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

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Prevention of Colorectal (Bowel) Cancer

Information Patients and the Public (18 links)

Information for Health Professionals / Researchers (12 links)

Herdiatry Colorectal Cancers (5 links)

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

Latest Research Publications

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

Maya S, Sarmento B, Lakshmanan VK, et al.
Actively targeted cetuximab conjugated gamma-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells.
J Biomed Nanotechnol. 2014; 10(8):1416-28 [PubMed] Related Publications
Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded gamma-poly (glutamic acid) (gamma-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-gamma-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-gamma-PGA NPs over DTXL-gamma-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-gamma-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-gamma-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-gamma-PGA Nps (targeted) and ICG-DTXL-gamma-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-gamma-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer.

Related: Docetaxel Cetuximab (Erbitux)

Baber J, Anusionwu C, Nanavaty N, Agrawal S
Anatomical distribution of colorectal cancer in a Veterans Affairs Medical Center.
South Med J. 2014; 107(7):443-7 [PubMed] Related Publications
OBJECTIVES: The incidence of sporadic colorectal cancer (CRC) among individuals younger than 50 years of age and the incidence of proximal cancers has varied based on demographic factors in previous studies, and multisociety screening guidelines advise various modalities for average-risk individuals beginning at age 50. We studied the incidence and anatomic distribution of CRC in a population of military veterans to determine whether screening at a younger age is warranted.
METHODS: In a retrospective review of the electronic medical records of patients diagnosed as having CRC at the Dayton Veterans Affairs Medical Center between 2000 and 2010, a descriptive analysis of age at diagnosis, race, indication for colonoscopy, and anatomical distribution of the tumor was performed.
RESULTS: A total of 280 patients with CRC were identified, 272 of whom were histologically confirmed as having adenocarcinoma. The majority (98.6%) were men, with 25.6% of them African American. The mean age at diagnosis was 68.9 years (range 41-89 years), with 35% diagnosed in the eighth decade of life. Only 8 patients (2.9%) were younger than age 50. Most tumors (55%) were located distal to the splenic flexure, with synchronous lesions identified in seven patients. Screening colonoscopy identified only 18 (3.6%) cases.
CONCLUSIONS: Sporadic colorectal adenocarcinoma in patients younger than age 50 was identified in only 2.9% of all cases, whereas 42.5% of all cases were located proximal to the splenic flexure. This reinforces the American College of Gastroenterology guideline recommendation to initiate CRC screening in average-risk individuals at age 50. This study supports optical colonoscopy as the preferred screening modality.

Related: Cancer Screening and Early Detection

Gidron Y, De Couck M, De Greve J
If you have an active vagus nerve, cancer stage may no longer be important.
J Biol Regul Homeost Agents. 2014 Apr-Jun; 28(2):195-201 [PubMed] Related Publications
The parasympathetic system, and primarily the vagus nerve, informs the brain about multiple signals and returns the body to homeostasis. Recent studies have shown that vagal nerve activity independently predicts prognosis in cancer. Here, we take this one step further and show that when vagal nerve activity is high, cancer stage no longer predicts tumor burden. We examined whether vagal nerve activity, indexed by Heart Rate Variability (HRV), moderated the effects of initial tumor stage on tumor burden at followup. Patients' HRVs were derived from ECGs near diagnosis in colorectal cancer (CRC) and in prostate cancer (PC) patients. Outcomes included the tumor markers carcinoembryonic antigen (CEA) at 12 months for CRC and prostate-specific antigen (PSA) at 6 months for PC. As would be expected, initially advanced tumor stages of CRC or PC predicted higher tumor marker levels at follow-up than did early stages. However, this occurred only in patients with low, not high, vagal activity (HRV). Furthermore, in patients with advanced tumor stage at diagnosis, high HRV predicted lower tumor marker levels than did low HRV, in both cancers. Estimating a cancer patient's prognosis by determining his tumor stage needs to also consider the vagal nerve activity. This activity is easily measurable, and it determines in which subjects the tumor stage is prognostic. Importantly, higher vagal activity may even protect against the adverse effects of advanced cancer stage. These findings, observed in two distinct cancers, support the hypothesized neuroimmunomodulatory effects of vagal nerve activity on tumors.

Related: Prostate Cancer

Sheets N, Powers J, Richmond B
Cutaneous metastasis of colon cancer: case report and literature review.
W V Med J. 2014 May-Jun; 110(3):22-4 [PubMed] Related Publications
Cutaneous metastases arising from an internal malignancy are a rare phenomenon, occurring in 0.001% of all skin biopsies performed. Of these, 6.5% originate from the a primary colon cancer. Colon cancer, when metastatic to the skin, typically appears as a painless flesh-colored nodule or as a mass with occasional ulceration. We report a case of a large cutaneous metastasis to the suprascapular region as the initial presenting symptom of an underlying colon cancer.

