Although colonoscopic surveillance is recommended both for individuals with known hereditary colorectal cancer (HCRC) syndromes and those with a more moderate familial colorectal cancer (FCRC) history, the evidence for the benefits of surveillance is limited and surveillance practices vary. This study evaluates the preventive effect for individuals with a family history of CRC of decentralized colonoscopic surveillance with the guidance of a cancer prevention clinic. We performed a population based prospective study of 261 patients with HCRC or FCRC, recorded in the colonoscopic surveillance registry at the Cancer genetics clinic, University Hospital of Umeå, Sweden. Colonoscopic surveillance was conducted every second (HCRC) or fifth (FCRC) year at local hospitals in Northern Sweden. Main outcome measures were findings of high-risk adenomas (HRA) or CRC, and patient compliance to surveillance. Estimations of the expected numbers of CRC without surveillance were made. During a total of 1256 person years of follow-up, one case of CRC was found. The expected numbers of cancers in the absence of surveillance was between 9.5 and 10.5, resulting in a standardized incidence ratio, observed versus expected cases of CRC, between 0.10 (CI 95 % 0.0012-0.5299) and 0.11 (CI 95 % 0.0014-0.5857). No CRC mortality was reported, but three patients needed surgical intervention. HRA were found in 5.9 % (14/237) of the initial and in 3.4 % (12/356) of the follow-up colonoscopies. Patient compliance to the surveillance program was 90 % as 597 of the planned 662 colonoscopies were performed. The study concludes that colonoscopic surveillance with high patient compliance to the program is effective in preventing CRC when using a decentralized method for colonoscopy surveillance with the guidance of a cancer prevention clinic.

Introduction Numerous prior studies, even from countries with free access to care, have associated long travel time to care with poor survival in patients with colorectal cancer. Methods This is a data-linkage study of all 3718 patients with colorectal cancer, diagnosed between 2007 and 2013 in Northern Sweden, one of the most sparsely populated areas in Europe. Travel time to nearest hospital was calculated based on GPS coordinates and multivariable Cox regression was used to analyse possible associations between travel time and causespecific survival.

Background: Geographic cancer health disparities have been reported in Sweden. The disparities are not fully understood, but may be attributed to differences in exposure to risk factors as well as differences in health care, socioeconomics and demography. The aim of this study was to describe the new nationwide population based RISK North database and its potential by analysing health disparities in colorectal cancer between Northern and Southern Sweden. Methods: Cancer-specific data from the National Cancer Quality Registers for colorectal, gastric and oesophageal cancer and brain tumours were linked to several nationwide registers hereby creating a new database-RISK North. To exemplify the potential of RISK North, we analyzed differences in colorectal cancer incidence, mortality and survival in relation to gender, age, cohabitation and education between Northern and Southern Sweden 2007-2013. Results: In colon cancer, the age-adjusted incidence per 100.000 was lower in Northern than Southern Sweden, 35.9 in the North vs. 41.1 in the South (p < .01); mortality rates were 11.0 vs. 12.2 (p < .01). For rectal cancer, incidence rates were 17.6 vs. 19.7 (p < .01) and mortality rates 5.33 vs. 5.89 (p ¼ .07), respectively. The largest difference in incidence was demonstrated for colon cancer among individuals >79 years old (190. vs. 237, i.e., $20%). Survival in colon cancer was higher in Southern Sweden, HR 0.92 (0.87-0.98) adjusted for age, gender, co-habiting, education and m-stage at diagnosis. No difference in survival was seen for rectal cancer. Conclusions: The new RISK North database enabled analysis of cancer disparities between Northern and Southern Sweden. The incidence of colorectal cancer were lower in the North of Sweden whereas colon cancer survival was higher in the South. These differences can be further analysed utilising the RISK North database.

