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).

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

Related: USA

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

Related: Monoclonal Antibodies Panitumumab (Vectibix) Cetuximab (Erbitux)

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

Related: Stomach Cancer Gastric Cancer

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

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

Related: Breast Cancer Prostate Cancer USA

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

Related: CTNNB1 gene TERT

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

Related: Fluorouracil Leucovorin Irinotecan

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

Related: Cancer Screening and Early Detection

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

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

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

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

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

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

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

Related: KRAS gene EGFR

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

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

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

Related: Cancer Screening and Early Detection

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

Related: KRAS gene

Asl JM, Almasi S, Tabatabaiefar MA
High frequency of BRAF proto-oncogene hot spot mutation V600E in cohort of colorectal cancer patients from Ahvaz City, southwest Iran.
Pak J Biol Sci. 2014; 17(4):565-9 [PubMed] Related Publications
Colorectal cancer (CRC) is one of the most common forms of cancer around the world. Sporadic CRCs are caused by accumulation of mutations in essential genes regulating normal proliferation and differentiation of cells. The proto-oncogene BRAF encoded by the BRAF gene is involved in the RAS/RAF/MAPK pathway of signal transduction during cell growth. Acquired mutations in BRAF have been found at high frequencies in adult patients with papillary thyroid carcinoma and sporadic CRC. One of the predominant hot spot point mutations is T1799A (V600E) mutation among a cohort of CRC patients from Ahvaz city, southwest Iran. The aim of this study was to estimate the frequency of V600E mutation in CRC patients from Ahvaz city, southwest Iran. We analyzed exon 15 of the BRAF gene in isolated DNA from 80 Formalin Fixed Paraffin-embedded (FFPE) CRC tumor tissues using PCR-RFLP method. Data were analyzed using SPSS statistical program. According to our results 37 out of 80 cases (46.25%) were heterozygous for the mutation while the remaining 43 cases (53.75%) had normal homozygous genotype. No homozygous mutant genotype was found. Based on our findings, the frequency of V600E mutation appears to be significantly increased among CRC patients of the studied population but there was no significant relationship between genotypes and age and sex. In conclusion, these findings might prove the effect of V600E mutation on CRC pathogenesis. However, the exact effect of the mutation in CRC progression requires further work.

Related: BRAF

Liu Y, Zhang X, Han C, et al.
TP53 loss creates therapeutic vulnerability in colorectal cancer.
Nature. 2015; 520(7549):697-701 [PubMed] Article available free on PMC after 30/10/2015 Related Publications
TP53, a well-known tumour suppressor gene that encodes p53, is frequently inactivated by mutation or deletion in most human tumours. A tremendous effort has been made to restore p53 activity in cancer therapies. However, no effective p53-based therapy has been successfully translated into clinical cancer treatment owing to the complexity of p53 signalling. Here we demonstrate that genomic deletion of TP53 frequently encompasses essential neighbouring genes, rendering cancer cells with hemizygous TP53 deletion vulnerable to further suppression of such genes. POLR2A is identified as such a gene that is almost always co-deleted with TP53 in human cancers. It encodes the largest and catalytic subunit of the RNA polymerase II complex, which is specifically inhibited by α-amanitin. Our analysis of The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases reveals that POLR2A expression levels are tightly correlated with its gene copy numbers in human colorectal cancer. Suppression of POLR2A with α-amanitin or small interfering RNAs selectively inhibits the proliferation, survival and tumorigenic potential of colorectal cancer cells with hemizygous TP53 loss in a p53-independent manner. Previous clinical applications of α-amanitin have been limited owing to its liver toxicity. However, we found that α-amanitin-based antibody-drug conjugates are highly effective therapeutic agents with reduced toxicity. Here we show that low doses of α-amanitin-conjugated anti-epithelial cell adhesion molecule (EpCAM) antibody lead to complete tumour regression in mouse models of human colorectal cancer with hemizygous deletion of POLR2A. We anticipate that inhibiting POLR2A will be a new therapeutic approach for human cancers containing such common genomic alterations.

