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Colorectal (Bowel) Cancer

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

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

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    MeSH term: Colorectal Neoplasms
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Herdiatry Colorectal Cancers (5 links)

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

Latest Research Publications

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

Meester RG, Doubeni CA, Lansdorp-Vogelaar I, et al.
Variation in Adenoma Detection Rate and the Lifetime Benefits and Cost of Colorectal Cancer Screening: A Microsimulation Model.
JAMA. 2015; 313(23):2349-58 [PubMed] Related Publications
IMPORTANCE: Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates (ADRs), varies widely among physicians, with unknown consequences for the cost and benefits of screening programs.
OBJECTIVE: To estimate the lifetime benefits, complications, and costs of an initial colonoscopy screening program at different levels of adenoma detection.
DESIGN, SETTING, AND PARTICIPANTS: Microsimulation modeling with data from a community-based health care system on ADR variation and cancer risk among 57,588 patients examined by 136 physicians from 1998 through 2010.
EXPOSURES: Using modeling, no screening was compared with screening initiation with colonoscopy according to ADR quintiles (averages 15.3%, quintile 1; 21.3%, quintile 2; 25.6%, quintile 3; 30.9%, quintile 4; and 38.7%, quintile 5) at ages 50, 60, and 70 years with appropriate surveillance of patients with adenoma.
MAIN OUTCOMES AND MEASURES: Estimated lifetime colorectal cancer incidence and mortality, number of colonoscopies, complications, and costs per 1000 patients, all discounted at 3% per year and including 95% confidence intervals from multiway probabilistic sensitivity analysis.
RESULTS: In simulation modeling, among unscreened patients the lifetime risk of colorectal cancer incidence was 34.2 per 1000 (95% CI, 25.9-43.6) and risk of mortality was 13.4 per 1000 (95% CI, 10.0-17.6). Among screened patients, simulated lifetime incidence decreased with lower to higher ADRs (26.6; 95% CI, 20.0-34.3 for quintile 1 vs 12.5; 95% CI, 9.3-16.5 for quintile 5) as did mortality (5.7; 95% CI, 4.2-7.7 for quintile 1 vs 2.3; 95% CI, 1.7-3.1 for quintile 5). Compared with quintile 1, simulated lifetime incidence was on average 11.4% (95% CI, 10.3%-11.9%) lower for every 5 percentage-point increase of ADRs and for mortality, 12.8% (95% CI, 11.1%-13.7%) lower. Complications increased from 6.0 (95% CI, 4.0-8.5) of 2777 colonoscopies (95% CI, 2626-2943) in quintile 1 to 8.9 (95% CI, 6.1-12.0) complications of 3376 (95% CI, 3081-3681) colonoscopies in quintile 5. Estimated net screening costs were lower from quintile 1 (US $2.1 million, 95% CI, $1.8-$2.4 million) to quintile 5 (US $1.8 million, 95% CI, $1.3-$2.3 million) due to averted cancer treatment costs. Results were stable across sensitivity analyses.
CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study, higher adenoma detection rates in screening colonoscopy were associated with lower lifetime risks of colorectal cancer and colorectal cancer mortality without being associated with higher overall costs. Future research is needed to assess whether increasing adenoma detection would be associated with improved patient outcomes.

Erdling A, Johansson A
Core temperature--the intraoperative difference between esophageal versus nasopharyngeal temperatures and the impact of prewarming, age, and weight: a randomized clinical trial.
AANA J. 2015; 83(2):99-105 [PubMed] Related Publications
Unplanned perioperative hypothermia is a well-known complication to anesthesia. This study compares esophageal and nasopharyngeal temperature measured in the same patient for a period of 210 minutes of anesthesia. Forty-three patients undergoing colorectal surgery were randomly assigned in 2 groups, with or without a prewarming period (group A = prewarming [n = 21] or group B = no prewarming [n = 22]). Demographics were similar in both groups. Mean temperatures at 210 minutes were statistically different between the groups at both sites of measurement. Esophageal temperature in group A was 36.5 ± 0.6 vs 35.8 ± 0.7 in group B (P = .001), and nasopharyngeal temperature was 36.7 ± 0.6 and 36.0 ± 0.6 in group A and group B, respectively (P = .002). A negative correlation was found between esophageal temperature and age (r2 = -.381, P < .012). Esophageal temperature was different with respect to BMI below or above 25. The temperatures were 35.81 ± 0.66 in the lower BMI group vs 36.46 ± 0.59 (P < .001). These results demonstrate a difference between the 2 measurement techniques and that prewarming, age and BMI have an impact on measured temperatures.

Jorgensen B, Knudtson J
Stop cancer colon. Colorectal cancer screening--updated guidelines.
S D Med. 2015; Spec No:82-7 [PubMed] Related Publications
Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers in the U.S. Its incidence and mortality have shown a decreasing trend over the last several decades. The greatest contribution to this trend has been colorectal cancer screening. Colonoscopy continues to be the preferred screening modality. However, recommendations for the use of screening tests other than colonoscopy have generated much interest. Guidelines regarding current screening and surveillance recommendations have recently been updated by expert panels, such as the U.S. Multi-Society Task Force, National Comprehensive Cancer Network and National Institute of Health. A review of the updated guidelines as well as a PubMed search for articles dating 2006 to present relating to colorectal cancer screening and surveillance was performed. We discuss the importance of colorectal screening and highlight updates to current colorectal cancer screening and surveillance guidelines.

