Search

Background Laparoscopic living donor right hepatectomy (LDRH) was a controversial topic due to its unknown safety and feasibility. Methods PubMed, EMBASE and Cochrane Library databases were searched for studies comparing LDRH with open living donor right hepatectomy (ODRH), which were published between the date of database establishment and June 2020. Revman5.3 was used for statistical analysis. Results Fourteen studies were included. For the donors, there was no significant difference in warm ischemic time, hospital stay, graft weight, hepatic arterial anomalies (HAA), hepatic vein anomalies (HVA), portal vein anomalies (PVA), biliary anomalies, bleeding, wound infection, severe complication rate and readmission rate. The estimated blood loss, incidence of complication, intra-abdominal fluid rate in the LDRH group were significantly lower than those in the ODRH group, while the operation time, time to remove liver in the LDRH group were significantly higher than those in the ODRH group. For the recipients, there was no significant difference in complication rate, bleeding, HAA, PVA, biliary anomalies, graft failure and mortality. The HVA rate in the LDRH group was significantly higher than that in the ODRH group. Conclusion LDRH is safe and feasible for adult living donor liver transplantation compared with ODRH and it can reduce intraoperative bleeding and postoperative complication in donors, which requires further verification by more multi-center comparative studies with large sample and high quality.

Objectives: To compare the efficacy of robot-assisted pancreaticoduodenectomy with that of laparotomy.Methods: The PubMed, EMBASE, Cochrane Library, and other databases were searched for literature available from their respective inception dates up to May 2020 to find studies comparing robot-assisted pancreaticoduodenectomy (RPD) with open pancreaticoduodenectomy (OPD). The RevMan 5.3 statistical software was used for analysis to evaluate surgical outcome and oncology safety. The combination ratio (RR) and weighted mean difference (WMD) and their 95% confidence intervals (CIs) were calculated using fixed effect or random effect models.Results: 18 cohort studies from 16 medical centers were eligible with a total of 5795 patients including 1420 RPD group patients and 4375 OPD group patients. The RPD group fared better than the OPD group in terms of estimated blood loss (EBL) (WMD =-175.65, 95% CI (-251.85, -99.44), PRR=0.60, 95%CI (0.44,0.81), P= 0.001), reoperation rate (RR=0.61, 95%CI (0.41,0.91), P=0.02), hospital day (WMD = -2.95, 95% CI (-5.33,-0.56), P = 0.02), intraoperative blood transfusion (RR = 0.56, 95% CI(0.42, 0.76), P=0.0001), overall complication (RR = 0.78, 95% CI(0.64,0.95), P = 0.01), and clinical pancreatic fistula (PF) (RR = 0.54, 95% CI(0.41,0.70), P < 0.0001). In terms of lymph node clearance (WMD = 0.48, 95% CI(-2.05,3.02), P = 0.71), R0 rate (RR = 1.05, 95% CI(1.00,1.11), P = 0.05), postoperative pancreatic fistula (POPF) (RR=1, 95% CI(0.85,1.19), P = 0.97), bile leakage (RR = 0.99, 95% CI(0.54,1.83), P = 0.98), delayed gastric emptying (DGE) (RR = 0.79, 95% CI(0.60,1.03), P = 0.08), mortality (RR = 0.82, 95% CI(0.62,1.10), P=0.19), and severe complication (RR = 0.98, 95% CI(0.71,1.36), P = 0.91), there were no significant differences between the two groups. Laparoscopic surgery was inferior to open surgery in terms of operational time (WMD = 80.85, 95% CI (16.09,145.61), P=0.01).Conclusions: RPD is not inferior to OPD, and it is even more advantageous for DGE, wound infection rate, reoperation rate, hospital stay, transfusion, overall complication and clinical PF. However, these findings need to be further verified by high-quality randomized controlled trials.

