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.

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Screening for Colorectal (Bowel) Cancer
Prevention of Colorectal (Bowel) Cancer

Information Patients and the Public (18 links)

Information for Health Professionals / Researchers (12 links)

Herdiatry Colorectal Cancers (5 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).

Bhushan M, Schnabel JA, Chappell M, et al.
The impact of heterogeneity and uncertainty on prediction of response to therapy using dynamic MRI data.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):316-23 [PubMed] Related Publications
A comprehensive framework for predicting response to therapy on the basis of heterogeneity in dceMRI parameter maps is presented. A motion-correction method for dceMRI sequences is extended to incorporate uncertainties in the pharmacokinetic parameter maps using a variational Bayes framework. Simple measures of heterogeneity (with and without uncertainty) in parameter maps for colorectal cancer tumours imaged before therapy are computed, and tested for their ability to distinguish between responders and non-responders to therapy. The statistical analysis demonstrates the importance of using the spatial distribution of parameters, and their uncertainties, when computing heterogeneity measures and using them to predict response on the basis of the pre-therapy scan. The results also demonstrate the benefits of using the ratio of Ktrans with the bolus arrival time as a biomarker.

Fanetti G, Ferrari LA, Pietrantonio F, Buzzoni R
Reversible bilateral blepharoptosis following oxaliplatin infusion: a case report and literature review.
Tumori. 2013 Sep-Oct; 99(5):e216-9 [PubMed] Related Publications
Oxaliplatin, a platinum analogue employed in the treatment of colorectal cancer and various other neoplasms, is characterized by a broad range of adverse events. Peripheral neuropathy is probably the most peculiar and clinically relevant toxicity associated with its use and can be distinguished into two types: acute and chronic neurotoxicity.We report a case of acute reversible bilateral palpebral ptosis and dyspnea without bronchospasm or laryngospasm which occurred at the end of the third administration of adjuvant oxaliplatin by infusion for stage III colon cancer in a 54-year-old woman. Chlorphenamine and hydrocortisone were administered with fast resolution of dyspnea and slight improvement of ptosis. Complete resolution with no sequelae occurred in one hour. No further recurrence of blepharoptosis was described during the following days. The subsequent cycles were prescribed at reduced dosage without acute complications.

Related: Oxaliplatin

Vasiliadisl K, Papavasiliou C, Pervana S, et al.
Acute pancreatitis as the initial manifestation of an adenocarcinoma of the major duodenal papilla in a patient with familial adenomatous polyposis syndrome: a case report and literature review.
Acta Chir Belg. 2013 Nov-Dec; 113(6):463-7 [PubMed] Related Publications
We report a case of an ampullary carcinoma presenting as acute pancreatitis in a patient with familial adenomatous polyposis (FAP) syndrome and severe duodenal adenomatosis. A 48-year-old woman was hospitalised because of an episode of acute pancreatitis. She had a history of prophylactic total colectomy for FAP 2 years earlier. On admission, abdominal ultrasonography and computed tomography revealed dilatation of the main pancreatic and common bile duct. Spigelman's stage IV duodenal adenomatosis involving the major duodenal papilla was diagnosed on endoscopy and a classical Whipple procedure was proposed. Pathologic examination of the duodenopancreatectomy specimen revealed a tubular adenocarcinoma of the papilla that occluded the major pancreatic ducts. The patient had no evidence of disease and experienced no recurrent attacks of acute pancreatitis during a 36-month period of follow-up.

Kornmann VN, Hagendoorn J, van Koeverden S, et al.
Totally laparoscopic right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure.
Acta Chir Belg. 2013 Nov-Dec; 113(6):439-43 [PubMed] Related Publications
BACKGROUND: During laparoscopic right hemicolectomy, most surgeons perform an extracorporeal anastomosis. A totally laparoscopic procedure with intracorporeal anastomosis may improve cosmesis because midline- or paraumbilical incisions can be avoided. Here, we investigate the safety of an intracorporeal anastomosis from a technical and oncological perspective.
METHODS: All patients who underwent right hemicolectomy with intracorporeal anastomosis between 2003-2011 were retrospectively analyzed. Parameters were duration of surgery, intraoperative blood loss, mortality and morbidity. Adequacy of oncologic resections was scored by resectional margins and number of harvested lymph nodes.
RESULTS: A total of 162 patients were included with a median age of 69 years (IQR60-76). The duration of surgery was 100 minutes (80-120) and intraoperative blood loss was 30 mL (10-100). Hundred-twenty patients (74%) underwent an oncologic resection. Number of harvested lymph nodes was 12 (9-18). RO-resection was achieved in 100%. Four patients died (2.5%). Postoperative complications were: anastomotic leakage (3.1%; n = 5), ileus (4.9%; n = 8), abscesses (2.5% ; n = 4), wound infection (3.1% ; n = 5) and cardiopulmonary complications (10.5% ; n = 17). Duration of oncological follow-up was 2.5 years (1.3-4.6). Local recurrence and overall survival rates at two years were 0.8% and 85.4%, respectively.
CONCLUSION: Right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure with acceptable operating time and low mortality.

