The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis.

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

Mitochondrial DNA copy number and cancer risks: A comprehensive Mendelian randomization analysis.

Mitochondrial DNA plays a critical role in the pathophysiology of cancer. However, the associations between mitochondrial DNA copy number (mtDNA-CN) and cancer risk are controversial. Mendelian randomization (MR) analyses were performed using three independent instrumental variables (IVs) to explore potential associations between mtDNA-CN and 20 types of cancer. The three sets of IVs were primarily obtained from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. The outcome data of cancers were investigated using summary statistics from the FinnGen cohort. The potential causal associations were evaluated using the MR-Egger regression, weighted median, inverse-variance weighted (IVW), and weighted mode methods. The robustness of IVW estimates was validated using leave-one-out sensitivity analysis. Additionally, a meta-analysis was conducted to pool results from three sets of IVs. The results revealed that genetically predicted mtDNA-CN was not associated with cancer risk (odds ratio = 1.02; 95% confidence interval: 0.95-1.10). Subgroup analyses indicated no causal association between mtDNA-CN and breast, lung, prostate, skin, colorectal, gastric, liver, cervical uteri, esophageal, thyroid, bladder, pancreas, kidney, corpus uteri, ovary, brain, larynx, and anus cancers. It was observed that mtDNA-CN was associated with lip, oral cavity, and testis cancers. However, these results should be interpreted with caution because a small number of patients with lip and oral cavity or testis cancers were included. The comprehensive MR analysis demonstrated that mtDNA-CN is not a suitable biomarker for tumor risk assessment.

Mitochondrial DNA copy number is associated with Crohn's disease: a comprehensive Mendelian randomization analysis.

Mitochondrial DNA plays a critical role in the pathophysiological process of inflammation. However, the relationship between mitochondrial DNA copy number (mtDNA-CN) and inflammatory bowel diseases (IBD) remains poorly understood. We conducted a comprehensive Mendelian randomization (MR) using three instrumental variables (IVs) to explore the causal associations between mtDNA-CN and IBD, including Crohn's disease (CD), ulcerative colitis (UC). MR-Egger regression, weighted median, inverse-variance weighted (IVW), and weighted mode methods were used to evaluate the potential causal associations. The robustness of the IVW estimates was determined using the leave-one-out sensitivity test. A meta-analysis was conducted to pool the results from the three sets of IVs. Upon analysis, the findings of the current study revealed that genetically predicted mtDNA-CN was not associated with IBD (CD + UC) and UC. The results of MR analyses between mtDNA-CN and CD risk were inconsistent by using three sets of IVs. After a meta-analysis, we found that genetically predicted mtDNA-CN was associated with CD risk (odds ratio = 2.09; 95% confidence interval: 1.37-3.18). This finding was also confirmed by multivariable MR analyses and remained robust when tested with the leave-one-out sensitivity test. In conclusion, genetically predicted mtDNA-CN was found to be associated with CD risk. Therefore, mtDNA levels in the blood could potentially be used as a marker for CD risk assessment. Further studies are needed to elucidate the underlying mechanisms and validate the results of this study.

High COL10A1 expression potentially contributes to poor outcomes in gastric cancer with the help of LEF1 and Wnt2.

BACKGROUND: COL10A1 is a secreted, short-chain collagen found in several types of cancer. Studies have shown that COL10A1 aberrant expression is considered an oncogenic factor. However, its underlying mechanisms and regulation of gastric cancer remain undefined. METHODS: The data on the expression of COL10A1, clinicopathological characteristics, and outcome of patients with GC were obtained from The Cancer Genome Atlas. The ALGGEN-PROMO database defined the related transcription factors. Quantitative real-time reverse transcription-polymerase chain reaction and western blotting analysis were used to identify the differential expression levels of COL10A1 and related transcription factors. RESULTS: We found that high COL10A1 expression is an independent risk factor for gastric cancer. Upregulation of LEF1 and Wnt2 was also observed in gastric cancer, suggesting a potential correlation between LEF1/COL10A1 regulation in the Wnt2 signaling pathway. CONCLUSION: High COL10A1 expression may contribute to poor outcomes via upregulation of LEF1 and Wnt2 in gastric cancer.

