Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions.

BACKGROUND & AIMS: Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis. METHODS: We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis. RESULTS: The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria. CONCLUSIONS: In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

Evaluation of Rosemont criteria for non-calcific chronic pancreatitis (NCCP) based on histopathology - A retrospective study.

BACKGROUND: Rosemont classification for chronic pancreatitis has not been evaluated specifically in non-calcific chronic pancreatitis (NCCP) patients and to this date, it has not been correlated with the gold standard namely histopathology. OBJECTIVE: To assess the correlation of EUS Rosemont criteria for NCCP with histopathology from surgical specimens and evaluate the impact of age, sex, BMI, smoking and alcohol on Rosemont classification. METHODS: Adult patients undergoing TPIAT for NCCP between July 2009 and January 2013 were identified from our institutional database. The presence or absence of standard and Rosemont (major and minor) criteria were determined by expert endosonographers using linear endosonography. Patients were categorized into normal, indeterminate and suggestive with CP based on Rosemont classification. Histology was obtained at time of TPIAT from the resected pancreas by wedge biopsy of head, body and tail. All histopathology were re-reviewed by a GI pathologist blinded to endosonographic features and clinical outcomes. Available pancreatic tissue was graded for severity of intralobular and perilobular pancreatic fibrosis by the Ammann classification system. RESULTS: 50 patients with NCCP (42 females, mean age± SD = 37.9 ± 10.8) underwent TPIAT with preoperative EUS during the study period. Univariate analysis of features such as age, sex, BMI, smoking and alcohol history showed no significant difference between patients identified as normal and those identified as indeterminate/suggestive (p > 0.05). Rosemont "Normal" was poor in excluding CP as 5/9 patients (55.5%) had CP on histopathology. 25/26 patients (96.2%) with features "suggestive" of CP had evidence of CP on histopathology. 12/15 patients (80.0%) with "indeterminate" features had CP on histopathology. CONCLUSIONS: Rosemont classification can be used independent of patient characteristics (age, sex and BMI) and environmental factors (smoking and alcohol exposure). In our cohort, Rosemont classification was strongly predictive of CP in patients with features "suggestive" of CP. However, "normal" Rosemont classification had poor correlation in this study. This is maybe due to lack of true comparator "normal" pancreas which cannot be obtained reasonably. The strength of agreement for diagnosis of CP was substantial between the standard and Rosemont criteria.

The Burden of Systemic Adiposity on Pancreatic Disease: Acute Pancreatitis, Non-Alcoholic Fatty Pancreas Disease, and Pancreatic Cancer.

Obesity is a global epidemic as recognized by the World Health Organization. Obesity and its related comorbid conditions were recognized to have an important role in a multitude of acute, chronic, and critical illnesses including acute pancreatitis, nonalcoholic fatty pancreas disease, and pancreatic cancer. This review summarizes the impact of adiposity on a spectrum of pancreatic diseases.

Diagnostic Performance of Endoscopic Ultrasound (EUS) for Non-Calcific Chronic Pancreatitis (NCCP) Based on Histopathology.

OBJECTIVES: Studies correlating endoscopic ultrasound (EUS) with histopathology for chronic pancreatitis (CP) are limited by small sample size, and/or inclusion of many patients without CP, limiting applicability to patients with painful CP. The aim of this study was to assess correlation of standard EUS features for CP with surgical histopathology in a large cohort of patients with non-calcific CP (NCCP). METHODS: Adult patients undergoing total pancreatectomy and islet autotransplantation (TPIAT) for NCCP, between 2008 and 2013, with EUS <1 year before surgery. Histology from resected pancreas at the time of TPIAT (from head, body, and tail) was graded by a GI pathologist blinded to the EUS features. A fibrosis score (FS) ≥2 was abnormal, and FS≥6 was considered severe fibrosis. A multivariate regression analysis for the EUS features predicting fibrosis, after taking age, sex, smoking, and body mass index into consideration, was performed. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation co-efficient (r) was calculated. RESULTS: 68 patients (56 females, mean±s.d. age-38.77±10.92) underwent TPIAT for NCCP with pre-operative EUS. ROC curve showed that four or more EUS features provided the best balance of sensitivity (61%), specificity (75%), and accuracy (63%). Although significant, correlation between standard EUS features and degree of fibrosis was poor (r=0.24, P<0.05). Multivariate regression analysis showed that main pancreatic duct irregularity was the only independent EUS feature (P=0.02) which predicted CP. CONCLUSIONS: Correlation between standard EUS features and histopathology is poor in NCCP. MPD irregularity is an independent predictor for NCCP.

