Colorectal (Bowel) Cancer
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Colorectal cancer (or bowel cancer) is one of the most common types of cancer in both men and women. Approximately four fifths of these cancers are found in the colon (large intestine), and one fifth in the rectum. Prevention and early detection of colorectal cancer is important. Some of most common symptoms include a change in bowel habit (eg. constipation, and bleeding), mucus discharge, and discomfort or pain in the lower abdomen. The vast majority of colon and rectum cancers are adenocarcinomas, around 10% of these are mucinous (protein contained in mucus). The median age at diagnosis is 70, age adjusted incidence rates are slightly higher in males compared to females. A substantial proportion of cases are in those with a genetic predisposition to colorectal cancer. Diet may also have an influence on the incidence of colorectal cancer, diatry fibre, retinoids, and calcium are thought to be protective, while high intake of animal fats may increases risk. Colorectal cancer may develop from benign polyps (a polyp is a tumour on a stem most commonly found on mucous membranes). World-wide about 782,000 people are diagnosed with colorectal cancer each year.

Menu: Colorectal (Bowel) Cancer

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Herdiatry Colorectal Cancers
Screening for Colorectal (Bowel) Cancer
Prevention of Colorectal (Bowel) Cancer

Information Patients and the Public (17 links)


Information for Health Professionals / Researchers (11 links)


Herdiatry Colorectal Cancers (3 links)

Between 15-20% of all colorectal cancers are thought to be familial. Some types of colon cancers and pre-disposing conditions are known to have an inherited element, in particular, Lynch Syndrome (hereditary non-polyposis colon cancer, HNPCC) and familial adenomatous polyposis (FAP).See also: Gene and Chromosome Abnormalities (Cancer GeneWeb)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Neufert C, Becker C, Türeci Ö, et al.
Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK.
J Clin Invest. 2013; 123(4):1428-43 [PubMed] Free Access to Full Article
Molecular mechanisms specific to colitis-associated cancers have been poorly characterized. Using comparative whole-genome expression profiling, we observed differential expression of epiregulin (EREG) in mouse models of colitis-associated, but not sporadic, colorectal cancer. Similarly, EREG expression was significantly upregulated in cohorts of patients with colitis-associated cancer. Furthermore, tumor-associated fibroblasts were identified as a major source of EREG in colitis-associated neoplasms. Functional studies showed that Ereg-deficient mice, although more prone to colitis, were strongly protected from colitis-associated tumors. Serial endoscopic studies revealed that EREG promoted tumor growth rather than initiation. Additionally, we demonstrated that fibroblast-derived EREG requires ERK activation to induce proliferation of intestinal epithelial cells (IEC) and tumor development in vivo. To demonstrate the functional relevance of EREG-producing tumor-associated fibroblasts, we developed a novel system for adoptive transfer of these cells via mini-endoscopic local injection. It was found that transfer of EREG-producing, but not Ereg-deficient, fibroblasts from tumors significantly augmented growth of colitis-associated neoplasms in vivo. In conclusion, our data indicate that EREG and tumor-associated fibroblasts play a crucial role in controlling tumor growth in colitis-associated neoplasms.


Yeo SG, Kim DY, Chang HJ, et al.
Reappraisal of pretreatment carcinoembryonic antigen in patients with rectal cancer receiving preoperative chemoradiotherapy.
Tumori. 2013 Jan-Feb; 99(1):93-9 [PubMed]
AIMS AND BACKGROUND: The pretreatment serum carcinoembryonic antigen (CEA) level is an independent prognostic factor in colorectal cancer. We aimed to investigate the significance of CEA as a prognostic or predictive factor in rectal cancer patients receiving preoperative chemoradiotherapy (CRT).
METHODS AND STUDY DESIGN: In total, 609 patients with locally advanced (cStage II-III) mid to distal rectal cancer who underwent preoperative CRT and radical surgery between 2001 and 2008 were analyzed retrospectively. Predictive factors for pathologic CRT response were determined using multivariate logistic regression. A prognostic factor analysis was performed using the log-rank test and Cox proportional hazards regression.
RESULTS: Elevated CEA levels (>5 ng/mL) were observed in 201 (33.0%) patients at diagnosis. Following preoperative CRT, downstaging (ypStage 0-I) occurred in 255 (41.9%) patients, of whom 88 had pathologic complete tumor regression. Pretreatment CEA was significantly associated with pathologic CRT response in terms of downstaging and tumor regression grade, and was the most relevant predictive factor. After a median follow-up period of 60 months, the 5-year disease-free and overall survival rates were 76.2% and 84.6%, respectively. Prognostic factors independently associated with recurrence or survival included ypStage, circumferential resection margin, and histologic grade.
CONCLUSIONS: In patients with rectal cancer who received preoperative CRT, the pretreatment CEA level was a significant and independent predictor of pathologic CRT response. However, it may not be able to predict long-term outcomes independently of ypStage.


Li XD, Ji M, Wu J, et al.
Clinical significance of CD44 variants expression in colorectal cancer.
Tumori. 2013 Jan-Feb; 99(1):88-92 [PubMed]
AIMS AND BACKGROUND: We designed the present study to observe CD44s and CD44v6 expressions in colorectal cancer and evaluate their clinical value.
METHODS: CD44s and CD44v6 expression in colorectal cancer tissues were examined by an immunohistochemical test. Survival analysis was performed with the Kaplan-Meier method, and the differences between the CD44-positive and -negative groups were evaluated with the logrank test.
RESULTS: The positive rates of CD44s and CD44v6 were 66.7% and 63.2%, respectively. There were significant associations between CD44s positive expression and Dukes' stage or tumor differentiation. There were significant associations between CD44v6 positive expression and tumor differentiation, Dukes' stage and lymph node metastasis. There was a significant difference in the 5-year survival rates between CD44v6-positive and CD44v6-negative groups (52.78% and 80.95%, respectively), but not between CD44s-positive and CD44s-negative groups (55.26% and 78.95%, respectively). Multivariate analysis indicated that CD44v6 positive expression predicts a poor prognosis.
CONCLUSIONS: CD44s and CD44v6 play important roles in the infiltration and metastasis of colorectal cancer. CD44v6 positive expression can be a predictor for a poor prognosis.


