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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) CancerInformation Patients and the Public (17 links)
- Colon Cancer video
NHS Choices
Celia Ingham Clark, a consultant surgeon, explains who's most at risk of bowel cancer, the questions to ask if you're diagnosed and the treatment options - Colon Cancer Treatment
National Cancer Institute
PDQ summaries are written and frequently updated by editorial boards of experts Further info. - Rectal Cancer Treatment National Cancer InstitutePDQ summaries are written and frequently updated by editorial boards of experts Further info.
- Bowel cancer (colorectal cancer) Cancer Research UKCancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info.
- Bowel cancer statistics Cancer Research UKCancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info.
Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief. - What You Need to Know About Cancer of the Colon and Rectum National Cancer InstituteBooklets written in simple language, which are regularly reviewed and updated Further info.
This site contains information about the disease, diagnosis, staging, and treatment options. - Bowel cancer explained - symptoms, diagnosis and treatment Macmillan Cancer Support
Video: Consultant Clinical Oncologist Amen Sibtain explains bowel cancer, which includes colon and rectal cancer. He gives an overview of the symptoms, diagnosis and treatment of bowel cancer. - Bowel Cancer FAQs
Association for International Cancer Research - Bowel Cancer UK Bowel Cancer UK
A UK charity which aims to save lives by raising awareness of bowel cancer, campaigning for best treatment and care and providing practical support and advice. - Cancer Advances In Focus: Colorectal Cancer National Cancer Institute
A factsheet about colorectal cancer in the past, today, and how current research may change treatment and prevention in the future. - Colon Cancer (Colorectal Cancer) Medicine.net.com
- Colon Cancer Alliance Colon Cancer Alliance
The Alliance was founded in 1998 by patients, survivors, cargivers and others whose lives have been toched by colorectal cancer. It provides information, support, advocacy, on-line chat and a toll free Helpline. - COLON Colorectal Cancer Discussion List ACOR
A discussion and support list sponsored by the Association of Cancer Online Resources - Colonoscopy Video Tour: Discovery of a Cancerous Polyp (Colon Cancer) New York University Langone Medical Center
Mark Pochapin MD, narrates a tour of a patient's colon during a colonoscopy where he discovers a cancerous polyp (colon cancer). The patient did not have any abdominal or rectal pain, or any other symptoms associated with colorectal cancer. However, prior to this colonoscopy the patient was diagnosed with anemia due the slow bleeding of this polyp in her colon. - Colorectal cancer The Royal Marsden
Summary of colorectal cancer, symptoms, diagnosis and treatment. - Colostomy Association Colostomy Association
The Colostomy Association is a UK registered charity representing the interests of people with a colostomy. The Website includes a range of information about colostomy and living with a colostomy. - Spot bowel cancer early Cancer Research UK
Dr Sarah Jarvis describes the signs and symptoms of bowel cancer (2012).
Information for Health Professionals / Researchers (11 links)
- PubMed search for publications about Bowel Cancer - Limit search to: [Reviews]
PubMed Central search for free-access publications about Bowel Cancer
MeSH term: Colorectal Neoplasms US National Library of MedicinePubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated. - Colon Cancer Treatment - Information for Health Professionals National Cancer InstitutePDQ summaries are written and frequently updated by editorial boards of experts Further info.
- Rectal Cancer Treatment National Cancer InstitutePDQ summaries are written and frequently updated by editorial boards of experts Further info.
- Bowel cancer statistics Cancer Research UKCancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info.
Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief. - Colorectal Cancer NHS EvidenceContent is regularly updated from selected sources. The site has input from an Editorial Board and Specialist Reference Groups. Further info.
- Colorectal Cancer Patient UKPatientUK content is peer reviewed. Content is reviewed by a team led by a Clinical Editor to reflect new or updated guidance and publications. Further info.
- American Society of Colon and Rectal Surgeons American Society of Colon and Rectal Surgeons
A professional society representing board certified Colon and Rectal surgeons. The site contains a section on patient information including pages on colorectal cancer, colonoscopy and polyps. - Cancer of the colon/rectum
Oncolex - Oslo University Hospital (Norway) and MD Andersen (USA)
Detailed reference article covering etiology, histology, staging, metastatic patterns, symptoms, differential diagnoses, prognosis, treatment and follow-up. - Colorectal cancer - clinical pathways National Institute for Clinical Excellence
Interactive pathway linked to guidelines and evidence. - Physician Module 3: Tumour Invasion NHS / ASKVisualScience
Animation covering tumour invasion and staging. - SEER Stat Fact Sheets: Colon and Rectum SEER, National Cancer Institute
Overview and specific fact sheets on incidence and mortality, survival and stage, lifetime risk, and prevalence.
Herdiatry Colorectal Cancers (4 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).- CaPP3 Cancer Prevention Study Newcastle University
A study recruit people with Lynch Syndrome to test different doses of aspirin to reduce the risk of colon cancer. - Hereditary Cancer Registry - NSW
Cancer Institute NSW
A screening reminder service established in 1990 to provide information and support to people affected by hereditary cancer, their family members, and their doctors in NSW and the ACT. - Hereditary Colorectal Cancer Registry Johns Hopkins Colon Cancer Center
- Introduction to Hereditary Colorectal Cancer Johns Hopkins Colon Cancer Center
Introduces hereditary colorectal cancer syndromes, with specific sections on Familial Adenomatous Polyposis (FAP), Hereditary Nonpolyposis Colorectal Cancer (HNPCC), APC I1307K gene mutation, Kid's FAP, and Hyperplastic Polyposis.
Gene and Chromosome Abnormalities (Cancer GeneWeb)Latest Research Publications
This list of publications is regularly updated (Source: PubMed).
Leroy J, Barry BD, Melani A, et al.
No-scar transanal total mesorectal excision: the last step to pure NOTES for colorectal surgery.
JAMA Surg. 2013; 148(3):226-30; discussion 231 [PubMed]
No-scar transanal total mesorectal excision: the last step to pure NOTES for colorectal surgery.
JAMA Surg. 2013; 148(3):226-30; discussion 231 [PubMed]
HYPOTHESIS: Because of the concerns over the operative platform, accidental organ injury, and viscerotomy closure, natural orifice transluminal endoscopic surgery (NOTES) currently remains an experimental technique. Transanal NOTES for colorectal surgery overcomes all of these issues; however, all of the reports to date have used hybrid laparoscopic techniques. We demonstrate herein the first case, to our knowledge, of pure transanal NOTES colorectal surgery.
DESIGN: Case report.
SETTING: University hospital.
PATIENT: The patient was a 56-year-old woman with a midrectal neoplasia.