Keskin S, Tas F, Karabulut S, et al.
The role of surgical methods in the treatment of anorectal malignant melanoma (AMM).
Acta Chir Belg. 2013 Nov-Dec; 113(6):429-33 [PubMed] Related Publications
PURPOSE: Anorectal malignant melanoma (AMM) is a rare tumor with a poor prognosis. The aim of this study was to investigate the clinicopathological characteristics and treatment outcomes in patients with AMM.
METHODS: The study included 21 patients diagnosed with AMM between 2000 and 2010 that were evaluated with regard to age, sex, disease stage, treatment modality, and survival. Stage I, II, and III were defined as localized primary malignant melanoma, regional lymph node metastasis, and distant metastasis, respectively.
RESULTS: In all, 12 (57%) patients were female and 9 (43%) were male ; median age was 61 years (range : 30-84 years). Among the 21 patients, 7 (47%) underwent abdominoperineal resection and 8 (53%) were treated using wide local excision. Four (19%) patients were classified as stage I, 10 (48%) as stage II, and 7 (33%) patients as stage III. In total, 10 patients received adjuvant therapy. Median overall and progression-free survival was 12 and 9 months, respectively. The 1-year and 5-year overall survival estimates were 59% and 42%, and progression free survival were 49% and 7%, respectively. Patients aged > 60 years (P = 0.145), female patients (P = 0.076), patients with localized disease (P = 0.045), patients that underwent wide local excision (P = 0.619), and patients that received adjuvant therapy (P = 0.962) had longer survival.
CONCLUSIONS: The prognosis of AMM remains very poor and disease stage is the only predictor of survival. Abdominoperineal resection does not confer an advantage, in terms of survival, in patients with AMM.

Related: Anal Cancer Melanoma

Debunne H, Ceelen W
Mucinous differentiation in colorectal cancer: molecular, histological and clinical aspects.
Acta Chir Belg. 2013 Nov-Dec; 113(6):385-90 [PubMed] Related Publications
UNLABELLED: BACKGROUND : Mucinous colorectal carcinoma represents a subtype of colorectal carcinoma (CRC), which is characterized by abundant amount of extracellular mucin. We reviewed the molecular, histological and clinical aspects of mucinous CRC as compared to the non-mucinous type.
METHODS: A systematic web-based research was performed using Web of Knowledge. The combination of the Boolean search terms "COLO" AND "MUC" was used. The literature was searched until July 2013.
RESULTS: Patients with mucinous CRC have distinct clinical and pathological features. Mucinous CRC tends to occur in younger patients, are often seen in the proximal colon, are more diagnosed at an advanced stage and are more frequently associated with hereditary non-polyposis colorectal cancer (HNPCC) and young-age sporadic colorectal cancer. The prognostic significance of mucinous differentiation remains uncertain; some studies have shown a poor response to oxaliplatin and/or irinotecan based chemotherapy. Mucinous CRC is associated with a higher expression of MUC2 and MUC5AC, but a lower expression of MUC1. The differential expression of mucins has been related to altered risk of metastasis and death. Recently, mucins have been used as targets for molecular therapy and as a source of immune therapy. Mucinous differentiation is associated with other specific genetic and molecular features such as increased BRAF mutation rate and microsatellite instability.
CONCLUSION: Mucinous CRC is a distinct clinical, pathological, and molecular entity. The implications of mucinous differentiation for treatment response and outcome are not fully elucidated, but the available data suggest an adverse effect. The use of mucins as immunotargets may show therapeutic promise for mucinous CRC.

Related: MUC2

Sokolov M, Toshev S, Todorov G, et al.
Per magna-ovarian metastases from primary locally advanced colorectal cancer--a review of the literature with a description of three clinical cases.
Khirurgiia (Sofiia). 2013; (3):39-47 [PubMed] Related Publications
Krukenberg tumor is defined as metastatic lesions of gastrointestinal cancers. Several specific immunohistochemical methods can identify the main focus of malignant neoplasm. Ovarian metastases from colorectal cancer are rarely seen phenomenon. The authors examine in detail the literature on this issue and describe three own clinical cases of metachronous ovarian meta lesions in women undergoing surgery for locally advanced colorectal cancer--two of these metastases are unilateral, while one--bilateral established in a short time interval despite the casuistic nature of the pathology. One of the patients died in the early postoperative period of co-morbid complications unrelated to the underlying disease, and the other two monitoring continues during the adjuvant. Krukenberg-metastases from colorectal cancer occur in the blood-vascular pattern in time without damage to the left or right ovary. Metachronous development and operative treatment of ovarian metastases is far better prognosis of the cases with and operated simultaneously established metastases in the ovaries.

