[Serrated polyps and their association with synchronous advanced colorectal neoplasia].

PubMed

Urman, Jesús; Gomez, Marta; Basterra, Marta; Mercado, María Del Rosario; Montes, Marta; Gómez Dorronsoro, Marisa; Garaigorta, Maitane; Fraile, María; Rubio, Eva; Aisa, Gregorio; Galbete, Arkaitz

2016-11-01

Large serrated polyps (SP), proximal SP, SP with dysplasia and the presence of multiple sessile serrated adenomas/polyps (SSA/P), which we refer to as SP with increased risk of metachronous lesions (SPIRML), have been associated with an increased risk of advanced colon lesions on follow-up. It is unclear, however, whether SPIRML are also associated with an increased risk of synchronous advanced colorectal neoplasia (ACN). The aim of this study was to estimate the prevalence of SPIRML and to evaluate the association between SPIRML and synchronous ACN. A cross-sectional population-based study in all patients (1,538) with histological diagnosis of SP obtained from colonoscopies, sigmoidoscopies and colonic surgery performed in Navarra Health Service hospitals (Spain) in 2011. Demographic parameters and synchronous colonic lesions (adenomas, advanced adenomas [AA] and ACN) were analyzed. One fourth of the sample (384 patients) presented SPIRML. These were older patients, with a slight predominance of women, and with no differences in body mass index (BMI) compared to patients without SPIRML. In the univariate analysis, patients with SPIRML showed an increased risk of adenoma, AA and ACN. In the multivariate analysis, the SPIRML group had a higher risk of synchronous AA and ACN (odds ratio [OR]: 2.38 [1.77-3.21] and OR: 2.29 [1.72-3.05], respectively); in the case of ACN, this risk was statistically significant in both locations (proximal or distal), with OR slightly higher for the proximal location. Different subtypes of SPIRML had a higher risk of AA and synchronous NA. SPIRML were common in patients with SP, and their presence was associated with an increased risk of synchronous ACN. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

A Risk Prediction Index for Advanced Colorectal Neoplasia at Screening Colonoscopy.

PubMed

Schroy, Paul C; Wong, John B; O'Brien, Michael J; Chen, Clara A; Griffith, John L

2015-07-01

Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer screening. Risk stratification for advanced colorectal neoplasia (ACN) might facilitate more effective shared decision making when selecting an appropriate screening option. Our objective was to develop and validate a clinical index for estimating the probability of ACN at screening colonoscopy. We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average-risk patients 50-79 years of age undergoing screening colonoscopy at two urban safety net hospitals. Predictors of ACN were identified using multiple logistic regression. Model performance was internally validated using bootstrapping methods. The final index consisted of five independent predictors of risk (age, smoking, alcohol intake, height, and a combined sex/race/ethnicity variable). Smoking was the strongest predictor (net reclassification improvement (NRI), 8.4%) and height the weakest (NRI, 1.5%). Using a simplified weighted scoring system based on 0.5 increments of the adjusted odds ratio, the risk of ACN ranged from 3.2% (95% confidence interval (CI), 2.6-3.9) for the low-risk group (score ≤2) to 8.6% (95% CI, 7.4-9.7) for the intermediate/high-risk group (score 3-11). The model had moderate to good overall discrimination (C-statistic, 0.69; 95% CI, 0.66-0.72) and good calibration (P=0.73-0.93). A simple 5-item risk index based on readily available clinical data accurately stratifies average-risk patients into low- and intermediate/high-risk categories for ACN at screening colonoscopy. Uptake into clinical practice could facilitate more effective shared decision-making for CRC screening, particularly in situations where patient and provider test preferences differ.

Systematic review with meta-analysis: the incidence of advanced neoplasia after polypectomy in patients with and without low-risk adenomas.

PubMed

Hassan, C; Gimeno-García, A; Kalager, M; Spada, C; Zullo, A; Costamagna, G; Senore, C; Rex, D K; Quintero, E

2014-05-01

Patients with one to two tubular adenomas <1 cm in size without high-grade dysplasia (low-risk group) are considered at low risk for colorectal cancer. However, it is uncertain whether they have the same risk of subsequent advanced neoplasia as those with no neoplasia at baseline colonoscopy. To compare incidence of metachronous advanced neoplasia between patients in the low-risk adenoma group and those without neoplasia at index colonoscopy. Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1992-2013. Studies comparing the incidence of post-polypectomy advanced neoplasia (adenomas ≥10 mm/high-grade dysplasia/villous or cancer) between the low-risk group and patients without colorectal neoplasia at the first colonoscopy were included. Detection rates for advanced neoplasia at endoscopic surveillance were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random-effect models. Inter-study heterogeneity was assessed using the I(2) statistic. Seven studies provided data on 11 387 patients. Mean surveillance periods ranged between 2 and 5 years. Altogether, 267 patients with post-polypectomy advanced neoplasia were detected in the two groups. The incidence of advanced neoplasia was 1.6% (119/7308) in those without neoplasia and 3.6% (148/4079) in those with low-risk adenoma, respectively, corresponding to a relative risk of 1.8 (95% CI: 1.3-2.6). Inter-study heterogeneity was only moderate (I(2) : 37%). No publication bias was present. Patients with low-risk adenomas at baseline had a higher risk of metachronous advanced neoplasia than the group with no adenomas at baseline, though the absolute risk was low in both groups. © 2014 John Wiley & Sons Ltd.

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

PubMed

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Risk of metachronous neoplasia on surveillance colonoscopy in young patients with colorectal neoplasia.

PubMed

Kim, Hyun Gun; Cho, Young-Seok; Cha, Jae Myung; Shin, Jeong Eun; Kim, Kyeong Ok; Yang, Hyo-Joon; Koo, Hoon Sup; Joo, Young-Eun; Boo, Sun-Jin

2018-03-01

Few prior reports exist that address the appropriate colonoscopy surveillance interval for individuals <50 years old. We compared the risk of metachronous neoplasia between younger (20-49 years) and older (50-54 years) cohorts. This multicenter retrospective cohort study compared the incidence of metachronous neoplasia in younger and older cohorts according to baseline risk stratification. Subjects were eligible if they underwent their first colonoscopy between June 2006 and May 2010 and had at least 1 or more surveillance colonoscopy up to June 2015. Among a total of 10,477 subjects who underwent baseline colonoscopy, 9722 were eligible after excluding 755 subjects. Of those 9722 subjects, 43% underwent surveillance colonoscopy. In the baseline high-risk adenoma group (n = 840), the 3-year risk of metachronous advanced neoplasia was 10.7% in the younger patients on screening colonoscopy and 8.9% in the older patients (P > .1). In the baseline low-risk adenoma group (n = 1869), the 5-year risk of metachronous advanced neoplasia was 4.9% in the younger patients on screening colonoscopy and 5.1% in the older patients (P > .1). Similarly, in the baseline no neoplasia group (n = 7013), the 5-year risk of metachronous advanced neoplasia was 4.1% in the younger patients on screening colonoscopy and 5.6% in the older patients (P > .1). Considering the similar risk of metachronous advanced neoplasia in younger and older individuals, we suggest a 3-year surveillance interval for high-risk adenoma and a 5-year surveillance interval for low-risk adenoma in young individuals without a strong family history. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis.

PubMed

Flores, Brisas M; O'Connor, Anthony; Moss, Alan C

2017-12-01

Long-standing ulcerative colitis is an established risk factor for colorectal neoplasia. A number of observational studies have suggested that evidence of mucosal inflammation (endoscopic or histologic) is associated with a greater risk for colorectal neoplasia than is mucosal healing. Our goal was to systematically analyze the risk of colorectal neoplasia in patients with ulcerative colitis who have ongoing mucosal inflammation to better inform surveillance strategies. We performed a systematic review and meta-analysis of the effect of endoscopic and/or histologic inflammation on the risk of colorectal neoplasia in cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. Six studies met the inclusion criteria, incorporating outcomes in 1443 patients. No study used a single validated measure for mucosal inflammation. The pooled odds ratio for colorectal neoplasia was 3.5 (95% confidence interval [CI], 2.6-4.8; P < .001) in those with any mucosal inflammation and 2.6 (95% CI, 1.5-4.5; P = .01) in those with histologic inflammation, when compared with those with mucosal healing. The overall quality of the studies was good. The presence of objective evidence of mucosal inflammation during follow-up in patients with ulcerative colitis is associated with a greater risk of subsequent colorectal neoplasia than in those with mucosal healing. This risk factor should be considered in guidelines on surveillance intervals for these patients. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

A scoring model for predicting advanced colorectal neoplasia in a screened population of asymptomatic Japanese individuals.

PubMed

Sekiguchi, Masau; Kakugawa, Yasuo; Matsumoto, Minori; Matsuda, Takahisa

2018-01-22

Risk stratification of screened populations could help improve colorectal cancer (CRC) screening. Use of the modified Asia-Pacific Colorectal Screening (APCS) score has been proposed in the Asia-Pacific region. This study was performed to build a new useful scoring model for CRC screening. Data were reviewed from 5218 asymptomatic Japanese individuals who underwent their first screening colonoscopy. Multivariate logistic regression was used to investigate risk factors for advanced colorectal neoplasia (ACN), and a new scoring model for the prediction of ACN was developed based on the results. The discriminatory capability of the new model and the modified APCS score were assessed and compared. Internal validation was also performed. ACN was detected in 225 participants. An 8-point scoring model for the prediction of ACN was developed using five independent risk factors for ACN (male sex, higher age, presence of two or more first-degree relatives with CRC, body mass index of > 22.5 kg/m 2 , and smoking history of > 18.5 pack-years). The prevalence of ACN was 1.6% (34/2172), 5.3% (127/2419), and 10.2% (64/627) in participants with scores of < 3, ≥ 3 to < 5, and ≥ 5, respectively. The c-statistic of the scoring model was 0.70 (95% confidence interval, 0.67-0.73) in both the development and internal validation sets, and this value was higher than that of the modified APCS score [0.68 (95% confidence interval, 0.65-0.71), P = 0.03]. We built a new simple scoring model for prediction of ACN in a Japanese population that could stratify the screened population into low-, moderate-, and high-risk groups.

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

Can gallbladder polyps predict colorectal adenoma or even neoplasia? A systematic review.

PubMed

Stergios, Konstantinos; Damaskos, Christos; Frountzas, Maximos; Nikiteas, Nikolaos; Lalude, Olutunde

2016-09-01

The purpose of the present systematic review is to identify whether an association between gallbladder polyps and colorectal adenoma or neoplasia exists. We conducted a systematic review searching the Medline (1966-2016), Scopus (2004-2016), ClinicalTrials.gov (2008-2016) and Cochrane Central Register of Controlled Trials CENTRAL (1999-2016) databases together with reference lists from included studies. All prospective and retrospective observational cohort studies were included. Four studies were finally included which included 17,437 patients. The association between gallbladder polyps and colorectal adenoma or even neoplasia is not unanimously supported. However, a possible association is clearly depicted. According to one study it seems that this correlation seems to become significant only when the gallbladder polyps exceed the size of 5 mm. However, the impact of size of gallbladder polyps was not investigated in the remaining studies. According to the results of our systematic review there is some evidence to support the hypothesis that gallbladder polyps might adequately predict future risk of colorectal neoplasia. At present, however, current knowledge is very limited and the available data scarce. In this context further studies are necessary to be carried out, before the presence of gallbladder polyps on ultrasound can be recommended as an indication to perform a screening colonoscopy on the same patient. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

5-Aminosalicylates Reduce the Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: An Updated Meta-Analysis

PubMed Central

Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui

2014-01-01

Background Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited. PMID:24710620

5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

PubMed

Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui

2014-01-01

Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies.

PubMed

Zheng, Han-Han; Jiang, Xue-Liang

2016-04-01

Ulcerative colitis (UC) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal neoplasia (dysplasia and cancer), whereas the association between PSC and the development of colorectal neoplasia in Crohn's disease (CD) is controversial. A meta-analysis was carried out to compare the risk of this neoplasia in patients with inflammatory bowel disease (IBD) with and without PSC. A systematic research of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was performed to identify studies that compared the risk of colorectal neoplasia (dysplasia and cancer) in patients with IBD with and without PSC. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model by STATA 12.0. A total of 16 studies (four cohort studies, 12 case-control studies; nine prospective studies and seven retrospective studies) were selected for further study. These studies included 13 379 IBD patients, of whom 1022 also had PSC. Patients with IBD and PSC were at an increased risk of colorectal dysplasia and cancer compared with patients with IBD alone [OR 3.24; 95% confidence interval (CI): 2.14-4.90]. This increased risk was present even when the risk of colorectal cancer alone was analysed (OR 3.41; 95% CI: 2.13-5.48). Data only from patients with UC showed that PSC was associated with an increased risk for the development of colorectal neoplasia and cancer in patients with UC (OR 2.98; 95% CI: 1.54-5.76) (OR 3.01; 95% CI: 1.44-6.29), but there were high heterogeneity among studies (I=76.9 and 62.8%, respectively). Heterogeneity of the studies was affected by the study design (prospective or retrospective). The OR of colorectal neoplasia was 2.32 (95% CI: 0.70-7.70, P=0.133) and that of cancer was 2.91 (95% CI: 0.84-10.16, P=0.388) for patients with CD and concurrent PSC. Patients with IBD and PSC have a markedly higher risk for the development of colorectal

Advances in Laparoscopic Colorectal Surgery.

PubMed

Parker, James Michael; Feldmann, Timothy F; Cologne, Kyle G

2017-06-01

Laparoscopic colorectal surgery has now become widely adopted for the treatment of colorectal neoplasia, with steady increases in utilization over the past 15 years. Common minimally invasive techniques include multiport laparoscopy, single-incision laparoscopy, and hand-assisted laparoscopy, with the choice of technique depending on several patient and surgeon factors. Laparoscopic colorectal surgery involves a robust learning curve, and fellowship training often lays the foundation for a high-volume laparoscopic practice. This article provides a summary of the various techniques for laparoscopic colorectal surgery, including operative steps, the approach to difficult patients, and the learning curve for proficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of Age on the Risk of Advanced Colorectal Neoplasia in a Young Population: An Analysis Using the Predicted Probability Model.

PubMed

Jung, Yoon Suk; Park, Chan Hyuk; Kim, Nam Hee; Lee, Mi Yeon; Park, Dong Il

2017-09-01

The incidence of colorectal cancer is decreasing in adults aged ≥50 years and increasing in those aged <50 years. We aimed to establish risk stratification model for advanced colorectal neoplasia (ACRN) in persons aged <50 years. We reviewed the records of participants who had undergone a colonoscopy as part of a health examination at two large medical examination centers in Korea. By using logistic regression analysis, we developed predicted probability models for ACRN in a population aged 30-49 years. Of 96,235 participants, 57,635 and 38,600 were included in the derivation and validation cohorts, respectively. The predicted probability model considered age, sex, body mass index, family history of colorectal cancer, and smoking habits, as follows: Y ACRN  = -8.755 + 0.080·X age  - 0.055·X male  + 0.041·X BMI  + 0.200·X family_history_of_CRC  + 0.218·X former_smoker  + 0.644·X current_smoker . The optimal cutoff value for the predicted probability of ACRN by Youden index was 1.14%. The area under the receiver-operating characteristic curve (AUROC) values of our model for ACRN were higher than those of the previously established Asia-Pacific Colorectal Screening (APCS), Korean Colorectal Screening (KCS), and Kaminski's scoring models [AUROC (95% confidence interval): model in the current study, 0.673 (0.648-0.697); vs. APCS, 0.588 (0.564-0.611), P < 0.001; vs. KCS, 0.602 (0.576-0.627), P < 0.001; and vs. Kaminski's model, 0.586 (0.560-0.612), P < 0.001]. In a young population, a predicted probability model can assess the risk of ACRN more accurately than existing models, including the APCS, KCS, and Kaminski's scoring models.

Changes in Adult BMI and Waist Circumference Are Associated with Increased Risk of Advanced Colorectal Neoplasia.

PubMed

Gathirua-Mwangi, Wambui G; Monahan, Patrick; Song, Yiqing; Zollinger, Terrell W; Champion, Victoria L; Stump, Timothy E; Imperiale, Thomas F

2017-11-01

Waist circumference (WC) is a stronger predictor of colon cancer (CRC) risk than body mass index (BMI). However, how well change in either WC or BMI predicts risk of advanced colorectal neoplasia (AN) is unclear. To determine the relationship between change in BMI and WC from early adulthood to later age and the risk of AN and which change measure is a stronger predictor. In 4500 adults, ages 50-80, with no previous neoplasia and undergoing screening colonoscopy, BMI and WC at age 21 and at time of screening were reported. Changes in BMI and WC were defined using universal risk cutoffs. Known CRC risk factors were controlled in the logistic models. Overall, model statistics showed WC change (omnibus test χ 2  = 10.15, 2 DF, p value = 0.006) was a statistically stronger predictor of AN than BMI change (omnibus test χ 2  = 5.66, 5 DF, p value = 0.34). Independent of BMI change, participants who increased WC (OR 1.44; 95% CI 1.05-1.96) or maintained a high-risk WC (OR 2.50; 95% CI 1.38-4.53) at age 21 and at screening had an increased risk of AN compared to those with a low-risk WC. Study participants who were obese at age 21 and at screening had an increased risk of AN (OR 1.87; 95% CI 1.08-3.23) compared to those who maintained a healthy BMI. Maintaining an overweight BMI or increasing BMI was not associated with AN. Maintaining an unhealthy BMI and WC throughout adult life may increase risk of AN. WC change may be a better predictor of AN than BMI change.

Advanced proximal neoplasia of the colon in average-risk adults.

PubMed

Rabeneck, Linda; Paszat, Lawrence F; Hilsden, Robert J; McGregor, S Elizabeth; Hsieh, Eugene; M Tinmouth, Jill; Baxter, Nancy N; Saskin, Refik; Ruco, Arlinda; Stock, David

2014-10-01

Estimating risk for advanced proximal neoplasia (APN) based on distal colon findings can help identify asymptomatic persons who should undergo examination of the proximal colon after flexible sigmoidoscopy (FS) screening. We aimed to determine the risk of APN by most advanced distal finding among an average-risk screening population. Prospective, cross-sectional study. Teaching hospital and colorectal cancer screening center. A total of 4651 asymptomatic persons at average risk for colorectal cancer aged 50 to 74 years (54.4% women [n = 2529] with a mean [± standard deviation] age of 58.4 ± 6.2 years). All participants underwent a complete colonoscopy, including endoscopic removal of all polyps. We explored associations between several risk factors and APN. Logistic regression was used to identify independent predictors of APN. A total of 142 persons (3.1%) had APN, of whom 85 (1.8%) had isolated APN (with no distal findings). APN was associated with older age, a BMI >27 kg/m(2), smoking, distal advanced adenoma and/or cancer, and distal non-advanced tubular adenoma. Those with a distal advanced neoplasm were more than twice as likely to have APN compared with those without distal lesions. Distal findings used to estimate risk of APN were derived from colonoscopy rather than FS itself. In persons at average risk for colorectal cancer, the prevalence of isolated APN was low (1.8%). Use of distal findings to predict APN may not be the most effective strategy. However, incorporating factors such as age (>65 years), sex, BMI (>27 kg/m(2)), and smoking status, in addition to distal findings, should be considered for tailoring colonoscopy recommendations. Further evaluation of risk stratification approaches in other asymptomatic screening populations is warranted. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Folate-genetics and colorectal neoplasia: What we know and need to know next

USDA-ARS?s Scientific Manuscript database

The metabolism of folate involves a complex network of polymorphic enzymes that may explain a proportion of the risk associated with colorectal neoplasia. Over 60 observational studies primarily in non-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTH...

Helicobacter pylori and colorectal neoplasia: Is there a causal link?

PubMed Central

Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

2016-01-01

Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

Performance of a quantitative fecal immunochemical test for detecting advanced colorectal neoplasia: a prospective cohort study.

PubMed

Liles, Elizabeth G; Perrin, Nancy; Rosales, Ana G; Smith, David H; Feldstein, Adrianne C; Mosen, David M; Levin, Theodore R

2018-05-02

The fecal immunochemical test (FIT) is easier to use and more sensitive than the guaiac fecal occult blood test, but it is unclear how to optimize FIT performance. We compared the sensitivity and specificity for detecting advanced colorectal neoplasia between single-sample (1-FIT) and two-sample (2-FIT) FIT protocols at a range of hemoglobin concentration cutoffs for a positive test. We recruited 2,761 average-risk men and women ages 49-75 referred for colonoscopy within a large nonprofit, group-model health maintenance organization (HMO), and asked them to complete two separate single-sample FITs. We generated receiver-operating characteristic (ROC) curves to compare sensitivity and specificity estimates for 1-FIT and 2-FIT protocols among those who completed both FIT kits and colonoscopy. We similarly compared sensitivity and specificity between hemoglobin concentration cutoffs for a single-sample FIT. Differences in sensitivity and specificity between the 1-FIT and 2-FIT protocols were not statistically significant at any of the pre-specified hemoglobin concentration cutoffs (10, 15, 20, 25, and 30 μg/g). There was a significant difference in test performance of the one-sample FIT between 50 ng/ml (10 μg/g) and each of the higher pre-specified cutoffs. Disease prevalence was low. A two-sample FIT is not superior to a one-sample FIT in detection of advanced adenomas; the one-sample FIT at a hemoglobin concentration cutoff of 50 ng/ml (10 μg/g) is significantly more sensitive for advanced adenomas than at higher cutoffs. These findings apply to a population of younger, average-risk patients in a U.S. integrated care system with high rates of prior screening.

Evaluation of a clinical risk index for advanced colorectal neoplasia among a North American population of screening age.

PubMed

Ruco, Arlinda; Stock, David; Hilsden, Robert J; McGregor, S Elizabeth; Paszat, Lawrence F; Saskin, Refik; Rabeneck, Linda

2015-11-19

A clinical risk index employing age, sex, family history of colorectal cancer (CRC), smoking history and body mass index (BMI) may be useful for prioritizing screening with colonoscopy. The aim of this study was to conduct an external evaluation of a previously published risk index for advanced neoplasia (AN) in a large, well-characterized cohort. Five thousand one hundred thirty-seven asymptomatic persons aged 50 to 74 (54.9 % women) with a mean age (SD) of 58.3 (6.2) years were recruited for the study from a teaching hospital and colorectal cancer screening centre between 2003 and 2011. All participants underwent a complete screening colonoscopy and removal of all polyps. AN was defined as cancer or a tubular adenoma, traditional serrated adenoma (TSA), or sessile serrated adenoma (SSA) with villous characteristics (≥25% villous component), and/or high-grade dysplasia and/or diameter ≥10 mm. Risk scores for each participant were summed to derive an overall score (0-8). The c-statistic was used to measure discriminating ability of the risk index. The prevalence of AN in the study cohort was 6.8 %. The likelihood of detecting AN increased from 3.6 to 13.1 % for those with a risk score of 1 to 6 respectively. The c-statistic for the multivariable logistic model in our cohort was 0.64 (95 % CI = 0.61-067) indicating modest overlap between risk scores. The risk index for AN using age, sex, family history, smoking history and BMI was found to be of limited discriminating ability upon external validation. The index requires further refinement to better predict AN in average risk persons of screening age.

Biomarkers of Risk for Colorectal Neoplasia (Team Project #2) — EDRN Public Portal

Cancer.gov

The goal of this project is to evaluate biomarkers in normal colonic mucosa to determine their relationship to the occurrence of short- and long-term colorectal neoplasia. Candidate markers have been proposed by participating investigators based on promising preliminary data. The purpose of this team project is to evaluate these markers in a common, tissue-based reference set, under a uniform, structured protocol.

Nutritional agents with anti-inflammatory properties in chemoprevention of colorectal neoplasia.

PubMed

Hull, Mark A

2013-01-01

The strong link between inflammation and colorectal carcinogenesis provides the rationale for using anti-inflammatory agents for chemoprevention of colorectal cancer (CRC). Several naturally occurring substances with anti-inflammatory properties, used in a purified 'nutraceutical' form, including omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and polyphenols such as curcumin and resveratrol, have been demonstrated to have anti-CRC activity in preclinical models. As expected, these agents have an excellent safety and tolerability profile in Phase II clinical trials. Phase III randomized clinical trials of these naturally occurring substances are now beginning to be reported. The omega-3 polyunsaturated fatty acid EPA, in the free fatty acid (FFA) form, has been demonstrated to reduce adenomatous polyp number and size in patients with familial adenomatous polyposis (FAP), a finding which has prompted evaluation of this formulation of EPA for prevention of 'sporadic' colorectal neoplasia. Anti-inflammatory 'nutraceuticals' require further clinical evaluation in polyp prevention trials as they exhibit many of the characteristics of the ideal cancer chemoprevention agent, including safety, tolerability and patient acceptability.

Clinical risk stratification model for advanced colorectal neoplasia in persons with negative fecal immunochemical test results.

PubMed

Jung, Yoon Suk; Park, Chan Hyuk; Kim, Nam Hee; Park, Jung Ho; Park, Dong Il; Sohn, Chong Il

2018-01-01

The fecal immunochemical test (FIT) has low sensitivity for detecting advanced colorectal neoplasia (ACRN); thus, a considerable portion of FIT-negative persons may have ACRN. We aimed to develop a risk-scoring model for predicting ACRN in FIT-negative persons. We reviewed the records of participants aged ≥40 years who underwent a colonoscopy and FIT during a health check-up. We developed a risk-scoring model for predicting ACRN in FIT-negative persons. Of 11,873 FIT-negative participants, 255 (2.1%) had ACRN. On the basis of the multivariable logistic regression model, point scores were assigned as follows among FIT-negative persons: age (per year from 40 years old), 1 point; current smoker, 10 points; overweight, 5 points; obese, 7 points; hypertension, 6 points; old cerebrovascular attack (CVA), 15 points. Although the proportion of ACRN in FIT-negative persons increased as risk scores increased (from 0.6% in the group with 0-4 points to 8.1% in the group with 35-39 points), it was significantly lower than that in FIT-positive persons (14.9%). However, there was no statistical difference between the proportion of ACRN in FIT-negative persons with ≥40 points and in FIT-positive persons (10.5% vs. 14.9%, P = 0.321). FIT-negative persons may need to undergo screening colonoscopy if they clinically have a high risk of ACRN. The scoring model based on age, smoking habits, overweight or obesity, hypertension, and old CVA may be useful in selecting and prioritizing FIT-negative persons for screening colonoscopy.

Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers.

PubMed

Wilhelmsen, Michael; Christensen, Ib J; Rasmussen, Louise; Jørgensen, Lars N; Madsen, Mogens R; Vilandt, Jesper; Hillig, Thore; Klaerke, Michael; Nielsen, Knud T; Laurberg, Søren; Brünner, Nils; Gawel, Susan; Yang, Xiaoqing; Davis, Gerard; Heijboer, Annemieke; Martens, Frans; Nielsen, Hans J

2017-03-15

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC. © 2016 UICC.

Advance notification letters increase adherence in colorectal cancer screening: a population-based randomized trial.

PubMed

van Roon, A H C; Hol, L; Wilschut, J A; Reijerink, J C I Y; van Vuuren, A J; van Ballegooijen, M; Habbema, J D F; van Leerdam, M E; Kuipers, Ernst J

2011-06-01

The population benefit of screening depends not only on the effectiveness of the test, but also on adherence, which, for colorectal cancer (CRC) screening remains low. An advance notification letter may increase adherence, however, no population-based randomized trials have been conducted to provide evidence of this. In 2008, a representative sample of the Dutch population (aged 50-74 years) was randomized. All 2493 invitees in group A were sent an advance notification letter, followed two weeks later by a standard invitation. The 2507 invitees in group B only received the standard invitation. Non-respondents in both groups were sent a reminder 6 weeks after the invitation. The advance notification letters resulted in a significantly higher adherence (64.4% versus 61.1%, p-value 0.019). Multivariate logistic regression analysis showed no significant interactions between group and age, sex, or socio-economic status. Cost analysis showed that the incremental cost per additional detected advanced neoplasia due to sending an advance notification letter was € 957. This population-based randomized trial demonstrates that sending an advance notification letter significantly increases adherence by 3.3%. The incremental cost per additional detected advanced neoplasia is acceptable. We therefore recommend that such letters are incorporated within the standard CRC-screening invitation process. Copyright © 2011 Elsevier Inc. All rights reserved.

DNA Mismatch Repair Status Predicts Need for Future Colorectal Surgery for Metachronous Neoplasms in Young Individuals Undergoing Colorectal Cancer Resection.

PubMed

Aronson, Melyssa; Holter, Spring; Semotiuk, Kara; Winter, Laura; Pollett, Aaron; Gallinger, Steven; Cohen, Zane; Gryfe, Robert

2015-07-01

The treatment of colorectal cancer in young patients involves both management of the incident cancer and consideration of the possibility of Lynch syndrome and the development of metachronous colorectal cancers. This study aims to assess the prognostic role of DNA mismatch repair deficiency and extended colorectal resection for metachronous colorectal neoplasia risk in young patients with colorectal cancer. This is a retrospective review of 285 patients identified in our GI cancer registry with colorectal cancer diagnosed at 35 years or younger in the absence of polyposis. Using univariate and multivariate analysis, we assessed the prognostic role of mismatch repair deficiency and standard clinicopathologic characteristics, including the extent of resection, on the rate of developing metachronous colorectal neoplasia requiring resection. Mismatch repair deficiency was identified in biospecimens from 44% of patients and was significantly associated with an increased risk for metachronous colorectal neoplasia requiring resection (10-year cumulative risk, 13.5% ± 4.2%) compared with 56% of patients with mismatch repair-intact colorectal cancer (10-year cumulative risk, 5.8% ± 3.3%; p = 0.011). In multivariate analysis, mismatch repair deficiency was associated with a HR of 3.65 (95% CI, 1.44-9.21; p = 0.006) for metachronous colorectal neoplasia, whereas extended resection with ileorectal or ileosigmoid anastomosis significantly decreased the risk of metachronous colorectal neoplasia (HR, 0.21; 95% CI, 0.05-0.90; p = 0.036). This study had a retrospective design, and, therefore, recommendations for colorectal cancer surgery and screening were not fully standardized. Quality of life after colorectal cancer surgery was not assessed. Young patients with colorectal cancer with molecular hallmarks of Lynch syndrome were at significantly higher risk for the development of subsequent colorectal neoplasia. This risk was significantly reduced in those who underwent extended

Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia.

PubMed

Chakrabarty, Sanjiban; Varghese, Vinay Koshy; Sahu, Pranoy; Jayaram, Pradyumna; Shivakumar, Bhadravathi M; Pai, Cannanore Ganesh; Satyamoorthy, Kapaettu

2017-06-27

Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia. Findings from the study are also compared with previously published genome wide and exome sequencing data in inflammatory bowel disease-associated and sporadic colorectal carcinoma. Next-generation sequencing analysis identified 1107 mutations in 275 genes in UCHR subjects. In addition to TP53 (17%) and KRAS (22%) mutations, recurrent mutations in APC (33%), ACVR2A (61%), ARID1A (44%), RAF1 (39%) and MTOR (61%) were observed in UCHR subjects. In addition, APC, FGFR3, FGFR2 and PIK3CA driver mutations were identified in UCHR subjects. Recurrent mutations in ARID1A (44%), SMARCA4 (17%), MLL2 (44%), MLL3 (67%), SETD2 (17%) and TET2 (50%) genes involved in histone modification and chromatin remodelling were identified in UCHR subjects. Our study identifies new oncogenic driver mutations which may be involved in the transition of non-dysplastic cells to dysplastic phenotype in the subjects with long-standing UC with high risk of progression into colorectal neoplasia.

A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples.

PubMed

Gallardo-Gómez, María; Moran, Sebastian; Páez de la Cadena, María; Martínez-Zorzano, Vicenta Soledad; Rodríguez-Berrocal, Francisco Javier; Rodríguez-Girondo, Mar; Esteller, Manel; Cubiella, Joaquín; Bujanda, Luis; Castells, Antoni; Balaguer, Francesc; Jover, Rodrigo; De Chiara, Loretta

2018-01-01

Colorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers. This study aimed to assess the feasibility of using cfDNA pooled samples to identify potential serum methylation biomarkers for the detection of advanced colorectal neoplasia (colorectal cancer or advanced adenomas) using microarray-based technology. cfDNA was extracted from serum samples from 20 individuals with no colorectal findings, 20 patients with advanced adenomas, and 20 patients with colorectal cancer (stages I and II). Two pooled samples were prepared for each pathological group using equal amounts of cfDNA from 10 individuals, sex-, age-, and recruitment hospital-matched. We measured the methylation levels of 866,836 CpG positions across the genome using the MethylationEPIC array. Pooled serum cfDNA methylation data meets the quality requirements. The proportion of detected CpG in all pools (> 99% with detection p value < 0.01) exceeded Illumina Infinium methylation data quality metrics of the number of sites detected. The differential methylation analysis revealed 1384 CpG sites (5% false discovery rate) with at least 10% difference in the methylation level between no colorectal findings controls and advanced neoplasia, the majority of which were hypomethylated. Unsupervised clustering showed that cfDNA methylation patterns can distinguish advanced neoplasia from healthy controls, as well as separate tumor tissue from healthy mucosa in an independent dataset. We also observed that advanced adenomas and stage I/II colorectal cancer methylation profiles, grouped as advanced

Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia.

PubMed

Li, J N; Mahmoud, M A; Han, W F; Ripple, M; Pizer, E S

2000-11-25

Endogenous fatty acid synthesis has been observed in certain rapidly proliferating normal and neoplastic tissues. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of lipogenic genes including fatty acid synthase (FAS), the major biosynthetic enzyme for fatty acid synthesis. We have previously shown that SREBP-1, FAS, and Ki-67, a proliferation marker, colocalized in the crypts of the fetal gastrointestinal tract epithelium. This study sought to determine whether SREBP-1 participates in the regulation of proliferation-associated fatty acid synthesis in colorectal neoplasia. An immunohistochemical analysis of SREBP-1, FAS, and Ki-67 expression in 25 primary human colorectal carcinoma specimens showed colocalization in 22 of these. To elucidate a functional linkage between SREBP-1 activation and proliferation-associated FA synthesis, SREBP-1 and FAS content were assayed during the adaptive response of cultured HCT116 colon carcinoma cells to pharmacological inhibition of FA synthesis. Cerulenin and TOFA each inhibited the endogenous synthesis of fatty acids in a dose-dependent manner and each induced increases in both precursor and mature forms of SREBP-1. Subsequently, both the transcriptional activity of the FAS promoter in a luciferase reporter gene construct and the FAS expression increased. These results demonstrate that tumor cells recognize and respond to a deficiency in endogenous fatty acid synthesis by upregulating both SREBP-1 and FAS expression and support the model that SREBP-1 participates in the transcriptional regulation of lipogenic genes in colorectal neoplasia. Copyright 2000 Academic Press.

The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

PubMed

Renaud, Florence; Mariette, Christophe; Vincent, Audrey; Wacrenier, Agnès; Maunoury, Vincent; Leclerc, Julie; Coppin, Lucie; Crépin, Michel; Van Seuningen, Isabelle; Leteurtre, Emmanuelle; Buisine, Marie-Pierre

2016-03-15

The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention. © 2015 UICC.

Evaluation of a risk index for advanced proximal neoplasia of the colon.

PubMed

Ruco, Arlinda; Stock, David; Hilsden, Robert J; McGregor, S Elizabeth; Paszat, Lawrence F; Saskin, Refik; Rabeneck, Linda

2015-01-01

A clinical risk index that uses distal colorectal findings at flexible sigmoidoscopy (FS) in conjunction with easily determined risk factors for advanced proximal neoplasia (APN) may be useful for tailoring or prioritizing screening with colonoscopy. To conduct an external evaluation of a previously published risk index in a large, well-characterized cohort. Cross-sectional. Teaching hospital and colorectal cancer screening center. A total of 5139 asymptomatic persons aged 50 to 74 (54.9% women) with a mean age (±SD) of 58.3 (±6.2) years. Between 2003 and 2011, all participants underwent a complete screening colonoscopy and removal of all polyps. Participants were classified as low, intermediate, or high risk for APN, based on their composite risk index scores. The concordance or c-statistic was used to measure discriminating ability of the risk index. A total of 167 persons (3.2%) had APN. The prevalence of those with APN among low-, intermediate-, and high-risk categories was 2.1%, 2.9%, and 6.5%, respectively. High-risk individuals were 3.2 times more likely to have APN compared with those in the low-risk category. The index did not discriminate well between those in the low- and intermediate-risk categories. The c-statistic for the overall index was 0.62 (95% confidence interval, 0.58-0.66). Distal colorectal findings were derived from colonoscopies and not FS itself. The risk index discriminated between those at low risk and those at high risk, but it had limited ability to discriminate between low- and intermediate-risk categories for prevalent APN. Information on other risk factors may be needed to tailor, or prioritize, access to screening colonoscopy. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Quality audit of colonoscopy reports amongst patients screened or surveilled for colorectal neoplasia.

PubMed

Beaulieu, Daphnée; Barkun, Alan; Martel, Myriam

2012-07-21

To complete a quality audit using recently published criteria from the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. Consecutive colonoscopy reports of patients at average/high risk screening, or with a prior colorectal neoplasia (CRN) by endoscopists who perform 11 000 procedures yearly, using a commercial computerized endoscopic report generator. A separate institutional database providing pathological results. Required documentation included patient demographics, history, procedure indications, technical descriptions, colonoscopy findings, interventions, unplanned events, follow-up plans, and pathology results. Reports abstraction employed a standardized glossary with 10% independent data validation. Sample size calculations determined the number of reports needed. Two hundreds and fifty patients (63.2 ± 10.5 years, female: 42.8%, average risk: 38.5%, personal/family history of CRN: 43.3%/20.2%) were scoped in June 2009 by 8 gastroenterologists and 3 surgeons (mean practice: 17.1 ± 8.5 years). Procedural indication and informed consent were always documented. 14% provided a previous colonoscopy date (past polyp removal information in 25%, but insufficient in most to determine surveillance intervals appropriateness). Most procedural indicators were recorded (exam date: 98.4%, medications: 99.2%, difficulty level: 98.8%, prep quality: 99.6%). All reports noted extent of visualization (cecum: 94.4%, with landmarks noted in 78.8% - photodocumentation: 67.2%). No procedural times were recorded. One hundred and eleven had polyps (44.4%) with anatomic location noted in 99.1%, size in 65.8%, morphology in 62.2%; removal was by cold biopsy in 25.2% (cold snare: 18%, snare cautery: 31.5%, unrecorded: 20.7%), 84.7% were retrieved. Adenomas were noted in 24.8% (advanced adenomas: 7.6%, cancer: 0.4%) in this population with varying previous colonic investigations. This audit reveals lacking reported items, justifying additional research to

Quality audit of colonoscopy reports amongst patients screened or surveilled for colorectal neoplasia

PubMed Central

Beaulieu, Daphnée; Barkun, Alan; Martel, Myriam

2012-01-01

AIM: To complete a quality audit using recently published criteria from the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. METHODS: Consecutive colonoscopy reports of patients at average/high risk screening, or with a prior colorectal neoplasia (CRN) by endoscopists who perform 11 000 procedures yearly, using a commercial computerized endoscopic report generator. A separate institutional database providing pathological results. Required documentation included patient demographics, history, procedure indications, technical descriptions, colonoscopy findings, interventions, unplanned events, follow-up plans, and pathology results. Reports abstraction employed a standardized glossary with 10% independent data validation. Sample size calculations determined the number of reports needed. RESULTS: Two hundreds and fifty patients (63.2 ± 10.5 years, female: 42.8%, average risk: 38.5%, personal/family history of CRN: 43.3%/20.2%) were scoped in June 2009 by 8 gastroenterologists and 3 surgeons (mean practice: 17.1 ± 8.5 years). Procedural indication and informed consent were always documented. 14% provided a previous colonoscopy date (past polyp removal information in 25%, but insufficient in most to determine surveillance intervals appropriateness). Most procedural indicators were recorded (exam date: 98.4%, medications: 99.2%, difficulty level: 98.8%, prep quality: 99.6%). All reports noted extent of visualization (cecum: 94.4%, with landmarks noted in 78.8% - photodocumentation: 67.2%). No procedural times were recorded. One hundred and eleven had polyps (44.4%) with anatomic location noted in 99.1%, size in 65.8%, morphology in 62.2%; removal was by cold biopsy in 25.2% (cold snare: 18%, snare cautery: 31.5%, unrecorded: 20.7%), 84.7% were retrieved. Adenomas were noted in 24.8% (advanced adenomas: 7.6%, cancer: 0.4%) in this population with varying previous colonic investigations. CONCLUSION: This audit reveals lacking reported items

Intestinal obstruction management in patients with advanced abdominal neoplasia.

PubMed

Simion, L; Straja, Nd; Alecu, M; Poroch, V; Moşoiu, D; Panti, C; Grigorean, V; Brătucu, E

2014-01-01

The present study describes the difficulties encountered in the diagnostic process and treatment of intestinal obstruction developed by patients with advanced abdominal neoplasia. This unicentric and retrospective study evaluates patients suffering from intestinal occlusion operated on at the First Surgical Clinic of the Oncology Institute in Bucharest, over a period of 4 years (2010 - 2013). Of these, 61 cases in which the occlusion occurred on the background of an advanced abdominal neoplasia were selected. We considered as advanced those cases of abdominal cancer where curative oncologic treatment is no longer possible due to the evolution stage. The random selection of the study period, the introduction of all the patients identified with this type of pathology, as well as the concentration of advanced abdominal neoplasia at the Oncology Institute in Bucharest are the elements that allow us to state that the results of this study are representative. Particularities related to the clinical aspects of the intestinal occlusion in these patients, as well as difficulties in establishing the correct diagnosis were encountered.Surgical cure of the occlusion, with palliative aim of course,was possible in only 47 cases (representing 77.05%). A standard treatment course cannot be devised for this type of patients. Palliative care, indispensable in cases of advanced neoplastic disease, remains the sole therapeutic method available for patients with no surgical cure for the obstruction. The main objective, for the entire study lot, was to ensure an as high as possible quality of life,a factor we must bear in mind as often as possible when choosing a surgical solution. Of course, when surgical treatment can be applied, overcoming the occlusive episode prolongs these patients' life and can even allow for other courses of complementary treatment to be undertaken. Celsius.

A Highly Predictive Model for Diagnosis of Colorectal Neoplasms Using Plasma MicroRNA: Improving Specificity and Sensitivity

PubMed Central

Carter, Jane V.; Roberts, Henry L.; Pan, Jianmin; Rice, Jonathan D.; Burton, James F.; Galbraith, Norman J.; Eichenberger, M. Robert; Jorden, Jeffery; Deveaux, Peter; Farmer, Russell; Williford, Anna; Kanaan, Ziad; Rai, Shesh N.; Galandiuk, Susan

2016-01-01

OBJECTIVE(S) Develop a plasma-based microRNA (miRNA) diagnostic assay specific for colorectal neoplasms, building upon our prior work. BACKGROUND Colorectal neoplasms (colorectal cancer [CRC] and colorectal advanced adenoma [CAA]) frequently develop in individuals at ages when other common cancers also occur. Current screening methods lack sensitivity, specificity, and have poor patient compliance. METHODS Plasma was screened for 380 miRNAs using microfluidic array technology from a “Training” cohort of 60 patients, (10 each) control, CRC, CAA, breast (BC), pancreatic (PC) and lung (LC) cancer. We identified uniquely dysregulated miRNAs specific for colorectal neoplasia (p<0.05, false discovery rate: 5%, adjusted α=0.0038). These miRNAs were evaluated using single assays in a “Test” cohort of 120 patients. A mathematical model was developed to predict blinded sample identity in a 150 patient “Validation” cohort using repeat-sub-sampling validation of the testing dataset with 1000 iterations each to assess model detection accuracy. RESULTS Seven miRNAs (miR-21, miR-29c, miR-122, miR-192, miR-346, miR-372, miR-374a) were selected based upon p-value, area-under-the-curve (AUC), fold-change, and biological plausibility. AUC (±95% CI) for “Test” cohort comparisons were 0.91 (0.85-0.96), 0.79 (0.70-0.88) and 0.98 (0.96-1.0), respectively. Our mathematical model predicted blinded sample identity with 69-77% accuracy between all neoplasia and controls, 67-76% accuracy between colorectal neoplasia and other cancers, and 86-90% accuracy between colorectal cancer and colorectal adenoma. CONCLUSIONS Our plasma miRNA assay and prediction model differentiates colorectal neoplasia from patients with other neoplasms and from controls with higher sensitivity and specificity compared to current clinical standards. PMID:27471839

Fusobacterium’s link to colorectal neoplasia sequenced: A systematic review and future insights

PubMed Central

Hussan, Hisham; Clinton, Steven K; Roberts, Kristen; Bailey, Michael T

2017-01-01

AIM To critically evaluate previous scientific evidence on Fusobacterium’s role in colorectal neoplasia development. METHODS Two independent investigators systematically reviewed all original scientific articles published between January, 2000, and July, 2017, using PubMed, EMBASE, and MEDLINE. A total of 355 articles were screened at the abstract level. Of these, only original scientific human, animal, and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer (CRC) were included in the analysis. Abstracts, review articles, studies investigating other colonic diseases, and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates, resolving disagreements between the two reviewers, and applying the above criteria. RESULTS Studies have consistently identified positive associations between Fusobacterium, especially Fusobacterium nucleatum (F. nucleatum), and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and CpG island methylator phenotype (CIMP)-high CRCs. There was evidence of temporality and a biological gradient, with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment; evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear; however, the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin (Gal-GalNAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors

Type 2 diabetes mellitus and colorectal neoplasia risk in Hispanics: a case-control study.

PubMed

Díaz-Algorri, Yaritza; Lozada, María Eugenia; López, Sofía M; Bertrán-Rodríguez, Carlos E; González-Hernández, Cinthia M; González, Dilka; Pérez-Cardona, Cynthia M; Hernández, Jessica; Pedrosa, Carmen; Toro, Doris H; González-Pons, María; Cruz-Correa, Marcia

2015-01-01

There is inconclusive evidence regarding the potential link between diabetes mellitus (DM) and colorectal cancer (CRC). Associations between type 2 DM and colorectal neoplasia (CRN; colorectal cancer and/or adenomas) have not been well studied in Hispanics, an ethnic minority at high risk for type 2 DM. This study aims to assess the association between type 2 DM and CRN in Hispanics. Hispanics with incident CRN and colonoscopy-negative controls from 2005 to 2009 were evaluated. Diagnosis of type 2 DM was established by previous medical diagnosis and/or use of DM treatments. Unconditional logistic regression was performed to estimate odds ratios for the association between type 2 DM and CRN. A total of 451 participants (mean age 61.1±11.9years, 59.6 % men) were evaluated (218 with incident CRC, 77 with colorectal adenomas, and 156 colonoscopy-negative controls). The prevalence of type 2 DM in this study was 25.1%. After adjusting for potential confounding variables, women with type 2 DM were 2.74 (95% CI: 0.94-7.99) times more likely to have CRN and 4.83 times more likely to present with proximal colonic CRN (95% CI: 1.25-18.58) than women without type 2 DM. No statistically significant associations were found between type 2 DM and CRN among men. An increased odds for CRN and proximal location of CRN was observed among Hispanic women with type 2 DM. Since DM is a highly prevalent disease in this population, adherence to routine CRC screening is of outmost importance. Copyright © 2015 Elsevier Inc. All rights reserved.

THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS

EPA Science Inventory

THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS.

Abstract:

The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (D...

Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening: A Case-Control Study.

PubMed

Bosch, Linda J W; de Wit, Meike; Pham, Thang V; Coupé, Veerle M H; Hiemstra, Annemieke C; Piersma, Sander R; Oudgenoeg, Gideon; Scheffer, George L; Mongera, Sandra; Sive Droste, Jochim Terhaar; Oort, Frank A; van Turenhout, Sietze T; Larbi, Ilhame Ben; Louwagie, Joost; van Criekinge, Wim; van der Hulst, Rene W M; Mulder, Chris J J; Carvalho, Beatriz; Fijneman, Remond J A; Jimenez, Connie R; Meijer, Gerrit A

2017-12-19

The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. Case-control study. Colonoscopy-controlled referral population from several centers. 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed

The association between Helicobacter pylori infection and the risk of advanced colorectal neoplasia may differ according to age and cigarette smoking.

PubMed

Park, Hyunsung; Park, Jae Jun; Park, Yoo Mi; Baik, Su Jung; Lee, Hyun Ju; Jung, Da Hyun; Kim, Jie-Hyun; Youn, Young Hoon; Park, Hyojin

2018-03-29

The association between Helicobacter pylori infection and advanced colorectal neoplasia (ACN) remains controversial. This study aimed to clarify the association between H. pylori infection and ACN according to age groups. We retrospectively analyzed the association between H. pylori infection and ACN in patients aged <50 and ≥50 years receiving a health checkup that included colonoscopy. Helicobacter pylori positivity was determined by the results of serum anti-H. pylori immunoglobulin G or rapid urease test, if the anti-H. pylori immunoglobulin G was in the borderline range. Among the 19 337 patients who were included, 56.2% and 3.4% were positive for H. pylori and ACN, respectively. Helicobacter pylori infection independently increased the risk of ACN in patients aged <50 years (odds ratio [OR], 1.602; 95% confidence intervals [CI], 1.194-2.150) but not in patients aged ≥50 years (OR, 1.046; 95% CI, 0.863-1.268). The positive association between H. pylori infection and ACN was affected by smoking history. When stratified by age and smoking history, H. pylori infection conferred an increased risk of ACN in patients aged <50 years with a history of smoking (OR, 1.926; 95% CI, 1.336-2.775) but not in the other 3 groups (3-way interaction test P = .023). Among patients aged <50 years with ACN, ACN in the left colon was found more frequently in patients with H. pylori infection and a history of smoking than in those without (69.3% vs 54.4%, respectively; P = .031). Helicobacter pylori infection confers an increased risk of ACN, but the association may differ according to age and smoking history. © 2018 John Wiley & Sons Ltd.

[Lesions Detected in Six Spanish Colorectal Cancer Screening Population Based Programmes. CRIBEA Project. Spain].

PubMed

Portillo Villares, Isabel; Arana-Arri, Eunate; Idigoras Rubio, Isabel; Espinás Piñol, Josep Alfons; Pérez Riquelme, Francisco; de la Vega Prieto, Mariola; González Aledo, Alvaro; Oceja Setien, Elena; Vanaclocha Espi, Mercedes; Ibáñez Cabanell, Josefa; Salas Trejo, Dolores

2017-02-20

In this study, the results of six Colorectal Cancer Screening Population Programmes are shown (Catalonia, Valence, Murcia, Cantabria, the Basque Country and the Canary Islands collected between 2005 and 2012. These programmes use the faeces occult blood test (FOBt) biennial. Objective: To determine and compare the results of lesions detected by the programmes, participation, sex, age and test used. Retrospective cohort study based on people invited, aged between 50-74 years, in at least a complete round. Lesions considered: Advanced Adenomas (AA), Colorectal Invasive Cancer (CRC) and both of them, known as Advanced Neoplasia (AN). Logistic Regression and time trends are used. 1,995,719 of invitations registered, with an average participation-rate of 46.7%. 21,228 Advanced Neoplasias (2,813 CRC and 18,415 AA). Differences in detection rates observed between programmes (varying from 15.1‰ to 35.8‰ between participants). Participation rates were related to lesions' detection rates (OR 1.25 in 40-60% of participation). . Inmunochemical qualitative test showed an OR of 4.79 and quantitative test an OR of 7.30 over the guaiac test. Men showed an OR of 2.73 with respect to women. In 2012 the Advanced Neoplasia rate for women and men was 33.1 and 14.2 by 1,000 participants. The test used was the most important factor for detecting lesions. Time trends showed an increase in detected lesions caused by the change of the type of test in 2010.

Race and colorectal cancer disparities: health-care utilization vs different cancer susceptibilities.

PubMed

Laiyemo, Adeyinka O; Doubeni, Chyke; Pinsky, Paul F; Doria-Rose, V Paul; Bresalier, Robert; Lamerato, Lois E; Crawford, E David; Kvale, Paul; Fouad, Mona; Hickey, Thomas; Riley, Thomas; Weissfeld, Joel; Schoen, Robert E; Marcus, Pamela M; Prorok, Philip C; Berg, Christine D

2010-04-21

It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility. A total of 60, 572 non-Hispanic white and black participants in the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial underwent trial-sponsored screening flexible sigmoidoscopy (FSG) without biopsy at baseline in 10 geographically dispersed centers from November 1993 to July 2001. Subjects with polyps or mass lesions detected by FSG were referred to their physicians for diagnostic workup, the cost of which was not covered by PLCO. The records of follow-up evaluations were collected and reviewed. We used log binomial modeling with adjustment for age, education, sex, body mass index, smoking, family history of colorectal cancer, colon examination within previous 3 years, personal history of polyps, and screening center to examine whether utilization of diagnostic colonoscopy and yield of neoplasia differed by race. Among 57 561 whites and 3011 blacks who underwent FSG, 13,743 (23.9%) and 767 (25.5%) had abnormal examinations, respectively. A total of 9944 (72.4%) whites and 480 (62.6%) blacks had diagnostic colonoscopy within 1 year following the abnormal FSG screening. When compared with whites, blacks were less likely to undergo diagnostic evaluation (adjusted risk ratio = 0.88, 95% confidence interval = 0.83 to 0.93). Overall, among subjects with diagnostic colonoscopy (n = 10 424), there was no statistically significant difference by race in the prevalence of adenoma, advanced adenoma, advanced pathology in small adenomas (high-grade dysplasia or villous histology in adenomas <10 mm), or colorectal cancer. We observed a lower follow-up for screen-detected abnormalities among blacks when compared with whites but little difference in the yield of colorectal neoplasia. Health-care utilization may be playing more of a role in

'Feeling someone is there for you' - experiences of women with vulvar neoplasia with care delivered by an Advanced Practice Nurse.