INTERVENTION: Pure transanal NOTES total mesorectal excision with a coloanal anastomosis and without a diverting stoma. Using a transanal endoscopic operation device as a surgical platform, we created a viscerotomy distal to an endoluminal purse-string suture. We performed a total mesorectal excision using a “bottom-up” approach. The sigmoid colon was mobilized by a posterior, retroperitoneal approach and the colon was divided intraperitoneally. A hand-sewn, side-to-end, coloanal anastomosis was performed. Because the viscerotomy was incorporated into the anastomosis, the concerns of both accidental organ damage and viscerotomy closure were abrogated.
RESULTS: The procedure was completed entirely by a transanal fashion. We successfully mobilized the rectum, mesorectum, and sigmoid colon. The specimen length was more than 20 cm. The patient required minimal analgesia and her pain was nonabdominal.
CONCLUSIONS: To our knowledge, the first pure transanal NOTES total mesorectal excision with retroperitoneal sigmoid mobilization and coloanal, side-to-end anastomosis was successfully performed using what we called a peri-rectal oncologic gateway for retroperitoneal endoscopic single site surgery (PROGRESSS). This monumental case could pave the way for a new era in pure transanal NOTES for colorectal surgery.
DESIGN: Case report.
SETTING: University hospital.
PATIENT: The patient was a 56-year-old woman with a midrectal neoplasia.
INTERVENTION: Pure transanal NOTES total mesorectal excision with a coloanal anastomosis and without a diverting stoma. Using a transanal endoscopic operation device as a surgical platform, we created a viscerotomy distal to an endoluminal purse-string suture. We performed a total mesorectal excision using a “bottom-up” approach. The sigmoid colon was mobilized by a posterior, retroperitoneal approach and the colon was divided intraperitoneally. A hand-sewn, side-to-end, coloanal anastomosis was performed. Because the viscerotomy was incorporated into the anastomosis, the concerns of both accidental organ damage and viscerotomy closure were abrogated.
RESULTS: The procedure was completed entirely by a transanal fashion. We successfully mobilized the rectum, mesorectum, and sigmoid colon. The specimen length was more than 20 cm. The patient required minimal analgesia and her pain was nonabdominal.
CONCLUSIONS: To our knowledge, the first pure transanal NOTES total mesorectal excision with retroperitoneal sigmoid mobilization and coloanal, side-to-end anastomosis was successfully performed using what we called a peri-rectal oncologic gateway for retroperitoneal endoscopic single site surgery (PROGRESSS). This monumental case could pave the way for a new era in pure transanal NOTES for colorectal surgery.
Choi YS, Lee JB, Lee EJ, et al.
Can endoscopic submucosal dissection technique be an alternative treatment option for a difficult giant (≥ 30 mm) pedunculated colorectal polyp?
Dis Colon Rectum. 2013; 56(5):660-6 [PubMed]
Can endoscopic submucosal dissection technique be an alternative treatment option for a difficult giant (≥ 30 mm) pedunculated colorectal polyp?
Dis Colon Rectum. 2013; 56(5):660-6 [PubMed]
BACKGROUND: Snare polypectomy of a giant pedunculated colorectal polyp is sometimes technically demanding, and, therefore, piecemeal resection is inevitable, despite the relative risk of invasive cancer and postpolypectomy bleeding.
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of endoscopic submucosal dissection in comparison with conventional snare polypectomy for giant pedunculated polyps
DESIGN AND SETTINGS: We retrospectively reviewed the clinical outcomes and complications of endoscopic polypectomy for giant pedunculated polyps from October 2006 to November 2011.
PATIENTS: All the patients who underwent endoscopic submucosal dissection (n = 23) or snare polypectomy (n = 20) for pedunculated polyps ≥ 3 cm were enrolled consecutively. In the case of a giant pedunculated polyp with 1) poor visualization of the stalk, 2) technical difficulties in snare positioning for en bloc resection, or 3) need for trimming of the head, we did not attempt piecemeal snare polypectomy, and we performed endoscopic submucosal dissection instead. (These were arbitrarily defined as "difficult" giant pedunculated polyps.)
MAIN OUTCOME MEASURES: Data on the patient's demography, endoscopic and histopathologic findings, clinical outcomes, and complications were analyzed.
RESULTS: Among the 43 giant pedunculated polyps, 23 polyps were defined as "difficult" polyps and were removed with endoscopic submucosal dissection. Subpedunculated (stalk <1 cm) type was more common in the "difficult" polyp group (p = 0.01). The overall incidence of cancer was 18.6% (8/43). En bloc resection rates were 100% (23/23) in the endoscopic submucosal dissection group and 90% (18/20) in the snare polypectomy group. The procedure times of snare polypectomy and endoscopic submucosal dissection group did not differ significantly (41.7 ± 13.7 minutes vs 44.9 ± 35.6 minutes, p = 0.70). Postpolypectomy bleeding was noted in 1 case (4.3%) in the endoscopic submucosal dissection group and in 3 cases (15%) in the snare polypectomy group.
CONCLUSIONS: Endoscopic submucosal dissection, as well as the snare polypectomy for giant pedunculated polyps, appeared to be effective without major complications and can be an alternative option to achieve en bloc resection, particularly for difficult cases, such as giant subpedunculated polyps.
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of endoscopic submucosal dissection in comparison with conventional snare polypectomy for giant pedunculated polyps
DESIGN AND SETTINGS: We retrospectively reviewed the clinical outcomes and complications of endoscopic polypectomy for giant pedunculated polyps from October 2006 to November 2011.
PATIENTS: All the patients who underwent endoscopic submucosal dissection (n = 23) or snare polypectomy (n = 20) for pedunculated polyps ≥ 3 cm were enrolled consecutively. In the case of a giant pedunculated polyp with 1) poor visualization of the stalk, 2) technical difficulties in snare positioning for en bloc resection, or 3) need for trimming of the head, we did not attempt piecemeal snare polypectomy, and we performed endoscopic submucosal dissection instead. (These were arbitrarily defined as "difficult" giant pedunculated polyps.)
MAIN OUTCOME MEASURES: Data on the patient's demography, endoscopic and histopathologic findings, clinical outcomes, and complications were analyzed.
RESULTS: Among the 43 giant pedunculated polyps, 23 polyps were defined as "difficult" polyps and were removed with endoscopic submucosal dissection. Subpedunculated (stalk <1 cm) type was more common in the "difficult" polyp group (p = 0.01). The overall incidence of cancer was 18.6% (8/43). En bloc resection rates were 100% (23/23) in the endoscopic submucosal dissection group and 90% (18/20) in the snare polypectomy group. The procedure times of snare polypectomy and endoscopic submucosal dissection group did not differ significantly (41.7 ± 13.7 minutes vs 44.9 ± 35.6 minutes, p = 0.70). Postpolypectomy bleeding was noted in 1 case (4.3%) in the endoscopic submucosal dissection group and in 3 cases (15%) in the snare polypectomy group.
