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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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  • PubMed search for publications about Colorectal Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Colorectal Cancer
    MeSH term: Colorectal Neoplasms
    International US National Library of Medicine
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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).

Dashti SG, Chau R, Ouakrim DA, et al.
Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome.
JAMA. 2015; 314(1):61-71 [PubMed] Related Publications
IMPORTANCE: Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome).
OBJECTIVE: To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand.
EXPOSURES: Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use.
MAIN OUTCOMES AND MEASURES: Self-reported diagnosis of endometrial cancer.
RESULTS: Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Endometrial cancer was diagnosed in 11% (n = 70) of women with age at menarche greater than or equal to 13 years compared with 12.6% (n = 57) of women with age at menarche less than 13 years (incidence rate per 100 person-years, 0.27 vs 0.31; rate difference, -0.04 [95% CI, -0.15 to 0.05]; hazard ratio per year, 0.85 [95% CI, 0.73 to 0.99]; P = .04). Endometrial cancer was diagnosed in 10.8% (n = 88) of parous women compared with 14.4% (n = 40) of nulliparous women (incidence rate per 100 person-years, 0.25 vs 0.43; rate difference, -0.18 [95% CI, -0.32 to -0.04]; hazard ratio, 0.21 [95% CI, 0.10 to 0.42]; P < .001). Endometrial cancer was diagnosed in 8.7% (n = 70) of women who used hormonal contraceptives greater than or equal to 1 year compared with 19.2% (n = 57) of women who used contraceptives less than 1 year (incidence rate per 100 person-years, 0.22 vs 0.45; rate difference, -0.23 [95% CI, -0.36 to -0.11]; hazard ratio, 0.39 [95% CI, 0.23 to 0.64]; P < .001). There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use.
CONCLUSIONS AND RELEVANCE: For women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.

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.

Shariff U, Seretis C, Youssef H
Management of colorectal cancer patients at high risk of peritoneal metastases.
J BUON. 2015; 20 Suppl 1:S71-9 [PubMed] Related Publications
PURPOSE: Colorectal cancer (CRC) has potential to spread within the peritoneal cavity, and this transcoelomic dissemination is termed "peritoneal metastases" (PM). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical strategy to treat selected CRC patients with PM. Studies suggest that identification of CRC patients at high risk of PM may lead to earlier treatment strategies and improve survival in this subset of patients. The aim of this article was to summarise the current evidence regarding CRC patients at high risk of PM.
METHODS: A retrospective review of articles on CRC patients with high risk of PM published up to December 2014 in PubMed, Medline, Embase, and Ovid search engines was conducted. The following combination of search terms were used: "intraperitoneal chemotherapy", "HIPEC", "colorectal cancer", "peritoneal carcinomatosis", "peritoneal metastases", "high risk", "peritoneal recurrence".
RESULTS: Although opinions differ, CRC patients identified as "high risk" of PM included: limited, synchronous PM completely resected with the primary tumor, ovarian metastases (synchronous or metachronous) and spontaneous or iatrogenic perforation of the bowel by the primary tumor. Aggressive early treatment strategies currently used are: CRS and HIPEC for high-risk primary tumors and second-look CRS and HIPEC often following systematic chemotherapy for the primary resection. Positive results have been shown with both approaches in a number of studies. With CRS/HIPEC for the primary tumor, the overall survival in the two groups (25 patients treated with CRS/HIPEC vs 50 treated with conventional surgery) was significantly improved (p<0.03), as was disease-free survival (p<0.04). For second look surgery, in 29 patients treated with CRS and HIPEC, this resulted in 14% morbidity and 0% mortality and a 2-year disease-free survival rate in excess of 50%.
CONCLUSIONS: We are progressively moving to an era of individualised treatment strategies. The management of CRC patients with high risk of PM is ever evolving, with early detection and early treatment strategies showing promising results. The optimal timing of early surgery remains unclear and requires further evaluation. Should current and future randomized trials demonstrate long-term survival benefit, we may potentially see a change in treatment paradigm from current conventional surgery to a more aggressive, early radical approach as the standard of care.

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.