Goh V, Glynne-Jones R
Perfusion CT imaging of colorectal cancer.
Br J Radiol. 2014; 87(1034):20130811 [PubMed] Related Publications
Imaging plays an important role in the assessment of colorectal cancer, including diagnosis, staging, selection of treatment, assessment of treatment response, surveillance and investigation of suspected disease relapse. Anatomical imaging remains the mainstay for size measurement and structural evaluation; however, functional imaging techniques may provide additional insights into the tumour microenvironment. With dynamic contrast-enhanced CT techniques, iodinated contrast agent kinetics may inform on regional tumour perfusion, shunting and microvascular function and provide a surrogate measure of tumour hypoxia and angiogenesis. In colorectal cancer, this may be relevant for clinical practice in terms of tumour phenotyping, prognostication, selection of individualized treatment and therapy response assessment.

Gorey KM, Luginaah IN, Bartfay E, et al.
Better colon cancer care for extremely poor Canadian women compared with American women.
Health Soc Work. 2013; 38(4):240-8 [PubMed] Related Publications
Extremely poor Canadian women were recently observed to be largely advantaged on most aspects of breast cancer care as compared with similarly poor, but much less adequately insured, women in the United States. This historical study systematically replicated the protective effects of single- versus multipayer health care by comparing colon cancer care among cohorts of extremely poor women in California and Ontario between 1996 and 2011. The Canadian women were again observed to have been largely advantaged. They were more likely to have received indicated surgery and chemotherapy, and their wait times for care were significantly shorter. Consequently, the Canadian women were much more likely to experience longer survival times. Regression analyses indicated that health insurance nearly completely explained the Canadian advantages. Implications for contemporary and future reforms of U.S. health care are discussed.

Related: Canada USA

Ueno H, Hase K, Hashiguchi Y, et al.
Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.
Am J Surg Pathol. 2014; 38(2):197-204 [PubMed] Related Publications
The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.

Bettington M, Walker N, Rosty C, et al.
Critical appraisal of the diagnosis of the sessile serrated adenoma.
Am J Surg Pathol. 2014; 38(2):158-66 [PubMed] Related Publications
The sessile serrated adenoma (SSA) is a relatively recently described polyp that can present diagnostic difficulties for the practicing pathologist. The frequency of SSA diagnoses varies dramatically in the reported literature. In addition, the histologic interface between the microvesicular hyperplastic polyp (MVHP) and the SSA continues to be a diagnostic problem. The trend in recent years has been toward a lower threshold for SSA diagnosis. Herein, we have performed a cross-sectional study of 6340 colorectal polyps received at a high-volume community-based pathology practice over a 3-month period. After central review, with strict application of the diagnostic criteria outlined in the 2010 edition of the World Health Organization Classification of Tumours of the Digestive Tract, we found that SSAs represented 12.1% of all polyps. In addition, we developed novel diagnostic subcategories in an attempt to determine the most appropriate cutoff for the interface between the MVHP and the SSA. We found that serrated polyps (MVHPs or SSAs) with any SSA-like crypts had clinical features more in common with the SSA than the MVHP and that this diagnostic cutoff showed good reproducibility between pathologists. This supports the position of a recent consensus publication proposing that polyps with as few as 1 SSA-type crypt should be diagnosed as an SSA. Applying these criteria to our cohort yields an overall SSA rate of 14.7%. In summary, we believe that SSAs continue to be underdiagnosed in pathologic practice and that this may result in inadequate surveillance and thus contribute to interval colorectal carcinomas.

Javed MA, Sheel AR, Sheikh AA, et al.
Size of metastatic deposits affects prognosis in patients undergoing pulmonary metastectomy for colorectal cancer.
Ann R Coll Surg Engl. 2014; 96(1):32-6 [PubMed] Related Publications
INTRODUCTION: Pulmonary metastectomy for colorectal cancer (CRC) is a well accepted procedure although data regarding indications and prognostic outcomes are inconsistent. This study aimed to analyse our experience with resection of pulmonary CRC metastases to evaluate clinically relevant prognostic factors affecting survival.
METHODS: A retrospective analysis was undertaken of the records of all patients with pulmonary metastases from CRC who underwent a thoracotomy between 2004 and 2010 at a single surgical centre.
RESULTS: Sixty-six patients with pulmonary metastases from the colon (n=34) and the rectum (n=32) were identified. The 30-day hospital mortality rate was 0%, with 63 patients undergoing a R0 resection and 3 having a R1 resection. The median survival was 45 months and the cumulative 3-year survival rate was 61%. Size of pulmonary metastasis and ASA (American Society of Anesthesiologists) grade were statistically significant prognostic factors (p=0.047 and p=0.009 respectively) with lesions over 20mm associated with a worse prognosis. Sex, age, site, disease free interval (cut-off 36 months), primary tumour stage, hepatic metastases, number of metastases (solitary vs multiple), type of operation (wedge vs lobe resection), hilar lymph node involvement and administration of adjuvant chemotherapy were not found to be statistically significant prognostic factors.
CONCLUSIONS: Pulmonary metastectomy has a potential survival benefit for patients with metastatic CRC. Improved survival even in the presence of hepatic metastases or multiple pulmonary lesions justifies aggressive surgical management in carefully selected patients. In our cohort, size of metastatic deposit was a statistically significant poor prognostic factor.

