical value of PMDGs. Results: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P

The protein 14-3-3σ is involved in numerous cellular processes through its ability to bind phosphorylated serine/threonine residues. It is a key regulator of the cell cycle involving in G2 arrest by p53. Deregulation of 14-3-3σ expression has been associated with a large variety of human cancers. However, its physiological function and therapeutic significance have rarely been investigated in cholangiocarcinoma. Using immunohistochemistry (IHC), we evaluated 14-3-3σ expression in 65 human extrahepatic cholangiocarcinomas. As a result, we found that 14-3-3σ is expressed in the tissue of 56 patients (86.2%), and its expression is positively correlated with tumor size, lymph node metastasis, and tumor stage. We also explored the significance of 14-3-3σ and found that 14-3-3σ exerts cell type-dependent effects on cell proliferation through PI3K/Akt signaling in both in vitro and in vivo xenograft models. These results suggest that 14-3-3σ assumes a constitutive role in tumorigenesis rather than acting as a cell cycle regulator in cholangiocarcinoma, which makes 14-3-3σ a new potential target for therapeutic intervention.

The protein 14-3-3δ interacts with Trp53 to maintain G2 arrest and thus regulates the cell cycle. Though dysfunction of 14-3-3δ caused by hyper-methylation of CpG islands was reported in several carcinomas, the exact role of this protein in the development of extrahepatic cholangiocarcinoma has not been fully elucidated. Here, we aim at investigating the clinical relevance between 14-3-3δ and human extrahepatic cholangiocarcinoma. We collected extrahepatic cholangiocarcinoma specimens of 65 patients in Beijing Chao Yang Hospital and evaluated their 14-3-3δ expression using immunohistochemistry. We categorized the patients into different subgroups according to clinic pathological factors, such as sex, age, tumor size, pathological classification, lymph node metastasis status, tumor stage, and serum markers including CEA, CA-242, or CA19-9, and further evaluated the correlation between 14-3-3δ expression and these potential prognostic factors. As a result, we detected 14-3-3δ expression in 53 out of 65 specimens (81.5%), and the expression was positively correlated with TNM stage, lymph node metastasis, and overall survival. Our results suggest that 14-3-3δ serves as an oncogenic driver in extrahepatic cholangiocarcinoma tumorigenesis rather than a cell cycle regulator; the overexpression of 14-3-3δ might be frequently acquired by tumor cells to escape appropriate cell cycle regulation. Thus, 14-3-3δ could be a potential target for extrahepatic cholangiocarcinoma diagnosis and therapy.

Objective The results of segmental venous resection (VR) combined with pancreatoduodenectomy (PD) are controversial but may be promising. Few studies have described reconstruction of the portal/superior mesenteric vein (PV/SMV) with the iliac vein harvested from donation after cardiac death (DCD). Methods From January 2014 to April 2016, PD combined with segmental excision of the PV/SMV (VR group) was performed in 21 patients with adenocarcinoma of the head of the pancreas (ADHP). The authors established a new technique of venous reconstruction using the iliac vein from DCD and analysed patients’ long-term survival. Results The tumour dimensions and tumour staging were greater and the operation time was longer in the VR than PD group; however, no differences in the resection degree, blood loss, complications, reoperation rate, or mortality rate were found. The median survival was similar between the VR and PD groups. The long-term patency of the donor iliac vein was 90%. The degree of resection was a strong predictor of long-term survival. Conclusion Segmental PV/SMV resection combined with PD is applicable to selective patients with venous invasion by ADHP if R0 resection has probably been achieved. An iliac vein obtained by DCD provides an effective graft for venous reconstruction.

Mesenchymal stem cells (MSCs) have emerged as a promising source of multipotent cells for various cell-based therapies due to their unique properties, and formation of 3D MSC aggregates has been explored as a potential strategy to enhance therapeutic efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human E-cadherin fusion protein (hE-cad-PLGA microparticles) have been fabricated and integrated with human MSCs to form 3D cell aggregates. The results show that, compared with the plain PLGA, the hE-cad-PLGA microparticles distribute within the aggregates more evenly and further result in a more significant improvement of cellular proliferation and secretion of a series of bioactive factors due to the synergistic effects from the bioactive E-cadherin fragments and the PLGA microparticles. Meanwhile, the hE-cad-PLGA microparticles incorporated in the aggregates upregulate the phosphorylation of epidermal growth factor receptors and activate the AKT and ERK1/2 signaling pathways in the MSCs. Additionally, the E-cadherin/β-catenin cellular membrane complex in the MSCs is markedly stimulated by the hE-cad-PLGA microparticles. Therefore, engineering 3D cell aggregates with hE-cad-PLGA microparticles can be a promising method for ex vivo multipotent stem-cell expansion with enhanced biological functions and may offer a novel route to expand multipotent stem-cell-based clinical applications.