Vedat Bayoglu I, Yildiz I, Varol U, et al.
Comparison of first-line bevacizumab in combination with mFOLFOX6 or XELOX in metastatic colorectal cancer.
J BUON. 2015 Mar-Apr; 20(2):460-7 [PubMed] Related Publications
PURPOSE: Currently, there are several oxaliplatin combination regimens for first-line therapy of metastatic colorectal cancer (mCRC). In this study, we compared the survival outcomes of mCRC patients treated with bevacizumab in combination with either modified 5-FU/FA/oxaliplatin (mFOL- FOX6) or capecitabine/oxaliplatin (XELOX).
METHODS: We designed a two-arm retrospective study of mCRC patients with adenocarcinoma of the colon or rectum who were treated with bevacizumab and either mFOLFOX6 or XELOX and who had complete clinical and treatment data. We analysed their therapeutic responses, adverse events, progression-free survival (PFS), and overall survival (OS), and then determined whether there were any statistically significant differences.
RESULTS: A total of 131 patients (85 male; 65% and 46 female; 35%) were evaluated. Fifty-seven patients (43.5%) were treated with bevacizumab and mFOLFOX6 and 74 (56.5%) with bevacizumab and XELOX. The median PFS was 9.1 months (95% CI, 4.9-13.1) and 10 months (95% CI, 4.2-15.9) in the mFOLFOX6 and XELOX arms, respectively (p=0.610). The median OS was 29 months (95% CI, 21.6- 34.3) and 27.5 months (95% CI 20-38) in the mFOLFOX6 and XELOX arms (p=0.812), respectively. The most common reason for treatment withdrawal was disease progression (102 patients; 91%) and the most common grade 3-4 toxicity was neuropathy (≤14%).
CONCLUSION: Our results show that XELOX is a safe and effective alternative to mFOLFOX6 when combined with bevacizumab as first-line treatment for mCRC patients.

Teker F, Demirag G, Erdem D, et al.
Quality of life in colorectal cancer patients during chemotherapy in the era of monoclonal antibody therapies.
J BUON. 2015 Mar-Apr; 20(2):443-51 [PubMed] Related Publications
PURPOSE: Colorectal cancer (CRC) survivors are currently living longer due to better therapies but they also need to maintain their quality of life (QoL). QoL is increasingly being used as primary outcome measure in clinical studies. This study was designed to gain knowledge about QoL during chemotherapy across different lines and different regimens.
METHODS: The study comprised 101 CRC out patients receiving chemotherapy who completed the EORTC QLQ-C30 questionnaire. The Shapiro-Wilk, Kruskal-Wallis, and Mann-Whitney U tests were used for statistical analyses.
RESULTS: The demographics of the patients were evaluated for QoL. Prior surgery, prior radiotherapy, working status, stage, comorbidity and sex had no effect on global health status in CRC patients, although some other demographics such as education, monthly income, age and type of chemotherapy regimen did have an effect on global health status. Role functioning was worse in older than in younger ones (p<0.05). Adjuvant chemotherapy did not affect the QoL scores negatively but palliative chemotherapy negatively affected the cognitive function, appetite loss and nausea/vomiting scores (p<0.05). According to chemotherapy regimen, the best QoL was observed with adjuvant FUFA regimen. In the palliative setting FOLFOX/Bevacizumab was associated with the best QoL scores whereas FOLFIRI/Cetuximab were associated with the worst QoL scores.
CONCLUSIONS: Palliative chemotherapy maintained QoL irrespective of the chemotherapy line in metastatic CRC (mCRC) patients. Some demographics affect QoL and different chemotherapy regimens showed different QoL scores.

Chen H, Wu Q
Expression of GW112 and GRIM-19 in colorectal cancer tissues.
J BUON. 2015 Mar-Apr; 20(2):438-42 [PubMed] Related Publications
PURPOSE: To investigate the expression of GW112 and GRIM-19 in colorectal cancer tissues.
METHODS: Immunohistochemistry and semi-quantitative PCR were used to simultaneously detect the levels of expression of GW112 and GRIM-19 in colorectal cancer tissues and normal colorectal tissues in 39 cases.
RESULTS: Expression of GW112 protein and mRNA were significantly higher in colorectal cancer tissues than in normal tissues (p<0.05). Expression of GRIM-19 protein and mRNA were significantly lower in colorectal cancer tissues than in normal tissues (p<0.05). GW112 gene mRNA copy number(GAPDH gene mRNA copy number were 0.53 ± 0.21 and 1.81 ± 0.65 in normal colorectal tissues and colorectal cancer tissues respectively, and GRIM-19 gene mRNA copy number/GAPDH gene mRNA copy number were 1.15 ± 0.29 and 1.74 ± 0.0.44 in colorectal cancer tissues and normal colorectal tissues, respectively. Expression of GW112 gene mRNA was significantly higher in colorectal cancer tissues than in normal tissues (p<0.05), and expression of GRIM- 19 gene mRNA was significantly lower in colorectal cancer tissues than in normal tissues (p<0.05).
CONCLUSION: High expression of GW112 in colorectal cancer tissues and reduced expression of GRIM-19 in colorectal cancer tissues may be associated with abnormal proliferation of cancer cells and are possibly one of the reasons for development of colorectal cancer, which can provide effective targets for clinical treatment of this disease.

