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

Information Patients and the Public (18 links)

Information for Health Professionals / Researchers (12 links)

Herdiatry Colorectal Cancers (5 links)

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

Latest Research Publications

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

Loupakis F, Cremolini C, Masi G, et al.
Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer.
N Engl J Med. 2014; 371(17):1609-18 [PubMed] Related Publications
BACKGROUND: A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects.
METHODS: We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival.
RESULTS: The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62 to 0.90; P=0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P=0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P=0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group.
CONCLUSIONS: FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; number, NCT00719797.).

Related: Fluorouracil Leucovorin Bevacizumab (Avastin)

Zare-Khormizi MR, Moghimi M, Pourrajab F
Giant pedunculated polypoid submucosal lipoma of the splenic flexure of colon: case report and review of the literature.
Pathologica. 2014; 106(2):77-81 [PubMed] Related Publications
Lipomas of the colon are rare but clinically important conditions that require suitable evaluation for guiding appropriate therapy. The majority of lipomas arise from the submucosal layer in the ascending colon, especially near the ileocecal valve, which causes difficulties in diagnosis. Giant lipomas may be misinterpreted as a premalignant adenomatous polyp, particularly when arising in the left colon. A 38-year-old man presented with manifestations including hypogastric pain, constipation, loss of appetite and weight, accompanied by anaemia, nausea, vomiting and haematochezia. Colonoscopy revealed a large submucosal polyp about 5 x 4 cm, which was located at the splenic flexure of colonic. Surgery detected an oval polypoid tumour measuring 70 x 50 x 45 mm in size, having a pedunculated appearance and a stalk diameter of 20 mm. Histopathologic examination of the biopsy from the lesion confirmed diagnosis of a giant submucosal lipoma. In our experience, most giant colonic lipomas are found to be sessile and occur in the ascending colon in older patients. Herein, we report a pedunculated tumour in a 38-year-old male located in the splenic flexure of colon.

John A, Al Kaabi S, Dweik N, et al.
Emerging role for colorectal cancer screening in Asian countries.
Trop Gastroenterol. 2014 Jan-Mar; 35(1):21-4 [PubMed] Related Publications
BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the leading causes of cancer related mortality globally. Though Asia has traditionally been considered a relatively low incidence area for colorectal cancer, the incidence is reportedly increasing. The Asia Pacific Working Group for Colorectal Cancer has recommended screening of individuals at average risk starting from 50 years of age. Based on these recommendations we conducted a pilot study to assess the need and feasibility of a colorectal cancer screening program in the state of Qatar.
METHODS AND RESULTS: We screened 1385 individuals by fecal immunochemical testing for occult blood, at the primary health center level and positive cases were referred for colonoscopy. Among those who tested positive for fecal occult blood, we picked up five patients with cancers and seven with neoplastic polyps.
CONCLUSION: Our results compare with the yield of screening programs in western countries thus suggesting an emerging role for colorectal cancer screening in Asian countries.

Mhaidat NM, Al-Wedyan TJ, Alzoubi KH, et al.
Measuring quality of life among colorectal cancer patients in Jordan.
J Palliat Care. 2014; 30(3):133-40 [PubMed] Related Publications
Quality of life among colorectal cancer (CRC) patients was evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and EORTC QLQ-CR29. We interviewed 74 CRC patients, and our results indicated lower anxiety functional scores and higher abdominal pain and embarrassment symptom scores among patients aged 55 and under. Patients with disease metastasis showed significantly lower global health scores and higher fatigue, loss of appetite, hair loss, and change in taste symptom scores. Scores for emotional functioning were significantly lower among patients with stage IV disease. Fatigue, nausea and vomiting, loss of appetite, abdominal pain, and change in taste symptom scores were significantly higher in patients treated with a combination of surgery and chemotherapy compared to surgery alone. Age, disease metastasis, late disease stage, and combined treatment modalities were associated with lower scores on health-related quality-of-life scales; patients likely to have low scores on these measures should receive special attention from healthcare providers and be targeted by supportive care strategies.

Gürses E
Impar ganglion radiofrequency application in successful management of oncologic perineal pain.
J Pak Med Assoc. 2014; 64(6):697-9 [PubMed] Related Publications
Impar ganglion is a solitary ganglion located retroperitoneally at the end of paravertebral sympathetic chain and usually in front of sacrococcygeal joint. Solitary or metastatic tumour in the surrounding tissues causes poorly localized pain. This case report presents a 75-year old male patient with colon cancer, whose severe pain during defecation could not be controlled with conventional high-dose opioid application but with transcoccygeal radiofrequency thermocoagulation. Radiofrequency thermocoagulation is promising not only for chronic pelvic pain control but also in pelvic pain secondary to malignancy particularly when the ganglion is localized by radiologic imaging techniques.

