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Background & Aims: A specific, occupation-related susceptibility of professional singers to experience gastroesophageal reflux was hypothesized. We investigated the prevalence of gastroesophageal reflux symptoms in a series of professional opera choristers in comparison with a general population sample. Methods: A total of 351 professional opera choristers from well-known choirs in different Italian regions were identified and a sample of 578 subjects residing in the same areas with a similar distribution in age and sex was selected. Reflux symptoms in the year preceding the survey together with selected individual characteristics and lifestyle habits were investigated in both study groups through a structured questionnaire. Prevalence rate ratios, adjusted for sex, age, body mass index, smoking status, alcohol consumption, and other confounding factors, were computed. Results: Opera choristers reported a statistically significant higher prevalence of heartburn, regurgitation, cough, and hoarse voice than the population sample, with adjusted prevalent rate ratios of 1.60 (95% confidence interval [CI], 1.32–1.94), 1.81 (95% CI, 1.42–2.30), 1.40 (95% CI, 1.18–1.67), and 2.45 (95% CI, 1.97–3.04), respectively. Regurgitation appeared to be associated consistently with the cumulative lifetime duration of singing activity (P = .04) and with the weekly duration of singing activity (P = .005) when different multivariate models were applied. Conclusions: Opera choristers reported a higher prevalence of reflux symptoms than the population sample. Future studies will be needed to clarify whether gastroesophageal reflux in professional opera choristers is stress-induced and therefore may be considered as a work-related disease.

Background & Aims: Several aspects of the pathogenesis of osteopenia in celiac disease are still unclear. Therefore, bone mass and metabolism were evaluated in adults with celiac disease in a cross-sectional study. Methods: Bone mineral density (BMD), assessed by total body dual-photon absorptiometry, and serum indices of bone metabolism and remodeling were evaluated in 17 patients with untreated celiac disease, 14 with celiac disease on a gluten-free diet, and 24 healthy volunteers. Results: BMD, expressed as a z score, was significantly lower in patients with untreated celiac disease than in patients with treated celiac disease and volunteers and lower in patients with treated celiac disease than in volunteers. Similar changes were observed in serum calcium level, whereas intact parathyroid hormone level was significantly higher in untreated than in treated patients with celiac disease and volunteers, and no difference was found between the latter two groups. 25-Vitamin D level was significantly lower and 1,25-vitamin D level significantly higher in untreated celiac disease than in treated celiac disease and volunteers. Indices of bone remodeling were significantly higher in untreated than in treated patients and volunteers and significantly and positively correlated with iPTH in untreated patients with celiac disease. Conclusions: BMD is almost invariably low in patients with untreated celiac disease. Results in treated patients suggest that gluten-free diet improves but does not normalize BMD. Untreated celiac disease is characterized by high levels of 1,25-vitamin D and by increased bone turnover, caused by the increase in intact parathyroid hormone level.

The reliability of a single jejunal culture in the diagnosis of small bowel bacterial overgrowth has recently been questioned. Seventy-seven patients thought to have bacterial overgrowth, defined as a jejunal culture yielding at least 10(6) organisms per milliliter of aspirate, took part in the study. Bacterial overgrowth was found in 74% of the patients with predisposing conditions and in 32% of those with no clear causes of bacterial colonization. The intestinal juice of some patients was taken at two different levels of the proximal jejunum, using both the closed- and open-tube systems. Highly significant correlations (rs = 0.90, p less than 0.001) were found between the numbers of bacteria per milliliter at the 2 jejunal levels and between the numbers of bacteria per milliliter of jejunal aspirate obtained from the closed and open tubes (rs = 0.84, p less than 0.001). Compared with the jejunal culture, the gas chromatography of volatile fatty acids in jejunal aspirate and the glucose- and lactulose-hydrogen breath tests showed sensitivities of 56%, 62%, and 68% and specificities of 100%, 83%, and 44%, respectively. This work demonstrates the reliability of jejunal cultures and the inadequacy of breath hydrogen testing in the prediction of positive jejunal cultures. When results of testing for volatile fatty acids in jejunal aspirates are positive, this always indicates the presence of bacterial overgrowth; thus, this procedure would avoid the more complicated, time-consuming, and costly bacteriological analysis of jejunal samples.