Shibutani M, Maeda K, Nagahara H, et al.
Significance of CEA and CA19-9 combination as a prognostic indicator and for recurrence monitoring in patients with stage II colorectal cancer.
Anticancer Res. 2014; 34(7):3753-8 [PubMed] Related Publications
BACKGROUND: The purpose of this study was to evaluate the significance of the combination of the carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels as a prognostic indicator and for monitoring for recurrence and metastasis after potentially curative surgery for patients with stage II colorectal cancer.
PATIENTS AND METHODS: A total of 238 patients with stage II colorectal cancer who underwent potentially curative surgery were enrolled in the study. A high CEA level was defined as a level exceeding 5 ng/ml and a high CA19-9 level was defined as a level exceeding 37 U/ml.
RESULTS: Out of these 238 patients, 92 (38.7%) patients had high CEA levels, 23 (9.7%) patients had high CA19-9 levels and 15 (6.3%) patients had both high CEA and CA19-9 levels. The disease-free and overall survival rates were significantly worse in patients with both a high CEA level and high CA19-9 level. Tumor marker(s) elevated before the operation tended to be elevated again at the time of relapse.
CONCLUSION: The combination of preoperative CEA and CA19-9 levels was useful for predicting the prognosis and for monitoring recurrence and metastasis after potentially curative surgery in patents with stage II colorectal cancer.

Farkouh A, Scheithauer W, Buchner P, et al.
Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab.
Anticancer Res. 2014; 34(7):3669-73 [PubMed] Related Publications
AIM: Capecitabine, designed as a pro-drug to the cytotoxic agent 5-fluorouracil, is widely used in the management of colorectal cancer. This study was designed to investigate whether co-administration of the monoclonal antibody bevacizumab (BVZ) shows potential to modulate the plasma disposition of capecitabine (CCB) and its metabolites.
PATIENTS AND METHODS: Nine patients treated with CCB and BVZ for advanced colorectal cancer entered this pharmacokinetic study. In the first cycle CCB was given alone at doses of 1,250 mg/m2 bi-daily for two weeks with one week rest. In the second cycle BVZ co-administration started simultaneously with oral intake of CCB by short infusion of 7.5 mg/kg.
RESULTS: Mean plasma concentration time curves of CCB and its metabolites were insignificantly lower in the BVZ combination regimen compared to CCB monotherapy. After repeated cycles of BVZ no significant pharmacokinetic interaction was observed.
CONCLUSION: From the pharmacokinetic point of view and in agreement with numerous clinical study data, co-administration of BVZ with CCB appears to be safe and efficient.

Related: Fluorouracil Bevacizumab (Avastin) Capecitabine

Kim YW, Kim SK, Kim CS, et al.
Association of serum and intratumoral cytokine profiles with tumor stage and neutrophil lymphocyte ratio in colorectal cancer.
Anticancer Res. 2014; 34(7):3481-7 [PubMed] Related Publications
BACKGROUND: We examined cytokine profiles and evaluated the association between cytokine levels, pathological stages, and neutrophil/lymphocyte ratio (NLR).
MATERIALS AND METHODS: Patients with colorectal cancer (n=20, TNM stage I, II, and III) were enrolled. Levels of nine cytokines [interleukin (IL)-4,-6, -8, -10, -12, tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-γ), and vascular endothelial growth factor (VEGF)] were measured in serum, normal mucosa, and tumor using the Bio-Plex® cytokine assay.
RESULTS: The mean IL8, GM-CSF and VEGF levels were higher in tumors, whereas the mean IL6 level was higher in serum. Cytokine levels correlated with TNM stage (IL6 and IL8 in serum, and IL8 and VEGF in tumor) and with NLR (IL6 and IL8 in serum, and IL8 in tumor).
CONCLUSION: Different cytokine profiles were observed in serum, normal mucosa, and tumor tissue. The elevation of specific cytokines in sera or tumors reflects features of advanced disease.

Related: Cytokines

Schreiber V, Kitzmueller M, Poxhofer M, et al.
Impact of co-administered drugs on drug monitoring of capecitabine in patients with advanced colorectal cancer.
Anticancer Res. 2014; 34(7):3371-6 [PubMed] Related Publications
BACKGROUND: Drug monitoring is a useful tool for obtaining detailed information about the disposition of a drug in an individual patient during chemotherapy. According to the international guidelines, the analytical assay for quantification of a compound in biological samples must be validated. Among a number of parameters, peak purity is an important requirement.
MATERIALS AND METHODS: We analyzed pharmacokinetics in patients who received chemotherapy with capecitabine and up to 10 various co-medications.
RESULTS: Out of seven investigated co-administered drugs, we found evidence that the proton pump inhibitor pantoprazole causes peak interferences with capecitabine during high-performance liquid chromatography analysis. Therefore quantification of capecitabine in plasma samples can be inaccurate.
CONCLUSION: We recommend an altered time schedule for co-administered drugs or changing the mobile phase used in the assay.

