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Introduction A significant proportion of patients with ulcerative colitis (UC) undergo colectomy. The aim was to assess the quality of life (QOL) of these patients. Material and methods All patients with UC who underwent colectomy at The National University Hospital of Iceland or Akureyri Hospital 1995-2009 were included. 106 patients received three questionnaires. SF-36v2 and EORTC are standardised QOL-questionnaires. The third contained functional questions designed by the researchers. Results Eighty-three patients replied (78%), 45 men (54%) and 38 women (46%). Average age at operation was 45 years (10-91 years). Forty-four (53%) had ileostomy, 28 (34%) ileal pouch-anal anastomosis (IPAA) and 11 (13%) ileorectal anastomosis. Among patients who had the rectum removed 37% described changes in urinary habits and 46% in sexual life after surgery. Among patients with IPAA 75% admitted to faecal incontinence but this was mild according to Wexner's scale in 83% of the cases. According to SF-36v2 there was no significant difference in the QOL of colectomy patients compared to the general population. Patients generally felt good about their health, body image and weight and had mild symptoms according to EORTC QLQ-CR29. Conclusions Urinary habits and sexual life were commonly affected after rectal removal. Faecal incontinence among IPAA-patients was much more common than expected. There was not much difference in quality of life compared to the general population. The results of the study are important for patient education and may aid them in their decision making since removing the colon or having a stoma does not seem to affect quality of life. Key words: Quality of life, ulcerative colitis, ileostomy, colectomy. Correspondence: Elsa B. Valsdottir, elsava@landspitali.is.

Background & Aims Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis. Methods We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95, 605 incident cases of Crohn’s disease (CD) (42, 831 male and 52, 774 female) and 112, 004 incident cases of ulcerative colitis (UC) (61, 672 male and 50, 332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis. Results Female patients had a lower risk of CD during childhood, until the age range of 10–14 years (incidence rate ratio, 0.70 ; 95% CI, 0.53– 0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25–29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5–9 years) until age 45 years ; thereafter, men had a significantly higher incidence of ulcerative colitis than women. Conclusions In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.

Diverticular disease is characterized by pouches (that is, diverticulae) due to weakness in the bowel wall, which can become infected and inflamed causing diverticulitis, with potentially severe complications. Here, we test 32.4 million sequence variants identified through whole-genome sequencing (WGS) of 15,220 Icelanders for association with diverticular disease (5,426 cases) and its more severe form diverticulitis (2,764 cases). Subsequently, 16 sequence variants are followed up in a diverticular disease sample from Denmark (5,970 cases, 3,020 controls). In the combined Icelandic and Danish data sets we observe significant association of intronic variants in ARHGAP15 (Rho GTPase-activating protein 15; rs4662344-T: P=1.9 × 10−18, odds ratio (OR)=1.23) and COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase; rs7609897-T: P=1.5 × 10−10, OR=0.87) with diverticular disease and in FAM155A (family with sequence similarity 155A; rs67153654-A: P=3.0 × 10−11, OR=0.82) with diverticulitis. These are the first loci shown to associate with diverticular disease in a genome-wide study., A hallmark of diverticular disease is pouches in the bowel wall which can become infected and inflamed, causing the more severe diverticulitis. Here, the authors report the first genome-wide association study on these interconnected conditions and identify ARHGAP15, COLQ and FAM155A as novel risk loci.

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000–2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations., This study was funded by the Ohio State University (OSU) Comprehensive Cancer Center P30 CA16058 grant (shared resource), the OSU R01-67941 grant, the OSU Colorectal Cancer Research fund, the Obrine-Weaver Fund, the Pelotonia Fellowship Award and deCODE genetics.

The aim of this study was to characterize the familial risk of colon and rectal cancer using 2 population-based registries in Iceland, the Icelandic Cancer Registry and a genealogy database. The standardized incidence ratio (SIR) was used to estimate the risk among relatives of colorectal cancer index cases diagnosed in Iceland over a 46-year period (1955-2000). The 2,770 colorectal cancer patients had 23,272 first-degree relatives. Among first-degree relatives, there was an increased risk of both colon (SIR 1.47, 95% confidence interval (CI) 1.34-1.62) and rectal cancer (SIR 1.24, 95% CI 1.04-1.47). An increased risk of colon cancer was observed among siblings of colon cancer patients (SIR 2.03, 95% CI 1.76-2.33), whereas no such increase was observed for parents or offspring. Furthermore, the risk of rectal cancer was only increased among brothers (SIR 2.46 95% CI 1.46-3.89) of rectal cancer patients and not among their sisters (SIR 1.0 95% CI 0.40-2.06). The added risk of colon cancer among first-degree relatives was independent of site of colon cancer in the proband. Our results confirm that family history of colorectal cancer is a risk factor for the disease. However, family history has a different association with colon cancer than with rectal cancer, suggesting that the 2 cancer types may have different etiologic factors. Our results have implications for colon and rectal cancer screening programs.

