Alessandra Losco

Epstein-Barr virus-associated lymphoma in Crohn's disease

Although no increased risk of developing lymphoproliferative disorders has been observed in population-based studies of patients with Crohns disease, the possibility has been suggested in the subset of patients previously treated with thiopurine metabolites and suffering from concomitant Epstein-Barr virus infection. A few cases of lymphomas have occurred in patients with Crohns disease treated with infliximab, only one of whom showed the presence of the Epstein-Barr virus genome. We here describe the case of a patient with steroid-dependent ileal Crohns disease treated with azathioprine and a single infusion of infliximab, who developed a diffuse large B cell ileal lymphoma. Epstein-Barr virus genome was detected in the neoplastic cells by means of polymerase chain reaction. Epstein-Barr virus may be detected in the neoplastic tissues of lymphomas of patients with Crohns disease treated with immunosuppressants and infliximab. The identification of such cases may help to define the frequency of this association and how to manage the lymphoproliferative disorder.

The use of methotrexate for treatment of inflammatory bowel disease in clinical practice

BACKGROUND Methotrexate is considered a treatment for Crohns disease, whilst few data in ulcerative colitis are available. AIM To evaluate frequency, indications, efficacy and safety of methotrexate in inflammatory bowel disease patients. METHODS 5420 case histories were reviewed. RESULTS Methotrexate was prescribed to 112 patients (2.1%; 89 Crohns disease, 23 ulcerative colitis). It was the first-line immunosuppressive option in 32 (28.6%), it was an alternative drug due to toxicity or failure of thiopurines in 80 (71.4%). Steroid-dependence represented the main indication both when it was used as first (13/32, 40.6%) and second option (41/80, 51.2%). Efficacy was considered optimal in 39/112 (34.8%), partial in 29/112 (25.9%), absent in 22/112 (19.6%), not assessable in 22/112 (19.6%). Side effects happened in 49 out of 112 patients (43.7%) (39 Crohns disease, 10 ulcerative colitis), leading to drug discontinuation in 38 (33.9%). The occurrence of side effects was approximately fivefold higher in patients who did not receive folic acid (14/19, 73.7%) than in those who did (35/93, 37.6%): odds ratio 4.64, 95% confidence interval 1.54-14.00; p=0.005. CONCLUSIONS The use of methotrexate appears to be negligible in clinical practice. However, our results suggest that, if appropriately used, methotrexate could be more widely administered to inflammatory bowel disease patients with complicated disease.

Assessing the activity of perianal Crohn's disease: Comparison of clinical indices and computer-assisted anal ultrasound

Background: Assessing perianal disease activity is important for the treatment and prognosis of Crohns disease (CD) patients, but the diagnostic accuracy of the activity indices has not yet been established. The aim of this study was to determine the accuracy and agreement of the Fistula Drainage Assessment (FDA), Perianal Disease Activity Index (PDAI), and computer‐assisted anal ultrasound imaging (AUS). Methods: Sixty‐two consecutive patients with CD and perianal fistulae underwent clinical, FDA, PDAI, and AUS evaluation. Perianal disease was considered active in the presence of visible fistula drainage and/or signs of local inflammation (induration and pain at digital compression) upon clinical examination. The AUS images were analyzed by calculating the mean gray‐scale tone of the lesion. The PDAI and gray‐scale tone values discriminating active and inactive perianal disease were defined using receiver operating characteristics statistics. Results: Perianal disease was active in 46 patients. The accuracy of the FDA was 87% (confidence interval [CI]: 76%–94%). A PDAI of >4 and a mean gray‐scale tone value of 117 maximized sensitivity and specificity; their diagnostic accuracy was, respectively, 87% (CI: 76%–94%) and 81% (CI: 69%–90%). The agreement of the 3 evaluations was fair to moderate. The addition of AUS to the PDAI or FDA increased their diagnostic accuracy to respectively 95% and 98%. Conclusions: The diagnostic accuracy of the FDA, PDAI, and computer‐assisted AUS imaging was good in assessing perianal disease activity in patients with CD. The agreement between the techniques was fair to moderate. Overall accuracy can be increased by combining the FDA or PDAI with AUS.

