Importance Colorectal cancer is a major health burden. Screening is recommended in many countries. Objective Estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial. Design Randomized controlled trial in individuals aged 50–64 years. Screening was performed in 1999–2000 (55–64 year age-group) and 2001 (50–54 year age-group). End of follow-up: Dec 31st 2011. Setting Population of Oslo city and Telemark County, Norway. Participants 100,210 individuals were identified in the screening areas. 1,415 individuals were excluded due to prior colorectal cancer, emigration, or death. Three individuals could not be traced in the population registry. Intervention Individuals randomized to the screening group were invited to screening. Within the screening group, individuals were randomized 1:1 to once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood-testing (FOBT). Individuals with positive screening test (cancer, adenoma, polyp ≥10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention. Main outcome measures Colorectal cancer incidence and mortality. Results 98,792 individuals were included in the intention to screen analyses; 78,220 in the control group and 20,572 in the screening group (10,283 randomized to flexible sigmoidoscopy and 10,289 to flexible sigmoidoscopy and FOBT). Compliance with screening was 63%. After median 10.9 years, 71 individuals had died from colorectal cancer in the screening group, and 330 in the control group (31.4 vs. 43.1 deaths, absolute rate difference 11.7 (95% CI 3.0–20.4) per 100,000 person-years); hazard ratio [HR] 0.73 (95% confidence interval [CI] 0.56–0.94). Colorectal cancer was diagnosed in 253 individuals in the screening group, and 1,086 in the control group (112.6 vs. 141.0 cases, absolute rate difference: 28.4 (95% CI 12.1–44.7) per 100,000 person-years); HR 0.80 (95% CI 0.70–0.92). Colorectal cancer incidence was reduced in both the 50–54 year age-group (HR 0.68; 95% CI 0.49–0.94) and the 55–64 year age-group (HR 0.83; 95% CI 0.71–0.96). There was no difference between the flexible sigmoidoscopy only and the flexible sigmoidoscopy/FOBT screening groups. Conclusion and relevance In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50–54 and the 55–64 year age-group. Trial registration ClinicalTrials identifier NTC00119912, http://clinicaltrials.gov

Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.

Herein we present a historical review of the development of systemic chemotherapy for colorectal cancer (CRC) in the metastatic and adjuvant treatment settings. We describe the discovery of 5-fluorouracil (5-FU) by Heidelberger and colleagues in 1957, the potentiation of 5-FU cytotoxicity by the reduced folate leucovorin, and the advent of novel cytotoxic agents, including the topoisomerase I inhibitor irinotecan, the platinum-containing agent oxaliplatin, and the 5-FU prodrug capecitabine. The combination therapies, FOLFOX (5-FU/leucovorin and oxaliplatin) and FOLFIRI (5-FU/leucovorin and irinotecan), have become established as efficacious cytotoxic regimens for the treatment of metastatic CRC, resulting in overall survival times of approximately 2 years. When used as adjuvant therapy, FOLFOX also improves survival and is now the gold standard of care in this setting. Biological agents have been discovered that enhance the effect of cytotoxic therapy, including bevacizumab (a humanized monoclonal antibody that targets vascular endothelial growth factor, a central regulator of angiogenesis) and cetuximab/panitumumab (monoclonal antibodies directed against the epidermal growth factor receptor). Despite the ongoing development of novel antitumor agents and therapeutic principles as we enter the era of personalized cancer medicine, systemic chemotherapy involving infusional 5-FU/leucovorin continues to be the cornerstone of treatment for patients with CRC.

CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.

Compared with chemotherapy, liver transplantation resulted in a marked increased OS in CRC patients with nonresectable liver-only metastases.

Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

No abstract

We present the results of a global study of dysregulated miRNAs in paired samples of normal mucosa and tumor from eight patients with colorectal cancer. Although there is existing data of miRNA contribution to colorectal tumorigenesis, these studies are typically small to medium scale studies of cell lines or non-paired tumor samples. The present study is to our knowledge unique in two respects. Firstly, the normal and adjacent tumor tissue samples are paired, thus taking into account the baseline differences between individuals when testing for differential expression. Secondly, we use high-throughput sequencing, thus enabling a comprehensive survey of all miRNAs expressed in the tissues. We use Illumina sequencing technology to perform sequencing and two different tools to statistically test for differences in read counts per gene between samples: edgeR when using the pair information and DESeq when ignoring this information, i.e., treating tumor and normal samples as independent groups. We identify 37 miRNAs that are significantly dysregulated in both statistical approaches, 19 down-regulated and 18 up-regulated. Some of these miRNAs are previously published as potential regulators in colorectal adenocarcinomas such as miR-1, miR-96 and miR-145. Our comprehensive survey of differentially expressed miRNAs thus confirms some existing findings. We have also discovered 16 dysregulated miRNAs, which to our knowledge have not previously been associated with colorectal carcinogenesis: the following significantly down-regulated miR-490-3p, -628-3p/-5p, -1297, -3151, -3163, -3622a-5p, -3656 and the up-regulated miR-105, -549, -1269, -1827, -3144-3p, -3177, -3180-3p, -4326. Although the study is preliminary with only eight patients included, we believe the results add to the present knowledge on miRNA dysregulation in colorectal carcinogenesis. As such the results would serve as a robust training set for validation of potential biomarkers in a larger cohort study. Finally, we also present data supporting the hypothesis that there are differences in miRNA expression between adenocarcinomas and neuroendocrine tumors of the colon.