A multidisciplinary evidence-based guideline for minimally invasive surgery.: Part 1: entry techniques and the pneumoperitoneum

The Dutch Society for Endoscopic Surgery together with the Dutch Society of Obstetrics and Gynecology initiated a multidisciplinary working group to develop a guideline on minimally invasive surgery to formulate multidisciplinary agreements for minimally invasive surgery aiming towards better patient care and safety. The guideline development group consisted of general surgeons, gynecologists, an anesthesiologist, and urologist authorized by their scientific professional association. Two advisors in evidence-based guideline development supported the group. The guideline was developed using the "Appraisal of Guidelines for Research and Evaluation" instrument. Clinically important aspects were identified and discussed. The best available evidence on these aspects was gathered by systematic review. Recommendations for clinical practice were formulated based on the evidence and a consensus of expert opinion. The guideline was externally reviewed by members of the participating scientific associations and their feedback was integrated. Identified important topics were: laparoscopic entry techniques, intra-abdominal pressure, trocar use, electrosurgical techniques, prevention of trocar site herniation, patient positioning, anesthesiology, perioperative care, patient information, multidisciplinary user consultation, and complication registration. The text of each topic contains an introduction with an explanation of the problem and a summary of the current literature. Each topic was discussed, considerations were evaluated and recommendations were formulated. The development of a guideline on a multidisciplinary level facilitated a broad and rich discussion, which resulted in a very complete and implementable guidelin

Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium

International audienceIncidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations

Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells

Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the highest known for cancers1. However, only a limited number of genetic risk loci have been identified, and the underlying biological mechanisms that lead to the acquisition of MPNs remain unclear. Here, by conducting a large-scale genome-wide association study (3,797 cases and 1,152,977 controls), we identify 17 MPN risk loci (P < 5.0 × 10-8), 7 of which have not been previously reported. We find that there is a shared genetic architecture between MPN risk and several haematopoietic traits from distinct lineages; that there is an enrichment for MPN risk variants within accessible chromatin of HSCs; and that increased MPN risk is associated with longer telomere length in leukocytes and other clonal haematopoietic states-collectively suggesting that MPN risk is associated with the function and self-renewal of HSCs. We use gene mapping to identify modulators of HSC biology linked to MPN risk, and show through targeted variant-to-function assays that CHEK2 and GFI1B have roles in altering the function of HSCs to confer disease risk. Overall, our results reveal a previously unappreciated mechanism for inherited MPN risk through the modulation of HSC function