Kåre Gotschalck Sunesen

Immunosuppressive disorders and risk of anal squamous cell carcinoma: A nationwide cohort study in Denmark, 1978–2005

Compromised immune function may increase the risk of anal squamous cell carcinoma (SCC). We examined the risk of anal SCC in patients with HIV infection and other chronic disorders associated with immunosuppression. A population‐based cohort study was conducted using the Danish National Patient Registry and the Danish Cancer Registry (DCR). We identified all patients with a first‐time hospital contact or procedure for HIV infection, solid organ transplantation or autoimmune disease or a first‐time record of haematologic malignancy in the DCR, 1978–2005, and followed these for a subsequent anal SCC, starting follow‐up 1 year after diagnosis of the index disease. Standardised incidence ratios (SIRs) were computed as the ratio of observed to expected numbers of anal SCCs, based on national age‐, sex‐ and period‐specific rates. Among 4,488 patients with HIV, we observed 21 anal SCCs with 0.3 expected (SIR: 81.1 (95% confidence interval (CI): 51.6–121.9)). Risk of anal SCC was markedly increased among 5,113 solid organ recipients (SIR: 14.4 (CI: 7.0–26.4)) and 30,165 patients with haematologic malignancies (SIR: 2.3 (CI: 1.1–4.2)) but only moderately increased among 242,114 patients with autoimmune diseases (SIR: 1.3 (CI: 1.0–1.6)). SIRs varied according to type of autoimmune disease and were high in patients with Crohns disease (SIR: 3.1 (CI: 1.2–6.4)), psoriasis (SIR: 3.1 (CI: 1.8–5.1)), polyarteritis nodosa (SIR: 8.8 (CI: 1.5–29.0)) and Wegeners granulomatosis (SIR: 12.4 (CI: 2.1–40.8)). In conclusion, we found HIV infection, solid organ transplantation, haematologic malignancies and a range of specific autoimmune diseases strongly associated with increased risk of anal SCC.

Cause-Specific Colostomy Rates After Radiotherapy for Anal Cancer: A Danish Multicentre Cohort Study

PURPOSE In anal cancer, colostomy-free survival is a measure of anal sphincter preservation after treatment with radiotherapy or chemoradiotherapy. Failure to control anal cancer and complications of treatment are alternative indications for colostomy. However, no data exist on cause-specific colostomy rates. We examined this in a cohort study. PATIENTS AND METHODS Through national registries and review of medical records, we identified patients with anal cancer diagnosed from 1995 to 2003 who had curative-intent radiotherapy or chemoradiotherapy in four Danish centers. We computed cumulative incidence of tumor-related colostomy and therapy-related colostomy, treating colostomy and death as competing events. Follow-up started at completion of radiotherapy and continued throughout 2008. We used competing risk regression to compute hazard ratios (HRs) to compare the cumulative incidence of cause-specific colostomies between age, sex, tumor size, chemotherapy, and local excision before radiotherapy. RESULTS We included 235 patients with anal cancer. The 5-year cumulative incidences of tumor-related and therapy-related colostomy were 26% (95% CI, 21% to 32%) and 8% (95% CI, 5% to 12%), respectively. Tumor size greater than 6 cm versus less than 4 cm was a risk factor for tumor-related colostomy (adjusted HR, 3.8; 95% CI, 1.7 to 8.1), and local excision before radiotherapy was a risk factor for therapy-related colostomy (adjusted HR, 4.5; 95% CI, 1.5 to 13.5). CONCLUSION After curative-intent radiotherapy or chemoradiotherapy, one third of patients had a colostomy, of which one third were related to therapy. Large tumor size was associated with a higher risk of tumor-related colostomy, whereas history of prior excision was associated with an increased incidence of therapy-related colostomy.

Hypermethylated DNA as a Biomarker for colorectal cancer: A systematic review

Improved methods for early detection of colorectal cancer (CRC) are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. Biochemical methods have improved in recent years, and several hypermethylated genes that are sensitive and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed.