Maglio R, Meucci M, Muzi MG, et al.
Laparoscopic total mesorectal excision for ultralow rectal cancer with transanal intersphincteric dissection as a first step: a single-surgeon experience.
Am Surg. 2014; 80(1):26-30 [PubMed] Related Publications
Laparoscopic intersphincteric resection (ISR) after neoadjuvant chemoradiation is helpful in the management of patients with low rectal cancer. With the advent of this technique, the need for performance of abdominoperineal resection seems to have decreased in patients with very low rectal tumors. The aim of the present study was to evaluate the feasibility of laparoscopic ISR preceded by transanal rectal dissection low rectal cancer. Between December 2009 and June 2011, we performed laparoscopic ISR for 30 patients with very low rectal cancer. Patients received preoperative concurrent chemoradiation (5 days a week for 5 weeks). The surgical procedure was performed 6 weeks after radiotherapy and included total mesorectal excision, ISR, transanal coloanal anastomosis with coloplasty and loop ileostomy. Clinical data of 30 patients were analyzed retrospectively. Thirty patients (21 men, nine women) had a median age of 65 years (range, 37 to 75 years), a median body weight of 67 kg (range, 43 to 96 kg), and body mass index of 24 kg/m(2) (range, 19 to 33 kg/m(2)). The distance of the tumor from the anal verge was 5 cm (range, 2 to 11 cm). The operative time was from 240 to 360 minutes, and estimated blood loss was 100 to 520 mL. There were no conversions and no postoperative mortality. This procedure is feasible and has favorable short-term results for radical treatment of very low rectal disease while preserving anal function.

Ortiz AP, Guiot HM, Díaz-Miranda OL, et al.
Recognizing and treating anal cancer: training medical students and physicians in Puerto Rico.
P R Health Sci J. 2013; 32(4):209-12 [PubMed] Related Publications
OBJECTIVE: This training activity aimed at increasing the knowledge of anal cancer screening, diagnostic and treatment options in medical students and physicians, to determine the interest of these individuals in receiving training in the diagnosis and treatment of anal cancer, and to explore any previous training and/or experience with both anal cancer and clinical trials that these individuals might have.
METHODS: An educational activity (1.5 contact hours) was attended by a group of medical students, residents and several faculty members, all from the Medical Sciences Campus of the University of Puerto Rico (n = 50). A demographic survey and a 6-item pre- and post-test on anal cancer were given to assess knowledge change.
RESULTS: Thirty-four participants (68%) answered the survey. Mean age was 29.6 +/- 6.6 years; 78.8% had not received training in anal cancer screening, 93.9% reported being interested in receiving anal cancer training, and 75.8% expressed an interest in leading or conducting a clinical trial. A significant increase in the test scores was observed after the educational activity (pre-test: 3.4 +/- 1.2; post-test: 4.7 +/- 0.71). Three of the items showed an increase in knowledge by the time the post-test was taken. The first of these items assessed the participants' knowledge regarding the existence of any guidelines for the screening/treatment of patients with human papillomavirus (HPV)-related anal disease. The second of these items attempted to determine whether the participants recognized that anal intraepithelial neoplasia (AIN) 2 is considered to be a high-grade neoplasia. The last of the 3 items was aimed at ascertaining whether or not the participants were aware that warty growths in the anus are not necessarily a manifestation of high-grade AIN.
CONCLUSION: This educational activity increased the participants' knowledge of anal cancer and revealed, as well, that most of the participants were interested in future training and in collaborating in a clinical trial. Training physicians from Puerto Rico on anal cancer clinical trials is essential to encourage recruitment of Hispanic patients in these studies now that the guidelines in anal cancer screening and treatment are on their way to be defined.

Related: Anal Cancer Cancer Screening and Early Detection

Haroon N, Khan S, Alvi R
Rectal carcinoma under 40 years of age: seven-year post-treatment follow-up at a tertiary care hospital in Pakistan.
J Pak Med Assoc. 2013; 63(12):1460-3 [PubMed] Related Publications
OBJECTIVES: To determine epidemiological characteristics, clinical presentation, histopathological features, and long-term follow-up of patients below 40 years of age with carcinoma rectum.
METHODS: The retrospective case series comprised all patients presenting with histopathological diagnosis of carcinoma rectum with age 15-40 years at the Aga Khan University Hospital between January 1994 and December 2004. Details regarding patient demographics, pre-operative assessment, management and tumour grade and stage were obtained from a prospectively maintained database. Continuous and categorical variables in the data were analysed.
RESULTS: Of the 23 patients in the study, 14 (60.89%) were male and 9 (39.13%) were female. Mean age of the subjects was 31+/- 5 years. Overall, 22 (95.6%) patients presented with rectal bleeding and 12 (52%) had altered bowel habit. The most common site for the tumour was lower rectum (n=20; 87%) and 13 (56.5%) required abdominoperineal resection. Local recurrence rate was 13% (n=3) and distant metastasis occurred in 2 (8.6%) patients during the seven year follow-up. Two (8.6%) patients died, and both had distant metastasis.
CONCLUSION: Carcinoma rectum is uncommon but an important malignancy in patients aged below 40 years. The clinician should have a high index of suspicion in young patients presenting with bleeding per rectum, altered bowel habit and weight-loss.