Tsvetanova Dimova R, Dimitrova Dimitrova D, Angelova Levterova B, et al.
Feasibility of immunochemical faecal occult blood testing for colorectal cancer screening in Bulgaria.
J BUON. 2015 Mar-Apr; 20(2):413-20 [PubMed] Related Publications
PURPOSE: Colorectal carcinoma (CRC) is the second most common cancer in Europe. Screening guidelines recommend a range of screening options that include faecal occult blood tests (FOBTs). The efficacy of FOBT-based CRC screening is dependent on the participation rate, thus emphasizing the importance of the latter. This study aimed at analysing the feasibility of CRC screening with immunochemical FOBT (iFOBT).
METHODS: A cross-sectional study of 600 asymptomatic persons at average risk, aged ≥45years from urban and rural municipalities was performed. An educational brochure, iFOBT kit with translated colored leaflet, informed consent form and questionnaire were administered to participants by 30 general practitioners. Faecal samples were analysed for occult blood using point-of-care rapid iFOBT (cut off 10 ng(GPs)Hb/ml) by the patients themselves at home. The questionnaire aimed to establish if they encountered difficulties in self-testing and self-analysing. Direct and indirect measures of test feasibility were used difficulties for reported study participation rate.
RESULTS: The participation rate was 78.8% (473 participants). Patients < 65 years (x² =70.8, Р<0.001), those with lower education level (x² =82.1, p<0.001), and patients living in villages (x² =4.3, p<0.05) reported difficulties more frequently and they needed help for self-testing by iFOBT. Positive test was found in 8.5% of all participants. Of them 19 persons (48.7%) had haemorrhoids, 8 (20.0%) benign neoplasms, and 3 (7.5%) had CRC.
CONCLUSIONS: CRC screening study by means of iFOBT as a point-of-care test proved to be feasible, since a high participation rate was obtained.

Papadimitriou G, Manganas D, Phedias Georgiades C, et al.
Emergency surgery for obstructing colorectal malignancy: prognostic and risk factors.
J BUON. 2015 Mar-Apr; 20(2):406-12 [PubMed] Related Publications
PURPOSE: Emergency surgery for colorectal malignant obstruction is thought to correlate with poor outcome. The main aim of our study was to identify possible factors that could predict obstruction, and risk factors of poor postoperative outcome. The second aim was to determine any differences between primary anastomosis and stoma creation in the obstruction population, especially in left-sided tumors.
METHODS: A retrospective review of 212 patients who underwent surgery for colorectal malignancy between January 2008 and January 2013 was performed. Fifty-five patients (26%) underwent emergency surgery for completely obstructing colorectal carcinoma, and 157 (74%) underwent elective surgery.
RESULTS: The groups were comparable for age, gender, ASA score, tumor location, tumor stage, lymph node metastasis and mortality. Advanced tumor stage was recorded as the only prognostic factor of obstruction (p=0.001). Postoperative mortality rate was 9.1% in the obstruction group and 6.4% in the elective group (p=0.498). Analysis didn't reveal any risk factors for poor early outcome in the obstruction group. All patients with right-sided obstructive cancer were treated with resection and primary anastomosis, while the same procedure was performed in almost 61% of operations for left-sided tumors with no anastomotic failure.
CONCLUSIONS: Obstructive colorectal malignancy presents at a more advanced stage compared with non-obstructive cancer, with, interestingly, no statistically significant differences in postoperative mortality. Risk factors of poor early outcome couldn't be identified. Resection and primary restitution of continuity is the surgical approach of choice for right-sided obstructive cancers, but it can be, also, safely performed in left-sided cancers.

