P.107 EFFECT OF BACILLUS CLAUSII ADMINISTRATION IN THE RECTAL MUCOSA OF MICE TREATED WITH INTRARECTAL INSTILLATION OF THE CARCINOGEN N-METHYLNITROSUREA

P.107 EFFECT OF BACILLUS CLAUSII ADMINISTRATION IN THE RECTAL MUCOSA OF MICE TREATED WITH INTRARECTAL INSTILLATION OF THE CARCINOGEN N-METHYLNITROSUREA

S140 Abstracts / Digestive and Liver Disease 42S (2010) S61–S192 derlie a field effect, and an inherited predisposition. S-CRCs are included in Bethe...

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S140

Abstracts / Digestive and Liver Disease 42S (2010) S61–S192

derlie a field effect, and an inherited predisposition. S-CRCs are included in Bethesda Criteria addressing to microsatellite instability (MSI) test to identify Hereditary Non-Polyps Colorectal Cancer (HNPCC). 1) to assess incidence, clinico-pathological features, MS_status, and prognosis of S-CRCs in a large, consecutive series of CRCs, and 2) to characterize molecular alterations of S-CRC pairs. Material and methods: Retrospective analysis of a series comprising 893 consecutive, mono-insitutional CRCs pts. In each pt, the more advanced lesion had been characterized for MS-status and inheritance (89, 10%, MSI-CRC pts, including 30, 3.3%, HNPCC). All S-CRCs were studied for MSI, hMLH1 hypermethilation, BRAFV600E and KRAScod12. Results: We identified 38 (4.2%) pts with S-CRCs (total of 79 lesions). S-CRCs were more frequent in MSI-CRC pts (9/89, 10.7%, vs 29/804, 3.6%, in MSS-CRC; p=0.006). HNPCC (3 hMSH2, 2 hMLH1, and 1 MSH6 defect) accounted for the excess rate of S-CRCs in pts with MSI CRC (p=0.0001). Adenomatous polyps and Tis associated with CRC (AP) occurred in 155 (17.4%) pts, more frequently in MSI-CRC pts (22/89, 24.7% vs 133/804, 16.5%, in MSS-CRC pts; p=0.04). In pts with AP, S-CRCs risk was independent of MS-status (2/2, 9.1%, in MSI-CRC pts vs 8/133, 6%, in MSS-CRC pts; p=0.6). Pts with S-CRCs did not differ in age, sex, and tumor site. Among MSS-CRC pts, stage IV cancer was more frequent in those with S-CRCs (13/29, 44.8%, vs 204/775, 26.3%; p=0.02). Consistently, DSS of pts with S-CRCs was worse (p=0.02), a difference that remained significant only for the MSS-CRC subgroup (p=0.02). In SCRCs, MSI status was concordant within pairs only in HNPCC. Discordance in SCRCs pairs was found for BRAFV600E and KRAScod12. BRAFV600E mutation and hMLH1 promoter hypermethylation were the hallmarks of MSI, sporadic CRC, and KRAScod12 mutation was independent of MS-status. Conclusions: S-CRCs are not rare, associated with MSI phenotype and thus HNPCC. However, pts with S-CRCs have a poorer prognosis due to the high rate of stage IV MSS S-CRCs. In patients with coexisting CRC and AP, the MS-status does not influence the risk of S-CRCs. # H. GI oncology - 4. Colon

P.105 AN UNUSUAL CASE OF PNEUMATOSIS CYSTOIDES GASTROINTESTINALIS CAUSED BY NON-HODGKIN LYMPHOMA S. Maiero ∗ ,1 , M. Fornasarig 1 , S. Venturini 2 , V. Canzonieri 3 , R. Cannizzaro 1 1

Gastroenterology, Centro di Riferimento Oncologico, IRCCS, Aviano (PN); Radiology, Centro di Riferimento Oncologico, IRCCS, Aviano (PN); 3 Pathology, Centro di Riferimento Oncologico, IRCCS, Aviano (PN) 2