Whole-genome sequencing is a promising approach for human autosomal dominant disease studies. However, the vast number of genetic variants observed by this method constitutes a challenge when trying to identify the causal variants. This is often handled by restricting disease studies to the most damaging variants, e.g. those found in coding regions, and overlooking the remaining genetic variation. Such a biased approach explains in part why the genetic causes of many families with dominantly inherited diseases, in spite of being included in whole-genome sequencing studies, are left unsolved today. Here we explore the use of a geographically matched control population to minimize the number of candidate disease-causing variants without excluding variants based on assumptions on genomic position or functional predictions. To exemplify the benefit of the geographically matched control population we apply a typical disease variant filtering strategy in a family with an autosomal dominant form of colorectal cancer. With the use of the geographically matched control population we end up with 26 candidate variants genome wide. This is in contrast to the tens of thousands of candidates left when only making use of available public variant datasets. The effect of the local control population is dual, it (1) reduces the total number of candidate variants shared between affected individuals, and more importantly (2) increases the rate by which the number of candidate variants are reduced as additional affected family members are included in the filtering strategy. We demonstrate that the application of a geographically matched control population effectively limits the number of candidate disease-causing variants and may provide the means by which variants suitable for functional studies are identified genome wide.

Background Electrolyte disturbances and dehydration are common after anterior resection for rectal cancer with a defunctioning loop ileostomy. High-quality population-based studies on the impact of a defunctioning loop ileostomy on renal failure are lacking. Methods This was a nationwide observational study, based on the Swedish Colorectal Cancer Registry of patients undergoing anterior resection for rectal cancer between 2008 and 2016, with follow-up until 2017. Patients with severe co-morbidity, with age greater than 80 years, and with pre-existing renal failure were excluded. Loop ileostomy at index surgery constituted exposure, while a diagnosis of renal failure was the outcome. Acute and chronic events were analysed separately. Inverse probability weighting with adjustment for confounding derived from a causal diagram was employed. Hazards ratios (HRs) with 95 per cent c.i. are reported. Results A total of 5355 patients were eligible for analysis. At 5-year follow-up, all renal failure events (acute and chronic) were 7.2 per cent and 3.3 per cent in the defunctioning stoma and no stoma groups respectively. In the weighted analysis, a HR of 11.59 (95 per cent c.i. 5.68 to 23.65) for renal failure in ostomates was detected at 1 year, with the largest effect from acute renal failure (HR 24.04 (95 per cent c.i. 8.38 to 68.93)). Later follow-up demonstrated a similar pattern, but with smaller effect sizes. Conclusion Patients having a loop ileostomy in combination with anterior resection for rectal cancer are more likely to have renal failure, especially early after surgery. Strategies are needed, such as careful fluid management protocols, and further research into alternative stoma types or reduction in stoma formation.

Objective: Approximately 20-30% of all colorectal cancer (CRC) cases may have a familial contribution. The family history of CRC can be prominent (e.g., hereditary colorectal cancer (HCRC)) or more moderate (e.g., familial colorectal cancer (FCRC)). For family members at risk, colonoscopic surveillance is a wellestablished method to prevent both HCRC and FCRC, although the evidence for the exact procedures of the surveillance is limited. Surveillance can come at a high price if individuals are frequently examined, as this may result in unnecessary colonoscopies in relation to actual risk for CRC. This study analyses the cost-effectiveness of a surveillance programme implemented in the Northern Sweden Health Care Region. Methods: The study includes 259 individuals prospectively recorded in the colonoscopic surveillance programme registry at the Cancer Prevention Clinic, Umeå University Hospital. We performed a cost-utility analysis with a contrafactual design: we compared observed costs and loss of quality-adjusted life years (QALYs) due to CRC with the surveillance programme to an expected outcome without surveillance. The main measure was the incremental cost-effectiveness ratio (ICER) between surveillance and non-surveillance. Scenario analysis was used to explore uncertainty. Results: The ICER between surveillance and non-surveillance in the base model was 3596e/QALY. The ICER varied from À4620e in the best-case scenario to 33,779e in the worst-case scenario. Conclusion: Colonoscopic surveillance is a very cost-effective method to prevent HCRC and FCRC compared to current thresholds for cost-effectiveness and other cancer preventive interventions. ARTICLE HISTORY