CONCLUSIONS: Endoscopic submucosal dissection, as well as the snare polypectomy for giant pedunculated polyps, appeared to be effective without major complications and can be an alternative option to achieve en bloc resection, particularly for difficult cases, such as giant subpedunculated polyps.
Yu ZQ, Zhang C, Wang H, et al.
Downregulation of ATP-binding cassette subfamily C member 4 increases sensitivity to neoadjuvant radiotherapy for locally advanced rectal carcinoma.
Dis Colon Rectum. 2013; 56(5):600-8 [PubMed]
Downregulation of ATP-binding cassette subfamily C member 4 increases sensitivity to neoadjuvant radiotherapy for locally advanced rectal carcinoma.
Dis Colon Rectum. 2013; 56(5):600-8 [PubMed]
OBJECTIVE: This study was designed to verify the effect of ATP-binding cassette subfamily C member 4 on radiosensitivity of locally advanced rectal carcinoma.
SETTING: The expression of ATP-binding cassette subfamily C member 4 protein in 121 pretreatment tissue samples from locally advanced rectal carcinoma patients was detected by immunohistochemistry.
DESIGN: Pathological response to radiotherapy was evaluated according to tumor regression grading by postoperative histological examinations after they received long-course preoperative neoadjuvant radiotherapy, and the association between clinicopathological data and tumor regression grading was analyzed retrospectively. For further validation, short hairpin RNA was constructed and transfected into colorectal carcinoma cell line HT29. The knockdown efficiency was confirmed at both RNA and protein levels. The altered radiosensitivity was evaluated by methylthiazolyl tetrazolium assay, colony formation assay, flow cytometry, and Hoechst 33258 staining.
RESULTS: Univariate analysis revealed that ATP-binding cassette subfamily C member 4 expression (p < 0.001), P53 type (p = 0.069), and CEA (p = 0.100) were possibly associated with tumor regression grading, and multivariate analysis demonstrated that ATP-binding cassette subfamily C member 4 expression (p < 0.001) and P53 type (p = 0.039) were positively correlated with response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients. Lentiviral vector was successfully introduced into HT29 cells and inhibited ATP-binding cassette subfamily C member 4 expression efficiently and persistently. Downregulation of ATP-binding cassette subfamily C member 4 expression significantly enhanced inhibition of cell proliferation, decreased colony formation capacity, and increased cell apoptosis induced by irradiation, as examined by a series of experiments in vitro. In addition, radiobiological parameters calculated according to the single-hit multitarget model were also decreased significantly.
CONCLUSIONS: Our data indicate that ATP-binding cassette subfamily C member 4 may be a useful molecular marker in predicting radiosensitivity, and a potential target in improving the response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients.
SETTING: The expression of ATP-binding cassette subfamily C member 4 protein in 121 pretreatment tissue samples from locally advanced rectal carcinoma patients was detected by immunohistochemistry.
DESIGN: Pathological response to radiotherapy was evaluated according to tumor regression grading by postoperative histological examinations after they received long-course preoperative neoadjuvant radiotherapy, and the association between clinicopathological data and tumor regression grading was analyzed retrospectively. For further validation, short hairpin RNA was constructed and transfected into colorectal carcinoma cell line HT29. The knockdown efficiency was confirmed at both RNA and protein levels. The altered radiosensitivity was evaluated by methylthiazolyl tetrazolium assay, colony formation assay, flow cytometry, and Hoechst 33258 staining.
RESULTS: Univariate analysis revealed that ATP-binding cassette subfamily C member 4 expression (p < 0.001), P53 type (p = 0.069), and CEA (p = 0.100) were possibly associated with tumor regression grading, and multivariate analysis demonstrated that ATP-binding cassette subfamily C member 4 expression (p < 0.001) and P53 type (p = 0.039) were positively correlated with response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients. Lentiviral vector was successfully introduced into HT29 cells and inhibited ATP-binding cassette subfamily C member 4 expression efficiently and persistently. Downregulation of ATP-binding cassette subfamily C member 4 expression significantly enhanced inhibition of cell proliferation, decreased colony formation capacity, and increased cell apoptosis induced by irradiation, as examined by a series of experiments in vitro. In addition, radiobiological parameters calculated according to the single-hit multitarget model were also decreased significantly.
CONCLUSIONS: Our data indicate that ATP-binding cassette subfamily C member 4 may be a useful molecular marker in predicting radiosensitivity, and a potential target in improving the response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients.
Pullens HJ, van Leeuwen MS, Laheij RJ, et al.
CT-colonography after incomplete colonoscopy: what is the diagnostic yield?
Dis Colon Rectum. 2013; 56(5):593-9 [PubMed]
CT-colonography after incomplete colonoscopy: what is the diagnostic yield?
Dis Colon Rectum. 2013; 56(5):593-9 [PubMed]
BACKGROUND: Computed tomography-colonography is a diagnostic modality that can be used when the colon is not completely intubated during colonoscopy. It may have the additional advantage that information on extracolonic lesions can be obtained.
OBJECTIVE: The aim of this study was to investigate the yield of CT-colonography of relevant intra- and extracolonic findings in patients after incomplete colonoscopy.
DESIGN: This was an observational, retrospective study.
DATA SOURCES: Data were be obtained from standardized radiology and endoscopy reports and electronic medical records.
STUDY SELECTION: In total, 136 consecutive CT-colonographies performed after incomplete colonoscopy were evaluated.
MAIN OUTCOME MEASURES: All intra- and extracolonic findings on CT-colonography were recorded and interpreted for clinical relevance, and it was determined whether further diagnostic and/or therapeutic workup was indicated.
RESULTS: Major indications for colonoscopy included iron-deficiency anemia (25.7%), hematochezia (20.6%), change in bowel habits (18.4%), and colorectal cancer screening or surveillance (11.0%). Major reasons for incomplete colonoscopy were a fixed colon (34.6%) and strong angulation of the sigmoid colon (17.6%). Introduction of the colonoscope was limited to the left-sided colon in 53.7% of cases. Incomplete colonoscopy detected colorectal cancer in 12 (8.8%) patients and adenomatous polyps in 27 (19.9%) patients. CT-colonography after incomplete colonoscopy additionally revealed 19 polyps in 15 (11.0%) and a nonsynchronous colorectal cancer in 4 (2.9%) patients. CT-colonography also detected extracolonic findings with clinical consequences in 8 (5.9%) patients, including fistulizing diverticulitis (n = 3), gastric tumor (n = 2), liver abscess (n = 1), osteomyelitis (n = 1), and an infected embolus in both renal arteries (n = 1).
LIMITATIONS: This study was limited by the lack of confirmation of intraluminal CT-colonography findings in a subset of patients.
