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No Association Between Pseudopolyps and Colorectal Neoplasia in Patients With Inflammatory Bowel Diseases.
Mahmoud R, Shah SC, Ten Hove JR, Torres J, Mooiweer E, Castaneda D, Glass J, Elman J, Kumar A, Axelrad J, Ullman T, Colombel JF, Oldenburg B, Itzkowitz SH, Dutch Initiative on Crohn and Colitis
(2019) Gastroenterology 156: 1333-1344.e3
MeSH Terms: Adult, Biopsy, Colectomy, Colitis, Ulcerative, Colonic Polyps, Colonoscopy, Colorectal Neoplasms, Crohn Disease, Early Detection of Cancer, Female, Humans, Male, Middle Aged, Neoplasm Grading, Netherlands, New York City, Prevalence, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors
Show Abstract · Added March 3, 2020
BACKGROUND & AIMS - Patients with inflammatory bowel diseases who have postinflammatory polyps (PIPs) have an increased risk of colorectal neoplasia (CRN). European guidelines propose that patients with PIPs receive more frequent surveillance colonoscopies, despite limited evidence of this increased risk. We aimed to define the risk of CRN and colectomy in patients with inflammatory bowel diseases and PIPs.
METHODS - We conducted a multicenter retrospective cohort study of patients with inflammatory bowel diseases who underwent colonoscopic surveillance for CRN, from January 1997 through January 2017, at 5 academic hospitals and 2 large nonacademic hospitals in New York or the Netherlands. Eligible patients had confirmed colonic disease with duration of at least 8 years (or any duration, if they also had primary sclerosing cholangitis) and no history of advanced CRN (high-grade dysplasia or colorectal cancer) or colectomy. The primary outcome was occurrence of advanced CRN according to PIP status; secondary outcomes were occurrence of CRN (inclusive of low-grade dysplasia) and colectomy.
RESULTS - Of 1582 eligible patients, 462 (29.2%) had PIPs. PIPs were associated with more severe inflammation (adjusted odds ratio 1.32; 95% confidence interval [CI] 1.13-1.55), greater disease extent (adjusted odds ratio 1.92; 95% CI 1.34-2.74), and lower likelihood of primary sclerosing cholangitis (adjusted odds ratio 0.38; 95% CI 0.26-0.55). During a median follow-up period of 4.8 years, the time until development of advanced CRN did not differ significantly between patients with and those without PIPs. PIPs did not independently increase the risk of advanced CRN (adjusted hazard ratio 1.17; 95% CI 0.59-2.31). The colectomy rate was significantly higher in patients with PIPs (P = .01).
CONCLUSIONS - In a retrospective analysis of data from 2 large independent surveillance cohorts, PIPs were associated with greater severity and extent of colon inflammation and higher rates of colectomy, but were not associated with development of any degree of CRN. Therefore, intervals for surveillance should not be shortened based solely on the presence of PIPs.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Statin Exposure Is Not Associated with Reduced Prevalence of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease.
Shah SC, Glass J, Giustino G, Hove JRT, Castaneda D, Torres J, Kumar A, Elman J, Ullman TA, Itzkowitz SH
(2019) Gut Liver 13: 54-61
MeSH Terms: Adult, Cholangitis, Sclerosing, Cohort Studies, Colitis, Colonoscopy, Colorectal Neoplasms, Early Detection of Cancer, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Inflammatory Bowel Diseases, Male, Middle Aged, Population Surveillance, Prevalence, Risk Factors, Time Factors
Show Abstract · Added March 3, 2020
Background/Aims - Statins have been postulated to lower the risk of colorectal neoplasia. No studies have examined any possible chemopreventive effect of statins in patients with inflammatory bowel disease (IBD) undergoing colorectal cancer (CRC) surveillance. This study examined the association of statin exposure with dysplasia and CRC in patients with IBD undergoing dysplasia surveillance colonoscopies.
Methods - A cohort of patients with IBD undergoing colonoscopic surveillance for dysplasia and CRC at a single academic medical center were studied. The inclusion criteria were IBD involving the colon for ≥8 years (or any colitis duration if associated with primary sclerosing cholangitis [PSC]) and at least two colonoscopic surveillance exams. The exclusion criteria were CRC or high-grade dysplasia (HGD) prior to or at enrollment, prior colectomy, or limited (<30%) colonic disease. The primary outcome was the frequency of dysplasia and/or CRC in statin-exposed versus nonexposed patients.