N6-methyladenosine modification and metabolic reprogramming of digestive system malignancies.

N6-methyladenosine (m6A) is a eukaryotic post-transcriptional modification involved in cell growth and developmental processes, including RNA transcription, alternative splicing, degradation, and translation. It is also involved in the development of various cancers. Metabolic reprogramming enables cancer cells to obtain nutrition from the tumor microenvironment, which is a hallmark of cancer. Numerous studies have shown that m6A modification induces metabolic reprogramming in cancer by regulating the expression of metabolic core genes or activation of metabolic signaling pathways. Digestive system malignancies include esophageal, gastric, colorectal, liver, pancreatic, and other cancers, all of which are associated with poor outcomes. This review summarizes the role of m6A modification in the metabolic reprogramming of digestive system malignancies, with the aim of identifying therapeutic strategies.

Single-Incision Laparoscopic Intragastric Surgery for Gastric Submucosal Tumors Located Near the Esophagogastric Junction.

Background: Laparoscopic local resection of the stomach for gastric submucosal tumors (SMTs) is widely accepted by surgeons. For SMTs located near the esophagogastric junction (EGJ), simple laparoscopic wedge resection is rarely performed owing to concerns of causing cardia deformities or stenosis. Single-incision laparoscopic intragastric surgery (sLIGS) has been used to treat SMTs located near the EGJ in carefully selected cases. Methods: We modified sLIGS using a subxiphoid incision. Thirteen consecutive patients with intraluminal or intramural growth type gastric SMTs located near the EGJ underwent sLIGS at our institution from July 2018 to April 2020. Results: Thirteen operations were successfully performed using sLIGS, including eight full-thickness resections and five submucosal resections. There were no conversions to an open procedure and all tumors were confirmed to have negative margins on pathology. The mean operation time was 100 ± 10 minutes (range, 85-160 minutes). The mean blood loss was 50 ± 10 mL (range, 50-100 mL). The mean length of postoperative hospital stay was 7 ± 1.5 days (6-10 days). One patient was found to have oozing of blood confirmed by gastroscopy postoperatively and recovered after stopping antiplatelet therapy. Ten cases were gastrointestinal stromal tumor (GIST), two cases were leiomyoma, and one case was neuroendocrine neoplasm. Of the 10 GISTs, 9 were classified as low risk; 1 showed medium risk and the patient received adjuvant imatinib therapy. There were no tumor recurrences during a mean follow-up of 14 ± 4 months (range, 5-25 months). Conclusions: This modified sLIGS for the treatment of the gastric SMTs located near the EGJ is simple and safe. This can be used as an alternative treatment for gastric SMTs near the EGJ.

Laparoscopic versus open pancreatic resection for ductal adenocarcinoma: separate propensity score matching analyses of distal pancreatectomy and pancreaticoduodenectomy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Currently, laparoscopic pancreatic resection (LPR) is extensively applied to treat benign and low-grade diseases related to the pancreas. The viability and safety of LPR for PDAC needs to be understood better. Laparoscopic distal pancreatectomy (LDP) and pancreaticoduodenectomy (LPD) are the two main surgical approaches for PDAC. We performed separate propensity score matching (PSM) analyses to assess the surgical and oncological outcomes of LPR for PDAC by comparing LDP with open distal pancreatectomy (ODP) as well as LPD with open pancreaticoduodenectomy (OPD). METHODS: We assessed the data of patients who underwent distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for PDAC between January 2004 and February 2020 at our hospital. A one-to-one PSM was applied to prevent selection bias by accounting for factors such as age, sex, body mass index, and tumour size. The DP group included 86 LDP patients and 86 ODP patients, whereas the PD group included 101 LPD patients and 101 OPD patients. Baseline characteristics, intraoperative effects, postoperative recovery, and survival outcomes were compared. RESULTS: Compared to ODP, LDP was associated with shorter operative time, lesser blood loss, and similar overall morbidity. Of the 101 patients who underwent LPD, 10 patients (9.9%) required conversion to laparotomy. The short-term surgical advantage of LPD is not as apparent as that of LDP due to conversions. Compared with OPD, LPD was associated with longer operative time, lesser blood loss, and similar overall morbidity. For oncological and survival outcomes, there were no significant differences in tumour size, R0 resection rate, and tumour stage in both the DP and PD subgroups. However, laparoscopic procedures appear to have an advantage over open surgery in terms of retrieved lymph nodes (DP subgroup: 14.4 ± 5.2 vs. 11.7 ± 5.1, p = 0.03; PD subgroup 21.9 ± 6.6 vs. 18.9 ± 5.4, p = 0.07). These two groups did not show a significant difference in the pattern of recurrence and overall survival rate. CONCLUSIONS: Laparoscopic DP and PD are feasible and oncologically safe procedures for PDAC, with similar postoperative outcomes and long-term survival among patients who underwent open surgery.

