The most cited articles published since 2010, extracted from Scopus
Volume 8, Issue 1, January 2010, Pages 23-29
Roos E. Pouw | Katja Wirths | Pierre Eisendrath | Carine M T Sondermeijer | Fiebo Jw W Ten Kate | Paul Fockens | Jacques Devière | Horst N. Neuhaus | Jacques J G H M Bergman
Background & Aims: Radiofrequency ablation (RFA) is safe and effective for eradicating intestinal metaplasia and neoplasia in patients with Barrett's esophagus. We sought to assess the safety and efficacy of RFA in conjunction with baseline endoscopic resection for high-grade intraepithelial neoplasia (HGIN) and early cancer. Methods: This multicenter, prospective cohort study included 24 patients (mean age, 65 years; median Barrett's esophagus, 8 cm), with Barrett's esophagus of ≤12 cm containing HGIN or early cancer, from 3 European tertiary-care medical centers. Visible lesions were endoscopically resected, followed by serial RFA. Focal escape endoscopic resection was used if Barrett tissue persisted despite RFA. Complete response, defined as all biopsies negative for intestinal metaplasia and neoplasia, was assessed during endoscopy with 4-quadrant biopsies taken every 1 cm of the original Barrett's segment 2 months after the patient was last treated. Results: Twenty-three patients underwent pre-RFA endoscopic resection for visible lesions; 16 patients had early cancer and 7 patients had HGIN. The worst residual histology results, pre-RFA (after any endoscopic resection) were: HGIN (10 patients), low-grade intraepithelial neoplasia (11 patients), and intestinal metaplasia (3 patients). Neoplasia and intestinal metaplasia were eradicated in 95% and 88% of patients, respectively; after escape endoscopic resection in 2 patients, rates improved to 100% and 96%, respectively. Complications after RFA included melena (n = 1) and dysphagia (n = 1). After additional follow-up (median, 22 months; interquartile range, 17.2-23.8 months) no neoplasia recurred. Conclusions: This European multicenter study to show that early neoplasia in Barrett's esophagus can be effectively and safely treated with RFA, in combination with prior endoscopic resection of visible lesions. © 2010 AGA Institute.
Volume 9, Issue 12, December 2011, Pages 1044-1049
Johan S. Bakken | Thomas Julius Borody | Lawrence Brandt | Joel V. Brill | Daniel C. DeMarco | Marc Alaric Franzos | Colleen R. Kelly | Alexander Khoruts | Thomas J. Louie | Lawrence P. Martinelli | Thomas A. Moore | George H. Russell | Christina M. Surawicz
Clostridium difficile infection is increasing in incidence, severity, and mortality. Treatment options are limited and appear to be losing efficacy. Recurrent disease is especially challenging; extended treatment with oral vancomycin is becoming increasingly common but is expensive. Fecal microbiota transplantation is safe, inexpensive, and effective; according to case and small series reports, about 90% of patients are cured. We discuss the rationale, methods, and use of fecal microbiota transplantation. © 2011 AGA Institute.
Volume 9, Issue 6, June 2011, Pages 509-516.e1
Lisa Ione Backus | Derek B. Boothroyd | Barbara R. Phillips | Pamela S. Belperio | James P. Halloran | Larry A. Mole
Background & Aims: The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities. Methods: From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009. Results: HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002). Conclusions: An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities. © 2011 AGA Institute.
Volume 9, Issue 6, June 2011, Pages 524-530.e1
Zabair M. Younossi | Maria S. Stepanova | Mariam Afendy | Yun Fang | Youssef Younossi | Heshaam M. Mir | Manirath K. Srishord
Background & Aims: Chronic liver diseases (CLDs) are major causes of morbidity and mortality worldwide. We assessed changes in the prevalence of different types of CLD in the United States. Methods: National Health and Nutrition Examination Surveys conducted between 1988 and 2008 were used to estimate changes in the prevalence and predictors of CLDs. Serologic and clinical data were used to establish the diagnoses of CLDs in 39,500 adults. Statistical analyses were conducted with SUDAAN 10.0 (SAS Institute, Inc, Cary, NC). Results: The prevalence rates for CLD were 11.78% (1988-1994), 15.66% (1999-2004), and 14.78% (2005-2008). During the same period, the prevalence of hepatitis B virus infection (0.36%, 0.33%, and 0.34%), hepatitis C virus (1.95%, 1.97%, and 1.68%), and alcoholic liver disease (1.38%, 2.21%, and 2.05%) remained generally stable. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD) increased from 5.51% to 9.84% to 11.01%. From 1988 to 1994, NAFLD accounted for 46.8% of CLD cases; from 1994 to 2004 its prevalence increased to 62.84%, and then to 75.1% from 2005 to 2008. During these time periods, steady increases were observed in obesity (21.74%, 30.02%, and 33.22%), visceral obesity (35.18%, 48.16%, and 51.43%), type II diabetes (5.55%, 7.88%, and 9.11%), insulin resistance (23.29%, 32.50%, and 35.00%), and hypertension (22.68%, 33.11%, and 34.08%). A multivariate analysis showed that during all time periods, obesity was an independent predictor of NAFLD. Conclusions: National Health and Nutrition Examination Surveys data collected from 1988 to 2008 show that the prevalence of major causes of CLD remained stable, except for NAFLD, which increased steadily, along with the prevalence of metabolic conditions. Given the increasing rates of obesity, NAFLD prevalence is expected to contribute substantially to the burden of CLD in the United States. © 2011 AGA Institute.
