Alterations in the Duodenal Fluid Microbiome of Patients With Pancreatic Cancer

Background & AimsThe tumor microbiome of patients with pancreas ductal adenocarcinoma (PDAC) includes bacteria normally present in the upper gastrointestinal tract. If the predominant source of intratumoral bacteria in patients with PDAC is retrograde migration from the duodenum, duodenal fluid could be a representative biospecimen for determining microbiome profiles of patients with PDAC or at risk of developing PDAC.MethodsWe performed a case-control study comparing bacterial and fungal (16S and 18S rRNA) profiles of secretin-stimulated duodenal fluid collections from 308 patients undergoing duodenal endoscopy including 134 normal pancreas control subjects, 98 patients with pancreatic cyst(s) and 74 patients with PDAC.ResultsAlterations in duodenal fluid microbiomes with diminished alpha diversity were significantly associated with age >70 and proton pump inhibitor use. Patients with PDAC had significantly decreased duodenal microbial alpha diversity compared with age-matched control subjects with normal pancreata and those with pancreatic cyst(s). There was evidence of enrichment of Bifidobacterium genera in the duodenal fluid of patients with PDAC compared with control subjects and those with pancreatic cyst(s). There were also enrichment of duodenal fluid Fusobacteria and Rothia bacteria among patients with PDAC with short-term survival. Duodenal fluid microbiome profiles were not significantly different between control subjects and patients with pancreatic cyst(s).ConclusionPatients with PDAC have alterations in their duodenal fluid microbiome profiles compared with patients with pancreatic cysts and those with normal pancreata. ClinicalTrials.gov, Number: NCT02000089     

Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: A meta-analysis

AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer.METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters.RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009).CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients.     

Hepatitis B and C viruses are not risks for pancreatic adenocarcinoma

AIM:To investigate whether hepatitis B virus(HBV)and hepatitis C virus(HCV)increase risk of pancreatic ductal adenocarcinoma(PDAC).METHODS:We recruited 585 patients with cytological and/or pathologically confirmed PDAC in National Taiwan University Hospital from September 2000 to September 2013,and 1716 age-,sex-,and race-matched controls who received a screening program in a community located in Northern Taiwan.Blood samples were tested for the presence of HCV antibodies(anti-HCV),HBV surface antigen(HBsAg),antibodies against HBsAg(anti-HBs),and hepatitis B core antigen(anti-HBc)in all cases and controls.The odds ratio(OR)of PDAC was estimated by logistic regression analysis with adjustment diabetes mellitus(DM)and smoking.RESULTS:HBsAg was positive in 73 cases(12.5%)and 213 controls(12.4%).Anti-HCV was positive in22 cases(3.8%)and 45 controls(2.6%).Anti-HBs was positive in 338 cases(57.8%)and 1047 controls(61.0%).The estimated ORs of PDAC in multivariate analysis were as follows:DM,2.08(95%CI:1.56-2.76,P<0.001),smoking,1.36(95%CI:1.02-1.80,P=0.035),HBsAg+/anti-HBc+/anti-HBs-,0.89(95%CI:0.89-1.68,P=0.219),HBsAg-/anti-HBc+/anti-HBs+,1.03(95%CI:0.84-1.25,P=0.802).CONCLUSION:HBV and HCV infection are not associated with risk of PDCA after adjustment for age,sex,DM and smoking,which were independent risk factors of PDAC.     

Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: A meta-analysis

AIM:To assess the effectiveness of pancreatic stents for preventing pancreatitis in high-risk patients after endoscopic retrograde cholangiopancreatography(ERCP).METHODS:PubMed,Embase,Science Citation Index,and Cochrane Controlled Trials Register were searched to identify relevant trials published in English.Inclu-sion and exclusion criteria were used to screen for suitable studies.Two reviewers independently judged the study eligibility while screening the citations.The methodological quality of the included trials was assessed using the Jadad scoring system.All results were expressed as OR and 95%CI.Data were analyzed using Stata12.0 software.RESULTS:Ten eligible randomized controlled trials were selected,including 1176 patients.A fixed-effects model in meta-analysis supported that pancreatic duct stents significantly decreased the incidence of postERCP pancreatitis(PEP)in high-risk patients(OR=0.25;95%CI:0.17-0.38;P<0.001).Pancreatic stents also alleviated the severity of PEP(mild pancreatitis after ERCP:OR=0.33;95%CI:0.21-0.54;P<0.001;moderate pancreatitis after ERCP:OR=0.30;95%CI:0.13-0.67;P=0.004).The result of severe pancreatitis after ERCP was handled more rigorously(OR=0.24;95%CI:0.05-1.16;P=0.077).Serum amylase levels were not different between patients with pancreatic stents and control patients(OR=1.08;95%CI:0.82-1.41;P=0.586).CONCLUSION:Placement of prophylactic pancreatic stents may lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate the severity of this condition.     

Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection

BACKGROUNDInflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors.AIMTo investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC).METHODSWe retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTSThe optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSIONThe increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.     

Pancreatic inflammation and atrophy are not associated with pancreatic cancer concomitant with intraductal papillary mucinous neoplasm

Background

Inflammation-induced carcinogenesis in pancreatic ductal adenocarcinoma (PDAC) has been reported; however, its involvement in PDAC with intraductal papillary mucinous neoplasm (IPMN) remains unclear. We herein investigated the relationship between pancreatic atrophy and inflammation and the incidence of PDAC concomitant with IPMN.

Preoperative predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma

BackgroundThis study aimed to identify predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) resection with and without neoadjuvant therapy.MethodsIncluded were patients who underwent PDAC resection (2014–2016). Multivariable multinomial regression was performed to identify preoperative predictors for manifestation of recurrence within 3, 6 and 12 months after PDAC resection.Results836 patients with a median follow-up of 37 (interquartile range [IQR] 30–48) months and overall survival of 18 (IQR 10-32) months were analyzed. 670 patients (80%) developed recurrence: 82 patients (10%) <3 months, 96 patients (11%) within 3–6 months and 226 patients (27%) within 6–12 months. LogCA 19–9 (OR 1.25 [95% CI 1.10–1.41]; P < 0.001) and neoadjuvant treatment (OR 0.09 [95% CI 0.01–0.68]; P = 0.02) were associated with recurrence <3 months. LogCA 19–9 (OR 1.23 [95% CI 1.10–1.38]; P < 0.001) and 0–90° venous involvement on CT imaging (OR 2.93 [95% CI 1.60–5.37]; P < 0.001) were associated with recurrence within 3–6 months. A Charlson Age Comorbidity Index ≥4 (OR 1.53 [95% CI 1.09–2.16]; P = 0.02) and logCA 19–9 (OR 1.24 [95% CI 1.14–1.35]; P < 0.001) were related to recurrence within 6–12 months.ConclusionThis study demonstrates preoperative predictors that are associated with the manifestation of early and very early recurrence after PDAC resection. Knowledge of these predictors can be used to guide individualized surveillance and treatment strategies.     

The quality of pain management in pancreatic cancer: A prospective multi-center study

Background/objectivesPancreatic ductal adenocarcinoma (PDAC) is frequently associated with severe pain. Given the almost inevitably fatal nature of the disease, pain control is crucial. However, data on quality of pain management in PDAC is scarce.MethodsThis is a multi-center, prospective study to evaluate the quality of pain management in PDAC. Insufficient pain treatment (undertreatment) was prevalent if there was an incongruence between the patients level of pain and the potency of analgesic drug therapy. Determinants of pain and undertreatment were identified using multivariable logistic regression.Results139 patients with histologically confirmed PDAC were analyzed. The prevalence of pain was 63%, with approximately one third of the patients grading their pain as moderate to severe. Palliative stage (OR: 3.37, 95%CI: 1.23–9.21, p = 0.018) and localization of the primary tumor in the body or tail (OR: 2.57, 95%CI: 1.05–6.31, p = 0.039) were independent determinants of pain. Of those reporting pain, 60% were undertreated and in 89% pain interfered with activities and emotions. Age ≥ 70 years (OR: 3.20, 95%CI: 1.09–9.41, p = 0.035) was an independent predictor of undertreatment. Patients with longer-known PDAC ( ≥ 30 days) showed improved pain management compared to new cases (OR: 0.19, 95%CI: 0.05–0.81, p = 0.025). Treatment by gastroenterologists (OR: 0.22, 95%CI: 0.05–0.89, p = 0.034) was associated with less undertreatment.ConclusionsThe results show a high proportion of PDAC patients with pain, pain interference and undertreatment, whose characteristics could help to identify patients at risk in the future. Several changes in the management of cancer-related pain are necessary to overcome barriers to optimal treatment.     

