Lorenzo Gentilini

Local injection of adalimumab for perianal Crohn's disease: Better than infliximab?†

To the Editor: In our experience, local injection of infliximab, after surgical drainage of the sepsis for treatment of complex perianal Crohn’s disease, is effective and associated with a low risk of recurrent abscesses. In fact, more than 70% of patients who underwent the treatment for the presence of contraindications to systemic infusion, such as fibrostenosing disease, had their fistulas finally closed with scar tissue, tested with probe examination and confirmed by pelvic magnetic resonance imaging (MRI). Less encouraging results were obtained in patients with different indications, such as failure of previous intravenous infusion of infliximab and/or associated severe proctocolitis. Therefore, we decided to evaluate the efficacy of local injection of adalimumab as a rescue therapy in patients who did not respond to infliximab local injection. The structural features of adalimumab, in fact, theoretically present the ideal prerequisites to work in a very effective way when injected in the mucosa surrounding the internal orifice of the fistula. In addition, it should be effective even in those patients who did not respond to infliximab since they had already developed antibodies to its murine protein. Finally, the close frequency of administrations could play a primary role in its successful power. Based on all those assumptions, we used the same procedure as infliximab injection, with 40 mg of adalimumab injected every 15 days in outpatient treatment. The procedure was well tolerated and no adverse events have been registered. The preliminary results are, so far, encouraging. Out of 16 patients with complex fistulas, 2 healed after 2 injections and 3 after 4. The remaining patients are still in treatment, with 1 patient not healed after 6 injections and all the others waiting for the second or third injection. Our feeling is that injection of adalimumab results in anal fibrosis but, even in the presence of scar tissue, which makes the anal tissues less flexible, it seems not to result in the same evolution toward stiffness that we observed after treatment with infliximab. Even considering the limit of the small number of patients treated so far, combined treatment with surgical sanitization of the sepsis and local injection of adalimumab seems to be a promising alternative treatment for those patients who do not respond to infliximab, either systemic or locally administered. However, our feeling is that it could be considered a first-line therapy in selected patients. Welldesigned controlled randomized trials are required to confirm the data and define the role of such cure in the treatment algorithm of complex perianal Crohn’s disease. Finally, concerning the dose finding, we think that half the dose we are actually using could be adequate to obtain the same good results, so that it is conceivable to require the companies to produce dedicated doses for local injection, with even lower related costs.

Risk of permanent stoma in extensive Crohn's colitis: the impact of biological drugs.

The overall risk of permanent stoma was determined in patients with extensive Crohns colitis. An attempt was made to analyse whether biological drugs have modified the surgical approach in patients with anorectal involvement.

Eviendep® reduces number and size of duodenal polyps in familial adenomatous polyposis patients with ileal pouch-anal anastomosis

AIM To evaluate if 3 mo oral supplementation with Eviendep® was able to reduce the number of duodenal polyps in familial adenomatous polyposis (FAP) patients with ileal pouch-anal anastomosis (IPAA). METHODS Eleven FAP patients with IPAA and duodenal polyps were enrolled. They underwent upper gastrointestinal (GI) endoscopy at the baseline and after 3 mo of treatment. Each patient received 5 mg Eviendep twice a day, at breakfast and dinner time, for 3 mo. Two endoscopists evaluated in a blinded manner the number and size of duodenal polyps. Upper GI endoscopies with biopsies were performed at the baseline (T0) with the assessment of the Spigelman score. Polyps > 10 mm were removed during endoscopy and at the end of the procedure a new Spigelman score was determined (T1). The procedure was repeated 3 mo after the baseline (T2). Four photograms were examined for each patient, at T1 and T2. The examined area was divided into 3 segments: duodenal bulb, second and third portion duodenum. Biopsy specimens were taken from all polyps > 10 mm and from all suspicious ones, defined by the presence of a central depression, irregular surface, or irregular vascular pattern. Histology was classified according to the updated Vienna criteria. RESULTS At baseline the mean number of duodenal detected polyps was 27.7 and mean sizes were 15.8 mm; the mean Spigelman score was 7.1. After polypectomy the mean number of duodenal detected polyps was 25.7 and mean sizes were 7.6 mm; the mean Spigelman score was 6.4. After 3 mo of Eviendep bid, all patients showed a reduction of number and size of duodenal polyps. The mean number of duodenal polyps was 8 (P = 0.021) and mean size was 4.4 mm; the mean Spigelman score was 6.6. Interrater agreement was measured. Lesions > 1 cm found a very good degree of concordance (kappa 0.851) and a good concordance was as well encountered for smaller lesions (kappa 0.641). CONCLUSION Our study demonstrated that short-term (90 d) supplementation with Eviendep® in FAP patients with IPAA and with recurrent adenomas in the duodenal mucosa, resulted effective in reducing polyps number of 32% and size of 51%.

1006 Combination of Laparoscopy and Enhanced Recovery Program Improves Outcomes After Ileocecal Resection for Crohn's Disease

Activation of sweet taste receptors may enhance glucose uptake several fold in rat intestine. AIM: To explore mechanisms of sweet taste receptor activation in glucose uptake in 3 intestinal cell lines. HYPOTHESIS: The artificial sweetener, acesulfame potassium (AceK), increases glucose uptake via activating sweet taste receptors to induce translocation GLUT2 to the apical membrane through the PLC βII pathway. METHODS: Caco-2, RIE-1, and IEC-6 cells (human, rat, and rat intestinal cell lines) were seeded on a 24-well plate at a density of 4x104 cells/cm2 in growth culture media and left to differentiate for 15 days after confluence. Caco-2 and RIE-1 cells express GLUT2, while IEC-6 cells do not. Cells were starved from glucose for 1 h and pre-incubated with and without 10 mM AceK for 30 min. Glucose uptake was measured by incubating the cells for 1 to 10 min with 0.5-50 mM glucose with and without 10 mM AceK. 14C-D-glucose was used to measure stereospecific, transporter-mediated uptake and 3H-L-glucose to measure passive uptake with or without the inhibitors 10 μM U-73122, a PLC βII inhibitor, 10 μM chelerythrine, a PKC inhibitor, and 2 μM cytochalasin B, a microtubular system disrupter. Glucose uptake was stopped by adding ice-cold PBS; cells were washed with PBS 2 times and solubilized with 0.1 N NaOH. All experiments were done on at least 3 separate occasions in triplicate. RESULTS: In Caco2 and RIE-1 cells, 10 mM AceK increased carrier-mediated glucose uptake by 20-30% at apical glucose concentrations >25 mM (p 25 mM) glucose concentrations during the 5-min incubation; chelerythrine and cytochalasin B had similar effects. No effect was seen in IEC-6 cells. CONCLUSION: The artificial sweetener AceK, a known sweet taste receptor agonist, has no effect on glucose uptake in low ( 25 mM) in our cell culture models when GLUT2 translocation occurs. The role of artificial sweeteners on glucose uptake appears to act in part by effects on the enterocyte itself. (Support: NIH DK39337-MGS)

Ileoanal Pouches and Indeterminate Colitis

Correct diagnosis of IC has become essential in the “pouch era” for the good outcome of patients submitted to IPAA.