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Biomedical subjects

Bret A Lashner

Publications and source records attributed to Bret A Lashner.

At least 19 recordsLinked to original sources

Risk factors for anemia in patients with ileal pouch-anal anastomosis.

PURPOSE: Anemia is frequently observed in patients with ileal pouch-anal anastomosis. The identification of the underlying causes can be challenging. This study was designed to define the prevalence and to identify etiologic factors for anemia in this patient population. METHODS: A prospectively maintained database and medical records of patients who had restorative proctocolectomy between 1998 and 2005 were reviewed. All patients with laboratory evaluation at least six months after the surgery were studied. The last reported hemoglobin served as the index value. All patients with anemia (hemoglobin < 13.5 g/dl for males, <12 g/dl for females) were identified. A second group of randomly selected, ileal-pouch patients with normal hemoglobin served as control. Demographic and clinical variables were evaluated. RESULTS: A total of 389 patients (214 males) had documented hemoglobin values. Sixty-seven patients (17 percent; 40 males) had anemia. The prevalence of anemia was 19 and 15 percent in males and females, respectively. The prevalence was 17 percent among patients with underlying ulcerative colitis vs. 26 percent in patients with familial adenomatous polyposis (P = 0.27). The mean hemoglobin in the anemia group was 11.4 (median, 11.7) g/dl. One patient (2 percent) had severe (<7 g/dl), 11 (16 percent) had moderate (7-9.9 g/dl), and 55 (82 percent) had mild (> or =10 g/dl) anemia. One patient (2 percent) had macrocytic, 16 (24 percent) had microcytic, and 49 (74 percent) had normocytic anemia. Sixteen patients (24 percent) had unidentified causes for anemia. Multivariable analysis showed that the presence of malignancy or desmoid tumor and the J-pouch configuration were the only independent risk factors associated with anemia. CONCLUSIONS: Anemia is common in ileal-pouch patients. Malignancy or desmoid tumor and J-pouch configuration are independent risk factors for anemia. One-fourth of the patients with anemia have unclear etiology.

Anemia↗

Risk factors for diseases of ileal pouch-anal anastomosis after restorative proctocolectomy for ulcerative colitis.

BACKGROUND & AIMS: Although pouchitis is considered the most common adverse sequela of ileal pouch-anal anastomosis (IPAA), inflammatory and noninflammatory conditions other than pouchitis are increasingly being recognized. The risk factors for these non-pouchitis conditions, including Crohn's disease (CD) of the pouch, cuffitis, and irritable pouch syndrome (IPS), have not been studied. The aim of this study was to assess risk factors for inflammatory and noninflammatory diseases of IPAA in a tertiary care setting. METHODS: The study consisted of 240 consecutive patients who were classified as having healthy pouches (N = 49), pouchitis (N = 61), CD of the pouch (N = 39), cuffitis (N = 41), or IPS (N =50). Demographic and clinical features were assessed to determine risk factors for each of these conditions by using logistic regression analysis. RESULTS: Risk factors remaining in the final logistic regression models were for pouchitis: IPAA indication for dysplasia (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.69-8.98), never having smoked (OR, 5.09; 95% CI, 1.01-25.69), no use of anti-anxiety agents (OR, 5.19; 95% CI, 1.45-18.59), or use of NSAIDs (OR, 3.24; 95% CI, 1.71-6.13); for CD of the pouch: a long duration of IPAA (OR, 1.20; 95% CI, 1.12-1.30) and current smoking (OR, 4.77; 95% CI, 1.39-16.25); for cuffitis: arthralgias (OR, 4.13; 95% CI, 1.91-8.94) and younger age (OR, 1.16; 95% CI, 1.01-1.33); and for IPS: use of antidepressants (OR, 4.17, 95% CI, 1.95-8.92) or anti-anxiety agents (OR, 3.21; 95% CI, 1.34-7.47). CONCLUSIONS: The majority of risk factors for the 4 inflammatory and noninflammatory conditions of IPAA are different, suggesting that each of these diseases has a different etiology and pathogenesis. The identification and modification of these risk factors might help patients and clinicians to make a preoperative decision for IPAA, reduce IPAA-related morbidity, and improve response to treatment.

Adult↗

Sensitivity-specificity trade-off for capsule endoscopy in IBD: is it worth it?