Meta-analysis of subtotal stomach-preserving pancreaticoduodenectomy vs pylorus preserving pancreaticoduodenectomy

AIM: To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy (PPPD) and subtotal stomach-preserving pancreaticoduodenectomy (SSPPD).METHODS: Major databases including PubMed (Medline), EMBASE and Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched for comparative studies between patients with PPPD and SSPPD published between January 1978 and July 2014. Studies were selected based on specific inclusion and exclusion criteria. The primary outcome was delayed gastric emptying (DGE). Secondary outcomes included operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay. The pooled odds ratios (OR) or weighted mean difference (WMD) with 95% confidence intervals (95%CI) were calculated using either a fixed-effects or random-effects model.RESULTS: Eight comparative studies recruiting 650 patients were analyzed, which include two RCTs, one non-randomized prospective and 5 retrospective trial designs. Patients undergoing SSPPD experienced significantly lower rates of DGE (OR = 2.75; 95%CI: 1.75-4.30, P < 0.00001) and a shorter period of nasogastric intubation (OR = 2.68; 95%CI: 0.77-4.58, P < 0.00001), with a tendency towards shorter time to liquid (WMD = 2.97, 95%CI: -0.46-7.83; P = 0.09) and solid diets (WMD = 3.69, 95%CI: -0.46-7.83; P = 0.08) as well as shorter inpatient stay (WMD = 3.92, 95%CI: -0.37-8.22; P = 0.07), although these latter three did not reach statistical significance. PPPD, however, was associated with less intraoperative blood loss than SSPPD [WMD = -217.70, 95%CI: -429.77-(-5.63); P = 0.04]. There were no differences in other parameters between the two approaches, including operative time (WMD = -5.30, 95%CI: -43.44-32.84; P = 0.79), pancreatic fistula (OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage (OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess (OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection (OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube (OR = 1.90; 95%CI: 0.91-3.97; P = 0.09) and mortality (OR = 0.31; 95%CI: 0.05-2.01; P = 0.22).CONCLUSION: SSPPD may improve intraoperative and short-term postoperative outcomes compared to PPPD, especially DGE. However, these findings need to be further ascertained by well-designed randomized controlled trials.     

Statin use improves survival in patients with pancreatic ductal adenocarcinoma: A meta-analysis

BackgroundPrevious studies on statins’ effect on survival of patients with pancreatic ductal adenocarcinoma (PDAC) report conflicting results.AimsTo evaluate the association between statin use and PDAC patients’ survival.MethodsA systematic review and meta-analysis was performed including case-control, cohort studies and randomized controlled trials assessing the association between statin use and survival in PDAC patients. Pooled HRs with 95%CIs were calculated using random effects model; publication bias was assessed through Begg and Mazumdar test and heterogeneity by I² value.Results14 studies with 33,137 PDAC patients, 40% under statins, were included. Statins use was associated to a reduced death risk (HR 0.871; 95%CI: 0.819; 0.927; p = 0.0001) suggesting a protective effect, homogeneous for different geographic areas. This effect was significant in surgically resected patients (HR 0.50; 95%CI: 0.32; 0.76; p = 0.001) but not in those with advanced disease (HR 0.78; 95%CI: 0.59; 1.02; p = 0.07). In studies providing information on statin type, only rosuvastatin resulted associated to a reduced risk of death (HR 0.88; 95%CI: 0.81; 0.96; p = 0.004).ConclusionsStatins use is significantly associated with a reduced risk of death in resected PDAC patients. This finding has to be considered with caution due to publication bias and the availability of only few studies for sensitivity analyses.     