PubMed

Kobleder, Andrea; Mayer, Hanna; Senn, Beate

2017-02-01

To explore the experiences of women with vulvar neoplasia with care delivered by an Advanced Practice Nurse. Women with vulvar neoplasia suffer from a high number of symptoms and report a lack of information and support by health care professionals. Further, talking about their disease, which is still a social taboo, is difficult for them. From approaches for other patients, it can be suggested that support from an Advanced Practice Nurse can be helpful. For Advanced Practice Nurse development, implementation and evaluation, it is important to assess patients' perceptions. But so far, little is known about how patients with vulvar neoplasia experience support of an Advanced Practice Nurse. A qualitative interview study was chosen to gain understanding of the experience of women with vulvar neoplasia who received care delivered by an Advanced Practice Nurse. Narrative interviews were conducted with a purposive sample of 13 women with vulvar neoplasia after they received care from an Advanced Practice Nurse for six months. Thematic analysis was used to analyse the data from the interviews. Four main themes could be identified: a trusting relationship; accessibility; feeling safe and secure; and feeling someone is there for you. Women felt more secure and less alone in the experience of their illness through having the possibility of contacting an Advanced Practice Nurse and getting sufficient information and psychosocial support. Women with vulvar neoplasia experienced care delivered by an Advanced Practice Nurse as 'feeling someone is there for you'. Due to the localisation of the disease and the associated social taboo, psychosocial support from the Advanced Practice Nurse beyond months after surgery was very important for them. Addressing psychosocial needs in caring for women with vulvar neoplasia must be given greater attention in clinical practice. Further, continuous nursing support delivered by an Advanced Practice Nurse beyond the acute treatment phase can

Treatment outcomes in locally advanced colorectal carcinoma

PubMed Central

Harish, K; Narayanaswamy, YV; Nirmala, S

2004-01-01

Background Locally advanced colorectal cancers form a distinct subgroup where contiguous organs could be involved without distant metastases and so may be amenable to curative surgical resection. It was our objective to report our experience in treating six such patients with operable locally advanced colorectal carcinomas. Methods We retrospectively reviewed the case notes of 47 patients who were diagnosed with colorectal cancers at M S Ramaiah Medical Teaching Hospital between the years 1996 – 2001. Six patients were identified with T4 lesions, adjacent organ involvement and with no nodal involvement. The treatments and outcomes for these patients were then reviewed. Results Two of three patients with rectal malignancies who underwent pelvic exenteration succumbed to disease recurrence within the first 18 months. One of the three patients with colonic cancers died of non malignant causes. The other two are disease free till date. Conclusions Aggressive multivisceral resections for locally advanced colonic cancers might be appropriate. Rectal cancers when locally advanced may be considered for pelvic exenteration, but a more guarded prognosis may apply. PMID:15527504

The Inflammatory Microenvironment in Colorectal Neoplasia

PubMed Central

McLean, Mairi H.; Murray, Graeme I.; Stewart, Keith N.; Norrie, Gillian; Mayer, Claus; Hold, Georgina L.; Thomson, John; Fyfe, Nicky; Hope, Mairi; Mowat, N. Ashley G.; Drew, Janice E.; El-Omar, Emad M.

2011-01-01

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified. PMID:21249124

The inflammatory microenvironment in colorectal neoplasia.

PubMed

McLean, Mairi H; Murray, Graeme I; Stewart, Keith N; Norrie, Gillian; Mayer, Claus; Hold, Georgina L; Thomson, John; Fyfe, Nicky; Hope, Mairi; Mowat, N Ashley G; Drew, Janice E; El-Omar, Emad M

2011-01-07

Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified.

Analysis of Fecal DNA Methylation to Detect Gastrointestinal Neoplasia

PubMed Central

Tanaka, Noriaki; Cullings, Harry M.; Sun, Dong-Sheng; Sasamoto, Hiromi; Uchida, Takuyuki; Koi, Minoru; Nishida, Naoshi; Naomoto, Yoshio; Boland, C. Richard; Matsubara, Nagahide; Goel, Ajay

2009-01-01

Background The development of noninvasive screening tests is important to reduce mortality from gastrointestinal neoplasia. We sought to develop such a test by analysis of DNA methylation from exfoliated cancer cells in feces. Methods We first analyzed methylation of the RASSF2 and SFRP2 gene promoters from 788 primary gastric and colorectal tissue specimens to determine whether methylation patterns could act as stage-dependent biomarkers of gastrointestinal tumorigenesis. Next, we developed a novel strategy that uses single-step modification of DNA with sodium bisulfite and fluorescence polymerase chain reaction methodology to measure aberrant methylation in fecal DNA. Methylation of the RASSF2 and SFRP2 promoters was analyzed in 296 fecal samples obtained from a variety of patients, including 21 with gastric tumors, 152 with colorectal tumors, and 10 with non-neoplastic or inflammatory lesions in the gastrointestinal lumen. Results Analysis of DNA from tissues showed presence of extensive methylation in both gene promoters exclusively in advanced gastric and colorectal tumors. The assay successfully identified one or more methylated markers in fecal DNA from 57.1% of patients with gastric cancer, 75.0% of patients with colorectal cancer, and 44.4% of patients with advanced colorectal adenomas, but only 10.6% of subjects without neoplastic or active diseases (difference, gastric cancer vs undiseased  =  46.5%, 95% confidence interval (CI)  =  24.6% to 68.4%, P < .001; difference, colorectal cancer vs undiseased = 64.4%, 95% CI = 53.5% to 75.2%, P < .001; difference, colorectal adenoma vs undiseased = 33.8%, 95% CI = 14.2% to 53.4%, P < .001). Conclusions Methylation of the RASSF2 and SFRP2 promoters in fecal DNA is associated with the presence of gastrointestinal tumors relative to non-neoplastic conditions. Our novel fecal DNA methylation assay provides a possible means to noninvasively screen not only for colorectal tumors but also for gastric tumors

Performance of a risk index for advanced proximal colorectal neoplasia among a racially/ethnically diverse patient population (risk index for advanced proximal neoplasia).

PubMed

Levitzky, Benjamin E; Brown, Colin C; Heeren, Timothy C; Schroy, Paul C

2011-06-01

Tailoring the use of screening colonoscopy based on the risk of advanced proximal neoplasia (APN) has been advocated as a strategy for reducing demand and optimizing effectiveness. A 7-point index based on age, sex, and distal findings at sigmoidoscopy has been proposed that stratifies individuals into low, intermediate, and high-risk categories. The aim of this cross-sectional analysis was to determine the validity of this index, which was originally derived and validated among mostly whites, for black and Hispanic patients. Data, including age, sex, colonoscopic findings, and pathology, were collected retrospectively from 1,481 white, 1,329 black, and 689 Hispanic asymptomatic, average-risk patients undergoing screening colonoscopy between 2000 and 2005. Cumulative scores ranging from 0 to 7 were derived for each subject and categorized as low, intermediate, or high risk. Rates of APN were assessed for each risk category after stratification by race/ethnicity. Index performance was assessed using the C-statistic and compared across the three racial groups. Rates of APN among patients categorized as low, intermediate, or high risk increased from 1.0 to 2.8 to 3.7% for whites, 1.0 to 2.2 to 4.2% for blacks, and 0.6 to 1.9 to 3.7% for Hispanics. The index performed similarly for all three groups, but showed limited ability to discriminate low from intermediate-risk patients, with C-statistic values of 0.62 for whites, 0.63 for blacks, and 0.68 for Hispanics. A risk index based on age, sex, and distal endoscopic findings has limited ability to discriminate low from intermediate-risk white, black, and Hispanic patients for APN.

Risk of Colorectal Neoplasia According to Fatty Liver Severity and Presence of Gall Bladder Polyps.

PubMed

Lee, Taeyoung; Yun, Kyung Eun; Chang, Yoosoo; Ryu, Seungho; Park, Dong Il; Choi, Kyuyong; Jung, Yoon Suk

2016-01-01

Fatty liver is the hepatic manifestation of metabolic syndrome (MetS) and is a known risk factor for colorectal neoplasia (CRN). Gallbladder (GB) polyps share many common risk factors with CRN. However, studies evaluating CRN risk according to fatty liver severity and the presence of GB polyps are rare. To investigate CRN risk according to the fatty liver severity and the presence of GB polyps. A retrospective cross-sectional study was performed on 44,220 participants undergoing colonoscopy and abdominal ultrasonography (US) as part of a health-screening program. Of the participants, fatty liver was diagnosed as mild in 27.7 %, moderate in 5.1 %, and severe in 0.4 % and 13.4 % were diagnosed with GB polyps. Mean age of participants was 42.7 years. In adjusted models, risk of overall CRN and non-advanced CRN increased with worsening fatty liver severity (P for trend = 0.007 and 0.020, respectively). Adjusted odd ratios for overall CRN and non-advanced CRN comparing participants with mild, moderate, and severe fatty liver to participants without fatty liver were 1.13 and 1.12 for mild, 1.12 and 1.10 for moderate, and 1.56 and 1.65 for severe. The presence of GB polyps did not correlate with CRN risk after adjusting for confounders. CRN risk increased with worsening fatty liver severity. However the association between GB polyp and CRN was not significant in the presence of other variables. Considering that many people undergo noninvasive abdominal US as a health screen, our study will contribute to colonoscopy screening strategies in people undergoing abdominal US.

Prevalence and management of colorectal neoplasia in surgically treated esophageal cancer patients.

PubMed

Takeuchi, Daisuke; Koide, Naohiko; Komatsu, Daisuke; Suzuki, Akira; Miyagawa, Shinichi

2015-05-01

The existence of other primary tumors during the treatment of esophageal cancer patients has been an important issue. Our aim is to investigate the prevalence and management of colorectal neoplasia (CRN) in surgically treated esophageal cancer patients. Between 2002 and 2008, 93 patients with esophageal cancer were surgically treated. Seventy-three patients underwent subtotal esophagectomy and 20 underwent lower esophagectomy for esophageal cancer. Colonoscopy was available for detecting CRN before and after surgery. Eighty-nine (95.7%) of the 93 patients were screened by colonoscopy preoperatively or within a year from the operation. Thirty-nine patients (43.8%) with CRN were synchronously identified: adenoma in 34 (38.2%) and adenocarcinoma in 5 patients (5.6%). Eleven adenomas with high grade-dysplasia and 8 adenomas with low grade-dysplasia were removed endoscopically. Three superficial adenocarcinomas were endoscopically removed before surgery, and 2 adenocarcinomas were surgically removed. Seventy-four patients (83.1%) were followed using colonoscopy, and 11 subsequent CRN, including 2 superficial adenocarcinomas, were endoscopically detected in 8 patients (10.8%). The size of esophageal cancer was larger in the patients with than without CRN (p = 0.036). The body mass index in esophageal cancer patients with CRN tended to be higher than in those without CRN (p = 0.065). We noted that esophageal cancer is frequently associated with synchronous and/or metachronous colorectal cancer and adenomas. Colonoscopy is useful to detect and manage CRN before and after esophagectomy, although a few limitations exist. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Herbal medicines for advanced colorectal cancer.

PubMed

Guo, Zhongning; Jia, Xiaoqiang; Liu, Jian Ping; Liao, Juan; Yang, Yufei

2012-05-16

Herbal medicine has been widely used in patients with advanced colorectal cancer in China, but its efficacy has not been confirmed. To evaluate the beneficial effect and safety on Chinese herbal medicine therapy for advanced stage colorectal cancer, and it's influence on the patients' quality of life. The following electronic databases were searched: BIOSIS Previews, Cochrane Controlled Trials Register, Medline EMBASE, Biological Abstracts, until Aug. 2011. Manual searching was performed on 16 types of Chinese journals which started from their respective first publication dates, as well as unpublished conference proceedings. No language restriction was applied. Randomized or quasi-randomised controlled trials on the treatment of advanced stage colorectal cancer by herbal medicines or herbal medicines combined with chemotherapy, regardless of blinding. The data were extracted independently by two reviewers. Methodological quality of the included in trials was assessed according to the following parameters: randomisation, allocation concealment, double blinding, and drop-out rates. A total of 20 randomised controlled trials with 1304 participants were identified. All the 20 trials compared the use of herbal medicines with chemotherapy and chemotherapy alone in the treatment of advanced stage colorectal cancers.Compared with chemotherapy alone, the use of Quxie capsule combined with chemotherapy could decrease mortality rate (RR 0.17, 95% CI 0.03 to 0.97); the use of Jianpi Jiedu formula, Xiaozheng formula and Yiqi Huoxue herbal medicine combined with chemotherapy respectively could improve 1-year survival rate significantly; the use of Xiaozheng Formula in conjunction with chemotherapy could improve 3-year survival rate. There were 10 herbal medicines showing benefit in improving quality of life. Herbal medicines did not show additional benefit in response rate or stability rate. No trials reported serious adverse effect from herbal medicine. Some herbal medicines

Surveillance colonoscopy after endoscopic treatment for colorectal neoplasia: From the standpoint of the Asia-Pacific region.

PubMed

Matsuda, Takahisa; Chiu, Han-Mo; Sano, Yasushi; Fujii, Takahiro; Ono, Akiko; Saito, Yutaka

2016-04-01

Colonoscopy is considered the gold standard to detect and remove colorectal neoplasia. The efficacy of colonoscopy with polypectomy to reduce colorectal cancer incidence and mortality has been demonstrated. Recently, post-polypectomy surveillance colonoscopy has become a necessary intervention in daily practice not only in Western countries but also in the Asia-Pacific region. Therefore, it is crucial to establish new clinical practice guidelines to reduce the number of unnecessary surveillance colonoscopies in order to create space for screening colonoscopy. The Asia-Pacific Consensus group recommended that surveillance colonoscopy interval should be tailored according to risk level of index colonoscopy. However, precise guidelines on interval of surveillance cannot be given because of a lack of prospective data. According to Korean and Australian guidelines, surveillance intervals after index colonoscopy of 5 years for low-risk subjects and 3 years for high-risk subjects are recommended in Asia-Pacific regions at present. Prospective data including long-term outcomes from the Japan Polyp Study, which is a multicenter randomized control trial, would be useful to establish the Asia-Pacific consensus in the near future. © 2016 Japan Gastroenterological Endoscopy Society.

Neoplasia: The Second Decade

PubMed Central

Rehemtulla, Alnawaz

2008-01-01

This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as technologies have advanced. Neoplasia is currently providing access to articles through PubMed Central to continue to facilitate rapid broad-based dissemination of published findings to the scientific community through an Open Access model. This has in part helped Neoplasia to achieve an improved impact factor this past year, demonstrating that the manuscripts published by Neoplasia are of great interest to the overall cancer research community. This past year, Neoplasia received a record number of articles for review and has had a 21% increase in the number of published articles. PMID:19048110

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

PubMed Central

Rhee, Ye-Young; Kim, Kyung-Ju; Kang, Gyeong Hoon

2017-01-01

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway. PMID:27885175

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway.

PubMed

Rhee, Ye-Young; Kim, Kyung-Ju; Kang, Gyeong Hoon

2017-01-15

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.

Multitarget stool DNA tests increases colorectal cancer screening among previously noncompliant Medicare patients

PubMed Central

Prince, Mark; Lester, Lynn; Chiniwala, Rupal; Berger, Barry

2017-01-01

AIM To determine the uptake of noninvasive multitarget stool DNA (mt-sDNA) in a cohort of colorectal cancer (CRC) screening non-compliant average-risk Medicare patients. METHODS This cross sectional primary care office-based study examined mt-sDNA uptake in routine clinical practice among 393 colorectal cancer screening non-compliant Medicare patients ages 50-85 ordered by 77 physicians in a multispecialty group practice (USMD Physician Services, Dallas, TX) from October, 2014-September, 2015. Investigators performed a Health Insurance Portability and Accountability Act compliant retrospective review of electronic health records to identify mt-sDNA use in patients who were either > 10 years since last colonoscopy and/or > 1 year since last fecal occult blood test. Test positive patients were advised to get diagnostic colonoscopy and thereafter patients were characterized by the most clinically significant lesion documented on histopathology of biopsies or excisional tissue. Descriptive statistics were employed. Key outcome measures included mt-sDNA compliance and diagnostic colonoscopy compliance on positive cases. RESULTS Over 12 mo, 77 providers ordered 393 mt-sDNA studies with 347 completed (88.3% compliance). Patient mean age was 69.8 (50-85) and patients were 64% female. Mt-sDNA was negative in 85.3% (296/347) and positive in 14.7% (51/347). Follow-up colonoscopy was performed in 49 positive patients (96.1% colonoscopy compliance) with two patients lost to follow up. Index findings included: colon cancer (4/49, 8.2%), advanced adenomas (21/49, 42.9%), non-advanced adenomas (15/49, 30.6%), and negative results (9/49, 18.4%). The positive predictive value for advanced colorectal lesions was 51.0% and for any colorectal neoplasia was 81.6%. The mean age of patients with colorectal cancer was 70.3 and all CRC's were localized Stage I (2) and Stage II (2), three were located in the proximal colon and one was located in the distal colon. CONCLUSION Mt-sDNA provided

Multitarget stool DNA tests increases colorectal cancer screening among previously noncompliant Medicare patients.

PubMed

Prince, Mark; Lester, Lynn; Chiniwala, Rupal; Berger, Barry

2017-01-21

To determine the uptake of noninvasive multitarget stool DNA (mt-sDNA) in a cohort of colorectal cancer (CRC) screening non-compliant average-risk Medicare patients. This cross sectional primary care office-based study examined mt-sDNA uptake in routine clinical practice among 393 colorectal cancer screening non-compliant Medicare patients ages 50-85 ordered by 77 physicians in a multispecialty group practice (USMD Physician Services, Dallas, TX) from October, 2014-September, 2015. Investigators performed a Health Insurance Portability and Accountability Act compliant retrospective review of electronic health records to identify mt-sDNA use in patients who were either > 10 years since last colonoscopy and/or > 1 year since last fecal occult blood test. Test positive patients were advised to get diagnostic colonoscopy and thereafter patients were characterized by the most clinically significant lesion documented on histopathology of biopsies or excisional tissue. Descriptive statistics were employed. Key outcome measures included mt-sDNA compliance and diagnostic colonoscopy compliance on positive cases. Over 12 mo, 77 providers ordered 393 mt-sDNA studies with 347 completed (88.3% compliance). Patient mean age was 69.8 (50-85) and patients were 64% female. Mt-sDNA was negative in 85.3% (296/347) and positive in 14.7% (51/347). Follow-up colonoscopy was performed in 49 positive patients (96.1% colonoscopy compliance) with two patients lost to follow up. Index findings included: colon cancer (4/49, 8.2%), advanced adenomas (21/49, 42.9%), non-advanced adenomas (15/49, 30.6%), and negative results (9/49, 18.4%). The positive predictive value for advanced colorectal lesions was 51.0% and for any colorectal neoplasia was 81.6%. The mean age of patients with colorectal cancer was 70.3 and all CRC's were localized Stage I (2) and Stage II (2), three were located in the proximal colon and one was located in the distal colon. Mt-sDNA provided medical benefit to screening

Advances in Hereditary Colorectal and Pancreatic Cancer

PubMed Central

Underhill, Meghan L.; Germansky, Katharine A.; Yurgelun, Matthew B.

2017-01-01

Purpose Innovations in genetic medicine have lead to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer. Methods This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer. Findings This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of novel genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. Implications Given the availability of novel diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk for colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention. PMID:27045993

In Vivo Biomarkers for Targeting Colorectal Neoplasms

PubMed Central

Hsiung, Pei-Lin; Wang, Thomas

2011-01-01

Summary Colorectal carcinoma continues to be a leading cause of cancer morbidity and mortality despite widespread adoption of screening methods. Targeted detection and therapy using recent advances in our knowledge of in vivo cancer biomarkers promise to significantly improve methods for early detection, risk stratification, and therapeutic intervention. The behavior of molecular targets in transformed tissues is being comprehensively assessed using new techniques of gene expression profiling and high throughput analyses. The identification of promising targets is stimulating the development of novel molecular probes, including significant progress in the field of activatable and peptide probes. These probes are being evaluated in small animal models of colorectal neoplasia and recently in the clinic. Furthermore, innovations in optical imaging instrumentation are resulting in the scaling down of size for endoscope compatibility. Advances in target identification, probe development, and novel instruments are progressing rapidly, and the integration of these technologies has a promising future in molecular medicine. PMID:19126961

Fecal Microbiota Differences According to the Risk of Advanced Colorectal Neoplasms.

PubMed

Yang, Hyo-Joon; Kwon, Min-Jung; Chang, Yoosoo; Song, Seul-Ki; Ahn, Kwang-Sung; Kim, Han-Na; Yun, Yeojun; Kim, Hyung-Lae; Park, Dong Il

2018-02-09

This study aimed to compare differences in the fecal microbiota according to the risk of advanced colorectal neoplasia (ACN) based on a risk-score model in a large Korean cohort. Stool samples were collected from 1122 health screening recipients: 404 enrolled in the average risk (AR) group, 514 in the moderate risk (MR) group, and 204 in the high risk (HR) group, in accordance with their risk of ACN. The fecal microbiota was characterized using pyrosequencing of the V3-V4 region of the 16S rRNA genes. The overall microbial diversity was significantly reduced with an increased risk of ACN [false discovery rate (FDR), P<0.001], and the composition was significantly different between the risk groups (Bonferroni corrected, P<0.05). On taxonomic comparison, 6 of 11 phyla and 39 of 88 genera were significantly different among the risk groups (all FDR P<0.05). These included under-representation of Bacteroides, Ruminococcus, and Bifidobacterium, and over-representation of Prevotella and Fusobacterium with an increased risk of ACN. In particular, we observed that the unknown genus of Ruminococcaceae were relatively abundant (16.2%) in the AR group and significantly depleted with an increased risk of ACN (13.5% in the HR group; FDR P<0.001). These findings support the hypothesis that the fecal microbiota is different according to the risk of ACN. An unknown genus of Ruminococcaceae, as novel potential butyrate producers, might have a possible role in colorectal tumorigenesis in the Korean population.

The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy.

PubMed

Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Sung, Joseph J Y

2015-09-04

Faecal immunochemical tests (FITs) and colonoscopy are two common screening tools for colorectal cancer(CRC). Most cost-effectiveness studies focused on survival as the outcome, and were based on modeling techniques instead of real world observational data. This study evaluated the cost-effectiveness of these two tests to detect colorectal neoplastic lesions based on data from a 5-year community screening service. The incremental cost-effectiveness ratio (ICER) was assessed based on the detection rates of neoplastic lesions, and costs including screening compliance, polypectomy, colonoscopy complications, and staging of CRC detected. A total of 5,863 patients received yearly FIT and 4,869 received colonoscopy. Compared with FIT, colonoscopy detected notably more adenomas (23.6% vs. 1.6%) and advanced lesions or cancer (4.2% vs. 1.2%). Using FIT as control, the ICER of screening colonoscopy in detecting adenoma, advanced adenoma, CRC and a composite endpoint of either advanced adenoma or stage I CRC was US$3,489, US$27,962, US$922,762 and US$23,981 respectively. The respective ICER was US$3,597, US$439,513, -US$2,765,876 and US$32,297 among lower-risk subjects; whilst the corresponding figure was US$3,153, US$14,852, US$184,162 and US$13,919 among higher-risk subjects. When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia, and a composite endpoint of advanced neoplasia or stage I CRC.

The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy

PubMed Central

Wong, Martin CS; Ching, Jessica YL; Chan, Victor CW; Sung, Joseph JY

2015-01-01

Faecal immunochemical tests (FITs) and colonoscopy are two common screening tools for colorectal cancer(CRC). Most cost-effectiveness studies focused on survival as the outcome, and were based on modeling techniques instead of real world observational data. This study evaluated the cost-effectiveness of these two tests to detect colorectal neoplastic lesions based on data from a 5-year community screening service. The incremental cost-effectiveness ratio (ICER) was assessed based on the detection rates of neoplastic lesions, and costs including screening compliance, polypectomy, colonoscopy complications, and staging of CRC detected. A total of 5,863 patients received yearly FIT and 4,869 received colonoscopy. Compared with FIT, colonoscopy detected notably more adenomas (23.6% vs. 1.6%) and advanced lesions or cancer (4.2% vs. 1.2%). Using FIT as control, the ICER of screening colonoscopy in detecting adenoma, advanced adenoma, CRC and a composite endpoint of either advanced adenoma or stage I CRC was US$3,489, US$27,962, US$922,762 and US$23,981 respectively. The respective ICER was US$3,597, US$439,513, -US$2,765,876 and US$32,297 among lower-risk subjects; whilst the corresponding figure was US$3,153, US$14,852, US$184,162 and US$13,919 among higher-risk subjects. When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia, and a composite endpoint of advanced neoplasia or stage I CRC. PMID:26338314

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry.

PubMed

Gordillo, Jordi; Cabré, Eduard; Garcia-Planella, Esther; Ricart, Elena; Ber-Nieto, Yolanda; Márquez, Lucía; Rodríguez-Moranta, Francisco; Ponferrada, Ángel; Vera, Isabel; Gisbert, Javier P; Barrio, Jesús; Esteve, Maria; Merino, Olga; Muñoz, Fernando; Domènech, Eugeni

2015-12-01

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Validation of Biomarkers for the Early Detection of Colorectal Adenocarcinoma (GLNE 010) — EDRN Public Portal

Cancer.gov

We propose a Phase 2 (large cross-sectional) PRoBE-compliant validation trial of stool-based and serum-based tests for the detection of colorectal neoplasia (1). The trial is powered to detect early stage colorectal adenocarcinoma or high grade dysplasia. This is the most stringent, conservative approach to the early diagnosis of colonic neoplasia and addresses the most important endpoint of identifying individuals with curable, early stage cancer and those with very high risk non-invasive neoplasia (high grade dysplasia).

Vegetarianism as a protective factor for colorectal adenoma and advanced adenoma in Asians.

PubMed

Lee, Chang Geun; Hahn, Suk Jae; Song, Min Keun; Lee, Jun Kyu; Kim, Jae Hak; Lim, Yun Jeong; Koh, Moon-Soo; Lee, Jin Ho; Kang, Hyoun Woo

2014-05-01

Although epidemiologic and animal studies suggest a vegetarian diet protects against the development of colorectal cancer, the relationship between vegetarian diet and incidence of colorectal adenoma is not yet conclusive, especially for Asians. The purpose of this study was to examine the protective effect of a vegetarian diet against colorectal adenoma and advanced adenoma. This cross-sectional study compared the prevalence of colorectal adenoma among Buddhist priests, who are obligatory vegetarians, with that among age and sex-matched controls. All the subjects underwent health checkups in a health-promotion center in Korea. Colorectal adenoma and advanced adenoma were both more prevalent in the general population group than in the Buddhist priest group (25.2 vs. 17.9 %, 6.7 vs. 2.0 %). However, the prevalence of metabolic syndrome, high body mass index, and waist circumference were higher in the Buddhist priest group. According to univariate analysis, non-vegetarian diet (general population) significantly increased the prevalence of colorectal adenoma and advanced adenoma compared with a vegetarian diet (Buddhist priests) (OR 1.54, 95 % CI 1.08-2.21, P = 0.018; OR 3.60, 95 % CI 1.53-8.48, P = 0.003). In a conditional regression analysis model, non-vegetarian diet was also a significant risk factor for colorectal adenoma and advanced adenoma (OR 1.52, 95 % CI 0.75-2.07, P = 0.043; OR 2.94, CI 0.97-7.18, P = 0.036). Vegetarianism may be effective in preventing both colorectal adenoma and advanced adenoma in Asians.

Regional colorectal cancer screening program using colonoscopy on an island: a prospective Nii-jima study.

PubMed

Hotta, Kinichi; Matsuda, Takahisa; Kakugawa, Yasuo; Ikematsu, Hiroaki; Kobayashi, Nozomu; Kushima, Ryoji; Hozawa, Atsushi; Nakajima, Takeshi; Sakamoto, Taku; Mori, Mika; Fujii, Takahiro; Saito, Yutaka

2017-02-13

Colorectal cancer screening program using fecal immunochemical test had been conducted on an isolated island named Nii-jima. However, the participation rate of the program had been approximately 12%, which was lower than average level of Japan. This study aimed to evaluate the participation rate, safety and efficacy of a colorectal cancer screening program using colonoscopy on the island. Educational campaigns were actively conducted every month using information bulletins and special propaganda pamphlets. The primary recommended modality was colonoscopy, followed by fecal immunochemical test. The participants of this program were 1671 individuals aged 40–79 years (men, 819; women, 852). A total of 789 (47.2%) individuals provided consent for this screening program, and 89.2% (704/789) of participants chose colonoscopy as the primary screening procedure. The completion rate of total colonoscopy was 99.7%, and there was no complication during this program. Detection rates of invasive cancer, intramucosal cancer, advanced neoplasia and any adenoma were 0.9% (n = 6), 2.4% (n = 17), 11.8% (n = 83) and 50.0% (n = 352), respectively. The adenoma detection rate and incidence of advanced neoplasia were significantly higher in men than in women in all age groups. The colorectal cancer screening program using colonoscopy that was conducted on an island achieved considerably higher participation rate than the conventional screening program using fecal immunochemical test. Completion rate and safety of screening colonoscopy were excellent during this program.

[Recent advance in chemotherapy for advanced colorectal cancer].

PubMed

Aiba, K

1996-04-01

Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in

Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study.

PubMed

Zhu, Xiangzhu; Shrubsole, Martha J; Ness, Reid M; Hibler, Elizabeth A; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Jiang, Ming; Hou, Lifang; Kabagambe, Edmond K; Zhang, Bing; Smalley, Walter E; Edwards, Todd L; Giovannucci, Edward L; Zheng, Wei; Dai, Qi

2016-10-01

Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18-0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54-0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study

PubMed Central

Zhu, Xiangzhu; Shrubsole, Martha J.; Ness, Reid M.; Hibler, Elizabeth A; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Ming, Jiang; Hou, Lifang; Kabagambe, Edmond K.; Zhang, Bing; Smalley, Walter E.; Edwards, Todd L.; Giovannucci, Edward L.; Zheng, Wei; Dai, Qi

2016-01-01

Background Some studies suggest that the calcium to magnesium ratio intakes modifies the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. Methods We conducted a two-phase study including 1,336 cases and 2,891 controls from the Tennessee Colorectal Polyp Study. Results In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (p for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥1000 mg/day) was significantly associated with 64% reduced adenoma risk (OR=0.36 (95% CI: 0.18–0.74)) among those homozygous for the minor allele (TT genotype) (p for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found highest magnesium intake was significantly associated with 27% reduced risk (OR=0.73 (95% CI: 0.54–0.97)) of colorectal adenoma (p for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype; whereas magnesium intake was not linked to risk among those with the TT genotype. Conclusions These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer. PMID:26333203

High resolution microendoscopy for classification of colorectal polyps.

PubMed

Chang, S S; Shukla, R; Polydorides, A D; Vila, P M; Lee, M; Han, H; Kedia, P; Lewis, J; Gonzalez, S; Kim, M K; Harpaz, N; Godbold, J; Richards-Kortum, R; Anandasabapathy, S

2013-07-01

It can be difficult to distinguish adenomas from benign polyps during routine colonoscopy. High resolution microendoscopy (HRME) is a novel method for imaging colorectal mucosa with subcellular detail. HRME criteria for the classification of colorectal neoplasia have not been previously described. Study goals were to develop criteria to characterize HRME images of colorectal mucosa (normal, hyperplastic polyps, adenomas, cancer) and to determine the accuracy and interobserver variability for the discrimination of neoplastic from non-neoplastic polyps when these criteria were applied by novice and expert microendoscopists. Two expert pathologists created consensus HRME image criteria using images from 68 patients with polyps who had undergone colonoscopy plus HRME. Using these criteria, HRME expert and novice microendoscopists were shown a set of training images and then tested to determine accuracy and interobserver variability. Expert microendoscopists identified neoplasia with sensitivity, specificity, and accuracy of 67 % (95 % confidence interval [CI] 58 % - 75 %), 97 % (94 % - 100 %), and 87 %, respectively. Nonexperts achieved sensitivity, specificity, and accuracy of 73 % (66 % - 80 %), 91 % (80 % - 100 %), and 85 %, respectively. Overall, neoplasia were identified with sensitivity 70 % (65 % - 76 %), specificity 94 % (87 % - 100 %), and accuracy 85 %. Kappa values were: experts 0.86; nonexperts 0.72; and overall 0.78. Using the new criteria, observers achieved high specificity and substantial interobserver agreement for distinguishing benign polyps from neoplasia. Increased expertise in HRME imaging improves accuracy. This low-cost microendoscopic platform may be an alternative to confocal microendoscopy in lower-resource or community-based settings.

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial.

PubMed

Dos Santos, Carlos Eduardo Oliveira; Moreira, Hamilton; Pereira-Lima, Julio Carlos; Ribas, Carmen Australia Paredes Marcondes; de Quadros Onófrio, Fernanda; Czecko, Alexandre Eduardo Augusti; Ramos, Rafael Koerich; de Carvalho, Caroline Aragão

2017-07-01

The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR.

Association between socioeconomic deprivation and colorectal cancer screening outcomes: Low uptake rates among the most and least deprived people

PubMed Central

Auge, Josep M.; Sala, Maria; Román, Marta; Castells, Antoni; Macià, Francesc; Comas, Mercè; Guiriguet, Carolina; Bessa, Xavier; Castells, Xavier

2017-01-01

Background Screening with faecal occult blood tests reduces colorectal cancer-related mortality; however, age, sex and socioeconomic factors affect screening outcomes and could lead to unequal mortality benefits. The aim of this study was to describe the main outcomes of the population-based Barcelona colorectal cancer screening programme (BCRCSP) by deprivation. Methods Retrospective study of the eligible population of the first round of the BCRCSP. Participants’ postal addresses were linked with the MEDEA database to obtain the deprivation quintiles (Dq). Chi-squared tests were used to compare proportions across variables and logistic regression was used to estimate the adjusted effects of age, sex and deprivation on uptake, FIT positivity, colonoscopy adherence and advanced neoplasia detection rate. Results Overall uptake was 44.7%, higher in Dq2, 3 and 4 (OR 1.251, 1.250 and 1.276, respectively) than in the least deprived quintile (Dq 1), and lowest in Dq5 (OR 0.84). Faecal immunochemical test (FIT) positivity and the percentage of people with detectable faecal haemoglobin below the positivity threshold increased with deprivation. The advanced neoplasia detection rate was highest in Dq4. Conclusion Unlike most regions where inequalities are graded along the socioeconomic continuum, inequalities in the uptake of colorectal cancer screening in Spain seem to be concentrated first in the most disadvantaged group and second in the least deprived group. The correlation of deprivation with FIT-positivity and faecal haemoglobin below the positivity threshold is worrying due to its association with colorectal cancer and overall mortality. PMID:28622365

A Blueprint to Advance Colorectal Cancer Immunotherapies.

PubMed

Le, Dung T; Hubbard-Lucey, Vanessa M; Morse, Michael A; Heery, Christopher R; Dwyer, Andrea; Marsilje, Thomas H; Brodsky, Arthur N; Chan, Emily; Deming, Dustin A; Diaz, Luis A; Fridman, Wolf H; Goldberg, Richard M; Hamilton, Stanley R; Housseau, Franck; Jaffee, Elizabeth M; Kang, S Peter; Krishnamurthi, Smitha S; Lieu, Christopher H; Messersmith, Wells; Sears, Cynthia L; Segal, Neil H; Yang, Arvin; Moss, Rebecca A; Cha, Edward; O'Donnell-Tormey, Jill; Roach, Nancy; Davis, Anjelica Q; McAbee, Keavy; Worrall, Sharyn; Benson, Al B

2017-11-01

Immunotherapy is rapidly becoming a standard of care for many cancers. However, colorectal cancer had been generally resistant to immunotherapy, despite features in common with sensitive tumors. Observations of substantial clinical activity for checkpoint blockade in colorectal cancers with defective mismatch repair (microsatellite instability-high tumors) have reignited interest in the search for immunotherapies that could be extended to the larger microsatellite stable (MSS) population. The Cancer Research Institute and Fight Colorectal Cancer convened a group of scientists, clinicians, advocates, and industry experts in colorectal cancer and immunotherapy to compile ongoing research efforts, identify gaps in translational and clinical research, and provide a blueprint to advance immunotherapy. We identified lack of a T-cell inflamed phenotype (due to inadequate T-cell infiltration, inadequate T-cell activation, or T-cell suppression) as a broad potential explanation for failure of checkpoint blockade in MSS. The specific cellular and molecular underpinnings for these various mechanisms are unclear. Whether biomarkers with prognostic value, such as the immunoscores and IFN signatures, would also predict benefit for immunotherapies in MSS colon cancer is unknown, but if so, these and other biomarkers for measuring the potential for an immune response in patients with colorectal cancer will need to be incorporated into clinical guidelines. We have proposed a framework for research to identify immunologic factors that may be modulated to improve immunotherapy for colorectal cancer patients, with the goal that the biomarkers and treatment strategies identified will become part of the routine management of colorectal cancer. Cancer Immunol Res; 5(11); 942-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

PubMed Central

Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

2011-01-01

Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

Total colonoscopy detects early colorectal cancer more frequently than advanced colorectal cancer in patients with fecal occult blood.

PubMed

Ozaki, Takuji; Tokunaga, Akira; Chihara, Naoto; Yoshino, Masanori; Bou, Hideki; Ogata, Masao; Watanabe, Masanori; Suzuki, Hideyuki; Uchida, Eiji

2010-08-01

The efficacy of total colonoscopy following a positive result of the fecal occult blood test (FOBT) for the early detection of colorectal cancer and polyps was evaluated. A total of 1,491 patients with positive FOBT results underwent total colonoscopy at the Institute of Gastroenterology, Nippon Medical School, Musashi Kosugi Hospital, from April 2002 through July 2009. Abnormalities were found in 1,312 of the 1,491 patients (88.0%). Ninety-six of the 1,491 patients (6.4%) were found to have early cancer, but 59 patients (4.0%) were found to have advanced cancer. The early cancers were treated with endoscopic mucosal resection or endoscopic submucosal dissection in 81 patients, with laparoscopy-assisted colectomy in 10 patients, and with open surgery in 5 patients. Fifty-one of the 59 patients with advanced colorectal cancer underwent conventional open surgery, and 8 patients underwent laparoscopic surgery. The cancers detected were more likely to be early cancers than advanced cancers. In addition to malignancies, other abnormalities found included inner or external hemorrhoids, diverticula of the colon, ulcerative colitis, ischemic colitis, infectious colitis, and colorectal polyps. Our results show that a high percentage of lesions detected with total colonoscopy following a positive FOBT result are early colorectal cancers and polyps.

POLE somatic mutations in advanced colorectal cancer.

PubMed

Guerra, Joana; Pinto, Carla; Pinto, Diana; Pinheiro, Manuela; Silva, Romina; Peixoto, Ana; Rocha, Patrícia; Veiga, Isabel; Santos, Catarina; Santos, Rui; Cabreira, Verónica; Lopes, Paula; Henrique, Rui; Teixeira, Manuel R

2017-12-01

Despite all the knowledge already gathered, the picture of somatic genetic changes in colorectal tumorigenesis is far from complete. Recently, germline and somatic mutations in the exonuclease domain of polymerase epsilon, catalytic subunit (POLE) gene have been reported in a small subset of microsatellite-stable and hypermutated colorectal carcinomas (CRCs), affecting the proofreading activity of the enzyme and leading to misincorporation of bases during DNA replication. To evaluate the role of POLE mutations in colorectal carcinogenesis, namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in tumor DNA samples from 307 cases. Microsatellite instability and mutation analyses of a panel of oncogenes were performed in the tumors harboring POLE mutations. Three heterozygous mutations were found in two tumors, the c.857C>G, p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the POLE-mutated CRCs, one tumor was microsatellite-stable and the other had low microsatellite instability, whereas KRAS and PIK3CA mutations were found in one tumor each. We conclude that POLE somatic mutations exist but are rare in advanced CRC, with further larger studies being necessary to evaluate its biological and clinical implications. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Cost analysis of colorectal cancer screening with CT colonography in Italy.

PubMed

Mantellini, Paola; Lippi, Giuseppe; Sali, Lapo; Grazzini, Grazia; Delsanto, Silvia; Mallardi, Beatrice; Falchini, Massimo; Castiglione, Guido; Carozzi, Francesca Maria; Mascalchi, Mario; Milani, Stefano; Ventura, Leonardo; Zappa, Marco

2018-06-01

Unit costs of screening CT colonography (CTC) can be useful for cost-effectiveness analyses and for health care decision-making. We evaluated the unit costs of CTC as a primary screening test for colorectal cancer in the setting of a randomized trial in Italy. Data were collected within the randomized SAVE trial. Subjects were invited to screening CTC by mail and requested to have a pre-examination consultation. CTCs were performed with 64- and 128-slice CT scanners after reduced or full bowel preparation. Activity-based costing was used to determine unit costs per-process, per-participant to screening CTC, and per-subject with advanced neoplasia. Among 5242 subjects invited to undergo screening CTC, 1312 had pre-examination consultation and 1286 ultimately underwent CTC. Among 129 subjects with a positive CTC, 126 underwent assessment colonoscopy and 67 were ultimately diagnosed with advanced neoplasia (i.e., cancer or advanced adenoma). Cost per-participant of the entire screening CTC pathway was €196.80. Average cost per-participant for the screening invitation process was €17.04 and €9.45 for the pre-examination consultation process. Average cost per-participant of the CTC execution and reading process was €146.08 and of the diagnostic assessment colonoscopy process was €24.23. Average cost per-subject with advanced neoplasia was €3777.30. Cost of screening CTC was €196.80 per-participant. Our data suggest that the more relevant cost of screening CTC, amenable of intervention, is related to CTC execution and reading process.

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial

PubMed Central

dos Santos, Carlos Eduardo Oliveira; Moreira, Hamilton; Pereira-Lima, Julio Carlos; Ribas, Carmen Australia Paredes Marcondes; de Quadros Onófrio, Fernanda; Czecko, Alexandre Eduardo Augusti; Ramos, Rafael Koerich; de Carvalho, Caroline Aragão

2017-01-01

OBJECTIVES: The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. METHODS: In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. RESULTS: A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). CONCLUSION: The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR. PMID:28792997

Immunoreactive transforming growth factor alpha is commonly present in colorectal neoplasia.

PubMed Central

Tanaka, S.; Imanishi, K.; Yoshihara, M.; Haruma, K.; Sumii, K.; Kajiyama, G.; Akamatsu, S.

1991-01-01

Surgical specimens from 19 patients with invasive colorectal cancers and 12 specimens of normal mucosa from the same patients were examined immunohistochemically for the production of the immunoreactive (IR-) transforming growth factor (TGF)-alpha and IR-epidermal growth factor (EGF) with an anti-TGF-alpha monoclonal antibody (MAb) OAL-MTG01 and anti-EGF MAb KEM-10. Immunoreactive TGF-alpha was detected in 16 (84.2%) of 19 colorectal cancers. In contrast, there was no IR-TGF-alpha in the gland cells of normal mucosa. Immunoreactive EGF was detected in 7 (36.8%) of 19 colorectal cancers and 1 (8.3%) of 12 cases of normal mucosa. The production of both IR-TGF-alpha and IR-EGF in colorectal cancer did not differ by histologic type and Dukes' stage. Immunoreactive TGF-alpha was detected at significantly higher incidence than IR-EGF in colorectal cancer. These results indicate that IR-TGF-alpha should prove valuable as a possible tumor marker in colorectal cancers, and it may be very useful in understanding the biology of colorectal cancer. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1853928

Colorectal endoscopic submucosal dissection: Recent technical advances for safe and successful procedures

PubMed Central

Yamamoto, Katsumi; Michida, Tomoki; Nishida, Tsutomu; Hayashi, Shiro; Naito, Masafumi; Ito, Toshifumi

2015-01-01

Endoscopic submucosal dissection (ESD) is very useful in en bloc resection of large superficial colorectal tumors but is a technically difficult procedure because the colonic wall is thin and endoscopic maneuverability is poor because of colonic flexure and extensibility. A high risk of perforation has been reported in colorectal ESD. To prevent complications such as perforation and unexpected bleeding, it is crucial to ensure good visualization of the submucosal layer by creating a mucosal flap, which is an exfoliated mucosa for inserting the tip of the endoscope under it. The creation of a mucosal flap is often technically difficult; however, various types of equipment, appropriate strategy, and novel procedures including our clip-flap method, appear to facilitate mucosal flap creation, improving the safety and success rate of ESD. Favorable treatment outcomes with colorectal ESD have already been reported in many advanced institutions, and appropriate understanding of techniques and development of training systems are required for world-wide standardization of colorectal ESD. Here, we describe recent technical advances for safe and successful colorectal ESD. PMID:26468335

American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data.

PubMed

Singhi, Aatur D; Zeh, Herbert J; Brand, Randall E; Nikiforova, Marina N; Chennat, Jennifer S; Fasanella, Kenneth E; Khalid, Asif; Papachristou, Georgios I; Slivka, Adam; Hogg, Melissa; Lee, Kenneth K; Tsung, Allan; Zureikat, Amer H; McGrath, Kevin

2016-06-01

The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI

Nutrients, Foods, and Colorectal Cancer Prevention

PubMed Central

Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.

2015-01-01

Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits and vegetables. Nutrients and foods may also interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of over-nutrition and obesity—risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. PMID:25575572

Performance of the Fecal Immunochemical Test for Colorectal Cancer Screening Using Different Stool-Collection Devices: Preliminary Results from a Randomized Controlled Trial.

PubMed

Shin, Hye Young; Suh, Mina; Baik, Hyung Won; Choi, Kui Son; Park, Boyoung; Jun, Jae Kwan; Hwang, Sang-Hyun; Kim, Byung Chang; Lee, Chan Wha; Oh, Jae Hwan; Lee, You Kyoung; Han, Dong Soo; Lee, Do-Hoon

2016-11-15

We are in the process of conducting a randomized trial to determine whether compliance with the fecal immunochemical test (FIT) for colorectal cancer screening differs according to the stool-collection method. This study was an interim analysis of the performance of two stool-collection devices (sampling bottle vs conventional container). In total, 1,701 individuals (age range, 50 to 74 years) were randomized into the sampling bottle group (intervention arm) or the conventional container group (control arm). In both groups, we evaluated the FIT positivity rate, the positive predictive value for advanced neoplasia, and the detection rate for advanced neoplasia. The FIT positivity rates were 4.1% for the sampling bottles and 2.0% for the conventional containers; these values were significantly different. The positive predictive values for advanced neoplasia in the sampling bottles and conventional containers were 11.1% (95% confidence interval [CI], -3.4 to 25.6) and 12.0% (95% CI, -0.7 to 24.7), respectively. The detection rates for advanced neoplasia in the sampling bottles and conventional containers were 4.5 per 1,000 persons (95% CI, 2.0 to 11.0) and 2.4 per 1,000 persons (95% CI, 0.0 to 5.0), respectively. The impact of these findings on FIT screening performance was unclear in this interim analysis. This impact should therefore be evaluated in the final analysis following the final enrollment period.

Parkin protein expression and its impact on survival of patients with advanced colorectal cancer.

PubMed

da Silva-Camargo, Claudia Caroline Veloso; Svoboda Baldin, Rosimeri Kuhl; Costacurta Polli, Nayanne Louise; Agostinho, Amanda Pereira; Olandosk, Marcia; de Noronha, Lúcia; Sotomaior, Vanessa Santos

2018-02-01

Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer. Tissue microarrays consisting of 73 tumor and 64 normal tissue samples were generated to examine parkin expression and localization by immunohistochemistry. A positive correlation of parkin and APC expression was observed in the superficial, intermediate, and profound regions of all cases (ρ = 0.37; P = 0.001). Parkin expression was also significantly associated with tumors in men ( P = 0.049), those of the mucinous subtype ( P = 0.028), and of advanced stage (III + IV, P = 0.041). In addition, increased parkin expression was observed in the invasive front tumor region ( P = 0.013). More importantly, a positive correlation was found between parkin expression and the overall survival of patients with advanced colorectal cancer ( P = 0.019). Multivariate analysis showed that parkin expression was independent of any of the clinicopathological parameters evaluated in relation to patient survival. These results suggest that parkin expression status can be used as a potential independent prognostic marker of survival in advanced colorectal cancer.

Unregulated smooth-muscle myosin in human intestinal neoplasia.

PubMed

Alhopuro, Pia; Phichith, Denis; Tuupanen, Sari; Sammalkorpi, Heli; Nybondas, Miranda; Saharinen, Juha; Robinson, James P; Yang, Zhaohui; Chen, Li-Qiong; Orntoft, Torben; Mecklin, Jukka-Pekka; Järvinen, Heikki; Eng, Charis; Moeslein, Gabriela; Shibata, Darryl; Houlston, Richard S; Lucassen, Anneke; Tomlinson, Ian P M; Launonen, Virpi; Ristimäki, Ari; Arango, Diego; Karhu, Auli; Sweeney, H Lee; Aaltonen, Lauri A

2008-04-08

A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia.

Dietary patterns and risk of advanced colorectal neoplasms: A large population based screening study in Germany.

PubMed

Erben, Vanessa; Carr, Prudence R; Holleczek, Bernd; Stegmaier, Christa; Hoffmeister, Michael; Brenner, Hermann

2018-06-01

Specific components of the diet such as red and processed meat have been associated with the risk of developing colorectal cancer. However, evidence on the association of dietary patterns with colorectal neoplasms is sparse. The aim of this study was to analyze the association of dietary patterns with prevalence of advanced colorectal neoplasms among older adults in Germany. A cross-sectional study was conducted among participants of screening colonoscopy in Saarland, Germany, who were enrolled in the KolosSal study (Effektivität der Früherkennungs-Koloskopie: eine Saarland-weite Studie) from 2005 to 2013. Information on diet and lifestyle factors was obtained through questionnaires and colonoscopy results were extracted from physicians' reports. Associations of a priori defined dietary patterns (vegetarian or adapted versions of the Healthy Eating Index [HEI] and the Dietary Approaches to Stop Hypertension [DASH] index) with the risk of advanced colorectal neoplasms were assessed by multiple logistic regression analyses with comprehensive adjustment for potential confounders. A total of 14,309 participants were included (1561 with advanced colorectal neoplasms). Healthier eating behavior was associated with lower prevalence of advanced colorectal neoplasms in a dose-response manner. Adjusted odds ratios (95% confidence intervals) comparing the highest with the lowest categories of adapted HEI and DASH were 0.61 (0.50, 0.76) and 0.70 (0.55, 0.89), respectively. No significant associations were observed for a vegetarian eating pattern (adjusted OR 0.80 (0.55, 1.17)). Healthy dietary patterns, as described by a high HEI or DASH score, but not a vegetarian diet alone, are associated with reduced risk of advanced colorectal neoplasms. Copyright © 2018 Elsevier Inc. All rights reserved.

Elevated serum gastrin is associated with a history of advanced neoplasia in Barrett's esophagus.

PubMed

Wang, Judy S; Varro, Andrea; Lightdale, Charles J; Lertkowit, Nantaporn; Slack, Kristen N; Fingerhood, Michael L; Tsai, Wei Yann; Wang, Timothy C; Abrams, Julian A

2010-05-01

Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett's esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. A total of 95 patients were enrolled. The mean age was 64.7 (+/-10.0) years, and 70.5% were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P=0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95% confidence interval (CI): 1.20-24.8). In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression.

The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia.

PubMed

Hanks, Joanna; Ayed, Iyeman; Kukreja, Neil; Rogers, Chris; Harris, Jessica; Gheorghiu, Alina; Liu, Chee Ling; Emery, Peter; Pufulete, Maria

2013-12-01

Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation. We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon. We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively. Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001). MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia.

[The clinico-genetic characteristics of the origin and manifestation of colorectal cancer].

PubMed

Nalieskina, L A; Polishchuk, L Z; Oliĭnichenko, P I; Hanina, K P; Oliĭnichenko, H P; Kukhar, I V; Hlushchenko, N M

1998-06-01

A clinical and genealogical investigation has been carried out in 169 subjects of both sexes, presenting with colorectal oncopathology. Particular features of the colorectal carcinoma in the patients have been recognized. The frequency of the tumours spread in the relatives of the probands is determined as is the spectrum of aggregation of large intestine carcinoma with neoplasia of other genesis in the pedigrees. The data obtained suggest an important contribution of genetic factors into the origination of colorectal carcinoma.

Family caregiving challenges in advanced colorectal cancer: patient and caregiver perspectives.

PubMed

Mosher, Catherine E; Adams, Rebecca N; Helft, Paul R; O'Neil, Bert H; Shahda, Safi; Rattray, Nicholas A; Champion, Victoria L

2016-05-01

Family caregivers of advanced colorectal cancer patients may be at increased risk for psychological distress. Yet their key challenges in coping with the patient's illness are not well understood. Soliciting both patient and caregiver perspectives on these challenges would broaden our understanding of the caregiving experience. Thus, the purpose of this research was to identify caregivers' key challenges in coping with their family member's advanced colorectal cancer from the perspective of patients and caregivers. Individual, semi-structured qualitative interviews were conducted with 23 advanced colorectal cancer patients and 23 primary family caregivers. Interview data were analyzed via thematic analysis. In nearly all cases, patient and caregiver reports of the caregiver's key challenge were discrepant. Across patient and caregiver reports, caregivers' key challenges included processing emotions surrounding the patient's initial diagnosis or recurrence and addressing the patient's practical and emotional needs. Other challenges included coping with continual uncertainty regarding the patient's potential functional decline and prognosis and observing the patient suffer from various physical symptoms. Findings suggest that eliciting the perspectives of both patients and caregivers regarding caregivers' challenges provides a more comprehensive understanding of their experience. Results also point to the need to assist caregivers with the emotional and practical aspects of caregiving.

Risk of colorectal adenomas in patients with celiac disease: a systematic review and meta-analysis.

PubMed

Lasa, J; Rausch, A; Zubiaurre, I

Whether celiac disease increases the risk of presenting with colorectal adenoma or not, has not been extensively evaluated. This question becomes relevant when considering early screening methods in patients with the disease. The aim of our article was to determine the risk of colorectal adenomas in celiac disease patients. A computer-assisted search of the MEDLINE-Pubmed, EMBASE, LILACS, Cochrane Library, and Google Scholar databases was carried out, encompassing the time frame of 1966 to December 2016. The search strategy consisted of the following MESH terms: 'celiac disease' OR 'celiac sprue' AND 'colorectal' OR 'colorectal neoplasia' OR 'colorectal adenoma'. A fixed-effect model was used for the analyses. The first analysis dealt with the prevalence of all presentations of colorectal adenoma in patients with celiac disease and the second was on the prevalence of advanced adenomas. The outcomes were described as odds ratios (OR) with their 95% confidence intervals. The search identified 480 bibliographic citations, 17 of which were chosen for evaluation. Fourteen of those studies were rejected, leaving a final total of three for the analysis. Those studies included 367 cases of celiac disease and 682 controls. No significant heterogeneity was observed (I 2 =26%). There was no increased prevalence of colorectal adenomas in the celiac disease patients, when compared with the controls (OR: 0.94 [0.65-1.38]), and no significant difference was observed when assessing the prevalence of advanced adenomas (OR: 0.97 [0.48-1.97]). Celiac disease was not associated with an increased risk of colorectal adenomas. However, due to the limited evidence available, more studies are necessary to determine whether there is an actual association. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

PubMed Central

Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

2014-01-01

Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma

USDA-ARS?s Scientific Manuscript database

Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a rand...

Should hot biopsy forceps be abandoned for polypectomy of diminutive colorectal polyps?

