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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Information Patients and the Public (18 links)

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Herdiatry Colorectal Cancers (5 links)

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

Latest Research Publications

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

Homayounfar K, Bleckmann A, Helms HJ, et al.
Discrepancies between medical oncologists and surgeons in assessment of resectability and indication for chemotherapy in patients with colorectal liver metastases.
Br J Surg. 2014; 101(5):550-7 [PubMed] Related Publications
BACKGROUND: Multidisciplinary discussion of the treatment of patients with colorectal liver metastases (CRLM) is advocated currently. The aim of this study was to investigate medical oncologists' and surgeons' assessment of resectability and indication for chemotherapy, and the effect of an educational intervention on such assessment.
METHODS: Medical histories of 30 patients with CRLM were presented to ten experienced medical oncologists and 11 surgeons at an initial virtual tumour board meeting (TB1). Treatment recommendations were obtained from each participant by voting for standardized answers. Following lectures on the potential of chemotherapy and surgery, assessment was repeated at a second virtual tumour board meeting (TB2), using the same patients and participants.
RESULTS: Overall, 630 answers (21 × 30) were obtained per tumour board meeting. At TB1, resectability was expected more frequently by surgeons. Participants changed 56·8 per cent of their individual answers at TB2. Assessment shifted from potentially resectable to resectable CRLM in 81 of 161 and from unresectable to (potentially) resectable CRLM in 29 of 36 answers. Preoperative chemotherapy was indicated more often by medical oncologists, and overall was included in 260 answers (41·3 per cent) at TB1, compared with only 171 answers (27·1 per cent) at TB2. Medical oncologists more often changed their decision to primary resection in resectable patients (P = 0·006). Postoperative chemotherapy was included in 51·9 and 52·4 per cent of all answers at TB1 and TB2 respectively, with no difference in changes between medical oncologists and surgeons (P = 0·980).
CONCLUSION: Resectability and indication for preoperative chemotherapy were assessed differently by medical oncologists and surgeons. The educational intervention resulted in more patients deemed resectable by both oncologists and surgeons, and less frequent indication for chemotherapy.

Ye HM, Lu YZ, Liang XM, et al.
Clinical significance of combined testing of YKL-40 with CEA in Chinese colorectal cancer patients.
Clin Lab. 2014; 60(3):397-405 [PubMed] Related Publications
BACKGROUND: To investigate the practical value of individual and combined testing of plasma levels of YKL-40, CEA, and CA199 for auxiliary diagnosis and detection of recurrence of colorectal cancer.
METHODS: ELISA and ECLIA were used to evaluate levels of YKL-40, CEA, and CA199 in 120 colorectal cancer patients (56 initial-diagnosis, 42 post-operative, and 22 recurrent cases). Forty-three patients with benign colorectal disease and 36 healthy patients were enrolled as controls. The relationship between YKL-40 and clinical indicators of tumor pathology was analyzed. The positive rate and diagnostic efficacy of single and combined YKL-40, CEA, and CA199 testing were assessed in patients with colorectal cancer.
RESULTS: Plasma YKL-40 in the cancer group was significantly higher than in the benign control and healthy control group, and the mean values were 145.4 ng/mL, 107.7 ng/mL, and 51.3 ng/mL (p < 0.05), respectively. With 72 ng/mL as the diagnostic threshold, the sensitivity and specificity of YKL-40 in colorectal cancer diagnosis were found to be 73.2% and 66.7%, respectively. Early-stage colorectal cancer patients showed a YKL-40 positive rate (73%) significantly higher than those of CEA and CA199 (50% and 32%, respectively; p < 0.05). When YKL-40 testing was combined with CEA or CA199, the positive rate increased to 82.1% and 80.3%, respectively. Through ROC curve analysis of the post-operative recurrent group against the non-recurrent group, the areas under the curve for YKL-40, CEA, and CA199 were found to be 0.907, 0.714, and 0.759, respectively. Based on the Dukes classification, the mean YKL-40 value for stages A/B, C, and D were 120.1 ng/mL, 131.7 ng/mL, and 226.8 ng/mL (p = 0.008), respectively. The plasma YKL-40 level gradually increased as the disease progressed. Lower degrees of tumor differentiation were correlated with higher YKL-40 levels. The mean YKL-40 values of high, medium, and low tumor differentiation groups were 96.8 ng/mL, 127.5 ng/mL, and 225.7 ng/mL (p = 0.004), respectively.
CONCLUSIONS: The benefits of using YKL-40 testing are higher than CEA and CA199 for the monitoring of colorectal cancer recurrence. Combined testing of both YKL-40 and CEA was found to be optimal for auxiliary diagnosis of colorectal cancer. Plasma YKL-40 was found to be suitable for auxiliary diagnosis of colorectal cancer.

Corley DA, Jensen CD, Marks AR, et al.
Adenoma detection rate and risk of colorectal cancer and death.
N Engl J Med. 2014; 370(14):1298-306 [PubMed] Related Publications
BACKGROUND: The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients' risks of a subsequent colorectal cancer (interval cancer) and death.
METHODS: Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions.
RESULTS: We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval [CI], 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98).
CONCLUSIONS: The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente Community Benefit program and the National Cancer Institute.).

Related: USA

Yalcin AD, Kargi A, Gumuslu S, Strauss LG
Blood eosinophil and platelet levels, proteomics patterns of trail and CXCL8 correlated with survival in bevacizumab treated metastatic colon cancers.
Clin Lab. 2014; 60(2):339-40 [PubMed] Related Publications
STrail (soluble TNF-related apoptosis-inducing-ligand) has also been observed where the cytotoxic effects of antiangiogenic agents are increased in clinical phase II and III studies when these agents are combined with TRAIL related therapies. Recent studies have shown that CXCL8 and its receptors are significantly up-regulated in CRC and act as regulators of proliferation, angiogenesis, and metastasis. sTRAIL, CXCL8, CEA, together with complete blood count parameters (hemoglobine, platelet, eosinophil, basophil, neutrophil, lymphocyte) were recorded in the beginning and every three months afterwards for a period of 4 years. The study population comprised 21 of the 42 patients with metastatic colorectal cancer (MCRC), undergoing 18 FDG-PET/CT scanning prior to treatment. Progression free survival was 262 days and overall survival was 1148 days. Overall survival was higher in patients whose Karnofsky Performance scores were above 86% (p = 0.003). Progression free survival was higher in patients whose blood eosinophil counts at 0, 6, and 9 months were higher than the mean levels of corresponding values (p-values are 0.016, 0.032, and 0.001, respectively). Another significant positive correlation was found between the platelet levels at 9 months and progression free survival (p = 0.019). There were significant changes (p < 0.05) prior to treatment and three months later for sTRAIL (p = 0.0060) and CXCL8 (p = 0.00001), based on the Wilcoxon matched pairs signed rank test. Generally, sTRAIL values increased during therapy, while a decrease was observed for CXCL8 without any significant differences for other variables.

