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Sprue-like enteropathy associated with olmesartan medoxomil use has been recently reported. Its clinical manifestations include diarrhea, weight loss and malabsorption. Duodenal biopsies show villous atrophy (VA) with or without intraepithelial lymphocytosis and inflammation of the lamina propria. Serology for celiac disease (CD) is negative and gluten-free diet does not result in clinical improvement. Symptoms resolve after olmesartan discontinuation. Follow-up biopsies show recovery/improvement of the duodenum. Whether sprue-like enteropathy is a specific adverse reaction to olmesartan or rather a class effect of angiotensin-receptor blockers (ARBs) remains a controversial issue. We report a case of sprue-like enteropathy associated with telmisartan. A 52-year-old man presented with chronic diarrhea, abdominal discomfort and significant weight loss. In the last 3 years, he had been treated with telmisartan 40 mg/day for hypertension after right adrenalectomy for an aldosterone-producing adenoma. Laboratory investigations showed no significant abnormalities: Hb 13.6 g/dL, serum albumin 3.9 g/dL, total cholesterol 193 mg/dL, serum creatinine 0.99 mg/dL, sodium 143.6 mmol/L, K+ 4.3 mmol/L, calcium 9.3 mg/dL, phosphorus 3.9 mg/dL and 25-OH-D3 27.7 ng/mL. Duodenal histology showed subtotal VA and inflammation of the lamina propria. CD serology was negative. HLA-DQ typing showed absence of the DQ2/DQ8 haplotypes. After telmisartan discontinuation, patient's symptoms subsided, and his body weight increased despite persistence of a gluten-containing diet. Follow-up biopsies at 3 showed progressive duodenal recovery. Very few cases of sprue-like enteropathy associated with ARBs other than olmesartan have been reported. Our case of telmisartan-associated enteropathy further suggests that sprue-like disease may be a class effect of ARBs.

Background:\ud The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD.\ud \ud Methods:\ud Thirty-one CD patients and 7 controls were enrolled. Circulating CD133+ and CD34+ HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3+ lymphoid cells) and the putative ISC compartment (CD133+ and Lgr5+ epithelial cells).\ud \ud Results: \ud At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal.\ud \ud Conclusions:\ud In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission.

Real-time sonoelastography is currently used for the characterization of superficial solid lesions such as thyroid and breast masses. This study evaluates the usefulness of percutaneous sonoelastography for the characterization of solid focal liver lesions.30 out of 43 patients with 38 known liver lesions were included in a prospective, diagnostic study. Qualitative analysis (pattern of deformation, elasticity type of liver tumour) and semi-quantitative measurements (strain ratio, hardness percentage, histogram) were evaluated. Sensitivity, specificity, positive and negative predictive values were calculated and the area under the receiver operating characteristics curve was constructed.Patterns A and C-D are specific of benign lesions and metastases respectively. The patterns for haemangiomas, focal nodular hyperplasia and metastases were significantly different to each other in terms of strain ratio, hardness percentage and histogram (p0.05). A statistically significant difference (p0.001) was observed between the median values of the 3 measured parameters for benign (1.02; 12%; 47) and malignant lesions (1.66; 65%; 20.5) respectively. The area under the receiver operating characteristics curve values for strain ratio, hardness percentage and histogram were 0.88, 0.89, and 0.86 respectively for cut-off values of 1.2, 45, and 30.By percutaneous sonoelastography it is possible to differentiate benign versus malignant focal liver lesions, metastases in particular, with good diagnostic performance.

Background Our aim was to evaluate the effectiveness of the single-step combined therapy with radiofrequency ablation and drug-eluting beads transarterial chemoembolization in single hepatocellular carcinoma (HCC) larger than 3 cm. Secondary aim was to compare the results with those obtained in a matched population treated with drug-eluting beads transarterial chemoembolization alone. Methods 40 consecutive cirrhotic patients with single HCC were prospectively enrolled and treated. Twenty-three patients had tumours between 3 and 5 cm (Group A), and 17 larger than 5 cm (Group B). Twenty cirrhotic patients with single HCC treated only with chemoembolization formed the control group. Results Complete response at 1 month was achieved in 32/40 tumours (80%). During follow-up, complete response was maintained in 25 patients (25/40, 62.5%), and this rate was higher in Group A (69.6% vs 53%, p = 0.008). The group treated with combined therapy showed a significantly lower 2-year recurrence (48.1% vs 78.2%, p p = 0.004) than the group treated with chemoembolization alone. Conclusions Balloon-occluded-radiofrequency ablation plus drug-eluting beads transarterial chemoembolization is an effective treatment of HCC larger than 3 cm not amenable to surgical resection, providing better results than transarterial chemoembolization alone. The best results are achieved in tumours up to 5 cm.