Diagnostic Performance of Contrast-Enhanced MRI With Secretin-Stimulated MRCP for Non-Calcific Chronic Pancreatitis: A Comparison With Histopathology.

OBJECTIVES: Diagnosis of non-calcific chronic pancreatitis (NCCP) in patients presenting with chronic abdominal pain is challenging and controversial. Contrast-enhanced magnetic resonance imaging (MRI) with secretin-stimulated MRCP (sMRCP) offers a safe and noninvasive modality to diagnose mild CP, but its findings have not been correlated with histopathology. We aimed to assess the correlation of a spectrum of MRI/sMRCP findings with surgical histopathology in a cohort of NCCP patients undergoing total pancreatectomy with islet autotransplantation (TPIAT). METHODS: Adult patients undergoing TPIAT for NCCP between 2008 and 2013 were identified from our institution's surgery database and were included if they had MRI/sMRCP within a year before surgery. Histology was obtained from resected pancreas at the time of TPIAT by wedge biopsy of head, body, and tail, and was graded by a gastrointestinal pathologist who was blinded to the imaging features. A fibrosis score (FS) of 2 or more was considered as abnormal, with FS ≥6 as severe fibrosis. A multivariate regression analysis was performed for MRI features predicting fibrosis, after taking age, sex, smoking, alcohol, and body mass index (BMI) into consideration. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation coefficient (r) was calculated. RESULTS: Fifty-seven patients (females=49, males=8) with NCCP and MRI/sMRCP were identified. ROC curve analysis showed that two or more MRI/sMRCP features provided the best balance of sensitivity (65%), specificity (89%), and accuracy (68%) to differentiate abnormal (FS≥2) from normal pancreatic tissue. Two or more features provided the best cutoff (sensitivity 88%, specificity 78%) for predicting severe fibrosis (FS≥6). There was a significant correlation between the number of features and severity of fibrosis (r=0.6, P<0.0001). A linear regression after taking age, smoking, and BMI into consideration showed that main pancreatic duct irregularity, T1-weighted signal intensity ratio between pancreas and paraspinal muscle, and duodenal filling after secretin injection to be significant independent predictors of fibrosis. CONCLUSIONS: A strong correlation exists between MRI/sMRCP findings and histopathology of NCCP.

Prediction of celiac disease at endoscopy.

BACKGROUND AND STUDY AIMS: Celiac disease is increasingly recognized worldwide, but guidelines on how to detect the condition and diagnose patients are unclear. In this study the prevalence and predictors of celiac disease were prospectively determined in a cross-sectional sample of Lebanese patients undergoing esophagogastroduodenoscopy (EGD). PATIENTS AND METHODS: Consecutive consenting patients (n = 999) undergoing EGD answered a questionnaire and had blood taken for serologic testing. Endoscopic markers for celiac disease were documented and duodenal biopsies were obtained. The diagnosis of celiac disease was based on abnormal duodenal histology and positive serology. Risk factors were used to classify patients to either high or low risk for celiac disease. Independent predictors of celiac disease were derived via multivariate logistic regression. RESULTS: Villous atrophy (Marsh 3) and celiac disease were present in 1.8 % and 1.5 % of patients, respectively. Most were missed on clinical and endoscopic grounds. The sensitivity of tissue transglutaminase (tTG) testing for the diagnosis of villous atrophy and celiac disease was 72.2 % and 86.7 %, respectively. The positive predictive value of the deamidated gliadin peptide (DGP) test was 34.2 % and that of a strongly positive tTG was 80 %. While the strongest predictor of celiac disease was a positive tTG (odds ratio [OR] 131.7, 95 % confidence interval [CI] 29.0 - 598.6), endoscopic features of villous atrophy (OR 64.8, 95 %CI 10.7 - 391.3), history of eczema (OR 4.6, 95 %CI 0.8 - 28.8), anemia (OR 6.7, 95 %CI 1.2 - 38.4), and being Shiite (OR 5.4, 95 %CI 1.1 - 26.6) significantly predicted celiac disease. A strategy of biopsying the duodenum based on independent predictors had a sensitivity of 93 % - 100 % for the diagnosis of celiac disease, with an acceptable (22 % - 26 %) rate of performing unnecessary biopsies. A strategy that excluded pre-EGD serology produced a sensitivity of 93 % - 94 % and an unnecessary biopsy rate of 52 %. CONCLUSION: An approach based solely on standard clinical suspicion and endoscopic findings is associated with a significant miss rate for celiac disease. A strategy to biopsy based on the derived celiac disease prediction models using easily obtained information prior to or during endoscopy, maximized the diagnosis while minimizing unnecessary biopsies.