Related: Bevacizumab (Avastin)

Lee JK, Liles EG, Bent S, et al.
Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.
Ann Intern Med. 2014; 160(3):171 [PubMed] Related Publications
BACKGROUND: Performance characteristics of fecal immunochemical tests (FITs) to screen for colorectal cancer (CRC) have been inconsistent.
PURPOSE: To synthesize data about the diagnostic accuracy of FITs for CRC and identify factors affecting its performance characteristics.
DATA SOURCES: Online databases, including MEDLINE and EMBASE, and bibliographies of included studies from 1996 to 2013.
STUDY SELECTION: All studies evaluating the diagnostic accuracy of FITs for CRC in asymptomatic, average-risk adults.
DATA EXTRACTION: Two reviewers independently extracted data and critiqued study quality.
DATA SYNTHESIS: Nineteen eligible studies were included and meta-analyzed. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FITs for CRC were 0.79 (95% CI, 0.69 to 0.86), 0.94 (CI, 0.92 to 0.95), 13.10 (CI, 10.49 to 16.35), 0.23 (CI, 0.15 to 0.33), respectively, with an overall diagnostic accuracy of 95% (CI, 93% to 97%). There was substantial heterogeneity between studies in both the pooled sensitivity and specificity estimates. Stratifying by cutoff value for a positive test result or removal of discontinued FIT brands resulted in homogeneous sensitivity estimates. Sensitivity for CRC improved with lower assay cutoff values for a positive test result (for example, 0.89 [CI, 0.80 to 0.95] at a cutoff value less than 20 µg/g vs. 0.70 [CI, 0.55 to 0.81] at cutoff values of 20 to 50 µg/g) but with a corresponding decrease in specificity. A single-sample FIT had similar sensitivity and specificity as several samples, independent of FIT brand.
LIMITATIONS: Only English-language articles were included. Lack of data prevented complete subgroup analyses by FIT brand.
CONCLUSION: Fecal immunochemical tests are moderately sensitive, are highly specific, and have high overall diagnostic accuracy for detecting CRC. Diagnostic performance of FITs depends on the cutoff value for a positive test result.
PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Cancer Institute.

Related: Cancer Screening and Early Detection

Imperiale TF, Ransohoff DF, Itzkowitz SH, et al.
Multitarget stool DNA testing for colorectal-cancer screening.
N Engl J Med. 2014; 370(14):1287-97 [PubMed] Related Publications
BACKGROUND: An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening.
METHODS: We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings.
RESULTS: Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.
CONCLUSIONS: In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; number, NCT01397747.).

Related: Cancer Screening and Early Detection KRAS gene

Sultan R, Chawla T, Zaidi M
Factors affecting anastomotic leak after colorectal anastomosis in patients without protective stoma in tertiary care hospital.
J Pak Med Assoc. 2014; 64(2):166-70 [PubMed] Related Publications
OBJECTIVE: To determine the factors associated with clinically significant anastomotic leak in patients having undergone large intestinal anastomosis.
METHOD: The retrospective study at the Aga Khan University Hospital, Karachi, comprised data between January 2000 and March 2010, related to patients who underwent colorectal anastomosis. Demographic details of the patients, as well as preop, intraop and postop risk factors were recorded. Anastomotic leak was identified as per the defined criteria. Outcome of patients was recorded as postop hospital stay and mortality. Univariate and Multivariate analyses were applied to identify risk factors for anastomotic leakage.
RESULTS: Among the total 127 patients in the study, anastomotic leak occurred in 19 (15%) patients (Group 1), while there was no clinical leak in 108 (85%) patients (Group 2). Univariate analysis showed 8 factors to be affecting the anastomotic leak: operation time (p = 0.003), intraoperative blood loss (p = 0.006), intraoperative blood transfusion (p = 0.013), indication of surgery malignancy vs. benign (p = 0.049), type of surgery elective vs. emergency (p = 0.037), intraop use of vasopressor (p = 0.019), segment of bowel anastomosed left side vs. right side (p = 0.012), and drain placement vs. no drain placed (p = 0.035). Preop immunosuppressive therapy was borderline significant (p = 0.089). Multivariate analysis showed that left vs. right sided anastomosis (p = 0.068), blood transfusion > 2 pack cells (p = 0.028), smoker vs. non-smoker (p = 0.049), elective vs. emergency surgery (p = 0.012) were the independent risk factors which significantly affected the outcome of bowel anastomosis. Mortality rate was 15.79% (n = 3/19) in Group 1, while it was 1.85% (n = 2/108) in Group 2 (p = 0.02).The postop hospital stay was 15 +/- 5.44 days in Group 1, while it was 7.51 +/- 4.04 days in Group 2 (p > 0.001).
CONCLUSION: In colorectal anastomotic surgeries temporary diversion stoma formation needs to be considered on the basis of risk factors to decrease mortality and morbidity associated with anastomotic leak.

Gershtein ES, Korotkova EA, Prorokov VV, Kushlinskii NE
Tumor associated proteases -- prognostic markers of colorectal cancer.
Klin Lab Diagn. 2013; (10):43-7, 5-10 [PubMed] Related Publications
Associations between matrix metalloproteinase (MMP) 2, 7, 9, tissue MMP inhibitor TIMP- I and plasminogen activation system components (uPA, tPA and PAl-1) plasma and/or tumor levels in colorectal cancer (CRC) patients were evaluated in order to reveal their potential clinical implications. Two groups of CRC patients monitored for 5 or 10 years were enclosed in the study. Earlier, corresponding markers 'levels were measured in their plasma and/or tumors by immunoenzymatic techniques. High tumor PAl-I (> or =1 4,0 ng/mg protein) was demonstrated to be a significant, but not independent unfavorable prognostic factor for 5 and I10 years overall survival. Its role was mostly pronounced in stage II1 patients. High preoperative plasma MMP-7 and TIMP-I levels (cut-offs - 4,0 and 347 ng/ml respectively) were shown to be independent unfavorable prognostic factors, and univariate analysis revealed unfavorable prognostic value of high tumor MMP-7 content (> or =7,8 ng/mg protein) in patients with disseminated process.