Kawee-Ai A, Kim SM
Application of microalgal fucoxanthin for the reduction of colon cancer risk: inhibitory activity of fucoxanthin against beta-glucuronidase and DLD-1 cancer cells.
Nat Prod Commun. 2014; 9(7):921-4 [PubMed] Related Publications
Intestinal bacterial beta-glucuronidases are capable of retoxifying compounds that have been detoxified by liver glucuronidation and are also known to accelerate colon cancer invasion and metastasis. In this study, fucoxanthin extracted from the microalga Phaeodactylum tricornutum was investigated for its inhibitory activity against Escherichia coli beta-glucuronidase and DLD-1 cancer cells. Fucoxanthin inhibited beta-glucuronidase in a concentration-dependent manner with an IC50 value of 2.32 mM and a mixed inhibition type. Fucoxanthin had more potent inhibitory activity on beta-glucuronidase at 37 degrees C and in alkaline conditions. Fucoxanthin also inhibited the beta-glucuronidase activity of DLD-1 cancer cells at a concentration of 20-50 microM. The presence of beta-glucuronidase and substrate in the medium decreased the inhibitory activity of fucoxanthin against DLD-1 cancer cells. Therefore, microalgal fucoxanthin might prevent colon cancer because of its strong beta-glucuronidase inhibitory activity and could be utilized as a novel functional ingredient of food and pharmaceutical supplements.

Bischoff-Ferrari HA
Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes.
Adv Exp Med Biol. 2014; 810:500-25 [PubMed] Related Publications
Recent evidence suggests that vitamin D deficiency has harmful effects on health and that recent vitamin D intake recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, fractures, cancer prevention, incident hypertension and mortality. For all endpoints, levels in the deficient range (< 50 nmol/l; < 20 ng/ml) are associated with no benefit or adverse effects, while the most advantageous serum levels for 25(OH)D appeared to be close to 75 nmol/l (30 ng/ml). An intake of 800 IU (20 microg) of vitamin D3 (cholecalciferol) per day for all adults may bring 97% of the population to level of at least 50 nmol/l and about 50% up to 75 nmol/l. Thus, higher doses of vitamin D than currently recommended are needed to bring most individuals to75 nmol/l. While estimates suggest that 1600 to 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of higher doses for the total adult population need to be addressed in future studies.

Gandini S, Gnagnarella P, Serrano D, et al.
Vitamin D receptor polymorphisms and cancer.
Adv Exp Med Biol. 2014; 810:69-105 [PubMed] Related Publications
It was suggested that vitamin D levels influence cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. In fact It has been hypothesized that polymorphisms in the VDR gene affect cancer risk and the relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies. However, results from previous studies on the association of VDR polymorphisms with different cancer types are somewhat contradictory, and the role of VDR in the etiology of cancer is still equivocal. We have performed a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies, including cancer of the skin (melanoma and nonmelanoma skin cancer), ovarian cancer, renal cell carcinoma, bladder cancer, non-Hodgkin lymphoma, leukemia, thyroid carcinoma, esophageal adenocarcinoma, hepatocellular carcinoma, sarcoma, head and neck and oral squamous cell carcinoma. Up to June 2012, we identified 79 independent studies for a total of 52427 cases and 62225 controls. Significant associations with VDR polymorphisms have been reported for prostate (Fok1, Bsm1, Taq1), breast (Fok1, Bsm1, Apa1), colon-rectum (Fok1, Bsm1, Taq1) and skin cancer (Fok1, Bsm1, Taq1). Very few studies reported risk estimates for the other cancer sites. Conflicting data have been reported for most malignancies and at present it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer risk. It seems probable that interactions with other factors such as calcium and vitamin D intake, 25(OH)D plasma levels and UV radiation exposure play a decisive role in cancer risk. To conclude, there is some indication that VDR polymorphisms may modulate the risk of some cancer sites and in future studies VDR genetic variation should be integrated also with prediagnostic indicator of vitamin D status.

Related: Breast Cancer Polymorphisms Prostate Cancer Skin Cancer

Grant WB
Solar ultraviolet irradiance and cancer incidence and mortality.
Adv Exp Med Biol. 2014; 810:52-68 [PubMed] Related Publications
The solar ultraviolet-B (UVB)/vitamin D/cancer hypothesis was proposed by the brothers Cedric and Frank Garland in 1980. In 2002, the list was increased to 15 types of cancer using data in the 1999 version of the atlas of cancer mortality rates in the United States. Ecological studies of cancer incidence and/or mortality rates with respect to indices of solar UVB doses have also been reported for Australia, China, France, Japan, and Spain with largely similar findings. In addition, several studies using nonmelanoma skin cancer as the index of solar UVB dose have found reduced internal cancer incidence and/or mortality rates, especially in sunny countries. A study of cancer incidence with respect to 54 categories of occupation in five Nordic countries, using lip cancer less lung cancer as the UVB index, found this index inversely correlated with 14 types of internal cancers for males and four for females. Observational studies with respect to UVB doses and serum 25-hydroxyvitamin D [25(OH)D] concentrations also support the hypothesis. Hill's criteria for causality in a biological system to assess whether solar UVB and vitamin D can be considered causal in reducing risk of cancer. The primary criteria for this analysis include strength of association, consistent findings in different populations, biological gradient, plausibility (e.g., mechanisms), and experimental verification (e.g., randomized controlled trials). The totality of evidence is judged to satisfy the criteria very well for breast and colorectal cancer, and moderately well for several other types of cancer.

