Muhammed Hadithi

A Prospective Study Comparing Video Capsule Endoscopy with Double-Balloon Enteroscopy in Patients with Obscure Gastrointestinal Bleeding

OBJECTIVE:Obscure gastrointestinal bleeding from jejunal and ileal lesions remains undiagnosed using traditional imaging techniques (radiologic, endoscopic). This prospective study compares the diagnostic detection rate of small-bowel lesions using wireless video capsule endoscopy (VCE) with the detection rate using double-balloon enteroscopy (DBE) in patients with obscure gastrointestinal bleeding (OGIB). Tolerance, adverse events, endoscopic interventions, and prognosis were described as secondary aims.METHODS:Thirty-five consecutive patients with obscure gastrointestinal bleeding were evaluated (22 males and 13 females; mean age 63.2 yr; range, 19–86 yr). The detection rates of the Given M2A wireless VCE and DBE were compared.RESULTS:Small-bowel abnormalities were detected using VCE in 28 (80%) of the 35 patients with OGIB, compared with 21 (60%) of the 35 patients using DBE (P = 0.01). Both examinations were well tolerated, but VCE was more acceptable to patients. No major adverse event occurred after either examination. Biopsies (n = 27), argon plasma coagulation (n = 19), tattoo injection (n = 8), and polypectomy (n = 2) were feasible with DBE when indicated in 27 of the 35 patients (77%). During a median (range) follow-up period of 5 (2–12) months, 26 (74%) patients remained clinically stable and did not require blood transfusions after DBE procedures. Eighteen (51%) of those who remained clinically stable had received APC therapy.CONCLUSIONS:High detection rates of the causes of OGIB are feasible with VCE and DBE. Although the detection rate of VCE was superior, our results indicate that the procedures are complementary; an initial diagnostic imaging employing VCE might be followed by therapeutic and interventional DBE.

Survival in Refractory Coeliac Disease and Enteropathy associated T cell Lymphoma: Retrospective evaluation of single centre experience

Background: Coeliac disease may be regarded as refractory disease (RCD) when symptoms persist or recur despite strict adherence to a gluten-free diet. RCD may be subdivided into types I and II with a phenotypically normal and aberrant intraepithelial T-cell population, respectively. RCD I seems to respond well to azathioprine/prednisone therapy. RCD II is usually resistant to any known therapy and transition into enteropathy-associated T-cell lymphoma (EATL) is common. Aim: To provide further insight into RCD and the development of EATL, by reporting on long-term survival and risk of transition of RCD into EATL in a large cohort of patients with complicated coeliac disease. Design and Methods: Retrospective comparison of responses to therapy in four groups of patients with complicated coeliac disease: 43, RCD I; 50, RCD II (total), of whom 26 with RCD II developed EATL after a period of refractoriness to a gluten-free diet (secondary EATL) and 13 were EATL patients without preceding history of complicated coeliac disease (de novo EATL). Results: No coeliac-disease-related mortality was recognised in the RCD I group. The overall 5-year survival in the RCD I group it was 96%; in the RCD II (total) group was 58%; and in the RCD II group after developing EATL it was only 8%. The 2-year survival in the de novo EATL group was 20% versus 15% in secondary EATL group (p = 0.63). Twenty-eight (56%) of the 50 patients with RCD II died, 23 (46%) due to EATL, 4 due to a progressive refractory state with emaciation and 1 from neurocoeliac disease. Conclusion: Remarkably, no patient with RCD I developed RCD II or EATL within the mean follow-up period of 5 years (range 2–15 years). A total of 52% of the RCD II patients developed EATL within 4–6 years after the diagnosis of RCD II. More aggressive and targeted therapies seem necessary in RCD II and EATL.

Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease

Context The value of adding HLA genetic typing to serologic testing for celiac disease is not well defined. Contribution In this prospective study of patients referred for evaluation of celiac disease, the test performance of combinations of genetic typing and serologic testing was similar to that of either strategy alone. Caution The small number of cases of celiac disease precluded meaningful comparisons of testing strategies. Implications The combination of genetic typing and serologic testing is about as accurate as either strategy alone. Neither is a substitute for small-bowel biopsy in the diagnosis of celiac disease. The Editors The high prevalence and clinical heterogeneity of celiac disease necessitate noninvasive tests for diagnosis. Specifically, tests are needed to select which patients should undergo small-bowel biopsy. Although celiac disease serologic tests, especially IgA tissue antitransglutaminase antibodies (TGA) and IgA antiendomysium antibodies (EMA), are often used for this purpose because of their reported high sensitivity (1), they may perform less well in the clinical setting (2). Most studies have not defined the usefulness of serologic tests prospectively (37), and in addition, some authors doubt the high sensitivity of these tests (8, 9). Susceptibility to celiac disease is related to the presence of distinct HLA-DQ heterodimersthe DQ2 heterodimer encoded by the alleles HLA-DQA1*05 and HLA-DQB1*02, and the DQ8 heterodimer encoded by the alleles HLA-DQA1*03 and HLA-DQB1*0302 (1014). One way to improve the selection of patients to undergo small-bowel biopsy may be to combine serologic tests with HLA-DQ typing (15, 16). We designed a prospective study to define the value of specific serologic tests, HLA-DQ typing, or both in diagnosing celiac disease. Methods The institutional review board of the VU University Medical Center, Amsterdam, the Netherlands, approved the study protocol. All participants received oral and written information according to the usual recommendations for medical research and the Declaration of Helsinki (17) and gave written informed consent. Patients The study was performed in an academic, mixed secondary and tertiary referral center that serves a population of about 200000 people. In the design phase of the study (19992000), the staff of departments of internal medicine and gastroenterology reviewed the literature and agreed that serologic tests could not substitute for small-bowel biopsy in the diagnostic work-up of celiac disease. Therefore, the policy was to perform small-bowel biopsy when celiac disease was suspected. Adults suspected of having celiac disease who were attending the endoscopy department for small-bowel biopsy were requested to give blood samples for serum antibody testing and HLA-DQ typing. We excluded patients younger than 18 years of age, those with known celiac disease, and patients who declined to undergo endoscopy. Endoscopy We performed upper gastrointestinal endoscopy with Olympus video endoscopes (GIF-NT140/160, Olympus Nederland, Zoeterwoude, the Netherlands) and obtained 4 oriented biopsy specimens from the distal duodenum (18). Serum Antibody Tests We performed serologic tests after obtaining small-bowel biopsy specimens in all patients to avoid referral bias. All serologic tests were determined anonymously without knowledge of the clinical status or histologic result. We determined IgA and IgG antigliadin antibodies (AGA-IgA and AGA-IgG, respectively) by using enzyme-linked immunosorbent assay (ELISA). We tested for EMA according to the method of Lerner and colleagues (19) by indirect immunofluorescence assay using monkey esophagus (16). Finally, TGA was determined by ELISA, essentially as described by Dieterich and colleagues (20), with guinea pig TGA (gp-TGA) (Sigma-Aldrich, Poole, United Kingdom; coating 10 g/mL in Tris hydrochloride [pH, 7.5] with 5-mmol/L of CaCl2) as the substrate (20). Sera were diluted and preincubated (30 minutes at room temperature) with 1% bovine serum albumin to avoid nonspecific binding (16, 21). The cutoff values for the titers of AGA and gp-TGA tests are based on measurements in control groups (blood donors, patients without celiac disease, and the general population age 2 to 4 years), and optimization was done by a receiver-operating characteristic curve analysis in well-defined patient groups. Because the recombinant human TGA (rh-TGA) assay became available when the study was already ongoing, we retrospectively reevaluated all samples from patients with an abnormal result on serologic testing or histologic examination by using rh-TGA as substrate (Roboscreen, Leipzig, Germany; coating 5 g/mL and same conditions as those for gp-TGA). When serologic test results did not match histologic findings, we measured total serum IgA and repeated the serologic tests. In cases of IgA deficiency, we evaluated TGA-IgG antibodies. We defined seropositivity as 1 or more positive