Use of a novel vitamin D bioavailability test demonstrates that vitamin D absorption is decreased in patients with quiescent Crohn's disease.

BACKGROUND: Vitamin D deficiency is a common problem in patients with Crohn's disease (CD). The aim of this study was to determine the ability of normal subjects and patients with quiescent CD to absorb vitamin D(2) using a novel vitamin D bioavailability test. In addition, we evaluated whether the location of disease or previous surgery had any influence on the bioavailability of vitamin D(2) in CD patients. METHODS: Ten normal subjects (50% female) and 37 CD patients with quiescent disease (51% female) were included in this study. Subjects who recently received any vitamin D(2) were excluded. The vitamin D bioavailability test was performed in all subjects. After a baseline blood draw, all subjects were then given a single 50,000 IU oral dose of vitamin D(2) in a capsule formulation and had their blood drawn 12 hours later to determine serum vitamin D(2), which reflected their vitamin D(2) absorption capacity. RESULTS: Forty-two percent and 29% of CD patients were found to be either vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] ≤20 ng/mL] or insufficient [25(OH)D 21-29 ng/mL], respectively. Twelve hours after ingesting 50,000 IU vitamin D(2) , vitamin D(2) levels rose from a baseline of 0.7 ± 0.7 ng/mL (mean ± SEM) to 49.8 ± 3.0 ng/mL in normal subjects. In CD patients, baseline vitamin D(2) levels rose from 0 ng/mL to 34.8 ± 2.8 ng/mL. CD patients had on average a 30% decrease in their ability to absorb vitamin D(2) (P = 0.01). Moreover, we found a wide variability of vitamin D(2) bioavailability in CD patients. Analysis of variance (ANOVA) revealed no statistical difference of vitamin D(2) bioavailability between patients in the CD subgroup stratified by the location of disease, the type of surgery, and receiving or not receiving surgery. CONCLUSIONS: More than 70% of the patients with quiescent CD were vitamin D-deficient or insufficient. The ability to absorb vitamin D(2) in CD patients is unpredictable and the only way to determine this is to perform a vitamin D bioavailability test. Use of this test may guide clinicians in administering the appropriate therapeutic dose of vitamin D for treating vitamin D deficiency in patients with CD.

Quality in the technical performance of screening flexible sigmoidoscopy: recommendations of an international multi-society task group.

BACKGROUND: Flexible sigmoidoscopy (FS) is a complex technical procedure performed in a variety of settings, by examiners with diverse professional backgrounds, training, and experience. Potential variation in technical quality may have a profound impact on the effectiveness of FS on the early detection and prevention of colorectal cancer. AIM: We propose a set of consensus and evidence based recommendations to assist the development of continuous quality improvement programmes around the delivery of FS for colorectal cancer screening. RECOMMENDATIONS: These recommendations address the intervals between FS examinations, documentation of results, training of endoscopists, decision making around referral for colonoscopy, policies for antibiotic prophylaxis and management of anticoagulation, insertion of the FS endoscope, bowel preparation, complications, the use of non-physicians as FS endoscopists, and FS endoscope reprocessing. For each of these areas, continuous quality improvement targets are recommended, and research questions are proposed.

Controlled trial of interventions to increase testing and treatment for Helicobacter pylori and reduce medication use in patients with chronic acid-related symptoms.

BACKGROUND: Many symptomatic patients take proton pump inhibitors or histamine-2 blockers for years and those without gastro-oesophageal reflux disease might benefit from Helicobacter pylori eradication. AIM: To increase testing and treatment of H. pylori and reduce chronic use of proton pump inhibitors and histamine-2 blockers. METHODS: We conducted a three-armed controlled trial in 14 managed care practices. We included adults who used proton pump inhibitors or histamine-2 blockers for >1 year and excluded those with gastro-oesophageal reflux disease or previous endoscopy. We compared usual care (n = 312 patients from 6 practices) to low-intensity (n = 147 from 3 practices) and high-intensity (n = 122 from 5 practices) interventions. Low-intensity intervention consisted of guidelines, patient-lists, and a "toolkit"; high-intensity intervention added academic group detailing by a gastroenterologist with reinforcement by pharmacists. RESULTS: Compared with usual care, the high-intensity intervention increased H. pylori test-ordering (29% versus 9% at 12 months, P = 0.02). About half (23 of 58) of patients tested positive and 22 received eradication treatments. The high-intensity intervention decreased proton pump inhibitor use by 9% per year (P = 0.028), but did not alter histamine-2 blocker use. The low intensity intervention was ineffective. CONCLUSIONS: Providing guidelines, patient-lists, and toolkits was no better than usual care. Adding group detailing and pharmacist reinforcements led to improvements in H. pylori management and decreases in proton pump inhibitor use.

