DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Peer reviewe

To års erfaring med endoskopisk colonstenting ved Akershus univeristetssykehus

Introductio: Emergency surgery performed on patients with acute bowel obstruction is associated with a high mortality and morbidity rate. Since 1991, the use of self-expanding metal stents (SEMS) has been introduced as an alternative management either as palliation or as a bridge to surgery. The use of SEMS as emergency management for patients with malignant bowel obstruction was introduced at Akershus Universitetssykehus (Ahus) in April 2008. The aim of our study was to evaluate the results of patients primarily treated with stents. Methods: From April 08 to June 10, 17 patients admitted with acute colorectal obstruction were treated with stents. 6 of these patients had known inoperable colorectal cancer, and the stents were placed as palliation. 11 stents were placed as a bridge to surgery. The site of obstruction varied with 5 in rectal colon, 9 in sigmoid colon and 3 in descending colon. In one patient, 2 stents were placed initially. With one exception, where the stent most likely perforated a few hours after placement, there were no problems associated with the procedure. Results: The overall technical and clinical success rates were 88% and 75% respectively. Among the 6 patients with palliative stents, the mean survival time from stent placement to death was 140 days [1-290]. The literature reports a mean duration of patency of approximately 145 days. 50% of the palliative patients did not require any further surgical treatment. One patient died of a possible stent-perforation one day after stent-placement, and two patients underwent emergency surgery due to a persistent colon obstruction. The literature reports a complication rate and re-intervention rate of 25% and 20% respectively Mean time for progression to surgery after stent placement in the bridge to surgery group was 15 days. The literature reports a mean time of 12 days. 2 of 11 patients underwent emergency surgery due to stent-perforation and stent-obstruction, giving a re-intervention rate of 18%. The literature reports a re-intervention rate of 19%. Conclusion: Our results are supported by a growing amount of evidence, and suggest that the use of SEMS as management of malignant colorectal obstruction is a safe and effective technique with a low mortality and morbidity rate. Patients with inoperable colorectal cancer can be spared the risks of emergency surgery, and placed as a bridge to surgery, the use of SEMS can lower the morbidity and mortality rate and reduce the need of stoma

Studies on the ileal pouch-anal anastomosis

Variability in functional outcome after ileal pouch-anal anastomsis is to a large extent unexplained. The aim of the thesis was to investigate postoperative function, and to examine well and poorly functioning patients to determine factors contributing to functional outcome. All patients operated on between 2000-2013 were interviewed regarding quality of life (QoL), sexual function and pouch function. The best and worst functioning patients were invited to undergo manovolumetric testing, pouch endoscopy and a pelvic MRI. The patients had similar QoL and sexual function as the Norwegian population. Poor pouch function was negatively correlated to QoL in all patients, and to sexual function in women. Well functioning patients had a larger pouch volume and shorter rectal cuff. Poor functioning patients had a higher prevalence of inflammation and hand sewn anastomosis. There were no differences in MRI findings between the groups. In conclusion, patients can expect good QoL and sexual function after surgery. Small improvements in function will impact QoL. Pouch volume was the most prominent predictor of functional outcome

Distinct gastric phenotype in patients with pathogenic variants in SMAD4: A nationwide cross-sectional study

Background and study aims In most patients with juvenile polyposis Syndrome, it is possible to detect a pathogenic germline variant in SMAD4 or BMPR1A. It is well known that patients with a pathogenic variant in SMAD4 have a higher risk of gastric polyposis and gastric cancer compared to BMPR1A carriers, but the natural history of gastric involvement is poorly described. We aimed to systematically review endoscopic and histopathological gastric findings in Danish patients with pathogenic variants in SMAD4. Patients and methods This was a retrospective, cross-sectional study including endoscopic and histological gastric findings in all known Danish patients with pathogenic variants in SMAD4. The patients were identified by data from various registries as well as from clinical genetic departments and laboratories. Results We identified 41 patients (2–72 years) with a pathogenic SMAD4 variant. In 31 patients, we were able to retrieve information on upper gastrointestinal endoscopy. Eighty-seven percent had at least one gastric abnormality including erythema (72 %) and edema (72 %). Half of the patients also had vulnerability of the mucosa and 68 % had gastric polyposis. An increasing frequency of abnormalities were observed with increasing age. Gastric cancer was diagnosed in 5 % of the cases and 22 % had a gastrectomy mainly because of massive polyposis. Conclusions This study showed that most patients with pathogenic SMAD4 variants have a distinct phenotype of the gastric mucosa, and with an increasing severity in the elderly patients. These findings provide new insights into the natural history of gastric manifestations in patients with pathogenic SMAD4 variants