Zhang H, Zhang X, Wang J, et al.
Comparison of high-resolution melting analysis, Sanger sequencing and ARMS for KRAS mutation detection in metastatic colorectal cancer.
Clin Lab. 2015; 61(3-4):435-9 [PubMed] Related Publications
BACKGROUND: Treatment of metastatic colon carcinoma with the anti-epidermal growth factor receptor antibody cetuximab/panitumumab is reported to be ineffective in KRAS-mutant tumors; therefore, it is necessary to perform KRAS mutation analysis before cetuximab or panitumumab treatment is initiated.
METHODS: This study was designed to compare and evaluate the efficacy of three different methodologies--high resolution melting (HRM), Sanger sequencing, and Amplification Refractory Mutation System (ARMS)--for KRAS mutation detection in a clinical setting.
RESULTS: In total, 55 samples from patients with metastatic colorectal cancer were analyzed. Compared to Sanger sequencing, good consistency was found between the results of the ARMS (Kappa = 0.839) and HRM (Kappa = 0.839). The sensitivities of the methods were compared after a consensus was reached: if two of the three methodologies showed a similar result, it was considered as the consensus result. The frequency of KRAS mutations in our population was 34.5%, and discordant findings were observed in five samples. No significant difference in sensitivity was found among the three methodologies.
CONCLUSIONS: From the results, we can conclude that after careful in-laboratory validation, HRM is a good alternative to the ARMS and Sanger sequencing for KRAS mutation testing.

Kong W, Wang J, Ping X, et al.
Biomarkers for assessing mucosal barrier dysfunction induced by chemotherapy: Identifying a rapid and simple biomarker.
Clin Lab. 2015; 61(3-4):371-8 [PubMed] Related Publications
BACKGROUND: Chemotherapy-induced mucosal barrier dysfunction is of clinical interest. However, the assessment of mucosal barrier dysfunction still poses challenges. In this study, we compared several biomarkers with the dual sugar gut permeability test for assessing mucosal barrier dysfunction during chemotherapy.
METHODS: Forty-two patients with gastric or colorectal cancer underwent chemotherapy, including FAM or FOLFOX4 regimens. Patients were asked to grade and record their symptoms of gastrointestinal toxicity daily. The urinary lactulose-mannitol ratio was measured to assess the intestinal permeability. Plasma levels of citrulline, diamine oxidase (DAO), D-lactic acid, and endotoxin were also measured. Intestinal permeability was observed in the subgroup of patients with diarrhea or constipation.
RESULTS: The urinary lactulose-mannitol ratio and plasma citrulline levels increased on the third and sixth post-chemotherapy days, respectively. There were no significant differences in the plasma levels of D-lactic acid, endotoxin or DAO activity compared to their levels before chemotherapy. The urinary lactulose-mannitol ratio in diarrhea patients was significantly higher than in constipation patients.
CONCLUSIONS: These results indicate that the urinary lactulose-mannitol ratio and plasma citrulline level are appropriate biomarkers for assessing mucosal barrier dysfunction in patients receiving chemotherapy. Mucosal barrier dysfunction in diarrhea patients was greater than in constipation patients.

Mayer RJ, Van Cutsem E, Falcone A, et al.
Randomized trial of TAS-102 for refractory metastatic colorectal cancer.
N Engl J Med. 2015; 372(20):1909-19 [PubMed] Related Publications
BACKGROUND: Early clinical trials conducted primarily in Japan have shown that TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride, was effective in the treatment of refractory colorectal cancer. We conducted a phase 3 trial to further assess the efficacy and safety of TAS-102 in a global population of such patients.
METHODS: In this double-blind study, we randomly assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo. The primary end point was overall survival.
RESULTS: The median overall survival improved from 5.3 months with placebo to 7.1 months with TAS-102, and the hazard ratio for death in the TAS-102 group versus the placebo group was 0.68 (95% confidence interval [CI], 0.58 to 0.81; P<0.001). The most frequently observed clinically significant adverse events associated with TAS-102 were neutropenia, which occurred in 38% of those treated, and leukopenia, which occurred in 21%; 4% of the patients who received TAS-102 had febrile neutropenia, and one death related to TAS-102 was reported. The median time to worsening performance status (a change in Eastern Cooperative Oncology Group performance status [on a scale of 0 to 5, with 0 indicating no symptoms and higher numbers indicating increasing degrees of disability] from 0 or 1 to 2 or more) was 5.7 months with TAS-102 versus 4.0 months with placebo (hazard ratio, 0.66; 95% CI, 0.56 to 0.78; P<0.001).
CONCLUSIONS: In patients with refractory colorectal cancer, TAS-102, as compared with placebo, was associated with a significant improvement in overall survival. (Funded by Taiho Oncology-Taiho Pharmaceutical; RECOURSE ClinicalTrials.gov number, NCT01607957.).

Beaber EF, Kim JJ, Schapira MM, et al.
Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.
J Natl Cancer Inst. 2015; 107(6):djv120 [PubMed] Related Publications
General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites.

