Double-balloon enteroscopy in Crohn's disease: findings and impact on management in a multicenter retrospective study.

BACKGROUND: Double-balloon enteroscopy (DBE) is effective in visualizing the small bowel to perform biopsy sampling and interventions. Few studies have evaluated the utility of DBE in patients with known or suspected Crohn's disease (CD). OBJECTIVE: To evaluate the use of DBE in the diagnosis and impact on patient management in known and suspected CD and to compare capsule endoscopy (CE) with DBE findings. DESIGN: Retrospective study from August 2004 to August 2009 of DBE procedures. SETTING: Five academic, tertiary U.S. centers. PATIENTS: Patients with known or suspected CD. MAIN OUTCOME MEASURES: Diagnostic yield, impact on patient management, and comparison of DBE to CE findings in patients with known and suspected CD. RESULTS: We analyzed 98 DBE procedures performed in 81 patients (38 with known CD and 43 with suspected CD). For patients with CD, common indications were abdominal pain and bleeding/anemia. The diagnostic yield was 87% (33/38 patients). The impact on subsequent management decisions was 82% (31/38). Common indications for DBE in patients with suspected CD were abnormal CE or other imaging. The diagnostic yield was 79% (34/43 patients). The impact on subsequent management decisions was 77% (33/43). In 17% of patients (14/81), DBE failed to reach the target lesion. There was 1 perforation, 3 strictures dilated, and 1 of 2 retained capsules recovered. When CE was followed by DBE, 46% of lesions were confirmed on DBE. LIMITATIONS: Retrospective analysis, imperfect criterion standard. CONCLUSIONS: DBE is an effective technique for assessment of the small bowel in known and suspected CD and affects management. Failure to reach target areas with DBE is not uncommon, and perforations can occur. There is poor correlation between CE and DBE.

A grading scale to evaluate colon cleansing for the PillCam COLON capsule: a reliability study.

BACKGROUND AND STUDY AIMS: The PillCam COLON capsule (Given Imaging, Ltd., Yoqneam, Israel) is an emerging technology for colon visualization. The aim of this prospective study was to assess the interobserver agreement of a new grading scale to evaluate colon cleansing for capsule use. PATIENTS AND METHODS: Healthy volunteers underwent colon preparation and ingested a PillCam COLON capsule. A RAPID 5 (Given Imaging, Ltd.) video was generated and de-identified, and the colon was divided into five segments. Two cleanliness grading scales were compared: a 2-point scale (adequate and inadequate) and a 4-point grading scale (poor, fair, good, and excellent). For assessment of interobserver variability, two experienced gastroenterologists independently rated the cleansing level for each colon segment and for the entire video. Investigators participated in a calibration session prior to reading the study videos. RESULTS: A total of 40 individuals (aged 40 - 74 years) completed the study. A total of 196 colon video segments were evaluated. Per segment, κ values for the 2-point and 4-point scales were 0.754 and 0.619, respectively, representing good interobserver agreement. For the overall grade of the 40 videos, κ values for the 2-point and 4-point scales were 0.647 and 0.44, respectively. CONCLUSIONS: This new cleanliness grading scale showed good interobserver agreement and may be used with the PillCam COLON capsule to assess preparation quality.

Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change.

BACKGROUND: Capsule endoscopy can identify small bowel mucosal inflammatory change. However, there has been no validated index for capsule endoscopy findings. This manuscript documents the development of such an index. AIM: To develop a capsule endoscopy scoring index for small bowel mucosal inflammatory change. METHODS: The index was created in four separate steps. First, parameters and descriptors of inflammatory change were identified. Secondly, blinded readers prospectively graded the presence or absence of each parameter on de-identified videos and graded a perceived global assessment of overall severity. Thirdly, the individual parameters and descriptors were ranked in order of severity. Fourthly, values for each parameter were created using the descent gradient methodology. The premise was to assure that the final numerical score reflected the global assessment and that the global assessment agreed with the ranking of finding severity. Results were compiled for the three categories: no or clinically insignificant change, mild change, and moderate or severe change. Thresholds were determined. RESULTS: The final index includes three parameters: villous oedema, ulcer and stenosis. A score <135 is designated normal or clinically insignificant mucosal inflammatory change, a score between 135 and 790 is mild, and a score > or = 790 is moderate to severe. CONCLUSION: This capsule endoscopy score provides a common language to quantify small bowel inflammatory changes.

Capsule endoscopy: a comprehensive review.

