Kenneth W. Schroeder

Small-bowel imaging in Crohn's disease: a prospective, blinded, 4-way comparison trial

BACKGROUND With the introduction of new techniques to image the small bowel, there remains uncertainty about their role for diagnosing Crohns disease. OBJECTIVE To assess the sensitivity and specificity of capsule endoscopy (CE), CT enterography (CTE), ileocolonoscopy, and small-bowel follow-through (SBFT) in the diagnosis of small bowel Crohns disease. METHODS Prospective, blinded trial. SETTING Inflammatory bowel disease clinic at an academic medical center. PATIENTS Known or suspected Crohns disease. Exclusion criteria included known abdominal abscess and non-steroidal anti-inflammatory drug (NSAID) use. Partial small-bowel obstruction (PSBO) at CTE excluded patients from subsequent CE. INTERVENTIONS Patients underwent all 4 tests over a 4-day period. MAIN OUTCOME MEASUREMENTS Sensitivity, specificity, and accuracy of each test to detect active small-bowel Crohns disease. The criterion standard was a consensus diagnosis based upon clinical presentation and all 4 studies. RESULTS Forty-one CTE examinations were performed. Seven patients (17%) had an asymptomatic PSBO. Forty patients underwent colonoscopy, 38 had SBFT studies, and 28 had CE examinations. Small-bowel Crohns disease was active in 51%, absent in 42%, inactive in 5%, and suspicious in 2% of patients. The sensitivity of CE for detecting active small-bowel Crohns disease was 83%, not significantly higher than CTE (83%), ileocolonoscopy (74%), or SBFT (65%). However, the specificity of CE (53%) was significantly lower than the other tests (P < .05). One patient developed a transient PSBO due to CE, but no patients had retained capsules. LIMITATION Use of a consensus clinical diagnosis as the criterion standard-but this is how Crohns disease is diagnosed in practice. CONCLUSIONS The sensitivity of CE for active small-bowel Crohns disease was not significantly different from CTE, ileocolonoscopy, or SBFT. However, lower specificity and the need for preceding small-bowel radiography (due to the high frequency of asymptomatic PSBO) may limit the utility of CE as a first-line test for Crohns disease.

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy. A prospective, randomized, double-blind clinical trial.

Study Objective. To determine if prophylactic use of cefazolin reduces peristomal wound infection associated with percutaneous endoscopic gastrostomy. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. Academic medical center, referral-based, gastroenterology service. Patients. One hundred thirty hospitalized patients, 23 of whom were excluded. Of the remaining 107 patients, 52 (group I) were already using antibiotics at the time of randomization for gastrostomy, whereas 55 (group II) were not. Interventions. Patients received either intravenous saline as a placebo or intravenous cefazolin (1 g) 30 minutes before gastrostomy. Measurements and Main Results. For 1 week after gastrostomy, the peristomal area was evaluated and a score assigned each day for erythema (0 to 4), induration (0 to 3), and exudate (0 to 4). A maximum combined score of 8 or more or the development of pus was a criterion for infection. None of the patients in group I developed a wound infection. Only 2 of 27 group II patients given prophylaxis developed a wound infection, compared with 9 of 28 patients not given prophylaxis, a difference of 25% (95% confidence interval, 4.8 to 44.6%; p less than 0.025). The number of patients who developed a wound infection was 0 of 52 in group I and 2 of 27 in group II patients who received cefazolin, a difference of 7.4% (95% confidence interval, -2.5 to 17.3%; p = 0.07). Conclusion. Cefazolin prophylaxis significantly reduces the risk for peristomal wound infection associated with percutaneous endoscopic gastrostomy. It is needed, however, only for patients not already receiving antibiotic treatment at the time of gastrostomy.

Dysplasia in chronic ulcerative colitis: Implications for colonoscopic surveillance

Mucosal dysplasia has been used as a marker for patients with chronic ulcerative colitis considered to be most at risk of developing cancer, and its identification is the basis for colonoscopic surveillance programs. To evaluate the reliability of this premise, colectomy specimens from two groups of patients who had undergone surgery for chronic ulcerative colitis (50 with cancer and 50 without) were retrieved. The groups were matched by age, sex, duration of disease, disease extent, and symptoms at the time of surgery. Using a standard technique of multiple random biopsies, we utilized the standard colonoscopic biopsy forceps to obtain four biopsies from mucosa that was not macroscopically suspicious for dysplasia or cancer in eight defined regions in each of the 100 colon specimens. This technique mimicked exactly the methods used in our clinical surveillance program. All 3,200 biopsies were evaluated blindly by one pathologist for presence and grade of dysplasia. Twenty-six percent of colons with an established cancer harbored no dysplasia inanybiopsy from any region in the colon. While an overall association between the presence of cancer and high-grade dysplasia was detected (relative risk = 900; 95 percent CI of 2.73-29.67), the sensitivity and specificity of random colonic biopsies to detect concomitant carcinoma were 0.74 and 0.74, respectively. These findings prompt concern that reliance on random biopsies, obtained during colonoscopic surveillance, may be misplaced.