Self-care for the inflammatory bowel disease patient: what can the professional recommend?

The management of patients with inflammatory bowel disease (IBD) continues to present a challenge for gastroenterologists. IBD constitutes a significant burden for the affected individual because of both intestinal and systemic manifestations. The lack of a specific cause and a definitive cure for this condition, as well as the potential for associated malignancy, leave patients unsettled and fearful of the future. Many patients and their families are significantly impaired by the limitations that IBD places on their lives. These limitations are frequently overlooked, and extend well beyond the boundaries of traditional medical practice. Patients often seek to become active participants in the management of their disease. An approach that includes discussion and education on lifestyle issues affecting IBD patients should be part of our routine practice. This article reviews lifestyle and self-care factors relevant to the IBD patient, and what the gastroenterologist can recommend based on current evidence.

Gastric dysplasia-like epithelial atypia associated with chemoradiotherapy for esophageal cancer: a clinicopathologic and immunohistochemical study of 15 cases.

Preoperative chemotherapy combined with radiotherapy (chemrad) is a common type of neoadjuvant treatment for esophageal adenocarcinoma or squamous cell carcinoma. The purpose of this study was to describe the clinical, histologic, proliferative (MIB-1), and oncogenetic (p53) features of 15 patients with gastric dysplasia-like epithelial atypical changes associated with preoperative chemrad for esophageal cancer. Two of these cases were initially misinterpreted as dysplasia, which led to partial gastrectomy. The findings were compared with 12 age- and sex-matched patients with known gastric dysplasia. Cases with gastric dysplasia-like epithelial atypia were significantly associated with a flat gross appearance, a patchy distribution, foveolar and gland involvement, surface maturation, an open nuclear chromatin pattern with prominent nucleoli, retention of nuclear polarity, mitoses confined to the pits, lack of atypical mitoses, cytoplasmic hypereosinophila and/or vacuolization, a lack of association with intestinal metaplasia, and finally, irregular glandular microcystic change, in comparison to the dysplasia controls. Furthermore, the study cases showed MIB-1 positivity restricted to the deep foveolar epithelium and an absence of p53 staining in 14 of 15 cases, in contrast to the dysplasia controls, in which MIB-1 stained both the deep and superficial foveolar epithelium and surface epithelium, and p53 was positive in all cases (100%). In summary, a number of histologic and immunohistochemical features may distinguish gastric dysplasia-like epithelial atypia associated with chemrad for esophageal cancer from true dysplasia. Pathologists should be aware of this entity and its histologic and immunohistochemical features to avoid misinterpretation and prevent unnecessary treatment.

Training of nurse practitioners and physician assistants to perform screening flexible sigmoidoscopy.

PURPOSE: To describe the colorectal cancer-screening program at Harvard Vanguard Medical Associates, a large multispecialty medical group, in which nurse practitioners (NPs) and physician assistants (PAs) perform screening flexible sigmoidoscopies. DATA SOURCES: Scientific literature, consensus statements and guidelines, and the protocol utilized to train NPs and PAs to perform flexible sigmoidoscopy. Data from 9,500 screening procedures are presented. CONCLUSIONS: In comparison with gastroenterologists, trained NP and PA endoscopists perform screening flexible sigmoidoscopy with similar accuracy and safety but at lower cost. IMPLICATIONS FOR PRACTICE: Screening flexible sigmoidoscopy performed by NPs and PAs may increase the availability and lower the cost of flexible sigmoidoscopy for colorectal cancer screening.

Phenotypic characteristics associated with the APC gene I1307K mutation in Ashkenazi Jewish patients with colorectal polyps.