Nakamoto T, Koyama F, Kobata Y, et al.
The "sliding door" technique for closure of abdominal wall defects after rectus abdominis musculocutaneous flap transposition.
Gan To Kagaku Ryoho. 2013; 40(12):2430-2 [PubMed] Related Publications
Radical surgery is often necessary in patients with local recurrence of rectal cancer or in those with carcinoma associated with an anal fistula. The surgery may include extended excision of the perineal area and can create a large dead space in the pelvis and a large skin defect, often necessitating reconstruction of the pelvic floor using rectus abdominis musculocutaneous (RAM) flap transposition. Wound dehiscence and incisional hernia are common complications of RAM flap transposition. We report herein our encounter with 3 patients in whom we used a "sliding door" technique for reconstruction of the abdominal wall after the creation of a RAM flap. One patient underwent abdominoperineal resection with sacrectomy and RAM flap transposition; he experienced a postoperative surgical site infection and wound dehiscence, which we urgently repaired by reconstructing the abdominal wall using the sliding door technique. Two other patients underwent posterior pelvic exenteration with sacrectomy and RAM flap transposition. These patients underwent simultaneous abdominal wall reconstruction using the sliding door technique. No patient experienced postoperative pelvic sepsis, wound dehiscence, or incisional hernia. The sliding door technique might be useful for preventing wound dehiscence and incisional hernia in patients undergoing RAM flap transposition.

Basar N, Ali A, Khan NA, Memon AS
Metastasis to ileostomy of mucinous adenocarcinoma of rectum.
J Pak Med Assoc. 2013; 63(10):1302-4 [PubMed] Related Publications
Carcinoma of colon and rectum is one of the most common malignancies of gastrointestinal tract. Primary ileostomy cancer following excision of primary tumour is a rare complication although a number of cases have been reported in the last 30 years. This case also reports lymph node metastasis to the adjacent mesenteric lymph nodes. Appearance of ileostomy tumour as synchronous or metachronous lesion is highly debatable. Once diagnosis is confirmed by biopsy enblock excision with or without stomal relocation is the main stay of treatment. Patient education and regular surveillance of patients with long-standing ileostomy is recommended for early detection of this unusual cancer.

Amini AQ, Samo KA, Memon AS
Colorectal cancer in younger population: our experience.
J Pak Med Assoc. 2013; 63(10):1275-7 [PubMed] Related Publications
OBJECTIVE: To promote awareness regarding increased occurrence of colorectal cancer in younger population and its clinicopathological features compared to older patients.
METHODS: The cross-sectional study was conducted from February 2010 to January 2011 on patients with diagnosis of colorectal carcinoma admitted through emergency or outpatients' departments to Surgical Unit 5, Civil Hospital, Karachi. Data regarding age, gender, presentation, site of tumour, surgery performed and Dukes staging was collected and analysed.
RESULTS: A total of 23 patients were operated during the study period: 13 (56.52%) males and 10 (43.47%) females. Of them 12 (52.17%) were below the age of 40 years, while 3 (13.04%) patients were in the 11-20 age group. In 7 (30.4%) patients, tumour was irresectable at the time of presentation so a palliative procedure (diversion colostomy or ileostomy) was performed.There was a higher proportion of younger patients with metastatic disease at the time of presentation (n = 9; 75%) while 10 out of 12 patients in the younger age group (83.3%) had a tumour of left colon, particularly rectum.
CONCLUSION: Although colorectal cancer is usually a disease of older patients, it is increasingly becoming more common in younger population. Data suggests a leftward distribution for colorectal carcinoma and that younger patients present with more advanced disease and poorer prognosis.

Saif MW, Lee AM, Offer SM, et al.
A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxic effects: potential for an individualized medicine approach.
Mayo Clin Proc. 2014; 89(1):131-6 [PubMed] Related Publications
5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have been associated with decreased levels of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Manifestations of 5-FU toxicity typically include cytopenia, diarrhea, stomatitis, mucositis, neurotoxicity, and, in extreme cases, death. A variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effect-associated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case suggests that Y186C may have contributed to 5-FU toxicity in this patient and supports the use of Y186C as a predictive marker for 5-FU toxic effects in individuals of African ancestry.

Related: Fluorouracil Leucovorin Polymorphisms

Kokki I, Papana A, Campbell H, Theodoratou E
Estimating the incidence of colorectal cancer in South East Asia.
Croat Med J. 2013; 54(6):532-40 [PubMed] Free Access to Full Article Related Publications
AIM: To estimate the burden of colorectal cancer (CRC) in South East Asia.
METHODS: We reviewed the evidence from the published literature found through a systematic review in Medline, Embase, and Global Health and from unpublished data on cancer registries, which were sourced from the International Agency for Research on Cancer. Incidence rates were summarized by calculating descriptive statistics and meta-analysis estimates.
RESULTS: The crude mean incidence of CRC in South East Asia for both sexes was 6.95/100000 population and the incidence increased with age. The crude meta-analysis estimate was 6.12/100000 population (95% confidence interval 5.64-6.60/100000) and the number of new CRC cases for 2000 was 32058 (29544-34573).
CONCLUSION: The rates of CRC in South East Asia were much lower than those reported for high-income countries, but higher than those reported for Sub Saharan Africa.