Vitamins and Helicobacter pylori: An Updated Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND: Over recent decades, epidemiological studies have shown relationships between vitamins and Helicobacter pylori (H. pylori) infection and eradication, but the results are controversial. METHODS: A comprehensive meta-analysis and systematic review were conducted to clarify the relationships between common types of vitamins and H. pylori. We applied meta-regression, subgroup analysis and sensitivity analysis to obtain available evidence. Articles published from January 1991 to June 2021 in PubMed, EMBASE, and the Cochrane Library were searched. RESULTS: In total, we identified 48 studies. The results indicate that H. pylori -positive patients had lower serum vitamin B12 [standardized mean difference (SMD) = -0.30; 95% confidence interval (CI): -0.53 - -0.08], folate (SMD = -0.69; 95% CI: -1.34 - -0.04), vitamin C (SMD = -0.37; 95%CI: -0.57 - -0.18) and vitamin D (SMD = -0.34; 95% CI: -0.49 - -0.18) levels than H. pylori-negative patients. Patients in which H. pylori had been successfully eradicated had higher serum vitamin D levels (SMD = 1.37; 95% CI: 0.37-2.38) than in patients in which eradication had been unsuccessful. The serum vitamin B12 levels of H. pylori-positive patients improved after successful H. pylori eradication therapy (SMD = 1.85; 95% CI: 0.81-2.90), and antioxidant vitamin supplementation to an H. pylori eradication regimen improved the eradication rate (risk ratio = 1.22; 95% CI: 1.02-1.44 for per-protocol analysis; risk ratio = 1.25; 95% CI: 1.06-1.47 for intention-to-treat analysis). CONCLUSIONS: H. pylori infections decrease the serum levels of several types of vitamins, eradication of H. pylori could rescue its adverse effects, and antioxidant vitamin supplementation may improve the H. pylori eradication rate. SYSTEMATIC REVIEW REGISTRATION: identifier: CRD42021268127.

Hypoxia induces sorafenib resistance mediated by autophagy via activating FOXO3a in hepatocellular carcinoma.

Sorafenib, a multikinase inhibitor, is considered as the only approved drug to cure the advanced hepatocellular carcinoma (HCC); however, the acquired chemoresistance caused by intratumoral hypoxia through sorafenib long term therapy induces sorafenib inefficacy. We demonstrated here that hypoxia significantly attenuated sensitivity of HCC cells to sorafenib treatment and reduced its proliferation. Autophagy was observed in sorafenib-treated HCC cells in hypoxia, and inhibition of autophagy by 3-MA eliminated hypoxia-induced sorafenib resistance. Further study revealed hypoxia-activated FOXO3a, an important cellular stress transcriptional factor, via inducing its dephosphorylation and nuclear location; and FOXO3a-dependent transcriptive activation of beclin-1 was responsible for hypoxia-induced autophagy in HCC cells. Knockout of FOXO3a inhibited the autophagy induced by sorafenib itself in normoxia and significantly enhanced the cytotoxicity of sorafenib in HCC cells; and it also inhibited the hypoxia-induced autophagy and achieved the same effect in sorafenib sensitivity-enhancement in HCC cells as it in normoxia. Finally, knockout of intratumoral FOXO3a significantly enhanced curative efficacy of sorafenib via inhibition of autophagy in xenograft tumors in nude mice. Collectively, our study suggests that FOXO3a plays a key role in regulating hypoxia-induced autophagy in sorafenib-treated HCC, and FOXO3-targeted therapy may serve as a promising approach to improve clinical prognosis of patients suffering from HCC.