The Helicobacter pylori eradication rate with standard triple therapy is very low. H. pylori is known to require the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive at the low pH environment in the stomach. To compare the H. pylori eradication rate of a nickel free-diet associated with standard triple therapy and standard triple therapy alone as the first-line regimen. Fifty-two sex- and age-matched patients at the first diagnosis of H. pylori infection were randomized 1:1 into two different therapeutic schemes: (1) standard LCA (26 patients): lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid for 7 days with a common diet; (2) standard LCA plus a nickel free-diet (NFD-LCA) (26 patients). Patients followed 30 days of a nickel-free diet plus a week of lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid starting from day 15 of the diet. All patients completed the study. A significantly higher eradication rate was observed in the NFD-LCA group (22/26) versus LCA group (12/26) (p

This study was undertaken to evaluate the feasibility, safety and efficacy of a new combined single-step therapy in patients with unresectable multinodular unilobar hepatocellular carcinoma (HCC), with at least one lesion3 cm, with balloon-occluded radiofrequency ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE) of the main lesion and TACE of the other lesions. The second purpose of our study was to compare the initial effects in terms of tumour necrosis of this new combined therapy with those obtained in a matched population treated with TACE alone in a singlestep treatment in our centre in the previous year.This pilot study was approved by the institutional review board, and informed consent was obtained from all patients. Ten consecutive patients with multinodular (two to six nodules) unilobar unresectable HCC and with a main target lesion3 cm (range, 3.5-6 cm) not suitable for curative therapy were enrolled in our single-centre multidisciplinary pilot study. The schedule consisted of percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumour, followed by selective TACE, plus lobar TACE for other lesions (450-mg carboplatin and lipiodol plus temporary embolisation with SPONGOSTAN). Adverse events and intra- and periprocedural complications were clinically assessed. Early local efficacy was evaluated on 1-month follow-up multiphasic computed tomography (CT) on the basis of the Modified Response Evaluation Criteria in Solid Tumors (m-RECIST). A separate evaluation of target lesions in terms of enhancement, necrotic diameter and presence and distribution of lipiodol uptake was also performed.No major complications occurred. Overall technical success, defined as complete devascularisation of all nodules during the arterial phase, was achieved in seven of 10 patients, with three cases of partial response (persistence of small hypervascular nodules). When considering only target lesions, technical success was obtained in all patients, with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter, 3.5-5 cm) and with circumferential peripheral lipiodol uptake (safety margin) of at least 0.5 cm (0.5-1.3cm).TACE and BO-RFA, plus TACE in a singlestep approach seems to be a safe and effective combined therapy for treating advanced, unresectable HCC lesions, allowing a high rate of complete local response to be achieved in large lesions also.

Alterations of commensal flora may cause various gastrointestinal and extraintestinal diseases, including food intolerances and food allergies. According to the ‘microflora hypothesis’, alterations in the composition of gut microbiota in industrialized countries have disturbed the mechanisms of mucosal immune tolerance. Over the past few years several studies have looked for a role for probiotics in the treatment of food allergies with promising results.

