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.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
National Cancer Institute Booklets written in simple language, which are regularly reviewed and updated Further info. This site contains information about the disease, diagnosis, staging, and treatment options.
Bowel cancer explained - symptoms, diagnosis and treatment
Macmillan Cancer Support Video: Consultant Clinical Oncologist Amen Sibtain explains bowel cancer, which includes colon and rectal cancer. He gives an overview of the symptoms, diagnosis and treatment of bowel cancer.
The Alliance was founded in 1998 by patients, survivors, cargivers and others whose lives have been toched by colorectal cancer. It provides information, support, advocacy, on-line chat and a toll free Helpline.
ACOR A discussion and support list sponsored by the Association of Cancer Online Resources
Colonoscopy Video Tour: Discovery of a Cancerous Polyp (Colon Cancer)
New York University Langone Medical Center Mark Pochapin MD, narrates a tour of a patient's colon during a colonoscopy where he discovers a cancerous polyp (colon cancer). The patient did not have any abdominal or rectal pain, or any other symptoms associated with colorectal cancer. However, prior to this colonoscopy the patient was diagnosed with anemia due the slow bleeding of this polyp in her colon.
PubMed Central search for free-access publications about Bowel Cancer MeSH term: Colorectal Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
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).
Cancer Institute NSW A screening reminder service established in 1990 to provide information and support to people affected by hereditary cancer, their family members, and their doctors in NSW and the ACT. Screening for Colorectal (Bowel) Cancer
InSiGHT InSiGHT is an international multidisciplinary, scientific organisation. Itaims to improve care of patients and their families with any condition resulting in hereditary gastrointestinal tumours by fostering research and educating health professionals.
Johns Hopkins Colon Cancer Center Introduces hereditary colorectal cancer syndromes, with specific sections on Familial Adenomatous Polyposis (FAP), Hereditary Nonpolyposis Colorectal Cancer (HNPCC), APC I1307K gene mutation, Kid's FAP, and Hyperplastic Polyposis.
This list of publications is regularly updated (Source: PubMed).
Burada F, Dumitrescu T, Nicoli R, et al. Cytokine promoter polymorphisms and risk of colorectal cancer. Clin Lab. 2013; 59(7-8):773-9 [PubMed] Related Publications
BACKGROUND: Cytokines and chemokines are involved in cancer development and progression, but their role in colorectal tumorigenesis is still far from well defined. This study investigated the association between five cytokine promoter polymorphisms and risk, stage, and histological grade of colorectal cancer (CRC) in a hospital-based case-control study. METHODS: A total of 377 Romanian subjects were included in this study: 144 patients with sporadic colorectal cancer and 233 controls. Cytokine polymorphisms (IL-1B -31T > C, IL-4R -3223C > T, IL-8 -251T > A, IL-10 -1082A > G, and TNF-A -308G > A) were genotyped by allelic discrimination TaqMan PCR assay with specific probes. RESULTS: A significant association was observed for IL-10 -1082A > G polymorphism, the subjects carrying AG genotype were at a lower risk for CRC (OR 0.63, 95% CI: 0.40 - 0.98) when compared with the more frequent AA genotype. Furthermore, in a dominant model the carriers of G allele were protected against CRC (OR 0.64, 95% CI: 0.42 - 0.97). In a stratified analysis the only association between CRC and cytokine polymorphisms was found for carriers of IL-10 -1082G allele and was restricted to poorly differentiated cases (OR 0.36, 95% CI: 0.16 - 0.81). No association was observed for the remaining polymorphisms and CRC risk. CONCLUSIONS: This study shows that IL-10 -1082A > G polymorphism may influence CRC risk, the carriers of G allele being protected against CRC in the Romanian population.
Munene G, Parker RD, Shaheen AA, et al. Disparities in the surgical treatment of colorectal liver metastases. J Natl Med Assoc. 2013; 105(2):128-37 [PubMed] Related Publications
BACKGROUND: Hepatectomy is an accepted standard of care for patients with resectable colorectal liver metastases (CLM). Given that it is unclear whether disparities exist between different patient populations, a population-based analysis was performed to analyze this issue with regards to resection rates and surgical mortality in patients with CLM. METHODS: Using the Nationwide Inpatient Sample, characteristics and outcomes of adult patients with a diagnosis of colorectal cancer and colorectal metastases that subsequently underwent a liver resection during the years 1993-2007 were identified. Multivariate analysis was used to determine the effects of demographic and clinical covariables on resection rates and in-hospital mortality. RESULTS: Incident colorectal and liver metastases were identified in 138,565 patients; 3,528 patients (2.6%) underwent subsequent resection. African American and Hispanic race were associated with lower resection rates compared to Caucasian patients (adjusted OR 0.61 (0.52 - 0.71) and 0.81 (0.68 - 0.96) respectively). Medicaid insurance was associated with decreased resection rates compared to private insurance (AOR 0.47 (0.40 - 0.56)). The overall inpatient mortality rate was 3.1%. Multivariate analysis determined that mortality rate was correlated to both insurance status and geographic region. CONCLUSIONS: The national resection rate is significantly lower than has been reported by most case series. Race and insurance status appear to be correlated to the likelihood of surgical resection. In-hospital mortality is equivalent to the rates reported elsewhere, but is correlated to insurance status and region.