Results - A total of 642 patients met the inclusion criteria (57 statin-exposed and 585 nonexposed). The statin-exposed group had a longer IBD duration, longer follow-up period, and more colonoscopies but lower inflammatory scores, less frequent PSC and less use of thiopurines and biologics. There were no differences in low-grade dysplasia, HGD, or CRC development during the follow-up period between the statin-exposed and nonexposed groups (21.1%, 5.3%, 1.8% vs 19.2%, 2.9%, 2.9%, respectively). Propensity score analysis did not alter the overall findings.
Conclusions - In IBD patients undergoing surveillance colonoscopies, statin use was not associated with reduced dysplasia or CRC rates. The role of statins as chemopreventive agents in IBD remains controversial.
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Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with inflammatory bowel disease with long-standing colitis: results of a 15-year multicentre, multinational cohort study.
Ten Hove JR, Shah SC, Shaffer SR, Bernstein CN, Castaneda D, Palmela C, Mooiweer E, Elman J, Kumar A, Glass J, Axelrad J, Ullman TA, Colombel JF, Torres J, van Bodegraven AA, Hoentjen F, Jansen JM, de Jong ME, Mahmmod N, van der Meulen-de Jong AE, Ponsioen CY, van der Woude CJ, Itzkowitz SH, Oldenburg B
(2019) Gut 68: 615-622
MeSH Terms: Adult, Colitis, Colonic Neoplasms, Colonoscopy, Disease Progression, Female, Humans, Male, Middle Aged, Neoplasm Grading, Population Surveillance, Precancerous Conditions, Predictive Value of Tests, Risk Factors
Show Abstract · Added March 3, 2020
OBJECTIVES - Surveillance colonoscopy is thought to prevent colorectal cancer (CRC) in patients with long-standing colonic IBD, but data regarding the frequency of surveillance and the findings thereof are lacking. Our aim was to determine whether consecutive negative surveillance colonoscopies adequately predict low neoplastic risk.
DESIGN - A multicentre, multinational database of patients with long-standing IBD colitis without high-risk features and undergoing regular CRC surveillance was constructed. A 'negative' surveillance colonoscopy was predefined as a technically adequate procedure having no postinflammatory polyps, no strictures, no endoscopic disease activity and no evidence of neoplasia; a 'positive' colonoscopy was a technically adequate procedure that included at least one of these criteria. The primary endpoint was advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia or CRC.
RESULTS - Of 775 patients with long-standing IBD colitis, 44% (n=340) had 1 negative colonoscopy. Patients with consecutive negative surveillance colonoscopies were compared with those who had at least one positive colonoscopy. Both groups had similar demographics, disease-related characteristics, number of surveillance colonoscopies and time intervals between colonoscopies. No aCRN occurred in those with consecutive negative surveillance, compared with an incidence rate of 0.29 to 0.76/100 patient-years (P=0.02) in those having 1 positive colonoscopy on follow-up of 6.1 (P25-P75: 4.6-8.2) years after the index procedure.
CONCLUSION - Within this large surveillance cohort of patients with colonic IBD and no additional high-risk features, having two consecutive negative colonoscopies predicted a very low risk of aCRN occurrence on follow-up. Our findings suggest that longer surveillance intervals in this selected population may be safe.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population.
Weigl K, Thomsen H, Balavarca Y, Hellwege JN, Shrubsole MJ, Brenner H
(2018) Gastroenterology 155: 88-98.e10
MeSH Terms: Adenoma, Aged, Carcinoma, Colonoscopy, Colorectal Neoplasms, Early Detection of Cancer, Female, Genetic Predisposition to Disease, Germany, Humans, Logistic Models, Male, Middle Aged, Neoplasm Staging, Odds Ratio, Polymorphism, Single Nucleotide, Prevalence, Risk Assessment, Tennessee
Show Abstract · Added March 3, 2020
BACKGROUND & AIMS - The presence of specific single nucleotide polymorphisms (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC), called a genetic risk score (GRS). We investigated whether GRS can identify individuals with clinically relevant neoplasms in a screening colonoscopy population.