Related: TIMP1

Paeck KH, Heo WJ, Park DI, et al.
Colonoscopy scheduling influences adenoma and polyp detection rates.
Hepatogastroenterology. 2013; 60(127):1647-52 [PubMed] Related Publications
BACKGROUND/AIMS: Because colonoscopy can be a technically challenging procedure, endoscopist fatigue, which usually increases as day progresses, may impact procedural performance. The aim of this study was to determine the influence of colonoscopy scheduling on adenoma and polyp detection rates (ADR and PDR, respectively).
METHODOLOGY: This was a retrospective study of data prospectively collected on 1,293 consecutive, asymptomatic, average-risk patients. Three separate timing variables were assessed, as follows: morning vs. afternoon procedures; start times throughout the day; and four groups by matching each subsequent passing hour in the morning and afternoon sessions.
RESULTS: 420 (32%) were performed in the morning and 881 (68%) were performed in the afternoon. There was a significantly higher ADR and PDR in the morning colonoscopies compared to the afternoon colonoscopies (42.3% vs. 34.7% [po=0.008] and 52.5% vs. 46.3% [p=0.038], respectively). Based on multivariable analysis, afternoon colonoscopies and colonoscopies performed during 4th hour of session were significantly associated with a decreased ADR (OR, 0.739 [0.576-0.949], p=0.018; and OR, 0.651 [0.443-0.975], p=0.029).
CONCLUSIONS: Colonoscopies scheduled in the morning have a significantly higher ADR and PDR as compared to colonoscopies scheduled in the afternoon. Also,colonoscopies performed during 4th hour of the session were associated with decreased ADR.

Wang S, Bao Z, Liang QM, et al.
Octreotide stimulates somatostatin receptor-induced apoptosis of SW480 colon cancer cells by activation of glycogen synthase kinase-3β, A Wnt/β-catenin pathway modulator.
Hepatogastroenterology. 2013; 60(127):1639-46 [PubMed] Related Publications
BACKGROUND/AIMS: Peptide hormone somatostatin and its receptors (SSTRs) have a wide range of physiological functions and play a role in the treatment of numerous human diseases, including colorectal cancer. Octreotide, a somatostatin-analog peptide, inhibits growth of colonic cancer SW480 cells through Wnt/β-catenin pathway modulation. However, the specific octreotide-stimulating SSTR subtypes and the signal-transduction mechanism responsible for the negative regulation of Wnt/β-catenin pathway by octreotide have not been fully elucidated.
METHODOLOGY: Octreotide-induced apoptosis in SW480 colon cancer cells mediated by SSTR2,SSTR5-dependent regulation of the Wnt/β-catenin pathway components GSK-3β and β-catenin was investigated. Cell apoptosis of SW480 cells was measured by apoptosis-DNA ladder assay. SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 mRNA expression levels were confirmed by RT-PCR; β-catenin, TCF-4, cyclin D1, c-Myc, and GSK-3β protein levels were examined by Western blot. The distribution of β-catenin in the cell was analyzed with immunocytochemistry.
RESULTS: Octreotide treatment increased SSTR2,SSTR5-induced apoptosis of SW480 colon cancer cells, promoted the plasma membrane accumulation of β-catenin, inactivated T-cell factor-dependent transcription, and downregulated Wnt target genes cyclin D1 and c-Myc. Further, octreotide treatment mediated the activation of GSK-3.
CONCLUSIONS: These preliminary findings showed the negative regulation of the Wnt/β-catenin pathway by peptide hormone G protein-coupled receptors SSTRs.

Related: Apoptosis

Haruki K, Shiba H, Fujiwara Y, et al.
Practice to extend indication of hepatic resection for colorectal liver metastasis.
Hepatogastroenterology. 2013; 60(127):1633-8 [PubMed] Related Publications
BACKGROUND/AIMS: Recent reports have demonstrated that patients with limited extrahepatic disease and bilobar disease can benefit from aggressive surgical resection in combination with chemotherapy. Therefore, we extended indication of hepatic resection for colorectal liver metastasis (CRLM) since 2004. In this report, we retrospectively assessed changes in our therapeutic strategy for CRLM.
METHODOLOGY: The subjects were 67 patients who underwent hepatic resection for CRLM between January 2000 and December 2008. Patients were classified into two groups; early period (2000-2003) and late period(2004-2008). We assessed prognostic factors and change in our hepatic resection policy on operative indication for CRLM in relation to therapeutic outcome. Results: In multivariate analysis, more than 4 lymph node metastases (p=0.0277) and bilobar disease (p=0.0142) were significant predictors of disease- free survival, while significant predictor of overall survival were more than four lymph node metastases (p=0.0014) and bilobar disease (p=0.0392). Bilobar disease and presence of extrahepatic disease were significantly greater in late period. However, incidence of postoperative complications, disease-free and overall survivals in both periods were comparable.
CONCLUSIONS: Practice to extend indication of hepatic resection for patients with advanced CRLM seems to increase the respectability rate without increasing morbidity and mortality, whenever a macroscopically curative resection with acceptable operative risk was thought possible.

Seo S, Hamaguchi Y, Okuda Y, et al.
Usefulness of endoscope guided transabdominal ultrasonography in T staging of colorectal cancer.
Hepatogastroenterology. 2013; 60(127):1627-32 [PubMed] Related Publications
BACKGROUND/AIMS: We investigated the efficacy of endoscope guided transabdominal ultrasonography (EGTUS) for the evaluating the depth of colorectal cancer invasion.
METHODOLOGY: The subjects were 52 patients with colon cancer and 30 patients with rectal cancer who underwent transabdominal US and curative surgery. During endoscopy, we applied transabdominal US by filling the area around the tumor with de-gassed water. The accuracy of depth invasion assessment using EGTUS was compared with that using endoscopic, computed tomography (CT), surgical or histological findings.
RESULTS: The tumor detection rate was 75.6% (62/82), 88.5% (46/52) for colon cancer and 53.3% (16/30) for rectal cancer. The diagnostic accuracies of EGTUS, endoscopic, CT and surgical findings were 87.1% (54/62), 73.2% (60/82), 66.7% (46/69), 65.9% (54/82), respectively. The diagnostic accuracy of EGTUS was 100% (2/2), 66.7% (4/6), and 90.0% (44/49) for T1, T2 and T3 cancer, respectively.
CONCLUSION: The results suggest that EGTUS is useful for evaluating preoperative T staging of colorectal cancer.

