The accuracy of intestinal ultrasound compared with small bowel capsule endoscopy in assessment of suspected Crohn's disease in patients with negative ileocolonoscopy.

BACKGROUND: Small bowel involvement in Crohn's disease (CD) is frequently proximal to the ileocecal valve and inaccessible by conventional ileocolonoscopy (IC). Small bowel capsule endoscopy (SBCE) is among the prime modalities for assessment of small bowel disease in these patients. Intestinal ultrasound (IUS) is an accurate bedside fast and low-cost diagnostic modality utilized in CD for both diagnosis and monitoring. The aim of this study was to examine the accuracy of IUS in patients with suspected CD after a negative IC, and to evaluate the correlation of IUS with SBCE, inflammatory biomarkers and other cross-sectional imaging techniques. METHODS: Prospective single center study in which patients with suspected CD underwent IUS and SBCE examinations within 3 days. IUS results were blindly compared with SBCE that served as the gold standard. A post hoc comparison was performed of IUS and SBCE results and available cross-sectional imaging results (computed tomography or magnetic resonance enterography) as well as inflammatory biomarkers if measured. The study cohort was followed for 1 year. In case of discordance between the IUS and SBCE results, the diagnosis at 1 year was reported. RESULTS: Fifty patients were included in the study. The diagnostic yield of both IUS and SBCE for the diagnosis of small bowel CD was 38%. The IUS findings significantly correlated to small bowel inflammation detected by SBCE (r = 0.532, p < 0.001), with fair sensitivity and specificity (72% and 84%). Cross-sectional imaging results significantly correlated to IUS as well (r = 0.46, p = 0.018). Follow up was available in 8 of the 10 cases of discordance between IUS and SBCE. In all of these cases, diagnosis of CD was not fully established at the end of the follow up. CONCLUSIONS: The diagnostic yield of CE and IUS for detection of CD in patients with negative ileocolonoscopy was similar. IUS can be a useful diagnostic tool in suspected CD when IC is negative.

Comparison of strategies and goals for treatment of chronic constipation among gastroenterologists and general practitioners.

BACKGROUND: Although guidelines have been published for the treatment of chronic constipation, little is known about the actual treatment strategies, the definitions of drug efficacy, the parameters for drug selection, and the conceived limitations of the available treatments. The purpose of this study was to address these issues by comparing treatment strategies among gastroenterology specialists (GIs) and general practitioners (GPs). METHODS: An internet survey was sent nationwide and at random to GIs and GPs in order to define treatment strategies, drug efficacy, main parameters for drug selections and the main limitations of the available drug therapy. RESULTS: Forty GIs and 132 GPs answered the survey. The maximal sample error was ±13.4% and ±8.8%. Treatment strategies varied considerably between GPs and GIs. The major parameters for drug selection were related to drug safety among GIs and to clinical outcome among GPs. The conceived limitations of drug therapy included lack of experience and unwanted side effects. CONCLUSIONS: Awareness of the possible treatment options and the recommended order of prescription differs between GIs and GPs. There are still unmet needs for optimizing the treatment for chronic constipation.

The Severity of Symptoms Related to Irritable Bowel Syndrome is a Risk Factor for the Misclassification of Significant Organic Disease.

BACKGROUND AND AIMS: The diagnosis of irritable bowel syndrome (IBS) is based mainly on clinical evaluation. The reported incidence of misclassification of significant organic diseases in previously diagnosed IBS patients differs between studies. The aim of this study was to examine the incidence and risk factors for the misclassification of significant organic disease [colon cancer, inflammatory bowel disease (IBD), Celiac disease, and thyroid dysfunction] in a cohort of young patients with symptoms attributed to IBS. METHODS: In this population-based cohort study, we examined the incidence and risk factors for the diagnosis of a new significant organic diseases in a cohort of 2645 IBS patients. RESULTS: During follow-up, organic disease was diagnosed in 27 subjects (1.03%): IBD in 23, Celiac disease in 2, IBD and Celiac disease in 1, and hypothyroidism in1. The mean interval from the diagnosis of IBS to the diagnosis of an organic disorder was 13.08±8.51 months. Increased symptom severity was the only significant risk factor for the misclassification of an organic disease (hazard ratio, 2.26; 95% confidence interval, 1.01-5.05; P=0.047). The risk ratio for misclassification of organic diseases in moderate to severe IBS was increased by 2.575 (95% confidence interval, 1.10-6.51; P=0.027) as compared with mild IBS. CONCLUSIONS: The incidence of misclassification of major organic disease in IBS patients was low. Increased symptoms severity was the only significant risk factor for the misclassification of organic disorders. Further gastrointestinal evaluation should be considered in patients with moderate to severe symptoms attributed to IBS.