Persiani R, Biondi A, Gambacorta MA, et al.
Prognostic implications of the lymph node count after neoadjuvant treatment for rectal cancer.
Br J Surg. 2014; 101(2):133-42 [PubMed] Related Publications
BACKGROUND: The aim of this study was to investigate the effect of neoadjuvant chemoradiotherapy on the lymph node yield of rectal cancer surgery.
METHODS: Data for patients who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from June 1992 to June 2009 were reviewed. The primary outcomes measured were the number of lymph nodes retrieved, their status, and patient survival.
RESULTS: In total, 345 patients underwent neoadjuvant chemoradiotherapy followed by surgery, and 95 patients had surgery alone. Neoadjuvant chemoradiotherapy decreased both the median (range) number of lymph nodes retrieved (7 (1-33) versus 12.5 (0-44) respectively; P < 0.001) and the number of positive lymph nodes (0 (0-11) versus 0 (0-16); P = 0.001). After neoadjuvant chemoradiotherapy, the number of retrieved lymph nodes was inversely correlated with tumour regression, and with the interval between treatment and surgery. The 5-year overall and disease-free survival rates were 86.5 and 79.1 per cent respectively. After neoadjuvant therapy, lymph node status was found to be an independent predictor of survival, whereas the number of retrieved lymph nodes did not represent a prognostic factor for either overall or disease-free survival.
CONCLUSION: Low lymph node count after neoadjuvant chemoradiotherapy for rectal cancer does not signify an inadequate resection or understaging, but represents an increased sensitivity to the treatment.

Virzì S, Iusco D, Baratti D, et al.
Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases.
Tumori. 2013 Sep-Oct; 99(5):589-95 [PubMed] Related Publications
AIMS AND BACKGROUND: The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant hyperthermic intraperitoneal chemotherapy has never been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of hyperthermic intraperitoneal chemotherapy combined with primary curative surgery in colorectal cancer at high risk for peritoneal metastases.
METHODS: Twelve patients were prospectively selected according to predetermined risk factors for the development of peritoneal metastases. Patients underwent conventional colon surgery, closed-abdomen mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy, and cytoreductive surgical procedures, as needed.
RESULTS: Preoperative tumor-related risk factors were confirmed by intraoperative findings and pathological examination in all patients: minimal synchronous peritoneal metastases (n = 2), synchronous ovarian metastases (n = 1), positive peritoneal washing cytology (n = 2), primary tumor directly invading other organs (n = 6), or penetrating visceral peritoneum (n = 1). Major morbidity occurred in 2 patients and operative death in none. Median follow-up was 49 months (range, 22-72). Peritoneal metastases occurred in 1 patient and distant metastases in 2. Five-year overall survival was 83.3%.
CONCLUSIONS: Preoperative/early intraoperative assessment can reliably identify colorectal cancer patients at high risk for peritoneal metastases. Adjuvant hyperthermic intraperitoneal chemotherapy is well tolerated and safe. These preliminary results would support the design of future phase-III trials of adjuvant hyperthermic intraperitoneal chemotherapy.

Related: Cisplatin Mitomycin

Karabulut M, Bas K, Gönenç M, et al.
Self-expanding metallic stents in acute mechanical intestinal obstructions resulting from colorectal malignancies.
Am Surg. 2013; 79(12):1279-82 [PubMed] Related Publications
Endoscopic colonic stenting with self-expanding metallic stents is now widely used to treat malignant large bowel obstruction, where temporary or permanent decompression of the large bowel is desired. The medical records of patients who underwent endoscopic colonic stenting for malignant large bowel obstruction between May 2004 and May 2011 were reviewed. Success rate, morbidity, and mortality rate along with patient characteristics were documented. Sixty-seven patients were included. The procedure was used as a bridge to surgery in 38 and as a palliative measure in 29. Success rate was 95.5 per cent. Perforation and reobstruction occurred in three and three patients, respectively. All of the patients who developed perforation or reobstruction underwent emergency surgery. Endoscopic stenting offers a safe and effective treatment option in patients with malignant large bowel obstruction with comparable outcomes.

