Colorectal (Bowel) Cancer
Colorectal cancer (or bowel cancer) is one of the most common types of cancer in both men and women. Approximately four fifths of these cancers are found in the colon (large intestine), and one fifth in the rectum. Prevention and early detection of colorectal cancer is important. Some of most common symptoms include a change in bowel habit (eg. constipation, and bleeding), mucus discharge, and discomfort or pain in the lower abdomen. The vast majority of colon and rectum cancers are adenocarcinomas, around 10% of these are mucinous (protein contained in mucus). The median age at diagnosis is 70, age adjusted incidence rates are slightly higher in males compared to females. A substantial proportion of cases are in those with a genetic predisposition to colorectal cancer. Diet may also have an influence on the incidence of colorectal cancer, diatry fibre, retinoids, and calcium are thought to be protective, while high intake of animal fats may increases risk. Colorectal cancer may develop from benign polyps (a polyp is a tumour on a stem most commonly found on mucous membranes). World-wide about 782,000 people are diagnosed with colorectal cancer each year.
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Herdiatry Colorectal Cancers
Screening for Colorectal (Bowel) Cancer
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MeSH term: Colorectal Neoplasms
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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).
This list of publications is regularly updated (Source: PubMed).
Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force.
JAMA. 2016; 315(23):2595-609 [PubMed] Related Publications
OBJECTIVE: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.
DESIGN, SETTING, AND PARTICIPANTS: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.
EXPOSURES: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed.
MAIN OUTCOMES AND MEASURES: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds.
RESULTS: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG).
CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.
Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
JAMA. 2016; 315(23):2576-94 [PubMed] Related Publications
OBJECTIVE: To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC.
DATA SOURCES: Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016.
STUDY SELECTION: English-language studies conducted in asymptomatic populations at general risk of CRC.
DATA EXTRACTION AND SYNTHESIS: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted.
MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events.
RESULTS: Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458,002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419,966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10,000 procedures, 95% CI, 2-5 in 10,000) and major bleeds (8/10,000 procedures, 95% CI, 5-14 in 10,000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings.
CONCLUSIONS AND RELEVANCE: Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.
Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.
JAMA. 2016; 315(23):2564-75 [PubMed] Related Publications
OBJECTIVE: To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer.
EVIDENCE REVIEW: The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods.
FINDINGS: The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States.
CONCLUSIONS AND RECOMMENDATIONS: The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient's overall health and prior screening history (C recommendation).
DCE-MRI-Derived Parameters as Predictors of Response to Neo-Adjuvant Chemoradiation Treatment of Rectal Carcinoma.
J Med Assoc Thai. 2016; 99(3):338-47 [PubMed] Related Publications
OBJECTIVE: To evaluate the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the treatment response.
MATERIAL AND METHOD: Nineteen patients with histologically proven rectal adenocarcinoma who were candidates for neo-adjuvant CRT were prospectively included. All patients were examined by conventional and DCE-MRi at three time points (pre-, during-, and post-CRT). Surgical resection was performed after complete CRT. The pathological response and Dworak regression grade were assessed. All parameters were blindly analyzed.
RESULTS: The median pathologic response rate for all patients was 40%. Dworak regression grades of 0, 1, 2, 3, and 4 were found in 0.0%, 21.1%, 42.1%, 26.3%, and 10.5% of patients, respectively. The tumor thickness and length were 30% and 32.9% lower at during-CRT and 40.6% and 44.7% lower post-CRT and had moderate and fair negative correlations with the pathologic response rate and Dworak regression rate, respectively. Among the DCE-MRI parameters, only a change in the time to peak between pre- and during-CRT was correlated with the Dworak regression grade (p = 0.01). The percentage change in the time to peak in patients with poor regression (grades 0-1) was significantly greater than in patients with intermediate/complete regression (grades 2-4) [139.25% vs. 6.13%].
CONCLUSION: Changes in the tumor thickness and length evaluated by conventional MRI and the time to peak evaluated by DCE-MRI during CRT may be useful for predicting the treatment response of rectal cancer patients.
Pelvic intraoperative iatrogenic oncosurgical injuries: single-center experience.
J BUON. 2016 Mar-Apr; 21(2):498-504 [PubMed] Related Publications
METHODS: The records of 2702 patients admitted to our clinic over a 15-year period, (January 2000-December 2014), were analyzed for type and frequency of intraoperative accidents.
