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Objective To evaluate potential linear and non-linear dose-response relations between blood glucose and risk of pancreatic cancer.Design Systematic review and dose-response meta-analysis of prospective observational studies.Data sources Search of PubMed, Scopus, and related reviews before 30 November 2013 without language restriction.Eligibility criteria Prospective studies evaluating the association between blood glucose concentration and pancreatic cancer. Retrospective and cross sectional studies excluded to avoid reverse causality.Data extraction and synthesis Two reviewers independently extracted relevant information and assessed study quality with the Newcastle-Ottawa scale. Random effects dose-response meta-analysis was conducted to assess potential linear and non-linear dose-response relations.Results Nine studies were included for analysis, with a total of 2408 patients with pancreatic cancer. There was a strong linear dose-response association between fasting blood glucose concentration and the rate of pancreatic cancer across the range of prediabetes and diabetes. No non-linear association was detected. The pooled rate ratio of pancreatic cancer per 0.56 mmol/L (10 mg/dL) increase in fasting blood glucose was 1.14 (95% confidence interval 1.06 to 1.22; P<0.001) without significant heterogeneity. Sensitivity analysis excluding blood glucose categories in the range of diabetes showed similar results (pooled rate ratio per 0.56 mmol/L increase in fasting blood glucose was 1.15, 95% confidence interval 1.05 to 1.27; P=0.003), strengthening the association between prediabetes and pancreatic cancer.Conclusions Every 0.56 mmol/L increase in fasting blood glucose is associated with a 14% increase in the rate of pancreatic cancer. As prediabetes can be improved or even reversed through lifestyle changes, early detection of prediabetes coupled with lifestyle changes could represent a viable strategy to curb the increasing incidence of pancreatic cancer.

Cyclooxygenase-2 (COX-2) is an inducible enzyme important in inflammation and which is overexpressed in a variety of cancers. This study investigated its role in angiogenesis of gastric carcinoma (GC). Immunohistochemical examination of surgical specimens showed a positive correlation among COX-2, vascular endothelial growth factor (VEGF), and vasculature in GC. After transfection with a COX-2-expressing vector, the AGS GC cell line showed increases in both proliferation and tube formation of human umbilical vein endothelial cells (HUVECs). These in vitro angiogenic effects on HUVECs were reduced either by blocking VEGF or NS-398, a COX-2 inhibitor. To elucidate the mechanism by which COX-2 increases angiogenesis, we established a COX-2-expressing clone, AGS/COX-2, and its vector control clone, AGS/pcDNA3, and verified their functions by determining prostaglandin E2 (PGE2). Among 6 angiogenesis-associated factors, VEGF was considerably expressed in AGS/COX-2. After reducing hypoxia-inducible factor-1alpha (HIF-1alpha) protein by antisense HIF-1alpha transfection, VEGF production was reduced in AGS/COX-2 cells in a dose-dependent manner. We found that HIF-1alpha increased concomitantly with VEGF after exogenous PGE2 stimulation to wild-type AGS cells, but this effect was blocked by SC19220, a PGE2 receptor antagonist. In addition, pretreatment with NS-398 to reduce PGE2 also effectively suppressed HIF-1alpha protein accumulation and achieved a similar inhibitory effect on VEGF production as did antisense HIF-1alpha transfection. Our work supports the COX-2/PGE2/HIF-1alpha/VEGF pathway possibly contributing to tumor angiogenesis in GC.

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Image-enhanced endoscopy is helpful for screening of a second primary neoplasm in patients with esophageal and head and neck cancer. The purpose of this meta-analysis was to determine the diagnostic efficacy of white-light imaging (WLI), narrow band imaging (NBI), and Lugol chromoendoscopy for second primary neoplasm detection. A review of the PubMed/Cochrane databases up to May 2014 was performed. Meta-analysis was done by Meta-DiSc software and the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 4918 patients from 16 prospective and randomized trials were enrolled. For WLI, NBI, and Lugol chromoendoscopy, the pooled sensitivities were 53% (95% confidence interval [CI] = 48% to 59%), 87% (95% CI = 83% to 90%), and 88% (95% CI = 85% to 91%), respectively; the pooled specificities were 99% (95% CI = 98% to 99%), 95% (95% CI = 94% to 96%), and 63% (95% CI = 61% to 66%), respectively; and the areas under the receiver-operating characteristic (ROC) curve were 66%, 97%, and 82%, respectively. NBI endoscopy has the most highly accurate diagnostic performance for detection of second primary neoplasms in high-risk patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2343-E2349, 2016.

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We quantified field cancerization of squamous cell carcinoma in the upper aerodigestive tract with epigenetic markers and evaluated their performance for risk assessment. Methylation levels were analyzed by quantitative methylation-specific PCR of biopsied specimens from a training set of 255 patients and a validation set of 224 patients. We also measured traditional risk factors based on demographics, lifestyle, serology, genetic polymorphisms, and endoscopy. The methylation levels of four markers increased stepwise, with the lowest levels in normal esophageal mucosae from healthy subjects without carcinogen exposure, then normal mucosae from healthy subjects with carcinogen exposure, then normal mucosae from cancer patients, and the highest levels were in cancerous mucosae (P < 0.05). Cumulative exposure to alcohol increased methylation of homeobox A9 in normal mucosae (P < 0.01). Drinkers had higher methylation of ubiquitin carboxyl-terminal esterase L1 and metallothionein 1M (P < 0.05), and users of betel quid had higher methylation of homeobox A9 (P ¼ 0.01). Smokers had increased methylation of all four markers (P < 0.05). Traditional risk factors allowed us to discriminate between patients with and without cancers with 74% sensitivity (95% CI: 67%-81%), 74% specificity (66%-82%), and 80% area under the curve (67%-91%); epigenetic markers in normal esophageal mucosa had values of 74% (69%-79%), 75% (67%-83%), and 83% (79%-87%); and both together had values of 82% (76%-88%), 81% (74%-88%), and 91% (88%-94%). Epigenetic markers done well in the validation set with 80% area under the curve (73%-85%). We concluded that epigenetics could improve the accuracies of risk assessment.