PubMed Central

Panteris, Vasileios; Vezakis, Antonios; Triantafillidis, JK

2018-01-01

Standardized approach to polypectomy of diminutive colorectal polyps (DCPs) is lacking since cold biopsy forceps have been associated with high levels of recurrence, hot biopsy forceps are considered inadequate and risky and cold snaring is currently under investigation for its efficacy and safety. This has led to confusion and a gap in clinical practice. This article discusses the usefulness and contemporary practical applicability of hot biopsy forceps and provides well-intentioned criticism of the new European guidelines for the treatment of DCPs. Diminutive colorectal polyps are a source of frustration for the endoscopist since their small size is accompanied by a considerable risk of premalignant neoplasia and a small but non-negligible risk of advanced neoplasia and even cancer. Since the proportion of diminutive colorectal polyps is substantial and exceeds that of larger polyps, their effective removal poses a considerable workload and a therapeutic challenge. During the last decade, the introduction of cold snaring to routine endoscopy practice has attempted to overcome the use of prior techniques, such as hot biopsy forceps. It is important to recognize that with the exception of endoscopic methods that are obviously unsafe and inadequate to serve their purpose, all other interventional endoscopic methods are operator-dependent in the sense that specific expertise and training are obligatory for the success of any therapeutic intervention. Since relevant publications on hot biopsy forceps are still in favor of its careful use, as it has not yet demonstrated inferiority compared with newer techniques, it would be prudent for any medical practitioner to evaluate the available tools and judge any new proposed technique based on the evidence before it is adopted. PMID:29662295

Vaginal reconstruction following resection of primary locally advanced and recurrent colorectal malignancies.

PubMed

D'Souza, Dougal N; Pera, Miguel; Nelson, Heidi; Finical, Stephan J; Tran, Nho V

2003-12-01

Vertical rectus abdominus myocutaneous flap reconstruction facilitates healing within the radiated pelvis and preserves the possibility of subsequent sexual function in patients with colorectal cancer who require partial or complete resection of the vagina. A retrospective review of a consecutive series of patients. A tertiary referral center. All patients undergoing surgical treatment of locally advanced or recurrent colorectal cancer and vertical rectus abdominus myocutaneous flap reconstruction of the vagina. Vertical rectus abdominus myocutaneous flap reconstruction. Operative feasibility, complications, and sexual function. Twelve patients underwent extended resection for primary locally advanced or recurrent colorectal cancer including total or near total vaginectomy. Median age was 47 years. Tumors included 9 rectal adenocarcinomas, 2 anal squamous cell carcinomas, and 1 recurrent cecal adenocarcinoma. Surgical procedures included 8 abdominoperineal resections with posterior exenteration; resection of pelvic tumor and partial vaginectomy in 2 patients with previous abdominoperineal resection; 1 total exenteration; and 1 total proctocolectomy with posterior exenteration. The average operative time for tumor extirpation, irradiation, and reconstruction was more than 9 hours and all patients required blood transfusions. Despite 2 patients having superficial necrosis and 4 having mild wound infections, no patient required reoperation and all achieved complete healing. Five patients reported resuming sexual intercourse. The vertical rectus abdominus myocutaneous flap can be successfully used for vaginal reconstruction following resection of locally advanced colorectal cancer. It provides nonirradiated, vascularized tissue that fills the pelvic dead space, allows for stomal placement, and provides a chance for sexual function.

Management of early colonic neoplasia: where are we now and where are we heading?

PubMed

Longcroft-Wheaton, Gaius; Bhandari, Pradeep

2017-03-01

There have been considerable advances in the endoscopic treatment of colorectal neoplasia. The development of endoscopic submucosal dissection and full thickness resection techniques is changing the way benign disease and early cancers are managed. This article reviews the evidence behind these new techniques and discusses where this field is likely to move in the future. Areas covered: A PubMed literature review of resection techniques for colonic neoplasia was performed. The clinical and cost effectiveness of endoscopic mucosal resection (EMR) is examined. The development of endoscopic submucosal dissection (ESD) and knife assisted resection is described and issues around training reviewed. Efficacy is compared to both EMR and transanal endoscopic microsurgery. The future is considered, including full thickness resection techniques and robotic endoscopy. Expert commentary: The perceived barriers to ESD are falling, and views that such techniques are only possible in Japan are disappearing. The key barriers to uptake will be training, and the development of educational programmes should be seen as a priority. The debate between TEMS and ESD will continue, but ESD is more flexible and cheaper. This will become less significant as the number of endoscopists trained in ESD grows and some TEMS surgeons may shift across towards ESD.

Advanced Endoscopic Imaging for Surveillance for Dysplasia and Colorectal Cancer in inflammatory Bowel Disease: Could the Pathologist be Further Helped?

PubMed Central

Sinagra, Emanuele; Tomasello, Giovanni; Raimondo, Dario; Sturm, Andreas; Giunta, Marco; Messina, Marco; Damiano, Giuseppe; Palumbo, Vincenzo D.; Spinelli, Gabriele; Rossi, Francesca; Facella, Tiziana; Marasà, Salvatore; Cottone, Mario; Lo Monte, Attilio I.

2014-01-01

Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal cancer. The magnitude of that increased risk as well as how best to mitigate it remain a topic of ongoing investigation in the field. It is important to quantify the risk of colorectal cancer in association with IBD. The reported risk varies widely between studies. This is partly due to the different methodologies used in the studies. Because of the limitations of surveillance strategies based on the detection of dysplasia, advanced endoscopic imaging and techniques involving the detection of alterations in mucosal antigens and genetic abnormalities are being investigated. Development of new biomarkers, predicting future occurrence of colonic neoplasia may lead to more biomarker-based surveillance. There are promising results that may lead to more efficient surveillance in IBD patients and more general acceptance of its use. A multidisciplinary approach, involving in particular endoscopists and pathologists, together with a centralized patient management, could help to optimize treatments and follow-up measures, both of which could help to reduce the IBD-associated cancer risk. PMID:24496155

Diagnostic accuracy of three biopsy techniques in 117 dogs with intra-nasal neoplasia.

PubMed

Harris, B J; Lourenço, B N; Dobson, J M; Herrtage, M E

2014-04-01

To determine if nasal biopsies taken at rhinoscopy are more accurate for diagnosing neoplasia than biopsies taken blindly or using advanced imaging for guidance. A retrospective study of 117 dogs with nasal mass lesions that were divided into three groups according to the method of nasal biopsy collection; advanced imaging-guided, rhinoscopy-guided and blind biopsy. Signalment, imaging and rhinoscopic findings, and histopathological diagnosis were compared between groups. The proportion of first attempt biopsies confirming neoplasia were determined for each group. There were no statistically significant differences in the proportion of biopsies that confirmed neoplasia obtained via advanced imaging-guided, rhinoscopy-guided or blind biopsy techniques. In dogs with a high index of suspicion of nasal neoplasia, blind biopsy may be as diagnostic as rhinoscopy-guided biopsy. Repeated biopsies are frequently required for definitive diagnosis. © 2014 British Small Animal Veterinary Association.

Asia Pacific consensus recommendations for colorectal cancer screening.

PubMed

Sung, J J Y; Lau, J Y W; Young, G P; Sano, Y; Chiu, H M; Byeon, J S; Yeoh, K G; Goh, K L; Sollano, J; Rerknimitr, R; Matsuda, T; Wu, K C; Ng, S; Leung, S Y; Makharia, G; Chong, V H; Ho, K Y; Brooks, D; Lieberman, D A; Chan, F K L

2008-08-01

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

[The necessary perseverance of surgery for the treatment of locally advanced colorectal cancer].

PubMed

Gu, Jin

2018-03-25

Colorectal cancer, a malignant tumor arising from the colon or rectum, is a common cancer in China, with most patients diagnosed at the advanced stage or locally advanced stage. Large tumor size results in the invasion of adjacent organs and the multiple organ involvement, which poses certain challenges for clinical treatment. When facing advanced stage colorectal cancer, some surgeons do not consider surgery, a reasonable option. However, in fact, multi-disciplinary treatment can achieve relatively good treatment outcomes in patients with advanced stage or locally advanced stage colorectal cancer. Therefore, reasonable surgery should not be hastily abandoned. For patients with large tumors without distant metastases but with multiple organ involvement, directly surgical resection is difficult, therefore, preoperative adjuvant therapy can be considered. The basic principle of surgical treatment is to accomplish maximum protection of organ functions and to perform reasonable regional lymph node dissection on the basis of achieving R0 resection. Common surgical procedures for locally advanced colorectal cancer are as follows: (1)Right-sided colon cancer with duodenal invasion: first, the colon must be freed from three directions, namely the right posterior surface of the colon, the left side of the tumor, and the upper side of the tumor inferior to the pylorus, so as to expose and assess the spatial relationship between the tumor and the duodenum; the actual tumor invasion depth in the duodenum may be shallow. (2) Splenic flexure colon cancer with invasion of the cauda pancreatis and hilum lienis: multivisceral resection must be performed without separating the attachment between the tumor and spleen. The tumor border can be found more easily through manipulations starting from the descending colon. (3) Giant sigmoid colorectal cancer with bladder invasion: invasion usually occurs at the bladder fundus. Therefore, during surgery, the attachment between the rectum and

Elevated Serum Gastrin Is Associated With a History of Advanced Neoplasia in Barrett’s Esophagus

PubMed Central

Wang, Judy S.; Varro, Andrea; Lightdale, Charles J.; Lertkowit, Nantaporn; Slack, Kristen N.; Fingerhood, Michael L.; Tsai, Wei Yann; Wang, Timothy C.; Abrams, Julian A.

2011-01-01

OBJECTIVES Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett’ s esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. METHODS We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. RESULTS A total of 95 patients were enrolled. The mean age was 64.7 (±10.0) years, and 70.5 % were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P = 0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95 % confidence interval (CI): 1.20–24.8). CONCLUSIONS In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression. PMID:19904251

Animal models of pituitary neoplasia

PubMed Central

Lines, K.E.; Stevenson, M.; Thakker, R.V.

2016-01-01

Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

Helicobacter pylori infection is an independent risk factor of early and advanced colorectal neoplasm.

PubMed

Kim, Tae Jun; Kim, Eun Ran; Chang, Dong Kyung; Kim, Young-Ho; Baek, Sun-Young; Kim, Kyunga; Hong, Sung Noh

2017-06-01

The role of Helicobacter pylori (H. pylori) in the development of colorectal neoplasm remains controversial. We examined the association between H. pylori infection and colorectal neoplasm in a large sample of healthy participants who underwent screening colonoscopy. A cross-sectional study of 8916 men, who participated in a regular health-screening examination that included an H. pylori-specific immunoglobulin G antibody test and colonoscopy, was conducted to evaluate the association between H. pylori and colorectal neoplasm. Multivariable analyses adjusted for age, body mass index, smoking status, alcohol intake, regular exercise, regular aspirin use, and family history of colorectal cancer showed that the odds ratio (OR) (95% confidence interval [CI]) for any adenoma and advanced neoplasm was 1.32 (1.07-1.61) and 1.90 (1.05-3.56) in participants with H. pylori infection and without H. pylori infection, respectively. The association persisted after further adjustment for inflammatory markers or metabolic variables including fasting blood glucose, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. Regarding the location, a positive association was confined to cases with proximal adenomas and was observed similarly in all the evaluated subgroups. In a large-scale study, carefully controlled for confounding factors, involving asymptomatic participants without a history of colonoscopy, H. pylori infection was significantly associated with the risk of any colorectal adenoma and advanced colorectal neoplasm. Prospective studies are necessary to determine whether H. pylori eradication can reduce this risk. © 2017 John Wiley & Sons Ltd.

Colorectal adenoma stem-like cell populations: Associations with adenoma characteristics and metachronous colorectal neoplasia

PubMed Central

Bartley, Angela N.; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J.; Buckmeier, Julie A.; Corley, Lynda; Phipps, Ron A.; Gallick, Gary; Lance, Peter; Thompson, Patricia A.; Hamilton, Stanley R.

2014-01-01

Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma (“recurrence”), have not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1 labeling indices (ALIs) were similar across patient characteristics and in advanced and non-advanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (p=0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma-free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (p=0.03). A best-fit algorithm-based cut-point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem-cell target for chemoprevention. PMID:24008128

Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications

NASA Astrophysics Data System (ADS)

Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

2008-02-01

Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

DTIC Science & Technology

2016-08-01

subsequent colorectal neoplasia and interval cancers were identified, the pathology review form and protocol were finalized, assays for 6 out of the 11...methylation markers were optimized, tissue blocks and clinical H&E slides were pulled for standard pathology review. Also, Dr. Burnett-Hartman...10 9. Appendix I: Pathology Review Form…………………………………….. 11 10. Appendix II: Research Support: Burnett-Hartman…………………….. 12 11. Appendix III

Repeated faecal occult blood testing is associated with decreased advanced colorectal cancer risk: A population-based study.

PubMed

James, Paul D; Rabeneck, Linda; Yun, Lingsong; Paszat, Lawrence; Baxter, Nancy N; Govindarajan, Anand; Antonova, Lilia; Tinmouth, Jill M

2017-01-01

Objective To evaluate the association between repeated faecal occult blood testing and advanced colorectal cancer risk at population level in Canada. Methods A retrospective cohort study of all Ontario residents aged 56-74 diagnosed with colorectal cancer from 1 April 2007 to 31 March 2010, identified using health administrative data. The primary outcome was stage IV colorectal cancer, and primary exposure was faecal occult blood testing use within five years prior to colorectal cancer diagnosis. Patients were categorized into four mutually exclusive groups based on their exposure to faecal occult blood testing in the five years prior to colorectal cancer diagnosis: none, pre-diagnostic, repeated, and sporadic. Logistic regression was utilized to adjust for confounders. Results Of 7753 patients (median age 66, interquartile range 61-70, 62% male) identified, 1694 (22%) presented with stage I, 2056 (27%) with stage II, 2428 (31%) with stage III, and 1575 (20%) with stage IV colorectal cancer. There were 4092 (53%) with no record of prior faecal occult blood testing, 1485 (19%) classified as pre-diagnostic, 1693 (22%) as sporadic, and 483 (6%) as repeated faecal occult blood testing. After adjusting for confounders, patients who had repeated faecal occult blood testing were significantly less likely to present with stage IV colorectal cancer at diagnosis (Odds ratio 0.46, 95% Confidence Interval 0.34-0.62) than those with no prior faecal occult blood testing. Conclusions Repeated faecal occult blood testing is associated with a decreased risk of advanced colorectal cancer. Our findings support the use of organized screening programmes that employ repeated faecal occult blood testing to improve colorectal cancer outcomes at population level.

Influence of intraoperative radiation therapy on locally advanced and recurrent colorectal tumors: A 16-year experience.

PubMed

Brady, Justin T; Crawshaw, Benjamin P; Murrell, Barrington; Dosokey, Eslam M G; Jabir, Murad A; Steele, Scott R; Stein, Sharon L; Reynolds, Harry L

2017-03-01

Intraoperative radiation therapy (IORT) has been proposed as a tool to improve local control in patients with locally advanced primary or recurrent colorectal cancer. A retrospective review (1999-2015) of all patients undergoing IORT for locally advanced or recurrent colorectal cancer at a single academic center was performed. Patient demographics, oncologic staging, short-term and long-term outcomes were reviewed. There were 77 patients (mean age 63 ± 11 years) identified, of whom 19 had colon cancer, 57 had rectal cancer, and 2 had appendiceal cancers. R0 resection was performed in 53 patients (69%), R1 in 19 (25%) and R2 in 5 (6%). Ten (13%) patients had a local recurrence at 18 ± 14 months and 34 (44%) had a distant recurrence at 18 ± 18 months. Mean survival was 47 ± 41 months. IORT resulted in low local failure rates and should be considered for patients with locally advanced or recurrent colorectal cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Improving colorectal cancer screening: fact and fantasy

NASA Astrophysics Data System (ADS)

Van Dam, Jacques

2008-02-01

procedure. Efforts to improve the practice of colonoscopy will be described. Another limitation of the current practice is the inability to detect polypoid neoplasia that is hidden from view under white light imaging by the natural folds that occur within the colon. A device to overcome this limitation will also be described. Efforts to improve colorectal cancer screening (and thereby decrease the death rate of this second leading cause of cancer death in the United States) are progressing in many arenas. The researcher, basic or clinical, should maintain an up to date overview of the field and how each new technological advance is likely to have a role in the screening and early detection of colorectal cancer.

Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection.

PubMed

Wang, Yu; Chen, Pei-Min; Liu, Rong-Bin

2018-01-15

This review article summarizes the research advances of the plasma-based SEPT9 gene methylation assay for the clinical detection of colorectal cancer and its limitations. Colorectal cancer is a common malignancy with a poor prognosis and a high mortality, for which early detection and diagnosis are particularly crucial for the high-risk groups. Increasing evidence supported that SEPT9 gene methylation is associated with the pathogenesis of colorectal cancer and that detecting the level of methylation of SEPT9 in the peripheral blood can be used for screening of colorectal cancer in susceptible populations. In recent years, the data obtained in clinical studies demonstrated that the SEPT9 gene methylation assay has a good diagnostic performance with regard to both sensitivity and specificity with the advantage of better acceptability, convenience and compliance with serological testing compared with fecal occult blood tests and carcinoembryonic antigen for colorectal cancer (CRC). Furthermore, the combination of multiple methods or markers has become a growing trend for CRC detection and screening. Nevertheless, the clinical availability of the methylated SEPT9 assay is still limited because of the large degree of sample heterogeneity caused by demographic characteristics, pathological features, comorbidities and/or technique selection. Another factor is the cost-effectiveness of colorectal cancer screening strategies that hinders its large-scale application. In addition, improvements in its accuracy in detecting adenomas and premalignant polyps are required.

Results of faecal immunochemical test for colorectal cancer screening, in average risk population, in a cohort of 1389 subjects.

PubMed

Miuţescu, Bogdan; Sporea, Ioan; Popescu, Alina; Bota, Simona; Iovănescu, Dana; Burlea, Amelia; Mos, Liana; Miuţescu, Eftimie

2013-01-01

The aim of this study is to evaluate the usefulness of the fecal immunochemical test (FIT) in colorectal cancer screening, detection of precancerous lesions and early colorectal cancer. The study evaluated asymptomatic patients with average risk (no personal or family antecedents of polyps or colorectal cancer), aged between 50 and 74 years. The presence of the occult haemorrhage was tested with the immunochemical faecal test Hem Check 1 (Veda Lab, France). The subjects were not requested to have any dietary or drug restrictions. Colonoscopy was recommended in all subjects that tested positive. In our study, we had a total of 1389 participants who met the inclusion criteria, with a mean age of 61.2 ± 12.8 years, 565 (40.7%) men and 824 (59.3%) women. FIT was positive in 87 individuals (6.3%). In 57/87 subjects (65.5%) with positive FIT, colonoscopy was performed, while the rest of the subjects refused or delayed the investigation. A number of 5 (8.8%) patients were not able to have a complete colonoscopy, due to neoplastic stenosis. The colonoscopies revealed in 10 cases (0.7%) cancer, in 29 cases (2.1%) advanced adenomas and in 15 cases (1.1%) non advanced adenomas from the total participants in the study. The colonoscopies performed revealed a greater percentage of advanced adenomas in the left colon compared to the right colon, 74.1% vs. 28.6% (p<0.001). In our study, FIT had a positivity rate of 6.3%. The detection rate for advanced neoplasia was 2.8% (0.7% for cancer, 2.1% for advanced adenomas) in our study group. Adherence to colonoscopy for FIT-positive subjects was 65.5%.

Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

PubMed Central

2013-01-01

Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

Controversies in colorectal cancer screening.

PubMed

Pox, Christian P

2014-01-01

Colorectal cancer (CRC) is one of the most common cancers worldwide and a good candidate for screening programmes. However, there is controversy concerning which of the available screening tests should be used. There is general agreement that screening for CRC in the asymptomatic population should begin at the age of 50. Several different screening methods are available which can be separated into those that mainly detect cancers: faecal occult blood tests [guaiac (FOBT) and immunochemical (FIT)], genetic stool tests, blood tests and the M2-pyruvate kinase (M2-PK) test. Methods that detect cancers and polyps are colonoscopy, sigmoidoscopy, CT-colonography (CT-C) and colon capsule endoscopy. The only tests for which a reduction in CRC mortality compared to no screening have been proven in randomized trials are FOBT and sigmoidoscopy. Several trials suggest that FIT are superior to FOBT in terms of detection rates of cancers and advanced adenomas and possibly compliance. There is indirect evidence suggesting efficacy of colonoscopy as a screening test. The role of CT-C is controversial. There is data suggesting a good sensitivity for neoplasia >9 mm with a lower sensitivity for smaller neoplasia. However, radiation exposure is considered a major limitation in some countries. Unresolved questions include the lesion cut-off for referral to colonoscopy and work-up of extracolonic findings. For other methods, like genetic stool testing using newer markers, blood tests, capsule endoscopy and M2-PK, there is currently insufficient data on screening of the asymptomatic population. Key Messages: Colorectal screening is recommended and should be performed in the form of an organized programme. If detection of early-stage cancers is the aim of a screening programme, FIT seem to be superior to FOBT. If detection and removal of adenomas is the aim of a screening programme, endoscopic methods seem to be good alternatives. Sigmoidoscopy is easier to perform but will likely only

Family history of gastric cancer is associated with the risk of colorectal neoplasia in Korean population.

PubMed

Jung, Yoon Suk; Kim, Nam Hee; Yang, Hyo-Joon; Park, Soo-Kyung; Park, Jung Ho; Park, Dong Il; Sohn, Chong Il

2017-10-01

Family history of cancers at different sites except for colorectum has not been evaluated as a risk factor for colorectal neoplasia (CRN). To investigate CRN risk according to family history of cancers at 12 different sites, including stomach and colorectum. A cross-sectional study was performed on 139,497 asymptomatic Koreans who underwent colonoscopy as part of a health check-up. The mean age of the study population was 41.6 and the prevalence of CRN was 16.3%. Multivariate analyses revealed that family histories of CRC (adjusted odds ratio; confidence interval, 1.26; 1.17-1.35) and gastric cancer (1.07; 1.01-1.13) were independent risk factors for CRN. Notably, the risk of CRN increased even more for participants with family histories of both CRC and gastric cancer (1.38; 1.12-1.70). Family history of CRC was associated with risk of CRN in participants aged both <50 and ≥50 years, whereas family history of gastric cancer was associated with risk of CRN in participants aged <50 years (1.22; 1.14-1.30), but not in participants aged ≥50 years (1.08; 0.99-1.18). Family history of gastric cancer was an independent risk factor for CRN, especially in those aged <50years. Persons with family histories of gastric cancer and CRC, especially those with family histories of both, may need to begin colonoscopy earlier. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Advances in immunotherapeutic strategies for colorectal cancer commentary on: tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients by Halama et al.

PubMed

Deming, Dustin A

2016-01-01

Colorectal cancer is a leading cause of cancer-related death in the United States, despite recent advances in treatment strategies. The immune system has been implicated in the pathogenesis of colorectal cancer, with numerous studies identifying either antagonistic or pro-tumorigenic effects of infiltrating immune cells. Therapeutic strategies harnessing the immune system to target cancers have evolved expediently over the last 5 years, especially the use of checkpoint inhibitors. Recently, a subset of patients whose colorectal cancers harbor a deficiency in mismatch repair proteins have demonstrated dramatic and durable response to checkpoint blockade. Unfortunately, the vast majority of colorectal cancers are mismatch repair proficient and resistant to these inhibitors. The tumor microenvironment has been implicated in the resistance to checkpoint block and ways to overcome these resistance mechanisms would be a major advance for the treatment of colorectal cancer. Here we provide commentary on a manuscript from Halama et al. examining CCL5/CCR5 as an immune biomarker and the potential role of anti-CCR5 agents for the treatment of patients with colorectal cancer.

Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection

PubMed Central

Wang, Yu; Chen, Pei-Min; Liu, Rong-Bin

2018-01-01

This review article summarizes the research advances of the plasma-based SEPT9 gene methylation assay for the clinical detection of colorectal cancer and its limitations. Colorectal cancer is a common malignancy with a poor prognosis and a high mortality, for which early detection and diagnosis are particularly crucial for the high-risk groups. Increasing evidence supported that SEPT9 gene methylation is associated with the pathogenesis of colorectal cancer and that detecting the level of methylation of SEPT9 in the peripheral blood can be used for screening of colorectal cancer in susceptible populations. In recent years, the data obtained in clinical studies demonstrated that the SEPT9 gene methylation assay has a good diagnostic performance with regard to both sensitivity and specificity with the advantage of better acceptability, convenience and compliance with serological testing compared with fecal occult blood tests and carcinoembryonic antigen for colorectal cancer (CRC). Furthermore, the combination of multiple methods or markers has become a growing trend for CRC detection and screening. Nevertheless, the clinical availability of the methylated SEPT9 assay is still limited because of the large degree of sample heterogeneity caused by demographic characteristics, pathological features, comorbidities and/or technique selection. Another factor is the cost-effectiveness of colorectal cancer screening strategies that hinders its large-scale application. In addition, improvements in its accuracy in detecting adenomas and premalignant polyps are required. PMID:29375744

Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

PubMed Central

Jaszewski, Richard; Misra, Sabeena; Tobi, Martin; Ullah, Nadeem; Naumoff, Jo Ann; Kucuk, Omer; Levi, Edi; Axelrod, Bradley N; Patel, Bhaumik B; Majumdar, Adhip PN

2008-01-01

AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia. PMID:18680228

Double-modulation of 5-Fluorouracil by methotrexate and leucovorin in advanced colorectal-carcinoma.

PubMed

Leone, B; Romero, A; Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Paris, A; Lacava, J

1993-11-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) as first line chemotherapy in advanced colorectal carcinoma. Between January 1990, and April 1992, 42 patients with metastatic or advanced recurrent (inoperable) colorectal cancer were entered into the study. Therapy consisted of a sequential combination of MTX, LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 minutes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 over 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeated every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective regression (OR) was observed in 14 of 38 patients (37%, 95% confidence interval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was observed. Double modulation of 5-FU with MTX and low dose of LV is an active regimen against advanced colorectal carcinoma and represents a promising strategy that should be further explored.

Malignant Neoplasia of the Sex Skin in 2 Chimpanzees (Pan troglodytes).

PubMed

Beck, Amanda P; Magden, Elizabeth R; Buchl, Stephanie J; Baze, Wallace B

2016-04-01

This report describes 2 cases of spontaneous malignant neoplasia within the sex skin of aged female chimpanzees. In both cases, the initial presentation resembled nonhealing traumatic wounds to the sex skin, with different degrees of infection, ulceration, and tissue necrosis. Histopathology of the lesions confirmed the diagnosis of squamous cell carcinoma in one case and of adenocarcinoma with metastasis in the other. Advanced age and previous trauma likely contributed to the development of the neoplasias in both cases; long-term sun exposure may also have contributed to the development of the squamous cell carcinoma. To our knowledge, these 2 cases represent the first reports of sex skin neoplasia in chimpanzees.

Aspirin for the prevention of colorectal cancer

PubMed Central

Garcia-Albeniz, X.; Chan, A.T.

2011-01-01

Over 600,000 people worldwide die of colorectal cancer (CRC) annually, highlighting the importance of developing effective prevention strategies. Among proposed chemopreventive interventions, aspirin is perhaps the agent with the strongest body of evidence that supports wider spread use to significantly reduce the population burden of CRC. Several epidemiological studies, four randomized controlled trials (RCTs) of colorectal polyp recurrence, and RCTs in patients with hereditary colorectal cancer syndromes, have shown that aspirin reduces incidence of colorectal neoplasia. Recently, in a pooled analysis of five cardiovascular-prevention RCTs linked to cancer outcomes, daily aspirin use at any dose reduced the risk of CRC by 24% and of CRC-associated mortality by 35% after a delay of 8–10 years. In an expanded meta-analysis of 8 cardiovascular-prevention RCTs, daily aspirin use at any dose was associated with a 21% lower risk of all cancer death, including CRC, with benefit only apparent after 5 years. In this review, we will summarize human studies of aspirin in CRC prevention as well as discuss the safety profile and mechanism of aspirin in CRC prevention. PMID:22122763

Increased risk of advanced neoplasms among asymptomatic siblings of patients with colorectal cancer.

PubMed

Ng, Siew C; Lau, James Y W; Chan, Francis K L; Suen, Bing Yee; Leung, Wai-Keung; Tse, Yee Kit; Ng, Simon S M; Lee, Janet F Y; To, Ka-Fai; Wu, Justin C Y; Sung, Joseph J Y

2013-03-01

Colorectal cancer (CRC) is the second-most common cancer in Hong Kong. Relatives of patients with CRC have an increased risk of colorectal neoplasm. We assessed the prevalence of advanced neoplasms among asymptomatic siblings of patients with CRC. Patients with CRC were identified from the Prince of Wales Hospital CRC Surgery Registry from 2001 to 2011. Colonoscopies were performed for 374 siblings of patients (age, 52.6 ± 7.4 y) and 374 age- and sex-matched siblings of healthy subjects who had normal colonoscopies and did not have a family history of CRC (controls, 52.7 ± 7.4 y). We identified individuals with advanced neoplasms (defined as cancers or adenomas of at least 10 mm in diameter, high-grade dysplasia, with villous or tubulovillous characteristics). The prevalence of advanced neoplasms was 7.5% among siblings of patients and 2.9% among controls (matched odds ratio [mOR], 3.07; 95% confidence interval [CI], 1.5-6.3; P = .002). The prevalence of adenomas larger than 10 mm was higher among siblings of patients than in controls (5.9% vs 2.1%; mOR, 3.34; 95% CI, 1.45-7.66; P = .004), as was the presence of colorectal adenomas (31.0% vs 18.2%; mOR, 2.19; 95% CI, 1.52-3.17; P < .001). Six cancers were detected among siblings of patients; no cancers were detected in controls. The prevalence of advanced neoplasms among siblings of patients was higher when their index case was female (mOR, 4.95; 95% CI, 1.81-13.55) and had distally located CRC (mOR, 3.10; 95% CI, 1.34-7.14). In Hong Kong, siblings of patients with CRC have a higher prevalence of advanced neoplasms, including CRC, than siblings of healthy individuals. Screening is indicated in this high-risk population. ClinicalTrials.gov number: NCT00164944. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Use of DNA from human stools to detect aberrant CpG island methylation of genes implicated in colorectal cancer.

PubMed

Belshaw, Nigel J; Elliott, Giles O; Williams, Elizabeth A; Bradburn, David M; Mills, Sarah J; Mathers, John C; Johnson, Ian T

2004-09-01

Hypermethylation of cytosine residues in the CpG islands of tumor suppressor genes is a key mechanism of colorectal carcinogenesis. Detection and quantification of CpG island methylation in human DNA isolated from stools might provide a novel strategy for the detection and investigation of colorectal neoplasia. To explore the feasibility of this approach, colorectal biopsies and fecal samples were obtained from 32 patients attending for colonoscopy or surgery, who were found to have adenomatous polyps, colorectal cancer, or no evidence of neoplasia. A further 18 fecal samples were obtained from healthy volunteers, with no bowel symptoms. Isolated DNA was modified with sodium bisulfite and analyzed by methylation-specific PCR and combined bisulfite restriction analysis for CpG island methylation of ESR1, MGMT, HPP1, p16(INK4a), APC, and MLH1. CpG island methylation was readily detectable in both mucosal and fecal DNA with methylation-specific PCR. Using combined bisulfite restriction analysis, it was established that, in volunteers from whom biopsies were available, the levels of methylation at two CpG sites within ESR1 assayed using fecal DNA were significantly correlated with methylation in DNA from colorectal mucosa. Thus, noninvasive techniques can be used to obtain quantitative information about the level of CpG island methylation in human colorectal mucosa. The methods described here could be applied to a much expanded range of genes and may be valuable both for screening purposes and to provide greater insight into the functional consequences of epigenetic changes in the colorectal mucosa of free-living individuals.

Synchronous fluorescence spectroscopy of colon neoplasia

NASA Astrophysics Data System (ADS)

Borisova, Ekaterina; Semyachkina-Glushkovskaya, Oxana; Genova, Tsanislava; Penkov, Nikolay; Terziev, Ivan; Vladimirov, Borislav; Avramov, Latchezar

2017-03-01

Synchronous fluorescence spectroscopy (SFS) is a steady-state approach that we used for evaluation of specific fluorescence characteristics of cancerous colorectal tissues. SFS allow narrowing of the fluorescence spectra received, which increase the spectral resolution and improve the analysis of the fluorescence origin in such complex objects, such as biological tissues. In our study we investigate the characteristic differences, with diagnostic meaning, in the synchronous fluorescence spectra (SFS) of cancerous and healthy colorectal tissues ex vivo using a spectrofluorimeter FluoroLog3 (HORIBA, JobinYvon, France) for obtaining of the SFS data in a broad spectral range (300-800 nm) using excitation in the range of 280-440 nm with a delta lambda between 0 and 200 nm with a 10 nm step between scanning excitation and emission data. The procedure of obtaining the investigated samples ex vivo includes their excision during surgery for removal of neoplasia lesions. After the surgical removal biological samples are transported in isothermal conditions and safekeeping solution from the hospital to the spectral laboratory, where their spectral properties were investigated. All patients received and signed written informed consent and this research is approved by Ethics committee of University Hospital "Tsaritsa Yoanna", Sofia. Histological analysis was used as "gold standard" for evaluation of tissue samples and comparison of the spectral data received.

Single-incision laparoscopic surgery for locally advanced colorectal cancer : feasibility, short-term and oncologic outcomes.

PubMed

Famiglietti, F; Leonard, D; Bachmann, R; Remue, C; Abbes Orabi, N; van Maanen, A; van den Eynde, M; Kartheuser, A

2018-01-01

Data about single-incision laparoscopic surgery (SILS) in locally advanced colorectal cancers are scarce. This study aimed to evaluate perioperative and shortterm oncologic outcomes of SILS in pT3-T4 colorectal cancer. From 2011 to 2015 data from 249 SILS performed in our Colorectal Unit were entered into a prospective database. Data regarding patients with a pT3-T4 colorectal adenocarcinoma were compared to those with pTis-pT2. Factors influencing conversion were assessed by multivariate analysis. There were 100 consecutive patients (T3-T4 = 70, Tis-T2 = 30). Demographics were similar. Tumor size was significantly larger in the T3-T4 group [3.9cm vs 2cm; p<0.001]. In T3-T4 patients we found a significant higher number of lymph nodes harvested [20 vs 13 ; p<0.001]. Early (<30 days) severe (Clavien-Dindo classification>2) postoperative complication rate was similar between groups (8.6% vs 10% ; p = 0.999), as well as conversion rate (18.6% vs 6.7% ; p = 0.220). Finally, there were no differences in terms of hospital stay and mortality rate. On multivariate analysis, age (OR = 1.06, 95%CI: 1.012-1.113 ; p = 0.015] and stage IV (OR = 5.372, 95%CI: 1.320-21.862, p = 0.019) were independently associated with conversion. SILS for locally advanced colorectal cancer did not affect the short-term outcomes in this series and oncological clearance remained satisfactory. Age and stage IV disease are independent risk factors for conversion. © Acta Gastro-Enterologica Belgica.

Epigenetics and Colorectal Cancer

PubMed Central

Lao, Victoria Valinluck; Grady, William M.

2012-01-01

Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and Meta-analysis.

PubMed

OʼConnor, Anthony; Packey, Christopher D; Akbari, Mona; Moss, Alan C

2015-11-01

In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined. We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies. Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3), regardless of study setting. Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.

Recommendations on rectal surveillance for colorectal cancer after subtotal colectomy in patients with inflammatory bowel disease.

PubMed

Derikx, Lauranne A A P; de Jong, Michiel E; Hoentjen, Frank

2018-05-17

Approximately 30% of patients with ulcerative colitis require a colectomy during their disease course. This substantially reduces colorectal cancer risk, although it is still possible to develop colorectal neoplasia in the remaining rectum. Although clear and well-accepted surveillance guidelines exist for patients with inflammatory bowel disease with an intact colon, specific surveillance recommendations following colectomy are less clear. Here, we aim to summarize the prevalence, incidence, and risk factors for developing colorectal cancer in patients with inflammatory bowel disease who underwent subtotal colectomy with a permanent end ileostomy and rectal stump, or with ileorectal anastomosis. Subsequently, gained insights are integrated into a proposed endoscopic surveillance strategy of the residual rectum.

Familial colorectal cancer.

PubMed

Lung, M S; Trainer, A H; Campbell, I; Lipton, L

2015-05-01

Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up. © 2015 Royal Australasian College of Physicians.

Colorectal adenoma stem-like cell populations: associations with adenoma characteristics and metachronous colorectal neoplasia.

PubMed

Bartley, Angela N; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J; Buckmeier, Julie A; Corley, Lynda; Phipps, Ron A; Gallick, Gary; Lance, Peter; Thompson, Patricia A; Hamilton, Stanley R

2013-11-01

Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma ("recurrence"), has not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1-labeling indices (ALI) were similar across patient characteristics and in advanced and nonadvanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (P = 0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (P = 0.03). A best-fit algorithm-based cutoff point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem cell target for chemoprevention. ©2013 AACR

Inflammation and colorectal cancer: colitis-associated neoplasia

PubMed Central

Grivennikov, Sergei I.

2013-01-01

Connection between inflammation and cancer is a rapidly developing field. Epidemiological data suggests that inflammation along with distinct arms of host immune system plays a very important role in development and progression of many different cancers. Inflammatory bowel diseases (IBD) is an important risk factor for the development of colon cancer, namely colitis-associated cancer (CAC). The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and may differ between CAC and other forms of colorectal cancer. Recent work has shed light on the role of distinct immune cells, cytokines and other immune mediators in virtually all of the steps of colonic tumorigenesis, including tumor initiation and promotion as well as progression and metastasis. The close proximity of colonic tumors to the myriad of intestinal microbes, as well as instrumental role of microbiota in IBD, introduces microbes as new players capable of triggering inflammation and possibly promoting tumorigenesis. Various mechanisms of CAC tumorigenesis as well as new possible hints for the future approaches for prevention and therapy are discussed in this review. PMID:23161445

CpG island methylator phenotype in colorectal cancer

PubMed Central

Toyota, Minoru; Ahuja, Nita; Ohe-Toyota, Mutsumi; Herman, James G.; Baylin, Stephen B.; Issa, Jean-Pierre J.

1999-01-01

Aberrant methylation of promoter region CpG islands is associated with transcriptional inactivation of tumor-suppressor genes in neoplasia. To understand global patterns of CpG island methylation in colorectal cancer, we have used a recently developed technique called methylated CpG island amplification to examine 30 newly cloned differentially methylated DNA sequences. Of these 30 clones, 19 (63%) were progressively methylated in an age-dependent manner in normal colon, 7 (23%) were methylated in a cancer-specific manner, and 4 (13%) were methylated only in cell lines. Thus, a majority of CpG islands methylated in colon cancer are also methylated in a subset of normal colonic cells during the process of aging. In contrast, methylation of the cancer-specific clones was found exclusively in a subset of colorectal cancers, which appear to display a CpG island methylator phenotype (CIMP). CIMP+ tumors also have a high incidence of p16 and THBS1 methylation, and they include the majority of sporadic colorectal cancers with microsatellite instability related to hMLH1 methylation. We thus define a pathway in colorectal cancer that appears to be responsible for the majority of sporadic tumors with mismatch repair deficiency. PMID:10411935

Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

ClinicalTrials.gov

2018-03-23

Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Piecemeal Versus En Bloc Resection of Large Rectal Adenomas

ClinicalTrials.gov

2018-06-04

Colorectal Adenoma With Mild Dysplasia; Colorectal Adenoma With Severe Dysplasia; Colorectal Adenomatous Polyp; Colorectal Low Grade Intraepithelial Neoplasia; Colorectal High Grade Intraepithelial Neoplasia

Identification of a region of frequent loss of heterozygosity at 11q24 in colorectal cancer.

PubMed

Connolly, K C; Gabra, H; Millwater, C J; Taylor, K J; Rabiasz, G J; Watson, J E; Smyth, J F; Wyllie, A H; Jodrell, D I

1999-06-15

Loss of heterozygosity (LOH) at 11q23-qter occurs frequently in ovarian and other cancers, but for colorectal cancer, the evidence is conflicting. Seven polymorphic loci were analyzed between D11S897 and D11S969 in 50 colorectal tumors. Two distinct LOH regions were detected, suggesting possible sites for tumor-suppressor genes involved in colorectal neoplasia: a large centromeric region between D11S897 and D11S925, and a telomeric 4.9-Mb region between D11S912 and D11S969. There was no correlation with clinicopathological features. This analysis describes a region of LOH in the region 11q23.3-24.3 for the first time in colorectal cancer and provides complementary evidence for the ongoing effort to identify the gene(s) involved.

DNA methylation of phosphatase and actin regulator 3 detects colorectal cancer in stool and complements FIT.

PubMed

Bosch, Linda J W; Oort, Frank A; Neerincx, Maarten; Khalid-de Bakker, Carolina A J; Terhaar sive Droste, Jochim S; Melotte, Veerle; Jonkers, Daisy M A E; Masclee, Ad A M; Mongera, Sandra; Grooteclaes, Madeleine; Louwagie, Joost; van Criekinge, Wim; Coupé, Veerle M H; Mulder, Chris J; van Engeland, Manon; Carvalho, Beatriz; Meijer, Gerrit A

2012-03-01

Using a bioinformatics-based strategy, we set out to identify hypermethylated genes that could serve as biomarkers for early detection of colorectal cancer (CRC) in stool. In addition, the complementary value to a Fecal Immunochemical Test (FIT) was evaluated. Candidate genes were selected by applying cluster alignment and computational analysis of promoter regions to microarray-expression data of colorectal adenomas and carcinomas. DNA methylation was measured by quantitative methylation-specific PCR on 34 normal colon mucosa, 71 advanced adenoma, and 64 CRC tissues. The performance as biomarker was tested in whole stool samples from in total 193 subjects, including 19 with advanced adenoma and 66 with CRC. For a large proportion of these series, methylation data for GATA4 and OSMR were available for comparison. The complementary value to FIT was measured in stool subsamples from 92 subjects including 44 with advanced adenoma or CRC. Phosphatase and Actin Regulator 3 (PHACTR3) was identified as a novel hypermethylated gene showing more than 70-fold increased DNA methylation levels in advanced neoplasia compared with normal colon mucosa. In a stool training set, PHACTR3 methylation showed a sensitivity of 55% (95% CI: 33-75) for CRC and a specificity of 95% (95% CI: 87-98). In a stool validation set, sensitivity reached 66% (95% CI: 50-79) for CRC and 32% (95% CI: 14-57) for advanced adenomas at a specificity of 100% (95% CI: 86-100). Adding PHACTR3 methylation to FIT increased sensitivity for CRC up to 15%. PHACTR3 is a new hypermethylated gene in CRC with a good performance in stool DNA testing and has complementary value to FIT.

Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex?

PubMed

Arana-Arri, Eunate; Idigoras, Isabel; Uranga, Begoña; Pérez, Raquel; Irurzun, Ana; Gutiérrez-Ibarluzea, Iñaki; Fraser, Callum G; Portillo, Isabel

2017-08-29

The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion. Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50-69 years. A result was considered positive at ≥20 μg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs. We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women). This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting

Clonal evolution of colorectal cancer in IBD.

PubMed

Choi, Chang-Ho R; Bakir, Ibrahim Al; Hart, Ailsa L; Graham, Trevor A

2017-04-01

Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.

Clinical application of a multi-modal endoscope with fluorescent peptide in detection of colorectal neoplasia (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dai, Zhenzhen; Joshi, Bishnu P.; Gao, Zhenghong; Lee, Jeonghoon; Ghimire, Navin; Prabhu, Anoop; Wamsteker, Erik J.; Kwon, Richard S.; Elta, Grace H.; Appelman, Henry D.; Owens, Scott R.; Kuick, Rork; Turgeon, Kim K.; Wang, Thomas D.

2017-02-01

Early detection of precursor lesions for colorectal cancer can greatly improve survival. Pre-neoplasia can appear flat with conventional white light endoscopy. Sessile serrated adenomas (SSA) are precursor lesions found primarily in the proximal colon and frequently appear flat and indistinct. We performed a clinical study of n=37 patients using a multimodal endoscopy with a FITC-labeled peptide specific for SSA. Lesions were imaged with white light, reflectance and fluorescence. White light images were acquired before the peptide was applied and were used to help localize regions of abnormal tissues rightly. Co-registered fluorescence and reflectance images were combined to get ratio images thus the distance was corrected. We calculated the target/background ratio (T/B ratio) to quantify the images and found 2.3-fold greater fluorescence intensity for SSA compared with normal tissues. We found the T/B ratio for SSA to be significantly greater than that for normal colonic mucosa with 89.47% sensitivity and 91.67% specificity at the threshold of 1.22. An ROC curve for SSA and normal mucosa was also plotted with area under curve (AUC) of 0.93. The result also shows that SSA and adenoma are statistically significant and can be identified with 78.95% sensitivity and 90.48% specificity at the threshold of 1.66. An ROC curve was plotted with AUC of 0.88. Therefore, our result shows that the application of a multimodal endoscope with fluorescently labeled peptide can quantify images and works especially good for the detection of SSA which is a premalignant flat lesion conferring a high risk of subsequently leading to a colon cancer.

Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages.

PubMed

Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

2014-12-28

To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.

Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages

PubMed Central

Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

2014-01-01

AIM: To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. METHODS: Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. RESULTS: The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. CONCLUSION: High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC. PMID:25561807

Molecular Triage Trials in Colorectal Cancer.

PubMed

O'Hara, Mark H; Hamilton, Stanley R; O'Dwyer, Peter J

2016-01-01

Advances in the understanding of genomic alterations in cancer, and the various therapies targeted to these alterations have permitted the design of trials directed to bringing this science to the clinic, with the ultimate goal of tailoring therapy to the individual. There is a high need for advances in targeted therapy in colorectal cancer, a disease in which only 2 classes of targeted therapies are approved for use in colorectal cancer, despite the majority of colorectal cancers containing a potentially targetable mutation. Here we outline the key elements to the design of these clinical trials and summarize the current active molecular triage trials in colorectal cancer.

Evaluation of the Effectiveness and Cost-Effectiveness of Personalized Surveillance After Colorectal Adenomatous Polypectomy.

PubMed

McFerran, Ethna; O'Mahony, James F; Fallis, Richard; McVicar, Duncan; Zauber, Ann G; Kee, Frank

2017-01-01

Lifetime risk of developing colorectal cancer is 5%, and 5-year survival at early stage is 92%. Individuals with precancerous lesions removed at primary screening are typically recommended surveillance colonoscopy. Because greater benefits are anticipated for those with higher risk of colorectal cancer, scope for risk-specific surveillance recommendations exists. This review assesses published cost-effectiveness estimates of postpolypectomy surveillance to consider the potential for personalized recommendations by risk group. Meta-analyses of incidence of advanced neoplasia postpolypectomy for low-risk cases were comparable to those without adenoma, with both rates under the lifetime risk of 5%. This group may not benefit from intensive surveillance, which risks unnecessary harm and inefficient use of often scarce colonoscopy capacity. Therefore, greater personalization through deintensified strategies for low-risk individuals could be beneficial. The potential for noninvasive testing, such as fecal immunochemical tests, combined with primary prevention or chemoprevention may reserve colonoscopy for targeted use in personalized risk-stratified surveillance. This review appraised evidence supporting a program of personalized surveillance in patients with colorectal adenoma according to risk group and compared the effectiveness of surveillance colonoscopy with alternative prevention strategies. It assessed trade-offs among costs, benefits, and adverse effects that must be considered in a decision to adopt or reject personalized surveillance. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diffuse reflectance spectroscopy as a tool for real-time tissue assessment during colorectal cancer surgery

NASA Astrophysics Data System (ADS)

Baltussen, Elisabeth J. M.; Snaebjornsson, Petur; de Koning, Susan G. Brouwer; Sterenborg, Henricus J. C. M.; Aalbers, Arend G. J.; Kok, Niels; Beets, Geerard L.; Hendriks, Benno H. W.; Kuhlmann, Koert F. D.; Ruers, Theo J. M.

2017-10-01

Colorectal surgery is the standard treatment for patients with colorectal cancer. To overcome two of the main challenges, the circumferential resection margin and postoperative complications, real-time tissue assessment could be of great benefit during surgery. In this ex vivo study, diffuse reflectance spectroscopy (DRS) was used to differentiate tumor tissue from healthy surrounding tissues in patients with colorectal neoplasia. DRS spectra were obtained from tumor tissue, healthy colon, or rectal wall and fat tissue, for every patient. Data were randomly divided into training (80%) and test (20%) sets. After spectral band selection, the spectra were classified using a quadratic classifier and a linear support vector machine. Of the 38 included patients, 36 had colorectal cancer and 2 had an adenoma. When the classifiers were applied to the test set, colorectal cancer could be discriminated from healthy tissue with an overall accuracy of 0.95 (±0.03). This study demonstrates the possibility to separate colorectal cancer from healthy surrounding tissue by applying DRS. High classification accuracies were obtained both in homogeneous and inhomogeneous tissues. This is a fundamental step toward the development of a tool for real-time in vivo tissue assessment during colorectal surgery.

Surrogate endpoints for overall survival in advanced colorectal cancer: a clinician's perspective.

PubMed

Piedbois, Pascal; Miller Croswell, Jennifer

2008-10-01

Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound. Even agreeing upon a definition of a "valid" surrogate endpoint has not been a straightforward exercise; this article begins by highlighting differences in how this term has been previously captured and applied, as well as laying out the basic criteria essential for its application in advanced colorectal cancer. Ideally, these elements include (but are not limited to) ease of measurement, rapid indication of treatment effect, and, most importantly, reliable and consistent prediction of the true impact of a treatment on the ultimate outcome of interest: overall survival. The strengths and weaknesses of current potential surrogate endpoints in advanced colorectal cancer, including performance status, carcinoembryonic antigen plasma level, overall response rate, time to progression, and disease-free survival, are each considered in turn. Finally, limitations of surrogate endpoints in the clinical setting, including challenges in extrapolation to new therapies, and the incomplete provision of information about potential adverse effects, are discussed. Work remains to be done between physicians and statisticians to bridge the gap between that which is statistically demonstrable and that which will be clinically useful.The term ;surrogate endpoint' was virtually unknown by most oncologists 15 years ago. A search in PubMed [http://www.ncbi.nlm.nih.gov] based on the words ;surrogate and cancer' shows that more than 2000 papers were published in medical journals in the last 20 years, with a dramatic increase of interest in the last five years. Interestingly, the same trend is observed when the words ;surrogate and heart' are entered into PubMed, suggesting that the

Molecular markers of carcinogenesis for risk stratification of individuals with colorectal polyps: a case-control study.

PubMed

Gupta, Samir; Sun, Han; Yi, Sang; Storm, Joy; Xiao, Guanghua; Balasubramanian, Bijal A; Zhang, Song; Ashfaq, Raheela; Rockey, Don C

2014-10-01

Risk stratification using number, size, and histology of colorectal adenomas is currently suboptimal for identifying patients at increased risk for future colorectal cancer. We hypothesized that molecular markers of carcinogenesis in adenomas, measured via immunohistochemistry, may help identify high-risk patients. To test this hypothesis, we conducted a retrospective, 1:1 matched case-control study (n = 216; 46% female) in which cases were patients with colorectal cancer and synchronous adenoma and controls were patients with adenoma but no colorectal cancer at baseline or within 5 years of follow-up. In phase I of analyses, we compared expression of molecular markers of carcinogenesis in case and control adenomas, blind to case status. In phase II of analyses, patients were randomly divided into independent training and validation groups to develop a model for predicting case status. We found that seven markers [p53, p21, Cox-2, β-catenin (BCAT), DNA-dependent protein kinase (DNApkcs), survivin, and O6-methylguanine-DNA methyltransferase (MGMT)] were significantly associated with case status on unadjusted analyses, as well as analyses adjusted for age and advanced adenoma status (P < 0.01 for at least one marker component). When applied to the validation set, a predictive model using these seven markers showed substantial accuracy for identifying cases [area under the receiver operation characteristic curve (AUC), 0.83; 95% confidence interval (CI), 0.74-0.92]. A parsimonious model using three markers performed similarly to the seven-marker model (AUC, 0.84). In summary, we found that molecular markers of carcinogenesis distinguished adenomas from patients with and without colorectal cancer. Furthermore, we speculate that prospective studies using molecular markers to identify individuals with polyps at risk for future neoplasia are warranted. ©2014 American Association for Cancer Research.

Robotic Colorectal Surgery

PubMed Central

2008-01-01

Robotic colorectal surgery has gradually been performed more with the help of the technological advantages of the da Vinci® system. Advanced technological advantages of the da Vinci® system compared with standard laparoscopic colorectal surgery have been reported. These are a stable camera platform, three-dimensional imaging, excellent ergonomics, tremor elimination, ambidextrous capability, motion scaling, and instruments with multiple degrees of freedom. However, despite these technological advantages, most studies did not report the clinical advantages of robotic colorectal surgery compared to standard laparoscopic colorectal surgery. Only one study recently implies the real benefits of robotic rectal cancer surgery. The purpose of this review article is to outline the early concerns of robotic colorectal surgery using the da Vinci® system, to present early clinical outcomes from the most current series, and to discuss not only the safety and the feasibility but also the real benefits of robotic colorectal surgery. Moreover, this article will comment on the possible future clinical advantages and limitations of the da Vinci® system in robotic colorectal surgery. PMID:19108010

Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.

PubMed

Nakagawa, Tateo; Shimada, Mitsuo; Kurita, Nobuhiro; Iwata, Takashi; Nishioka, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Utsunomiya, Tohru

2012-06-01

The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.

Factors that influence treatment strategies in advanced colorectal cancer.

PubMed

Nesbitt, C; Glendinning, R J; Byrne, C; Poston, G J

2007-12-01

This review focuses on the factors that now influence our treatment strategies designed to increase the pool of patients with colorectal liver metastases for whom curative treatment may be possible. These strategies include improved preoperative staging techniques, new standards for surgical resection, novel surgical strategies, the application of modern systemic chemotherapy in a neoadjuvant setting, an emerging role for ablative therapies and an emphasis on the collaborative, a reappraisal of staging advanced disease, multidisciplinary management, and defining the role of the patient in managing their disease. It is now clear that an aggressive multi-disciplinary approach to the management of this problem will lead to nearly one third of these patients being considered for treatment that even if not achieving complete cure, offers significant long-term survival.

Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer.

