Comprehensive analysis of differential methylation genes in cholangiocarcinoma and identification of prognosis-related genes glucosaminyl (N-acetyl) transferase 1 and neurotrophic receptor tyrosine kinase 3 / 肿瘤研究与临床

Objective:To identify and screen the differential methylation genes in patients with cholangiocarcinoma and to predict the prognosis of patients with CCA.Methods:Cholangiocarcinoma tissues and paracancerous tissues of 8 patients with cholangiocarcinoma in Fujian Provincial Hospital from October 2019 to May 2020 were selected for 850K methylation sequencing analysis to obtain differentially methylated genes. The 2018 genome-wide methylation data and clinical information of 36 patients with cholangiocarcinoma were download from The Cancer Genome Atlas (TCGA) database, the 2012 cholangiocarcinoma methylation data (GSE32879) were download from the Gene Expression Omnibus (GEO) database, and the 2018 TCGA database differential survival genomic data of overall survival (OS) and disease-free survival (DFS) of cholangiocarcinoma were download from the GEPIA2 database. The differentially methylated positions (DMP) and differentially methylated regions (DMR) results of 850K methylation sequencing analysis of submitted samples, methylated genes in TCGA and GEO databases, and cholangiocarcinoma survival genes of samples were jointly submitted for testing, multi-data set analysis was performed by the Sangerbox VENN tool, and common differentially methylated genes were obtained by intersection screening. The minimum P value method was used to determine the cut-off value of gene expression in Sangerbox, and the patients were divided into high and low expression groups of differentially methylated genes. The OS, DFS, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI) of cholangiocarcinoma patients were compared between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Results:A total of 121 954 DMP were identified by 850K methylation sequencing of cholangiocarcinoma tissues and paracancerous tissues of 8 patients; a total of 1 399 differentially methylated genes were identified in DMR, and the common prognosis related genes glucosaminyl (N-acetyl) transferase 1 (GCNT1) and neurotrophic receptor tyrosine kinase 3 (NTRK3) were identified by intersection identification. The expression of GCNT1 in the cholangiocarcinoma tissues was higher than that in the paracancerous tissues, and the difference was statistically significant ( P = 0.040). The expression of NTRK3 in cholangiocarcinoma tissues was higher than that in the paracancerous tissues, but the difference was not statistically significant ( P = 0.790). The minimum P value method was used to predict the prognosis of patients with cholangiocarcinoma based on the combined expression of GCNT1 and NTRK3, and the order was based on the sum of the expression levels of the two genes. When 30% of the ranking was taken as the cut-off value, the difference in DFS between the high expression group and the low expression group in cholangiocarcinoma was the most significant ( P < 0.001); there was no significant difference in OS between the two groups ( P = 0.065). The results of GO functional analysis showed that GCNT1 was involved in protein glycosylation, macromolecule glycosylation, glycosylation, glycoprotein biosynthetic process, glycoprotein metabolic process, transferase activity and transferring glycosyl groups, protein O-linked glycosylation, O-glycan processing, etc., and NTRK3 was involved in neurotrophin signaling pathway, Ras signaling pathway, EGFR tyrosine kinase inhibitor resistance, ErbB signaling pathway, phospholipase D signaling pathway, central carbon metabolism in cancer, natural killer cell mediated cytotoxicity, etc. The results of KEGG analysis showed that GCNT1 was mainly associated with system functions such as mucin-type O-glycan biosynthesis and metabolic pathways, and NTRK3 was mainly associated with cell surface receptor pathways, intracellular signal transduction, positive regulation of stimulatory responses, transmembrane receptor protein tyrosine kinase signaling pathway, enzyme-linked receptor protein signaling pathway, MAPK signaling pathway cascade and regulation, protein phosphorylation signal transduction and other system functions. Conclusions:The expressions of differentially methylated genes GCTNT1 and NTRK3 in cholangiocarcinoma have certain predictive effects on the prognosis of patients with cholangiocarcinoma.