Hompes R, Rauh SM, Ris F, et al.
Robotic transanal minimally invasive surgery for local excision of rectal neoplasms.
Br J Surg. 2014; 101(5):578-81 [PubMed] Related Publications
BACKGROUND: Robotic transanal minimally invasive surgery (TAMIS) may be an option for rectum-preserving excision of neoplasms. Recent cadaveric studies showed improved vision, control and manoeuvrability compared with use of laparoscopic instruments. This study reports the clinical application.
METHODS: Consecutive patients eligible for transanal endoscopic microsurgery (TEM) or TAMIS in three participating centres were operated on using a robotic platform and transanal glove port. Patient demographics, lesion characteristics, perioperative data, complications and follow-up of all patients were recorded prospectively.
RESULTS: Sixteen patients underwent robotic TAMIS for rectal lesions with a median (range) distance from the anal verge of 8 (range 3-10) cm. The median size of the resected specimen was 5·3 (0·5-21) cm(2) . The median docking time and duration of operation were 36 (18-75) and 108 (40-180) min respectively. One conversion to regular (non-robotic) TAMIS was needed owing to difficulties accessing the rectum. Glove puncture necessitated replacement in four procedures, an unstable pneumorectum arose during one operation and one patient developed a pneumoperitoneum. One patient required catheterization for urinary retention. The median hospital stay was 1·3 (0-4) days. The additional cost of the robotic approach was approximately €1000 per procedure (excluding the capital expenditure on the robotic system and its maintenance).
CONCLUSION: Robotic TAMIS is feasible in patients with rectal lesions. Potential advantages over TEM and non-robotic TAMIS will need to be balanced against the cost of the robotic system.

Sagar AJ, Koshy A, Hyland R, et al.
Preoperative assessment of retrorectal tumours.
Br J Surg. 2014; 101(5):573-7 [PubMed] Related Publications
BACKGROUND: Retrorectal tumours present diagnostic and surgical challenges. This study aimed to identify whether preoperative imaging and/or biopsy provide diagnostic accuracy.
METHODS: A consecutive series of patients who had undergone excision of a retrorectal tumour were identified from a database (2002-2013). Details of patient demographics, preoperative presentation, imaging, biopsy, surgical procedure, and gross and microscopic pathology were reviewed. Preoperative imaging and/or biopsies were compared with eventual pathology findings.
RESULTS: In total, 76 patients were identified, all of whom had undergone preoperative cross-sectional imaging whereas only 22 had preoperative biopsy. Imaging correctly discriminated benign from malignant tumours in 72 of the 76 patients (specificity 97 per cent, sensitivity 88 per cent, positive predictive value 88 per cent and negative predictive value 97 per cent). The corresponding values for preoperative biopsy (benign versus malignant) were 100, 83, 100 and 93 per cent. None of the four patients who were assessed incorrectly as having benign or malignant disease on imaging would have undergone an alternative procedure had this been known before surgery. Preoperative biopsy did not significantly influence patient management, and the absence of preoperative biopsy had no detrimental effect; a definitive preoperative histological diagnosis would not have influenced subsequent management.
CONCLUSION: Preoperative imaging was accurate in the assessment of retrorectal tumours, whereas biopsy did not add to the surgical strategy.

Velciov S, Hoinoiu B, Hoinoiu T, et al.
Aspects of renal function in patients with colorectal cancer in a gastroenterology clinic of a county hospital in Western Romania.
Rom J Intern Med. 2013 Jul-Dec; 51(3-4):164-71 [PubMed] Related Publications
Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.

Pais R, Dumitraşcu DL
Do antioxidants prevent colorectal cancer? A meta-analysis.
Rom J Intern Med. 2013 Jul-Dec; 51(3-4):152-63 [PubMed] Related Publications
BACKGROUND: Oxidative stress is the first step involved in mutagenesis, carcinogenesis and aging. There has been great interest in recent years in potentially health benefits of dietary and antioxidant supplements in cancer prevention.
OBJECTIVES: Our primary objectives were to estimate the global effect of antioxidants on colorectal cancer incidence, adenomatous polyp recurrence, overall mortality and cancer related mortality. A secondary aim was to evaluate these effects across specific antioxidant compounds, dose and duration of antioxidant supplementation.
METHODS: Using Cochrane Collaboration methodology we searched for all randomized controlled trials (RCTs) from 1966 till May 2009 (MEDLINE, Cochrane Controlled Clinical Trials Registry), comparing antioxidant supplements with placebo or no intervention on the occurrence of colorectal cancer or adenoma. The results expressed as relative risk (RR) and 95% confidence intervals (95% CI) were obtained using random and fixed effect meta-analysis.
RESULTS: Twenty RCTs, including 26 8590 participants, were eligible: 12 analyzing the colorectal cancer incidence included 25 0676 participants and 8 analyzing colorectal adenoma recurrence included 17914 participants. Antioxidant supplements had no significant effect on colorectal cancer incidence or colorectal adenoma recurrence (RR = 0. 94, 95% CI, 0.84-1.06, p = 0.32) in a random-effect meta-analysis. The antioxidant supplements had no significant effect on overall mortality (RR = 1.03, 95% CI, 0.99-1.07, p = 0.12) or cancer related mortality (RR = 1.05, 95% CI, 0.94-1.16, p = 0.38) in a random effect meta-analysis. Selenium supplementation was associated with a trend in reducing colorectal cancer incidence, (RR = 0.88, 95% CI, 0.55-1.40, p = 0.59), colorectal adenoma recurrence (RR = 0.70, 95% CI, 0.43-1.14, p = 0.16) and overall mortality (RR = 0.91, 95% CI, 0.82-1.02, p = 0.09). Beta carotene alone was associated with a slight increase in colorectal cancer incidence (RR = 1.09, 95% CI, 0.92-1.29, p = 0.34) and in combination with other antioxidants it was associated with an increase in mortality (RR = 1.05, 95% CI, 0.99-1.11, p = 0.10). For both selenium and beta carotene, the effect was not statistically significant. Vitamin C and Vitamin E combination slightly reduced colorectal cancer incidence with no effect on overall mortality.
CONCLUSIONS: This meta-analysis found no evidence in favor of a protective effect of the studied antioxidant supplements in the prevention of colorectal cancer or cancer related mortality. Only selenium supplementation might have anticarcinogenic effects and requires further research.

Jurisić I, Paradzik MT, Jurić D, et al.
National program of colorectal carcinoma early detection in Brod-Posavina County (east Croatia).
Coll Antropol. 2013; 37(4):1223-7 [PubMed] Related Publications
Colorectal carcinoma (CRC) is a major public health problem as the third leading malignant tumor in men and fourth in women in Croatia. Prognosis and treatment greatly depend on tumor stage at the time of detection. Therefore, the National Program of Colorectal Carcinoma Early Detection has been performed since 2007. The aim is to present the response rate, colonoscopy findings and number of newly detected CRC cases in Brod-Posavina County. During five years of the National Program performance, 28 CRC cases were detected in Brod-Posavina County, with the 3.3% rate of carcinoma detection. The majority of CRC cases were found in the 50-64 age group. The response rate in the County was low (20.4%), corresponding to the national rate but far from the recommended one. Such a result could be attributed to the low level of awareness in the population at large, complex testing technique for general population, fear from disease detection and from colonoscopy as a diagnostic procedure. Note should be made of the underestimated role of family physicians; their involvement in the National Program should certainly result in better response rate in our County as well as at the national level.