Maffione AM, Marzola MC, Capirci C, et al.
Value of (18)F-FDG PET for Predicting Response to Neoadjuvant Therapy in Rectal Cancer: Systematic Review and Meta-Analysis.
AJR Am J Roentgenol. 2015; 204(6):1261-8 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to assess the predictive value of (18)F-FDG PET/ CT for pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
MATERIALS AND METHODS: A systematic search was performed (PubMed and Cochrane databases) for potentially relevant studies up to January 2014. Pooled sensitivity and specificity were calculated. The AUCs of the global cohort and for "major response," "complete response," "only PET after chemoradiotherapy," "ad interim PET," "major response excluding ad interim studies," "complete response excluding ad interim studies," "response index (RI)," "posttreatment maximum standardized uptake value (SUV(max) post)," "visual response analysis (VRA)," "percentage reduction of the total lesion glycolysis (ΔTLG)," and "percentage reduction of the metabolic tumor volume (ΔMTV)" were analyzed. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% CI were calculated.
RESULTS: Thirty-four of 131 (26%) initial articles met the inclusion criteria. Those articles included 1526 patients. PET/CT showed good pooled accuracy both in the global cohort (pooled sensitivity, 73%; pooled specificity, 77%; pooled AUC, 0.83) and for subgroups. Pooled accuracy was similar for early PET restaging and at 1 and 2 weeks after beginning chemoradiotherapy (pooled sensitivity, 84%; pooled specificity, 81%; pooled AUC, 0.89). The major response group showed similar sensitivity to the complete response group (74% and 71%, respectively). RI, SUV(max), and VRA were the most frequent parameters used. Pooled RI and SUV(max) postcutoff values were 63% and 4.4. Pooled time to PET during and after chemoradiotherapy was 1.5 and 6.5 weeks, respectively.
CONCLUSION: This meta-analysis supports the use of FDG PET for restaging locally advanced rectal cancer.

Basyigit S, Ozkan S, Uzman M, et al.
Should screening for colorectal neoplasm be recommended in patients at high risk for coronary heart disease: a cross-sectional study.
Medicine (Baltimore). 2015; 94(20):e793 [PubMed] Related Publications
Colorectal neoplasm (CRN) and coronary heart disease (CHD) share common risk factors. We aimed to assess the risk for CRN in patients who are at high risk for developing CHD determined by measurements, which are independent from the risk factors for CRN.This study was conducted on individuals who underwent total colonoscopic examination and were without history of CHD. Two-hundred thirty-five subjects (82 with CRN and 153 with normal colonoscopic findings) participated in the study. Colorectal carcinoma (CRC) was defined as the presence of adenocarcinoma. We measured carotid intima media thickness (CIMT), flow-mediated dilation (FMD), and calculated Framingham risk score (FRS) for all participants. An increased CIMT (≥1.0 mm), a decreased FMD (<10%), and a high FRS (>20%) were defined as high risks for developing CHD. The risk and the prevalence of CRN were analyzed in relation to the risk for developing CHD.The ratio of the patients with overall-CRN and CRC was significantly higher in individuals who are at high risk for developing CHD compared with individuals who are at low risk for developing CHD by each 3 risk estimation method (P < 0.05 for all). An increased CIMT, a decreased FMD, and a high FRS score were significantly associated with the high risk for the presence of CRC (odds ratio [OR]: 6.018, OR: 3.699, and OR: 4.120, respectively). An increased CIMT, a decreased FMD, and an intermediate FRS were significantly associated with the risk for the presence of overall-CRN (OR: 3.607, OR: 1.866 and OR: 2.889, respectively).The risk for CRN increases as the risk for developing CHD increases. It can be suggested that screening for CRN can be recommended for individuals who are at high risk for developing CHD.

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.