Related: Fluorouracil Capecitabine

Lee WY, Hong HK, Ham SK, et al.
Comparison of colorectal cancer in differentially established liver metastasis models.
Anticancer Res. 2014; 34(7):3321-8 [PubMed] Related Publications
BACKGROUND: Metastasis is one of the main reasons for colorectal cancer (CRC)-related deaths due to the lack of effective therapeutics mainly for liver metastasis. In the present study, we established an orthotopic colorectal cancer mouse model using different transplantation protocols to determine the optimal conditions for CRC liver metastasis.
MATERIALS AND METHODS: Luciferin-expressing HCT116 cells were used to induce liver metastasis models of colorectal cancer following both intra-splenic and cecal injections. Magnetic resonance imaging (MRI) and the In Vivo Imaging system were used to monitor internal growth of the primary tumor and metastasis.
RESULTS: The intra-splenic injection with high cell number (5×10(6) cells/50 μL)-group achieved rapid tumor formation, and the highest metastatic rate. However, survival rates were shorter than those of the other groups. The time to develop primary tumors and liver metastases was slightly different between the two transplantation protocols followed and should be considered depending on the specific aim of each experiment. MRI and optical images correlated well with the pathological findings at necropsy with respect to both tumor growth and location.
CONCLUSION: The model described herein will be effective in studying new therapeutic strategies against metastatic disease when used in conjunction with small animal MRI and optical imaging.

Weeks JC, Uno H, Taback N, et al.
Interinstitutional variation in management decisions for treatment of 4 common types of cancer: A multi-institutional cohort study.
Ann Intern Med. 2014; 161(1):20-30 [PubMed] Related Publications
BACKGROUND: When clinical practice is governed by evidence-based guidelines and there is consensus about their validity, practice variation should be minimal. For areas in which evidence gaps exist, greater variation is expected.
OBJECTIVE: To systematically assess interinstitutional variation in management decisions for 4 common types of cancer.
DESIGN: Multi-institutional, observational cohort study of patients with cancer diagnosed between July 2006 through May 2011 and observed through 31 December 2011.
SETTING: 18 cancer centers participating in the formulation of treatment guidelines and systematic outcomes assessment through the National Comprehensive Cancer Network.
PATIENTS: 25 589 patients with incident breast cancer, colorectal cancer, lung cancer, or non-Hodgkin lymphoma.
MEASUREMENTS: Interinstitutional variation for 171 binary management decisions with varying levels of supporting evidence. For each decision, variation was characterized by the median absolute deviation of the center-specific proportions.
RESULTS: Interinstitutional variation was high (median absolute deviation >10%) for 35 of 171 (20%) oncology management decisions, including 9 of 22 (41%) decisions for non-Hodgkin lymphoma, 16 of 76 (21%) for breast cancer, 7 of 47 (15%) for lung cancer, and 3 of 26 (12%) for colorectal cancer. Forty-six percent of high-variance decisions involved imaging or diagnostic procedures and 37% involved choice of chemotherapy regimen. The evidence grade underpinning the 35 high-variance decisions was category 1 for 0%, 2A for 49%, and 2B/other for 51%.
LIMITATION: Physician identifiers were unavailable, and results may not generalize outside of major cancer centers.
CONCLUSION: The substantial variation in institutional practice manifest among cancer centers reveals a lack of consensus about optimal management for common clinical scenarios. For clinicians, awareness of management decisions with high variation should prompt attention to patient preferences. For health systems, high variation can be used to prioritize comparative effectiveness research, patient-provider education, or pathway development.
PRIMARY FUNDING SOURCE: National Cancer Institute and National Comprehensive Cancer Network.

Related: Breast Cancer Lung Cancer Non Hodgkin's Lymphoma

Noreen F, Röösli M, Gaj P, et al.
Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Aberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa.
METHODS: We measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided.
RESULTS: Of 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥ 2 years) and hormonal replacement therapy (HRT age ≥ 50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥ 20 years) and individuals with a body mass index (BMI) of 25 kg/m(2) and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2 × 10(-16)). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2 × 10(-76)) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it.
CONCLUSIONS: Lifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.

