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Douglas Rex

Publications and source records attributed to Douglas Rex.

8 recordsLinked to original sources
PubMed2006

Improved marker combination for detection of de novo genetic variation and aberrant DNA in colorectal neoplasia.

BACKGROUND: The genetic heterogeneity of sporadic colorectal cancer (CRC) makes the choice of genetic markers and sequence variation-detection technologies critical to the performance of screening assays. We have previously described the effectiveness of a CRC assay composed of 22 known variants in KRAS, APC, TP53, and BAT-26 (V1). We introduce a new marker formulation (V2) that includes detection of de novo variation in APC, PIK3CA, and CTNNB1, hypermethylated sequences within SMARCA3 and VIM, and a single-base variation within BRAF. We compared the abilities of the V1 and V2 markers to detect aberrant DNA in colorectal neoplasias. METHODS: V1 and V2 marker formulations were used to analyze 144 colorectal tissue samples comprising 50 precancerous adenomas, 94 carcinomas, and 11 nonpathologic tissues. V1 analysis consisted of single-base extension analysis of the 22 V1 variants. V2 analysis consisted of DNA scanning of the APC mutation cluster region, PIK3CA exons 9 and 20, CTNNB1 exon 3, analysis for the BRAF Val600Glu substitution, and methylation-specific PCR analysis of VIM and SMARCA3. RESULTS: The V2 marker formulation had significantly higher sensitivity than the V1 markers for carcinomas (93.6% and 72.3%, respectively; P = 0.0002) and adenomas (92.0% and 62.0%, respectively; P = 0.0006). None of the nonpathologic samples were positive for any marker. CONCLUSIONS: We demonstrate improved sensitivity of a new marker formulation (V2) to detect aberrant DNA in CRC and precancerous adenoma tumor tissues.

Adenomatous Polyps↗
PubMed2006

The aer-o-scope: proof of concept of a pneumatic, skill-independent, self-propelling, self-navigating colonoscope.

BACKGROUND & AIMS: Endoscopic screening of the colon with available instruments requires considerable training, is often painful, and carries a risk of perforation. New instrument platforms for endoscopic screening could be useful. The aim of this study was to evaluate the extent of colonic intubation by using a novel self-propelled, self-navigating endoscope (the Aer-O-Scope; GI View Ltd, Ramat Gan, Israel). METHODS: Twelve young healthy volunteers underwent complete bowel preparation followed by a nonsedated examination using the novel device. Each examination was followed by a standard colonoscopy for safety evaluation. Cecal intubation was confirmed by endoscopic landmarks and fluoroscopy. RESULTS: In 10 out of 12 subjects (83%) the cecum was successfully reached, whereas in 2 cases the Aer-O-Scope advanced to the hepatic flexure. The time to complete advancement to cecum averaged 14.0 +/- 7 minutes, and the driving pressures averaged 34 +/- 2.3 milibar. Two subjects requested analgesics during the procedures (in both cases the cecum was reached). Four subjects experienced sweating and a bloating sensation that resolved spontaneously. All subjects were followed up to 48 hours and then for 30 days postprocedure, and no complications were observed. CONCLUSIONS: In a preliminary pilot feasibility study of this new instrument, the Aer-O-Scope effectively intubated all or most of the colon. Further clinical studies are warranted.

Adult↗
PubMed2004

Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia.

CONTEXT: Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers. OBJECTIVE: To assess the accuracy of CTC in a large number of participants across multiple centers. DESIGN, SETTING, AND PARTICIPANTS: A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results. MAIN OUTCOME MEASURES: The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience. RESULTS: A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique. CONCLUSIONS: Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.

Colonography, Computed Tomographic↗
PubMed2004

AGA future trends report: CT colonography.

BACKGROUND & AIMS: Computed tomographic colonography (CTC) was first described more than a decade ago. Recent advances in imaging hardware and software and results of clinical trials based on new methods for performing and interpreting images suggest that CTC may now be assessed as a method for colorectal cancer screening. METHODS: The Research Policy Committee of the American Gastroenterological Association assembled a task force to review the results of recent clinical trials and quantitative mathematical models pertaining to CTC. The goal of the task force was to assess the current knowledge about CTC and to evaluate the issues that will define its impact. RESULTS: Limitations in evaluating the current state of CTC technology include a wide variation in results of clinical trials. There are as yet insufficient data on the use of CTC in routine clinical practice. Limitations in the use of quantitative mathematical models make predictions based on such models of limited value. The cancer risk and therefore clinical importance of small colorectal polyps detected by CTC and/or nonpolypoid neoplasia not detected by CTC remains largely unknown. CONCLUSIONS: CTC is attractive as a colon imaging modality. It is therefore anticipated that CTC will have a significant impact on the practice of gastroenterology. However, the magnitude of the impact is currently unknown. Whether the ongoing implementation of CTC will increase or decrease the number of referrals for colonoscopy or shift the procedure from colorectal cancer screening to therapeutic interventions (e.g., polypectomy) is unknown at the present time. Multidisciplinary collaboration between gastroenterology and radiology to promote effective implementation and ongoing quality assurance will be important.