Endoscopic or laparoscopic resection for small gastrointestinal stromal tumors: a cumulative meta-analysis.

BACKGROUND: Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection. METHODS: The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results. RESULTS: A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = -27.1 min, 95% confidence interval [CI]: -40.8 min to -13.4 min) and lengths of hospital stay (WMD = -1.43 d, 95% CI: -2.31 d to -0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 - 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 - 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = -41.03 min, 95% CI: -59.53 min to -22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 - 10.34). CONCLUSIONS: In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.

Delayed gastric emptying after Pancreaticoduodenectomy: a propensity score-matched analysis and clinical Nomogram study.

BACKGROUND: Delayed gastric emptying (DGE) is a common and frustrating complication of pancreaticoduodenectomy (PD). Studies suggest that surgical methods and other clinical characteristics may affect the occurrence of DGE. Nevertheless, the results of such studies are conflicting. The objective of this work was to perform a propensity score matching analysis to compare the differences between pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-removing pancreaticoduodenectomy (PrPD) and to develop and validate a nomogram to predict the probability of severe DGE (SDGE). METHODS: This retrospective study enrolled patients who underwent PD at our institution from December 2009 to December 2018. Propensity score matching was applied at a ratio of 1:1 to compare PPPD and PrPD groups. We compared incidence of complications, DGE, lengths of hospital stay, hospitalization costs, and mortality. Univariate and multivariate logistic regression analysis were performed to identify potential risk factors of severe DGE. Finally, a nomogram was developed and validated to predict severe DGE. RESULTS: The PPPD group had a significantly higher rate of postoperative pancreatic fistula (29.9% versus 17.4%, P < 0.05) and less blood loss (463.7 ml versus 694.9 ml, P < 0.05). After propensity score matching, the PPPD group had a significantly higher rate of postoperative DGE (19.2% versus 3.8%, P < 0.05), especially severe DGE (17.3% versus 0%) than the PrPD group. There were no significant differences in terms of lengths of hospital stay, hospitalization costs or mortality between the groups. Surgical method, biliary leakage, abdominal infection, and diabetes were independent risk factors for SDGE. The nomogram predicted SDGE with a training C - index of 0.798 and a validation C - index of 0.721. CONCLUSION: PPPD increases the risk of DGE than PrPD, especially SDGE. Our prediction nomogram gives good prediction of SDGE after pancreaticoduodenectomy.

INHBA is a prognostic predictor for patients with colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is one of the most lethal cancers. It is particularly important to accurately predict prognosis and to provide individualized treatment. Several lines of evidence suggest that genetic factors and clinicopathological characteristics are related to cancer onset and progression. The aim of this study was to identify potential prognostic genes and to develop a nomogram to predict survival and recurrence of COAD. METHODS: To identify potential prognostic genes in COAD, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained from GEO2R. Venn diagram was drawn to select those genes that were overexpressed in all datasets, and survival analyses were performed to determine the prognostic values of the selected genes. New nomograms were developed based on the genes that were significantly associated with prognosis. Clinicopathological data were obtained from The Cancer Genome Atlas (TCGA). Finally, the new nomograms were compared head-to-head comparison with the TNM nomogram. RESULTS: From GSE21510, GSE110223, GSE113513 and GSE110224, a total of 834, 218, 236 and 613 overexpressed DEGs were screened out, respectively. The Venn diagram revealed that 12 genes appeared in all four profiles. After survival analyses, only INHBA expression was associated with both overall survival (OS) and disease-free survival (DFS). Multivariate analyses revealed that age, pathological N and pathological M were significant independent risk factors for OS. Age, pathological N, pathological M and INHBA were significant independent risk factors for DFS. Two prediction models predicted the probability of 3-year survival and 5-year survival for OS and DFS, respectively. The concordance indexes were 0.785 for 3-year overall survival, 0.759 for 5-year overall survival, 0.789 for 3-year disease-free survival and 0.757 for 5-year disease-free survival. The head-to-head comparison according to time-dependent ROC curves indicated that the new models had higher predictive accuracy. Decision curve analyses (DCA) indicated that the clinical value of the new models were higher than TNM models for predicting disease-free survival. CONCLUSION: The combination of INHBA expression with a clinical nomogram improves prognostic power in colon adenocarcinoma, especially for predicting recurrence.

