Epidermal growth factor for ulcerative colitis.
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Administration, Oral↗
Biomedical subjects
Richard J Farrell
Publications and source records attributed to Richard J Farrell.
Colorectal neoplasms: role of intravenous contrast-enhanced CT colonography.
PURPOSE: To evaluate whether computed tomographic (CT) colonography with intravenously administered contrast material can help predict malignant differentiation of colorectal neoplasms (> or =10 mm in diameter). MATERIALS AND METHODS: Enhancement of 29 consecutive colorectal neoplasms on pre- and postcontrast CT colonographic images was retrospectively measured. The neoplasms were subsequently resected. Enhancement was calculated by subtraction of attenuation values (in Hounsfield units) obtained with precontrast and postcontrast 45-second-delay prone CT colonographic sequences. The neoplasms were graded as follows: grade 1, adenoma; grade 2, adenoma with high-grade dysplasia; grade 3, well-differentiated adenocarcinoma; grade 4, moderately differentiated adenocarcinoma; and grade 5, poorly differentiated adenocarcinoma. Correlation among size, histologic grade, and degree of enhancement was made with Pearson and Spearman coefficients. The ability of the degree of enhancement to help predict adenocarcinoma (histologic grade, > or =3) was calculated. RESULTS: Histologic-CT colonographic correlation was performed in 29 neoplasms (mean diameter, 27.9 mm; range, 10-65 mm). There was no correlation between size and degree of enhancement, size and histologic grade (R = -0.17, P =.33), or histologic grade and degree of enhancement (R = 0.23, P =.23). However, increasing enhancement was noted between grades 2 and 5. When an enhancement threshold of 40 HU was used for the diagnosis of adenocarcinoma (grades 3-5), sensitivity was 92%, specificity was 20%, positive predictive value was 50%, and negative predictive value was 75%. CONCLUSION: The degree of contrast enhancement on a 45-second-delay CT colonographic image does not correlate with size or degree of histologic differentiation, although increasing enhancement with lesser degrees of differentiation was noted.
Adenocarcinoma↗
Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.
BACKGROUND & AIMS: We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI. METHODS: Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat. RESULTS: Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06. CONCLUSIONS: Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions.
Adult↗
Ulcerative colitis.
Ulcerative colitis is a chronic inflammatory disease of the rectum and colon. Results from many studies in people and animals of intestinal inflammation suggest that ulcerative colitis results from environmental factors triggering a loss of tolerance for normal intestinal flora in genetically susceptible individuals. Although progress has been made in the overall management of the disease, no innovative treatment has been developed. By contrast with Crohn's disease, there are few clinical data on biological agents. Probiotics seem the most promising of several experimental and traditional agents that have been investigated in controlled clinical trials.
Colitis, Ulcerative↗
CT colonography: colonic distention improved by dual positioning but not intravenous glucagon.
The aim of this study was to determine whether intravenous (IV) glucagon and dual positioning administered prior to CT colonography enhances colonic distention. We assessed the effect of dual positioning and IV glucagon on colonic distention in 96 patients who underwent CT colonography examinations. The CT colonography was performed in both supine and prone positions. Seventy-four patients received glucagon (1 mg i.v.) immediately prior to CT scanning and 22 patients did not. The bowel was divided into ten segments and colonic distention was scored by two radiologists in the supine, prone, and combined supine/prone positions using a five-point scale: 1=collapsed; 2=poorly visualized; > or = 3=adequate distention; 4=entire segment visualized and well distended; 5=excellent distention). A combined segmental and overall supine/prone distention score was calculated based on the sum of the mean score for each position. There was no significant difference in the degree of colonic distention between patients who received glucagon and those who did not [supine/prone distention score (mean +/- SE): 3.63 +/- 0.2 vs 3.85 +/- 0.2; p=n.s.]. The degree of colonic distention was greater in the prone position in both the glucagon (3.87 +/- 0.2 vs 3.38 +/- 0.2; p<0.05) and non-glucagon groups (4.01 +/- 0.2 vs 3.69 +/- 0.2; p=N.S.) particularly in the proximal colon. There was almost perfect agreement between both radiologists in their scoring of colonic distention on a per-patient basis ( k=0.9; p<0.001). Of 1480 bowel segments, 1261 (85.2%) were adequately distended in the glucagon group compared with 370 of 440 bowel segments (84%) in the non-glucagon group ( p=n.s.) Colonic distention at CT colonography is improved by dual positioning but not by the administration of intravenous glucagon. While our results suggest that other smooth muscle relaxants, including butyl scopolamine, may only have a limited role in improving colonic distention in CT colonography, further studies are required.