RESULTS: Urinary tract lesions were the most common injuries seen in this series (63.1%), followed by enteral (28.1%) and vascular (8.8%) injuries, with an overall incidence of 2.9% for the whole group. Iatrogenic injuries showed a statistically significant difference in incidence depending on the type of primary malignancy (p<0.002). Cervical cancer was associated with a higher rate of ureteral lesions, whereas enteral injuries occurred predominantly during surgical resection for ovarian cancer. The use of neoadjuvant radiotherapy or chemotherapy has been associated with a significantly lower risk of surgical iatrogenic injuries (p=0.004).
CONCLUSION: Immediate recognition of the lesion and prompt treatment are recommended in order to lower postoperative complications and to avoid a second operation.
Identification of disrupted pathways in ulcerative colitis-related colorectal carcinoma by systematic tracking the dysregulated modules.
J BUON. 2016 Mar-Apr; 21(2):366-74 [PubMed] Related Publications
METHODS: We firstly recruited the UC- and CRC-related microarray data from ArrayExpress database, and obtained 8 expression profiles which contained 5 conditions (normal, UC, early stage CRC, stage II CRC and stage III CRC). Then, the PPI networks of normal and different disease stages were constructed and re-weighted using Pearson correlation coefficient (PCC). Next, the condition-specific modules were extracted from 5 PPI networks via clique-merging algorithm, and altered modules were captured on the basis of module correlation density (MCD). Subsequently, the gene compositions of altered modules and gene differential expressions in different disease stages were identified to screen the dysregulated genes. Finally, pathways enrichment analyses for the genes in altered modules and differentially expressed genes (DEGs) were implemented.
RESULTS: The extensive changes of gene correlations existed in 5 condition-specific PPI networks, which made different MCDs among different disease stages. The same number of modules (N=1952) were explored in 5 PPI networks. By comparing with normal condition, there were 463, 791, 1060 and 345 altered modules in UC, early stage CRC, stage II and III CRC, respectively. Overall, 77, 110, 170 and 110 common genes were identified between genes of altered modules and DEGs in UC, early stage CRC, stage II CRC and stage III CRC, respectively. Functional enrichment analyses indicated that cell cycle and oocyte meiosis were the common and most significant pathways in colonic diseases.
CONCLUSIONS: Tracking the altered modules from PPI networks is useful to uncover disrupted pathways in colonic diseases. Cell cycle and oocyte meiosis might be associated with the pathophysiological background of colonic diseases.
Colonoscopy Atlas of Colon Polyps and Neoplasms.
J Miss State Med Assoc. 2016; 57(3):68-71 [PubMed] Related Publications
The Impact of Colorectal Cancer (CRC) in Mississippi, and the need for Mississippi to Eliminate its CRC Burden.
J Miss State Med Assoc. 2016; 57(3):62-7 [PubMed] Related Publications
COLORECTAL CANCER SCREENING PRACTICES AMONG THREE AMERICAN INDIAN COMMUNITIES IN MINNESOTA.
J Cult Divers. 2016; 23(1):21-7 [PubMed] Related Publications
STC1 and NF-κB p65 (Rel A) is Constitutively Activated in Colorectal Cancer.
Clin Lab. 2016; 62(3):463-9 [PubMed] Related Publications
METHODS: Tumor tissue samples were collected from 48 patients with CRC. RT-PCR and Real-time PCR analysis was performed to examine mRNA levels of STC1 and NF-κB p65.
RESULTS: The relative mRNA levels of STC1 and NF-κB p65 were significantly higher in tumor tissues than in adjacent mucosa (p = 0.025 and p = 0.044, respectively). The data also showed that STC1 and NF-κB p65 mRNA levels were not significantly associated with clinicopathological characteristics. In addition, there was no association between expression levels of STC1 and NF-κB p65 in tumor samples.
CONCLUSIONS: Our data indicate that STC1 and NF-κBp65 is activated constitutively in colorectal carcinoma tissues, suggesting that activation of these factors might play an important role in colorectal tumorigenesis. Future studies should examine STC1 and NF-κBp65 as a molecular target for the treatment of CRC.
Is Serum Caveolin-1 a Useful Biomarker for Progression in Patients with Colorectal Cancer?.
Clin Lab. 2016; 62(3):401-8 [PubMed] Related Publications
METHODS: A total of 61 patients with CRC (26 male, 35 female) and 46 controls (38 male, 8 female) were enrolled. Serum CAV-1 levels were measured by ELISA. The relationship between CAV-1 and progression-free survival (PFS) was analyzed with use of receiver operating characteristic (ROC) and Kaplan-Meier analysis. Results were given as median (95% CI). Mann-Whitney test was used for the comparison of groups.