Shah M, Denlinger CS
Optimal post-treatment surveillance in cancer survivors: is more really better?
Oncology (Williston Park). 2015; 29(4):230-40 [PubMed] Related Publications
A substantial rise in the number of cancer survivors has led to management questions regarding effective post-treatment surveillance strategies. Although a number of professional societies have proposed surveillance guidelines, clinical practice varies; the general trend is toward more intensive strategies. The evidence supporting intensive surveillance is relatively lacking, with most studies showing that more intense surveillance regimens have minimal, if any, impact on outcomes in terms of survival, quality of life, or overall cost-effectiveness. This has been demonstrated in breast cancer, and data supporting a similar conclusion may be evolving in colorectal cancer, where large prospective studies call into question the utility of intensive surveillance; in prostate cancer, retrospective data suggest a similar trend. In this review, we discuss the established guidelines and current evidence regarding post-treatment surveillance, and we propose general management strategies in prostate, colorectal, and breast cancers.

Saha A, Shree Padhi S, Roy S, Banerjee B
HCT116 colonospheres shows elevated expression of hTERT and β-catenin protein - a short report.
J Stem Cells. 2014; 9(4):243-51 [PubMed] Related Publications
AIM: Clonospheres formed due to modified culture conditions are often studied for their stem cell like behaviour. The main objective of the current study is to compare the stem cell markers and link it to hTERT levels by monitoring their quantitative gene expression as they are potential targets for new generation combination therapeutics.
METHOD: In the present study we created stable colonospheres of Human colon cancer cell line HCT-116 long term culture conditions of Serum deprivation. Clonospheres formed after 15 days were collected by gentle and enzymatic dissociation was performed. Single cell suspension was obtained by mechanically dissociating the cells through a 22G needle. Single cells were replanted at a density 1200 cells/ml in Serum Free Medium in the 6 well plates for further passage. Passaging of cells was done at an interval of 8 days. The spheres formed were cyto-spun in special slides for Immunocytochemistry (ICC) studies for β-catenin protein and hTERT. The colonospheres were also processed for real time PCR expression studies for the same genes to confirm.
RESULTS: In this present study, immunofluorescence studies revealed high β-catenin expression in the nucleus in colonospheres as compared to that of differentiated cancer cell line HCT-116 where the signal was localized mostly in the membranous and non-nuclear regions. Also increased TRF2 signal in colonospheres indicated higher activity of hTERT gene as TRF2 is the direct activator of hTERT to protect the telomere. Quantitative PCR studies showed that there was a significant over expression (p<0.05) at the mRNA level of the hTERT, TRF2, Rap1 genes along with the β-catenin over expression. Immunofluorescence analysis also revealed higher expression of CSC marker CD44 and ALDH1in colonospheres compared to the parental population.
CONCLUSION: Clonospheres sub-population is showing higher degree of hTERT gene expression along with β-catenin when compared to the parental HCT-116 cancer cells. We also checked the co expression of other telomere maintenance genes mainly TRF 2 and Rap1 which also showed similar results. Therefore, we conclude that not only hTERT but possibly other Sheltrin proteins are regulated by β-catenin which is co expressed.

Wiela-Hojeńska A, Kowalska T, Filipczyk-Cisarż E, et al.
Evaluation of the toxicity of anticancer chemotherapy in patients with colon cancer.
Adv Clin Exp Med. 2015 Jan-Feb; 24(1):103-11 [PubMed] Related Publications
BACKGROUND: Modern anticancer chemotherapy can cause numerous adverse effects in the organism, whose functioning has already been disrupted by the neoplastic process itself.
OBJECTIVES: The aim of the study was to evaluate and compare the frequency and severity of the toxicity of FOLFOX-4 and CLF-1 anticancer therapy in patients with colon cancer, and to analyze certain factors that might have increased the toxicity of the chemotherapy.
MATERIAL AND METHODS: The study involved 64 patients suffering from generalized colon cancer, including 48 patients treated according to the FOLFOX-4 regimen and 16 patients treated according to the CLF-1 regimen. The toxicity of each regimen was analyzed on the basis of a confidential questionnaire formulated by the authors and laboratory research according to the extended WHO toxicity criteria.
RESULTS: The analysis of the symptoms of toxicity symptoms associated with the use of the FOLFOX-4 and CLF-1 therapeutic regimens revealed that the most common side effects included nausea and vomiting, despite ondansetron premedication, and neurotoxicity. Disruption of the functioning of the nervous system under the FOLFOX-4 regimen statistically significant exacerbation that increased with the number of chemotherapy cycles administered; this was more common and more severe in women. Paresthesia was also revealed to be a neurotoxic effect of the FOLFOX-4 regimen after termination of therapy. A statistically significant relationship was observed between the use of vitamin supplements and the incidence and severity of the toxicity of the FOLFOX-4 regimen.
CONCLUSIONS: The findings of the current study regarding the toxicity of the FOLFOX-4 and CLF-1 therapy regimens should be taken into consideration when monitoring chemotherapy safety in colon cancer. The patients' tolerance of the administered medication and the side effects reported by patients should be constantly evaluated, which will help prevent these side effects, apply appropriate therapy and contribute to the improvement of the patients' quality of life. The functioning of the central nervous system should be carefully evaluated when planning the anticancer therapy, especially if repeated administration of neurotoxic drugs is necessary in cases of a recurrence of the disease. Chemotherapy should be thoroughly monitored for safety, especially in women over 65 years of age suffering from coexisting diseases. Colon cancer patients and their families should be informed of the risks of nutritional supplements before the start of the anticancer chemotherapy, and may need to dispense with their use.