measured antibody test results and seronegativity as negative results on all 4 tests. HLA-DQ Typing Whole blood was obtained for HLA-DQA1 and HLA-DQB1 genotyping. Polymerase chain reactionamplified exon 2 amplicons were generated for low- to medium-resolution typing in a combined, single-stranded conformation polymorphismheteroduplex assay by a semiautomated electrophoresis and gel-staining method on the PhastSystem (Amersham Pharmacia Biotech, Uppsala, Sweden). Alleles DQA1*05 and DQB1*02 (encoding the HLA-DQ2 heterodimer) and alleles DQA1*03 and DQB1*0302 (encoding the HLA-DQ8 heterodimer) could be reliably characterized in homozygous and heterozygous states. This method has been validated by using a panel of reference DNA against the Dynall Allset sequence-specific primers high-resolution typing kits (Dynal A.S., Oslo, Norway) (16, 22). Histologic Studies A gastrointestinal pathologist who was masked to clinical data evaluated the biopsy material, and an independent pathologist reviewed the samples when histologic examination was abnormal. Consensus was reached on the final diagnosis. Villous (crypt) anatomy and density of intraepithelial lymphocytes were assessed uniformly by using hematoxylineosin and immunohistologic anti-CD3 staining, respectively. Appendix Figures 1 and 2 show the histologic grading of abnormalities, based on the most severe change found according to the modified Marsh classification (23, 24). Appendix Figure 1. Small-bowel histologic findings (Marsh 0 to II). A. B. C. Appendix Figure 2. Small-bowel histologic findings (Marsh IIIa to IIIc). A. B. C. Diagnosis and Follow-up of Celiac Disease The diagnosis of celiac disease was based on the European Society for Paediatric Gastroenterology, Hepatology and Nutrition criteria, revised in 1989 and published in 1990, by identifying characteristic histologic findings (Marsh III) on small-bowel biopsy and unequivocal clinical resolution after a gluten-free diet was initiated (25). Thus, by this definition and for this study, the diagnosis of celiac disease did not require follow-up biopsy. However, we assessed histologic response in most patients and serologic response in all patients who were found to have celiac disease. We defined a serologic response as the disappearance of initially positive celiac disease antibody test results and histologic response as the regression of villi to Marsh 0 to II on a repeated biopsy at least 12 months after a gluten-free diet was initiated (24). Statistical Analysis We compared results of serologic tests and HLA-DQ typing with the diagnosis of celiac disease as previously defined. We performed statistical analysis by using SPSS software, version 11.0 (SPSS, Chicago, Illinois). To calculate exact binomial CIs, we used StatXact software, version 7.0.0 (Cytel Software, Cambridge, Massachusetts). We used 2 2 tables (Bayes theorem) to calculate sensitivities and specificities, predictive values, and likelihood ratios. We used the t test and Fisher exact test to compare continuous data and categorical data, respectively. We calculated posttest probabilities (and CIs) of celiac disease for different diagnostic tests or a combination thereof by using the method recommended by Altman (26). Role of the Funding Source The study received no funding. Results Patients Between January 2001 and January 2004, 502 consecutive patients (originally from community practices in the Amsterdam area) were referred from outpatient internal medicine and gastroenterology clinics for endoscopy and small-bowel biopsy for the diagnosis of celiac disease. Another 16 inpatients were referred from the internal medicine and gastroenterology inpatient wards. No referred patient was under the care of the investigators. We excluded 55 (10.6%) patients because they declined to participate in the study after the small-bowel biopsy. Age, sex, body mass index, ethnicity, and indications for referral did not statistically significantly differ between those included in and those excluded from the study (data not shown). The available serologic data (n = 20), HLA-DQ data (n = 4), and histologic examinations (n = 55) suggested the absence of celiac disease in excluded patients. Therefore, 463 patients were included in the study: 346 (75%) were unrelated Dutch Caucasian persons and 117 (25%) were not Caucasian (Indian, Chinese, North African [Arab], and Central African [black], in descending order of frequency). All patients were on a normal diet at the time of inclusion. Table 1 summarizes the general characteristics and indications for small-bowel biopsy of patients without and with celiac disease. Table 1. Characteristics of and Indications for Referral in Patients without and with Celiac Disease Patients with Celiac Disease Of the 463 patients enrolled, 16 (3.46% [95% CI, 1.99% to 5.55%]) fulfilled the diagnostic criteria for celiac disease (Figure) (25) within a median follow-up interval of 22 months (range, 11 to 44 months). Biopsy readings of the 2 pathologists were concor