RESULTS: CAV-1 levels were found to be 11.5 ng/mL (10.4-12.9) in CRC and 11.9 ng/mL (10.7-14.4) in controls (p = 0.465). The serum CAV-1 levels in CRC patients with disease progression and without progression were respectively 10.0 ng/mL (8.5-11.3) and 12.2 ng/mL (11.1-14.8) (p = 0.023). In ROC analysis, if CAV-1 levels are equal or lesser than 10.73 ng/mL, it might show presence of progression with a sensitivity 73.3% and specificity 66.7% in patients with CRC (area under the ROC curve (AUC) = 0.697, p = 0.005). The mean PFS time was found to be 29.7 months (19.8-39.7, 95% CI for the mean) in patients who have CAV-1 level ≤ 10.73 ng/mL and 61.9 months (44.2-79.6) in patients who have CAV-1 level > 10.73 ng/mL [hazard ratios (HR) with 95% CI = 3.49 (1.26 - 9.68) (p = 0.017)].
CONCLUSIONS: Our results strongly suggest that CAV-1 levels might be used as a marker to determine progression of CRC. When considered in combination with other biomarkers of CRC, CAV-1 is clinically informative and instructive.
Detection of EGFR expression in patients with colorectal cancer and the therapeutic effect of cetuximab.
J BUON. 2016 Jan-Feb; 21(1):95-100 [PubMed] Related Publications
METHODS: This study used paraffin-embedded tumor specimens of 70 CRC patients who were treated with cetuximab. Immunohistochemistry (IHC) was used to detect the expression of EGFR in CRC tumor specimens. The patient clinical features and treatment administered were recorded and then, the therapeutic effect of cetuximab was evaluated. Progression-free survival (PFS) and overall survival (OS) were assessed.
RESULTS: The positive expression rate of EGFR was 64% (45/70), while 18 patients had negative expression. Twenty-two cases had weak positive expression, 15 cases positive expression and another 15 strongly positive expression. Of 70 specimens, 27 (38.6%) had high EGFR expression belonging to 20 (50%) males and 7 (23%) females (p<0.05). However, age, Karnofsky performance status (KPS), tumor site, grade of differentiation and clinical stage showed no significant difference in relation to EGFR expression (p>0.05). No patient achieved complete remission (CR), 15 (21.4%) had partial remission (PR), 12 (17.1%) were in stable state (SD) and 40 (57.1%) patients had disease progression (PD). Disease control rate (DCR) was 39.02% (16/41) in the group with low EGFR expression and 48.28% (14/29) in the group with high EGFR expression (p>0.05).
CONCLUSION: EGFR expression in CRC tissue is correlated with patient gender. In the group with higher EGFR expression, the effectiveness of cetuximab was significantly higher than that in the low EGFR expression group, indicating correlation between the high expression of EGFR and the short-term effect of cetuximab.
Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.
J BUON. 2016 Jan-Feb; 21(1):87-94 [PubMed] Related Publications
METHODS: Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line.
RESULTS: MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure.
CONCLUSION: Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.
Outcomes of laparoscopic surgery for rectal cancer in elderly patients.
J BUON. 2016 Jan-Feb; 21(1):80-6 [PubMed] Related Publications
METHODS: Three-hundred ten patients who underwent laparoscopic surgery with radical intent for rectal cancer at our institution between January 2008 and December 2014 were included in this retrospective study. Patients were divided into two age groups (younger than 70 years and older than 70 years) and were evaluated with respect to short- and long-term outcomes.
RESULTS: Postoperative morbidity was similar in elderly and young groups (p=0.718). Overall survival and disease-free survival were not significantly different between the two groups. Advanced age was not independent predictor of overall survival and disease-free survival by univariate and multivariate analysis.
CONCLUSION: Our data indicate that laparoscopic surgery with radical intent can be performed as safely in elderly patients as in young patients, with comparable postoperative results and long-term outcomes.
Cetuximab in third-line therapy of patients with metastatic colorectal cancer: A single institution experience.
J BUON. 2016 Jan-Feb; 21(1):70-9 [PubMed] Related Publications
METHODS: 72 patients with wild-type KRAS mCRC were enrolled. All of them had previously been treated with a fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy. Patients received cetuximab as monotherapy or in combination with irinotecan-based chemotherapy. All patients were to be treated until the occurrence of disease progression or unacceptable toxicity.
