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Background: The performance of magnetic resonance imaging (MRI) interpretation and communication of findings and its implication on treatment decisions has not fully been explored in rectal cancer. Purpose: To investigate in a region the adherence to MRI protocol standards and the relation between MRI interpretation and selection to preoperative therapy in rectal cancer. Material and Methods: Data on consecutive patients who underwent elective rectal cancer surgery in the region from January to June 2010 were obtained from the National Colorectal Cancer Registry. Pretherapeutic MRI images were re-evaluated. Agreement between the original reports and the re-evaluation was compared using Cohen's kappa coefficient. Results: Among the 94 patients included, 81 (86%) had pretherapeutic MRI in accordance with defined imaging guidelines. In 34% of the original MR reports, data on extramural venous invasion (mrEMVI) and mrT category were not reported. Complete tumor staging was not possible because of missing data in 33 (35%) of the patients. The agreement between the original MR reports and the re-evaluation regarding tumor stage was moderate (kappa = 0.48). For decided treatment compared to recommended preoperative treatment according to the re-evaluation, the agreement was fair (kappa = 0.33). Conclusion: Established MRI protocol standards were not universally applied. Missing data and inadequacies in original MRI reports resulted in moderate agreement between the original report and the re-evaluation indicating a risk of inappropriate treatment selection. The results call for further educational efforts in rectal cancer MRI acquisition and repeated audits of image protocol adherence and interpretation quality.

Previous studies describing the cumulative failure rate after reconstructive surgery in patients with inflammatory bowel disease have been restricted to specific hospitals, and the generalizability of these results in a population-based setting is unknown. The aim of this study was to investigate the cumulative failure rate and risk factors for failure after reconstructive surgery in patients with inflammatory bowel disease. The study cohort includes all patients with inflammatory bowel disease in Sweden who underwent colectomy in 2000 through 2013 who were later treated with reconstructive surgery with ileal pouch-anal anastomosis or ileorectal anastomosis. Each patient was followed from admission for reconstructive surgery until admission for failure (a diverting stoma or permanent stoma), date of death, migration or December 31, 2013. Cumulative failure distributions were obtained with the Kaplan-Meier method, and multivariable Cox regression models were used to calculate the risk of failure. Of the 1809 patients with inflammatory bowel disease treated with colectomy and reconstructive surgery, 83% had ulcerative colitis. During follow-up, 270 patients failed, and the cumulative failure rate was 4.1%, 13.2%, and 15.3% after 1, 3, and 5 years, respectively. The risk of failure was lower after treatment with ileal pouch-anal anastomosis than with ileorectal anastomosis [hazard ratio (95% confidence interval): 0.72 (0.56-0.93)]. Gender, hospital volume, and timing of reconstruction were not significantly associated with the risk of failure. The 5-year cumulative failure rate in a nationwide setting was 15.3%, and hospital volume was not associated with the risk of failure., Funding Agencies|Swedish Society of Medical Research; Mjolkdroppen foundation; Swedish Medical association; Strategic Research Area Funding in Epidemiology at the Karolinska Institutet; Bengt Ihre Research Fellowship in Gastroenterology

Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Methods and design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradi

BACKGROUND: Preoperative irradiation with 5 x 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer. OBJECTIVE: The aim of this study was to determine whether the same favorable effects could be observed in a population-based study. DESIGN: This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry. SETTINGS: This study examined population-based data from Sweden. PATIENTS: All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry. INTERVENTIONS: Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann's procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm). MAIN OUTCOME MEASURES: Five-year cumulative local recurrence and survival rates. RESULTS: The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors. CONCLUSIONS: In this population-based analysis, the favorable effect of preoperative short-course irradiation on local

PURPOSE: To determine the sites of local recurrence after total mesorectal excision for rectal cancer in an effort to optimize the radiation target. METHODS AND MATERIALS: A total of 155 patients with recurrence after abdominal resection for rectal cancer were identified from a population-based consecutive cohort of 2,315 patients who had undergone surgery by surgeons trained in the total mesorectal excision procedure. A total of 99 cross-sectional imaging studies were retrieved and re-examined by one radiologist. The clinical records were examined for the remaining patients. RESULTS: Evidence of residual mesorectal fat was identified in 50 of the 99 patients. In 83 patients, local recurrence was identified on the imaging studies. All recurrences were within the irradiated volume if the patients had undergone preoperative radiotherapy or within the same volume if they had not. The site of recurrence was in the lower 75% of the pelvis, anatomically below the S1-S2 interspace for all patients. Only 5 of the 44 recurrences in patients with primary tumors >5 cm from the anal verge were in the lowest 20% of the pelvis. Six recurrences involved the lateral lymph nodes. CONCLUSION: These data suggest that a lowering of the upper limit of the clinical target volume could be introduced. The anal sphincter complex with surrounding tissue could also be excluded in patients with primary tumors >5 cm from the anal verge.