The development of wireless capsule endoscopy (CE) has been a significant technologic advancement for the non-invasive visual evaluation of the entire small bowel and esophagus. The capsule endoscope is disposable and measures 11 x 26 mm. There are two capsule endoscopes currently available: PillCam ESO and PillCam SB for the evaluation of the esophagus and the small bowel, respectively. The PillCam ESO has two cameras on each end and captures images 7 frames per second per each camera, while the PillCam SB has one camera and captures images at a rate of 2 frames per second. Both capsule endoscopes transmit the image data using a radiofrequency signal to a recording device worn on the patient's waist. Once image acquisition is completed, the data from the recording device is downloaded to a computer workstation and analyzed by a gastroenterologist. Common indications for the small bowel CE include obscure gastrointestinal bleeding (OGIB), suspected Crohn disease (CD), as well as other suspected small bowel pathologies, while indications for the esophageal CE include screening of Barrett esophagus and esophageal varices. Small bowel CE appears to be more sensitive in the evaluation of OGIB and small bowel CD compared with other conventional radiological and endoscopic modalities. Preliminary results for the esophageal CE reveal good accuracy for screening of both Barrett and esophageal varices. CE is well tolerated by most patients, requires no sedation, and carries few side effects. One of the complications of CE is capsule retention; however, a patency capsule system has been developed, which can indicate whether an obstructing lesion is present before CE is performed. Finally, there are preliminary data suggesting that a new capsule endoscope for the colon may be useful in the evaluation of patients for colon polyps and possibly, screening for colon cancer.

The yield of capsule endoscopy in patients with abdominal pain or diarrhea.

BACKGROUND AND STUDY AIMS: Capsule endoscopy, proven effective for evaluation of obscure gastrointestinal bleeding and suspected Crohn's disease, is increasingly used to investigate other small-intestine disorders, but its yield for other indications is not well known. We sought to evaluate its yield and findings for abdominal pain or diarrhea. PATIENTS AND METHODS: Medical records of patients with abdominal pain or diarrhea (> 6 weeks' duration) who underwent capsule endoscopy between August 2001 and June 2004 were retrospectively reviewed for demographic data, indications, findings, diagnoses, complications, and radiologic studies. All patients had previous endoscopic or radiologic examinations (colonoscopy, enteroscopy, upper endoscopy, small-bowel series, computed tomography enterography, or computed tomography) demonstrating no abnormalities sufficient for diagnosis. RESULTS: 64 patients (26 men; 38 women; mean age, 43 years; age range, 19 - 83 years) who met study criteria had 68 capsule endoscopy studies. Indications were abdominal pain (35 patients), diarrhea (14), or both (15). Complete small-bowel visualization with identification of the cecum was achieved in 81 %; yield of positive findings was 9 % (6 patients). By indications, the yield was 6 % for abdominal pain, 14 % for diarrhea, and 13 % for both. Diagnoses included Crohn's disease (3), enteropathy induced by nonsteroidal anti-inflammatory drugs (2), and submucosal tumor (1). Capsule retention occurred in two patients, requiring surgical removal. CONCLUSIONS: Capsule endoscopy had a low yield for evaluation of abdominal pain or diarrhea and cannot be recommended as a first-line test without further study. Nonetheless, it facilitated diagnosis in 9 % of patients with negative endoscopic and radiologic examinations.

Gastrointestinal basidiobolomycosis in Arizona: clinical and epidemiological characteristics and review of the literature.

Gastrointestinal basidiobolomycosis (GIB) is an unusual fungal infection that is rarely reported in the medical literature. From April 1994 through May 1999, 7 cases of GIB occurred in Arizona, 4 from December 1998 through May 1999. We reviewed the clinical characteristics of the patients and conducted a case-control study to generate hypotheses about potential risk factors. All patients had histopathologic signs characteristic of basidiobolomycosis. Five patients were male (median age, 52 years; range, 37--59 years) and had a history of diabetes mellitus (in 3 patients), peptic ulcer disease (in 2), or pica (in 1). All patients underwent partial or complete surgical resection of the infected portions of their gastrointestinal tracts, and all received itraconazole postoperatively for a median of 10 months (range, 3--19 months). Potential risk factors included prior ranitidine use and longer residence in Arizona. GIB is a newly emerging infection that causes substantial morbidity and diagnostic confusion. Further studies are needed to better define its risk factors and treatment.

Endoscopic perforation of the colon: lessons from a 10-year study.

OBJECTIVES: To assess the incidence, clinical features, and management of endoscopic colon perforations in a large number of patients at a major medical teaching center. METHODS: A retrospective review of medical records of all patients with colon perforations from endoscopy over a 10-yr period. RESULTS: A total of 10,486 colonoscopies were performed over a 10-yr period. There were 20 (0.19%) perforations and two (0.019%) deaths related to colonoscopy and two perforations with no deaths in 49,501 sigmoidoscopies (0.004%). The majority of perforations (65%) occurred in the sigmoid colon. The mean age of the patients was 72 yr (range, 48-87 yr). Multivariate analysis using gender and age showed that female gender was an independent predictor of a higher risk of perforation (p < 0.05). Electrocautery injury (36%) and mechanical injury (32%) from the tip and shaft of the endoscope were the major causes for perforation. Most patients (91%) presented within 48 h of endoscopy. Nine patients (47%) required a surgical resection with primary anastomosis; seven (37%) required a simple closure. The average hospital length of stay was 7.7 +/- 2.8 days. Although trainee endoscopists were involved in only 20% of the colonoscopies performed, eight (40%) perforations occurred while the training fellow was involved in the case. However, this increased risk of perforation with a training fellow was not statistically significant (p = 0.625). CONCLUSIONS: Colonoscopy can result in significant morbidity and carries a small risk of death. Sigmoidoscopy has lower risk. The following situations may represent increased risk to colonoscopy patients: unusual difficulty in traversing the sigmoid colon; difficult examinations in female patients, and difficult examinations performed by trainee physicians.

