Showing papers in "Journal of Clinical Gastroenterology in 2009"

Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent clostridium difficile-associated diarrhea

Abstract: Clostridium difficile-associated disease (CDAD) is the major known cause of antibiotic-induced diarrhea and colitis, and the disease is thought to result from persistent disruption of commensal gut microbiota. Bacteriotherapy by way of fecal transplantation can be used to treat recurrent CDAD, which is thought to reestablish the normal colonic microflora. However, limitations of conventional microbiologic techniques have, until recently, precluded testing of this idea. In this study, we used terminal-restriction fragment length polymorphism and 16S rRNA gene sequencing approaches to characterize the bacterial composition of the colonic microflora in a patient suffering from recurrent CDAD before and after treatment by fecal transplantation from a healthy donor. Although the patient's residual colonic microbiota, prior to therapy was deficient in members of the bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic impact on the composition of the patient's gut microbiota. By 14 days posttransplantation, the fecal bacterial composition of the recipient was highly similar to that of the donor and was dominated by Bacteroides spp. strains and an uncharacterized butyrate producing bacterium. The change in bacterial composition was accompanied by resolution of the patient's symptoms. The striking similarity of the recipient's and donor's intestinal microbiota following after bacteriotherapy suggests that the donor's bacteria quickly occupied their requisite niches resulting in restoration of both the structure and function of the microbial communities present.

Acetaminophen hepatotoxicity and acute liver failure.

Abstract: Acetaminophen-induced hepatotoxicity is a common consequence of acetaminophen overdose and may lead to acute liver failure (ALF). Currently acetaminophen is the most common cause of ALF in both United States and United Kingdom, with a trend to increasing incidence in the United States. N-acetylcysteine is the most effective drug to prevent progression to liver failure with acetaminophen hepatotoxicity. Liver transplantation is the only definitive therapy that will significantly increase the chances of survival for advanced ALF. This communication reviews current information regarding causes and management of acetaminophen-induced hepatotoxicity and ALF.

Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis.

Abstract: Background Treatment of portal vein thrombosis (PVT) in patients with liver cirrhosis is not well established. Aim We intended to assess the safety and efficacy of low molecular weight heparin (LMWH) to treat PVT in cirrhotic patients. Study All 39 patients diagnosed with non-neoplastic PVT and cirrhosis from June 2005 to December 2006 were evaluated for anticoagulation therapy (AT). PVT was occludent in 15.4%, partial in 64.1%, and portal cavernoma presented in 20.5%. Twenty-eight patients received 200 U/kg/d of enoxaparin for at least 6 months. In 39.3% of patients PVT was an occasional finding, in 10.7% presented with acute abdominal pain, in 50% with bleeding from gastroesophageal varices. In this last group LMWH was started after endoscopic eradication of varices by band ligation. Results Complete recanalization of portal vein occurred in 33.3%, partial recanalization in 50% and no response in 16.7% of patients. Further 12 patients who continued AT obtained complete recanalization at a median time of 11 months (range 7 to 17 mo). Overall, a complete response was obtained in 75% of patients. No significant side effects, particularly bleeding complications, were observed during the treatment. Conclusions LMWH demonstrated safe and effective in the treatment of PVT in patients with liver cirrhosis.

A Pilot Study Using Simvastatin in the Treatment of Nonalcoholic Steatohepatitis: A Randomized Placebo-controlled Trial

Abstract: Goals This study was designed to assess the utility of statin therapy in patients with biopsy proven nonalcoholic steatohepatitis (NASH) and hyperlipidemia. Background Nonalcoholic fatty liver disease, as the hepatic manifestation of the metabolic syndrome, has become a growing public health concern. Nonalcoholic steatohepatitis (NASH) represents a subset of nonalcoholic fatty liver disease manifested by hepatic fatty infiltration and inflammation which may progress to cirrhosis and its subsequent complications, to include hepatocellular carcinoma. As the metabolic syndrome is thought to be central in the pathogenesis of NASH, it has been speculated that medications that improve metabolic profiles may be beneficial in treatment. In fact, recent studies have demonstrated potential benefit of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), which are used in clinical practice to improve lipid panels. Study This double-blinded randomized placebo-controlled trial compared the HMG-CoA reductase inhibitor, simvastatin, with placebo in the treatment of NASH over a 12-month period using serum aminotransferases and repeat liver biopsy to assess for improvement. Results Sixteen patients with biopsy proven NASH were enrolled: 14 completed the study and 10 underwent 1-year repeat liver biopsy. Mean age: 53 years (±10.1), mean body mass index: 32.4 (±6.1) with 11 male and 5 female patients. Although a 26% reduction in low-density lipoprotein was seen in the simvastatin group compared with placebo, there was no statistically significant improvement in serum aminotransferases, hepatic steatosis, necroinflammatory activity or stage of fibrosis within or between groups. Conclusions In this pilot trial, monotherapy with simvastatin does not seem to be an effective treatment for NASH.

