Piero Bazzi

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.

Laparoscopic Surgery for Recurrent Crohn's Disease

In spite of the recent improvements in drug therapy, surgery still represents the most frequent treatment for Crohns disease (CD) complications. Laparoscopy has been widely applied over the last twenty years in colorectal surgery and was associated with lower postoperative pain, shorter hospitalization, faster return to daily activities, and better cosmetic results. Laparoscopy experienced a slower diffusion in inflammatory bowel disease surgery than in oncologic colorectal surgery, but proved to be safe and effective, and is currently considered the gold standard for the treatment of primary uncomplicated ileocolic CD. Indications for laparoscopy in CD have recently been widened to embrace more complicated or recurrent CD. This paper reviews the available data on the subset of recurrent CD patients. The reported results indicate that laparoscopy may be safely applied even in selected recurrent CD cases in hands of IBD surgeons with broad laparoscopic experience.

Surgical Approach to Ulcerative Colitis: When is the Best Timing after Medical Treatment?

Ulcerative colitis (UC) is a chronic inflammatory condition of the mucosa affecting the rectum and extending up the colon in a continuous manner. Its etiology is unknown, but is most probably the result of the interaction of genetic and environmental factors. Approximately 30% of UC patients will need to undergo surgery at some point during their lifetime, despite progresses made in medical therapies. Indications for surgery include acute severe colitis with its complications, steroid-or antiTNF-refractory colitis (or growth impairment in children), and the onset of colorectal dysplasia/cancer. Recently, the introduction of biologic agents has provided a rationale for prolonging medical therapy before considering surgery in the treatment of active, moderate to severe colitis. When surgery becomes indicated, especially in the urgent setting, it usually involves dealing with immunosuppressive medications, possibly impacting the onset of post-operative septic complications. In both acute and chronic settings, patients should be informed about the medical and surgical options and their respective prognoses; the crucial decision regarding the timing for surgery should be shared by both gastroenterologists and colorectal surgeons. The aim of the present review is to highlight surgical indications and options for UC patients as well as the evidence about surgical complications following medical therapies, in order to aid clinicians in determining the best timing for surgery.

Surgical conduct in case of intraoperative detection of a Meckel's diverticulum in Crohn's disease.

Dear Sir, Meckels diverticulum (MD) is a congenital alteration (found in about 2% of the population) due to incomplete involution of the omphalomesenteric tract, appearing as an outpouching of the intestine located approximately 60 cm from the ileocecal valve. Its prevalence among Crohns disease (CD) patients is debated: Andreyev reported a three-fold higher prevalence in pathology specimens after 294 ileocolic resections,1 while Freeman more recently refuted this assertion reporting a 1% prevalence of MD among 877 patients with CD.2 At our institution a 40-year-old woman with a long history of …

Minimally Invasive Surgical Treatment in Crohn’s Disease

Crohn’s disease is a chronic and idiopathic inflammation that can affect any part of the gastrointestinal tract and the terminal ileum is the most frequently involved site; moreover, the first peak of the disease is between 20 and 30 years of age. Surgery plays a very important role in its management: the lifetime risk of surgery is about 70% – 90% [1], for its complications or failure of medical treatment and the reoperation rate is approximately 40% 50% within 10-15 years after the first operation [2]. Laparoscopic colorectal surgery began in the early 90’s; nowadays the equipment development, the surgeons experience and the results of clinical trials lead to affirm the feasibility and safety of laparoscopic surgery, which should be considered as the first line surgical approach in selected patients. In fact, a less surgical trauma should lead to a better preservation of immune response, better cosmetic result, less post-operative pain and faster return of bowel functionality with faster hospital discharge [3].

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.