Related: TP53

Tang V, Boscardin WJ, Stijacic-Cenzer I, Lee SJ
Time to benefit for colorectal cancer screening: survival meta-analysis of flexible sigmoidoscopy trials.
BMJ. 2015; 350:h1662 [PubMed] Article available free on PMC after 30/10/2015 Related Publications
OBJECTIVE: To determine the time to benefit of using flexible sigmoidoscopy for colorectal cancer screening.
DESIGN: Survival meta-analysis.
DATA SOURCES: A Cochrane Collaboration systematic review published in 2013, Medline, and Cochrane Library databases.
ELIGIBILITY CRITERIA: Randomized controlled trials comparing screening flexible sigmoidoscopy with no screening. Trials with fewer than 100 flexible sigmoidoscopy screenings were excluded.
RESULTS: Four studies were eligible (total n = 459,814). They were similar for patients' age (50-74 years), length of follow-up (11.2-11.9 years), and relative risk for colorectal cancer related mortality (0.69-0.78 with flexible sigmoidoscopy screening). For every 1000 people screened at five and 10 years, 0.3 and 1.2 colorectal cancer related deaths, respectively, were prevented. It took 4.3 years (95% confidence interval 2.8 to 5.8) to observe an absolute risk reduction of 0.0002 (one colorectal cancer related death prevented for every 5000 flexible sigmoidoscopy screenings). It took 9.4 years (7.6 to 11.3) to observe an absolute risk reduction of 0.001 (one colorectal cancer related death prevented for every 1000 flexible sigmoidoscopy screenings).
CONCLUSION: Our findings suggest that screening flexible sigmoidoscopy is most appropriate for older adults with a life expectancy greater than approximately 10 years.

Related: Cancer Screening and Early Detection

Simkens LH, van Tinteren H, May A, et al.
Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group.
Lancet. 2015; 385(9980):1843-52 [PubMed] Related Publications
BACKGROUND: The optimum duration of first-line treatment with chemotherapy in combination with bevacizumab in patients with metastatic colorectal cancer is unknown. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation.
METHODS: In this open-label, phase 3, randomised controlled trial, we recruited patients in 64 hospitals in the Netherlands. We included patients older than 18 years with previously untreated metastatic colorectal cancer, with stable disease or better after induction treatment with six 3-weekly cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B), WHO performance status of 0 or 1, and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) to either maintenance treatment with capecitabine and bevacizumab (maintenance group) or observation (observation group). Randomisation was done centrally by minimisation, with stratification according to previous adjuvant chemotherapy, response to induction treatment, WHO performance status, serum lactate dehydrogenase concentration, and treatment centre. Both patients and investigators were aware of treatment assignment. We assessed disease status every 9 weeks. On first progression (defined as PFS1), patients in both groups were to receive the induction regimen of CAPOX-B until second progression (PFS2), which was the study's primary endpoint. All endpoints were calculated from the time of randomisation. Analyses were done by intention to treat. This trial is registered with, number NCT00442637.
FINDINGS: Between May 30, 2007, and Oct 15, 2012, we randomly assigned 558 patients to either the maintenance group (n=279) or the observation group (n=279). Median follow-up was 48 months (IQR 36-57). The primary endpoint of median PFS2 was significantly improved in patients on maintenance treatment, and was 8·5 months in the observation group and 11·7 months in the maintenance group (HR 0·67, 95% CI 0·56-0·81, p<0·0001). This difference remained significant when any treatment after PFS1 was considered. Maintenance treatment was well tolerated, although the incidence of hand-foot syndrome was increased (64 [23%] patients with hand-foot skin reaction during maintenance). The global quality of life did not deteriorate during maintenance treatment and was clinically not different between treatment groups.
INTERPRETATION: Maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer is effective and does not compromise quality of life.
FUNDING: Dutch Colorectal Cancer Group (DCCG). The DCCG received financial support for the study from the Commissie Klinische Studies (CKS) of the Dutch Cancer Foundation (KWF), Roche, and Sanofi-Aventis.