International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit.

Abstract: BackgroundAlthough clinicians generally make treatment decisions in irritable bowel syndrome (IBS) related to the type of symptoms, other factors such as the perceived severity and the risks patients are willing to tolerate for effective treatment are also important to consider. These factors are no

Patient factors predictive of inadequate bowel preparation using polyethylene glycol: a prospective study in Korea.

Abstract: Background: Inadequate bowel preparation is important because it can result in missed lesions, cancelled procedures, increased procedural time, and a potential increase in complication rates. This prospective study was designed to look at the quality of colon preparation using polyethylene glycol solution and evaluate potential associations between specific patient characteristics and inadequate bowel preparation. Methods: A total of 362 patients who were compliant with preparation instructions were enrolled. All colonoscopic examinations were performed by an experienced endoscopist and the quality of the preparation was graded by the endoscopist (excellent to poor). Patient demographic and medical history information was gathered before the procedure. Possible predictors of inadequate colonic preparation were analyzed using univariate statistics and multivariate logistic regression models. Results: An inadequate bowel preparation was reported in 28.2% of observed colonoscopies. In multivariate regression analysis, age greater than 60 years [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.04-7.4], a history of diabetes (OR 8.6, 95% Cl 6.3-19.4), a history of appendectomy (OR 4.6, 95% CI 2.0-10.5), a history of colorectal resection (OR 7.5, 95% CI 3.4-17.6), and a history of hysterectomy (OR 3.4, 95% CI 1.1-10.4) were independent predictors of an inadequate colon preparation. Conclusions: This prospective study identified several factors that may predict inadequate polyethylene glycol preparation independent of compliance with preparation instructions and procedure starting time. This result may help to identify patients at an increased risk for inadequate bowel preparation for whom alternative preparation protocols would be beneficial.

IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy.

Abstract: Background and aims Patients with liver cirrhosis may present minimal hepatic encephalopathy (MHE) that can be unveiled using specific neuropsychologic examination. Evaluation of MHE in cirrhotic patients might have prognostic value. The psychometric HE score (PHES) has been recommended as the "gold standard" in the diagnosis of MHE. It has been proposed that critical flicker frequency (CFF) analysis would be useful for easier detection of MHE. It would also be useful to have some peripheral parameter that could reflect the presence of MHE. It has been recently proposed that inflammation-associated alterations and hyperammonemia may cooperate in the induction of hepatic encephalopathy. The aim of the present work was to assess whether there is a correlation between the alterations in parameters reflecting inflammation, hyperammonemia, and the presence of MHE. Methods We have studied in 55 patients with liver cirrhosis and 26 controls the performance in the PHES battery and the CFF, ammonia, and some interleukins (ILs) as inflammatory markers. Results IL-6 and IL-18 were significantly higher (2.5-fold and 2.2-fold, respectively) in patients with MHE than in those without MHE. There were significant correlations between IL-6 or IL-18 levels and PHES score and CFF. Moreover, all patients with MHE had IL-6 levels higher than 11 ng/mL, whereas all patients without MHE had IL-6 levels lower than 11 ng/mL. Conclusions Inflammatory alterations related with IL-6 and IL-18 may contribute to MHE. Serum concentration of IL-6 and IL-18 may be useful to discriminate cirrhotic patients with and without MHE.

Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis.

Abstract: GOALS AND BACKGROUND: The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib. METHODS: Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors. RESULTS: Fifteen patients presented without LCI or with LCI Child- Pugh A, 15/4 patients had LCI Child-Pugh B/C. Barcelona Clinic Liver Cancer stage was B/C/D in 4/22/8 patients. During treatment period (median 2.2 mo), therapy was discontinued in 61.8% of patients due to tumor progression (32.3%), death (17.6%), AEs (8.8%), or noncompliance (2.9%). Most common grade 3/4 AEs included liver dysfunction (23.5%), diarrhea (14.7%), increased lipase (8.8%), fatigue (8.8%), and hand-foot skin reaction (5.9%). Worsening liver dysfunction/failure was more frequent (P=0.036) in patients with LCI Child-Pugh B/C compared with patients with maintained liver function (no LCI/LCI Child-Pugh A). Median overall survival was 7.2 months for patients with maintained liver function versus 3.3/3.4 months for patients with LCI Child-Pugh B/C.M CONCLUSIONS: These data do not support the use of sorafenib in patients with LCI Child-Pugh C, and patients with LCI Child-Pugh B should be treated with caution until larger trials provide more safety data and a clinically relevant survival benefit under sorafenib therapy.