Hall DJ, Farmer KC, Roth HS, Warrier SK
Transanal endoscopic microsurgery colorectal anastomosis: a critical step to natural orifice colorectal surgery in humans.
Dis Colon Rectum. 2014; 57(4):549-52 [PubMed] Related Publications
BACKGROUND: Transanal endoscopic microsurgery is used in the surgical management of advanced rectal polyps and early rectal cancers. There are case reports of transanal endoscopic microsurgery colorectal anastomoses being performed with laparoscopic assistance in humans.
METHODS: The concept of a transanal endoscopic microsurgery colorectal anastomosis without laparoscopic assistance has been discussed and trialed on animal and cadaveric specimens; however, to date, there have been no technical reports of this particular procedure in the literature.
RESULTS: We present a technical note describing a transanal endoscopic microsurgery intraperitoneal colorectal anastomosis in a live human without laparoscopic assistance.

Gross ME, Vogler SA, Mone MC, et al.
The importance of extended postoperative venous thromboembolism prophylaxis in IBD: a National Surgical Quality Improvement Program analysis.
Dis Colon Rectum. 2014; 57(4):482-9 [PubMed] Related Publications
BACKGROUND: The National Comprehensive Cancer Network recommends that patients who have colorectal cancer receive up to 4 weeks of postoperative out-of-hospital venous thromboembolism prophylaxis. Patients with IBD are at high risk for venous thromboembolism, but there are no recommendations for routine postdischarge prophylaxis.
OBJECTIVE: The purpose of this study was to compare the postoperative venous thromboembolism rate in IBD patients versus patients who have colorectal cancer to determine if IBD patients warrant postdischarge thromboembolism prophylaxis.
DESIGN: This study is a retrospective review of IBD patients and patients who had colorectal cancer who underwent major abdominal and pelvic surgery.
PATIENTS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program (2005-2010).
MAIN OUTCOME MEASURES: The primary outcome was 30-day postoperative venous thromboembolism in IBD patients and patients who had colorectal cancer. Risk factors for venous thromboembolism were analyzed with the use of univariate testing and stepwise logistic regression.
RESULTS: A total of 45,964 patients were identified with IBD (8888) and colorectal cancer (37,076). The 30-day postoperative rate of venous thromboembolism in IBD patients was significantly higher than in patients who had colorectal cancer (2.7% vs 2.1%, p < 0.001). In a model with 15 significant covariates, the OR for venous thromboembolism was 1.26 (95% CI, 1.021-1.56; p = 0.03) for the IBD patients in comparison with the patients who have colorectal cancer.
LIMITATIONS: This study was limited by the retrospective design and the limitations of the data included in the database.
CONCLUSIONS: Patients with IBD had a significantly increased risk for postoperative venous thromboembolism in comparison with patients who had colorectal cancer. Therefore, postdischarge venous thromboembolism prophylaxis recommendations for IBD patients should mirror that for patients who have colorectal cancer. This would suggest a change in clinical practice to extend out-of-hospital prophylaxis for 4 weeks in postoperative IBD patients.

Sendagorta E, Herranz P, Guadalajara H, et al.
Prevalence of abnormal anal cytology and high-grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with men.
Dis Colon Rectum. 2014; 57(4):475-81 [PubMed] Related Publications
BACKGROUND: The incidence of anal cancer among HIV-infected patients is higher than that in other populations. Anal high-grade squamous intraepithelial lesions are considered precursors to invasive squamous-cell carcinomas and are strongly associated to high-risk human papillomavirus infection.
OBJECTIVE: The aim of this study is to determine the prevalence of anal high-grade squamous intraepithelial lesions through screening based on cytology and high-resolution anoscopy with biopsy in a cohort of HIV-infected men who have sex with men.
DESIGN: This investigation is an observational cross-sectional cohort study.
SETTING: The study was conducted in the HIV unit of a tertiary hospital in Spain.
PATIENTS: Three hundred HIV-infected men who have sex with men participated. Physical examination led to a diagnosis of perianal squamous-cell carcinoma and high-grade squamous intraepithelial lesions in 2 patients who were then excluded.
INTERVENTIONS: Anal liquid cytology was performed. Patients with cytological abnormalities underwent high-resolution anoscopy and biopsy.
MAIN OUTCOME MEASURE: The primary outcome measured was biopsy-proven high-grade squamous intraepithelial lesions.
RESULTS: The median age was 41 ± 10.5 years. The mean and nadir CD4 cell counts were 651 ± 205 cells/mm(3) (interquartile range, 438-800) and 273 ± 205 cells/mm(3) (interquartile range, 131-362). High-risk human papillomavirus was detected in 80.9% of patients, and human papillomavirus 16 was detected in 35.9% of patients. The mean number of human papillomavirus genotypes was 4.6 ± 2.9 (CI, 2-6). Anal cytology was abnormal in 40.9% of patients (n = 122/298; interquartile range, 35.4%-46.6%). High-resolution anoscopy and biopsies were performed in 119 patients. The results of histological analyses were as follows: normal, 7.7% (n = 23); condyloma, 4.3% (n = 13); anal intraepithelial neoplasia 1, 5.7% (n = 17); anal intraepithelial neoplasia 2, 14% (n = 42); and anal intraepithelial neoplasia 3, 8% (n = 24). The overall prevalence of high-grade squamous intraepithelial lesions among patients with abnormal cytology was 54% (95% CI, 45.1%-62.8%). A diagnosis of high-grade squamous intraepithelial lesions was associated with human papillomavirus 16 and human papillomavirus 51 infection, and with detection of a higher number of human papillomavirus genotypes.
LIMITATIONS: High-resolution anoscopy was only performed in patients with abnormal cytology.
CONCLUSIONS: The prevalence of high-risk human papillomavirus infection and high-grade squamous intraepithelial lesions is high in our cohort. Physical examination enabled straightforward diagnosis of perianal high-grade squamous intraepithelial lesions and squamous-cell carcinoma in 2 patients.

