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Background Pouchitis and other inflammatory disorders of the pouch (IDP), such as Crohn′s-like disease of the pouch (CDP), are frequent in patients operated for a previous diagnosis of ulcerative colitis. Many different therapies have been used, but the effectiveness of immunosupresants (IMM) has been poorly explored in this setting. Our aim was to evaluate the use, efficacy and safety of IMM in patients with pouchitis or another IDP. Methods Retrospective and multicentric study of a Spanish cohort of pouch-carrying patients with previous diagnosis of ulcerative colitis, and subsequent diagnosis of IDP, following ECCO diagnostic criteria. Patients who used IMM to treat these conditions were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission, and non-response as no improvement or worsening symptoms. Endoscopic response was evaluated when possible using modified pouchitis disease activity index (PDAI) endoscopic subscore. Adverse events were collected. We used descriptive statistics. Results In the overall cohort of 338 patients with IDP, 93 (27%) were treated with IMM. Of those, 57% males, median age 40 (20-71) ys, and 72% non-smokers. Colectomy was performed at a median age of 31 (18-63) ys and IPD was diagnosed 25 (1-235) months after ileostomy closure. IMM used were thiopurines (n=86), methotrexate (n=4), cyclosporine (n=2) and tacrolimus (n=1). IMM were used as monotherapy in 66 (71%) cases and were indicated as treatment of pouchitis (n=60, 65%), CDP (n=32, 34.4%) and cuffitis (n=1, 1%). Effectiveness was evaluated only for thiopurine monotherapy (n=62). After a median follow-up of 23 (1-234) months, clinical remission was achieved in 31%, clinical response in 31% and non-response in 38% (Figure 1). There were no differences in effectiveness between pouchitis and CDP (63.9% vs 57.7%, p= 0.62). Endoscopic response was evaluated in 19 (30.6%) cases. After a median of 9 months of follow-up median PDAI endoscopic subscore dropped from 3 (range 2-4) to 1 (range 0-3), (Figure 2). Adverse events related with treatment appeared in 28 patients (45%). Thiopurines were discontinued in 39 cases (63%) due to failure (17), toxicity (16) and long remission (6 cases). Conclusion In our cohort, thiopurines were used in 27% of patients with IDP, with long-term benefit (remission or response) in around two-thirds of them. This therapy could be one more option to manage these disorders.

Background Pouchitis and Crohn′s-like disease of the pouch (CDP) can be refractory to conventional therapy. Evidence of biological therapy has been rarely reported in large patient cohorts. We explored the use and effectiveness of these therapies and compared the success of a second biologic after antiTNF failure. Methods This is a retrospective RESERVO study of the Spanish cohort of GETECCU, that included patients operated for ulcerative colitis, with pouch construction, and subsequent diagnosis of pouchitis, CDP or cuffitis second ECCO diagnostic criteria1. Patients treated with antiTNF, Vedolizumab and/or Ustekinumab were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission and non-response as no change or worsening of these symptoms. We also compared the effectiveness of second biologic (antiTNF vs vedolizumab-ustekinumab) after antiTNF failure, using descriptive and comparative statistics. Results The cohort comprised 145 patients. Demographic and clinical characteristics are represented in Table 1. A total of 232 biologic therapies were indicated. Of the total cohort, 60 (41.3%), 21 (14.4%) and 6 (4.1%) used two, three and four lines, respectively. Biologics used were Infliximab (n=95), Adalimumab (n=69), Vedolizumab (n=35), Ustekinumab (n=26) and Golimumab (n=7). Therapy characteristics, clinical effectiveness, need for intensification, discontinuation, and therapy duration for each biological therapy are represented in Table 2. Global rates of clinical remission, response, non-response and loss of response to a first biologic were 21.8%, 27.5%, 21.1% and 29.6%. Female gender was the only factor associated with effectiveness to a first biologic in univariate analysis (OR 2.16, CI 1.08–4.32, p 0.027). There were no significant differences regarding efectiveness between type of pouch disorder (pouchitis vs CDP, 51.6 vs 47.6%, p 0.48) or biologic agents. Thirty-nine patients received a second biologic after prior antiTNF failure (28 a second antiTNF and 11 non-antiTNF: 6 Vedolizumab, 5 Ustekinumab). Basal characteristics in this subgroup showed no significant differences. Clinical response (21.4 vs 63.6%, p 0.02) and discontinuation therapy rates (82.2 vs 54.5 %, p 0.04) after 11 months showed a more favorable profile for non-antiTNF therapy. Conclusion Biologics represent an effective option in the management of pouchitis and Crohn′s like disease of the pouch. Despite our small sample size, non-antiTNF therapy could be the best option after antiTNF failure. 1Fernando Magro. J Crohns Colitis 2017; 11(6): 649–670.