CONCLUSIONS: Computed tomography-colonography can be of added value in patients with incomplete colonoscopy, because it revealed 27 relevant additional (both intra- and extracolonic) lesions in 19.1% of patients. In cases where CT-colonography detected colorectal cancer after incomplete colonoscopy, it can also be used for staging purposes.
OBJECTIVE: The aim of this study was to investigate the yield of CT-colonography of relevant intra- and extracolonic findings in patients after incomplete colonoscopy.
DESIGN: This was an observational, retrospective study.
DATA SOURCES: Data were be obtained from standardized radiology and endoscopy reports and electronic medical records.
STUDY SELECTION: In total, 136 consecutive CT-colonographies performed after incomplete colonoscopy were evaluated.
MAIN OUTCOME MEASURES: All intra- and extracolonic findings on CT-colonography were recorded and interpreted for clinical relevance, and it was determined whether further diagnostic and/or therapeutic workup was indicated.
RESULTS: Major indications for colonoscopy included iron-deficiency anemia (25.7%), hematochezia (20.6%), change in bowel habits (18.4%), and colorectal cancer screening or surveillance (11.0%). Major reasons for incomplete colonoscopy were a fixed colon (34.6%) and strong angulation of the sigmoid colon (17.6%). Introduction of the colonoscope was limited to the left-sided colon in 53.7% of cases. Incomplete colonoscopy detected colorectal cancer in 12 (8.8%) patients and adenomatous polyps in 27 (19.9%) patients. CT-colonography after incomplete colonoscopy additionally revealed 19 polyps in 15 (11.0%) and a nonsynchronous colorectal cancer in 4 (2.9%) patients. CT-colonography also detected extracolonic findings with clinical consequences in 8 (5.9%) patients, including fistulizing diverticulitis (n = 3), gastric tumor (n = 2), liver abscess (n = 1), osteomyelitis (n = 1), and an infected embolus in both renal arteries (n = 1).
LIMITATIONS: This study was limited by the lack of confirmation of intraluminal CT-colonography findings in a subset of patients.
CONCLUSIONS: Computed tomography-colonography can be of added value in patients with incomplete colonoscopy, because it revealed 27 relevant additional (both intra- and extracolonic) lesions in 19.1% of patients. In cases where CT-colonography detected colorectal cancer after incomplete colonoscopy, it can also be used for staging purposes.
Sirois-Giguère E, Boulanger-Gobeil C, Bouchard A, et al.
Transanal drainage to treat anastomotic leaks after low anterior resection for rectal cancer: a valuable option.
Dis Colon Rectum. 2013; 56(5):586-92 [PubMed]
Transanal drainage to treat anastomotic leaks after low anterior resection for rectal cancer: a valuable option.
Dis Colon Rectum. 2013; 56(5):586-92 [PubMed]
BACKGROUND: Anastomotic leaks after low anterior resection for rectal cancer remain a major cause of morbidity and mortality. Few studies have focused on their management, particularly on the technique of transanal drainage.
OBJECTIVE: The aim of this study was to assess the short- and long-term outcomes according to the initial management of clinical leaks.
DESIGN AND SETTINGS: This study is a retrospective review of a single institution experience.
PATIENTS: All patients treated for a symptomatic anastomotic leak after low anterior resection for rectal cancer between January 2000 and March 2011 were included.
MAIN OUTCOME MEASURES: The primary outcomes were mortality attributed to the leak, sepsis control, stoma closure rate, and functional results.
RESULTS: A total of 37 patients (35 men/2 women) developed a symptomatic leak. Leaks were initially managed by transanal drainage in 16 patients, abdominal reintervention in 12 patients, and medical treatment in 9 patients. The only death attributed to the leak occurred in the abdominal reintervention group. In the transanal drainage group, antibiotics were administered for a median length of 9 days, and the drain was left in place for a median length of 30 days. One patient underwent percutaneous drainage of a collection in addition to transanal drainage, but no patient required abdominal reintervention. Of the treatment modalities applied, transanal drainage was associated with the highest stoma closure rate (93%), after a median postoperative time of 7 months. Complications observed after transanal drainage were anastomotic strictures in 33% and the creation of a permanent stoma due to poor function in 13%.
LIMITATIONS: This study was limited by its nonrandomized retrospective design and the presence of selection bias.
CONCLUSIONS: : For the management of low anastomotic leaks, transanal drainage allows preservation of the anastomosis and sepsis control with a high rate of ileostomy closure. It is a valuable option in patients with a diverting ileostomy.
OBJECTIVE: The aim of this study was to assess the short- and long-term outcomes according to the initial management of clinical leaks.
DESIGN AND SETTINGS: This study is a retrospective review of a single institution experience.
PATIENTS: All patients treated for a symptomatic anastomotic leak after low anterior resection for rectal cancer between January 2000 and March 2011 were included.
MAIN OUTCOME MEASURES: The primary outcomes were mortality attributed to the leak, sepsis control, stoma closure rate, and functional results.
RESULTS: A total of 37 patients (35 men/2 women) developed a symptomatic leak. Leaks were initially managed by transanal drainage in 16 patients, abdominal reintervention in 12 patients, and medical treatment in 9 patients. The only death attributed to the leak occurred in the abdominal reintervention group. In the transanal drainage group, antibiotics were administered for a median length of 9 days, and the drain was left in place for a median length of 30 days. One patient underwent percutaneous drainage of a collection in addition to transanal drainage, but no patient required abdominal reintervention. Of the treatment modalities applied, transanal drainage was associated with the highest stoma closure rate (93%), after a median postoperative time of 7 months. Complications observed after transanal drainage were anastomotic strictures in 33% and the creation of a permanent stoma due to poor function in 13%.
LIMITATIONS: This study was limited by its nonrandomized retrospective design and the presence of selection bias.
CONCLUSIONS: : For the management of low anastomotic leaks, transanal drainage allows preservation of the anastomosis and sepsis control with a high rate of ileostomy closure. It is a valuable option in patients with a diverting ileostomy.
Madbouly KM, Hussein AM, Zeid A
Colorectal cancer surgery in portal hypertensive patients: does adjuvant oxaliplatin affect prognosis?
Dis Colon Rectum. 2013; 56(5):577-85 [PubMed]
Colorectal cancer surgery in portal hypertensive patients: does adjuvant oxaliplatin affect prognosis?
Dis Colon Rectum. 2013; 56(5):577-85 [PubMed]
BACKGROUND: Oxaliplatin is used in adjuvant treatment of colorectal cancer and is associated with sinusoidal obstruction syndrome. Few data are available on its effects in patients in whom portal hypertension was diagnosed before cancer treatment.
