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Aim Cytoreductive surgery ( CRS) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC) is a treatment option with curative intent for selected patients with peritoneal carcinomatosis ( PC). CRS and HIPEC have been implemented in Denmark at a single centre since 2006. Six years of data on these patients were analysed. Method Patients with PC from colorectal or appendiceal cancer, pseudomyxoma peritonei or malignant peritoneal mesothelioma referred to the single national HIPEC centre were prospectively registered from June 2006 to July 2012. Morbidity, 30-day mortality and long-term survival of patients who underwent CRS and HIPEC were analysed. Results In total, 80 patients underwent CRS and HIPEC. PC originated from colorectal cancer in 34 patients, pseudomyxoma peritonei in 29, appendiceal cancer in 13 and malignant peritoneal mesothelioma in four patients. Thirty-two patients had one or more complications during the hospital stay. The 30-day mortality rate was 1.3%. The predicted 2-, 3- and 5-year survival was 60%, 47% and 38% in patients with PC from colorectal cancer, and 100%, 93% and 73% in pseudomyxoma peritonei patients. Conclusion CRS and HIPEC is a safe procedure when centralized as in Denmark. Favourable long-term outcome was achieved in selected patients with PC from colorectal cancer and pseudomyxoma peritonei. Short-term and long-term outcomes were comparable to results from international centres. [ABSTRACT FROM AUTHOR]

Background: Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in FIT-positive screening populations. We evaluated the CRC and advanced adenoma risk within the recommended surveillance periods in the Danish FIT-based CRC screening program for participants with intermediate or high risk adenomas according to 2010 European guidelines. Furthermore, we estimated CRC risk for those who were not recommended surveillance according to European Society of Gastrointestinal Endoscopy (ESGE) 2020 guidelines., Methods: Using nationwide health registries, we identified 17 936 FIT-screening participants from 2014-2017 with adenomas undergoing surveillance (high risk 1 year, intermediate risk 3 years). Participants with a follow-up examination were included (N = 10 068). Relative risk (RR) of CRC and advance adenoma was compared between intermediate and high risk groups and between intermediates who were recommended surveillance (S) or no surveillance (NS) according to 2020 ESGE guidelines., Results: During surveillance, CRC occurred in 0.59% of the high risk group and 1.11% of the intermediate risk group (RR 0.53 [95%CI 0.34-0.84]). The high risk group had a 24% increased risk of advanced adenoma. CRC occurred in 1.69% of the intermediateNS group and 0.87% of the intermediateS group (RR 1.94 [95%CI 1.18-3.21]), and RR for advanced adenoma was 1.19 (95%CI 1.03-1.37)., Conclusion: CRC detection was lower among participants rated at higher risk at initial CRC screening. Findings at first screen-derived colonoscopy might not be as good a predictor of CRC risk in a FIT-positive screening population., Competing Interests: Berit Andersen is head of the colorectal cancer screening programme in Central Denmark Region and member of the National Steering committee for Colorectal cancer screening and the Danish Colorectal Cancer Screening Database, but has no other conflicts of interest. Morten Rasmussen is head of the colorectal cancer screening programme in the capital Region, head of the Colorectal Cancer Screening Database, member of the National Steering Committee for Colorectal cancer screening and has received speaking fees from Norgine for giving speeches at sponsored meetings. The money obtained through this has not been used to finance this manuscript. Sisse Helle Njor, Susanne Fogh Jørgensen and Rikke Hagemann-Madsen declares no conflict of interest, (Thieme. All rights reserved.)

