The impact of young age on cancer-specific and non-cancer-related survival after surgery for colorectal cancer: 10-year follow-up

<b>Background</b>: It has been reported that although young patients present with more advanced disease, when adjusted for stage, cancer-specific survival is not different after surgery for colorectal cancer. However, few studies have examined non-cancer survival in young patients and 10-year survival has rarely been reported. Moreover, the largest study included patients of old age as a comparator. The aim of this study was to compare cancer-specific and non-cancer-related survival at 10 years in a young age cohort and a middle age cohort in patients undergoing surgery for colorectal cancer. <b>Methods</b>: Two thousand and seventy seven patients who underwent surgery for colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the study. Ten-year cancer-specific and non-cancer-related survival and the hazard ratios (HR) were calculated according to age groups (<45/45–54/55–64/65–74 years). <b>Results</b>: On follow-up, 1066 patients died of their cancer and 369 died of non-cancer-related causes. At 10 years, overall survival was 32%, cancer-specific was 45%, and non-cancer-related survival was 72%. On multivariate analysis of all factors, sex (HR 0.77, 95% CI 0.68–0.88, P<0.001), mode of presentation (HR 1.64, 95% CI 1.44–1.87, P<0.01), Dukes' stage (HR 2.69, 95% CI 2.49–2.90, P<0.001), and specialisation (HR 1.24, 95% CI 1.04–1.44, P<0.01) were independently associated with cancer-specific survival. On multivariate analysis of all factors, age (HR 2.46, 2.04–2.97, P<0.001), sex (HR 0.56, 0.45–0.70, P<0.001), and deprivation (HR 1.16, 1.10–1.24, P<0.001) were independently associated with non-cancer-related survival. <b>Conclusion</b>: The results of this study confirm that young age does not have a negative impact on cancer-specific survival. Moreover, they show that, with 10-year follow-up, young age does not have a negative impact on non-cancer-related survival

The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

<p>Abstract</p> <p>Background</p> <p>This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells.</p> <p>Methods</p> <p>The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions <it>in vitro</it>. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect.</p> <p>Results</p> <p>Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration.</p> <p>Conclusion</p> <p>Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner.</p

The impact of age on post-operative outcomes of colorectal cancer patients undergoing surgical treatment

BACKGROUND: the purpose of study was to evaluate the impact of age on outcomes in colorectal cancer surgery. METHODS: patients on hospital database treated for colorectal cancer during the period 1995 – 2002 were divided into two groups: Group 1 – patients of 75 years or older (n = 154), and Group 2 – those younger than 75 years (n = 532). RESULTS: In Group 1, for colon cancers, proximal tumors were significantly more common (23% vs. 13.5%, p < 0.05), complicated cases were more frequent (46 % vs. 33%, p = 0.002), bowel obstruction more common at presentation (40% vs. 26.5%, p = 0.001), and more frequent emergency surgery required (24% vs. 14%, p = 0.003). Postoperative overall morbidity was higher in the elderly group, but with no differences in surgical complications rate. Overall 5 year survival was 39% vs. 55% (p = 0.0006) and cancer related 5 year survival was 44% vs. 62% (p = 0.0006). Multivariate Cox analysis showed that age was not an independent risk factor for postoperative mortality. CONCLUSION: Preoperative complications and co-morbidities, more advanced disease, and higher postoperative nonsurgical complication rates adversely affect postoperative outcomes after surgery for colorectal cancer in the elderly

The use of preoperative radiotherapy in the management of patients with clinically resectable rectal cancer: a practice guideline