Alcohol consumption is a risk factor for colonic diverticulosis.

BACKGROUND AND AIM: The exact factors predisposing to colonic diverticulosis other than age are unknown. METHODS: Cross-sectional study of asymptomatic subjects undergoing screening colonoscopy. A detailed dietary and social questionnaire was completed on all participants. A worldwide review of the literature was performed to further investigate any association between identified risk factors and diverticulosis. RESULTS: Seven hundred forty-six consecutive individuals were enrolled (mean age, 61.1±8.3 y; female: male=0.98). Overall, the prevalence of diverticulosis was 32.8% (95% CI, 29.5-36.2). Diverticula were left-sided, right-sided, or both in 71.5%, 5.8%, and 22.7% of affected subjects, respectively. On univariate analysis, age, sex, adenomatous polyps, advanced neoplasia (adenoma≥1 cm, villous histology, or cancer), aspirin, and alcohol use were significantly associated with diverticulosis. Diet, body mass index, physical activity, and bowel habits were not associated with the disease. On multivariate analysis, increasing age (P<0.001), advanced neoplasia (P=0.021), and alcohol consumption (P<0.001) were significantly associated with diverticulosis. The adjusted odds ratio for diverticulosis in alcohol users was 1.91 (1.36 to 2.69), with increasing prevalence with higher alcohol consumption (P-value for trend=0.001). When the prevalence of diverticulosis reported from 18 countries was analyzed against alcohol use, there was a strong correlation with national per-capita alcohol consumption rates (Pearson correlation coefficient r=0.68; P=0.002). CONCLUSIONS: Alcohol use is a significant risk factor for colonic diverticulosis and may offer a partial explanation for the existing East-West paradox in disease prevalence and phenotype. Further studies are needed to investigate this association and its putative pathophysiological mechanisms.

CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel.

The aim of this study is to investigate the effect of CYP2C19 polymorphism and cotherapy with rabeprazole or esomeprazole on the antiplatelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and CYP2C19*3, and vasodilator-stimulated phosphoprotein testing to measure platelet reactivity index (PRI). Two hundred thirty-nine consecutive patients were enrolled as follows: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). Forty-five patients had loss of function (LOF) polymorphism (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean PRI was 20.7% ± 21.9% in the C group, 19.1% ± 20.9% in the CR group, and 24.5% ± 22.9% in the CE group (P = NS). High on-treatment platelet reactivity (HPR), defined as PRI >50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE, respectively (P = NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor proton pump inhibitor cotherapy were associated with HPR. The use of proton pump inhibitors was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.

Spontaneous Pancreatic Pseudocyst-Superior Mesenteric Vein Fistula.

Pancreatic pseudocyst formation is a common complication of chronic pancreatitis. Rarely, a fistula develops between the pseudocyst and the portal venous system. We present a case of a 50-year-old man who was found to have a pancreatic pseudocyst-superior mesenteric vein fistula after being evaluated for several months of abdominal pain and weight loss. The patient was treated with endoscopic stenting of the pancreatic duct along with early enteral nutrition and suppressive antibiotics, which resulted in improvement in his condition. This case report highlights clinical presentation and the complexity of treatment of this rare diagnosis.

Incarcerated Colonoscope in a Left Inguinal Hernia During Diagnostic Colonoscopy.

Colonoscope entrapment in an inguinal hernia is rare and few cases have been described in the literature. We present a 54-year-old patient who underwent a diagnostic colonoscopy which was complicated by incarceration of the colonoscope in a left inguinal hernia. This rare complication occurs more frequently during withdrawal, and our case was unique, given the incarceration of the colonoscope occurred during the insertion phase. Recognizing this scenario is very important to immediately proceed with general anesthesia and surgical consultation for successful nonoperative hernia reduction and colonoscope removal. We recommend reattempting colonoscopy after surgical hernia repair or proceed with computed tomography colonography if appropriate for the indication.