Related: Breast Cancer Lung Cancer Skin Cancer

Shui I, Giovannucci E
Vitamin D status and cancer incidence and mortality.
Adv Exp Med Biol. 2014; 810:33-51 [PubMed] Related Publications
The role of vitamin D in cancer incidence and mortality has been investigated using several approaches, including using sun exposure as a proxy for vitamin D status, assessing vitamin D intake from food and supplements, using a predicted score to estimate vitamin D status, and directly measuring circulating 25(OH)D. A variety of complementary study designs have been implemented with various strengths and limitations. Although definitive randomized control trial data are lacking, there is strong evidence for a protective relationship of vitamin D and colorectal cancer incidence. Evidence for other cancers is not as consistent. More recently, large pooling projects have begun to investigate rarer cancers, studies have investigated common variation and expression of vitamin D-related genes and their relationships to cancer, and evidence has emerged on the role of vitamin D in cancer survival. Further study is needed to answer important questions that remain about the most affected cancer sites, the timing of vitamin D exposure in relation cancer etiology duringthe life span (e.g., adolescence or adulthood), the dose-response/optimal levels required for the most benefit, and which stages of carcinogenesis (e.g., incidence or progression) are most relevant.

Related: Breast Cancer Prostate Cancer

Ordóñez Mena JM, Brenner H
Vitamin D and cancer: an overview on epidemiological studies.
Adv Exp Med Biol. 2014; 810:17-32 [PubMed] Related Publications
In recent years, a rapidly increasing number of studies have investigated the relationship of vitamin D with total cancer and site-specific cancer obtaining diverse findings. In this chapter we provide an overview of epidemiological studies of vitamin D intake, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels and vitamin D associated polymorphisms in relation to total and site-specific cancer risk. Overall, epidemiological evidence for total cancer is inconclusive. However, a large number of studies support a relationship of vitamin D with colorectal cancer and to a lesser extent with breast cancer. Findings are inconsistent for other cancers including all other gastrointestinal cancers and prostate cancer. Different vitamin D associated polymorphisms were found to be significantly associated to colorectal, breast and prostate cancer risk.

Related: Breast Cancer Polymorphisms Prostate Cancer

Monson JR, Probst CP, Wexner SD, et al.
Failure of evidence-based cancer care in the United States: the association between rectal cancer treatment, cancer center volume, and geography.
Ann Surg. 2014; 260(4):625-31; discussion 631-2 [PubMed] Related Publications
OBJECTIVE: This study examines recent adherence to recommended neoadjuvant chemoradiotherapy guidelines for patients with rectal cancer across geographic regions and institution volume and assesses trends over time.
BACKGROUND: A recent report by the Institute of Medicine described US cancer care as chaotic. Cited deficiencies included wide variation in adherence to evidence-based guidelines even where clear consensus exists.
METHODS: Patients operated on for clinical stage II and III rectal cancer were selected from the 2006-2011 National Cancer Data Base. Multivariable logistic regressions were used to assess variation in chemotherapy and radiation use by cancer center type, geographical location, and hospital volume. The analysis controlled for patient age at diagnosis, sex, race/ethnicity, primary payer, average household income, average education, urban/rural classification of patient residence, comorbidity, and oncologic stage.
RESULTS: There were 30,994 patients who met the inclusion criteria. Use of neoadjuvant radiation therapy and chemotherapy varied significantly by type of cancer center. The highest rates of adherence were observed in high-volume centers compared with low-volume centers (78% vs 69%; adjusted odds ratio = 1.46; P < 0.001). This variation is mirrored by hospital geographic location. Primary payer and year of diagnosis were not predictive of rates of neoadjuvant chemoradiotherapy.
CONCLUSIONS: Adherence to evidence-based treatment guidelines in rectal cancer is suboptimal in the United States, with significant differences based on hospital volume and geographic regions. Little improvement has occurred in the last 5 years. These results support the implementation of standardized care pathways and a Centers of Excellence program for US patients with rectal cancer.

Related: USA

Wertzberger BE, Sherman SK, Byrn JC
Differences in short-term outcomes among patients undergoing IPAA with or without preoperative radiation: a National Surgical Quality Improvement Program analysis.
Dis Colon Rectum. 2014; 57(10):1188-94 [PubMed] Article available free on PMC after 01/10/2015 Related Publications
BACKGROUND: Single-institution studies demonstrate a correlation between preoperative pelvic radiation and poor long-term pouch function after IPAA. The rarity of the radiated pelvis before these procedures limits the ability to draw conclusions on the effects of preoperative radiation on short-term outcomes, which may contribute to long-term pouch dysfunction.
OBJECTIVE: The purpose of this work was to better understand the impact of pelvic radiation on short-term outcomes in patients undergoing IPAA.
DESIGN: We conducted a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database (2005-2011).
SETTINGS: The study was conducted at all participating NSQIP institutions.
PATIENTS: The cohort was composed of patients undergoing nonemergent IPAA procedures.
MAIN OUTCOME MEASURES: Proportions of patients experiencing postoperative complications within 30 days were compared by Fisher exact and Wilcoxon rank-sum tests based on whether they received preoperative radiation. Multivariate logistic regression models controlled for the effects of multiple risk factors.
RESULTS: Included were 3172 patients receiving IPAA; 162 received pelvic radiation. The postoperative complication rate was not significantly different in patients receiving pelvic radiation versus not receiving pelvic radiation (p = 0.06). In a subset of patients with cancer diagnoses (n = 598), 157 received pelvic radiation; complication rates were not significantly different (p = 0.16). Patients receiving pelvic radiation had significantly lower rates of sepsis in both the overall and cancer diagnosis groups (p = 0.005 and p = 0.047), a finding which persisted after controlling for the effects of multiple risk factors (multivariate p values = 0.030 and 0.047).
LIMITATIONS: This was a retrospective database design with short-term follow-up.
CONCLUSIONS: Patients who received radiation before IPAA had no difference in overall 30-day complication rates but had significantly lower rates of sepsis when compared with patients not receiving pelvic radiation. The perceived inferior long-term pouch function in patients undergoing preoperative pelvic radiation does not appear to be attributable to increases in 30-day complications.