Related: Fluorouracil Oxaliplatin Bevacizumab (Avastin) Capecitabine

Huang LC, Tran TB, Ma Y, et al.
Factors that influence minority use of high-volume hospitals for colorectal cancer care.
Dis Colon Rectum. 2015; 58(5):526-32 [PubMed] Article available free on PMC after 01/05/2016 Related Publications
BACKGROUND: Previous studies suggest that minorities cluster in low-quality hospitals despite living close to better performing hospitals. This may contribute to persistent disparities in cancer outcomes.
OBJECTIVE: The purpose of this work was to examine how travel distance, insurance status, and neighborhood socioeconomic factors influenced minority underuse of high-volume hospitals for colorectal cancer.
DESIGN: The study was a retrospective, cross-sectional, population-based study.
SETTINGS: All hospitals in California from 1996 to 2006 were included.
PATIENTS: Patients with colorectal cancer diagnosed and treated in California between 1996 and 2006 were identified using California Cancer Registry data.
MAIN OUTCOME MEASURES: Multivariable logistic regression models predicting high-volume hospital use were adjusted for age, sex, race, stage, comorbidities, insurance status, and neighborhood socioeconomic factors.
RESULTS: A total of 79,231 patients treated in 417 hospitals were included in the study. High-volume hospitals were independently associated with an 8% decrease in the hazard of death compared with other settings. A lower proportion of minorities used high-volume hospitals despite a higher proportion living nearby. Although insurance status and socioeconomic factors were independently associated with high-volume hospital use, only socioeconomic factors attenuated differences in high-volume hospital use of black and Hispanic patients compared with white patients.
LIMITATIONS: The use of cross-sectional data and racial and ethnic misclassifications were limitations in this study.
CONCLUSIONS: Minority patients do not use high-volume hospitals despite improved outcomes and geographic access. Low socioeconomic status predicts low use of high-volume settings in select minority groups. Our results provide a roadmap for developing interventions to increase the use of and access to higher quality care and outcomes. Increasing minority use of high-volume hospitals may require community outreach programs and changes in physician referral practices.

Chandra A, Mishra B, Kumar S, et al.
Dynamic article: composite antropyloric valve and gracilis muscle transposition for total anorectal reconstruction: a preliminary report.
Dis Colon Rectum. 2015; 58(5):508-16 [PubMed] Related Publications
BACKGROUND: Technique and functional outcomes of anorectal reconstruction using an antropyloric graft have been reported previously. This technique had reasonable initial outcomes but lacked voluntary function.
OBJECTIVE: We hereby report the initial results of patients who underwent gracilis muscle wrapping around the perineally transposed antropyloric valve in an attempt to improve voluntary fecal control.
SETTING: This study was conducted at a single tertiary care institution.
PATIENTS: Eight adult patients (7 men and 1 woman) with a median age of 38 years (range, 19-51 years) underwent this procedure. Seven patients already had anorectal reconstruction with a transposed antropyloric valve, and 1 patient with severely damaged anal sphincter complex underwent single-stage composite antropylorus transposition with a gracilis muscle wrap.
MAIN OUTCOME MEASURES: The primary outcome measures were anatomical integrity and functional status of the composite graft in the perineum.
RESULTS: No operative mortality or serious procedure-related morbidity occurred in any patient. The median postoperative resting pressure was 29 mmHg (range, 22-38 mmHg) and squeeze pressure was 72.5 mmHg (range, 45-267 mmHg). There was a significant improvement in the squeeze pressure following surgery (p = 0.039). Also, the St. Mark's incontinence scores significantly improved in all patients and varied between 7 and 9 (p = 0.003). The ability to defer defecation and the reduced frequency of leakage accidents were the prime reasons for improved postgraciloplasty outcomes in these patients. On personal interviews, all patients who underwent this procedure were satisfied with the results of their surgery.
LIMITATIONS: A longer follow-up with a larger sample size is required. Quality-of-life data have not been evaluated in this study.
CONCLUSIONS: Gracilis muscle wrapping around a perineally transposed antropyloric valve is possible and improves the voluntary control and overall functional outcomes in a select group of patients with end-stage fecal incontinence requiring anal replacement (Supplemental Digital Content 1,