Prognosis of huge hepatocellular carcinoma after hepatectomy / 中华普通外科杂志

Objective:To evaluate the risk factors on prognosis after resection of huge hepatocellular carcinoma.Methods:The clinical and followup data of 146 patients undergoing radical resection at Fujian Province Hospital from Jan 2012 to Dec 2017 was analyzed retrospectively.Results:Independent risk factors for tumor recurrence were neutrophil/lymphocyte ratio ≥2.49, serum alpha-fetoprotein ≥400 ng/ml, non-anatomical hepatectomy, ruptured huge hepatocellular carcinoma, multiple tumor and microvascular invasion and macrovascular invasion. These seven factors were used to develop a risk prediction model, in which 1-year recurrence-free rates in patients with low, middle, high risk group were 68.5%, 23.5%, and 0, respectively, and 3-year recurrence-free rates were 34.2%,15.3% and 0, respectively. Independent risk factors for tumor overall survival were neutrophil/lymphocyte ratio≥2.49, serum alpha-fetoprotein ≥400 ng/ml, HBV-DNA ≥2 000 IU/ml, multiple tumor, microvascular invasion, macrovascular invasion and hepatic capsule invasion. These seven factors were used to develop a risk prediction model, in which 1-year survival rates in patients with low, middle, high risk group were 94.7%, 74% and 40%, respectively, and 3-year survival rates were 68.4%,30.1%, and 5.7%, respectively.Conclusions:The recurrence rate of patients with huge hepatocellular carcinoma is high. Independent risk factors affecting prognosis were high neutrophil/lymphocyte ratio, high AFP level, high HBV-DNA, non-anatomical hepatectomy,ruptured,multiple tumor, microvascular and macrovascular invasion.

Efficacy of laparoscopic surgery on the treatment of Dong Type C adult biliary dilatation / 国际外科学杂志

Objective To investigate the technical and therapeutic effects of laparoscopic surgery for adult patients with Dong Type C bile duct dilatation.Methods A retrospective cohort study approach was used.The clinical data of 47 patients with Dong Type C adult biliary dilatation who underwent surgery in Fujian Provincial Hospital from January 2014 to December 2017 were collected.There were 12 males and 35 females.The age ranged from 16 to 68 years,with a median age of 30 years.According to different surgical methods,the patients were divided into the laparoscopic group (treated with laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy,n =21) and the open group (treated with traditional open operation,n =26).The intraoperative blood loss,complication rate,operation time,postoperative intestinal function recovery time and postoperative hospital stay were observed.Measurement data with normal distribution were expressed as mean ± standard deviation (Mean ±SD) and analyzed by t test.Comparison of count data was done by the chi-square test.Results There was no perioperative deaths in either group.There was no significant difference in intraoperative blood loss and complication rate between the two groups (P ＞ 0.05).The operation time of the laparoscopic group was significantly longer than that of the open group[(333.7 ±61.1) min vs (235.9 ±64.3) min],with statistically significant difference between graps (P =0.000).The recovery time for the intestinal function of the laparoscopic group was significantly shorter than that of the open group [(2.2 ± 0.5) d vs (2.9 ± 0.6) d],with statistically significant difference between groups (P =0.000).The postoperative hospital stay in the laparoscopic group was significantly shorter than the open group [(7.1 ± 1.8) d vs (12.0 ± 5.9) d],with statistically significant difference between groups (P =0.001).Conclusion For adult biliary dilatation patiens with Dong Type C,laparoscopic surgery is safe and feasible with the advantages of mini-invasive and quick recovery.

Expression of eEF1A2 in hepatocellular carcinoma / 中国病理生理杂志

eEF1A2 might be a putative oncoprotein in HCC .eEF1A2 over-expression has noticeable effects on the HCC cell prolifera-tion enhancement , differentiation inhibition , and cell cycle acceleration through the G 0/G1 phase to S phase and G 2/M phases.

Diagnosis and treatment of mucin-producing intrahepatic biliary tumors / 中华普通外科杂志

Objective To investigate the diagnosis and treatment of mucin-producing intrahepatic biliary tumor (MPIBT).Methods We retrospectively analyzed the clinical,radiologic,surgical and pathologic findings of 16 MPIBT cases from January 2004 to December 2011.Results There were six men and ten women,age ranged from 44 to 69 years (mean 60 years).Clinical presentation included jaundice with abdominal dull pain in 5 patients,acute cholangitis in 4 patients,painless jaundice in 2 patients,upper abdominal dull pain in 3 patients,no obvious symptoms in 1 patient,body weight loss more than 5 kg within 3 months in 5 patients.The most characteristic appearance of MPIBT on magnetic resonance cholangiopancreatography were asymmetry of intrahepatic bile duct dilatation and the dilatation in both extraand intrahepatic bile duct distal to the hepatic mass and not sudden interruption in extrahepatic bile duct.The primary tumor located in the left hepatic bile duct in 15 cases,in the right hepatic bile duct in one.13 MPIBT cases received hemihepatectomy and extrahepatic bile duct resection and Roux-en-Y anastomosis was done in 8 cases,3 received palliative biliary drainage.Pathologically 13 was papillary adenocarcinoma and 3 was papillary adenoma.The 1-,2-,3-year survival rates for the 16 MPIBT patients were 81％,66％,56％,respectively.Conclusions MPIBT had no specific clinical manifestations,MRCP might be an effective means for the diagnositic strategy and assessment of tumor extension before surgery,radical resection was the first choice of treatment,palliative biliary drainage could prolong the survival time.