Related: USA

Ricciardi R, Burks E, Schoetz DJ, et al.
Is there a gain in chromosome 3q in the pathway to anal cancer?
Dis Colon Rectum. 2014; 57(10):1183-7 [PubMed] Related Publications
BACKGROUND: Chromosome 3q gain has been identified in human papillomavirus-infected cervical cancer cells.
OBJECTIVE: We sought to identify the presence of chromosomal 3q gain in anal neoplasia.
DESIGN: This was a retrospective cohort.
SETTINGS: The study was conducted in a group colorectal surgery practice.
PATIENTS: Fifty-two patients with no dysplasia, low-grade dysplasia, high-grade dysplasia, or anal cancer were studied.
INTERVENTIONS: Pairs of biopsy specimens were paraffin embedded and reviewed. One of each slide pair was stained with hematoxylin and eosin and the second processed for fluorescence in situ hybridization. The hybridized set was deparaffinized first and then hybridized with a probe for the chromosome 3q26 region. Then, slides were scanned using an automated fluorescence microscopy system that analyzed defined areas of the tissue to enumerate all of the nuclei for hybridized probe signals to detect chromosome 3q gain.
MAIN OUTCOME MEASURES: We measured for gain in chromosome 3q26.
RESULTS: We identified chromosome 3q gain in 7 (78%) of 9 patients with squamous-cell cancer, 8 (53%) of 15 high-grade dysplasia samples, 0 of 12 low-grade dysplasia samples, and 0 of 16 samples with no dysplasia. The sensitivity for high-grade or invasive neoplasia was 58%, with a specificity of 100%. The positive predictive value of the test was 100% for detecting high-grade dysplasia and/or squamous-cell cancer from no dysplasia, and the negative predictive value of the test was 62%.
LIMITATIONS: This study was limited by its small sample size and retrospective design.
CONCLUSIONS: Chromosome 3q gain represents an important shared pathway to tumorigenesis in cervical and anal neoplasia. Multiple potential diagnostic roles exist for this easily performed test in the evaluation of anal neoplasia.

Related: Anal Cancer Chromosome 3 FISH

Marks JH, Frenkel JL, Greenleaf CE, D'Andrea AP
Transanal endoscopic microsurgery with entrance into the peritoneal cavity: is it safe?
Dis Colon Rectum. 2014; 57(10):1176-82 [PubMed] Related Publications
BACKGROUND: Relative contraindications for transanal endoscopic microsurgery include high, anterior-based lesions for full-thickness excisions because of worries about entering the peritoneal cavity. Concerns exist regarding safety and oncological outcome.
OBJECTIVE: We examined the outcomes of transanal endoscopic microsurgery excisions with entry into the peritoneal cavity and compared them with those that did not to address our hypothesis that entry is safe with no ill infectious or oncological consequences.
DESIGN: This single-institution retrospective review uses a prospectively maintained database.
SETTINGS: This study was conducted at a tertiary colorectal surgery referral center.
PATIENTS: From 1997 to 2012, we identified 303 patients who underwent transanal endoscopic microsurgery resections, with 26 patients having entrance into the peritoneal cavity.
MAIN OUTCOME MEASURES: Perioperative data, postoperative morbidities, delayed morbidities, and oncological outcomes were the primary outcomes measured.
RESULTS: Of 26 patients, there were 8 women with a mean age of 67.5 years. Mean BMI was 31 kg/m, and ASA class was III or IV in 69%. Mean superior border of the lesion was 10.4 cm (4.5-16). Forty-eight percent had anterior-based lesions. Anterior location, level from anorectal ring, and diagnosis of cancer were significantly higher in the peritoneal entry group (p = 0.003, p = 0.007, and p = 0.007). Preoperative diagnoses included 16 adenocarcinomas, 8 polyps, and 2 carcinoid tumors. Thirteen patients had preoperative chemoradiation. Median estimated blood loss was 15 mL (5-400), and 3 patients underwent diversions. Median time to discharge was 3 days (2-10). There were no perioperative mortalities. Median follow-up time was 21.0 months. There was 1 local recurrence (3.8%), and there was no development of carcinomatosis.
LIMITATIONS: This review was limited by its retrospective nature.
CONCLUSIONS: High anterior location rectal lesions should be considered candidates for transanal endoscopic microsurgery excision in experienced hands. After obtaining considerable transanal endoscopic microsurgery experience, our use of transanal endoscopic microsurgery in a high-risk patient population allowed us to definitively treat 88% of patients without an abdominal operation and the need for a temporary or permanent colostomy. Theoretic concerns of abscess or carcinomatosis were not experienced (see Video, Supplemental Digital Content 1,