RESULTS: All patients were evaluated for progression free survival (PFS), overall survival (OS) and safety. The median PFS was 4.77 months (95% CI: 4.08-5.45), with an actuarial 47.22% without progression at 3 months and 16.67% at 6 months. The median OS was 11.35 months (95% CI: 9.64-13.06), with 79.17% of the patients being alive at 6 months and 30.56% at 12 months. PFS was significantly higher in patients with skin toxicity as compared to those without skin toxicity (5.31 vs 2.61 months, p<0.001) and with smaller number of metastatic organs vs greater number of metastatic organs (p=0.05). OS was significantly higher in patients with good performance status (p=0.004), with skin toxicity (p=0.013) and with smaller number of metastatic organs (p<0.001). Superior survival rates with higher grades of skin toxicity were noticed. As for patient characteristics, there were no significant differences in age, gender, and primary site localization.
CONCLUSION: Cetuximab improved PFS, OS and preserved the quality of life in patients with mCRC whose previous treatments had failed.
Breast and Colorectal Cancer Survival Disparities in Southeastern Wisconsin.
WMJ. 2016; 115(1):17-21 [PubMed] Related Publications
METHODS: This paper examines breast and colorectal cancer survival disparities in an 8-county region in southeastern Wisconsin, including the City of Milwaukee. Cox proportional hazards models were used to examine survival trends, and a new adaptation of adaptive spatial filtering--a disease mapping method--was used to examine spatial patterns of survival.
RESULTS: Disparities by race and ethnicity are revealed, and spatial analyses identify specific areas within the study region that have lower than expected survival rates.
CONCLUSIONS: Cancer control efforts in southeastern Wisconsin should focus on black/African American and Hispanic/Latina women to reduce breast cancer survival disparities, and black/African American populations to reduce colorectal cancer disparities. Evidence indicates that targeted interventions may be needed to serve populations in the Milwaukee and Kenosha metropolitan areas, as well as areas of Walworth, Ozaukee, and Waukesha counties.
Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial.
JAMA. 2016 Mar 22-29; 315(12):1266-75 [PubMed] Related Publications
OBJECTIVE: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah.
INTERVENTIONS: Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months.
MAIN OUTCOMES AND MEASURES: The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden.
RESULTS: Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. [table: see text].
CONCLUSIONS AND RELEVANCE: Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 01187901.
Colorectal cancer detection in an asymptomatic population: fecal immunochemical test for hemoglobin vs. fecal M2-type pyruvate kinase.
Biochem Med (Zagreb). 2016; 26(1):114-20 [PubMed] Free Access to Full Article Related Publications
MATERIALS AND METHODS: A total of 1027 asymptomatic subjects (median age 66 [59-74] years; females 504 [49.1%]), identified through the general practitioners' rosters, were invited for the collection of 2 fecal samples for FIT and M2-PK evaluation. Participants with at least positive one fecal test were referred for colonoscopy. Quality indicators for screening performance were calculated and analyzed using Fisher's exact test.
RESULTS: Overall, 572 subjects underwent both FIT and M2-PK assessment (participation rate 55.7%): 93 participants showed positive results for at least one test (positivity rate 16.3%). Only 10 patients were positive for both tests. Attendance rate to colonoscopy was 86.0% and a total of 65 adenomas and 7 cancers were detected. Combined use of FIT and fecal M2-PK permitted the identification of 18 more neoplasm (25%) without improving colonoscopy workload, as deduced by the comparable number needed to scope (P = 0.402).
CONCLUSION: The addition of M2-PK testing to FIT offers the potential to detect additional neoplasms that either do not bleed or only bleed intermittently without reducing participation rate and without increasing endoscopy workload.
Bariatric surgery and implications for stoma care.
Br J Nurs. 2016 Mar 10-23; 25(5):S22, S24-7 [PubMed] Related Publications
KLF17 Expression in Colorectal Carcinoma and Its Clinical Significance.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2016; 38(1):69-72 [PubMed] Related Publications
METHODS: Immunohistochemistry was performed to detect the expression of KLF17 in CRC and matched pericarcinous tissue,and the relationship between KLF17 expression and disease-free survival (DFS) was analyzed.
RESULTS: Of 73 CRC patients, KLF17 expression was positive in 32 patients and negative in 41 patients. KLF17 expression rate was significantly lower in CRC tissue than in pericarcinous tissue (χ(2)=12.418, P=0.001). The DFS of KLF17-positive stage III colon cancer patients was (56.3±7.2) months (95% CI: 42-70 months), which was significantly longer than that [(32.3±5.5) months (95% CI: 22-43 months)] of KLF17-negative patients (P=0.039).