Absence of infliximab in infants and breast milk from nursing mothers receiving therapy for Crohn's disease before and after delivery.

Abstract: GOALS The objective of this study was to determine whether infliximab, an antitumor necrosis factor monoclonal antibody, is transferred in utero or through breast milk from nursing Crohn's disease patients to their newborns. BACKGROUND Crohn's disease most often occurs in women of childbearing age. Many of these women receive treatment for their disease, but are advised to terminate therapy while pregnant or nursing. STUDY Three patients diagnosed with Crohn's disease who had a history of infliximab use during and after pregnancy were followed prospectively. Patients received 5-mg/kg infliximab at regular intervals until approximately gestational week 30, and resumed infliximab treatment within 3 to 14 days after giving birth. Serum samples from patients and children and breast milk samples were collected postpartum. The concentration of infliximab in the serum and milk samples was measured using an enzyme-linked immmunosorbent assay. RESULTS The levels of infliximab detected in the mothers' serum samples postpartum were 74.27, 62.62, and 59.97 microg/mL, respectively. However, infliximab was undetectable (<0.10 microg/mL) in the sera of the newborn children. Likewise, infliximab was undetectable in the breast milk of the nursing mothers. CONCLUSIONS Infliximab was detected in the mothers' sera, but not in the breast milk of nursing mothers or in the sera of the breast-fed newborns. Data from this small series of patients suggest that infliximab was not transferred from mother to child, either in utero or through breast milk. These data suggest that mothers receiving infliximab should not be discouraged from nursing their children.

The Effects of Genetic Polymorphisms of il-6 , il-8 , and il-10 on helicobacter pylori- induced Gastroduodenal Diseases in Korea

Abstract: Supported by the Korean Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (no A060266) and by grant no 06- 2006-009 from the Seoul National University Bundang Hospital Research fund

Efficacy of high-dose Lactobacillus rhamnosus GG in controlling acute watery diarrhea in Indian children: a randomized controlled trial.

Abstract: AimTo evaluate the effective dose of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhea (AWD) in Indian children.SettingHospital-based study.DesignRandomized, controlled, blinded trial.MethodsAll patients of AWD admitted over 1 year were included in the study. They were randomize

Why don't gastroenterologists follow colon polyp surveillance guidelines?: results of a national survey.

Abstract: GoalsTo measure knowledge and acceptance of colon polyp surveillance guidelines among gastroenterologists.BackgroundGastroenterologists often perform surveillance colonoscopy sooner than recommended by guidelines. Lack of knowledge may be an important factor, but gastroenterologists could also simpl

Combination Treatment With Octreotide, Midodrine, and Albumin Improves Survival in Patients With Type 1 and Type 2 Hepatorenal Syndrome

Abstract: IntroductionFew therapeutic modalities exist for the treatment of hepatorenal syndrome (HRS). The combination of octreotide, midodrine, and albumin has shown possible benefit in small preliminary studies in improving renal function and short-term survival.MethodsWe examined the effect of octreotide,

Surgical versus nonsurgical management of pancreatic pseudocysts.

Abstract: Goals: Compare patient characteristics and outcome and also physician referral patterns between surgically and nonsurgically managed patients with pancreatic pseudocysts. Background: Treatment of pancreatic pseudocysts can be accomplished by surgical, endoscopic, or percutaneous procedures. The ideal treatment method has not yet been defined. Patients: All patients treated for pancreatic pseudocyst between 1999 and 2005 were identified in our health services database. Patients were treated with surgical, endoscopic, and percutaneous drainage procedures at the discretion of the treating physician. Main outcome measures included complications, pseudocyst resolution, and treatment modality as a function of the treating physician's specialty. Results: Thirty patients (49%) were treated surgically, 24 endoscopically (39%), and 7 (11%) with percutaneous drainage. The most common indications for treatment were symptoms of pain, and biliary or gastric outlet obstruction (81%). Patients treated surgically and endoscopically were similar in terms of age (49 vs. 52y), mean cyst diameter (9.1 vs. 9.5 cm, P = 0.74), incidence of chronic pancreatitis (50% vs. 32%, P = 0.26) and complicated pancreaticobiliary disease (69% vs. 60%). There were no differences in complications (20% vs. 21%) or pseudocyst resolution (93.3% vs. 87.5%, P = 0.39) between the surgical and endoscopic groups. There was no significant difference in the rate of surgical versus nonsurgical treatment in patients initially evaluated by surgeons versus nonsurgeons. Conclusions: Surgical and endoscopic interventions for pancreatic pseudocysts are equally safe and effective with percutaneous drainage playing a less important role. Endoscopic drainage should be considered for initial therapy in appropriate patients.

Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease.

Abstract: Celiac disease (CD), also known as gluten-sensitive enteropathy or celiac sprue, is defined as a permanent intolerance to ingested gluten (the storage protein components of wheat, barley, and rye) that damages the small intestine characteristically inducing crypt hyperplasia and villous atrophy, which resolves with removal of gluten from the diet.1 Nonresponsive CD can be described in terms of the clinical scenario of a lack of initial response to a prescribed gluten-free diet (GFD), or the recurrence of gastrointestinal (GI) symptoms despite maintenance of GFD in a patient who responded initially to GFD.2 The prevalence of nonresponsive CD is unknown, but chronic diarrhea can be present in as many as 17% of the patients with CD after gluten withdrawal.3 Gluten contamination is the leading reason for nonresponsive CD, but other causes have been identified including small intestine bacterial overgrowth (SIBO).2-5 SIBO is a condition caused by an abnormal number of bacteria in the small intestine.6 The stomach and proximal small bowel normally contain relatively small numbers of bacteria in adults. The intestine, however, contains 300 to 500 different species of bacteria.7 The concentration of gut flora increases from 100 – 4 colony forming units/mL (CFU/mL) in the duodenum and the jejunum, to 100 – 5 in the proximal ileum, 105 – 8 in the terminal ileum, and 1010 – 12 CFU/mL in the cecum.8,9 Symptoms related to bacterial overgrowth are diarrhea, bloating, weight loss, anemia, and malabsorption. SIBO is especially common among the elderly, patients with previous GI surgery (Billroth II or small intestine anastomosis), decreased gastric acid secretion, intestinal diverticulosis, and motor disorders.10 To date, there is no general agreement as to which test should be preferred for the diagnosis of SIBO, but culture of intestinal aspirates is usually considered the standard for detecting bacterial overgrowth.6,7,11-13 SIBO has been suggested to be associated with a large number of different GI conditions, such as cirrhosis, chronic pancreatitis, and irritable bowel syndrome.14-16 However, in most cases the diagnosis of SIBO has been established by the use of hydrogen-breath tests (H2-BT), as a noninvasive alternative to quantitative culture of small intestinal aspirate. Data obtained from breath testing need a cautious interpretation, because the results vary significantly even with minor modifications to the used technique, and the definition of normal and abnormal varies in the literature.17,18 This test-to-test and center-to-center variability may explain the contradictory results obtained after comparing breath testing with other diagnostic test (specifically with quantitative culture of intestinal aspirate) or even among researchers using the same breath test for assessment of the frequency of SIBO in a particular disease.19 The lactulose H2-BT is an indirect test for SIBO, based on the fact that lactulose passes unabsorbed through the small bowel into the colon. The original definition of a positive lactulose test was an early hydrogen peak ( > 20 ppm), due to the presence of small intestine bacteria, occurring at least 15 minutes before the later prolonged peak secondary to colonic fermentation (double-peak criterion).18,20 However, in a study that examined and compared the diagnostic value of the lactulose H2-BT and of a scintigraphic orocecal transit study, with that of culture of intestinal aspirate, showed a poor sensitivity (16.7%) and specificity (70%) of the lactulose H2-BT for SIBO, when the definition of an abnormal test was based on the occurrence of the double-peak criterion. The combination with scintigraphy increased specificity to 100%, but sensitivity was only 38.9%.21 In another study, using the double-peak criterion, 20% of healthy volunteers showed a positive lactulose H2-BT.19 Other studies demonstrated the poor reliability of lactulose H2-BT for SIBO diagnosis as compared with culture of intestinal aspirate.6,13 A recent study using lactulose H2-BT as diagnostic tool suggested that SIBO was present in 66% of patients with CD and persistent GI symptoms after gluten withdrawal.4 The prevalence of SIBO in patients with CD based on the result of culture of proximal small intestinal aspirate is not known. The aim of this study is to evaluate the prevalence and clinical significance of SIBO in patients with CD based on the result of culture of proximal small intestinal aspirate.

Rifaximin in treatment of recurrent Clostridium difficile-associated diarrhea: an uncontrolled pilot study.