OBJECTIVE: Our aim was to investigate short- and long-term outcomes of surgery for colorectal cancer in patients with portal hypertension with or without cirrhosis, particularly regarding effects of adjuvant chemotherapy with oxaliplatin.
DESIGN AND SETTING: This was a prospective cohort study performed at an academic medical center.
PATIENTS: Patients with stage II or III colorectal cancer and portal hypertension who underwent curative resection were included.
INTERVENTION: All patients received adjuvant chemotherapy with oxaliplatin (FOLFOX 4) or 5-fluorouracil and leucovorin.
MAIN OUTCOME MEASURES: Potential predictive laboratory and clinical variables and postoperative (30-day) and long-term morbidity and mortality were recorded.
RESULTS: Of 63 patients enrolled, 23 (37%) had a total of 82 postoperative complications; 5 patients (8%) died within 30 days postoperatively. Univariate analysis showed that severe portal hypertension, preoperative Child class B, low albumin, the presence of ascites, preoperative upper GI tract bleeding, and high intraoperative blood loss were linked to postoperative morbidity. Presence of postoperative infection (p = 0.004), presence of preoperative ascites (p = 0.01), high intraoperative blood loss (p = 0.02), and preoperative upper GI tract bleeding (p = 0.03) were significantly related to mortality. Of 58 patients receiving adjuvant chemotherapy, 20 received the oxaliplatin regimen and 38 received 5-fluorouracil/leucovorin without oxaliplatin. The median length of follow-up was 26 (range, 6-36) months. Kaplan-Meier analyses showed that patients who received oxaliplatin had higher cumulative incidences of newly developed esophageal varices (p = 0.002), GI tract bleeding (p = 0.02), and newly formed ascites (p = 0.03). Death occurred in 8 of 20 patients (40%) in the oxaliplatin group and in 5 of 38 patients (13%) in the 5-fluorouracil group. Kaplan-Meier estimates of mean survival time were 34.4 months (95% CI, 32.4-36.5) in the 5-fluorouracil/leucovorin group vs 29.9 months (95% CI, 26-33.7) in the oxaliplatin group, and patients receiving oxaliplatin had a significantly higher relative risk of death (HR = 2.98; 95% CI, 1.03-8.65). Cancer-specific mortality was not related to treatment type.
LIMITATIONS: The study was limited by the relatively small sample size and lack of randomization, which may have led to selection bias in treatment regimens.
CONCLUSIONS: Colorectal cancer surgery can be done safely in portal hypertensive patients with good hepatic function; however, higher mortality is expected in patients with compromised hepatic function reserve. Compared with adjuvant chemotherapy without oxaliplatin, oxaliplatin-based chemotherapy does not significantly reduce cancer-specific mortality and may increase overall morbidity and mortality. Therefore, oxaliplatin-based chemotherapy should be used with caution in patients who have portal hypertension, even in those with good liver function.
OBJECTIVE: Our aim was to investigate short- and long-term outcomes of surgery for colorectal cancer in patients with portal hypertension with or without cirrhosis, particularly regarding effects of adjuvant chemotherapy with oxaliplatin.
DESIGN AND SETTING: This was a prospective cohort study performed at an academic medical center.
PATIENTS: Patients with stage II or III colorectal cancer and portal hypertension who underwent curative resection were included.
INTERVENTION: All patients received adjuvant chemotherapy with oxaliplatin (FOLFOX 4) or 5-fluorouracil and leucovorin.
MAIN OUTCOME MEASURES: Potential predictive laboratory and clinical variables and postoperative (30-day) and long-term morbidity and mortality were recorded.
RESULTS: Of 63 patients enrolled, 23 (37%) had a total of 82 postoperative complications; 5 patients (8%) died within 30 days postoperatively. Univariate analysis showed that severe portal hypertension, preoperative Child class B, low albumin, the presence of ascites, preoperative upper GI tract bleeding, and high intraoperative blood loss were linked to postoperative morbidity. Presence of postoperative infection (p = 0.004), presence of preoperative ascites (p = 0.01), high intraoperative blood loss (p = 0.02), and preoperative upper GI tract bleeding (p = 0.03) were significantly related to mortality. Of 58 patients receiving adjuvant chemotherapy, 20 received the oxaliplatin regimen and 38 received 5-fluorouracil/leucovorin without oxaliplatin. The median length of follow-up was 26 (range, 6-36) months. Kaplan-Meier analyses showed that patients who received oxaliplatin had higher cumulative incidences of newly developed esophageal varices (p = 0.002), GI tract bleeding (p = 0.02), and newly formed ascites (p = 0.03). Death occurred in 8 of 20 patients (40%) in the oxaliplatin group and in 5 of 38 patients (13%) in the 5-fluorouracil group. Kaplan-Meier estimates of mean survival time were 34.4 months (95% CI, 32.4-36.5) in the 5-fluorouracil/leucovorin group vs 29.9 months (95% CI, 26-33.7) in the oxaliplatin group, and patients receiving oxaliplatin had a significantly higher relative risk of death (HR = 2.98; 95% CI, 1.03-8.65). Cancer-specific mortality was not related to treatment type.
LIMITATIONS: The study was limited by the relatively small sample size and lack of randomization, which may have led to selection bias in treatment regimens.
CONCLUSIONS: Colorectal cancer surgery can be done safely in portal hypertensive patients with good hepatic function; however, higher mortality is expected in patients with compromised hepatic function reserve. Compared with adjuvant chemotherapy without oxaliplatin, oxaliplatin-based chemotherapy does not significantly reduce cancer-specific mortality and may increase overall morbidity and mortality. Therefore, oxaliplatin-based chemotherapy should be used with caution in patients who have portal hypertension, even in those with good liver function.
Bot J, Piessen G, Robb WB, et al.
Advanced tumor stage is an independent risk factor of postoperative infectious complications after colorectal surgery: arguments from a case-matched series.
Dis Colon Rectum. 2013; 56(5):568-76 [PubMed]
Advanced tumor stage is an independent risk factor of postoperative infectious complications after colorectal surgery: arguments from a case-matched series.
Dis Colon Rectum. 2013; 56(5):568-76 [PubMed]
BACKGROUND: Patient and technical factors influencing postoperative infectious complications after elective colorectal resections for cancer are well described. Tumor related factors, however, have not been extensively evaluated.
OBJECTIVE: This study aimed to measure the effect of tumor stage on postoperative surgical site and extra surgical site infections after elective colorectal cancer resection.
DESIGN: This was a retrospective matched-cohort analysis of prospectively gathered data.
SETTINGS: The study was conducted in a tertiary referral center and a private hospital specializing in colorectal surgery.
