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Background There is concern but no solid evidence that morcellation during laparoscopic or vaginal hysterectomy may cause abdominal spread and thereby impaired prognosis of incidental uterine sarcomas. Objective Our purpose was to compare survival among patients with uterine sarcomas who underwent hysterectomy with or without morcellation to test the hypothesis that morcellation impairs prognosis. Study design We identified all women in Norway diagnosed with uterine sarcoma between 1953 and 2012 through national registries and retrieved data on surgical technique and morcellation by evaluation of patient files. Patients were categorised into abdominal, laparoscopic or vaginal hysterectomy with or without morcellation. Vaginal and laparoscopic hysterectomies were introduced in 1991; our main comparison is from 1991 to 2012. We compared age-adjusted disease-specific survival of sarcoma patients treated with or without morcellation and calculated age-adjusted hazard ratios (HRs) and subdistribution HR (accounting for competing risk) with 95% confidence intervals (CIs). Results Among 1367 patients with uterine sarcoma between 1953 and 2012 in Norway, 653 were diagnosed after 1991, and 23 of these patients (3.5%) underwent morcellation. Uterine sarcoma prevalence was 3.6 per 1000 laparoscopic hysterectomies. Mean follow-up was 6.0 years in the morcellated group and 6.9 years in the non-morcellated group. The risk of dying from uterine sarcoma after morcellation was 1.5 per 1000 procedures. Sarcoma mortality was higher in the morcellated group than in the non-morcellated group (age-adjusted HR 1.90, CI 1.05–3.44; multivariate HR, 2.50, 95% CI 0.57–10.9). Age-adjusted 10-year uterine sarcoma survival was 32.2% for women treated with morcellation compared with 57.2% for non-morcellated group (difference 25.5%; CI −55.7 to 18.1). All-cause 10-year survival was 32.2% in the morcellated group and 44.1% in the non-morcellated group (difference 11.9%; CI −40.9 to 32.7). Conclusion Our results strengthen the evidence that morcellation during hysterectomy in patients with incidental uterine sarcoma may cause impaired survival. These results can guide shared decision-making in clinical practice.

Background & aims Partner burden is common in celiac disease (CD), but it is unclear if parents of children with CD have increased burden, and if this may translate into depression and anxiety meriting healthcare. Methods Nationwide population-based study of 41,753 parents and spouses (“caregivers”) to 29,096 celiac patients and 215,752 caregivers to 144,522 matched controls. Caregivers were identified from the Swedish Total Population Register, and linked to data on psychiatric disease in the National Patient Registry. Hazard ratios (HRs) for depression, anxiety, and (as a reference outcome measure) bipolar disorder were examined in a lifetime fashion but also in temporal relationship to date of CD diagnosis using Cox regression. A priori, we focused on parents of individuals diagnosed ≤19 years of age (children at the age of disease onset) and spouses of individuals diagnosed in adulthood, as such parents and spouses (“high-risk caregivers”) were most likely to live together with the patient at time of disease onset. Results On Cox analysis, depression was 11% more common in high-risk caregivers (HR = 1.11: 95%CI = 1.03–1.19) than in control caregivers while anxiety was 7% more common (HR = 1.07: 95%CI = 0.98–1.16). Combining anxiety and depression into a composite outcome measure, there was an 8% statistically significant risk increase (95%CI = 1.02–1.14). The highest excess risks for both depression and anxiety were seen just before and 4–8 years after the CD diagnosis. In contrast, bipolar disorder was not more common in caregivers to CD patients. Conclusion Caregivers to patients with CD may be at increased risk of severe burden.

The view, that rapidly growing tumours are more likely than slow-growing tumours to metastasize and become lethal, has remained almost axiomatic for decades. Unaware of any solid evidence supporting this view, we undertook an exhaustive system-level analysis of intra- and intercellular signalling networks. This analysis indicated that rapid growth and metastasis are often different outcomes of complex integrated molecular events. Evidence from humans can be derived chiefly from screening interventions because interval cancers that surface clinically shortly after a negative screening test are, on average, more rapidly growing than cancers not detected by screening. We reviewed all available data limited to cancers of the breast, cervix and large bowel. The evidence from humans provides no support for the theory that rapidly growing cancers are more prone to metastasize. These findings indicate that the prevailing view should be reconsidered, as should the impact of length-biased sampling in cancer screening, and the findings provide no support for treating interval cancers more aggressively than non-interval cancers.

Several studies have shown an excess mortality in individuals with celiac disease (CD). However, it is unknown if also first-degree relatives (FDRs) to celiac patients are at increased risk of death.We aimed to assess mortality in FDRs to celiac patients.Individuals with CD were identified through biopsy reports (equal to Marsh grade III). Each celiac individual was matched on sex, age, county and calendar year with up to five control individuals. Through Swedish healthcare registries we identified all FDRs (father, mother, sibling, offspring) of CD individuals and controls. Through Cox regression we calculated hazard ratios (HRs) for mortality (all-cause death, circulatory, cancer and other).We identified 109,309 FDRs of celiac individuals and 549,098 FDRs of controls. Overall mortality was increased in FDRs to celiac individuals (HR=1.02, 95%CI=1.00-1.04, p=0.03). This corresponded to an excess risk of 5.9 deaths per 100,000 person-years of follow-up. When limiting follow-up to time since celiac diagnosis in the index individual, we found no increased risk of death (HR=1.01; 95%CI=0.98-1.03).FDRs to individuals with CD are at increased risk of death. This excess risk is however minimal and unlikely to be of any clinical importance to the individual.