Background Adalimumab (ADA) dose escalation from 40 mg SC every other week (EOW) to 40 mg weekly is approved for IBD patients with loss of response. A recently registered device containing 80 mg of ADA will allow an alternative dose escalation regimen with SC doses of 80 mg EOW. The ADASCAL study aimed to evaluate the preferences and satisfaction of patients with modifying the ADA regimen from 40 mg weekly to 80 mg EOW. Methods This multicentre cross-sectional study included patients with IBD in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW according to clinical practice. Patients who have received at least 4 doses of 80 mg EOW completed a 4-item self-questionnaire (a Likert-like 5-point scale for preferences, 2 closed questions for convenience, and a 100-point visual analogue scale [VAS] to evaluate patient’s preference for weekly or EOW ADA) (Figure 1); and the 14-item Treatment Satisfaction Questionnaire for medication (TSQM 1.4) that covers 4 domains: effectiveness, side effects, convenience, and overall satisfaction. Results Seventy-seven patients (64 CD, 13 UC; 67.5% men; mean age 48 years, SD 14.1) were included. The overall mean duration of exposure to ADA was 66 months (SD 34), with mean exposure to ADA 40 mg weekly of 40 months (SD 25), and mean exposure to ADA 80 mg EOW of 12 months (SD 5). At the time of the survey, 87.1% of CD patients and all UC patients were in clinical remission (Harvey-Bradshaw index ≤4 for CD, Partial Mayo score ≤1 for UC). According to the results of the questionnaires, 74% of the patients preferred the 80 mg EOW ADA regimen (59.7% had a strong preference and 14.3% had a slight preference) (Figure 1). Patients referred that ADA EOW regimen interferes less with daily activity and with travel plans. Most patients wanted to continue with ADA 80 mg EOW, as reflected by a mean VAS score of 84.7 (SD 24.1), where 0 indicated a choice for weekly ADA, 100 for ADA EOW, and 50 indifferent. Overall, 77% of patients preferred to continue with ADA EOW, 4% with ADA weekly, and 17% were indifferent. Attending physicians also reported a greater preference for the EOW ADA regimen (mean VAS score 93, SD 7.8). The mean global satisfaction according to the TSQM was 84.3% (SD 13.5), where 0 indicated extremely dissatisfied and 100 extremely satisfied. Patients reported very high TSQM scores for individual components: effectiveness 77.6% (SD 16.9), convenience 83.7% (SD 14.5), and side effects 86.1% (SD 23.4). Conclusion IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen. TSQM results indicated that patients had a high level of satisfaction with the current EOW regimen. Therefore, most patients wanted to continue with ADA 80 mg EOW.

Background The aim of this study was to investigate the association of serum golimumab concentrations (SGC) during maintenance therapy in UC with clinical outcomes including endoscopic and histologic healing. Methods This multicentre, cross-sectional cohort study included UC patients who had received at least 5 maintenance doses of golimumab. A colonoscopy was scheduled, and study-specific recto-colonic biopsies were taken for blind central histologic reading. Samples for trough SGC and anti-golimumab antibodies (AGA) were collected on the day of the scheduled golimumab administration closest to the colonoscopy. Definitions: clinical remission = partial Mayo score (PMS) ≤2 with no individual subscore >1, combined clinical-biochemical remission = PMS ≤2 + faecal calprotectin Results Fifty-two patients were included. The overall median SGC was 1.79 µg/ml (interquartile range [IQR] 0.87–2.79). Three patients (5.7%) had undetectable SGC together with positive AGA. With a median of 23 [IQR 15–32] months of golimumab therapy, 46 patients (88%) were in clinical remission, 26 (52%) had combined clinical-biochemical remission, 18 patients (35%) had both endoscopic healing and deep remission, 21 (40%) had histologic remission, and 14 (27%) had disease clearance. Median SGC were significantly higher in patients who were in clinical remission (2.01 versus 0.72 µg/mL, P=0.047) µg/mL, combined clinical-biochemical remission (2.21 versus 1.47 µg/mL, P=0.041), mucosal healing and deep remission (2.52 versus 1.47 µg/mL, P=0.003), histologic remission (2.33 versus 1.50 µg/mL, P=0.02), and disease clearance (2.52 versus 1.70 µg/mL, P=0.009), compared with those not meeting these criteria. (Figure 1) The higher SGC quartiles were associated with higher rates of mucosal healing (P=0.005), and histologic remission (P=0.006). (Figure 2) Receiver-operating characteristic analyses identified SGC thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.65], 2.29 [0.75], and 2.29 [0.72] µg/mL be associated with clinical remission, combined remission, deep remission, and disease clearance, respectively. (Table 1) On multivariate analysis, body mass index (P=0.021) and CRP level (P=0.040) were linearly associated with lower SGC, and concomitant immunosuppressant with higher SGC (P=0.47). (Table 2) Conclusion We identified SGC thresholds during maintenance most closely associated with clinical outcomes including endoscopic and histologic healing. Higher SGC are needed to achieve increasingly stringent therapeutic targets.

Background Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

Background Perianal Crohn’s disease (pCD) is difficult to treat. Although anti-TNF, are the medical mainstay in fistula treatment, many patients become refractory. Recent data suggested that ustekinumab (UST) might be effective in pCD. This study aims to assess the effectiveness of UST in refractory pCD in the real-world practice. Methods This is a retrospective cohort of patients with pCD treated with UST in our IBD Unit between march 2015 and october 2020. We analyze demographics, disease charactersistics, surgical for pCD and prior exposure including inmunomodulators and biologic agents. The success of UST was defined on the physician judgment (improvement or absence of drainage). In patients with inactive pCD we analyzed rate of relapse. To analyze predictive factors of treatment success we performed a univariate and multivariable analysis. Results Fifty three patients were included (54.72 % female). Twenty four of them were smokers. The median age was 54 years (45–62). The mean duration of CD was 19 years and 50.94% had an intestinal resection. Fifty one patients (96,22%) had been treated with at least 1 anti-TNF and 38 (71.7%) with at least 2 anti-TNF. Sixteen had failed to vedolizumab. The median follow-up was 26 months (15–36). Twenty two (22/53) had active pCD. Eleven (50%) had intensified UST out of technical sheet (8 with 90 mg sc every 4 to 6 w, and 3 had 130 mg iv every 4 w). Fifteen patients (68.18 %; p Two of 32 patients (6.45%) with inactive pCD relapsed during the follow-up. Eleven patients (20.75%) discontinued UST: 6/53 (11.3%) due to adverse events (infections and arthralgia), 4/53 (7,54) patient′s choice or physician judment. One patient who had been treated with four biologics before UST developed a pleomorphic cutaneous sarcoma Conclusion Ustekinumab might by an effective treatment in refractory pCD. More studies are needed to confirm our data