Abstract: To the Editor: Clostridium difficile is a sporeforming, Gram-positive anaerobic bacillus that is the most common cause of diarrhea in hospitalized patients. The incidence of C. difficile-associated diarrhea (CDAD) is increasing worldwide, likely due to increased use of broadspectrum antibiotics and the introduction of a clonal, hypervirulent strain associated with increased mortality and recurrent disease. The pathogenesis of CDAD involves exogenous infection by spores, often from a hospital environment, and disruption of the patient’s normal flora, usually with broad-spectrum antibiotics allowing for overgrowth of C. difficile. Recommended treatment for CDAD is oral metronidazole or oral vancomycin for 10 to 14 days. Although most patients respond initially to antibiotic therapy, 15% to 40% of patients experience a posttreatment recurrence of diarrhea in association with a positive stool test for C. difficile toxin. Patients can experience from 3 to 10 or more relapses and may require repeat courses of vancomycin or metronidazole, anion-binding agents, probiotics, immunotherapy, or a combination of these treatments. Although these therapies have proven effective in case series, none of them are ideal. Rifaximin is a minimally absorbed rifamycin antibiotic currently approved for travelers’ diarrhea caused by noninvasive Escherichia coli and is being investigated for hepatic encephalopathy and nonsystemic infectious gastrointestinal diseases. Rifaximin has excellent in vitro activity against C. difficile, is well tolerated, and does not seem to promote development of resistance against enteric organisms; thus, it may be a therapeutic option for CDAD. Clinical evidence for rifaximin use for recurrent CDAD stems from a case series of 8 patients given serial therapy with vancomycin immediately followed by rifaximin for 2 weeks started only if the patient was asymptomatic. In this case series, 7 of 8 patients responded to rifaximin therapy, whereas the remaining patients responded after 1 additional course of rifaximin therapy. The purpose of the current study was to expand this previous case series by reporting 6 cases of recurrent CDAD treated with rifaximin while patients were symptomatic. All patients were part of the authors’ clinical practice and had experienced at least 1 recurrence of CDAD before starting rifaximin therapy. In addition, this case series includes a patient with hepatic encephalopathy who developed newonset CDAD during treatment with rifaximin and concomitant systemic antibiotics. All 7 patients were identified on the basis of the clinical symptoms suggestive of CDAD and diagnosed using the C. difficile cytotoxin B test. Stool cultures were performed at the research laboratory of the authors using prereduced selective cycloserine cefoxitin fructose agar with taurocholate supplementation.

Follow-up of pregnant women with autoimmune hepatitis: the disease behavior along with maternal and fetal outcomes.

Abstract: GoalsTo assess maternal and fetal outcomes and clinical management of pregnancy in patients with autoimmune hepatitis (AIH).BackgroundThere is a paucity of information about maternal and fetal outcomes, and AIH activity during pregnancy and in the postpartum period. There is no consensus about the a

Imbalanced intrahepatic cytokine expression of interferon-gamma, tumor necrosis factor-alpha, and interleukin-10 in patients with acute-on-chronic liver failure associated with hepatitis B virus infection.

Abstract: Goals This study attempts to determine expressions of intrahepatic proinflammatory and anti-inflammatory cytokines and their secreting immunocytes to evaluate their roles in the pathogenesis of acute-on-chronic liver failure (ACLF) in chronically hepatitis B virus (HBV)-infected patients. Background ACLF generally affects patients with established, compensated chronic liver diseases who develop an acute deterioration in liver function. In China, HBV-associated ACLF patients account for more than 80% of ACLF patients owing to a high prevalence of chronic HBV infection. Clinical observation showed that the deterioration of this disease may correlate with host immune responses, but related underlying mechanism remains largely unknown. Study In situ expressions of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and their secreting CD4, CD8 T cells, and Kupffer cells (KCs) were analyzed in the livers of patients with ACLF, chronic hepatitis B (CHB), and normal controls (NC) using immunohistochemistry. Results Intrahepatic proinflammatory IFN-gamma and TNF-alpha expressions were markedly up-regulated in ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10 expressions were observed in ACLF and CHB. IFN-gamma overexpression correlated significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up-regulation also correlated significantly with increased KCs. Conclusions The imbalanced expression of proinflammatory and anti-inflammatory cytokines and increased accumulation of CD4, CD8 T cells, and KCs may contribute to immunopathogenesis in HBV-infected ACLF.

Nonacid reflux episodes reaching the pharynx are important factors associated with cough.

Abstract: BACKGROUND: Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. METHODS: Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. RESULTS: A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P<0.05] and a higher proportion of reflux episodes crossing the UES into the pharynx [25%(14% to 28%) vs. 7% (2% to 14%), P<0.02]. There was no difference in the number of reflux episodes or acid exposure time in the distal esophagus between SAP-positive and SAP-negative patients. Only 1% to 2% of episodes were detected by the pharyngeal pH sensor. CONCLUSIONS: Impedance detected pharyngeal reflux episodes are important factors in symptom production in cough patients.

A pilot study on the noninvasive evaluation of intestinal damage in celiac disease using I-FABP and L-FABP.