Background: Optimal management of patients with upper rectal cancer remains unclear. Partial mesorectal excision (PME) without neoadjuvant therapy is currently advocated for the majority of patients. Recent studies, however, reported a high risk of local recurrence and suboptimal surgery. The aim of this study was to evaluate the effects of a quality assurance initiative with postoperative MRI to improve outcomes in these patients., Methods: Patients who underwent mesorectal excision with curative intent for rectal cancer in 2007-2013 were included. Postoperative MRI of the pelvis was performed 1 year after surgery. In 2011, a multidisciplinary workshop with focus on extent and completeness of surgery was held for training surgeons, pathologists and radiologists involved in treatment planning. Images of residual mesorectum and histopathological reports were reviewed with regard to the distal resection margin. Local recurrence after a minimum of 3 years' follow-up was compared between two cohorts from 2007-2010 and 2011-2013., Results: A total of 627 patients were included; postoperative MRI of the pelvis was done in 381 patients. The 3-year actuarial local recurrence rate in patients with upper rectal cancer improved from 12·9 to 5·0 per cent (P = 0·012). After the workshop, fewer patients with cancer of the upper rectum were selected to have PME (90·8 per cent in 2007-2010 versus 80·2 per cent in 2011-2013; P = 0·023), and fewer patients who underwent PME had an insufficient distal resection margin (61·7 versus 31 per cent respectively; P < 0·001)., Conclusion: Quality assessment of surgical practice may have a major impact on oncological outcome after surgery for upper rectal cancer., (© 2019 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Background: This study aimed to identify the cumulative incidence and risk factors of metachronous peritoneal metastasis (M-PM) from colorectal cancer in patients who had intended curative treatment., Methods: Patients with colorectal cancer were identified using the Danish Colorectal Cancer Group database for 2006-2015. The Danish Pathology Registry and the Danish National Patient Registry were used to identify M-PM to 2017. Risk factors were estimated by multivariable absolute risk regression, treating death and other cancers as competing risks. Overall risk and risk differences (RDs) were estimated at 1, 3 and 5 years., Results: In 22 586 patients with colorectal cancer, the overall risk of M-PM was reported to be 0·9 (95 per cent c.i. 0·8 to 1·0) per cent at 1 year, 1·9 (1·8 to 2·1) per cent at 3 years and 2·2 (2·0 to 2·4) per cent at 5 years. Advanced tumour category ((y)pT4 versus (y)pT1) increased the RD of both M-PM (2·9 (95 per cent c.i. 2·1 to 3·7) at 1 year and 6·0 (4·9 to 7·2) at 3 years) and lymph node involvement ((y)pN2 versus (y)pN0) (2·5 (1·8 to 3·2) at year and 4·3 (3·2 to 5·3) at 3 years). No further increase in risk was observed at 5 years. In a subanalysis, tumour-involved resection margin (R1 versus R0) was associated with M-PM with a RD of 3·9 (1·6 to 6·2) at 1 year and 5·9 (2·6 to 9·3) at 3 years., Conclusion: The overall risk of M-PM in patients with colorectal cancer is low, but is increased in advanced T and N status. Follow-up of at least 3 years after colorectal cancer surgery may be necessary, given the potential curative treatment of early diagnosed M-PM., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Background: Cystic fibrosis(CF) related diabetes(CFRD) and osteoporosis are prevalent in adult patients with CF. We aimed to evaluate if CFRD and markers of glucose metabolism and inflammation are associated with bone turnover in CF., Methods: Cross sectional study at the adult section at the Copenhagen CF Center from January-October 2017. Fasting blood samples, including bone turnover markers(BTMs) and cytokines, Dual-x-ray absorptiometry scan and oral glucose tolerance test were performed. Lung-transplanted participants and patients in antiosteoporotic treatment were excluded from analyses., Results: 102 patients were included of whom 19 had a prior CFRD diagnosis. CFRD patients had lower procollagen type 1 N-terminal propeptide(P1NP) and C-Terminal cross-linked Telopeptide(CTX) levels compared to CF patients without diabetes (median[IQR]) 49.5 μg/l [29.6,57.1] vs 56.9 μg/l [38.2,74.3], p = .03 and 0.2 μg/l [0.1,0.3] vs 0.4 μg/l [0.3,0.6], p < .01, respectively. Fasting plasma glucose(FPG) was negatively associated with the bone formation markers P1NP and osteocalcin and bone resorption marker CTX. In multivariate linear regression FPG remained a significant predictor of P1NP -1.07 [-1.09;-0.01] and CTX -1.13 [-1.21;-1.06]. Bone mineral density Z-score was not different between patients with and without CFRD but FPG was negatively associated with hip and femoral neck Z-score. There was no consistent association between inflammatory cytokines and BTMs., Conclusions: Bone turnover markers are reduced in CF patients with CFRD and negatively associated with glucose levels. Extra attention towards frequent hyperglycemia in CF patients should be taken when evaluating decreased BMD. Glycemia may be a future target for improving outcome in CFBD., (Copyright © 2019. Published by Elsevier B.V.)