Nazarian RM, Primiani A, Doyle LA, et al.
Cytokeratin 17: an adjunctive marker of invasion in squamous neoplastic lesions of the anus.
Am J Surg Pathol. 2014; 38(1):78-85 [PubMed] Related Publications
Diagnosing anal squamous cell carcinoma (SCC), which is often preceded by anal intraepithelial neoplasia (AIN), may be challenging in small biopsies. Cytokeratin 17 (CK17) is a basal/myoepithelial cell keratin induced in activated keratinocytes and associated with disease progression in SCC of the uterine cervix, esophagus, and oral cavity. We investigated the utility of CK17 in diagnosing invasion in anal squamous neoplastic lesions. Immunohistochemical staining for CK17 was evaluated in 11 AINs, 12 invasive SCCs, 8 invasive SCCs with basaloid features (BSCC), and 2 invasive pure basaloid carcinomas. The pattern of staining was scored as surface/central, peripheral/rim, diffuse, or absent. All cases of invasive SCC and BSCC stained positive for CK17. Eleven of 12 (92%) SCCs showed diffuse staining, and 1 of 12 (8%) showed peripheral staining. Six of 8 (75%) BSCCs showed diffuse staining, and 2 of 8 (25%) showed peripheral staining. Both pure basaloid carcinomas were negative for CK17. One of 11 (9%) AINs was diffusely positive for CK17; all other AINs had surface or absent CK17. Of the 6 patients with concurrent AIN and invasive carcinoma, superficial expression of CK17 was present in 1 AIN, whereas all invasive components showed diffuse staining. The sensitivity and specificity of CK17 for identifying invasion in SCC and BSCC was 100% and 91%, respectively. Peripheral or diffuse staining for CK17 is a useful marker of invasion in anal squamous neoplastic lesions. A potential pitfall in the utility of CK17 is that the pure basaloid variant of anal carcinoma is negative for CK17.

Related: Anal Cancer

Mege D, Ouaissi M, Fuks D, et al.
Patients with brain metastases from colorectal cancer are not condemned.
Anticancer Res. 2013; 33(12):5645-8 [PubMed] Related Publications
BACKGROUND: Brain metastases (BMs) from colorectal cancer are rare (2-3%). They usually occur in advanced stages of the disease and their prognosis is poor. The aim of this study was to assess the impact of surgical resection of BMs from colorectal cancer in terms of overall survival.
PATIENTS AND METHODS: A retrospective bi-centric study included all patients with resected BMs from primary colorectal adenocarcinoma from 1998 to 2009.
RESULTS: Twenty-eight patients [13 males, median: 62 (range: 44-86) years old) were included. Fifteen patients presented with other metastatic sites (lung, liver). BMs were metachronous in 16/28 (57%) of patients [median: 19 months (range: 7-97)]. Median overall survival reached 12 months. Brain recurrences occurred in 32% of patients and were treated by curative intent in 5/9 cases.
CONCLUSION: When indicated, an aggressive management based on surgical resection of BMs from colorectal cancer, must be performed, in order to improve overall survival to at least 12 months.

Maeda K, Shibutani M, Otani H, et al.
Prognostic value of preoperative inflammation-based prognostic scores in patients with stage IV colorectal cancer who undergo palliative resection of asymptomatic primary tumors.
Anticancer Res. 2013; 33(12):5567-73 [PubMed] Related Publications
BACKGROUND: The need for palliative resection of asymptomatic primary tumor in patients with unresectable metastatic colorectal cancer (CRC) is still controversial. In order to identify predictors of survival after palliative resection, we investigated the correlations between clinicopathological factors, preoperative Glasgow prognostic score (GPS) and neutrophil-to-lymphocyte ratio (NLR), and survival.
PATIENTS AND METHODS: A total of 94 patients were enrolled in the present study. The prognostic value of the clinicopathological factors, GPS and NLR were analyzed retrospectively.
RESULTS: A multivariate analysis revealed that both the GPS and NLR were independent predictors of survival along with the preoperative Eastern Cooperative Oncology Group performance status (PS) and extent of distant metastasis. We classified the patients using a combination of these factors, and categorized them into three risk groups. The median survival time was five months in the high-risk group, compared to 21.5 months in the intermediate-risk group and 37 months in the low-risk group.
CONCLUSION: Sub-classification based on the GPS, NLR, PS and extent of distant metastasis can classify patients into three independent groups. There may be no survival benefits associated with palliative resection in the high-risk group.

Fujii H, Iihara H, Ishihara M, et al.
Improvement of adherence to guidelines for antiemetic medication enhances emetic control in patients with colorectal cancer receiving chemotherapy of moderate emetic risk.
Anticancer Res. 2013; 33(12):5549-56 [PubMed] Related Publications
Prevention of chemotherapy-induced nausea and vomiting (CINV) according to the clinical practice guidelines is particularly important. In the present study, we investigated the adherence to the guidelines for antiemetic medication and the control of CINV in 61 patients with colorectal cancer receiving the first course of chemotherapy of moderate emetic risk at our outpatient cancer chemotherapy clinic. Furthermore, we carried out intervention to improve evidence-based antiemetic medication in another 64 patients. The rate of adherence to the antiemetic guidelines was only 6.6%; non-adherence was due mostly to the lack of dexamethasone treatment on days 2 and 3. In the interventional group, antiemetic medication adherence was markedly enhanced to 89%, which led to a significant enhancement of complete protection from nausea and vomiting during-delayed period (days 2-5 after chemotherapy) from 54% to 74% (p<0.05), although the daily dose of dexamethasone was 4 mg, lower than that recommended by the guidelines (8 mg). Finally, we evaluated the effect of dexamethasone at a daily dose of 4 mg, since little is known about the efficacy of such dose. Dexamethasone at this dose was found to be effective at elevating the rate of complete protection from nausea and vomiting during-delayed period (increase of 20%, p<0.05). These findings suggest that medication intervention to reduce the gap between guidelines and clinical practice improves the emetic control in patients with colorectal cancer receiving moderately-emetic chemotherapy.

