Optimal timing of simethicone administration prior to upper endoscopy: A multicenter, single-blind, randomized controlled trial.

Background and study aims Simethicone is useful as premedication for upper endoscopy because of its antifoaming effects. We aimed to evaluate the effect of timing of simethicone administration on mucosal visibility. Patients and methods In this multicenter, randomized, endoscopist-blinded study, patients scheduled for upper endoscopy were randomized to receive 40 mg simethicone at the following time points prior to the procedure: 20 to 30 minutes (early group), 0 to 10 minutes (late group) or 20 mg simethicone at both time points (split-dose group). Images were taken from nine predefined locations in the esophagus, stomach, and duodenum before endoscopic flushing. Each image was scored on mucosal visibility by three independent endoscopists on a 4-point scale (lower scores indicating better visibility), with adequate mucosal visibility defined as a score ≤ 2. Primary outcome was the percentage of patients with adequate total mucosal visibility (TMV), reached if all median subscores for each location were ≤ 2. Results A total of 386 patients were included (early group: 132; late group: 128; split-dose group: 126). Percentages of adequate TMV were 55%, 42%, and 61% in the early, late, and split-dose group, respectively ( P < 0.01). Adequate TMV was significantly higher in the split-dose group compared to the late group ( P < 0.01), but not compared to the early group ( P = 0.29). Differences between groups were largest in the stomach, where percentages of adequate mucosal visibility were higher in the early (68% vs 53%, P = 0.03) and split-dose group (69% vs 53%, P = 0.02) compared to the late group. Conclusions Mucosal visibility can be optimized with early simethicone administration, either as a single administration or in a split-dose regimen.

Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy.

Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory disease, in both malignancies and severe autoimmune diseases. It seems feasible and safe for refractory celiac disease (RCD) type II, although long-term results have not been evaluated yet. With current therapies, progression into enteropathy-associated T-cell lymphoma (EATL) occurs in 60-80% patients, with a high mortality rate. Therefore, it is important to evaluate new treatment strategies. Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto-SCT preceded by conditioning with fludarabine and melphalan, as a consequence of unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL development and change in clinical, histological and immunological course were monitored. Thirteen patients were transplanted successfully and followed up for >2 years, 4-year survival rate was 66%. Only one patient died because of transplant-related complications. The majority of patients showed an impressive clinical improvement and five a complete histological remission. In five patients, auto-SCT could not be performed; they all died with a median survival of 5.5 months. EATL was observed in one transplanted patient, only after 4 years of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II patients unresponsive to cladribine therapy is feasible and seems promising.

The management of complicated celiac disease.

Refractory celiac disease (RCD) is being defined as persisting or recurring villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes (IELs) in spite of a strict gluten-free diet (GFD) for >12 months or when severe persisting symptoms necessitate intervention independent of the duration of the GFD. RCD may not respond primarily or secondarily to GFD. All other causes of malabsorption must be excluded and additional features supporting the diagnosis of CD must be looked for, including the presence of antibodies in the untreated state and the presence of celiac-related HLA-DQ markers. In contrast to patients with a high percentage of aberrant T-cells, patients with RCD I seem to profit from an immunosuppressive treatment. RCD II is usually resistant to medical therapies. Response to corticosteroid treatment does not exclude underlying enteropathy-associated T-cell lymphoma. Cladribine seems to have a role, although it is less than optimal in the treatment of these patients. It may be considered, however, as the only treatment thus far studied that showed significant reduction of aberrant T cells, seems to be well tolerated, and may have beneficial long-term effects in a subgroup of patients showing significant reduction of the aberrant T-cell population. Autologous stem cell transplantation (ASCT) seems promising in those patients with persisting high percentages of aberrant T cells. The first group of patients treated with ASCT showed improvement in the small intestinal histology, together with an impressive clinical improvement. However, it remains to be proven if this therapy delays or prevents lymphoma development.

Disappointing outcome of autologous stem cell transplantation for enteropathy-associated T-cell lymphoma.