PATIENTS: Between 2004 and 2011, 740 consecutive patients underwent elective resection for colorectal cancer in 2 centers. Patients undergoing resection for advanced tumors (group A, ≥ stage IIB, n = 177) were matched to randomly selected patients with localized disease (group L,
RESULTS: Group A had a higher overall rate of IC (44.6 vs 25.4 %, p < 0.001), with a higher risk of infectious complications at both the resection site (p < 0.001) and distant to the resection site (p = 0.015). Independent risk factors for infectious complications were advanced tumors (OR = 2.70; p < 0.001), obesity (OR = 1.89; p = 0.018), malnutrition (OR = 2.22; p = 0.008), and open rather than laparoscopic procedure (OR = 5.11; p < 0.001).
LIMITATIONS: This study is limited by its retrospective methodology.
CONCLUSION: Advanced tumors increase the risk of infectious complications after colorectal resection, with other risk factors including malnutrition, obesity, and resection by laparotomy. Optimization of modifiable risk factors through nutritional repletion and the choice of a minimally invasive operation should be considered.
OBJECTIVE: This study aimed to measure the effect of tumor stage on postoperative surgical site and extra surgical site infections after elective colorectal cancer resection.
DESIGN: This was a retrospective matched-cohort analysis of prospectively gathered data.
SETTINGS: The study was conducted in a tertiary referral center and a private hospital specializing in colorectal surgery.
PATIENTS: Between 2004 and 2011, 740 consecutive patients underwent elective resection for colorectal cancer in 2 centers. Patients undergoing resection for advanced tumors (group A, ≥ stage IIB, n = 177) were matched to randomly selected patients with localized disease (group L,
RESULTS: Group A had a higher overall rate of IC (44.6 vs 25.4 %, p < 0.001), with a higher risk of infectious complications at both the resection site (p < 0.001) and distant to the resection site (p = 0.015). Independent risk factors for infectious complications were advanced tumors (OR = 2.70; p < 0.001), obesity (OR = 1.89; p = 0.018), malnutrition (OR = 2.22; p = 0.008), and open rather than laparoscopic procedure (OR = 5.11; p < 0.001).
LIMITATIONS: This study is limited by its retrospective methodology.
CONCLUSION: Advanced tumors increase the risk of infectious complications after colorectal resection, with other risk factors including malnutrition, obesity, and resection by laparotomy. Optimization of modifiable risk factors through nutritional repletion and the choice of a minimally invasive operation should be considered.
Rullier E, Denost Q, Vendrely V, et al.
Low rectal cancer: classification and standardization of surgery.
Dis Colon Rectum. 2013; 56(5):560-7 [PubMed]
Low rectal cancer: classification and standardization of surgery.
Dis Colon Rectum. 2013; 56(5):560-7 [PubMed]
BACKGROUND: Surgical treatment of low rectal cancer is controversial, and one of the reasons is the lack of definition and standardization of surgery in low rectal cancer.
OBJECTIVE: We classified low rectal cancers in 4 groups with the aim of demonstrating that most patients with low rectal cancer can receive conservative surgery without compromising oncologic outcome.
DESIGN: Patients with low rectal cancer <6 cm from anal verge were defined in 4 groups: type I (supra-anal tumors: >1 cm from anal ring) had coloanal anastomosis, type II (juxta-anal tumors: <1 cm from anal ring) had partial intersphincteric resection, type III (intra-anal tumors: internal anal sphincter invasion) had total intersphincteric resection, and type IV (transanal tumors: external anal sphincter invasion) had abdominoperineal resection. Patients with ultra-low sphincter-preserving surgery (types II-III) were compared with those with conventional sphincter-preserving surgery (type I).
OUTCOME MEASURES: Postoperative mortality, morbidity, surgical margins, local and distant recurrence, and survival were analyzed.
RESULTS: Of 404 patients with low rectal cancer, 135 were type I, 131 type II, 55 type III, and 83 type IV. There was no difference in local recurrence (5% to 9% vs 6%), distant recurrence (23% vs 23%), and disease-free survival (70%-73% vs 68%) at 5 years between ultra-low (types II-III) and conventional (type I) sphincter-preserving surgery. Predictive factors of survival were tumor stage and R1 resection but not the type of tumor or type of surgery.
LIMITATIONS: This study is limited by the retrospective analysis of a database, obtained from a single institution and covering a 16-year period.
CONCLUSION: Classification of low rectal cancers and standardization of surgery permitted sphincter-preserving surgery in 79% of patients with low rectal cancer without compromising oncologic outcome. This new surgical classification should be used to standardize surgery and increase sphincter-preserving surgery in low rectal cancer.
OBJECTIVE: We classified low rectal cancers in 4 groups with the aim of demonstrating that most patients with low rectal cancer can receive conservative surgery without compromising oncologic outcome.
DESIGN: Patients with low rectal cancer <6 cm from anal verge were defined in 4 groups: type I (supra-anal tumors: >1 cm from anal ring) had coloanal anastomosis, type II (juxta-anal tumors: <1 cm from anal ring) had partial intersphincteric resection, type III (intra-anal tumors: internal anal sphincter invasion) had total intersphincteric resection, and type IV (transanal tumors: external anal sphincter invasion) had abdominoperineal resection. Patients with ultra-low sphincter-preserving surgery (types II-III) were compared with those with conventional sphincter-preserving surgery (type I).
OUTCOME MEASURES: Postoperative mortality, morbidity, surgical margins, local and distant recurrence, and survival were analyzed.
RESULTS: Of 404 patients with low rectal cancer, 135 were type I, 131 type II, 55 type III, and 83 type IV. There was no difference in local recurrence (5% to 9% vs 6%), distant recurrence (23% vs 23%), and disease-free survival (70%-73% vs 68%) at 5 years between ultra-low (types II-III) and conventional (type I) sphincter-preserving surgery. Predictive factors of survival were tumor stage and R1 resection but not the type of tumor or type of surgery.
LIMITATIONS: This study is limited by the retrospective analysis of a database, obtained from a single institution and covering a 16-year period.
CONCLUSION: Classification of low rectal cancers and standardization of surgery permitted sphincter-preserving surgery in 79% of patients with low rectal cancer without compromising oncologic outcome. This new surgical classification should be used to standardize surgery and increase sphincter-preserving surgery in low rectal cancer.
Bowles TL, Hu CY, You NY, et al.
An individualized conditional survival calculator for patients with rectal cancer.
Dis Colon Rectum. 2013; 56(5):551-9 [PubMed]
An individualized conditional survival calculator for patients with rectal cancer.
Dis Colon Rectum. 2013; 56(5):551-9 [PubMed]
BACKGROUND: Conditional survival estimates account for time survived since diagnosis to provide prognostic information for long-term cancer survivors. For rectal cancer, stage-related treatment (eg, neoadjuvant radiotherapy) affects pathologic stage and therefore stage-associated survival estimates.
OBJECTIVES: The aim of this study is to estimate conditional survival for patients who have rectal cancer and to develop an interactive calculator to use for individualized patient counseling.
