PREDICTIVE FACTORS OF MORTALITY IN UPPER NONVARICEAL GI BLEEDING: VALIDATION OF A NEW PROGNOSTIC MODEL FROM A MULTICENTER ITALIAN STUDY

Abstracts / Digestive and Liver Disease 41S (2009), S1–S167 lesions were identified as independent predictors of survival. Patients eligible to LT according to AASLD guidelines were 228 (11% of the series). In this group, best results in terms of survival were achieved by LT in comparison with other treatments. Treatment, tumour size, AFP and Child-Pugh class were the independent predictors of survival. Conclusions: Patients undergoing LT represent a tiny minority of the overall cases of HCC detected in Italy and the number of those transplanted according to the AASLD guidelines is even lower (1%). LT represents the best therapeutic option for selected patients, but it remains a strategy for few cases, both because of the strict criteria and because of the limited availability of organs. Finally, in contrast with the Milan criteria, the AASLD therapeutic algorithm is not crucial, as most of the patients transplanted do not fulfil these indications and, whether or not they do, has no impact on survival. # K. Pancreatic and liver oncology 6. HCC

CS.1.6 ORAL CYCLOSPORIN VS INFLIXIMAB IN PATIENTS WITH SEVERE ULCERATIVE COLITIS REFRACTORY TO IV STEROIDS. PRELIMINARY DATA OF A CONTROLLED, RANDOMIZED STUDY F. Bossa ∗ , N. Caruso, L. Accadia, A. Merla, A.G. Niro, A. Iacobellis, E. Colombo, D. Siena, A. Ippolito, A. Andriulli, V. Annese IRCCS Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo Background and aim: IV steroids are the mainstay of therapy for severe Ulcerative Colitis (UC). IV cyclosporine and infliximab (IFX) are accepted rescue therapies in steroid-refractory patients. Oral microemulsion cyclosporine (Neoral) seems to be equivalent to iv cyclosporine. We aimed to compare efficacy and safety of Neoral vs IFX in severe steroid-refractory UC. Material and methods: Starting from May 2006, all consecutive hospitalized patients with severe UC (Truelove-Witts criteria) were treated with iv steroids (Methilprednisolone 1 mg/kg, max 60 mg daily) and hydrocortisone enemas daily (100 mg). After 1 week, patients non responder and not candidate to urgent colectomy, were randomised (2:1 ratio according to Ethical Committee requirement) to IFX 5 mg/kg (induction regimen 0, 2, 6 weeks) (group A) or Neoral (5 mg/kg adjusted upon plasma levels)(group B). Responder patients (Powell-Tuck index = 3) at 1 month, started Azathioprine 2 mg/kg. Results: A total of 21 patients have been so far randomised (13 males,), 14 in the group A and 7 in the group B. No significant differences between the two groups for mean age (39±12 vs 36±13 yrs, p=0.5), mean duration of disease (48±36 vs 35±34 months, p=0.41), extension (85% of pancolitis in both groups), mean ESR values (48±16 vs 67±40 mm/hr, p=0.1), mean CRP values (5.9±5 vs 4.5±4 mg/dl, p=0.5), mean Powell-Tuck index (15±1 in both groups), previous use of AZT/6-MP (50% vs 43%, p=1), and steroids (85% vs 100%, p=0.5), were found. After 1 month, 8 patients of the group A (57%) and 3 pts of the group B (43%) were in clinical remission (p=0.65). Six (43%) and 3 (43%) patients of the groups A and B, respectively, underwent a colectomy along the follow-up. The timing of colectomy was 2±1 months, and 5±3 months in the IFX and Neoral group, respectively (p=0.02). No serious adverse events occurred in the Neoral group; while in the IFX group 1 case of systemic CMV infection, and 1 death following pneumocystis carinii pneumonitis were reported (p=0.5). The crude mean cost of therapy for patient was 4-fold greater in the IFX compared to the Neoral group. Conclusions: In patients with severe UC refractory to iv steroids Infliximab achieved a trend towards a greater clinical remission compared to Neoral (57% vs 43%). Patients treated with IFX experienced earlier colectomy, and more serious opportunistic infections. # L. Inflammatory bowel diseases 3. Ulcerative colitis

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CS.1.7 PREDICTIVE FACTORS OF MORTALITY IN UPPER NONVARICEAL GI BLEEDING: VALIDATION OF A NEW PROGNOSTIC MODEL FROM A MULTICENTER ITALIAN STUDY R. Marmo ∗ ,1 , G. Rotondano 1 , M. Koch 1 , L. Cipolletta 1 , L. Capurso 1 , G. Trallori 1 , R. Cestari 1 , G. Frosini 1 , G. Imperiali 1 , T. Casetti 1 , S. Boschetto 1 , S. Di Mitri 1 , I. Stroppa 1 , M. Del Piano 1 , M. Salvagnini 1 , G. Gatto 1 , I. Sorrentini 1 , S. De Stefano 1 , M. Di Cicco 1 , P. Michetti 1 , I. Lorenzini 1 , F. Fornari 1 , W. Piubello 1 , A. Dezi 1 , M. Milla 1 , M.A. Bianco 1 , N. Della Casa 1 , G. Longobardi 1 , O. Triossi 1 , A. Gigliozzi 1 , S. Carmagnola 1 , D. Di Muzio 1 , M. Marino 1 , F. Russo 1 , R. Lamanda 1 , M. Proietti 1 , A. Allegretti 1 , U. Germani 1 , F. Giangregorio 1 , I. Zagni 1 , E. Grossi 2 1 Aigo - Sied, Progetto Nazionale Emorragia Digestiva, Italy; 2 Bracco S.P.A, Milano