High Centromere Protein-A (CENP-A) Expression Correlates with Progression and Prognosis in Gastric Cancer.

PURPOSE: Recent studies have established the ability of centromere protein-A (CENP-A) to perform as an oncogene, regulating tumor progression. The aim of this research was to explore the relationship between CENP-A expression and clinical significance in gastric cancer (GC) patients. MATERIALS AND METHODS: Experiments with a microarray were conducted using the Affymetrix U133 plus 2.0 GeneChip Array. Upregulated differentially expressed genes (DEGs) were identified via the GEO2R and intersected using a Venn diagram. Bioinformatic databases Omcomine, GEPIA, and Ualcan were applied to investigate the expression level of CENP-A in GC. The real-time quantitative RT-PCR (qRT-PCR) was used to validate the level of CENP-A mRNA in GC. Immunohistochemistry (IHC) was employed to verify the protein levels of CENP-A, while the relationship between CENP-A expression and patients' clinical parameters in GC was explored through the use of IHC. Kaplan-Meier analysis was conducted to evaluate the prognostic significance of CENP-A. Additionally, the Kaplan-Meier plotter database (KM plotter) was used to verify the prognostic function of CENP-A in GC patients. RESULTS: The results indicated that CENP-A was significantly overexpressed, both in protein and mRNA levels of GC tissues, compared to adjacent noncancerous tissues (P<0.05). Furthermore, we observed that CENP-A expression was positively associated with TNM stage, tumor classification, lymph node metastasis, distant metastasis, and Lauren type (P<0.05). Kaplan-Meier analysis showed that patients with an overexpression of CENP-A had significantly poorer overall survival (OS) times (P<0.05). Multivariate analysis suggested CENP-A may serve as an independent predicting factor for the poor outcome of GC patients. CONCLUSION: Our results show that CENP-A upregulation is significantly correlated with advanced tumor progression and poor prognosis. CENP-A may function as a novel potential biomarker for predicting the clinical outcomes of GC patients.

Effects of intraoperative PEEP on postoperative pulmonary complications in high-risk patients undergoing laparoscopic abdominal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative pulmonary complications (PPCs), strongly associated with higher mortality risk, can develop in up to 58% of patients undergoing abdominal surgery. More and more evidence shows that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery, however, the role of positive end-expiratory pressure (PEEP) during the intraoperative period in preventing PPCs for laparoscopic surgery is not clearly defined. METHODS AND ANALYSIS: A total of 208 patients with a high risk of PPC, undergoing laparoscopic abdominal surgery, will be enrolled and randomised into a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive a fraction of inspired oxygen of 0.50 and a tidal volume of 8 mL/kg ideal body weight (IBW). Standard perioperative fluid management and analgesic treatments are applied in both groups. The primary end point is PPC within 7 days after surgery. Secondary end points are the modified Clinical Pulmonary Infection Score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, 30-day mortality. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medicine College) (registration number KY2018026) on 22 October 2018. The first participant was recruited on 15 April 2019 and the estimated completion date of the study is October 2021. The results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: http://www.chictr.org.cn, ID: ChiCTR1800019865. Registered on 2 December 2018; preresults.

Evolution of Laparoscopic Pancreatic Resections for Pancreatic and Periampullary Diseases: Perioperative Outcomes of 605 Patients at a High-Volume Center.