Bai H, Huangz X, Jing L, et al.
The effect of radiofrequency ablation vs. liver resection on survival outcome of colorectal liver metastases (CRLM): a meta-analysis.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):373-7 [PubMed] Related Publications
BACKGROUND/AIMS: For patients with solitary colorectal liver metastasis (CRLM), it is still controversial whether radiofrequency ablation (RFA) has the same effect as liver resection (LR). This study aims to pool available evidence and to analyze the effect of RFA versus LR for resectable solitary CRLM in sur- vival indicators.
METHODOLOGY: Relevant studies were searched among databases and a meta-analysis was performed to pool the hazard ratio (HR) of RFA versus LR in overall survival (OS) and disease free survival (DFS).
RESULTS: A total of 10 studies were included in this meta-analysis. Pooled results showed poorer OS (HR: 1.85, 95% CI: 1.48 to 2.32, p < 0.00001) and DFS (HR: 1.68, 95% CI: 1.14 to 2.48, p = 0.009) among the patient received RFA compared those received LR. Sensitivity analysis confirmed high robustness of the findings.
CONCLUSION: In patients with resectable CRLM, LR is superior to RFA in survival outcomes. RFA should be reserved for patients who are not optimal candidates for resection until new supportive evidence is obtained from large RCTs.

Katayose Y, Yamamoto K, Nakagawal K, et al.
Feasibility Assessment of Modified FOLFOX-6 as adjuvant treatment after resection of liver metastases from colorectal cancer: analyses of a multicenter phase II clinical trial (Miyagi-HBPCOG Trial-001).
Hepatogastroenterology. 2015 Mar-Apr; 62(138):303-8 [PubMed] Related Publications
BACKGROUND/AIMS: This multicenter and single arm phase II clinical trial was performed to examine the safety and efficacy of modified FOLFOX6 (mFOLFOX6) as adjuvant treatment after resection of liver metastases from colorectal cancer.
METHODOLOGY: Patients who had undergone R0-1 resection of liver metastases were assigned to 12 cycles of mFOLFOX6. The primary end point was disease-free survival (DFS).
RESULTS: We enrolled 49 cases and analyzed adverse events in 48 cases, since in one patient cancer recurred before starting treatment. As to the relative dose intensity, 5-FU was 78.8%, and oxaliplatin was 75.9%. Adverse events of Grade 3 and above includ- ed 18 cases of neutropenia (37.5%), 4 cases of sensory neuropathy (8.3%), 4 cases of thrombocytopenia (8.3%) and 4 cases of allergy (8.3%), and there were no cases of fatality caused by adverse events. The most difference of adverse event compared with MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) was thrombocytopenia. The 2-year DFS was 59.2% (95% CI: 36.7-78.4) in the 49 enrolled cases.
CONCLUSION: mFOLFOX6 after hepatectomy was tolerable. And mFOLFOX6 also seemed to improve DFS. mFOLFOX is one of the options for such patients and appears promising as an adjuvant treatment.

Sun X, Yang C, Li K, Ding S
The impact of anesthetic techniques on survival for patients with colorectal cancer: evidence based on six studies.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):299-302 [PubMed] Related Publications
BACKGROUND/AIMS: Epidural-supplemented general anesthesia is perceived as a more beneficial method over general anesthesia since it reduces incidence of side effects, provides better postoperative pain relief and lowers the possibility to use immunosuppressive anesthetics. However, previous prospective and retrospective studies reported conflicting results in the effects of epidural anesthesia on post-operative outcomes of colorectal cancer surgery. Therefore, this study aims to pool available evidence to assess the association between epidural anesthesia and the post- operative outcomes in this group of patients.
METHODOLOGY: Relevant studies were searched in databases and a meta-analysis was performed to estimate the association between epidural anesthesia and overall survival and recurrence free survival.
RESULTS: Compared with the anesthetic choice without epidural anesthesia, epidural-supplemented anesthesia is associated with significantly longer overall survival (HR: 0.72, 95% CI: 0.55-0.94, p = 0.01) but not with prolonged recurrence free survival (HR: 1.06, 95% CI: 0.96-1.16, p = 0.23). These results showed a highlevel of robustness in sensitive test.
CONCLUSION: Although epidural anesthesia might not lead to improved recurrence free survival, it had significant benefit in improving overall survival and reducing all-cause of death. It might be a useful anesthetic technique for colorectal cancer patients undergoing surgery. However, prospective studies are required to confirm whether this benefit is causative with epidural anesthesia.

