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Biomedical subjects

David T Rubin

Publications and source records attributed to David T Rubin.

18 recordsLinked to original sources
PubMed2007

5-Aminosalicylic acid therapy and the risk of colorectal cancer among patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) affecting the colon are at increased risk of developing colorectal cancer (CRC). Published data are conflicting about whether 5-aminosalicylic acid (5-ASA) has chemopreventive properties against IBD-related carcinogenesis. The objective of this observational study was to determine if an association between 5-ASA therapy and CRC risk exists in IBD patients. METHODS: Adult patients with a new CRC diagnosis (n = 18,440) were identified from 2 large administrative claims databases. For each case, 20 control patients with no record of CRC diagnosis or bowel surgery (n = 368,800) were identified. RESULTS: An IBD diagnosis was associated with a 6- to 7-fold increased risk of CRC (ulcerative colitis, crude odds ratio [OR] = 6.72, 95% CI, 5.79-7.81; Crohn's disease, crude OR = 6.60, 95% CI, 5.56-7.82). Among patients with IBD (364 CRC cases, 1172 controls), exposure to 5-ASA therapy of any dose or duration during the 12 months before CRC diagnosis was not associated with a reduced risk of CRC (OR = 0.97; 95% CI, 0.77-1.23). However, there was a trend toward a decreased risk of CRC with increasing number of mesalamine prescriptions in the previous year, though statistical significance was not achieved (trend P = 0.08). CONCLUSIONS: Treating IBD patients with 5-ASA medications was not found to have a protective effect against colitis-related CRC when assessed over a short period of exposure.

Aged↗
PubMed2006

Aminosalicylate therapy in the prevention of dysplasia and colorectal cancer in ulcerative colitis.

BACKGROUND & AIMS: Aminosalicylates have been suggested as chemopreventive agents for colorectal cancer (CRC) in ulcerative colitis (UC). We studied the effect of aminosalicylate use on dysplasia and CRC risk in chronic UC. METHODS: UC patients with dysplasia or CRC were matched with controls by disease duration, extent, and age at diagnosis. The total amount of aminosalicylates over the duration of the disease and the mean daily amount of drug was calculated. Conditional logistic regression was used to examine the relationship of aminosalicylates to the risk of neoplasia; potential confounders were controlled in a multivariable model. RESULTS: Twenty-six cases (8 CRC, 18 dysplasia) were matched with 96 controls. Cases and controls were similar in age (median, 43 vs 42.5 y), age at diagnosis of UC (median, 29.5 vs 30.5 y), duration of UC (median, 11.5 vs 9 y), and extent of disease (58% pancolitis), sex, family history of UC, history of primary sclerosing cholangitis, and smoking history. Cases were more likely to have a family history of CRC than controls (27% of cases, 9% of controls, P = .036). Conditional logistic regression adjusted for disease duration, age at diagnosis, and family history of CRC showed that aminosalicylate use of 1.2 g/day or more was associated with a 72% reduction in the odds of dysplasia/CRC (odds ratio, 0.28; 95% confidence interval, 0.09-0.85). As the total dose of aminosalicylates increased, the odds of dysplasia/CRC decreased (P = .056). CONCLUSIONS: This case-control study shows a significant risk reduction of dysplasia and CRC in UC patients exposed to aminosalicylate therapy.

Adult↗
PubMed2006

Comparison of routine and unprepped CT colonography augmented by low fiber diet and stool tagging: a pilot study.