There are a growing number of reports comparing wireless capsule endoscopy (CE) to other diagnostic tests for use in patients with Crohn's disease. A meta-analysis of these studies in this issue of the Journal showed that the "diagnostic yield" of detecting lesions suggestive of active Crohn's disease is much higher with CE compared to other tests. Routine use of CE in Crohn's disease will increase true-positive testing, but also will increase the number of false-positive tests. Since the penalty of false-positive testing is very high (unnecessary use of toxic and expensive medications, and the stigma of being diagnosed with a serious chronic disease), CE should be used only in limited clinical situations. In particular, CE may be helpful in Crohn's disease patients without a stricture whose physician needs an added measure of certainty that active disease is present.

Capsules↗

True or false? The hygiene hypothesis for Crohn's disease.

The "hygiene hypothesis" for Crohn's disease postulates that multiple childhood exposures to enteric pathogens protect an individual from developing Crohn's disease later in life, while individuals raised in a more sanitary environment are more likely to develop Crohn's disease. In this issue of the American Journal of Gastroenterology, two Canadian case-control studies come to diametrically opposed conclusions regarding the hygiene hypothesis for Crohn's disease. This difference may be partially related to differences in study population (population based vs hospital based), age of onset, different genetic determinants, urban/rural residence (40% rural vs principally urban), or different exposures from the putative causative agent. As of now, the veracity of the hygiene hypothesis for Crohn's disease is not confirmed.

Crohn Disease↗

Pouchitis: a spectrum of diseases.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for ulcerative colitis and familial adenomatous polyposis patients who require surgery. Pouchitis is the most common long-term complication after IPAA. Patients with pouchitis represent a heterogeneous group in terms of pathogenesis, clinical presentation, disease course, and prognosis, suggesting a wide range of disease mechanisms. Before the diagnosis of pouchitis is made, other inflammatory and non-inflammatory disease conditions, such as Crohn's disease, cuffitis, and irritable pouch syndrome, should be ruled out. Pouch endoscopy is the most important tool for diagnosis and differential diagnosis. Accurate diagnosis and classification are essential for appropriate management. Although the majority of patients with pouchitis respond to antibiotic therapy, a subset of these patients cannot achieve remission by means of antibiotics and thus require anti-inflammatory or immunosuppressive treatment.

Clinical Trials as Topic↗

An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial.

BACKGROUND & AIMS: N-3 fatty acids from fish oil, antioxidants, and short-chain fatty acids (SCFAs) produced during the fermentation of soluble fiber may attenuate inflammation associated with ulcerative colitis (UC). We assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil, fructooligosaccharides, gum arabic, vitamin E, vitamin C, and selenium on disease activity and medication use in adults with mild to moderate UC. METHODS: A total of 121 patients with UC and a disease activity index (DAI) from 3-9 on a 12-point scale were block randomized for extent of disease and smoking status. In addition to their usual diet, patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for 6 months. Clinical and histologic responses were assessed at 3 and 6 months or at the final visit. A change in average prednisone use between groups was tested by using a linear mixed-effects model. RESULTS: Eighty-six patients completed the study. Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group (7.3 +/- 1.3; n = 36) compared with the placebo group (6.2 +/- 2.0; n = 50) ( P < .05). Both groups showed significant and similar degree of improvement at 6 months in DAI (-2.5 for oral supplement and -2.8 for placebo) and histologic index (-1.9 for oral supplement vs. -2.0 for placebo). Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over 6 months as compared with the placebo group ( P < .001). CONCLUSIONS: The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with UC.

Administration, Oral↗

Clinical approach to diseases of ileal pouch-anal anastomosis.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for ulcerative colitis (UC) patients with medically refractory disease or dysplasia. IPAA significantly improves quality of life in UC patients who require surgery. However, certain inflammatory and noninflammatory diseases can develop after the surgery, including pouchitis, Crohn's disease of the pouch, cuffitis, and irritable pouch syndrome. The etiology and pathogenesis of these disease conditions of IPAA are largely unknown. Accurate diagnosis and classification are important for appropriate management. Endoscopic evaluation is the most important tool for the diagnosis and differential diagnosis.

Adrenal Cortex Hormones↗

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↗

Infliximab maintenance therapy for fistulizing Crohn's disease.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

Adult↗

Left-sided ulcerative colitis.

Left-sided ulcerative colitis is not a distinct entity, but a less extensive form of pancolitis. The epidemiologic and genetic characteristics are thought to be analogous. The rate of colorectal cancer, however, seems to be proportional to the extent of disease. Primary treatment for left-sided disease is topical 5-aminosalicyclic acid (5ASA) agents. In patients who do not respond to topical therapy, oral 5ASA agents of differing delivery methods to the distal bowel can be used. There is much debate pertaining to the clinical superiority of the oral 5ASA agents.