Lange EO, Jensen CC, Melton GB, et al.
Relationship between model for end-stage liver disease score and 30-day outcomes for patients undergoing elective colorectal resections: an American college of surgeons-national surgical quality improvement program study.
Dis Colon Rectum. 2015; 58(5):494-501 [PubMed] Related Publications
BACKGROUND: Patients with liver disease face significant risk of complications and death when considering elective colorectal resection for benign or malignant indications.
OBJECTIVE: We sought to determine the relationship between Model of End-Stage Liver Disease score and 30-day outcomes in patients undergoing elective colorectal resections.
DESIGN: This was a retrospective cohort study.
SETTINGS: The study included hospitals participating in the National Surgical Quality Improvement Program.
PATIENTS: Adult patients who underwent elective colorectal resection from 2005 to 2011 were identified from the National Surgical Quality Improvement Program database. Patients missing laboratory values necessary to calculate the Model of End-Stage Liver Disease score were excluded (61% of 81,346 patients identified).
MAIN OUTCOME MEASURES: Differences in patient- and disease-related characteristics by Model of End-Stage Liver Disease categories were assessed with χ analyses. Thirty-day mortality and major morbidity were examined using logistic regression.
RESULTS: Of 31,950 patients undergoing elective colorectal resections (14% including proctectomy), most (60%) were performed for colon or rectal cancer; other benign indications included diverticulitis (20%), polyp (10%), and IBD (10%). A total of 58% of patients had a Model of End-Stage Liver Disease score of ≥7. Increasing scores were associated with older age; higher BMI; higher ASA class; lower albumin level; and higher incidence of diabetes mellitus, pulmonary and cardiac disease, hypertension, and dependent functional status. In univariate analysis, patients with higher scores had a greater risk of 30-day mortality (score = 6 (0.69%); 7-11 (1.62%); 11-15 (4.52%); >15, (5.01%); p < 0.0001). After controlling for other comorbidities, Model of End-Stage Liver Disease score remained a significant predictor of 30-day mortality, major complications, and respiratory complications.
LIMITATIONS: This was a retrospective analysis of administrative data, limiting some access to clinically relevant data.
CONCLUSIONS: Consistent with previous reports, patients with higher Model of End-Stage Liver Disease scores have a significantly higher risk of death and major morbidity in the 30 days after elective colorectal resection (see Video, Supplemental Digital Content,

Maya AM, Boutros M, DaSilva G, Wexner SD
IPAA-related sepsis significantly increases morbidity of ileoanal pouch excision.
Dis Colon Rectum. 2015; 58(5):488-93 [PubMed] Related Publications
BACKGROUND: Perineal wound complications after ileoanal pouch excision remain a significant cause of morbidity.
OBJECTIVE: The purpose of this work was to describe the incidence, outcomes, and predictors of perineal wound complications after pouch excision.
DESIGN: This was a retrospective medical chart review.
SETTINGS: The study was conducted in a single clinical institution.
PATIENTS: Patients who underwent pouch excision at our institution from July 1992 through July 2012 were identified. Patient and perioperative variables were reviewed. Multivariate and univariate analyses were undertaken.
MAIN OUTCOME MEASURES: Perineal wound (including perineal wound infection and persistent perineal sinus [nonhealing by 6 months]) and perineal hernia were measured.
RESULTS: A total of 47 patients (mean age, 46 years; 42.6% men) with familial adenomatous polyposis (10.6%), mucosal ulcerative colitis (61.7%), or Crohn's disease (27.7%) underwent pouch excision, including 36.2% for IPAA-related sepsis (presacral abscess; perineal-, sacral-, or pouch-vaginal fistula; and anastomotic defect), 44.7% for pouch dysfunction, 10.6% for refractory pouchitis, and 8.5% for neoplasia. Fourteen (29.8%) developed perineal wound complications, including 100% perineal wound infection, 28.6% persistent perineal sinus, and 7.1% perineal hernia. Perineal wound infection was associated with delayed healing (>6 weeks; 71.4% vs 24.2%; p = 0.002) and IPAA-related sepsis (28.6% vs 0%; p = 0.001). Patients with and without perineal wound complications were similar in age, diagnoses, fecal diversion, immunosuppression, comorbid conditions, nutrition, and surgical variables. Most patients underwent intersphincteric dissection (87.2%) with primary perineal closure (97.0%). Perineal wound complications were significantly associated with IPAA-related sepsis as an indication for pouch excision (57.1% vs 27.2%; p = 0.05), intraoperative pouch perforation (35.7% vs 9.1%, p =0.03), and smoking (21.4% vs 3.0%; p = 0.04). IPAA-related sepsis and a current smoking status (OR, 19.3 [95% CI, 1.8 -488.1]) are significant independent predictors on multivariate logistic regression (OR, 6.4 [95% CI, 1.4-30.2]) of perineal wound complications. All of the patients with persistent perineal sinus achieved successful healing at a median of 734 days (range, 363-2182 days), requiring a median of 1.5 procedures.
LIMITATIONS: This was a single-center retrospective review with a small sample size.
CONCLUSIONS: Preoperative IPAA-related sepsis and current smoking are significant risk factors for perineal wound complications after pouch excision.