Background: Exercise reduces the amount of visceral adipose tissue (VAT) and the risk of cardiometabolic diseases. The underlying mechanisms responsible for these exercise-induced adaptations are unclear, but they may involve lipolytic actions of interleukin-6 (IL-6). Contracting skeletal muscles secrete IL-6, leading to increased circulating IL-6 levels in response to exercise. The aim of this study is to investigate whether IL-6 is involved in mediating the effects of exercise on visceral and epicardial adipose tissue volume and glycaemic control., Methods/design: Seventy-five physically inactive males and females aged > 18 years with a waist-to-height ratio > 0.5 and/or waist circumference ≥ 88 cm (females) or ≥ 102 cm (males) are being recruited to participate in a 12-week intervention study. Participants are randomly allocated to one of five groups (1:1:1:1:1). Two groups consist of supervised endurance exercise training combined with the IL-6 blocker tocilizumab (ET) or saline used as placebo (EP), two groups consist of no exercise combined with tocilizumab (NT) or placebo (NP), and one group consists of resistance exercise and placebo (RP). Although the study is an exploratory trial, the primary outcome is change in VAT volume from before to after intervention, with secondary outcomes being changes in (1) epicardial adipose tissue, (2) pericardial adipose tissue and (3) gastric emptying. Depots of adipose tissue are quantitated by magnetic resonance imaging Gastric emptying and glucose metabolism are assessed using mixed-meal tolerance tests., Discussion: Understanding the role of IL-6 in mediating the effects of exercise on visceral and epicardial adipose tissue and glycaemic control may lead to novel therapeutic approaches in the prevention of cardiometabolic diseases., Trial Registration: ClinicalTrials.gov, NCT02901496 . Registered on 1 August 2016 and posted retrospectively on 15 September 2016.

Background: After the introduction of complete mesocolic excision, a new pathological evaluation of the resected colon cancer specimen was introduced. This concept has quickly gained acceptance and is often used to compare surgical quality. The grading of colon cancer specimens is likely to depend on both surgical quality and the training of the pathologist., Objective: The purpose of this study was to validate the principles of the pathological evaluation of colon cancer specimens., Design: This was an exploratory study., Settings: The study was conducted in Aarhus, Denmark, and Leeds, United Kingdom., Patients: Colon cancers specimens were used., Main Outcome Measures: The agreement of gradings between participants was of interest. Four specialist GI pathologists and 2 abdominal surgeons evaluated 2 rounds of colon cancer specimens, each at 2 separate time points. Each round contained 50 specimens. After the first round, a protocol of detailed principles for the grading procedure was agreed on. Results from an experienced pathologist were considered as the reference results., Results: In the first round, the distribution of gradings between participants showed substantial variation. In the second round, the variation was reduced. Intraobserver agreement was mostly fair to good, whereas interobserver agreement was frequently poor. This did not significantly change from round 1 to round 2., Limitations: The small sample size of 100 specimens provided a very small number of specimens resected in the muscularis propria plane, which renders the evaluation of this group potentially unreliable. The evaluations were made on photos and not on fresh specimens., Conclusions: This study demonstrates significant variation in the pathological evaluation of colon cancer specimens. It demonstrates that it cannot be used in clinical studies, and care should be taken when comparing results between different hospitals.