CONCLUSION: KLF17 expression decreases in CRC tissue, and a positivie KLF17 expression predicts a better prognosis in stage III CRC patients.
Cancer Stem Cell-Based Models of Colorectal Cancer Reveal Molecular Determinants of Therapy Resistance.
Stem Cells Transl Med. 2016; 5(4):511-23 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
SIGNIFICANCE: Colorectal cancer stem cells (CSCs) have been shown to be responsible for tumor propagation, metastatic dissemination, and relapse. However, molecular pathways present in CSCs, as well as mechanisms of therapy resistance, are mostly unknown. Taking advantage of genetically characterized CSC lines derived from colorectal tumors, this study provides an extensive analysis of CSC response to EGFR-targeted therapy in vivo and an overview of factors implicated in therapy response or resistance. Furthermore, the implementation of a biobank of molecularly annotated CSC lines provides an innovative resource for future investigations in colorectal cancer.
Solitary thyroid metastasis from colon cancer: fine-needle aspiration cytology and molecular biology approach.
Pathologica. 2015 Sep-Dec; 107(3-4):192-6 [PubMed] Related Publications
Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review.
Clin Epigenetics. 2016; 8:25 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
LEIOMYOSARCOMA OF THE COLON.
Med Pregl. 2015 Nov-Dec; 68(11-12):413-7 [PubMed] Related Publications
CASE REPORT: We present a case of a 59-year-old male with anemia, weight loss, intermittent abdominal pain and right abdominal mass. Colonoscopy revealed an exophytic ulcerated neoplastic mass in the ascending colon and abdominal computed tomography scan showed an ill-defined heterogeneous tumor mass which surrounded almost the whole ascending colon. The patient underwent right hemicolectomy and partial resection of ileum. Histopathological examination revealed a leiomyosarcoma composed of atypical spindle cells positive for a smooth muscle actin, desmin and vimentin, and negative for c-kit, CD34, S100 and neuron specific enolase. The patient is alive 8 months after the operation, undergoing chemotherapy.
CONCLUSION: We have concluded that the multimodal approach comprising chemotherapy and complete surgical resection controls the leiomyosarcomas.
DIAGNOSTIC ROLE OF FLUORINE-18 (18F) FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY COMPUTED TOMOGRAPHY IN DETECTING RECURRENT DISEASE IN PATIENTS WITH COLORECTAL CANCER AND ELEVATED CARCINOEMBRYONIC ANTIGEN.
Med Pregl. 2015 Nov-Dec; 68(11-12):376-81 [PubMed] Related Publications
MATERIAL AND METHODS: The patients with colorectal cancer who underwent curative surgical resection and/ or chemotherapy, who were found in our database, were analyzed retrospectively. Forty-eight 18F-fluorodeoxyglucose positron emission tomography-computed tomography studies including 45 patients (14 women, 31 men; mean age: 62.93 years) with elevated serum, carcinoembryonic antigen levels, which had been performed between January 2011 and January 2014, were evaluated. Serum levels of carcinoembryonic antigen were measured within 3 months after positron emission tomography-computed tomography examination. Final diagnosis of recurrence was made by histopathological findings, radiology studies or clinical follow-up.
RESULTS: Recurrences were diagnosed in 37 patients, the prevalence being 77.1%. Liver metastases were found in 18 patients, abdominal, pelvic and/or mediastinal lymph nodes were positive in 19 patients, 11 patients had loco regional recurrences and 4 patients had pulmonary metastasis, and bone metastases were found in one patient. One patient was diagnosed with metastasis in scar tissue. The overall sensitivity and specificity of positron emission tomography-computed tomography was 90.24% and 71.42%, respectively. The positive and negative predictive values were 94.87% and 55.56%, respectively.
CONCLUSION: 18F-fluorodeoxyglucose positron emission tomography-computed tomography is a powerful tool that could be used in determining colorectal cancer recurrence in patients with elevated carcinoembryonic antigen levels and could have an important clinical impact on the management in patients with suspected recurrent colorectal cancer.
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.
Nature. 2016; 531(7592):53-8 [PubMed] Article available free on PMC after 03/09/2016 Related Publications
MRI Detection of Extramural Venous Invasion in Rectal Cancer: Correlation With Histopathology Using Elastin Stain.