Related: Cancer Screening and Early Detection

Apisarnthanarak P, Pansri C, Maungsomboon K, Thamtorawat S
The CT appearances for differentiating of peripheral, mass-forming cholangiocarcinoma and liver meatastases from colorectal adenocarcinoma.
J Med Assoc Thai. 2014; 97(4):415-22 [PubMed] Related Publications
OBJECTIVE: To evaluate the computed tomographic (CT) appearances for differentiating of primary hepatic adenocarcinoma (peripheral, mass-forming cholangiocarcinoma) and secondary hepatic adenocarcinoma (liver metastases from colorectal carcinoma).
MATERIAL AND METHOD: Between January 2004 and December 2010, 45 patients with peripheral, mass-forming cholangiocarcinoma (Group 1) and 45 patients with liver metastases from colorectal adenocarcinoma (Group 2) who underwent abdominal CT scan at the authors' institution were included in the present retrospective study. Two experienced, abdominal radiologists blinded to the participants 'clinical histories and pathological results, separately reviewed the CT findings of each participant (number of liver mass(es), size, margin, internal calcification, hepatic capsule retraction, vascular invasion, peripheral bile duct dilatation, proximal bile duct enhancement, extrahepatic spreading, nearby lymphadenopathy and nearby organ invasion) and gave the presumed diagnosis of each individual case. Any discrepancies were solved by a consensus review. Finally, the authors conducted a stratified analysis of the patients in both groups based on their CT appearances.
RESULTS: Ninety participants were 35 (38.9%) female, 55 (61.1%) male, age range from 43 to 88 years (mean 63.4 years, SD = 10.7). There were 28.9% vs. 48.9% female with the mean age (SD) of 61.5 (9.4) vs. 65.4 (11.6) years in Group 1 and 2, respectively. The mean size (SD) were 7.4 (3.7) cm vs. 4.0 (2.1) cm, in Group 1 and 2, respectively (p < 0.001). The presence of hepatic capsule retraction, vascular invasion, peripheral bile duct dilatation, proximal bile duct enhancement, extrahepatic spreading, nearby lymphadenopathy, and nearby organ invasion were significantly higher in Group 1 than Group 2 (p < 0.001). In contrary, the presence of multiple lesions with separated locations, and smooth margin were significantly suggested of Group 2 (p < 0.001 and p = 0.007, respectively). By logistic regression analysis, peripheral bile duct dilatation, extrahepatic spreading, and proximal bile duct enhancement were the sole predictors of peripheral, mass-forming cholangiocarcinoma. The interobserver agreement for the presumed diagnosis of liver mass was good (kappa = 0.76).
CONCLUSION: The presence of peripheral bile duct dilatation, extrahepatic spreading, and proximal bile duct enhancement were highly suggestive of peripheral, mass-forming cholangiocarcinoma.

Cotto M, Rosado-Orozco KE, Rizek R, et al.
Clinical and pathological features of colorectal cancer in patients at a community hospital in Puerto Rico.
P R Health Sci J. 2014; 33(2):65-70 [PubMed] Related Publications
OBJECTIVE: Colorectal cancer (CRC) is among the most common cancers in Puerto Rico. Few studies have correlated clinical and pathological variables with the overall survival of CRC patients in Puerto Rico. We report the clinical and pathological characteristics of patients who underwent surgical resection at a community hospital in Puerto Rico.
METHODS: Demographic and pathological variables of patients who underwent CRC surgery at Hospital del Maestro from 2006 through 2011 were reviewed. Descriptive statistics (mean, range, and frequency) and the Cox proportional hazards model were used to determine the influence of demographic and pathological variables on survival, after adjusting for age.
RESULTS: Two hundred and five CRC pathology reports were reviewed. Adenocarcinoma represented the most common pathology (202/205; 98.5%). Females represented 52% of the population (106/202) while males represented 48% (96/202). The median age was 71 years (30-96). The right colon was the most common site of presentation (49.7%; 100/201). Stage III was the most common stage at presentation. The presence of mucin, perineural or lymphatic invasion and tumor size were not related to decreased survival. Being male, having a higher stage at diagnosis, and having a moderately or poorly differentiated tumor were characteristics related to decreased survival.
CONCLUSION: This study provides information on clinical and pathological variables and their influence on the overall survival of CRC patients at a community hospital in Puerto Rico. Further research must be performed to identify potential disparities and their influence on the prognosis of this patients.

Sclafani F, Gonzalez D, Cunningham D, et al.
TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Related Publications
In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging-defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found (P < .05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS.