Abstract: Background and Goals: In the clinical management of celiac disease, new noninvasive tools for evaluation of intestinal damage are needed for diagnosis and for follow-up of diet effects. Fatty acid binding proteins (FABP) are potentially useful for this purpose as these arc small cytosolic proteins present in enterocytes and sensitive markers for intestinal mucosal damage. First, the distribution and microscopic localization of FABP in the healthy human intestine was examined. Second. levels of circulating FABP were measured in patients with celiac disease before and after introducing a gluten-free diet (GFD) and in healthy controls. Study: The distribution and microscopic localization of FABP in normal human intestinal tissue was assessed using surgical intestinal specimens of 39 patients. Circulating levels of intestinal (I)-FABP and liver (L)-FABP were determined in 26 healthy volunteers and 13 patients with biopsy proven celiac disease. Ten of these patients were reevaluated within 1 year after starting GFD. Results: I-FABP and L-FABP are predominantly present in the small intestine, mainly the jejunum. Moreover, FABP are expressed in cells on the upper part of the villi, the initial site of destruction in celiac disease. Circulating levels of FABP are significantly elevated in untreated patients with biopsy proven celiac disease compared with healthy controls (I-FABP: 784.7 pg/mL vs. 172.7 pg/mL, P <0.001: L-FARP: 48.4 ng/mL vs. 10.4 ng/mL, P <0.001). In response to GFD, these concentrations normalize. Conclusions: Results of this pilot study strongly suggest that FABP can be used as a noninvasive method for assessment of intestinal damage in celiac disease. Besides an additional role in the diagnosis of celiac disease. FABP potentially enable noninvasive monitoring of the GFD effects.

Microscopic colitis associated with omeprazole and esomeprazole exposure.

Abstract: Goals The aim of this study was to determine whether proton pump inhibitors other than lansoprazole might be associated with microscopic colitis. Background Lansoprazole exposure has been associated with diarrhea and microscopic colitis, but this relationship has not been described with other proton pump inhibitors. Study Cases of microscopic colitis from a consultative gastroenterology practice were collected and reviewed for proton pump inhibitor exposure. Standard clinical, endoscopic, and biopsy findings were analyzed. Results A case series of 4 patients is described in which subjects developed classic symptoms of lymphocytic-collagenous colitis with typical mucosal histopathology during treatment with omeprazole/esomeprazole. Symptoms promptly stopped and mucosal biopsies returned to normal with drug withdrawal. Disease quickly recurred in 2 patients who were reexposed to the drugs, one with biopsy documented recurrent collagenous colitis. Conclusions Some cases of microscopic colitis seem to be associated with omeprazole/esomaprazole exposure. These results have epidemiologic, diagnostic, and therapeutic ramifications, which are discussed.

Endoscopic ultrasound versus CT scan for detection of the metastases to the liver: results of a prospective comparative study.

Abstract: Background Computed tomography (CT) scan is a standard test for the detection of the liver metastases; however, metastases are often missed on the CT scan. Objective To compare the accuracy of the endoscopic ultrasound (EUS)/endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with CT scan for detection of the liver metastases. Design Prospective study. Patients Subjects with newly diagnosed tumors of the lung, pancreas, biliary tree, esophagus, stomach, and colon were enrolled. Interventions A CT scan and EUS examination of the liver was performed. EUS-FNA was performed on noncystic liver lesions. Results One hundred thirty-two cases were enrolled. The presence of liver metastasis was established in 26 cases. The diagnostic accuracy of EUS/EUS-FNA and CT scan was 98% and 92%, respectively (P=0.0578). In comparison to CT scan, EUS detected significantly higher number of metastatic lesions in the liver (40 vs.19; P=0.008). CT scan detected lesions in liver that were too small to be characterized in 8 cases (malignant-3; benign-5). Of these, EUS-FNA correctly characterized the lesion to be malignant in 3/3 cases and benign in 4/5 cases. No complications were observed as a result of EUS-FNA. Limitations Endoscopist was not blinded to the findings of the CT scan. Conclusions In comparison with the CT scan, there was trend in favor of EUS/EUS-FNA for the superior diagnostic accuracy. EUS was distinctly superior to the CT scan in detecting the number of metastatic lesions. EUS-FNA was also useful to identify the nature of lesions that were too small to be characterized on the CT scan.

Comparison of commercially available serologic kits for the detection of celiac disease.