Volume 8, Issue 3, March 2010, Pages 235-244
Marjolein Sikkema | Pieter Jan F De Jonge | E. W. Steyerberg | Ernst Johan Kuipers
Background & Aims: As the risk of esophageal adenocarcinoma (EAC) and mortality in patients with Barrett's esophagus (BE) are important determinants of the potential yield and cost-effectiveness of BE surveillance, clarification of these factors is essential. We therefore performed a systematic review and meta-analysis to determine the incidence of EAC and mortality due to EAC in BE under surveillance. Methods: Databases were searched for relevant cohort studies in English language that reported EAC risk and mortality due to EAC in BE. Studies had to include patients with histologically proven BE, documented follow-up, and histologically proven EAC on surveillance. A random effects model was used with assessment of heterogeneity by the I2-statistic and of publication bias by Begg's and Egger's tests. Results: Fifty-one studies were included in the main analysis. The overall mean age of BE patients was 61 years; the mean overall proportion of males was 64%. The pooled estimate for EAC incidence was 6.3/1000 person-years of follow-up (95% confidence interval, 4.7-8.4) with considerable heterogeneity (P < .001; I2 = 79%). Nineteen studies reported data on mortality due to EAC. The pooled incidence of fatal EAC was 3.0/1000 person-years of follow-up (95% confidence interval, 2.2-3.9) with no evidence for heterogeneity (P = .4; I2 = 7%). No evidence of publication bias was found. Conclusions: Patients with BE are at low risk of malignant progression and predominantly die due to causes other than EAC. This undermines the cost-effectiveness of BE surveillance and supports the search for valid risk stratification tools to identify the minority of patients that are likely to benefit from surveillance. © 2010 AGA Institute.
Volume 9, Issue 2, February 2011, Pages 110-117
Javier Molina-Infante | Luci´a Ferrando-Lamana | Cristina Ripoll | Moisés Hernández-Alonso | Jose M. Mateos | Miguel Fernández-Bermejo | Carmen Dueñas | Nuria Fernández-González | Eva M. Quintana | Maria Ángeles González Núñez
Background & Aims: Despite consensus recommendations, eosinophilic esophagitis (EoE) is commonly diagnosed upon esophageal eosinophilic infiltration (EEI; based on ≥15 eosinophils per high power field; eo/HPF). We evaluated the prevalence of EEI before and after proton pump inhibitor (PPI) therapy and assessed the accuracy of EEI and pH monitoring analyses. Methods: Biopsies were taken from the upper-middle esophagus of 712 adults with upper gastrointestinal symptoms who were referred for endoscopy due to upper gastrointestinal symptoms. Patients with EEI were treated with rabeprazole (20 mg, twice daily) for 2 months. EoE was defined by persistent symptoms and >15 eo/HPF following PPI therapy. Results: Thirty-five patients (4.9%) had EEI, of whom 55% had a history of allergies, and 70% had food impaction or dysphagia as their primary complaint. Twenty-six EEI patients (75%) achieved clinicopathological remission with PPI therapy; of these, 17 had GERD-like profile (EEI <35 eo/HPF and objective evidence of reflux, based on endoscopy or pH monitoring), and 9 had EoE-like profile (EEI 35-165 eo/HPF, typical EoE symptoms and endoscopic findings). The PPI response was 50% in the EoE-like profile patients. The PPI-response was 50% in EoE-like profile patients. Likewise, PPI-responsive EEI occurred with normal (33%) and pathologic (80%) pH monitoring. Higher histologic cut-off values improved specificity and positive predictive for EoE (35%-35% for >20 eo/HPF; 46%-39% for >24 eo/HPF; 65%-50% for 35 eo/HPF). Conclusions: In adults with EEI, 75% of unselected patients and 50% with an EoE phenotype respond to PPI therapy; pH monitoring is poorly predictive of response. Patients with PPI-responsive EEI >35 eo/HPF are phenotypically undistinguishable from EoE patients. EoE might be overestimated without clinical and pathologic follow-up of patient response to PPI. © 2011 AGA Institute.