Computer-assisted evaluation of perianal fistula activity by means of anal ultrasound in patients with Crohn's disease

OBJECTIVES:Assessment of the activity of perianal fistulas may be of clinical relevance in patients with Crohns disease. Fistula activity is currently evaluated by means of magnetic resonance imaging; anal ultrasound can also be used, but its diagnostic performance in this setting remains to be defined. Our aims were to evaluate the agreement between clinical examination, magnetic resonance imaging, and anal ultrasound in assessing perianal fistula activity, and to apply computerized analysis to improve the assessment of ultrasound images.METHODS:Thirty-one consecutive patients with Crohns perianal fistulas underwent clinical examination, and magnetic resonance and anal ultrasound imaging. Active fistulas were defined as the presence of active drainage or signs of local inflammation on clinical examination, and the definition was confirmed by surgical examination. Activity was assessed on the basis of T2 hyperintensity on magnetic resonance imaging and the degree of hypoechogenicity on anal ultrasound; the anal ultrasound images were also analyzed using dedicated computer image-analysis software.RESULTS:Twenty-five patients had an active fistula at clinical examination. The agreement between clinical examination and magnetic resonance imaging was good (k-value = 0.739), whereas that with anal ultrasound was only fair (k-value = 0.266–0.294); computer-assisted analysis of the anal ultrasound images improved the agreement from fair to good (k-value = 0.608–0.670).CONCLUSIONS:Anal ultrasound can be used to assess fistula track activity in patients with Crohns disease. The diagnostic performance of the technique can be improved to values comparable with those of magnetic resonance imaging by using a computer-assisted evaluation of the anal ultrasound images.

Incidence and clinical outcomes of intersphincteric abscesses diagnosed by anal ultrasonography in patients with crohn's disease

Background: Intersphincteric abscesses have been reported as uncommon manifestations of perianal Crohns disease (CD) in surgical series, and may be diagnosed earlier by means of anal ultrasonography. The aim of this study was to evaluate the incidence and outcomes of intersphincteric abscess in a prospective cohort of patients with CD referred for perianal symptoms. Methods: Of the 420 patients with CD attending our outpatient clinic over a period of 5 years, 55 (31 males, mean age 38 ± 13 years) underwent anal ultrasonography because of newly developed symptoms suggesting perianal disease; a clinical evaluation and perianal examination was performed on the same day. Results: An intersphincteric abscess was diagnosed in 23 (42%) of the 55 patients with perianal symptoms, for a total cumulative 5‐year incidence of 5% (95% confidence interval [CI]: 3%–7%). During a median follow‐up period of 23 months (range 6–53), four of these patients required surgery, four developed a perianal fistula or small ischiorectal abscess not requiring surgery, and 15 experienced a benign course. The patients with a benign course had a longer duration of CD at the time of onset of the perianal symptoms. Conclusions: Intersphincteric abscesses frequently cause perianal symptoms in patients with CD, and their clinical outcomes vary from rapidly progressive inflammation to a benign self‐limiting course. The favorable outcome observed in some patients supports a first‐line conservative approach to the condition. (Inflamm Bowel Dis 2011;)

Clinical nutrition practice in Italian Gastroenterology Units

BACKGROUND Nutritional status affects the course, ensuing complications and prognosis of virtually all diseases. AIMS To define the role of nutrition in Gastroenterology Units by means of two investigations that analyse: a) availability of devices for assessing nutritional status; b) nutritional treatment in clinical practice: incidence and frequency of indications for its use, together with type of treatment adopted. PATIENTS AND METHODS Two questionnaires were sent to Italian Academic and Hospital Gastroenterology Units, all with clinical wards. RESULTS Results refer to 27 Units, 22 of which took part in both parts of the analysis, enrolling 547 patients during the two-week study The first analysis shows that scales and the altimeter are not available everywhere, while more specific tools, such as skinfold calipers are available in 54% of the Units, and caloric intake can be assessed in 22-41%. The second analysis reveals that nutritional treatment was necessary in 50% of patients in the series examined, and that this was taken into account and prescribed in almost all cases (91%). Of the patients treated, 69% received dietetic supplementation and 31% artificial nutrition [12% enteral, 88% parenteral), although supportive parenteral nutrition is often contraindicated in conditions where good bowel function provides the conditions for enteral nutrition. CONCLUSION Data emerging from the investigation showed that i) artificial nutrition is commonly used in gastroenterology Units in Italy although 23% of them never consider either enteral or parenteral nutrition as medical treatment of gastrointestinal disease; ii) malnutrition is a very frequent complication (mean 27%; range 4-55%0) in Gastroenterology Unit patients albeit only 42% of malnourished patients received artificial nutrition; iii) indications for enteral and parenteral nutrition are not always respected, as there is an excessive use of parenteral nutrition and an unjustified resistance to the use of enteral nutrition; iv] nutritional treatment is often administered without adequate nutritional assessment and without a complete adherence to the standards recommended for preparation of parenteral bags, supported by suitable technology; v) only two Gastroenterology Units report admitting and following patients in a home parenteral nutrition programme; vi) this investigation probably reflects the response of those Gastroenterology Units most aware of the importance of nutritional problems. Better awareness of correct practices for nutritional support should be promoted, encouraging greater use of diagnostic and monitoring techniques and a more discerning choice of the most suitable type of artificial nutrition to be administered in gastroenterology