Aim: Over recent years there has been a new focus on the quality of colon cancer surgery following the description and introduction of complete mesocolic excision (CME). In the same period, laparoscopic surgery has been widely applied to the treatment of colon cancer. We aimed to evaluate the introduction of both CME and laparoscopic-assisted surgery at Aarhus University Hospital, Denmark between 2008 and 2011. Secondly we aimed to evaluate the impact on the quality of surgery of post-operative team meetings where pathologists demonstrated the plane of surgery on the specimens., Method: A series of 209 consecutive and prospectively collected colon cancer specimens were evaluated by assessing the plane of surgery and measuring the amount of tissue resected. Multivariate analyses were used to control for influencing factors., Results: The proportion of specimens resected in the mesocolic plane was high and increased significantly following the introduction of post-operative team meetings (52%-76%, p = 0.02). Laparoscopic surgery enhanced the distance between the tumour and the arterial tie by a mean of 27 mm (p < 0.0001) and the distance between the nearest bowel wall and the arterial tie by 26 mm (p < 0.0001) when compared to an open approach. Factors such as body mass index and age influenced the outcome for surgical quality., Conclusion: Implementation of CME and laparoscopic-assisted surgery for colon cancer is a challenge and requires continuous training and feedback. Post-operative multidisciplinary team meetings may be a key element in this process., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Obesity amongst children is a growing problem worldwide. In contrast to adults, little is known on the effects of controlled weight loss on components of the metabolic syndrome in children. The primary aim of the study was to evaluate the effects of a 20-week exercise and diet guidance intervention on body mass index (BMI) in a group of overweight children. Our hypothesis was an observed reduction in BMI and secondarily in body fat content, insulin insensitivity, and other components of the metabolic syndrome in the intervention group., Methods: School children from Copenhagen were randomly allocated to an intervention group (n = 19) or a control group (n = 19). Anthropometric assessment, whole body dual-energy X-ray absorptiometry scan, two hours oral glucose tolerance test, steps measured by pedometer, and fitness tests were measured at baseline and at 20 weeks., Results: Thirty-seven children (30 girls) participated at baseline, aged 8.7 ± 0.9 years with a BMI of 21.8 ± 3.7 kg/m2 (mean ± SD), and 36 children completed the study. The intervention group decreased their BMI (the intervention effect is the difference in change between the groups adjusted for the respective baseline values (DELTA) = -2.0 kg/m2, 95% CI: -2.5; -1.5, P <0.001), total body mass (DELTA = -4.0 kg, 95% CI: -4.9; -3.0, P <0.001), and fat mass (DELTA = -3.3 kg, 95% CI: -4.2; -2.7, P <0.001) compared to the control group after the intervention. The intervention group displayed decreased waist, hip and waist-to-height ratio (WHtR) (all three variables; P <0.001), area under curve for plasma insulin (P <0.05), and increased mean and minimum steps/day (P <0.05 and P <0.01, respectively)., Conclusions: The multicomponent intervention had significant favorable effects on BMI, weight, WHtR, mean and minimum steps/day, and fat mass. In addition, similar beneficial metabolic effects were found in the children as shown in adults, e.g. increase in peripheral insulin sensitivity., Trial Registration: Clinicaltrials.gov Identifier number NCT01660789.

Objective: Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present a 2-year evaluation of a nationwide prenatal RHD screening., Methods: Blood samples were drawn from RhD-negative women in gestational week 25. DNA was extracted from maternal plasma and analyzed for the RHD gene. The prenatal RHD results were compared with the serological typing of newborns in 12,668 pregnancies. Early compliance was assessed for 690 pregnancies., Results: The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD were not detected in 11 pregnancies (0.087%). The sample uptake percentage was 84.2%, and the compliance for prenatal anti-D administration was 93.2%., Conclusion: The high sensitivity, maintained over 2 years, underlines the reliability of routine prenatal fetal RHD screening in RhD-negative pregnant women, specifically at 25 weeks of gestation. The remaining challenges are logistical and are related to program compliance., (© 2014 John Wiley & Sons, Ltd.)

Objective: Genome-wide association studies have identified genetic variants associating with BMI, however, it is un-clarified whether the same variants also influence body weight fluctuations., Methods: Among 3,982 adult individuals that attended both a baseline and a five-year follow-up examination in the Danish Inter99 intervention study, a genetic risk score (GRS) was constructed based on 30 BMI variants to address whether it is associated with body weight changes. Moreover, it was examined whether the effect of lifestyle changes was modulated by the GRS., Results: The GRS associated strongly with baseline body weight, with a per risk allele increase of 0.45 (0.33-0.58) kg (P = 2.7 × 10(-12) ), corresponding to a body weight difference of 3.41 (2.21-4.60) kg comparing the highest (≥ 30 risk alleles) and lowest (≤ 26 risk alleles) risk allele tertile. No association was observed with changes in body weight during the five years. Changes in lifestyle, including physical activity, diet and smoking habits associated strongly with body weight changes, however, no interactions with the GRS was observed., Conclusion: The GRS associated with body weight cross-sectionally, but not with changes over a five-year period. Body weight changes were influenced by lifestyle changes, however, independently of the GRS., (Copyright © 2013 The Obesity Society.)