METHODS - We derived a GRS based on 48 SNPs associated with CRC, identified in a comprehensive literature search. We obtained genetic data from 1043 participants (50-79 years old) in a screening colonoscopy study in Germany, recruited from 2005 through 2013 (294 with advanced neoplasms, 249 with non-advanced adenoma (NAAs), and 500 without neoplasms). Each participant was assigned a GRS by aggregating their risk alleles (0, 1, or 2). Risk of advanced neoplasms and NAA according to GRS was calculated by multiple logistic regression. Risk advancement periods were calculated. We replicated our findings using data from a subset of the Tennessee Colorectal Polyp Study.
RESULTS - An increased GRS was associated with higher prevalence of advanced neoplasms, but not NAAs. Participants in the middle and upper tertiles of GRS had a 2.2-fold and 2.7-fold increase in risk, respectively, of advanced neoplasms compared to those in the lower tertile. Adjusted odds ratios (ORs) were 1.09 (95% confidence interval [CI], 0.76-1.57) for NAA in the middle tertile and 1.05 (95% CI, 0.70-1.55) for NAA in the upper tertile. The ORs were largest for proximal advanced neoplasms for participants in the middle tertile (OR, 3.55; 95% CI 1.85-6.82) and the upper tertile (OR, 3.61; 95% CI 1.84-7.10). The risk advancement period for medium vs low GRS was 13.4 years (95% CI 4.8-22.0) and for high vs low GRS was 17.5 years (95% CI, 7.8-27.3).
CONCLUSIONS - In a genetic analysis of participants in a CRC screening study in Germany, an increased GRS (based on CRC-associated SNPs) was associated with increased prevalence of advanced neoplasms. These findings might be used in defining risk-adapted screening ages.
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
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High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease.
Shah SC, Ten Hove JR, Castaneda D, Palmela C, Mooiweer E, Colombel JF, Harpaz N, Ullman TA, van Bodegraven AA, Jansen JM, Mahmmod N, van der Meulen-de Jong AE, Ponsioen CY, van der Woude CJ, Oldenburg B, Itzkowitz SH, Torres J
(2018) Clin Gastroenterol Hepatol 16: 1106-1113.e3
MeSH Terms: Adolescent, Adult, Cholangitis, Sclerosing, Colonoscopy, Colorectal Neoplasms, Female, Histocytochemistry, Humans, Inflammatory Bowel Diseases, Longitudinal Studies, Male, Middle Aged, Netherlands, Retrospective Studies, Risk Assessment, United States, Young Adult
Show Abstract · Added March 3, 2020
BACKGROUND & AIMS - Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC, termed PSC-IBD) are at increased risk for colorectal cancer, but their risk following a diagnosis of low-grade dysplasia (LGD) is not well described. We aimed to determine the rate of advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia and/or colorectal cancer, following a diagnosis of indefinite dysplasia or LGD in this population.
METHODS - We performed a retrospective, longitudinal study of 1911 patients with colonic IBD (293 with PSC and 1618 without PSC) who underwent more than 2 surveillance colonoscopies from 2000 through 2015 in The Netherlands or the United States (9265 patient-years of follow-up evaluation). We collected data on clinical and demographic features of patients, as well as data from each surveillance colonoscopy and histologic report. For each surveillance colonoscopy, the severity of active inflammation was documented. The primary outcome was a diagnosis of aCRN during follow-up evaluation. We also investigated factors associated with aCRN in patients with or without a prior diagnosis of indefinite dysplasia or LGD.
RESULTS - Patients with PSC-IBD had a 2-fold higher risk of developing aCRN than patients with non-PSC IBD. Mean inflammation scores did not differ significantly between patients with PSC-IBD (0.55) vs patients with non-PSC IBD (0.56) (P = .89), nor did proportions of patients with LGD (21% of patients with PSC-IBD vs 18% of patients with non-PSC IBD) differ significantly (P = .37). However, the rate of aCRN following a diagnosis of LGD was significantly higher in patients with PSC-IBD (8.4 per 100 patient-years) than patients with non-PSC IBD (3.0 per 100 patient-years; P = .01). PSC (adjusted hazard ratio [aHR], 2.01; 95% CI, 1.09-3.71), increasing age (aHR 1.03; 95% CI, 1.01-1.05), and active inflammation (aHR, 2.39; 95% CI, 1.63-3.49) were independent risk factors for aCRN. Dysplasia was more often endoscopically invisible in patients with PSC-IBD than in patients with non-PSC IBD.