The incidence of gastrointestinal pathology and subsequent anemia in young men presenting with iron deficiency without anemia.

BACKGROUND AND AIMS: The etiology of iron deficiency (ID) without anemia in young men is unclear, and there are no evidence-based recommendations for the required gastrointestinal (GI) evaluation. The aims of this study were to examine the incidence of significant GI pathology and the development of anemia during the follow-up of young men presenting with ID, but without anemia. METHODS: All young men (18-30 years) who served in the Israel Defense Forces during the years 2005-2013 and had at least a single laboratory test indicative of ID without anemia were followed until the diagnosis of significant GI pathology or discharge from military service. RESULTS: The study population included 2061 young men (mean age 20.7±1.8). During follow-up of 3150 person years, significant GI pathologies were diagnosed in 39 patients: inflammatory bowel disease in 25 (1.2%), celiac disease in 8 (0.4%), and peptic disease in 4 (0.1%). No cases of GI-related cancer were diagnosed. ID anemia developed during follow-up in 203 (9.8%). Lower baseline hemoglobin levels, lower ferritin levels, and younger age at diagnosis were more common among those who developed anemia. The development of anemia was a predisposing factor for the diagnosis of GI pathology (risk ratio=3.60, 95% confidence interval 1.34-8.32, P=0.012). CONCLUSION: Significant GI pathology is very uncommon in young men presenting with ID. Overt anemia developed in close to 10% of the study cohort. Therefore, we advise simple GI evaluation (celiac serology, C-reactive protein or fecal calprotectin, and urease breath test) as well as follow-up in this population.

Comparison of procedural sequence in same-day consecutive bidirectional endoscopy using moderate sedation: a prospective randomized study.

BACKGROUND: A sequential bidirectional endoscopy is commonly performed. However, the optimal sequence of procedures for same-day bidirectional endoscopy using moderate sedation has not been established. GOALS: The aim of this study was to characterize the optimal sequence of endoscopies for sequential bidirectional endoscopy. STUDY: This was a single-center, prospective, randomized study. A total of 163 patients aged 18 to 80 years, who were referred for bidirectional endoscopy for any indication, were randomized to start with upper or lower endoscopy. Initially, all patients received intravenously 50 mg of meperidine and 2.5 mg of midazolam. Patient's discomfort and satisfaction, as expressed by the amount of analgesia added to sustain conscious sedation, and the postprocedure satisfaction reported by the patients were set as primary outcomes. RESULTS: There was no significant difference in the total dose of midazolam added, patient's pain assessment and satisfaction from the anesthesia and the procedure, duration of endoscopies, or the time to cecal intubation between the esophagogastroduodenoscopy first and colonoscopy first groups. The rate of diagnosis of significant pathologies and the rate of procedures performed during the examinations were similar in both the study groups. Evaluation of patient's postprocedural recovery did not reveal significant differences. There was no significant variance between the performing physicians regarding anesthetic dosing, duration of examination, pain scoring, and the related patient's pain postprocedural assessment. CONCLUSIONS: There were no significant differences in the patient's discomfort and satisfaction, regardless of the procedural sequence.

PillCam small bowel capsule endoscopy gastric passage interval association with patient's complaints and pathological findings: a prospective study.

BACKGROUND AND AIMS: Prolonged gastric transit interval of small bowel video capsule endoscopy (SBCE) can potentially indicate a motility disorder and disrupt whole small bowel visualization. The aim of this study was to prospectively examine the association of prolonged gastric passage interval with symptoms, anthropometric and laboratory factors, and factors related to the SBCE examination, such as indications and pathological findings. MATERIALS AND METHODS: This was a prospective single-center study that included 100 patients who underwent SBCE for any indication. Before the examination, clinical, demographic, and anthropometric data were recorded. The patients filled the Gastroparesis Cardinal Symptoms Index (GCSI) questionnaire. We assessed the difference in the study parameters between the prolonged gastric transit (≥45 min) group and the group with a normal gastric transit. RESULTS: Seventy-six patients had normal gastric passage interval and 24 patients had prolonged gastric passage interval. No significant differences were found between the groups in age, sex, prevalence of diabetes mellitus, use of antimotility drugs, indications for the exam and levels of hemoglobin, C-reactive protein, and albumin. Esophageal and small bowel transition intervals did not vary between both groups. The mean score for any GCSI item and the mean total GCSI score did not differ significantly between the normal and the prolonged gastric passage interval groups. There were no significant differences between the groups in pathological findings in the small bowel. CONCLUSION: In the study population, prolonged SBCE gastric transit interval had no clinical significance, and therefore, probably does not mandate any further gastrointestinal evaluation.