Volume 10, Issue 7, July 2012, Pages 712-721
Rebecca M. Lovell | Alexander Charles Ford
Background & Aims: Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global prevalence and risk factors. Methods: MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Results: Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data. Conclusions: The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described. © 2012 AGA Institute.
Volume 9, Issue 1, January 2011, Pages 42-46
Charles J. Kahi | David G. Hewett | Dustin Lee Norton | George Joseph Eckert | Douglas Kevin Rex
Background & Aims: Colonoscopy may have a greater protective effect for distal colorectal cancer (CRC) than proximal CRC. Serrated polyps are frequently located in the proximal colon, can be missed during colonoscopy, and may progress to CRC. We investigated the prevalence and endoscopist detection rates of proximal serrated polyps in a large cohort of average risk patients undergoing screening colonoscopy. Methods: Screening colonoscopies performed by 15 attending gastroenterologists at 2 academic endoscopy units between 2000 and 2009 were reviewed. Serrated polyps included hyperplastic polyps, sessile serrated adenomas, and traditional serrated adenomas. Endoscopist-level detection rates for adenomas and serrated polyps were calculated. Pearson correlation coefficients were calculated to evaluate the associations of adenoma and proximal serrated polyp detection rates. Logistic regression was used to compare endoscopists' detection rates. Results: A total of 11,049 polyps were detected in 6681 colonoscopies (adenomas: 5637, 51%; serrated: 3984, 36%; proximal serrated: 1238, 11%). The proportion of colonoscopies with at least one proximal serrated polyp was 13% (range 1%-18%). Proximal serrated polyp detection rates per colonoscopy ranged from 0.01 to 0.26. Adenoma and proximal serrated polyp detection rates per colonoscopy were strongly correlated (R = 0.76, P = .0005). The odds of detecting at least one proximal serrated polyp for individual endoscopists ranged from 0.05 to 0.67 compared to the highest level detector. Endoscopist (P < .0001), but not patient age (P = .76) or gender (P = .95), was associated with proximal serrated polyp detection. Conclusions: In an average-risk screening cohort, the detection of proximal serrated polyps was highly variable and endoscopist dependent. A significant proportion of proximal serrated polyps may be missed during colonoscopy. High-quality colonoscopy is important for the detection and resection of all polyps with neoplastic potential. © 2011 AGA Institute.
Volume 9, Issue 1, January 2011, Pages 36-41
David S. Kotlyar | Mark T. Osterman | Robert H. Diamond | David L. Porter | Wojciech C. Błoński | Mariusz A. Wasik | Sami Sampat | Manuel Mendizábal | Mingvalerie Lin | Gary R. Lichtenstein
Background & Aims: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and usually fatal lymphoma that primarily affects men younger than 35 years old. Treatment of patients with inflammatory bowel disease (IBD) using antibodies to tumor necrosis factor (anti-TNFs) and thiopurines has been associated with HSTCL. We investigated the medications, duration of therapy, and ages of patients associated with HSTCL. Methods: We collected and analyzed data on the association between HSTCL, and anti-TNF and thiopurine therapies in patients with IBD from published reports and the MedWatch reporting system of the US Food and Drug Administration. Results: Of 36 patients with HSTCL, 20 received therapy with infliximab and a thiopurine and 16 received a thiopurine as monotherapy for IBD. Four patients who had been treated with infliximab and a thiopurine also received adalimumab. One of these patients had been given infliximab, adalimumab, and natalizumab. Of 31 patients of known gender, only 2 were female. Twenty-seven of the 30 patients of known age were younger than 35 years old. Conclusions: Most patients with HSTCL who received long-term therapy (at least 2 y) with thiopurines for IBD were men younger than 35 years old. There were no reported cases of HSTCL in patients with IBD who received only anti-TNF therapy. Physicians should consider giving thiopurines and anti-TNF agents to young male patients with IBD only in cases in which a clear benefit is expected, such as in early stage disease in untreated patients or possibly in very severe cases. © 2011 AGA Institute.
