Fred Saibil

Low-Dose Cyclosporine for the Treatment of Crohn's Disease

BACKGROUND Long-term corticosteroid therapy for Crohns disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohns disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohns disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohns Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohns disease, defined as a 100-point increase in the Crohns Disease Activity Index from the patients base-line value. Secondary outcomes were the use of prednisone and 5-amino-salicylates, mean score on the Crohns Disease Activity Index and mean quality-of-life score, and the need for surgery. RESULTS The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohns Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohns disease did not improve symptoms or reduce requirements for other forms of therapy.

Omeprazole (20 mg daily) versus cimetidine (1200 mg daily) in duodenal ulcer healing and pain relief

We conducted a double-blind, randomized, parallel group study in 169 patients with acute duodenal ulcers to compare omeprazole, 20 mg daily, with cimetidine, 600 mg twice daily. After 2 wk, 58% of the omeprazole-treated patients and 46% of the cimetidine-treated patients were completely healed (p = 0.056). After 4 and 6 wk 84% and 88% healed with omeprazole, and 80% and 89% healed with cimetidine (p = NS). After 2 wk, pain was completely gone in 62% of the omeprazole-treated patients versus 46% of the cimetidine-treated patients (p = 0.04). Clinical or laboratory adverse events were reported in 6 (7%) of the omeprazole-treated patients and 11 (13%) of the cimetidine-treated patients (p = NS). An adverse event caused withdrawal of 1 patient on omeprazole (anxiety and depression) and 2 patients on cimetidine (diarrhea and fall in hemoglobin). We conclude that omeprazole (20 mg daily) resulted in a trend toward more rapid ulcer healing compared with a relatively high dose of cimetidine (600 mg b.i.d.), and was preferred by patients for relief of ulcer pain.

Acute Pancreatitis Due to 5-Aminosalicylate

Excerpt Acute pancreatitis has been described as a complication of sulfasalazine therapy in patients with inflammatory bowel disease (1-3). In a critical review, Mallory and Kern (4) suggested that...

Cyclooxygenase-2 Polymorphisms, Aspirin Treatment, and Risk for Colorectal Adenoma Recurrence—Data from a Randomized Clinical Trial

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the production of prostaglandins, potent mediators of inflammation. Chronic inflammation plays an important role in the development and progression of colorectal cancer. Aspirin inhibits COX-2 activity and lowers the risk for colorectal adenomas and cancer. We investigated whether common genetic variation in COX-2 influenced risk for colorectal adenoma recurrence among 979 participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or aspirin and followed for 3 years for the occurrence of new adenomas. Of these participants, 44.2% developed at least one new adenoma during follow-up. Adjusted relative risks and 95% confidence intervals (95% CI) were calculated to test the association between genetic variation at six COX-2 single-nucleotide polymorphisms and adenoma occurrence and interaction with aspirin treatment. Two single-nucleotide polymorphisms were significantly associated with increased adenoma recurrence: for rs5277, homozygous carriers of the minor C allele had a 51% increased risk compared with GG homozygotes (relative risk, 1.51; 95% CI, 1.01-2.25), and for rs4648310, heterozygous carriers of the minor G allele had a 37% increased risk compared with AA homozygotes (relative risk, 1.37; 95% CI, 1.05-1.79). (There were no minor allele homozygotes.) In stratified analyses, there was suggestive evidence that rs4648319 modified the effect of aspirin. These results support the hypothesis that COX-2 plays a role in the etiology of colon cancer and may be a target for aspirin chemoprevention and warrant further investigation in other colorectal adenoma and cancer populations.(Cancer Epidemiol Biomarkers Prev 2009;18(10):2726–33)

Perspectives on colorectal cancer screening: a focus group study.

Objective  To assess attitudes and acceptability of Ontario consumers and doctors towards colorectal screening with faecal occult blood testing (FOBT) and colonoscopy.

The primary care physician role in cancer genetics: a qualitative study of patient experience

BACKGROUND Increased availability of genetic testing is changing the primary care role in cancer genetics. The perspective of primary care physicians (PCPs) regarding their role in support of genetic testing has been explored, but little is known about the expectations of patients or the PCP role once genetic test results are received. METHODS Two sets of open-ended semi-structured interviews were completed with patients (N=25) in a cancer genetic programme in Ontario, Canada, within 4 months of receiving genetic test results and 1 year later; written reports of test results were collected. RESULTS Patients expected PCPs to play a role in referral for genetic testing; they hoped that PCPs would have sufficient knowledge to appreciate familial risk and supportive attitudes towards genetic testing. Patients had more difficulty in identifying a PCP role following receipt of genetic test results; cancer patients in particular emphasized this as a role for cancer specialists. Still, some patients anticipated an ongoing PCP role comprising risk-appropriate surveillance or reassurance, especially as specialist care diminished. These expectations were complicated by occasional confusion regarding the ongoing care appropriate to genetic test results. CONCLUSIONS The potential PCP role in cancer genetics is quite broad. Patients expect PCPs to play a role in risk identification and genetics referral. In addition, some patients anticipated an ongoing role for their PCPs after receiving genetic test results. Sustained efforts will be needed to support PCPs in this expansive role if best use is to be made of investments in cancer genetic services.