Related: TP53 Cetuximab (Erbitux)

Rotimi O, Abdulkareem FB
Fifty-three years of reporting colorectal cancer in Nigerians--a systematic review of the published literature.
Niger Postgrad Med J. 2014; 21(1):68-73 [PubMed] Related Publications
AIMS AND OBJECTIVES: This study aimed to perform a systematic review of all the available published data on CRC in Nigerians over a period of 53 years as a proximate indication of the burden of the disease.
MATERIALS & METHODS: The data were sourced from PubMed, MEDLINE, EMBASE and Google Scholar search engines as well as direct contact with some authors. All published studies on histologically confirmed CRC in Nigerians constitute the materials. Selected papers were independently reviewed by the authors.
RESULTS: Of 35 papers found, 19 met the criteria and a total of 2497 cases reported in these 19 publications constituted the materials utilised for the review. There is increasing incidence as evident by increase in annual frequency increased from 18.2/annum in the early years (1954-1969) to 86.8/annum in the latter years (1991-2007). The average age incidence was 46 years (peak=41-50 age group); 674 (32%) of all the cases were aged below 40 years. The male to female ratio was 1.3:1. Of the 2238 cases in which site was reported, rectum 1349 (60%) was the commonest site followed by caecum 260 (17%). All the cases were adenocarcinomas and 1043 (56%) were well differentiated. Mucinous carcinoma and signet ring type accounted for 309 (17%) and 32 (2%) respectively. Of 1061 cases in which Duke's staging was reported, 622 (59%) presented in stage B disease followed by stage C 266 (25%).
CONCLUSIONS: The incidence is of CRC is increasing in Nigeria. The mean age is low and incidence appears to be increasing in younger patients.

Grigorean VT, Ciuhu AN, Rahnea Nita G, et al.
Efficacy of cetuximab in metastatic colon cancer - case report.
Chirurgia (Bucur). 2014 May-Jun; 109(3):383-9 [PubMed] Related Publications
In recent years, targeted therapies have proved effective in the treatment of colon cancer, but even in these conditions,metastatic disease is generally considered incurable.Cetuximab is approved for the treatment of advanced colorectal cancer patients with KRAS wild-type, in order to increase survival and hinder progression of the disease. We report a case of a 55 year-old woman, diagnosed with stenosing sigmoid cancer and liver metastases, which underwent multimodal treatment: palliative surgery -Hartmann segmental colectomy, and adjuvant chemotherapy -second line monotherapy with cetuximab, according to standard protocols. After 6 months of XELOX chemotherapy,during which she showed progression of metastatic disease, she was switched to monotherapy with cetuximab, with favorable outcome. Comparing relevant literature, in which complete response to treatment with cetuximab is obtained in low percentages ( 3%) after 3 months of treatment with cetuximab the patient shows clinical and paraclinical complete response and increased quality of life. Proper selection of patients with metastatic colon cancer for treatment with anti-EGFR therapy may lead to prolonged survival and time to progression.

Related: Cetuximab (Erbitux)

Grama FA, Burcoş T, Bordea A, Cristian D
Localisation and preservation of the autonomic nerves in rectal cancer surgery - technical details.
Chirurgia (Bucur). 2014 May-Jun; 109(3):375-82 [PubMed] Related Publications
Iatrogenic surgical injury to pelvic autonomic nerves followed by genitourinary dysfunctions are well known problems after total partial mesorectal excision for rectal cancer. The purpose of our paper is to present the useful anatomical landmarks for a safe nerve-sparing surgery in rectal oncology. Over the course of a total mesorectal excision we describe and illustrate the key risk zones of autonomic nerve injury based on our experience in rectal surgery and on the revised literature.

Alecu M, Simion L, Straja N, Brătucu E
Multiple polyps and colorectal cancer.
Chirurgia (Bucur). 2014 May-Jun; 109(3):342-6 [PubMed] Related Publications
INTRODUCTION: Malignant degeneration as a possible course of evolution of colorectal polyps renders their diagnosis and therapeutic management a prophylactic act in the prevention of colorectal cancer (CRC).
MATERIAL AND METHOD: The study was conducted over a period of 3 years (2008-2011), during which 1,368 colonoscopies were performed in our service. The aim of the study was to identify patients presenting multiple colorectal polyps and to determine their risk factors for developing CRC, as well as to establish the appropriate therapeutic conduct.
RESULTS: Presence of multiple polyps was recorded in over 40% of the patients identified with colorectal polyps of any kind. Dysplastic modifications observed during the histopathology exam presented a high incidence in the case of patients with multiple polyps, ranging from low-grade dysplasia to incipient CRC.
CONCLUSIONS: Dysplastic modifications and carcinomatous foci were identified mostly among patients with multiple polyps.Only benign lesions or in situ carcinomas benefited from endoscopic treatment, poorly differentiated carcinomas or those invading the submucosa being treated by conventional surgery. Patients diagnosed with colorectal polyps require a rigorous post-therapy follow-up protocol, able to identify any eventual polyposis recurrence.