Bogaards JA, Wallinga J, Brakenhoff RH, et al.
Direct benefit of vaccinating boys along with girls against oncogenic human papillomavirus: bayesian evidence synthesis.
BMJ. 2015; 350:h2016 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To assess the reduction in the vaccine preventable burden of cancer in men if boys are vaccinated along with girls against oncogenic human papillomavirus (HPV).
DESIGN: Bayesian evidence synthesis approach used to evaluate the impact of vaccination against HPV types 16 and 18 on the burden of anal, penile, and oropharyngeal carcinomas among heterosexual men and men who have sex with men. The reduced transmission of vaccine-type HPV from vaccination of girls was assumed to lower the risk of HPV associated cancer in all men but not to affect the excess risk of HPV associated cancers among men who have sex with men.
SETTING: General population in the Netherlands.
INTERVENTION: Inclusion of boys aged 12 into HPV vaccination programmes.
MAIN OUTCOME MEASURES: Quality adjusted life years (QALYs) and numbers needed to vaccinate.
RESULTS: Before HPV vaccination, 14.9 (95% credible interval 12.2 to 18.1) QALYs per thousand men were lost to vaccine preventable cancers associated with HPV in the Netherlands. This burden would be reduced by 37% (28% to 48%) if the vaccine uptake among girls remains at the current level of 60%. To prevent one additional case of cancer among men, 795 boys (660 to 987) would need to be vaccinated; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2162, 3486, and 1975, respectively. The burden of HPV related cancer in men would be reduced by 66% (53% to 805) if vaccine uptake among girls increases to 90%. In that case, 1735 boys (1240 to 2900) would need to be vaccinated to prevent an additional case; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2593, 29107, and 6484, respectively.
CONCLUSIONS: Men will benefit indirectly from vaccination of girls but remain at risk of cancers associated with HPV. The incremental benefit of vaccinating boys when vaccine uptake among girls is high is driven by the prevention of anal carcinomas, which underscores the relevance of HPV prevention efforts for men who have sex with men.

Anderson BJ, Hill EG, Sweeney RE, et al.
The impact of surgical diversion before neoadjuvant therapy for rectal cancer.
Am Surg. 2015; 81(5):444-9 [PubMed] Related Publications
Up-front fecal diversion can palliate emergent symptoms related to locally advanced rectal cancer (LARC) allowing patients to receive neoadjuvant chemoradiation therapy (nCRT). We analyzed outcomes of pretreatment-diverted LARC patients relative to nondiverted patients to define the impact of this management strategy. We retrospectively collected data on 103 LARC patients treated with nCRT and surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. Thirteen LARC patients underwent pretreatment diversion for urgent symptoms and 90 LARC patients proceeded directly to nCRT. In all, 50 per cent of diverted patients presented with T4 tumor compared with 14 per cent in the nondiverted patients (P = 0.003). Diverted patients experienced a delay in time-to-treatment initiation of 12 days, although this difference was not statistically significant. Similar rates of chemoradiation and surgical toxicities were observed. Even though diverted patients demonstrated less pathologic response to nCRT compared with nondiverted patients (P = 0.04), there was no significant difference in overall survival. In conclusion, our study demonstrates the effectiveness of up-front fecal diversion at managing emergent obstructive symptoms related to advanced rectal cancer without additional complications, allowing patients to proceed with nCRT followed by radical surgery.

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.

Gleeson FC, Kipp BR, Voss JS, et al.
Endoscopic ultrasound fine-needle aspiration cytology mutation profiling using targeted next-generation sequencing: personalized care for rectal cancer.
Am J Clin Pathol. 2015; 143(6):879-88 [PubMed] Related Publications
OBJECTIVES: In an era of precision medicine, our aim was to determine the frequency and theranostic potential of mutations identified in malignant lymph nodes (LNs) sampled by endoscopic ultrasound fine-needle aspiration (EUS FNA) of patients with rectal cancer by targeted next-generation sequencing (NGS).
METHODS: The NGS Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, CA) and MiSeq (Illumina, San Diego, CA) sequencers were used to sequence and assess for 2,800 or more possible mutations in 50 established cancer-associated genes.
RESULTS: Among 102 patients, 89% had 194 pathogenic alterations identified in 19 genes. The identification of KRAS, NRAS, or BRAF mutations suggests that 42% are likely nonresponders to anti-epidermal growth factor receptor therapy. Among KRAS, NRAS, or BRAF wild-type patients, alterations in eight genes linked to alternative therapies were identified in 44%.
CONCLUSIONS: Our data demonstrate the successful ability to apply a single multiplex test to allow multigene mutation detection from malignant LN cytology specimen DNA collected by EUS FNA.

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.

Tu HC, Schwitalla S, Qian Z, et al.
LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans.
Genes Dev. 2015; 29(10):1074-86 [PubMed] Article available free on PMC after 15/11/2015 Related Publications
Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in Apc(Min/+) mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target.

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.