Unavailability of Endoscopic Retrograde Cholangiography Adversely Impacts Hospital Outcomes of Acute Biliary Pancreatitis: A National Survey and Propensity-Matched Analysis.

OBJECTIVES: There is a paucity of literature assessing the impact of endoscopic retrograde cholangiopancreatography (ERCP) availability at hospitals and the management of acute biliary pancreatitis (ABP). Thus, we sought to evaluate the impact of ERCP availability on the clinical outcomes of ABP. METHODS: The Nationwide Inpatient Sample (2004-2013) was reviewed to identify adult inpatients (≥18 years) with ABP. Clinical outcomes (mortality, severe acute pancreatitis, and health care resource utilization) between hospitals that perform ERCP versus hospitals that do not perform ERCP were compared using multivariate and propensity score-matched analyses. RESULTS: A majority of the non-ERCP hospitals were rural (73%) in location. Multivariate analysis demonstrated that the lack of ERCP availability was independently associated with increased mortality from ABP (odds ratio, 1.83; 95% confidence interval, 1.16-2.88). A propensity score-matched cohort analysis confirmed a significant increase in mortality from ABP in non-ERCP hospitals (1.1% vs 0.53%; odds ratio, 2.08; 95% confidence interval, 1.05-4.15, P = 0.037) compared with ERCP hospitals. CONCLUSIONS: This national survey reveals increased mortality for patients with ABP admitted to hospitals lacking ERCP services. While there is a need to increase ERCP availability in rural areas, optimizing strategies for early transfer of patients with ABP to hospitals with ERCP availability can potentially offset these limitations.

Risk prediction rule for advanced neoplasia on screening colonoscopy for average-risk individuals.

BACKGROUND: In resource-limited countries, risk stratification can be used to optimize colorectal cancer screening. Few prospective risk prediction models exist for advanced neoplasia (AN) in true average-risk individuals. AIM: To create and internally validate a risk prediction model for detection of AN in average-risk individuals. METHODS: Prospective study of asymptomatic individuals undergoing first screening colonoscopy. Detailed characteristics including diet, exercise and medications were collected. Multivariate logistic regression was used to elucidate risk factors for AN (adenoma ≥1 cm, villous histology, high-grade dysplasia or carcinoma). The model was validated through bootstrapping, and discrimination and calibration of the model were assessed. RESULTS: 980 consecutive individuals (51% F; 49% M) were enrolled. Adenoma and AN detection rates were 36.6% (F 29%: M 45%; P < 0.001) and 5.1% (F 3.8%; M 6.5%) respectively. On multivariate analysis, predictors of AN [OR (95%CI)] were age [1.036 (1.00-1.07); P = 0.048], BMI [overweight 2.21 (0.98-5.00); obese 3.54 (1.48-8.50); P = 0.018], smoking [< 40 pack-years 2.01 (1.01-4.01); ≥ 40 pack-years 3.96 (1.86-8.42); P = 0.002], and daily red meat consumption [2.02 (0.92-4.42) P = 0.079]. Nomograms of AN risk were developed in terms of risk factors and age separately for normal, overweight and obese individuals. The model had good discrimination and calibration. CONCLUSION: The prevalence of adenoma and AN in average-risk Lebanese individuals is similar to the West. Age, smoking, and BMI are important predictors of AN, with obesity being particularly powerful. Though external validation is needed, this model provides an important platform for improved risk-stratification for screening programs in regions where universal screening is not currently employed.

Acute liver failure due to liver parenchymal infiltration with acute myelogenous leukaemia in a patient with myelodysplastic syndrome.

Liver involvement by acute leukaemia is rare and has a high mortality rate despite treatment. We report a case of a 66-year-old woman undergoing treatment for myelodysplastic syndrome with Vidaza (azacitidine) who presented with abnormal liver function tests. Despite negative serologic testing and unremarkable abdominal MRI, she continued to have significant elevation in bilirubin and international normalised ratio and worsening mental status. Liver biopsy was obtained and consistent with acute myelogenous leukaemia. The patient had rapid demise due to acute liver failure and was unable to undergo treatment.