BACKGROUND: We performed a pilot study examining the feasibility of a new unprepped CT colonography (CTC) strategy: low fiber diet and tagging (unprepped) vs. low fiber diet, tagging and a magnesium citrate cleansing preparation (prepped). Prior reports of tagging were limited in that the residual stool was neither measured and stratified by size nor did prior reports subjectively evaluate the ease of interpretation by a reader experienced in interpreting CTC examinations. METHODS: Prospective randomized to unprepped n = 14 and prepped n = 14. Colonic segments were subjectively evaluated for residual stool that would potentially interfere with interpretation. Scores were given in the following categories: percentage of residual stool that was touching or nearly touching mucosa, the largest piece of retained stool, effectiveness of tagging, height of residual fluid, degree of distention, ease of interpretation, and reading time. RESULTS: Ease of the CT read (scale where 4 = optimal read) averaged 1.3 for the unprepped group and 2.3 for the prepped group. The mean read time averaged 17.5 min for unprepped and 17.9 min for prepped. The degree of distention (scale where 4 = well distended) averaged 3.7 for unprepped and 3.6 for prepped. Supine and prone images combined, the unprepped group had 160 segments with stool; prepped group had 58 segments. The amount of stool covering the mucosa in all segments averaged 1.6 (33%-66% coverage) in the unprepped group and 0.35 (<33% mucosal coverage) in the prepped group. The mean size of the largest piece of stool was 33.67 mm for unprepped and 4.01 mm for prepped. Percentage of tagged stool was not significantly different between the groups (range of 94-98%). The height of residual fluid averaged 8.37 mm for unprepped and 13.4 mm for prepped. Three polyps in three patients were found during optical colonoscopy (OC) in the unprepped group (5, 6, and 10 mm), none of which were prospectively detected at CTC. Three polyps in three patients were detected during OC in the prepped group (5, 10, and 15 mm), two of which were prospectively detected at CTC. Two false-positive lesions were observed at CTC in one patient in the prepped group. CONCLUSION: There was more stool in the unprepped group and while this factor did not slow down the reading time, it made the examination subjectively harder to interpret and likely caused the three polyps in this group to be missed. We conclude that a truly unprepped strategy that leaves significant residual stool, even if well tagged, is not desirable.

Adult↗
PubMed2006

The complexity and challenges of genetic counseling and testing for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an umbrella term referring to two chronic idiopathic intestinal diseases: ulcerative colitis (UC) and Crohn's disease (CD). Both UC and CD are characterized by immune activation that leads to symptoms, but the location, severity and behavior of the inflammation varies among individuals and in characteristic ways between UC and CD. A majority of patients with IBD are diagnosed in young adulthood, but the response to therapy is variable and difficult to predict, with some patients demonstrating a prompt and effective remission while others have continuous symptoms that do not respond to existing medical options. Surgery remains a frequent and necessary occurrence among patients with IBD, but in UC it is considered curative, while in CD only temporizing. Clinical observations, epidemiological studies, and molecular genetics have provided strong evidence that both genetic and environmental factors are important determinants for disease susceptibility. In recent years, a number of genes have been identified that associate with CD and UC, although the clinical utility of these discoveries in patients or in susceptible family members has not been determined. Nonetheless, it is hoped that these fundamental advances in our understanding of IBD will lead to better therapies for patients and prevention strategies for those who are susceptible. Effective incorporation of clinical genetic testing for IBD into practice will require appropriate education and counseling.

Crohn Disease↗
PubMed2006

Colorectal cancer in inflammatory bowel disease: molecular and clinical considerations.

Adenocarcinoma of the colon is an accepted and feared complication of chronic ulcerative colitis (UC) and colonic Crohn's disease (CD). When cancer is identified, surgery is necessary, and unlike with sporadic colorectal cancer (CRC), in which partial colectomy is effective, proctocolectomy is required. As CRC is a rare complication of these diseases, studies of the pathogenesis are limited primarily to observational studies; thus, the mechanism and molecular events that lead to neoplastic change are not fully understood or well known. Precancerous dysplasia has been associated with concurrent or future CRC in UC and, although less studied, in CD, and is therefore considered a marker of cancer risk in inflammatory bowel disease (IBD). Risk factors for dysplasia and CRC in IBD include longer duration of disease, greater extent of disease, younger age at diagnosis, diagnosis with primary sclerosing cholangitis (PSC), family history of CRC, and possibly backwash ileitis and degree of inflammation of the bowel over time. Prevention of cancer in IBD has been focused on secondary measures of identifying dysplasia in flat mucosa or protruding lesions during surveillance colonoscopy with random biopsies and, when confirmed, performing proctocolectomy. Studies of primary prevention of dysplasia and CRC using chemopreventive agents have suggested a possible benefit with a number of agents. These include ursodeoxycholic acid (in patients with PSC and UC), aminosalicylates, and possibly statins.