Wilcox ML, Acuña JM, de la Vega PR, et al.
Factors affecting compliance with colorectal cancer screening among households residing in the largely Haitian community of Little Haiti, Miami-Dade County, Florida: an observational study.
Medicine (Baltimore). 2015; 94(18):e806 [PubMed] Related Publications
The United States Black population is disproportionately affected by colorectal cancer (CRC) in terms of incidence and mortality. Studies suggest that screening rates are lower among Blacks compared with non-Hispanic Whites (NHWs). However, studies on CRC screening within Black subgroups are lacking. This study examined disparities in blood stool test (BST) compliance and colonoscopy use by race/ethnicity (Haitian, NHW, non-Hispanic Black [NHB], and Hispanic) among randomly selected households in Little Haiti, Miami-Dade County, Florida.This study used cross-sectional, health and wellness data from a random-sample, population-based survey conducted within 951 households in Little Haiti between November 2011 and December 2012. BST compliance and colonoscopy use were self-reported and defined, conservatively, as the use of BST within the past 2 years and the ever use of colonoscopy by any household member. Factors associated with BST compliance and colonoscopy use were identified using logistic regression models. Analyses were restricted to households containing at least 1 member ≥50 years (n = 666).Nearly half of the households were compliant with BST (rate [95% confidence interval (CI)] = 45% [41%-49%]) and completed colonoscopy (rate [95% CI] = 53% [49%-58%]). Compliance with BST was not associated with race/ethnicity (P = 0.76). Factors independently associated with BST compliance included low educational attainment (adjusted odds ratio [AOR] = 0.63, P = 0.03), being single (AOR = 0.47, P = 0.004), retirement (AOR = 1.96, P = 0.01), and the presence of diagnosed health problems (AOR = 1.24, P = 0.01). Colonoscopy use was lower among Haitian households (46%) compared with NHW (63%), NHB (62%), and Hispanic households (54%) (P = 0.002). Factors independently associated with colonoscopy use included identifying as NHB (compared with Haitian) (AOR = 1.80, P = 0.05), being single (AOR = 0.44, P = 0.001), retirement (AOR = 1.86, P = 0.02), lack of continuous insurance (AOR = 0.45, P < 0.001), and the presence of diagnosed health problems (AOR = 1.44, P < 0.001) and physical limitations/disabilities (AOR = 1.88, P = 0.05).Compliance with BST and use of colonoscopy are low within households in the Little Haiti community. Significant disparities in the use of colonoscopy exist between Haitian and NHB households. Barriers and facilitators of colonoscopy within each racial/ethnic group need to be identified as the next step to developing culturally appropriate, community-based interventions aimed at increasing colonoscopy use in this large minority population.

Sabatino SA, White MC, Thompson TD, et al.
Cancer screening test use - United States, 2013.
MMWR Morb Mortal Wkly Rep. 2015; 64(17):464-8 [PubMed] Related Publications
Regular breast, cervical, and colorectal cancer (CRC) screening with timely and appropriate follow-up and treatment reduces deaths from these cancers. Healthy People 2020 targets for cancer screening test use have been established, based on the most recent U.S. Preventive Services Task Force (USPSTF) guidelines. National Health Interview Survey (NHIS) data are used to monitor progress toward the targets. CDC used the 2013 NHIS, the most recent data available, to examine breast, cervical, and CRC screening use. Although some demographic subgroups attained targets, screening use overall was below the targets with no improvements from 2010 to 2013 in breast, cervical, or CRC screening use. Cervical cancer screening declined from 2010 to 2013. Increased efforts are needed to achieve targets and reduce screening disparities.

Leonard D, Penninckx F, Laenen A, et al.
Quantitative contribution of prognosticators to oncologic outcome after rectal cancer resection.
Dis Colon Rectum. 2015; 58(6):566-74 [PubMed] Related Publications
BACKGROUND: Prognostication is an important aspect of medical practice. It relies on statistical modeling testing the correlation of variables with the outcome of interest.
OBJECTIVE: In contrast with the classic approach of predictive modeling, this study aimed to estimate the unique, individual, and relative contributions. This includes the quantitative contributions of patient-, tumor-, and treatment-related factors to oncologic outcome after rectal cancer resection.
DESIGN: This was a retrospective analysis of prospectively registered data.
SETTINGS: The study included 65 hospitals participating on a voluntary basis in the Project on Cancer of the Rectum, a Belgian multidisciplinary improvement project of rectal cancer care.
PATIENTS: A total of 1470 patients presenting midrectal or low-rectal adenocarcinoma without distant metastasis were included.
INTERVENTION: The study intervention was total mesorectal excision with or without sphincter preservation.
MAIN OUTCOME MEASURES: The unique, individual, and relative contributions of a set of covariables to the statistical variability of the distant metastasis rate and overall survival have been calculated.
RESULTS: The 5-year distant metastasis rate was 21% and overall survival 76%. A large amount of the variability of the outcomes (ie, 83.6% to 84.2%) could not be predicted by the prognostic factors. Unique contributions of the predictors ranged from 0.1% to 3.1%. The 3 risk factors with the highest unique contribution for distant metastasis were lymph node ratio, pathologic tumor stage, and total mesorectal quality; for overall survival they were age, lymph node ratio, and ASA score.
LIMITATIONS: The main weakness of this study was incomplete participation and registration in the Project on Cancer of the Rectum.
CONCLUSIONS: Several factors influence oncologic outcomes and are present in prediction models. However, the models predict relatively little of outcome variation.