Lee S, Kim DY, Kim SY, et al.
Curative radiotherapy using different radiation techniques for isolated lung metastasis from colorectal cancer.
Tumori. 2013 Jan-Feb; 99(1):68-75 [PubMed]
AIMS AND BACKGROUND: Surgical resection remains the mainstay for the treatment of colorectal lung metastasis, but a group of patients who are medically inoperable or unsuitable for surgery are treated with radiotherapy. The purpose of this multi-institutional study was to evaluate the clinical outcome and investigate the prognostic factors affecting local control and survival in this subset of patients.
METHODS: We retrospectively analyzed 30 patients with 43 lesions who underwent curative radiotherapy for isolated lung metastasis from colorectal cancer at nine institutions from 2003 and 2008. A total dose of 42-75 Gy at the peripheral planning target volume was administered in 3-35 fractions. The median biologically equivalent dose was 84 Gy (range, 58.5-180).
RESULTS: Treatment response was complete in 10 (33.3%), partial in 13 (43.3%), stable in six (20.0%), and progressive in one patient (3.3%). The median follow-up period for all patients was 29.0 months (range, 5.0-93.8). Kaplan-Meier local control at 5 years was 44%. The median survival was 46.2 months, and the 5-year overall survival was 47%. Twenty-three patients (77%) experienced treatment failure, most of which were intrapulmonary failure. The intrapulmonary relapse-free survival and overall relapse-free survival at 5 years were 22% and 19%, respectively. Treatment response and preradiotherapy carcinoembryonic antigen level were significant prognostic factors for local control and survival. Grade 3-5 toxicity occurred in 7 patients. Three patients had grade 5 toxicity, including radiation pneumonitis, a tracheoesophageal fistula, and hemoptysis.
CONCLUSIONS: . Curative radiotherapy for isolated lung metastasis from colorectal cancer in patients who are medially inoperable or unsuitable for surgery results in long-term survival, comparable to surgical resection. Curative radiotherapy could be an effective and noninvasive alternative if dose-limiting toxicity is carefully considered, particularly in patients with bilateral or central lesions.


Di Genesio Pagliuca M, Turri L, Munoz F, et al.
Patterns of practice in the radiation therapy management of rectal cancer: survey of the Interregional Group Piedmont, Valle d'Aosta and Liguria of the "Associazione Italiana di Radioterapia Oncologica (AIRO)".
Tumori. 2013 Jan-Feb; 99(1):61-7 [PubMed]
AIMS AND BACKGROUND: To report the survey about the main aspects on the use of radiotherapy for the treatment of rectal cancer in Piedmont and Liguria.
METHODS AND STUDY DESIGN: Sixteen centers (11 from Piedmont and 5 from Liguria) received and answered by email a questionnaire data base about clinical and technical aspects of the treatment of rectal cancer. All data were incorporated in a single data base and analyzed.
RESULTS: Data regarding 593 patients who received radiotherapy for rectal cancer during the year 2009 were collected and analyzed. Staging consisted in colonoscopy, thoracic and abdominal CT, pelvic MRI and endoscopic ultrasound. PET/CT was employed to complete staging and in the treatment planning in 12/16 centers (75%). Neoadjuvant radiotherapy was employed more frequently than adjuvant radiotherapy (50% vs 36.4%), using typically a total dose of 45 Gy with 1.8 Gy/fraction. Concurrent chemoradiation with 5-fluorouracil or capecitabine was mainly employed in neoadjuvant and adjuvant settings, whereas oxaliplatin alone or in combination with 5-FU or capecitabine and leucovorin was commonly employed as the adjuvant agent. The median interval from neoadjuvant treatment to surgery was 7 weeks after long-course radiotherapy and 8 days after short-course radiotherapy. The pelvic total dose of 45 Gy in the adjuvant setting was the same in all the centers. Doses higher than 45 Gy were employed with a radical intent or in case of positive surgical margins. Hypofractionated regimens (2.5, 3 Gy to a total dose of 35-30 Gy) were used in the palliative setting. No relevant differences were observed in target volume definition and patient setup. Twenty-six patients (4.4%) developed grade 3 acute toxicity. Follow-up was scheduled in a similar way in all the centers.
CONCLUSIONS: No relevant differences were found among the centers involved in the survey. The approach can help clinicians to address important clinical questions and to improve consistency and homogeneity of treatments.


Wong CK, Lam CL, Wan YF, Rowen D
Predicting SF-6D from the European Organization for Treatment and Research of Cancer Quality of Life Questionnaire scores in patients with colorectal cancer.
Value Health. 2013 Mar-Apr; 16(2):373-84 [PubMed]
OBJECTIVES: To develop a mapping model for estimating six-dimensional health state short form (SF-6D) utility scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (QLQ-C30 and QLQ-CR29) scores in patients with colorectal cancer (CRC), with and without adjustment for clinical and demographic characteristics.
METHODS: Ordinary least squares regression models were applied to a cross-sectional data set of 216 patients with CRC collected from a regional hospital in Hong Kong. Item responses or scale scores of cancer-specific (QLQ-C30) and colorectal-specific health-related quality-of-life (QLQ-CR38/CR29) data and selected demographic and clinical characteristics of patients were used to predict the SF-6D scores. Model goodness of fit was examined by using exploratory power (R(2) and adjusted R(2)), Akaike information criterion, and Bayesian information criterion, and predictive performance was evaluated by using root mean square error, mean absolute error, and Spearman's correlation coefficients between predicted and observed SF-6D scores. Models were validated by using an independent data set of 56 patients with CRC.
RESULTS: Both scale and item response models explained more than 67% of the variation in SF-6D scores. The best-performing model based on goodness of fit (R(2) = 75.02%), predictive ability in the estimation (root mean square error = 0.080, mean absolute error = 0.065), and validation data set prediction (root mean square error = 0.103, mean absolute error = 0.081) included variables of main and interaction effects of the QLQ-C30 supplemented by QLQ-CR29 subset scale responses and a demographic (sex) variable.
CONCLUSIONS: SF-6D scores can be predicted from QLQ-C30 and QLQ-CR38/CR29 scores with satisfactory precision in patients with CRC. The mapping model can be applied to QLQ-C30 and QLQ-CR38/CR29 data sets to produce utility scores for the appraisal of clinical interventions targeting patients with CRC using economic evaluation.