Adult↗
Microbial factors in inflammatory bowel disease.
An unsolved puzzle in IBD research is whether germs, genes, or a combination of the two with excessive immune responses to gut-associated bacteria explains the pathogenesis of UC and CD. Whatever the answer, there is little doubt that microbial factors are involved intimately in IBD pathogenesis. Although a long search has failed to confirm a direct pathogenic role for a specific infectious agent, compelling evidence suggests that commensal enteric bacteria and their products provide a local environmental trigger that initiates and perpetuates IBD, reactivates quiescent disease, results in the frequent septic complications of CD, and contributes to the development of several extraintesinal manifestations. The most compelling evidence for involvement of the enteric flora in the pathogenesis of IBD has been generated from studies of animal models, which collectively support the view that IBD is due to genetically determined dysregulation of the mucosal immune response to luminal antigens derived from the normal bacterial flora. Although removing or dampening the dominant antigenic stimuli with antibiotics or probiotics is conceptually superior to the current array of immunosuppressive and anti-inflammatory agents that nonspecifically block the inflammatory cascade, more definitive, rigorously designed, controlled trials of treatments directed at the microflora are needed. Future research investigating mechanisms of tolerance to luminal bacteria and an understanding of how probiotics can manipulate the intestinal flora beneficially will bring clinicians closer to identifying potential therapeutic targets and unraveling the bacterial connection to IBD pathogenesis.
Humans↗
Intraductal US is a useful adjunct to ERCP for distinguishing malignant from benign biliary strictures.
BACKGROUND: Distinguishing malignant from benign biliary strictures remains a challenge. This prospective study assessed intraductal US as an adjunct to endoscopic retrograde cholangiography and tissue sampling for diagnosis of malignant and benign biliary strictures. METHODS: Sixty-two patients were enrolled who had biliary strictures suspected to be malignant but with negative tissue sampling by endoscopic retrograde cholangiography, or suspected biliary strictures based on clinical manifestations and/or cross-sectional imaging. Intraductal US was performed with an over-the-wire 2.4-mm diameter 20 MHz catheter US probe. The diagnostic accuracy of endoscopic retrograde cholangiography plus tissue sampling with and without intraductal US was compared with surgical findings or clinical outcome at a 12-month follow-up (benign/malignant) in nonsurgical cases. Tissue sampling results were reported as malignant, suspicious for malignancy, atypical, or normal. Analysis was by intention-to-treat. RESULTS: Two patients (3%) were excluded from analysis because the stricture could not be traversed with the intraductal US probe. Of the 60 remaining patients (37 men, mean age 64 years, range 27-89 years), 31 had malignant strictures (12 cholangiocarcinoma, 8 pancreatic, 5 metastatic, 3 gallbladder, 3 papilla), and 29 had benign strictures. Sphincterotomy was not required in any case to facilitate intraductal US. Fourteen patients (23%) underwent subsequent surgery including 11 with a preoperative diagnosis of resectable tumor. Endoscopic retrograde cholangiography/tissue sampling (atypia considered equivalent to benign) correctly identified 15 of 31 malignant strictures (p = 0.001) and all 29 benign strictures (p = 0.16) (accuracy 73%, sensitivity 48%, specificity 100%). The addition of intraductal US correctly identified 28 of 31 malignant strictures and 27 of 29 benign strictures (accuracy 92%, sensitivity 90%, specificity 93%). Of 11 patients with tumors who came to surgery, intraductal US correctly staged 4 (36%), understaged 5 (45%), missing metastatic lymph nodes in all cases and vascular invasion in 1 patient, and overstaged 2 (18%), with a false-positive diagnosis of metastatic lymph nodes in 1 and tumor mass in 1 patient who had no cancer at surgery. CONCLUSION: Technically easy, intraductal US is a valuable adjunct to endoscopic retrograde cholangiography/tissue sampling that increases the ability to distinguish malignant from benign strictures. Intraductal US is unsuitable for assessing lymph nodes associated with malignant strictures.
Adult↗
Crohn's disease: not all anti-TNFs are the same!
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Comment↗
Equimolar doses of balsalazide and mesalamine: are we comparing apples and oranges?
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Aminosalicylic Acids↗