A randomized, double-blind, placebo-controlled trial of the oral mesalamine (5-ASA) preparation, Asacol, in the treatment of symptomatic Crohn's colitis and ileocolitis

Oral mesalamine (Asacol) in a dose of 3.2 g/day was administered in a 16-week placebo-controlled trial in 38 patients for the treatment of mildly to moderately active Crohns colitis or ileocolitis. Eighteen patients continued a stable dose of prednisone of no more than 20 mg/day and 20 patients did not take prednisone. Changes in the Crohns Disease Activity Index (CDAI) were used as the primary measure of efficacy. Oral mesalamine was effective in achieving partial or complete remission in 60% of patients as compared with 22% of placebo-treated patients. However, only 20 of 38 patients completed the 17-week study. The others withdrew early because of worsening of symptoms or were dropouts counted as failures. The high percentage of early withdrawals prevented comparison of mean 17-week CDAI scores. Although the number of patients in this study was relatively small, Asacol 3.2 g/day appears to be safe and effective treatment for mildly to moderately active Crohns colitis and ileocolitis as compared with placebo, and this regimen is an option for treatment of patients who fail or are intolerant of sulfasalazine.

A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis

BACKGROUND/AIMS Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration. The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed. METHODS Steroid and mesalamine enemas were withdrawn before the study. Forty patients were assigned to 1 of 4 strata: no concomitant therapy, oral steroids, oral salicylates, or oral steroids and salicylates. After stratification, patients were randomized to nightly treatment with 350 mg cyclosporine (n = 20) or placebo (n = 20) enemas. Clinical response was determined at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Trough blood cyclosporine levels were measured by high-performance liquid chromatography. RESULTS At 4 weeks, 8 of 20 patients (40%) who received cyclosporine showed clinical improvement compared with 9 of 20 patients (45%) who received placebo. One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine, and another patient receiving cyclosporine was unable to tolerate the enema vehicle. No other toxicity was noted during the trial. Blood cyclosporine levels were detectable in only two patients. CONCLUSIONS Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left-sided ulcerative colitis.

Collagenous Colitis: A Clinicopathologic Correlation

Collagenous colitis is an unusual cause of chronic, watery diarrhea. To characterize this disease, we reviewed biopsy specimens and the clinical records of 17 patients (9 women and 8 men) with this diagnosis. Intermittent diarrhea with symptom-free intervals lasting years was found in 7 of the 17 patients. Two patients had incapacitating arthralgias, and nine had a mild weight loss. Collagen deposition beneath the surface epithelium formed a continuous layer in 11 but was discontinuous in 5 of the 16 patients who had undergone rectal or colonic biopsies at our institution. The thickness of the collagen band was variable (maximum, 93 microns). The symptoms of the patients did not correlate with the thickness of the collagen layer. Variability in collagen thickness may be related to disease phase and increases the need to obtain multiple biopsy specimens from the sigmoid colon and rectum. The optimal treatment for collagenous colitis is difficult to determine because three of six patients treated only symptomatically in our study had resolution of their diarrhea.

Acute gastrointestinal bleeding: Experience of a specialized management team

The initial experience of a specialized management team organized to provide expedient care for all acute major gastrointestinal bleeding in protocolized fashion at a large referral center is presented. Of the 417 patients, 56% developed bleeding while hospitalized. Upper gastrointestinal bleeding accounted for 82%. The five most common etiologies included gastric ulcers (83 patients), duodenal ulcers (67 patients), erosions (41 patients), varices (35 patients), and diverticulosis (29 patients). Nonsteroidal anti-inflammatory drugs were implicated in 53% of gastroduodenal ulcers. The incidence of nonbleeding visible vessels was 42% in gastric and 54% in duodenal ulcers. The rates of rebleeding were 24% (20 patients) in gastric ulcers and 28% (19 patients) in duodenal ulcers. Predictive factors for rebleeding included copious bright red blood, active arterial streaming, spurting, or a densely adherent clot. The rebleeding rate for esophagogastric varices was 57%. The mortality rate overall was 6% (27 patients), with rates varying from 3% (five patients) for gastroduodenal ulcers to 40% (14 patients) for esophagogastric varices. The morbidity rate for the entire patient population was 18% (77 patients), dominated by myocardial events (34 patients). The average length of hospitalization for gastroduodenal ulcers was 5 days, for diverticulosis 8 days, and for varices 10 days. The major efforts of a specialized Gastrointestinal Bleeding Team would be best directed at both reducing the morbidity associated with acute bleeding and reducing the overall cost of care.