Background and aim: Predictors of mortality in non variceal upper GI bleeding are changing according to increasing patients’ age, severe comorbidities, co-prescription of ulcerogenic drugs, and newer endoscopic or pharmacologic treatment to control bleeding. Data from the Italian PNED study identified 10 independent predictors of mortality that were used to develop a new predictive model (training sample). 1) to validate this new prediction rule on a subsequent independent population (testing sample); 2) introduce a user-friendly score to calculate the risk of death. Material and methods: A multicenter, prospective database study in 21 hospitals throughout Italy. Outcome measure was 30-day mortality. To validate the new Italian score, in order to evaluate the discriminative ability of the scoring system model, we built receiver operating characteristic (ROC) curves. The area under the curve (AUC) along with 95% confidence intervals was calculated. The calibration of the model was tested using the Hosmer-Lemeshow χ2 goodness-of-fit Results: Over a 16 month period (April 2007 - June 2008), a total of 1360 patients with non variceal UGIB were entered in a prospective national database and analysed. Peptic ulcer was the cause of bleeding in 825 patients (60.7%). Ulcerogenic co-prescriptions were recorded in 56.6%. Overall, 66% of patients had one or more comorbidities at the time of presentation. Endoscopic therapy was delivered in all patients with high-risk stigmata (38.7%). IV PPIs were administered in 95% of patients after endoscopic treatment. Overall mortality was 4.56% [95% CI 3.54-5.77]. The 10-variables previsional model (recurrent bleeding, ASA score 3 and 4, time to admission < 8 hrs, haemoglobin < 7 gr/L, age > 80 years, renal failure, disseminated neoplasia, liver cirrhosis, failure of endoscopic treatment) give an AUC of 0.81 [95% CI 0.75-0.86]. The Hosmer-Lemeshow χ2 goodness-of-fit test to assess the degree of calibration evaluated on 10 percentiles of the score distribution was 6.31 Prob ≥ 0.6122

Conclusions: Predictive factors of mortality identified in the training

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Abstracts / Digestive and Liver Disease 41S (2009), S1–S167

model were successfully validated in the subsequent independent sample. This Italian 10-points model for the prediction of death includes new risk factors, and shows a high discriminant capability with a good calibration between the observed and expected values. # R. Therapeutic endoscopy 1. GI bleeding

diverticulotomy seems to completely resolve the symptoms in almost 2/3 of patients. # A. Oesophagus 7. Endoscopic therapies

CS.2.2 CS.2.1 PROSPECTIVE SINGLE-CENTER COHORT STUDY FOR THE EVALUATION OF THE LONG-TERM CLINICAL EFFICACY OF FLEXIBLE ENDOSCOPIC DIVERTICULOSCOPE-ASSISTED ZENKER’S DIVERTICULOTOMY F. Iacopini ∗ ,2 , A. Tringali 3 , A. Bizzotto 1 , M. Marchese 1 , V. Perri 1 , M. Mutignani 1 , M.E. Riccioni 1 , G. Costamagna 1 1 Surgical

Digestive Endoscopy Unit, Department of Clinical Surgery, University La Cattolica, Roma; 2 Gastroenterology and Endoscopy Unit, Ospedale S.Giuseppe, Albano Laziale (RM); 3 Surgical Endoscopy Unit, Department of Clinical Surgery, University La Cattolica, Roma Background and aim: Zenker’s diverticulum arises from the hypopharinx. Main symptoms comprise oropharyngeal dysphagia and food regurgitation, but choking, chronic cough, and aspiration can also occur. Surgical approach through a laterocervical access and endoscopic stapling technique are the standard treatments. Although flexible endoscopic diverticulotomy is less invasive, there are no prospective data of the long-term clinical results. To prospectively assess clinical efficacy of flexible endoscopic diverticulotomy of Zenker’s diverticulum by the diverticuloscope-assisted technique. Material and methods: From March 2005 to November 2007, 21 consecutive patients with Zenker’s diverticulum were enrolled. All patients were treated by the soft diverticuloscope-assisted technique. After the placement of the soft diverticuloscope, the septum was cut with a needle-knife with endocut currents, and the distal margin was sealed with an endoclip. Dysphagia, pharyngo-oral regurgitation, daytime respiratory symptoms (cough, asthma, hoarseness), and nightly symptoms were prospectively recorded before the procedure, 1 month postoperatively (early), and in November 2008 (late follow-up). Symptoms were scored according to frequency: 0 = absent; 1 = occasional (once or twice per week); 2 = frequent (daily); and 3 = constant (at each meal) (Eckardt score). Clinical remission was defined as the disappearance of all symptoms or as the occasional persistence of no more than 2 symptoms. Results: Compared to pre-treatment, severity of all symptoms was significantly lower both early after treatment (P<0.001) and at the end of follow-up (median 2.1 yrs, range 1-4) (P=0.001). However, severity of dysphagia increased within the long-term follow-up (P=0.02) recurring severely in 4 patients, whereas regurgitation, day-time respiratory and night-time symptoms were persistently absent in almost all patients (P=n.s.). Clinical remission was achieved in 16/21(76%) in the early, and 62% (13/21) in late follow-up (median 2 yrs, range 1-3). The multivariate analysis showed that neither sex, age (=70/>70 yrs), or size of the diverticulum (=3/>3 cm) were significant independent prognostic factor for clinical efficacy. Severity of Zenker’s-related symptoms before and after flexible endoscopic treatment (mean ± SD)