Hoyle M, Peters J, Crathorne L, et al.
Cost-effectiveness of cetuximab, cetuximab plus irinotecan, and panitumumab for third and further lines of treatment for KRAS wild-type patients with metastatic colorectal cancer.
Value Health. 2013 Mar-Apr; 16(2):288-96 [PubMed]
OBJECTIVES: To estimate the cost-effectiveness of cetuximab monotherapy, cetuximab plus irinotecan, and panitumumab monotherapy compared with best supportive care (BSC) for the third and subsequent lines of treatment of patients with Kirsten rat sarcoma wild-type metastatic colorectal cancer from the perspective of the UK National Health Service.
METHODS: An "an area under the curve" cost-effectiveness model was developed. The clinical effectiveness evidence for both cetuximab and panitumumab was taken from a single randomized controlled trial (RCT) in each case and for cetuximab plus irinotecan from several sources.
RESULTS: Patients are predicted to survive for approximately 6 months on BSC, 8.5 months on panitumumab, 10 months on cetuximab, and 16.5 months on cetuximab plus irinotecan. Panitumumab is dominated, and cetuximab is extended dominated. An incremental cost-effectiveness ratio (ICER) of £95,000 per quality-adjusted life-year (QALY) was estimated for cetuximab versus BSC and is likely to be relatively accurate, because the relevant clinical evidence is taken from a high-quality RCT. The estimated ICER for panitumumab versus BSC, at £187,000 per QALY, is less certain due to assumptions in the adjustment for the substantial crossing-over of patients in the RCT. The ICER for cetuximab plus irinotecan versus BSC, at £88,000 per QALY, is least certain due to substantial uncertainty about progression-free survival, treatment duration, and overall survival. Nonetheless, when key parameters are varied within plausible ranges, all three treatments always remain poor value for money.
CONCLUSIONS: All three treatments are highly unlikely to be considered cost-effective in this patient population in the United Kingdom. We explain how the reader can adapt the model for other countries.


Ueno H, Hashiguchi Y, Shimazaki H, et al.
Objective criteria for crohn-like lymphoid reaction in colorectal cancer.
Am J Clin Pathol. 2013; 139(4):434-41 [PubMed]
We aimed to determine semiquantitative evaluation criteria for Crohn-like lymphoid reaction (CLR). We reviewed 1,032 patients with colorectal cancer and evaluated CLR by counting all peritumoral lymphoid aggregates (LAs) and by measuring the maximum diameter of the largest LA. The maximum diameter of the largest LA, rather than the number, had a significant impact on survival. Active CLR determined by the 1-mm rule was significantly associated with MLH1/MSH2 immunohistochemical staining deficiency. The group with LAs 1 mm or larger had lower recurrence (P = .0008) and a higher survival rate (P < .0001) than that without LAs 1 mm or larger. These results were similarly observed in another cohort of 500 patients with colorectal cancer. The k values for CLR evaluation among 8 observers were 0.67 for the 1-mm rule and 0.50 for Graham's criteria. The size of the largest LA best reflects the specific characteristics of CLR, and the 1-mm rule is expected to improve assessment reproducibility.


Deenen MJ, Dewit L, Boot H, et al.
Simultaneous integrated boost-intensity modulated radiation therapy with concomitant capecitabine and mitomycin C for locally advanced anal carcinoma: a phase 1 study.
Int J Radiat Oncol Biol Phys. 2013; 85(5):e201-7 [PubMed]
PURPOSE: Newer radiation techniques, and the application of continuous 5-FU exposure during radiation therapy using oral capecitabine may improve the treatment of anal cancer. This phase 1, dose-finding study assessed the feasibility and efficacy of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with concomitant capecitabine and mitomycin C in locally advanced anal cancer, including pharmacokinetic and pharmacogenetic analyses.
METHODS AND MATERIALS: Patients with locally advanced anal carcinoma were treated with SIB-IMRT in 33 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 33 fractions of 1.5 Gy electively to the bilateral iliac and inguinal lymph node areas. Patients received a sequential radiation boost dose of 3 × 1.8 Gy on macroscopic residual tumor if this was still present in week 5 of treatment. Mitomycin C 10 mg/m(2) (maximum 15 mg) was administered intravenously on day 1, and capecitabine was given orally in a dose-escalated fashion (500-825 mg/m(2) b.i.d.) on irradiation days, until dose-limiting toxicity emerged in ≥2 of maximally 6 patients. An additional 8 patients were treated at the maximum tolerated dose (MTD).
RESULTS: A total of 18 patients were included. The MTD of capecitabine was determined to be 825 mg/m(2) b.i.d. The predominant acute grade ≥3 toxicities included radiation dermatitis (50%), fatigue (22%), and pain (6%). Fifteen patients (83% [95%-CI: 66%-101%]) achieved a complete response, and 3 (17%) patients a partial response. With a median follow-up of 28 months, none of the complete responders, and 2 partial responders had relapsed.
CONCLUSIONS: SIB-IMRT with concomitant single dose mitomycin C and capecitabine 825 mg/m(2) b.i.d. on irradiation days resulted in an acceptable safety profile, and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer.