Yu SK, Tait D, Chau I, Brown G MRI predictive factors for tumor response in rectal cancer following neoadjuvant chemoradiation therapy--implications for induction chemotherapy? Int J Radiat Oncol Biol Phys. 2013; 87(3):505-11 [PubMed] Related Publications
PURPOSE: Clinical and magnetic resonance imaging (MRI) characteristics at baseline and following chemoradiation therapy (CRT) most strongly associated with histopathologic response were investigated and survival outcomes evaluated in accordance with imaging and pathological response. METHODS AND MATERIALS: Responders were defined as mrT3c/d-4 downstaged to ypT0-2 on pathology or low at risk mrT2 downstaged to ypT1 or T0. Multivariate logistic regression of baseline and posttreatment MRI: T, N, extramural venous invasion (EMVI), circumferential resection margin, craniocaudal length <5 cm, and MRI tumor height ≤5 cm were used to identify independent predictor(s) for response. An association between induction chemotherapy and EMVI status was analyzed. Survival outcomes for pathologic and MRI responders and nonresponders were analyzed. RESULTS: Two hundred eighty-one patients were eligible; 114 (41%) patients were pathology responders. Baseline MRI negative EMVI (odds ratio 2.94, P=.007), tumor height ≤5 cm (OR 1.96, P=.02), and mrEMVI status change (positive to negative) following CRT (OR 3.09, P<.001) were the only predictors for response. There was a strong association detected between induction chemotherapy and ymrEMVI status change after CRT (OR 9.0, P<.003). ymrT0-2 gave a positive predictive value of 80% and OR of 9.1 for ypT0-2. ymrN stage accuracy of ypN stage was 75%. Three-year disease-free survival for pathology and MRI responders were similar at 80% and 79% and significantly better than poor responders. CONCLUSIONS: Tumor height and mrEMVI status are more important than baseline size and stage of the tumor as predictors of response to CRT. Both MRI- and pathologic-defined responders have significantly improved survival. "Good response" to CRT in locally advanced rectal cancer with ypT0-2 carries significantly better 3-year overall survival and disease-free survival. Use of induction chemotherapy for improving mrEMVI status and knowledge of MRI predictive factors could be taken into account in the pursuit of individualized neoadjuvant treatments for patients with rectal cancer.
BACKGROUND: In Canada, provincial cancer registries have been established to provide rigorous population-based data for patients with colorectal cancer. Databases maintained by regional cancer agencies contain a broader scope of information and have been used as a surrogate source of information for colorectal cancer research. It is unclear whether these data can be reliably extrapolated to all patients affected by colorectal cancer. We sought to determine whether patients included in a referral-based database are systematically different from patients who are not included. METHODS: We conducted a retrospective cohort study to compare patients referred to the British Columbia Cancer Agency with those who were not referred. Comparison was based on age, sex and geographic location. We used univariate and logistic regression analysis to identify significant differences between the cohorts. RESULTS: Univariate analysis demonstrated that the referral and nonreferral cohorts differed in sex, age and geographic location. For patients with rectal cancer, the referral and nonreferral cohorts varied in age and geographic location. Multivariate analysis demonstrated significant differences in age and geographic location but not sex for patients with colon and rectal cancer. CONCLUSION: Patients included in the referral database differed in age and geographic location from those included only in the provincial database. Studies using large data sets from referral centres must be interpreted with caution and may not be representative of the entire patient population.
Morneau M, Boulanger J, Charlebois P, et al. Laparoscopic versus open surgery for the treatment of colorectal cancer: a literature review and recommendations from the Comité de l'évolution des pratiques en oncologie. Can J Surg. 2013; 56(5):297-310 [PubMed] Free Access to Full ArticleRelated Publications
BACKGROUND: Adoption of the laparoscopic approach for colorectal cancer treatment has been slow owing to initial case study results suggesting high recurrence rates at port sites. The use of laparoscopic surgery for colorectal cancer still raises a number of concerns, particularly with the technique's complexity, learning curve and longer duration. After exploring the scientific literature comparing open and laparoscopic surgery for the treatment of colorectal cancer with respect to oncologic efficacy and shortterm outcomes, the Comité de l'évolution des pratiques en oncologie (CEPO) made recommendations for surgical practice in Quebec. METHODS: Scientific literature published from January 1995 to April 2012 was reviewed. Phase III clinical trials and meta-analyses were included. RESULTS: Sixteen randomized trials and 10 meta-analyses were retrieved. Analysis of the literature confirmed that for curative treatment of colorectal cancer, laparoscopy is not inferior to open surgery with respect to survival and recurrence rates. Moreover, laparoscopic surgery provides short-term advantages, including a shorter hospital stay, reduced analgesic use and faster recovery of intestinal function. However, this approach does require a longer operative time. CONCLUSION: Considering the evidence, the CEPO recommends that laparoscopic resection be considered an option for the curative treatment of colon and rectal cancer; that decisions regarding surgical approach take into consideration surgeon experience, tumour stage, potential contraindications and patient expectations; and that laparoscopic resection for rectal cancer be performed only by appropriately trained surgeons who perform a sufficient volume annually to maintain competence.
Peungjesada S, Aloia TA, Kaur H, et al. Intrabiliary growth of colorectal liver metastasis: spectrum of imaging findings and implications for surgical management. AJR Am J Roentgenol. 2013; 201(4):W582-9 [PubMed] Related Publications
OBJECTIVE: The propensity for colorectal liver metastasis to invade the biliary tree is increasingly recognized, placing particular emphasis on the risk of postoperative recurrence. This article illustrates the spectrum of imaging findings when colorectal metastasis invades the biliary tree. CONCLUSION: Knowledge of the imaging features of intrabiliary invasion by colorectal liver metastasis improves the quality of preoperative staging and is crucial in an era in which nonanatomic wedge resection and radiofrequency ablation are routinely performed.
Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013; 369(12):1106-14 [PubMed] Related Publications
BACKGROUND: In randomized trials, fecal occult-blood testing reduces mortality from colorectal cancer. However, the duration of the benefit is unknown, as are the effects specific to age and sex. METHODS: In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008. RESULTS: Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction). CONCLUSIONS: The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy. (Funded by the Veterans Affairs Merit Review Award Program and others.).
Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med. 2013; 369(12):1095-105 [PubMed] Article available free on PMC after 19/03/2014 Related Publications
BACKGROUND: Colonoscopy and sigmoidoscopy provide protection against colorectal cancer, but the magnitude and duration of protection, particularly against cancer of the proximal colon, remain uncertain. METHODS: We examined the association of the use of lower endoscopy (updated biennially from 1988 through 2008) with colorectal-cancer incidence (through June 2010) and colorectal-cancer mortality (through June 2012) among participants in the Nurses' Health Study and the Health Professionals Follow-up Study. RESULTS: Among 88,902 participants followed over a period of 22 years, we documented 1815 incident colorectal cancers and 474 deaths from colorectal cancer. With endoscopy as compared with no endoscopy, multivariate hazard ratios for colorectal cancer were 0.57 (95% confidence interval [CI], 0.45 to 0.72) after polypectomy, 0.60 (95% CI, 0.53 to 0.68) after negative sigmoidoscopy, and 0.44 (95% CI, 0.38 to 0.52) after negative colonoscopy. Negative colonoscopy was associated with a reduced incidence of proximal colon cancer (multivariate hazard ratio, 0.73; 95% CI, 0.57 to 0.92). Multivariate hazard ratios for death from colorectal cancer were 0.59 (95% CI, 0.45 to 0.76) after screening sigmoidoscopy and 0.32 (95% CI, 0.24 to 0.45) after screening colonoscopy. Reduced mortality from proximal colon cancer was observed after screening colonoscopy (multivariate hazard ratio, 0.47; 95% CI, 0.29 to 0.76) but not after sigmoidoscopy. As compared with colorectal cancers diagnosed in patients more than 5 years after colonoscopy or without any prior endoscopy, those diagnosed in patients within 5 years after colonoscopy were more likely to be characterized by the CpG island methylator phenotype (CIMP) (multivariate odds ratio, 2.19; 95% CI, 1.14 to 4.21) and microsatellite instability (multivariate odds ratio, 2.10; 95% CI, 1.10 to 4.02). CONCLUSIONS: Colonoscopy and sigmoidoscopy were associated with a reduced incidence of cancer of the distal colorectum; colonoscopy was also associated with a modest reduction in the incidence of proximal colon cancer. Screening colonoscopy and sigmoidoscopy were associated with reduced colorectal-cancer mortality; only colonoscopy was associated with reduced mortality from proximal colon cancer. Colorectal cancer diagnosed within 5 years after colonoscopy was more likely than cancer diagnosed after that period or without prior endoscopy to have CIMP and microsatellite instability. (Funded by the National Institutes of Health and others.).
Kershaw SK, Byrne HM, Gavaghan DJ, Osborne JM Colorectal cancer through simulation and experiment. IET Syst Biol. 2013; 7(3):57-73 [PubMed] Related Publications
Colorectal cancer (CRC) has formed a canonical example of tumourigenesis ever since its use in Fearon and Vogelstein's linear model of genetic mutation, and continues to generate a huge amount of research interest. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical and computational modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the 'Hallmarks of Cancer' has been extended in recent times and provides an excellent basis for future research. The authors present a timely summary of the literature relating to CRC, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. The authors conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that theoretical modelling can provide.
Lee CK, Shim JJ, Jang JY Cold snare polypectomy vs. Cold forceps polypectomy using double-biopsy technique for removal of diminutive colorectal polyps: a prospective randomized study. Am J Gastroenterol. 2013; 108(10):1593-600 [PubMed] Related Publications
OBJECTIVES: There are few data on cold snare polypectomy (CSP) in direct comparison with cold forceps polypectomy (CFP) for colonoscopic resection of diminutive colorectal polyps (DCPs; ≤5 mm). The primary aim of this study was to compare the histologic polyp eradication rate of CSP with that of CFP using double-biopsy technique. METHODS: This was a randomized controlled trial at a single academic hospital. Of the 165 patients invited, 54 consecutive patients having 117 eligible polyps were enrolled in this study. To evaluate histologic eradication of polyps, two or more additional biopsies were taken from the base and edges of the polypectomy site. RESULTS: The mean size of polyps was 3.66 mm (±1.13). Most polyps evaluated were tubular adenomas (69.9%). The rate of histologic eradication was significantly higher in the CSP group than in the CFP group (93.2% vs. 75.9%, P=0.009). The time taken for polypectomy was significantly shorter in the CSP group (14.29 vs. 22.03 s, P<0.001). Failure of tissue retrieval was noted in 6.8% of polyps resected by CSP. Multivariate analysis revealed that the method of polypectomy (CFP) and the polyp size (≥4 mm) were independent predictors associated with incomplete histologic eradication (odds ratio (OR) 4.750 (95% confidence interval (CI): 1.459-15.466), OR 4.375 (95% CI: 1.345-14.235); all P<0.05, respectively). CONCLUSIONS: CSP is superior to CFP for the endoscopic removal of DCPs with regard to completeness of polypectomy. CSP technique should be considered the primary method for endoscopic treatment of polyps in the 4-5-mm size range (ClinicalTrials.gov number: NCT01646242).
Kostakis ID, Agrogiannis G, Vaiopoulos AG, et al. KISS1 expression in colorectal cancer. APMIS. 2013; 121(10):1004-10 [PubMed] Related Publications
Kisspeptins, the products of the KISS1 gene, are involved in cancer invasion, migration, metastasis and angiogenesis, while they induce apoptosis in various cancers. Herein, we studied KISS1 expression in colorectal cancer. We analyzed KISS1 expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 60 patients with colorectal adenocarcinoma. The results correlated with various clinicopathological parameters. The expression of KISS1 was much higher in normal than in malignant colonic mucosa. However, among malignant tissues, KISS1 expression was higher in larger tumors (>4 cm) than in smaller ones (≤4 cm) and in stages III and IV than in stages I and II. In addition, it was higher in patients with lymph node metastases. Moreover, KISS1 levels in the normal mucosa and their difference from those in the malignant mucosa were higher in the right part of the large intestine than in the left one. KISS1 expression is reduced during the malignant transformation of the colonic mucosa and there is a difference in the expression pattern between the right and the left part of the large intestine. However, larger and advanced colorectal tumors express higher KISS1 levels than smaller and localized ones.
van Meer S, Leufkens AM, Bueno-de-Mesquita HB, et al. Role of dietary factors in survival and mortality in colorectal cancer: a systematic review. Nutr Rev. 2013; 71(9):631-41 [PubMed] Related Publications
The role of dietary factors in the outcome of colorectal cancer (CRC) has been the subject of many studies, but results are inconclusive. Presented here are the results of a systematic review of studies published on dietary factors and CRC outcome in the English literature between March 2002 and March 2012. Studies were subdivided into survival studies in CRC patients and CRC mortality studies in the general population. Sixteen of the 636 studies identified--5 on survival and 11 on mortality--met the predefined inclusion criteria. No consistent association between individual dietary components and CRC outcome was detected in the survival studies. In the mortality studies, an association between meat intake and increased CRC mortality was found in two ecologic studies; however, two prospective cohort studies did not confirm this association. An inverse association between cereal intake and CRC mortality was found in two ecologic studies. In conclusion, published studies investigating dietary factors and outcome in CRC are heterogeneous in design and findings. No dietary component was conclusively and consistently associated with survival in CRC patients. The results of mortality studies seem to indicate that meat intake has an adverse effect on CRC mortality, while cereal intake may be protective.