Background and aim: Pneumatosis intestinalis (PI) is a rare disorder of undedetermined etiology, characterized by presence of multilocular gas-filled cysts in the submucosa and subserosa of the gastrointestinal wall. It can occur in any part of the gastrointestinal tract, but is most common in colon. PI is classified in primitive, about 15% of cases, and secondary but localized of coexisting diseases as pulmonary emphysema or malignancy overall adenocarcinoma, about 85% of cases. Material and methods: A 71 year old man was referred for colonoscopic workout because of positive hemocult and symptoms as abdominal pain, alternated diarrhea and costipation, fatigue, weight loss (2kg) and disconfort started 2 months previously. He had gastric resection 37 years before for peptic ulcer. The physical examination was negative. The laboratory results were: Hb 14.6g/dl, WBC 11.09×103 /μl, RBC 4.08×106 /μl, platelets 232×103 /μl, CRP 1.6 (n.v.<0.5), alkaline phosphatase 139 U/l (n.v.), ALT, AST, CEA and Ca19.9 in normal range. The mean corpuscolate volume of 101.9 fl (n.v. 83-99 fl) was secondary to folate and vitamine B12 deficiency. Results: We reported a diffuse multiple small bubbles pneumatosis cystoides at colonoscopy. Histologic examination of biopsies revealed a specific flogosis. Abdominal CT scan and virtual colonoscopy reported multiple pseudopolipoid lesions alternated to multiple small gas-filled bubbles in stomach, small bowel and colon. In celiac and mesenteric region there were some lymph nodes of 10 to 23 mm of diameter. Upper GI endoscopy and capsule enteroscopy confirmed the presence of multiple small cystis in the gastric stump and small bowel. Patient was treated with 15 sessions of high flow oxygen therapy without relief of symptoms and then he was revaluated by colonoscopy

and CT abdominal scan. CT scan reported a decrease of the multiple small gas-filled bubbles in stomach, small bowel and colon but an enlargement of lymph nodes. At colonoscopy as well, we observed a consistent decreased in number and size of cysts and at histology of repeated biopsies small cells nonHodgkin lymphoma, phenotype B in WHO 2008 (mantellar histotype) was diagnosed. Immunoistochemistry showed: CD20/L26+, CD5/4C7+, Ciclina D1+, Ki67(30.9)+ (40%), CD3-, CD10/56C6-. Conclusions: This is the first case of diffuse pneumatosis cystoid involving stomach, small bowel and colon-rectum associated to non-hodgkin lymphoma. # H. GI oncology - 4. Colon

P.106 ATTENUATED FAMILIAL ADENOMATOUS POLYPOSIS: CLINICAL AND MOLECULAR CHARACTERIZATION L. Sanchez-Mete ∗ , A. Martayan, P. Giacomini, G. Viceconte Regina Elena National Cancer Institute, Rome Background and aim: Attenuated familial adenomatous polyposis (AFAP) is characterized by less than 100 colorectal adenomas, a later onset than classic feature (FAP) and a high lifetime risk of colorectal cancer (CCR). A causative germline mutation is identified in 30% of cases in both MUTYH and APC genes. As to this milder form, some critical areas remain to be clarified: there is no consensus on the minimum number of polyps to suspect the syndrome and on surveillance programs. Aim of the study was to provide a better definition of the critical areas above described. Material and methods: Among FAP affected in follow-up at Hereditary Colorectal Cancer Outpatients of Regina Elena National Cancer Institute we selected those subjects displaying an attenuated feature and compared to those with a classic feature. For each patient we evaluated: age at onset, genealogical tree, number and histology of polyps, extracolonic polyps/tumours and germline mutation. Results: In 15/65 FAP families a total of 22 patients had an attenuated phenotype. Mean age at diagnosis was 54.9 years in AFAP and 26,1 years in FAP. Duodenal polyps were present in 9% of AFAP and 25.9% of FAP. No extraintestinal tumours (ET) were found in AFAP, vs.13% of FAP. AFAP patients were stratified according to number of polyps (<10; 11-30; 31-50; >50) and 86.4% of patients had less than 30 polyps (40.9% < 10 polyps). A familial history of polyposis/CCR was present in 77.2% of AFAP. In 7 patients (31.8%) germline mutations in MUTYH gene were identified and none in the APC gene. 21% of cases with less than 30 polyps had a germline mutation in MUTYH gene. Conclusions: 86,4% of AFAP patients had less than 30 polyps, 4 out of the 7 MUTYH mutation carrier belong to this subset of patients and one of them had 8 polyps. On this basis, we could consider 5 the minimum number of polyps to suspect AFAP. The age at diagnosis was 20 years later than FAP, ET were not present and gastroduodenal polyps were found in a small percentage. Endoscopic surveillance should be performed in all affected individuals starting 10 years later than FAP. Cancer surveillance of other target organs seems to be not necessary. 31.8% of AFAP patients carried a germline mutation of MUTYH gene that must be considered as first in the mutational analysis. Our results contributed to provide partial answers to the critical areas above considered and must be confirmed by further studies on larger series. # H. GI oncology - 4. Colon