PubMed

Rex, Douglas K; Boland, C Richard; Dominitz, Jason A; Giardiello, Francis M; Johnson, David A; Kaltenbach, Tonya; Levin, Theodore R; Lieberman, David; Robertson, Douglas J

2017-07-01

This document updates the colorectal cancer (CRC) screening recommendations of the U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy. CRC screening tests are ranked in 3 tiers based on performance features, costs, and practical considerations. The first-tier tests are colonoscopy every 10 years and annual fecal immunochemical test (FIT). Colonoscopy and FIT are recommended as the cornerstones of screening regardless of how screening is offered. Thus, in a sequential approach based on colonoscopy offered first, FIT should be offered to patients who decline colonoscopy. Colonoscopy and FIT are recommended as tests of choice when multiple options are presented as alternatives. A risk-stratified approach is also appropriate, with FIT screening in populations with an estimated low prevalence of advanced neoplasia and colonoscopy screening in high prevalence populations. The second-tier tests include CT colonography every 5 years, the FIT-fecal DNA test every 3 years, and flexible sigmoidoscopy every 5 to 10 years. These tests are appropriate screening tests, but each has disadvantages relative to the tier 1 tests. Because of limited evidence and current obstacles to use, capsule colonoscopy every 5 years is a third-tier test. We suggest that the Septin9 serum assay (Epigenomics, Seattle, Wash) not be used for screening. Screening should begin at age 50 years in average-risk persons, except in African Americans in whom limited evidence supports screening at 45 years. CRC incidence is rising in persons under age 50, and thorough diagnostic evaluation of young persons with suspected colorectal bleeding is recommended. Discontinuation of screening should be considered when persons up to date with screening, who have prior negative screening (particularly colonoscopy), reach age 75 or have <10 years of life

Colorectal Cancer Screening: Recommendations for Physicians and Patients From the U.S. Multi-Society Task Force on Colorectal Cancer.

PubMed

Rex, Douglas K; Boland, C Richard; Dominitz, Jason A; Giardiello, Francis M; Johnson, David A; Kaltenbach, Tonya; Levin, Theodore R; Lieberman, David; Robertson, Douglas J

2017-07-01

This document updates the colorectal cancer (CRC) screening recommendations of the U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy. CRC screening tests are ranked in 3 tiers based on performance features, costs, and practical considerations. The first-tier tests are colonoscopy every 10 years and annual fecal immunochemical test (FIT). Colonoscopy and FIT are recommended as the cornerstones of screening regardless of how screening is offered. Thus, in a sequential approach based on colonoscopy offered first, FIT should be offered to patients who decline colonoscopy. Colonoscopy and FIT are recommended as tests of choice when multiple options are presented as alternatives. A risk-stratified approach is also appropriate, with FIT screening in populations with an estimated low prevalence of advanced neoplasia and colonoscopy screening in high prevalence populations. The second-tier tests include CT colonography every 5 years, the FIT-fecal DNA test every 3 years, and flexible sigmoidoscopy every 5 to 10 years. These tests are appropriate screening tests, but each has disadvantages relative to the tier 1 tests. Because of limited evidence and current obstacles to use, capsule colonoscopy every 5 years is a third-tier test. We suggest that the Septin9 serum assay (Epigenomics, Seattle, Wash) not be used for screening. Screening should begin at age 50 years in average-risk persons, except in African Americans in whom limited evidence supports screening at 45 years. CRC incidence is rising in persons under age 50, and thorough diagnostic evaluation of young persons with suspected colorectal bleeding is recommended. Discontinuation of screening should be considered when persons up to date with screening, who have prior negative screening (particularly colonoscopy), reach age 75 or have <10 years of

Colorectal carcinogenesis: Review of human and experimental animal studies

PubMed Central

Tanaka, Takuji

2009-01-01

This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model) will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma). These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries. PMID:19332896

Layer-oriented total pelvic exenteration for locally advanced primary colorectal cancer.

PubMed

Koda, Keiji; Shuto, Kiyohiko; Matsuo, Kenichi; Kosugi, Chihiro; Mori, Mikito; Hirano, Atsushi; Hiroshima, Yukihiko; Tanaka, Kuniya

2016-01-01

The clinical outcomes of patients who have undergone total pelvic exenteration (TPE) for locally advanced primary colorectal cancer have not been satisfactory. For the last 13 years, we have performed layer-oriented, en bloc resection of tumor for which TPE is indicated, in the hope of improving postoperative outcomes. The clinical outcomes of these cases were retrospectively analyzed. A total of 54 patients who underwent TPE from 1986 to 2013 were retrospectively analyzed. Since 2002, a layer-oriented removal for clinical T4 colorectal cancer, as in T3 or less invasive tumors removed by total mesorectal excision, was applied to 23 cases for which TPE was indicated. Postoperative mortality, morbidity, overall survival (OS), and disease-free survival (DFS) were evaluated. On univariate analysis, good postoperative OS and DFS were associated with the layer-oriented operative maneuver, blood loss less than 2000 mL, negative nodal metastasis, and no preoperative radiation therapy. Male sex was the marginal determinant correlated with good OS and DFS. Depth of invasion to T3 was the marginal determinant correlated with good DFS. On multivariate analysis using the 4 factors identified on univariate analyses, the layer-oriented operative procedure was a significant determinant for both good OS and DFS, together with negative nodal metastases. Postoperative mortality and morbidity in the layer-oriented excision were acceptable. For primary colorectal cancers for which TPE is indicated, layer-oriented excision was a safe and effective procedure, and it may be recommended as one of the standard surgical approaches in TPE.

The potential usefulness of the Response Index in positron emission tomography assessing the therapeutic effect of pre-operative chemotherapy for advanced colorectal cancer.

PubMed

Nomura, Masatoshi; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Ikenaga, Masakazu; Yamamoto, Hirofumi; Murata, Kohei; Doki, Yuichiro; Mori, Masaki; Mizushima, Tsunekazu

2017-12-01

Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUV max ) in 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer. Retrospective cohort study from January 2011 to October 2015. We examined 28 patients with pathologically confirmed sigmoid or rectal cancer that underwent pre-operative chemotherapy and surgery. The correlation between Response Index (RI), calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy), and the therapeutic effect on the primary tumor in advanced colorectal cancer. The degree of differentiation (p = 0.04), SUV max in the primary tumor after chemotherapy (p = 0.02), and RI (p = 0.008) were significant predictors of the therapeutic effect in univariate analysis. The areas under the ROC curve constructed with RI and therapeutic effect was 0.77. The optimal cut-off values for the RI in the responder group was < 0.32. RI calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy) in the primary tumor significantly correlated with the therapeutic effect of chemotherapy on advanced colorectal cancer. Thus, RI is potentially useful for predicting the therapeutic effect in advanced colorectal cancer.

Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

PubMed Central

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-01-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

Preoperative carcinoembryonic antigen and prognosis of colorectal cancer. An independent prognostic factor still reliable.

PubMed

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-04-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

The association of Streptococcus bovis/gallolyticus with colorectal tumors: The nature and the underlying mechanisms of its etiological role

PubMed Central

2011-01-01

Streptococcus bovis (S. bovis) bacteria are associated with colorectal cancer and adenoma. S. bovis is currently named S. gallolyticus. 25 to 80% of patients with S. bovis/gallolyticus bacteremia have concomitant colorectal tumors. Colonic neoplasia may arise years after the presentation of bacteremia or infectious endocarditis of S. bovis/gallolyticus. The presence of S. bovis/gallolyticus bacteremia and/or endocarditis is also related to the presence of villous or tubular-villous adenomas in the large intestine. In addition, serological relationship of S. gallolyticus with colorectal tumors and direct colonization of S. gallolyticus in tissues of colorectal tumors were found. However, this association is still under controversy and has long been underestimated. Moreover, the etiological versus non-etiological nature of this associationis not settled yet. Therefore, by covering the most of up to date studies, this review attempts to clarify the nature and the core of S. bovis/gallolyicus association with colorectal tumors and analyze the possible underlying mechanisms. PMID:21247505

Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

PubMed Central

Sharma, Anjana; Panda, Anita

2007-01-01

Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

CT Colonographic Screening of Patients With a Family History of Colorectal Cancer: Comparison With Adults at Average Risk and Implications for Guidelines.

PubMed

Pickhardt, Perry J; Mbah, Ifeanyi; Pooler, B Dustin; Chen, Oliver T; Hinshaw, J Louis; Weiss, Jennifer M; Kim, David H

2017-04-01

The purposes of this study were to compare rates of lesion detection at CT colonographic (CTC) screening of adults without symptoms who had and who did not have a family history of colorectal cancer according to American Cancer Society guidelines and to consider the clinical implications. Over 134 months, consecutively registered CTC cohorts of adults without symptoms who had (n = 156; 88 [56.4%] women; 68 [43.6%] men; mean age, 56.3 years) and who did not have (n = 8857; 4757 [53.7%] women; 4100 [46.3%] men; mean age, 56.6 years) an American Cancer Society-defined family history of colorectal cancer (first-degree relative with diagnosis before age 60 years or two first-degree relatives with diagnosis at any age) were compared for relevant colorectal findings. For the family history versus no family history cohorts, the frequency of all nondiminutive polyps (≥ 6 mm) reported at CTC was 23.7% versus 15.5% (p = 0.007); small polyps (6-9 mm), 13.5% versus 9.1% (p = 0.068); and large polyps (≥ 10 mm), 10.2% versus 6.5% (p = 0.068). The rate of referral for colonoscopy was greater for the family history cohort (16.0% vs 10.5%; p = 0.035). However, the frequencies of proven advanced adenoma (4.5% vs 3.2%; p = 0.357), nonadvanced adenoma (5.1% vs 2.6%; p = 0.070), and cancer (0.0% vs 0.4%; p = 0.999) were not significantly increased. The difference in positive rates between the two cohorts (11.5% vs 4.3%; p < 0.001) was primarily due to nonneoplastic findings of no colorectal cancer relevance, such as small hyperplastic polyps, diverticular disease, and false-positive CTC findings. Although the overall CTC-positive and colonoscopy referral rates were higher in the family history cohort, the clinically relevant frequencies of advanced neoplasia and cancer were not sufficiently increased to preclude CTC screening. These findings support the use of CTC as a front-line screening option in adults with a family history of colorectal cancer.

Pathology of serrated colorectal lesions.

PubMed

Bateman, Adrian C

2014-10-01

The concept of serrated colorectal neoplasia has become recognised as a key process in the development of colorectal cancer (CRC) and an important alternative pathway to malignancy compared with the long established ‘adenoma-carcinoma’ sequence. Increasing recognition of the morphological spectrum of serrated lesions has occurred in parallel with elucidation of the distinct molecular genetic characteristics of progression from normal mucosa, via the ‘serrated pathway’, to CRC. Some of these lesions can be difficult to identify at colonoscopy. Challenges for pathologists include the requirement for accurate recognition of the forms of serrated lesions that are associated with a significant risk of malignant progression and therefore the need for widely disseminated reproducible criteria for their diagnosis. Alongside this process, pathologists and endoscopists need to formulate clear guidelines for the management of patients with these lesions, particularly with respect to the optimal follow-up intervals. This review provides practical guidance for the recognition of these lesions by pathologists, a discussion of ‘serrated adenocarcinoma’ and an insight into the distinct molecular genetic alterations that are seen in this spectrum of lesions in comparison to those that characterise the classic ‘adenoma-carcinoma’ sequence.

Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study.

PubMed

Amitay, Efrat L; Werner, Simone; Vital, Marius; Pieper, Dietmar H; Höfler, Daniela; Gierse, Indra-Jasmin; Butt, Julia; Balavarca, Yesilda; Cuk, Katarina; Brenner, Hermann

2017-08-01

Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role. In the current study, fecal samples were collected prior to bowel preparation from participants of screening colonoscopy in the German BliTz study. Using 16S rRNA gene analysis, we examined the presence and relative abundance of Fusobacterium in fecal samples from 500 participants, including 46, 113, 110 and 231 individuals with colorectal cancer, advanced adenomas, non-advanced adenomas and without any neoplasms, respectively. We found that the abundance of Fusobacterium in feces was strongly associated with the presence of colorectal cancer (P-value < 0.0001). This was confirmed by PCR at the species level for Fusobacterium nucleatum. However, no association was seen with the presence of advanced adenomas (P-value = 0.80) or non-advanced adenomas (P-value = 0.80), nor were there any associations observed with dietary or lifestyle habits. Although a causal role cannot be ruled out, our observations, based on fecal microbiome, support the hypothesis that Fusobacterium is a passenger that multiplies in the more favorable conditions caused by the malignant tumor rather than a causal factor in colorectal cancer development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Racial disparities in advanced stage colorectal cancer survival

PubMed Central

Wallace, Kristin; Hill, Elizabeth G.; Lewin, David N.; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E.; Wargovich, Michael J.; Berger, Franklin G.; Bolick, Susan W.; Thomas, Melanie B.; Alberg, Anthony J.

2013-01-01

Purpose African Americans (AA) have a higher incidence and lower survival from colorectal cancer (CRC) compared to European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry (SCCCR) is used to investigate the relationship between race and age on advanced stage CRC survival. Methods The study population was comprised of 3865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2673 (69%) EA and 1192 (31%) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95% confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% CI. Results We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (< 50 years), AA race was associated with a 1.34 (95% CI 1.06-1.71) higher risk of death compared to EA. Among older patients, we observed a modest increase risk of death among AA men compared to EA (HR 1.16 (95% CI 1.01-1.32) but no difference by race among women (HR 0.94 (95% CI 0.82-1.08)). Moreover, we observed that the disparity in survival has worsened over the past 15 years. Conclusions Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those < 50 years old. PMID:23296454

Association between folate levels and CpG island hypermethylation in normal colorectal mucosa

PubMed Central

Wallace, Kristin; Grau, Maria V.; Levine, Joan A.; Shen, Lanlan; Hamdan, Randala; Chen, Xinli; Gui, Jiang; Haile, Robert W.; Barry, Elizabeth L.; Ahnen, Dennis; McKeown-Eyssen, Gail; Baron, John A.; Issa, Jean Pierre J.

2010-01-01

Background Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association among blood folate levels, and dietary and lifestyle factors with CpG island methylation in normal colorectal mucosa. Methods Subjects were enrolled in a multi-center chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas. We collected 1000 biopsies from 389 patients, 501 samples from the right colon and 499 from the rectum at the follow-up colonoscopy. We measured DNA methylation of estrogen receptor alpha (ERα) and secreted frizzled related protein-1 (SFRP1) using bisulfite pyrosequencing. We used Generalized Estimating Equations regression analysis to examine the association between methylation and selected variables. Results For both ERα and SFRP1, percent methylation was significantly higher in the rectum compared to the right colon (p = 0.001). For each 10 years of age, we observed a 1.7 % increase in methylation level for ERα and a 2.9 % increase for SFRP1 (P < 0.0001). African Americans had a significantly lower level of ERα and SFRP1 methylation compared to Caucasians and Hispanics. Higher RBC folate levels were associated with higher levels of both ERα (p=0.03) and SFRP1 methylation (p=0.01). Conclusions Our results suggest that CpG island methylation in normal colorectal mucosa is related to advancing age, race, rectal location, and RBC folate levels. These data have important implications regarding the safety of supplementary folate administration in healthy adults given the hypothesis that methylation in normal mucosa may predispose to colorectal neoplasia. PMID:21149331

PTEN status in advanced colorectal cancer treated with cetuximab

PubMed Central

Negri, F V; Bozzetti, C; Lagrasta, C A; Crafa, P; Bonasoni, M P; Camisa, R; Pedrazzi, G; Ardizzoni, A

2009-01-01

Background: Loss of phosphatase and tensin homologue deleted in chromosome 10 (PTEN) function in advanced colorectal cancer (CRC) may represent one of the resistance mechanisms to cetuximab by interfering with the epidermal growth factor receptor signal transduction pathway. Methods: PTEN expression tested by indirect immunofluorescence was evaluated both on primary (n=43) and on metastatic (n=24) sites in CRC patients treated with cetuximab. Results: The loss of PTEN expression tested on metastatic sites was negatively associated with response (100% progressive disease (PD) in PTEN-negative cases vs 30% PD in PTEN-positive cases; P<0.05), PFS (0.8 vs 8.2 months; P<0.001) and OS (2.9 vs 14.2 months; P<0.001). Conclusion: A potential role of PTEN in the anti-tumour activity of cetuximab could be hypothesised. PMID:19953097

False-negative rate cannot be reduced by lowering the haemoglobin concentration cut-off in colorectal cancer screening using faecal immunochemical test.

PubMed

Ibañez-Sanz, Gemma; Garcia, Montse; Milà, Núria; Rodríguez-Moranta, Francisco; Binefa, Gemma; Gómez-Matas, Javier; Benito, Llúcia; Padrol, Isabel; Barenys, Mercè; Moreno, Victor

2017-09-01

The aim of this study was to analyse false-negative (FN) results of the faecal immunochemical test (FIT) and its determinants in a colorectal cancer screening programme in Catalonia. We carried out a cross-sectional study among 218 screenees with a negative FIT result who agreed to undergo a colonoscopy. A false-negative result was defined as the detection, at colonoscopy, of intermediate/high-risk polyps or colorectal cancer in a patient with a previous negative FIT (<20 µgHb/g). Multivariate logistic regression models were constructed to identify sociodemographic (sex, age) and screening variables (quantitative faecal haemoglobin, colonoscopy findings) related to FN results. Adjusted odds ratios and their 95% confidence intervals were estimated. There were 15.6% FN FIT results. Faecal haemoglobin was undetected in 45.5% of these results and was below 4 µgHb/g in 94.0% of the individuals with a FN result. About 60% of the lesions were located in the proximal colon, whereas the expected percentage was 30%. Decreasing the positivity threshold of FIT does not increase the detection rate of advanced neoplasia, but may increase the costs and potential adverse effects.

Risk assessment and clinical decision making for colorectal cancer screening.

PubMed

Schroy, Paul C; Caron, Sarah E; Sherman, Bonnie J; Heeren, Timothy C; Battaglia, Tracy A

2015-10-01

Shared decision making (SDM) related to test preference has been advocated as a potentially effective strategy for increasing adherence to colorectal cancer (CRC) screening, yet primary care providers (PCPs) are often reluctant to comply with patient preferences if they differ from their own. Risk stratification advanced colorectal neoplasia (ACN) provides a rational strategy for reconciling these differences. To assess the importance of risk stratification in PCP decision making related to test preference for average-risk patients and receptivity to use of an electronic risk assessment tool for ACN to facilitate SDM. Mixed methods, including qualitative key informant interviews and a cross-sectional survey. PCPs at an urban, academic safety-net institution. Screening preferences, factors influencing patient recommendations and receptivity to use of a risk stratification tool. Nine PCPs participated in interviews and 57 completed the survey. Despite an overwhelming preference for colonoscopy by 95% of respondents, patient risk (67%) and patient preferences (63%) were more influential in their decision making than patient comorbidities (31%; P < 0.001). Age was the single most influential risk factor (excluding family history), with <20% of respondents choosing factors other than age. Most respondents reported that they would be likely to use a risk stratification tool in their practice either 'often' (43%) or sometimes (53%). Risk stratification was perceived to be important in clinical decision making, yet few providers considered risk factors other than age for average-risk patients. Providers were receptive to the use of a risk assessment tool for ACN when recommending an appropriate screening test for select patients. © 2013 John Wiley & Sons Ltd.

Colorectal cancer risk in hamartomatous polyposis syndromes

PubMed Central

Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real

2015-01-01

Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as “hamartomatous polyposis syndromes”, “Peutz-Jeghers syndrome”, “juvenile polyposis syndrome”, “juvenile polyp”, and “PTEN hamartoma tumour syndrome” (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented. PMID:25848489

Primary care visit use after positive fecal immunochemical test for colorectal cancer screening.

PubMed

Hillyer, Grace Clarke; Jensen, Christopher D; Zhao, Wei K; Neugut, Alfred I; Lebwohl, Benjamin; Tiro, Jasmin A; Kushi, Lawrence H; Corley, Douglas A

2017-10-01

For some patients, positive cancer screening test results can be a stressful experience that can affect future screening compliance and increase the use of health care services unrelated to medically indicated follow-up. Among 483,216 individuals aged 50 to 75 years who completed a fecal immunochemical test to screen for colorectal cancer at a large integrated health care setting between 2007 and 2011, the authors evaluated whether a positive test was associated with a net change in outpatient primary care visit use within the year after screening. Multivariable regression models were used to evaluate the relationship between test result group and net changes in primary care visits after fecal immunochemical testing. In the year after the fecal immunochemical test, use increased by 0.60 clinic visits for patients with true-positive results. The absolute change in visits was largest (3.00) among individuals with positive test results who were diagnosed with colorectal cancer, but significant small increases also were found for patients treated with polypectomy and who had no neoplasia (0.36) and those with a normal examination and no polypectomy performed (0.17). Groups of patients who demonstrated an increase in net visit use compared with the true-negative group included patients with true-positive results (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.54-1.66), and positive groups with a colorectal cancer diagnosis (OR, 7.19; 95% CI, 6.12-8.44), polypectomy/no neoplasia (OR, 1.37; 95% CI, 1.27-1.48), and normal examination/no polypectomy (OR, 1.24; 95% CI, 1.18-1.30). Given the large size of outreach programs, these small changes can cumulatively generate thousands of excess visits and have a substantial impact on total health care use. Therefore, these changes should be included in colorectal cancer screening cost models and their causes investigated further. Cancer 2017;123:3744-3753. © 2017 American Cancer Society. © 2017 American Cancer Society.

A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia.

PubMed

Wu, Chung Wah; Evans, Jared M; Huang, Shengbing; Mahoney, Douglas W; Dukek, Brian A; Taylor, William R; Yab, Tracy C; Smyrk, Thomas C; Jen, Jin; Kisiel, John B; Ahlquist, David A

2018-05-25

MicroRNA (miRNA) profiling is an important step in studying biological associations and identifying marker candidates. miRNA exists in isoforms, called isomiRs, which may exhibit distinct properties. With conventional profiling methods, limitations in assay and analysis platforms may compromise isomiR interrogation. We introduce a comprehensive approach to sequence-oriented isomiR annotation (CASMIR) to allow unbiased identification of global isomiRs from small RNA sequencing data. In this approach, small RNA reads are maintained as independent sequences instead of being summarized under miRNA names. IsomiR features are identified through step-wise local alignment against canonical forms and precursor sequences. Through customizing the reference database, CASMIR is applicable to isomiR annotation across species. To demonstrate its application, we investigated isomiR profiles in normal and neoplastic human colorectal epithelia. We also ran miRDeep2, a popular miRNA analysis algorithm to validate isomiRs annotated by CASMIR. With CASMIR, specific and biologically relevant isomiR patterns could be identified. We note that specific isomiRs are often more abundant than their canonical forms. We identify isomiRs that are commonly up-regulated in both colorectal cancer and advanced adenoma, and illustrate advantages in targeting isomiRs as potential biomarkers over canonical forms. Studying miRNAs at the isomiR level could reveal new insight into miRNA biology and inform assay design for specific isomiRs. CASMIR facilitates comprehensive annotation of isomiR features in small RNA sequencing data for isomiR profiling and differential expression analysis.

Evaluation of risk factors for the recurrence of colorectal polyps and colorectal cancer

PubMed

Ateş, Öztürk; Sivri, Bülent; Kılıçkap, Saadettin

2017-11-13

Background/aim: Colorectal adenomatous polyps are precursors of colorectal cancer (CRC), which can be prevented with surveillance colonoscopy. This study aimed to assess risk factors for the recurrence of colorectal polyps and CRC following polypectomy. Materials and methods: In this single-center trial, a total of 510 patients who applied to the endoscopy unit of Hacettepe University Hospital for various reasons and who were diagnosed with at least one colorectal adenomatous polyp between 2000 and 2010 were retrospectively analyzed. Patients with colorectal adenomatous polyps or CRC recurrences were examined in terms of clinical and histological risk factors. Results: A total of 190 (37.1%) patients had surveillance colonoscopy. Among them, 127 (66.3%) were found to have polyp recurrence. Of the parameters defined for polyp recurrence, no association was found between the number of polyps (1-2, ≥3) (1-3, ≥4) in the first colonoscopy and diabetes mellitus, hypertension, hyperlipidemia, sex, family history of colon malignancy, smoking, alcohol usage, size of polyp (<10 mm, ≥10 mm), or advanced histologic type of polyp. The only significant difference was observed in patients who had left-sided colon polyps. In the basal colonoscopy, 130 patients had been diagnosed with CRC, and a significant correlation was found between the number of polyps (1, ≥2) and polyp size (≥10 mm), anemia, high sedimentation rate (>25), and CRC. In the first surveillance colonoscopy, CRC was detected in 12 patients. There was a significant correlation between the development of CRC and advanced histological type, anemia with high erythrocyte sedimentation rate, polyp size (<10 mm, ≥10 mm), and the number of polyps (<3, ≥3). Conclusion: Patients with left-sided colon polyps had a high risk of developing colorectal polyp recurrence. Moreover, the risk of developing CRC increased in patients who had advanced histology, a polyp larger than 10 mm, or more than three polyps.

Racial disparities in advanced-stage colorectal cancer survival.

PubMed

Wallace, Kristin; Hill, Elizabeth G; Lewin, David N; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E; Wargovich, Michael J; Berger, Franklin G; Bolick, Susan W; Thomas, Melanie B; Alberg, Anthony J

2013-03-01

African-Americans (AA) have a higher incidence of and lower survival from colorectal cancer (CRC) compared with European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry are used to investigate the relationship between race and age on advanced-stage CRC survival. The study population was comprised of 3,865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2,673 (69 %) EA and 1,192 (31 %) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95 % confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards regression models to generate hazard ratios (HR) and 95 % CI. We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (<50 years), AA race was associated with a 1.34 times (95 % CI 1.06-1.71) higher risk of death compared with EA. Among older patients, we observed a modest increase in risk of death among AA men compared with EA [HR 1.16 (95 % CI 1.01-1.32)] but no difference by race between women [HR 0.94 (95 % CI 0.82-1.08)]. Moreover, we observed that the disparity in survival has worsened over the past 15 years. Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those <50 years old.

High-frequency ultrasound probe sonography staging for colorectal neoplasia with superficial morphology: its utility and impact on patient management.

PubMed

Urban, Ondrej; Kliment, Martin; Fojtik, Petr; Falt, Premysl; Orhalmi, Julius; Vitek, Petr; Holeczy, Pavol

2011-10-01

This prospective study aimed to evaluate the impact of high-frequency ultrasound probe sonography (HFUPS) staging on the management of patients with superficial colorectal neoplasia (SCN) as determined by the endoscopic characteristics of lesions. Consecutive patients referred for endoscopic treatment of nonpedunculated SCN were enrolled in this study. A lesion was considered high risk if a depressed area or invasive pit pattern was present. The gold standard for final staging included histology from endoscopic or surgical resection. The impact on treatment was defined as any modification of the therapeutic algorithm based on the result of the HFUPS examination compared with that based on endoscopy alone. In this study, 48 lesions in 48 patients were evaluated. Of these, 28 (58%) were considered high risk, and the remaining 20 (42%) were regarded as low risk. A total of seven lesions (15%) that could not be examined with HFUPS and another non-neoplastic lesion were excluded from final analysis. For the remaining 40 lesions, the overall accuracy of the HFUPS examination to predict the correct T-stage was 90% (95% confidence interval [CI], 77-96%). The HFUPS examination had a positive impact on the treatment of 0 low-risk and 11 high-risk (42%) lesions. The impact of HFUPS on the treatment of SCN depends on their endoscopic characteristics. It is negligible for low-risk SCNs, and these lesions can be treated on the basis of their endoscopic appearance alone. Nevertheless, compared with endoscopy alone, HFUPS changed the subsequent therapeutic approach in a positive way for up to 42% of high-risk lesions, including those with a depressed component and an invasive pit pattern. These endoscopic features can therefore be recommended as the entry criteria for an HFUPS examination.

The role of surgery in the management of gestational trophoblastic neoplasia.

PubMed

Doll, Kemi M; Soper, John T

2013-07-01

Although sensitive human chorionic gonadotropin assays and advances in chemotherapy have assumed primary importance in the management of gestational trophoblastic neoplasia, surgery remains important in the overall care of these patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy decreases the risk of post-molar trophoblastic disease in appropriate patients and, when incorporated to primary management of gestational trophoblastic neoplasia, can decrease the chemotherapy requirements of patients with low-risk disease. In patients with high-risk disease, surgical intervention is frequently required to control complications of disease or as therapy to stabilize patients during chemotherapy. Hysterectomy, thoracotomy, or other extirpative procedures may be integrated into the management of patients with chemorefractory disease. Interventional procedures are useful adjuncts to control bleeding from metastases.

[Early flat colorectal cancer].

PubMed

Castelletto, R H; Chiarenza, C; Ottino, A; Garay, M L

1991-01-01

We report three cases of flat early colorectal carcinoma which were detected during the examination of 51 surgical specimens of colorectal resection. Two of them were endoscopically diagnosed, but the smallest one was not seen in the luminal instrumental examination. From the bibliographic analysis and our own experience we deduce the importance of flat lesions in the development of early colorectal carcinoma, either originated from pre-existent adenoma or de novo. Flat variants of adenoma, and presumably flush or depressed ones, must be considered as important factors in the early sequence adenoma-cancer. An appropriate endoscopic equipment with employment of additional staining techniques (such as carmine indigo and methylene blue) and the correct investigation during inflation-deflation procedures facilitates the identification of small lesions, their eradication and prevention from advanced forms of colorectal carcinoma.

Colorectal tumors: the histology report.

PubMed

Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

2011-03-01

Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Disease course and management strategy of pouch neoplasia in patients with underlying inflammatory bowel diseases.

PubMed

Wu, Xian-Rui; Remzi, Feza H; Liu, Xiu-Li; Lian, Lei; Stocchi, Luca; Ashburn, Jean; Shen, Bo

2014-11-01

To evaluate the disease course and management strategy for pouch neoplasia. Patients undergoing ileal pouch surgery for underlying ulcerative colitis who developed low-grade dysplasia (LGD), high-grade dysplasia, or adenocarcinoma in the pouch were identified. All eligible 44 patients were evaluated. Of the 22 patients with initial diagnosis of pouch LGD, 6 (27.3%) had persistence or progression after a median follow-up of 9.5 (4.1-17.6) years. Family history of colorectal cancer was shown to be a risk factor associated with persistence or progression of LGD (P = 0.03). Of the 12 patients with pouch high-grade dysplasia, 5 (41.7%) had a history of (n = 2, 16.7%) or synchronous (n = 4, 33.3%) pouch LGD. Pouch high-grade dysplasia either persisted or progressed in 3 patients (25.0%) after the initial management, during a median time interval of 5.4 (2.2-9.2) years. Of the 14 patients with pouch adenocarcinoma, 12 (85.7%) had a history of (n = 2, 14.3%) or synchronous dysplasia (n = 12, 85.7%). After a median follow-up of 2.1 (0.6-5.2) years, 6 patients with pouch cancer (42.9%) died. Comparison of patients with a final diagnosis of pouch adenocarcinoma (14, 32.6%), and those with dysplasia (29, 67.4%) showed that patients with adenocarcinoma were older (P = 0.04) and had a longer duration from IBD diagnosis or pouch construction to the detection of pouch neoplasia (P = 0.007 and P = 0.0013). The risk for progression of pouch dysplasia can be stratified. The presence of family history of colorectal cancer seemed to increase the risk for persistence or progression for patients with pouch LGD. The prognosis for pouch adenocarcinoma was poor.

Identification of Kininogen 1 as a Serum Protein Marker of Colorectal Adenoma in Patients with a Family History of Colorectal Cancer.

PubMed

Yu, Jiekai; Huang, Yanqin; Lin, Chen; Li, Xiaofen; Fang, Xuefeng; Zhong, Chenhan; Yuan, Ying; Zheng, Shu

2018-01-01

The serum protein markers of colorectal adenoma in patients with a family history of colorectal cancer have been rarely reported. Serum samples from colorectal adenoma patients with or without a family history of colorectal cancer and healthy controls were profiled using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The model to distinguish colorectal adenoma patients with a family history of colorectal cancer from atypical hereditary colorectal families (CRA-H) and sporadic colorectal adenoma patients without a family history of colorectal cancer (CRA-S) was established with 85.0% accuracy. The model distinguishing CRA-H from healthy individuals was established with 90.0% specificity and 86.7% sensitivity. Additionally, five peaks (2202, 5821, 3260, 2480, and 2218) showing differential expression in advanced colorectal adenoma patients with a family history of colorectal cancer were selected. The protein Kininogen 1 (KNG1) was identified in colorectal adenoma patients and validated using Western Blotting. KNG1 may be a biomarker for colorectal adenoma patients with a family history of colorectal cancer.

Screening for colorectal cancer: medical and economic aspects.

PubMed

Sanduleanu, S; Stockbrügger, R W

2003-01-01

Colorectal cancer (CRC) is the second commonest cause of cancer death in the Western world. In The Netherlands, CRC causes about 4400 deaths per year, and its diagnosis and treatment make up for a large share of health-care costs. Review and discussioN. Experts in the field presently assume that screening for CRC and its precursor lesions, colorectal adenomas (CRAs), could prevent death from colorectal neoplasia by more than 80%. Additionally, there is increasing acknowledgement that CRC screening programmes can save lives at a cost similar to, or even less than, the generally accepted breast cancer or cervical cancer screening programmes. Nonetheless, while neighbouring countries have taken vigorous measures to fight CRC, the Dutch are still hesitating in this matter. This is partly due to some yet unanswered questions concerning the acceptability of screening for CRC in the general population, the starting age and the frequency of screening, the type of screening tests to be used, and the programme organization. In this commentary, general epidemiological and pathogenetic aspects of CRC are addressed. In addition, some frequently asked questions (FAQ) and (very subjective) answers about screening for CRC are offered, as potential substrate for further in-depth discussions. The emerging message for the community is that an effective national screening programme is urgently required to reduce the substantial morbidity and mortality from this disease.

A randomised tandem colonoscopy trial of narrow band imaging versus white light examination to compare neoplasia miss rates.

PubMed

Kaltenbach, T; Friedland, S; Soetikno, R

2008-10-01

Colonoscopy, the "gold standard" screening test for colorectal cancer (CRC), has known diagnostic limitations. Advances in endoscope technology have focused on improving mucosal visualisation. In addition to increased angle of view and resolution features, recent colonoscopes have non-white-light optics, such as narrow band imaging (NBI), to enhance image contrast. We aimed to study the neoplasia diagnostic characteristics of NBI, by comparing the neoplasm miss rate when the colonoscopy was performed under NBI versus white light (WL). Randomised controlled trial. US Veterans hospital. Elective colonoscopy adults. We randomly assigned patients to undergo a colonoscopic examination using NBI or WL. All patients underwent a second examination using WL, as the reference standard. The primary end point was the difference in the neoplasm miss rate, and secondary outcome was the neoplasm detection rate. In 276 tandem colonoscopy patients, there was no significant difference of miss or detection rates between NBI or WL colonoscopy techniques. Of the 135 patients in the NBI group, 17 patients (12.6%; 95% confidence interval (CI) 7.5 to 19.4%) had a missed neoplasm, as compared with 17 of the 141 patients (12.1%; 95% CI 7.2 to 18.6%) in the WL group, with a miss rate risk difference of 0.5% (95% CI -7.2 to 8.3). 130 patients (47%) had at least one neoplasm. Missed lesions with NBI showed similar characteristics to those missed with WL. All missed neoplasms were tubular adenomas, the majority (78%) was < or = 5 mm and none were larger than 1 cm (one-sided 95% CI up to 1%). Nonpolypoid lesions represented 35% (13/37) of missed neoplasms. NBI did not improve the colorectal neoplasm miss rate compared to WL; the miss rate for advanced adenomas was less than 1% and for all adenomas was 12%. The neoplasm detection rates were similar high using NBI or WL; almost a half the study patients had at least one adenoma. Clinicaltrials.gov identifier: NCT00628147.

Cost-effectiveness of an advance notification letter to increase colorectal cancer screening.

PubMed

Cronin, Paula; Goodall, Stephen; Lockett, Trevor; O'Keefe, Christine M; Norman, Richard; Church, Jody

2013-07-01

The aim of this study is to evaluate the cost-effectiveness of a patient-direct mailed advance notification letter on participants of a National Bowel Cancer Screening Program (NBCSP) in Australia, which was launched in August 2006 and offers free fecal occult blood testing to all Australians turning 50, 55, or 65 years of age in any given year. This study followed a hypothetical cohort of 50-year-old, 55-year-old, and 65-year-old patients undergoing fecal occult blood test (FOBT) screening through a decision analytic Markov model. The intervention compared two strategies: (i) advance letter, NBCSP, and FOBT compared with (ii) NBCSP and FOBT. The main outcome measures were life-years gained (LYG), quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio. An advance notification screening letter would yield an additional 54 per 100,000 colorectal cancer deaths avoided compared with no letter. The estimated cost-effectiveness was $3,976 per LYG and $6,976 per QALY gained. An advance notification letter in the NBCSP may have a significant impact on LYG and cancer deaths avoided. It is cost-effective and offers a feasible strategy that could be rolled out across other screening program at an acceptable cost.

Computed tomographic colonography to screen for colorectal cancer, extracolonic cancer, and aortic aneurysm: model simulation with cost-effectiveness analysis.

PubMed

Hassan, Cesare; Pickhardt, Perry J; Pickhardt, Perry; Laghi, Andrea; Kim, Daniel H; Kim, Daniel; Zullo, Angelo; Iafrate, Franco; Di Giulio, Lorenzo; Morini, Sergio

2008-04-14

In addition to detecting colorectal neoplasia, abdominal computed tomography (CT) with colonography technique (CTC) can also detect unsuspected extracolonic cancers and abdominal aortic aneurysms (AAA).The efficacy and cost-effectiveness of this combined abdominal CT screening strategy are unknown. A computerized Markov model was constructed to simulate the occurrence of colorectal neoplasia, extracolonic malignant neoplasm, and AAA in a hypothetical cohort of 100,000 subjects from the United States who were 50 years of age. Simulated screening with CTC, using a 6-mm polyp size threshold for reporting, was compared with a competing model of optical colonoscopy (OC), both without and with abdominal ultrasonography for AAA detection (OC-US strategy). In the simulated population, CTC was the dominant screening strategy, gaining an additional 1458 and 462 life-years compared with the OC and OC-US strategies and being less costly, with a savings of $266 and $449 per person, respectively. The additional gains for CTC were largely due to a decrease in AAA-related deaths, whereas the modeled benefit from extracolonic cancer downstaging was a relatively minor factor. At sensitivity analysis, OC-US became more cost-effective only when the CTC sensitivity for large polyps dropped to 61% or when broad variations of costs were simulated, such as an increase in CTC cost from $814 to $1300 or a decrease in OC cost from $1100 to $500. With the OC-US approach, suboptimal compliance had a strong negative influence on efficacy and cost-effectiveness. The estimated mortality from CT-induced cancer was less than estimated colonoscopy-related mortality (8 vs 22 deaths), both of which were minor compared with the positive benefit from screening. When detection of extracolonic findings such as AAA and extracolonic cancer are considered in addition to colorectal neoplasia in our model simulation, CT colonography is a dominant screening strategy (ie, more clinically effective and more cost

Genetic biomarkers for neoplastic colorectal cancer in peripheral lymphocytes.

PubMed

Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-04-01

Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer.

Genetic Biomarkers for Neoplastic Colorectal Cancer in Peripheral Lymphocytes

PubMed Central

Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-01-01

ABSTRACT Background: Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Method: Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. Results: We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Conclusion: Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer. PMID:22205889

Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial.

PubMed

Samadder, N Jewel; Kuwada, Scott K; Boucher, Kenneth M; Byrne, Kathryn; Kanth, Priyanka; Samowitz, Wade; Jones, David; Tavtigian, Sean V; Westover, Michelle; Berry, Therese; Jasperson, Kory; Pappas, Lisa; Smith, Laurel; Sample, Danielle; Burt, Randall W; Neklason, Deborah W

2018-02-08

Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial. To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP. Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah. Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months. The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment. Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009). In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum. clinicaltrials.gov Identifier: NCT01187901.

Nivolumab for the treatment of colorectal cancer.

PubMed

Smith, Kortnye Maureen; Desai, Jayesh

2018-05-24

Despite a variety of therapies for advanced metastatic colorectal cancer being available, the outcomes in this malignancy remain sub-optimal. Immunotherapy has been slow to impact the management of this patient group. Checkpoint inhibitors, such as nivolumab, have had disappointing results when used broadly. However, for the subset of patients with microsatellite unstable colorectal cancer the use of checkpoint inhibitors such as nivolumab appears to be transformative, and will provide a new therapeutic option for patient with advanced disease. Areas covered: Nivolumab gained regulatory approval for the treatment of dMMR/MSI-H metastatic colorectal cancer in mid 2017. The current review will summarize the clinical evidence of checkpoint inhibitors in metastatic colorectal cancer, with a focus on nivolumab. Expert commentary: For patients with dMMR/MSI-H mCRC the use of nivolumab has now been shown to have objective and sustained clinical responses in a pivotal phase II trial. While additional data is limited, the therapeutic role for augmenting an immune response in metastatic colorectal cancer is likely to continue to expand. Further combination trials of nivolumab with immunologic and non-immunologic agents are ongoing.

The effects of selected drugs and dietary compounds on proliferation and apoptosis in colorectal carcinoma.

PubMed

Kiedrowski, Miroslaw; Mroz, Andrzej

2014-01-01

Like many malignancies, the development of colorectal carcinoma (CRC) can be considered as an imbalance between the compromised process of programmed cell death (apoptosis) and excessive, uncontrolled proliferation. Several mutations and epigenetic alterations are acquired during colorectal carcinogenesis. These are responsible for the cell cycle regulation, cellular sensitivity to pro- and antiapoptotic factors, cell proliferation, angiogenesis, invasiveness, as well as metastatic potential. The molecular alterations, along with their morphological expressions, have been recognised in detail, and most of the CRC cases can be attributed to either adenoma-carcinoma or serrated neoplasia pathways: in the first, the antiapoptotic features prevail; while in the second, the proliferative activity is of the utmost importance. The aim of the work is to discuss the influence of selected drugs and dietary compounds on the proliferation and apoptosis in CRC.

Prevalence and risk factors of advanced colorectal neoplasms in asymptomatic Korean people between 40 and 49 years of age.

PubMed

Koo, Ja Eun; Kim, Kyung-Jo; Park, Hye Won; Kim, Hong-Kyu; Choe, Jae Won; Chang, Hye-Sook; Lee, Ji Young; Myung, Seung-Jae; Yang, Suk-Kyun; Kim, Jin-Ho

2017-01-01

Current guidelines recommend colon cancer screening for persons aged over 50 years. However, there are few data on colorectal cancer screening in 40- to 49-year-olds. This study assessed the prevalence and risk factors of colorectal neoplasms in 40- to 49-year-old Koreans. We analyzed the results of screening colonoscopies of 6680 persons 40-59 years of age (2206 aged 40-49 and 4474 aged 50-59 years). The prevalence of overall and advanced neoplasms in the 40- to 49-year age group was lower than in the 50- to 59-year age group (26.7% and 2.4% vs 37.8% and 3.5%, respectively). However, the prevalence of overall and advanced neoplasms increased to 39.1% and 5.4%, respectively, in 45- to 49-year-old individuals with metabolic syndrome. In the 40- to 49-year age group, age, current smoking, and metabolic syndrome were associated with an increased risk of advanced neoplasms (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.30; OR 3.12, 95% CI 1.20-8.12; and OR 2.00, 95% CI 1.09-3.67, respectively). Individuals aged 40-49 years had a lower prevalence of colorectal neoplasms than those aged 50-59 years, but some 40- to 49-year-olds showed a similar prevalence to those aged 50-59 years. Age, current smoking habits, and metabolic syndrome are associated with an increased risk of advanced neoplasms in subjects aged 40-49 years. Further studies are needed to stratify the risks of colon cancer and guide targeted screening in persons younger than 50 years old. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Metachronous colon polyps in younger versus older adults: a case-control study.

PubMed

Nagpal, Sajan Jiv Singh; Mukhija, Dhruvika; Sanaka, Madhusudhan; Lopez, Rocio; Burke, Carol A

2018-03-01

The incidence of colorectal cancer in the United States has decreased substantially in individuals aged 50 and older. In contrast, it is increasing in young adults. The polyp characteristics on baseline and follow-up colonoscopy in young adults are not well characterized. We describe the polyp characteristics on baseline and follow-up colonoscopy in adults <40 years and determined factors associated with the occurrence of metachronous, advanced neoplasia or high-risk (HR) polyp features. We compared the occurrence of metachronous advanced neoplasia in young adults with those 50 years and older to assess whether postpolypectomy surveillance guidelines seem appropriate for polyp-bearing adults less than age 40 years. Patients <40 years of age with >1 polyp removed on colonoscopy followed by a postpolypectomy colonoscopy were eligible. The primary outcome was the occurrence of advanced neoplasia or HR polyp features on follow-up colonoscopy. Secondary endpoints included factors associated with metachronous advanced neoplasia in young adults. The occurrence of metachronous advanced neoplasia in young adults was compared with a cohort of patients aged 50 years and older. Included were 128 patients with a mean age of 34.9 years; 124 patients (97%) had adenomas and 7% had sessile serrated polyps (SSPs). Advanced neoplasia was seen in 35% of patients at baseline. The median follow-up time was 33.6 months. Metachronous advanced neoplasia was identified in 7% of patients on follow-up colonoscopy. Baseline factors associated with metachronous advanced neoplasia included the presence of an SSP (hazard ratio, 7.8; 95% CI, 1.09-56.3; P = .041) with a trend in those with advanced neoplasia (hazard ratio, 3.4; 95% confidence interval, .89-12.8; P = .072). The occurrence of metachronous advanced neoplasia did not differ between the young and older cohorts (7% vs 12.2%, P = .58); however, young adults were less likely to have HR polyp features on follow-up (8.6% vs 20.3%, P�

Incidence of macroscopically occult neoplasias in Barrett's esophagus: are random biopsies dispensable in the era of advanced endoscopic imaging?

PubMed

Pohl, Juergen; Pech, Oliver; May, Andrea; Manner, Hendrik; Fissler-Eckhoff, Annette; Ell, Christian

2010-11-01

The gold standard for endoscopic surveillance of Barrett's esophagus (BE) includes targeted biopsies (TBs) from abnormalities as well as stepwise four-quadrant biopsies (4QBs) for detection of invisible high-grade intraepithelial neoplasias (HGINs) or early carcinomas (ECs). In a large mixed BE population, we investigated the rate of HGINs/ECs that are macroscopically occult to enhanced visualization with high-resolution endoscopy plus acetic acid chromoendoscopy. From January 2007 to December 2009, 701 consecutive BE patients were enrolled in a prospective study at a tertiary referral center. Of these, 406 patients had a history of HGIN/EC (high-risk group) and 295 patients did not (low-risk group). In 701 patients, 459 TBs and 5,485 4QBs were obtained. Altogether, 92 patients with 132 lesions containing HGINs/ECs were detected. For the diagnosis of HGINs/ECs, patient-related sensitivity and specificity rates of endoscopic imaging with TBs were 96.7 and 66.5%, with a positive and negative predictive value of 30.4 and 99.3%, respectively. In the high-risk group, 4QBs identified three additional patients (3.3%) with macroscopically occult HGINs/ECs. In the low-risk group, no HGINs/ECs were identified with either biopsy approach. Advanced endoscopic imaging identifies the vast majority of BE patients with early neoplasias, and the additive effect of 4QB is minimal. Therefore, in low- and high-risk patients, limiting endoscopic surveillance to guided biopsies is justified in specialized high-volume centers with permanent quality control. However, we do not advocate abandoning 4QB outside this setting.

p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

PubMed

Paradiso, A; Rabinovich, M; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriquez, R; Leone, B; Sapia, M G; Simone, G; De Lena, M

1996-12-20

In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

Update on Sporadic Colorectal Cancer Genetics.

PubMed

Hardiman, Karin M

2018-05-01

Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients.

PubMed

Paradiso, A; Simone, G; Petroni, S; Leone, B; Vallejo, C; Lacava, J; Romero, A; Machiavelli, M; De Lena, M; Allegra, C J; Johnston, P G

2000-02-01

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated-5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53- cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively; P < 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P < 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34-1.01; two-sided P < 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85-1.26; two-sided P < 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy.

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients

PubMed Central

Paradiso, A; Simone, G; Petroni, S; Leone, B; Vallejo, C; Lacava, J; Romero, A; Machiavelli, M; Lena, M De; Allegra, C J; Johnston, P G

2000-01-01

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53– cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively;P< 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P< 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34–1.01; two-sided P< 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85–1.26; two-sided P< 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. © 2000 Cancer Research Campaign PMID:10682666

Chemoprevention of Colorectal Cancer

PubMed Central

Lang, Michaela; Gasche, Christoph

2017-01-01

Colorectal cancer has become one of the most prevalent malignant diseases for both men and women. Patients with inflammatory bowel diseases or certain inherited cancer syndromes are at extremely high risk of developing colorectal cancer and have naturally the highest need for cancer prevention. In familial adenomatous polyposis (FAP) and Lynch syndrome most of the underlying germline mutations can be detected by DNA sequencing, and medical counselling of affected individuals involves both surveillance tests and chemopreventive measures. However, as the mechanisms leading to colorectal cancer differ in these high risk groups, the molecular action of chemopreventive drugs needs to be adjusted to the certain pathway of carcinogenesis. In the last decades a number of drugs have been tested, including sulindac, aspirin, celecoxib, and mesalazine, but some of them are still controversially discussed. This review summarizes the advances and current standards of colorectal cancer prevention in patients with inflammatory bowel disease, FAP and Lynch syndrome. PMID:25531498

Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database.

PubMed

Giusti, Francesca; Cianferotti, Luisella; Boaretto, Francesca; Cetani, Filomena; Cioppi, Federica; Colao, Annamaria; Davì, Maria Vittoria; Faggiano, Antongiulio; Fanciulli, Giuseppe; Ferolla, Piero; Ferone, Diego; Fossi, Caterina; Giudici, Francesco; Gronchi, Giorgio; Loli, Paola; Mantero, Franco; Marcocci, Claudio; Marini, Francesca; Masi, Laura; Opocher, Giuseppe; Beck-Peccoz, Paolo; Persani, Luca; Scillitani, Alfredo; Sciortino, Giovanna; Spada, Anna; Tomassetti, Paola; Tonelli, Francesco; Brandi, Maria Luisa

2017-11-01

The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management. Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011-2013), to build a national electronic database. The Italian multiple endocrine neoplasia type 1 database includes 475 patients (271 women and 204 men), of whom 383 patients (80.6%) were classified as familial cases (from 136 different pedigrees), and 92 (19.4%) patients were sporadic cases. A MEN1 mutation was identified in 92.6% of familial cases and in 48.9% of sporadic cases. Four hundred thirty-six patients were symptomatic, presenting primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary tumors in 93, 53, and 41% of cases, respectively. Thirty-nine subjects, belonging to affected pedigrees positive for a MEN1 mutation, were asymptomatic at clinical and biochemical screening. Age at diagnosis of multiple endocrine neoplasia type 1 probands was similar for both familial and simplex cases (mean age 47.2 ± 15.3 years). In familial cases, diagnosis of multiple endocrine neoplasia type 1 in relatives of affected probands was made more than 10 years in advance (mean age at diagnosis 36.5 ± 17.6 years). The analysis of Italian registry of multiple endocrine neoplasia type 1 patients revealed that clinical features of Italian multiple endocrine neoplasia type 1 patients are similar to those of other western countries, and confirmed that the genetic test allowed multiple endocrine neoplasia type 1 diagnosis 10 years earlier than biochemical or clinical diagnosis.

KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer: An Evidence-Based and Economic Analysis.

PubMed

2010-01-01

In February 2010, the Medical Advisory Secretariat (MAS) began work on evidence-based reviews of the literature surrounding three pharmacogenomic tests. This project came about when Cancer Care Ontario (CCO) asked MAS to provide evidence-based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario.Evidence-based analyses have been prepared for each of these technologies. These have been completed in conjunction with internal and external stakeholders, including a Provincial Expert Panel on Pharmacogenomics (PEPP). Within the PEPP, subgroup committees were developed for each disease area. For each technology, an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative (THETA) and is summarized within the reports.THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE MAS WEBSITE AT: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER: An Evidence-Based and Economic AnalysisEpidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: an Evidence-Based and Economic AnalysisK-RAS testing in Treatment Decisions for Advanced Colorectal Cancer: an Evidence-Based and Economic Analysis. The objective of this systematic review is to determine the predictive value of KRAS testing in the treatment of metastatic colorectal cancer (mCRC) with two anti-EGFR agents, cetuximab and panitumumab. Economic analyses are also being conducted to evaluate the cost-effectiveness of KRAS testing. CONDITION AND TARGET POPULATION Metastatic colorectal cancer (mCRC) is usually defined as stage IV disease according to the American Joint Committee on Cancer tumour node metastasis (TNM) system or stage D in

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

PubMed Central

Isidro, Raymond A; Cruz, Myrella L; Isidro, Angel A; Baez, Axel; Arroyo, Axel; González-Marqués, William A; González-Keelan, Carmen; Torres, Esther A; Appleyard, Caroline B

2015-01-01

AIM: To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. METHODS: Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sporadic dysplasia, and sporadic colorectal cancer (CRC), as well as normal controls, were identified at several centers in Puerto Rico. Archival formalin-fixed, paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R, pEGFR, Cox-2, and VDR. Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a 4-point scale that assessed intensity of staining. Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia, in addition to the areas of cancer, within each tissue. Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test. The mean scores for normal tissues and tissues with IBD, dysplasia, CRC, and CAC were calculated and statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test. Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient. Data are presented as mean ± SE. RESULTS: On average, patients with IBD were younger (34.60 ± 5.81) than normal (63.20 ± 6.13, P < 0.01), sporadic dysplasia (68.80 ± 4.42, P < 0.01), sporadic cancer (74.80 ± 4.91, P < 0.001), and CAC (57.50 ± 5.11, P < 0.05) patients. NK-1R in cancer tissue (sporadic CRC, 1.73 ± 0.34; CAC, 1.57 ± 0.53) and sporadic dysplasia (2.00 ± 0.45) were higher than in normal tissues (0.73 ± 0.19). pEGFR was significantly increased in sporadic CRC (1.53 ± 0.43) and CAC (2.25 ± 0.47) when compared to

Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer

PubMed Central

Chau, I; Webb, A; Cunningham, D; Hill, M; Waters, J S; Norman, A; Massey, A

2001-01-01

The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg m−2) was given every 2 weeks and PVI 5-FU (300 mg m−2day−1) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15–46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n= 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3–4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7–73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer. © 2001 Cancer Research Campaign PMID:11720458

The association between cecal insertion time and colorectal neoplasm detection

PubMed Central

2013-01-01

Background Information on the impact of cecal insertion time on colorectal neoplasm detection is limited. Our objective was to determine the association between cecal insertion time and colorectal neoplasm detection rate in colonoscopy screening. Methods We performed a cross-sectional study of 12,679 consecutive subjects aged 40–79 years undergoing screening colonoscopy in routine health check-ups at the Center for Health Promotion of the Samsung Medical Center from December 2007 to June 2009. Fixed effects logistic regression conditioning on colonoscopist was used to eliminate confounding due to differences in technical ability and other characteristics across colonoscopists. Results The mean cecal insertion time was 5.9 (SD, 4.4 minutes). We identified 4,249 (33.5%) participants with colorectal neoplasms, of whom 1,956 had small single adenomas (<5 mm), 595 had medium single adenomas (5–9 mm), and 1,699 had multiple adenomas or advanced colorectal neoplasms. The overall rates of colorectal neoplasm detection by quartiles of cecal insertion time were 36.8%, 33.4%, 32.7%, and 31.0%, respectively (p trend <0.001).The odds for small single colorectal adenoma detection was 16% lower (adjusted OR 0.84; 95% CI 0.71 to 0.99) in the fourth compared to the first quartile of insertion time (p trend 0.005). Insertion time was not associated with the detection rate of single adenomas ≥5 mm, multiple adenomas or advanced colorectal neoplasms. Conclusion Shorter insertion times were associated with increased rates of detection of small colorectal adenomas <5 mm. Cecal insertion time may be clinically relevant as missed small colorectal adenomas may progress to more advanced lesions. PMID:23915303

[HPV type 33-associated penile intraepithelial neoplasia (PIN)].