Journal Article↗
PubMed2006

Prospective comparison of patient experience with colon imaging tests.

PURPOSE: Patient experience varies with the currently available colon imaging tests, including air contrast barium enema, computed tomographic colonography, and colonoscopy. We examined differences in patient experience with colon imaging tests and whether they varied with gender, age, and race. SUBJECTS AND METHODS: Patients with fecal occult blood, hematochezia, iron-deficiency anemia, or a family history of colon cancer underwent air contrast barium enema followed 7 to 14 days later by computed tomographic colonography and colonoscopy. Validated patient experience questionnaires that measured the experience for each test and a separate questionnaire that obtained an overall summary measure were administered after testing. Eleven patient experiences including pain, embarrassment, difficulty with bowel preparation, and satisfaction with tests were examined. RESULTS: A total of 614 subjects completed all 3 imaging tests. The test most patients were willing to repeat was colonoscopy; it also was reported to be the least painful procedure. Patients were least satisfied with air contrast barium enema, and fewer would undergo air contrast barium enema compared with computed tomographic colonography or colonoscopy. There were limited racial and gender differences in perceptions of the tests. Younger adults perceived air contrast barium enema to be more painful than older adults. CONCLUSION: Taking into account a wide variety of patient experience measures, patients preferred colonoscopy to air contrast barium enema and computed tomographic colonography. This finding has important implications for physicians considering different colon imaging tests.

Barium Sulfate↗
PubMed2006

Surveillance of dysplasia in inflammatory bowel disease: The gastroenterologist-pathologist partnership.

Cancer prevention in inflammatory bowel disease depends on the detection of precancerous dysplasia during scheduled screening and surveillance colonoscopy, but the detection and diagnosis of dysplasia remain challenging. In this article, we review the risks of cancer and dysplasia in ulcerative colitis and the current prevention recommendations, and through a sample case, we demonstrate an approach that involves an active partnership between the gastroenterologist or surgeon and pathologist. We address the challenge of management of polypoid lesions and incorporate new information about degree of inflammation as an additional risk of neoplasia in these patients.

Adenocarcinoma↗
PubMed2006

Surveillance for cancer and dysplasia in inflammatory bowel disease.

There remain technical challenges to the accurate prediction and diagnosis of neoplasia in IBD; therefore, prevention strategies are based on limited evidence and instead, consensus opinions and guidelines. Existing guidelines and published expert opinions are in agreement that given the increased risk of cancer in IBD and well-described associated risks, prevention strategies are warranted. The preponderance of existing prevention is focused on secondary prevention by performance of screening and surveillance colonoscopies with random biopsies to identify neoplasia and trigger surgical resection for prevention of invasive cancer and death. Substantial technical and practical challenges remain, however, and there is a great need for improved understanding of the compounded risks of neoplasia, the natural history of dysplasia, and more accurate detection and diagnostic techniques. A future approach to prevention is likely to stratify patients based on individualized risks that include, among things, the histologic degree of inflammation present. In meantime, existing guidelines should be emphasized and ongoing education of clinicians and patients must occur.

Biomarkers↗
PubMed2006

Do patients with inflammatory bowel disease want genetic testing?