Related: Gastrointestinal Carcinoid Tumours Fluorouracil

Açar Hİ, Cömert A, Avşar A, et al.
Dynamic article: surgical anatomical planes for complete mesocolic excision and applied vascular anatomy of the right colon.
Dis Colon Rectum. 2014; 57(10):1169-75 [PubMed] Related Publications
BACKGROUND: Lower local recurrence rates and better overall survival are associated with complete mesocolic excision with central vascular ligation for treatment of colon cancer. To accomplish this, surgeons need to pay special attention to the surgical anatomical planes and vascular anatomy of the colon. However, surgical education in this area has been neglected.
OBJECTIVE: The aim of this study is to define the correct surgical anatomical planes for complete mesocolic excision with central vascular ligation and to demonstrate the correct dissection technique for protecting anatomical structures.
DESIGN AND SETTINGS: Macroscopic and microscopic surgical dissections were performed on 12 cadavers in the anatomy laboratory and on autopsy specimens. The dissections were recorded as video clips.
METHODS: Dissections were performed in accordance with the complete mesocolic excision technique on 10 male and 2 female cadavers. Vascular structures, autonomic nerves, and related fascias were shown. Within each step of the surgical procedure, important anatomical structures were displayed on still images captured from videos by animations.
RESULTS: Three crucial steps for complete mesocolic excision with central vascular ligation are demonstrated on the cadavers: 1) full mobilization of the superior mesenteric root following the embryological planes between the visceral and the parietal fascias; 2) mobilization of the mesocolon from the duodenum and the pancreas and identification of vascular structures, especially the veins around the pancreas; and 3) central vascular ligation of the colonic vessels at their origin, taking into account the vascular variations within the mesocolonic vessels and the autonomic nerves around the superior mesenteric artery.
LIMITATIONS: The limitation of this study was the number of the cadavers used.
CONCLUSIONS: Successful complete mesocolic excision with central vascular ligation depends on an accurate knowledge of the surgical anatomical planes and the vascular anatomy of the colon.

Floodeen H, Lindgren R, Hallböök O, Matthiessen P
Evaluation of long-term anorectal function after low anterior resection: a 5-year follow-up of a randomized multicenter trial.
Dis Colon Rectum. 2014; 57(10):1162-8 [PubMed] Related Publications
BACKGROUND: Anorectal function after rectal surgery with low anastomosis is often impaired. Outcome of long-term anorectal function is poorly understood but may improve over time.
OBJECTIVE: We evaluated anorectal function 5 years after low anterior resection for cancer with regard to whether patients had a temporary stoma at initial resection. The objective of this study was to assess changes in anorectal function over time by comparing the results with anorectal function 1 year after rectal resection.
DESIGN: This study was a secondary end point of a randomized, multicenter controlled trial.
SETTINGS: The study was conducted at 21 Swedish hospitals performing rectal cancer surgery from 1999 to 2005.
PATIENTS: Patients included were those operated on with low anterior resection.
INTERVENTIONS: Patients were randomly assigned to receive or not receive a defunctioning stoma.
MAIN OUTCOME MEASURES: We evaluated anorectal function in patients who were initially randomly assigned to the defunctioning stoma or no stoma group, who had been free of stoma for 5 years, by means of using a standardized patient questionnaire. Questions addressed stool frequency, urgency, fragmentation of bowel movements, evacuation difficulties, incontinence, lifestyle alterations, and patient preference regarding permanent stoma formation. Results were compared with the same patient cohort at 1-year follow-up.
RESULTS: A total of 123 patients answered the bowel function questionnaire (65 in the no-stoma group and 58 in the stoma group). No differences were found between groups regarding the number of passed stools, need for medication to open the bowel, evacuation difficulties, incontinence, and urgency. General well-being was significantly better in the no-stoma group (p = 0.033). Comparison with anorectal function at 1 year showed no further changes over time.
LIMITATIONS: The study was based on a limited sample size (n = 123) and formed a secondary end point of a randomized trial.
CONCLUSIONS: Anorectal function was impaired for many patients, but the temporary presence of a defunctioning stoma after rectal resection did not affect long-term outcome. Anorectal function did not change between 1-year and 5-year follow-up.