Abstract: Background: The sensitivity and specificity of current antihuman tissue transglutaminase (tTG) IgA assays used to detect celiac disease reportedly approach 100%. In addition, the sensitivity of new generation deamidated gliadin peptide (a-DGP) antibody assays has also been reported to be similar to the tTG IgA assays. In routine clinical practice, however, the sensitivities and specificities of these tests for diagnosing celiac disease seem to be lower. Aim: We analyzed sensitivities and specificities of 4 IgA tTG and 3 deamidated gliadin peptide (a-DGP) kits. Methods: The performance of 4 tTG IgA assays, A: Inova (Hu red blood cell), B: Binding site (rHu Ag), C: Eurospital (rHu Ag), D: Immco (rHu Ag) and 3 Inova a-DGP assays, E: a-DGP-IgA, F: a-DGP-IgG, and G: a-DGP-IgA+G was evaluated using sera from different subsets of celiac disease patients and controls; group 1: active celiac disease n = 28, group 2: gluten-free diet n = 54, group 3: healthy controls n = 40, group 4: disease controls n = 57(Crohn’s disease n = 17, chronic hepatitis n = 40). Results: Using the manufacturer’s cut-off values, the sensitivities and specificities of different kits ranged from 71.4% to 96.4% and 87.5% to 100%, respectively. When group 1 was compared with disease controls, sensitivities remained the same but specificities decreased. Receiver operating characteristic plot derived cut-off values modified decision thresholds in all assays except kit (G). Kappa analysis demonstrated variable degrees of agreement. All assays demonstrated higher sensitivities for patients with higher grades of villous atrophy. Conclusions: Overall sensitivity was at or below 90%, which is lower than that reported in the literature. Performance of the recombinant and red blood cell antigen-based tTG assays was similar, whereas the a-DGP assays demonstrated lower values. Receiver operating characteristic plot derived cut-off values altered test results. Many factors affect the results of these tests and clinicians should be aware of their limitations.

Small intestinal nonmeckelian diverticulosis.

Abstract: Nonmeckelian jejunoileal diverticula (JID) are rare, but potentially clinically significant lesions. Despite recent advances in modern diagnostic modalities, diagnosis of JID may be problematic. Upper gastrointestinal contrast series with small bowel follow-through examination and mainly enteroclysis are the 2 main diagnostic methods. In selected cases (mainly complicated JID), the physician could use other diagnostic methods, such as ultrasound, computed tomography, endoscopy, intraoperative endoscopy, laparoscopy, radiotagged erythrocyte bleeding scans, and selective mesenteric arteriography. JID may be clinically silent or symptomatic causing chronic pain or malabsorption or other acute complications, such as hemorrhage, inflammation, perforation, etc. Laparotomy remains the gold standard for definite diagnosis of asymptomatic and complicated diverticula. Treatment should be individualized. Surgery could be indicated, mainly in symptomatic diverticula. The extent of resection may be a problem, especially in patients with extensive disease involving large parts of the bowel. In these cases, clinical judgment is required from the part of surgeon to avoid short bowel syndrome.

A Combination of Rifaximin and Neomycin Is Most Effective in Treating Irritable Bowel Syndrome Patients With Methane on Lactulose Breath Test

Abstract: There is a growing interest in methane and its association with constipation in functional bowel disease. Neomycin-based treatment of methane-positive subjects has resulted in improvement of constipation. Rifaximin, although superior for the treatment of irritable bowel syndrome compared with other

Gastroesophageal reflux disease (GERD): risk factors, and impact on quality of life-a population-based study.

Abstract: Background: We aimed to determine the prevalence of gastroesophageal reflux disease (GERD) and associated risk factors, and assess quality of life (QoL) in relation to the frequency and severity of reflux symptoms. Methods: A random sample of 1000 residents of Western Sydney were mailed a validated self-report questionnaire. GERD symptoms, risk factors, psychologic distress, QoL, and demographics were measured. Results: The response rate was 73% (n = 672; mean age, 46 y; 52% female). A total of 78 [12%, 95% confidence interval (CI): 9-14] had GERD (at least weekly heartburn and/or acid regurgitation). Independent risk factors for GERD were high cholesterol [odds ratio (OR) = 3.28, 95% CI: 1.42-7.57, P = 0.005] and current smoker (OR = 2.47, 95% CI: 1.07-5.70, P = 0.03). Anxiety, depression, and neuroticism were not risk factors. Worse physical functioning was the only QoL domain associated with GERD (OR = 0.98, 95% CI: 0.97-0.99, P = 0.006). QoL was significantly impaired regardless of the severity of GERD for the QoL domains physical function, body pain, vitality, and social function. The frequency of heartburn and acid regurgitation were not associated with significantly reduced QoL domain scores. Conclusions: Cardiac risk factors (high cholesterol and smoking) were independently associated with GERD. Increasing GERD symptom severity is associated with worse QoL scores, whereas GERD symptom frequency did not impact the QoL scores.

Large size balloon dilation of the ampulla after biliary sphincterotomy can facilitate endoscopic extraction of difficult bile duct stones.