Tomizawa M, Shinozaki F, Hasegawa R, et al.
Factors affecting the detection of colorectal cancer and colon polyps on screening abdominal ultrasonography.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):295-8 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to identify factors affecting the detection of colorectal cancer (CRC) and colon polyps (CPs) using abdominal ultrasonography (US).
METHODOLOGY: Patient records were analyzed retrospectively. Those diagnosed as having either CRC or CPs by colonoscopy performed after screening abdominal US were enrolled. The diagnostic criterion for CRC was an irregularly thickened wall or mass. CPs were diagnosed as spherical or ovoid hypoechoic lesions arising within the colonic lumen as seen on abdominal US.
RESULTS: Sixteen patients had a total of 16 CRC lesions and 11 patients had a total of 17 CPs. All CRC lesions invaded deeper than the subserosa. Cancer cell invasion limited to the submucosa was noted in the two 1.5-cm CPs. Detection of these lesions was not associated with invasion to lymph or blood vessels. These results suggest that wall thickening might be the consequence of cancer cells invading below the subserosa, thereby resulting in the lesions becoming detectable on abdominal US.
CONCLUSIONS: Detection of CRC and CPs on abdominal US was associated with lesion size and depth of invasion.

Zekri J, Ahmad I, Fawzy E, et al.
Lymph node ratio may predict relapse free survival and overall survival in patients with stage II & III colorectal carcinoma.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):291-4 [PubMed] Related Publications
BACKGROUND/AIMS: Lymph node ratio (LNR) defined as the number of lymph nodes (LNs) involved with metastases divided by number of LNs examined, has been shown to be an independent prognostic factor in breast, stomach and various other solid tumors. Its significance as a prognostic determinant in colorectal cancer (CRC) is still under investigation. This study investigated the prognostic value of LNR in patients with resected CRC.
METHODOLOGY: We retrospectively ex- amined 145 patients with stage II & III CRC diagnosed and treated at a single institution during 9 years pe- riod. Patients were grouped according to LNR in three groups. Group 1; LNR < 0.05, Group 2; LNR = 0.05-0.19 & Group 3 > 0.19. Chi square, life table analysis and multivariate Cox regression were used for statistical analysis.
RESULTS: On multivariate analysis, number of involved LNs (NILN) (HR = 1.15, 95% CI 1.055-1.245; P = 0.001) and pathological T stage (P = 0.002) were statistically significant predictors of relapse free survival (RFS). LNR as a continuous variable (but not as a categorical variable) was statistically significant predictor of RFS (P = 0.02). LNR was also a statistically significant predictor of overall survival (OS) (P = 0.02).
CONCLUSION: LNR may predict RFS and OS in patients with resected stage II & III CRC. Studies with larger cohorts and longer follow up are needed to further examine and validate theprognostic value of LNR.

Huang CS, Yang SH, Lin CC, et al.
Synchronous and metachronous colorectal cancers: distinct disease entities or different disease courses?
Hepatogastroenterology. 2015 Mar-Apr; 62(138):286-90 [PubMed] Related Publications
BACKGROUND/AIMS: This study aimed to investigate the clinicopathological characteristics of synchronous and metachronous colorectal cancers (CRCs).
METHODOLOGY: From January 1, 2001 to December 31, 2010, 5898 patients who underwent surgical resection for CRCs were enrolled. Synchronous CRC was defined as presence of more than one primary CRC within 6 months of resection of the primary tumor; while CRC that occurred at least 6 months later was regarded as metachronous CRC.
RESULTS: 5346 patients were eligible for the study and divided into three groups: solitary, synchronous and metachronous CRC. The overall prevalence of the synchronous CRC was 2.2% and the 10-year cumulative incidence of metachronous cancer was 0.84%. 29 (64%) metachronous cancers were diagnosed within 3 years of the index cancer and the mean time interval was 3.2 years. Male gender and presence of associated adenoma were significant risk factors for both synchronous and metachronous CRC. Synchronous and metachronous CRC patients shared similar clinicopathological features except that the former were older than the latter by 3.7 years. The five-year survival rates were not different among the three groups.
CONCLUSIONS: Our study indicates that synchronous and metachronous CRC might represent similar disease entity with different courses.

Fujii T, Sutoh T, Kigure W, et al.
C-reactive protein level as a possible predictor for early postoperative ileus following elective surgery for colorectal cancer.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):283-5 [PubMed] Related Publications
BACKGROUND/AIMS: Inflammatory reactions are par- tially responsible for postoperative ileus (POI). Serum C-reactive protein (CRP) is an acknowledged marker of inflammation. In this study the CRP response with respect to POI in elective colorectal surgery was exam- ined to define the role of serum CRP as an early predic- tor of POI.
METHODOLOGY: Three hundred eighty-three patients who underwent elective colorectal resection were identified for inclusion in this study. We defined early POI as that occurring within 30 days following the surgery. Thirty-five patients with POI were com- pared to a subgroup of 348 patients with an unevent- ful postoperative course, and the correlation between postoperative serum CRP levels and POI in colorectal surgery was investigated.
RESULTS: In the univariate analysis, length of operation, surgical blood loss, and serum CRP were factors significantly associated with POI following colorectal surgery; however, these fac- tors lost their significance on multivariate analysis.
CONCLUSION: Our results suggest that an increase in CRP levels alone is not a predictor for POI following surgery for colorectal surgery. Although inflammatory responses are known to contribute to the ileus, ad- ditional study is required to identify risk factors that would be more useful for prediction of POI.

