A Validation of the Swedish Colorectal Cancer Register – With Focus on Histopathology, Complications and Recurrences

Örvar Arnarson,1,* Peter Moberger,2,3,* Filip Sköldberg,4,5 Kenneth Smedh,2,3 Helgi Birgisson,4,5 Ingvar Syk1 1Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden; 2Centre for Clinical research Västerås, Uppsala University, Uppsala, Sweden; 3Department of Surgery Västmanlands Hospital Västerås, Västerås, Sweden; 4Gastrointestinal Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; 5Department of Surgery, Uppsala University Hospital, Uppsala, Sweden*These authors contributed equally to this workCorrespondence: Ingvar Syk, Department of Surgery, Skåne University Hospital, Malmö, SE-214 28, Email [email protected]: There is an urgent need to evaluate the quality of healthcare systems to improve and deliver high-quality care. Clinical registries have become important platforms for performance measurements, improvements, and clinical research. Hence, the quality of data in registries is crucial. This study aimed to assess the validity of data in the Swedish Colorectal Cancer Register (SCRCR).Methods: Seven hundred patients from 12 hospitals were randomly selected and proportionally distributed among three different hospital categories in Sweden using two-stage cluster sampling. Validity was assessed by re-abstracting data from the medical files of patients reported to the SCRCR in 2015. Data on histopathology, postoperative complications, and a 3-year follow-up were selected for validation. Re-abstracted data were defined as source data, and validity was defined as the proportion of cases in the SRCRC dataset that agreed with the source data. Validity was expressed as the percentage of exact agreement of non-missing data in both data sets, and Cohen´s kappa coefficient (κ) was used to measure the strength of the agreement.Results: The median agreement of the categorical histopathology variables was 93.4% (κ = 0.83). The general postoperative complication variable showed substantial agreement (84.3%, κ = 0.61). Likewise, the variable for overall cancer recurrence showed an almost perfect agreement (95.7%, κ = 0.86), whereas specific variables for local recurrence and distant recurrence displayed only moderate and fair agreement (85.9% and 89.1%, κ = 0.58 and 0.34, respectively).Conclusion: Validation of the SCRCR data showed high validity of pathology data and recurrence rates, whereas detailed data on recurrence were not as good. Data on postoperative complications were less reliable, although the incidence and Clavien–Dindo grading of severe complications (grade 3b or higher) were reliable.Keywords: quality registry, national registry, validation, colorectal cancer, Swedish registr

Association studies on 11 published colorectal cancer risk loci

Colorectal cancer (CRC) is the third most common cancer type in the Western world. Over one million patients are diagnosed worldwide yearly. A family history of CRC is a major risk factor for CRC. The total genetic contribution to disease development is estimated to be 35%. High-risk syndromes caused by known genes such as familial adenomatous polyposis (FAP) and Lynch Syndrome (LS) explain less than 5% of that number. Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. In total, germline mutations in known genes and moderate- and low risk variants are today suggested to explain 10-15% of the total genetic burden. Hence, predisposed genetic factor are still left to be found. The aim of paper I was to investigate if 11 published loci reported to be associated with an increased or decreased risk of colorectal cancer could be confirmed in a Swedish-based cohort. The cohort was composed of 1786 cases and 1749 controls that were genotyped and analyzed statistically. Genotype– phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumor location, was performed. Of 11 loci, 5 showed statistically significant odds ratios similar to previously published findings. Most of the remaining loci showed similar OR to previous publications. Four statistically significant genotype–phenotype associations were reported. The aim of paper II was to further study these 11 SNPs and their possible correlation with morphological features in tumors. We analyzed 15 histological features in 1572 CRC cases. Five SNPs showed statistically significant associations with morphological parameters. The parameters were poor differentiation, mucin production, decreased frequency of Crohn-like peritumoral reaction and desmoplastic response. The aim of paper III was to identify new CRC loci using a genome wide linkage analysis. We used 121 non-FAP/LS colorectal cancer families and genotyped 600 subjects using SNP array chips. No statistically significant result was found. However, suggestive linkage was found in the parametric analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2) and one on 17p13.2 (LOD/HLOD=2.0). Our linkage study adds support for the previously suggested region on chromosome 9 and suggests three additional loci to be involved in colorectal cancer risk. It is debated whether CRC is a single entity or two different entities, colon- and rectal cancer. Studies have recognized their molecular differences. The aim of paper IV was to identify novel colon- and rectal loci. We performed a genome wide linkage analysis using 32 colon- and 56 rectal cancer families. No LOD or HLOD score above three was observed. However, results close to three could be demonstrated. A maximum HLOD= 2.49 at locus 6p21.1-p12.1 and HLOD= 2.55 at locus 18p11.2 was observed for the colon- and rectal cancer families respectively. Exome sequencing was done, on colon and rectal patients, in these regions of interest. We report 25 variants mutated in family members on chromosome 6 and 27 variants on chromosome 18. Further studies are ongoing to elucidate the importance of these variants

Use of prophylactic stoma mesh is a risk factor for developing rectus abdominis muscle atrophy

Purpose The aim of this study was to evaluate the possible risk factors for developing a parastomal hernia (PSH) in a cohort of rectal cancer patients with and without the application of a retro-muscular prophylactic mesh. The evaluated risk factors included the position of the stoma in the rectus abdominis muscle (RAM), RAM atrophy and shift of abdominal wall midline structures. Methods Rectal cancer patients treated with an abdominoperineal excision or Hartmann's procedure between 2002 and 2015 at Vastmanland Hospital, Sweden was included. Postoperative CT examinations were retrospectively reviewed regarding the presence of PSH and RAM atrophy and for measurements such as position of the stoma in the RAM. Results 116 patients were included, with a median age of 71 years. 70 patients received a prophylactic stoma mesh. 55 patients (47%) had a parastomal hernia at three-year follow-up. Rectus abdominis muscle atrophy was significantly higher in the mesh group compared with the non-mesh group (37% vs 2%; P = 0.04). RAM atrophy was a significant independent protective factor for developing a PSH (P = 0.007; OR 0.15; 95% CI 0.03-0.55). Conclusion Placement of a prophylactic retro-muscular stoma mesh resulted in a high frequency of RAM atrophy distal to the stomal aperture and patients with such atrophy had a lower risk of developing a PSH