BACKGROUND: Inflammatory bowel disease (IBD) is a complex genetic disorder characterized by nonmendelian inheritance, incomplete penetrance, and disease susceptibility but not disease certainty. Genotype and phenotype associations are described, but the level of interest of patients with IBD in genetic testing for themselves or at-risk family members remains unknown. Thus, the goal of this study was to assess the interest of patients with IBD in genetic testing and their willingness to accept the uncertainty inherent in complex genetics. MATERIALS AND METHODS: Consecutive outpatients with IBD were recruited to complete a 57-item self-administered survey. The survey included a layperson explanation of the limits of IBD genetics. A 5-point Likert scale was used to determine willingness to undergo genetic testing to determine diagnosis, prognosis, and treatment; to help their family; and to advance medical knowledge. The IBD Questionnaire, a validated measure of the health status attitudes of patients with IBD, was used. To determine limits of patient interest in testing family members, the standard reference gamble paradigm was used. Patients were presented with situations for the genetic test with various levels of certainty in 10% decrements starting with 100%. They indicated the lowest degree of certainty that they would accept to test their family member. RESULTS: One hundred fourteen patients (mean age 38.4 years; 48.2% women) completed the survey. Of these 114, 71.9% (82) had Crohn's disease. Among the patients who answered questions on self-willingness, 76.8% (86 of 112) would undergo testing for diagnostic confirmation, 81.3% (91 of 112) for prognostic value, 88.4% (99 of 112) for therapeutic decision making, and 85.0% (96 of 113) for advancement of medical knowledge. We found that 28.1% of patients (32 of 114) had a first-degree relative with IBD. Those patients with a first-degree relative with IBD were more willing to undergo genetic testing than those without a first-degree relative with IBD (raw score on self-willingness 4.62 vs 4.36; P=0.026). There was no significant association between patients' health status and their willingness to undergo genetic testing (IBD Questionnaire score and raw score on self-willingness; Spearman's correlation coefficient -0.06; P=0.51). We also found that 88.6% of patients (93 of 105) indicated an interest in testing family members if the test provided absolute certainty of future disease. The average lowest level of certainty these patients were willing to accept was 42.2%. CONCLUSIONS: Despite the complexity of IBD genetics, most patients with IBD are interested in testing and willing to accept a variable degree of uncertainty about the results. An important minority of patients does not wish to be tested. Future work should better identify the reasons for these different attitudes. This information should be factored into plans for widespread clinical testing.

Adult↗
PubMed2005

Superior mesenteric vein thrombosis after colectomy in a patient with Crohn's disease.

BACKGROUND: An 18-year-old woman with a history of Crohn's disease presented in January 2004 with severe epigastric pain, nausea and vomiting of 4 hours' duration. The patient was diagnosed with inflammatory bowel disease, thought to be consistent with ulcerative colitis, in March 2003, but had no medical history up until this point. Initial treatment with mesalamine was unsuccessful and she subsequently presented with medically resistant fulminant colitis and required an urgent colectomy in June 2003. Her immediate postoperative course was uneventful and she was discharged on tapering doses of prednisone. In August 2003, an ileoscopy revealed inflamed, mildly ulcerated mucosa, and biopsies were consistent with Crohn's disease. Azathioprine was added to the treatment regimen and the patient tapered off prednisone. At this stage the patient continued to do well clinically up until presentation. INVESTIGATIONS: Small bowel series, abdominal CT scan, abdominal ultrasound, exploratory laparotomy. DIAGNOSIS: Acute mesenteric ischemia secondary to superior mesenteric vein thrombosis. MANAGEMENT: Resection of necrotic bowel, antibiotics and systemic anticoagulation.

Adolescent↗
PubMed2005

Will a 5-ASA a day keep the cancer (and dysplasia) away?

Prevention strategies for colorectal cancer in chronic ulcerative colitis (UC) are currently based on the identification of neoplasia by surveillance colonoscopy, but there is a great interest in the possibility of primary chemoprevention. 5-aminosalicylic acid (5-ASA) therapy is an attractive option for chemoprevention in UC due to the fact that it is a derivative of aspirin and has been shown to have a variety of other molecular and genetic targets of cancer prevention, but human studies in UC have been limited by observational design and limited data collection or follow-up. The recently performed metaanalysis of 5-ASA chemoprevention trials shows a favorable role of 5-ASA in the prevention of cancer and dysplasia in patients with UC, and adds to the available evidence favoring its use. This editorial discusses the substantial logistical and ethical challenges in designing a randomized double-blind trial to measure the effect of 5-ASA on cancer risk in UC. The authors conclude that the safety and current maintenance use of 5-ASA warrant its acceptance as a probable chemopreventive agent at this time.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Fever and right upper quadrant pain in a pregnant woman at 30 weeks' gestation.