Ueno H, Shirouzu K, Eishi Y, et al. Characterization of perineural invasion as a component of colorectal cancer staging. Am J Surg Pathol. 2013; 37(10):1542-9 [PubMed] Related Publications
Perineural invasion (PN) in colorectal cancer (CRC) is a site-specific prognostic marker, as mentioned by the AJCC Cancer Staging Manual, but it remains to be clearly defined. We aimed to identify an optimal characterization of PN as a component of cancer staging. On the basis of the anatomic features of the nervous system of the large bowel, site-specific pathologic criteria were assigned to PN according to the location of PN. Multi-institutional pathologic review based on these criteria was performed for 962 patients with stage I to III CRC at 2 institutions (1999 to 2004, cohort 1) and 1883 patients from 8 other institutions (2000 to 2004, cohort 2). In cohort 1, intramural and extramural PN were observed in 152 and 101 patients, respectively, which had a different impact on disease-free survival (hazard ratio, 2.6 [1.9 to 3.5] vs. 4.7 [3.4 to 6.5], respectively). A 3-tiered grading system (Pn0; Pn1a, intramural PN; Pn1b, extramural PN) distinguished 5-year disease-free survival as 88%, 70%, and 48%, respectively; and multivariate analysis identified PN grade as a significant prognostic marker independent of T or N stage. These results were similar in cohort 2. Interinstitutional difference of the prognostic impact of PN grade was acceptably small among all institutions. Interobserver study among 6 gastrointestinal pathologists showed superior judgment reproducibility for PN compared with vascular invasion. The results of our study indicate that PN is an important prognostic marker in CRC. The value of cancer staging could be enhanced by PN assessment using site-specific criteria and a simple grading system based on PN location within the bowel.
Kim JH, Rhee YY, Bae JM, et al. Loss of CDX2/CK20 expression is associated with poorly differentiated carcinoma, the CpG island methylator phenotype, and adverse prognosis in microsatellite-unstable colorectal cancer. Am J Surg Pathol. 2013; 37(10):1532-41 [PubMed] Related Publications
Several previous studies have demonstrated that the CDX2-negative (CDX2) and/or CK20-negative (CK20) phenotypes of colorectal cancers (CRCs) might be associated with high levels of microsatellite instability (MSI-H). The aim of this study was to investigate the clinicopathologic and molecular features of MSI-H CRCs with different CDX2/CK20 expression statuses. The CDX2 and CK20 expression statuses were immunohistochemically evaluated in 109 MSI-H CRC tissue samples, and the correlations of these statuses with clinicopathologic, molecular, and survival data were statistically analyzed. Of the 109 MSI-H CRCs, 15 were CDX2 (13.8%), and 19 were CK20 (17.4%). The simultaneous loss of CDX2 and CK20 expression (CDX2/CK20) was observed in 9 cases (8.3%). CDX2 loss was correlated with lymph node metastasis, poor differentiation, MLH1 loss, the mutation of BRAF, and CpG island methylator phenotype-high (CIMP-H) status. Right-sided tumor location, nodal metastasis, poor differentiation, and CIMP-H status were significant characteristics of CK20 tumors. The CDX2/CK20 phenotype was associated with older age (above 56 y), higher stage (stage III or IV), deep invasion (pT3 or pT4), lymph node metastasis (pN1 or pN2), poor differentiation (nonmedullary/non-signet ring cell type), the mutation of BRAF, and CIMP-H status among MSI-H CRCs. Patients with CDX2/CK20 tumors exhibited worse overall and disease-free survival compared with the patients with CDX2 and/or CK20 tumors (P<0.001). In the multivariate analysis for disease-free survival, the CDX2/CK20 phenotype was an independent prognostic factor for MSI-H CRC (P=0.030, hazard ratio=3.288). The CDX2/CK20 phenotype defines a distinct subgroup of MSI-H CRCs with poor differentiation, CIMP-H status, and unfavorable prognosis.
Antonowicz SS, Al-Whouhayb M, Middleton S Total mesorectal excision for cancer following ventral mesh rectopexy. Ann R Coll Surg Engl. 2013; 95(6):e95-6 [PubMed] Related Publications
Since the introduction of ventral mesh rectopexy for rectal prolapse, concern exists as to how this may interfere with subsequent rectal cancer surgery. To our knowledge, this is the first report of total mesorectal excision for cancer after such a rectopexy. We discuss surgical technique, pitfalls encountered and oncological outcome.
Grey T, Lindsay K, Bhowmick A Actinomycosis: an unusual cause of unresectable rectal cancer. Ann R Coll Surg Engl. 2013; 95(6):e92-4 [PubMed] Related Publications
We present a very unusual case of a woman with an intrauterine contraceptive device (IUCD) who developed pelvic actinomycosis during long course chemoradiotherapy for rectal cancer, which presented a significant diagnostic challenge and eventually rendered the cancer unresectable. IUCDs are often implicated in the development of pelvic actinomycosis but there is no current evidence or guideline to suggest that they should be removed prior to oncological treatment. Owing to the devastating consequences of this combination of disease, we suggest that it may be prudent to remove IUCDs in this setting.
Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013; 369(11):1023-34 [PubMed] Related Publications
BACKGROUND: Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy. METHODS: In this prospective-retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15. The overall rate of ascertainment of RAS status was 90%. RESULTS: Among 512 patients without RAS mutations, progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for progression or death with combination therapy, 0.72; 95% confidence interval [CI], 0.58 to 0.90; P=0.004). Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for death, 0.78; 95% CI, 0.62 to 0.99; P=0.04). A total of 108 patients (17%) with nonmutated KRAS exon 2 had other RAS mutations. These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2. BRAF mutations were a negative prognostic factor. No new safety signals were identified. CONCLUSIONS: Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, NCT00364013.).