To evaluate the use of health care resources and the associated costs of complex perianal Crohn's disease (CD) from the National Health System perspective.We conducted a multicenter, retrospective, observational study in which gastroenterologists from 11 hospitals in the Community of Madrid took part. Data was collected on the direct healthcare resources (pharmacological treatments, surgical procedures, laboratory/diagnostic tests, visits to specialists and emergency departments, and hospitalizations) consumed by 97 adult patients with complex perianal CD which was active at some point between January 1, 2005, and case history review.We recorded 527 treatments: 73.1% pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and 26.9% surgical. Mean annual global cost was €8,289/patient, 75.3% (€6,242) of which was accounted for by pharmacological treatments (€13.44 antibiotics; €1,136 immunomodulators; €5,093 biological agents), 12.4% (€1,027) by hospitalizations and surgery, 7.7% (€640) by medical visits, 4.2% (€350) by laboratory/diagnostic tests, and 0.4% (€30) by emergency department visits.Pharmacological therapies, and in particular biological agents, are the main cost driver in complex perianal CD; costs due to surgery and hospitalizations are much lower.

To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response.Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed.174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to every week. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them.Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab.

Efficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response.Multicenter retrospective survey of all CD patients treated with infliximab in 8 University hospitals of the Madrid area (Spain) with a minimum follow up of 14 wks.169 patients included (48%males, mean age 39 +/- 12 yrs). 64% of them had perianal disease. 82% were under immunosuppressants. 1,355 infliximab infusions administered (mean 8, range 1-30). 90% response rate and 48% remission rate were obtained with induction therapy. 73% followed maintenance treatment, and 78% of them maintained or improved the response after a mean follow up of 28 months (range 3.5-86). 24 patients lost response during the follow up, after a mean of 41 wks (range 6-248). Only the prescription of maintenance therapy was predictive factor for favourable response (p0.01). 17 infusion reactions were reported (10% of the patients, 1.2% of the infusions; only one case was severe) and were the cause of treatment withdrawal in 7 patients. Co-treatment with immunosuppressive drugs and maintenance infliximab therapy were protective factors for infusion reactions (p0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients.Infliximab is effective and safe for CD management but concomitant immunosuppressive drugs and maintenance treatment should be prescribed to obtain the best outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials.

MP Martínez-Montiel, B Casis-Herce , GJ Gómez-Gómez, A Masedo-González, C Yela-San Bernardino, C Piedracoba, G Castellano-Tortajada Division of Gastroenterology, Hospital 12 de Octubre, Madrid, SpainAbstract: Although corticosteroids are an effective treatment for induction of remission in inflammatory bowel disease (IBD), many patients are dependent on or refractory to corticosteroids. This review is based on scrutinizing current literature with emphasis on randomized controlled trials, meta-analyses, and Cochrane reviews on the management of IBD refractory to corticosteroids. Based on this evidence, we propose algorithms and optimization strategies for use of immunomodulator and biologic therapy in IBD refractory to corticosteroids.Keywords: immunomodulators, anti-tumor necrosis factor alpha, Crohn's disease, ulcerative colitis, drug levels, treatment optimization

Background and aims: P atients with inflammatory bowel disease [IBD] are at increased risk for developing some types of neoplasia. Our aims were to determin the risk for cancer in patients with IBD and to describe the relationship with immunosuppressive therapies and clinical management after tumor diagnosis. Methods: R etrospective, multicenter, observational, 5-year follow-up, cohort study. Relative risk [RR] of cancer in the IBD cohort and the background population, therapeutic strategies, and cancer evolution were analyzed. Results: A total of 1 45 cancers were diagnosed in 133 of 9100 patients with IBD (global cumulative incidence 1.6% vs 2.4% in local population; RR = 0.67; 95% confidence interval [CI]: 0.57–0.78). Patients with IBD had a significantly increased RR of non-melanoma skin cancer [RR = 3.85; 2.53– 5.80] and small bowel cancer [RR = 3.70; 1.23–11.13]. After cancer diagnosis, IBD treatment was maintained in 13 of 27 [48.1%] patients on thiopurines, in 2 of 3 on methotrexate [66.6%], none on anti-TNF-α monotherapy [n = 6] and 4 of 12 [33.3%] patients on combined therapy. Rate of death and cancer remission during follow-up did not differ [p > 0.05] between patients who maintained the treatment compared with patients who withdrew [5% vs 8% and 95% vs 74%, respectively]. An association between thiopurines [p = 0.20] or anti-TNF-α drugs [p = 0.77] and cancer was not found. Conclusions: P atients with IBD have an increased risk for non-melanoma skin cancer and small bowel cancer. Immunosuppresive therapy is not related to a higher overall risk for cancer or worse tumor evolution in patients who maintain these drugs after cancer diagnosis.