Related: Familial Adenomatous Polyposis (FAP)

Beppu N, Matsubara N, Kakuno A, et al.
Feasibility of modified short-course radiotherapy combined with a chemoradiosensitizer for T3 rectal cancer.
Dis Colon Rectum. 2015; 58(5):479-87 [PubMed] Related Publications
BACKGROUND: 5-Fluorouracil-based chemotherapy is considered to be a radiosensitizer; however, conventional short-course radiotherapy combined with chemotherapy is generally thought to not be feasible because of the prevalence of side effects.
OBJECTIVE: The aim of this study was to evaluate the feasibility of modified short-course radiotherapy combined with a chemoradiosensitizer for T3 rectal cancer.
DESIGN AND SETTINGS: This study was retrospective in nature and used a prospectively collected database.
PATIENTS: Patients with T3 rectal cancer located below the peritoneum reflection were selected.
INTERVENTIONS: A total dose of 25 Gy of radiotherapy was administered in 10 fractions of 2.5 Gy each for 5 days. Radiotherapy was performed with S-1 as a radiosensitizer from day 1 to day 10. Surgery was targeted to be performed 4 weeks after radiotherapy.
MAIN OUTCOME MEASUREMENTS: The morbidity, sphincter-preserving rate, anal function, and long-term outcomes were assessed.
RESULTS: All patients (n = 170) completed the radiotherapy regimen and 166 (97.6%) completed the combination regimen with chemotherapy. A total of 149 patients (87.6%) had sphincter-preserving surgery (double stapling technique (DST), 58 patients; intersphincteric resection (ISR), 91 patients), and postoperative complications were relatively mild (anastomotic leakage, 15.4%; intra-abdominal infection, 8.2%). Among those undergoing sphincter preserving surgery, the 5-year local relapse-free survival rate was 94.3% in the DST group, and 89.8% in the ISR group. With respect to the anal function, the Wexner score the first year after stoma closure for the double-stapling technique group was 6 and that for intersphincteric resection was 15; however, the score for the intersphincteric resection group was improved to 8 at 4 years after stoma closure.
LIMITATIONS: This study had limitations because it was an uncontrolled, 1-arm, retrospective review with a small sample size.
CONCLUSIONS: Modified short-course radiotherapy combined with chemoradiosensitizer is a feasible approach for treating T3 rectal cancer. With the use of the short-course approach, efforts to reduce the incidence of side effects by appropriately prolonging the waiting period enable the administration of combination treatment with short-course radiotherapy and chemotherapy.