PATIENTS: Patients with rectal adenocarcinoma were identified by using the Surveillance Epidemiology and End Results registry (1988-2002, N = 22,610).
DESIGN: Cox regression models were developed to determine adjusted survival estimates (years 1-10) and used to calculate 5-year adjusted conditional survival. Models were built separately for no radiotherapy, preoperative radiotherapy, postoperative radiotherapy, and patients with stage IV disease. Covariates included age, sex, race, tumor grade, and type of surgery. An Internet-based conditional survival calculator was developed.
RESULTS: Radiotherapy was given to 42.6% of patients (14.1% preoperative, 28.4% postoperative). Significant improvements in 5-year conditional survival were observed for all stages, with the exception of stage I because of the initial high survival probability at diagnosis. Patients with advanced stage had the greatest improvements in conditional survival, with 5-year absolute increases of 33% (stage IIIC) and 54% (IV). Other factors associated with conditional survival included sequence of radiotherapy and surgery, age, race, and tumor grade. The Internet-based conditional survival calculator can be accessed at www.mdanderson.org/rectalcalculator.
LIMITATIONS: The data source used does not include information on chemotherapy treatment, change in staging after neoadjuvant treatment, or patient comorbidities.
CONCLUSION: Conditional survival estimates improve over 5 years in patients who have rectal cancer; the greatest improvements are observed among patients with advanced stage disease. The conditional survival calculator is an individualized decision support tool that informs patients, who must make non-treatment-related life decisions, and their clinicians planning follow-up and surveillance.
OBJECTIVES: The aim of this study is to estimate conditional survival for patients who have rectal cancer and to develop an interactive calculator to use for individualized patient counseling.
PATIENTS: Patients with rectal adenocarcinoma were identified by using the Surveillance Epidemiology and End Results registry (1988-2002, N = 22,610).
DESIGN: Cox regression models were developed to determine adjusted survival estimates (years 1-10) and used to calculate 5-year adjusted conditional survival. Models were built separately for no radiotherapy, preoperative radiotherapy, postoperative radiotherapy, and patients with stage IV disease. Covariates included age, sex, race, tumor grade, and type of surgery. An Internet-based conditional survival calculator was developed.
RESULTS: Radiotherapy was given to 42.6% of patients (14.1% preoperative, 28.4% postoperative). Significant improvements in 5-year conditional survival were observed for all stages, with the exception of stage I because of the initial high survival probability at diagnosis. Patients with advanced stage had the greatest improvements in conditional survival, with 5-year absolute increases of 33% (stage IIIC) and 54% (IV). Other factors associated with conditional survival included sequence of radiotherapy and surgery, age, race, and tumor grade. The Internet-based conditional survival calculator can be accessed at www.mdanderson.org/rectalcalculator.
LIMITATIONS: The data source used does not include information on chemotherapy treatment, change in staging after neoadjuvant treatment, or patient comorbidities.
CONCLUSION: Conditional survival estimates improve over 5 years in patients who have rectal cancer; the greatest improvements are observed among patients with advanced stage disease. The conditional survival calculator is an individualized decision support tool that informs patients, who must make non-treatment-related life decisions, and their clinicians planning follow-up and surveillance.
Carter XW, Topolski R, Hatzigeorgiou C, Fincher RK
Role of anxiety in the comfort of nonsedated average-risk screening sigmoidoscopy.
South Med J. 2013; 106(4):280-4 [PubMed]
Role of anxiety in the comfort of nonsedated average-risk screening sigmoidoscopy.
South Med J. 2013; 106(4):280-4 [PubMed]
OBJECTIVES: The aim of this prospective study was to assess the role of generalized anxiety disorder in the comfort of nonsedated, average-risk screening sigmoidoscopy.
METHODS: Patients were asked to complete a screening questionnaire before undergoing average-risk colon cancer screening with nonsedated sigmoidoscopy. The questionnaire included demographic information and a series of Likert-based and visual analog scales designed to assess patient comfort, procedural symptom severity, and satisfaction. The Primary Care Evaluation of Mental Disorders questionnaire was used to assess for generalized anxiety disorder. Comfort levels and postprocedural symptom severity were recorded immediately after the procedure and 1 week postprocedure. χ and t tests were used to analyze the data.
RESULTS: Eighty-one patients were enrolled in the study. Twenty-seven patients tested positive for anxiety (high anxiety), whereas 54 tested negative (low anxiety). There were no differences in anxiety according to sex (P = 0.53), or age (P = 0.32). There was no difference in reaching the splenic flexure between high- and low-anxiety patients (P = 0.15); however, pairwise comparisons revealed patients with high anxiety reported significantly higher levels of abdominal pain after the procedure (P < 0.01) and still recalled higher pain from the procedure 1 week later (P < 0.01) than those patients with low anxiety scores. Furthermore, those patients with high anxiety reported significantly more procedure-related cramping and bloating both immediately after the procedure and again 1 week later (P < 0.01). Finally, patients with high anxiety reported the procedure as being more uncomfortable 1 week later, when compared with low-anxiety patients (P = 0.01).
CONCLUSIONS: The level of anxiety correlated directly to pain and discomfort postprocedure and related inversely to the level of satisfaction. Better management of anxiety may lead to better procedural comfort in nonsedated procedures.
METHODS: Patients were asked to complete a screening questionnaire before undergoing average-risk colon cancer screening with nonsedated sigmoidoscopy. The questionnaire included demographic information and a series of Likert-based and visual analog scales designed to assess patient comfort, procedural symptom severity, and satisfaction. The Primary Care Evaluation of Mental Disorders questionnaire was used to assess for generalized anxiety disorder. Comfort levels and postprocedural symptom severity were recorded immediately after the procedure and 1 week postprocedure. χ and t tests were used to analyze the data.
RESULTS: Eighty-one patients were enrolled in the study. Twenty-seven patients tested positive for anxiety (high anxiety), whereas 54 tested negative (low anxiety). There were no differences in anxiety according to sex (P = 0.53), or age (P = 0.32). There was no difference in reaching the splenic flexure between high- and low-anxiety patients (P = 0.15); however, pairwise comparisons revealed patients with high anxiety reported significantly higher levels of abdominal pain after the procedure (P < 0.01) and still recalled higher pain from the procedure 1 week later (P < 0.01) than those patients with low anxiety scores. Furthermore, those patients with high anxiety reported significantly more procedure-related cramping and bloating both immediately after the procedure and again 1 week later (P < 0.01). Finally, patients with high anxiety reported the procedure as being more uncomfortable 1 week later, when compared with low-anxiety patients (P = 0.01).
CONCLUSIONS: The level of anxiety correlated directly to pain and discomfort postprocedure and related inversely to the level of satisfaction. Better management of anxiety may lead to better procedural comfort in nonsedated procedures.