The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies

BackgroundPreoperative chemo- or chemoradiotherapy is recommended for borderline-resectable pancreatic cancer. The aim of this study was to determine the impact of preoperative therapy on surgical complications in patients with resected pancreatic cancer.MethodsThis systematic review and meta-analysis included studies reporting on the rate of surgical complications after preoperative chemo- or chemoradiotherapy versus immediate surgery in pancreatic cancer patients. The primary endpoint was the rate of grade B/C POPF. Pooled odds ratios were calculated using random-effects models.ResultsForty-one comparative studies including 25,389 patients were included. Vascular resections were more often performed after preoperative therapy (29.4% vs. 15.7%, p < 0.001). Preoperative therapy was associated with a lower rate of grade B/C POPF as compared to immediate surgery (pooled OR 0.47, 95%CI 0.38–0.58). This reduction was mostly obtained by preoperative chemoradiotherapy (OR 0.46, 95%CI 0.29–0.73), but not by preoperative chemotherapy alone (OR 0.83, 95%CI 0.59–1.16). No difference was demonstrated for major morbidity, mortality, postpancreatectomy haemorrhage, delayed gastric emptying and overall morbidity.ConclusionPreoperative chemo- and chemoradiotherapy in patients with pancreatic cancer appears to be safe with respect to POPF and other surgical complications as compared to immediate surgery. The reduced rate of POPF appears to be attributable to preoperative chemoradiation.     

The impact of extent of pancreatic and venous resection on survival for patients with pancreatic cancer

BackgroundBorderline resectable pancreatic cancer may require extended resections in order to achieve tumor-free margins, especially in the case of up-front resections, but it is important to know the limits of surgical therapy in this disease. This study aimed to investigate the impact of extent of pancreatic and venous resection on short- and long-term outcomes in patients with pancreatic adenocarcinoma (PDAC).MethodsThis was a retrospective study from a prospectively maintained database of pancreatic resections for PDAC. Short- and long-term outcomes were analyzed in patients having borderline resectable PDAC submitted to up-front total pancreatectomy (TP) or pancreaticoduodenectomy (PD) with simultaneous portal vein (PV) and/or superior mesenteric vein (SMV) resection. Venous resections were carried out as tangential venous resection (TVR) or segmental venous resection (SVR). Patients were divided into 4 groups: (1) PD + TVR, (2) PD + SVR, (3) TP + TVR, (4) TP + SVR. Uni- and multivariate Cox regression analysis were performed to identify factors associated with survival.ResultsNinety-nine patients were submitted to simultaneous pancreatic and venous resection for PDAC. Among them, 25 were submitted to PD + TVR (25.3%), 12 to PD + SVR (12.1%), 23 to TP + TVR (23.2%), and 39 to TP + SVR (39.4%). Overall, major morbidity (Clavien-Dindo grade ≥ IIIA) was 26.3%. Thirty- and 90-day mortality were 3% and 11.1%, respectively. There were no significant differences among groups in terms of short-term outcomes. Median overall survival of patients submitted to PD + TVR was significantly higher than those to TP+SVR (29.5 vs 7.9 months, P = 0.001). Multivariate analysis identified TP (HR = 2.11; 95% CI: 1.31–3.44; P = 0.002) and SVR (HR = 2.01; 95% CI: 1.27–3.15; P = 0.003) as the only independent prognostic factors for overall survival.ConclusionsUp-front TP associated to SVR was predictive of worse survival in borderline resectable PDAC. Perioperative treatments in high-risk surgical groups may improve such poor outcomes.     

Effectiveness and safety of 1L PEG-ASC preparation for colonoscopy in patients with inflammatory bowel diseases

IntroductionThe effectiveness of bowel cleansing is a key element for high-quality colonoscopy. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution has been introduced, but effectiveness and safety of this preparation have not been assessed in IBD patients. This study aims to evaluate effectiveness and safety of 1 L PEG-ASC solution in patients with IBD compared to controls.MethodsWe retrospectively analysed prospectively collected data on a cohort of 411 patients performing a colonoscopy after preparation with 1 L PEG-ASC, consecutively enrolled in 5 Italian centres.ResultsOverall, 185/411 (45%) were patients with IBD and 226/411 (55%) served as controls. A significantly higher cleansing success was achieved in IBD patients (92.9% vs 85.4%, p = 0.02). The multiple regression model showed that presence of IBD (OR=2.514, 95%CI=1.165–5.426; P = 0.019), lower age (OR=0.981, 95%CI=0.967–0.996; P = 0.014), split preparation (OR=2.430, 95%CI=1.076–5.492; P = 0.033), absence of diabetes (OR=2.848, 95%CI=1.228–6.605; P = 0.015), and of chronic constipation (OR=3.350, 95%CI=1.429–7.852; P = 0.005), were independently associated with cleansing success. The number of treatment-emergent adverse events (TEAEs) (51 vs 62%, p = 0.821), and of patients with TEAEs (22.2% vs 21.2%, p = 0.821), were similar in IBD patients and in controls, respectively.ConclusionsResults from this study support the effectiveness and safety of 1 L PEG-ASC solution in IBD patients, which may improve the definition of endoscopic outcomes both in Crohn’s disease and ulcerative colitis.     