Tanis PJ, Doeksen A, van Lanschot JJ
Intentionally curative treatment of locally recurrent rectal cancer: a systematic review.
Can J Surg. 2013; 56(2):135-44 [PubMed] Free Access to Full Article
BACKGROUND: There is a lack of outcome data beyond local recurrence rates after primary treatment in rectal cancer, despite more information being necessary for clinical decision-making. We sought to determine patient selection, therapeutic modalities and outcomes of locally recurrent rectal cancer treated with curative intent.
METHODS: We searched MEDLINE (1990-2010) using the medical subject headings "rectal neoplasms" and "neoplasm recurrence, local." Selection of cohort studies was based on the primary intention of treatment and availability of at least 1 outcome variable.
RESULTS: We included 55 cohort studies comprising 3767 patients; 8 studies provided data on the rate of intentionally curative treatment from an unselected consecutive cohort of patients (481 of 1188 patients; 40%). Patients were symptomatic with pain in 50% (796 of 1607) of cases. Overall, 3088 of 3767 patients underwent resection. The R0 resection rate was 56% (1484 of 2637 patients). The rate of external beam radiotherapy was 100% in 9 studies, 0% in 5 studies, and ranged from 12% to 97% in 37 studies. Overall postoperative mortality was 2.2% (57 of 2515 patients). Five-year survival was at least 25%, with an upper limit of 41% in 11 of 18 studies including at least 50 resections. We found a significant increase in reported survival rates over time (r2 = 0.214, p = 0.007).
CONCLUSION: More uniformity in treatment protocols and reporting on outcomes for locally recurrent rectal cancer is warranted. The observed improvement of reported survival rates in time is probably related to better patient selection and optimized multimodality treatment in specialized centres.


Danese E, Minicozzi AM, Montagnana M, et al.
Lack of an association between circulating adiponectin levels and risk of colorectal adenoma.
Clin Lab. 2013; 59(1-2):211-4 [PubMed]
BACKGROUND: The putative association between serum adiponectin levels and colorectal adenomas is actually under debate. The aim of this study was to investigate this association in relation to factors known to influence the levels of adiponectin such as anthropometric, metabolic, inflammatory parameters as well as lifestyle individual characteristics.
METHODS: 40 patients with adenomas and 40 controls were enrolled. Body weight, height, waist circumference, and blood pressure were recorded. Fasting plasma glucose, lipids, C-reactive protein, and adiponectin levels were measured. Metabolic Syndrome was defined and lifestyle characteristics assessed.
RESULTS: No differences were found in adiponectin values between patients and controls (p = 0.101). Adiponectin levels were significantly higher in females than in males (p = 0.004). Adiponectin levels did not result in significant association with colorectal adenomas even after adjustment for metabolic and life style parameters.
CONCLUSIONS: This study did not confirm the hypothesis that high levels of adiponectin confer decreased risk of colorectal adenomas.


Yin H, Liang Y, Yan Z, et al.
Mutation spectrum in human colorectal cancers and potential functional relevance.
BMC Med Genet. 2013; 14:32 [PubMed] Free Access to Full Article
BACKGROUND: Somatic variants, which occur in the genome of all cells, are well accepted to play a critical role in cancer development, as their accumulation in genes could affect cell proliferations and cell cycle.
METHODS: In order to understand the role of somatic mutations in human colorectal cancers, we characterized the mutation spectrum in two colorectal tumor tissues and their matched normal tissues, by analyzing deep-sequenced transcriptome data.
RESULTS: We found a higher mutation rate of somatic variants in tumor tissues in comparison with normal tissues, but no trend was observed for mutation properties. By applying a series of stringent filters, we identified 418 genes with tumor specific disruptive somatic variants. Of these genes, three genes in mucin protein family (MUC2, MUC4, and MU12) are of particular interests. It has been reported that the expression of mucin proteins was correlated with the progression of colorectal cancer therefore somatic variants within those genes can interrupt their normal expression and thus contribute to the tumorigenesis.
CONCLUSIONS: Our findings provide evidence of the utility of RNA-Seq in mutation screening in cancer studies, and suggest a list of candidate genes for future colorectal cancer diagnosis and treatment.


Wassira LN, Pinheiro PS, Symanowski J, Hansen A
Racial-ethnic colorectal cancer survival disparities in the mountain west region: the case of Blacks compared to Whites.
Ethn Dis. 2013; 23(1):103-9 [PubMed]
BACKGROUND: Substantial disparities in colorectal cancer (CRC) survival among racial-ethnic groups, especially between Blacks and Whites, have been extensively documented in the Northeast, California and South of the United States. The purpose of this study was to ascertain the determinants of colorectal cancer racial-ethnic survival disparities in a state of the Mountain West region, Nevada.
METHODS: The study population consisted of a cohort of 12,181 men and women with a first primary invasive carcinoma in the colon and rectum diagnosed between 1995 and 2007, identified through the Nevada Central Cancer Registry and followed for vital status until 31 December 2007. Likelihood ratio chi-square statistics were used to compare the sociodemographic and clinical characteristics for race-ethnicity. Cox proportional regression modeling and partial likelihood tests were used to estimate the hazard ratios and assess interaction effects in CRC cause-specific death.
RESULTS: Blacks and Hispanics were more likely to be diagnosed with distant stage disease, 22.4% and 21.5% respectively, compared to 17.9% in Whites. No difference was observed between racial-ethnic groups for diagnoses in regional stage. Univariate analysis yielded a 20.1% higher risk of CRC death for Blacks compared to Whites [95% CI = 1.05-1.37]. Adjustment for tumor stage, sex, age, diagnosis period, tumor sublocation, marital status, and economic status in the multivariate model showed a persistently increased risk of CRC death for Blacks (HR = 1.17, 95% CI = 1.02-1.33) in relation to Whites.
CONCLUSIONS AND IMPLICATIONS: Survival disparities persisted among Blacks in our study even after adjusting for common demographic and tumor factors. Further determinants of survival disparities between race/ethnicities, such as course of treatment, should be investigated. Additionally, more public health intervention programs should tailor CRC screening awareness towards minorities as well as ensuring equal access to health care and quality treatment.