Milne T, Solomon MJ, Lee P, et al.
Sacral resection with pelvic exenteration for advanced primary and recurrent pelvic cancer: a single-institution experience of 100 sacrectomies.
Dis Colon Rectum. 2014; 57(10):1153-61 [PubMed] Related Publications
BACKGROUND: Recurrent and advanced primary pelvic cancers present a complex clinical issue requiring multidisciplinary care and radical extended surgery. Sacral resection is necessary for tumors that invade posteriorly but is associated with increased morbidity and mortality.
OBJECTIVE: This study aimed to analyze the morbidity and survival associated with pelvic exenteration involving sacrectomy for advanced pelvic cancers at a single institution.
DESIGN: This study used patient demographics, operative and pathologic reports, and prospective survival data to determine factors affecting patient outcomes.
SETTINGS: Data were collected for patients who had operations between July 1998 and April 2012 at Royal Prince Alfred Hospital.
PATIENTS: One hundred patients underwent pelvic exenteration with a sacrectomy for advanced pelvic cancers. Sacrectomy was performed for 18 primary and 61 recurrent rectal cancers, 17 anal cancers, and 4 other cancers.
MAIN OUTCOME MEASURES: This study looked at postoperative major and minor morbidity rates, as well as disease-free and overall survival rates after sacral resection. It compared the outcomes of high sacrectomy (at or above S2) versus low sacrectomy.
RESULTS: Clear margins were achieved in 72 of 100 patients. The overall complication rate was 74% (43% major and 67% minor) with no 30-day or in-hospital mortality. Estimated overall and disease-free survival rates after curative resection were 38% and 30% at 5 years. Involved margins (p = 0.006), lymph node involvement (p = 0.008), and anterior organ invasion (p = 0.008) had a negative impact on patient survival. High sacrectomy increased the incidence of neurologic deficit postoperatively (p = 0.04) but did not alter the rate of R0 resection or patient survival.
LIMITATIONS: Retrospective data were required to analyze patient morbidity, as well as operative and pathologic factors.
CONCLUSIONS: This series supports sacral resection for curative surgery in advanced pelvic cancers, achieving excellent R0 and long-term survival rates. Cortical bone invasion and high sacrectomy were not contraindications to surgery and had acceptable outcomes.

Related: Anal Cancer

Shanahan F, O'Toole PW
Host-microbe interactions and spatial variation of cancer in the gut.
Nat Rev Cancer. 2014; 14(8):511-2 [PubMed] Related Publications
The small intestine has a greater cell mass than the colon, it is longer and with greater surface area and has a faster rate of epithelial turnover. At first, this might suggest that the small bowel epithelium could be at greater risk of the cumulative genetic errors that predispose to cancer. However, the incidence of cancer of the small bowel is more than tenfold lower than that of colorectal cancer.

Pavlov V
Synchronous and metachronous primary malignant colorectal tumors and associated primary extracolonic malignant tumors--diagnostics and surgical treatment.
Khirurgiia (Sofiia). 2014; (1):15-22 [PubMed] Related Publications
The publications considering multiple primary tumors date back even to the XIXth century, however the scientific interest towards this problem still remains significant. The classification of these tumors is changing through the years, and their frequency remains higher than the expected one. The colon is one of the organs, where multiple primary lesions are often found, as well as primary lesions, associated with extracolonic primary malignant tumors. The multiple primary tumors are still found to be a diagnostic challenge, while there is still no complete solidarity regarding the surgical treatment of lesions found simultaneously. The question whether the multiple primary lesions have a poorer prognosis as regards the survival rate, compared to the solitary tumors, has always aroused interest.

Tignanelli CJ, Herrera Loeza SG, Yeh JJ
KRAS and PIK3CA mutation frequencies in patient-derived xenograft models of pancreatic and colorectal cancer are reflective of patient tumors and stable across passages.
Am Surg. 2014; 80(9):873-7 [PubMed] Related Publications
One obstacle in the translation of advances in cancer research into the clinic is a deficiency of adequate preclinical models that recapitulate human disease. Patient-derived xenograft (PDX) models are established by engrafting patient tumor tissue into mice and are advantageous because they capture tumor heterogeneity. One concern with these models is that selective pressure could lead to mutational drift and thus be an inaccurate reflection of patient tumors. Therefore, we evaluated if mutational frequency in PDX models is reflective of patient populations and if crucial mutations are stable across passages. We examined KRAS and PIK3CA gene mutations from pancreatic ductal adenocarcinoma (PDAC) (n = 30) and colorectal cancer (CRC) (n = 37) PDXs for as many as eight passages. DNA was isolated from tumors and target sequences were amplified by polymerase chain reaction. KRAS codons 12/13 and PIK3CA codons 542/545/1047 were examined using pyrosequencing. Twenty-three of 30 (77%) PDAC PDXs had KRAS mutations and one of 30 (3%) had PIK3CA mutations. Fifteen of 37 (41%) CRC PDXs had KRAS mutations and three of 37 (8%) had PIK3CA mutations. Mutations were 100 per cent preserved across passages. We found that the frequency of KRAS (77%) and PIK3CA (3%) mutations in PDAC PDX was similar to frequencies in patient tumors (71 to 100% KRAS, 0 to 11% PIK3CA). Similarly, KRAS (41%) and PIK3CA (8%) mutations in CRC PDX closely paralleled patient tumors (35 to 51% KRAS, 12 to 21% PIK3CA). The accurate mirroring and stability of genetic changes in PDX models compared with patient tumors suggest that these models are good preclinical surrogates for patient tumors.