Confocal endomicroscopy and cyst fluid molecular analysis: Comprehensive evaluation of pancreatic cysts.

Increases in the quality as well as utilization of cross-sectional imaging have led to rising diagnoses of pancreatic cystic lesions (PCL). Accurate presurgical diagnosis enables appropriate triage of PCLs. Unfortunately, current diagnostic approaches have suboptimal accuracy and may lead to unnecessary surgical resections or missed diagnoses of advanced neoplasia. Additionally, early detection represents an opportunity for intervention to prevent the progression to pancreatic adenocarcinoma. Our aim for this review is to systematically review the current literature on confocal endomicroscopy and molecular biomarkers in the evaluation of PCLs. Confocal laser endomicroscopy is a novel technology that allows for real-time in vivo microscopic imaging with multiple clinical trials identifying characteristic endomicroscopy findings of various pancreatic cystic lesions. DNA-based molecular markers have also emerged as another diagnostic modality as the pattern of genetic alternations present in cyst fluid can provide both diagnostic and prognostic data. We propose that both techniques can be utilized to improve patient outcomes.

Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions.

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss' kappa) and IOR (Cohen's kappa), blinded nCLE-naïve observers (n = 6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94 %, 82 %, and 89 %, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was "substantial" (κ = 0.67, 95 %CI 0.57, 0.77). The mean (± standard deviation) IOR was "substantial" (κ = 0.78 ±â€Š0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were "substantial" for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κ = 0.63; IOR κ = 0.76 ±â€Š0.11), bright particles on a dark background of pseudocysts (IOA κ = 0.71; IOR κ = 0.78 ±â€Š0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κ = 0.62; IOR κ = 0.68 ±â€Š0.20). Three (6.1 % of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events. STUDY REGISTRATION: NCT02516488.

Opposing effects of aspirin and anticoagulants on morbidity and mortality in patients with upper gastrointestinal bleeding.

OBJECTIVE: We aimed to determine the effect of antithrombotics on in-hospital mortality and morbidity in patients with peptic ulcer disease-related upper gastrointestinal bleeding (PUD-related UGIB). METHODS: The study cohort was retrospectively selected from a tertiary center database of patients with PUD-related UGIB, defined as bleeding due to gastric or duodenal ulcers, or erosive duodenitis, gastritis or esophagitis. Outcomes were compared among patient groups based on their antithrombotic medications before admission. Patients on no antithrombotics served as controls. The composite adverse outcomes, in-hospital mortality, rebleeding and/or need for surgery were measured. Severe bleeding and in-hospital complications were also recorded. RESULTS: Of 398 patients with PUD-related UGIB, 44.5% were on aspirin or anticoagulants only. The composite adverse outcome was most common in patients taking anticoagulants only (40.5%), intermediate in controls (23.1%) and least in those taking aspirin only (12.1%). On multivariate analysis, patients taking aspirin alone had a significantly lower risk of adverse outcome events (odds ratio [OR] 0.4, 95% CI 0.2-0.8) and a shorter length of hospital stay (regression coefficient = -3.4, 95% CI [-6.6, -0.6]). In contrast, taking anticoagulants was associated with a greater risk of adverse outcome events (OR 2.3, 95% CI 1.0-5.3), severe bleeding (OR 2.6, 95% CI 1.2-5.8) and in-hospital complications (OR 2.9, 95% CI 1.3-6.6). CONCLUSIONS: Patients with PUB-related UGIB while taking aspirin had fewer adverse outcomes compared with those taking anticoagulants. Aspirin may have beneficial effects in this population.

Challenging the dogma: a randomized trial of standard vs. half-dose concomitant nonbismuth quadruple therapy for Helicobacter pylori infection.