Background Coeliac disease has been associated with an increased risk of cardiovascular disease in some studies, whereas other studies have shown no association. We performed a systematic review and meta-analysis of cardiovascular disease in celiac disease. Methods Pubmed, Cinahl, EMBASE and Medline via Ovid were searched for relevant articles published until January 5, 2015. English-language articles on studies with more than 20 patients were included, and were quality rated using the GRADE risk of bias tool. We used random-effects models and assessed heterogeneity using the I 2 statistic. Results Ten studies were relevant, reporting the risk of myocardial infarction, cardiovascular death and stroke in 33,128/32,903/32,466 coeliac disease patients respectively. Only one study examined celiac disease and a composite measure of cardiovascular disease and this study found a hazard ratio of 1.10 (95%CI 1.03–1.28). In a meta-analysis, we observed an increased risk of stroke (OR 1.11; 95%CI 1.02–1.20). The risks of myocardial infarction (OR 1.12; 95%CI 0.83–1.40) and cardiovascular death (OR 1.12; 95%CI 0.96–1.29) were similar but were estimated with less certainty. Heterogeneity was low for all outcomes except for myocardial infarction where it was moderate. Conclusion Coeliac disease was associated with a modestly increased risk of cardiovascular disease, but the evidence base is limited.

Background & Aims There have been inconsistent reports of prenatal and perinatal factors that affect risk for development of celiac disease. We assessed the association of fetal growth, birth weight, and mode of delivery with development of celiac disease within the Norwegian Mother and Child (MoBa) Cohort Study. Methods The MoBa cohort contains pregnancy information on 95,200 women and data on their 114,500 children, which were collected in Norway from 1999 through 2008; it is linked to the Medical Birth Registry. Women and children with celiac disease were identified from the National Patient Registry and from women's responses to MoBa questionnaires. We calculated odds ratios (ORs) for celiac disease by using a multivariable logistic regression model, adjusting for maternal celiac disease, sex of children, and children's age (model 1); in a second model, we adjusted for age of gluten introduction and duration of breastfeeding (model 2). Results We identified 650 children with celiac disease and 107,828 controls in the MoBa database. We found no association between birth weight or height with celiac disease (born small for gestational age was not associated). Celiac disease was not associated with mode of delivery (cesarean section, model 1: OR, 0.84; 95% confidence interval [CI], 0.65–1.09, and model 2: OR, 0.83; 95% CI, 0.63–1.09). Maternal celiac disease, adjusted for age and sex of the children (OR, 12.45; 95% CI, 8.29–18.71) and type 1 diabetes (model 1: OR, 2.58; 95% CI, 1.19–5.53, and model 2: OR, 2.61; 95% CI, 1.14–5.98) were associated with development of celiac disease in children, whereas maternal type 2 diabetes and gestational diabetes were not. Conclusions On the basis of analysis of the Norwegian MoBa cohort, development of celiac disease in children is significantly associated with sex of the child, maternal celiac disease, and type 1 diabetes but not with intrauterine growth.

Background & Aims Endoscopic screening for colorectal cancer (CRC) is performed at longer time intervals than the fecal occult blood test or screenings for breast or prostate cancer. This causes concerns about interval cancers, which have been proposed to progress more rapidly. We compared outcomes of patients with interval CRCs after sigmoidoscopy screening vs outcomes of patients with CRC who had not been screened. Methods We performed a secondary analysis of a randomized sigmoidoscopy screening trial in Norway with 98,684 participants (age range, 50–64 years) who were randomly assigned to groups that were (n = 20,552) or were not (n = 78,126) invited for sigmoidoscopy screening from 1999 through 2001; participants were followed up for a median 14.8 years. We compared CRC mortality and all-cause mortality between individuals who underwent screening and were diagnosed with CRC 30 days or longer after screening (interval cancer group, n = 163) and individuals diagnosed with CRC in the nonscreened group (controls, n = 1740). All CRCs in the control group were identified when they developed symptoms (clinically detected CRCs). Analyses were stratified by cancer site. We used Cox regression to estimate hazard ratio (HRs), adjusted for age and sex. Results Over the follow-up period, 43 individuals in the interval cancer group died from CRC; among controls, 525 died from CRC. CRC mortality (adjusted HR, 0.98; 95% confidence interval, 0.72–1.35; P = .92), rectosigmoid cancer mortality (adjusted HR, 1.10; 95% confidence interval, 0.63–1.92; P = .74), and all-cause mortality (adjusted HR, 0.99; 95% confidence interval, 0.76–1.27; P = .91) did not differ significantly between the interval cancer group and controls. Conclusions In this randomized sigmoidoscopy screening trial, mortality did not differ significantly between individuals with interval CRCs and unscreened patients with clinically detected CRCs. ClinicalTrials.gov identifier: NCT00119912 .

High experienced continuity in breast cancer care is associated with high health related quality of life and compatible with good medical quality and approved lead times

Olmesartan-Associated Sprue: A French National Study Lysiane Marthey, Guillaume Cadiot, Philippe Seksik, Philippe Pouderoux, Joel Lacroute, Florence Skinazi, Bruno Mesnard, Jean Alain Chayvialle, Eric Lerebours, Anne Druez, David Parlier, Vered Abitbol, Michel Gompel, Matthieu Eoche, Eric Poncin, Roland Bobichon, Philippe Colardelle, Pauline Wils, Nadine Cerf Bensussan, Georgia Malamut, Franck Carbonnel