Management of antithrombotic agents for colonoscopic polypectomies in Israeli gastroenterologists relative to published guidelines.

BACKGROUND: Endoscopic procedures are commonly performed in patients taking antithrombotic agents. OBJECTIVE: To examine the correlation between the management of antithrombotic drugs for colonoscopic polypectomies and the published guidelines. DESIGN AND SETTINGS: A structured survey delivered to gastroenterologists in 15 major Israeli hospitals and three central HMO clinics. RESULTS: We collected 100 filled out surveys. Polypectomies on aspirin were performed by 78%. Most physicians did not perform polypectomies on clopidogrel. None of the physicians performed polypectomies on warfarin. Cessation of aspirin for ≥ 3 days post-polypectomy was recommended by 60%. Renewal of LMWH or warfarin was recommended ≥ 2 days post-polepectomy in 91% and 71%, respectively. The greatest variation in recommendations was found for clopidogrel, where the majority of gastroenterologists advised renewal after 1-2 days (38%). Years in practice and increasing colonoscopy volume work had no significant association with management of antithrombotic agents. Working in a HMO clinic was associated with lower rates of polypectomies on aspirin (P=0.036). DISCUSSION: When the guidelines are clear, most gastroenterologists practice according to the existing recommendation. However, lack of prospective studies limits the ability to publish evidence-based recommendation and guidelines. We found that the practice of our cohort study varies in these situations.

A survey of colonoscopic polypectomy practice amongst Israeli gastroenterologists.

BACKGROUND: Polypectomy techniques have been implicated as factors in the effectiveness of polyp resection. The range of polypectomy practices among gastroenterologists in Israel is unknown. METHODS: A structured survey was sent to all Israeli gastroenterology departments in all 15 major academic hospitals and to 3 central outpatient clinics. RESULTS: The survey was completed by 100 clinicians (45% contacted) derived from 13 of 15 academic centers (85%) and from all 3 outpatient clinics. Significant differences were noted in the preferred polypectomy for the resection of polyps 1-3 mm and 7-9 mm in diameter whereas for those polyps 4-6 mm in diameter, both the hot forceps and hot snare were most commonly used technique. Coagulation was employed in 42% of cases, pure cutting in 20% and blend current in 38% of cases. Narrow band imaging was used by 54% of practitioners, and only 33% of gastroenterologists regularly used dye spraying techniques. When removing pedunculated polyps >1 cm in diameter, 75% did not use any specific measures designed to prevent perforation or hemorrhage. Performance of >300 colonoscopies per year was associated with a greater use of dye spraying techniques and working in a hospital was more likely to be accompanied by clip deployment to larger polypectomy stalks as part of the procedure. CONCLUSION: Our results demonstrate considerable heterogeneity in the techniques used for removal of polyps <1 cm. Most practitioners do not regularly use advanced techniques for polyp detection or for the prevention of post-polypectomy bleeding.

Endoscopic ultrasound (EUS) before gastric polyp resection: is it mandatory?

INTRODUCTION: Gastric polypectomy is associated with increased risk of bleeding. The use of endoscopic ultrasound (EUS) before polypectomy to decrease the rate of bleeding in such patients has not been studied. METHODS: All gastric polyps excised by snare polypectomy were evaluated. The primary outcome was the occurrence of immediate or delayed bleeding episodes. Postpolypectomy bleeding was correlated with the presence of blood vessels at the base of the polyp on EUS examination. Characteristics of both patients and polyps were analyzed as risk factors for postpolypectomy bleeding. RESULTS: One-hundred and two snare polypectomies were performed. Fifty-seven polyps (56%) had been evaluated by prior EUS. Bleeding occurred in 7 (7%) patients. Of these, 4 had not undergone EUS evaluation, whereas in 3 patients who had had a prepolypectomy EUS evaluation, none were found to harbor a visible blood vessel. Bleeding did not occur in any of the 8 patients in whom EUS suggested the presence of blood vessel. The size, location, type, and histology did not show any significance in predicting postpolypectomy bleeding. CONCLUSIONS: The risk of bleeding after endoscopic resection of gastric polyps was 7%. EUS evaluation before gastric polypectomy does not seem to contribute to the safety of such a procedure.