Abstract: Goals Evaluate the efficacy and safety of large size balloon dilation of the biliary orifice after maximal biliary sphincterotomy to facilitate removal of difficult bile duct stones in a Western population. Background Some bile duct stones may be difficult to remove with standard endoscopic retrograde cholangiopancreatography (ERCP) techniques. Even after multiple procedures, and the use of advanced, labor-intense techniques complete stone clearance may be difficult to achieve. Study This is retrospective review of prospectively collected data. Patients who had failed stone extraction with standard balloon technique after maximal biliary sphincterotomy at the index ERCP underwent large size balloon dilation of the biliary orifice to facilitate stone removal. The main outcomes were complete stone clearance and complications. Result Forty-four patients were evaluated. Thirty-one (70%) had a prior failed ERCP in the past. Periampullary diverticulum was present in 13 patients (30%). Complete stone removal was accomplished in 42 patients (95%). In 37 patients (84%), complete stone clearance was accomplished at the index ERCP without the need for mechanical lithotripsy. Three patients (6%) required an additional ERCP and 2 patients (5%) required 2 additional ERCPs to accomplish complete stone removal. Three mild complications occurred (6.8%). None of the patients developed perforation or pancreatitis. Conclusions Large size balloon dilation after biliary sphincterotomy is simple, safe, and highly effective technique that can greatly assist in the management of difficult to extract bile duct stones.

Serum retinol-binding protein 4 levels in patients with nonalcoholic fatty liver disease.

Abstract: Background: Nonalcoholic fatty liver disease (NAFLD), one of the most common forms of chronic liver disease, is closely associated with obesity and insulin resistance (IR). Recent studies suggest serum retinol-binding protein 4 (RBP4) plays a key role in the pathogenesis of IR. The aims of this study were to determine serum RBP4 levels in patients with biopsy proven NAFLD, and to correlate these levels with the metabolic profile and histologic features in this population. Methods: Our cohort consisted of 51 consecutive patients undergoing liver biopsy for clinical suspicion of NAFLD. Patients were subsequently divided into 3 groups: simple steatosis (n = 16), borderline nonalcoholic steatohepatitis (NASH) (n = 2) and NASH (n = 33). The stage of fibrosis was measured using a 4-point scale. RBP4 was measured in triplicates by a specific enzyme-linked immunosorbent assay. The degree of insulin resistance was determined by the homeostatic model assessment. Results: Serum RBP4 levels did not correlate with body mass index, homeostatic model assessment, fasting glucose, or insulin levels in patients with simple steatosis and NASH. Moreover, RBP4 levels were lower in patients with NASH compared with those with simple steatosis (21.3 and 26.8 mg/L, respectively) although the difference did not reach statistical significance (P = 0.21). A stepwise decrease in RBP4 levels from patients without fibrosis (27.9mg/L) to patients with cirrhosis (14.1mg/L) was noted (P = 0.03). Conclusions: Our study demonstrates that in adult patients with NAFLD, serum RBP4 levels do not correlate with body mass index or insulin resistance and identifies a novel association between serum RBP4 levels and hepatocellular injury in these patients.

Liver stiffness measurement in combination with noninvasive markers for the improved diagnosis of B-viral liver cirrhosis.

Abstract: Goal: To investigate the performance of liver stiffness measurement (LSM) in combination with available noninvasive markers in hepatitis B virus-related chronic liver disease. Background: Few noninvasive methods are available for predicting liver cirrhosis in chronic hepatitis B (CHB). Study: Between January 2006 and June 2007, we studied 130 consecutive treatment-naive CHB patients who underwent liver biopsy (LB) and LSM. The aspartate to alanine aminotransferase ratio, age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), LSM, and their combinations were compared with liver histology. Results: The API, APRI, and LSM, but not the aspartate to alanine aminotransferase ratio, correlated significantly with liver cirrhosis (all P < 0.001). The diagnostic accuracy of LSM and API exceed that of the other diagnostic methods for predicting liver cirrhosis (area under the receiver operating characteristic curve = 0.840 and 0.818). When LSM was combined with API and APRI, the diagnostic accuracy was improved markedly (area under the receiver operating characteristic curve = 0.871, and 0.846). When both LSM and API results were in agreement, LB confirmed them in 89.1% (41/46) of cases for liver cirrhosis. LB could have been avoided in 41 (31.5%) of the 130 patients who were examined for the potential diagnosis of liver cirrhosis. Conclusions: The combination of LSM and API can avoid unnecessary invasive LB procedures in CHB patients.

Characteristics and Long-term Prognosis of the Autoimmune Hepatitis/Primary Sclerosing Cholangitis Overlap Syndrome

Abstract: Goals/BackgroundDiagnosis, treatment, and prognosis of the overlap syndrome of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are controversial. Our aim was to assess the clinical characteristics and long-term prognosis of the AIH/PSC overlap syndrome.StudyWe reviewed the data o