Deng H, Chen H, Zhao L, et al.
Quality of laparoscopic total mesorectal excision: results from a single institution in China.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):264-7 [PubMed] Related Publications
BACKGROUND/AIMS: Incomplete total mesorectal excision (TME) may lead to local recurrence. Factors predicting suboptimal quality of laparoscopic TME have not been well documented. The aim of the prospective observational study was to evaluate factors influencing the quality of laparoscopic TME.
METHODOLOGY: Patients undergoing laparoscopic TME for rectal cancer between October 2012 and March 2013 were included. Uni- and multivariate logistic analysis were performed to identify factors independently predicting the suboptimal quality of laparoscopic TME.
RESULTS: A total of 52 patients undergoing laparoscopic TME for rectal cancer were included for analysis. Mesorectal resection was complete in 71.2%, nearly complete in 17.3%, and incomplete in 11.5%. Factors found to be significantly related to suboptimal TME in univariate analysis were as follows: BMI ≥ 25 kg/ cm2 (OR = 11.79, 95% CI: 2.88-48.25; p = 0.003) and advanced tumor stage (pT3/4) (OR = 1.90, 95% CI: 1.41-100.00; p = 0.023). Multivariate analysis identified BMI ≥ 25 kg/m2 (OR = 21.05, 95%CI: 3.26-136.06; p = 0.010), advanced tumor stage (pT3/4) (OR = 19.03, 95% CI: 1.55-233.88; p = 0.021) and neoadjuvant radiochemotherapy (OR = 29.76, 95% CI: 1.65-537.93; p = 0.022) as factors that were independently related to suboptimal TME.
CONCLUSIONS: Laparoscopic TME is feasible with the quality of mesorectal excision which was influenced by patient-, tumor-, and treat- ment-related factors.

Zani A, De Masi S, Maffei C, et al.
The colorectal cancer screening program in the local health unit n. 6 of Livorno: evaluation of the screening activity in the period 2000-2011.
J Prev Med Hyg. 2014; 55(1):4-9 [PubMed] Related Publications
INTRODUCTION: The colorectal cancer screening program in the Local Health Unit n. 6 of Livorno is running since July 2000 and is meant to residents, aged between 50 and 70, who are invited to perform the test for faecal occult blood every 2 years. The aim of this work is an evaluation of the screening activity in the period 2000-2011.
METHODS: The evaluation is based on the analysis of the main quality indicators formulated by GISCoR (Italian Group for Colorectal screening).
RESULTS: The screening activity extension reached 93% in 2006 and 100% in 2009. The compliance level was maintained above the acceptable GISCoR value (> 45%) with a maximum of 54.9%. Values around 80% were recorded for the compliance to colonoscopy. The detection rate (DR) for cancer and advanced adenoma showed, as expected, the highest values in the early years and then move on values consistently lower than the regional average. In 2011, the raw DR for cancer was 0.9 x 1000 and the raw DR for advanced adenoma 5.3 x 1000. The distribution by stage at diagnosis of screen-detected carcinomas shows that 58.1% of these were identified at stage I while the proportion of cases in stage III+ is 19.5%.
CONCLUSIONS: The overall analysis shows a good performance of the program. The proportion of colonoscopies performed on the total number of positive subjects remains a critical point of the system. The distribution by stage of screen-detected cancers shows an excellent diagnostic anticipation of the screening program.

Komeda K, Hayashi M, Inoue Y, et al.
A new strategy with a grading system for liver metastases from colorectal cancer.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):111-7 [PubMed] Related Publications
BACKGROUND/AIMS: The optimal indications, including timing, for resection of liver metastases from colorectal cancer (CRCLM) remain controversial. The Japanese Society of Cancer of the Colon and Rectum has proposed "H-classification" based on the maximum size and number of CRCLM, and has advocated the "CRCLM-grade system", which involves adding the presence of primary lymph node metastasis status to H-classification. We evaluated clinicopathological factors in order to elucidate the optimal indications for and timing of hepatectomy.
METHODOLOGY: Ninety-six patients who underwent initial hepatectomy for CRCLM between August 1995 and May 2009 were retrospectively analyzed with respect to characteristics of primary colorectal metastatic hepatic tumors, operation details and prognosis.
RESULTS: Multivariate analysis identified depth of invasion in primary colorectal cancer (within sub-serosal (non-se) vs. beyond serosal (se)) and CRCLM-grade as independent risk factors. We then performed analyses using the combination of non-se/se and CRCLM-grade. Kaplan-Meier analysis identified significant differences between non-se+gradeA and se+gradeA, between non-se+gradeB and se+gradeB, and between non-se+gradeC and se+gradeC groups.
CONCLUSIONS: We could retrospectively predict survival in CRCLM patients by adopting this new simple classification. This method may allow more precise assessment of operative indications and timing for both operations and perioperative adjuvant treatment.

Engstrand J, Nilsson H, Jansson A, et al.
Fate of necrotic volume after microwave ablation of multiple liver metastases.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):108-10 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to find the rate of shrinkage of necrosis and time of peak ablation volume after multiple microwave ablations in the treatment of multiple liver metastases of colorectal cancer. These factors are not known and are important in evaluation of treatment and identification of local recurrence, as microwave treatment is becoming more used thanks to improved technology in diagnostics and interventional therapy.
METHODOLOGY: A retrospective analysis of non-cirrhotic patients with multiple liver only metastases of colorectal cancer, not suited for resection for this reason. Patients were selected for palliative microwave treatment at a liver multidisciplinary team conference. 68 ablations were made in six patients. Ablation volume was analysed with repeated imaging and computer analyses.
RESULTS: The ablation volume peeks after 5-7 days where after reduction of the necrosis in the liver occurs logarithmically with a 60% reduction of ablation volume after 100 days and 80% after a year.
DISCUSSION: Liver regeneration after microwave ablations occurs at a constant logarithmic rate after an initial expansion of the ablation volume during the first five days. Evaluation of ablation volume in comparison to tumour volume must take this into account so that follow-up imaging is properly timed.