Racial/ethnic disparities in hepatocellular carcinoma treatment and survival in California, 1988-2012

AIMTo describe racial/ethnic differences in treatment and survival among liver cancer patients in a population-based cancer registry.METHODSInvasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White (White, n = 12710), Hispanic (n = 8500), Chinese (n = 2723), non-Hispanic Black (Black, n = 2609), Vietnamese (n = 2063), Filipino (n = 1479), Korean (n = 1099), Japanese (n = 658), American Indian/Alaskan Native (AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian (n = 233), South Asian (n = 190), Hawai`ian/Pacific Islander (n = 172), Thai (n = 95), and Other Asian (n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause mortality.RESULTSAfter adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio (OR) = 0.30, 95%CI: 0.17-0.53], Cambodian (OR = 0.65, 95%CI: 0.45-0.96), AIAN (OR = 0.66, 95%CI: 0.46-0.93), Black (OR = 0.76, 95%CI: 0.67-0.86), and Hispanic (OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese (OR = 1.58, 95%CI: 1.42-1.77), Koreans (OR = 1.45, 95%CI: 1.24-1.70), Japanese (OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese (OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio (HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians (HR = 1.35, 95%CI: 1.16-1.58), and Blacks (HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese (HR = 0.82, 95%CI: 0.77-0.86), Filipinos (HR = 0.84, 95%CI: 0.78-0.90), Vietnamese (HR = 0.85, 95%CI: 0.80-0.90), Koreans (HR = 0.90, 95%CI: 0.83-0.97), and Hispanics (HR = 0.91, 95%CI: 0.88-0.94); results were similar for all-cause mortality.CONCLUSIONDisaggregated data revealed substantial racial/ethnic differences in liver cancer treatment and survival, demonstrating the need for development of targeted interventions to mitigate disparities.     

Lower serum folate is associated with development and invasiveness of gastric cancer

AIM: To evaluate the associations of serum folate level with development, invasiveness and patient survival of gastric cancer.METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.RESULTS: The mean serum folate level was significantly lower in gastric cancer patients than that in controls (3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender (all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population (OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata (age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years (OR = 21.67, 95%CI: 8.27-56.80), males (OR = 17.95, 95%CI: 7.93-40.62), and females (OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion (OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion (OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis (OR = 6.67, 95%CI: 1.28-34.91) of gastric cancer (all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival (HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.CONCLUSION: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.     

Association between cadherin-17 expression and pathological characteristics of gastric cancer:A meta-analysis

AIM: To construct a meta-analysis in order to examine the relationship between cadherin-17(CDH17) andgastric cancer(GC). METHODS: Related articles were selected by searching the following English or Chinese electronic databases: CINAHL, MEDLINE, Science Citation Index, the Chinese Journal Full-Text, and the Weipu Journal. NewcastleOttawa Scale(NOS) criteria were used to ensure consistency in reviewing and reporting results. Statistical analyses were conducted with Version 12.0 STATA statistical software.RESULTS: Ultimately, 11 articles, with a total of 2,120 GC patients, were found to be eligible for study inclusion. In comparisons of GC patients by TNM stage(Ⅲ-Ⅳ vs ?Ⅰ-Ⅱ: OR = 2.35, 95%CI: 1.15-4.825, P = 0.019), histologic grade(3-4 vs 1-2: OR = 3.48, 95%CI: 1.36-8.92, P = 0.009), invasion grade(T3-4 vs T1-2: OR = 2.86; 95%CI: 1.69-4.83; P = 0.000), and lymph node metastasis(positive vs negative: OR = 2.64; 95%CI: 1.33-5.27; P = 0.006), it was found that CDH17 showed more positive expressions in each of the more severe cases. Country-stratified analyses from all four experimental subgroups showed that high CDH17 expression levels may be related to GC among Chinese and Korean populations(all P < 0.05), with the exception of the invasion grade T3-4 vs T1-2 comparison, where the relation only held among the Chinese population(OR = 2.86, 95%CI: 1.69-4.83, P = 0.000). CONCLUSION: Collectively, the data reflects the capacity of CDH17 in tumor proliferation and metastasis among GC patients.     

