Objective To investigate the expressions of Yes-associated protein-1 (YAP1) in gallbladder mucosal epithelium of normal persons,in patients with simple/calculous cholecystitis,and in patients with gallbladder carcinoma;and to study the mechanism of YAP1 in gallbladder carcinoma development.Methods Immunohistochemistry was used to detect the expression and distribution of YAP1 protein in 50 persons with normal gallbladder,101 patients with simple cholecystitis/calculous cholecystitis and 100 patients with gallbladder carcinoma.RT-PCR and western-blot were used to detect the mRNA and protein levels of YAP1 in normal and malignant gallbladder mucosal epithelium cells.siRNA was used to shut down the expression of YAP1 in SGC996 cells.MTT was used to test cell vitality.Flow cytometry was used to measure cell cycle.Results Immunohistochemistry revealed the expression rates of YAP1 in the gallbladder carcinoma group,the cholecystitis/gallstone group and the control group to be 87.0％ (87/100),56.4％ (57/101) and 5.0％ (1/20),respectively (P ＜ 0.01).The YAP1 protein levels were higher in gallbladder carcinoma tissues and cells when compared to normal tissues and cells.RT-PCR showed the mRNA levels of gallbladder carcinoma cells to be 12.5 ± 1.2 times of normal gallbladder mucosal epithelial cells (P ＜ 0.05).After using siRNA to shut down the YAP1 expression,EMT associated proteins were down-regulated,cell vitality was decreased,and cell cycle was arrested in the S-phase.Conclusions YAP1 is closely related to cell proliferation and metastasis of gallbladder carcinoma.It may promote tumor progression through epithelial-mesenchymal transition.transition;Tumor progress

Pancreatic fistula is one of the most common and serious complications after digestive tract reconstruction.Grade A pancreatic fistula is defined as biochemical fistula only when the drainage fluid amylase level is elevated without affecting clinical decision-making.It is not a true pancreatic fistula, or a real surgical complication.Surgeons should pay more attention to the diagnosis and treatment of B and C pancreatic fistula, and it is more valuable to reduce the occurrence of B and C pancreatic fistula.Pancreatic fistula is not a purely surgical technical problem, but the quality of surgical reconstruction is very important.For pancreatic surgeons, the reconstruction of the pancreatic stump digestive tract after pancreaticoduodenectomy is accompanied by both opportunities and challenges.

Objective To study the expression of MREll-RAD50-NBS1 complex in normal gallbladder tissues,simple cholecystitis,calculous cholecystitis and gallbladder carcinoma.Methods The expression of MRN complex in different gallbladder lesion tissues were detected by immunohistochemistry.Western blot,Methyl thiazolyl tetrazolium(MTT) assay and flow cytometry were used to detect the influence of apoptosis and proliferation induced by NBS1.Results The differences between the expression of MRE11,RAD50 and different gallbladder lesion tissues were not statistically significant (respectively x2 =2.724,1.697,all P ＞ 0.05).The expression of NBS1 in GBC tissues [15.3％ (9/59)] was prominently lower than that in the normal gallbladder tissues [84.7％ (50/59)],simple cholecystitis [87.8％ (36/41)],calculous cholecystitis [61.2％ (30/49)] (x2 =87.388,P ＜ 0.01).The Western blot results reveal that NBS1 can mediate apoptosis by up-regulate Bax and down-regulate Bcl-2.The MTT assay results showed that the relative absorbance of treatment and control group after 24,48,72 h were[(1.120 ± 0.006)vs.(1.350±0.009),(1.600±0.004)vs.(1.99±0.01),(1.83±0.01)vs.(2.260±0.003)(F=7.659,P ＜0.01).The apoptosis rate in treatment group(17.23％ ± 0.56％)was higher than that in the control group (4.13％ ± 0.67％) (t =9.133,P ＜ 0.01).Conclusion NBS1 is closely related to gallbladder carcinoma.NBS1 can inhibit the proliferation and promote apoptosis of GBC-SD cells.

Myeloid derived suppressor cell (MDSC) is a kind of myogenic stem cells that are induced by tumor-derived cytokines.MDSCs not only have their own immunosuppressive effects,but also can mediate the immunosuppressive effects of T lymphocytes through different mechanisms.Recent studies have shown that MDSCs involved in tumor immune escape,immune tolerance as well as other pathological processes,and played an important role in promoting the generation and development of tumors.The advances of the generation,immunosuppressive effects of MDSCs and their relation with digestive system tumors were summarized in this paper,which would provide evidences for the clinical use of MDSCs in treating digestive system tumors.