Tripterygium wilfordii Hook F (TwHF) exhibits anti-tumor efficacy in pancreatic ductal adenocarcinoma (PDAC), however the pharmacological mechanisms are unclear due to complicated formulae and target genes. Using Traditional Chinese Medicine Systems Pharmacology and GeneCards databases, we performed a network pharmacology (NP) of TwHF and screened out 22 ingredients and 25 target genes associated with PDAC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the 25 target genes were performed. Using STRING database, protein-protein interaction network of the 25 target genes was constructed, and indicated that triptolide (TL)-plasminogen activator urokinase (PLAU) as a potential target for PDAC treatment. Hence, in vitro experiments were performed and validated that TL inhibited PDAC cell proliferation and migration by suppressing PLAU expression. The results of Western blot suggested that PLAU activated endothelial-mesenchymal transition (EMT) progression. In two Gene Expression Omnibus datasets (GSE16515 and GSE28735), PLAU was up-regulated in tumor tissues, and PLAU overexpression was associated with poor overall survival of PDAC cohort of The Cancer Genome Atlas (P 0.01). Immunohistochemistry illustrated that overexpression of PLAU protein was related to lymph node metastasis in 20 PDAC patients (P 0.01). Based on NP of TwHF, we identified and validated that TL-PLAU could serve as a potential target for PDAC treatment.

Background There are few reports about resection of portal vein (PV)/superior mesenteric vein (SMV) and reconstruction by using allogeneic vein. This case-control study was designed to explore the feasibility and safety of this operation type in patients with T3 stage pancreatic head cancer. Methods A total of 42 patients (Group A) underwent PV/SMV resection and reconstruction by using allogeneic vein were 1:1 matched to 42 controls (Group B) with other types of resection and reconstruction. The two groups were well matched. Results There was no significantly prolonged total operation time (Group A vs. Group B [490.0 min vs. 470 min], P = 0.067) and increased intraoperative blood loss (Group A vs. Group B [650.0 min vs. 450 min], P = 0.108) was found between the two groups. R1 rate of PV/SMV was slightly reduced in group A compared to group B (4.8% vs. 14.3%, P = 0.137), although no significant difference was found. The incidences of main postoperative complications between the two groups were similar. A slightly increased 1-year and 2-year overall survival rate (OS) (Group A vs. Group B [1-year OS: 62.9% vs. 57.0%; 2-year OS: 31.5% vs. 25.6%], P = 0.501) and disease-free survival rate (DFS) (Group A vs. Group B [1-year DFS: 43.9% vs. 36.6%; 2-year DFS: 10.5% vs. 7.4%], P = 0.502) could be found in group A compared to group B, although the differences were not significant. Conclusions The operation types of PV/SMV resection and reconstruction by using allogeneic vein is safety and feasible, it might have a potential benefit for patients.

Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability.

Jianyu Lin,1,* Jing Wang,2,* Peng Yue,3 Xingmao Zhang,4 Ren Lang,4 Yuan Wang,4 Chen Cui,4 Qiang He4 1Integrated Department, 2Patient Service Center, The Affiliated Hospital to Capital Medical University, Beijing Chaoyang Hospital, 3School of Nursing, Department of Basic Nursing, Capital Medical University, 4Department of Hepatobiliary Surgery, The Affiliated Hospital to Capital Medical University, Beijing Chaoyang Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: Intestinal perforation is a rare complication after liver transplantation. This study was designed to calculate the incidence and investigate the outcomes of intestinal perforation in adult liver transplant patients.Materials and methods: The clinical records of liver transplant recipients between January 2014 and June 2016 were obtained. The incidence of intestinal perforation was calculated, and high risk factors were analyzed.Results: The mean operative time was 8.5h (range: 6–11h). The mean portal vein occlusion time was 66.5min (range: 58–72min), and the mean cold ischemia time was 7.9h (range: 6.5–9.5h). Four (2.7%) patients developed intestinal perforation from 9 to 14days postliver transplant. All perforations were single and repaired by interrupted silk sutures. Two patients uneventfully recovered, but intestinal perforation recurred in two other patients. Simple repair was undertaken in one patient, and terminal ileum resection and ileostomy were performed in the other patient. There were no perioperative deaths.Conclusion: The incidence of intestinal perforation after liver transplantation is low. Prompt diagnosis and treatment should be carried out to reduce comorbidities and mortality. Keywords: liver transplant, intestinal perforation, incidence, treatment, nursing