Administration, Cutaneous↗

Ex vivo histology-correlated optical coherence tomography in the detection of transmural inflammation in Crohn's disease.

BACKGROUND AND AIMS: Distinguishing Crohn's disease (CD) from ulcerative colitis (UC) can be difficult. Transmural inflammation, a key feature of CD, cannot be assessed by conventional colonoscopy with biopsy. Optical coherence tomography (OCT) provides high-resolution, cross-sectional images of the gut wall and might become a new diagnostic tool. The aims of this study were to perform histology-correlated OCT on surgical specimens of CD and UC and to determine its diagnostic accuracy. METHODS: Colectomy specimens from patients with a preoperative diagnosis of CD (N = 24) or UC (N = 24) were studied with OCT in the operating room. OCT and histopathology were assessed blindly, and diagnostic accuracy of OCT was assessed. RESULTS: Eight preoperatively identified UC patients (33%) with transmural inflammation on postoperative histology were diagnosed with CD, and all 8 had a disrupted layered structure on OCT, a characteristic feature of transmural disease. Sixteen UC patients (67%) had superficial inflammation on histology; of them, 13 (81%) had an intact layered structure on OCT. All 24 preoperative CD patients had transmural inflammation on histology, and 23 (96%) had a disrupted layered structure on OCT. Of 585 histology-OCT image sets from the 48 patients, 152 sets (26%) had transmural inflammation on histology. The sensitivity and specificity for OCT to detect transmural disease were 86% and 91%, respectively. CONCLUSIONS: Transmural inflammation, as characterized by disruption of the layered structure of colon wall on OCT, is an accurate marker for the diagnosis of CD. Ex vivo OCT predicted transmural inflammation on postoperative histopathology.

Adult↗

In vivo colonoscopic optical coherence tomography for transmural inflammation in inflammatory bowel disease.

BACKGROUND & AIMS: Transmural inflammation, a distinguishing feature of Crohn's disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. METHODS: OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. RESULTS: Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The kappa coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). CONCLUSIONS: In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC.

Adult↗

Fecal lactoferrin for diagnosis of symptomatic patients with ileal pouch-anal anastomosis.

BACKGROUND & AIMS: Increased stool frequency, urgency, and abdominal pain in patients with ileal pouch-anal anastomosis (IPAA) may be due to inflammatory conditions, including pouchitis, cuffitis, or Crohn's disease or noninflammatory conditions such as irritable pouch syndrome. Distinction among these entities requires pouch endoscopy and biopsy. Noninvasive means of diagnosis are preferable. METHODS: Sixty consecutive subjects with IPAA for inflammatory bowel disease had measurements of fecal lactoferrin and alpha1-antitrypsin and underwent pouch endoscopy with biopsy, with calculation of the pouchitis disease activity index in a prospective cross-sectional study. RESULTS: Symptomatic patients with an inflammatory condition had significantly higher fecal lactoferrin concentrations (median, 176.0 microg/mL, interquartile range [IQR] 79.0-450.8) compared with those with a noninflammatory condition (median, 4.8 microg/mL; IQR, 1.2-11.0) or those who were asymptomatic (median, 7.8 microg/mL; IQR, 1.4-12.9), P < 0.001. At a cutoff level of 7 microg/mL, fecal lactoferrin could distinguish patients with irritable pouch syndrome from those with pouchitis, cuffitis, or Crohn's disease with a sensitivity of 100% and specificity of 85%. Fecal alpha1-antitrypsin was not able to distinguish symptomatic patients with and without an inflammatory condition. CONCLUSIONS: Fecal lactoferrin can serve as a sensitive and noninvasive initial screening test in an algorithm for evaluation of symptomatic patients with IPAA. If fecal lactoferrin levels are low (<7 microg/mL), IPS can be diagnosed. If fecal lactoferrin levels are high, pouch endoscopy with biopsy is warranted to distinguish among different causes of inflammation. Longitudinal studies are needed to define better the role of this test in the management of patients with IPAA.

Adult↗

Afferent limb ulcers predict Crohn's disease in patients with ileal pouch-anal anastomosis.