OBJECTIVES: Current treatment for small intestinal bacterial overgrowth (SIBO) is based on courses of broad-spectrum antibiotics. No data concerning SIBO recurrence are available. The aims of the present study were to investigate SIBO recurrence as assessed by glucose breath test (GBT) after antibiotic treatment and conditions associated to SIBO recurrence. METHODS: Eighty consecutive patients affected by SIBO and decontaminated by rifaximin (1,200 mg per day for 1 wk) were enrolled. Diagnosis of SIBO was based on GBT. GBT was reassessed at 3, 6, and 9 months after evidence of GBT normalization. GBT positivity recurrence, predisposing conditions, and gastrointestinal symptoms were evaluated. RESULTS: Ten (10/80, 12.6%), 22 (22/80, 27.5%), and 35 (35/80, 43.7%) patients showed positivity to GBT at 3, 6, and 9 months after successful antibiotic treatment, respectively. At multivariate analysis, older age (OR 1.09, 95% CI 1.02-1.16), history of appendectomy (OR 5.9, 95% CI 1.45-24.19), and chronic use of proton pump inhibitors (PPIs) (OR 3.52, 95% CI 1.07-11.64) were significantly associated to GBT positivity recurrence. All gastrointestinal symptoms significantly increased at 3, 6, and 9 months in patients with evidence of GBT positivity recurrence. CONCLUSIONS: GBT positivity recurrence rate was high after antibiotic treatment. Older age, history of appendectomy, and chronic use of PPIs were associated with GBT positivity recurrence. Patients with evidence of GBT positivity recurrence showed gastrointestinal symptoms relapse thus suggesting SIBO recurrence.

Partially Hydrolyzed Guar Gum (PHGG) Attenuates Nonalcoholic Steatohepatitis (NASH) in Mice Through the Gut-Liver Axis Kazuhiro Katada, Yuji Naito, Tomohisa Takagi, Katsura Mizushima, Yasuki Higashimura, Tetsuya Okayama, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiko Uchiyama, Ishikawa Takeshi, Osamu Handa, Hideyuki Konishi, Nobuaki Yagi, Hiroshi Ichikawa, Zenta Yasukawa, Makoto Tokunaga, Tsutomu Okubo, Lekh R. Juneja, Yoshito Itoh

Background/Aims: Hepatolithiasis is a well known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. Methods: Among a total of 257 patients who received treatment for hepatolithiasis from 2002 to 2011 at Korea University Anam and Guro Hospital, 236 patients were eligible for analysis; 92 patients underwent liver resection (resection group) and 144 patients did not (non-resection group). The data were retrospectively collected and analyzed. Results: The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41±41 months). The median tumor occurrence time was 28 (13-111) months. Cholangiocarcinoma occurred 6.5% (6/92) and 6.9% (10/144) in resection and non-resection group respectively (P=0.425). In resection group, cholangiocarcinoma occurred in 3.6% (2/56) of patients with complete stone removal, and in 13.3% (4/ 30) of patients with incomplete stone removal (p=0.591). In non-resection group, cholangiocarcinoma occurred in 5.7% (3/53) of patients with complete stone removal, and in 8.9% (7/79) of patient with incomplete stone removal (p=0.738). When analyzed according to completeness of stone removal regardless of treatment modality, cholangiocarcinoma occurred in 4.6% (5/109) of patients with complete stone removal, and in 10.1% (11/109) of patients with incomplete stone removal (p=0.429). Although the site of stone and tumor occurrence concurred in 10/16 patients (3/6 patients in the resection group, 7/10 patient in the non-resection group), it did not match in 6 patients. On univariate analysis, none of the factors (age, gender, abdominal pain, bile duct stenosis, bile duct dilatation, liver atrophy, residual stone, stone recurrence and liver resection) showed relationship with the incidence of cholangiocarcinoma. Conclusion: There was no difference in the incidence of cholangiocarcinoma according to the treatment modality or completeness of stone removal. Therefore, patients with hepatolithiasis should carefully be followed-up to detect cholangiocarcinoma even after treatment.

Background : Endoscopic ultrasonography (EUS) is considered to be the best modality to predict the neoplastic polyps of the gallbladder. However, EUS has several limitations following as 1) the considerable experience of investigators, 2) presence of the interobserver variations and 3) unavailability of EUS in some centers. Multidetector computed tomography (MDCT) provides fine section image of gallbladder and allows to reduce the interobserver variations. We evaluated the accuracy of MDCT combined with high resolution ultrasonography (HRUS) for gallbladder polyps smaller than 2cm compared with EUS. Methods : From Dec 2005 to June 2010, 109 patients who underwent cholecystectomy due to gallbladder polyps were enrolled. Subjects were divided in two groups (reference group : 63 patients who were performed MDCT and HRUS vs. validation group : 46 patients who underwent MDCT, HRUS, and EUS). New scoring system was developed from reference group, and applied to validation group, while previously reported EUS scoring system was applied to the same validation group. Results : In reference group, size (p,0.001), number (p=0.015), shape (p=0.001), and CT/US size ratio of polyps (p=0.008) were significant variables in univariate analysis. Area under the ROC curve draw by new scoring system was 0.859 and cut-off value was set to 3. In validation group, new scoring system showed comparable accuracy (65.2%) with previously reported EUS scoring system(73.9%, p=0.434). Conclusion : MDCT combined with HRUS provide comparatively high accuracy in small gallbladder polyps in distinguishing between neoplastic and non-neoplastic polyps as preoperative diagnostic modality.