T lymphocytes play a crucial role in the pathogenesis of inflammatory bowel disease. Achieving stable T-cell lines, rather than continuous bleeding of patients, is desirable in order to dissect their implication in the disease.Long-lasting T-cell lines from patients with Crohn disease and ulcerative colitis and from healthy volunteers have been obtained by transformation of T lymphocytes using the lymphotropic Herpesvirus saimiri. Lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells.Fresh cells revealed only minor differences between patients and controls, with regard to phenotype and proliferative capacity. In contrast, the use of T-cell lines showed that cells from Crohn disease patients, but not ulcerative colitis patients, over-responded to several membrane or cytoplasmic stimuli when compared to control T-cell lines. Thus, higher responses were found when stimulated with alphaCD3 and IL2, alphaCD3 and alphaCD28, IL2 alone, phorbol esters (PMA) and alphaCD3 and, finally, PMA and alphaCD2 (P0.05 in all instances). Further, lines from patients with Crohn disease responded more vigorously to alphaCD3 and alphaCD28 or alphaCD3 and PMA when compared to ulcerative colitis (P0.05 in both instances).The data obtained with these lines suggest that T cells from patients with Crohn disease differ in vivo in their proliferative capacity, as compared with those from ulcerative colitis patients, a finding that may reflect the clear Th-1 phenotype found in the former and absent in the latter.

We describe the case of a 58-year-old woman with autoimmune enteropathy associated with thyroiditis, gastritis, transitory neutropenia, sicca syndrome and severe axonal polyneuropathy of autoimmune origin. Enterocyte autoantibodies were not detected. However, predisposition to autoimmune disease was indicated by the presence of high titres of anti-gastric parietal cell, anti-thyroglobulin, anti-thyroid peroxidase and anti-neutrophil antibodies. CD4+ and CD8+ lymphocytes were equally distributed in the lamina propria of the small intestine, but CD8+ cells were highly represented among intraepithelial lymphocytes.

A case is reported of collagenous gastrobulbitis on collagenous colitis in a 57-year-old woman with a 6-month history of watery diarrhea. Low serum levels of total proteins and albumin and increased fecal elimination of alpha1-antitrypsin were the only abnormal laboratory test results. Biopsy specimens from the colon, rectum, antrum, fundus, and duodenal bulb showed a thick subepithelial band composed of ultrastructurally normal collagen immunohistochemically negative for collagen IV and laminin. The diarrhea resolved with prednisone and responded to this treatment after a relapse 6 months later. One year later the patient developed severe alimentary intolerance and secondary weight loss. This symptom also responded to the same treatment. However, the collagen deposition did not disappear in the second biopsy samples of colonic and gastric mucosa. Only six cases have been previously reported with gastric and/or duodenal subepithelial collagenous deposition. Four were associated with collagenous colitis. One of these presented a subepithelial collagenous band in the terminal ileum. All these features suggest that this collagen deposition may affect the entire digestive tract with variable intensity, extension, and symptoms.

Introduccion: La ultrasonografia endoanal (USEA) es una tecnica sencilla y de gran utilidad en el diagnostico y manejo terapeutico de las enfermedades anorrectales, mejorando su resolucion espacial con el uso de la sonda en 3D. Objetivo: Estudiar la utilidad de la USEA con la sonda rigida 3D desde su implantacion en nuestro hospital. Material y Metodo: Estudio retrospectivo de las USEA-3D realizadas en nuestro centro desde noviembre-2008 hasta junio-2013. Analizamos las caracteristicas demograficas de los pacientes, indicaciones y diagnosticos. Resultados: Se realizaron 755 USEA (exploraciones/ano: 116/2009; 146/2010; 183/2011; 195/2012; 114/junio-2013); 58% mujeres/42% varones; edad 47 ± 14 anos. Motivos de solicitud: sepsis perianal (fistula y/o absceso) (49%; 367/755); incontinencia (32%; 241/755); proctalgia (6%; 42/755); neoplasia anal (1%; 7/755); otros (12%; 92/755). Procedencia de peticiones: Ap. Digestivo (57%), Cirugia General (39%). Diagnosticos: sepsis perianal (41%); normalidad (25%); defectos esfinterianos (13%); cicatriz obstetrica (9%); otros (12%). La incontinencia se asocio a USEA normal en el 44% de casos; Caracteristicas de las fistulas: transesfinterianas (44%; 140/316); interesfinterianas (32%; 101/316); extraesfinterianas (10%; 32/316); supraesfinterianas (6%; 19/316); otras (8%; 24/316); complejas 59% (186/316); asociadas a Crohn (22%; 71/316). Se inyecto H2O2 en 259/316 (82%), identificandose el orificio fistuloso interno (OFI) en 77% (199/259); Localizacion de abscesos: peri/postanal 66% (93/141), isquiorrectal 24% (34/141), otras 10% (14/141). Conclusiones: 1. En nuestro hospital, el numero de solicitudes de USEA ha aumentado progresivamente (fundamentalmente desde gastroenterologia y cirugia general); 2. La principal indicacion de USEA en nuestra serie ha sido la sepsis perianal; 3. Cerca de la mitad de los pacientes con incontinencia fecal no presentaron alteraciones en la USEA; 4. La fistula perianal fue el diagnostico mas frecuente en nuestro centro; 5. La inyeccion de H2O2 permitio localizar el OFI en el 77% de los casos; 6. El 66% de abscesos se localizaron en el espacio peri/postanal.