BACKGROUND & AIMS: Some patients who undergo ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC) or indeterminate colitis are subsequently diagnosed with Crohn's disease (CD). Making the diagnosis of CD in patients with IPAA can be difficult, but it is important for prognostic and therapeutic purposes. The aim of this study was to identify diagnostic features of CD in patients with IPAA. METHODS: We evaluated 87 patients who had undergone IPAA for inflammatory bowel disease. Patients were classified as having UC (n = 28), CD (n = 27), or indeterminate colitis (n = 32) based on review of the original colectomy pathology and the postoperative clinical course. Each patient underwent a pouch endoscopy with biopsies of the pouch and afferent limb. Both the endoscopist and pathologist were blinded to the patient's diagnosis. RESULTS: Afferent limb ulcers (ALUs) were seen on endoscopy in 12 of 27 patients with CD (45%) and 4 of 28 patients with UC (14%) (P = 0.019). After excluding patients who had taken nonsteroidal anti-inflammatory drugs (NSAIDs) within the past month, ALUs were found in 7 of 18 patients with CD (39%) and 0 of 17 patients with UC (P = 0.010). Controlling for NSAID use and smoking, the odds ratio for ALUs indicating CD was 4.67 (P = 0.03). In the UC population, ALUs were seen in 4 of 11 patients (36%) who had taken NSAIDs in the past month and 0 of 17 patients who had not taken NSAIDs (P = 0.016). CONCLUSIONS: ALUs seen on endoscopy are suggestive of CD in patients with inflammatory bowel disease who are not taking NSAIDs.

Adult↗

Type of fistula determines response to infliximab in patients with fistulous Crohn's disease.

OBJECTIVES: Infliximab has been shown to be efficacious for treating perianal fistulae in patients with Crohn's disease. There is limited information regarding response to infliximab in patients with other types of fistulae. METHODS: Sixty consecutive patients with fistulous Crohn's disease and at least three months of follow-up after three infliximab infusions were evaluated. Patients with enteroenteric fistulae were excluded. Complete response was defined as complete closure of the fistulae or complete cessation of fistula drainage. RESULTS: Thirty-five patients had external fistulae, 16 had internal fistulae, and 9 had mixed (both external and internal) fistulae. Complete response rates were significantly higher in patients with external fistulae (69%) compared to those with internal fistulae (13%); p= 0.001, or those with mixed fistulae (11%); p= 0.01. In the external fistula group, patients with perianal fistulae had a higher rate of complete response (78%) compared to those with abdominal wall fistulae (38%); p= 0.04. The rate of complete response to infliximab was significantly lower among 14 patients with rectovaginal fistulae (14%) compared to those with perianal fistulae (78%); p= 0.0007. In the mixed fistula group only 11% of the patients achieved complete response. This is significantly lower than the rate observed for patients with perianal fistulae (78%); p= 0.004. The Cox proportional hazards model showed that the hazard of relapse for smokers who achieved complete response was nearly twice that of nonsmokers; however, this difference did not reach statistical significance. CONCLUSION: There is an association between type of fistulae and complete response to infliximab in patients with fistulous Crohn's disease. External fistulae in general and perianal fistulae in particular have a higher rate of closure in response to infliximab compared to other types of fistulae.

Adolescent↗

Treatment of rectal cuff inflammation (cuffitis) in patients with ulcerative colitis following restorative proctocolectomy and ileal pouch-anal anastomosis.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice in the majority of patients with ulcerative colitis (UC) who require surgery. To ease the construction of the IPAA and improve functional outcome by minimizing sphincter related stretch injury, a stapling technique is being commonly used in the pouch-anal anastomosis. Despite its advantages, the procedure normally leaves a 1-2 cm of anal transitional zone or rectal cuff, which is susceptible to recurrence of residual UC or cuffitis. Cuffitis can cause symptoms mimicking pouchitis. AIM: To conduct an open-labeled trial of topical mesalamine in patients with cuffitis. METHODS: We treated 14 consecutive patients with cuffitis by giving mesalamine suppositories 500 mg b.i.d. (mean 3.2 months, range 1-9 months). The Cuffitis Activity Index (adapted from the Pouchitis Disease Activity Index) scores and improvement in symptoms of bloody bowel movements and arthralgias were measured as primary and secondary outcomes. RESULTS: All patients had surgery for medically refractory UC. There were significant reductions in the total Cuffitis Activity Index scores after the therapy (11.93 +/- 3.17 vs 6.21 +/- 3.19, p < 0.001). Symptom (3.24 +/- 1.28 vs 1.79 +/- 1.31), endoscopy (3.14 +/- 1.29 vs 1.00 +/- 1.52), and histology (4.93 +/- 1.77 vs 3.57 +/- 1.39) scores each were significantly reduced (p < 0.05). Ninety-two percent of patients with bloody bowel movements and 70% of patients with arthralgias improved after the therapy. No systemic or topical adverse effects were reported. CONCLUSION: Topical mesalamine appears well tolerated and effective in treating patients with cuffitis, with improvement in symptom as well as endoscopic and histologic inflammation.

Adult↗