Biliary tract cancers (BTC), a heterogeneous disease with poor prognosis, including gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC). Although surgery is currently the primary regimen to treat BTC, most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication. As a result, non-surgical therapy serves as the main intervention for advanced BTC. In recent years, immunotherapy has emerged as one of the most promising therapies in a number of solid cancers, and it includes immune checkpoint inhibitors (ICIs) monotherapy or combined therapy, tumor vaccines, oncolytic virus immunotherapy, adoptive cell therapy (ACT), and cytokine therapy. However, these therapies have been practiced in limited clinical settings in patients with BTC. In this review, we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

Objective:To explore the predictive values of preoperative CT and MRI features in intraoperative liquefaction degrees of hematoma in patients with chronic subdural hematoma (CSDH).Methods:Sixty-nine patients (83 sides) with CSDH, admitted to Department of Neurosurgery, Affiliated Hospital of Qingdao University were chosen; preoperative CT and/or MRI were performed in all patients. According to hematoma density in CT images, hematoma was divided into high-density, medium density and low-density hematoma; according to the proportion of hematoma part enjoying uniform signal in MRI images, hematoma was divided into heterogeneous signal hematoma and homogenized signal hematoma. The liquefaction degrees of hematoma in patients with different densities of hematoma, and heterogeneous signal hematoma and homogenized signal hematoma were compared, and the liquefaction degrees of hematoma in patients with special-shaped hematoma were summarized.Results:A total of 58 patients (69 sides) with CSDH completed preoperative CT examination; the intraoperative liquefaction degrees of hematoma in patients with different hematoma densities in CT images were significantly different ( P<0.05); the liquefaction degree of hematoma in patients with medium density hematoma was better than that of high-density hematoma and low-density hematoma (average rank: 40.71, 34.67 and 25.27). A total of 50 patients (63 sides) with CSDH completed preoperative MRI examination; the intraoperative liquefaction degrees of hematoma in patients with homogenized signal hematoma was better than that of heterogeneous signal hematoma, with significant difference (average rank: 46.53 and 17.00, P<0.05). The hematoma with soapy signs on preoperative CT or MRI images had blood clots mainly. Hematoma with fluid-fluid levels and fluid gradual changes had good liquefaction. Conclusion:Preoperative CT and(or) MRI images can effectively help to predict the intraoperative liquefaction degrees of hematoma in CSDH patients.

Objective To study the expressions of Nodal in normal gallbladder,and gallbladders with cholelithiasis,cholecystitis and carcinoma;and to study the impact of inhibiting or promoting Nodal expressions in gallbladder carcinoma on the Smad2/4 pathway and epithelial-mesenchymal transition.Methods Immunohistochemistry was used to detect the expressions and distributions of Nodal protein in 30 normal gallbladders,96 simple cholecystitis/calculous cholecystitis specimens and 42 gallbladder carcinoma specimens.The mRNA and protein expressions of Nodal in normal and malignant gallbladdcr mucosal epithelium cells and breast cancer cells were detected by RT-PCR,western blotting and wound healing tests.The impact of activating agents and inhibitors on the expression levels of Nodal and its signaling pathway Smad2/4 and EMT-related proteins were analyzed.Results Immunohistochemistry showed that the positive rates of Nodal in the gallbladder cancer group was significantly higher than that in the gallbladder stone group and the normal gallbladder group.The results were 83.3％ (35/42),44.8％ (43/96),6.7％ (2/30) respectively (P＜ 0.01).RT-PCR and Western blotting showed the expressions of Nodal in gallbladder carcinoma cells were higher than normal gallbladder cells (P＜0.05).After using rhNodal to up regulate the Nodal expression,the Smad2 protein phosphorylation was promoted and the EMT associated proteins were up-regulated.After using the inhibitor SB431542 to suppress the Nodal expression,the Smad2 protein phosphorylation decreased and the EMT associated proteins were down-regulated.Conclusions The expression of Nodal was closely related to cell proliferation and metastasis in gallbladder carcinoma.Tumor progression was promoted via the smad2/4 pathway through epithelial-mesenchymal transition.