Related: Cancer of the Pancreas Pancreatic Cancer KRAS gene

Rex DK
Water exchange vs. water immersion during colonoscope insertion.
Am J Gastroenterol. 2014; 109(9):1401-3 [PubMed] Related Publications
Water exchange (water infusion with water removal primarily during insertion) and water immersion (water infusion with water removal during withdrawal) reduce patient discomfort during colonoscope insertion compared with air insufflation, and represent a major achievement in colonoscopy. Hsieh et al. found that water exchange, relative to water immersion, resulted in more painless insertions to the cecum and improved adenoma detection in the right colon. However, water exchange is also associated with better bowel cleansing and longer insertion and procedure times. These factors are not specific to water exchange, but could account for all or part of the better results with water exchange. Additional controlled investigation is needed to define the benefits of water exchange compared with water immersion.

Wong J, Xu B, Yeung HN, et al.
Age disparity in palliative radiation therapy among patients with advanced cancer.
Int J Radiat Oncol Biol Phys. 2014; 90(1):224-30 [PubMed] Article available free on PMC after 01/09/2015 Related Publications
PURPOSE/OBJECTIVE: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population.
METHODS AND MATERIALS: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy.
RESULTS: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001).
CONCLUSIONS: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end of life.

Related: Breast Cancer Lung Cancer Prostate Cancer USA

Buturovic S
Multiple colon polyposis.
Med Arh. 2014; 68(3):221-2 [PubMed] Related Publications
INTRODUCTION: Familial adenomatous polyposis (FAP) is a rare autosomal, dominant hereditary disease, which affects both sexes equally (1-10). FAP accounts for less than 1% of all colon cancers and is estimated to occur in one of 8,300 live births. It is characterized by numerous adenomas scattered throughout mucosa of the colon and rectum.
CASE REPORT: The patient is a 62 years old man, admitted at the Surgical Department of the General Hospital in Konjic on May 18 2010 with gastrointestinal problems including: hard stool, often splattered with fresh blood, irregular and that causes the patient a lot of problems. The final diagnosis was median laparatomy supra et infraumibilicalis. Exploratio cavi abdominalis. Colectomy totalis et ileo-recto anastomosis TT cum staypler (33Ch). Loop ileostomy. Drainage cavi abdominalis N I (uno). Early postoperative course was generally regular. Control laboratory findings show the reference value. After ten days of hospitalization, the patient was discharged on the home recovery, with practically given instructions for care and use of stoma bags. For the secondary surgery was planned ileostomy closure, and regular post-operative endoscopic control.
CONCLUSION: Most of the listed surgical intervention in case of FAP treatment localized in the colon can be performed by open (classic), or laparoscopic methods. Duration of postoperative stay in the hospital depends on the patient's general condition and the type of performed surgery. It is usually about 7 days. After hospital treatment, recovery at home is from 4-6 weeks. Patients can usually return to work or school 6-8 weeks after surgery. After surgery, patients lives will be completely normal. Sexual and social activities remain the same, while either procedure does not affect the ability of a man or woman to have offspring.

Løberg M, Kalager M, Holme Ø, et al.
Long-term colorectal-cancer mortality after adenoma removal.
N Engl J Med. 2014; 371(9):799-807 [PubMed] Related Publications
BACKGROUND: Although colonoscopic surveillance of patients after removal of adenomas is widely promoted, little is known about colorectal-cancer mortality among these patients.
METHODS: Using the linkage of the Cancer Registry and the Cause of Death Registry of Norway, we estimated colorectal-cancer mortality among patients who had undergone removal of colorectal adenomas during the period from 1993 through 2007. Patients were followed through 2011. We calculated standardized incidence-based mortality ratios (SMRs) using rates for the Norwegian population at large for comparison. Norwegian guidelines recommended colonoscopy after 10 years for patients with high-risk adenomas (adenomas with high-grade dysplasia, a villous component, or a size ≥10 mm) and after 5 years for patients with three or more adenomas; no surveillance was recommended for patients with low-risk adenomas. Polyp size and exact number were not available in the registry. We defined high-risk adenomas as multiple adenomas and adenomas with a villous component or high-grade dysplasia.
RESULTS: We identified 40,826 patients who had had colorectal adenomas removed. During a median follow-up of 7.7 years (maximum, 19.0), 1273 patients were given a diagnosis of colorectal cancer. A total of 398 deaths from colorectal cancer were expected and 383 were observed, for an SMR of 0.96 (95% confidence interval [CI], 0.87 to 1.06) among patients who had had adenomas removed. Colorectal-cancer mortality was increased among patients with high-risk adenomas (expected deaths, 209; observed deaths, 242; SMR, 1.16; 95% CI, 1.02 to 1.31), but it was reduced among patients with low-risk adenomas (expected deaths, 189; observed deaths, 141; SMR, 0.75; 95% CI, 0.63 to 0.88).
CONCLUSIONS: After a median of 7.7 years of follow-up, colorectal-cancer mortality was lower among patients who had had low-risk adenomas removed and moderately higher among those who had had high-risk adenomas removed, as compared with the general population. (Funded by the Norwegian Cancer Society and others.).

Sabbaga J, Braghiroli MI, Hoff PM
Is surgery always necessary in rectal cancer?
Oncology (Williston Park). 2014; 28(7):607-11 [PubMed] Related Publications
Rectal cancer is a major health problem around the world, representing about one-third of the total colorectal cancer cases. Because of its anatomical location, there is a higher risk of local recurrence, and treatment often requires a complex multidisciplinary approach which includes neoadjuvant radiotherapy, chemotherapy, and a radical surgical procedure that commonly leads to a permanent colostomy. The cure rate with this strategy is good, with some patients having no residual disease in the surgical specimen. While the prognosis for those patients is excellent, their quality of life is permanently compromised. In this article, we review risks and benefits of the standard treatment approach and compare standard treatment with alternative methods aimed at rectal preservation.