Necrotizing granulomata in the lung preceding colonic involvement in 2 patients with Crohn's disease.

Extraintestinal involvement, including the chest, is common in the late course of Crohn's disease. We describe 2 female patients in whom the course of the disease was unique in two aspects: (1) each had a pulmonary mass with granulomatous inflammation and necrosis, and (2) these findings had preceded the colonic involvement by 5 years. This sequence supports some of the theories on the pathogenesis of Crohn's disease and on its possible relation with sarcoidosis, another idiopathic granulomatous disease.

Diverticulitis in the young patient--is it different ?

AIM: To prospectively study the incidence and the natural history of acute diverticulitis in young patients. METHODS: A total of 207 patients hospitalized at our hospital between January 2000 to February 2005 with the diagnosis of acute diverticulitis were included. Their demographic characteristics, medical history, physical, radiographic and endoscopic findings as well as therapy were recorded. Patients were followed every 6 mo for the first year and later annually. RESULTS: The mean patients' age was 61 (range 27-92) years. Twenty-five patients (12%) were younger than 45 years. Acute diverticulitis was significantly more prevalent among male in the young age group as compared to the older age group (19/25, 76% vs 61/182, 33%, respectively, P = 0.0001). Complications occurred more often in the young age group; 32% vs 13%, (P = 0.002). During follow-up, 6 patients (28%) remained asymptomatic in the young age group as compared to 87 patients (55%) in the older age group (P = 0.024). As a result, sigmoidectomies were performed twice as often in the young age group (38% vs 13%, P = 0.002). CONCLUSION: Diverticulitis in young patients has a male predominance, a more aggressive course with a higher rate of complications and a higher recurrence rate. An earlier surgical approach might be considered in young patients with acute diverticulitis.

Effect of aging on bolus kinematics during the pharyngeal phase of swallowing.

Swallowing difficulty is a common complaint in the elderly and, although there are data for the biomechanics of liquid swallows, little is known about solid bolus motion, or kinematics, in the elderly. The aims of this study were as follows: 1) to characterize and compare solid and liquid bolus kinematics in the elderly and compare the findings with those in young subjects and 2) to correlate bolus kinematics and dynamics. Concurrent manometric-fluoroscopic techniques were used to study eight young and eight elderly subjects. The subjects performed four swallows each of 0.2-cm-diameter solid barium pellets and 5 ml of liquid barium during sagittal fluoroscopy and six-channel pharyngoesophageal manometry. Images were digitized for analysis of kinematic properties such as velocity and acceleration. Dynamic pressures were recorded and coordinated with kinematic events. Image analysis showed that velocity varied as the pellet passed through the hypopharynx, pharynx, and upper esophageal sphincter. In young subjects, pellet kinematics were characterized by two zones of pellet acceleration: one over the tongue base and another as the pellet passed through the upper esophageal sphincter. Although the elderly showed a similar zone of acceleration over the base of the tongue, the second zone of pellet acceleration was not seen. Decreasing pressure gradients immediately distal to the position of the solid pellet and liquid bolus characterized dynamics for all subjects. This decreasing pressure gradient was significantly larger in elderly than in young subjects. Bolus kinematics and dynamics were significantly altered among elderly compared with young subjects. Among these differences were the absence of hypopharyngeal bolus acceleration and a significant increase in the trans-sphincteric pressure gradient in the elderly.

Increasing the infliximab dose is beneficial in Crohn's disease patients who responded to a lower dose and relapsed.

BACKGROUND: Relapse after an initial response to infliximab therapy poses a problem for maintenance treatment. AIM: To assess the effects of increasing the infliximab dosage in Crohn's disease (CD) patients who initially responded but flared during maintenance therapy. METHODS: This was an observational study. Twelve CD patients with both inflammatory and fistulizing manifestations were included. All patients initially responded to 5 mg/kg of infliximab, relapsed during maintenance therapy, and were treated with 10 mg/kg. The Harvey-Bradshaw index, the fistula activity, and steroid use were assessed before and after treatment with the increased dose of infliximab. RESULTS: The mean Harvey-Bradshaw index score after flare-up during treatment with 5 mg/kg of infliximab was 13.5+/-3.7. Treatment with 10 mg/kg, in a mean of 3.3 infusions, decreased the activity score to a mean of 8.8+/-2.5. Two patients were weaned off prednisone, and a reduced dose was possible in the other steroid-treated patients. CONCLUSIONS: Increasing the infliximab dose may be beneficial in CD patients who initially responded to therapy, but relapsed during maintenance with the lower dosage.