The objective of the study is to compare the safety and efficacy of robot-assisted pancreaticoduodenectomy (PD) with open PD. The PubMed, EMBASE and Cochrane Library databases were searched for the literature available from their respective inception dates up to May 2020 to find studies comparing robot-assisted pancreaticoduodenectomy (RPD) with open pancreaticoduodenectomy (OPD). The RevMan 5.3 statistical software was used for analysis to evaluate surgical outcome and oncology safety. The combination ratio (RR) and weighted mean difference (WMD) and their 95% confidence intervals (CIs) were calculated using fixed-effect or random effect models. 18 cohort studies from 16 medical centers were eligible with a total of 5795 patients including 1420 RPD group patients and 4375 OPD group patients. The RPD group fared better than the OPD group in terms of estimated blood loss (EBL) (WMD = − 175.65, 95% CI (− 251.85, − 99.44), P

BACKGROUND: Effect of laparoscopic approach in the treatment of gallbladder cancer (GBC) is still controversial. MATERIALS AND METHODS: Literature published before December 2019 was retrieved from PubMed, EMBASE, and Cochrane Library databases for a comparative study between laparoscopic group (LG) and open group (OG) for GBC. Revman 5.3 statistical software was used for analysis. RESULTS: Nine comparative studies were eligible and included 654 patients, 287 were in LG and 367 were in OG. Meta-analysis showed that the operation time, estimated blood loss, drainage tube time, and hospitalization time after LG were significantly less than those in the OG [weighted mean difference (WMD)=-27.5; 95% confidence interval (CI), -36.6 to -18.4; P

The transformer winding deformation and the insulation damage will occur under the impact of huge electromagnetic forces caused by the short circuit faults. In this paper, the electromagnetic-mechanical (E-M) field coupling 3D FE model was used for analyzing the transient characteristics of power transformer under short circuit faults. Considering the process of the transformer winding suffering short circuit current is a complicated multi-field coupling problem, this paper explores the inter-relationship between the short circuit fault topology, electromagnetic field and the mechanical field. Both the mathematical model of each field involved and the E-M field coupling model have been built. By the use of 3D FEM, the transient characteristics such as the electromagnetic forces, stress distribution and displacement of the transformer model have been calculated and simulated. Additionally, by analyzing the results from the simulation example, the radial and axial forces characteristics and the structure design suggestion for the winding have been obtained and proposed.

Genetic variation (rs372883C/T) in the 3'-untranslated region of BTB and CNC homology 1 (BACH1) has been associated with pancreatic ductal adenocarcinoma (PDAC) risk in our previous genome-wide association study; however, the action roles of this genetic variation in PDAC remains unknown. Methods:BACH1 expression was measured by quantitative real-time PCR, Western blot and immunohistochemistry. The effects of BACH1 on cell proliferation and sensitivity to gemcitabine were examined by alteration of BACH1 expression in PDAC cells. Angiogenesis was determined in vitro using a human umbilical vein endothelial cell model. Reporter gene assays were conducted to compare the effects of microRNA-1257 on rs372883 variation. The associations between rs372883 variants and survival time in patients treated with gemcitabine were estimated by logistic regression. Results: We found substantially lower BACH1 expression in PDAC compared with normal pancreatic tissues and the rs372883T allele had significantly lower BACH1 levels than the rs372883C allele in both tumor and normal tissues. Knockdown of BACH1 expression provoked proliferation of PDAC cells and angiogenesis, which might result from upregulation of hemeoxygenase-1 that evokes oncogenic AKT and ERK signaling. The rs372883T>C change inhibits interaction of BACH1 with microRNA-1257, resulting in increased BACH1 expression. PDAC patients with the rs372883T allele were more resistant to gemcitabine and had shorter survival time compared with those with the rs372883C allele. Conclusion: These results shed light on the mechanism underlying the associations of BACH1 rs372883 variation with risk of developing PDAC and differential gemcitabine sensitivity in patients.