The value of double-balloon enteroscopy in patients with refractory celiac disease

OBJECTIVE:Patients with refractory celiac disease can develop enteropathy-associated T-cell lymphoma (EATL) or ulcerative jejunitis. Double-balloon enteroscopy allows examination of the small bowel. We prospectively assessed the value of this technique in patients with refractory celiac disease in a tertiary referral center.METHODS:Small bowel enteroscopy was performed in a total of 21 consecutive patients for lesions like ulcerations (high risk). Biopsy specimens were taken from such lesions and from examined small bowel at three different levels of scope insertion depth. Tissue specimens were evaluated for the modified Marsh classification and for the presence of EATL.RESULTS:Twenty-four procedures were successfully performed without complications. EATL was found in five patients (24%, 95% CI 10–45%) as circumferential, discrete, or confluent ulcerations. In three of them, Marsh III was found while in the other two patients with EATL Marsh I was found. Another two patients (9%, 95% CI 2–28%) had ulcerative jejunitis in the absence of EATL and histology was compatible with Marsh III. In the remaining 14 patients (54%, 95% CI 35–73%), no high-risk lesions were found. Double-balloon enteroscopy could exclude the presence of EATL in four patients that was suggested by abdominal computerized tomography.CONCLUSIONS:Complications of refractory celiac disease like ulcerative jejunitis or EATL could efficiently be detected or excluded by double-balloon enteroscopy. This technique should be reserved for patients with refractory celiac disease or patients with a past history of EATL.

Endoscopic ultrasound-guided drainage of pelvic abscess: A case series of 8 patients

AIM To show the safety and effectiveness of endoscopic ultrasound (EUS)-guided drainage of pelvic abscess that were inaccessible for percutaneous drainage. METHODS Eight consecutive patients with pelvic abscess that were not amenable to drainage under computed tomography (CT) guidance were referred for EUS-guided drainage. The underlying cause of the abscesses included diverticulitis in 4, postsurgical surgical complications in 2, iatrogenic after enema in 1, and Crohns disease in 1 patient. Abscesses were all drained under EUS guidance via a transrectal or transsigmoidal approach. RESULTS EUS-guided placement of one or two 7 Fr pigtail stents was technically successful and uneventful in all 8 patients (100%). The abscess was perisigmoidal in 2 and was multilocular in 4 patients. All procedures were performed under conscious sedation and without fluoroscopic monitoring. Fluid samples were successfully retrieved for microbiological studies in all cases and antibiotic policy was adjusted according to culture results in 5 patients. Follow-up CT showed complete recovery and disappearance of abscess. The stents were retrieved by sigmoidoscopy in only two patients and had spontaneously migrated to outside in six patients. All drainage procedures resulted in a favourable clinical outcome. All patients became afebrile within 24 h after drainage and the mean duration of the postprocedure hospital stay was 8 d (range 4-14). Within a median follow up period of 38 mo (range 12-52) no recurrence was reported. CONCLUSION We conclude that EUS-guided drainage of pelvic abscesses without fluoroscopic monitoring is a minimally invasive, safe and effective approach that should be considered in selected patients.

Fluid hydration to prevent post-ERCP pancreatitis in average- to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial) : study protocol for a randomized controlled trial

BackgroundPost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP.MethodsThe FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer’s solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness.DiscussionThe FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs.Trial registrationEudraCT: 2015-000829-37. Registered on 18 February 2015.ISRCTN: 13659155. Registered on 18 May 2015.