BACKGROUND: This systematic review with meta-analysis was designed to evaluate the literature and to develop recommendations regarding the use of preoperative radiotherapy in the management of patients with resectable rectal cancer. METHODS: The MEDLINE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings of the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were systematically searched for evidence. Relevant reports were reviewed by four members of the Gastrointestinal Cancer Disease Site Group and the references from these reports were searched for additional trials. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Two meta-analyses of preoperative radiotherapy versus surgery alone, nineteen trials that compared preoperative radiotherapy plus surgery to surgery alone, and five trials that compared preoperative radiotherapy to alternative treatments were obtained. Randomized trials demonstrate that preoperative radiotherapy followed by surgery is significantly more effective than surgery alone in preventing local recurrence in patients with resectable rectal cancer and it may also improve survival. A single trial, using surgery with total mesorectal excision, has shown similar benefits in local recurrence. CONCLUSION: For adult patients with clinically resectable rectal cancer we conclude that: • Preoperative radiotherapy is an acceptable alternative to the previous practice of postoperative radiotherapy for patients with stage II and III resectable rectal cancer; • Both preoperative and postoperative radiotherapy decrease local recurrence but neither improves survival as much as postoperative radiotherapy combined with chemotherapy. Therefore, if preoperative radiotherapy is used, chemotherapy should be added postoperatively to at least patients with stage III disease

Colonoscopic perforation leading to a diagnosis of Ehlers Danlos syndrome type IV: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Colonoscopic perforation is a rare but serious complication of colonoscopy. Factors known to increase the risk of perforation include colonic strictures, extensive diverticulosis, and friable tissues. We describe the case of a man who was found to have perforation of the sigmoid colon secondary to an undiagnosed connective tissue disorder (Ehlers-Danlos syndrome type IV) while undergoing surveillance for hereditary non-polyposis colorectal cancer.</p> <p>Case presentation</p> <p>A 33-year-old Caucasian man presented to our hospital with an acute abdomen following a colonoscopy five days earlier as part of hereditary non-polyposis colorectal cancer screening. His medical history included bilateral clubfoot. His physical examination findings suggested left iliac fossa peritonitis. A computed tomographic scan revealed perforation of the sigmoid colon and incidentally a right common iliac artery aneurysm as well. Hartmann's procedure was performed during laparotomy. The patient recovered well post-operatively and was discharged. Reversal of the Hartmann's procedure was performed six months later. This procedure was challenging because of dense adhesions and friable bowel. The histology of bowel specimens from this surgery revealed thinning and fibrosis of the muscularis externa. The patient was subsequently noted to have transparency of truncal skin with easily visible vessels. An underlying collagen vascular disorder was suspected, and genetic testing revealed a mutation in the collagen type III, α1 (<it>COL3A1</it>) gene, which is consistent with a diagnosis of Ehlers-Danlos syndrome type IV.</p> <p>Conclusions</p> <p>Ehlers-Danlos syndrome type IV, the vascular type, is a rare disorder caused by mutations in the <it>COL3A1 </it>gene on chromosome 2q31. It is characterized by translucent skin, clubfoot, and the potentially fatal complications of spontaneous large vessel rupture, although spontaneous uterine and colonic perforations have also been reported in the literature. The present case presentation describes the identification of Ehlers-Danlos syndrome type IV in a patient with a non-spontaneous colonic perforation secondary to an invasive investigation for another hereditary disorder pre-disposing him to colorectal cancer. Invasive procedures such as arteriograms and endoscopies are relatively contra-indicated in Ehlers-Danlos syndrome type IV. Alternatives with a lower risk of perforation, such as computed tomographic colonography, need to be considered for patients requiring ongoing colorectal cancer surveillance. Furthermore, management of vascular aneurysms in patients with Ehlers-Danlos syndrome type IV requires consideration of the risks of endovascular stenting, as opposed to open surgical intervention, because of tissue friability. Genetic and reproductive counseling should be offered to affected individuals and their families.</p

An individual patient data meta-analysis of adjuvant therapy with uracil–tegafur (UFT) in patients with curatively resected rectal cancer

Uracil–Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70–0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63–0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer

Importance of the First Postoperative Year in the Prognosis of Elderly Colorectal Cancer Patients

Surgical oncolog