CONTEXT: The I1307K mutation of the APC gene is found in approximately 6% of the Ashkenazi Jewish population and is associated with elevated risk of colorectal cancer. The incidence of the mutation in patients with colorectal adenomas is unknown. OBJECTIVES: To determine the carrier rate of the I1307K mutation in Ashkenazi Jewish patients with a history of colorectal polyps but without colorectal cancer and to compare phenotypic characteristics and family history of carriers vs noncarriers. DESIGN, SETTING, AND PATIENTS: A total of 231 patients who had at least 1 large bowel polyp diagnosed between January 1, 1992, and January 31, 1999, at 1 of 5 centers in Boston, Mass, were included, of whom 183 were Ashkenazi Jewish. DNA was isolated from cheek swab samples. MAIN OUTCOME MEASURES: Presence of the I1307K variant in the APC gene. RESULTS: The I1307K variant was identified in 22 (14%) of 161 Ashkenazi Jewish patients with a history of adenomatous polyps and in 1 (5%) of 20 Ashkenazi Jewish patients with hyperplastic polyps. The phenotypic features of adenomas, family history of polyps, colorectal cancer, and other cancers were indistinguishable between I1307K carriers and noncarriers. CONCLUSIONS: The frequency of the APC I1307K mutation is elevated in Ashkenazi Jewish patients with adenomatous polyps, but not hyperplastic polyps. The I1307K mutation represents a novel paradigm for cancer-predisposing genes, as it is associated with moderately increased risk of neoplasia without other associated distinguishing phenotypic features. JAMA. 2000;284:857-860

Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis.

BACKGROUND & AIMS: Chronic ulcerative colitis (CUC)-associated adenoma-like DALMs (dysplasia-associated lesions or masses) pose a difficult clinical problem to both gastroenterologists and pathologists because they are difficult to distinguish endoscopically and pathologically from sporadic adenomas that develop coincidentally in patients with CUC. The aim of this study was to evaluate the outcome of CUC patients with an adenoma-like DALM treated conservatively and to compare the findings with CUC patients with a coincidental sporadic adenoma. METHODS: Clinical, endoscopic, and pathological features and outcome of 24 CUC patients with an adenoma-like DALM were compared with those of 10 CUC patients with a coincidental sporadic adenoma and 49 non-CUC (control) patients with a sporadic adenoma. Patients were followed up for a mean of 42.4 and 41.2 months for the 2 CUC groups, respectively, and 37.0 months for the non-CUC controls by endoscopic surveillance. RESULTS: Of the 24 CUC patients with adenoma-like DALMs (male/female ratio, 14/10; mean age, 61.5 years; mean duration of colitis, 10.4 years), 14 (58%) developed further adenoma-like DALMs within the follow-up interval. Only 1 patient (4%) developed an isolated focus of low-grade dysplasia, and none developed adenocarcinoma. Five of 10 (50%) CUC patients with sporadic adenomas developed further adenomas, and none of the patients in this group developed either dysplasia or adenocarcinoma. Of the 49 non-CUC control patients, 39% developed further adenomas. CONCLUSIONS: CUC patients who develop an adenoma-like DALM that endoscopically and histologically resembles a sporadic adenoma, regardless of its location (either within or outside areas of documented colitis), may be treated with polypectomy and endoscopic surveillance because of its relatively benign course.

A randomized controlled trial of an enhanced patient compliance program for Helicobacter pylori therapy.

OBJECTIVES: To determine whether an enhanced compliance program (ECP) improves patient compliance with bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (BMT) triple therapy for the treatment of Helicobacter pylori infection and to identify factors that affect compliance with therapy. DESIGN: A randomized controlled trial conducted in 4 staff-model health centers of a health maintenance organization in Massachusetts. PATIENTS AND METHODS: A total of 125 patients 18 years of age or older with peptic ulcer disease or dyspepsia whose clinicians prescribed BMT triple therapy for 14 days were randomized to a control group or to the ECP group. The ECP group received medication counseling (written and oral) from a pharmacist, along with a medication calendar and a minipillbox, as well as a follow-up telephone call after initiation of therapy. Compliance was assessed by a pill count, and factors affecting adherence to the regimen were identified by patients' reports. RESULTS: There was no statistically significant difference between the 2 groups in the number of patients taking more than 60% of the medications (89% of the control group vs 95% of the ECP group; P>.30). However, there was a statistically significant difference in the number of patients taking more than 90% of the medications (67% of the control group vs 89% of the ECP group; P<.01). An intention-to-treat analysis confirmed these results. The most frequently reported adverse effect was gastrointestinal intolerance. Other factors reported to affect compliance included the frequency of dosing and the number of pills. CONCLUSIONS: These findings suggest that although adverse effects were common, most patients were able to complete 60% or more of the 2-week regimen. An ECP further improved the percentage of medications taken.