Pre-treatment After 1 month After 2 years P=

Dysphagia

Food regurgitation

Daytime respiratory symptoms

Night-time symptoms

2.7±0.7 0.6±0.8 1.1±1.2 0.003

2.5±0.5 0.8±1.0 1.0±1.1 0.003

1.2±1 0.2±0.5 0.4±0.9 0.001

1.0±1.0 0.1±0.2 0.2±0.7 0.0005

Conclusions: Flexible endoscopic diverticuloscope-assisted Zenker’s

N-ACETIL-CYSTEINE PRE-TREATMENT AND TISSUE CULTURE INDICATIONS-BASED APPROACH FOR THE ERADICATION OF SEVERAL THERAPIES-RESISTANT HELICOBACTER PYLORI G. Cammarota 1 , G. Ianiro 1 , A. Cazzato 1 , A.C. Piscaglia 1 , C. Lauritano 1 , G. Gigante 1 , F. Fiore 1 , F. Barbaro 1 , F. Ardito 2 , G. Branca 2 , R. Torelli 2 , G. Fadda 2 , G. Gasbarrini 1 , A. Gasbarrini 1 1 Catholic 2 Catholic

University, Department of Internal Medicine, Roma; University, Institute of Microbiology, Roma

Background and aim: Some resistant strains of Helicobacter pylori display a dense biofilm with with mucus and microorganisms in a coccoid shape on the mucosal surface of stomach. We hypothesized a role for H pylori biofilm in determining the resistance to the common antibiotic therapies. Possibly, N-acetil-cysteine (NAC) may dissolve biofilm architecture and therefore have a role in eradicating resistant strains of H pylori. Our aim was to evaluate the usefulness of NAC as pre-treatment attempt associated with a culture-guided antibiotic therapy as rescue therapy after multi-attempts antibiotic failure. Material and methods: Thirty patients, after at least two antibiotic unsuccessful eradication attempts for H pylori, were consecutively recruited. In all patients H pylori culture for antibiotic susceptibility following upper endoscopy was performed. Subjects were subsequently subdivided into 2 groups and randomly assigned to two different eradication schedules: group A patients received NCA 600mg once a day for a week and subsequently a culture-guided one-week antibiotic regimen (including a PPI plus two antibiotics) against H pylori; group B patients received solely a culture-guided one week antibiotic treatment, including omeprazole plus two antibiotics. Sensitive antibiotic were always chosen on the basis of the more favorable minimum inhibiting concentration value. All patients took a control C13 urea breath test two months after the end of therapy. Results: Nine of 15 group A patients (60%) returned H pylori negative at the follow-up, while only 4 of 15 group B patients (27%) were successfully treated (p= 0,03). Conclusions: This pilot-study shows that NAC pre-treatment may be useful in eradicating H pylori when associated to a culture-guided one-week antibiotic rescue regimen. Possibly, NAC could dissolve the mucus biofilm making H pylori strains vulnerable to the antibiotic attack. Further larger studies are needed to confirm our preliminary results. # B. Gastric diseases 4. H. Pylori/diagnosis/therapy

CS.2.3 POLYCYSTIN-1 AND -2 PLAY A KEY ROLE IN THE MODULATION OF CHOLANGIOCYTE PROLIFERATION M. Gatto ∗ ,1 , V. Cardinale 1 , A. Torrice 1 , M.C. Bragazzi 1 , M.G. Mancino 1 , R. Semeraro 1 , G. Alpini 2 , D. Alvaro 1 1 Università

degli Studi di Roma “Sapienza”, Roma; 2 Scott & White Hospital and Texas A&M Univ. System Health Science Ctr., Temple TX, USA Background and aim: Cholangiocyte proliferation is fundamental for liver repair and regeneration. Polycystin-1 and -2 (PC-1,-2) play a key role in the function of primary cilia, which act as mechanosensors detecting changes in bile flow or cell injury and driving cell response. Mechanisms of PC-1 activation involve the cleavage of the PC-1 cytoplasmic tail, mostly driven by RIP (Regulated Intramembrane Pro-