Monocytes are precursors of macrophages and key players during inflammation and pathogen challenge in the periphery, whereas intestinal resident macrophages act as innate effector cells to engulf and clear bacteria, secrete cytokines, and maintain intestinal immunity and homeostasis. However, perturbation of toll-like receptor signaling pathway in intestinal macrophages has been associated with tolerance breakdown in autoimmune diseases. In the present review, we have summarized and discussed the role of toll-like receptor signals in human intestinal macrophages, and the role of human intestinal macrophages in keeping human intestinal immunity, homeostasis, and autoimmune diseases.

Purpose The aim of this study was to establish enhanced recovery protocols for the management of mild gallstone pancreatitis. Methods Sixty consecutive patients were divided into enhanced recovery and traditional recovery (TR) groups in a randomized observational study. The basic enhanced recovery elements included early laparoscopic cholecystectomy, restrictive endoscopic intervention, and early oral nutrition. The incidence of complications, readmission, length of stay, and total medical cost were analyzed during the hospital course. Results The length of hospital stay and medical cost were significantly lower in the enhanced recovery group in comparison to the TR group: 5.9 days vs. 10.6 days (P

Early diagnosis of superior mesenteric artery (SMA) involvement is vital for patients with a borderline resectable cancer of the pancreatic head to achieve an R0 resection. We aimed to detect the effect of the inferior infracolic 'superior mesenteric artery first' approach with a no-touch isolation surgical technique in these patients.The data of 21 patients who were consecutively diagnosed with a borderline resectable cancer of the pancreatic head and treated with our technique between July 2014 and September 2015 were analyzed.During the exploration, five patients were confirmed to have invasion to the SMA. Fourteen patients underwent a pancreaticoduodenectomy, and two patients underwent a total pancreatectomy due to a positive margin at the pancreatic neck on frozen sections. Ten men and six women, with a mean age of 64.1 years, were included in the study. Pathologic stage was T1, T2, and T3 in 1, 3, and 12 patients, respectively. Venous resection was performed in 8 patients, and an R0 resection was achieved in all patients (16/16). The mean intraoperative blood loss was 532 ml (range 200-1800 ml). At median follow-up time after surgery (12.8 months; range 4.5-18 months), two patients had a recurrence in the liver. The 1-year survival rate was 75 %, and the 1-year tumor-free survival rate was 62.5 %.Our technique facilitates early diagnosis of arterial involvement and the achievement of an R0 resection. This technique allows the tumor to be resected in situ, and removed en bloc, and is associated with decreased blood loss.

There is currently no optimal system to expand and maintain the function of human adult hepatocytes in culture. Recent studies have demonstrated that specific tissue-derived extracellular matrix (ECM) can serve as a culture substrate and that cells tend to proliferate and differentiate best on ECM derived from their tissue of origin. The goal of this study was to investigate whether three-dimensional (3D) ECM derived from porcine liver can facilitate the growth and maintenance of physiological functions of liver cells. Optimized decellularization/oxidation procedures removed up to 93% of the cellular components from porcine liver tissue and preserved key molecular components in the ECM, including collagen-I, -III, and -IV, proteoglycans, glycosaminoglycans, fibronectin, elastin, and laminin. When HepG2 cells or human hepatocytes were seeded onto ECM discs, uniform multi-layer constructs of both cell types were formed. Dynamic culture conditions yielded better cellular infiltration into the ECM discs. Human hepatocytes cultured on ECM discs expressed significantly higher levels of albumin over a 21-day culture period compared to cells cultured in traditional polystyrene cultureware or in a collagen gel “sandwich”. The culture of hepatocytes on 3D liver-specific ECM resulted in considerably improved cell growth and maintained cell function; therefore, this system could potentially be used in liver tissue regeneration, drug discovery or toxicology studies.