Screening for colorectal cancer with flexible sigmoidoscopy by nonphysician endoscopists.

PURPOSE: Screening with sigmoidoscopy reduces the risk of death from colorectal cancer. Only 30% of eligible patients have undergone sigmoidoscopy, in part because of a limited supply of endoscopists. We evaluated the performance and safety of screening sigmoidoscopic examinations by trained nonphysician endoscopists in comparison with board-certified gastroenterologists. SUBJECTS AND METHODS: Asymptomatic patients 50 years or older without evidence of fecal occult blood and no personal history or family history of a first-degree relative with colorectal cancer under age 55 years were offered sigmoidoscopy. All examinations were performed either by a gastroenterologist or a trained nonphysician endoscopist at a staff model health maintenance organization. Outcomes included the depth of examination, number and histology of polyps, and complications. RESULTS: Nonphysicians performed 2,323 sigmoidoscopic examinations, and physicians performed 1,378 examinations. The mean (+/-SD) depth of sigmoidoscopy examinations performed by nonphysicians was 52 +/- 10 cm compared with 55 +/- 9 cm (P <0.001) in physicians. Nonphysicians detected neoplastic polyps in a greater proportion of patients (7.8%) than physicians (5.8%), but this difference was not significant after adjusting for differences in the age, sex, and family history of the patients (P = 0.35). No major complications occurred. The cost per examination, including the nonphysician training cost, was lower for nonphysicians ($186 per examination) than for physicians ($283 per examination). CONCLUSIONS: Appropriately trained nonphysicians may be capable of performing safe and effective screening for colorectal cancer with flexible sigmoidoscopy. An increased use of nonphysicians to perform sigmoidoscopy may increase the availability and reduce the cost of the procedure.

Is colonoscopy indicated for small adenomas found by screening flexible sigmoidoscopy?

BACKGROUND: There is controversy over whether patients who have a small tubular adenoma on screening flexible sigmoidoscopy should undergo colonoscopic examination of the proximal colon. OBJECTIVE: To prospectively determine the prevalence of advanced polyps in the proximal colon among patients who have small adenomas on screening sigmoidoscopy. DESIGN: Prospective cohort study. SETTING: A health maintenance organization and a Veterans Affairs medical center. PATIENTS: Asymptomatic patients older than 50 years of age who had no risk factors for colon cancer and underwent sigmoidoscopy. INTERVENTION: At the time of sigmoidoscopy, all polyps were biopsied and characterized. All patients with distal adenomas were offered colonoscopy. MEASUREMENTS: The size and histology of polyps identified by sigmoidoscopy and colonoscopy were noted. Polyps were considered advanced if they were larger than 10 mm or were tubulovillous, villous, or malignant. The prevalence of advanced proximal polyps was determined, and patients were stratified by the size and number of distal polyps found by sigmoidoscopy. RESULTS: Among 4490 patients who underwent sigmoidoscopy, a neoplastic lesion was detected in 401 (8.9%) and colonoscopy was done in 301 (75%). Of 90 patients with a single tubular adenoma 1 to 5 mm in diameter in the distal colon, 0% (95% CI, 0.0% to 4.0%) had an advanced proximal polyp compared with 5.4% (CI, 2.4% to 10.4%) of those who had multiple distal polyps 1 to 5 mm or 6 to 10 mm in diameter and 7.9% (CI, 2.6% to 17.6%) of those who had advanced distal polyps (P = 0.013 for trend). The low-risk group with a single tubular adenoma 1 to 5 mm in diameter represented 44% of all patients with distal adenomas or cancers found at flexible sigmoidoscopy. CONCLUSIONS: Among patients undergoing screening sigmoidoscopy, those with single tubular adenomas of 5 mm or less had a low prevalence of advanced proximal polyps. These patients may not benefit from colonoscopy.