Sericin, a bioactive protein forming the outer layer of silk, promotes cell proliferation and cell adhesion, inhibits inflammation, and provides nutrition. Here, we obtain endotoxin-free sericin and explore its potential property in antiviral activity towards infectious diseases. In vesicular stomatitis virus (VSV) infection model, pre-treatment with sericin obviously inhibits VSV replication and reduces organ injury in infected mice. Further studies reveal that pre-incubating cells with sericin results in suppressing the infections of VSV and Enterovirus 71 (EV71) in infected cells. More evidences show that upon virus infection, the levels of interferons (IFNs) are significantly elevated in the cells pre-incubated with sericin as compared to untreated cells, indicating that sericin promotes virus-induced antiviral immune responses. Mechanistically, sericin attenuates cell glycolysis rate and reduces lactate production. Low level of lactate benefitting from sericin treatment facilitates the RIG-I-MAVS signaling pathway to initiate interferon activation. Notably, like sericin, a sericin-derived peptide F5-SP shares the same functions to exert antiviral activity both in vitro and in vivo. Therefore, we report that sericin and sericin-derived peptide F5-SP enhance antiviral innate immune response through inhibiting lactate production, which discovers a promising biomedical application of sericin in the prevention and treatment of viral infectious diseases.

e16234 Background: Pancreatic cancer (PC) is a highly malignant tumor with poor prognosis. Among them, pancreatic ductal adenocarcinoma (PDAC) accounts for 80-90% of pancreatic cancer. While, the treatment of PDAC has always been a clinical challenge. PDAC with mutations in homologous recombination repair (HRR) genes such as BRCA are particularly sensitive to platinum agents. The POLO study has shown that Olaparib was efficient and well-tolerated as maintenance therapy in patients with germline BRCA1/2 mutation and a metastatic PDAC controlled after a platinum-based induction chemotherapy. However, investigation of prevalence of HRR gene mutations in Chinese PDAC patients need to be well defined. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples from PDAC patients were collected and sequenced using next-generation sequencing (NGS) targeting 450 cancer genes. Genomic alterations and tumor mutational burden (TMB) values were assessed. The association of HRR gene mutations with TMB was assessed. The testing was carried out by OrigiMed (Shanghai, China) witch a College of American Pathologists accredited and Clinical Laboratory Improvement Amendments certified laboratory. Using targeted capture genomic sequencing, we assessed 98 PDAC patients for germline and somatic loss-of-function mutations in 14 genes, including BRCA1, BRCA2, and 12 other genes in the HR pathway. Results: In total, 98 PDAC patients were recruited including 48 females and 50 males with a median age of 58 (range 35-84). The most frequently mutated genes were KRAS (94%), TP53 (74%), CDKN2A (36%), SMAD4 (27%), GATA6 (9%) and ATM (5%). Mutation rates varied in pancreatic cancer signaling pathway: WNT (35.71%), PI3K (11.22%), HRR (11.22%), NOTCH (3.06%), FGF (2.04%). 2.04% (2/98) patients had high TMB (defined as ≥10 muts/Mb) with a median of 2.2 muts/Mb (0-47 mus/Mb). 34.69% (34/98) of the patients had one or more actionable genetic mutations. We identified that 11.2% (11/98) patients had at least one mutation in HRR genes. The most frequently mutated HRR genes were ATM (50%), BRCA1 (16.7%), BRCA2 (25%) and PALB2 (8.3%). The most common mutation type in HRR-related gene was truncation (75%, 9/12). HRR-related germline mutations in BRCA (71.43%, 5/7), ATM (28.57%, 2/7) were detected in seven patients, six of them with cancer related family history. We confirmed that patients with HRR mutations were younger than wild type HRR (52.6 years vs. 59.3 years, p < 0. 05). We demonstrated that patients with HRR mutations had a significantly higher TMB than patients with wild type HRR (median TMB: 3.4 vs. 1.8 muts/Mb, p < 0. 05). Conclusions: HRR gene alterations occurred in 11.2% of Chinese PDAC patients HRR pathway alterations are relatively frequent in PDAC patients and consideration for biomarker-enriched clinical trials with PARP, immune checkpoint inhibitors, and novel combinations are warranted.