Yacob M, Raju RS, Vyas FL, et al.
Management of colorectal cancer liver metastasis in a patient with immune thrombocytopaenia.
Ann R Coll Surg Engl. 2013; 95(2):e50-1 [PubMed]
Immune thrombocytopaenia (ITP) was referred to previously as idiopathic thrombocytopaenic purpura and is usually of autoimmune or viral aetiology. Colorectal cancer liver metastasis with concomitant ITP is rare and only three cases have been reported in the English literature. Adverse effects of adjuvant chemotherapy may aggravate ITP. The sequencing of chemotherapy, operation for the primary and liver metastasis, and a decision on splenectomy is important. We present our experience in the management of a 52-year-old man who, having undergone anterior resection one year earlier for carcinoma of the rectum, presented with liver metastasis and ITP. He underwent splenectomy with hepatectomy prior to chemotherapy.


Somasundaram SK, Akritidis G, Alagaratnam S, et al.
Extraluminal colonic arteriovenous haemangioma: an unusual cause of chronic lower gastrointestinal bleeding.
Ann R Coll Surg Engl. 2013; 95(2):e44-6 [PubMed]
Lower gastrointestinal bleeding is a common general surgical presentation in acute and chronic settings. Vascular anomalies account for 2% of such cases and can therefore be missed. We discuss a rare vascular anomaly in one of our patients where the diagnosis was not established for a ten-year period. We describe the subsequent management and a brief review of the literature of this uncommon condition.


Komori K, Kanemitsu Y, Kimura K, et al.
Tumor necrosis in patients with TNM stage IV colorectal cancer without residual disease (R0 Status) is associated with a poor prognosis.
Anticancer Res. 2013; 33(3):1099-105 [PubMed]
AIM: To examine the usefulness of the histopathological finding of tumor necrosis for stratifying TNM stage IV colorectal cancer in R0 status.
PATIENTS AND METHODS: We enrolled 98 patients with stage IV colorectal cancer, without residual disease after resection. The extent of necrosis was assessed using published thresholds, the extent was graded as "absent", "moderate" (<30% of tumor area), or "severe" (≥30%) in each section.
RESULTS: In multivariate analysis, the only significant difference in the disease-free survival rate was related to tumor necrosis (p=0.01) and the significant differences in the overall survival rates were related to the maximum tumor size and the degree of tumor necrosis (p=0.02 and p=0.001, respectively).
CONCLUSION: Tumor necrosis is associated with a poor prognosis in colorectal cancer and may allow the stratification of TNM stage IV patients without residual disease after surgery.


Healey E, Stillfried GE, Eckermann S, et al.
Comparative effectiveness of 5-fluorouracil with and without oxaliplatin in the treatment of colorectal cancer in clinical practice.
Anticancer Res. 2013; 33(3):1053-60 [PubMed]
BACKGROUND: First-line chemotherapeutic treatment of colorectal cancer (CRC) typically comprises oral (capecitabine) or intravenous 5-fluorouracil (5-FU) plus leucovorin (LV), in combination with oxaliplatin (XELOX or FOLFOX, respectively), although debate exists regarding the best course of treatment by modality in clinical practice. Evidence from practice comparisons is important in considering the net benefit of alternative chemotherapy regimens, given expected differences in survival associated with compliance and age of patients treated in real life versus controlled trial settings.
PATIENTS AND METHODS: Practice variation in 5-FU treatment (i.e. 5-FU/leucovorin, FOLFOX, capecitabine and XELOX) of patients with CRC from an Australian area health service (n=636) was analyzed between modalities by patient age, tumour stage and site using non-parametric tests. Survival analyses (n=434) were conducted over a three-year follow-up period using Cox regression, adjusting for observed confounders.
RESULTS: FOLFOX was the most commonly administered regimen. 5-FU modality was significantly associated with patient age (p<0.001), tumour stage (p<0.001) and site (p<0.001). Cox regression analyses found no significant difference in survival with the addition of oxaliplatin to 5-FU regimens.
CONCLUSION: Our findings suggested no survival benefit with the addition of oxaliplatin to 5-FU modalities in treating CRC in practice. This raises questions as to the net benefit of oxaliplatin, given its known toxicity profile and expense.


Atanda A, Chambers T, Beech DJ
Situs inversus.
Tenn Med. 2013; 106(1):33-4 [PubMed]
Situs Inversus is a rare condition with unique clinical and radiographic characteristics. We present a case highlighting important clinical factors associated with Situs Inversus.


Rogers JP, Dobradin A, Kar PM, Alam SE
Overnight hospital stay after colon surgery for adenocarcinoma.
JSLS. 2012 Apr-Jun; 16(2):333-6 [PubMed] Free Access to Full Article
A short hospital stay is one of the main advantages of the laparoscopic surgical technique. The process of developing and studying the "fast-track" process has contributed to a better understanding of the elements of perioperative care and has resulted in the reduction in length of stay (LOS) after colectomies. As we follow and refine this well-recognized multimodal approach, further decreases in the LOS can be expected. We present 2 octogenarian patients who, after receiving laparoscopic hemicolectomies for malignant disease, were discharged home < 24 hours after their operations. Postoperative follow-ups did not show any adverse reaction to the early discharge. Modifying the multimodal perioperative technique with further refinement to the surgical technique appears to allow patients to be discharged home in the first 24 hours following laparoscopic colectomy.