Hypermethylated DNA, a circulating biomarker for colorectal cancer detection

Background Colorectal cancer (CRC) is one of the most common cancers in the western world. Screening is an efficient method of reducing cancer-related mortality. Molecular biomarkers for cancer in general and CRC in particular have been proposed, and hypermethylated DNA from stool or blood samples are already implemented as biomarkers for CRC screening. We aimed to evaluate the performance of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC detection. Methods We conducted a cross-sectional case-control study of 193 CRC patients and 102 colonoscopy-verified healthy controls. Using methylation specific polymerase chain reaction, we evaluated 30 DNA promoter regions previously found to be CRC specific. We used multivariable logistic regression with stepwise backwards selection, and subsequent leave-pair-out cross validation, to calculate the optimism corrected area under the receiver operating characteristics curve (AUC) for all stage as well as early stage CRC. Results None of the individual DNA promoter regions provided an overall sensitivity above 30% at a reasonable specificity. However, seven hypermethylated promoter regions (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5% specificity using a cut point value of 0.5. Conclusions Individual hypermethylated DNA promoter regions have limited value as CRC screening markers. However, a panel of seven hypermethylated promoter regions show great promise as a model for CRC detection.

Long-term anorectal, urinary and sexual dysfunction causing distress after radiotherapy for anal cancer: a Danish multicentre cross-sectional questionnaire study.

The objective of primary radiotherapy for anal cancer is to remove cancer while maintaining anorectal function. However, little is known about anorectal function among long‐term survivors without colostomy. Using a cross‐sectional questionnaire study, we examined symptoms and distress related to the dysfunction of pelvic organs after radiotherapy for anal cancer.

The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer

Epigenetic alterations in colorectal cancer (CRC) cause important differences in the underlying tumor biology and aggressiveness. DNA hypermethylation is central for the development of CRC but the prognostic impact remains elusive. We aimed to assess the association between cell-free hypermethylated DNA and stage and survival in colorectal cancer (CRC). We analyzed pre-treatment plasma samples from 193 patients with CRC. Thirty gene-promoter regions were analyzed using methylation specific PCR. We compared the median number (range) of hypermethylated promoter regions with CRC stage, and constructed a multivariable Cox-regression model adjusted for stage, to evaluate the added prognostic information. The median number of hypermethylated promoter regions was nine (0-28) in patients with distant metastasis compared to five (0-19) in patients without metastatic disease (p < 0.0001). The majority of the hypermethylated promoter regions inferred a poor prognosis. Cox-regression analysis adjusted for patient age, sex, pre-treatment CEA-levels, and disease stage, showed that RARB (HR = 1.99, 95% CI [1.07, 3.72]) and RASSF1A (HR = 3.35, 95% CI [1.76, 6.38]) hypermethylation inferred a significant effect on survival. The risk of metastasis increase with the number of cell-free hypermethylated promoter regions. The presence of RARB and RASSF1A hypermethylation indicated aggressive disease, regardless of stage at the time of diagnosis.

Risk of pelvic and hip fracture after anal cancer: a Danish nationwide cohort study

Aim: Sinusectomy is a technique first described by Lord-Milllar then modified by Marti for the treatment of pilonidal disease. This study describes our ten years’ experience with long-term outcomes in over 292 patients. We aimed to demonstrate that sinusectomy is an efficient procedure even performed under local anesthesia for pilonidal sinus management. Method: Retrospective study for all primary pilonidal sinus treated between 01/07/ 2005 to 30/06/2015. We compared the outcomes of our patients with the results from other centers described in the literature. The outcomes were: time off work, healing time, complications and recurrence rate. We also observed the type of anesthesia used and the length of hospitalization. Results: Sinusectomy was achieved in 94.5% under local anesthesia. 99.3% of patients were ambulatory. With a median follow-up of 34 months [range 1– 124 months], we observed a recurrence rate of 7.19%. The time off work was 12 days. Healing time was 26 days. Complication rate was 5.14% and included bleeding in 2.40% and infection 2.74%. Conclusion: Sinusectomy is a simple and efficient procedure that can be done under local anesthesia in an ambulatory setting. Our ten years’ experience is that sinusectomy is an ideal procedure for primary pilonidal sinus disease with a short recovery time, and a low recurrence and complication rate.