Marinello FG, Frasson M, Baguena G, et al.
Selective approach for upper rectal cancer treatment: total mesorectal excision and preoperative chemoradiation are seldom necessary.
Dis Colon Rectum. 2015; 58(6):556-65 [PubMed] Related Publications
BACKGROUND: The implementation of preoperative chemoradiation combined with total mesorectal excision has reduced local recurrence rates in rectal cancer. However, the use of both types of treatment in upper rectal cancer is controversial.
OBJECTIVE: The purpose of this work was to assess oncological results after radical resection of upper rectal cancers compared with sigmoid, middle, and lower rectal cancers and to determine risk factors for local recurrence in upper rectal cancer.
DESIGN: This was a retrospective analysis of prospectively collected data.
SETTINGS: This study was conducted in a tertiary care referral hospital in Valencia, Spain.
PATIENTS: Analysis included 1145 patients who underwent colorectal resection with primary curative intent for primary sigmoid (n = 450), rectosigmoid (n = 70), upper rectal (n = 178), middle rectal (n = 186), or lower rectal (n = 261) cancer.
MAIN OUTCOME MEASURES: Oncological results, including local recurrence, disease-free survival, and cancer-specific survival, were compared between the different tumor locations. Univariate and multivariate analyses were performed to identify risk factors for local recurrence in upper rectal cancer.
RESULTS: A total of 147 patients (82.6%) with upper rectal tumors underwent partial mesorectal excision, and only 10 patients (5.6%) of that group received preoperative chemoradiation. The 5-year actuarial local recurrence, disease-free survival, and cancer-specific survival rates for upper rectal tumors were 4.9%, 82.0%, and 91.6%. Local recurrence rates showed no differences when compared among all of the locations (p = 0.20), whereas disease-free survival and cancer-specific survival were shorter for lower rectal tumors (p = 0.006; p = 0.003). The only independent risk factor for local recurrence in upper rectal cancer was an involved circumferential resection margin at pathologic analysis (HR, 14.23 (95% CI, 2.75-73.71); p = 0.002).
LIMITATIONS: This was a single-institution, retrospective study.
CONCLUSIONS: Most upper rectal tumors can be treated with partial mesorectal excision without the systematic use of preoperative chemoradiation. Involvement of the mesorectal fascia was the only independent risk factor for local recurrence in these tumors.