CONCLUSIONS - In a longitudinal study of almost 2000 patients with colonic IBD, PSC remained a strong independent risk factor for aCRN. Once LGD is detected, aCRN develops at a higher rate in patients with PSC and is more often endoscopically invisible than in patients with only IBD. Our findings support recommendations for careful annual colonoscopic surveillance for patients with IBD and PSC, and consideration of colectomy once LGD is detected.
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Management of colonoscopic perforations: A systematic review.
Hawkins AT, Sharp KW, Ford MM, Muldoon RL, Hopkins MB, Geiger TM
(2018) Am J Surg 215: 712-718
MeSH Terms: Algorithms, Colonoscopy, Comorbidity, Humans, Intestinal Perforation
Show Abstract · Added December 14, 2017
BACKGROUND - Perforation during colonoscopy is a rare but well recognized complication with significant morbidity and mortality. We aim to systematically review the currently available literature concerning care and outcomes of colonic perforation. An algorithm is created to guide the practitioner in management of this challenging clinical scenario.
DATA SOURCES - A systematic review of the literature based on PRISMA-P guidelines was performed. We evaluate 31 articles focusing on findings over the past 10 years.
CONCLUSION - Colonoscopic perforation is a rare event and published management techniques are marked by their heterogeneity. Reliable conclusions are limited by the nature of the data available - mainly single institution, retrospective studies. Consensus conclusions include a higher rate of perforation from therapeutic colonoscopy when compared to diagnostic colonoscopy and the sigmoid as the most common site of perforation. Mortality appears driven by pre-existing conditions. Treatment must be tailored according to the patient's comorbidities and clinical status as well as the specific conditions during the colonoscopy that led to the perforation.
Copyright © 2017 Elsevier Inc. All rights reserved.
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5 MeSH Terms
Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.
Sun P, Zhu X, Shrubsole MJ, Ness RM, Hibler EA, Cai Q, Long J, Chen Z, Li G, Hou L, Smalley WE, Edwards TL, Giovannucci E, Zheng W, Dai Q
(2017) J Nutr Biochem 47: 35-40
MeSH Terms: Adenoma, Amino Acid Transport Systems, Basic, Calcium, Dietary, Case-Control Studies, Colonic Polyps, Colonoscopy, Colorectal Neoplasms, Diet, Healthy, Dietary Supplements, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Magnesium, Male, Middle Aged, Neoplasm Grading, Patient Compliance, Polymorphism, Single Nucleotide, Self Report, Tennessee, Tumor Burden
Show Abstract · Added April 3, 2018
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.
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22 MeSH Terms
Watch and Wait: Is Surgery Always Necessary for Rectal Cancer?
Hawkins AT, Hunt SR
(2016) Curr Treat Options Oncol 17: 22
MeSH Terms: Chemoradiotherapy, Colonoscopy, Humans, Rectal Neoplasms, Salvage Therapy, Treatment Outcome
Show Abstract · Added September 27, 2016
OPINION STATEMENT - Despite decades of high-quality research, the treatment of rectal cancer remains a work in progress. The interplay between chemotherapy, radiotherapy, and surgery is under constant rearrangement and refinement. Through this all, the desire to preserve the anal sphincters and quality of life remains at the forefront. In the past decade, standard of care for stage II or III rectal cancers in the USA has been neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection of the rectum. While timing and sequence of the CRT continues to evolve, surgical resection has remained essential in treatment. This stands in contrast to anal cancer, where surgery is reserved purely for salvage. This article describes a treatment strategy that attempts to treat rectal adenocarcinoma with CRT alone, reserving surgery for failure or salvage. Of the studies performed to date, a number are methodologically sound and show promise. However, the body of evidence has yet to reach a size to sway practitioners from the established trinity of chemotherapy, radiotherapy, and surgery. Interestingly, few trials administer post treatment full-dose systemic chemotherapy, which is the standard of care in patients undergoing surgical resection. Better identification of patients that will have complete cure from this approach, combined with long-term outcome data on salvage patients, is necessary for this therapy to be universally embraced.
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Restoration of normal colonic motor patterns and meal responses after distal colorectal resection.