Aslak KK, Bulut O
The implementation of a standardized approach to laparoscopic rectal surgery.
JSLS. 2012 Apr-Jun; 16(2):264-70 [PubMed] Free Access to Full Article
BACKGROUND AND OBJECTIVES: The purpose of this study was to audit our results after implementation of a standardized operative approach to laparoscopic surgery for rectal cancer within a fast-track recovery program.
METHODS: From January 2009 to February 2011, 100 consecutive patients underwent laparoscopic surgery on an intention-to-treat basis for rectal cancer. The results were retrospectively reviewed from a prospectively collected database. Operative steps and instrumentation for the procedure were standardized. A standard perioperative care plan was used.
RESULTS: The following procedures were performed: low anterior resection (n = 26), low anterior resection with loop-ileostomy (n = 39), Hartmann's operation (n = 14), and abdominoperineal resection (n = 21). The median length of hospital stay was 7 days; 9 patients were readmitted There were 9 cases of conversion to open surgery. The overall complication rate was 35%, including 6 cases (90/%) of anastomotic leakages requiring reoperation. The 30-day mortality was 5%. The median number of harvested lymph nodes was 15 (range, 2 to 48). There were 6 cases of positive circumferential resection margins. The median follow-up was 9 (range, 1 to 27) months. One patient with disseminated cancer developed port-site metastasis.
CONCLUSIONS: The results confirm the safety of a standardized approach, and the oncological outcomes are comparable to those of similar studies.


Singh PP, Hill AG
Fast-track elective colectomy: single-surgeon experience of 100 consecutive cases.
N Z Med J. 2013; 126(1369):8-15 [PubMed]
AIMS: In 2005, the senior author (AGH) initiated an Enhanced Recovery After Surgery (ERAS) or 'fast-track' programme for elective colonic surgery at the Manukau Surgery Centre aimed at improving perioperative care. We reviewed the senior author's experience of elective colectomy conducted within the ERAS programme and evaluated clinical outcomes.
METHODS: Using a prospectively maintained database, consecutive patients who underwent elective colonic resection by the senior author within the ERAS programme at the Manukau Surgery Centre between December 2005 and March 2012 were reviewed. Demographic and operative data were recorded and clinical outcomes including complications, hospital stay and readmissions were evaluated for 30 days postoperatively.
RESULTS: 100 consecutive patients were reviewed. The median age of patients was 70 years (range: 16-92) and the most common indication for surgery was malignancy (81 cases). Right-sided colectomy was performed in 52 cases while 45 patients had a left-sided colectomy and 3 patients underwent subtotal colectomy. The median day to discharge was 3 days while total hospital stay was 4 days which incorporated 21 readmissions for mostly minor complications. Major complications occurred in only 8 patients and included 4 anastomotic leaks.
CONCLUSION: In one surgeon's experience, elective colectomy performed within an optimised perioperative care environment achieves shorter hospital stay with a low rate of major complications.


Trombold J, Farmer RW, McCafferty M
The impact of colorectal cancer screening in a veteran hospital population.
Am Surg. 2013; 79(3):296-300 [PubMed]
Colon and rectal cancer is the second most common cause of cancer death in the United States. Screening effectively decreases colorectal cancer mortality. This study aims to evaluate the impact of colorectal cancer screening within a Veterans Affairs Medical Center and treatment outcomes. Institutional Review Board approval was obtained for a retrospective analysis of all colorectal cancer cases that were identified through the Tumor Registry of the Robley Rex VA Medical Center from 2000 to 2009. Data collected included age at diagnosis, race, risk factors, diagnosis by screening versus symptomatic evaluation, screening test, tumor location and stage, operation performed, operative mortality, and survival. A value of P < 0.05 on Fisher's exact, χ(2), analysis of variance, or Cox regression analyses was considered significant. Three hundred fifty-four patients with colorectal cancer (255 colon, 99 rectal) were identified. One hundred twenty-one patients (34%) were diagnosed by screening. In comparison with those diagnosed by symptom evaluation (n = 233), these patients had earlier stage cancers, were more likely to have a curative intent procedure, and had improved 5-year survival rates. Older patients (older than 75 years old) were more likely to present with symptoms. High-risk patients were more likely to have colonoscopic screening than fecal occult blood testing. More blacks had Stage IV disease than nonblacks. Curative intent 30-day operative mortality was 2.1 per cent for colectomy and 0 per cent for rectal resection. Screening for colorectal cancer in the veteran population allows for better survival, detection at an earlier stage, and higher likelihood of resection.


Brescia A, Mari FS, Favi F, et al.
Laparoscopic lower anterior rectal resection using a curved stapler: original technique and preliminary experience.
Am Surg. 2013; 79(3):253-6 [PubMed]
Laparoscopic low anterior rectal resection (LLAR), allowing better visualization and rectal mobilization, can reduce postoperative pain and recovery. A contour curved stapler (CCS) is a very helpful device because of its curved profile that consents better access into the pelvic cavity and allows to perform rectal closure and section in one shot, especially in the presence of a narrow pelvis, complex anatomy, or large tumors. We developed an original technique of laparoscopic rectal resection using CCS. Between 2005 and 2009, in 36 cases, we performed LLAR with a three-trocar technique, starting with mobilization of left colonic flexure followed by the section of inferior mesenteric vessels. The rectum was prepared up to the levator ani with total mesorectal excision. The Lapdisc was inserted trough a suprapubic midline incision, allowing the CCS stapler placement into the pelvic cavity. After the rectal section, the anastomosis was then performed with a circular stapler. Ileostomy was performed if neoadjuvant radiotherapy and chemotherapy have been carried out or if the anastomosis was below 4 cm from the anal verge. Mean operative time was 135 minutes and no intra- or postoperative bleeding occurred. In 27 patients we performed temporary ileostomy. In two cases we observed anastomotic leakage; one of these patients already had ileostomy. No anastomotic stenosis occurred after one-year follow-up. This procedure simplifies the section of the lower rectum, reduces leaking rate resulting from technical difficulties, and does not nullify the benefits of laparoscopy.


Doubeni CA, Weinmann S, Adams K, et al.
Screening colonoscopy and risk for incident late-stage colorectal cancer diagnosis in average-risk adults: a nested case-control study.
Ann Intern Med. 2013; 158(5 Pt 1):312-20 [PubMed]
BACKGROUND: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer.
OBJECTIVE: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC).
DESIGN: Nested case-control study.
SETTING: Four U.S. health plans.
PATIENTS: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration.
MEASUREMENTS: Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures.
RESULTS: In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer.
LIMITATION: The small number of screening colonoscopies affected the precision of the estimates.
CONCLUSION: Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.