e16178 Background: There is little evidence for the association between neoadjuvant radiotherapy (NRT) and improved overall survival (OS) in patients with resectable hepatocellular carcinomas (HCCs). This study aimed to determine whether NRT provides a survival benefit in these patients. Methods: We enrolled patients with resected HCC identified in the Surveillance, Epidemiology, and End Results database (2004–2015). Multiple imputation plus inverse probability of treatment weighting (IPTW) reduced selection bias. IPTW-adjusted Kaplan-Meier curves and IPTW-adjusted Cox proportional hazards models compared OS between different treatment groups. Sensitivity analyses tested the robustness of the estimates. Subgroup analysis identified the patients who could benefit most from NRT. Results: We enrolled a total of 11920 patients diagnosed between 2004 and 2015 in the study. Of these, 134 patients underwent NRT, the others underwent surgery alone (SA). The median OS in NRT was not approached, whereas in SA it was 52.0 (interquartile range, 34.25, 100.75) months. The 5-year IPTW-adjusted rates of OS in NRT versus SA were 65.3% and 46.6%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, NRT was associated with a significant OS benefit (hazard ratio [HR], 0.549; 95% confidence interval [CI], 0.327-0.921; p = 0.023). The results were robust in sensitivity analysis (E-value 2.39). Subgroup analysis demonstrated improved OS in the NRT cohort among younger patients (HR, 0.46; 95% CI, 0.26-0.83), N0 status (HR, 0.51; 95% CI, 0.28-0.94), and alpha-fetoprotein (AFP)-positive patients (HR, 0.28; 95% CI, 0.12-0.65). Conclusions: Patients with resectable HCCs may derive a survival benefit from NRT. Younger age ( < 65 years) with a positive AFP level at N0 status could be indicators for NRT. These findings enlighten current guidelines to consider NRT in patients with resectable HCCs. The present study establishes a reasonable basis for further prospective studies.

Background Small bowel tumors are relatively rare. Accumulation of data regarding their clinical presentation, pathologic features, prognostic factors, treatment modalities, and outcome has been an issue. We summarize the clinicopathologic features and evaluate the long-term outcome of patients with small bowel tumors who underwent surgery. Methods This is a retrospective study of medical records of 456 patients with small bowel tumors treated surgically at a Cancer Hospital between 1999 and 2016. Results The study included 275 males (60.3%) and 181 females (39.7%). Small bowel tumors were difficult to diagnose because of non-specific symptoms. The most common symptoms were alimentary symptoms (56.8%) and abdominal pain (37.3%). Final histopathology revealed 241 adenocarcinomas (52.9%), 153 gastrointestinal stromal tumors (GISTs; 33.6%), 16 neuroendocrine tumors (NETs; 3.5%), and 46 other types of tumors (10.1%). The 456 surgeries performed included 153 pancreaticoduodenectomies, 241 limited duodenum resections, 60 palliative bypass surgeries, and 2 abdominal explorations. The 5-year overall survival and progression-free survival rates for patients with small bowel tumor were 57.2% and 44.6%, respectively. Adenocarcinomas resulted in the worst overall survival compared to GISTs or NETs, and tumors with duodenal location resulted in a worse survival compared to those with non-duodenal location. Conclusion Surgery is the mainstay of treatment for small bowel tumors. Adenocarcinomas and duodenal involvement seem to contribute to poor outcomes.

Pancreatic cancer (PC), one of the most lethal malignancies, accounts for 8%-10% of digestive system cancers, and the incidence is increasing. Surgery, chemotherapy, and radiotherapy have been the main treatment methods but are not very effective. However, only 20% of patients have the opportunity to undergo surgical operation. Approximately 30-40% of patients present with locally advanced, unresectable pancreatic cancer because of invasion of mesenteric vessels or adjacent organs. The first patient with unresectable pancreatic cancer was treated with Intraoperative radiotherapy (IORT) in 1959 [1]. Since then, new surgical and radiotherapeutic techniques have been developed, clinical trials have provided new evidence, and intriguing long-term effects have emerged from global metadatabases. IORT has the advantages of more accurate target, better local control rate, less complications, longer survival time and better life quality. During the past decade, IORT has been applied in some hospitals in the world, but there is little agreement on technical details and standards. A guidelines of IORT in pancreatic cancer is therefore necessary and timely. To develop standardized criteria for the application of IORT in pancreatic cancer, the experts from China to discuss treatment methods and arrive at a consensus on the indications, contraindications, and preferred techniques of IORT in pancreatic cancer. This detailed and agreed technical description of IORT may have implications on training, assessment, quality control, and future research.