P.107 EFFECT OF BACILLUS CLAUSII ADMINISTRATION IN THE RECTAL MUCOSA OF MICE TREATED WITH INTRARECTAL INSTILLATION OF THE CARCINOGEN N-METHYLNITROSUREA F. Franceschi ∗ , M. Marini, A. Piscaglia, N. Soulier, A. Puglisi, R. Ricci, B. Giupponi, G. De Marco, D. Roccarina, G. Gigante, F. Barbaro, F. Mancini, N. Gentiloni Silveri, G. Gasbarrini, A. Gasbarrini Univerità Cattolica Del Sacro Cuore, Policlinico A. Gemelli, Roma Background and aim: Some probiotics, such as Bifidobacteria, Lactobacilli and Saccharomyces boulardii, have been shown to exert a protective role in

Abstracts / Digestive and Liver Disease 42S (2010) S61–S192 the colorectal carcinogenic process. However, there are no data concerning the possible effect of Bacillus clausii on this matter; therefore, we designed a study aimed at assessing whether the administration of this microorganism in mice treated with the carcinogen N-methylnitrosurea (NMU) may prevent colorectal cancer development. Material and methods: The study has been conducted on 10 six weeks old C57/BL6 mice. Five mice were pre-treated with Bacillus clausii for one month before receiving intrarectal instillation of NMU twice a week for 3 weeks, while another group of 5 mice were only treated with intrarectal NMU. All animals were then sacrificed; samples of rectal tissue were collected and prepared for histology assessment, gene microarray analysis focused on tumor suppressor genes and RT-PCR. Results: One of 5 animals treated with intrarectal NMU showed dysplasia compared to none of the mice treated with NMU plus Bacillus clausii. Microarray analysis showed an up regulation of some tumor suppressor genes, such as ENPP5, SCL 25a20 and RPL11 in mice treated with NMU plus Bacillus clausii compared to those treated with NMU only. RT-PCR performed on ENPP5, SCL 25a20 and RPL11 fully confirmed the results of microarray analysis. Conclusions: Bacillus clausii showed to have an antitumorigenic activity, by up-regulating ENPP5, SCL 25a20 and RPL11. Further studies are now needed in order to assess the exact mechanisms by which Bacillus clausii may interact with those tumor suppressor genes. # H. GI oncology - 4. Colon

P.108 EUS ACCURACY IN RESTAGING RECTAL CANCER AFTER NEOADJUVANT CHEMORADIOTHERAPY: A PRELIMINARY REPORT A. Caruso ∗ ,1 , G. Del Vecchio Blanco 1 , M. Cretella 1 , E. Mannisi 1 , V. Formica 2 , I. Portarena 2 , G. Sica 3 , P. Sileri 3 , M. Roselli 2 , A. Gaspari 3 , F. Pallone 1 1 Unità

Operativa di Gastroenterologia, Università Tor Vergata, Roma; di Oncologia, Università Tor Vergata, Roma; 3 Unità di Chirurgia, Università Tor Vergata, Roma

2 Unità

Background and aim: Colorectal cancer (CRC) is the second most frequent cause of cancer-related death in Western countries: one third of CRC is represented by rectal cancer (RC).Accurate staging is recommended to provide an optimal treatment strategy. Neoadjuvant chemo radiotherapy (NCRT) is increasingly used in the treatment of advanced RC with the intention of downsizing and downstaging the tumour and to reduce tumour recurrence. Accuracy of EUS staging is reported to be 75–94% for tumour penetration and 72–83% for nodal metastases. However after NCRT the EUS accuracy for T staging decrease because fibrosis, peritumoral inflammation and necrosis. The aim of this study was to verify the accuracy of EUS in restaging RC after neoadjuvant CRT and the efficacy of the therapy in the downstaging and downsizing the tumour. Material and methods: We prospectively enrolled consecutive patients affected by RC in stage II-b and III who underwent EUS and MRI or CT or PET before and after neoadjuvant CRT.EUS scanning was performed by one endosonographer using an electronic radial ecoendoscope (Olympus GF UE 160-AL5) with imaging at 7,5-10MHz. Patients underwent surgical resection after reassessment staging. The reduction of diameter of RC was evaluated using RECIST criteria. Pathological staging was undertaken according to the TNM classification. Results: 14 patients with locally advanced RC were assessed: 10 male, median age 64 yrs (range 56-73). The median distance from the anus was 5 cm. Seven patients were in stage II-b and 7 in stage III. All patients underwent