Related: Tegafur-uracil

Tawadros PS, Paquette IM, Hanly AM, et al.
Adenocarcinoma of the rectum in patients under age 40 is increasing: impact of signet-ring cell histology.
Dis Colon Rectum. 2015; 58(5):474-8 [PubMed] Related Publications
BACKGROUND: Overall, the incidence of colorectal cancer appears to be stable or diminishing. However, based on our practice pattern, we observed that the incidence of rectal cancer in patients under 40 is increasing and may be associated with a prominence of signet-ring cell histology.
OBJECTIVE: The aim of this study was to verify the rising trend in rectal cancer in patients under 40 and describe the histology prominent in that cohort.
DESIGN: This is a retrospective cohort study.
SETTING AND PATIENTS: We performed a retrospective cohort study of all patients diagnosed with rectal adenocarcinoma from 1980 to 2010 using the Surveillance, Epidemiology, and End Results cancer registry.
MAIN OUTCOME MEASURES: Rectal cancer incidence, histology, and associated staging characteristics were the primary outcomes measured.
RESULTS: Although the incidence of rectal cancer for all ages remained stable from 1980 to 2010, we observed an annual percent change of +3.6% in the incidence of rectal cancer in patients under 40. The prevalence of signet cell histology in patients under 40 was significantly greater than in patients over 40 (3% vs 0.87%, p < 0.01). A multivariate regression analysis revealed an adjusted odds ratio of 3.6 (95% CI, 2.6-5.1) for signet cell histology in rectal adenocarcinoma under age 40. Signet cell histology was also significantly associated with a more advanced stage at presentation, poorly differentiated tumor grade, and worse prognosis compared with mucinous and nonmucinous rectal adenocarcinoma.
LIMITATIONS: The study was limited by its retrospective nature and the information available in the Surveillance, Epidemiology, and End Results database.
CONCLUSIONS: Despite a stable incidence of rectal cancer for all ages, the incidence in patients under 40 has quadrupled since 1980, and cancers in this group are 3.6 times more likely to have signet cell histology. Given the worse outcomes associated with signet cell histology, these data highlight a need for thorough evaluation of young patients with rectal symptoms.

Related: USA

Fernández-Esparrach G, Alberghina N, Subtil JC, et al.
Endoscopic ultrasound-guided fine needle aspiration is highly accurate for the diagnosis of perirectal recurrence of colorectal cancer.
Dis Colon Rectum. 2015; 58(5):469-73 [PubMed] Related Publications
BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration is highly accurate for the diagnosis of malignancies surrounding the gastrointestinal tract. There is a lack of information on the usefulness of this technique in the diagnosis of colorectal cancer recurrence.
OBJECTIVE: The purpose of this work was to investigate the performance characteristics of endoscopic ultrasound-guided fine needle aspiration for the cytologic diagnosis of perirectal recurrence of colorectal cancer.
DESIGN: This was a retrospective study on the clinical and radiologic suspicion of perirectal recurrence of colorectal cancer.
SETTINGS: The study was conducted at 4 tertiary hospitals.
PATIENTS: Consecutive patients with suspicion of perirectal recurrence of colorectal cancer undergoing endoscopic ultrasound-guided fine needle aspiration between 2000 and 2013 were included in this study.
INTERVENTIONS: The study intervention was endoscopic ultrasound-guided fine needle aspiration.
MAIN OUTCOME MEASURES: Endoscopic ultrasound-guided fine needle aspiration performance characteristics and outcome (malignant or benign) were analyzed. The gold standard was cytologic results if malignancy or follow-up if benignity.
RESULTS: A total of 58 patients were included (32 men; mean age, 64.2 ± 10.0 years [range, 44-88 years]). The location of the initial neoplasm was the rectum for 42 patients and the colon for 16 patients. Endoscopic ultrasound findings included a mass in the anastomosis (n = 8), perirectal fat (n = 23), lymph nodes (n = 20), or asymmetric thickness of the rectal wall (n = 6). Cytology showed malignancy in 38 patients (67%), benign features in 17 (30%), and was not evaluable in 2. Mean follow-up to confirm a benign outcome was 51.3 ± 30.3 months (range, 5.2-180.0 months). Final outcome was recurrence in 40 patients (69%) and benignity in 18 patients (31%). Performance characteristics of endoscopic ultrasound-guided fine needle aspiration were sensitivity (97%), specificity (100%), positive predictive value (100%), negative predictive value (94%), and accuracy (98%). In the intention to diagnose analysis, the corresponding values were 95%, 100%, 100%, 90%, and 96%.
LIMITATIONS: This was a retrospective series with a limited number of patients.
CONCLUSIONS: Endoscopic ultrasound-guided fine needle aspiration is a highly accurate tool for the cytologic diagnosis of perirectal recurrence in patients with previous colorectal cancer.

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