AIM: To explore a method to establish an animal model of ischemic type intrahepatic biliary lesion in rabbits. METHODS: Forty Japanese white rabbits of clean grade were divided randomly into four groups (10 rabbits per group) including sham operation (SO) group, and artery-bile obstruction (ABO)-1 h group, ABO-2 h group and ABO-3 h group. All the rabbits in this study underwent the same initial surgical procedure in which the liver was prepared as for graft removal during liver transplantation. Subsequently in the SO group, no additional vascular intervention was performed, while in groups ABO-1 h, ABO-2 h and ABO-3 h, the animals underwent combined clamping of the hepatic artery and common bile duct with microvascular clips for 1, 2 and 3 h, respectively. After the scheduled occlusion time, the clip was removed to recover blood supply. The animals were killed 4 wk after operation. The survival rate, liver function, cholangiography and histopathological manifestation of the rabbits in each group were observed. RESULTS: The survival rate was 100% in groups SO, ABO-1 h and ABO-2 h, while it was 60% in group ABO-3 h. At each observation time, the change degree of the indexes of liver function was proportional to the clamping time (ABO-3 h > ABO-2 h > ABO-1 h > SO, P < 0.05). Cholangiographical and histopathologic manifestations both showed that intrahepatic biliary lesion aggravated proportionally with the increase of the clamping time. CONCLUSION: An animal model of ischemic type intrahepatic biliary lesion in rabbits is successfully established, which may provide a reliable technique for basic and clinical research into the etiology, development and prophylaxis of ischemic type intrahepatic biliary lesion after liver transplantation. © 2009 The WJG Press and Baishideng. All rights reserved.

AIM: To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions (IITBLs). METHODS: A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions. The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year. The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year. In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver. The incidence of IITBLs was compared between the two groups. RESULTS: In the control group, the incidence of IITBLs was 5.9% (13/220 cases) after 3-11 mo of transplantation. In the experimental group, two recipients (1.4%) developed IITBLs at 3 and 6 mo after transplantation, respectively. The difference in the incidence between the two groups was statistically significant (P < 0.05). CONCLUSION: Double perfusion of cadaveric livers from non-heart-beating donors with urokinase may reduce the incidence of IITBLs.

Pancreatic pseudocysts (PPs) are collections of pancreatic secretions that are lined by fibrous tissues and may contain necrotic debris or blood. The interventions including percutaneous, endoscopic or surgical approaches are based on the size, location, symptoms and complications of a pseudocyst. With the availability of advanced imaging systems and cameras, better hemostatic equipments and excellent laparoscopic techniques, most pseudocysts can be found and managed by laparoscopy. We describe a case of a 30-year-old male patient with a pancreatic pseudocyst amenable to laparoscopic cystogastrostomy. An incision was made through the anterior gastric wall to expose the posterior gastric wall in close contact with the pseudocyst using an ultrasonically activated scalpel. Then, another incision was made for cystogastrostomy to obtain complete and unobstructed drainage. The patient recovered well after operation and was symptom-free during a 6-mo follow-up, suggesting that laparoscopic cystogastrostomy is a safe and effective alternative to open cystogastrostomy for minimally invasive management of PPs.

Background A moderate insufflation pressure and deep neuromuscular blockade (NMB) have been recommended in laparoscopic surgery in consideration of the possible reduction in splanchnic perfusion due to the CO2-pneumoperitoneum. Since the liver is the major organ for rocuronium metabolism, the question of whether NMB of rocuronium would change with the variation of liver perfusion during pneumoperitoneum during laparoscopic surgery merits investigation. Methods In this prospective study, a total of sixty female patients scheduled for either selective laparoscopic gynaecological surgery (group laparoscopy) or laparotomy for gynaecological surgery (group control) were analyzed. Rocuronium was administered with closed-loop feedback infusion system, which was also applied to monitor NMB complied with good clinical research practice (GCRP). The onset time, clinical duration, and recovery index were measured. Hepatic blood flow was assessed by laparoscopic intraoperative ultrasonography before insufflation/after entering the abdominal cavity (T1), 5 min after insufflation in the Trendelenburg position/5 min after skin incision (T2), 15 min after insufflation in the Trendelenburg position/15 min after skin incision (T3), 30 min after insufflation in the Trendelenburg position/30 min after skin incision (T4), and 5 min after deflation/before closing the abdomen (T5) in group laparoscopy/group control respectively. The relationship between the clinical duration of rocuronium and portal venous blood flow was analyzed using linear or quadratic regression. Result The clinical duration and RI of rocuronium were both prolonged significantly in group laparoscopy (36.8 ± 8.3 min; 12.8 ± 5.5 min) compared to group control (29.0 ± 5.8 min; 9.8 ± 4.0 min) (P