A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS: The optimum initial dose of methotrexate for steroid-requiring inflammatory bowel disease is not known. AIM: To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome. METHODS: A 16-week randomized single-blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid-requiring Crohn's disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels. RESULTS: After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S. ). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity. CONCLUSIONS: For induction of remission in steroid-requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.

Evaluation of 5-aminosalicylic acid (5-ASA) for cancer chemoprevention: lack of efficacy against nascent adenomatous polyps in the Apc(Min) mouse.

Recent experimental and epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the prevention of colorectal cancer. However, the toxicity associated with the long-term use of most classical NSAIDs has limited their usefulness for the purpose of cancer chemoprevention. Inflammatory bowel disease (IBD) patients, in particular, are sensitive to the adverse side effects of NSAIDs, and these patients also have an increased risk for the development of intestinal cancer. 5-Aminosalicylic acid (5-ASA) is an anti-inflammatory drug commonly used in the treatment of IBD and may provide protection against the development of colorectal cancer in these patients. To directly evaluate the ability of 5-ASA to suppress intestinal tumors, we studied several formulations of 5-ASA (free acid, sulfasalazine, and Pentasa) at multiple oral dosage levels [500, 2400, 4800, and 9600 parts/million (ppm)] in the adenomatous polyposis coli (Apc) mouse model of multiple intestinal neoplasia (Min). Although the ApcMin mouse is not a model of colitis-associated neoplasia, it is, nonetheless, a useful model for assessing the ability of anti-inflammatory agents to prevent tumor formation in a genetically preinitiated population of cells. We used a study design in which drug was provided ad libitum through the diet beginning at the time of weaning (28 days of age) until 100 days of age. We included 200 ppm of piroxicam and 160 ppm of sulindac as positive controls, and the negative control was AIN-93G diet alone. Treatment with either piroxicam or sulindac produced statistically significant reductions in intestinal tumor multiplicity (95% and 83% reductions in tumor number, respectively; P < 0.001 versus controls). By contrast, none of the 5-ASA drug formulations or dosage levels produced consistent dose-progressive changes in polyp number, distribution, or size, despite high luminal and serum concentrations of 5-ASA and its primary metabolite N-acetyl-5-ASA. Thus, 5-ASA does not seem to possess direct chemosuppressive activity against the development of nascent intestinal adenomas in the ApcMin mouse. However, because intestinal tumor development in the ApcMin mouse is driven by a germline mutation in the Apc gene rather than by chronic inflammation, we caution that these findings do not definitively exclude the possibility that 5-ASA may exert a chemopreventive effect in human IBD patients.

Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study.

BACKGROUND: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption. AIM: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study. METHODS: Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. RESULTS: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 +/- 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas. CONCLUSIONS: Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.

Rectal bleeding from a mucous fistula secondary to a Dieulafoy's lesion.

Dieulafoy's lesion is a submucosal artery associated with a minute mucosal defect, and it is an extremely rare cause of profuse but intermittent gastrointestinal bleeding. Most cases have occurred in the proximal stomach within 6 cm of the gastroesophageal junction. Less commonly, cases are encountered in the antrum, duodenum, jejunum, colon, and rarely the rectum. Only three cases of rectal Dieulfoy's lesion have been reported in the English medical literature: one in a child and two in otherwise healthy young men. We report a case of a rectal Dieulafoy's lesion in an elderly man with a mucous fistula. Successful treatment was administered with a combination of injection therapy and heater-probe coagulation followed by elective surgical oversewing. Rectal Dieulafoy's lesions should be included in the differential diagnosis of unexplained rectal bleeding in the elderly.

Basidiobolomycosis: an unusual fungal infection mimicking inflammatory bowel disease.

Basidiobolus ranarum is a fungus belonging to the Entomophthoraceae family and is mainly associated with subcutaneous soft tissue infection. The disease is usually characterized by an insidious onset of massive induration of the subcutaneous tissue involving the limbs, trunk, or buttocks. Most cases of basidiobolomycosis have been reported from Africa, South America, and tropical Asia. Visceral involvement is extremely rare. Only 4 cases with involvement of the gastrointestinal tract, including 1 fatal case originating in the United States, have been well documented in the English-language literature. This case report describes the first successfully treated patient residing in the United States who had B. ranarum infection involving the gastrointestinal tract.

Radical resection of malignant thymoma with reconstruction of the mediastinal venous confluence.

Thymic tumors are classified as epithelial neoplasm, thymic carcinoids, and thymic carcinoma. Differentiation between benignity and malignancy of thymic epithelial tumors is determined on the basis of local tissue invasion. Surgery is the treatment of choice for locally invasive disease without signs of metastasis. We present a patient who underwent en bloc tumor excision with reconstruction of the mediastinal venous confluence using pericardium.