Hogan J, Chang KH, Duff G, et al.
Lymphovascular invasion: a comprehensive appraisal in colon and rectal adenocarcinoma.
Dis Colon Rectum. 2015; 58(6):547-55 [PubMed] Related Publications
BACKGROUND: Colon and rectal adenocarcinomas differ at a multitude of levels. The association between outcome and predictor in 1 group may obscure the relationship between outcome and predictor in the other.
OBJECTIVE: The current study aims to evaluate the prognostic properties of lymphovascular invasion in colon and rectal adenocarcinoma separately.
MATERIALS AND METHODS (DESIGN, SETTING AND PATIENTS): A comparative retrospective analysis was undertaken to determine the prognostic properties of lymphovascular invasion in colon and rectal adenocarcinomas. Patients were classified as lymphovascular invasion positive and lymphovascular invasion negative in separate colon and rectal cancer cohorts. Within cohorts, a univariate analysis was undertaken to determine the association between lymphovascular invasion positivity and local/systemic recurrence and overall/disease-free survival. Findings were evaluated by using Kaplan-Meier estimates, log-rank analysis, and a Cox proportional hazards multivariate model.
MAIN OUTCOME MEASURE: The primary outcomes measured were overall and disease-free survival.
RESULTS: Five hundred twenty-seven patients were included in the analysis (379 with colon cancer and 148 with rectal cancer). On univariate analysis, lymphovascular invasion positivity was associated with adverse locoregional recurrence in colon (p = 0.002) but not rectal adenocarcinoma (p = 0.13). Conversely, lymphovascular invasion positivity was associated with adverse systemic recurrence in rectal (p = 0.002) but not colon adenocarcinoma (p = 0.35). On multivariate analysis, lymphovascular invasion positivity was an independent predictor of adverse disease-free survival in colon (p = 0.02) and rectal adenocarcinoma (p < 0.001). Regarding overall survival, lymphovascular invasion positivity was a poor prognostic indicator in rectal adenocarcinoma only (p = 0.04).
LIMITATIONS AND CONCLUSIONS: In this retrospective analysis, lymphovascular invasion positivity was associated with different patterns of disease recurrence in colon and rectal cancer. Lymphovascular invasion positivity was associated with adverse overall survival in rectal cancer only.

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.

Kobayashi H, Kotake K, Sugihara K,
Impact of adjuvant chemotherapy in patients with curatively resected stage IV colorectal cancer.
Medicine (Baltimore). 2015; 94(17):e696 [PubMed] Related Publications
The aim of this study was to investigate the impact of adjuvant chemotherapy on survival of patients who had curative resection for stage IV colorectal cancer.The efficacy of adjuvant chemotherapy after curative resection for stage IV colorectal cancer remains unclear.The database of 3695 patients with stage IV colorectal cancer between 1991 and 2007 collected from 16 member hospitals of the Japanese Society for Cancer of the Colon and Rectum was used for this investigation. The survivals of patients with and without adjuvant chemotherapy after curative resection for stage IV colorectal cancer were evaluated using a propensity score matching method.The data of 689 patients who underwent curative resection for both primary and synchronous metastatic tumors were extracted from the database and used for analysis in this study. The 5-year overall survival rates of the patients with and without adjuvant chemotherapy were 41.8% and 33.9%, respectively. A Cox proportional hazards model showed that adjuvant chemotherapy (P = 0.0042), regional lymph node metastasis (P < 0.0001), and peritoneal metastasis (P = 0.0006) were independent factors for overall survival. In the propensity score-matched cohort, patients with adjuvant chemotherapy had better overall survival than those without (P = 0.026).The present study demonstrated that adjuvant chemotherapy improved overall survival after curative resection for stage IV colorectal cancer. The efficacy of each chemotherapeutic regimen in the adjuvant setting for stage IV colorectal cancer should be clarified in the future.

Kato T, Uehara K, Maeda A, et al.
Phase II multicenter study of adjuvant S-1 for colorectal liver metastasis: survival analysis of N-SOG 01 trial.
Cancer Chemother Pharmacol. 2015; 75(6):1281-8 [PubMed] Related Publications
PURPOSE: We previously showed that S-1 after curative resection of colorectal liver metastasis had acceptable toxicity and a high rate of completion of therapy in a prospective phase II trial. We here reported the primary endpoint of disease-free survival (DFS).
METHODS: Between October 2008 and August 2010, 60 patients were eligible for this study and received S-1 for 28 days followed by a 2-week rest period. Treatment was started within 8 weeks after surgery and repeated for eight cycles.
RESULTS: Median follow-up was 41 months. Among 60 patients, 45 had solitary metastasis, and the median maximum tumor diameter was 2.6 cm. The 3-year DFS and overall survival were 47.4 and 80.0 %, respectively. Recurrences developed in 31 patients, with the remnant liver the most common site (19 patients). Multivariate analysis showed that positive lymph node metastasis around the primary site (p = 0.013) and early liver metastasis (synchronous disease or metachronous disease within 12 months) (p = 0.041) were independent poor prognostic factors for DFS. Patients having both risk factors had a significantly worse DFS than those without these risk factors (p < 0.001). Early liver metastasis was an independent indicator of early recurrence within 1 year.
CONCLUSIONS: S-1 after curative liver resection yielded promising survival in patients with a low tumor burden. Outcome in patients having both positive lymph node metastasis around the primary site and early liver metastasis was much worse than in patients without these conditions; therefore, they might warrant more aggressive therapy.

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.

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