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Considerable attention has been focused on long‐term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA‐damaged cells. The aim of this study is to examine the dose‐dependent effect of PPI on periampullary cancers in a national population‐based cohort. A nested case–control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A “PPI user” was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow‐up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16–1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose‐dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long‐term PPI use was associated with an increased risk of periampullary cancers in the current population‐based study. Physicians must weigh potential risks of long‐term maintenance against therapeutic benefit., What's new? Proton pump inhibitor (PPI) medications are a common treatment for gastroesophageal reflux disease and peptic ulcer disease. However, some evidence indicates that long‐term use of PPIs might increase cancer risk. This large Taiwanese study found that PPI exposure was indeed slightly linked to an increased risk of periampullary cancers, in a dose‐dependent manner. (This was not seen in patients undergoing H. pylori eradication therapy, however.) These results indicate that physicians must weigh the potential risks of long‐term maintenance use of PPIs against their therapeutic benefit.

For surface modification and nerve regeneration, chitosan, followed by nerve growth factor (NGF), was immobilized onto the interior surface of poly (lactic acit-co-glycolic) conduits, using EDC/NHS/MES system (EDCs) and genipin (GP). Four new conduits were, therefore, obtained and named by immobilizing order-EDCs/EDCs, GP/EDCs, EDCs/GP, and GP/GP groups. The immobilized methods used were evaluated and compared, respectively. The researchers found that the EDCs- and GP-cross-linked chitosan displayed higher hydrophilic than pure poly (DL-lactic acid-co-glycolic acid) (PLGA) in water contact angle experiment, which meant the cell compatibility was improved by the modification. Scanning electron microscopic observations revealed that the GP-cross-linking of chitosan greatly improved cell compatibility while cultured rat PC12 cells were flatter and more spindle-shaped than EDCs-cross-linked chitosan. The results concerning the GP-cross-linked chitosan revealed significant proliferation of the seeded cells relative to pure PLGA films, as determined by counting cells and MTT assay. The NGF was released from the modified conduits in two separate periods--an initial burst in 5 days and then slow release from day 10 to day 40. The GP/EDCs group had the highest NGF value among all groups after the 5th day. Finally, the controlled-release conduits were used to bridge a 10 mm rat sciatic nerve defect. Six weeks following implantation, morphological analysis revealed the highest numbers of myelinated axons in the midconduit and distal regenerated nerve in GP/EDCs group. Therefore, the results confirm that GP/EDCs groups with good cell compatibility and effective release of NGF can considerably improve peripheral nerve regeneration.