Introduction The response of Crohn's disease (CD) to infliximab is initially good, although a loss of efficacy is observed over time. Dose escalation has been recommended in such cases. Aims To study the response to an intensified infliximab regimen in patients with CD; and to evaluate the adverse effects associated with intensification of therapy and identify predictors of loss of response. Methods We performed a retrospective multicenter survey of all patients with CD who had been treated with at least the 3 induction doses of standard infliximab therapy, and for whom treatment had to be intensified due to loss of response. We analyzed the efficacy of the intensified regimen. Results Thirty-three patients were included. After the first intensification dose, 79% of patients had a clinical response (33.5% complete response, 45.5% partial response). In the long term, 83%, 69%, 47%, and 29% of patients who had an initial response to the intensification maintained the response at 6, 12, 18, and 36months, respectively. The loss of efficacy after escalation was 43% per patient-year of follow-up. One patient had an infusion reaction after 36 doses. One patient developed a herpes zoster infection. Conclusions A high proportion of patients whose dose of infliximab is increased due to loss of efficacy respond initially. However, nearly half lose the response after one year. The safety profile of an intensified infliximab regimen is good.

A continuous IV infusion of vasopressin was administrated to a patient with cirrhosis of the liver and acute gastrointestinal bleeding from esophageal varices. In the first 24 hours, the patient developed rhabdomyolysis and cutaneous necrosis. Stopping vasopressin infusion resulted in relief of these lesions. The rarity of these complications suggests an idiosyncratic reaction of susceptible individuals that may be related to previous vascular disease or a failure in baroreceptor regulation.

Hyperhomocysteinemia has been recently described in patients with inflammatory bowel disease (IBD), that could be related to the increased risk for thrombosis that exists in this disease. The aim of this study was the assessment of hyperhomocysteinemia in patients with IBD and its relation among vitamin B12 and folate levels, and methylenetetrahydrofolate reductase (MTHFR) 677C--T and 1298A--C mutations.Fifty two consecutive patients with IBD were studied (29 women and 23 men); age: mean (standard deviation 41.7 [11.9] years) and 186 controls with no difference in age and gender. Hyperhomocysteinemia was considered as homocysteine levels higher than mean plus two standard deviations of the control group (or = 13 micromol/l).patients had an elevated prevalence of hyperhomocysteinemia (17.3 vs. 3.7%; p = 0.002) and lower folate (7.6 [4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499 [287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia was higher (14.3 [5.8] vs. 9.1 [3.9] micromol/l; p = 0.006) in 6 patients (11.5%) that had suffered thromboembolism. Frequency of MTHFR 677C--T (13.5 vs. 11.3%; p = 0.66) and 1298A--C (7.8 vs. 7.0%; p = 0.76) mutations was not increased in patients. Odds ratio (OR) for IBD in hyperhomocysteinemic patient was 5.51, 95% confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemia was negatively associated with feminine gender (OR 0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04, 95%CI: 0.007-0.20; p0.001).hyperhomocysteinemia is associated with IBD and low folate levels, and could be involved in development of thromboembolism. MTHFR 677C--T and 1298A--C mutations are not related with the disease.

We report the case of a patient that developed hepatic hydrothorax as the first complication of liver cirrhosis. Due to the lack of response to diuretics, pleurodesis and TIPS, treatment with octreotide was started with resolution of hydrothorax. To the best of our knowledge, this is the third reported case of refractory hepatic hydrothorax with complete and sustained response to octreotide.

Background: hyperhomocysteinemia has been recently described in patients with inflammatory bowel disease (IBD), that could be related to the increased risk for thrombosis that exists in this disease. The aim of this study was the assessment of hyperhomocysteinemia in patients with IBD and its relation among vitamin B12 and folate levels, and methylenetetrahydrofolate reductase (MTHFR) 677C→ T and 1298A→C mutations. Patients and methods: fifty two consecutive patients with IBD were studied (29 women and 23 men); age: mean (standard deviation 41.7 [11.9] years) and 186 controls with no difference in age and gender. Hyperhomocysteinemia was considered as homocysteine levels higher than mean plus two standard deviations of the control group (≥ 13 ∝mol/l). Results: patients had an elevated prevalence of hyperhomocysteinemia (17.3 vs. 3.7%; p = 0.002) and lower folate (7.6 [4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499 [287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia was higher (14.3 [5.8] vs. 9.1 [3.9] ∝mol/l; p = 0.006) in 6 patients (11.5%) that had suffered thromboembolism. Frequency of MTHFR 677C→T (13.5 vs. 11.3%; p = 0.66) and 1298A→C (7.8 vs. 7.0%; p = 0.76) mutations was not increased in patients. Odds ratio (OR) for IBD in hyperhomocysteinemic patient was 5.51, 95% confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemia was negatively associated with feminine gender (OR 0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04, 95%CI: 0.007-0.20; p < 0.001). Conclusions: hyperhomocysteinemia is associated with IBD and low folate levels, and could be involved in development of thromboembolism. MTHFR 677C→T and 1298A→C mutations are not related with the disease.

Objective To evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn's disease. Methods Consecutive patients with fistulizing Crohn's disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. Results 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (%) rates (partial/complete) depending on fistula location were: enterocutaneous (25/68%), perianal (35/60%), rectovaginal (36/64%), and enterovesical (20/40%). None of the studied variables (including concomitant immunosuppressive therapy) correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21%) depending on the dose of infliximab was: first dose (5.6%), second (7.4%), and third (11.1%). Conclusions Infliximab is an efficacious treatment for fistulizing Crohn's disease. Partial response was achieved in approximately one third of the patients, and complete response in more than half. No studied variable was predictive of response. Adverse effects were relatively infrequent and mild.