Sturesson C, Hoekstra L, Andersson R, van Gulik TM
Importance of thrombocytes for the hypertrophy response after portal vein embolization.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):98-101 [PubMed] Related Publications
BACKGROUND/AIMS: Thrombocytes have proved to be important for liver regeneration after liver resection in the experimental setting. The aim of our study is to examine the effects of thrombocytes on liver hypertrophy after portal vein embolization (PVE).
METHODOLOGY: This retrospective cohort study comprised 75 patients with liver metastases from colorectal cancer subjected to PVE in preparation for major liver resection. Patients were divided into 2 groups depending on if chemotherapy was given within 6 weeks before PVE or not.
RESULTS: The chemotherapy group showed lower levels of thrombocytes (p=0.003) and lower degree of hypertrophy (p=0.030) as compared to the group without chemotherapy. No correlation within groups between level of thrombocytes and degree of hypertrophy was found. However, in the chemotherapy group, a positive linear correlation between the degree of hypertrophy and the difference in thrombocytes between the time points of PVE and 2 months preceding PVE was found (p=0.0006).
DISCUSSION: Preprocedural chemotherapy results in decreased hypertrophy of the liver after PVE and lower levels of thrombocytes at the time for PVE. The absolute number of thrombocytes does not influence liver regeneration after PVE. For patients receiving preprocedural chemotherapy, PVE performed at a time when thrombocytes are decreasing is associated with a reduced regeneration.

Ozturk MA, Dane F, Karagoz S, et al.
Is perineural invasion (PN) a determinant of disease free survival in early stage colorectal cancer?
Hepatogastroenterology. 2015 Jan-Feb; 62(137):59-64 [PubMed] Related Publications
BACKGROUND/AIMS: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy.
METHODOLOGY: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test.
RESULTS: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect.
CONCLUSIONS: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

Liu W, Li J, Jin K, Liu Q
Totally laparoscopic right colectomy: technique description.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):51-4 [PubMed] Related Publications
BACKGROUND/AIMS: Total laparoscopic right colectomy (TLRC) with intracorporeal anastomosis is not widely performed as it requires adequate skills and competence in the use of mechanical linear staplers. Here we describe the technique of TLRC for resection for right colon cancer.
METHODOLOGY: We have performed TLRC in a patient for right colon cancer. Technique description of TLRC as well as short-term outcomes is reported.
RESULTS: A TLRC for the right colon adenocarcinoma has been successfully performed in a male patient. The specimen included 11 lymph nodes, all of which were free of metastasis.
CONCLUSIONS: TLRC for right colon cancer was safe and feasible.

Ma CC, Li P, Wang LH, et al.
The value of single-incision laparoscopic surgery for colorectal cancer: a systematic literature review.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):45-50 [PubMed] Related Publications
BACKGROUND/AIMS: Recently, single-incision laparoscopic colectomy (SILC) for colorectal malignancy is rapidly becoming the central issue for explorers of minimally invasive surgery worldwide. The aim of this systematic review was to establish the safety and efficacy of SILC for colorectal malignancy when implemented by experienced surgeons.
METHODOLOGY: PubMed, WHO international trial register and Embase were searched for publications concerning SILC and MLC from 2000 to 2013, with the last search on September 10, 2013. Only pure single-incision laparoscopic colonic surgery for malignant disease was included. Primary outcomes were the early postoperative complication profiles of SILC. Secondary outcomes were duration of operation time, blood loss, lymph node yields, conversion rate, distal margin of the resected tumor, and duration of hospital stay.
RESULTS: Eight studies involving 547 patients met the inclusion criteria. Compared with multiport laparoscopic colectomy (MLC), SILC has less postoperative complication and bleeding. The conversion, the median lymph node retrieval, proximal margin of the resected tumor and distal margin of the resected tumor for malignant disease achieved with SILC was acceptable. There was no significant reduction in length of hospital stay with SILC.
CONCLUSION: SILC is a technically reliable and realistic approach with short-term results similar to those obtained with the MLC procedure.