Inhibition of allogeneic T-cell responses by Kupffer cells expressing indoleamine 2,3-dioxygenase in vitro / 中华肝胆外科杂志

Objective To investigate kupffer cells (KCs) expressing indoleamine 2,3-dioxygenase(IDO)in the inhibition of allogeneic T-cell proliferation in vitro. Methods Real-time PCR was used to investigate the expression of IDO mRNA and FasL mRNA in KCs pretreated with or without IFNγ. High performance liquid chromatography was used to analyze the catabolism of tryptophan by IDO from KCs. Allogeneic T-cell response was used to confirm the inhibition of KCs in vitro. The proliferation of lymphocytes was detected using [3 H] thymidine incorporation. Cell cycle and lymphocyte apoptosis were evaluated by flow cytometric assay. Results Real-time PCR revealed IDO mRNA and FasL mRNA expression in KCs pretreated with IFN-γ. IDO catabolic effect was confirmed by a decrease in tryptophan and increase in kynurenine concentration. KCs expressing IDO and FasL from BABL/c mice acquire the ability to suppress the proliferation of T-cells from C57BL/6, which could be blocked by the addition of 1-methyl-tryptophan and anti-FasL antibody. The co-cultured T-cells with KCs expressing IDO and FasL could induce allogeneic T-cell apoptosis and exhibited cell-cycle arrest in G1. Conclusion In addition to the Fas/FasL pathway, IDO may also play an important role in KCs to inhibit allogeneic T-cell proliferation in vitro.

Effects of postopertive anti-viral therapy using adefovir dipivoxil on recurrence of hepatocellular carcinoma with HBV infection / 国际外科学杂志

Objective To investigate the effect of postoperative anti-viral therapy using adefovir dipivoxil in recurrence of hepatocellular carcinoma HCC with HBV infection. Methods Sixty HCC patients with HBV infection were randomized into two groups:Group A (n=23) received hepatectomy only, and Group B (n=37) received hepatectomy and postoperative therapy using adefovir dipivoxil. The changes in liver func-tion, the suppression of HBV-DNA, HBeAg seroconversion rate, tumor recurrence rate and median survival in the two groups were observed and compared. Results In Group B, serum albumin, total bilirubin, AST and ALT were significantly improved compared with Group A (P < 0.05). Furthermore, the rate of 6-month and 1-year HBV-DNA suppression, the rate of 6-month and 1-year HBeAg seroconversion were significantly improved compared with Group A (P < 0.05). In Group A and Group B the tumor recurrence rate was 82. 6% (19/23) vs 78.4% (29/37) (P > 0.05), the recurrence time was 7.3 vs9.6 months (P > 0.05) and the median survival time was 17.4 vs 24.9 months (P < 0.01). Conclusion The results suggest that an-ti-viral therapy using adefovir dipivoxil postoperatively may improve the remnant liver function, suppress the HBV reaction, prolong the survival for patients with HCC with HBV infection.

The value and significance of standardization regional lymphadenectomy in pancreaticoduodenectomy / 国际外科学杂志

Objective To investigate the effect of standardization regional lymphadenectomy in radical resection of ductal adenocareinoma in the pancreatic head.Methods On the basis of routine panereaticoduodenectomy(whipple proceduce),we performed the standardization regional lymphadenectomy,the emphasis of the procedure was the resection of wide nodes,particularly the mesenteric root lymph nodes(14abcd),the paraaortic lymph nodes(16a2b1),the hepatoduodenal ligament lymph nodes(12abpeh),hepatic artery(Group 8)and coeliacus lymph nodes(Group 9). Results Eleven patients underwent this procedure,there was no operative mortality,1 case occurred pancreatic fistula,the lymph nodes metastasis occurred in 7(63.6%)patients,the posterior pancreaticoduodenal lymph nodes(Groupl3)and superior mensenteric artery(Groupl4)was the predominant metastatic site of the tumor,the rate of the second site metastasis to lymph nodes was 57.1%.of the 11 cases follow-up 1 died. Conclusion The radical pancreaticoduodenectomy combined with wide resection of standardization regional lymph nodes is a safe and effective procedure of the treatment of adenocarcinoma of the head of the pancreas.but the long-term survivalrate must be valued objectively with many cases.

The comparison between laparoscopic repair and traditional open surgery in perforation of duodenal ulcer / 中华消化内镜杂志

Objective To compare the results between laparoscopic repair and surgical procedures in perforation of duodenal ulcer. Methods Fifteen p atients were operated on perforation of duodenal were by laparoscopic repair, an d thirty patients performed open repair or partial gastrectomy at the same peri od were chosen as control groups. Results The operating time in laparoscopic group and other two surgical groups were 59 min, 84 min and 204 min; postoperati ve requirement of analgesic was 7％(1/15), 73％(11/15) and 80％(12/15) in three groups respectively. The recovery time of gastrointestinal function was 25 h, 56 h, and 72 h. the mean time of hospitalization was 6 d, 8 d and 10 d. The differ ences among groups were significant (P