DOP071 Inflammatory bowel diseases: a new cardiovascular risk factor? L. Caillo1 *, G. Danan1, V. Georgescu2, L. Papineau1, F. Gonzalez1, J.-F. Bourgaux3, F. Guillon4, G.-P. Pageaux1, R. Altwegg1 *. 1University Hospital of St Eloi, Departement of Hepatology and Gastroenterology, Montpellier, France, 2University Hospital, Department of Medical Information, Montpellier, France, 3University Hospital, Department of Hepatology and Gastroenterology, Nimes, France, 4University Hospital of St Eloi, Department of Digestive Surgery, Montpellier, France

Common variable hypogammaglobulinemia syndrome with lymphoid nodular hyperplasia of the intestine forms part of the so-called hypogammaglobulinemic enteropathies. It is characterized by decreased serum immunoglobulins, recurrent respiratory tract infections and chronic diarrhea. The development of systemic amyloidosis is infrequent, but it can be explained by the multiple infections in this setting. The case of a 47-years old woman with hypogammaglobulinemic enteropathy, who developed systemic amyloidosis is presented. It was manifested as a nephrotic syndrome. The previously published reports include 12 cases of common variable hypogammaglobulinemia with systemic amyloidosis. Half of them presented nephrotic syndrome as a manifestation of their amyloidosis. It is important to keep in mind this complication in these patients' follow-up in order to increase the doses of gammaglobulin. That is the way to compensate their additional losses because of the nephrotic syndrome that they usually develop.

To compare the two most frequently used methods of percutaneous endoscopic gastrostomy: Pull-string Ponsky-Gauderer type and Push-over-wire Sachs-Vine gastrostomy.Forty-four patients with oral feeding incapacity were prospectively randomized to one of the two methods of percutaneous endoscopic gastrostomy. In 22 patients the Ponsky-Gauderer type were used and in the other 22 the Sachs-Vine gastrostomy were employed. In every case the gastrostomy tube was replaced 4-5 months after its placement by a Flexiflo tube. The mean follow-up of the patients was 7.3 months (range: 4-18).Gastrostomy was successful in every case. No differences were found between the two procedures in technical difficulties or complications during gastrostomy placement. Wound infection occurred in 6 patients (13%), 3 in each group, and in all cases it was cured with topic antibiotic treatment administered through the gastrostomy. Tube dislodgement was observed in 3 patients in the Ponsky-Gauderer group (soft internal with-holder). The only significant difference between the two procedures was found at the removal of the gastrostomy tube. In the Sachs-Vine type the removal of the tube was always endoscopically performed (due to the presence of a rigid internal with-holder), while the Ponsky-Gauderer type was always done by traction (soft internal with-holder). No related procedure mortality was found with any of the two techniques.Both percutaneous endoscopic gastrotomy techniques are similar in efficacy, safety and morbidity and they prove to be a valid alternative to surgical gastrostomy in patients with oral feeding incapacity.

The aim of this study was to determine the histogram patterns and the diagnostic efficacy of liver echohistogram in chronic diffuse liver diseases. Abdominal ultrasound and liver echo-histogram were prospectively and blindly performed on 21 healthy controls, 24 patients with chronic hepatitis, 26 patients with liver cirrhosis, and 22 patients with fatty liver disease. Maximum liver echo intensity and echogenicity were decreased in chronic hepatitis. Increased anterior maximum liver echo intensity and echogenicity, decreased posterior maximum liver echo intensity and echogenicity, and reduced posterior/anterior maximum liver echogenicity ratio were found in fatty liver disease. The diagnostic efficacy indexes of abdominal ultrasound were enhanced by some echo-histogram data: anterior maximum echo intensity of the liver less than 20.52 decibels for chronic hepatitis and posterior/anterior maximum liver echogenicity ratio less than 0.231 for fatty liver disease. In liver cirrhosis, echohistogram showed a high dispersion of values and not enhanced the abdominal ultrasound diagnostic efficacy. In fatty liver disease, a positive correlation was found between percentage of hepatocytes with fatty change and anterior maximum echo intensity of the liver (rs = 0.47, p0.05), as well as between percentage of hepatocytes with fatty change and anterior maximum echogenicity of the liver (rs = 0.68, p0.01). These findings indicate that the liver echo-histogram improves the diagnostic efficacy of abdominal ultrasound in chronic hepatitis and fatty liver disease. We suggest that combined abdominal ultrasound and liver echo-histogram should be performed in the investigation of chronic diffuse liver diseases.