Validation of the Ulcerative Colitis Colonoscopic Index of Severity and Its Correlation With Disease Activity Measures

BACKGROUND & AIMS Endoscopic healing is likely to become an important goal for treatment of patients with ulcerative colitis (UC). A simple validated endoscopic index is needed. We validated the previously developed UC Colonoscopic Index of Severity (UCCIS). METHODS In a prospective study, 50 patients with UC were examined by colonoscopy; we analyzed videos of rectum and sigmoid, descending, transverse, and cecum/ascending colon. Eight gastroenterologists blindly rated 4 mucosal lesions (for vascular pattern, granularity, friability, ulceration) and severity of damage to each segment and overall. The global assessment of endoscopic severity (GAES) was based on a 4-point scale and 10-cm visual analogue scale. Correlation of the UCCIS score with clinical indexes (clinical activity index and simple clinical colitis activity index), patient-defined remission, and laboratory measures of disease activity (levels of C-reactive protein, albumin, and hemoglobin and platelet counts) were estimated by using the Pearson (r) or Spearman (r(s)) method. RESULTS Interobserver agreement was good to excellent for the 4 mucosal lesions evaluated by endoscopy and the GAES. The UCCIS calculated for our data accounted for 74% (R(2) = 0.74) and 80% (R(2) = 0.80) of the variation in the GAES and visual analogue scores, respectively (P < .0001). The UCCIS also correlated with clinical activity index (r = 0.52, P < .001), simple clinical colitis activity index (r = 0.62, P < .0001), and patient-defined remission (r = 0.43, P < .01). The UCCIS also correlated with levels of C-reactive protein (r(s) = 0.56, P < .001), albumin (r = -0.55, P < .001), and hemoglobin (r = -0.39, P < .01). A rederivation of the equation for the UCCIS by using the data from a previous study combined with those of the current study (n = 101) yielded similar results. CONCLUSIONS The UCCIS is a simple tool that provides reproducible results in endoscopic scoring of patients with UC.

Benefit of computed tomography enterography in Crohn's disease: Effects on patient management and physician level of confidence

Background: Computed tomographic enterography (CTE) has been shown to have a high sensitivity and specificity for active small bowel inflammation. There are only sparse data on the effect of CTE results on Crohns disease (CD) patient care. Methods: We prospectively assessed 273 patients with established or suspected CD undergoing a clinically indicated CTE. Providers were asked to complete pre‐ and postimaging questionnaires regarding proposed clinical management plans and physician level of confidence (LOC) for the presence or absence of active small bowel disease, fistula(s), abscess(es), or stricturing disease. Correlative clinical, serologic, and histologic data were recorded. Following revelation of CTE results, providers were questioned if CTE altered their management plans, and whether LOC changes were due to CTE findings (on a 5‐point scale). Results: CTE altered management plans in 139 cases (51%). CTE changed management in 70 (48%) of those with established disease, prompting medication changes in 35 (24%). Management changes were made post‐CTE in 69 (54%) of those with suspected CD, predominantly due to excluding CD (36%). CTE‐perceived changes in management were independent of clinical, serologic, and histologic findings (P < 0.0001). Clinically meaningful LOC changes (2 or more points) were observed in 212 (78%). Conclusions: CTE is a clinically useful examination, altering management plans in nearly half of patients with CD, while increasing physician LOC for the detection of small bowel inflammation and penetrating disease. These findings further support the use of CTE in CD management algorithms. (Inflamm Bowel Dis 2011;)

Treatment of Benign Esophageal Stricture by Eder-Puestow or Balloon Dilators: A Comparison Between Randomized and Prospective Nonrandomized Trials

To determine whether the natural history of strictures is affected by the type of dilator used to treat newly diagnosed peptic strictures, we designed a prospective randomized trial to compare the results after Eder-Puestow or Medi-Tech balloon dilation. We entered 31 patients into the trial. We also prospectively followed up all 92 nonrandomized patients who underwent their first dilation for a benign stricture during the same period as the prospective randomized trial. The nonrandomized patients also underwent dilation with either the Eder-Puestow or the balloon technique at the discretion of the gastroenterologist performing the endoscopy. We found no statistically significant differences in the immediate or long-term results of the two methods among the randomized, nonrandomized, and overall combined groups. All but 1 of the 123 patients had immediate relief of dysphagia. Within each group of patients, the probability of remaining free of dysphagia 1 year after the initial dilation was approximately 20%, and the probability of not requiring a second dilation was approximately 65% with either technique. Major (esophageal rupture) and minor (bleeding or chest pain) complications occurred in 1% and 5% of the patients and 0.4% and 3% of the total dilation procedures, respectively. The esophageal rupture and four of six minor complications occurred after repeated dilations. Five of the six minor complications occurred with use of the Eder-Puestow dilators. We conclude that Eder-Puestow and balloon dilations of benign esophageal strictures are associated with similar outcomes, but repeated dilations and the Eder-Puestow technique may be associated with an increased risk of complications.