PubMed

Wahl, R U; Knückel, R; Megahed, M

2009-12-01

For appoximately 6 month a 69-year old man had been suffering from an itching scaly skin change of the penis. Virological and histological examinations confirmed the diagnosis of an intraepithelial neoplasia induced by an infection with human papillomavirus (HPV) type 33. HPV type 33 is comparatively rarely detected in intraepithelial neoplasia. In anogenital lesions intraepithelial neoplasia should be considered and confirmed via histological and virological examinations.

Serrated Colon Polyps as Precursors to Colorectal Cancer

PubMed Central

Sweetser, Seth; Smyrk, Thomas C.; Sinicrope, Frank A.

2013-01-01

Identification of the serrated neoplasia pathway has improved our understanding of the pathogenesis of colorectal cancer (CRC). Insights have included an increased recognition of the malignant potential of different types of serrated polyps, such as sessile and traditional serrated adenomas. Sessile serrated adenomas share molecular features with colon tumors, such as microsatellite instability and a methylator phenotype, indicating that these lesions are precursors that progress via the serrated neoplasia pathway. There is evidence that the serrated pathway contributes to interval or missed cancers. These data have important implications for clinical practice and CRC prevention, since hyperplastic polyps were previously regarded as having no malignant potential. Endoscopic detection of serrated polyps is a challenge because they are often inconspicuous with indistinct margins, and are frequently covered by adherent mucus. It is important for gastroenterologists to recognize the subtle endoscopic features of serrated polyps, which would facilitate their detection and removal, to ensure a high-quality colonoscopy examination. Recognition of the role of serrated polyps in colon carcinogenesis has led to the inclusion of these lesions in post-polypectomy surveillance guidelines. However, an enhanced effort is needed to identify and completely remove serrated adenomas, with the goal of increasing the effectiveness of colonoscopy to reduce CRC incidence. PMID:23267866

Molecular alterations and biomarkers in colorectal cancer

PubMed Central

Grady, William M.; Pritchard, Colin C.

2013-01-01

The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

PubMed

Sung, J J Y; Ng, S C; Chan, F K L; Chiu, H M; Kim, H S; Matsuda, T; Ng, S S M; Lau, J Y W; Zheng, S; Adler, S; Reddy, N; Yeoh, K G; Tsoi, K K F; Ching, J Y L; Kuipers, E J; Rabeneck, L; Young, G P; Steele, R J; Lieberman, D; Goh, K L

2015-01-01

Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Atrial Fibrillation and Colonic Neoplasia in African Americans.

PubMed

Nouraie, Mehdi; Kansal, Vandana; Belfonte, Cassius; Ghazvini, Mohammad; Haidari, Tahmineh; Shahnazi, Anahita; Brim, Hassan; Soliman, Elsayed Z; Ashktorab, Hassan

2015-01-01

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American. We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression. The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9-2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7-1.6, P = 0.7) were not significantly associated AF compared to control group. AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.

Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

PubMed Central

Long, Yadong; Xu, Ye; Guan, Zuqing; Lian, Peng; Peng, Junjie

2014-01-01

Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P = 0.049) and CIMP positive (P = 0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P = 0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P = 0.023). Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy. PMID:24822060

A ‘modified de Gramont’ regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer

PubMed Central

Cheeseman, S L; Joel, S P; Chester, J D; Wilson, G; Dent, J T; Richards, F J; Seymour, M T

2002-01-01

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified ‘Modified de Gramont’ (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m−2), then ambulatory 46-h fluorouracil infusion (2000–3600 mg m−2, cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m−2. Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m−2 bolus + 2800 mg m−2 46-h infusion. A lower dose of 400 mg m−2 bolus + 2400 mg m−2 infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC0–48 h) at this lower dose is equivalent to dG. With OxMdG, grade 3–4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial. British Journal of Cancer (2002) 87, 393–399. doi:10

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting.

PubMed

Werner, Simone; Krause, Friedemann; Rolny, Vinzent; Strobl, Matthias; Morgenstern, David; Datz, Christian; Chen, Hongda; Brenner, Hermann

2016-04-01

In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population. We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results. AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68-0.87] and 0.56 (95% CI, 0.53-0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings. Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer. ©2015 American Association for Cancer Research.

Intraoperative radiotherapy and colorectal cancer.

PubMed

Yeung, J M C; Ngan, S; Lynch, C; Heriot, A G

2010-04-01

Intraoperative radiotherapy (IORT) is a highly specialized component of multidisciplinary management of advanced and recurrent colorectal cancer. The aim of this review was to assess its role and effectiveness in the management of colorectal cancer. A literature search was performed using Medline, Embase, Ovid and Cochrane to identify English language studies which have used IORT in the multidisciplinary management of primary and recurrent colon and rectal cancers. Improved survival and local control in patients with involved surgical margins treated with IORT have been shown in many studies, but these results have been mainly from retrospective studies. There is associated morbidity from IORT. IORT does have a role in the management of colorectal cancer. Further research needs to be performed to optimize the application of this therapy.

Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

PubMed

Garcia, Mila Trementosa; Lin, Lawrence Hsu; Fushida, Koji; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

2016-12-01

The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

NEOPLASIA IN SNAKES AT ZOO ATLANTA DURING 1992-2012.

PubMed

Page-Karjian, Annie; Hahne, Megan; Leach, Kate; Murphy, Hayley; Lock, Brad; Rivera, Samuel

2017-06-01

A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8-19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1-24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.

Oral fluoropyrimidine versus intravenous 5-fluorouracil for the treatment of advanced gastric and colorectal cancer: Meta-analysis.

PubMed

Zhang, Linlin; Xing, Xiaoli; Meng, Fanlu; Wang, Yan; Zhong, Diansheng

2018-01-01

5-Fluorouracil (5-Fu) is one of the most commonly prescribed antineoplastic agents against gastric and colorectal cancers. Continuous infusion would be the optimal way of its administration, however, may usually cause thrombosis, infection, and prolonged hospital stay. Oral fluoropyrimidines would be an attractive alternative, but their efficiency and toxicities for the treatment of gastric and colorectal cancer are still obscure as compared with infusion 5-Fu. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook. The outcome measures were tumor response rate, progression-free survival, overall survival, and adverse effects. Twenty-nine randomized controlled trials, comprising totally 15 154 patients, were included. Meta-analysis showed similar overall outcome in terms of response rate (1.01; 95% confidence interval [CI], 0.92-1.12), progression-free survival (hazard ratio 1.00; 95%CI, 0.94-1.06), and overall survival (hazard ratio 0.96; 95%CI, 0.92-1.01) between oral fluoropyrimidine-based and intravenous 5-Fu-based regimens in gastric and colorectal cancer patients. The risk of grade 3/4 neutropenia, thrombocytopenia, and stomatitis was more prominent in intravenous 5-Fu-based regimens; while more frequent grade 3/4 hand-foot syndrome, diarrhea, and anorexia were detected in oral fluoropyrimidine-based regimens. Oral-fluoropyrimidines showed equivalent response and similar survival outcomes, but different toxicity profiles, as compared with intravenous 5-Fu. Thus, it would be a more convenient and adjustable alternative in treatment of advanced gastric and colorectal cancer. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Apolipoprotein E Polymorphism and Colorectal Neoplasm: Results from a Meta-Analysis

PubMed Central

Tian, Yun; Wang, Jirong; Ye, Ying; Sun, Liqun; Fan, Yingrui; Wang, Li; Li, Juan; Wang, Zhaoxia; Wang, Keming

2014-01-01

To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 participants and 4310 CRN cases which including 438 patients with colorectal adenoma (CRA), and 3873 patients with colorectal carcinoma (CRC). The pooled data from this meta-analysis indicated there was no significant association between APOE polymorphism and CRN (ε2: P = 0.51, OR 1.04 95% CI 0.93 to 1.16; ε4: P = 0.72, OR 0.98 95% CI 0.90 to 1.07). Interestingly, subgroup analysis demonstrated there was a significant decreased risk for proximal CRN in patients with APOE ε4 (P = 0.0007, OR 0.52 95% CI 0.35 to 0.76). Data showed no significant association between APOE genotype and overall CRN. However, compared with those carry APOE ε3 alleles, persons with APOE ε4 genotype have significant decreased risk suffering from proximal CRN but not from distal CRN. PMID:25029444

Colorectal cancer screening of immigrants to Italy. Figures from the 2013 National Survey.

PubMed

Turrin, Anna; Zorzi, Manuel; Giorgi Rossi, Paolo; Senore, Carlo; Campari, Cinzia; Fedato, Chiara; Naldoni, Carlo; Anghinoni, Emanuela; Carrozzi, Giuliano; Sassoli De' Bianchi, Priscilla; Zappa, Marco

2015-12-01

Colorectal cancer screening programmes in Italy invite 50-69-year-old residents for a faecal immunochemical test every two years, regardless of their citizenship. The 2013 National Survey on Italian colorectal cancer screening programmes compared immigrants born in low- or middle-income countries with subjects who were born in Italy, by collecting aggregated data on compliance, faecal immunochemical test results, compliance with colonoscopy, detected lesions and stage at diagnosis separately for Italians and immigrants. Overall, 85 screening programmes invited 3,292,451 subjects, of whom 192,629 had been born abroad (5.9%). Compliance with invitation was lower in immigrants (34.3% vs. 51.3% in Italians), with p<0.001. Compliance was higher in females, regardless of the country of birth, in the youngest age group of immigrants but in the oldest of Italians. Immigrants showed a borderline excess of standardised faecal immunochemical test positivity rate at first screening (5.4% vs. 5.1% in Italians, p=0.05) and a significant excess at repeat screenings (4.8% vs. 4.4%, p=0.002). The detection rates for carcinoma and advanced adenomas were lower in immigrants than in Italians at first screening (respectively 1.34‰ vs. 1.62‰ and 8.41‰ vs. 9.25‰) - although the differences were not statistically significant - but not at repeat screening (respectively 1.06‰ vs. 0.98‰ and 6.90‰ vs. 6.79‰). Migrants showed a lower compliance with screening than Italians. The prevalence of neoplasia was lower at first screening and similar to the Italians' at repeat screenings. Copyright © 2015 Elsevier Inc. All rights reserved.

New endoscopy advances to refine adenoma detection rate for colorectal cancer screening: None is the winner.

PubMed

Maida, Marcello; Camilleri, Salvatore; Manganaro, Michele; Garufi, Serena; Scarpulla, Giuseppe

2017-10-15

Colorectal cancer (CRC) is the third most common cancer in males and second in females, and globally the fourth cause for cancer death worldwide. Oncological screening of CRC has a major role in the management of the disease and it is mostly performed by colonoscopy. Anyway, effectiveness of endoscopic screening for CRC strictly depends on adequate detection and removal of potentially precancerous lesions, and accuracy of colonoscopy in detection of adenomas is still suboptimal. For this reason, several technological advances have been implemented in order to improve the diagnostic sensitivity of colonoscopy in adenoma detection. Among these: (1) Visual technologies such as chromoendoscopy and narrow band imaging; (2) optical innovation as high definition endoscopy, full-spectrum endoscopy or Third Eye Retroscope; and (3) mechanical advances as Cap assisted colonoscopy, Endocuff, Endoring and G-Eye endoscope. All these technologies advances have been tested over time by clinical studies with mixed results. Which of them is more likely to be successful in the next future?

Napabucasin versus placebo in refractory advanced colorectal cancer: a randomised phase 3 trial.

PubMed

Jonker, Derek J; Nott, Louise; Yoshino, Takayuki; Gill, Sharlene; Shapiro, Jeremy; Ohtsu, Atsushi; Zalcberg, John; Vickers, Michael M; Wei, Alice C; Gao, Yuan; Tebbutt, Niall C; Markman, Ben; Price, Timothy; Esaki, Taito; Koski, Sheryl; Hitron, Matthew; Li, Wei; Li, Youzhi; Magoski, Nadine M; Li, Chiang J; Simes, John; Tu, Dongsheng; O'Callaghan, Christopher J

2018-04-01

Napabucasin is a first-in-class cancer stemness inhibitor that targets STAT3, which is a poor prognostic factor in colorectal cancer. This study aimed to test napabucasin in advanced colorectal cancer. This study was a double-blind randomised phase 3 trial done at 68 centres in Canada, Australia, New Zealand, and Japan. Patients with advanced colorectal cancer with a good Eastern Cooperative Oncology Group (ECOG) performance status (0-1) for whom all available standard therapies had failed were eligible for the study. Patients were randomly assigned (1:1) to receive placebo or napabucasin through a web-based system with a permuted block method, after stratification by ECOG performance status, KRAS status, previous VEGF inhibitor treatment, and time from diagnosis of metastatic disease. Napabucasin 480 mg or matching placebo was taken orally every 12 h. All patients received best supportive care. The primary endpoint was overall survival assessed in an intention-to-treat analysis. This is the final analysis of this trial, which is registered at ClinicalTrials.gov, number NCT01830621. Accrual began on April 15, 2013, and was stopped for futility on May 23, 2014, at which point 282 patients had undergone randomisation (138 assigned to the napabucasin group and 144 to the placebo group). Overall survival did not differ significantly between groups: median overall survival was 4·4 months (95% CI 3·7-4·9) in the napabucasin group and 4·8 months (4·0-5·3) in the placebo group (adjusted hazard ratio [HR] 1·13, 95% CI 0·88-1·46, p=0·34). The safety population included 136 patients in the napabucasin group and 144 patients in the placebo group. More patients who received napabucasin had any grade of treatment-related diarrhoea (108 [79%] of 136 patients), nausea (69 [51%]), and anorexia (52 [38%]) than did patients who received placebo (28 [19%] of 144 patients, 35 [24%], and 23 [16%], respectively). The most common severe (grade 3 or worse) treatment

Spontaneous neoplasia in four captive greater hedgehog tenrecs (Setifer setosus).

PubMed

Khoii, Mina K; Howerth, Elizabeth W; Burns, Roy B; Carmichael, K Paige; Gyimesi, Zoltan S

2008-09-01

Little information is available about diseases and pathology of species within the family Tenrecidae, including the greater hedgehog tenrec (Setifer setosus), a Madagascan insectivore. This report summarizes necropsy and histopathologic findings of neoplasia in four captive greater hedgehog tenrecs. Although only four animals are included in this report, neoplasia seems to be a common and significant source of morbidity and mortality in greater hedgehog tenrecs. Types of neoplasia identified include a thyroid follicular-solid carcinoma, two urinary bladder transitional cell carcinomas, uterine endometrial polyps, and multicentric B-cell lymphoma. Due to small sample size, no etiology could be determined, but genetics, viral infection, pesticide treatment, nutrition, or other environmental factors might contribute to the development of neoplasia in this species. This is the first report of neoplasia in greater hedgehog tenrecs.

RAS testing in metastatic colorectal cancer: advances in Europe.

PubMed

Van Krieken, J Han J M; Rouleau, Etienne; Ligtenberg, Marjolijn J L; Normanno, Nicola; Patterson, Scott D; Jung, Andreas

2016-04-01

Personalized medicine shows promise for maximizing efficacy and minimizing toxicity of anti-cancer treatment. KRAS exon 2 mutations are predictive of resistance to epidermal growth factor receptor-directed monoclonal antibodies in patients with metastatic colorectal cancer. Recent studies have shown that broader RAS testing (KRAS and NRAS) is needed to select patients for treatment. While Sanger sequencing is still used, approaches based on various methodologies are available. Few CE-approved kits, however, detect the full spectrum of RAS mutations. More recently, "next-generation" sequencing has been developed for research use, including parallel semiconductor sequencing and reversible termination. These techniques have high technical sensitivities for detecting mutations, although the ideal threshold is currently unknown. Finally, liquid biopsy has the potential to become an additional tool to assess tumor-derived DNA. For accurate and timely RAS testing, appropriate sampling and prompt delivery of material is critical. Processes to ensure efficient turnaround from sample request to RAS evaluation must be implemented so that patients receive the most appropriate treatment. Given the variety of methodologies, external quality assurance programs are important to ensure a high standard of RAS testing. Here, we review technical and practical aspects of RAS testing for pathologists working with metastatic colorectal cancer tumor samples. The extension of markers from KRAS to RAS testing is the new paradigm for biomarker testing in colorectal cancer.

High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial

PubMed Central

Lanza, Elaine; Hartman, Terryl J.; Albert, Paul S.; Shields, Rusty; Slattery, Martha; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Schatzkin, Arthur

2006-01-01

Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence. PMID:16772456

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel.

PubMed

Fernandez-Rozadilla, Ceres; Kartsonaki, Christiana; Woolley, Connor; McClellan, Michael; Whittington, Deb; Horgan, Gareth; Leedham, Simon; Kriaucionis, Skirmantas; East, James; Tomlinson, Ian

2018-03-06

Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors. We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms. Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations. PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.

Genetic polymorphisms of alcohol dehydrogense-1B and aldehyde dehydrogenase-2, alcohol flushing, mean corpuscular volume, and aerodigestive tract neoplasia in Japanese drinkers.

PubMed

Yokoyama, Akira; Mizukami, Takeshi; Yokoyama, Tetsuji

2015-01-01

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1%) and head and neck SCC (1.0%). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0% of 4,879 alcoholics had a history of (4.0%) or newly diagnosed (1.0%) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7% of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5% of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV≥106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia.

The prevalence of colorectal adenomas in asymptomatic Korean men and women.

PubMed

Yang, Moon Hee; Rampal, Sanjay; Sung, Jidong; Choi, Yoon-Ho; Son, Hee Jung; Lee, Jun Haeng; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Rhee, Jong Chul; Guallar, Eliseo; Cho, Juhee

2014-03-01

Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans. Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009. Among participants at average risk, those without a history of colorectal polyps or a family history of colorectal cancer, the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence of adenomas increased with age in both men and women, with a more marked increase for advanced adenoma. Participants with a family history of colorectal cancer or with a history of colorectal polyps had significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and sex-adjusted prevalence ratio = 1.16; 95% confidence interval, 1.09-1.22). The prevalence of adenomas increased annually in both men and women. In this large study of asymptomatic Korean men and women participating in a colonoscopy screening program, the prevalence of colorectal adenomas was comparable and possibly higher than previously reported in Western countries. Cost-effectiveness studies investigating the optimal age for starting colonoscopy screening and etiological studies to identify the reasons for the increasing trend in colorectal adenomas in Koreans are needed. ©2014 AACR.

Lifestyle predictors for non-participation and outcome in the second round of faecal immunochemical test in colorectal cancer screening.

PubMed

Knudsen, Markus Dines; Berstad, Paula; Hjartåker, Anette; Gulichsen, Elisabeth Haagensen; Hoff, Geir; de Lange, Thomas; Bernklev, Tomm; Botteri, Edoardo

2017-08-08

To reduce colorectal cancer (CRC) mortality through population-based screening programmes using faecal tests, it is important that individuals continue to participate in the repeated rounds of screening. We aimed to identify lifestyle predictors for discontinuation of faecal immunochemical test (FIT) screening after the first round, as well as lifestyle predictors for colorectal neoplasia detected in the second-round FIT screening. In this longitudinal study, we invited 6959 individuals aged 50-74 years from south-east Norway for a first round of FIT screening and to complete a self-reported lifestyle questionnaire on demographic factors, body mass index (BMI, kg m -2 ), smoking habits, physical activity, consumption of alcohol and dietary items. Two years later, we estimated the associations between these factors, non-participation and screening results in the second round of FIT screening using adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Of the 3114 responders to the questionnaire who completed the first-round FIT and who were invited to participate in second-round FIT screening, 540 (17%) did not participate. The OR and (95% CI) for discontinuation of FIT screening after the first round was 1.61 (1.24-2.10) for current smoking compared with non-smoking; 2.01 (1.25-3.24) for BMI⩾35 kg m -2 compared with BMI 16.9-24.9 kg m -2 and 0.70 (0.52-0.94) for physical activity in the third quartile vs the first. Among participants, smoking, high BMI and high alcohol consumption were associated with an increased odds of detecting colorectal neoplasia (n=107). These results may indicate that Norwegian FIT screening participants who discontinue after the first round have lifestyle behaviours associated with increased risk of CRC.

Ultrathin endoscopy versus high-resolution endoscopy for diagnosing superficial gastric neoplasia.

PubMed

Toyoizumi, Hirobumi; Kaise, Mitsuru; Arakawa, Hiroshi; Yonezawa, Jin; Yoshida, Yukinaga; Kato, Masayuki; Yoshimura, Noboru; Goda, Ken-ichi; Tajiri, Hisao

2009-08-01

Ultrathin endoscopy (UTE) is an acceptable and cost-effective alternative to EGD with the patient under sedation, although the diagnostic accuracy of UTE is not well established. To compare the diagnostic accuracy of UTE and high-resolution endoscopy (HRE) for superficial gastric neoplasia. Prospective comparative study. Academic center. Patients with or without superficial gastric neoplasia underwent peroral UTE and HRE, back-to-back in a random order while under standard sedation. The procedures were performed by 2 endoscopists who were blinded to the clinical information. The rate of missed lesions and misdiagnosis, sensitivity, and specificity for the diagnosis of gastric neoplasia when using pathology as the reference standard. In total, 126 lesions (41 superficial gastric neoplasias, 85 nonneoplastic lesions) were recorded in 57 enrolled patients. For the diagnosis of gastric neoplasia, the sensitivity of UTE (58.5%) was significantly (P = .021) lower than that of HRE (78%), and the specificity of UTE (91.8%) was significantly (P = .014) lower than that of HRE (100%). The rate of missed lesions and misdiagnosis of gastric neoplasias when using UTE (41.5%) was significantly (P > .001) higher than that of HRE (22.0%). The corresponding rate of neoplasias at the proximal portion (fornix and corpus) when using UTE (29%) was significantly (P = .002) higher than that of HRE (7.2%), although the rates of neoplasias at the distal portion (angulus and antrum) were comparable for UTE and HRE. Small sample numbers in an enriched population. The diagnostic accuracy of UTE is significantly lower than that of HRE for superficial gastric neoplasia, and this difference is particularly striking for neoplasias in the proximal stomach. For UTE to be used as an alternative modality, improvements in optical quality and the incorporation of additional procedures, including close-range observations and chromoendoscopy, are required to enhance visualization.

Profile of colorectal cancer in Eastern India.

PubMed

Sarkar, Snigdha; Mukherjee, Ramanuj; Paira, Susil Kumar; Roy, Bipradas; Banerjee, Shubhabrata; Mukherjee, Saibal Kumar

2012-12-01

Although colorectal cancer is a major cause of concern in the western population, recent studies are showing the incidence and mortality of colorectal cancer to be rapidly rising in Asia. The present study is an insight into the epidemiological profile of colorectal cancer of a representative Eastern Indian population. Over a period of three years, all histologically proved patients with colorectal cancer were assessed for age, sex, body mass index, dietary habits, socioeconomic status and stage of disease. Of a total of 168 patients male to female ratio was 1.7:1.The mean age of presentation was 47.01 years. Although colorectal cancer has been known as a disease of sedentary obese men, 41.66% of the patients were from a low socioeconomic rural set-up and 40.47% were involved in heavy physical labour with only 15% of being obese; 62% patients were harbouring a locally advanced disease at the time of presentation. The epidemiological pattern of colorectal cancer in India is different from that of the west as regards to earlier age of presentation, prevalence in low socio economic class with low fat diet and scanty meat intake.

Modeling human endothelial cell transformation in vascular neoplasias

PubMed Central

Wen, Victoria W.; MacKenzie, Karen L.

2013-01-01

Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia. PMID:24046386

MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

PubMed

Farchoukh, Lama; Kuan, Shih-Fan; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

2016-10-01

Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (P<0.001). Both MLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P<0.001). There was no significant difference in mucinous differentiation, tumor-infiltrating lymphocytes, Crohn-like reaction, and medullary differentiation between the 3 tumor groups. Using Kaplan-Meier survival functions, there was no significant difference in disease-specific survival between the 3 patient groups (P>0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas

Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer.

PubMed

Yalcin, Suayib; Oksuzoglu, Berna; Tekuzman, Gülten; Engin, Hüseyin; Celik, Ismail; Turker, Alev; Barista, Ibrahim; Gullu, Ibrahim; Guler, Nilufer; Altundag, Kadri; Ozisik, Yavuz; Kars, Ayse

2003-11-01

In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.

Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis.

PubMed

Yang, Hua; Xia, Bing-Qing; Jiang, Bo; Wang, Guozhen; Yang, Yi-Peng; Chen, Hao; Li, Bing-Sheng; Xu, An-Gao; Huang, Yun-Bo; Wang, Xin-Ying

2013-08-01

The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation

Effect of KRAS codon13 mutations in patients with advanced colorectal cancer (advanced CRC) under oxaliplatin containing chemotherapy. Results from a translational study of the AIO colorectal study group

PubMed Central

2012-01-01

Background To evaluate the value of KRAS codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines. Methods Tumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS). Results 201 patients were analysed for KRAS mutation (61.2% males; mean age 64.2 ± 8.6 years). KRAS mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three KRAS genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens. Conclusions Our data suggest that the type of KRAS mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important. Trial registration number 2002-04-017 PMID:22876876

The role of APC in WNT pathway activation in serrated neoplasia.

PubMed

Borowsky, Jennifer; Dumenil, Troy; Bettington, Mark; Pearson, Sally-Ann; Bond, Catherine; Fennell, Lochlan; Liu, Cheng; McKeone, Diane; Rosty, Christophe; Brown, Ian; Walker, Neal; Leggett, Barbara; Whitehall, Vicki

2018-03-01

Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively. WNT pathway activation was seen to a lesser extent in serrated pathway lesions. It occurred at the transition to dysplasia in serrated polyps with a significant increase in nuclear β-catenin labeling from sessile serrated adenomas (10%) to sessile serrated adenomas with dysplasia (55%) and traditional serrated adenomas (9%) to traditional serrated adenomas with dysplasia (39%) (P=0.0001). However, unlike the conventional pathway, truncating APC mutations were rare in the serrated pathway lesions especially sessile serrated adenomas even when dysplastic (15%) and in the BRAF mutant cancers with microsatellite instability that arise from them (8%). In contrast, APC missense mutations that were rare in conventional pathway adenomas and cancers (3% in BRAF wild-type cancers) were more frequent in BRAF mutant cancers with microsatellite instability (32%). We conclude that increased WNT signaling is important in the transition to malignancy in the serrated pathway but that APC mutation is less common and the spectrum of mutations is different than in conventional colorectal carcinogenesis. Moderate impact APC mutations and non-APC-related causes of increased WNT signaling may have a more important role in serrated neoplasia than the truncating APC mutations

B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

PubMed

Wang, Jiasheng; He, Gan; Yang, Qiang; Bai, Lian; Jian, Bin; Li, Qugang; Li, Zhongfu

2018-06-01

The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (P<0.001). Spearman's rank correlation analysis revealed that Bcl-2 expression was negatively correlated with pathological grade and Tumor-Node-Metastasis (TNM) stage (-0.827 and -0.388, respectively; P<0.05). Bcl-2 expression was revealed to be a significant prognostic indicator of colorectal carcinoma [relative risk (95% CI), 0.703 (0.552-0.895); P<0.05]. The log-rank test revealed a significant association between low Bcl-2 expression and reduced overall survival (P=0.039), as well as a significant association between older age (>55 years) and reduced overall survival (P<0.001) in Chinese patients with colorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in

An Optimal Mean Based Block Robust Feature Extraction Method to Identify Colorectal Cancer Genes with Integrated Data.

PubMed

Liu, Jian; Cheng, Yuhu; Wang, Xuesong; Zhang, Lin; Liu, Hui

2017-08-17

It is urgent to diagnose colorectal cancer in the early stage. Some feature genes which are important to colorectal cancer development have been identified. However, for the early stage of colorectal cancer, less is known about the identity of specific cancer genes that are associated with advanced clinical stage. In this paper, we conducted a feature extraction method named Optimal Mean based Block Robust Feature Extraction method (OMBRFE) to identify feature genes associated with advanced colorectal cancer in clinical stage by using the integrated colorectal cancer data. Firstly, based on the optimal mean and L 2,1 -norm, a novel feature extraction method called Optimal Mean based Robust Feature Extraction method (OMRFE) is proposed to identify feature genes. Then the OMBRFE method which introduces the block ideology into OMRFE method is put forward to process the colorectal cancer integrated data which includes multiple genomic data: copy number alterations, somatic mutations, methylation expression alteration, as well as gene expression changes. Experimental results demonstrate that the OMBRFE is more effective than previous methods in identifying the feature genes. Moreover, genes identified by OMBRFE are verified to be closely associated with advanced colorectal cancer in clinical stage.

Colorectal Cancer Screening Based on Age and Gender

PubMed Central

Wong, Martin C.S.; Ching, Jessica Y.L.; Chan, Victor C.W.; Lam, Thomas Y.T.; Luk, Arthur K.C.; Wong, Sunny H.; Ng, Siew C.; Ng, Simon S.M.; Wu, Justin C.Y.; Chan, Francis K.L.; Sung, Joseph J.Y.

2016-01-01

Abstract We evaluated whether age- and gender-based colorectal cancer screening is cost-effective. Recent studies in the United States identified age and gender as 2 important variables predicting advanced proximal neoplasia, and that women aged <60 to 70 years were more suited for sigmoidoscopy screening due to their low risk of proximal neoplasia. Yet, quantitative assessment of the incremental benefits, risks, and cost remains to be performed. Primary care screening practice (2008–2015). A Markov modeling was constructed using data from a screening cohort. The following strategies were compared according to the Incremental Cost Effectiveness Ratio (ICER) for 1 life-year saved: flexible sigmoidoscopy (FS) 5 yearly; colonoscopy 10 yearly; FS for each woman at 50- and 55-year old followed by colonoscopy at 60- and 70-year old; FS for each woman at 50-, 55-, 60-, and 65-year old followed by colonoscopy at 70-year old; FS for each woman at 50-, 55-, 60-, 65-, and 70-year old. All male subjects received colonoscopy at 50-, 60-, and 70-year old under strategies 3 to 5. From a hypothetical population of 100,000 asymptomatic subjects, strategy 2 could save the largest number of life-years (4226 vs 2268 to 3841 by other strategies). When compared with no screening, strategy 5 had the lowest ICER (US$42,515), followed by strategy 3 (US$43,517), strategy 2 (US$43,739), strategy 4 (US$47,710), and strategy 1 (US$56,510). Strategy 2 leads to the highest number of bleeding and perforations, and required a prohibitive number of colonoscopy procedures. Strategy 5 remains the most cost-effective when assessed with a wide range of deterministic sensitivity analyses around the base case. From the cost effectiveness analysis, FS for women and colonoscopy for men represent an economically favorable screening strategy. These findings could inform physicians and policy-makers in triaging eligible subjects for risk-based screening, especially in countries with limited colonoscopic

Effect of rising chemotherapy costs on the cost savings of colorectal cancer screening.

PubMed

Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Zauber, Ann G; Habbema, J Dik F; Kuipers, Ernst J

2009-10-21

Although colorectal cancer screening is cost-effective, it requires a considerable net investment by governments or insurance companies. If screening was cost saving, governments and insurance companies might be more inclined to invest in colorectal cancer screening programs. We examined whether colorectal cancer screening would become cost saving with the widespread use of the newer, more expensive chemotherapies. We used the MISCAN-Colon microsimulation model to assess whether widespread use of new chemotherapies would affect the treatment savings of colorectal cancer screening in the general population. We considered three scenarios for chemotherapy use: the past, the present, and the near future. We assumed that survival improved and treatment costs for patients diagnosed with advanced stages of colorectal cancer increased over the scenarios. Screening strategies considered were annual guaiac fecal occult blood testing (FOBT), annual immunochemical FOBT, sigmoidoscopy every 5 years, colonoscopy every 10 years, and the combination of sigmoidoscopy every 5 years and annual guaiac FOBT. Analyses were conducted from the perspective of the health-care system for a cohort of 50-year-old individuals who were at average risk of colorectal cancer and were screened with 100% adherence from age 50 years to age 80 years and followed up until death. Compared with no screening, the treatment savings from preventing advanced colorectal cancer and colorectal cancer deaths by screening more than doubled with the widespread use of new chemotherapies. The lifetime average treatment savings were larger than the lifetime average screening costs for screening with Hemoccult II, immunochemical FOBT, sigmoidoscopy, and the combination of sigmoidoscopy and Hemoccult II (average savings vs costs per individual in the population: Hemoccult II, $1398 vs $859; immunochemical FOBT, $1756 vs $1565; sigmoidoscopy, $1706 vs $1575; sigmoidoscopy and Hemoccult II $1931 vs $1878). Colonoscopy did

Lymph Node Size on Computed Tomography Images Is a Predictive Indicator for Lymph Node Metastasis in Patients with Colorectal Neuroendocrine Tumors.

PubMed

Tanaka, Toshiaki; Nozawa, Hiroaki; Kawai, Kazushige; Hata, Keisuke; Kiyomatsu, Tomomichi; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Murono, Koji; Watanabe, Toshiaki

2017-01-01

Colorectal neuroendocrine tumors (NET) are a rare manifestation of colorectal neoplasia, requiring for radical dissection of the regional lymph nodes along with colorectal resection similar to that required for colorectal cancer. However, thus far, no reports have described the ability of computed tomography (CT) to predict lymph node involvement. In this study, we revealed the prediction rate of lymph node metastasis using contrast-enhanced CT. A total of 21 patients with colorectal NET undergoing colorectal resection were recruited from January 2010 to June 2016. We compared the CT findings between samples with or without pathologically proven lymph node metastasis, in each field (pericolic/perirectal and intermediate nodes). Within the pericolic/perirectal field, any lymph node larger than 5 mm in the CT images was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and area under ROC curve (AUC) of 66.7%, 87.5%, and 0.844, respectively. Within the intermediate field, any visible lymph node on the CT was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and AUC of 100%, 76.4%, and 0.890, respectively. In addition, when we observed lymph nodes larger than 3 mm on the CT images, the sensitivity and specificity were 100% and 82.4%, respectively, with an AUC of 0.8971. CT images provide predictive information for lymph node metastasis with a high rate of accuracy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Aspirin and the Risk of Colorectal Cancer in Relation to the Expression of 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH, HPGD)

PubMed Central

Fink, Stephen P.; Yamauchi, Mai; Nishihara, Reiko; Jung, Seungyoun; Kuchiba, Aya; Wu, Kana; Cho, Eunyoung; Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji; Markowitz, Sanford D.; Chan, Andrew T.

2014-01-01

Aspirin use reduces the risk of colorectal neoplasia, at least in part, through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2)-related pathways. Hydroxyprostaglandin dehydrogenase 15-(NAD) (15-PGDH, HPGD) is downregulated in colorectal cancers and functions as a metabolic antagonist of PTGS2. We hypothesized that the effect of aspirin may be antagonized by low 15-PGDH expression in the normal colon. In the Nurses’ Health Study and the Health Professionals Follow-up Study, we collected data on aspirin use and other risk factors every two years and followed up participants for diagnoses of colorectal cancer. Duplication-method Cox proportional, multivariable-adjusted, cause-specific hazards regression for competing risks data was used to compute hazard ratios (HRs) for incident colorectal cancer according to 15-PGDH mRNA expression level measured in normal mucosa from colorectal cancer resections. Among 127,865 participants, we documented 270 colorectal cancer cases that developed during 3,166,880 person-years of follow-up and from which we could assess 15-PGDH expression. Compared with nonuse, regular aspirin use was associated with lower risk of colorectal cancer that developed within a background of colonic mucosa with high 15-PGDH expression (multivariable HR=0.49; 95% CI, 0.34–0.71), but not with low 15-PGDH expression (multivariable HR=0.90; 95% CI, 0.63–1.27) (P for heterogeneity=0.018). Regular aspirin use was associated with lower incidence of colorectal cancers arising in association with high 15-PGDH expression, but not with low 15-PGDH expression in normal colon mucosa. This suggests that 15-PGDH expression level in normal colon mucosa may serve as a biomarker which may predict stronger benefit from aspirin chemoprevention. PMID:24760190

Distinguishing rhinitis and nasal neoplasia by radiography.

PubMed

Russo, M; Lamb, C R; Jakovljevic, S

2000-01-01

To compare the incidence of radiographic signs in dogs with rhinitis and primary nasal neoplasia and to assess the performance of observers for distinguishing these conditions, the nasal radiographs of 72 dogs with either rhinitis (n = 42) or primary nasal neoplasia (n = 30) were examined by two independent observers using custom-designed forms to record their interpretations. Rhinitis was associated with a higher incidence of focal or multifocal lesions, localised soft tissue opacities, lucent foci, and a lack of frontal sinus involvement. Neoplasia was associated with soft tissue opacities and loss of turbinate detail that affected the entire ipsilateral nasal cavity, signs of invasion of the bones surrounding the nasal cavity, and soft tissue/fluid opacities within the ipsilateral frontal sinus. The signs with the highest positive predictive value (PPV) for rhinitis were absence of frontal sinus lesions and lucent foci in nasal cavity (PPV of each 82%), and invasion of surrounding bones for neoplasia (PPV 88%). There were no significant differences in the position of the lesion within the nasal cavity, incidence of unilateral versus bilateral lesions, calcified lesions, or absence of teeth. There was moderate agreement between observers about the diagnosis (kappa 0.59). Areas (SE) under ROC curves were 0.94 (0.03) and 0.96 (0.03) for observers A and B, respectively (not significantly different; P = 0.68). These results indicate a high accuracy for radiologists examining dogs with nasal diseases. Differentiation of rhinitis and nasal neoplasia should be based on finding combinations of radiologic signs that together have a high PPV. Differences in interpretation between experienced observers in this study suggest that certain signs are potential sources of error.

Surgery for cervical intraepithelial neoplasia

PubMed Central

Martin-Hirsch, Pierre PL; Paraskevaidis, Evangelos; Bryant, Andrew; Dickinson, Heather O; Keep, Sarah L

2014-01-01

Background Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. Objectives To assess the effectiveness and safety of alternative surgical treatments for CIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to April 2009). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. Main results Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. Authors’ conclusions The evidence

PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk.

PubMed

Rifkin, Samara B; Shrubsole, Martha J; Cai, Qiuyin; Smalley, Walter E; Ness, Reid M; Swift, Larry L; Zheng, Wei; Murff, Harvey J

2017-06-01

Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.

Experience in colon sparing surgery in North America: advanced endoscopic approaches for complex colorectal lesions.

PubMed

Gorgun, Emre; Benlice, Cigdem; Abbas, Maher A; Steele, Scott

2018-07-01

Need for colon sparing interventions for premalignant lesions not amenable to conventional endoscopic excision has stimulated interest in advanced endoscopic approaches. The aim of this study was to report a single institution's experience with these techniques. A retrospective review was conducted of a prospectively collected database of all patients referred between 2011 and 2015 for colorectal resection of benign appearing deemed endoscopically unresectable by conventional endoscopic techniques. Patients were counseled for endoscopic submucosal dissection (ESD) with possible combined endoscopic-laparoscopic surgery (CELS) or alternatively colorectal resection if unable to resect endoscopically or suspicion for cancer. Lesion characteristic, resection rate, complications, and outcomes were evaluated. 110 patients were analyzed [mean age 64 years, female gender 55 (50%), median body mass index 29.4 kg/m 2 ]. Indications for interventions were large polyp median endoscopic size 3 cm (range 1.5-6.5) and/or difficult location [cecum (34.9%), ascending colon (22.7%), transverse colon (14.5%), hepatic flexure (11.8%), descending colon (6.3%), sigmoid colon (3.6%), rectum (3.6%), and splenic flexure (2.6%)]. Lesion morphology was sessile (N = 98, 93%) and pedunculated (N = 12, 7%). Successful endoscopic resection rate was 88.2% (N = 97): ESD in 69 patients and CELS in 28 patients. Complication rate was 11.8% (13/110) [delayed bleeding (N = 4), perforation (N = 3), organ-space surgical site infection (SSI) (N = 2), superficial SSI (N = 1), and postoperative ileus (N = 3)]. Out of 110 patients, 13 patients (11.8%) required colectomy for technical failure (7 patients) or carcinoma (6 patients). During a median follow-up of 16 months (range 6-41 months), 2 patients had adenoma recurrence. Advanced endoscopic surgery appears to be a safe and effective alternative to colectomy for patients with complex premalignant lesions deemed

The gut microbiota in conventional and serrated precursors of colorectal cancer.

PubMed

Peters, Brandilyn A; Dominianni, Christine; Shapiro, Jean A; Church, Timothy R; Wu, Jing; Miller, George; Yuen, Elizabeth; Freiman, Hal; Lustbader, Ian; Salik, James; Friedlander, Charles; Hayes, Richard B; Ahn, Jiyoung

2016-12-30

Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types. Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases (n = 144), serrated polyp cases (n = 73), or polyp-free controls (n = 323). CA cases were further classified as proximal (n = 87) or distal (n = 55) and as non-advanced (n = 121) or advanced (n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups. CA cases had lower species richness in stool than controls (p = 0.03); in particular, this association was strongest for advanced CA cases (p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls (p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases. Our results indicate that

Reduced 30-Day Mortality After Laparoscopic Colorectal Cancer Surgery: A Population Based Study From the Dutch Surgical Colorectal Audit (DSCA).

PubMed

Gietelink, Lieke; Wouters, Michel W J M; Bemelman, Willem A; Dekker, Jan Willem; Tollenaar, Rob A E M; Tanis, Pieter J

2016-07-01

To evaluate the impact of a laparoscopic resection on postoperative mortality after colorectal cancer surgery. The question whether laparoscopic resection (LR) compared with open surgery [open resection (OR)] for colorectal cancer influences the risk of postoperative mortality remains unresolved. Several meta-analyses showed a trend but failed to reach statistical significance. The exclusion of high-risk patients and insufficient power might be responsible for that. We analyzed the influence of LR on postoperative mortality in a risk-stratified comparison and secondly, we studied the effect of LR on postoperative morbidity. Data from the Dutch Surgical Colorectal Audit (2010-2013) were used. Homogenous subgroups of patients were defined on the basis of factors influencing the choice of surgical approach and risk factors for postoperative mortality. Crude mortality rates were compared between LR and OR. The influence of LR on postoperative complications was evaluated using both univariable and multivariable analyses. In patients undergoing elective surgery for nonlocally advanced, nonmetastasized colon cancer, LR was associated with a significant lower risk of postoperative mortality than OR in 20/22 subgroups. LR was independently associated with a lower risk of cardiac (odds ratio: 0.73, 95% confidence interval: 0.66-0.82) and respiratory (odds ratio: 0.73, 95% confidence interval: 0.64-0.84) complications. LR reduces the risk of postoperative mortality compared with OR in elective setting in patients with nonlocally advanced, nonmetastasized colorectal cancer. Especially elderly frail patients seem to benefit because of reduced cardiopulmonary complications. These findings support widespread implementation of LR for colorectal cancer also in patients at high operative risk.

Advanced imaging technologies increase detection of dysplasia and neoplasia in patients with Barrett's esophagus: a meta-analysis and systematic review.

PubMed

Qumseya, Bashar J; Wang, Haibo; Badie, Nicole; Uzomba, Rosemary N; Parasa, Sravanthi; White, Donna L; Wolfsen, Herbert; Sharma, Prateek; Wallace, Michael B

2013-12-01

US guidelines recommend surveillance of patients with Barrett's esophagus (BE) to detect dysplasia. BE conventionally is monitored via white-light endoscopy (WLE) and a collection of random biopsy specimens. However, this approach does not definitively or consistently detect areas of dysplasia. Advanced imaging technologies can increase the detection of dysplasia and cancer. We investigated whether these imaging technologies can increase the diagnostic yield for the detection of neoplasia in patients with BE, compared with WLE and analysis of random biopsy specimens. We performed a systematic review, using Medline and Embase, to identify relevant peer-review studies. Fourteen studies were included in the final analysis, with a total of 843 patients. Our metameter (estimate) of interest was the paired-risk difference (RD), defined as the difference in yield of the detection of dysplasia or cancer using advanced imaging vs WLE. The estimated paired-RD and 95% confidence interval (CI) were obtained using random-effects models. Heterogeneity was assessed by means of the Q statistic and the I(2) statistic. An exploratory meta-regression was performed to look for associations between the metameter and potential confounders or modifiers. Overall, advanced imaging techniques increased the diagnostic yield for detection of dysplasia or cancer by 34% (95% CI, 20%-56%; P < .0001). A subgroup analysis showed that virtual chromoendoscopy significantly increased the diagnostic yield (RD, 0.34; 95% CI, 0.14-0.56; P < .0001). The RD for chromoendoscopy was 0.35 (95% CI, 0.13-0.56; P = .0001). There was no significant difference between virtual chromoendoscopy and chromoendoscopy, based on Student t test analysis (P = .45). Based on a meta-analysis, advanced imaging techniques such as chromoendoscopy or virtual chromoendoscopy significantly increase the diagnostic yield for identification of dysplasia or cancer in patients with BE. Copyright © 2013 AGA Institute. Published by

How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials.

PubMed

Bonnetain, F; Borg, C; Adams, R R; Ajani, J A; Benson, A; Bleiberg, H; Chibaudel, B; Diaz-Rubio, E; Douillard, J Y; Fuchs, C S; Giantonio, B J; Goldberg, R; Heinemann, V; Koopman, M; Labianca, R; Larsen, A K; Maughan, T; Mitchell, E; Peeters, M; Punt, C J A; Schmoll, H J; Tournigand, C; de Gramont, A

2017-09-01

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All

[Nutrition and colorectal cancer].

PubMed

Ströhle, Alexander; Maike, Wolters; Hahn, Andreas

2007-01-01

Diet plays an important role in the pathogenesis of colorectal cancer. Current prospective cohort studies and metaanalysis enable a reevaluation of how food or nutrients such as fiber and fat influence cancer risk. Based on the evidence criteria of the WHO/FAD, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. e available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to an evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. The available data on alcohol consumption indicate a possible risk increasing effect. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today. Prospective cohort studies suggest that people who get higher than average amounts of folic acid from multivitamin supplements have lower risks of colorectal cancer. The evidence for a risk reducing effect of calcium, selenium, vitamin D and vitamin E on colorectal cancer is insufficient. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by low-fat dairy products, fish, and poultry can be recommended. In

Radiology of colorectal cancer.

PubMed

Pijl, M E J; Chaoui, A S; Wahl, R L; van Oostayen, J A

2002-05-01

In the past 20 years, the radiology of colorectal cancer has evolved from the barium enema to advanced imaging modalities like phased array magnetic resonance imaging (MRI), virtual colonoscopy and positron emission tomography (PET). Nowadays, primary rectal cancers are preferably imaged with transrectal ultrasound or MRI, while barium enema is still the most often used technique for imaging of colonic cancers. Virtual colonoscopy is rapidly evolving and might considerably change the imaging of colorectal cancer in the near future. The use of virtual colonoscopy for screening purposes and imaging of the colon in occlusive cancer or incomplete colonoscopies is currently under evaluation. The main role of PET is in detecting tumour recurrences, both locally and distantly. Techniques to fuse cross-sectional anatomical (computer tomography (CT) and MRI) and functional (PET) images are being developed. Apart from diagnostic imaging, the radiologists has added image-guided minimally invasive treatments of colorectal liver metastases to their arsenal. The radio-frequency ablation technique is now widely available, and can be used during laparotomy or percutaneously in selected cases.

Obesity-related parameters and colorectal adenoma development.

PubMed

Kim, Tae Jun; Kim, Jee Eun; Choi, Yoon-Ho; Hong, Sung Noh; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Kim, Min-Ji; Jung, Sin-Ho; Son, Hee Jung

2017-12-01

Obesity increases the risk of colorectal adenoma and colorectal cancer. However, the obesity-related parameters that are best for assessing the risk of colorectal adenoma development remain unclear. We analyzed the parameters that may best describe the association between obesity and colorectal adenoma development. In this retrospective cohort study, 3405 individuals underwent screening colonoscopy during routine health examinations. We measured body mass index; waist circumference; and metabolic parameters such as high-density lipoprotein-cholesterol, glucose, triglyceride, and systolic blood pressure. We analyzed the risk of developing colorectal adenoma, relative to obesity-related parameters, over a mean interval of 5.8 years from baseline colonoscopy. In a multivariate analysis, waist circumference was the only obesity-related marker associated with an increased risk of metachronous colorectal adenoma. Men with waist circumferences ≥85 cm and women with waist circumference ≥82 cm had a 31% increased risk of metachronous colorectal adenoma compared to those with smaller waist circumferences [odds ratio (OR) 1.31; 95% confidence interval (CI, 1.09-1.57)]. Other factors associated with metachronous colorectal adenoma were age (OR, 1.03; 95% CI 1.02-1.04), male sex (OR 1.49; 95% CI 1.17-1.88), alcohol consumption ≥3/week (OR 1.33; 95% CI 1.10-1.62), the number of adenoma at baseline (OR 1.21; 95% CI 1.10-1.33), and the presence of advanced adenoma at baseline (OR 1.60; 95% CI 1.24-2.06). Our findings suggest that central obesity, represented by waist circumference, is a significant predictor of metachronous colorectal adenoma, independent of body mass index and other metabolic variables.

[Future of laparoscopy in colorectal cancer surgery].

PubMed

Grotowski, Maciej

2004-07-01

Laparoscopic surgery has been associated with less postoperative pain, an early return of bowel function, a shorter period of hospitalization and disability, and better cosmetic results. In the past decade laparoscopic techniques are increasingly being applied to colorectal surgical procedures. Diagnostic laparoscopy, the creation of stomas, and limited resections are becoming reasonable indications for benign diseases. However, the application of laparoscopic techniques to the curative resection of colorectal cancer is still controversial, owing to reports of cancer recurrence at the port site wounds. Port-site recurrence remains a leading concern regarding the widespread acceptance of laparoscopic resection for colorectal carcinoma. The last reports has presented that with careful technique, training and experience wound recurrences are rarely seen, suggesting that this phenomenon is primarily technique and advanced cancer stages related. The final results of the large randomized prospective studies may well determine the role of laparoscopy for colorectal cancer in the near future.

Crypt dynamics and colorectal cancer: advances in mathematical modelling.

PubMed

van Leeuwen, I M M; Byrne, H M; Jensen, O E; King, J R

2006-06-01

Mathematical modelling forms a key component of systems biology, offering insights that complement and stimulate experimental studies. In this review, we illustrate the role of theoretical models in elucidating the mechanisms involved in normal intestinal crypt dynamics and colorectal cancer. We discuss a range of modelling approaches, including models that describe cell proliferation, migration, differentiation, crypt fission, genetic instability, APC inactivation and tumour heterogeneity. We focus on the model assumptions, limitations and applications, rather than on the technical details. We also present a new stochastic model for stem-cell dynamics, which predicts that, on average, APC inactivation occurs more quickly in the stem-cell pool in the absence of symmetric cell division. This suggests that natural niche succession may protect stem cells against malignant transformation in the gut. Finally, we explain how we aim to gain further understanding of the crypt system and of colorectal carcinogenesis with the aid of multiscale models that cover all levels of organization from the molecular to the whole organ.

Secondary intracranial neoplasia in the dog: 177 cases (1986-2003).

PubMed

Snyder, J M; Lipitz, L; Skorupski, K A; Shofer, F S; Van Winkle, T J

2008-01-01

This study investigates the frequency, location, and clinical findings associated with 177 secondary brain tumors in dogs. Secondary intracranial neoplasia is more common than primary intracranial neoplasia in dogs during the time period studied, and hemangiosarcoma (HSA) is the most common secondary intracranial tumor. One hundred and seventy-seven client-owned dogs presented to the Matthew J. Ryan Veterinary Hospital between 1986 and 2003. Medical records were searched for a diagnosis of intracranial neoplasia in dogs who underwent complete postmortem examination. Of these dogs, those with a diagnosis of primary intracranial neoplasia were excluded. Of the 177 secondary brain tumors, 51 (29%) were HSAs, 44 (25%) were pituitary tumors, 21 (12%) were lymphosarcomas, and 21 (12%) were metastatic carcinomas. The average age at diagnosis was 9.6 +/- 3.0 years. Most tumors were located in the cerebrum, and a mentation change was the most common presenting clinical sign. On postmortem examination, the same tumor that was in the brain was also present in the lung in 84 cases (47%), in the kidney in 62 cases (35%), and in the heart in 55 cases (31%). Secondary intracranial neoplasia in dogs was more common than primary intracranial neoplasia during the time period studied. Many of these dogs had related disease in other body systems that was apparent on diagnostic tests such as thoracic radiography.

Toward the Elimination of Colorectal Cancer Disparities Among African Americans.

PubMed

Coughlin, Steven S; Blumenthal, Daniel S; Seay, Shirley Jordan; Smith, Selina A

2016-12-01

In the USA, race and socioeconomic status are well-known factors associated with colorectal cancer incidence and mortality rates. These are higher among blacks than whites and other racial/ethnic groups. In this article, we review opportunities to address disparities in colorectal cancer incidence, mortality, and survivorship among African Americans. First, we summarize the primary prevention of colorectal cancer and recent advances in the early detection of the disease and disparities in screening. Then, we consider black-white disparities in colorectal cancer treatment and survival including factors that may contribute to such disparities and the important roles played by cultural competency, patient trust in one's physician, and health literacy in addressing colorectal cancer disparities, including the need for studies involving the use of colorectal cancer patient navigators who are culturally competent. To reduce these disparities, intervention efforts should focus on providing high-quality screening and treatment for colorectal cancer and on educating African Americans about the value of diet, weight control, screening, and treatment. Organized approaches for delivering colorectal cancer screening should be accompanied by programs and policies that provide access to diagnostic follow-up and treatment for underserved populations.