Context: Recently, 10 novel type 2 diabetes (T2D) susceptibility single nucleotide polymorphisms (SNPs) in ZMIZ1, ANK1, KLHDC5, TLE1, ANKRD55, CILP2, MC4R, BCAR1, HMG20A, and GRB14 loci were discovered in MetaboChip-genotyped populations of European ancestry., Objective: The aim of the present study was to characterize prediabetic quantitative traits underlying these SNP associations and to calculate the amount of interindividual variation in glycemic traits explained by these and previous T2D susceptibility variants., Design and Participants: A total of 5739 Danish individuals naive to glucose-lowering medication were included in quantitative trait studies, and case-control analyses were performed in 1892 patients with T2D and 6603 normoglycemic control subjects. Participants without known T2D underwent an oral glucose tolerance test, and measures of insulin release and sensitivity were estimated from insulinogenic, disposition, BIGTT, and Matsuda indexes., Results: We confirmed associations of ZMIZ1, KLHDC5, CILP2, HMG20A, ANK1, ANKRD55, and BCAR1 with T2D. The risk T allele of BCAR1 rs7202877 associated with decreased disposition index (P = .02). The C allele of ANK1 rs516946 associated with decreased insulinogenic (P = .005) and disposition (P = .002) indexes. The G allele of ANKRD55 rs459193 associated with decreased Matsuda index (P = .02) adjusted for waist circumference. The C allele of GRB14 rs13389219 associated with both increased insulinogenic (P = .04) and decreased Matsuda (P = .05) indexes. All validated European T2D variants still only explained a few percentage points of glycemic trait variation., Conclusions: BCAR1 rs7202877 may mediate its diabetogenic impact through impaired β-cell function, but this finding needs to be replicated in independent studies. In addition, we substantiated previous evidence that ANK1 rs516946 confers impaired insulin release and that ANKRD55 rs459193 and GRB14 rs13389219 associate with insulin resistance.

Previous studies have shown an association between oxidative stress and various diseases in humans including cancer, cardiovascular disease, diabetes, and chronic respiratory disease. To what extents this damage is determined by genetic and environmental factors is unknown. In a classical twin study with 198 elderly twins we examined the contributions of genetic versus environmental factors to nucleic acid oxidation and lipid peroxidation. Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and dinor,dihydro F₂-isoprostane metabolites (F₂-IsoP-M) was measured using liquid chromatography-tandem mass spectrometry. The environmental influence on nucleic acid oxidation and lipid peroxidation was predominant, leaving only little influence from genetic factors, as evidenced by no differences in intraclass correlations between monozygotic (MZ) and dizygotic (DZ) twins, neither for 8-oxodG (r(MZ)=0.55, r(DZ)=0.47; P=0.43), F(2)-IsoP-M (r(MZ)=0.33, r(DZ)=0.22; P=0.42), nor 8-oxoGuo (r(MZ)=0.45, r(DZ)=0.58; P=0.21). Accordingly, heritability estimates for the three markers of oxidative damage were low (h²=0.17-0.22). The three urinary markers of oxidative stress were closely correlated (r=0.60-0.84). In conclusion, we demonstrated in a large population of elderly Danish twins that "whole-body" oxidative damage to nucleic acids and lipids is predominantly determined by potentially modifiable nongenetic factors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Ascaris lumbricoides as the etiology to acute pancreatitis has never been described in Denmark, whereas in India it is a common cause. In most cases symptoms lead to investigations with high diagnostic sensitivity end specificity. Treatment with antihelminthics and ERCP is efficient. A case of a 25 years-old pregnant woman with acute pancreatitis caused by Ascaris lumbricoides is reported.