Leşe M, Szasz A, Leşe I
Emergency surgery in colorectal cancer: experience of a county hospital at a 10-year interval. Comparison of immediate postoperative results.
Chirurgia (Bucur). 2014 May-Jun; 109(3):335-41 [PubMed] Related Publications
UNLABELLED: A great majority of procedures for colorectal cancer are performed as emergencies, implying a high morbidity and mortality. The aim of this study is to compare the immediate postoperative results of emergency procedures for colorectal cancer between a 10 year interval in a single centre. We performed a retrospective research of the patients files, totalizing 24 emergency operations in 2001 and 22 emergency operations in 2011. We followed demographic data, the complication which lead to emergency surgery, the time interval between the onset of the complication and the time of surgery, the type of procedure performed, postoperative morbidity and mortality. In 2001 we noticed morbidity in 66.66% of the cases (16 patients)and a mortality of 41.66% (10 patients), while in 2011 the postoperative morbidity was 54.54% (12 patients) and a mortality of 36.36% (8 patients).
CONCLUSION: although both morbidity and mortality rates decreased in a 10 year interval, they still present high values, and the difference is not statistically significant(p = 0.21 and 0.40).

Van Loo S, Vanderputte S
Transanal resection: a novel approach.
Acta Chir Belg. 2013 May-Jun; 113(3):213-6 [PubMed] Related Publications
Due to the increase in screening programs, more rectal polyps and early rectal cancers are detected. Transanal resection of these lesions is less invasive than a transabdominal approach. Transanal endoscopic microsurgery (TEM) has gained a lot of interest, but the technique has several drawbacks such as the expensive instrumentation and considerable learning curve. With the evolution of single incision laparoscopic surgery (SILS), laparo-endoscopic single-site surgery (LESS) and natural orifice transluminal endoscopic surgery (NOTES), new devices have become available. This led to the development of a hybrid technique of transanal surgery. The technique combines a transanal approach, a SILS port and standard laparoscopic instruments. We used this technique in 2 cases.

Wells JS, Holstad MM, Thomas T, Bruner DW
An integrative review of guidelines for anal cancer screening in HIV-infected persons.
AIDS Patient Care STDS. 2014; 28(7):350-7 [PubMed] Related Publications
HIV-infected individuals are 28 times more likely than the general population to be diagnosed with anal cancer. An integrative review of recommendations and guidelines for anal cancer screening was performed to provide a succinct guide to inform healthcare clinicians. The review excluded studies that were of non-HIV populations, redundant articles or publications, non-English manuscripts, or nonclinical trials. The review found no formal national or international guidelines exist for routine screening of anal cancer for HIV-infected individuals. To date, no randomized control trial provides strong evidence supporting efficaciousness and effectiveness of an anal cancer screening program. The screening recommendations from seven international-, national-, and state-based reports were reviewed and synthesized in this review. These guidelines suggest anal cancer screening, albeit unproven, may be beneficial at decreasing the incidence of anal cancer. This review highlights the paucity of screening-related research and is an area of need to provide clear direction and to define standard of care for anal cancer screening in HIV-infected persons.

Related: Anal Cancer Cancer Screening and Early Detection

Shenoy S
Perianal giant condyloma acuminatum (Buschke-Löwenstein tumor).
Skinmed. 2014 Mar-Apr; 12(2):114-5 [PubMed] Related Publications
A 50-year-old heterosexual, HIV-negative man presented with a giant anal condyloma (Figure). He had iron deficiency anemia, a slow-growing anal wart for many years, and intermittent bleeding and pruritus. Esophagogastroduodenoscopy and colonoscopy findings were normal. Endoscopic ultrasound of the anorectum showed no anal sphincter involvement, and computed tomography did not reveal any pelvic inguinal lymph nodes. Wide-staged excision was performed and the patient recovered well with resolution of symptoms and no local recurrence at 1-year follow-up. Final pathology confirmed human papillomavirus (HPV) 6 strain and a giant condyloma acuminatum with mild atypia and no malignancy. Further examination of his oropharynx showed additional small HPV lesions, which were removed locally.

Related: Anal Cancer

Nakamura T, Yamashita K, Sato T, et al.
Neoadjuvant chemoradiation therapy using concurrent S-1 and irinotecan in rectal cancer: impact on long-term clinical outcomes and prognostic factors.
Int J Radiat Oncol Biol Phys. 2014; 89(3):547-55 [PubMed] Related Publications
PURPOSE: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy.
METHODS AND MATERIALS: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months.
RESULTS: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung.
CONCLUSIONS: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Related: Fluorouracil Leucovorin Tegafur-uracil Irinotecan