BACKGROUND: A 34-year-old gravid woman with a history of ileal Crohn's disease presented at 30 weeks' gestation with a 2-week history of fever and right upper quadrant pain. An intra-abdominal abscess was suspected. Ultrasound and MRI failed to demonstrate the suspected abscess. Owing to ongoing pain and fever, the risk to the fetus of a CT scan were discussed with the patient, obstetricians and radiologists, with considerable debate about the possibility of other explanations for her symptoms. Ultimately, a CT scan revealed marked thickening of the distal ileum and confirmed diagnosis of an abscess in continuity with the inflamed bowel. INVESTIGATIONS: Ultrasound, MRI, CT scan, urinalysis, urine culture and liver function tests. DIAGNOSIS: Crohn's disease flare complicated by an intra-abdominal abscess. MANAGEMENT: Antibiotics (ceftizoxime, metronidazole and amoxicillin/clavulanate potassium), parenteral nutrition and ileocecectomy.

Abdominal Abscess↗
PubMed2002

Computerized detection of colonic polyps at CT colonography on the basis of volumetric features: pilot study.

PURPOSE: To develop a computer-aided diagnosis (CAD) scheme for automated detection of colonic polyps on the basis of volumetric features and to assess its accuracy on the basis of colonoscopy, the standard. MATERIALS AND METHODS: Computed tomographic (CT) colonography was performed in patients with use of standard bowel cleansing, air insufflation, and helical scanning in supine and prone positions. The colon was extracted from volumetric data sets generated from transverse CT sections. Volumetric features characterizing polyps were computed at each point in the extracted colon. Polyps were detected by means of hysteresis thresholding and fuzzy clustering followed by a rule-based test on the basis of feature values. Locations of the detected polyps were compared with those detected at conventional colonoscopy. RESULTS: Forty-one cases were analyzed: nine cases with polyps and 32 without polyps. Each case with polyps had one polyp of clinically important size (six were 5-9 mm; three, 10 mm). Thus, there were 82 volumetric data sets, 18 included polyps. Eighty-nine percent (16 of 18) of the polyps were detected. Each of the two false-negative findings was detected in the other position; thus, 100% of polyp cases were detected, with 2.5 false-positive findings per patient. The false-positive findings were similar to those due to common perceptual errors. Most of the false-positive findings were easily distinguishable from true polyps by experienced radiologists. CONCLUSION: The CAD scheme has the potential to depict polyps with high sensitivity and an acceptable false-positive rate.

Adult↗
PubMedDate not supplied

Computer-aided diagnosis scheme for detection of polyps at CT colonography.

Colon cancer is one of the leading causes of cancer deaths in the United States. However, most colon cancers can be prevented if precursor colonic polyps are detected and removed. An advanced computer-aided diagnosis (CAD) scheme was developed for the automated detection of polyps at computed tomographic (CT) colonography. A region encompassing the colonic wall is extracted from an isotropic volume data set obtained by interpolating CT colonographic scans along the axial direction. Polyp candidates are detected with computation of three-dimensional (3D) geometric features that characterize polyps, followed by extraction of polyps with hysteresis thresholding and fuzzy clustering using these geometric features. The number of false-positive findings is reduced by extracting 3D texture features from polyp candidates and applying quadratic discriminant analysis to the candidates. This CAD scheme was applied in 71 patients who underwent CT colonography, 14 of whom had colonoscopically confirmed polyps (n = 21). At by-patient analysis, sensitivity was 100%, with an average false-positive rate of 2.0 per patient. At by-polyp analysis, the scheme detected 90% of the polyps at the same false-positive rate. This CAD scheme permits accurate detection of suspicious lesions and thus has the potential to reduce radiologists' interpretation time and improve their diagnostic accuracy in the detection of polyps at CT colonography.

Adult↗