BACKGROUND AND AIM : Several studies have indicated that continuous exposure to high concentrations of Nitric Oxide (NO), produced by inducibile-NO synthase (iNOS), promote neoplastic transformation within many human cancers, including colon cancer (CC). Recently, it has also been suggested that high NO synthesis is a distinctive feature of "cancer stem cells" (CSC), a tumor subpopulation with self-renewal capacity, that may be identified by the expression of the CD133 surface marker. Aims of this study were to explore the contribution of NO in the definition of colon CSC features and evaluate potential strategies to treat CC by modulating NO production. MATERIAL AND METHODS : By immunohistochemistry analysis we evaluated iNOS and CD133 expression in 20 samples of human CC. Using the DAF-2DA detection system, we assayed the production of intracellular NO in 5 colon CSC lines obtained from human CC tissues. By FACS sorter, we purified the NO high andNO low fractions from all colon CSC lines and we compared the tumorigenic potential of both cell fractions by in vitro and in vivo assays. To tested the potential antitumor effects of iNOS modulation, we treated colon CSCs with the selective iNOS inhibitor 1400W or we stably transfected these cells with two distinct iNOS-directed short-harpin RNA(shRNAs). RESULTS : Immunohistochemistry analysis revealed that, irrespective of grade, higher iNOS expression was associated with increased CD133 levels in all CC samples. Moreover, we observed that NOhigh cells display higher expression levels of stem cell markers and increased tumorigenic properties in vitro and in vivo than NOlow fraction. Both iNOSdirected shRNAs and iNOS inhibitor treatment decreased the rate of cell-cycle transit in colon CSCs and reduced tumorigenic capacity in vitro and in vivo, confirming an integral role for NO and endogenous iNOS activity in the biology of colon CSCs. Interestingly, the knockdown of iNOS expression was associated with a significant down regulation of stem cell markers, such as CD133, BMI and b-Catenin. CONCLUSIONS : This study identifies for the first time a cell-autonomous colon CSC specific source of NO, and it highlights the biological effects of the iNOS within colon CSCs. In the long run, these data could serve as an impetus for evaluation of iNOS-directed therapies as a component of multimodal treatment regimens for human CC.

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

Although the accuracy of breath H2 testing to detect malabsorption of small (50 g) doses of carbohydrate has never been evaluated, studies suggest that its accuracy is limited by a high prevalence of "H2 nonproducers." The aim of this study was to determine the accuracy of H2 breath testing in the detection of malabsorption of 10 g of carbohydrate.In 55 healthy subjects, we determined the ability of breath H2 measurements to distinguish between the ingestion of 10 g of a nonabsorbable carbohydrate (lactulose) and two control meals, a nonabsorbable electrolyte solution or glucose (10 g).The conventional criterion of a 20 ppm increase in breath H2 had 100% specificity but failed to identify lactulose malabsorption in 47% and 24% of subjects at 4 and 8 hours of testing. In contrast, a breath H2 of6 ppm at 5 or 6 hours had near perfect specificity and sensitivity. A sum of breath H2 at 5, 6, and 7 hours of15 ppm yielded perfect separation between lactulose and control solutions.True "H2 nonproducers" are extremely rare. Using appropriate criteria, breath H2 testing provides a very accurate means of identifying malabsorption of low doses of carbohydrate.

Purpose: Celiac crisis is a life-threatening syndrome where celiac disease presents with profuse diarrhea and severe metabolic disturbances. Celiac crisis in adults is believed to be uncommon and is not well documented. However, it is likely that many patients with celiac crisis are not definitively diagnosed. In order to improve awareness and to facilitate diagnosis, we reviewed cases of celiac crisis seen at Beth Israel Deaconess Medical Center in Boston, MA and Mayo Clinic in Rochester, MN. These data were used to identify presenting features, formulate diagnostic criteria for celiac crisis in adults and develop treatment strategies. Methods: We reviewed cases of biopsy proven celiac disease in the last 5 years. Celiac crisis was defined as acute onset or rapid progression of gastrointestinal symptoms attributable to celiac disease requiring hospitalization and/or parenteral nutrition along with at least 2 of the 7 factors listed below: 1.Signs of severe dehydration including hemodynamic instability or orthostasis 2.Neurologic dysfunction 3.Renal dysfunction: creatinine >2.0 4.Metabolic acidosis: pH 10 lbs Results: Twelve patients met the above criteria. Of these, 8 were women and 4 were men. 11 developed celiac crisis prior to diagnosis of celiac disease. IgA tissue transglutaminase titer was available for 11 patients. Of these, one had IgA deficiency, and all of the others had elevated tTG, eight with levels greater than 4 times the normal limits. Biopsies of the duodenum in all patients were consistent with a Marsh 3 score. HLA type was available for 10, of which 9 were positive for DQ2 and 1 for DQ8. Patients presented with severe dehydration, renal dysfunction, and electrolyte disturbances, of which hypocalemia was most common. All patients required hospitalization and intravenous fluids and five required parenteral nutrition. Six patients required corticosteroids. All patients had a rapid clinical response to gluten free diet. Conclusion: Celiac crisis is associated with high morbidity and although rarely described, does occur in adults, often without a clear precipitating factor. Patients presentingwith severe unexplained diarrhea and malabsorption should be tested for celiac disease and treatment with systemic steroids or oral budesonide considered. Nutritional support is often required in the short term but most patients ultimately respond to gluten avoidance. We are hopeful that our delineation of formal diagnostic criteria for celiac crisis will aid in identification and management of these patients.

Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test, candidates for jejunal biopsy were selected from 328 first-degree relatives of 128 adult celiac patients. All relatives geographically available were willing to participate in the study. Twenty-one turned out to be positive for antigliadin antibodies, and in 13 jejunal histology was consistent with celiac disease. In the remaining 8, the morphometric evaluation of jejunal biopsy specimens showed a mean surface to volume ratio that, although in the normal range, was significantly lower than that of other 10 relatives negative for antigliadin antibodies and 16 biopsied controls. It was concluded that antigliadin antibody testing is a valuable method for the screening of celiac disease among family members and that relatives with genetically predisposed gliadin sensitivity, without gross histological lesions but with minor morphometric abnormalities of the jejunal mucosa, may be regarded as subjects with latent celiac disease.