Gonsalves WI, Mahoney MR, Sargent DJ, et al.
Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Article available free on PMC after 01/07/2015 Related Publications
BACKGROUND: KRAS and BRAF (V600E) mutations are important predictive and prognostic markers, respectively, in colon cancer, but little is known about patient and clinical factors associated with them.
METHODS: Two thousand three hundred twenty-six of 3397 patients in the N0147 phase III adjuvant trial for stage III colon cancer completed a patient questionnaire. Primary tumors were assessed for KRAS and BRAF (V600E) mutations and defective mismatch repair (dMMR) status. Logistic regression models and categorical data analysis were used to identify associations of patient and tumor characteristics with mutation status. All statistical tests were two-sided.
RESULTS: KRAS (35%) and BRAF (V600E) (14%) mutations were nearly mutually exclusive. KRAS mutations were more likely to be present in patients without a family history of colon cancer and never smokers. Tumors with KRAS mutations were less likely to have dMMR (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.15 to 0.31; P < .001) and high-grade histology (OR = 0.73; 95% CI = 0.59 to 0.92; P < .001) but were more often right-sided. Among KRAS-mutated tumors, those with a Gly13Asp mutation tended to have dMMR and high-grade histology. Tumors with BRAF (V600E) mutations were more likely to be seen in patients who were aged 70 years or older (OR = 3.33; 95% CI = 2.50 to 4.42; P < .001) and current or former smokers (OR = 1.64; 95% CI = 1.26 to 2.14; P < .001) but less likely in non-whites and men. Tumors with BRAF (V600E) mutations were more likely to be right-sided and to have four or more positive lymph nodes, high-grade histology, and dMMR.
CONCLUSIONS: Specific patient and tumor characteristics are associated with KRAS and BRAF (V600E) mutations.

Related: BRAF gene KRAS gene

Yun JA, Kim SH, Hong HK, et al.
Loss of E-Cadherin expression is associated with a poor prognosis in stage III colorectal cancer.
Oncology. 2014; 86(5-6):318-28 [PubMed] Related Publications
PURPOSE: The epithelial-mesenchymal transition (EMT) is known to be associated with tumor progression, invasion and metastasis in colorectal cancer (CRC).
MATERIALS AND METHODS: Tissue samples obtained from 409 patients with stage III CRC treated from 2006 to 2007 were examined by immunohistochemistry to reveal the expression levels of E-cadherin, fibronectin, vimentin and α-smooth muscle actin (SMA).
RESULTS: Among the 409 patients, 402 cases (98.3%) showed positive E-cadherin expression. Positive E-cadherin expression was associated with well or moderately differentiated cell types and a stable microsatellite status. In multivariate analysis, a preoperative carcinoembryonic antigen level >5 ng/ml (p = 0.021), advanced N stage (p = 0.017), positive vascular invasion (p = 0.048), positive perineural invasion (p = 0.002) and negative E-cadherin expression (p = 0.002, relative risk = 5.098, 95% CI = 1.801-14.430) were poor prognostic factors affecting disease-free survival. The declining E-cadherin expression was associated with a poor outcome in terms of overall survival in univariate (p = 0.016) but not in multivariate analyses (p = 0.303, relative risk = 1.984, 95% CI = 0.539-7.296). Fibronectin, vimentin and α-SMA were of no prognostic value in this study.
CONCLUSION: The expression pattern of EMT markers in stage III CRC suggests that declining E-cadherin expression is a possible immunohistochemical predictor of patient prognosis.

Pietrantonio F, Biondani P, Perrone F, et al.
TP53 mutations in advanced colorectal cancer: the dark side of the moon.
Oncology. 2014; 86(5-6):289-94 [PubMed] Related Publications
BACKGROUND: Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting.
METHODS: We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28).
RESULTS: Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes.
CONCLUSION: TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease.

Related: TP53

Hotnog D, Mihăilă M, Lancu IV, et al.
Resveratrol modulates apoptosis in 5-fluorouracyl treated colon cancer cell lines.
Roum Arch Microbiol Immunol. 2013 Oct-Dec; 72(4):255-64 [PubMed] Related Publications
Since cancer is a cellular disease, it is essential to identify the development stages and use the information in the prediction, prevention, early detection and design of drug targets. Colon cancer represents a malignancy with high incidence and mortality throughout the world, its etiology involving many genetic, immunological and biochemical factors. 5-fluorouracyl (5-FU) is one of the most effective anti-cancer agents used in the treatment of colorectal cancers, but tumor chemoresistance is a major limiting factor of its use. In order to choose the most effective chemotherapeutic doses of 5-FU, and thereby diminish the side-effects, we tried to modulate the anticancer properties of 5-FU by adding dietary natural compounds. The study focused on the role of natural compounds as resveratrol (RSV) in sensitization of LoVo human colon adenocarcinoma cell line to 5-FU action. Real-time cell analysis (RTCA) by xCELLigence System was used to continuously monitor the cytotoxic effects of drug treatments on LoVo cells. RTCA allowed us to choose the proper concentrations for further end-point assays, such as flow-cytometry techniques used for the evaluation of apoptotic events, progression through cell cycle phases or nuclear antigen expression of compound-treated LoVo cells. Data obtained showed additional effects of RSV to 5-FU treatments on the increase ofapoptotic events, and suggested alternative approaches to obtain a stronger antitumor response, and diminished side-effects when low concentrations of anti-cancer drugs are used. Modulation of the mechanisms of programmed cell death process seem to be of great importance for malignant transformation, and therefore for anti-cancer therapeutic approaches.