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radiotherapy with no complication associated with chemotherapy (10 pts with CDDP, 2 pts with FOLFOX and 2 pts with FUFA). The downstaging after neadjuvant therapy was observed in 7/14 patients, and significant reduction of tumor diameter in 13/14 patients. There were 13 anterior resections and 1 abdominoperineal resections. EUS post-NCRT T stage was correctl in 11/14 pts (3 T0, 5 T3, 3 T2), while 3 pts were over staged (2T2 and 1 T1). Overall accuracy of EUS post-RCT for pathologic T stage was 93% for T0-T1 stage and 86% for T3 stage. EUS accuracy for N-stage was 79%. Conclusions: In our preliminary study neoadjuvant CRT was useful to downstage and downsize locally advanced RC. EUS seems to be an accurate tool to restage RC after neoadjuvant CRT. However our results needed to be confirmed in a large cohort of patients with locally advanced RC. # H. GI oncology - 4. Colon

P.109 PREOPERATIVE COLONOSCOPY IN ACUTE MALIGNANT OBSTRUCTION AFTER SELF-EXPANDABLE METALLIC STENT PLACEMENT AS A BRIDGE TO SURGERY F. Iacopini ∗ ,1 , W. Elisei 1 , G. Marino 2 , V. Barbaliscia 3 , S. Di Paola 3 , C. Grossi 1 , A. Scozzarro 1 1 Gastroenterology,

S. Giuseppe, Albano L, Roma; 2 Surgery, Ospedale Colombo, Velletri; 3 Surgery, S. Giuseppe, Albano L, Roma

Background and aim: In case of resecable colorectal cancer (CRC) a preoperative colonoscopy is necessary to exclude possible synchronous lesions present in 2-11% of cases. That is not possible in up to 30% of CRC presenting with a colonic obstruction. Self-expanding metallic stents (SEMS) placement and the resolution of colon obstruction, allow a preoperative complete colonoscopy to diagnose synchronous lesions, and if necessary change the operative surgical plan. To evaluate if a complete preoperative colonoscopy after effective stent placement in patients with acute neoplastic obstruction is an ordinary, safe and useful procedure. Material and methods: Within 12 months, 4 patients with an acute colonic obstruction who were considered candidates for curative colon resection, underwent a successfully SEMS placement within 24 hours from the diagnosis. After correct placement, the full expansion of the SEMS, and the improvement of intestinal obstruction, a preoperative colonoscopy with standard preparation was attempted. Results: The preoperative colonoscopy was attempted at least 72 hours after SEMS placement. SEMS were uncovered in all cases. No SEMS migration occurred after preparation. A complete colonoscopy was uneventfully achieved in all patients without complications, stent displacement, endoscope impaction in or damage from the stent. The passage of the endoscope above the SEMS at proximal transverse colon was difficult for a fixed angulation between the proximal end of the stent and the ascending colon. Demographic, comorbidities, types of SEMS and synchronous lesions detected are reported in the Table. In one patient (25%), the two synchronous proximal adenomas were consensually removed en bloc. Histology confirmed the complete resection of both lesions. All patients underwent a surgical resection of the obstructing CRC without changing the surgical plan. Conclusions: After relief of acute colonic obstruction with SEMS, Patients with a resecable CRC could undergo a standard bowel preparation and a preoperative pancolonoscopy few days after. The presence of ynchronous cancers or incompletely removed superficial neoplastic lesions may change the surgical plan. # H. GI oncology - 4. Colon

Abstract P.109 – Table 1 Patient

Gender

Age

Comorbidity

Obstruent cancer location

Proximal synchronous lesions

SEMS (diameter – length)

1 2 3 4

Male Male Female Male

64 55 68 72

Hypertension COPD Past history of breast ca. Hypertension

Proximal transverse Sigmoid Sigmoid descending

– – – 25 mm sessile polyp + 20 mm granular LST

24 mm – 8 cm 22 mm – 10 cm 24 mm – 8 cm 22 mm – 12 cm