Related: Anal Cancer

Nagayoshi K, Ueki T, Nishioka Y, et al.
Tumor deposit is a poor prognostic indicator for patients who have stage II and III colorectal cancer with fewer than 4 lymph node metastases but not for those with 4 or more.
Dis Colon Rectum. 2014; 57(4):467-74 [PubMed] Related Publications
BACKGROUND: Extranodal tumor deposits are involved in TNM classification. However, it is uncertain whether a tumor deposit is a regular lymph node metastasis, and its prognostic significance in patients with stage II or III colorectal cancer remains to be established.
OBJECTIVE: This study aimed to determine the prognostic significance of tumor deposits for stage II and III colorectal cancer.
DESIGN: This study is a retrospective review of clinicopathological data.
SETTING: This study was conducted at a tertiary care hospital/referral center in Japan.
PATIENTS: We reviewed the clinical course of 171 stage II and 173 stage III consecutive patients between January 1999 and December 2006.
MAIN OUTCOME MEASURES: We examined the clinicopathological features of colorectal cancers with tumor deposits and calculated overall survival and recurrence-free survival of the patients according to the status of tumor deposits. The primary outcome was the impact of tumor deposits on patient survival.
RESULTS: Thirty-five (10.2%) patients with colorectal cancers had tumor deposits in the pericolic and/or mesocolic region. Survival rates among the patients with tumor deposits were significantly lower than those without (5-year overall survival: 58.4% vs 81.0%, p < 0.0001; 5-year recurrence-free survival: 47.1% vs 73.4%, p < 0.0001). Tumor deposit was an independent prognostic factor for patients with colorectal cancer in multivariate analysis (overall survival: HR, 2.30; 95% CI, 1.26-4.04; p = 0.04; recurrence-free survival: HR, 2.42; 95% CI, 1.04-4.90; p = 0.04). Tumor deposit was an independent prognostic factor in N0 and N1 colorectal cancer, whereas N2 cancer had poor survival outcome regardless of tumor deposit.
LIMITATIONS: Our study was a single-institution retrospective study, and the numbers of patients were relatively small to draw firm conclusions.
CONCLUSION: Tumor deposit may be an independent adverse prognostic factor for stage II and III N1 colorectal cancer.

van Leersum NJ, Aalbers AG, Snijders HS, et al.
Synchronous colorectal carcinoma: a risk factor in colorectal cancer surgery.
Dis Colon Rectum. 2014; 57(4):460-6 [PubMed] Related Publications
BACKGROUND: Synchronous colorectal carcinoma occurs in 1% to 8% of cases. There are little data on the impact of synchronous colorectal cancer on surgical treatment and short-term postoperative outcomes.
OBJECTIVE: The purpose of this work was to evaluate clinical characteristics and treatment patterns of synchronous colorectal carcinoma and their influence on short-term postoperative outcomes in comparison with solitary colorectal carcinoma.
DESIGN: This was a population-based observational study. Patient and tumor characteristics, treatment patterns, and postoperative outcomes are described for patients with a solitary and synchronous colorectal carcinoma separately. Multivariable logistic regression analysis was used to analyze the association between synchronous colorectal carcinoma and postoperative complications in comparison with a solitary colorectal carcinoma.
SETTINGS: The study included in-hospital registration for the Dutch Surgical Colorectal Audit.
PATIENTS: Patients were those with primary colorectal carcinoma from 2009 to 2011.
MAIN OUTCOME MEASURES: Severe postoperative complications, reinterventions, and 30-day mortality were measured.
RESULTS: Of 25,413 patients with colorectal cancer, 884 (3.5%) had synchronous colorectal tumors. Patients with synchronous colorectal carcinoma were older and more often of male sex compared with patients with solitary colorectal carcinoma. In ≥ 35% of cases, an extended surgical procedure was conducted (n = 310). In multivariable logistic regression analysis, synchronous colorectal carcinoma was associated with a higher risk of severe postoperative complications (OR, 1.40; 95% CI, 1.20-1.63) and reinterventions (OR, 1.37; 95% CI, 1.14-1.65) compared with solitary colorectal carcinoma but not with higher 30-day mortality (OR, 1.34; 95% CI, 0.96-1.88).
LIMITATIONS: This study was limited by the data being self-reported. Case-mix adjustment was limited to information available in the data set, and no long-term outcome data were available.
CONCLUSIONS: Synchronous colorectal carcinomas are prevalent in 3.5% of patients and require a different treatment strategy in comparison with solitary colorectal carcinoma. Postoperative outcomes are unfavorable, most likely because of extensive surgery.

Patel SA, Chen YH, Hornick JL, et al.
Early-stage rectal cancer: clinical and pathologic prognostic markers of time to local recurrence and overall survival after resection.
Dis Colon Rectum. 2014; 57(4):449-59 [PubMed] Article available free on PMC after 01/04/2015 Related Publications
BACKGROUND: Resection without adjuvant therapy results in a low recurrence rate for patients with stage I (T1/2 N0) rectal cancer in the range of 4% to 16% at 5 years. There are limited data, however, regarding clinical or pathologic prognostic markers for recurrence in this population.
OBJECTIVE: The aim of this study is to assess the clinical and pathologic factors associated with local recurrence and overall survival in patients with early-stage rectal cancer after resection.
DESIGN: This is a retrospective study.
SETTING: This study was conducted at 2 tertiary care centers in Boston, Massachusetts.
PATIENTS: From 2000 to 2008, 175 patients with stage I rectal cancer treated with local or total mesorectal excision without adjuvant therapy were identified.
MAIN OUTCOME MEASURES: Time to local recurrence after resection and overall survival were evaluated for all patients with complete follow-up data. Perioperative data were reviewed to identify staging method, preoperative CEA, type of surgery, tumor size, number of lymph nodes resected, histological grade, circumferential resection margin, perineural invasion, lymphovascular invasion, and tumor ulceration. Data were analyzed by using a Cox proportional hazards regression model.
RESULTS: Of the eligible cohort, 137 patients had complete follow-up data for analysis of time to local recurrence, and only 23 (16.8%) patients had local recurrence. Among these 23 patients, the median time to recurrence was 1.1 years (0.1-7.8). On multivariate analysis, male sex, current alcohol use, and tumor ulceration were associated with heightened risk of local recurrence. Of the original cohort, 173 patients had complete follow-up for overall survival analysis. Among these patients, the median overall survival was 12 years. On multivariable analysis, age at diagnosis >65 years and T2 pathologic stage were associated with decreased survival.
LIMITATIONS: As in any retrospective study, there is a potential for selection bias. Several patients were excluded from the analysis due to inadequate follow-up data. These results from two academic medical centers with specialized colorectal surgeons may not be generally applicable. The relatively small number of events, ie, recurrences, suggest the findings should be validated in a larger study.
CONCLUSIONS: For patients with stage I rectal cancer treated with resection alone, these results provide important prognostic information and may help identify those who could benefit from additional therapy.