Human papillomavirus (HPV) infections of the genital tract are sexually transmitted and prevalent worldwide. In this study, the role of HPV in 72 patients with anal squamous cell carcinoma was investigated. Patients and Methods: Polymerase chain reaction (PCR) in combination with in situ hybridization was used to identify HPV-DNA in the patients' biopsies. The HPV typing was conducted by pyrosequencing. Cell cycle and DNA content were analysed by cytometry. Results: Ninety percent of the carcinoma biopsies carried high-risk oncogenic HPV in their malignant cells. Eighty-one percent of these demonstrated a single infection with HPV16, 18 or 33 and 19% were double infected with HPV16 and HPV18. Accumulations of viral genes were seen at the necrotic area of the tumours. The HPV genome in the tumour cell influenced significantly the host cell cycle progression, but not DNA aberrations. Within these patients, HPV status in the malignant cells was not found to be associated with patient survival time. Conclusion: High-risk oncogenic HPV may play an important role in the initiation of host cell proliferation in anal squamous cell carcinoma. However, infection with HPV may not have any direct influence itself on the clinical outcome of these patients considering the treatments currently available.

Epidermoid anal cancer is an uncommon, malignant disease that is diagnosed in approximately 100 patients annually in Sweden. The incidence is increasing worldwide. Over the past 30 years, a dramatic change in the therapeutic approach has occurred leading to non-surgical treatment with radiotherapy and chemotherapy being primary options. Inter-individual variation in treatment response exists and a proportion of patients require radical surgery for cure. Treatment regimens in current use yield good survival rates, but treatment related morbidity and the need for surgery still represent a problem. Reliable prognostic markers are lacking. The aims of this thesis are to extend present knowledge on treatment, including surgery, and to explore different potential prognostic markers for the benefit of epidermoid anal cancer patients. The basis for this thesis was a consecutive, population-based cohort of 308 anal cancer patients from Stockholm-Gotland, collected 1985-2000. Therapeutic results were reviewed and prognostic markers explored. It is concluded that results comparable to those in clinical trials are possible to achieve in an unselected, population-based series. Adherence to pre-determined treatment protocols, centralised management of patients within a multidisciplinary team and close follow-up may be key elements in the treatment of epidermoid anal cancer patients. In locally advanced cases, treatment results appear to be superior when neoadjuvant platinum-based chemotherapy is added to radiotherapy. Assessment of treatment response after initial radiotherapy is of great importance, as further irradiation adds morbidity, but no survival benefits in poor responders. Salvage surgery can result in >50 per cent long-time survivors, but is associated with considerable post-operative morbidity. Clinicopathological parameters should be used for prognostic information with caution; however, stage appears to be of prognostic importance. Archived tumour material was inves

BACKGROUND: Markers for guidance with regard to individual prognosis and treatment planning are sought in epidermoid anal cancer. This study assessed the prognostic and predictive value of tumour budding. PATIENTS AND METHODS: From a population-based consecutive series of patients who were prospectively recorded, it was possible to investigate 209 (76%) of the pretreatment biopsies. Immunohistochemistry with a monoclonal antibody for the gamma2 chain of laminin-5 was used to detect tumour budding (defined as dissociated single cancer cells or clusters of up to five cells). RESULTS: Tumour budding was detected in 104 (50%) of the 209 samples. No significant correlation was found between tumour budding and clinicopathological characteristics. Patients with tumour budding had a statistically significantly better 5-year overall survival rate compared with patients lacking tumour budding (74% versus 64%, P <0.05). Albeit not statistically significant, other outcome variables such as tumour-specific survival, recurrence after initial complete response and rate of distant metastases, were all in favour of patients with tumour budding. Multivariate analysis reveals tumour budding as an independent positive prognostic factor. CONCLUSIONS: Tumour budding detected by laminin-5 immunohistochemistry may be of prognostic value in the treatment of epidermoid anal cancer. However, further studies are needed to clarify the possible clinical implications.

Purpose: The primary therapy in epidermoid anal cancer is radiotherapy, generally with chemotherapy. The use of neoadjuvant chemotherapy has been infrequently reported in the literature. This study presents results from a large population-based series and provides comparisons between different treatments. Methods and materials: Between 1985 and 2000, 308 patients with invasive epidermoid anal cancer were diagnosed in the Stockholm Health Care Region. Treatment was given according to defined protocols. External beam radiotherapy alone or with concomitant bleomycin and neoadjuvant chemotherapy followed by radiotherapy alone were the primary treatments. Radical surgery was reserved for poor responders or recurrences. Data were reviewed with regard to treatment, outcome, and prognostic factors. Results: Among the 276 patients (90%) treated with curative intent, 264 (96%) received treatment in accordance with the protocols. The overall 5-year survival rate was 68%. Among the 142 patients with locally advanced tumors (T > or =4 cm or N+), patients treated with neoadjuvant platinum-based chemotherapy (n = 91) had significantly better complete response rates compared with patients treated with radiotherapy with or without bleomycin (n = 51) (92% vs. 76%, p < 0.01). A significantly increased overall 5-year survival rate was also found among patients receiving neoadjuvant therapy (63% vs. 44%, p < 0.05). Conclusion: Structured treatment protocols result in favorable outcome on a population level. The results further suggest a significant therapeutic gain from including neoadjuvant chemotherapy in the treatment of locally advanced anal cancer.