Background: Laparoscopic pancreatectomy (LP) is increasingly performed with several institutional series and comparative studies reported. We have applied LP to a variety of pancreatic resections since 2004. This article is to report results of 15-year practice of 605 LPs for pancreatic and periampullary diseases. Methods: Patients with benign or malignant diseases in the pancreas and periampullary region, who underwent LP from June 2004 to June 2018, were retrospectively reviewed. The demographics and indications, and intraoperative and perioperative outcomes were evaluated. Results: A total of 605 consecutive LPs were analyzed, including 237 (39.2%) distal pancreatectomy with splenectomy (DPS), 116 (19.2%) spleen-preserving distal pancreatectomy (SPDP), 30 (5.0%) enucleation (EN), 30 (5.0%) central pancreatectomy (CP), 186 (30.7%) pancreatoduodenectomy (PD), and 6 (1.0%) pancreatoduodenectomy with total pancreatectomy (PDTP). The most common pathologic finding was pancreatic ductal adenocarcinomas (146, 24.1%). Conversion to open procedure was required in 22 patients (3.6%) (12 with PD, 8 with DPS, 1 with CP, and 1 with PDTP). The mean operative time was 241.5 ± 105.5 minutes (range 50-550 minutes) for the entire population and 367.1 ± 61.8 minutes (range 230-550 minutes) for PD. Clinically significant pancreatic fistula (ISGPF grade B and C) rate was 12.4% for the entire cohort and 16.1% for PD. Rate of Clavien-Dindo III-V complications was 17.4% for the entire cohort and 23.7% for PD. Ninety-day mortality was observed only in the cohort of patients undergoing PD (n = 4). Conclusions: The LP procedure appears to be technically safe and feasible, with an acceptable rate of morbidity when performed at our experienced, high-volume center. However, PD has less favorable outcomes and needs further evaluation.

Effects of intraoperative PEEP on postoperative pulmonary complications in patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer: study protocol for a randomized controlled trial.

BACKGROUND: There are increasing studies showing that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery; however, the appropriate positive end-expiratory pressure (PEEP) has not yet defined. Adopting a suitable PEEP may prevent postoperative pulmonary complications. Robot-assisted laparoscopic surgery is the newest and most minimally invasive treatment for bladder cancer or prostate cancer. It is also necessary to consider the effects of Trendelenburg position with pneumoperitoneum on airway pressure and pulmonary function. The role of PEEP during the intraoperative period in preventing postoperative pulmonary complications for robot-assisted laparoscopic surgery is not clearly defined. METHODS/DESIGN: A total of 208 patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer will be enrolled and then randomly assigned to a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive an inspired oxygen fraction of 0.50 and a tidal volume of 8 mL/kg ideal body weight. Standard perioperative fluid management standardization and analgesic treatments will be applied in both groups. The primary endpoint is postoperative pulmonary complications within 7 days after surgery. Secondary endpoints are the modified clinical pulmonary infection score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, and 30-day mortality. DISCUSSION: This trial aimed to assess the effects of low tidal volumes combined with intraoperative PEEP ventilation strategy on postoperative pulmonary complications in patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer. TRIAL REGISTRATION: ID: ChiCTR1800019867 . Registered on December 2, 2018.

Dietary carbohydrate intake, glycaemic index, glycaemic load and digestive system cancers: an updated dose-response meta-analysis.

Several studies analysed the associations between dietary carbohydrate intake, glycaemic index (GI) and glycaemic load (GL) and digestive system cancers; however, the results remain controversial. This study was to perform a meta-analysis evaluating the quantitative and dose-response associations between carbohydrate intake, GI and GL, and risk of digestive system cancers. We searched medical and biological databases up to June 2018 and identified twenty-six cohort studies and eighteen case-control studies. Meta-analytic fixed or random effects models were applied to process data. We also performed dose-response analysis, meta-regression and subgroup analyses. We found that high levels of GI were significantly associated with the risk of digestive system cancers at the highest compared with the lowest categories from cohort studies (summary relative risk (RR)=1·10, 95 % CI 1·05, 1·15). Similar effects were observed from case-control studies of the comparison between the extreme categories, but the difference did not reach statistical significance (summary OR=1·28, 95 % CI 0·97, 1·69). We also observed significant dose-response association between GI and digestive system cancers, with every 10-unit increase in GI (summary RR=1·003; 95 % CI 1·000, 1·012 for cohort studies; summary OR=1·09; 95 % CI 1·06, 1·11 for case-control studies). In addition, both cohort studies and case-control studies indicated that neither dietary carbohydrate intake nor GL bore any statistical relationship to digestive system cancers from the results of the highest compared with the lowest categories analyses and dose-response analyses. The results suggest a moderate association between high-GI diets and the risk of digestive system cancers.