Related: Apoptosis Fluorouracil

Cunliffe S, Milosevic A
The clinical features and their impact on the prosthodontic management in a case of Gardner's syndrome.
Eur J Prosthodont Restor Dent. 2014; 22(1):7-10 [PubMed] Related Publications
Gardner's syndrome is a variant of Familial Adenomatous Polyposis (FAP), a condition that manifests as hundreds of colorectal polyps likely to undergo malignant change by the fourth decade. Early diagnosis of this condition has the potential to be life saving for individuals and due to its inherited nature other family members can often also be affected. Additional features of Gardner's Syndrome include multiple jaw osteomas with missing teeth that can make prosthodontic treatment a challenge. This case report highlights the presenting features and the prosthodontic problems faced when treating a patient with Gardner's syndrome.

Brenner H, Stock C, Hoffmeister M
Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies.
BMJ. 2014; 348:g2467 [PubMed] Article available free on PMC after 01/07/2015 Related Publications
OBJECTIVES: To review, summarise, and compare the evidence for effectiveness of screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal cancer occurrence and deaths.
DESIGN: Systematic review and meta-analysis of randomised controlled trials and observational studies.
DATA SOURCES: PubMed, Embase, and Web of Science. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings.
ELIGIBILITY CRITERIA: Randomised controlled trials and observational studies in English on the impact of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality in the general population at average risk.
RESULTS: For screening sigmoidoscopy, four randomised controlled trials and 10 observational studies were identified that consistently found a major reduction in distal but not proximal colorectal cancer incidence and mortality. Summary estimates of reduction in distal colorectal cancer incidence and mortality were 31% (95% confidence intervals 26% to 37%) and 46% (33% to 57%) in intention to screen analysis, 42% (29% to 53%) and 61% (27% to 79%) in per protocol analysis of randomised controlled trials, and 64% (50% to 74%) and 66% (38% to 81%) in observational studies. For screening colonoscopy, evidence was restricted to six observational studies, the results of which suggest tentatively an even stronger reduction in distal colorectal cancer incidence and mortality, along with a significant reduction in mortality from cancer of the proximal colon. Indirect comparisons of results of observational studies on screening sigmoidoscopy and colonoscopy suggest a 40% to 60% lower risk of incident colorectal cancer and death from colorectal cancer after screening colonoscopy even though this incremental risk reduction was statistically significant for deaths from cancer of the proximal colon only.
CONCLUSIONS: Compelling and consistent evidence from randomised controlled trials and observational studies suggests that screening sigmoidoscopy and screening colonoscopy prevent most deaths from distal colorectal cancer. Observational studies suggest that colonoscopy compared with flexible sigmoidoscopy decreases mortality from cancer of the proximal colon. This added value should be examined in further research and weighed against the higher costs, discomfort, complication rates, capacities needed, and possible differences in compliance.

Related: Canada Cancer Screening and Early Detection USA

Bats AS, Blons H, Narjoz C, et al.
Microsatellite instability analysis in uterine cavity washings to detect endometrial cancer in Lynch syndrome.
Anticancer Res. 2014; 34(6):3211-5 [PubMed] Related Publications
AIM: To assess the feasibility of Microsatellite Instability (MSI) analysis in uterine cavity washings for detecting endometrial cancer in Lynch syndrome.
MATERIALS AND METHODS: This was a proof-of-concept study in Lynch syndrome patients, scheduled for hysterectomy. At the beginning of surgical procedure, uterine cavity washings were performed, and sent for MSI analysis. Pathological examination of the uterus was associated with mismatch repair protein expression and MSI analysis.
RESULTS: Nine patients were included in the study. Uterine cavity washings were feasible and interpretable in all cases. Final histological report identified 2 endometrial cancers and 7 benign specimens. There was no atypical hyperplasia. Sensitivity, specificity, positive predictive value, and negative predictive value of MSI analysis in uterine washings reached 100% in all cases. Concordance of MSI presence or absence was absolute between uterine washings and final histology.
CONCLUSION: MSI analysis in uterine cavity washings may be a promising screening tool for Lynch syndrome-associated endometrial cancer diagnosis.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

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