A prospective study of the diagnostic accuracy of PillCam ESO esophageal capsule endoscopy versus conventional upper endoscopy in patients with chronic gastroesophageal reflux diseases.

INTRODUCTION: Endoscopy is commonly performed to evaluate for suspected or established esophageal diseases including gastroesophageal reflux disease (GERD) and its complications. The newly developed PillCam ESO Esophageal Capsule offers an alternative approach to visualize the esophagus and to evaluate patients with suspected esophageal disease. AIM: Compare the accuracy (specificity, sensitivity, positive predictive value [PPV], and negative predictive value [NPV]) of esophageal capsule endoscopy (ECE) compared with esophagogastroduodenoscopy (EGD) in evaluating patients with GERD. METHODS: A multicenter pivotal trial was conducted at seven sites. The PillCam ESO esophageal capsule is similar to the standard capsule endoscope used for the small bowel but acquires video images from both ends of the device at 2 frames/second/end. A total of 106 patients (93 GERD; 13 Barrett) underwent ECE followed by EGD. ECE videos were evaluated by an investigator blinded to EGD findings. A blinded adjudication committee reviewed all discrepant findings between ECE and EGD. RESULTS: Sixty-six of 106 patients had positive esophageal findings, ECE identified esophageal abnormalities in 61 (sensitivity, 92%; specificity, 95%). The per-protocol sensitivity, specificity, PPV, and NPV of ECE for Barrett esophagus were 97%, 99%, 97%, and 99%, respectively, and for esophagitis 89%, 99%, 97%, and 94%, respectively. ECE was preferred over EGD by all patients. There were no adverse events related to ECE. CONCLUSIONS: ECE is a convenient and sensitive method for visualization of esophageal mucosal pathology and may provide an effective method to evaluate patients for esophageal disease.

Second capsule endoscopy for patients with severe iron deficiency anemia.

BACKGROUND: Patients with iron deficiency anemia are subjected to multiple endoscopic and radiologic examinations of the GI tract. If negative, some of the examinations are repeated, occasionally with positive findings. The diagnostic yield of a second capsule endoscopy in such patients is unknown. The aim of the current study was to assess the diagnostic yield of a second capsule endoscopy in patients with significant iron deficiency anemia and a previous negative evaluation. METHODS: Twenty patients with iron deficiency anemia (Hb < 10 g/dL) were enrolled. All had at least one normal evaluation of the GI tract, including capsule endoscopy. A second capsule endoscopy examination was offered to all patients. RESULTS: The time between the first and the second capsule endoscopy ranged from 2 months to 1 year. Depending on the nature of an abnormality and its relevance to blood loss, the findings were classified as positive, suspicious, clinically irrelevant, or negative. In 7 patients, the second capsule endoscopy disclosed findings that were classified as either positive or suspicious findings, including arteriovenous malformations (2), flat polypoid lesion (1), edematous inflamed mucosa (1), erosions (1), and hemorrhagic gastritis (1). Lesions were located in the small intestine (5), the stomach (1), and the cecum (1). Based on the findings of the second capsule endoscopy, therapy was changed in two patients (10%). CONCLUSIONS: A second capsule endoscopy should be considered for patients with severe iron deficiency anemia and negative initial evaluation.

Effect of lower esophageal sphincter tone and crural diaphragm contraction on distensibility of the gastroesophageal junction in humans.

Previous studies of distensibility of the gastroesophageal junction (GEJ) in humans have not tried to distinguish between the effects of muscle action and passive elastic tissue properties of the GEJ. We studied 15 healthy subjects (ages 23-67 yr, 11 men/4 women) by using a catheter with a highly complaint bag positioned manometrically at the GEJ. The bag was distended with air at a rate of 20 ml/min while intrabag pressure was recorded. Distensions were performed during normal breathing, with breath held at maximum inspiration (MI) to activate the diaphragmatic crura, and with midesophageal balloon distension (BD) to relax the lower esophageal sphincter. In 10 subjects, distensions were performed after atropine injection (12 microg/kg iv). Pressure-volume curves and incremental distensibility values were calculated and compared among the different conditions. Both MI and BD significantly altered the slopes of the pressure-volume curves, whereas no effect was seen with atropine. Maximum distensibility was seen at the volume increment of 5-10 ml and was reduced with larger volumes. Distensibility measurements for the various test conditions tended to converge at the largest volume increment, suggesting that distensibility at this degree of distension was more related to the passive elastic properties of the GEJ. On the basis of these findings, we conclude that there can be significant active muscular contributions to recordings of distensibility at the GEJ, variations that must be controlled for during different study conditions.