Objective: To investigate the feasibility and effectiveness of endoscopicretrograde cholangio-pancreatography(ERCP)in the management of long-term complications after pancreaticoduodenectomy. Methods: From January 2009 to July 2018, the clinical data of 62 patients with biliary or pancreatic long-term complications after pancreatoduodenectomy were reviewed at Department of General Surgery, and the corresponding ERCP were carried out in the multi-disciplinary cooperation.There were 39 males and 24 females.The age was 56.5 years(aging from 13 to 76 years). The time of treatment was 3 months to 20 years after pancreatoduodenectomy.The long-term biliopancreatic complications after pancreatoduodenectomy included 51 cases of biliary calculi, 42 cases of bilioenteric anastomotic stenosis with proximal bile duct dilatation, and 11 cases of pancreaticointestinal anastomosis stenosis with distal pancreatic duct dilatation.All patients received conventional duodenoscopy or single-balloon enteroscopy assisted ERCP under general anesthesia. Results: A total of 95 ERCP were performed in 62 patients, averaging 1.5 times per case.The long-term complications of cholangiopancreatic after pancreatoduodenectomy(ERCP indications) included 56 times of bile duct stones(58.9%), 45 times of bilioenteric anastomatic stricture(47.4%), 11 times of recurrent pancreatitis(11.6%), 6 cases(6.3%) of bilioenteric anastomatic foreign body, 3 times of intrahepatic bile duct stenosis(3.2%). Among the 95 times, 82 times(86.3%) achieved endoscopic endoscopy, 76 times(80.0%) were diagnosed successfully, and 72 times(75.8%) were successfully treated with ERCP.Small intestinal perforation occurred in 1 patient undergoing duodenoscopy, and then healed by surgical repair. Conclusion Multi-disciplinary collaboration of ERCP is safe and effective in the treatment of long-term complications after pancreaticoduodenectomy, but the long-term effect still needs further clinical follow-up.

Objective: To evaluate the role of anatomical hepatectomy in the treatment of intrahepatic cholangiocarcinoma. Methods: The cases of intrahepatic cholangiocarcinoma who received curative surgery in two hospitals from 2010 to 2015 were analyzed retrospectively. Among the 98 patients enrolled in this study, 55 were male and 43 were female. The median age was 61 years. According to receiving anatomical hepatectomy or not, the 98 cases were divided into two groups: non-anatomical hepatectomy(n=30) and anatomical hepatectomy(n=68). The surgical results were compared between the two groups.Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. The influence of each prognostic factor identified by univariate analysis was multivariate analysis by Cox′s proportional hazard regression. Results: The duration of surgery was significantly prolonged in the anatomical hepatectomy group((196.4±94.9)minutes vs. (166.2±65.7)minutes, P=0.027), while there was no significant difference in terms of other surgical results such as intraoperative blood transfusion, postoperative morbidity and mortality rate. Compared to non-anatomical hepatectomy, anatomical hepatectomy significantly improved long-term survival results(14 months vs. 11 months)(χ²=4.641, P=0.031). Single variable analysis indicated that tumor differentiation, tumor numbers, T stage, N stage, anatomical hepatectomy and adjuvant therapy significantly affected overall survival. Multivariate analysis demonstrated that tumor numbers(HR=0.522, 95% CI: 0.259-0.974, P=0.042) and anatomical hepatectomy(HR=1.858, 95%CI: 1.092-3.161, P=0.022) were two independent prognostic factors for overall survival. Conclusion Compared to non-anatomical hepatectomy, anatomical hepatectomy performed for intrahepatic cholangiocarcinoma is not only safe but also beneficial for long-term survival.

Objective:To establish donor liver quality related risk factors for the loss of function of transplanted liver.Methods:The data of donors and recipients of liver transplantation at the Organ Donation and Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University from Nov 2011 to Dec 2018 were analyzed retrospectively. Propensity score matching (PSM) was performed to evaluate and screen the data of donors and recipients, in order to balance the covariates.Results:Of the organ donation, there were 70 males and 20 females , aging (40.6±16.3) years. Of the liver transplantation recipients, there were 70 males and 20 females , aging (41.8±20.3) years. Liver dysfunction after transplantation was significantly correlated with the following variables: the donor's CPR time( t=0.429, P=0.000), 15-minute retention rate of indocyanine green ( χ2=67.151, P=0.000), liver function grading ( χ2=54.154, P=0.000), bullae fatty liver grading ( χ2=8.120, P=0.017), vesicular fatty liver grading ( χ2=16.000, P=0.001), ICU stay time ( χ2=14.900, P=0.001)and serum creatinine level ( χ2=44.685, P=0.000). The donor scoring system was established in our studying. For the 90 organ donation cases, the donated liver quality were classified into four levels,which were of good correspondence to the prognosis of the recipients. Conclusion:This donor scoring system and grading standards established by analyzing the high-risk factors of liver dysfunction after transplantation helps evaluate the quality of donor liver in China.