Yanmaz MT, Demir G, Erdamar S, et al.
Epidermal growth factor receptor in CRC patients in the era of the RAS.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):40-4 [PubMed] Related Publications
The aim of this study was to investigate EGFR expression patterns and the effect of EGFR expression on stage, prognosis and response to conventional chemotherapy agents other than monoclonal antibodies in CRC patients. This study included 59 metastatic CRC patients. The expression of EGFR was quantified by immunochemistry in biopsy specimens that were obtained before treatment was initiated. The cases were considered to be positive for EGFR if >1% of the tumor cells had complete circumferential membranous staining. The median age of the patients was 54.6 years, and 59% of the patients were male. Twenty-six patients presented with stage IV disease, and the remaining patients developed distant metastasis during follow-up. Fifty-one patients were treated with regimens containing irinotecan. The numbers of patients with EGFR expression in the primary tumors, the metastatic lymph nodes and the normal colonic tissue were 34 (65.4%), 10 (76.9%) and 34 (65.4%) respectively. The initial disease stage and lymph node stage were correlated with EGFR expression (p<0.05). Additionally, EGFR positivity was correlated with a statistically significant reduction in the response rate to chemotherapy, the overall survival (21 vs. 28 months) and the progression-free survival (15 vs. 22 months) in metastatic patiens treated with chemotherapy other than targeted therapies. In conclusion, EGFR expression in correlated with stage in all CRC patients and response to chemotherapy and survival in metastatic CRC patients.

Yoon SN, Kim KY, Kim JW, et al.
Comparison of short- and long-term outcomes of an early experience with robotic and laparoscopic-assisted resection for rectal cancer.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):34-9 [PubMed] Related Publications
BACKGROUND/AIMS: Robotic surgery is increasingly used for rectal cancer. We compared the short- and long-term outcomes between robotic- and laparoscopic-assisted resection for rectal cancer.
METHODOLOGY: A retrospective chart review was performed between 2006 and 2010.
RESULTS: Seventeen robotic and 61 laparoscopic surgeries were performed consecutively. Median follow-up time was 58.2 months. No operation was converted to open surgery. No difference was observed between the groups for types of operations, diverting ileostomy rate, operation time, blood loss, and postoperative hospital stay, tumor diameter, distal margin, circumferential margin, tumor stage, differentiation, lymphovascular, or perineural invasion. However, the number of harvested lymph nodes was higher in the robot than that in the laparoscopy group (p = 0.017). Overall morbidity and reoperation rates were similar between the groups. The 5-yr overall and disease-free survival rates of all patients were 82.5% and 81.3%, respectively. The 5-yr overall and disease-free survival rates of the robotic and the laparoscopy groups were 94.1% and 79.7% (p = 0.241), and 94.1% and 77.9% (p = 0.159), respectively.
CONCLUSIONS: Robot-assisted resection for rectal cancer resulted in harvesting more lymph nodes without increasing morbidity and showed a comparable survival rate, compared with those of laparoscopy.

Ishibe A, Ota M, Kanazawa A, et al.
Nutritional management of anastomotic leakage after colorectal cancer surgery using elemental diet jelly.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):30-3 [PubMed] Related Publications
BACKGROUND/AIMS: Anastomotic leakage is major complication of colorectal surgery. Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage.
METHODOLOGY: Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study.
RESULTS: Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter.
CONCLUSION: Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.

Cha JM, Lee JI, Joo KR, et al.
Clinicopathological risk factors of early carcinoma in colorectal neoplasias according to Japanese and Western criteria.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):25-9 [PubMed] Related Publications
BACKGROUND AND AIMS: There are discrepancies in the classification of early carcinoma in colorectal neoplasia between Japanese and Western criteria. However, no studies have investigated the clinicopathological risk factors associated with early carcinoma according to these criteria.
METHODOLOGY: We compared the clinicopathological risk factors of early carcinoma with those of dysplasia, and used multivariate analysis to elucidate the independent risk factors associated with early carcinoma. Lesions with severe cytologic or architectural changes confined to the mucosa are classified as carcinoma in Japanese criteria and as high grade dysplasia (HGD) in Western criteria.
RESULTS: Pathologically, 625 total patients were diagnosed with low grade dysplasia (n=321), HGD (n=244), intramucosal carcinoma (n=35) or submucosal carcinoma (n=25). In multivariate analysis, age, large lesion size, and non-polypoid appearance were associated with carcinoma in Japanese criteria; however, only large lesion size was associated with carcinoma in Western criteria. The clinicopathological characteristics of intramucosal carcinoma were similar to those of submucosal carcinoma rather than HGD.
CONCLUSIONS: The clinicopathological characteristics for early carcinoma were not identical between Japanese and Western criteria. Japanese criteria classifying intramucosal carcinoma as carcinoma rather than HGD may be supported by our findings.

Rui Y, Wang C, Zhou Z, et al.
K-Ras mutation and prognosis of colorectal cancer: a meta-analysis.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):19-24 [PubMed] Related Publications
BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Kirsten ras (K-ras) gene is considered to participate in the progression from adenoma to carcinoma of colorectal neoplasms. The correlation between K-ras mutation and the prognosis of CRC is sill controversial. This study aimed at quantitatively summarizing the evidence for such a relationship.
METHODOLOGY: The literature search was based on Pub Med. Population-based and hospital-based case-control studies concerning K-ras mutation and prognosis were eligible for analysis.
RESULTS: 13 literatures were included in the meta-analysis, with 1 multicenter study and 12 case control studies. Totally, 3771 patients were enrolled in the analysis, 1202 of which had K-ras mutation. There were significant difference between the survival of patients with normal and mutated K-ras gene, but no statistic differences were found between either Condon 12 or Condon 13 mutations and prognosis.
CONCLUSION: Current available evidences demonstrated the K-ras mutation is a predictive molecular mark of colorectal cancer patients' survivals, further studies are needed to investigate the race difference and the relationship between certain K-ras mutation and prognosis.

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