The Feasibility and Safety of Same-Day Discharge for All Comers after Elective Percutaneous Coronary Interventions

BackgroundThe safety of same day discharge (SDD) after percutaneous coronary interventions (PCI) has been demonstrated in several studies. However, SDD was only allowed in patients meeting strict criteria. We aimed to evaluate the feasibility and safety of SDD following elective-PCI in all comers.MethodsIn 2012, we implemented a strategy of SDD for all elective PCI (no exclusion) but admissions were allowed at the discretion of the treating physician. We assessed the feasibility and safety of this approach in consecutive patients who underwent elective PCI at WVU.ResultsOut of 3355 patients who underwent PCI between 2012 and 2016, 691 (21%) presented electively. Radial access was utilized in 480 (69.5%). Same day discharge was achieved in 539/691 (78%), and there was no difference between patients who had SDD and those who were admitted with regards to the 30-day major adverse cardiovascular and cerebrovascular events (3.2% vs. 3.5% respectively, P = 0.195). Predictors of SDD failure were procedural complications (OR 12.08, 95%CI 2.20–57.8. P = 0.002), use of Glycoprotein IIB-IIIA inhibitors (OR 3.45, 95%CI 1.067–11.41, P = 0.039), femoral access (OR 2.067, 95%CI 1.25–3.419, p = 0.005), anemia (OR 1.80, 95%CI 1.06–3.04, P = 0.029), home distance ≥60 miles (OR 1.68, 95%CI 1.03–2.72, P = 0.037).ConclusionSDD is feasible in the majority of all-comers after elective PCI, and is not associated with increase in adverse events at 30-days. Certain procedural and patient's characteristics predict SDD failure. If validated in prospective studies, these factors can possibly be integrated in a predictive tool to aid in triaging patients, post-elective PCI.     

Meta-analysis of laparoscopic vs open liver resection for hepatocellular carcinoma

AIM: To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection (LLR) and open liver resection (OLR) for hepatocellular carcinoma (HCC).METHODS: PubMed (Medline), EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012. Two authors independently assessed the trials for inclusion and extracted the data. Meta-analysis was performed using Review Manager Version 5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either fixed effects (Mantel-Haenszel method) or random effects models (DerSimonian and Laird method). Evaluated endpoints were operative outcomes (operation time, intraoperative blood loss, blood transfusion requirement), postoperative outcomes (liver failure, cirrhotic decompensation/ascites, bile leakage, postoperative bleeding, pulmonary complications, intraabdominal abscess, mortality, hospital stay and oncologic outcomes (positive resection margins and tumor recurrence).RESULTS: Fifteen eligible non-randomized studies were identified, out of which, 9 high-quality studies involving 550 patients were included, with 234 patients in the LLR group and 316 patients in the OLR group. LLR was associated with significantly lower intraoperative blood loss, based on six studies with 333 patients [WMD: -129.48 mL; 95%CI: -224.76-(-34.21) mL; P = 0.008]. Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups. The LLR group had lower blood transfusion requirement (OR: 0.49; 95%CI: 0.26-0.91; P = 0.02). While analyzing hospital stay, six studies with 333 patients were included. Patients in the LLR group were found to have shorter hospital stay [WMD: -3.19 d; 95%CI: -4.09-(-2.28) d; P < 0.00001] than their OLR counterpart. Seven studies including 416 patients were pooled together to estimate the odds of developing postoperative ascites in the patient groups. The LLR group appeared to have a lower incidence of postoperative ascites (OR: 0.32; 95%CI: 0.16-0.61; P = 0.0006) as compared with OLR patients. Similarly, fewer patients had liver failure in the LLR group than in the OLR group (OR: 0.15; 95%CI: 0.02-0.95; P = 0.04). However, no significant differences were found between the two approaches with regards to operation time [WMD: 4.69 min; 95%CI: -22.62-32 min; P = 0.74], bile leakage (OR: 0.55; 95%CI: 0.10-3.12; P = 0.50), postoperative bleeding (OR: 0.54; 95%CI: 0.20-1.45; P = 0.22), pulmonary complications (OR: 0.43; 95%CI: 0.18-1.04; P = 0.06), intra-abdominal abscesses (OR: 0.21; 95%CI: 0.01-4.53; P = 0.32), mortality (OR: 0.46; 95%CI: 0.14-1.51; P = 0.20), presence of positive resection margins (OR: 0.59; 95%CI: 0.21-1.62; P = 0.31) and tumor recurrence (OR: 0.95; 95%CI: 0.62-1.46; P = 0.81).CONCLUSION: LLR appears to be a safe and feasible option for resection of HCC in selected patients based on current evidence. However, further appropriately designed randomized controlled trials should be undertaken to ascertain these findings.     