Buchs NC, Pugin F, Volonte F, et al. Robotic transanal endoscopic microsurgery: technical details for the lateral approach. Dis Colon Rectum. 2013; 56(10):1194-8 [PubMed] Related Publications
BACKGROUND: Transanal endoscopic microsurgery is a minimally invasive approach reserved for the resection of selected rectal tumors. However, this approach is technically demanding. Although robotic technology may overcome the limitations of this approach, the system can be difficult to dock, especially in the lithotomy position. OBJECTIVE: The study aim is thus to report the technical details of robotic transanal endoscopic microsurgery with the use of a lateral approach. DESIGN AND SETTINGS: This study is a prospective evaluation of robotic transanal endoscopic microsurgery in a single tertiary institution, under a protocol approved by our local ethics committee. INTERVENTION: Patients underwent a routine mechanical bowel preparation and were placed in the left or right lateral position according to the tumor location. A circular anal dilatator was used together with the glove port technique. The robotic system was then docked over the hip. A 30° optic and 2 articulated instruments were used with an additional assistant trocar. The tumor excision was realized with an atraumatic grasper and an articulated cautery hook, and the defect was closed with barbed continuous stiches in each case. MAIN OUTCOME MEASURE: The primary outcome was the safety and feasibility of the procedure. RESULTS: Three patients underwent a robotic transanal endoscopic microsurgery with the use of the lateral approach. Mean operative time was 110 minutes, including 20 minutes for the docking of the robot. There was 1 intraoperative complication (a pneumoperitoneum without intraabdominal lesion) and no postoperative complications. Mean hospital stay was 3 days. Margins were negative in all the cases. LIMITATIONS: The study was limited by the small number of patients. CONCLUSION: Robotic transanal endoscopic microsurgery with use of the lateral approach is feasible and may facilitate the local resection of small lesions of the mid and lower rectum. It might assume an important place in sphincter-preserving surgery, especially for selected and early rectal cancer (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A114).
Souadka A, Majbar MA, Bougutab A, et al. Risk factors of poor functional results at 1-year after pseudocontinent perineal colostomy for ultralow rectal adenocarcinoma. Dis Colon Rectum. 2013; 56(10):1143-8 [PubMed] Related Publications
BACKGROUND: Pseudocontinent perineal colostomy is one of the techniques that helps recover the body image of patients undergoing abdominoperineal resection. This technique is rarely used internationally given its unknown functional results. OBJECTIVE: The study aimed to evaluate 1-year functional outcomes of perineal pseudocontinent colostomy and to determine the risk factors for "poor" functional results. DESIGN: This study is a retrospective interventional case series. SETTINGS: This study was conducted at a tertiary care university hospital and oncological center in Morocco. PATIENTS: From January 1993 to December 2007, 149 patients underwent pseudocontinent perineal colostomy after abdominoperineal resection for low rectal adenocarcinoma. INTERVENTION: Pseudocontinent perineal colostomy was performed with the use of the Schmidt technique after abdominoperineal resection. MAIN OUTCOME MEASURES: One-year functional results were assessed according to the Kirwan classification system. Functional results were considered "poor" when the Kirwan score was C, D, or E. Univariable and multivariable analyses were used to evaluate the impact of age, sex, type of surgery, irrigation frequency, palpable muscular ring, concomitant chemoradiotherapy, stage, and perineal complications on functional results. RESULTS: One hundred forty-six patients were analyzed. According to the Kirwan system, the scores showed that 100 (68.5%) patients had "good" continence results (stage A-B) and 46 (31.5%) patients had altered functional results (stage C-D-E). With the exception of pelvic recurrences, no conversions from a perineal colostomy to an abdominal colostomy were performed for dissatisfactory functional results. In multivariate analysis, the only independent predictive factors of poor functional results were the occurrence of perineal complications (OR, 3.923; 95% CI, 1.461-10.35; p = 0.007) and extended resection (OR, 3.03; 95% CI, 1.183-7.750; p = 0.021) LIMITATION OF THE STUDY:: This study is an observational retrospective study on selected patients (mainly a young population). CONCLUSIONS: This study showed that perineal complications and extended resection are associated with poor functional results after pseudocontinent perineal colostomy. These data can help clinicians to better inform patients about the outcomes of this technique and to assist them in choosing the right reconstruction technique after abdominoperineal resection.
Dinnewitzer A, Jäger T, Nawara C, et al. Cumulative incidence of permanent stoma after sphincter preserving low anterior resection of mid and low rectal cancer. Dis Colon Rectum. 2013; 56(10):1134-42 [PubMed] Related Publications
BACKGROUND: Changes in the treatment of rectal cancer during the past decades have led to an increase in sphincter preservation with a consecutive decline in abdominoperineal resection rates. OBJECTIVE: The aim of this study was to analyze the cumulative incidence of permanent stoma in patients undergoing sphincter-preserving resection of mid and low rectal cancer. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a tertiary referral cancer hospital. PATIENTS: From 2003 to 2010, 125 patients with primary mid and low rectal cancer who underwent sphincter-preserving low anterior resection were included. MAIN OUTCOME MEASURES: The occurrence of a permanent stoma over time was investigated by using a Cox proportional hazards regression model and competing-risk models, with death as a competing risk. The risk factors were assessed by computing HRs and a Cox proportional hazards regression. RESULTS: After a median follow-up time of 61 months (range, 22-113), 15 of 125 patients ended up with a permanent stoma, accounting for a 5-year cumulative incidence of 6% (95% CI, 4%-11%). The reasons for obtaining a permanent stoma were anastomotic leakage (60%, 9/15), intractable fecal incontinence (27%, 4/15), and local recurrence (13%, 2/15). The Cox proportional hazards regression identified anastomotic leakage (HR, 6.10; 95% CI, 2.23-16.71; p = 0.0004) and coloanal anastomosis (HR, 4.31; 95% CI, 1.49-12.47; p = 0.007) as statistically significant risk factors. LIMITATIONS: Because of the small number of events in this sample, further investigations with a larger number of patients are required. Fecal incontinence was assessed by patient self-reported data without the use of a validated score. CONCLUSION: The 5-year cumulative incidence of a permanent stoma was 6%. Anastomotic leakage and coloanal anastomosis were identified as risk factors. These details should be considered before sphincter-preserving surgery.