IMPORTANCE Although some countries have implemented widespread colonoscopy screening, most European countries have not introduced it because of uncertainty regarding participation rates, procedure-related pain and discomfort, endoscopist performance, and effectiveness. To our knowledge, no randomized trials on colonoscopy screening currently exist. OBJECTIVE To investigate participation rate, adenoma yield, performance, and adverse events of population-based colonoscopy screening in several European countries. DESIGN, SETTING, AND POPULATION A population-based randomized clinical trial was conducted among 94959 men and women aged 55 to 64 years of average risk for colon cancer in Poland, Norway, the Netherlands, and Sweden from June 8, 2009, to June 23, 2014. INTERVENTIONS Colonoscopy screening or no screening. MAIN OUTCOMES AND MEASURES Participation in colonoscopy screening, cancer and adenoma yield, and participant experience. Study outcomes were compared by country and endoscopist. RESULTS Of 31 420 eligible participants randomized to the colonoscopy group, 12 574 (40.0%) underwent screening. Participation rates were 60.7% in Norway (5354 of 8816), 39.8% in Sweden (486 of 1222), 33.0% in Poland (6004 of 18 188), and 22.9% in the Netherlands (730 of 3194) (P < .001). The cecum intubation rate was 97.2%(12 217 of 12 574), with 9726 participants (77.4%) not receiving sedation. Of the 12 574 participants undergoing colonoscopy screening, we observed 1 perforation (0.01%), 2 postpolypectomy serosal burns (0.02%), and 18 cases of bleeding owing to polypectomy (0.14%). Sixty-two individuals (0.5%) were diagnosed with colorectal cancer and 3861 (30.7%) had adenomas, of which 1304 (10.4%) were high-risk adenomas. Detection rates were similar in the proximal and distal colon. Performance differed significantly between endoscopists; recommended benchmarks for cecal intubation (95%) and adenoma detection (25%) were not met by 6 (17.1%) and 10 of 35 endoscopists (28.6%), respectively. Moderate or severe abdominal pain after colonoscopy was reported by 601 of 3611 participants (16.7%) examined with standard air insufflation vs 214 of 5144 participants (4.2%) examined with carbon dioxide (CO2) insufflation (P < .001). CONCLUSIONS AND RELEVANCE Colonoscopy screening entails high detection rates in the proximal and distal colon. Participation rates and endoscopist performance vary significantly. Postprocedure abdominal pain is common with standard air insufflation and can be significantly reduced by using CO2.

Background and study aim: While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. Study design: Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. Power analysis: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. Conclusions: The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population. Trial registration: NCT 00883792.

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

Objective. We analyzed the incidence of inflammatory bowel disease (IBD) in Iceland for the period 1995–2009. Material and methods. New cases of ulcerative colitis (UC) and Crohn’s disease (CD) were retrieved by thorough review of all small and large intestinal pathology reports with any type of inflammation from all the pathology departments in Iceland for the period 1995–2009. All suspicious new cases of IBD were then scrutinized retrospectively by examination of their clinical records. Results. A total of 1175 cases of IBD were diagnosed, 884 UC, 279 CD and 12 IBD unclassified. The crude annual incidence of UC was 20.5/100,000, increasing from 18.1 the first 5-year period to 22.1 the last 5-year period. The crude annual incidence of CD was 6.5/100,000, 6.7 the first 5-year period and 6.6 the last 5-year period. Conclusions. This study shows statistically significant increase in the incidence of UC during the study period. The incidence of CD has however remained stable.

According to clinical guidelines, a colonoscopy is recommended after an attack of diverticulitis in order to exclude colorectal cancer (CRC). This is based on studies prior to the use of computerized tomography (CT) for confirmation of the diagnosis. We aimed to investigate the findings of a subsequent colonoscopy after an attack of uncomplicated diverticulitis.The study cohort consisted of all patients with the diagnosis of uncomplicated diverticulitis, who underwent a subsequent colonoscopy 6-8 weeks later during a 6-years period in the National University Hospital of Iceland. The diagnosis of diverticulitis was based on clinical symptoms verified with a CT of the abdomen. Relevant clinical information was obtained from medical records and from the Icelandic Cancer Registry.A total of 282 patients had uncomplicated diverticulitis and 199 patients underwent endoscopy. Two patients had CRC (0.7%), diagnosed with diverticulitis but did not recover clinically. All other patients recovered clinically. Colonic polyps were found in 33 of 195 (17%) cases. In 19/33 (58%) cases the histology demonstrated hyperplastic polyps, and in 13/33 (39%) adenoma with mild dysplasia. Only 1/33 (3%) of the colonic polyps were1 cm in size.Among patients experiencing an attack of uncomplicated diverticulitis the frequency of CRC was equal to what might be expected compared to the average risk in the population. In these patients a routine colonoscopy in the absence of other clinical signs of CRC seems hardly necessary, if the clinical course is uneventful and the patient recovers.

Purpose: to evaluate the use of laparoscopy, CT, colonic enema (CE), and laboratory tests (white blood cell count (WBC), sedimentation rate (SR), and C-reactive protein (CRP)) in diagnosing diverticulitis of the sigmoid colon. Material and Methods: the diagnostic methods were prospectively evaluated in 88 patients, 30 of whom were referred for laparoscopy. Results: Fifty-two patients were found to have sigmoid diverticulitis: 20 patients by laparoscopy, 21 by CT, and 11 by CE combined with one positive laboratory test. Laparoscopy proved to be superior to the other diagnostic methods in diagnosing diverticulitis of the sigmoid colon. CT had a high specificity (1.0; 95% CI: 0.92–1.0) but low sensitivity (0.69; 95% CI: 0.56–0.79) in detecting diverticulitis. CE had a higher sensitivity (0.82; 95% CI: 0.71–0.90) but a lower specificity (0.81; 95% CI: 0.67–0.91) than CT. Conclusion: CT was the best method for diagnosing abdominal pathology outside the colon. CT can be recommended as the first examination in seriously ill patients where abscesses and other causes of the symptoms than diverticulitis must first be ruled out. Laparoscopy is probably the most accurate method in diagnosing diverticulitis.

Contains fulltext : 97569.pdf (Publisher’s version ) (Closed access) To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 x 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 x 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 x 10(-6)), glioma (OR = 2.35, P = 1.0 x 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 x 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).