Drug side-effects in IBD

Sirs, We read with interest the review article by Cunliffe and Scott, who propose a practical scheme for the monitoring of the main groups of drugs used in inflammatory bowel disease. However, although the authors considered the haematological, renal, hepatic and bone mineral side-effects of 5-aminosalicylates, thiopurines, methotrexate and corticosteroids, they did not consider pancreatic sideeffects. The risk of pancreatic toxicity amongst patients taking thiopurines is not negligible. Drug-induced pancreatitis has been reported in 3.25% of a group of such patients, which occurred during the first 5 weeks of treatment in all but one case. Pancreatitis is also an absolute contraindication to continued therapy and recurs with the re-introduction of either azathioprine or mercaptopurine. 4 As pancreatic enzyme levels are high in 8– 21% of patients with inflammatory bowel disease, and this increase is associated with more extensive and active disease, the monitoring of serum amylase and lipase may not be helpful in preventing pancreatic sideeffects, but the possibility of drug-induced pancreatitis in the presence of acute abdominal pain during treatment should at least have been mentioned.

P.81 IS METHOTREXATE FOR INFLAMMATORY BOWEL DISEASES UNDERUSED IN CLINICAL PRACTICE

IS METHOTREXATE FOR INFLAMMATORY BOWEL DISEASES UNDERUSED IN CLINICAL PRACTICE? S. Saibeni∗ ,1, S. Bollani 1 , A. Losco2, A. Michielan3 , G. Lupinacci 4, L. Pirola5, C. Cucino6, G. Meucci 7, G. Basilisco8, R. D’Inca3, S. Bruno1 1Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milano; 2Universita degli Studi di Milano, Milano; 3Department of Surgical and Gastroenterological Sciences and University of Padua, Padova; 4Azienda Ospedaliera “Ospedale Maggiore”, Crema; 5Azienda Ospedaliera San Gerardo, Monza; 6Istituto Clinico Citta Studi, Milano; 7Ospedale San Giuseppe, Milano; 8Fondazione IRCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano

SMALL BOWEL ULTRASOUND (US) AND COMPUTED TOMOGRAPHY ENTEROGRAPHY (CT): CHARACTERISTICS OF BOWEL WALL AND MESENTERIC TISSUE IN THE FIRST DIAGNOSIS OF ILEAL CROHN'S DISEASE (CD)

recorded from 12 rats 10 hrs after cisplatin (5 mg/kg). Basal firings increased to 9.5±3.5 impulses/20s. 12/45 neurons responded to SP. SP 5 and 10 μg/kg increased firings to 27 ± 4, and 64±7 impulses/20 s, respectively. 7/12 SP sensitive neurons also responded to 5HT. Luminal perfusion of 10-7M increased firings to 17±3 impulses/20 s. Combined 10-7M 5-HT and 5, 10 μg/kg of SP enhanced neuronal firings to 60 ± 5, and 133±11 impulses/ 20 s, respectively. Western blot studies demonstrated a 1.1 fold increase in NK1 receptor expression but no change in 5HT3 receptor in the NG 10 hrs following cisplatin. Similar increase in vagal NK1 receptor expression was observed with perfusion of 5-HT (10-5M) for 5 hrs. Administration PCPA, a 5-HT synthesis inhibitor suppressed cisplatin-induced increased in NK1 receptor and completely abolished the enhanced neuronal responses to SP. Conclusion: Anti-cancer therapy with cisplatin causes plastic changes in the NG characterized by upregulation of NK1 receptor in the vagal NG. This is mediated by the 5-HT pathways. Enhanced activation of NK1 receptor in the vagal afferent neurons and its interaction with 5-HT appear to be responsible for the delay emesis observed in anti-cancer chemotherapy.