Doyen J, Benezery K, Follana P, et al. Predictive factors for early and late local toxicities in anal cancer treated by radiotherapy in combination with or without chemotherapy. Dis Colon Rectum. 2013; 56(10):1125-33 [PubMed] Related Publications
BACKGROUND: The treatment of anal cancer is based on concomitant radiotherapy and chemotherapy and is associated with a nonnegligible rate of local severe toxicities that can strongly impair the quality of life. OBJECTIVE: A retrospective analysis was performed to screen the following factors as potential predictive factors for local skin and digestive toxicities, and as potential prognostic factors for cumulative colostomy incidence: sex, age, tumor size, clinical T and N stage, circumferential extension, invasion of anal margin, HIV status, type of chemotherapy, and type of radiotherapy and dose delivered. METHODS: One hundred five patients in our database treated between January 2000 and February 2010 met the eligibility criteria. RESULTS: Median follow-up was 54.1 months (range, 1-133). Early and late severe local toxicities occurred in 33 patients (31.4%) and 18 patients (17.1%). The 5-year cumulative rate of colostomy was 26.6%. Predictive factors for local severe early toxicities were as follows: clinical stage III/IV (p = 0.01), no brachytherapy boost (p = 0.003), and use of chemotherapy (p = 0.01). Only brachytherapy retained its independence in multivariate analysis (OR = 4.8 (1.4-16.3), p = 0.01). Human immunodeficiency virus positivity (p = 0.04) was the only predictive factor for late toxicities in univariate analysis; it was linked independently to the occurrence of ulcer (OR = 0.1 (0.01-0.66), p = 0.01). Tumor size ≥4 cm (p < 0.001) and occurrence of grade 2 to 3 ulcers (p < 0.001) were correlated with greater cumulative colostomy incidence. CONCLUSIONS: In this cohort, nonuse of brachytherapy was an independent predictive factor for local acute toxicity. Human immunodeficiency virus positivity was the only predictive factor for local late toxicities and strongly influenced the onset of ulcer.
Rollot F, Chauvenet M, Roche L, et al. Long-term net survival in patients with colorectal cancer in France: an informative contribution of recent methodology. Dis Colon Rectum. 2013; 56(10):1118-24 [PubMed] Related Publications
BACKGROUND: Net survival, the survival that might occur if cancer was the only cause of death, is a major epidemiological indicator. Recent findings have shown that the classical methods used for the estimation of net survival from cancer registry data, referred as to "relative-survival methods," provided biased estimates. OBJECTIVES: The aim of this study was to provide, for the first time, long-term net survival rates for colorectal cancer by using a population-based digestive cancer registry. DESIGN: This study is a population-based cancer registry analysis. The recently proposed unbiased nonparametric Pohar-Perme estimator was used. PATIENTS: Overall, 14,715 colorectal cancers diagnosed between 1976 and 2005 and registered in the population-based digestive cancer registry of Burgundy (France) were included. MAIN OUTCOME MEASURES: The primary outcome measured was cancer net survival, ie, the survival that might occur if all risks of dying of other causes than cancer were removed RESULTS: : Ten-year net survival increased from 31% during the 1976 to 1985 period to 47% during the 1986 to 1995 period and then leveled out (48% during the 1996-2005 period). There was a major improvement in 10-year net survival after resection for cure and for stage I to III. It was striking for stage III cancers, for which 10-year net survival increased from 21% (1976-1985) to 49% (1996-2005). The corresponding net survivals were 70% and 87% for stage I and 49% and 65% for stage II. These trends can be related to the decrease in operative mortality, the increase in the proportion of patients resected for cure, and the improvement in stage at diagnosis. They were mainly seen between 1976 and 1995, explaining why survival leveled out after 1995. LIMITATIONS: The study was limited by its retrospective and population-based nature. CONCLUSIONS: Further improvements for colorectal cancer management can be expected from more effective treatments and from the implementation of organized cancer screening.
Habr-Gama A, Sabbaga J, Gama-Rodrigues J, et al. Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon Rectum. 2013; 56(10):1109-17 [PubMed] Related Publications
BACKGROUND: No immediate surgery (Watch and Wait) has been considered in select patients with complete clinical response after neoadjuvant chemoradiation to avoid postoperative morbidity and functional disorders after radical surgery. OBJECTIVE: The purpose of this study was to demonstrate the long-term results of patients who had a complete clinical response following an alternative chemoradiation regimen and were managed nonoperatively. DESIGN: This is a prospective study. SETTINGS: This study was conducted at a single center. PATIENTS: Seventy consecutive patients with T2-4N0-2M0 distal rectal cancer were studied. Neoadjuvant chemoradiotherapy included 54 Gy and 5-fluorouracil/leucovorin delivered in 6 cycles every 21 days. Patients were assessed for tumor response at 10 weeks from radiation completion. Patients with incomplete clinical response were referred to immediate surgery. Patients with complete clinical response were not immediately operated on and were monitored. MAIN OUTCOME MEASURES: The primary outcomes measured were the initial complete clinical response rates after 10 weeks and the sustained complete clinical response rates after 12 months from chemoradiotherapy. RESULTS: One patient died during chemoradiotherapy because of cardiac complications. Forty-seven (68%) patients had initial complete clinical response. Of these, 8 developed local regrowth within the first 12 months of follow-up (17%). Thirty-nine sustained complete clinical response at a median follow-up of 56 months (57%). An additional 4 patients (10%) developed late local recurrences (>12 months of follow-up). Overall, 35 patients never underwent surgery (50%). LIMITATIONS: This study is limited by the short follow-up and small sample size. CONCLUSION: Extended chemoradiation therapy with additional chemotherapy cycles and 54 Gy of radiation may result in over 50% of sustained (>12 months) complete clinical response rates that may ultimately avoid radical rectal resection. Local failures occur more frequently during the initial 12 months of follow-up in up to 17% of cases, whereas late recurrences are less common but still possible, leading to 50% of patients who never required surgery. Strict follow-up may allow salvage therapy in the majority of these patients (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A113.).