Hallemeier CL, You YN, Larson DW, et al.
Multimodality therapy including salvage surgical resection and intraoperative radiotherapy for patients with squamous-cell carcinoma of the anus with residual or recurrent disease after primary chemoradiotherapy.
Dis Colon Rectum. 2014; 57(4):442-8 [PubMed] Related Publications
BACKGROUND: For patients with residual or recurrent squamous-cell carcinoma of the anus after primary chemoradiotherapy, the standard treatment is surgical salvage. Patients with unresectable or borderline unresectable disease have poor outcomes, thus adjunctive treatments should be explored.
OBJECTIVE: The aim of this study is to report outcomes for patients with residual/recurrent anal cancer treated with multimodality therapy including salvage surgical resection and intraoperative radiotherapy.
DESIGN: This is an observational study.
SETTINGS: This study was conducted at a tertiary referral center.
PATIENTS: Thirty-two patients were treated between 1993 and 2012. Median age was 53 years (range, 34-87). Salvage treatment was performed for residual disease (n = 9), first recurrence (n = 17), or second recurrence (n = 6) after primary chemoradiotherapy.
INTERVENTIONS: Patients with recurrent disease received preoperative external beam reirradiation with concurrent chemotherapy. All patients underwent salvage surgical resection and intraoperative radiotherapy. Extent of surgical resection was R0 (negative margins, n = 16), R1 (microscopic residual, n = 13), or R2 (macroscopic residual, n = 3). The median intraoperative radiotherapy dose was 12.5 Gy.
MAIN OUTCOME MEASURES: Treatment-related adverse events were classified according to the National Cancer Institute - Common Toxicity Criteria. Overall and disease-free survival were estimated by using the Kaplan-Meier technique. Central, local-regional, and distant failure were estimated by the use of the cumulative incidence method.
RESULTS: Median length of hospital stay was 9 days. Mortality at 30 days after surgery and intraoperative radiotherapy was 0%. Fifteen patients (47%) experienced a total of 16 grade 3 treatment-related adverse events (wound complication (n = 6), bowel obstruction (n = 5), and ureteral obstruction (n = 3)). The 5-year estimates of overall and disease-free survival were 23% and 17%. The 5-year estimates of central, local-regional, and distant failure were 21%, 51%, and 40%.
LIMITATIONS: This was a single-institution observational study with limited patient numbers.
CONCLUSIONS: In this heavily pretreated, high-risk patient population, multimodality therapy including salvage surgery and intraoperative radiotherapy was associated with long-term survival in a small, but significant subset of patients.

Related: Anal Cancer Brachytherapy

Eyvazzadeh DJ, Lee JT, Madoff RD, et al.
Outcomes after transanal endoscopic microsurgery with intraperitoneal anastomosis.
Dis Colon Rectum. 2014; 57(4):438-41 [PubMed] Related Publications
BACKGROUND: Transanal endoscopic microsurgery has gained increasing popularity as a treatment alternative for early stage rectal neoplasms. With continued advances in technique and experience, more proximal rectal tumors are being surgically managed by using transanal endoscopic microsurgery with an intraperitoneal anastomosis.
OBJECTIVE: The purpose of this study was to review the outcomes of patients who have undergone intraperitoneal anastomosis with the use of the transanal endoscopic microsurgery technique.
DESIGN: A prospective, single-surgeon database documented 445 consecutive patients undergoing transanal endoscopic microsurgery from October 1, 1996 through January 1, 2012. We retrospectively reviewed information from all patients who underwent transanal endoscopic microsurgery with an intraperitoneal anastomosis in this prospective database.
SETTINGS: All procedures took place in an inpatient hospital setting.
PATIENTS: All patients satisfied workup criteria to undergo surgery for rectal neoplasm.
INTERVENTIONS: All patients underwent transanal endoscopic microsurgery for rectal neoplasm.
MAIN OUTCOME MEASURES: Size and pathology of lesion, length of procedure, hospital stay, estimated blood loss, margin status, and complications were the outcomes measured.
RESULTS: Twenty-eight patients who underwent transanal endoscopic microsurgery had definitively documented intraperitoneal entry and anastomosis. Median follow-up was 12 months (range, 0.5-111 months). There were no operative mortalities. Procedure-related complications included urinary retention (11%), fever (11%), and fecal seepage (4%). Four patients (14%) had positive margins on final pathology. One patient (3%) required abdominal exploration for an anastomotic leak but did not require diversion.
LIMITATIONS: Although this study analyzes prospectively collected data, it is nonetheless a retrospective analysis that can introduce bias. Because this is a single-center study with a relatively homogenous population, the results may not be generalizable. Our sample size may also be underpowered to detect clinically significant outcomes.
CONCLUSIONS: Transanal endoscopic microsurgery with intraperitoneal anastomosis can be safely performed without fecal diversion by experienced surgeons.

Chen L, Kalady MF, Goldblum J, et al.
Does reevaluation of colorectal cancers with inadequate nodal yield lead to stage migration or the identification of metastatic lymph nodes?
Dis Colon Rectum. 2014; 57(4):432-7 [PubMed] Related Publications
BACKGROUND: The National Comprehensive Cancer Network recommends routine reevaluation of all stage II colon cancer specimens with fewer than 12 lymph nodes. However, there are few data demonstrating the effect of reevaluation on stage.
OBJECTIVE: The aim of this study was to demonstrate the effect of pathologic reevaluation for colorectal cancers with fewer than 12 lymph nodes on stage.
DESIGN: This study entailed a retrospective review of pathology reports.
SETTINGS: This study was conducted at 2 large multispecialty referral centers.
INTERVENTIONS: Pathologic reevaluation was performed to look for additional lymph nodes.
PATIENTS: All patients with stage I through III colorectal cancers with inadequate lymph node yields who underwent reevaluation from January 1, 2007 through March 31, 2011 were identified.
MAIN OUTCOME MEASURES: We recorded initial pathologic stage and new stage following reevaluation. The following variables before and after reevaluation were also recorded: 1) total lymph node count, 2) metastatic node count, 3) negative node count, and 4) lymph node ratio.
RESULTS: Eighty-three patients underwent pathologic reevaluation from a total of 1682 cancer specimens. Mean nodal yields were 7.2 ± 2.6 on the first pathologic review. On reevaluation, 80% of patients had one or more newly identified nodes. On average, 6.9 ± 9.6 more lymph nodes were identified with a metastatic node detected in 4 of 83 patients (4.8%). After pathologic reevaluation, 1 patient (1.2%) had a change in TNM stage from N1 to N2 disease. The lymph node ratio changed in 13 of 15 patients (87% of stage III cancers). Only 4 of these had a change in lymph node quartile.
LIMITATIONS: The study was limited by its retrospective nature and small sample size.
CONCLUSION: Few patients have a newly discovered metastatic node or stage change following pathologic reevaluation. The effect of pathologic reevaluation on treatment and outcome should be further investigated.