Introduction: A significant proportion of Crohn's Disease (CD) patients have already been treated with two biologic therapies. Follow-up from current published retrospective or prospective open label studies on patients who have already received 2 biologics does not extend beyond 1 year (1-4) Methods: Our aim was to collect ‘real-life', long-term data on the tolerability and efficacy of the second biologic agent in (re)-capturing response, and to assess whether the reason for stopping the first agent impacted on the successful use of the second agent. We carried out secure data collection from 3 teaching IBD centres on CD patients currently on, or already failed a second biologic. We collected data on disease duration, distribution and behaviour, and report on the aetiology in the failure of the first biologic and the subsequent outcome of the second biologic agent. Response to biologics was assessed by Harvey Bradshaw Index or Physicians Global Assessment. Results: We collected data on 66 patients (F 46%, mean age at diagnosis: 25). The disease distribution was characterised as L1: 11%, L2:32% L3:56% L4:1% and the behaviour as B1: 41% B2: 35% B3: 24% . 17% of our cohort had perianal involvement. 36 patients have had a total of 41 resectional operations. 1st biologic: 64/66 patients had infliximab (IFX) first-line, followed by adalimumab (ADA), and 2/66 patients had ADA followed by IFX. Reasons for swapping were 1o failure in 23%, secondary-loss of response in 38%, intolerance to the first agent in 29%, and fear of hypersensitivity reaction due to previous episodic exposure to IFX in 10% (irrespective of efficacy or tolerance) 2nd biologic: 70% of patients remained on the second biologic after a median follow-up of 22 months. Reasons for discontinuing therapy were 1o failure in 35%, secondary loss of response in 25%, intolerance (or patient concerns regarding potential side-effects) in 25%, and achieving remission in 5%; no reason provided for the remainder 5%. Neither the demographics, disease characteristics nor the reason for failing the first biologic had a statistically significant bearing in predicting the initial response to and subsequent outcome of the second biologic. Conclusion: 1. We report an overall 70% retention on the second biologic at 22 months following all-cause failure of the first agent in CD patients from England and Ireland. 2. Patients responded equally well to the second biologic, irrespective of the reason for the failure of the first biologic. References: 1.Swaminath A et al, APT 2009 2. Seiderer J et al, APT 2007, Peyrin-Biroulet L et al, APT 2007, 4. Papadakis KA et al, AJG 2005.

Antecedentes La respuesta al tratamiento con IFX es inicialmente elevada, aunque con el paso del tiempo se ha observado, con cierta frecuencia, una perdida de eficacia. En estos pacientes con perdida de respuesta se ha recomendado “intensificar” el tratamiento con IFX. No obstante, se desconoce si el efecto beneficioso de esta estrategia se mantiene en el tiempo o es solo transitorio. Objetivos 1) Estudiar la respuesta (tanto a corto como a largo plazo) de los pacientes que precisan intensificar el tratamiento con IFX (aumentando la dosis o disminuyendo el intervalo). 2) Evaluar los efectos adversos asociados a la intensificacion del tratamiento. Metodos Estudio multicentrico retrospectivo. Se incluyeron pacientes con enfermedad de Crohn que hubieran recibido al menos las 3 dosis de induccion del tratamiento estandar con IFX (5 mg/kg) y que despues precisaran intensificacion del tratamiento (10 mg/kg cada 8 semanas o 5 mg/kg cada 4 semanas) por perdida de respuesta. Se analizo la eficacia del tratamiento intensificado en el momento inicial (tras la 1a infusion de la dosis intensificada) y final (en la ultima revision). Se utilizo el indice de Harvey-Bradshaw en el caso de enfermedad de Crohn no fistulizante. En la enfermedad fistulizante, la respuesta completa se definio como el cese del drenaje de todas las fistulas y la respuesta parcial como la reduccion en al menos un 50% del numero o del debito fistuloso. Se valoro la seguridad del tratamiento con la dosis intensificada. Resultados Se incluyeron 34 pacientes (edad media, 43 anos; 50% varones; 31% fumadores; 64% con afectacion ileocolica; 47% con patron fistulizante; 60% con enfermedad perianal). La mayoria (72%) recibia tratamiento concomitante con inmunomoduladores. El tiempo medio de seguimiento con el tratamiento intensificado fue de 56 semanas (rango: 4–169 semanas). El tiempo medio de tratamiento con IFX antes de la intensificacion de la dosis fue de 15 meses (rango: 3–43 meses). Con la primera dosis de tratamiento intensificado respondio el 78% de los pacientes (32% respuesta completa y 46% parcial). Mientras que con la ultima dosis de tratamiento intensificado solo un 61% de los pacientes presentaban respuesta (22% respuesta completa y 39% respuesta parcial). Un paciente sufrio una reaccion infusional tras 36 dosis de tratamiento intensificado, que se soluciono con el enlentecimiento de la infusion. Otro paciente presento infeccion por virus del herpes zoster, no precisando suspension del tratamiento. Conclusiones En ocasiones se requiere la intensificacion del tratamiento con IFX, una media de 15 meses despues del inicio del tratamiento con este farmaco. Un alto porcentaje de pacientes responden inicialmente al tratamiento intensificado, aunque este pierde de nuevo su eficacia en mas de un 10% de los casos. La intensificacion del tratamiento presenta un buen perfil de seguridad, sin observarse reacciones adversas graves.