Toward the Elimination of Colorectal Cancer Disparities Among African Americans

PubMed Central

Blumenthal, Daniel S.; Seay, Shirley Jordan; Smith, Selina A.

2015-01-01

Background In the USA, race and socioeconomic status are well-known factors associated with colorectal cancer incidence and mortality rates. These are higher among blacks than whites and other racial/ethnic groups. Methods In this article, we review opportunities to address disparities in colorectal cancer incidence, mortality, and survivorship among African Americans. Results First, we summarize the primary prevention of colorectal cancer and recent advances in the early detection of the disease and disparities in screening. Then, we consider black-white disparities in colorectal cancer treatment and survival including factors that may contribute to such disparities and the important roles played by cultural competency, patient trust in one’s physician, and health literacy in addressing colorectal cancer disparities, including the need for studies involving the use of colorectal cancer patient navigators who are culturally competent. Conclusion To reduce these disparities, intervention efforts should focus on providing high-quality screening and treatment for colorectal cancer and on educating African Americans about the value of diet, weight control, screening, and treatment. Organized approaches for delivering colorectal cancer screening should be accompanied by programs and policies that provide access to diagnostic follow-up and treatment for underserved populations. PMID:27294749

Obesity Increases Prevalence of Colonic Adenomas at Screening Colonoscopy: A Canadian Community-Based Study

PubMed Central

Chen, Grant I.; Devlin, Tim; Gibbs, Alison; Murray, Iain C.; Tran, Stanley; Weigensberg, Corey

2017-01-01

Background and Aims Obesity is a risk factor for colorectal neoplasia. We examined the influence of obesity and metabolic syndrome (MetS) on prevalence of neoplasia at screening colonoscopy. Methods We evaluated 2020 subjects undergoing first screening colonoscopy. Body mass index (BMI) was calculated at enrolment. Hyperlipidemia (HL), hypertension (HT), and diabetes mellitus (DM) were identified. Details of colonoscopy, polypectomy, and histology were recorded. Odds for adenomas (A) and advanced adenomas (ADV) in overweight (BMI 25.1–30) and obese (BMI > 30) subjects were assessed by multinomial regression, adjusted for covariates. Analyses included relationships between HL, HT, DM, age, tobacco usage, and neoplasia. Discriminatory power of HT, HL, DM, and BMI for neoplasia was assessed by binary logistic regression. Odds were calculated for neoplasia in each colonic segment related to BMI. Results A and ADV were commoner in overweight and obese males, obese females, older subjects, and smokers. HL, HT, and DM were associated with increased odds for neoplasia, significantly for A with hypertension. BMI alone predicted neoplasia as well as HT, HL, DM, or combinations thereof. All segments of the colon were affected. Multiple polyps were particularly prevalent in the obese. Conclusions Obesity and MetS are risk factors for colonic neoplasia in a Canadian population. PMID:28781966

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

PubMed

Petry, K U; Köchel, H; Bode, U; Schedel, I; Niesert, S; Glaubitz, M; Maschek, H; Kühnle, H

1996-01-01

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

Examining racial disparities in colorectal cancer care.

PubMed

Berry, Jamillah; Bumpers, Kevin; Ogunlade, Vickie; Glover, Roni; Davis, Sharon; Counts-Spriggs, Margaret; Kauh, John; Flowers, Christopher

2009-01-01

African Americans are disproportionately burdened with colorectal cancer. Although incidence and mortality rates have declined in the past two decades, the disparity in health outcomes has progressively increased. This comprehensive review examines the existing literature regarding racial disparities in colorectal cancer screening, stage at diagnosis, and treatment to determine if differences exist in the quality of care delivered to African Americans. A comprehensive review of relevant literature was performed. Two databases (EBSCOHOST Academic Search Premier and Scopus) were searched from 2000 to 2007. Articles that assessed racial disparities in colorectal cancer screening, stage of disease at diagnosis, and treatment were selected. The majority of studies identified examined colorectal cancer screening outcomes. Although racial disparities in screening have diminished in recent years, African American men and women continue to have higher colorectal cancer incidence and mortality rates and are diagnosed at more advanced stages. Several studies regarding stage of disease at diagnosis identified socioeconomic status (SES) and health insurance status as major determinants of disparity. However, some studies found significant racial disparities even after controlling for these factors. Racial disparities in treatment were also found at various diagnostic stages. Many factors affecting disparities between African Americans and Whites in colorectal cancer incidence and mortality remain unexplained. Although the importance of tumor biology, genetics, and lifestyle risk factors have been established, prime sociodemographic factors need further examination to understand variances in the care of African Americans diagnosed with colorectal cancer.

Molecular Diagnostics in Colorectal Carcinoma: Advances and Applications for 2018.

PubMed

Bhalla, Amarpreet; Zulfiqar, Muhammad; Bluth, Martin H

2018-06-01

The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk Stratification and Shared Decision Making for Colorectal Cancer Screening: A Randomized Controlled Trial.

PubMed

Schroy, Paul C; Duhovic, Emir; Chen, Clara A; Heeren, Timothy C; Lopez, William; Apodaca, Danielle L; Wong, John B

2016-05-01

Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer (CRC) screening, yet providers often fail to comply with patient preferences that differ from their own. To determine whether risk stratification for advanced colorectal neoplasia (ACN) influences provider willingness to comply with patient preferences when selecting a desired CRC screening option. Randomized controlled trial. Asymptomatic, average-risk patients due for CRC screening in an urban safety net health care setting. Patients were randomized 1:1 to a decision aid alone (n= 168) or decision aid plus risk assessment (n= 173) arm between September 2012 and September 2014. The primary outcome was concordance between patient preference and test ordered; secondary outcomes included patient satisfaction with the decision-making process, screening intentions, test completion rates, and provider satisfaction. Although providers perceived risk stratification to be useful in selecting an appropriate screening test for their average-risk patients, no significant differences in concordance were observed between the decision aid alone and decision aid plus risk assessment groups (88.1% v. 85.0%,P= 0.40) or high- and low-risk groups (84.5% v. 87.1%,P= 0.51). Concordance was highest for colonoscopy and relatively low for tests other than colonoscopy, regardless of study arm or risk group. Failure to comply with patient preferences was negatively associated with satisfaction with the decision-making process, screening intentions, and test completion rates. Single-institution setting; lack of provider education about the utility of risk stratification into their decision making. Providers perceived risk stratification to be useful in their decision making but often failed to comply with patient preferences for tests other than colonoscopy, even among those deemed to be at low risk of ACN. © The Author(s) 2016.

Evolving concepts in the management of lobular neoplasia.

PubMed

Anderson, Benjamin O; Calhoun, Kristine E; Rosen, Eric L

2006-05-01

Lobular neoplasia broadly defines the spectrum of changes within the lobule, ranging from atypical lobular hyperplasia (ALH) to lobular carcinoma in situ (LCIS). This continuum of lesions is associated with an increased risk for developing subsequent invasive breast cancer, with the magnitude of that risk corresponding to the degree of proliferative change. The associated risk for developing invasive breast cancer after a diagnosis of lobular neoplasia is multicentric, bilateral, and equal in both breasts. Lobular neoplasia itself may transform into invasive carcinoma, although the frequency of this occurrence is unknown. Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition.

Colonoscopy uptake for high-risk individuals with a family history of colorectal neoplasia: A multicenter, randomized trial of tailored counseling versus standard information.

PubMed

Ingrand, Isabelle; Defossez, Gautier; Richer, Jean-Pierre; Tougeron, David; Palierne, Nicolas; Letard, Jean-Christophe; Beauchant, Michel; Ingrand, Pierre

2016-08-01

Colonoscopic screening is recommended for first-degree relatives of patients diagnosed with colorectal cancer (CRC) or colorectal adenomatous polyps (CAP) before the age of 60 years. This has the potential to reduce CRC-related morbidity and mortality, but uptake is currently inadequate. The aim of the study was to compare the effectiveness of standard information versus a nurse-led tailored intervention designed to promote uptake of colonoscopy screening by siblings of CRC or CAP patients. A randomized controlled trial was conducted. Digestive surgeons and gastroenterologists recruited index patients who developed CRC or CAP before the age of 60 years. All index patients received standard screening information for their siblings, in keeping with current guidelines. Centrally computerized randomization of index patients resulted in allocating all their siblings to the same group, intervention or control. The tailored intervention targeted the index patient first, to help them convey information to their siblings. The nurse then provided the siblings with tailored information based on their answers to a self-questionnaire which explored health behaviors, derived from psychosocial models of prevention. Then the siblings were given a personalized information leaflet to hand to their regular physician. The primary endpoint was the rate of documented colonoscopy performed in siblings within 1 year after diagnosis of the index patient. The intent-to-treat analysis included siblings who refused to participate in the study. Statistical analysis was adjusted for intrafamilial correlation. A total of 304 siblings of 125 index patients were included: 160 in the intervention group and 144 in the control group. The rate of colonoscopy uptake among siblings was 56.3% in the intervention group and 35.4% in the control group (P = 0.0027). The respective rates after exclusion of refusals were 69.2% and 37.0% (P < 0.0001). More lesions were detected in the intervention group (1

Sensitivity of 2-[18F]fluoro-2-deoxyglucose positron emission tomography for advanced colorectal neoplasms: a large-scale analysis of 7505 asymptomatic screening individuals.

PubMed

Sekiguchi, Masau; Kakugawa, Yasuo; Terauchi, Takashi; Matsumoto, Minori; Saito, Hiroshi; Muramatsu, Yukio; Saito, Yutaka; Matsuda, Takahisa

2016-12-01

The sensitivity of 2-[ 18 F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for advanced colorectal neoplasms among healthy subjects is not yet fully understood. The present study aimed to clarify the sensitivity by analyzing large-scale data from an asymptomatic screening population. A total of 7505 asymptomatic screenees who underwent both FDG-PET and colonoscopy at our Cancer Screening Division between February 2004 and March 2013 were analyzed. FDG-PET and colonoscopy were performed on consecutive days, and each examination was interpreted in a blinded fashion. The results of the two examinations were compared for each of the divided six colonic segments, with those from colonoscopy being set as the reference. The relationships between the sensitivity of FDG-PET and clinicopathological features of advanced neoplasms were also evaluated. Two hundred ninety-one advanced neoplasms, including 24 invasive cancers, were detected in 262 individuals. Thirteen advanced neoplasms (advanced adenomas) were excluded from the analysis because of the coexistence of lesions in the same colonic segment. The sensitivity, specificity, and positive and negative predictive values of FDG-PET for advanced neoplasms were 16.9 % [95 % confidence interval (CI) 12.7-21.8 %], 99.3 % (95 % CI 99.2-99.4 %), 13.5 % (95 % CI 10.1-17.6 %), and 99.4 % (95 % CI 99.3-99.5 %), respectively. The sensitivity was lower for lesions with less advanced histological grade, of smaller size, and flat-type morphology, and for those located in the proximal part of the colon. FDG-PET is believed to be difficult to use as a primary screening tool in population-based colorectal cancer screening because of its low sensitivity for advanced neoplasms. Even when it is used in opportunistic cancer screening, the limit of its sensitivity should be considered.

Multitarget stool DNA testing for colorectal-cancer screening.

PubMed

Imperiale, Thomas F; Ransohoff, David F; Itzkowitz, Steven H; Levin, Theodore R; Lavin, Philip; Lidgard, Graham P; Ahlquist, David A; Berger, Barry M

2014-04-03

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

Adenovirus-mediated suicide gene therapy under the control of Cox-2 promoter for colorectal cancer.

PubMed

Wang, Zhao-Xia; Bian, Hai-Bo; Yang, Jing-Song; De, Wei; Ji, Xiao-Hui

2009-08-01

Colorectal cancer is a most frequent type of gastrointestinal tract cancers. The prognosis of patients with colorectal cancer remains poor despite intensive interventions. Tumor specific promoter-directed gene therapy and adenoviral technology can be promising strategies for such advanced disease. This study was conducted to explore the possible therapeutic approach of Cox-2 promoter-directed suicide gene therapy with herpes simplex virus thymidine kinase (HSV-tk) in combination with adenoviral technology for advanced colorectal cancer. Firstly, the activity of Cox-2 promoter was assessed by dual luciferase and enhanced green fluorescent protein reporter gene assays in colorectal cancer cell lines and normal human intestinal epithelial cell line. Then, the expression of coxsackievirus and adenovirus receptor (CAR) was detected in colorectal cancer cell lines. The Cox-2 promoter-directed HSV-tk/ganciclovir (GCV) system mediated by adenovirus (Ad-Cp-TK) was developed (Ad-CMVp-TK, Ad-null and no Ad as controls). In vitro cytoxicity, colony formation and apoptosis assays were performed using Ad-Cp-TK. An animal study was carried out in which BALB/C nude mice bearing tumors were treated with Ad-Cp-TK and GCV treatments. Results showed that Cox-2 promoter possessed high transcriptional activity in a tumor-specific manner. All colorectal cancer cells were detected CAR-positive. In vitro cytotoxic and colony formation assays showed that colorectal cancer cells infected with Ad-Cp-TK became more sensitive to GCV but the sensitivity of normal cells infected with Ad-Cp-TK to GCV were not altered. Moreover, the Ad-Cp-TK system combined with GCV treatment could significantly induce apoptosis of colorectal cancer cells but not normal intestinal epithelial cells. Furthermore, this system also significantly inhibited the growth of subcutaneous tumors and prolonged survival of mice. Thus, adenovirus primary receptor was positive in colorectal cancer cells and adenovirus

Coffee Intake and Risk of Colorectal Cancer Among Chinese in Singapore: The Singapore Chinese Health Study

PubMed Central

Peterson, Sabrina; Yuan, Jian-Min; Koh, Woon-Puay; Sun, Can-Lan; Wang, Renwei; Turesky, Robert J.; Yu, Mimi C.

2012-01-01

We prospectively investigated whether coffee consumption was associated with decreased risk of colorectal cancer and whether cigarette smoking and stage of disease modify the association in the Singapore Chinese Health Study. During the first 12 years of follow-up, 961 colorectal cancer cases occurred in the cohort of over 60,000 middle-aged or older Chinese men and women living in Singapore. Baseline dietary exposures were assessed through in-person interviews using a validated food frequency questionnaire. The relation between coffee consumption and colorectal cancer risk was assessed by proportional hazards (Cox) regression. No overall association between coffee intake and colorectal cancer was observed. However, in analysis by subsite and stage restricted to ever smokers, the coffee–colon cancer association became statistically significant for advanced disease (P for trend = 0.01). The hazard ratio was 0.56 (95% confidence interval = 0.35–0.90) for advanced colon cancer in drinkers of 2 or more cups per day compared with those who drank no coffee or less than 1 cup per day. Although there is a null association between coffee intake and risk of colorectal cancer overall, coffee may protect against smoking related advanced colon cancer. PMID:20043256

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

PubMed

Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-02-07

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

Polymorphisms in genes related to inflammation and obesity and colorectal adenoma risk.

PubMed

Huang, Brian Z; Tsilidis, Konstantinos K; Smith, Michael W; Hoffman-Bolton, Judith; Visvanathan, Kala; Platz, Elizabeth A; Joshu, Corinne E

2018-05-26

We previously investigated the association between single nucleotide polymorphisms (SNPs) in genes related to obesity and inflammation and colorectal cancer in the CLUE II cohort. However, the relationships between these SNPs and colorectal adenomas have not been well evaluated. In a nested case-control study of 135 incident adenoma cases and 269 matched controls in the CLUE II cohort (1989-2000), we genotyped 17 candidate SNPs in 12 genes (PPARG, TCF7L2, ADIPOQ, LEP, IL10, CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and 19 tagSNPs in three genes (IL10, CRP, and TLR4). Conditional logistic regression was used to calculate odds ratios (OR) for adenomas (overall and by size, histology, location, number). Polymorphisms in the inflammatory-related genes CRP, ADIPOQ, IL6, and TLR4 were observed to be associated with adenoma risk. At rs1205 in CRP, T (minor allele) carriers had a higher risk (OR 1.67, 95%CI 1.07-2.60; reference: CC) of adenomas overall and adenomas with aggressive characteristics. At rs1201299 in ADIPOQ, the AC genotype had a higher risk (OR 1.58, 95%CI 1.00-2.49) of adenomas, while the minor AA genotype had a borderline inverse association (OR 0.44, 95%CI 0.18-1.08; reference: CC). At rs1800797 in IL6, the AA genotype had a borderline inverse association (OR 0.53, 95%CI 0.27-1.05; reference: GG). Three TLR4 tagSNPs (rs10116253, rs1927911, rs7873784) were associated with adenomas among obese participants. None of these SNPs were associated with colorectal cancer in our prior study in CLUE II, possibly suggesting a different genetic etiology for early colorectal neoplasia. © 2018 Wiley Periodicals, Inc.

[Antigens (CEA and CA 19-9) in diagnosis and prognosis colorectal cancer].

PubMed

Grotowski, Maciej

2002-01-01

carcinoembryonic antigen (CEA) was first described more than three decades ago, when its presence was demonstrated in fetal gut tissue and in tumors from gastrointestinal tract. Subsequently, CEA was detected in the circulation of patients and recognized as a serum marker for colorectal cancer. This tumor marker has not been advocated as a screening test for colorectal cancer, however a preoperative CEA serum level is useful for diagnosis and prognosis of recurrence and survival in colorectal cancer patients. The levels of CEA increased with increasing tumor stage. Expression of carbohydrate antigen (CA 19-9) has been described in various malignancies and also in colorectal cancer. This antigen also has not been advocated as a screening test for colorectal cancer. The levels of CA 19-9 increased in advanced stages of colorectal cancer. Despite its lower sensitivity than CEA in early stages of colorectal cancer, the combination of both antigens can provided more information than CEA alone for prognosis of recurrence and survival in those patients.

US pivotal studies of irinotecan in colorectal carcinoma.

PubMed

Pitot, H C

1998-08-01

Phase I trials of irinotecan (CPT-11 [Camptosar]), conducted at Johns Hopkins and the University of Texas, San Antonio, demonstrated some activity in patients with refractory advanced cancer. Three pivotal phase II studies of irinotecan in advanced colorectal carcinoma were conducted at The University of Texas, San Antonio, Mayo/North Central Cancer Treatment Group (NCCTG), and the CPT-11 Study Group in a total of 304 patients. All patients had received prior fluorouracil (5-FU) chemotherapy, and over 90% had progressed while on treatment within the last 6 months. The initial starting dose of irinotecan ranged from 100 to 150 mg/m2. The overall response rate was 12.8% (95% confidence interval, 9.1% to 16.6%) with a 15% response rate at a recommended starting dose of 125 mg/m2. The response durations and overall median survivals were similar in the three studies. The principal toxicities included diarrhea, nausea, vomiting, and neutropenia. Severe diarrhea was limited by use of an intensive loperamide regimen and appropriate dose modification. The three pivotal studies of irinotecan in advanced colorectal carcinoma demonstrate consistent response rates and duration, with manageable toxicity. Future studies will focus on the use of irinotecan in chemotherapeutically naive colorectal carcinoma, the adjuvant treatment of colon carcinoma, combination chemotherapeutic regimens, and treatment of other malignant diseases.

Comparison of fecal occult blood tests for colorectal cancer screening in an Alaska Native population with high prevalence of Helicobacter pylori infection, 2008-2012.

PubMed

Redwood, Diana; Provost, Ellen; Asay, Elvin; Roberts, Diana; Haverkamp, Donald; Perdue, David; Bruce, Michael G; Sacco, Frank; Espey, David

2014-04-10

Alaska Native colorectal cancer (CRC) incidence and mortality rates are the highest of any ethnic/racial group in the United States. CRC screening using guaiac-based fecal occult blood tests (gFOBT) are not recommended for Alaska Native people because of false-positive results associated with a high prevalence of Helicobacter pylori-associated hemorrhagic gastritis. This study evaluated whether the newer immunochemical FOBT (iFOBT) resulted in a lower false-positive rate and higher specificity for detecting advanced colorectal neoplasia than gFOBT in a population with elevated prevalence of H. pylori infection. We used a population-based sample of 304 asymptomatic Alaska Native adults aged 40 years or older undergoing screening or surveillance colonoscopy (April 2008-January 2012). Specificity differed significantly (P < .001) between gFOBT (76%; 95% CI, 71%-81%) and iFOBT (92%; 95% CI, 89%-96%). Among H. pylori-positive participants (54%), specificity of iFOBT was even higher (93% vs 69%). Overall, sensitivity did not differ significantly (P = .73) between gFOBT (29%) and iFOBT (36%). Positive predictive value was 11% for gFOBT and 32% for iFOBT. The iFOBT had a significantly higher specificity than gFOBT, especially in participants with current H. pylori infection. The iFOBT represents a potential strategy for expanding CRC screening among Alaska Native and other populations with elevated prevalence of H. pylori, especially where access to screening endoscopy is limited.

[Cost-effectiveness analysis on colorectal cancer screening program].

PubMed

Huang, Q C; Ye, D; Jiang, X Y; Li, Q L; Yao, K Y; Wang, J B; Jin, M J; Chen, K

2017-01-10

Objective: To evaluate the cost-effectiveness of colorectal cancer screening program in different age groups from the view of health economics. Methods: The screening compliance rates, detection rates in different age groups were calculated by using the data from colorectal cancer screening program in Jiashan county, Zhejiang province. The differences in indicator among age groups were analyzed with χ (2) test or trend χ (2) test. The ratios of cost to the number of case were calculated according to cost statistics. Results: The detection rates of immunochemical fecal occult blood test (iFOBT) positivity, advanced adenoma and colorectal cancer and early stage cancer increased with age, while the early diagnosis rates were negatively associated with age. After exclusion the younger counterpart, the cost-effectiveness of individuals aged >50 years could be reduced by 15 %- 30 % . Conclusion: From health economic perspective, it is beneficial to start colorectal cancer screening at age of 50 years to improve the efficiency of the screening.

Management of Colorectal Trauma

PubMed Central

2011-01-01

Although the treatment strategy for colorectal trauma has advanced during the last part of the twentieth century and the result has improved, compared to other injuries, problems, such as high septic complication rates and mortality rates, still exist, so standard management for colorectal trauma is still a controversial issue. For that reason, we designed this article to address current recommendations for management of colorectal injuries based on a review of literature. According to the reviewed data, although sufficient evidence exists for primary repair being the treatment of choice in most cases of nondestructive colon injuries, many surgeons are still concerned about anastomotic leakage or failure, and prefer to perform a diverting colostomy. Recently, some reports have shown that primary repair or resection and anastomosis, is better than a diverting colostomy even in cases of destructive colon injuries, but it has not fully established as the standard treatment. The same guideline as that for colonic injury is applied in cases of intraperitoneal rectal injuries, and, diversion, primary repair, and presacral drainage are regarded as the standards for the management of extraperitoneal rectal injuries. However, some reports state that primary repair without a diverting colostomy has benefit in the treatment of extraperitoneal rectal injury, and presacral drainage is still controversial. In conclusion, ideally an individual management strategy would be developed for each patient suffering from colorectal injury. To do this, an evidence-based treatment plan should be carefully developed. PMID:21980586

Fluorescence detection of esophageal neoplasia

NASA Astrophysics Data System (ADS)

Borisova, E.; Vladimirov, B.; Avramov, L.

2008-06-01

White-light endoscopy is well-established and wide used modality. However, despite the many technological advances that have been occurred, conventional endoscopy is suboptimal and usually detects advanced stage lesions. The limitations of standard endoscopy initiate development of spectroscopic techniques, additional to standard endoscopic equipment. One of the most sensitive approaches is fluorescence spectroscopy of gastrointestinal mucosa for neoplasia detection. In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. Excitation source has max of emission at 405 nm and light is delivered by the standard light guide of the endoscopic equipment. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to reabsorption of blood. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of 5-ALA/PpIX only in abnormal sites Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis.

PubMed

Matsuzaki, K

2006-06-01

Transforming growth factor-beta (TGF-beta) signaling occurring during human colorectal carcinogenesis involves a shift in TGF-beta function, reducing the cytokine's antiproliferative effect, while increasing actions that promote invasion and metastasis. TGF-beta signaling involves phosphorylation of Smad3 at serine residues 208 and 213 in the linker region and serine residues 423 and 425 in the C-terminal region. Exogenous TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), changing unphosphorylated Smad3 to its phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker phosphorylated Smad3 (pSmad3L). Either pSmad3C or pSmad3L oligomerizes with Smad4, and translocates into nuclei. While the TbetaRI/pSmad3C pathway inhibits growth of normal epithelial cells in vivo, JNK/pSmad3L-mediated signaling promotes tumor cell invasion and extracellular matrix synthesis by activated mesenchymal cells. Furthermore, hepatocyte growth factor signaling interacts with TGF-beta to activate the JNK/pSmad3L pathway, accelerating nuclear transport of cytoplasmic pSmad3L. This reduces accessibility of unphosphorylated Smad3 to membrane-anchored TbetaRI, preventing Smad3C phosphorylation, pSmad3C-mediated transcription, and antiproliferative effects of TGF-beta on epithelial cells. As neoplasia progresses from normal colorectal epithelium through adenoma to invasive adenocarcinoma with distant metastasis, nuclear pSmad3L gradually increases while pSmad3C decreases. The shift from TbetaRI/pSmad3C-mediated to JNK/pSmad3L-mediated signaling is a major mechanism orchestrating a complex transition of TGF-beta signaling during sporadic human colorectal carcinogenesis. This review summarizes the recent understanding of Smad3 phosphoisoform-mediated signaling, particularly 'cross-talk' between Smad3 and JNK pathways that cooperatively promote oncogenic activities. Understanding of these actions should help to develop more effective

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.

PubMed

Bullman, Susan; Pedamallu, Chandra S; Sicinska, Ewa; Clancy, Thomas E; Zhang, Xiaoyang; Cai, Diana; Neuberg, Donna; Huang, Katherine; Guevara, Fatima; Nelson, Timothy; Chipashvili, Otari; Hagan, Timothy; Walker, Mark; Ramachandran, Aruna; Diosdado, Begoña; Serna, Garazi; Mulet, Nuria; Landolfi, Stefania; Ramon Y Cajal, Santiago; Fasani, Roberta; Aguirre, Andrew J; Ng, Kimmie; Élez, Elena; Ogino, Shuji; Tabernero, Josep; Fuchs, Charles S; Hahn, William C; Nuciforo, Paolo; Meyerson, Matthew

2017-12-15

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome-including Bacteroides , Selenomonas , and Prevotella species-is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium -associated colorectal cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Referring patients to nurses: Outcomes and evaluation of a nurse flexible sigmoidoscopy training program for colorectal cancer screening

PubMed Central

Dobrow, Mark J; Cooper, Mary Anne; Gayman, Karen; Pennington, Jason; Matthews, Joanne; Rabeneck, Linda

2007-01-01

Colorectal cancer is a significant health burden. Several screening options exist that can detect colorectal cancer at an early stage, leading to a more favourable prognosis. However, despite years of knowledge on best practice, screening rates are still very low in Canada, particularly in Ontario. The present paper reports on efforts to increase the flexible sigmoidoscopy screening capacity in Ontario by training nurses to perform this traditionally physician-performed procedure. Drawing on American, British and local experience, a professional regulatory framework was established, and training curriculum and assessment criteria were developed. Training was initiated at Princess Margaret Hospital and Sunnybrook and Women’s College Health Sciences Centre in Toronto, Ontario. (During the study, Sunnybrook and Women’s College Health Sciences Centre was deamalgamated into two separate hospitals: Women’s College Hospital and Sunnybrook Health Sciences Centre.) Six registered nurses participated in didactic, simulator and practical training. These nurses performed a total of 77 procedures in patients, 23 of whom had polyps detected and biopsied. Eight patients were advised to undergo colonoscopy because they had one or more neoplastic polyps. To date, six of these eight patients have undergone colonoscopy, one patient has moved out of the province and another patient is awaiting the procedure. Classifying the six patients according to the most advanced polyp histology, one patient had a negative colonoscopy (no polyps found), one patient’s polyps were hyperplastic, one had a tubular adenoma, two had advanced neoplasia (tubulovillous adenomas) and one had adenocarcinoma. All these lesions were excised completely at colonoscopy. Overall, many difficulties were anticipated and addressed in the development of the training program; ultimately, the project was affected most directly by challenges in encouraging family physicians to refer patients to the program. As

Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

PubMed

Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

2016-07-03

Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

[Clinical administration of oxaliplatin for patients previously treated for refractory advanced or recurrent colorectal cancer].

PubMed

Takahari, Daisuke; Tsuji, Yasushi; Sagawa, Tamotsu; Honda, Kana; Sumiyoshi, Tetsuya; Yoshizaki, Naohito; Kuroiwa, Ganji; Kondo, Hitoshi

2006-01-01

Oxaliplatin (L-OHP) was administered to 10 patients previously treated for refractory advanced or recurrent colorectal cancer. The number of times each had received previous chemotherapy treatment ranged from 1 to 5 (median 3) for durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet approved for sale in Japan, and could only be imported from overseas for personal use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body. Combinations with 5-FU were administered differently from previous regimens; these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was administered from 1 to 14 times (median 4.5), and the response to treatment was PR in 2 patients and NC in 5. The response rate was 22.2%. Although in NC there was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had to be suspended because of their financial situations. Overall survival from commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events included bone marrow suppression in three patients, 3 cases of leukocytopenia (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two patients. All reactions were able to be controlled except for one patient with Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy can possibly contribute to prolongation of survival time in cases of refractory advanced colorectal cancer. It is useful to combine L-OHP with high-dose continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most useful of the FOLFOX regimens because it is simple and can be administered on an outpatient basis.

Serrated pathway colorectal cancer in the population: genetic consideration

PubMed Central

Young, Joanne; Jenkins, Mark; Parry, Susan; Young, Bruce; Nancarrow, Derek; English, Dallas; Giles, Graham; Jass, Jeremy

2007-01-01

A significant proportion of colorectal cancer (CRC) develops through the serrated neoplasia pathway. Such tumours show a distinctive molecular phenotype of somatic BRAF mutations and widespread concordant methylation events in CpG islands (CIMP). These features are also observed in the polyps developing in individuals with hyperplastic polyposis syndrome (HPS). In HPS, multiple serrated polyps develop in the colorectum, and approximately 50% of cases present with at least one CRC. Observations of rare affected sibships including identical twins, suggest a recessive or co‐dominant mode of inheritance. In addition, up to 50% of individuals with HPS report a family history of CRC. At a population level, recent work has demonstrated that patients with serrated pathway cancers characterised by BRAF mutation are four times more likely to have a family history of CRC than patients with common CRC. These findings suggest an increased genetic predisposition for serrated pathway CRC in the wider population. We propose that HPS results from the inheritance of two putative co‐dominant alleles in approximately 1 in 2000 individuals. Therefore carriers of one co‐dominant allele may number up to 1 in 25, and it is likely that these carriers are at increased risk of CRC, accounting for, at least in part, the burden of serrated pathway CRC in the population. This proposition may have important implications for screening and prevention of CRC in individuals who have an increased risk for development of serrated pathway cancers, namely those with multiple, proximal, large or advanced serrated polyps, and their relatives. PMID:17566021

Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988).

PubMed

O'Brien, R T; Evans, S M; Wortman, J A; Hendrick, M J

1996-02-01

To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Retrospective study. Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia.

The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia.

PubMed

Clark, Leslie H; Staley, S Allison; Barber, Emma L; Wysham, Weiya Z; Kim, Kenneth H; Soper, John T

2016-08-01

Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecology and Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes. Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the χ(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normally or not normally distributed. Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P = .03), but there was no difference in recurrence (13% vs 11%, P = .89). Patients with high-risk gestational

Prevalence and features of colorectal lesions among Hispanics: A hospital-based study.

PubMed

Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

2015-12-14

To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ(2) statistics and t-test. The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies.

Prevalence and features of colorectal lesions among Hispanics: A hospital-based study

PubMed Central

Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

2015-01-01

AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. METHODS: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ2 statistics and t-test. RESULTS: The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. CONCLUSION: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies. PMID:26673447

Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease.

PubMed

Chan, Annie On On; Jim, Man Hong; Lam, Kwok Fai; Morris, Jeffrey S; Siu, David Chun Wah; Tong, Teresa; Ng, Fook Hong; Wong, Siu Yin; Hui, Wai Mo; Chan, Chi Kuen; Lai, Kam Chuen; Cheung, Ting Kin; Chan, Pierre; Wong, Grace; Yuen, Man Fung; Lau, Yuk Kong; Lee, Stephen; Szeto, Ming Leung; Wong, Benjamin C Y; Lam, Shiu Kum

2007-09-26

Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated. To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases. Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years. The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex. The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by chi2 test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the

Tumoral Versus Flat Intraepithelial Neoplasia of Pancreatobiliary Tract, Gallbladder, and Ampulla of Vater.

PubMed

Jang, Kee-Taek; Ahn, Sangjeong

2016-05-01

-The identification of a precursor lesion is important to understanding the histopathologic and genetic alterations in carcinogenesis. There are a plethora of terminologies that describe precursor lesions of the pancreatobiliary tract, ampulla of Vater, and gallbladder. The current terminologies for precursor lesions may make it difficult to understand the tumor biology. Here, we propose the concept of tumoral and flat intraepithelial neoplasia to improve our understanding of precursor lesions of many epithelial organs, including the pancreatobiliary tract, ampulla of Vater, and gallbladder. -To understand the dichotomous pattern of tumoral and flat intraepithelial neoplasia in carcinogenesis of pancreatobiliary tract, ampulla of Vater, and gallbladder. -Review of relevant literatures indexed in PubMed. -Tumoral intraepithelial neoplasia presents as an intraluminal or intraductal, mass-forming, polypoid lesion or a macroscopic, visible, cystic lesion without intracystic papillae. Microscopically, tumoral intraepithelial neoplasia shows various proportions of papillary and tubular architecture, often with a mixed pattern, such as papillary, tubular, and papillary-tubular. The malignant potential depends on the degree of dysplasia and the cell phenotype of the epithelium. Flat intraepithelial neoplasia presents as a flat or superficial, spreading, mucosal lesion that is frequently accompanied by an invasive carcinoma. Tumoral and flat intraepithelial neoplasias are not homogeneous entities and may exhibit histopathologic spectrum changes and different genetic profiles. Although intraepithelial neoplasia showed a dichotomous pattern in the tumoral versus flat types, they can coexist. Tumoral and flat intraepithelial neoplasia can be interpreted as part of a spectrum of changes in the carcinogenesis pathway of each organ.

Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

Cancer.gov

Genetics of Endocrine and Neuroendocrine Neoplasias discusses inherited syndromes multiple endocrine neoplasia types 1, 2, and 4 (MEN1, MEN2, MEN4), familial pheochromocytoma and paraganglioma, Carney-Stratakis syndrome, and familial nonmedullary thyroid cancer. Learn more in this clinician summary.

Cross-sectional study of anal intraepithelial lesions in women with cervical neoplasia without HIV.

PubMed

Heráclio, Sandra A; de Souza, Alex S R; de Souza, Paulo R E; Katz, Leila; Lima Junior, Sergio F; Amorim, Melania M R

2018-02-01

To evaluate the prevalence of anal intraepithelial lesions and associated risk factors in women with cervical neoplasia. The present cross-sectional study enrolled patients with intraepithelial or invasive cervical neoplasia who had been referred to the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil, between December 1, 2008, and December 31, 2009; patients with HIV infections were excluded. All participants underwent anal cytology and high-resolution anoscopy; sociodemographic and clinical risk factors were identified using multivariate analysis. There were 324 patients included and 37 (11.4%) had anal intraepithelial neoplasia. Factors associated with anal intraepithelial neoplasia in the multivariate analysis were being older than 35 years of age (P=0.002), having completed no more than 4 years of education (P=0.012), anomalous anal cytology (P=0.003), and anomalous high-resolution anoscopy findings (P<0.001); subclinical HPV lesions on vulvoscopy (P=0.057) were not associated with anal intraepithelial neoplasia. The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years. © 2017 International Federation of Gynecology and Obstetrics.

In vivo and in vitro hyperspectral imaging of cervical neoplasia

NASA Astrophysics Data System (ADS)

Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

2014-02-01

Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

Minimally invasive colorectal surgery: status and technical specifications.

PubMed

Keller, D S; Ibarra, S; Haas, E M

2015-10-01

Laparoscopy was the most significant technologic advance in colorectal surgery in the last quarter century. The safety, feasibility and oncologic equivalence have been proven, and undisputed clinical benefits have also been demonstrated over open approaches. Despite proven benefits, laparoscopic has not dominated the market, especially for colon and rectal cancer cases. Adaptations in laparoscopic technique were developed to increase use of minimally invasive surgery. Concurrently, there has been a paradigm shift toward less invasive technologies to further optimize patient outcomes. From these needs, hand assisted laparoscopic surgery (HALS), single incision laparoscopic surgery (SILS), and robotic assisted laparoscopic surgery (RALS) were applied to colorectal surgery. Each platform has unique costs and benefits, and similar outcomes when likened to each other in comparative studies. However, conventional laparoscopy, HALS, SILS, and RALS actually serve a complementary role as tools to increase the use of minimally invasive colorectal surgery. The goal of this paper is to review the history, current status, technical specifications, and evolution of the major minimally invasive platforms for colorectal surgery.

DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia.

PubMed

Ashktorab, Hassan; Daremipouran, M; Goel, Ajay; Varma, Sudhir; Leavitt, R; Sun, Xueguang; Brim, Hassan

2014-04-01

The identification of genes that are differentially methylated in colorectal cancer (CRC) has potential value for both diagnostic and therapeutic interventions specifically in high-risk populations such as African Americans (AAs). However, DNA methylation patterns in CRC, especially in AAs, have not been systematically explored and remain poorly understood. Here, we performed DNA methylome profiling to identify the methylation status of CpG islands within candidate genes involved in critical pathways important in the initiation and development of CRC. We used reduced representation bisulfite sequencing (RRBS) in colorectal cancer and adenoma tissues that were compared with DNA methylome from a healthy AA subject's colon tissue and peripheral blood DNA. The identified methylation markers were validated in fresh frozen CRC tissues and corresponding normal tissues from AA patients diagnosed with CRC at Howard University Hospital. We identified and validated the methylation status of 355 CpG sites located within 16 gene promoter regions associated with CpG islands. Fifty CpG sites located within CpG islands-in genes ATXN7L1 (2), BMP3 (7), EID3 (15), GAS7 (1), GPR75 (24), and TNFAIP2 (1)-were significantly hypermethylated in tumor vs. normal tissues (P<0.05). The methylation status of BMP3, EID3, GAS7, and GPR75 was confirmed in an independent, validation cohort. Ingenuity pathway analysis mapped three of these markers (GAS7, BMP3 and GPR) in the insulin and TGF-β1 network-the two key pathways in CRC. In addition to hypermethylated genes, our analysis also revealed that LINE-1 repeat elements were progressively hypomethylated in the normal-adenoma-cancer sequence. We conclude that DNA methylome profiling based on RRBS is an effective method for screening aberrantly methylated genes in CRC. While previous studies focused on the limited identification of hypermethylated genes, ours is the first study to systematically and comprehensively identify novel hypermethylated

Immunosignature Differentiation of Non-Infectious Meningoencephalomyelitis and Intracranial Neoplasia in Dogs.

PubMed

Lake, Bathilda B; Rossmeisl, John Henry; Cecere, Julie; Stafford, Phillip; Zimmerman, Kurt L

2018-01-01

A variety of inflammatory conditions of unknown cause (meningoencephalomyelitis of unknown etiology-MUE) and neoplastic diseases can affect the central nervous system (CNS) of dogs. MUE can mimic intracranial neoplasia both clinically, radiologically and even in some cases, histologically. Serum immunosignature protein microarray assays have been used in humans to identify CNS diseases such as Alzheimer's and neoplasia, and in dogs, to detect lymphoma and its progression. This study evaluated the effectiveness of immunosignature profiles for distinguishing between three cohorts of dogs: healthy, intracranial neoplasia, and MUE. Using the learned peptide patterns for these three cohorts, classification prediction was evaluated for the same groups using a 10-fold cross validation methodology. Accuracy for classification was 100%, as well as 100% specific and 100% sensitive. This pilot study demonstrates that immunosignature profiles may help serve as a minimally invasive tool to distinguish between MUE and intracranial neoplasia in dogs.

Advanced endoscopic imaging in gastric neoplasia and preneoplasia

PubMed Central

Lee, Jonathan W J; Lim, Lee Guan; Yeoh, Khay Guan

2017-01-01

Conventional white light endoscopy remains the current standard in routine clinical practice for early detection of gastric cancer. However, it may not accurately diagnose preneoplastic gastric lesions. The technological advancements in the field of endoscopic imaging for gastric lesions are fast growing. This article reviews currently available advanced endoscopic imaging modalities, in particular chromoendoscopy, narrow band imaging and confocal laser endomicroscopy, and their corresponding evidence shown to improve diagnosis of preneoplastic gastric lesions. Raman spectrometry and polarimetry are also introduced as promising emerging technologies. PMID:28176895

The Role of Photodynamic Therapy in the Treatment of Vulvar Intraepithelial Neoplasia

PubMed Central

Tosti, Giulio; Iacobone, Anna Daniela; Preti, Eleonora Petra; Vaccari, Sabina; Barisani, Alessia; Pennacchioli, Elisabetta

2018-01-01

Background: vulvar intraepithelial neoplasia is a non-invasive precursor lesion found in 50–70% of patients affected by vulvar squamous cell carcinoma. In the past, radical surgery was the standard treatment for vulvar intraepithelial neoplasia, however, considering the psychological and physical morbidities related to extensive surgery, several less aggressive treatment modalities have been proposed since the late 1970s. Photodynamic therapy is an effective and safe treatment for cutaneous non-melanoma skin cancer, with favorable cosmetic outcomes. Methods: in the present paper, the results of selected studies on photodynamic therapy in the treatment of vulvar intraepithelial neoplasia are reported and discussed. Results: Overall, complete histological response rates ranged between 20% and 67% and symptom response rates ranged between 52% and 89% according to different studies and case series. Conclusions: the real benefit of photodynamic therapy in the setting of vulvar intraepithelial neoplasia lies in its ability to treat multi-focal disease with minimal tissue destruction, preservation of vulvar anatomy and excellent cosmetic outcomes. These properties explain why photodynamic therapy is an attractive option for vulvar intraepithelial neoplasia treatment. PMID:29393881

CRNDE: An important oncogenic long non-coding RNA in human cancers.

PubMed

Zhang, Jiaming; Yin, Minuo; Peng, Gang; Zhao, Yingchao

2018-06-01

Aberrant overexpression of long non-coding RNA CRNDE (Colorectal Neoplasia Differentially Expressed) is confirmed in various human cancers, which is correlated with advanced clinicopathological features and poor prognosis. CRNDE promotes cancer cell proliferation, migration and invasion, and suppresses apoptosis in complicated mechanisms, which result in the initialization and development of human cancers. In this review, we provide an overview of the oncogenic role and potential clinical applications of CRNDE. © 2018 John Wiley & Sons Ltd.

Fusobacterium nucleatum and T Cells in Colorectal Carcinoma.

PubMed

Mima, Kosuke; Sukawa, Yasutaka; Nishihara, Reiko; Qian, Zhi Rong; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A; Masuda, Atsuhiro; Nowak, Jonathan A; Nosho, Katsuhiko; Kostic, Aleksandar D; Giannakis, Marios; Watanabe, Hideo; Bullman, Susan; Milner, Danny A; Harris, Curtis C; Giovannucci, Edward; Garraway, Levi A; Freeman, Gordon J; Dranoff, Glenn; Chan, Andrew T; Garrett, Wendy S; Huttenhower, Curtis; Fuchs, Charles S; Ogino, Shuji

2015-08-01

Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity. To test the hypothesis that a greater amount of F nucleatum in colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue. A cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses' Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount of F nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount of F nucleatum with densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing. Densities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+ T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis. F nucleatum was detected in colorectal carcinoma

Advances in diagnostic and treatment modalities for intracranial tumors.

PubMed

Dickinson, P J

2014-01-01

Intracranial neoplasia is a common clinical condition in domestic companion animals, particularly in dogs. Application of advances in standard diagnostic and therapeutic modalities together with a broad interest in the development of novel translational therapeutic strategies in dogs has resulted in clinically relevant improvements in outcome for many canine patients. This review highlights the status of current diagnostic and therapeutic approaches to intracranial neoplasia and areas of novel treatment currently in development. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis.

PubMed

Fumery, Mathurin; Dulai, Parambir S; Gupta, Samir; Prokop, Larry J; Ramamoorthy, Sonia; Sandborn, William J; Singh, Siddharth

2017-05-01

Little is known about outcomes of patients with ulcerative colitis with low-grade dysplasia (UC-LGD). We estimated the incidence of and risk factors for progression to colorectal cancer (CRC) in cohorts of patients with UC-LGD who underwent surveillance (surveillance cohort), and the prevalence of dysplasia-related findings among patients who underwent colectomy for UC-LGD (surgical cohort). We performed a systematic literature review through June 1, 2016, to identify cohort studies of adults with UC-LGD. We estimated pooled incidence rates of CRC and risk factors associated with dysplasia progression in surveillance cohorts, and prevalence of synchronous advanced neoplasia (CRC and/or high-grade dysplasia) in surgical cohorts. In 14 surveillance cohort studies of 671 patients with UC-LGD (52 developed CRC), the pooled annual incidence of CRC was 0.8% (95% confidence interval [CI], 0.4-1.3); the pooled annual incidence of advanced neoplasia was 1.8% (95% CI, 0.9-2.7). Risk of CRC was higher when LGD was diagnosed by expert gastrointestinal pathologist (1.5%) than by community pathologists (0.2%). Factors significantly associated with dysplasia progression were concomitant primary sclerosing cholangitis (odds ratio [OR], 3.4; 95% CI, 1.5-7.8), invisible dysplasia (vs visible dysplasia; OR, 1.9; 95% CI, 1.0-3.4), distal location (vs proximal location; OR, 2.0; 95% CI, 1.1-3.7), and multifocal dysplasia (vs unifocal dysplasia; OR, 3.5; 95% CI, 1.5-8.5). In 12 surgical cohort studies of 450 patients who underwent colectomy for UC-LGD, 34 patients had synchronous CRC (pooled prevalence, 17%; 95% CI, 8-33). In a systematic review of the literature, we found that among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%; differences in rates of LGD diagnosis varied with pathologists' level of expertise. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high-risk features

Preliminary results of 'liver-first' reverse management for advanced and aggressive synchronous colorectal liver metastases: a propensity-matched analysis.

PubMed

Tanaka, Kuniya; Murakami, Takashi; Matsuo, Kenichi; Hiroshima, Yukihiko; Endo, Itaru; Ichikawa, Yasushi; Taguri, Masataka; Koda, Keiji

2015-01-01

Although a 'liver-first' approach recently has been advocated in treating synchronous colorectal metastases, little is known about how results compare with those of the classical approach among patients with similar grades of liver metastases. Propensity-score matching was used to select study subjects. Oncologic outcomes were compared between 10 consecutive patients with unresectable advanced and aggressive synchronous colorectal liver metastases treated with the reverse strategy and 30 comparable classically treated patients. Numbers of recurrence sites and recurrent tumors irrespective of recurrence sites were greater in the reverse group then the classic group (p = 0.003 and p = 0.015, respectively). Rates of freedom from recurrence in the remaining liver and of freedom from disease also were poorer in the reverse group than in the classical group (p = 0.009 and p = 0.043, respectively). Among patients treated with 2-stage hepatectomy, frequency of microvascular invasion surrounding macroscopic metastases at second resection was higher in the reverse group than in the classical group (p = 0.011). Reverse approaches may be feasible in treating synchronous liver metastases, but that strategy should be limited to patients with less liver tumor burden. © 2015 S. Karger AG, Basel.

Microwave ablation for treatment of hepatic neoplasia in five dogs.

PubMed

Yang, Toni; Case, J Brad; Boston, Sarah; Dark, Michael J; Toskich, Beau

2017-01-01

CASE DESCRIPTION 5 dogs between 9 and 11 years of age were evaluated for treatment of primary (n = 2) or metastatic (3) hepatic neoplasia. CLINICAL FINDINGS Patients were evaluated on an elective (n = 3) or emergency (2) basis. Two dogs with primary hepatic neoplasia were evaluated because of lethargy and inappetence. One dog was referred after an enlarged anal sac was detected via palpation per rectum during a routine physical examination. Two dogs were evaluated on an emergency basis because of lethargy and weakness, and hemoabdomen in the absence of a history of trauma was detected. All 5 dogs underwent thoracic radiography and abdominal ultrasonography, with CT performed in both dogs with primary hepatic neoplasia. All dogs had preoperative evidence of abdominal neoplasia, and none had evidence of thoracic metastasis. TREATMENT AND OUTCOME All dogs underwent ventral midline laparotomy and had diffuse hepatic neoplasia that precluded complete resection. Locoregional treatment with MWA was applied to hepatic lesions (0.5 to 2.5 cm diameter) without procedural complications. Histopathologic diagnoses were biliary adenocarcinoma (n = 1), hemangiosarcoma (2), hepatocellular carcinoma (1), and apocrine gland adenocarcinoma (1). CLINICAL RELEVANCE MWA is being increasingly used as an adjunct in the surgical treatment of human patients with primary and metastatic liver disease. Results of the present small case series suggested that MWA is feasible and potentially effective as an adjunctive treatment for appropriately selected dogs with nonresectable hepatic tumors. Further investigation is indicated.

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases.

PubMed

Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

2016-11-01

The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response.

Dysregulation of the Phosphatidylinositol 3-kinase Pathway in Thyroid Neoplasia

PubMed Central

Paes, John E.; Ringel, Matthew D.

2008-01-01

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is an important regulator of many cellular events, including apoptosis, proliferation, and motility. Enhanced activation of this pathway can occur through several mechanisms, such as inactivation of its negative regulator, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and activating mutations and gene amplification of the gene encoding the catalytic subunit of PI3K (PIK3CA). These genetic abnormalities have been particularly associated with follicular thyroid neoplasia and anaplastic thyroid cancer, suggesting an important role for PI3K signaling in these disorders. In this review, the role of PI3K pathway activation in thyroid cancer will be discussed, with a focus on recent advances. PMID:18502332

Expending Role of Microsatellite Instability in Diagnosis and Treatment of Colorectal Cancers.

PubMed

Chang, Liisa; Chang, Minna; Chang, Hanna M; Chang, Fuju

2017-12-01

Colorectal carcinomas with high-frequency microsatellite instability (MSI-H) account for 15% of all colorectal cancers, including 12% of sporadic cases and 3% of cancers associated with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome, HNPCC). Lynch syndrome is an autosomal dominant hereditary cancer syndrome, caused by germline mutations in mismatch repair genes, including MLH1, MSH2, MSH6 and PMS2. Published articles from peer-reviewed journals were obtained from PubMed, Google Scholar and Clinicaltrials.gov . Based on the recent research data, we provide an update on the MSI testing, along with the evolving role of MSI in diagnosis, prognosis and treatment of colorectal cancers. Studies have led to significant advances in the molecular pathogenesis and clinicopathological characteristics of MSI-H colorectal cancers. Emerging evidence suggests that colorectal cancers with MSI-H show different outcome and treatment response from those with microsatellite stable (MSS) tumors. Therefore, MSI testing is essential not only in the genetic context, but it may also have important prognostic and predictive value of response to chemotherapy and immunotherapy. Many experts and professional authorities have recommended a universal MSI testing in all individuals newly diagnosed with colorectal cancers.

Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

Cancer.gov

Endocrine and neuroendocrine neoplasias may be inherited in syndromes such as multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), familial pheochromocytoma and paraganglioma, and Carney-Stratakis syndrome. Learn about the genetics, clinical manifestations, and management of these hereditary cancer syndromes in this expert-reviewed summary.

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

PubMed

Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

Risk factors for persistent gestational trophoblastic neoplasia.

PubMed

Kuyumcuoglu, Umur; Guzel, Ali Irfan; Erdemoglu, Mahmut; Celik, Yusuf

2011-01-01

This retrospective study evaluated the risk factors for persistent gestational trophoblastic disease (GTN) and determined their odds ratios. This study included 100 cases with GTN admitted to our clinic. Possible risk factors recorded were age, gravidity, parity, size of the neoplasia, and beta-human chorionic gonadotropin levels (beta-hCG) before and after the procedure. Statistical analyses consisted of the independent sample t-test and logistic regression using the statistical package SPSS ver. 15.0 for Windows (SPSS, Chicago, IL, USA). Twenty of the cases had persistent GTN, and the differences between these and the others cases were evaluated. The size of the neoplasia and histopathological type of GTN had no statistical relationship with persistence, whereas age, gravidity, and beta-hCG levels were significant risk factors for persistent GTN (p < 0.05). The odds ratios (95% confidence interval (CI)) for age, gravidity, and pre- and post-evacuation beta-hCG levels determined using logistic regression were 4.678 (0.97-22.44), 7.315 (1.16-46.16), 2.637 (1.41-4.94), and 2.339 (1.52-3.60), respectively. Patient age, gravidity, and beta-hCG levels were risk factors for persistent GTN, whereas the size of the neoplasia and histopathological type of GTN were not significant risk factors.

Prospective Trial Evaluating the Surgical Anastomosis at One-Year Colorectal Cancer Surveillance: CT Colonography Versus Optical Colonoscopy and Implications for Patient Care.

PubMed

Pickhardt, Perry J; Edwards, Kristin; Bruining, David H; Gollub, Marc; Kupfer, Sonja; Lubner, Sam J; Kim, David H; Ross, Eric; Keenan, Eileen; Weinberg, David S

2017-11-01

The aim of this study was to compare the accuracy of CT colonography versus optical colonoscopy for neoplastic involvement at the surgical anastomosis 1 year after curative-intent colorectal cancer resection. Two hundred one patients (mean age, 58.6 years; 117 men, 84 women) underwent same-day contrast-enhanced CT colonography and colonoscopy approximately 1 year (mean, 12.1 months; median, 11.9 months) after colorectal cancer resection as part of a prospective, multicenter trial. All patients enrolled were without clinical evidence of disease and considered low risk for recurrence (stage I-III). Suspected neoplastic lesions within 5 cm of the colonic anastomosis were recorded at CT colonography, with subsequent colonoscopy performed for the same, with segmental unblinding of colonography findings. Anastomotic region biopsy or polypectomy was performed at the endoscopist's discretion. None of the 201 patients had intraluminal anastomotic cancer recurrence or advanced neoplasia (or metachronous cancers). CT colonography detected extramural perianastomotic recurrence in 2 patients (1.0%); neither was detected at colonoscopy. Only 2 patients (1.0%; 2/201) were called positive at CT colonography for intraluminal anastomotic nondiminutive lesions (7- to 8-mm polyps), which were confirmed at colonoscopy but nonneoplastic at histopathology. At optical colonoscopy, the anastomosis was deemed abnormal and/or biopsied in 10.0% (20/201), yielding only 1 nondiminutive benign neoplasm (7-mm tubular adenoma). The lack of luminal cancer recurrence in our lower-risk cohort precludes assessment of sensitivity for detection, rendering the study underpowered in this regard. Potential cost savings of combined CT/CT colonography over the standard CT/colonoscopy approach were not assessed. Relevant intraluminal anastomotic pathology appears to be very uncommon 1 year after colorectal cancer resection in lower-risk cohorts. Unlike colonoscopy, diagnostic contrast-enhanced CT

Circular stapler introducer: a novel device to facilitate stapled colorectal anastomosis.