N6-methyladenosine (m6A) modification is an important mechanism in miRNA processing and maturation, but the role of its aberrant regulation in human diseases remained unclear. Here, we demonstrate that oncogenic primary microRNA-25 (miR-25) in pancreatic duct epithelial cells can be excessively maturated by cigarette smoke condensate (CSC) via enhanced m6A modification that is mediated by NF-κB associated protein (NKAP). This modification is catalyzed by overexpressed methyltransferase-like 3 (METTL3) due to hypomethylation of the METTL3 promoter also caused by CSC. Mature miR-25, miR-25-3p, suppresses PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2), resulting in the activation of oncogenic AKT-p70S6K signaling, which provokes malignant phenotypes of pancreatic cancer cells. High levels of miR-25-3p are detected in smokers and in pancreatic cancers tissues that are correlated with poor prognosis of pancreatic cancer patients. These results collectively indicate that cigarette smoke-induced miR-25-3p excessive maturation via m6A modification promotes the development and progression of pancreatic cancer., Cigarette smoke induces microRNA dysregulation in cancers. Here, the authors show that cigarette smoke promotes the maturation of oncogenic primary miR-25 due to METTL3 hypomethylation, and mature miR-25 suppresses PH domain leucine-rich repeat protein phosphatase 2, resulting in oncogenic AKT activation in pancreatic cancer.

Mucinous gastric carcinoma (MGC) is a rare kind of malignancy with unclear prognosis. This study aims to assess the clinicopathological features and prognosis of MGC. We retrospectively analyzed a consecutive series of 244 MGC patients who underwent radical gastrectomy with D2 lymphadenectomy, and compared the data with 260 gastric signet ring cell carcinoma (SRC) patients. The univariate survival analysis showed that the surgical types, diameter of the primary tumor, the Borrmann type, pathological depth of tumor invasion (pT), pathological number of metastatic lymph node (pN), pathological tumor lymph metastasis (pTNM), and vascular invasion were all significant predictors of survival (all P

Supplemental Digital Content is available in the text, Postoperative pancreatic fistula (POPF) is the most common and intractable complication after partial pancreatectomy, with an incidence of 13% to 64%. Polyglycolic acid (PGA) mesh is a new technique that is designed to prevent POPF, and its effect has been evaluated in several randomized controlled trials and some retrospective cohort studies. In this study, we systematically and comprehensively analyzed the efficacy of PGA mesh based on reported studies. We searched Medline, Embase, and Cochrane Library databases in English between January 2010 and October 2019. Analysis was performed by using Review Manger 5.3 software. Three RCTs and 8 nonrandomized studies were eligible with a total of 1598 patients including 884 PGA group patients and 714 control group patients. For pancreatoduodenectomy (PD), distal pancreatectomy (DP), and the 2 partial pancreatectomy (PD or DP), we found significant statistical differences in overall POPF (relative risk [RR] = 0.75, 95% confidence interval [CI] = 0.61–0.91, P = .004; RR = 0.74, 95% CI = 0.57–0.96, P = .02; RR = 0.76, 95% CI = 0.64–0.89, P = .0009, respectively) and clinical pancreatic fistula (PF) (RR = 0.5, 95% CI = 0.37–0.68, P