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S73 Conclusions: This study reveals discrepancy in psychosocial symptoms, and competence between reports of parents and adolescents with IBD. Chronically ill adolescents may deny their problems as part of coping strategy. Further, it is possible that the parents of chronically ill IBD patients observe their children more than the parents of healthy children, and thus report more concerns. Complementary methods should be used while assessing psychosocial well-being of adolescents with IBD. P157 Intensification of infliximab (IFX) therapy in Crohn’s disease: efficacy and safety M. Chaparro1, P. Martinez-Montiel2, M. Van Domselaar3, F. Bermejo4, J.L. Perez-Calle5, B. Casis2, A. Lopez-Sanroman3, A. Algaba4, J. Mate1, J.P. Gisbert1 *. 1La Princesa Hospital, Madrid, Spain, 212 de Octubre Hospital, Madrid, Spain, 3Ramon y Cajal Hospital, Madrid, Spain, 4Fuenlabrada Hospital, Madrid, Spain, 5Alcorcon Hospital, Madrid, Spain Introduction: The response of Crohn’s disease to IFX therapy is initially high. However, a loss of efficacy is observed in some cases over time. In such patients with loss of response, an IFX therapy “intensification” has been recommended. Nevertheless, it is still unknown whether the beneficial effect of this intensification is prolonged or just transient. Aims: (1) To study the shortand long-term response of Crohn’s disease patients treated with IFX intensification (e.g., higher doses or shortened intervals). (2) To evaluate the adverse effects associated to therapy intensification. Methods: Retrospective multicenter survey. We included Crohn’s disease patients who had been treated with at least the three induction doses of the standard IFX therapy (5mg/kg 0 2 6w), and who later on needed treatment intensification (10mg/kg/8w or 5mg/kg/4w), because of loss of response. Short-term (after the first intensification dose) and the longterm (at the end of follow-up) efficacy of the intensified therapy was analyzed. Harvey Bradshaw’s index was used in luminal Crohn’s disease. In fistulizing Crohn’s disease, complete response was defined as closure of all fistulas, and partial response as a 50% or more reduction in the number or the debit of fistulas. Safety was evaluated by collection of adverse effects. Results: We included 34 patients (mean age, 43 years; 50% male; 31% smokers; 64% with ileocolic (L3) disease; 47% with fistulizing (B3) phenotype; 60% with perianal (p) disease). The majority (72%) of the patiens was treated with immunomodulators. The mean follow-up for intensified treatment was 56 weeks (range: 4 169 w). Mean time of IFX exposure before intensification was 15 months (range: 3 43 m). On the short-term, after the first intensification dose, 78% responded (32% complete response, 46% partial response). On the long-term, after the last intensification dose, only 61% were still responding (22% complete response, 39% partial response). One patient suffered an infusion reaction after 36 doses of intensified treatment, which subsided with slower infusion. One patient suffered an episode of herpes zoster, that did not interrupt the treatment. Conclusions: The intensification of IFX therapy is sometimes necessary after a mean drug exposure of 15 months. A high proportion will initially respond, but >10% of all cases lose effect again. Safety profile of IFX therapy intensification is good, having no severe adverse effects. P158 Safety of once daily versus twice daily dosing with mesalazine (Pentasa®) sachets. Results from a 12 month randomised controlled trial in maintenance of remission of ulcerative colitis A. Dignass1 *, B. Bokemeyer2, T. Stijnen3, H. Veerman4. 1Markus-Krankenhaus, Frankfurt/ Main, Germany, 2Gastroenterologische Gemeinschaftspraxis, Minden, Germany, 3University Leiden, Leiden, Netherlands, 4Ferring Pharmaceuticals, Hoofddorp, Netherlands Aims: Patients with quiescent ulcerative colitis (UC) are often non-compliant with their treatment for maintenance of remission. Non-compliance can lead to relapse and the return of symptoms. This study investigated remission and relapse rates in patients with UC in remission receiving once (OD) or twice (BD) daily mesalazine sachets. The primary endpoint was non-inferiority of the OD treatment regime compared to BD dosing. Safety data were collected as a secondary endpoint. Materials and Methods: A 12-month, investigator-blinded, randomised controlled trial was conducted. Patients with mild to moderate UC in remission who had experienced a relapse within the past year were randomised to receive 2 g/day mesalazine sachets given either in a OD or BD regime. Results: 362 patients were randomised. The primary endpoint UC-DAI remission rate at 1 year as measured by the Kaplan Meier showed a statistically significant difference of 11.9% in favour of the OD treatment group. Overall, 42.9% of the patients in the OD group and 36.4% of the patients in the BD group reported one or more adverse events (AE) during the study. The difference in overall incidence was not statistically significant (P= 0.24) and there was no clear difference between the described AEs in the different treatment arms. Six patients from the OD group and four patients from the BD group experienced a serious AE (SAE). All SAEs were not, or unlikely, related to the study medication. The SAEs experienced by the OD group were metastatic prostate cancer, myocardial ischemia, pyrexia, postoperative wound infection, squamous cell carcinoma, coronary artery disease, gastrointestinal ulcer haemorrhage, and cerebral haemorrhage. The SAE experienced in the BD group were meningioma, migraine with aura, spondylolisthesis, chest pain, convulsion, and hypokalaemia. None were related to the study medication. Overall, the most frequently reported treatment emergent AEs (TEAE) were gastrointestinal disorders (abdominal pain, diarrhoea and flatulence) or infections and infestations (bronchitis, gastroenteritis, nasopharyngitis and sinusitis). The majority of the TEAEs were mild or moderate in intensity and considered by the investigator to be unrelated, or unlikely related, to the study medication. P159 Ulcerative colitis might prevent colonic diverticulosis O. Yonal *, S. Ilhan, O. Atug, H. Over Hamzaoglu. Marmara University Hospital Gastroenterology, Istanbul, Turkey Background: Diverticulosis coli is characterized by abnormal thickening of the large bowel wall, luminal overpressure and an increase in sigmoid contractility. The anatomic features intrinsic to the colon, alterations in colonic wall with aging, motor dysfunction, and increased intraluminal pressure, may all play role in the development of diverticulosis. In ulcerative colitis (UC) chronic inflammatory activity causes reduction in bowel wall muscle tone and contractility. Patients with UC often have liquid stools and might result in low intracolonic pressure Aim: To evaluate the frequency of colonic diverticulosis in patients with UC and compare with control group. Methods: Colonoscopy results of patients with ulcerative colitis older than 50 years were retrospectively evaluated and by gest on M arch 1, 2016 http://eccoxfordjournals.org/ D ow nladed from