Targeted Codelivery of Docetaxel and Atg7 siRNA for Autophagy Inhibition and Pancreatic Cancer Treatment.

As the fourth leading cause of cancer-related deaths worldwide, pancreatic cancer has a higher basal level of autophagy as compared to other epithelial tumors. Recently, increasing evidence suggested that docetaxel (DTX) triggered autophagy in pancreatic cancer cells which promoted cancer cell survival after chemotherapy. Therefore, we constructed an amphiphilic block copolymer that can form micelles to simultaneously codeliver with siAtg7 and DTX for effective inhibition of tumor cells grown in vitro and in vivo. The iRGD peptide internalized on the surface of the vehicle could target to tumors and increase the penetration of vehicle into solid tumors. By downregulating the expression of Atg7 gene, the DTX-induced autophagy was inhibited, which improved the DTX therapeutic outcomes during the treatment of pancreatic cancer.

Surgical outcomes of laparoscopic distal pancreatectomy in elderly and octogenarian patients: a single-center, comparative study.

BACKGROUND: Although recent reports have suggested the advantages of laparoscopic distal pancreatectomy (LDP), the potential benefits of this approach in elderly patients remain unclear. The aim of this study was to clarify the value of LDP in the elderly, in whom co-morbid diseases were generally more common. METHODS: Seventy elderly patients (≥ 70 years) and 264 non-elderly patients (40-69 years) who underwent LDP, and 48 elderly patients (≥ 70 years) who underwent open distal pancreatectomy (ODP) between May 2005 and May 2018 were studied. Demographics, intraoperative, and postoperative outcomes were compared. RESULTS: Comorbidity was more common in elderly patients than in non-elderly patients who underwent LDP (57.1 vs. 38.3%, p < 0.01). The intraoperative factors, postoperative complication rate, and length of hospital stay were comparable in these two groups. Elderly patients who underwent LDP had a significantly shorter operative time (185.5 vs. 208.0 min, p = 0.02), less blood loss (191.0 vs. 291.8 mL, p < 0.01), and reduced length of postoperative hospital stay (11.4 vs. 15.1 days, p < 0.01) than elderly patients who had ODP. The overall complication rate tended to be lower in LDP group than that in ODP group (20.0 vs. 33.3%, p = 0.07). CONCLUSION: LDP performed on the elderly is safe and feasible, leading to short-term outcomes similar to those of non-elderly patients. LDP could be an alternative to ODP in elderly patients, providing a lower rate of morbidity and favorable postoperative recovery and outcomes.

Overexpression of BCAT1 is a prognostic marker in gastric cancer.

As one form of branched-chain amino-acid transaminase (BCAT) enzymes, It has been found that up-regulation of BCAT1 is associated with poor prognosis in numerous types of tumors, but studies on the role of BCAT1 expression in gastric cancer (GC) are rare. The aims of this study were to detect BCAT1 expression in GC and to analyze its association with prognosis of GC patients. Microarray experiments were performed on the Affymetrix U133 plus 2.0 GeneChip Array. The protein and messenger RNA levels of BCAT1 were validated by immunohistochemistry and real-time quantitative polymerase chain reaction in GC tissues and adjacent noncancerous tissues. Our study shows that the expression of BCAT1 significantly increased in human GC. Furthermore, it can also be found that BCAT1 overexpression was associated with TNM stage (P < .05), local invasion (P < .05), Lauren type (P < .05), tumor classification (P < .05), lymph node metastasis (P < .05), and presence of distant metastasis (P < .05). Kaplan-Meier survival analysis revealed that high BCAT1 expression predicted significantly worse overall survival (P < .05), whereas multivariate Cox regression analysis showed that BCAT1 affects GC independently. In conclusion, up-regulation of BCAT1 indicated a poor survival rate of GC and may serve as a useful marker for predicting the outcome of patients with GC.