Green BB, Wang CY, Anderson ML, et al.
An automated intervention with stepped increases in support to increase uptake of colorectal cancer screening: a randomized trial.
Ann Intern Med. 2013; 158(5 Pt 1):301-11 [PubMed]
BACKGROUND: Screening decreases colorectal cancer (CRC) incidence and mortality, yet almost half of age-eligible patients are not screened at recommended intervals.
OBJECTIVE: To determine whether interventions using electronic health records (EHRs), automated mailings, and stepped increases in support improve CRC screening adherence over 2 years.
DESIGN: 4-group, parallel-design, randomized, controlled comparative effectiveness trial with concealed allocation and blinded outcome assessments. (ClinicalTrials.gov: NCT00697047)
SETTING: 21 primary care medical centers.
PATIENTS: 4675 adults aged 50 to 73 years not current for CRC screening.
INTERVENTION: Usual care, EHR-linked mailings ("automated"), automated plus telephone assistance ("assisted"), or automated and assisted plus nurse navigation to testing completion or refusal ("navigated"). Interventions were repeated in year 2.
MEASUREMENTS: The proportion of participants current for screening in both years, defined as colonoscopy or sigmoidoscopy (year 1) or fecal occult blood testing (FOBT) in year 1 and FOBT, colonoscopy, or sigmoidoscopy (year 2).
RESULTS: Compared with those in the usual care group, participants in the intervention groups were more likely to be current for CRC screening for both years with significant increases by intensity (usual care, 26.3% [95% CI, 23.4% to 29.2%]; automated, 50.8% [CI, 47.3% to 54.4%]; assisted, 57.5% [CI, 54.5% to 60.6%]; and navigated, 64.7% [CI, 62.5% to 67.0%]; P < 0.001 for all pair-wise comparisons). Increases in screening were primarily due to increased uptake of FOBT being completed in both years (usual care, 3.9% [CI, 2.8% to 5.1%]; automated, 27.5% [CI, 24.9% to 30.0%]; assisted, 30.5% [CI, 27.9% to 33.2%]; and navigated, 35.8% [CI, 33.1% to 38.6%]).
LIMITATION: Participants were required to provide verbal consent and were more likely to be white and to participate in other types of cancer screening, limiting generalizability.
CONCLUSION: Compared with usual care, a centralized, EHR-linked, mailed CRC screening program led to twice as many persons being current for screening over 2 years. Assisted and navigated interventions led to smaller but significant stepped increases compared with the automated intervention only. The rapid growth of EHRs provides opportunities for spreading this model broadly.


Ogundiran T, Tuupanen S, Aaltonen LA, et al.
delGA (rs67491583) variant and colorectal cancer risk in an indigenous African population.
Afr J Med Med Sci. 2012; 41(3):271-5 [PubMed]
BACKGROUND: A recent study showed a higher frequency of GA deletion at rs67491583 in African American colorectal cancer (CRC) patients compared to controls, suggesting a likely contribution of this allele to racial disparity in CRC risk predisposition. We conducted a pilot study in an indigenous African population to evaluate this potential CRC risk variant.
METHODS: We collected epidemiological data and biological specimen from consenting consecutive CRC cases and controls presenting at the Oncology Clinic of University College Hospital, Ibadan from 2001 to 2007. We examined germline DNA for delGA by PCR-amplification of two overlapping fragments using standard primers. The products were directly sequenced using Applied Biosystems BigDye v3.1 sequencing chemistry and AB 13730 automatic DNA sequencer.
RESULTS: There were 45 cases and 45 controls of which genotyping was successful in 39 cases and 38 controls. There were 5 heterozygous and 2 homozygous GA deletions with frequency of 11.54% (9/78) among cases whereas there were 8 heterozygous and 1 homozygous GA deletions among controls with frequency of 13.15% (10/76). (p= 0.79, OR 0.88, 95% CI 0.34-2.28).
CONCLUSION: This study suggests that there is no association between the delGA (rs67491583) variant and CRC risk in this indigenous African population. However our sample size was small and the participants were not ethnically homogenous. Further studies are required to evaluate this marker in African CRC.


Liu C, Billadeau DD, Abdelhakim H, et al.
IQGAP1 suppresses TβRII-mediated myofibroblastic activation and metastatic growth in liver.
J Clin Invest. 2013; 123(3):1138-56 [PubMed] Free Access to Full Article
In the tumor microenvironment, TGF-β induces transdifferentiation of quiescent pericytes and related stromal cells into myofibroblasts that promote tumor growth and metastasis. The mechanisms governing myofibroblastic activation remain poorly understood, and its role in the tumor microenvironment has not been explored. Here, we demonstrate that IQ motif containing GTPase activating protein 1 (IQGAP1) binds to TGF-β receptor II (TβRII) and suppresses TβRII-mediated signaling in pericytes to prevent myofibroblastic differentiation in the tumor microenvironment. We found that TGF-β1 recruited IQGAP1 to TβRII in hepatic stellate cells (HSCs), the resident liver pericytes. Iqgap1 knockdown inhibited the targeting of the E3 ubiquitin ligase SMAD ubiquitination regulatory factor 1 (SMURF1) to the plasma membrane and TβRII ubiquitination and degradation. Thus, Iqgap1 knockdown stabilized TβRII and potentiated TGF-β1 transdifferentiation of pericytes into myofibroblasts in vitro. Iqgap1 deficiency in HSCs promoted myofibroblast activation, tumor implantation, and metastatic growth in mice via upregulation of paracrine signaling molecules. Additionally, we found that IQGAP1 expression was downregulated in myofibroblasts associated with human colorectal liver metastases. Taken together, our studies demonstrate that IQGAP1 in the tumor microenvironment suppresses TβRII and TGF-β dependent myofibroblastic differentiation to constrain tumor growth.