BACKGROUND: Current treatment of Helicobacter pylori consists of three or four drugs for 7-14 days with important associated cost and adverse events. AIMS: This study compared efficacy and safety of standard dose vs. half-dose concomitant nonbismuth quadruple therapy (NBQT) for 7 days. The standard dose consisted of twice daily rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg. METHODS: This was a prospective randomized trial. (14)C-urea breath test was performed ≥4 weeks after treatment and ≥2 weeks off acid suppressive therapy. Compliance and adverse events were monitored during treatment. RESULTS: A total of 200 consecutive treatment-naïve patients were enrolled. Baseline characteristics were similar between groups, with 15.5% of subjects reporting prior macrolide use. Eradication occurred in 78% (95% CI 68.6-85.7%) in both groups on intention-to-treat analysis. Per-protocol rates were 82.1 vs. 83.9% for standard-dose patients vs. half-dose patients, respectively (p = NS). Adverse events (only mild) were reported in 57 vs. 41% of standard-dose patients vs. half-dose patients (p = 0.024), with metallic taste and nausea notably less frequent in the latter (36 vs. 12% and 18 vs. 7%, respectively; p < 0.05 for both). Overall, eradication failed in 38.7% of prior macrolide users vs. 18.9% without such exposure (p = 0.019). On multivariate logistic regression, prior macrolide exposure was the only factor associated with failed eradication (OR 2.60, 95% CI 1.06-6.39; p = 0.038). Treatment was cheaper with the half-dose regimen. INTERPRETATION: A 50% reduction in antibiotic dosage does not diminish efficacy of concomitant nonbismuth quadruple therapy but leads to significant reduction in cost and adverse events. Seven-day concomitant NBQT is suboptimal for H. pylori independent of prior macrolide exposure.

Proton pump inhibitors have no measurable effect on calcium and bone metabolism in healthy young males: a prospective matched controlled study.

OBJECTIVES: Proton pump inhibitors (PPIs) are associated with an increased risk of bone fractures. This study sought to evaluate the effect of PPIs on biochemical markers of calcium and bone metabolism. METHODS: Prospective matched controlled study involving healthy adult males (age 18-50years) suffering from frequent heartburn. Patients received standard-dose PPI for 12weeks and were matched by age with healthy controls. Blood studies were taken at 0, 1 and 3months for biochemical markers of mineral and bone metabolism. Two-way (time and PPI treatment) repeated measures analysis of variance (RM-ANOVA) and multiple linear regression were used for analysis. RESULTS: A total of 58 participants (29 per group) completed the study. Mean age of participants was 33.2±7.5years. Baseline characteristics and biomarkers were similar for both groups except for higher BMI (28.6 vs. 25.6kg/m(2), p=0.008) and serum C-terminal cross linked telopeptides of type I collagen [CrossLaps, (300 vs. 228pg/ml, p=0.028)] in the PPI group. There was no difference in parathormone (PTH), ionized calcium, vitamin D, osteocalcin and CrossLaps between the PPI and control subjects (all non-significant; 2-way RM-ANOVA). Multiple linear regression modeling showed no effect of PPIs on any of the studied calcium or bone metabolism biomarkers. CONCLUSION: PPI intake for 12weeks has no measurable effect on calcium or bone metabolism in healthy young males.

Association of Streptococcus bovis endocarditis and advanced colorectal neoplasia: a case-control study.

OBJECTIVE: To study the association between Streptococcus bovis (S. bovis) endocarditis and advanced colorectal neoplasia. METHODS: This was a case-control study of patients with S. bovis endocarditis undergoing colonoscopic evaluation. Patients were matched 1:20 with controls by gender and age (±2 years) from a large screening colonoscopy database. The baseline, colonoscopic and clinicopathological characteristics of patients with S. bovis endocarditis were analyzed. RESULTS: From 1996 to 2010, 18 adult patients with S. bovis bacteremia were identified, of whom 10 with infective endocarditis (IE) underwent colonoscopic evaluation. Endocarditis involved a native or prosthetic valve in six and four of those patients, respectively. All 10 patients recovered without recurrence of IE (mean follow-up duration 49.6 months). None had a concurrent or preceding history of colon disease and only one had subclinical chronic liver disease. Advanced neoplasia, defined as the presence of polyps ≥1 cm (n = 6), villous histology (n = 3), high-grade focal dysplasia (n = 1) or cancer (n = 1), was found under colonoscopy in 6 of the 10 cases (60.0%) compared with 13/200 (6.5%) matched controls (OR 21.6, 95% CI 5.4-86.1, P < 0.0001). CONCLUSIONS: S. bovis endocarditis is strongly associated with the presence of advanced colorectal neoplasia. In the absence of any contraindication, colonoscopic examination is strongly recommended in patients with endocarditis. The exact pathophysiological mechanisms underlying this association and the predilection for S. bovis bacteremia in patients with advanced colonic neoplasia remain unclear.