Glynne-Jones R, Tan D, Goh V
Pelvic MRI for guiding treatment decisions in rectal cancer.
Oncology (Williston Park). 2014; 28(8):667-77 [PubMed] Related Publications
Fluoropyrimidine-based chemoradiation (CRT) is used routinely for locally advanced rectal cancer to shrink the tumor preoperatively, improve lateral surgical clearance at total mesorectal excision, prevent local recurrence, and preserve organ function. In Northern Europe, short-course preoperative radiotherapy (SCPRT) is preferred to achieve locoregional control. However, with recent improvements in the quality of surgery, in magnetic resonance imaging (MRI), and in pathologic reporting, we question whether "routine" CRT or SCPRT should be offered indiscriminately for all patients.MRI is considered the optimal modality for locoregional staging and evaluation of the potential for an involved circumferential resection margin. MRI also provides detailed anatomic information for surgical planning, and may identify poor prognostic features, which influence the way in which the pathologist processes specimens. MRI can predict the likelihood of good/poor tumor response to neoadjuvant CRT and can categorize responders/nonresponders following treatment.Using MRI to define the risk of both local recurrence and metastatic spread allows clinicians to determine which patients might benefit from or safely avoid neoadjuvant treatment. We have arrived at these views after comparing data from published observational studies, results from randomized trials, and outcome analyses of the Norwegian National Cancer Registry.

Benning TM, Dellaert BG, Severens JL, Dirksen CD
The effect of presenting information about invasive follow-up testing on individuals' noninvasive colorectal cancer screening participation decision: results from a discrete choice experiment.
Value Health. 2014; 17(5):578-87 [PubMed] Related Publications
OBJECTIVES: Many national colorectal cancer screening campaigns have a similar structure. First, individuals are invited to take a noninvasive screening test, and, second, in the case of a positive screening test result, they are advised to undergo a more invasive follow-up test. The objective of this study was to investigate how much individuals' participation decision in noninvasive screening is affected by the presence or absence of detailed information about invasive follow-up testing and how this effect varies over screening tests.
METHODS: We used a labeled discrete choice experiment of three noninvasive colorectal cancer screening types with two versions that did or did not present respondents with detailed information about the possible invasive follow-up test (i.e., colonoscopy) and its procedure. We used data from 631 Dutch respondents aged 55 to 75 years. Each respondent received only one of the two versions (N = 310 for the invasive follow-up test information specification version, and N = 321 for the no-information specification version).
RESULTS: Mixed logit model results show that detailed information about the invasive follow-up test negatively affects screening participation decisions. This effect can be explained mainly by a decrease in choice shares for the most preferred screening test (a combined stool and blood sample test). Choice share simulations based on the discrete choice experiment indicated that presenting invasive follow-up test information decreases screening participation by 4.79%.
CONCLUSIONS: Detailed information about the invasive follow-up test has a negative effect on individuals' screening participation decisions in noninvasive colorectal cancer screening campaigns. This result poses new challenges for policymakers who aim not only to increase uptake but also to provide full disclosure to potential screening participants.

Related: Cancer Screening and Early Detection

Wiland HO, Shadrach B, Allende D, et al.
Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum.
Am J Surg Pathol. 2014; 38(9):1290-7 [PubMed] Related Publications
Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.

Related: BRAF gene KRAS gene

Barresi V, Branca G, Vitarelli E, Tuccari G
Micropapillary pattern and poorly differentiated clusters represent the same biological phenomenon in colorectal cancer: a proposal for a change in terminology.
Am J Clin Pathol. 2014; 142(3):375-83 [PubMed] Related Publications
OBJECTIVES: Colorectal carcinomas (CRCs) with a micropapillary pattern and those showing high counts of poorly differentiated clusters (PDCs) are characterized by a higher probability to develop nodal metastases and have a worse prognosis. In light of the morphologic similarity to the micropapillary component, we aimed to verify whether PDCs also display an inverted secretory pattern.
METHODS: The immunohistochemical expression of MUC1 and E-cadherin was assessed in a cohort of CRCs with PDCs and compared with that observed in CRCs without PDCs.
RESULTS: PDCs in our cases always displayed an inverted MUC1 pattern. In addition, we found abnormal (lost or cytoplasmic) expression of E-cadherin in PDCs.
CONCLUSIONS: The altered expression of MUC1 and E-cadherin may account for the aggressive behavior and higher metastatic potential of CRCs with high PDC counts and indicate an epithelial-mesenchymal transition. Our findings suggest that regardless of the morphologic aspect, PDCs and the micropapillary component may reflect the same biological phenomenon in CRCs. Thus, we wonder whether the micropapillary areas should be considered a variant of CRCs or more objectively counted as PDCs to predict prognosis. We also believe that the term PDC better describes the biological phenomena underlying this peculiar morphologic aspect in comparison with the misnomer micropapillary.

Related: MUC1 gene

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