Background/Aims: Hepatolithiasis is a well known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. Methods: Among a total of 257 patients who received treatment for hepatolithiasis from 2002 to 2011 at Korea University Anam and Guro Hospital, 236 patients were eligible for analysis; 92 patients underwent liver resection (resection group) and 144 patients did not (non-resection group). The data were retrospectively collected and analyzed. Results: The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41±41 months). The median tumor occurrence time was 28 (13-111) months. Cholangiocarcinoma occurred 6.5% (6/92) and 6.9% (10/144) in resection and non-resection group respectively (P=0.425). In resection group, cholangiocarcinoma occurred in 3.6% (2/56) of patients with complete stone removal, and in 13.3% (4/ 30) of patients with incomplete stone removal (p=0.591). In non-resection group, cholangiocarcinoma occurred in 5.7% (3/53) of patients with complete stone removal, and in 8.9% (7/79) of patient with incomplete stone removal (p=0.738). When analyzed according to completeness of stone removal regardless of treatment modality, cholangiocarcinoma occurred in 4.6% (5/109) of patients with complete stone removal, and in 10.1% (11/109) of patients with incomplete stone removal (p=0.429). Although the site of stone and tumor occurrence concurred in 10/16 patients (3/6 patients in the resection group, 7/10 patient in the non-resection group), it did not match in 6 patients. On univariate analysis, none of the factors (age, gender, abdominal pain, bile duct stenosis, bile duct dilatation, liver atrophy, residual stone, stone recurrence and liver resection) showed relationship with the incidence of cholangiocarcinoma. Conclusion: There was no difference in the incidence of cholangiocarcinoma according to the treatment modality or completeness of stone removal. Therefore, patients with hepatolithiasis should carefully be followed-up to detect cholangiocarcinoma even after treatment.

New Therapeutic Perspectives for Management of Advanced Hepatocellular Carcinoma With Hepatic Arteriovenous Fistula: Balloon-Occluded Percutaneous Radio-Frequency Thermal Ablation (RFA) Plus Transcatheter Arterial Chemoembolization (TACE) Roberto Iezzi, Valentina Cesario, Mariachiara Campanale, Silvia Pecere, Federico Barbaro, Emanuele Rinninella, Francesca Romana Ponziani, Michele La Torre, Brigida E. Annicchiarico, Massimo Siciliano, Maurizio Pompili, Antonio Grieco, Luca Miele, Gian Ludovico Rapaccini, Laura Riccardi, Maria Assunta Zocco, Alessandro Milani, Anna Maria De Gaetano, Giovanni B. Gasbarrini, Lorenzo Bonomo, Antonio Gasbarrini

NEW THERAPEUTIC PERSPECTIVES FORMANAGEMENT OF ADVANCED HEPATOCELLULAR CARCINOMAWITH HEPATIC ARTERIOVENOUS FISTULA: BALLOON-OCCLUDED PERCUTANEOUS RADIO-FREQUENCY THERMAL ABLATION (RFA) PLUS TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) V. Cesario ∗ ,1, R. Iezzi 2, M.C. Campanale1 , E. Rinninella1 , F.R. Ponziani1, T.A. Di Rienzo1, F. Barbaro1 , B.E. Annicchiarico1 , M. Siciliano1 , M. Pompili 1, G.L. Rapaccini 1 , A. Grieco1, L. Miele1 , A. Milani 1 , L. Riccardi 1 , M.A. Zocco1, M. Santoro2, M. La Torre2, A.M. De Gaetano2 , G.B. Gasbarrini 3 , L. Bonomo2, A. Gasbarrini 1 1Medicina Interna, Ucsc, Policlinico Gemelli, Roma, Italy; 2Radiologia, Ucsc, Policlinico Gemelli, Roma, Italy; 3Fondazione Ricerca In Medicina, Bologna, Italy