Vather R, O'Grady G, Arkwright JW, Rowbotham DS, Cheng LK, Dinning PG, Bissett IP
(2016) Br J Surg 103: 451-61
MeSH Terms: Adolescent, Adult, Aged, Colectomy, Colon, Colonoscopy, Colorectal Neoplasms, Female, Gastrointestinal Motility, Humans, Male, Manometry, Middle Aged, Pressure, Prognosis, Recovery of Function, Young Adult
Show Abstract · Added April 26, 2016
BACKGROUND - Colorectal resections alter colonic motility, including disruption of control by neural or bioelectrical cell networks. The long-term impact of surgical resections and anastomoses on colonic motor patterns has, however, never been assessed accurately. Fibreoptic high-resolution colonic manometry was employed to define motility in patients who had undergone distal colorectal resection.
METHODS - Recruited patients had undergone distal colorectal resections more than 12 months previously, and had normal bowel function. Manometry was performed in the distal colon (36 sensors; 1-cm intervals), with 2-h recordings taken before and after a meal, with comparison to controls. Analysis quantified all propagating events and frequencies (cyclical, short single, and long single motor patterns), including across anastomoses.
RESULTS - Fifteen patients and 12 controls were recruited into the study. Coordinated propagating events directly traversed the healed anastomoses in nine of 12 patients with available data, including antegrade and retrograde cyclical, short single and long single patterns. Dominant frequencies in the distal colon were similar in patients and controls (2-3 cycles/min) (antegrade P = 0·482; retrograde P = 0·178). Compared with values before the meal, the mean(s.d.) number of dominant cyclical retrograde motor patterns increased in patients after the meal (2·1(2·7) versus 32·6(31·8) in 2 h respectively; P < 0·001), similar to controls (P = 0·178), although the extent of propagation was 41 per cent shorter in patients, by a mean of 3·4 cm (P = 0·003). Short and long single propagating motor patterns were comparable between groups in terms of frequency, velocity, extent and amplitude.
CONCLUSION - Motility patterns and meal responses are restored after distal colorectal resection in patients with normal bowel function. Coordinated propagation across healed anastomoses may indicate regeneration of underlying cellular networks.
© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.
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Evaluation of pro-inflammatory markers plasma C-reactive protein and urinary prostaglandin-E2 metabolite in colorectal adenoma risk.
Davenport JR, Cai Q, Ness RM, Milne G, Zhao Z, Smalley WE, Zheng W, Shrubsole MJ
(2016) Mol Carcinog 55: 1251-61
MeSH Terms: Adenoma, Aged, Biomarkers, Tumor, C-Reactive Protein, Case-Control Studies, Colonoscopy, Colorectal Neoplasms, Dinoprostone, Early Detection of Cancer, Female, Humans, Male, Middle Aged, Risk Assessment, Risk Factors
Show Abstract · Added September 28, 2015
C-reactive protein (CRP) is a pro-inflammatory protein with potential as a biomarker in predicting colon cancer risk. However, little is known regarding its association with risk of colorectal adenomas, particularly by subtypes. We conducted a colonoscopy-based matched case-control study to assess whether elevated plasma CRP levels may be associated with colorectal adenoma risk and further whether this association may be modified by urinary prostaglandin E2 metabolite (PGE-M), a biomarker of systemic prostaglandin E2 production. Included in the study were 226 cases with a single small tubular adenoma, 198 cases with multiple small tubular adenomas, 283 cases with at least one advanced adenoma, and 395 polyp-free controls. No apparent association between CRP level and risk of single small tubular adenomas was found (ptrend  = 0.59). A dose-response relationship with CRP level was observed for risk of either multiple small tubular adenomas (OR = 2.01, 95%CI = 1.10-3.68 for the highest versus lowest tertile comparison; ptrend   = 0.03) or advanced adenomas (OR = 1.81, 95%CI = 1.10-2.96 for the highest versus lowest tertile comparison; ptrend  = 0.02). In a joint analysis of CRP level and PGE-M, risk of multiple or advanced adenoma was greatest among those with highest levels of both CRP and PGE-M in comparison to those with low CRP and low PGE-M (OR = 3.72, 95%CI = 1.49-9.72). Our results suggest that elevated CRP, particularly in the context of concurrent elevated PGE-M, may be a biomarker of multiple or advanced adenoma risk in a screening age population. © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.
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15 MeSH Terms