PubMed

Guweidhi, Ahmed; Steffen, Rudolf; Metzger, Alejandro; Teuscher, Jürg; Flückiger, Petra; Z'graggen, Kaspar

2009-04-01

A circular stapler introducer was developed to protect the head of the circular stapler and enable atraumatic introduction and advancement of the circular stapler without interfering with the application and safety of an anastomosis. In a Phase I prospective study, we tested the feasibility and safety of the novel circular stapler introducer device in 60 consecutive patients undergoing left-sided colorectal resections. The median distance of the anastomoses from the anal verge was 12 cm (7-20, n = 60). Total morbidity was 15 percent. No mortality was observed. Handling of the circular stapler introducer was considered nonproblematic by all surgeons who participated in the study. No interference of the circular stapler introducer with the circular stapling devices used was encountered. The advancement of the stapler into the end of the colorectal stump was always possible with the aid of the circular stapler introducer. Use of the circular stapler introducer facilitates the double-stapling technique of colorectal anastomosis. The circular stapler introducer has great potential and should be tested in larger studies.

Difficulty in diagnosis and different prognoses between colorectal cancer with ovarian metastasis and advanced ovarian cancer: An empirical study of different surgical adoptions.

PubMed

Lee, Ko-Chao; Lin, Hao; ChangChien, Chan-Chao; Fu, Hung-Chun; Tsai, Ching-Chou; Wu, Chen-Hsuan; Ou, Yu-Che

2017-02-01

To determine the clinical manifestations and optimal management of female patients with advanced colorectal cancer (CRC) metastasis in ovaries mimicking advanced ovarian malignancy. A retrospective medical records review of female patients with primary CRC metastasis to ovaries, which were initially diagnosed as ovarian malignancy, and treated between 2001 and 2013. Clinical presentations, pathologic findings, and treatment outcomes were analyzed. In total, 19 cases were collected in the study through a hospital tumor registry. The mean age of the patients at the time of diagnosis was 45 years (range, 28-63 years). The most common symptoms were abdominal pain or increased abdominal girth (63%). None of them had rectal bleeding. The ratio of cancer antigen-125 to carcinoembryonic antigen was available in 13 out 19 patients (less than 25 in 76.9%). Barium enema or colonoscopic exam was only performed in 10 outpatients. None of them had a positive finding. All 19 patients went for surgery, all of them had ovarian metastasis but only eight of them had bilateral involvement, and 14 of them had carcinomatosis. All patients went for either optimal cytoreduction surgery or suboptimal cytoreduction surgery. The patients who received optimal cytoreduction surgery had a significant better progression-free and overall survival than those who did not. Clinical manifestations of primary CRC with ovarian metastasis may be confused with advanced ovarian cancer. Negative barium enema or colonoscopic exam cannot rule out the possibility of CRC. For patients with a cancer antigen-125 to carcinoembryonic antigen ratio less than 25, 76% are good reference of CRC metastasis to ovaries. Optimal cytoreduction surgery like that used for treating advanced ovarian cancer had a better prognosis than suboptimal cytoreduction colorectal cancer treatment. Copyright © 2017. Published by Elsevier B.V.

The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.

PubMed

Srigley, John R; Delahunt, Brett; Eble, John N; Egevad, Lars; Epstein, Jonathan I; Grignon, David; Hes, Ondrej; Moch, Holger; Montironi, Rodolfo; Tickoo, Satish K; Zhou, Ming; Argani, Pedram

2013-10-01

The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC

[Colorectal cancer in spouses of colorectal cancer patients].

PubMed

Matsumata, T; Shikada, Y; Hasuda, S; Kishihara, F; Suehiro, T; Funahashi, S; Nagamatsu, Y; Iso, Y; Shima, I; Koga, C; Osamura, S; Ueda, M; Furuya, K; Sakino, I

2000-06-01

Married couples share home environments and life style for years. In the case of colorectal cancer, an association with insulin resistance was reported. We determined the presence of the insulin-resistance syndrome (IRS, 1 or more of the following: body mass index of > 25 kg/m2, diabetes, or hyperlipidemia) in 84 colorectal cancer patients, of whom 61 patients (73%) had IRS. The incidence of the distal colorectal cancer, which has been declining in the United States, was significantly higher in the IRS group than in the non-IRS group (75.4 vs 52.2%, p = 0.0400). Some mechanisms may promote the progression of mucosal lesions to invasive cancers in the distal colorectum. There were no significant differences with respect to the age (64.6 +/- 9.4 vs 64.3 +/- 11.3 yr, p = 0.8298), height (159 +/- 9 vs 157 +/- 8 cm, p = 0.1375), and body mass index (22.2 +/- 3.6 vs 22.4 +/- 2.7 kg/m2, p = 0.6364) between the patients and their spouses. In 84 couples in whom colorectal cancer develops at least in one may then not illustrate the nursery rhyme: "Jack Sprat could eat no fat, His wife could eat no lean...". The spouses had been married for an average of 38 years, and in 30 spouses who had been followed in a colorectal cancer screening, 5 developed colorectal cancer. To diminish the incidence of colorectal cancer in Japan, we might advise screening colonoscopy to the spouses of colorectal cancer patients, or déjà vu all over again?

Neoplasia in Turner syndrome. The importance of clinical and screening practices during follow-up.

PubMed

Larizza, Daniela; Albanesi, Michela; De Silvestri, Annalisa; Accordino, Giulia; Brazzelli, Valeria; Maffè, Gabriella Carnevale; Calcaterra, Valeria

2016-05-01

Turmer syndrome (TS) patients show increased morbidity due to metabolic, autoimmune and cardiovascular disorders. A risk of neoplasia is also reported. Here, we review the prevalence of neoplasia in a cohort of Turner patients. We retrospectively evaluated 87 TS women. Follow-up included periodic ultrasound of the neck, abdominal and pelvic organs, dermatologic evaluation and fecal occult blood test. Karyotype was 45,X in 46 patients. During follow-up, 63 girls were treated with growth hormone, 65 with estro-progestin replacement therapy and 20 with L-thyroxine. Autoimmune diseases were present in 29 TS. A total of 17 neoplasms in 14 out of 87 patients were found. Six skin neoplasia, 3 central nervous system tumors, 3 gonadal neoplasia, 2 breast tumors, 1 hepatocarcinoma, 1 carcinoma of the pancreas and 1 follicular thyroid cancer were detected. Age at tumor diagnosis was higher in 45,X pts than in those with other karyotypes (p = 0.003). Adenomioma gallbladdder (AG) was detected in 15.3% of the patients, with a lower age in girls at diagnosis with an associated neoplasia in comparison with TS without tumors (p = 0.017). No correlation between genetic make up, treatment, associated autoimmune diseases and neoplastia was found. In our TS population an increased neoplasia prevalence was reported. A high prevalence of AG was also noted and it might be indicative of a predisposition to neoplasia. Further studies are needed to define the overall risk for neoplasia, and to determine the role of the loss of the X-chromosome and hormonal therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The role of human papillomavirus vaccines in cervical neoplasia.

PubMed

Stern, P L; Faulkner, R; Veranes, E C; Davidson, E J

2001-10-01

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.

DNA Methylation and Mutation of Small Colonic Neoplasms in Ulcerative Colitis and Crohn's Colitis: Implications for Surveillance.

PubMed

Johnson, David H; Taylor, William R; Aboelsoud, Mohammed M; Foote, Patrick H; Yab, Tracy C; Cao, Xiaoming; Smyrk, Thomas C; Loftus, Edward V; Mahoney, Douglas W; Ahlquist, David A; Kisiel, John B

2016-07-01

Stool DNA testing in patients with inflammatory bowel disease (IBD) may detect colorectal cancer and advanced precancers with high sensitivity; less is known about the presence of DNA markers in small IBD lesions, their association with metachronous neoplasia, or contribution to stool test positivity. At a single center in 2 blinded phases, we assayed methylated bone morphogenic protein 3, methylated N-Myc downstream-regulated gene 4, and mutant KRAS in DNA extracted from paraffin-embedded benign lesions, and matched control tissues of patients with IBD, who were followed for subsequent colorectal dysplasia. Stool samples from independent cases and controls with lesions <1 cm or advanced neoplasms were assayed for the same markers. Among IBD lesions (29 low-grade dysplasia, 19 serrated epithelial change, and 10 sessile serrated adenoma/polyps), the prevalence of methylation was significantly higher than in mucosae from 44 matched IBD controls (P < 0.0001 for methylated bone morphogenic protein 3 or methylated N-Myc downstream-regulated gene 4). KRAS mutations were more abundant in serrated epithelial change than all other groups (P < 0.001). Subsequent dysplasia was not associated with DNA marker levels. In stools, the sensitivity of methylated bone morphogenic protein 3 as a single marker was 60% for all lesions <1 cm, 63% for low-grade dysplasia ≥1 cm and 81% for high-grade dysplasia/colorectal cancer, all at 91% specificity (P < 0.0001). Selected DNA markers known to be present in advanced IBD neoplasia can also be detected in both tissues and stools from IBD patients with small adenomas and serrated lesions. Mutant KRAS exfoliated from serrated epithelial change lesions might raise false-positive rates. These findings have relevance to potential future applications of stool DNA testing for IBD surveillance.

Pembrolizumab, Capecitabine, and Bevacizumab in Treating Patients With Microsatellite Stable Colorectal Cancer That Is Locally Advanced, Metastatic, or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-04

Microsatellite Stable; Mismatch Repair Protein Proficient; Stage III Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Selection Bias in Colorectal Surgery in a Non-Tertiary Hospital: Laparoscopic Versus Open Surgery.

PubMed

Verzaro, Roberto; Mattia, Simona; Rago, Teresa; Casella, Francesco; Ferroni, Andrea; Gianfreda, Valeria; Cofini, Vincenza; Necozione, Stefano

2018-03-01

Laparoscopy is used increasingly to treat malignant and benign colorectal surgical diseases. However, this practice is still not offered to all patients. Many barriers halt the widespread use of laparoscopic colorectal surgery. Both surgeon's and patient's factors contribute to limit a wider use of laparoscopy in colorectal surgery. We retrospectively analyzed 408 consecutive colorectal resections in a 4-year period, to find out if a selection bias exists in using laparotomy or laparoscopy for colorectal surgical diseases, and which factors are associated with a poor use of laparoscopy or to a preferred laparotomy. In our practice, advanced disease, American Society of Anesthesiologist class III and IV, and emergency status are all patient-related factors associated with laparotomy. Surgeon's age more than 52 years and lack of laparoscopic training are surgeon-related factors that negatively affect the chance of being operated on with the laparoscopic technique. An extensive laparoscopic colorectal training and a supporting environment, especially during the night shift, are needed to facilitate the use of laparoscopy in colorectal surgery avoiding a bias in selecting surgical candidates to one technique or another.

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases

PubMed Central

Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

2016-01-01

Background The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). Summary and Key Messages (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response. PMID:27995091

Gut microbiome development along the colorectal adenoma-carcinoma sequence.

PubMed

Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun

2015-03-11

Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

Identifying patients with undetected colorectal cancer: an independent validation of QCancer (Colorectal).

PubMed

Collins, G S; Altman, D G

2012-07-10

Early identification of colorectal cancer is an unresolved challenge and the predictive value of single symptoms is limited. We evaluated the performance of QCancer (Colorectal) prediction model for predicting the absolute risk of colorectal cancer in an independent UK cohort of patients from general practice records. A total of 2.1 million patients registered with a general practice surgery between 01 January 2000 and 30 June 2008, aged 30-84 years (3.7 million person-years) with 3712 colorectal cancer cases were included in the analysis. Colorectal cancer was defined as incident diagnosis of colorectal cancer during the 2 years after study entry. The results from this independent and external validation of QCancer (Colorectal) prediction model demonstrated good performance data on a large cohort of general practice patients. QCancer (Colorectal) had very good discrimination with an area under the ROC curve of 0.92 (women) and 0.91 (men), and explained 68% (women) and 66% (men) of the variation. QCancer (Colorectal) was well calibrated across all tenths of risk and over all age ranges with predicted risks closely matching observed risks. QCancer (Colorectal) appears to be a useful tool for identifying undetected cases of undiagnosed colorectal cancer in primary care in the United Kingdom.

Equine orbital neoplasia: a review of 10 cases (1983-1998).

PubMed Central

Baptiste, K E; Grahn, B H

2000-01-01

The clinical manifestations, laboratory findings, and survival times of 10 horses with orbital neoplasms are reported. In all cases, orbital neoplasms were malignant and locally invasive with no defined surgical circumscribed edges. It was often difficult to identify the primary cell type of the neoplasia in histologic specimens due to the poorly differentiated, anaplastic nature of the majority of cases. All except one horse were eventually euthanized 2 mo to 5 y after diagnosis due to poor response to treatment, metastasis, or unrelenting orbital neoplasia. Mean survival time increased with surgical treatment, but no significant difference was found among no treatment, chemotherapy, surgical mass removal, or exenteration/enucleation. Equine practitioners should be aware of the marked difference in prognosis of orbital neoplasms compared with ocular or localized eyelid neoplasia. Images Figure 1. Figure 2. Figure 3. PMID:10769765

Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma.

PubMed

Chen, Hui-Min; Yu, Ya-Nan; Wang, Ji-Lin; Lin, Yan-Wei; Kong, Xuan; Yang, Chang-Qing; Yang, Li; Liu, Zhan-Ju; Yuan, Yao-Zong; Liu, Fei; Wu, Jian-Xin; Zhong, Liang; Fang, Dian-Chun; Zou, Weiping; Fang, Jing-Yuan

2013-05-01

Accumulating evidence indicates that diet is one of the most important environmental factors involved in the progression from advanced colorectal adenoma (A-CRA) to colorectal cancer. We evaluated the possible effects of dietary fiber on the fecal microbiota of patients with A-CRA. Patients with a diagnosis of A-CRA by pathological examination were enrolled in the A-CRA group. Patients with no obvious abnormalities or histopathological changes were enrolled in the healthy control (HC) group. Dietary fiber intake was assessed in all patients. Short-chain fatty acids (SCFAs) in feces were detected by gas chromatography. The fecal microbiota community was analyzed by 454 pyrosequencing based on 16S ribosomal RNA. Lower dietary fiber patterns and consistently lower SCFA production were observed in the A-CRA group (n = 344). Principal component analysis showed distinct differences in the fecal microbiota communities of the 2 groups. Clostridium, Roseburia, and Eubacterium spp. were significantly less prevalent in the A-CRA group (n = 47) than in the HC group (n = 47), whereas Enterococcus and Streptococcus spp. were more prevalent in the A-CRA group (n = 47) (all P < 0.05). Butyrate and butyrate-producing bacteria were more prevalent in a subgroup of HC subjects with a high fiber intake than in those in both the low-fiber HC subgroup and the high-fiber A-CRA subgroup (all P < 0.05). A high-fiber dietary pattern and subsequent consistent production of SCFAs and healthy gut microbiota are associated with a reduced risk of A-CRA. This trial was registered at www.chictr.org as ChiCTR-TRC-00000123.

Minimally Invasive Surgery for the Treatment of Colorectal Cancer

PubMed Central

Karcz, W. Konrad; von Braun, William

2016-01-01

Background Reduction in operative trauma along with an improvement in endoscopic access has undoubtedly occupied surgical minds for at least the past 3 decades. It is not at all surprising that minimally invasive colon surgery has come a long way since the first laparoscopic appendectomy by Semm in 1981. It is common knowledge that the recent developments in video and robotic technologies have significantly furthered advancements in laparoscopic and minimally invasive surgery. This has led to the overall acceptance of the treatment of benign colorectal pathology via the endoscopic route. Malignant disease, however, is still primarily treated by conventional approaches. Methods and Results This review article is based on a literature search pertaining to advances in minimally invasive colorectal surgery for the treatment of malignant pathology, as well as on personal experience in the field over the same period of time. Our search was limited to level I and II clinical papers only, according to the evidence-based medicine guidelines. We attempted to present our unbiased view on the subject relying only on the evidence available. Conclusion Focusing on advances in colorectal minimally invasive surgery, it has to be stated that there are still a number of unanswered questions regarding the surgical management of malignant diseases with this approach. These questions do not only relate to the area of boundaries set for the use of minimally invasive techniques in this field but also to the exact modality best suited to the treatment of every particular case whilst maintaining state-of-the-art oncological principles. PMID:27493947

Meat intake and risk of colorectal polyps: results from a large population-based screening study in Germany.

PubMed

Carr, Prudence R; Holleczek, Bernd; Stegmaier, Christa; Brenner, Hermann; Hoffmeister, Michael

2017-06-01

Background: Red and processed meats have been shown to be associated with colorectal adenomas in many, but not all, studies, and the association according to the type of colorectal adenoma or the location in the colorectum is unclear. Objectives: We investigated the association of meat intake in relation to colorectal polyps and further investigated the association according to histologic subtypes and subsites in a large population-based screening study in Germany. Design: In this cross-sectional study, 15,950 participants aged ≥55 y underwent a screening colonoscopy. We calculated prevalence ratios (PRs) and 95% CIs for associations between meat intake and the most-advanced findings from a colonoscopy with the use of log binomial regression. Results: Overall, 3340 participants (20.4%) had nonadvanced adenomas, 1643 participants (10.0%) had advanced adenomas, and 189 participants (1.2%) had colorectal cancer. We observed no statistically significant association between red or processed meat consumption and the prevalence of any adenomas or advanced adenomas [highest compared with lowest: red meat, PR: 1.07 (95% CI: 0.83, 1.37); processed meat, PR: 1.11 (95% CI: 0.91, 1.36)]. In site-specific analyses, although no dose-response relation was observed, processed meat was positively associated with the prevalence of advanced adenomas in the rectum only (multiple times per day compared with <1 time/wk, PR: 1.87; 95% CI: 1.19, 2.95). Poultry intake was not associated with any outcome. Conclusions: On the basis of this large colonoscopy-based study, there are no significant associations between red or processed meat intake and the prevalence of any adenomas or advanced adenomas. However, processed meat may be positively associated with the prevalence of advanced adenomas in the rectum, but prospective cohort studies are needed to further clarify this association. There is no association between poultry consumption and the prevalence of colorectal polyps in this study. �

Overview of robotic colorectal surgery: Current and future practical developments

PubMed Central

Roy, Sudipta; Evans, Charles

2016-01-01

Minimal access surgery has revolutionised colorectal surgery by offering reduced morbidity and mortality over open surgery, while maintaining oncological and functional outcomes with the disadvantage of additional practical challenges. Robotic surgery aids the surgeon in overcoming these challenges. Uptake of robotic assistance has been relatively slow, mainly because of the high initial and ongoing costs of equipment but also because of limited evidence of improved patient outcomes. Advances in robotic colorectal surgery will aim to widen the scope of minimal access surgery to allow larger and more complex surgery through smaller access and natural orifices and also to make the technology more economical, allowing wider dispersal and uptake of robotic technology. Advances in robotic endoscopy will yield self-advancing endoscopes and a widening role for capsule endoscopy including the development of motile and steerable capsules able to deliver localised drug therapy and insufflation as well as being recharged from an extracorporeal power source to allow great longevity. Ultimately robotic technology may advance to the point where many conventional surgical interventions are no longer required. With respect to nanotechnology, surgery may eventually become obsolete. PMID:26981188

Endoscopic submucosal dissection for early Barrett's neoplasia.

PubMed

Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas; Prat, Frédéric

2016-04-01

The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett's esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett's neoplasia. All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett's esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett's segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. In this early experience, ESD yielded a moderate curative resection rate in Barrett's neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett's neoplasia.

The Multidisciplinary Management of Colorectal Cancer: Present and Future Paradigms

PubMed Central

Sievers, Chelsie K.; Kratz, Jeremy D.; Zurbriggen, Luke D.; LoConte, Noelle K.; Lubner, Sam J.; Uboha, Natalya; Mulkerin, Daniel; Matkowskyj, Kristina A.; Deming, Dustin A.

2016-01-01

As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences. This review highlights the role of multidisciplinary team conferences, advances in perioperative chemotherapy, current clinical biomarkers, and emerging therapeutic agents for molecular subtypes of metastatic colon cancer. As our understanding of relevant molecular subtypes increases and as data becomes available on treatment response, the treatment of colorectal cancer will become more precise and effective. PMID:27582648

The Multidisciplinary Management of Colorectal Cancer: Present and Future Paradigms.

PubMed

Sievers, Chelsie K; Kratz, Jeremy D; Zurbriggen, Luke D; LoConte, Noelle K; Lubner, Sam J; Uboha, Natalya; Mulkerin, Daniel; Matkowskyj, Kristina A; Deming, Dustin A

2016-09-01

As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences. This review highlights the role of multidisciplinary team conferences, advances in perioperative chemotherapy, current clinical biomarkers, and emerging therapeutic agents for molecular subtypes of metastatic colon cancer. As our understanding of relevant molecular subtypes increases and as data becomes available on treatment response, the treatment of colorectal cancer will become more precise and effective.

High-resolution anoscopy or expectant management for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference?

PubMed

Crawshaw, Benjamin P; Russ, Andrew J; Stein, Sharon L; Reynolds, Harry L; Marderstein, Eric L; Delaney, Conor P; Champagne, Bradley J

2015-01-01

High-resolution anoscopy has been shown to improve identification of anal intraepithelial neoplasia but a reduction in progression to anal squamous-cell cancer has not been substantiated when serial high-resolution anoscopy is compared with traditional expectant management. The aim of this study was to compare high-resolution anoscopy versus expectant management for the surveillance of anal intraepithelial neoplasia and the prevention of anal cancer. This is a retrospective review of all patients who presented with anal squamous dysplasia, positive anal Pap smears, or anal squamous-cell cancer from 2007 to 2013. This study was performed in the colorectal department of a university-affiliated, tertiary care hospital. Included patients had biopsy-proven anal intraepithelial neoplasia from 2007 to 2013. Patients were treated with high-resolution anoscopy with ablation or standard anoscopy with ablation. Both groups were treated with imiquimod and followed every 6 months indefinitely. The incidence of anal squamous-cell cancer in each group was the primary end point. From 2007 to 2013, 424 patients with anal squamous dysplasia were seen in the clinic (high-resolution anoscopy, 220; expectant management, 204). Three patients (high-resolution anoscopy, 1; expectant management, 2) progressed to anal squamous-cell cancer; 2 were noncompliant with follow-up and with HIV treatment, and the third was allergic to imiquimod and refused to take topical 5-fluorouracil. The 5-year progression rate was 6.0% (95% CI, 1.5-24.6) for expectant management and 4.5% (95% CI, 0.7-30.8) for high-resolution anoscopy (p = 0.37). This was a retrospective review. There is potential for selection and referral bias. Because of the rarity of the outcome, the study may be underpowered. Patients with squamous-cell dysplasia followed with expectant management or high-resolution anoscopy rarely develop squamous-cell cancer if they are compliant with the protocol. The cost, morbidity, and value of high

Subependymal Heterotopia Mimicking Mass in Conventional Magnetic Resonance Imaging: Demonstration With 3T Advanced Neuroimages.

PubMed

Aktas, Filiz; Ogul, Hayri

2017-10-01

The authors reported a rare patient with large subependymal heterotopia mimicking cerebral neoplasia. A 22-year-old female was admitted with a history of right-sided paresthesia accompanied by progressive headache. Cerebral magnetic resonance (MR) imaging showed a large solid lesion in the left frontal lobe. Advanced MR images proved that the lesion was compatible with subependymal heterotopia. Large subependymal heterotopia may mimick cerebral neoplasia.

Australian contemporary management of synchronous metastatic colorectal cancer.

PubMed

Malouf, Phillip; Gibbs, Peter; Shapiro, Jeremy; Sockler, Jim; Bell, Stephen

2018-01-01

This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice. © 2016 Royal Australasian College of Surgeons.

Colorectal Cancer Prevention

MedlinePlus

... Colorectal cancer is the second leading cause of death from cancer in the United States. The number ... new colorectal cancer cases and the number of deaths from colorectal cancer are both decreasing a little ...

Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival

PubMed Central

Sawai, Hirozumi; Yasuda, Akira; Ochi, Nobuo; Ma, Jiachi; Matsuo, Yoichi; Wakasugi, Takehiro; Takahashi, Hiroki; Funahashi, Hitoshi; Sato, Mikinori; Takeyama, Hiromitsu

2008-01-01

Background The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases. Methods Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls. Results PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012). Conclusion Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients. PMID:19036165

Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia.

PubMed

Drees, R; Forrest, L J; Chappell, R

2009-07-01

Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging. Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia. Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities. We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity.

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

ClinicalTrials.gov

2018-06-08

Advanced Malignant Solid Neoplasm; KRAS Gene Mutation; Metastatic Malignant Solid Neoplasm; NRAS Gene Mutation; Recurrent Colorectal Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Colorectal Cancer AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Malignant Neoplasm

Colorectal cancer surgery in the very elderly patient: a systematic review of laparoscopic versus open colorectal resection.

PubMed

Devoto, Laurence; Celentano, Valerio; Cohen, Richard; Khan, Jim; Chand, Manish

2017-09-01

Colorectal cancer is the second most common cause of death from neoplastic disease in men and third in women of all ages. Globally, life expectancy is increasing, and consequently, an increasing number of operations are being performed on more elderly patients with the trend set to continue. Elderly patients are more likely to have cardiovascular and pulmonary comorbidities that are associated with increased peri-operative risk. They further tend to present with more locally advanced disease, more likely to obstruct or have disseminated disease. The aim of this review was to investigate the feasibility of laparoscopic colorectal resection in very elderly patients, and whether there are benefits over open surgery for colorectal cancer. A systematic literature search was performed on Medline, Pubmed, Embase and Google Scholar. All comparative studies evaluating patients undergoing laparoscopic versus open surgery for colorectal cancer in the patients population over 85 were included. The primary outcomes were 30-day mortality and 30-day overall morbidity. Secondary outcomes were operating time, time to oral diet, number of retrieved lymph nodes, blood loss and 5-year survival. The search provided 1507 citations. Sixty-nine articles were retrieved for full text analysis, and only six retrospective studies met the inclusion criteria. Overall mortality for elective laparoscopic resection was 2.92% and morbidity 23%. No single study showed a significant difference between laparoscopic and open surgery for morbidity or mortality, but pooled data analysis demonstrated reduced morbidity in the laparoscopic group (p = 0.032). Patients undergoing laparoscopic surgery are more likely to have a shorter hospital stay and a shorter time to oral diet. Elective laparoscopic resection for colorectal cancer in the over 85 age group is feasible and safe and offers similar advantages over open surgery to those demonstrated in patients of younger ages.

Reduced miR-433 expression is associated with advanced stages and early relapse of colorectal cancer and restored miR-433 expression suppresses the migration, invasion and proliferation of tumor cells in vitro and in nude mice.

PubMed

Zhang, Jian; Zhang, Lei; Zhang, Tong; Dong, Xin-Min; Zhu, Yu; Chen, Long-Hua

2018-05-01

The expression of microRNA (miR-433) is altered in various types of human cancer. The present study analyzed the prognostic and biological value of miR-433 expression in colorectal cancer using reverse transcription-quantitative polymerase chain reaction in 125 colorectal tissue specimens (including a test cohort of 40 cases of paired colorectal cancer and adjacent normal mucosae and a confirmation cohort of 85 cases of stage I-III colorectal cancer). In vitro and nude mouse xenograft experiments were subsequently used to assess the effects of miR-433 expression on the regulation of colorectal cancer cell proliferation, adhesion, migration, and invasion. The data indicated that miR-433 expression was significantly downregulated in colorectal cancer tissues in the test and confirmation patient cohorts and that low miR-433 expression was associated with advanced tumor stage and early relapse. Furthermore, the restoration of miR-433 expression was able to significantly inhibit the proliferation of tumor cells by inducing G1-S cell cycle arrest, suppressing cyclinD1 and CDK4 expression, and markedly inhibited the migratory and invasive capacities of tumor cells in vitro . The restoration of miR-433 expression or liposome-based delivery of miR-433 mimics suppressed the growth of colorectal cancer cell xenografts in nude mice. In conclusion, miR-433 may be a putative tumor suppressor in colorectal cancer, and the detection of low miR-433 expression will be investigated in further studies as a putative biomarker for the detection of early relapse in patients with colorectal cancer.

Reduced miR-433 expression is associated with advanced stages and early relapse of colorectal cancer and restored miR-433 expression suppresses the migration, invasion and proliferation of tumor cells in vitro and in nude mice

PubMed Central

Zhang, Jian; Zhang, Lei; Zhang, Tong; Dong, Xin-Min; Zhu, Yu; Chen, Long-Hua

2018-01-01

The expression of microRNA (miR-433) is altered in various types of human cancer. The present study analyzed the prognostic and biological value of miR-433 expression in colorectal cancer using reverse transcription-quantitative polymerase chain reaction in 125 colorectal tissue specimens (including a test cohort of 40 cases of paired colorectal cancer and adjacent normal mucosae and a confirmation cohort of 85 cases of stage I–III colorectal cancer). In vitro and nude mouse xenograft experiments were subsequently used to assess the effects of miR-433 expression on the regulation of colorectal cancer cell proliferation, adhesion, migration, and invasion. The data indicated that miR-433 expression was significantly downregulated in colorectal cancer tissues in the test and confirmation patient cohorts and that low miR-433 expression was associated with advanced tumor stage and early relapse. Furthermore, the restoration of miR-433 expression was able to significantly inhibit the proliferation of tumor cells by inducing G1-S cell cycle arrest, suppressing cyclinD1 and CDK4 expression, and markedly inhibited the migratory and invasive capacities of tumor cells in vitro. The restoration of miR-433 expression or liposome-based delivery of miR-433 mimics suppressed the growth of colorectal cancer cell xenografts in nude mice. In conclusion, miR-433 may be a putative tumor suppressor in colorectal cancer, and the detection of low miR-433 expression will be investigated in further studies as a putative biomarker for the detection of early relapse in patients with colorectal cancer. PMID:29740483

Detection of colorectal cancer using time-resolved autofluorescence spectrometer

NASA Astrophysics Data System (ADS)

Fu, Sheng; Kwek, Leong-Chuan; Chia, Teck-Chee; Lim, Chu-Sing; Tang, Choong-Leong; Ang, Wuan-Suan; Zhou, Miao-Chang; Loke, Po-Ling

2006-04-01

As we know Quantum mechanics is a mathematical theory that can describe the behavior of objects that are at microscopic level. Time-resolved autofluorescence spectrometer monitors events that occur during the lifetime of the excited state. This time ranges from a few picoseconds to hundreds of nanoseconds. That is an extremely important advance as it allows environmental parameters to be monitored in a spatially defined manner in the specimen under study. This technique is based on the application of Quantum Mechanics. This principle is applied in our project as we are trying to use different fluorescence spectra to detect biological molecules commonly found in cancerous colorectal tissue and thereby differentiate the cancerous and non-cancerous colorectal polyps more accurately and specifically. In this paper, we use Fluorescence Lifetime Spectrometer (Edinburgh Instruments FL920) to measure decay time of autofluorescence of colorectal cancerous and normal tissue sample. All specimens are from Department of Colorectal Surgery, Singapore General Hospital. The tissues are placed in the time-resolved autofluorescence instrument, which records and calculates the decay time of the autofluorescence in the tissue sample at the excitation and emission wavelengths pre-determined from a conventional spectrometer. By studying the decay time,τ, etc. for cancerous and normal tissue, we aim to present time-resolved autofluorescence as a feasible technique for earlier detection of malignant colorectal tissues. By using this concept, we try to contribute an algorithm even an application tool for real time early diagnosis of colorectal cancer for clinical services.

Broad Detection of Alterations Predicted to Confer Lack of Benefit From EGFR Antibodies or Sensitivity to Targeted Therapy in Advanced Colorectal Cancer.

PubMed

Rankin, Andrew; Klempner, Samuel J; Erlich, Rachel; Sun, James X; Grothey, Axel; Fakih, Marwan; George, Thomas J; Lee, Jeeyun; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A; Ali, Siraj M; Schrock, Alexa B

2016-09-28

A KRAS mutation represented the first genomic biomarker to predict lack of benefit from anti-epidermal growth factor receptor (EGFR) antibody therapy in advanced colorectal cancer (CRC). Expanded RAS testing has further refined the treatment approach, but understanding of genomic alterations underlying primary and acquired resistance is limited and further study is needed. We prospectively analyzed 4,422 clinical samples from patients with advanced CRC, using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians. Comparison with prior molecular testing results, when available, was performed to assess concordance. We identified a RAS/RAF pathway mutation or amplification in 62% of cases, including samples harboring KRAS mutations outside of the codon 12/13 hotspot region in 6.4% of cases. Among cases with KRAS non-codon 12/13 alterations for which prior test results were available, 79 of 90 (88%) were not identified by focused testing. Of 1,644 RAS/RAF wild-type cases analyzed by CGP, 31% harbored a genomic alteration (GA) associated with resistance to anti-EGFR therapy in advanced CRC including mutations in PIK3CA, PTEN, EGFR, and ERBB2. We also identified other targetable GA, including novel kinase fusions, receptor tyrosine kinase amplification, activating point mutations, as well as microsatellite instability. Extended genomic profiling reliably detects alterations associated with lack of benefit to anti-EGFR therapy in advanced CRC, while simultaneously identifying alterations potentially important in guiding treatment. The use of CGP during the course of clinical care allows for the refined selection of appropriate targeted therapies and clinical trials, increasing the chance of clinical benefit and avoiding therapeutic futility. Comprehensive genomic profiling (CGP) detects diverse genomic alterations associated with lack of benefit to anti-epidermal growth factor receptor therapy in advanced

[Initial experience in robot-assisted colorectal surgery in Mexico].

PubMed

Villanueva-Sáenz, Eduardo; Ramírez-Ramírez, Moisés Marino; Zubieta-O'Farrill, Gregorio; García-Hernández, Luis

Colorectal surgery has advanced notably since the introduction of the mechanical suture and the minimally invasive approach. Robotic surgery began in order to satisfy the needs of the patient-doctor relationship, and migrated to the area of colorectal surgery. An initial report is presented on the experience of managing colorectal disease using robot-assisted surgery, as well as an analysis of the current role of this platform. A retrospective study was conducted in order to review five patients with colorectal disease operated using a robot-assisted technique over one year in the initial phase of the learning curve. Gender, age, diagnosis and surgical indication, surgery performed, surgical time, conversion, bleeding, post-operative complications, and hospital stay, were analysed and described. A literature review was performed on the role of robotic assisted surgery in colorectal disease and cancer. The study included 5 patients, 3 men and 2 women, with a mean age of 62.2 years. Two of them were low anterior resections with colorectal primary anastomoses, one of them extended with a loop protection ileostomy, a Frykman-Goldberg procedure, and two left hemicolectomies with primary anastomoses. The mean operating time was 6hours and robot-assisted 4hours 20minutes. There were no conversions and the mean hospital stay was 5 days. This technology is currently being used worldwide in different surgical centres because of its advantages that have been clinically demonstrated by various studies. We report the first colorectal surgical cases in Mexico, with promising results. There is enough evidence to support and recommend the use of this technology as a viable and safe option. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

PubMed

Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

2016-09-01

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

Interventions Promoting Colorectal Cancer Screening Among Latino Men: A Systematic Review.

PubMed

Mojica, Cynthia M; Parra-Medina, Deborah; Vernon, Sally

2018-03-08

Colorectal cancer, the second leading cause of cancer death in the United States, is also among the most preventable cancers. However, Latino men are less likely than non-Latino men to engage in preventive screening. Compared with 60% of non-Latino white men and women, only 42% of Latino men are up to date with colorectal cancer screening guidelines, which may result in diagnosis at advanced disease stages and increased deaths. We evaluated the literature on colorectal cancer screening interventions among Latino men to characterize intervention components effective in increasing colorectal cancer screening. Two independent reviewers searched MEDLINE, CINAHL, and PsycINFO to identify articles on intervention studies that promote colorectal cancer screening among Latino men. Inclusion criteria were randomized controlled or comparative effectiveness trials, an outcome of any colorectal cancer screening test, published in English, US-based, results published from January 2004 through December 2016, Latino or Spanish-speaking male participants, and a minimum of one patient-level component. Two other reviewers independently assessed article quality and conducted data abstraction. Forty-four studies met the inclusion criteria; only 7 studies with 20% or more Latinos and 39% or more men were included in the final analyses. The most common intervention strategies included one-on-one interactions with a patient navigator and reducing structural barriers (eg, providing fecal occult blood tests). Interventions using small media produced mixed results. Although intervention studies focused on colorectal cancer screening among men of racial/ethnic minorities are scarce, our findings highlight promising strategies that were effective at increasing colorectal cancer screening among Latino men. Additional research in the area of Latino men's health is needed, especially to further develop and test theoretically grounded interventions that promote colorectal cancer screening with

Role of β1-Integrin in Colorectal Cancer: Case-Control Study

PubMed Central

Oh, Bo-Young; Kim, Kwang Ho; Chung, Soon Sup; Hong, Kyoung Sook

2014-01-01

Purpose In the metastatic process, interactions between circulating tumor cells (CTCs) and the extracellular matrix or surrounding cells are required. β1-Integrin may mediate these interactions. The aim of this study was to investigate whether β1-integrin is associated with the detection of CTCs in colorectal cancer. Methods We enrolled 30 patients with colorectal cancer (experimental group) and 30 patients with benign diseases (control group). Blood samples were obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and β1-integrin mRNA levels were estimated by using reverse transcription-polymerase chain reaction, and the results were compared between the two groups. In the experimental group, preoperative results were compared with postoperative results for each marker. In addition, we analyzed the correlation between the expressions of β1-integrin and CEA. Results CEA mRNA was detected more frequently in colorectal cancer patients than in control patients (P = 0.008). CEA mRNA was significantly reduced after surgery in the colorectal cancer patients (P = 0.032). β1-Integrin mRNA was detected more in colorectal cancer patients than in the patients with benign diseases (P < 0.001). In colorectal cancer patients, expression of β1-integrin mRNA was detected more for advanced-stage cancer than for early-stage cancer (P = 0.033) and was significantly decreased after surgery (P < 0.001). In addition, expression of β1-integrin mRNA was significantly associated with that of CEA mRNA in colorectal cancer patients (P = 0.001). Conclusion In conclusion, β1-integrin is a potential factor for forming a prognosis following surgical resection in colorectal cancer patients. β1-Integrin may be a candidate for use as a marker for early detection of micrometastatic tumor cells and for monitoring the therapeutic response in colorectal cancer patients. PMID:24851215

Prevalence of colorectal cancer in acute uncomplicated diverticulitis and the role of the interval colonoscopy.

PubMed

Soh, Nicholas Yock Teck; Chia, Daryl Kai Ann; Teo, Nan Zun; Ong, Calvin Jian Ming; Wijaya, Ramesh

2018-04-16

Although computed tomography (CT) is the imaging modality of choice for diagnosing colonic diverticulitis today, there remains a risk of colorectal cancer mimicking diverticulitis due to overlapping imaging features. Current practice guidelines recommend interval colonoscopy after diverticulitis to exclude occult malignancy. Some authors have suggested that this may be unnecessary in patients with uncomplicated diverticulitis. The aim of our study was to examine the prevalence of occult colorectal cancer in patients with CT-proven acute uncomplicated diverticulitis in an Asian population. This was a retrospective study of all patients admitted for CT-proven acute uncomplicated diverticulitis between 2007 and 2011 in a single institution. Colonoscopy and histopathology reports were reviewed for patients who underwent interval colonic evaluation. For patients who defaulted follow-up, national health records were reviewed for any subsequent diagnoses of colorectal cancer. The primary outcome was prevalence of colorectal cancer in the cohort. Secondary outcome was prevalence of advanced adenomas. A total of 227 patients with acute uncomplicated diverticulitis were included in our study. One hundred and thirty-five patients (59.5%) underwent follow-up colonic evaluation. The overall prevalence of colorectal cancer was 1.8%, with half these patients presenting with acute colonic obstruction after defaulting follow-up evaluation. Of the patients, 1.5% who underwent colonoscopy had advanced adenomas. Prevalence of colorectal cancer in patients with CT-proven acute uncomplicated diverticulitis may not be as low as previously suggested. We recommend that patients with acute uncomplicated diverticulitis continue to be offered interval colonoscopy until larger studies demonstrate the safety of omission.

A transposon-based genetic screen in mice identifies genes altered in colorectal cancer.

PubMed

Starr, Timothy K; Allaei, Raha; Silverstein, Kevin A T; Staggs, Rodney A; Sarver, Aaron L; Bergemann, Tracy L; Gupta, Mihir; O'Sullivan, M Gerard; Matise, Ilze; Dupuy, Adam J; Collier, Lara S; Powers, Scott; Oberg, Ann L; Asmann, Yan W; Thibodeau, Stephen N; Tessarollo, Lino; Copeland, Neal G; Jenkins, Nancy A; Cormier, Robert T; Largaespada, David A

2009-03-27

Human colorectal cancers (CRCs) display a large number of genetic and epigenetic alterations, some of which are causally involved in tumorigenesis (drivers) and others that have little functional impact (passengers). To help distinguish between these two classes of alterations, we used a transposon-based genetic screen in mice to identify candidate genes for CRC. Mice harboring mutagenic Sleeping Beauty (SB) transposons were crossed with mice expressing SB transposase in gastrointestinal tract epithelium. Most of the offspring developed intestinal lesions, including intraepithelial neoplasia, adenomas, and adenocarcinomas. Analysis of over 16,000 transposon insertions identified 77 candidate CRC genes, 60 of which are mutated and/or dysregulated in human CRC and thus are most likely to drive tumorigenesis. These genes include APC, PTEN, and SMAD4. The screen also identified 17 candidate genes that had not previously been implicated in CRC, including POLI, PTPRK, and RSPO2.

Concurrent endocrine neoplasias in dogs and cats: a retrospective study (2004-2014).

PubMed

Beatrice, Laura; Boretti, Felicitas Schär; Sieber-Ruckstuhl, Nadja S; Mueller, Claudia; Kümmerle-Fraune, Claudia; Hilbe, Monika; Grest, Paula; Reusch, Claudia E

2018-03-17

Multiple endocrine neoplasia (MEN) is a well-known syndrome in human medicine, whereas only a few cases of concurrent endocrine neoplasias have been reported in dogs and cats. The aim of this study was to evaluate the prevalence of concurrent endocrine neoplasias in dogs and cats at our clinic, identify possible breed and sex predispositions and investigate similarities with MEN syndromes in humans. Postmortem reports of 951 dogs and 1155 cats that died or were euthanased at the Clinic for Small Animal Internal Medicine, University of Zurich, between 2004 and 2014 were reviewed, and animals with at least two concurrent endocrine neoplasias and/or hyperplasias were included. Twenty dogs and 15 cats met the inclusion criteria. In dogs, the adrenal glands were most commonly affected. Multiple tumours affecting the adrenal glands and the association of these tumours with pituitary adenomas were the most common tumour combinations. Only one dog had a combination resembling human MEN type 1 syndrome (pituitary adenoma and insulinoma). In cats, the thyroid glands were most commonly affected and there were no similarities to human MEN syndromes. The prevalence of concurrent endocrine neoplasia was 2.1 per cent in dogs and 1.3 per cent in cats and MEN-like syndromes are very rare in these species. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia

PubMed Central

Drees, R.; Forrest, L. J.; Chappell, R.

2009-01-01

Objectives Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging. Methods Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia. Results Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities. Clinical Significance We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity. PMID:19508490

[Aspirin and colorectal cancer].

PubMed

Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

2018-02-01

Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Colorectal cancer development and advances in screening.

PubMed

Simon, Karen

2016-01-01

Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective.

Colorectal cancer development and advances in screening

PubMed Central

Simon, Karen

2016-01-01

Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective. PMID:27486317

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.

PubMed

Sun, Pin; Zhu, Xiangzhu; Shrubsole, Martha J; Ness, Reid M; Hibler, Elizabeth A; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Hou, Lifang; Smalley, Walter E; Edwards, Todd L; Giovannucci, Edward; Zheng, Wei; Dai, Qi

2017-09-01

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)]. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of new technology on surgery for colorectal cancer

PubMed Central

Makin, Gregory B; Breen, David J; Monson, John RT

2001-01-01

Advances in technology continue at a rapid pace and affect all aspects of life, including surgery. We have reviewed some of these advances and the impact they are having on the investigation and management of colorectal cancer. Modern endoscopes, with magnifying, variable stiffness and localisation capabilities are making the primary investigation of colonic cancer easier and more acceptable for patients. Imaging investigations looking at primary, metastatic and recurrent disease are shifting to digital data sets, which can be stored, reviewed remotely, potentially fused with other modalities and reconstructed as 3 dimensional (3D) images for the purposes of advanced diagnostic interpretation and computer assisted surgery. They include virtual colonoscopy, trans-rectal ultrasound, magnetic resonance imaging, positron emission tomography and radioimmunoscintigraphy. Once a colorectal carcinoma is diagnosed, the treatment options available are expanding. Colonic stents are being used to relieve large bowel obstruction, either as a palliative measure or to improve the patient’s overall condition before definitive surgery. Transanal endoscopic microsurgery and minimally invasive techniques are being used with similar outcomes and a lower mortality, morbidity and hospital stay than open trans-abdominal surgery. Transanal endoscopic microsurgery allows precise excision of both benign and early malignant lesions in the mid and upper rectum. Survival of patients with inoperable hepatic metastases following radiofrequency ablation is encouraging. Robotics and telemedicine are taking surgery well into the 21st century. Artificial neural networks are being developed to enable us to predict the outcome for individual patients. New technology has a major impact on the way we practice surgery for colorectal cancer. PMID:11819841

[Colorectal cancer screening: follow-up of patients with adenomatous and colorectal cancer].

PubMed

Antonino, Anca-Teodora; Anca, Antonino; Frei, Alain; Ali-el-Wafa, Abdou; Kessler-Brondolo, Véra; Dorta, Gian

2008-01-23

The different methods of colorectal cancer screening are discussed. Our recommendations had not changed: we recommend as colorectal cancer screening a colonoscopy at the age of 50 years in all healthy persons with average risk for colorectal cancer. A 2007 interdisciplinary consensus conference revised the Swiss recommendations for the follow-up of patients with operated colorectal cancer or after polypectomy.

[Economic Evaluation of mFOLFOX6-based First-line Regimens for Unresectable Advanced or Recurrent Colorectal Cancer Using Clinical Decision Analysis].

PubMed

Shida, Toshihiro; Endo, Yuji; Shiraishi, Tadashi; Yoshioka, Takashi; Suzuki, Kaoru; Kobayashi, Yuka; Ono, Yuki; Ito, Toshinori; Inoue, Tadao

2018-01-01

 We evaluated four representative chemotherapy regimens for unresectable advanced or recurrent KRAS-wild type colorectal cancer: mFOLFOX6, mFOLFOX6+bevacizumab (Bmab), cetuximab (Cmab), or panitumumab (Pmab). We employed a decision analysis method in combination with clinical and economic evidence. The health outcomes of the regimens were analyzed on the basis of overall and progression-free survival. The data were drawn from the literature on randomized controlled clinical trials of the above-mentioned drugs. The total costs of the regimens were calculated on the basis of direct costs obtained from the medical records of patients diagnosed with unresectable advanced or recurrent colorectal cancer at Yamagata University Hospital and Yamagata Prefecture Central Hospital. Cost effectiveness was analyzed using a Markov chain Monte Carlo (MCMC) method. The study was designed from the viewpoint of public medical care. The MCMC analysis revealed that expected life months and expected cost were 20 months/3,527,119 yen for mFOLFOX6, 27 months/8,270,625 yen for mFOLFOX6+Bmab, 29 months/13,174,6297 yen for mFOLFOX6+Cmab, and 6 months/12,613,445 yen for mFOLFOX6+Pmab. Incremental costs per effectiveness ratios per life month against mFOLFOX6 were 637,592 yen for mFOLFOX6+Bmab, 1,075,162 yen for mFOLFOX6+Cmab, and 587,455 yen for mFOLFOX6+Pmab. Compared to the conventional mFOLFOX6 regimen, molecular-targeted drug regimens provide better health outcomes, but the cost increases accordingly. mFOLFOX 6+Pmab is the most cost-effective regimen among those surveyed in this study.

Endoscopic diagnosis and treatment of early esophageal squamous neoplasia

PubMed Central

Shimamura, Yuto; Ikeya, Takashi; Marcon, Norman; Mosko, Jeffrey D

2017-01-01

Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality. It carries a poor prognosis as more than half of patients present with advanced and unresectable disease. One contributing factor is the increased risk of lymph node metastases at early stages of disease. As such, it is essential to detect squamous cell neoplasia (SCN) at an early stage. In order to risk stratify lesions, endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol’s chromoendoscopy. The assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to treatment. Endoscopic mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective use. Radiofrequency ablation and other endoscopic treatments are currently available although should not be considered first line at this time. Our objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN. PMID:28979708

Racial differences in colorectal cancer mortality. The importance of stage and socioeconomic status.

PubMed

Marcella, S; Miller, J E

2001-04-01

This investigation studies racial and socioeconomic differences in mortality from colorectal cancer, and how they vary by stage and age at diagnosis. Cox proportional hazards models were used to estimate the hazard ratio of dying from colorectal cancer, controlling for tumor characteristics and sociodemographic factors. Black adults had a greater risk of death from colorectal cancer, especially in early stages. The gender gap in mortality is wider among blacks than whites. Differences in tumor characteristics and socioeconomic factors each accounted for approximately one third of the excess risk of death among blacks. Effects of socioeconomic factors and race varied significantly by age. Higher stage-specific mortality rates and more advanced stage at diagnosis both contribute to the higher case-fatality rates from colorectal cancer among black adults, only some of which is due to socioeconomic differences. Socioeconomic and racial factors have their most significant effects in different age groups.

COLORECTAL CANCER

PubMed Central

Kuipers, Ernst J.; Grady, William M.; Lieberman, David; Seufferlein, Thomas; Sung, Joseph J.; Boelens, Petra G.; van de Velde, Cornelis J. H.; Watanabe, Toshiaki

2016-01-01

Colorectal cancer had a low incidence several decades ago. However, it has become a predominant cancer and now accounts for approximately 10% of cancer-related mortality in western countries. The ‘rise’ of colorectal cancer in developed countries can be attributed to the increasingly ageing population, unfavourable modern dietary habits and an increase in risk factors such as smoking, low physical exercise and obesity. New treatments for primary and metastatic colorectal cancer have emerged, providing additional options for patients; these treatments include laparoscopic surgery for primary disease, more-aggressive resection of metastatic disease (such as liver and pulmonary metastases), radiotherapy for rectal cancer and neoadjuvant and palliative chemotherapies. However, these new treatment options have had limited impact on cure rates and long-term survival. For these reasons, and the recognition that colorectal cancer is long preceded by a polypoid precursor, screening programmes have gained momentum. This Primer provides an overview of the current state of art knowledge on the epidemiology and mechanisms of colorectal cancer, as well as on diagnosis and treatment. PMID:27189416

Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Bibbins-Domingo, Kirsten; Grossman, David C; Curry, Susan J; Davidson, Karina W; Epling, John W; García, Francisco A R; Gillman, Matthew W; Harper, Diane M; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Owens, Douglas K; Phillips, William R; Phipps, Maureen G; Pignone, Michael P; Siu, Albert L

2016-06-21

Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134,000 persons will be diagnosed with the disease, and about 49,000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 68 years. To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer. 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. 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. 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

Dietary Intakes of Red Meat, Poultry, and Fish During High School and Risk of Colorectal Adenomas in Women

PubMed Central

Nimptsch, Katharina; Bernstein, Adam M.; Giovannucci, Edward; Fuchs, Charles S.; Willett, Walter C.; Wu, Kana

2013-01-01

Adolescent diet may be etiologically relevant for colorectal carcinogenesis. We examined the association between meat and fish intakes during adolescence and the risk of colorectal adenomas later in life among 19,771 women participating in the Nurses' Health Study II. Subjects had completed a validated food frequency questionnaire in 1998 (when aged 34–51 years) about their diets during high school and subsequently underwent at least 1 lower-bowel endoscopy during the study period (1998–2007). During this period, 1,494 subjects were diagnosed with colorectal adenomas. Intake of red meat during adolescence was not associated with colorectal adenoma risk when comparing those in the highest versus lowest category of intake (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.81, 1.35). Similarly, intake of fish during adolescence was not associated with colorectal adenoma risk (OR = 0.96, 95% CI: 0.78, 1.17). Intake of poultry during adolescence was associated with a lower risk of total colorectal (OR = 0.80, 95% CI: 0.64, 0.99), distal (OR = 0.71, 95% CI: 0.51, 0.99), rectal (OR = 0.51, 95% CI: 0.29, 0.90), and advanced (OR = 0.60, 95% CI: 0.38, 0.93) adenomas. Replacement of 1 serving per day of red meat with 1 serving per day of poultry or fish was associated with 41% and 35% decreased risks for rectal adenomas and advanced adenomas, respectively. Our findings do not suggest an association between red meat intake during adolescence and colorectal adenomas later in life, but higher poultry intake during this time was associated with a lower risk of colorectal adenomas. PMID:23785116

Colorectal Cancer

MedlinePlus

... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

Safety of laparoscopic colorectal surgery in a low-volume setting: review of early and late outcome.