Colorectal cancer screening in patients presenting with an inguinal hernia: is it necessary?

BACKGROUND: It has been suggested that patients presenting with an inguinal hernia have an increased risk for colorectal cancer. Therefore, surgeons frequently request screening for colorectal cancer before surgery. The aim of this study was to assess the frequency of premalignant and malignant colonic lesions in a group of patients with an inguinal hernia, and to compare this with a control group of subjects undergoing screening colonoscopy. METHODS: In a case-control study, 243 patients with an inguinal hernia and no history of colonic neoplasia or symptoms suggestive of colorectal cancer underwent perioperative colonoscopy. The patients were stratified into two age groups: less than 50 years old (Group I) and more than 50 years old (Group II). The colonoscopic findings were compared with findings in 534 asymptomatic control patients who underwent screening colonoscopy. RESULTS: The mean age of patients (n=64) and control subjects (n=200) in Group I was similar, at 44 (3) years. The mean age of the patients (n=179) and control subjects (n=334) in Group II was, respectively, 70 (9) years and 64 (7) years (p<0.001). In Group I, no colorectal cancer was found in patients with inguinal hernia, and only one colorectal cancer was found among control subjects (p=0.571). In Group II, a diagnosis of colorectal cancer was made in 7 patients (4%) with inguinal hernia as compared with 10 patients (3%) among the control subjects (p=0.769). In both groups, the size and the histopathologic type of the polyps were not significantly different. CONCLUSIONS: In otherwise asymptomatic patients, the presence of inguinal hernia is not associated with an increased risk for colorectal cancer. Therefore, the presence of an inguinal hernia alone does not justify screening colonoscopy before herniorrhaphy.

Pharyngoesophageal pH monitoring.

Pharyngeal acid reflux events may be significant in the pathogenesis of various supraesophageal manifestations of gastroesophageal reflux disease. Intragroup variation and an extensive overlap among subject groups and normal controls make proximal esophageal 24-hour pH monitoring studies unreliable for the diagnosis of pharyngeal reflux. However, the clinical value of pharyngeal pH monitoring still remains uncertain. A 24-hour pharyngeal pH monitoring study has shown that at least some pharyngeal reflux events occur in most healthy subjects, mainly in the upright position. Based on these data, values for the upper limits of normal for total pharyngeal acid exposure time and pharyngeal acid events have been determined. This study provides clinicians with reference values for physiologic pharyngeal reflux, but the parameters of abnormal pharyngeal reflux events are still unknown. More research is needed before this practice can become part of the routine evaluation of patients with pharyngeal, laryngeal, respiratory, or ear, nose, and throat symptoms or disorders.

Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients.

Ulcerative colitis (UC) and Crohn's disease (CD) are heterogeneous disorders characterized by chronic intestinal inflammation. Genetic predisposition is a major risk factor in both diseases. The CARD15 (NOD2) gene has been implied as a candidate gene in the pathogenesis CD. Our aim was to delineate the frequency of three missense and one frameshift variant of CARD15 in Israeli Jewish CD and UC patients. DNA was extracted from blood samples from 238 unrelated inflammatory bowel disease (IBD) patients, 68 with UC and 170 with CD. The DNA was genotyped for two missense mutations, R675W and G881R, and one frameshift mutation, 980FS981X. Mutations in CARD15 were observed with significantly greater frequency in CD patients (46/170, 27%) than in UC patients (7/68, 10%) (P = 0.005). Homozygous and compound heterozygous carriers were restricted to seven (4%) patients with CD as compared to none of the UC patients (P = 0.01). Similar rates in Ashkenazi and non-Ashkenazi Jewish patients were observed. Age-of-onset of disease was lower in Ashkenazi mutation carriers as compared to non-carriers of Ashkenazi origin (18.7 +/- 8.6 years vs. 25.8 +/- 13.4 years, respectively, P = 0.03). No other phenotypic characteristics could distinguish mutation carriers from non-carriers. We conclude that germline mutations in the CARD15 gene are more frequently found in CD than UC patients and appear to predict an earlier age-of-onset in Ashkenazi Jewish patients. No association could be demonstrated between CARD15 mutations and specific disease course or behavior.