// Xiaozhun Huang 1, * , Chunling Wang 2, * , Zhangkan Huang 1 , Houhong Zhou 1 , Han Li 1 , Fengxiang Shi 3 , Longde Du 4 , Xianni Ke 5 , Biao Zheng 1 , Shuisheng Zhang 6 and Xu Che 6 1 Department of Abdominal Surgery, National Cancer Center/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China 2 Department of Hepatology, Huizhou Municipal Central Hospital, Huizhou 516000, China 3 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China 4 Department of Thoracic Surgery, National Cancer Center/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China 5 Department of Medical Oncology, National Cancer Center/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China 6 Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China * These authors have contributed equally to this work Correspondence to: Xu Che, email: drchexu@126.com Shuisheng Zhang, email: thelifeofwater@126.com Keywords: temporary ileostomy; early closure; late closure; complication; hospital stay Received: November 08, 2017 Accepted: January 03, 2018 Published: January 08, 2018 ABSTRACT Background: A temporary ileostomy is frequently constructed to reduce the risk of symptomatic anastomotic leakage. An ostomy is a heavy burden on both patient and society, and early closure is therefore desirable to counteract increased morbidity. The optimal time for stoma closure has been investigated in some studies, although it remains controversial. Methods: We conducted a literature search of PubMed, Wiley, Web of Science, and the Cochrane Library to identify studies published till 2017 that focused on perioperative complications and details related to early( 4weeks) closure of temporary ileostomies after proctectomy. Results: Six studies (three randomized controlled trials, two prospective non-randomized trials, and one retrospective trial) satisfied our inclusion criteria, and the outcomes of 767 patients (356 early closures and 411 late closures) were analyzed. There was a significantly lower prevalence of skin irritation ( p =0.0002) in the early group, but no worse morbidity outcomes were observed between the early and late closure groups. Hospital stay length after an ileostomy closure was not prolonged following early closure, suggesting that the increased wound infection risk did not significantly delay discharge. Also, the overall hospital stay length, when time since admission for the original operation was included in the late closure group, showed no significantly longer duration in the early closure group ( p = 0.02). Conclusions: We found that early closure of a temporary ileostomy after proctectomy was feasible in selected patients, with some advantages and disadvantages that need to be weighed by the patient and surgeon.

Table S1. List of antibodies used in the different applications. (DOC 50 kb)

To examine the impact of body mass index (BMI) on outcomes following pancreatic resection in the Chinese population.A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Individuals who underwent pancreatic resection between January 2004 and December 2013 were identified and included in the study. Persons were classified as having a normal weight if their BMI was24 kg/m(2) and overweight/obese if their BMI was ≥ 24 kg/m(2) as defined by the International Life Sciences Institute Focal Point in China. A χ(2) test (for categorical variables) or a t test (for continuous variables) was used to examine the differences in patients' characteristics between normal weight and overweight/obese groups. Multiple logistic regression models were used to assess the associations of postoperative complications, operative difficulty, length of hospital stay, and cost with BMI, adjusting for age, sex, and type of surgery procedures.A total of 362 consecutive patients with data available for BMI calculation underwent pancreatic resection for benign or malignant disease from January 1, 2004 to December 31, 2013. Of the 362 patients, 156 were overweight or obese and 206 were of normal weight. One or more postoperative complications occurred in 35.4% of the patients following pancreatic resection. Among patients who were overweight or obese, 42.9% experienced one or more complications, significantly higher than normal weight (29.6%) individuals (P = 0.0086). Compared with individuals who had normal weight, those with a BMI ≥ 24.0 kg/m(2) had higher delayed gastric emptying (19.9% vs 5.8%, P0.0001) and bile leak (7.7% vs 1.9%, P = 0.0068). There were no significant differences seen in pancreatic fistula, gastrointestinal hemorrhage, reoperation, readmission, or other complications. BMI did not show a significant association with intraoperative blood loss, operative time, length of hospital stay, or cost.Higher BMI increases the risk for postoperative complications after pancreatectomy in the Chinese population. The findings require replication in future studies with larger sample sizes.

To assess the suitability of the 7th AJCC/UICC TNM staging system in predicting the prognosis of synchronous multiple gastric carcinomas (SMGCs). A total of 129 SMGC patients who underwent gastrectomy with D2 lymphadenectomy from January 1999 to January 2009 were enrolled in this study. The location, diameter, and depth of invasion of the main tumor were all related to prognosis (P0.05). Multivariate analysis revealed depth of invasion as an independent predictive factor for survival (P0.05). Interestingly, logistic regression analysis showed that the 7th AJCC/UICC N staging system was unable to significantly predict survival in SMGCS patients (P0.05). Cut-point survival analysis identified the most appropriate cut-offs for metastatic lymph nodes (MLNs) as 0, 1, 6, 10, and 19: patients with 0, 1-6, 7-10, and 11-19, and ≥ 20 MLNs had median survival times of 70, 56, 35, 52, and 32 months, respectively. Multivariate analysis suggested this new categorization of MLNs to be a significant predictor of survival (P0.05). Preoperative assessment of depth of invasion can help in the prognosis of SMGCs patients. The 7th UICC TNM staging system may be not suitable for SMGC patients and needs improvement for rational grading of SMGCs.