Kanaan Z, Roberts H, Eichenberger MR, et al. A plasma microRNA panel for detection of colorectal adenomas: a step toward more precise screening for colorectal cancer. Ann Surg. 2013; 258(3):400-8 [PubMed] Related Publications
OBJECTIVE: The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of colorectal (CR) adenomas. BACKGROUND: Detection of precancerous lesions such as CR adenoma is a key to reduce CR cancer (CRC) mortality. There is a great need for accurate, noninvasive biomarkers for detection of CR adenoma and CRC. MiRNAs are non-protein-coding RNAs that regulate gene expression. Our prior work investigated the dysregulation of 5 plasma miRNAs in CRC patients. As intended, we undertook a more comprehensive plasma-miRNA screening study in patients with CR adenoma and CRC. METHODS: We screened for 380 plasma-miRNAs using microfluidic array technology (Applied BioSystems) in a screening cohort of 12 healthy controls, 9 patients with CR adenomas, and 20 patients with CRC. A panel of the most dysregulated miRNAs (P < 0.05, False Discovery Rate: 5%) was then validated in a blinded cohort of 26 healthy controls, 16 patients with large adenomas, and 45 patients with CRC. RESULTS: A panel of 8 plasma miRNAs (miR-532-3p, miR-331, miR-195, miR-17, miR-142-3p, miR-15b, miR-532, and miR-652) distinguished polyps from controls with high accuracy [area under curve (AUC) = 0.868 (95% confidence interval [CI]: 0.76-0.98)]. In addition, a panel of 3 plasma miRNAs (miR-431, miR-15b, and miR-139-3p) distinguished Stage IV CRC from controls with an [AUC = 0.896 (95% CI: 0.78-1.0)]. Receiver-operating-characteristic curves of miRNA panels for all CRC versus controls and polyps versus all CRC showed AUC values of 0.829 (95% CI: 0.73-0.93) and 0.856 (95% CI: 0.75-0.97), respectively. CONCLUSIONS: Plasma miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This miRNA panel warrants study in larger cohorts. Plasma-based assays could provide better screening compliance compared to fecal occult blood or endoscopic screening.
Vauthey JN, Zimmitti G, Kopetz SE, et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013; 258(4):619-26; discussion 626-7 [PubMed] Related Publications
OBJECTIVE: To determine the impact of RAS mutation status on survival and patterns of recurrence in patients undergoing curative resection of colorectal liver metastases (CLM) after preoperative modern chemotherapy. BACKGROUND: RAS mutation has been reported to be associated with aggressive tumor biology. However, the effect of RAS mutation on survival and patterns of recurrence after resection of CLM remains unclear. METHODS: Somatic mutations were analyzed using mass spectroscopy in 193 patients who underwent single-regimen modern chemotherapy before resection of CLM. The relationship between RAS mutation status and survival outcomes was investigated. RESULTS: Detected somatic mutations included RAS (KRAS/NRAS) in 34 (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%) patients. At a median follow-up of 33 months, 3-year overall survival (OS) rates were 81% in patients with wild-type versus 52.2% in patients with mutant RAS (P = 0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild-type versus 13.5% with mutant RAS (P = 0.001). Liver and lung recurrences were observed in 89 and 83 patients, respectively. Patients with RAS mutation had a lower 3-year lung RFS rate (34.6% vs 59.3%, P < 0.001) but not a lower 3-year liver RFS rate (43.8% vs 50.2%, P = 0.181). In multivariate analyses, RAS mutation predicted worse OS [hazard ratio (HR) = 2.3, P = 0.002), overall RFS (HR = 1.9, P = 0.005), and lung RFS (HR = 2.0, P = 0.01), but not liver RFS (P = 0.181). CONCLUSIONS: RAS mutation predicts early lung recurrence and worse survival after curative resection of CLM. This information may be used to individualize systemic and local tumor-directed therapies and follow-up strategies.
Gavert N, Shvab A, Sheffer M, et al. c-Kit is suppressed in human colon cancer tissue and contributes to L1-mediated metastasis. Cancer Res. 2013; 73(18):5754-63 [PubMed] Related Publications
The transmembrane neural cell adhesion receptor L1 is a Wnt/β-catenin target gene expressed in many tumor types. In human colorectal cancer, L1 localizes preferentially to the invasive front of tumors and when overexpressed in colorectal cancer cells, it facilitates their metastasis to the liver. In this study, we investigated genes that are regulated in human colorectal cancer and by the L1-NF-κB pathway that has been implicated in liver metastasis. c-Kit was the most highly suppressed gene in both colorectal cancer tissue and the L1-NF-κB pathway. c-Kit suppression that resulted from L1-mediated signaling relied upon NF-κB, which directly inhibited the transcription of SP1, a major activator of the c-Kit gene promoter. Reconstituting c-Kit expression in L1-transfected cells blocked the biological effects conferred by L1 overexpression in driving motility and liver metastasis. We found that c-Kit expression in colorectal cancer cells is associated with a more pronounced epithelial morphology, along with increased expression of E-cadherin and decreased expression of Slug. Although c-Kit overexpression inhibited the motility and metastasis of L1-expressing colorectal cancer cells, it enhanced colorectal cancer cell proliferation and tumorigenesis, arguing that separate pathways mediate tumorigenicity and metastasis by c-Kit. Our findings provide insights into how colorectal cancer metastasizes to the liver, the most common site of dissemination in this cancer.
Ferguson E, Starmer C Incentives, expertise, and medical decisions: testing the robustness of natural frequency framing. Health Psychol. 2013; 32(9):967-77 [PubMed] Related Publications
OBJECTIVES: The natural frequency effect (NF effect)-whereby framing health risks using information presented as natural frequencies (NFs), instead of conditional probabilities (CPs), results in improved diagnostic problem solving-has led to the recommended use of NFs in clinical practice. This experiment tests, via incentivization of a lab-based decision, the hypothesis that the NF effect reflects differential motivation applied to solving problems that differ in complexity. The study examines if incentive effects are moderated by task complexity and expertise and also explores the extent to which NF frames improve diagnostic understanding. METHODS: Three-hundred and 25 participants (235 novices and 90 medical experts) were randomly allocated to a frame (NF vs. CP) by task difficulty (short vs. standard menus) by incentive (present vs. absent) between-subjects design. The task was to calculate the positive predictive value (PPV) of the hemoccult test for colorectal cancer. Effort, self-efficacy, and diagnostic understanding were assessed. RESULTS: Incentives increased correct problem solving and the NF effect was replicated. The NF effect did not vary as a function of incentivization, but was slightly attenuated by task complexity and expertise. There was no evidence that effort mediated the incentive effect. The correct PPV (which is low) was associated with reduced trust in the test's diagnostic accuracy. For those who committed errors, NF frames increased the likelihood of underestimating the PPV, with underestimation associated with greater trust in the test. CONCLUSIONS: The NF effect is robust to incentives supporting the use of NF frames in clinical settings. When errors occur, however, NF frames are linked to underestimation.