Fraunholz IB, Haberl A, Klauke S, et al.
Long-term effects of chemoradiotherapy for anal cancer in patients with HIV infection: oncological outcomes, immunological status, and the clinical course of the HIV disease.
Dis Colon Rectum. 2014; 57(4):423-31 [PubMed] Related Publications
BACKGROUND: Despite the increasing evidence for chemoradiotherapy as standard treatment for anal cancer in patients with HIV infection, there is still some uncertainty regarding increased toxicity and adverse effects on the immune status.
OBJECTIVE: We report the clinical outcome of 5-fluorouracil/mitomycin C-based concurrent chemoradiotherapy for anal carcinoma in patients with HIV infection with an emphasis on the long-term course of CD4 counts and the HIV-related morbidity during follow-up.
DESIGN AND SETTINGS: A retrospective single-institution chart review was performed.
PATIENTS: Between 1997 and 2012, 36 HIV-positive patients were treated with standard chemoradiotherapy (median tumor dose, 54 (range, 50.4-60.4) Gy at 1.8 Gy/fraction; 5-fluorouracil, 800-1000 mg/m(2), days 1-4 or 1-5; mitomycin C, 10 mg/m(2), day 1, in the first and fifth week).
MAIN OUTCOME MEASURES: A retrospective analysis was performed with respect to tumor response, local control, cancer and overall survival, and toxicity. Immunological parameters, including pre- and posttreatment CD4 counts, viral load, and HIV-specific morbidity were recorded during follow-up.
RESULTS: Chemoradiotherapy could be completed in all patients. Acute grade 3 toxicities occurred in 17/36 patients (47%). Complete response was achieved in 31 patients (86%). Five-year local control, colostomy-free, cancer-specific, and overall survival were 72%, 87%, 77%, and 74%. The median pretreatment CD4 count significantly decreased from 367 cells/μL to 139 cells/μL, 3 to 7 weeks after completion of chemoradiotherapy (p < 0.001). Four patients (11%) experienced opportunistic illnesses during the follow-up (median, 66; range, 10-164 months).
LIMITATIONS: This study is limited by its retrospective design and its small sample size.
CONCLUSIONS: Our data confirm again that, in the highly active antiretroviral therapy era, anal cancer can be treated in HIV-positive patients with standard chemoradiotherapy, with a clinical outcome similar to their HIV-negative counterparts. The chemoradiotherapy-related decline of the CD4 counts, which remain decreased up to 6 years after chemoradiotherapy, was not associated with increased HIV-related clinical morbidity.

Related: Anal Cancer Fluorouracil Mitomycin

Dobbins TA, Young JM, Solomon MJ
Uptake and outcomes of laparoscopically assisted resection for colon and rectal cancer in Australia: a population-based study.
Dis Colon Rectum. 2014; 57(4):415-22 [PubMed] Related Publications
BACKGROUND: Meta-analyses of randomized controlled trials support the use of laparoscopically assisted resection for colon cancer. The evidence supporting its use in rectal cancer is weak.
OBJECTIVE: The purpose of this work was to investigate the uptake of laparoscopically assisted resection for colon and rectal cancer and to compare short- and long-term outcomes using population data.
DESIGN: This was a retrospective cohort study using linked administrative health data.
SETTINGS: The study encompassed all of the public and private hospitals in New South Wales, Australia, between 2000 and 2008.
PATIENTS: A total of 27,947 patients with colon or rectal cancer undergoing surgery with curative intent were included in the study.
MAIN OUTCOME MEASURES: We summarized the proportion of resections performed laparoscopically. Short-term outcomes were extended stay, 28-day readmission, 28-day emergency readmission, 30- and 90-day mortality, and 90-day readmission with pulmonary embolism or deep-vein thrombosis. Long-term outcomes were all-cause and cancer-specific death and admission with obstruction or incisional hernia repair.
RESULTS: Laparoscopic procedures increased between 2000 and 2008 for colon (1.5%-20.7%) and rectal cancer (0.6%-15.5%). Laparoscopic procedures reduced rates of extended stay (OR, 0.60; 95% CI, 0.49-0.72) and 28-day readmission (OR, 0.86; 95% CI, 0.74-0.99) for colon cancer. For rectal cancer, laparoscopic procedures had lower rates of 28-day readmission (OR, 0.58; 95% CI, 0.42-0.78) and 28-day emergency readmission (OR, 0.54; 95% CI, 0.34-0.85). Laparoscopic procedures improved cancer-specific survival for rectal cancer (HR, 0.71; 95% CI, 0.51-1.00). Survival benefits were observed for laparoscopically assisted colon resection in higher-caseload hospitals but not lower-caseload hospitals.
LIMITATIONS: It was not possible to identify laparoscopically assisted resections converted to open procedures because of the claims-based nature of the data.
CONCLUSIONS: Despite increases in laparoscopically assisted resections for colon and rectal cancer, the majority of resections are still treated by open procedures. Our data suggest that laparoscopic resection reduces the lengths of stay and rates of readmission and may result in improved cancer-specific survival for both colon and rectal resections.

Myerson RJ, Tan B, Hunt S, et al.
Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.
Int J Radiat Oncol Biol Phys. 2014; 88(4):829-36 [PubMed] Related Publications
BACKGROUND: Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy.
METHODS AND MATERIALS: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls.
RESULTS: 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%).
CONCLUSION: This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.

Related: Fluorouracil Leucovorin

Xu D, Wang C, Shen X, et al.
Apoptotic block in colon cancer cells may be rectified by lentivirus mediated overexpression of caspase-9.
Acta Gastroenterol Belg. 2013; 76(4):372-80 [PubMed] Related Publications
BACKGROUND AND AIM: At present, the inhibition of apoptosis during pathogenesis of colorectal cancer is widely recognized while the role of caspase-9 in this process remains controversial. We aimed to investigate the differential expression of caspase-9 and evaluate the therapeutic potential of expression intervention in this study.
METHODS: We first examined the different expression of caspase-9 in normal colon mucosa, adenoma and cancer, investigating the relationship between its expression and clinico-pathological characteristics. Secondly, overexpression of caspase-9 was established in colon cancer cell lines by lentivirus infection to study the changes in growth, proliferation and apoptosis. RESULTS : Compared with normal colon mucosa, the expression of caspase-9 was higher in adenoma while lower in cancer both at mRNA and protein level (P < 0.05). In addition, the down-regulation of caspase-9 expression is more common in poorly differentiated cancers (P < 0.05). Concerning cell lines, overexpression cell groups showed higher expression of caspase-9, poorer colony formation and slower cell proliferation. In terms of apoptosis related indicators, caspase-9 overexpression leads to higher apoptosis rate and GO/G1 arrest, while up-regulating the expression of caspase-3 (P <0.05). Interestingly, down-regulation of carcinoembryonic antigen secretion was also observed in caspase-9 overexpression cells (P <0.05).
CONCLUSION: The change of caspase-9 expression from colon mucosa, adenoma to cancer suggested it may be involved in the carcinogenesis of colon cancer. The overexpression of caspase-9 exhibits an inhibitory role in cancer growth and proliferation while promoting apoptosis. However, a non-apoptotic role of caspase-9 facilitating differentiation was also implied.

Related: Apoptosis

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