Rubio CA, Jaramillo E
Advanced microtubular colorectal adenomas: a 10-year survey at a single hospital.
Anticancer Res. 2013; 33(12):5471-6 [PubMed] Related Publications
BACKGROUND: Colorectal carcinoma, the third most commonly diagnosed type of cancer in Europe and the USA, usually originates from colorectal adenoma (CRA). Three main histological phenotypes of CRA are usually recognized: tubular, villous and traditional serrated (TA, VA and TSA, respectively). In 1997, we reported a novel histological phenotype, the microtubular adenoma (MTA), epitomized by dysplastic epithelium arranged in closed rings (microtubules), with sideways-elongated outgrowth.
MATERIALS AND METHODS: The material includes 4,446 CRAs diagnosed at our Department during a 10-year period (2001-2010).
RESULTS: Out of 4,446 CRAs, 68 (1.5%) were MTA; of these, 38 (55.9%) exhibited low-grade dysplasia (LGD), 17 (25.0%), high-grade-dysplasia, two (2.9%) intraepithelial carcinoma and three (4.4%), intramucosal carcinoma. Out of the 68 MTA, 22 (32.3%) were advanced MTA. Submucosal carcinoma (SMC) was present in eight (11.8%) MTAs. Ninety-four per cent (64/68) of the MTAs were left-sided adenomas. In previous work, we found that cell proliferation occurred in the dysplastic microtubules in MTA, initially in the luminal dysplastic epithelium in TA and VA, and initially at the bottom of the serrated dysplastic crypts in TSA.
CONCLUSION: Due to these distinctive microscopic and cell proliferative attributes, a predominant left-sided location and the absence of serrated configurations, it is submitted that MTA is a specific CRA phenotype, at variance with TA, VA, and TSA. The high frequency of SMC strongly suggests that MTA is an important alternative pathway in colorectal carcinogenesis.

Related: USA

Moseley VR, Morris J, Knackstedt RW, Wargovich MJ
Green tea polyphenol epigallocatechin 3-gallate, contributes to the degradation of DNMT3A and HDAC3 in HCT 116 human colon cancer cells.
Anticancer Res. 2013; 33(12):5325-33 [PubMed] Related Publications
BACKGROUND: Colon cancer is still the second leading cause of cancer deaths in the United States. Epigenetic gene silencing involving DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) plays an important role in the progression of colon cancer.
MATERIALS AND METHODS: In the present study we found that the sensitivity of colon cancer cells to methylation plays a role in its response to alternative therapy involving the green tea polyphenol, epigallocatechin 3-gallate. HDAC and DNMT protein expression were reduced when methylation-sensitive HCT 116 human colon cancer cells was treated with EGCG, but was relatively stable in the HT-29 cell line. This decrease in expression may be partially explained by our finding that DNMT3A and HDAC3 are degraded in the methylation-sensitive colon cancer cells in part by inhibiting their association with the E3 ubiquitin ligase, UHRF1.
CONCLUSION: These findings provide a rationale for the development of a targeted therapy for methylation-sensitive colon cancer that can include EGCG in combination with other DNMT and HDAC inhibitors.

Lotti F, Jarrar AM, Pai RK, et al.
Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A.
J Exp Med. 2013; 210(13):2851-72 [PubMed] Article available free on PMC after 16/06/2014 Related Publications
Many solid cancers display cellular hierarchies with self-renewing, tumorigenic stemlike cells, or cancer-initiating cells (CICs) at the apex. Whereas CICs often exhibit relative resistance to conventional cancer therapies, they also receive critical maintenance cues from supportive stromal elements that also respond to cytotoxic therapies. To interrogate the interplay between chemotherapy and CICs, we investigated cellular heterogeneity in human colorectal cancers. Colorectal CICs were resistant to conventional chemotherapy in cell-autonomous assays, but CIC chemoresistance was also increased by cancer-associated fibroblasts (CAFs). Comparative analysis of matched colorectal cancer specimens from patients before and after cytotoxic treatment revealed a significant increase in CAFs. Chemotherapy-treated human CAFs promoted CIC self-renewal and in vivo tumor growth associated with increased secretion of specific cytokines and chemokines, including interleukin-17A (IL-17A). Exogenous IL-17A increased CIC self-renewal and invasion, and targeting IL-17A signaling impaired CIC growth. Notably, IL-17A was overexpressed by colorectal CAFs in response to chemotherapy with expression validated directly in patient-derived specimens without culture. These data suggest that chemotherapy induces remodeling of the tumor microenvironment to support the tumor cellular hierarchy through secreted factors. Incorporating simultaneous disruption of CIC mechanisms and interplay with the tumor microenvironment could optimize therapeutic targeting of cancer.

Related: Cytokines Signal Transduction

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