Matkowskyj KA, Chen ZE, Rao MS, Yang GY
Dysplastic lesions in inflammatory bowel disease: molecular pathogenesis to morphology.
Arch Pathol Lab Med. 2013; 137(3):338-50 [PubMed]
Context.-Inflammatory bowel disease (IBD) is a long-standing chronic active inflammatory process in the bowel with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic active inflammatory processes contribute to multistage progression of human cancer development, including reactive oxygen and nitrogen species, aberrant arachidonic acid metabolites and cytokines/growth factors, and immune dysfunction. These molecular events in IBD lead to genetic abnormality and promote aberrant cell proliferation, which further lead to epithelial changes encompassing a broad spectrum from inflammation-induced hyperplasia to dysplasia. Objective.-To review the (1) epidemiologic and molecular pathogenesis of the risk for colorectal cancer in IBD, (2) morphologic characterization, biomarker(s), and classification of dysplastic lesions, and (3) clinical management of dysplastic lesions arising in IBD. Data Sources.-The different IBD-related dysplastic lesions are illustrated by using morphology in conjunction with molecular pathways, and the "field cancerization" theory and its potential significance are discussed with a review of the literature. Conclusions.-Patients with IBD are at increased risk of developing colorectal cancer. The risk of developing carcinoma is related to the extent/duration/activity of the patient's disease. There is no consensus regarding the extent of carcinoma risk associated with IBD; however, all would agree that patients with IBD represent a group at significant risk for developing carcinoma and as such, warrant adequate surveillance and prevention. With better screening modalities and detection/characterization of dysplastic lesions, IBD-associated serrated lesions, and "field cancerization," we will improve our understanding of and approach to risk stratification.


De Caluwé L, Van Nieuwenhove Y, Ceelen WP
Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer.
Cochrane Database Syst Rev. 2013; 2:CD006041 [PubMed]
BACKGROUND: Preoperative radiotherapy (RT) decreases local recurrence rate and improves survival in stage II and III rectal cancer patients. The combination of chemotherapy with RT has a sound radiobiological rationale, and phase II trials of combined chemoradiation (CRT) have shown promising activity in rectal cancer.
OBJECTIVES: To compare preoperative RT with preoperative CRT in patients with resectable stage II and III rectal cancer.
SEARCH METHODS: We searched the Cochrane Register of Controlled Trials, Web of Science, Embase.com, and Pubmed from 1975 until June 2012. A manual search was performed of Ann Surg, Arch Surg, Cancer, J Clin Oncol, Int J Radiat Oncol Biol Phys and the proceedings of ASTRO, ECCO and ASCO from 1990 until June 2012.
SELECTION CRITERIA: Relevant studies randomized resectable stage II or III rectal cancer patients to at least one arm of preoperative RT alone or at least one arm of preoperative CRT.
DATA COLLECTION AND ANALYSIS: Primary outcome parameters included overall survival (OS) at 5 years and local recurrence (LR) rate at 5 years. Secondary outcome parameters included disease free survival (DFS) at 5 years, metastasis rate, pathological complete response rate, clinical response rate, sphincter preservation rate, acute toxicity, postoperative mortality and morbidity, and anastomotic leak rate. Outcome parameters were summarized using the Odds Ratio (OR) and associated 95% confidence interval (CI) using the fixed effects model.
MAIN RESULTS: Five trials were identified and included in the meta-analysis. From one of the included trials only preliminary data are reported. The addition of chemotherapy to preoperative RT significantly increased grade III and IV acute toxicity (OR 1.68-10, P = 0.002) and marginally affected postoperative overall morbidity (OR 0.67-1.00, P = 0.05) while no differences were observed in postoperative mortality or anastomotic leak rate. Compared to preoperative RT alone, preoperative CRT significantly increased the rate of complete pathological response (OR 2.12-5.84, P < 0.00001) although this did not translate into a higher sphincter preservation rate (OR 0.92-1.30, P = 0.32). The incidence of local recurrence at five years was significantly lower in the CRT group compared to RT alone (OR 0.39-0.72, P < 0.001). No statistically significant differences were observed in DFS (OR 0.92-1.34, P = 0.27) or OS (OR 0.79-1.14, P = 0.58) at five years.
AUTHORS' CONCLUSIONS: Compared to preoperative RT alone, preoperative CRT enhances pathological response and improves local control in resectable stage II and III rectal cancer, but does not benefit disease free or overall survival. The effects of preoperative CRT on functional outcome and quality of life are incompletely understood and should be addressed in future trials.


Burrell RA, McClelland SE, Endesfelder D, et al.
Replication stress links structural and numerical cancer chromosomal instability.
Nature. 2013; 494(7438):492-6 [PubMed]
Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity. CIN is observed in most solid tumours and is associated with both poor prognosis and drug resistance. Understanding a mechanistic basis for CIN is therefore paramount. Here we find evidence for impaired replication fork progression and increased DNA replication stress in CIN(+) colorectal cancer (CRC) cells relative to CIN(-) CRC cells, with structural chromosome abnormalities precipitating chromosome missegregation in mitosis. We identify three new CIN-suppressor genes (PIGN (also known as MCD4), MEX3C (RKHD2) and ZNF516 (KIAA0222)) encoded on chromosome 18q that are subject to frequent copy number loss in CIN(+) CRC. Chromosome 18q loss was temporally associated with aneuploidy onset at the adenoma-carcinoma transition. CIN-suppressor gene silencing leads to DNA replication stress, structural chromosome abnormalities and chromosome missegregation. Supplementing cells with nucleosides, to alleviate replication-associated damage, reduces the frequency of chromosome segregation errors after CIN-suppressor gene silencing, and attenuates segregation errors and DNA damage in CIN(+) cells. These data implicate a central role for replication stress in the generation of structural and numerical CIN, which may inform new therapeutic approaches to limit intratumour heterogeneity.


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