Hyperglycemia as a risk factor in pancreatic cancer: A nested case-control study using prediagnostic blood glucose levels

ObjectiveTo determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.MethodsProspective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.ResultsThe unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05–1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05–2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26–12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08–8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04–2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.ConclusionsHigh fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.     

Efficacy and tolerability of high and low-volume bowel preparation compared: A real-life single-blinded large-population study

BACKGROUNDLow-volume preparations for colonoscopy have shown similar efficacy compared to high-volume ones in randomized controlled trials (RCT). However, most RCTs do not provide data about clinical outcomes including lesions detection rate. Moreover, real-life comparisons are lacking. AIMTo compare efficacy (both in terms of adequate bowel preparation and detection of colorectal lesions) and tolerability of a high-volume (HV: 4 L polyethylene glycol, PEG) and a low-volume (LV: 2 L PEG plus bisacodyl) bowel preparation in a real-life setting.METHODSConsecutive outpatients referred for colonoscopy were prospectively enrolled between 1 December 2014 and 31 December 2016. Patients could choose either LV or HV preparation, with a day-before schedule for morning colonoscopies and a split-dose for afternoon procedures. Adequate bowel preparation according to Boston Bowel Preparation Scale (BBPS), clinical outcomes including polyp detection rate (PDR), adenoma detection rate (ADR), advanced adenoma detection rate (AADR), sessile/serrated lesion detection rate (SDR) and cancer detection rate and self-reported tolerability of HV and LV were blindly assessed.RESULTSTotal 2040 patients were enrolled and 1815 (mean age 60.6 years, 50.2% men) finally included. LV was chosen by 52% of patients (50.8% of men, 54.9% of women). Split-dose schedule was more common with HV (44.7% vs 38.2%, P = 0.005). High-definition scopes were used in 33.4% of patients, without difference in the two groups (P = 0.605). HV and LV preparations showed similar adequate bowel preparation rates (89.2% vs 86.6%, P = 0.098), also considering the two different schedules (HV split-dose 93.8% vs LV split-dose 93.6%, P = 1; HV day-before 85.5% vs LV day-before 82.3%, P = 0.182). Mean global BBPS score was higher for HV preparations (7.1 ± 1.7 vs 6.8 ± 1.6, P < 0.001). After adjustment for sex, age and indications for colonoscopy, HV preparation resulted higher in PDR [Odds ratio (OR) 1.32, 95%CI: 1.07-1.63, P = 0.011] and ADR (OR 1.29, 95%CI 1.02–1.63, P = 0.038) and comparable to LV in AADR (OR 1.51, 95%CI 0.97-2.35, P = 0.069), SDR and cancer detection rate. The use of standard-definition colonoscopes was associated to lower PDR (adjusted OR 1.59, 95%CI: 1.22-2.08, P < 0.001), ADR (adjusted OR 1.71, 95%CI: 1.26–2.30, P < 0.001) and AADR (adjusted OR 1.97, 95%CI: 1.09-3.56, P = 0.025) in patients receiving LV preparation. Mean Visual Analogue Scale tolerability scored equally (7, P = 0.627) but a ≥ 75% dose intake was more frequent with LV (94.6% vs 92.1%, P = 0.003). CONCLUSIONIn a real-life setting, PEG-based low-volume preparation with bisacodyl showed similar efficacy and tolerability compared to standard HV preparation. However, with higher PDR and ADR, HV should still be considered as the reference standard for clinical trials and the preferred option in screening colonoscopy, especially when colonoscopy is performed with standard resolution imaging.