BACKGROUND: Despite treatment, enteropathy-associated T-cell lymphoma has a very poor outcome. Chemotherapy can be complicated by small bowel perforation, gastrointestinal bleeding and development of enterocolic fistulae. Here we report on the feasibility, safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation in patients with enteropathy-associated T-cell lymphoma (three upfront and one at relapse), with or without prior partial small bowel resection. METHODS: Four patients [two males, two females, mean age 65 years (range 60-69 years)] received high-dose chemotherapy followed by autologous stem cell transplantation. Partial small bowel resection has been performed in three patients. RESULTS: All four patients completed the mobilization and leucopheresis procedures successfully and subsequently received conditioning chemotherapy and transplantation. Engraftment occurred in all patients. No major non-haematological toxicity or transplantation-related mortality was observed. One patient has ongoing complete remission 32 months after transplantation. Three patients died from relapse within few months after autologous stem cell transplantation. CONCLUSIONS: Autologous stem cell transplantation seems unsatisfactory for patients with enteropathy-associated T-cell lymphoma. More intensive conditioning and aggressive chemotherapy with/or without targeted immunotherapy as well as allogenous stem cell transplantation needs to be explored.

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.

Review article: Stem cell transplantation for the treatment of gastrointestinal diseases--current applications and future perspectives.

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) can be used to cure or ameliorate a variety of non-malignant diseases. These range from inherent defects of haematopoiesis, through metabolic diseases, to severe autoimmune diseases. The rationale for this strategy is based on the concept of immunoablation using high-dose chemotherapy, with subsequent regeneration of naïve T-lymphocytes derived from reinfused haematopoietic progenitor cells. Possibly the use of SCT allows the administration of high-dose chemotherapy resulting in a prompt remission in these therapy-refractory patients. AIM: This review highlights the major scientific developments and defines the areas of successful use of HSCT in gastrointestinal disorders and gives a perspective on possible future applications. METHODS: A search in the Medline has been conducted and all relevant published data were analysed. RESULTS: HSCT has been proved successful in treating refractory Crohn's disease. A selected group of refractory coeliac patients having a high risk of developing enteropathy associated T-cell lymphoma has been recently treated with promising results. In cryptogenic cirrhosis, basic research and unpublished data concerning mesenchymal SCT are encouraging. CONCLUSION: In refractory autoimmune gastrointestinal diseases, it seems that high-dose chemotherapy followed by HSCT is feasible and safe and might result in long-term improvement of disease activity.

Milestone in gastrointestinal endoscopy: double-balloon enteroscopy of the small bowel.

The small bowel (SB) has been largely bypassed by flexible endoscopy because of inaccessibility. Push enteroscopy is now in the past, with recent innovations now making visualization of the SB possible. Wireless capsule endoscopy (CE) and double-balloon endoscopy (DBE) have been introduced. In this review, we focus on the diagnostic and therapeutic modalities of DBE, which may be a suitable replacement for push enteroscopy, preoperative endoscopy and to some extent of SB fall-through and CT scan. DBE is a new method of endoscopy developed and described by Yamamoto et al. in Jichi, Japan, in cooperation with Fujinon. Introduced to the market in 2003, it is possible with this endoscope to observe the entire SB in steps of 20-40 cm. Measuring the depth of insertion is also possible. Obscure gastrointestinal bleeding can be explained and treated in the majority of cases. Biopsy sampling, hemostasis, polypectomy, dilatation and tattoo are possible in the SB. Guidelines for FAB and Peutz-Jeghers syndrome will probably be reviewed in the next few years. The safety and efficacy of DBE have been demonstrated. DBE improves SB disease management and can substitute for more complex investigations. Additional data will come to light in years to come. Combining DBE with CE, CT/MRI enteroclysis in a new era for SB work-up and treatment is the likely future.

Postpartum ovarian vein thrombosis: report of a case and review of literature.

Postpartum ovarian vein thrombosis (POVT) is an uncommon disease and it may complicate streptococcal group B infection of the vagina and endometrium. Obstruction of the right ureter is an uncommon complication of POVT. We present a case of POVT complicated by thrombus extension in the inferior vena cava and ureteral obstruction with urinary leakage, and outline the clinical presentation, radiological investigations useful in diagnosis and treatment of the disease process.