The protective effect of γ-hydroxybutyrate in regional intestinal ischemia in the hamster

Abstract The purpose of this study was to determine whether γ-hydroxybutyrate provides protection against intestinal ischemia/reperfusion injury and to compare its effect with that of allopurinol and vitamin E. Thirty minutes of total regional ischemia, followed by 3 hours of reperfusion, produced intestinal damage that was completely prevented by γ-hydroxybutyrate pretreatment. Naloxone partially blocked this protective effect. Allopurinol provided only partial protection against this injury, whereas vitamin E provided none. Treatment with γ-hydroxybutyrate after ischemia but before reperfusion also provided significant protection. This study clearly demonstrates that γ-hydroxybutyrate provides significant protection against intestinal ischemic injury and that it may do so via an opiate receptor-mediated mechanism.

Self-management for people with inflammatory bowel disease

In North America and the United Kingdom, we are in the age of self-management. Many patients with chronic diseases are ready to participate in the therapeutic decision-making process, and join their physicians in a co-management model. It is particularly useful to consider this concept at a time when physician shortages and waiting times are on the front page every day, with no immediate prospect of relief. Conditions such as diabetes, asthma, chronic obstructive pulmonary disease, recurrent urinary tract infections and others lend themselves to this paradigm of medical care for the informed patient. The present paper reviews some of the literature on self-management for the patient with inflammatory bowel disease (IBD), and provides a framework for the use of self-management in the IBD population, with emphasis on the concept of a patient passport, and the use of e-mail, supported by an e-mail contract, as proposed by the Canadian Medical Protective Association. Examples of specific management strategies are provided for several different IBD scenarios. Eliminating the need for some office visits has clear environmental and economical benefits. Potential negative consequences of this form of patient care are also discussed.

The impact of magnetic resonance enterography and capsule endoscopy on the re-classification of disease in patients with known Crohn’s disease: A PROSPECTIVE ISRAELI IBD RESEARCH NUCLEUS (IIRN) STUDY

BACKGROUND AND AIMS The classification of Crohns disease (CD) is usually determined at initial diagnosis and is frequently based on ileocolonoscopic and cross-sectional imaging data. Advanced endoscopic and imaging techniques such as small-bowel video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) may provide additional data regarding disease extent and phenotype. Our aim was to examine whether VCE or MRE performed after the initial diagnosis may alter the original disease classification. METHODS Consecutive patients with known small-bowel CD in clinical remission or mild disease were prospectively recruited and underwent MRE and VCE (if small-bowel patency was confirmed by a patency capsule (PC). Montreal classifications before and after evaluation were compared. RESULTS Seventy-nine patients underwent MRE and VCE was performed in 56. Previously unrecognized disease locations were detected with VCE and MRE in 51 and 25%, respectively (p < 0.01) and by both modalities combined in 44 patients (55%). Twenty-two patients (27%) were reclassified as having an advanced phenotype (B2/B3). MRE and VCE reclassified the phenotype in 26 and 11% of cases, respectively (p < 0.05). Overall, both modalities combined altered the original Montreal classification in 49/76 patients (64%). CONCLUSION VCE and MRE may lead to reclassification of the original phenotype in a significant percentage of CD patients in remission. VCE was more sensitive for detection of previously unrecognized locations, while MRE was superior for detection of phenotype shift. The described changes in the disease classification may have an important impact on both clinical management and long-term prognosis in these patients.

Antagonistic Effects of Aspirin and Folic Acid on Inflammation Markers and Subsequent Risk of Recurrent Colorectal Adenomas

The Aspirin/Folate Polyp Prevention Trial found that aspirin, but not folic acid, reduced recurrence of colorectal adenomas. This study examined whether treatment effects on inflammation markers explained the trial results. The trial had a factorial design with three aspirin (placebo, 81, and 325 mg/d) and two folic acid (placebo and 1 mg/d) groups. There were 884 subjects who had colonoscopic evaluation for adenomas at year 3 and plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNF-R2), and IL-1 receptor antagonist (IL-1Ra) measured at baseline and year 3. Among individuals not receiving folic acid, there was a 4% decrease (mean ratio of year 3 to baseline levels = 0.96, 95% confidence interval [CI] = 0.82 to 1.14) in CRP for a period of 3 years in the 325 mg of aspirin group vs a 20% increase (mean ratio = 1.20, 95% CI = 1.03 to 1.41) in the placebo group (P = .027). By contrast, the reverse was observed among individuals who also received folic acid (P(interaction) = .013). Changes in inflammation markers were not associated with adenoma recurrence. Low-dose aspirin (325 mg/d) is beneficial in stabilizing CRP levels, which may be abrogated by folate. Nevertheless, inflammation markers do not mediate the chemopreventive effect of aspirin on colorectal adenomas.