Advisory Committees↗
PubMed2003

Classification of small bowel Crohn's subtypes based on multimodality imaging.

This article has reviewed the imaging features that correspond to and support the classification of patients into clinical subtypes of Crohn's disease. One study showed that radiologic features on barium studies closely correlated with the Crohn's Disease Activity Index, and another study indicated that CT findings changed patient management in up to 29% of cases. Knowledge of the location, severity, and presence of complications assist in providing patients with appropriate treatment options. Reports of radiologic studies in Crohn's disease should include the presence or absence of imaging features that support these different subtypes. An additional advantage of the use of a reproducible imaging classification that emphasizes morphologic features would be improved comparison of the results of different investigators and treatment protocols. Whatever method of radiologic investigation is employed, it should be targeted to answer questions relevant to patient management. The imaging modalities used should be able to classify the small bowel Crohn's subtypes and should be reflected in the radiologists' reports.

Barium Sulfate↗
PubMed2003

Predictive value of diminutive colonic adenoma trial: the PREDICT trial.

BACKGROUND & AIMS: Diminutive adenomas (1-9 mm in diameter) are frequently found during colon cancer screening with flexible sigmoidoscopy (FS). This trial assessed the predictive value of these diminutive adenomas for advanced adenomas in the proximal colon. METHODS: In a multicenter, prospective cohort trial, we matched 200 patients with normal FS and 200 patients with diminutive adenomas on FS for age and gender. All patients underwent colonoscopy. The presence of advanced adenomas (adenoma >or= 10 mm in diameter, villous adenoma, adenoma with high grade dysplasia, and colon cancer) and adenomas (any size) was recorded. Before colonoscopy, patients completed questionnaires about risk factors for adenomas. RESULTS: The prevalence of advanced adenomas in the proximal colon was similar in patients with diminutive adenomas and patients with normal FS (6% vs. 5.5%, respectively) (relative risk, 1.1; 95% confidence interval [CI], 0.5-2.6). Diminutive adenomas on FS did not accurately predict advanced adenomas in the proximal colon: sensitivity, 52% (95% CI, 32%-72%); specificity, 50% (95% CI, 49%-51%); positive predictive value, 6% (95% CI, 4%-8%); and negative predictive value, 95% (95% CI, 92%-97%). Male gender (odds ratio, 1.63; 95% CI, 1.01-2.61) was associated with an increased risk of proximal colon adenomas. CONCLUSIONS: Diminutive adenomas on sigmoidoscopy may not accurately predict advanced adenomas in the proximal colon.

Adenoma↗
PubMed2003

Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence.

We have updated guidelines for screening for colorectal cancer. The original guidelines were prepared by a panel convened by the U.S. Agency for Health Care Policy and Research and published in 1997 under the sponsorship of a consortium of gastroenterology societies. Since then, much has changed, both in the research rature and in the clinical context. The present report summarizes new developments in this field and suggests how they should change practice. As with the previous version, these guidelines offer screening options and encourage the physician and patient to decide together which is the best approach for them. The guidelines also take into account not only the effectiveness of screening but also the risks, inconvenience, and cost of the various approaches. These guidelines differ from those published in 1997 in several ways: we recommend against rehydrating fecal occult blood tests; the screening interval for double contrast barium enema has been shortened to 5 years; colonoscopy is the preferred test for the diagnostic investigation of patients with findings on screening and for screening patients with a family history of hereditary nonpolyposis colorectal cancer; recommendations for people with a family history of colorectal cancer make greater use of risk stratification; and guidelines for genetic testing are included. Guidelines for surveillance are also included. Follow-up of postpolypectomy patients relies now on colonoscopy, and the first follow-up examination has been lengthened from 3 to 5 years for low-risk patients. If this were adopted nationally, surveillance resources could be shifted to screening and diagnosis. Promising new screening tests (virtual colonoscopy and tests for altered DNA in stool) are in development but are not yet ready for use outside of research studies. Despite a consensus among expert groups on the effectiveness of screening for colorectal cancer, screening rates remain low. Improvement depends on changes in patients' attitudes, physicians' behaviors, insurance coverage, and the surveillance and reminder systems necessary to support screening programs.

Colorectal Neoplasms↗