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
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]
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.
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]
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.
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]
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.
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]
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.
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, Law WL, et al.
Condition-specific measure was more responsive than generic measure in colorectal cancer: all but social domains.
J Clin Epidemiol. 2013; 66(5):557-65 [PubMed]
Condition-specific measure was more responsive than generic measure in colorectal cancer: all but social domains.
J Clin Epidemiol. 2013; 66(5):557-65 [PubMed]
OBJECTIVE: To examine the responsiveness of generic and condition-specific instruments based on the anchor of self-reported level of global change in patients with colorectal cancer (CRC).
STUDY DESIGN AND SETTING: Three hundred thirty-three patients with CRC were surveyed at two assessments at baseline and follow-up at 6 months from September 2009 to July 2010 using the Short Form-12 Health Survey version 2 (SF-12v2) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C) measures. The responsiveness of the two measures was evaluated using standardized effect size, standardized response mean, responsiveness statistic, and receiver operating characteristic (ROC) curve analysis.
RESULTS: In worsened group, internal responsiveness of detecting negative changes was satisfactory for most subscales of FACT-C and SF-12v2. The FACT-C subscales were significantly more responsive to positive changes detection than the SF-12v2 subscales in improved group. Physical well-being subscale, Trial Outcome Index (TOI), and total score of FACT-C were more externally responsive to ROC curve analysis. The FACT-C measure was generally more responsive to changes in health status compared with SF-12v2 measure.
CONCLUSION: TOI and total score of FACT-C were the most responsive among subscales of condition-specific measure, which were more responsive than all generic subscales with the exception of social domain. Complementary use of condition-specific and generic instruments to evaluate the health-related quality of life of CRC patients is encouraged.
STUDY DESIGN AND SETTING: Three hundred thirty-three patients with CRC were surveyed at two assessments at baseline and follow-up at 6 months from September 2009 to July 2010 using the Short Form-12 Health Survey version 2 (SF-12v2) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C) measures. The responsiveness of the two measures was evaluated using standardized effect size, standardized response mean, responsiveness statistic, and receiver operating characteristic (ROC) curve analysis.
RESULTS: In worsened group, internal responsiveness of detecting negative changes was satisfactory for most subscales of FACT-C and SF-12v2. The FACT-C subscales were significantly more responsive to positive changes detection than the SF-12v2 subscales in improved group. Physical well-being subscale, Trial Outcome Index (TOI), and total score of FACT-C were more externally responsive to ROC curve analysis. The FACT-C measure was generally more responsive to changes in health status compared with SF-12v2 measure.
CONCLUSION: TOI and total score of FACT-C were the most responsive among subscales of condition-specific measure, which were more responsive than all generic subscales with the exception of social domain. Complementary use of condition-specific and generic instruments to evaluate the health-related quality of life of CRC patients is encouraged.
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]
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.
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]
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.
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]
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]
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.
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
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.
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]
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.
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
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.
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]
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.
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.
Wicherts DA, de Haas RJ, Salloum C, et al.
Repeat hepatectomy for recurrent colorectal metastases.
Br J Surg. 2013; 100(6):808-18 [PubMed]
Repeat hepatectomy for recurrent colorectal metastases.
Br J Surg. 2013; 100(6):808-18 [PubMed]
BACKGROUND: The oncological benefit of repeat hepatectomy for patients with recurrent colorectal metastases is not yet proven. This study assessed the value of repeat hepatectomy for these patients within current multidisciplinary treatment.
METHODS: Consecutive patients treated by repeat hepatectomy for colorectal metastases between January 1990 and January 2010 were included. Patients undergoing two-stage hepatectomy were excluded. Postoperative outcome was analysed and compared with that of patients who had only a single hepatectomy.
RESULTS: A total of 1036 patients underwent 1454 hepatectomies for colorectal metastases. Of these, 288 patients had 362 repeat hepatectomies for recurrent metastases. Some 225 patients (78·1 per cent) had two hepatectomies, 52 (18·1 per cent) had three hepatectomies, and 11 patients (3·8 per cent) had a fourth hepatectomy. Postoperative morbidity following repeat hepatectomy was similar to that after initial liver resection (27·1 per cent after first, 34·4 per cent after second and 33·3 per cent after third hepatectomy) (P = 0·069). The postoperative mortality rate was 3·1 per cent after repeat hepatectomy versus 1·6 per cent after first hepatectomy. Three- and 5-year overall survival rates following first hepatectomy in patients who underwent repeat hepatectomy were 76 and 54 per cent respectively, compared with 58 and 45 per cent in patients who had only one hepatectomy (P = 0·003). In multivariable analysis, repeat hepatectomy performed between 2000 and 2010 was the sole independent factor associated with longer overall survival.
CONCLUSION: Repeat hepatectomy for recurrent colorectal metastases offers long-term survival in selected patients.
METHODS: Consecutive patients treated by repeat hepatectomy for colorectal metastases between January 1990 and January 2010 were included. Patients undergoing two-stage hepatectomy were excluded. Postoperative outcome was analysed and compared with that of patients who had only a single hepatectomy.
RESULTS: A total of 1036 patients underwent 1454 hepatectomies for colorectal metastases. Of these, 288 patients had 362 repeat hepatectomies for recurrent metastases. Some 225 patients (78·1 per cent) had two hepatectomies, 52 (18·1 per cent) had three hepatectomies, and 11 patients (3·8 per cent) had a fourth hepatectomy. Postoperative morbidity following repeat hepatectomy was similar to that after initial liver resection (27·1 per cent after first, 34·4 per cent after second and 33·3 per cent after third hepatectomy) (P = 0·069). The postoperative mortality rate was 3·1 per cent after repeat hepatectomy versus 1·6 per cent after first hepatectomy. Three- and 5-year overall survival rates following first hepatectomy in patients who underwent repeat hepatectomy were 76 and 54 per cent respectively, compared with 58 and 45 per cent in patients who had only one hepatectomy (P = 0·003). In multivariable analysis, repeat hepatectomy performed between 2000 and 2010 was the sole independent factor associated with longer overall survival.
CONCLUSION: Repeat hepatectomy for recurrent colorectal metastases offers long-term survival in selected patients.
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]
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]
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]
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.
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]
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.
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.
Li P, Fang YJ, Li F, et al.
ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.
Br J Cancer. 2013; 108(6):1238-44 [PubMed] Article available free on PMC after 02/04/2014
ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.
Br J Cancer. 2013; 108(6):1238-44 [PubMed] Article available free on PMC after 02/04/2014
BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy.
METHODS: Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression.
RESULTS: Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group.
CONCLUSION: Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.
METHODS: Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression.
RESULTS: Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group.
CONCLUSION: Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.
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