AJR Am J Roentgenol. 2016; 206(4):747-55 [PubMed] Related Publications
MATERIALS AND METHODS: Forty-nine patients with rectal cancer who had undergone surgical resection with preoperative MRI were identified. Thirty-seven patients had received preoperative chemoradiation therapy (CRT). Sixty-nine MRI studies were independently reviewed by two blinded radiologists for EMVI using a score of 0-4. Comparison was made with histopathologic results obtained by two pathologists reviewing the elastin-stained slides in consensus. EMVI status was also correlated with other tumoral and prognostic features on imaging and pathologic analysis. Statistical analysis was performed using Fisher exact and McNemar tests.
RESULTS: EMVI was present in 31% of the pathology specimens. An MRI EMVI score of 3-4 was 54% sensitive and 96% specific in detecting EMVI in veins 3 mm in diameter or larger. Inclusion of a score of 2 as positive for EMVI increased the sensitivity to 79% but decreased the specificity to 74%, with poor positive predictive value. Preoperative CRT had no significant effect on the diagnostic performance of MRI. Contrast-enhanced MRI increased reader confidence for diagnosis or exclusion of EMVI compared with T2-weighted imaging. EMVI status correlated with depth of extramural invasion and proximity to mesorectal fascia.
CONCLUSION: Despite an anticipated increase in sensitivity for EMVI detection by histopathologic analysis using elastin compared with H and E staining, MRI maintains a high specificity and moderate sensitivity for the detection of EMVI.
Radiosensitizing potential of rutin against human colon adenocarcinoma HT-29 cells.
Bratisl Lek Listy. 2016; 117(3):171-8 [PubMed] Related Publications
MATERIALS AND METHODS: HT-29 cells were pre-treated with rutin and the effect on cell proliferation was determined by MTT assay followed by exposure to radiation. After irradiation, experimental groups were sham control, rutin alone, radiation alone, rutin along with radiation-treated HT-29 cells.
RESULTS: Cytotoxicity study illustrated that treatment of HT-29 cells with different concentrations of rutin reduced cell proliferation in a dose- and time-dependent manner. After irradiation, the HT-29 cells revealed that the combined effect of 4 Gy radiation and rutin at 80 µM concentration showed a decrease in cell viability as compared to rutin‑alone treated and 4 Gy‑alone irradiated HT-29 cells. Furthermore, the increase in apoptotic cells, change from normal nuclei to abnormal nuclei, alterations in mitochondrial membrane potential, increase in DNA damage, increase in levels of lipid peroxidative markers, and decrease in antioxidant status were observed in 4 Gy‑ and rutin-treated group as compared to the other treated groups.
CONCLUSIONS: Combined effect of rutin and radiation in HT-29 cells leads to a more pronounced cell death rate. Thus, rutin exhibits radiosensitizing effects on HT-29 cells (Tab. 4, Fig. 8, Ref. 42).
Use of Evidence-Based Interventions to Address Disparities in Colorectal Cancer Screening.
MMWR Suppl. 2016; 65(1):21-8 [PubMed] Related Publications
Rapamycin-Mediated mTOR Inhibition Reverses Drug Resistance to Adriamycin in Colon Cancer Cells.
Hepatogastroenterology. 2015; 62(140):880-6 [PubMed] Related Publications
METHODOLOGY: LoVo/Adr cells were designated accordingly into ADR group, Rapamycin (RAPA) group, ADR plus RAPA, and control group in main observations. Autophage, cell death and mdr1 were examined.
RESULTS: IC50 value of ADR in LoVo/Adr was significantly decreased in response to RAPA (P < 0.05). Autophagy rate of LoVo/Adr cells was higher in the ADR or RAPA-alone group than in control (p < 0.05), while ADR/RAPA combination has significantly increased autophagy rate compared to ADR or RAPA alone (p < 0.05). Compared with controls, apoptosis rate in the RAPA group had no difference (p > 0.05); whereas there was significant difference in ADR group (p < 0.05). Furthermore, apoptosis rate was significantly different in combined RAPA/ADR compared to ADR (p < 0.05). Expression of mRNA and protein P-gp level of mdr 1 gene in LoVo/Adr cells were significantly decreased under RAPA-treated groups at 25 µmol/L and 50 µmol/L (p < 0.05).
CONCLUSION: This study has indicated that the inhibition of the mTOR pathway reverses multidrug resistance in colorectal cancer cells, which is associated with increased autophagy, apoptosis and reduced mdr1 gene expression in drug-resistant cells treated with Adriamycin.