Chronic upper abdominal pain occurs as a complication of various malignant and benign diseases including pancreatic cancer and chronic pancreatitis, and when present may contribute to lower quality of life and higher mortality. Though various pain management strategies are available as part of a multimodal approach, they are often incompletely effective and accompanied by side effects. Pain originating in upper abdominal viscera is transmitted through the celiac plexus, which is an autonomic plexus located in the retroperitoneum at the root of the celiac trunk. Direct intervention at the level of the plexus, referred to as celiac plexus block or neurolysis depending on the injectate, is a minimally invasive therapeutic strategy which has been demonstrated to decrease pain, improve function, and reduce opiate dependence. Various percutaneous techniques have been reported, but, with appropriate preprocedural planning, use of image guidance (usually computed tomography), and postprocedural care, the frequency and severity of complications is low and the success rate high regardless of approach. The main benefit of the intervention may be in reduced opiate dependence and opiate-associated side effects, which in turn improves quality of life. Celiac plexus block and neurolysis are safe and effective treatments for chronic upper abdominal pain and should be considered early in patients experiencing such symptoms.

BackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive correction. We have produced a ranked list of variants with the strongest association signals. Variants in the highest rank of associations are likely to include true associations and should be high priority candidates for further study of NTD risk.