PubMed

Gandy, Robert C; Berney, Christophe R

2014-01-01

Background. There is increasing evidence suggesting that the laparoscopic technique is the treatment of choice for large bowel resection, including for malignancy. The purpose of the study was to assess whether general surgeons, with particular skills in advanced laparoscopy, can adequately provide safe laparoscopic colorectal resections in a low-volume setting. Methods. A retrospective review of prospectively collected case series of all laparoscopic colorectal resections performed under the care of a single general surgeon is presented. The primary endpoint was postoperative clinical outcome in terms of morbidity and mortality. Secondary endpoints were adequacy of surgical margins and number of lymph nodes harvested for colorectal cancer cases. Results. Seventy-three patients underwent 75 laparoscopic resections between March, 2003, and May, 2011. There was no elective mortality and the overall 30-day postoperative morbidity was 9.3%. Conversion and anastomotic leakage rates were both 1.3%, respectively. None of the malignant cases had positive margins and the median number of lymph nodes retrieved was 17. Conclusions. Our results support the view that general surgeons with advanced skills in minimally invasive surgery may safely perform laparoscopic colorectal resection in a low-volume setting in carefully selected patient cases.

Safety of Laparoscopic Colorectal Surgery in a Low-Volume Setting: Review of Early and Late Outcome

PubMed Central

Gandy, Robert C.; Berney, Christophe R.

2014-01-01

Background. There is increasing evidence suggesting that the laparoscopic technique is the treatment of choice for large bowel resection, including for malignancy. The purpose of the study was to assess whether general surgeons, with particular skills in advanced laparoscopy, can adequately provide safe laparoscopic colorectal resections in a low-volume setting. Methods. A retrospective review of prospectively collected case series of all laparoscopic colorectal resections performed under the care of a single general surgeon is presented. The primary endpoint was postoperative clinical outcome in terms of morbidity and mortality. Secondary endpoints were adequacy of surgical margins and number of lymph nodes harvested for colorectal cancer cases. Results. Seventy-three patients underwent 75 laparoscopic resections between March, 2003, and May, 2011. There was no elective mortality and the overall 30-day postoperative morbidity was 9.3%. Conversion and anastomotic leakage rates were both 1.3%, respectively. None of the malignant cases had positive margins and the median number of lymph nodes retrieved was 17. Conclusions. Our results support the view that general surgeons with advanced skills in minimally invasive surgery may safely perform laparoscopic colorectal resection in a low-volume setting in carefully selected patient cases. PMID:24799890

Mathematical models for the early detection and treatment of colorectal cancer.

PubMed

Harper, P R; Jones, S K

2005-05-01

Colorectal cancer is a major cause of death for men and women in the Western world. When the cancer is detected through an awareness of the symptoms by a patient, typically it is at an advanced stage. It is possible to detect cancer at an early stage through screening and the marked differences in survival for early and late stages provide the incentive for the primary prevention or early detection of colorectal cancer. This paper considers mathematical models for colorectal cancer screening together with models for the treatment of patients. Illustrative results demonstrate that detailed attention to the processes involved in diseases, interventions and treatment enable us to combine data and expert knowledge from various sources. Thus a detailed operational model is a very useful tool in helping to make decisions about screening at national and local levels.

The research on the influences of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis.

PubMed

Sun, J-J; Fan, G-L; Wang, X-G; Xu, K

2017-07-01

To investigated the influence of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis. We enrolled 98 advanced colorectal cancer patients with liver metastasis that were admitted to this hospital for treatment and were randomly divided into two groups, the observation group (n = 49) and the control group (n = 49). We administered systemic vein chemotherapy for patients in the control group, and hyperthermal perfusion chemotherapy for the patients in the observation group in order to compare the subgroup levels of T lymphocytes, NK cells and immunoglobulin (IgG, IgA, and IgM) in the immune system of patients in both groups. We also assayed the circulating tumor cells (CTC) in the peripheral blood of patients in both groups using the cell search method, and compared the efficacy using response evaluation criteria in solid tumors and the survival rates of patients in both groups using the Kaplan-Meier method. After two treatment courses, the levels of CD3+, CD4+ and CD4+/CD8+ of the patients in the observation group were significantly higher than those of the control group, but the levels of CD8+ of patients in the observation group was lower than that in the control group (p< 0.05). The levels of immunoglobulins (IgG, IgA, and IgM) in the observation group were higher than the control group (p < 0.05). The levels of NK cell cells were significantly lower than the control group (p < 0.05). The objective response rate, as well as the disease control rate of the observation group, were remarkably higher than those of the control group (p < 0.05). Compared to the control group, the observation group enjoyed a prolonged survival time, higher survival rate and significantly lower positive rate of CTC (p < 0.05). Better efficacy and tolerance, fewer toxic and side effects, improvement in the immunologic functions of patients for

Anal and Cervical High-Risk Human Papillomavirus Genotyping in Women With and Without Genital Neoplasia.

PubMed

Bregar, Amy J; Cronin, Beth; Luis, Christine; DiSilvestro, Paul; Schechter, Steven; Pisharodi, Latha; Raker, Christina; Clark, Melissa; Robison, Katina

2018-04-01

The aim of the study was to compare the prevalence, genotypes, and rates of concomitant anal and cervical high-risk human papillomavirus (HR-HPV) in women with and without a history of HPV-related genital neoplasia. This was a prospective cohort study conducted from December 2012 to February 2014. Women with a history of neoplasia were considered the high-risk group. Women without a history of neoplasia were considered the low-risk group. Cervical and anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for anoscopy. One hundred eighty-four women met inclusion criteria. High-risk HPV was detected in the anal canal of 17.4% of the high-risk group and 1.5% of the low-risk group (p = .003). High-risk HPV was detected in the cervix of 30.5% of the high-risk group and 7.6% of the low-risk group (p < .001). Concomitant anal and cervical high-risk HPV was detected in 4.4% of the high-risk group and was not detected in the low-risk group (p = .2). Among women with anal intraepithelial neoplasia 2 or greater (n = 5), 60% had HR-HPV detected in the anal canal while none had HR-HPV detected in the cervix. Women with a history of genital neoplasia are more likely to be positive for anal and cervical HR-HPV compared with women without a history of genital neoplasia. Although there was no significant difference in rates of concomitant HR-HPV between low- and high-risk groups, HR-HPV can be found concomitantly in the anus and the cervix and may be associated with anal intraepithelial neoplasia or carcinoma.

Endoscopic submucosal dissection for early Barrett’s neoplasia

PubMed Central

Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas

2015-01-01

Introduction The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett’s esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett’s neoplasia. Methods All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett’s esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Results Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett’s segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. Conclusion In this early experience, ESD yielded a moderate curative resection rate in Barrett’s neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett’s neoplasia. PMID:27087948

Colorectal cancer mortality in Poland – analysis of regional variation

PubMed Central

Kempińska-Mirosławska, Bogumiła; Mik, Michał; Dziki, Łukasz; Dziki, Adam

2012-01-01

Introduction In 1999 in Poland 7,139 people died of colon cancer, while in 2008 this number rose to 9,915. Among malignant tumours, colorectal cancer is the second most commonly occurring one, frequently leading to death. The main reason for this is the fact that in 50% of patients with this cancer the illness is diagnosed at an advanced stage already. The risk increases significantly after 60 years of age. The aim of study was analysing the mortality of patients with colorectal cancer over 10 years in Poland (1999-2008), in both men and women from all provinces in the country. Material and methods The basis for the study was the number of deaths caused by colorectal cancer taking into account sex. Statistical data were drawn from the National Cancer Registry. Results In 1999 in Poland 3,706 men and 3,433 women died of colorectal cancer, while in 2008 the number of deaths stood at 5,385 and 4,530 respectively. In the years 1999-2008, colorectal cancer mortality rates among men were approximately 1.5 times higher than among women, and the majority of provinces demonstrate an upward trend. Among women the differences in the values of the coefficients are less clear. Conclusions Early detection of cancer could significantly reduce mortality among patients with colon cancer. Screening for colorectal cancer and colonoscopy are tests that should permanently become a part of preventive measures aimed at detecting disease and teaching risk factors, particularly in males and people over 60 years of age. PMID:24701216

Lower limb compartment syndrome following laparoscopic colorectal surgery: a review.

PubMed

Rao, M M; Jayne, D

2011-05-01

  In spite of recent advances in technology and technique, laparoscopic colorectal surgery is associated with increased operating times when compared with open surgery. This increases the risk of acute lower limb compartment syndrome. The aim of this review was to gain a better understanding of postoperative lower limb compartment syndrome following laparoscopic colorectal surgery and to suggest strategies to avoid its occurrence. A MEDLINE search was performed using the keywords 'compartment syndrome', 'laparoscopic surgery' and 'Lloyd-Davies position' between 1970 and 2008. All relevant articles were retrieved and reviewed. A total of 54 articles were retrieved. Of the 30 articles in English, five were reviews, six were original articles and 19 were case reports, of which only one was following laparoscopic colorectal surgery. The remaining 24 were non-English articles. Of these, two were reviews and 22 were case reports, of which only one was following laparoscopic colorectal surgery. The incidence of acute compartment syndrome following laparoscopic colorectal surgery is unknown. The following are believed to be risk factors for acute lower limb compartment syndrome: the Lloyd-Davies operating position with exaggerated Trendelenburg tilt, prolonged operative times and improper patient positioning. Simple strategies are suggested to reduce its occurrence. Simple preventative measures have been identified which may help to reduce the incidence of acute lower limb compartment syndrome. However, if suspected, timely surgical intervention with four-compartment fasciotomy remains the standard of care. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

The Expression and Significance of Feces Cyclooxygensae-2 mRNA in Colorectal Cancer and Colorectal Adenomas

PubMed Central

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

Background/Aim: This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. Materials and Methods: The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. Results: The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842, P = 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525, P = 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. Conclusions: High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer. PMID:28139497

The expression and significance of feces cyclooxygensae-2 mRNA in colorectal cancer and colorectal adenomas.

PubMed

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842,P= 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525,P= 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer.

Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy

PubMed Central

Murcia, Oscar; Juárez, Miriam; Hernández-Illán, Eva; Egoavil, Cecilia; Giner-Calabuig, Mar; Rodríguez-Soler, María; Jover, Rodrigo

2016-01-01

Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer (CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of CpG islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy. PMID:27053844

Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC).

PubMed

Hammoudi, Abeer; Song, Fei; Reed, Karen R; Jenkins, Rosalind E; Meniel, Valerie S; Watson, Alastair J M; Pritchard, D Mark; Clarke, Alan R; Jenkins, John R

2013-10-25

Colorectal cancer (CRC) is the fourth most common cause of cancer-related death worldwide. Accurate non-invasive screening for CRC would greatly enhance a population's health. Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation. Acute conditional transgenic deletion of Apc in murine intestinal epithelium (AhCre(+)Apc(fl)(/)(fl)) causes phenotypic changes similar to those found during colorectal tumourigenesis. This study comprised a proteomic analysis of murine small intestinal epithelial cells following acute Apc deletion to identify proteins that show altered expression during human colorectal carcinogenesis, thus identifying proteins that may prove clinically useful as blood/serum biomarkers of colorectal neoplasia. Eighty-one proteins showed significantly increased expression following iTRAQ analysis, and validation of nine of these by Ingenuity Pathaway Analysis showed they could be detected in blood or serum. Expression was assessed in AhCre(+)Apc(fl)(/)(fl) small intestinal epithelium by immunohistochemistry, western blot and quantitative real-time PCR; increased nucelolin concentrations were also detected in the serum of AhCre(+)Apc(fl)(/)(fl) and Apc(Min)(/)(+) mice by ELISA. Six proteins; heat shock 60kDa protein 1, Nucleolin, Prohibitin, Cytokeratin 18, Ribosomal protein L6 and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5,were selected for further investigation. Increased expression of 4 of these was confirmed in human CRC by qPCR. In conclusion, several novel candidate biomarkers have been identified from analysis of transgenic mice in which the Apc gene was deleted in the intestinal epithelium that also showed increased expression in human CRC. Some of these warrant further investigation as potential serum-based biomarkers of human CRC. Copyright © 2013 Elsevier Inc. All rights reserved.

Surveillance of individuals at intermediate risk of colorectal cancer--the impact of new guidelines.

PubMed

Clark, S K; Carpenter, S; Broughton, C I M; Marks, C G

2003-11-01

Individuals with two first degree relatives, or one diagnosed at age < 45 years, with colorectal cancer are at sufficient risk to merit surveillance. Most undergo colonoscopy four to five yearly, starting 10 years before the youngest case. The aim of this study was to assess the impact of a proposed new surveillance protocol. We identified individuals with these risk criteria seen in our clinic from 1989 to 2001 and reviewed their notes with respect to colonoscopy. Colonoscopy (n = 295) was performed on 186 patients in accordance with current recommendations. Cancer was detected in three and adenoma in 21 individuals. Applying the proposed protocol, 123 (42%) fewer colonoscopies would have been performed. No cancers would have been missed, but in five cases a small adenoma would not have been detected. Proposed new guidelines for surveillance of those at intermediate risk reduce the burden of colonoscopy without compromising identification of significant neoplasia.

Severe Phenotype of Keratitis-Ichthyosis-Deafness Syndrome With Presumed Ocular Surface Squamous Neoplasia.

PubMed

Serrano-Ahumada, Ana Silvia; Cortes-González, Vianney; González-Huerta, Luz María; Cuevas, Sergio; Aguilar-Lozano, Luis; Villanueva-Mendoza, Cristina

2018-02-01

The aim of this study was to describe a case of severe keratitis-ichthyosis-deafness (KID) syndrome with ocular surface squamous neoplasia. The affected patient underwent complete ocular and systemic examinations. The molecular studies included polymerase chain reaction amplification and automated DNA sequencing of the complete gap junction beta-2 (GJB2) gene coding sequence. A 30-year-old man presented with generalized erythro-hyperkeratosis and deafness and complaints of decreased visual acuity, tearing, and photophobia. Ophthalmic examination showed corneal erosion, vascularization, and a gray gelatinous lesion partially covering the right cornea, suggestive of squamous neoplasia. The clinical features were characteristic of KID syndrome. This diagnosis was confirmed with a DNA analysis showing the pathogenic variant p.D50N in the GJB2 gene. Presumed squamous neoplasia was treated with topical interferon α2b. KID syndrome is a very rare disease that has been reported with an incremental incidence of squamous cell carcinoma of the mucous membranes and skin (12%-15%). Here, we presented a case of severe systemic KID syndrome with ocular surface squamous neoplasia.

Fecal immunochemical tests in combination with blood tests for colorectal cancer and advanced adenoma detection—systematic review

PubMed Central

Niedermaier, Tobias; Weigl, Korbinian; Hoffmeister, Michael; Brenner, Hermann

2017-01-01

Background Colorectal cancer (CRC) is a common but largely preventable cancer. Although fecal immunochemical tests (FITs) detect the majority of CRCs, they miss some of the cancers and most advanced adenomas (AAs). The potential of blood tests in complementing FITs for the detection of CRC or AA has not yet been systematically investigated. Methods We conducted a systematic review of performance of FIT combined with an additional blood test for CRC and AA detection versus FIT alone. PubMed and Web of Science were searched until June 9, 2017. Results Some markers substantially increased sensitivity for CRC when combined with FIT, albeit typically at a major loss of specificity. For AA, no relevant increase in sensitivity could be achieved. Conclusion Combining FIT and blood tests might be a promising approach to enhance sensitivity of CRC screening, but comprehensive evaluation of promising marker combinations in screening populations is needed. PMID:29435309

Cetuximab Plus Oxaliplatin May Not Be Effective Primary Treatment for Metastatic Colorectal Cancer

Cancer.gov

In a randomized phase III trial, the addition of the targeted therapy cetuximab to oxaliplatin and fluoropyrimidine chemotherapy did not prolong survival or time to disease progression of patients with advanced colorectal cancer.

Future of Minimally Invasive Colorectal Surgery

PubMed Central

Whealon, Matthew; Vinci, Alessio; Pigazzi, Alessio

2016-01-01

Minimally invasive surgery is slowly taking over as the preferred operative approach for colorectal diseases. However, many of the procedures remain technically difficult. This article will give an overview of the state of minimally invasive surgery and the many advances that have been made over the last two decades. Specifically, we discuss the introduction of the robotic platform and some of its benefits and limitations. We also describe some newer techniques related to robotics. PMID:27582647

Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III).

PubMed

Alam, N N; White, D A; Narang, S K; Daniels, I R; Smart, N J

2016-02-01

There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment. An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence. The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies

A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment.

PubMed

Liu, Ko-Jiunn; Chao, Tsu-Yi; Chang, Jang-Yang; Cheng, Ann-Lii; Ch'ang, Hui-Ju; Kao, Woei-Yau; Wu, Yu-Chen; Yu, Wei-Lan; Chung, Tsai-Rong; Whang-Peng, Jacqueline

2016-08-24

To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment. Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA. No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients. The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in

Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients.

PubMed

Pouw, Roos E; Seewald, Stefan; Gondrie, Joep J; Deprez, Pierre H; Piessevaux, Hubert; Pohl, Heiko; Rösch, Thomas; Soehendra, Nib; Bergman, Jacques J

2010-09-01

Endoscopic resection is safe and effective to remove early neoplasia (ie,high-grade intra-epithelial neoplasia/early cancer) in Barrett's oesophagus. To prevent metachronous lesions during follow-up, the remaining Barrett's oesophagus can be removed by stepwise radical endoscopic resection (SRER). The aim was to evaluate the combined experience in four tertiary referral centres with SRER to eradicate Barrett's oesophagus with early neoplasia. Retrospective cohort study. Four tertiary referral centres. 169 patients (151 males, age 64 years (IQR 57-71), Barrett's oesophagus 3 cm (IQR 2-5)) with early neoplasia in Barrett's oesophagus < or = 5 cm, without deep submucosal infiltration or lymph node metastases, treated by SRER between January 2000 and September 2006. Endoscopic resection every 4-8 weeks, until complete endoscopic and histological eradication of Barrett's oesophagus and neoplasia. According to intention-to-treat analysis complete eradication of all neoplasia and all intestinal metaplasia by the end of the treatment phase was reached in 97.6% (165/169) and 85.2% (144/169) of patients, respectively. One patient had progression of neoplasia during treatment and died of metastasised adenocarcinoma (0.6%). After median follow-up of 32 months (IQR 19-49), complete eradication of neoplasia and intestinal metaplasia was sustained in 95.3% (161/169) and 80.5% (136/169) of patients, respectively. Acute, severe complications occurred in 1.2% of patients, and 49.7% of patients developed symptomatic stenosis. SRER of Barrett's oesophagus < or = 5 cm containing early neoplasia appears to be an effective treatment modality with a low rate of recurrent lesions during follow-up. The procedure, however, is technically demanding and is associated with oesophageal stenosis in half of the patients.

Improved anti-tumor efficacy via combination of oxaliplatin and fibrin glue in colorectal cancer

PubMed Central

Hu, Yuzhu; Yu, Ting; Liu, Xiaoxiao; He, Yihong; Deng, Lihong; Guo, Jiajuan; Hua, Yuanqi; Luo, Ting; Gao, Xiang

2018-01-01

Colorectal cancer is very common worldwide and advanced colorectal cancer exhibited very poor clinical outcome. Oxaliplatin (OXP) is one of the principal chemotherapeutic agents in colorectal cancer treatment presenting impressive anti-tumor ability, limited by adverse effect in clinical practice. Fibrin glue (FG) is a biocompatible formulation made of fibrinogen and thrombin, extensively used in surgery for hemostasis, tissue adhesion and sealing. In this study, FG was innovatively applied as OXP delivery system and results showed enhanced anti-tumor performance in subcutaneous model and abdominal metastasis model of murine colorectal cancer compared with that of OXP used alone. It is revealed that combination of OXP and FG could increase activated CD8+ T cells, reduce regulatory T (Treg) cells and increase interferon-γ (IFN-γ). Furthermore, results showed promoted tumor apoptosis, decreased proliferation and inhibited tumor angiogenesis by OXP and FG combination. No obvious systemic toxicity was observed in this study. Finally, our findings provided basis for promising application of OXP and FG combination in colorectal cancer treatment. PMID:29416788

Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

PubMed

Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

2013-02-01

To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

Current State of Colorectal Surgery Training: A Survey of Program Directors, Current and Recently Matched Colorectal Residents, and Recent Colorectal Graduates.

PubMed

Bailey, Matthew B; Miller, Peter E; Pawlak, Stephanie E; Thomas, Michael S; Beck, David E; Vargas, H David; Whitlow, Charles B; Margolin, David A

2016-02-01

Colorectal residency has become one of the more competitive postgraduate training opportunities; however, little information is available to guide potential applicants in gauging their competitiveness. The aim of this study was to identify the current trends colorectal residency training and to identify what factors are considered most important in ranking a candidate highly. We hypothesized that there was a difference in what program directors, current and recently matched colorectal residents, and recent graduates consider most important in making a candidate competitive for a colorectal residency position. Three 10-question anonymous surveys were sent to 59 program directors, 87 current and recently matched colorectal residents, and 119 recent graduates in March 2015. The study was conducted as an anonymous internet survey. Current trends in applying for a colorectal residency, competitiveness of recent colorectal residents, factors considered most important in ranking a candidate highly, and what future colorectal surgeons can expect after finishing their training were measured. The study had an overall response rate of 43%, with 28 (47%) of 59 program directors, 46 (53%) of 87 current and recently matched colorectal residents, and 39 (33%) of 119 recent graduates responding. The majority of program directors felt that a candidate's performance during the interview process was the most important factor in making a candidate competitive, followed by contact from a colleague, letters of recommendation, American Board of Surgery In-Training Exam scores, and number of publications/presentations. The majority of current and recently matched colorectal residents felt that a recommendation/telephone call from a colleague was the most important factor, whereas the majority of recent graduates favored letters of recommendation as the most important factor in ranking a candidate highly. Limitations to the study include its small sample size, selection bias, responder

Linear array ultrasonography to stage rectal neoplasias suitable for local treatment.

PubMed

Ravizza, Davide; Tamayo, Darina; Fiori, Giancarla; Trovato, Cristina; De Roberto, Giuseppe; de Leone, Annalisa; Crosta, Cristiano

2011-08-01

Because of the many therapeutic options available, a reliable staging is crucial for rectal neoplasia management. Adenomas and cancers limited to the submucosa without lymph node involvement may be treated locally. The aim of this study is to evaluate the diagnostic accuracy of endorectal ultrasonography in the staging of neoplasias suitable for local treatment. We considered all patients who underwent endorectal ultrasonography between 2001 and 2010. The study population consisted of 92 patients with 92 neoplasias (68 adenocarcinomas and 24 adenomas). A 5 and 7.5MHz linear array echoendoscope was used. The postoperative histopathologic result was compared with the preoperative staging defined by endorectal ultrasonography. Adenomas and cancers limited to the submucosa were considered together (pT0-1). The sensitivity, specificity, overall accuracy rate, positive predictive value, and negative predictive value of endorectal ultrasonography for pT0-1 were 86%, 95.6%, 91.3%, 94.9% and 88.7%. Those for nodal involvement were 45.4%, 95.5%, 83%, 76.9% and 84%, with 3 false positive results and 12 false negative. For combined pT0-1 and pN0, endorectal ultrasonography showed an 87.5% sensitivity, 95.9% specificity, 92% overall accuracy rate, 94.9% positive predictive value and 90.2% negative predictive value. Endorectal linear array ultrasonography is a reliable tool to detect rectal neoplasias suitable for local treatment. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Resilience and hope during advanced disease: a pilot study with metastatic colorectal cancer patients.

PubMed

Solano, Joao Paulo Consentino; da Silva, Amanda Gomes; Soares, Ivan Agurtov; Ashmawi, Hazem Adel; Vieira, Joaquim Edson

2016-08-02

The balance between hope-hopelessness plays an important role in the way terminally ill patients report quality of life, and personal resilience may be related to hope at the end of life. The objective of this study was to explore associations between personal resilience, hope, and other possible predictors of hope in advanced cancer patients. A cross-sectional pilot study was carried out with metastatic colorectal cancer patients in a tertiary hospital. The patients answered the Connor-Davidson Resilience Scale, Herth Hope Index, Barthel Index, an instrument addressing family and social support, visual-numeric scales for pain and suffering, a two-item screening for depression, socio-demographic and socio-economic information about the family. Forty-four patients were interviewed (mean age 56 years; range 29-86). A strong correlation was noted between resilience and hope (0.63; p < 0.05). No correlation was found between hope and independence for activities of daily living, support from family and community, and pain and suffering levels. Of the 44 patients, 20 presented with depressive symptoms. These depressive patients had lower resilience (p = 0.005) and hope (p = 0.003), and higher scores of suffering (p < 0.001). The association between resilience and hope kept stable after adjusting for age, gender, and presence of depression (p < 0.001). Given that resilience is a dynamic, changeable path that can improve hope, resilience-fostering interventions should be most valued in palliative care settings and should be commenced as soon as possible with cancer patients. Patients with advanced stages of non-malignant conditions would also probably benefit from such interventions.

Phase IIA Clinical Trial of Curcumin for the Prevention of Colorectal Neoplasia

PubMed Central

Carroll, Robert E.; Benya, Richard V.; Turgeon, Danielle Kim; Vareed, Shaiju; Neuman, Malloree; Rodriguez, Luz; Kakarala, Madhuri; Carpenter, Philip M.; McLaren, Christine; Meyskens, Frank L.; Brenner, Dean E.

2014-01-01

Curcumin is derived from the spice tumeric and has anti-inflammatory and antineoplastic effects in vitro and in animal models, including preventing aberrant crypt foci (ACF) and adenomas in murine models of colorectal carcinogenesis. Inhibiting the production of the procarcinogenic eicosanoids prostaglandin E2 (PGE2) and 5-hydroxyeicosatetraenoic acid (5-HETE) can suppress carcinogenesis in rodents. Curcumin reduces mucosal concentrations of PGE2 (via inhibition of cyclooxygenases 1 and 2) and 5-HETE (via inhibition of 5-lipoxygenase) in rats. Although preclinical data support curcumin acitivity in many sites, the reported poor bioavailability of this agent supports its use in the colorectum We assessed the effects of oral curcumin (2 g or 4 g per day for 30 days) on PGE2 within ACF (primary endpoint), 5-HETE, ACF number, and proliferation in a non-randomized, open-label clinical trial in 44 eligible smokers with 8 or more ACF on screening colonoscopy. We assessed pre- and post-treatment concentrations of PGE2 and 5-HETE by liquid chromatography tandem mass spectroscopy in ACF and normal-tissue biopsies, ACF number via rectal endoscopy, proliferation by Ki-67 immunohistochemistry; and curcumin concentrations by high-performance liquid chromatography in serum and rectal mucosal samples. 41 Subjects completed the study. Neither dose of curcumin reduced PGE2 or 5-HETE within ACF or normal mucosa or Ki-67 in normal mucosa. A significant 40% reduction in ACF number occurred with the 4 g dose (P < 0.005); while ACF were not reduced in the 2 g group. This reduction was associated with a significant change in plasma curcumin/conjugate levels pre- and post-treatmeeng (5-fold increase; P = 0.009) in the 4 g group. Curcumin was well tolerated at both 2 g and 4g. Our data suggest that curcumin can decrease ACF number, and this is potentially mediated by curcumin conjugates delivered systemically. PMID:21372035

A Double-Blinded Randomized Clinical Study on the Therapeutic Effect of Gastrografin in Prolonged Postoperative Ileus After Elective Colorectal Surgery.

PubMed

Biondo, Sebastiano; Miquel, Jordi; Espin-Basany, Eloy; Sanchez, Jose Luis; Golda, Thomas; Ferrer-Artola, Ana Maria; Codina-Cazador, Antonio; Frago, Ricardo; Kreisler, Esther

2016-01-01

Postoperative ileus is a common problem with significant clinical and economic consequences. We hypothesized that Gastrografin may have therapeutic utility by accelerating the recovery of postoperative ileus after colorectal surgery. The aim of this trial was to study the impact of oral Gastrografin administration on postoperative prolonged ileus (PPI) after elective colorectal surgery. The main endpoint of this randomized, double-blinded, controlled trial was time of resolution of PPI. The secondary endpoints were overall hospital length of stay, time to start oral intake, time to first passage of flatus or stools, time of need of nasogastric tube, and need of parenteral nutrition. Included criteria were patients older than 18 years, operated for colonic neoplasia, inflammatory bowel disease, or diverticular disease. There were two treatments: Gastrografin administration and placebo. The sample size was calculated taking into account the average length of postoperative ileus after colorectal resection until tolerance to oral intake. Statistical analysis showed that 29 subjects in each group were needed. Twenty-nine patients per group were randomized. Groups were comparable for age, gender, ASA Physical Status Classification System, stoma construction, and surgical technique. No statistical differences were observed in mean time to resolution between the two groups, 9.1 days (CI 95%, 6.51-11.68) in Gastrografin group versus 10.3 days (CI 6.96-10.29) in Placebo group (P = 0.878). Even if not statistically significant, time of resolution of PPI, overall length of stay, time of need of nasogastric tube, and time to tolerance of oral intake were shorter in the G group. Gastrografin does not accelerate significantly the recovery of prolonged postoperative ileus after elective colorectal resection when compared with placebo. However, it seems to clinically improve all the analyzed variables.

Natural history of diminutive colorectal polyps: long-term prospective observation by colonoscopy.

PubMed

Mizuno, Ken-Ichi; Suzuki, Yutaka; Takeuchi, Manabu; Kobayashi, Masaaki; Aoyagi, Yutaka

2014-04-01

Endoscopic removal of colorectal adenomatous polyps effectively prevents cancer. However, the treatment strategy for diminutive polyps (diameter ≤ 5 mm) remains controversial. Understanding the natural history of diminutive polyps is a prerequisite to their effective management. We prospectively examined the natural history of diminutive polyps by long-term surveillance colonoscopy. A total of 207 polyps detected in 112 patients from December 1991 through March 2002 were studied. To avoid potential effects on size and morphological characteristics, all polyps were selected randomly and were followed without biopsy. Polyp size was estimated by comparing the lesion with the diameter of a biopsy forceps. Mean follow up was 7.8 years (SD, 4.8; range, 1.0-18.6; median, 7.5; interquartile range 3.4-11.2). Twenty-four polyps were resected endoscopically, and the histopathological diagnosis was mucosal high-grade neoplasia (Category 4) for one polyp, and mucosal low-grade neoplasia (Category 3) for 23 polyps. Mean linear size of the polyps was 3.2 mm (SD, 1.0; range, 1.3-5.0) at initial colonoscopy and 3.8 mm (SD 1.6; range 1.3-10.0) at final colonoscopy (P<0.01). Left-sided polyps showed a higher growth rate than right-sided polyps, and a type IIIL2 pit pattern was associated with a lower growth rate than a type IIIL1 pattern. We clarified the natural history of diminutive polyps by long-term follow-up colonoscopy. The benign course of diminutive polyps should be considered in the design of treatment strategies. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

Intraocular ALλ amyloidoma with plasma cell neoplasia in a cat.

PubMed

Kershaw, Olivia; Linek, Jens; Linke, Reinhold P; Gruber, Achim D

2011-09-01

An 11-year-old, neutered male domestic short-hair cat was presented with buphthalmos of the right eye and diagnosed with advanced glaucoma. Sonographic examination revealed an iridial thickening. Neoplasia was suspected and an enucleation was performed. Histopathology of the enucleated eye revealed abundant amyloid deposition predominantly in the anterior uveal tract accompanied by few to moderate numbers of well-differentiated plasma cells. The amyloid deposits were identified by staining with Congo red and showing green birefringence under polarized light. Immunohistochemically, amyloid and plasma cells stained intensely only with anti-ALλ antibody, supporting the amyloid tumor being an immunoglobulin-λ-light chain origin. Additional abnormalities included narrowing of the filtration angle and collapse of the ciliary cleft, and trabecular meshwork. One year post-enucleation, the cat was still healthy without signs of systemic amyloidosis or apparent metastatic disease. This is the first report of a cat with noncutaneous extramedullary plasmacytoma originating in the anterior uveal tract with resulting local amyloid. © 2011 American College of Veterinary Ophthalmologists.

Colorectal cancer model of health disparities: understanding mortality differences in minority populations.

PubMed

Polite, Blase N; Dignam, James J; Olopade, Olufunmilayo I

2006-05-10

African Americans are more likely to be diagnosed with and die as a result of colorectal cancer than white patients. This review briefly documents these differences and explores the factors that may contribute to advanced stage at diagnosis and reduced survival once African Americans are diagnosed with colorectal cancer. Attention is focused on what is known about the role of socioeconomic status, cancer screening, comorbidities and lifestyle factors, tumor biology and genetics, and the differences in the receipt of and benefit of appropriate therapy. Finally, areas of ongoing and future research and policy initiatives aimed at reducing disparities are discussed.

SEPT9 and SHOX2 DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas.

PubMed

Semaan, Alexander; van Ellen, Anne; Meller, Sebastian; Bergheim, Dominik; Branchi, Vittorio; Lingohr, Philipp; Goltz, Diane; Kalff, Jörg C; Kristiansen, Glen; Matthaei, Hanno; Pantelis, Dimitrios; Dietrich, Dimo

2016-01-01

Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation of SEPT9 and SHOX2 has been suggested as a biomarker for various solid malignant tumors. Hence, the present study aimed to test their biomarker potential in CRC and precursor lesions. Assessment of promoter methylation of SEPT9 distinguished adenomas and CRC from controls as well as advanced from non-advanced adenomas (all p  < 0.001). Correspondingly, SHOX2 methylation levels in adenomas and colorectal carcinomas were significantly higher compared to those in normal control tissues ( p  < 0.001). Histologic transition from adenomas to CRC was paralleled by amplification of the SEPT9 gene locus. SEPT9 / SHOX2 methylation assays may help to distinguish colorectal cancer and adenomas from normal and inflammatory colonic tissue, as well as advanced from non-advanced adenomas. Further studies need to validate these findings before introduction in clinical routine.

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

Gender Modifies the Effect of Ursodeoxycholic Acid (UDCA) in a Randomized Controlled Trial in Colorectal Adenoma Patients

PubMed Central

Thompson, Patricia A.; Wertheim, Betsy C.; Roe, Denise J.; Ashbeck, Erin L.; Jacobs, Elizabeth T.; Lance, Peter; Martínez, María Elena; Alberts, David S.

2014-01-01

Background Ursodeoxycholic acid (UDCA) was one of the earliest agents investigated as a drug for colorectal cancer prevention. However, UDCA failed to demonstrate efficacy to prevent the development of colorectal adenomas in a large phase III randomized controlled trial. We re-evaluated the effect of UDCA in men and women separately, based on sex-specific differences in bile acid metabolism and suspected variation in etiologic factors contributing to colorectal cancer risk. Method We conducted a secondary analysis of the efficacy of UDCA to prevent colorectal adenoma in men (n = 804) and women (n = 388). Results We found no reduction in risk of any metachronous adenoma with UDCA treatment in men or women. However, UDCA treatment significantly lowered the odds of advanced lesions (OR = 0.62, 95% CI = 0.43 to 0.89) in men, but not women. We also observed significantly higher odds of advanced lesions with UDCA treatment in women who were younger (age < 65 y; OR = 3.24, 95% CI = 1.10 to 9.56), obese (body mass index ≥ 30 kg/m2; OR = 5.45, 95% CI = 1.42 to 20.9), or in the highest tertile of total dietary fat (≥ 56.2 g/day; OR = 3.48, 95% CI = 1.35 to 8.95). The interactive effect of fat intake accounted for the modulating effects of age and BMI in women. Conclusion Our findings support the use of UDCA for preventing advanced colorectal adenomas in men. The increased odds of adenoma among women with high fat intake suggest a previously unrecognized harm that warrants further study, especially given some patients’ chronic exposure to UDCA for the treatment of primary biliary cirrhosis and the rising investigational use of this drug for several other conditions. PMID:19952360

Quality assurance in the treatment of colorectal cancer: the EURECCA initiative.

PubMed

Breugom, A J; Boelens, P G; van den Broek, C B M; Cervantes, A; Van Cutsem, E; Schmoll, H J; Valentini, V; van de Velde, C J H

2014-08-01

Colorectal cancer is one of the most common cancers in Europe. Over the past few decades, important advances have been made in screening, staging and treatment of colorectal cancer. However, considerable variation between and within European countries remains, which implies that further improvements are possible. The most important remaining question now is: when are we, health care professionals, delivering the best available care to patients with colon or rectal cancer? Currently, quality assurance is a major issue in colorectal cancer care and quality assurance awareness is developing in almost all disciplines involved in the treatment of colorectal cancer patients. Quality assurance has shown to be effective in clinical trials. For example, standardisation and quality control were introduced in the Dutch TME trial and led to marked improvements of local control and survival in rectal cancer patients. Besides, audit structures can also be very effective in monitoring cancer management and national audits showed to further improve outcome in colorectal cancer patients. To reduce the differences between European countries, an international, multidisciplinary, outcome-based quality improvement programme, European Registration of Cancer Care (EURECCA), has been initiated. In the near future, the EURECCA dataset will perform research on subgroups as elderly patients or patients with comorbidities, which are often excluded from trials. For optimal colorectal cancer care, quality assurance in guideline formation and in multidisciplinary team management is also of great importance. The aim of this review was to create greater awareness and to give an overview of quality assurance in the management of colorectal cancer. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Analysis of community colorectal cancer screening in 50-74 years old people in Guangzhou, 2015-2016].

PubMed

Li, Y; Liu, H Z; Liang, Y R; Lin, G Z; Li, K; Dong, H; Xu, H; Wang, M

2018-01-10

Objective: To analyze the effect of colorectal cancer screening in the general population in Guangzhou, and provide evidence for the for development of colorectal cancer screening policy and strategy. Methods: The data of colorectal cancer screening in Guangzhou during 2015- 2016 were collected. The participation, the positive rate of fecal occult blood test, the detection rate of colonoscopy and screening effect of colonoscopy were evaluated. Results: A total of 220 834 residents aged 50-74 years received the screening, and the positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively. The detection rates of all colorectal lesions were higher in men than in women (all P <0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer cases were found, accounting for 46.26% of the total cases. The overall screening detection rate of colorectal cancer was 104.15/100 000, higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance ( P <0.001), but age group <70 years had higher detection rate, age group ≥70 years had higher incidence rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk, increase the detection rate of colorectal lesions, early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer. The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years. It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.

High Resolution Microendoscopy for Quantitative Diagnosis of Esophageal Neoplasia

NASA Astrophysics Data System (ADS)

Shin, Dongsuk

Esophageal cancer is the eighth most common cancer in the world. Cancers of the esophagus account for 3.8% of all cases of cancers, with approximately 482,300 new cases reported in 2008 worldwide. In the United States alone, it is estimated that approximately 18,000 new cases will be diagnosed in 2013, and 15,210 deaths are expected. Despite advances in surgery and chemoradiation therapy, these advances have not led to a significant increase in survival rates, primarily because diagnosis often at an advanced and incurable stage when treatment is more difficult and less successful. Accurate, objective methods for early detection of esophageal neoplasia are needed. Here, quantitative classification algorithms for high resolution miscroendoscopic images were developed to distinguish between esophageal neoplastic and non-neoplastic tissue. A clinical study in 177 patients with esophageal squamous cell carcinoma (ESCC) was performed to evaluate the diagnostic performance of the classification algorithm in collaboration with the Mount Sinai Medical Center in the United States, the First Hospital of Jilin University in China, and the Cancer Institute and Hospital, the Chinese Academy of Medical Science in China. The study reported a sensitivity and specificity of 93% and 92%, respectively, in the training set, 87% and 97%, respectively, in the test set, and 84% and 95%, respectively, in an independent validation set. Another clinical study in 31 patients with Barrett's esophagus resulted in a sensitivity of 84% and a specificity of 85%. Finally, a compact, portable version of the high resolution microendoscopy (HRME) device using a consumer-grade camera was developed and a series of biomedical experimental studies were carried out to assess the capability of the device.

Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer.

PubMed

Ribeiro, Sofia Miranda de Figueiredo; Braga, Camila Bitu Moreno; Peria, Fernanda Maris; Martinez, Edson Zangiacomi; Rocha, José Joaquim Ribeiro da; Cunha, Selma Freire Carvalho

2017-01-01

To investigate the effects of oral zinc supplementation on fatigue intensity and quality of life of patients during chemotherapy for colorectal cancer. A prospective, randomized, double-blinded, placebo-controlled study was conducted with 24 patients on chemotherapy for colorectal adenocarcinoma in a tertiary care public hospital. The study patients received zinc capsules 35mg (Zinc Group, n=10) or placebo (Placebo Group, n=14) orally, twice daily (70mg/day), for 16 weeks, from the immediate postoperative period to the fourth chemotherapy cycle. Approximately 45 days after surgical resection of the tumor, all patients received a chemotherapeutic regimen. Before each of the four cycles of chemotherapy, the Functional Assessment of Chronic Illness Therapy-Fatigue scale was completed. We used a linear mixed model for longitudinal data for statistical analysis. The scores of quality of life and fatigue questionnaires were similar between the groups during the chemotherapy cycles. The Placebo Group presented worsening of quality of life and increased fatigue between the first and fourth cycles of chemotherapy, but there were no changes in the scores of quality of life or fatigue in the Zinc Group. Zinc supplementation prevented fatigue and maintained quality of life of patients with colorectal cancer on chemotherapy. Investigar os efeitos da suplementação oral de zinco sobre a intensidade da fadiga e a qualidade de vida de pacientes durante a quimioterapia para neoplasia colorretal. Estudo prospectivo, randomizado, controlado e duplo-cego conduzido em um hospital universitário público terciário, com 24 pacientes em regime quimioterápico para adenocarcinoma colorretal. Os pacientes receberam cápsulas de zinco 35mg (Grupo Zinco, n=10) ou placebo (Grupo Placebo, n=14) por via oral, duas vezes ao dia (70mg/dia), durante 16 semanas, desde o período pós-operatório imediato até o quarto ciclo de quimioterapia. Todos os pacientes receberam quimioterapia por

Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.

PubMed

Owston, Michael A; Ramsay, Edward C; Rotstein, David S

2008-12-01

A review of medical records and necropsy reports from 1979-2003 found 40 neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and three females), three leopards (Panthera pardus, two males and one female), one jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight females), two snow leopards (Panthera uncia, one male and one female), two cougars (Felis concolor, one male and one female), one bobcat (Felis rufus, male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3 yr of age or had been housed in the collection less than 3 yrs were not included in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence of felid neoplasia during the study period was 25% (26/103). Neoplasia was identified as the cause of death or reason for euthanasia in 28% (13/47) of those necropsied. Neoplasms were observed in the integumentary-mammary (n=11), endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5), digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified by system. Multiple neoplasms were observed in 11 animals. Both benign and malignant neoplasms were observed in all systems except for the hematopoietic-lymphoreticular systems where all processes were malignant. Of the endocrine neoplasms, those involving the thyroid and parathyroid glands predominated (n=8) over other endocrine organs and included adenomas and carcinomas. In the integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia at this institution, during the given time period, appears to be greater than rates found in the one other published survey of captive felids.

Alternate pathogenesis of systemic neoplasia in the bivalve mollusc Mytilus.

PubMed

Moore, J D; Elston, R A; Drum, A S; Wilkinson, M T

1991-09-01

The proliferative disease systemic neoplasia, also termed hemic neoplasia or disseminated sarcoma, was studied in four Puget Sound, Washington populations of the bay mussel (Mytilus sp.). Using flow cytometric measurement of DAPI-stained cells withdrawn from the hemolymph, DNA content frequency histograms were generated for 73 individuals affected by the disease. The cells manifesting systemic neoplasia were found to exist as either of two separate types, characterized by G0G1 phase nuclear DNA contents of either approximately 4.9 x haploid (pentaploid form) or approximately 3.8 x haploid (tetraploid form). The two disease forms were found to coexist in all four mussel populations sampled, with overall relative prevalences of 66% pentaploid form, 29% tetraploid form, and 5% exhibiting both disease forms simultaneously. These findings represent the first unequivocal demonstration of multiple cell types in a bivalve neoplasia. The two forms appear to represent separate pathogenetic processes rather than sequential stages of a single pathogenesis. Two cell cycling parameters associated with proliferative activity were employed to compare the alternate forms: (i) the percentage of cells assigned to the DNA Synthesis (S) phase of the neoplastic cell cycle, and (ii) the proportion of neoplastic cell mitotic figures in hemocytological preparations. Mean values for both parameters were significantly higher for mussels with the tetraploid form of the disease, suggesting a higher rate of proliferation relative to the pentaploid form. Qualitatively, cells of the tetraploid form contained slightly lower nuclear and cytoplasmic volumes compared to those of the pentaploid form. An observed wide variation in neoplastic cell nuclear size within either disease form may reflect the distribution of cells in the G0G1, S, and G2M phases of the cell cycle. Potential etiologic relationships between the two forms are discussed.

First-line treatment with capecitabine combined with irinotecan in patients with advanced colorectal carcinoma: a phase II study.

PubMed

Assy, Nimer; Basher, Walid; Chetver, Lika; Shnaider, Julia; Zidan, Jamal

2012-04-01

To evaluate the efficacy and toxicity of capecitabine with irinotecan as first-line treatment in metastatic colorectal cancer. The addition of irinotecan to infusional 5 fluorouracil and leucovorin significantly improves the response rate and survival compared with 5 fluorouracil/leucovorin alone in metastatic colorectal cancer. Capecitabine with irinoteacan was reported to yield comparable results in phase II studies. Patients older than 75 years, Eastern Cooperative Oncology Group ≤0 to 3, with measurable disease, no previous treatment for advanced disease, previous adjuvant chemotherapy >6 months, and adequate hepatic, renal, and hematological function were included. The treatment protocol included capecitabine 1000 mg/m twice daily given for 14 days (days 1 to 14) and irinotecan (100 mg/m) given on days 1 and 8. Treatment was repeated on day 21. Thirty patients were included. All were assessable for response and toxicity. Average age was 64 years, male/female ratio 20/10. Fifteen had liver metastases; 9 had abdominal metastases; 5 had liver and lymph nodes metastases; and 1 had lung metastases. The median number of cycles was 8. Grades III and IV diarrheas were observed in 20%, mild vomiting in 20%, grades III and IV leukopenia in 23%, and hand and foot syndrome grade III in 1 patient (3%). A complete response was achieved in 3 (10%) patients, a partial response in 16 (53%), disease stabilization in 6 (20%), and tumor progression in 5 (17%). Progression-free survival was 8.4 months. Overall survival was 19.3 months. This regimen was provided on an outpatient basis with significant antitumor activity and without the need for indwelling catheters and seems to be feasible for patients of all ages, with acceptable toxicity.

Associations of dietary fat with risk of early neoplasia in the proximal colon in a population-based case-control study.

PubMed

Mo, Allen; Wu, Rong; Grady, James P; Hanley, Matthew P; Toro, Margaret; Swede, Helen; Devers, Thomas J; Hartman, Terryl J; Rosenberg, Daniel W

2018-07-01

Excess dietary fat consumption is strongly associated with the risk of colorectal cancer, but less is known about its role in the earliest stages of carcinogenesis, particularly within the proximal colon. In the following case-control study, we evaluated the relationship between the intake of dietary fats and the frequency of early proximal neoplasia [aberrant crypt foci (ACF) or polyps], detectable by high-definition colonoscopy with contrast dye-spray. Average-risk screening individuals underwent a high-definition colonoscopy procedure as part of larger ongoing clinical study of precancerous lesions in the proximal colon. Dietary fat intake was assessed using the Block Brief Food Frequency Questionnaire, which estimates average dietary intake based on 70 food items. The diets of individuals with no endoscopically identifiable lesions (n = 36) were compared to those with either ACF or polyps detected in the proximal colon. In multivariate analysis, high dietary intake of total polyunsaturated fatty acids (PUFAs) and intake of omega-6 and omega-3 fatty acids were positively associated with neoplastic lesions in the proximal colon. When comparing ACF and polyp groups separately, a positive association was observed for both proximal polyps (OR 2.28; CI 1.16-7.09) and ACF (OR 2.86; CI 1.16-7.09) for total PUFA intake. Furthermore, the prevalence of proximal ACF was increased with higher intake of omega-6 (OR 3.54; CI 1.32-9.47) and omega-3 fatty acids (OR 2.29; CI 1.02-5.13), although there was no discernible difference in the omega-6/omega-3 ratio. These results suggest that dietary PUFAs may be positively associated with risk of early neoplasia in the proximal colon. This study provides further evidence that dietary PUFA composition may play an important role in altering the microenvironment within the human colon.

Establishing an Australian nurse practitioner-led colorectal cancer screening clinic.

PubMed

Morcom, Joylene; Dunn, Sandra V; Luxford, Yoni

2005-01-01

In Australia, colorectal cancer is the most commonly occurring internal cancer affecting both men and women, and the second most common cause of cancer-related death. Flexible sigmoidoscopy has not been commonly used as a screening tool in Australia due primarily to lack of resources. Until now, people at average risk of developing bowel cancer frequently undergo colonoscopy after referral to a specialist. To fill an identified need, a nurse practitioner-led colorectal screening service providing fecal occult blood testing and flexible sigmoidoscopy, health education and promotion, patient counseling, information and a referral point for general practitioners, and a referral service for above average-risk patients was established in a South Australian metropolitan teaching hospital. Establishment of this clinic required advanced and extended theoretical and clinical preparation for the nurse practitioner, as well as development of interdisciplinary relationships, referral processes, clinical infrastructure, and a marketing strategy. An audit of the first 100 flexible sigmoidoscopy patients revealed service and procedural outcomes that compared favorably with other colorectal screening services as well as a high level of patient satisfaction.

Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms.

PubMed

Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

2016-03-01

Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.

The effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma.

PubMed

Han, Min Seok; Lee, Hyun Jung; Park, Soo Jung; Hong, Sung Pil; Cheon, Jae Hee; Kim, Won Ho; Kim, Tae Il

2017-08-01

Existing studies suggest that metformin lowers the risk and mortality of colorectal cancer. However, the effect of metformin on the suppression and prevention of colorectal adenomas is not clear. The aim of this study was to evaluate the effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma. Among 423 diabetic patients who underwent surveillance colonoscopy after resection of colorectal adenoma between 2005 and 2011, 257 patients were retrospectively reviewed. The patients were divided into two groups: one group comprising 106 patients who took metformin and another group comprising 151 patients who did not take metformin. The clinical characteristics, colorectal adenoma recurrence, and valuable factors for adenoma recurrence were analyzed. At surveillance colonoscopy after colonoscopic polypectomy for adenoma, 38 patients (35.8%) exhibited colorectal adenoma among 106 patients who took metformin, compared with 85 patients (56.3%) with colorectal adenoma among 151 patients who did not take metformin (odds ratio 0.434, 95% confidence interval 0.260-0.723, P = 0.001). Multivariate Cox analysis showed that metformin was associated with decreased recurrence of colorectal adenoma (hazard ratio 0.572, 95% confidence interval 0.385-0.852, P = 0.006) in diabetic patients with previous colorectal adenoma. The cumulative probability of colorectal adenoma recurrence was significantly lower in the metformin group than in the non-metformin group (P = 0.001). Metformin use in diabetic patients with previous colorectal adenoma is associated with a lower risk of colorectal adenoma recurrence.

A nurse-led model at public academic hospitals maintains high adherence to colorectal cancer surveillance guidelines.

PubMed

Symonds, Erin L; Simpson, Kalindra; Coats, Michelle; Chaplin, Angela; Saxty, Karen; Sandford, Jayne; Young Am, Graeme P; Cock, Charles; Fraser, Robert; Bampton, Peter A

2018-06-18

To examine the compliance of colorectal cancer surveillance decisions for individuals at greater risk with current evidence-based guidelines and to determine whether compliance differs between surveillance models. Prospective auditing of compliance of surveillance decisions with evidence-based guidelines (NHMRC) in two decision-making models: nurse coordinator-led decision making in public academic hospitals and physician-led decision making in private non-academic hospitals. Selected South Australian hospitals participating in the Southern Co-operative Program for the Prevention of Colorectal Cancer (SCOOP). Proportions of recall recommendations that matched NHMRC guideline recommendations (March-May 2015); numbers of surveillance colonoscopies undertaken more than 6 months ahead of schedule (January-December 2015); proportions of significant neoplasia findings during the 15 years of SCOOP operation (2000-2015). For the nurse-led/public academic hospital model, the recall interval recommendation following 398 of 410 colonoscopies (97%) with findings covered by NHMRC guidelines corresponded to the guideline recommendations; for the physician-led/private non-academic hospital model, this applied to 257 of 310 colonoscopies (83%) (P < 0.001). During 2015, 27% of colonoscopies in public academic hospitals (mean, 27 months; SD, 13 months) and 20% of those in private non-academic hospitals (mean, 23 months; SD, 12 months) were performed more than 6 months earlier than scheduled, in most cases because of patient-related factors (symptoms, faecal occult blood test results). The ratio of the numbers of high risk adenomas to cancers increased from 6.6:1 during 2001-2005 to 16:1 during 2011-2015. The nurse-led/public academic hospital model for decisions about colorectal cancer surveillance intervals achieves a high degree of compliance with guideline recommendations, which should relieve burdening of colonoscopy resources.

[Results of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years from 1993 to 2012].

PubMed

Korbeľ, M; Šufliarsky, J; Danihel, Ľ; Vojtaššák, J; Nižňanská, Z

2016-01-01

Analysis and epidemiology of gestational trophoblastic neoplasia treatment in the Slovak Republic in the years 1993-2012. Retrospective epidemiological national study. Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic, Bratislava. Retrospective analysis results of gestational trophoblastic neoplasia treatment according to prognostic scoring and staging system FIGO/WHO in Centre for gestational trophoblastic disease Ministry of Health the Slovak Republic Bratislava in the years 1993-2012. The treatment of gestational trophoblastic neoplasia (GTN) in the Czech and Slovak Republics started in 1955 and lasted till 1993. After the split of the former Czechoslovakia the Centre for gestational trophoblastic disease was created in Slovakia. 75 patients were treated in this Centre in the years 1993-2012. According to prognostic scoring and staging system FIGO/WHO 56 (75%) patients had low-risk gestational trophoblastic neoplasia and 19 (25%) of patients had high-risk gestational trophoblastic neoplasia. There were 41 patients (55%), 2 (3%), 24 (32%) and 8 (11%) in stage I., II., III. and IV. respectively. Total curability rate was 94.7% and mortality rate was 5.3%. Curability rate 100% was achieved in stage I & II and all placental site trophoblastic tumours (PSTT), 98.3% in stage III and 50% stage IV. In the years 1993-2012 the incidence of choriocarcinoma was one in 76 273 pregnancies and one in 53 203 deliveries. The incidence of other gestational trophoblastic neoplasia in the same years was for PSTT one in 533 753 pregnancies and one in 372 422 deliveries, invasive mole one in 145 611 pregnancies and one in 101 569 deliveries, and persistent GTN one in 40 043 pregnancies and one in 27 932 deliveries. 225-241 patients were treated in the same period of time in the Czech Republic with curability rate 98.2-98. 3%. Early detection and treatment in the centre for trophoblastic disease are crucial points in the manage-ment of gestational