The effects of alcohol drinking and smoking on pancreatic ductal adenocarcinoma (PDAC) mortality are contradictory. Individuals who were diagnosed as PDAC and hospitalized at the China National Cancer Center between January 1999 and January 2016 were identified and included in the study. Ultimately, 1783 consecutive patients were included in the study. Patients were categorized as never, ex-drinkers/smokers or current drinkers/smokers. Hazard ratios (HRs) of all-cause mortality and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Compared with never drinkers, the HRs were 1.25 for ever drinkers, 1.24 for current drinkers, and 1.33 for ex-drinkers (trend P = 0.031). Heavy drinking and smoking period of 30 or more years were positive prognostic factors for PDAC. For different smoking and alcohol drinking status, only subjects who are both current smokers and current drinkers (HR, 1.45; 95% CI, 1.03–2.05) were associated with reduced survival after PDAC compared to those who were never smokers and never drinkers. Patients who are alcohol drinkers and long-term smokers before diagnosis have a significantly higher risk of PDAC mortality. Compared to those who neither smoker nor drink, only patients who both smokers and drinkers were associated with reduced survival from PDAC.

Pancreatic adenocarcinoma is still widely considered as a deadly disease even though there are substantial therapeutic developments in the past decade. Using combinational chemotherapy regimens, represented by gemcitabine plus nab-paclitaxel and FOLFIRINOX, was able to improve overall survival in patients with advanced disease to a limited extent. It has been a challenge to develop targeted therapies that are focused on the neoplasm cells of pancreatic adenocarcinoma. Recently, targeting the stroma and immune compartments of pancreatic adenocarcinoma has shown promising results. The paradigm of biologics drug development therefore has been shifted by extending to these exciting areas. Although some of the preclinical and clinical researches in targeting the tumor microenvironment of pancreatic adenocarcinoma have shown promising results, others have resulted in controversial findings. Both comprehensive and in-depth researches on the basic science of the tumor microenvironment of pancreatic adenocarcinoma are thus warranted for the development of effective biologics that target the tumor microenvironment. Moreover, an ideal treatment for pancreatic adenocarcinoma shall be a combination of targeting both neoplastic cells and the tumor microenvironment.

The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth. Here we summarize recent studies about how DNA methylation affects tumorigenesis through regulating tumor-associated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers.

AIM To evaluate the association of body mass index (BMI) with the overall survival of pancreatic ductal adenocarcinoma (PDAC) patients. METHODS A retrospective analysis of PDAC patients diagnosed in the National Cancer Center of China between January 1999 and December 2014 was performed. These patients were categorized into four BMI groups (< 18.5, 18.5-22.9, 23-27.4 and ≥ 27.5 kg/m2). χ2 tests for comparison of the proportions of categorical variables, and Student's t-test or Mann-Whitney test for continuous variables were employed. Survival analysis was performed with the Kaplan-Meyer method. Their HRs of mortality and 95%CIs were estimated using the Cox proportional hazards model. RESULTS With a median age of 59.6 years (range: 22.5-84.6 years), in total 1783 PDAC patients were enrolled in this study. Their mean usual BMI was 24.19 ± 3.53 for the whole cohort. More than half of the patients (59.3%) experienced weight loss during the disease onset and progression. Compared with healthy-weight individuals, newly diagnosed patients who were overweight or obese had more severe weight loss during their disease onset and progression (P < 0.001). Individuals who were overweight or obese were associated with positive smoking history (P < 0.001). A significant difference in comorbidity of diabetes (P = 0.044) and coronary artery disease (P < 0.001) was identified between high BMI and normal-weight patients. After a median follow-up of 8 mo, the survival analysis showed no association between BMI and the overall survival (P = 0.90, n = 1783). When we stratified the whole cohort by pancreatic cancer stage, no statistically significant association between BMI and overall survival was found for resectable (P = 0.99, n = 217), unresectable locally advanced (P = 0.90, n = 316) and metastatic patients (P = 0.88, n = 1250), respectively. The results did not change when we used the BMI at diagnosis. CONCLUSION Our results showed no significance of BMI for the overall survival of PDAC patients.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.