Patil S, Shah AG, Bhatt H, et al. Tuberculosis of rectum simulating malignancy and presenting as rectal prolapse - a case report and review. Indian J Tuberc. 2013; 60(3):184-5 [PubMed] Related Publications
Tuberculosis of the gastrointestinal tract (GIT) occurs as a primary lesion or secondary to a focus of tuberculosis elsewhere in the body, most commonly in the lungs. Tuberculosis can affect any part of the GIT from the oesophagus to the anal canal. Two main types are - the tuberculous ulcer and the rarer hypertrophic type which is generally found at the ileocecal junction, less commonly in the colon or rectum. Tuberculosis of bowel distal to ileocecal junction is rare and is seldom considered as a differential diagnosis of rectal stricture (2%). We report a case of rectal tuberculosis presenting with rectal prolapse and masquerading as malignancy, clinically, radiologically as well as on colonoscopy. The diagnosis was confirmed by repeated histopathological examination. The patient underwent definitive surgery along with anti-tuberculous therapy.
Gulubova M, Manolova I, Ananiev J, et al. Relationship of TGF-β1 and Smad7 expression with decreased dendritic cell infiltration in liver gastrointestinal cancer metastasis. APMIS. 2013; 121(10):967-75 [PubMed] Related Publications
Immune responses and their modulation within the liver are critical to the outcome of liver malignancies. In late-stage tumors, secreted TGF-β promotes oncogenic functions and can confer tolerogenicity to some immune cells like DCs. The TGF-β signaling pathway is involved in the control of several biological processes, including immunosurveillance. The aim of the present study was to assess CD1a(+) and CD83(+) DCs and to evaluate the impact of TGF-β pathway on DCs maturation and distribution in the liver metastases from gastric and colorectal tumors. The percentage of CD83(+) DCs in the liver tissue, surrounding metastasis and in the metastasis-free liver was measured by flow cytometry, and TGF-β levels were assessed in the tissue supernatant from the peritumoral liver after mononuclear cell isolation and in the sera of the same patients. CD1a(+) and CD83(+) DCs were observed in the tumor stroma and border. Out of 73 patients, there was cytoplasmic reactivity: of TGF-β1 in 37 (50.7%); of Smad4 in 62 (84.9%); of Smad7 in 46 (63%), and of TGFβRII in 39 (53.4%) of the metastases. The TGF-β1 expression in tumor cell cytoplasm correlated with low CD1a(+) and low CD83(+) DCs infiltration. The tissue levels of TGF-β1, measured by ELISA in the supernatant were significantly increased in metastases than in normal liver. Using a two-color FACS analysis, we found that the percentage of HLA-DR(+) CD83(+) DCs in metastases was significantly decreased as compared with metastasis-free liver tissue. In conclusion, the positive and negative correlations between the mediators from the TGF-β pathway implied the existence of imbalance and suppression of this cytokine activity. The presence of increased TGF-β expression by immunohistochemistry in tumor cells was confirmed by detection of increased TGF-β tissue level in the supernatant from the tissue homogenate. The observation of low numbers of CD1a(+) and CD83(+) DCs in tumor stroma correlated with TGF-β overexpression in tumor cells, a fact that well documents the immunosuppressive role of TGF-β in metastasis development. The increased percentage of CD83(+) DCs in the peritumoral tissue supposes that there could be active recruitment or local differentiation of DCs in the metastasis border, but inside the tumor the immune cells recruitment and activity are suppressed by TGF-β and by other cytokines.
Tam HH, Collins DJ, Brown G, et al. The role of pre-treatment diffusion-weighted MRI in predicting long-term outcome of colorectal liver metastasis. Br J Radiol. 2013; 86(1030):20130281 [PubMed] Article available free on PMC after 01/10/2014 Related Publications
OBJECTIVE: To determine the prognostic value of pre-treatment apparent diffusion coefficient (ADC) of colorectal liver metastases in predicting disease response, progression-free survival (PFS) and overall survival (OS). METHODS: We retrospectively reviewed 102 patients who underwent pre-treatment diffusion-weighted MRI using a breath-hold (b=0, 150, 500) or a free-breathing (b=0, 50, 100, 250, 500, 750) technique. The mean ADC (b=0-500) and mean flow-insensitive ADC (ADChigh) values (breath-hold: b=150 and 500; free-breathing: b=100 and 500) of up to three hepatic lesions were evaluated in each patient. Clinical and laboratory parameters were recorded. Tumour response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 12 weeks after treatment. Associations between tumour response, ADC values and clinical/laboratory parameters were examined by one-way analysis of variance. The relationship of ADC with PFS and OS was determined by Kaplan-Meier analysis. RESULTS: 62 patients responded to chemotherapy at 12 weeks. The pre-treatment mean ADC and mean ADChigh were higher in the non-responding group than in the responding group (1.55 vs 1.36, p=0.033; 1.40 vs 1.16, p=0.024). However, the PFS and OS of the two groups of patients stratified by the median of mean ADC values or threshold derived by receiver operating characteristic analysis were not statistically significant. By multivariate Cox regression analysis, patients with ≤2 metastases and response to chemotherapy showed better PFS; white cell count ≤10 and surgical treatment were associated with better OS. CONCLUSION: Colorectal liver metastasis with higher pre-treatment mean ADC and mean ADChigh was associated with poorer response to chemotherapy. However, ADC and ADChigh values did not predict the patient outcome in this study cohort. ADVANCES IN KNOWLEDGE: High mean ADC values of colorectal liver metastases on pre-treatment diffusion-weighted MRI is associated with poorer response to chemotherapy.