Volume 9, Issue 4, April 2011, Pages 344-350.e2
Albert Friedrich Stättermayer | Rudolf E. Stauber | Harald Hofer | Karoline Rutter | Sandra Beinhardt | Thomas Matthias Scherzer | Kerstin Zinober | Christian Datz | Andreas Maieron | Emina Dulic-Lakovic | Harald H. Kessler | Petra Steindl-Munda | Michael Strasser | Christoph Krall | Péter Ferenci
Background & Aims: Single nucleotide polymorphisms (SNPs) in the gene that encodes interleukin (IL)-28B predict response of patients with chronic hepatitis C to antiviral therapy. We investigated the roles of polymorphisms rs12979860 and rs8099917 on the early virologic response of treatment-naïve patients. Methods: SNPs were identified by real-time polymerase chain reaction analysis of samples from 682 patients (genotype [GT]1 = 372, GT2/3 = 208, GT4 = 102) who were treated with 180 μg pegylated interferon-α2a and 400 or 800 mg (GT2/3, depending on the protocol) or 1000-1200 mg (GT1/4) ribavirin/day. The duration of treatment was 24 (GT2/3) or 24-72 weeks (GT1/4). Results: Patients with C/C also had higher rates of rapid virologic response (RVR) (GT1, 38.3% vs 11.6%; GT4, 76.5% vs 23.5%; both P < .001) and sustained virologic responses (SVRs) (GT1, 79.1% vs 43.2%; GT4, 85.3% vs 44.1%; both P < .001). In patients with GT2/3, the RVR was more frequent in carriers of C/C (75.3% vs 52.6%, P < .01), but SVR rates were similar between those with C/C and T (80.5% vs 74.4%, P = .31). Results for rs8099917 were comparable. The positive predictive value of rs12979860 C/C for SVR was higher than that of rs8099917 T/T (80.5% vs 71.6%). Overall, RVR was the best predictor of SVR. In patients who did not have GT1, IL28B polymorphisms did not affect the SVR if RVR data were included in the multivariate analysis. Conclusions: An early virologic response to pegylated interferon and ribavirin is more likely among carriers of rs12979860 C/C and rs8099917 T/T, which might underlie their high rates of SVR. Determination of the IL28B genotype and whether patients have an RVR might be used in future studies of patients with hepatitis C virus genotype 1 or 4. © 2011 AGA Institute.
Volume 8, Issue 1, January 2010, Pages 36-41.e1
Dengchyang Wu | PingI I. Hsu | Jengyih Wu | Antone R. Opekun | Chaohung Kuo | I. Chen Wu | Sophiesw Wang | Angela Chen | Wenchun Hung | David Yates Graham
Background & Aims: Sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole agent reportedly have a better rate of curing Helicobacter pylori infection than PPI, amoxicillin, and clarithromycin triple therapy. The concomitant administration of these 4 drugs (concomitant therapy) is also an effective treatment strategy. We compared the efficacies of sequential and concomitant therapy and analyzed the effects of antibiotic resistance in patients with H pylori infection. Methods: In a randomized trial of 232 H pylori-infected patients from 3 hospitals in Kaohsiung, Taiwan, patients were given 10 days of sequential (n = 115) or concomitant (n = 117) therapy. H pylori status was confirmed by endoscopy or urea breath test. Results: Intention-to-treat analysis demonstrated similar eradication rates for sequential (92.3%; 95% confidence interval [CI], 87.5%-97.1%) and concomitant therapy (93.0%; 95% CI, 88.3%-97.7%)(P = .83). Per-protocol eradication results were similar for sequential (93.1%; 95% CI, 90.7%-95.5%) and concomitant therapy (93.0%; 95% CI, 88.3%-97.7%) (P = .99). Univariate analysis showed that compliance and resistance to clarithromycin were independent determinants of eradication. Dual resistance did not influence the level of eradication in the concomitant group, but significantly affected that of the sequential therapy group. Clarithromycin resistance was less frequent than expected. Conclusions: Sequential or concomitant therapy with a PPI, amoxicillin, clarithromycin, and an imidazole agent are equally effective and safe for eradication of H pylori infection. Resistance to clarithromycin, compliance, and adverse events reduced the level of eradication. Concomitant therapy may be more suitable for patients with dual resistance to antibiotics. © 2010 AGA Institute.
Volume 8, Issue 3, March 2010, Pages 280-288.e1
Amit G. Singal | Michael L. Volk | Donald M. Jensen | Adrian M. Di Bisceglie | Philip S. Schoenfeld
Background & Aims: The incidences of decompensated cirrhosis (defined by ascites, hepatic encephalopathy, or bleeding esophageal varices), hepatocellular carcinoma (HCC), and liver-related mortality among patients infected with hepatitis C virus (HCV) who achieve a sustained viral response (SVR), compared with patients who fail treatment (treatment failure), are unclear. We performed a meta-analysis to quantify the incidences of these outcomes. Methods: This meta-analysis included observational cohort studies that followed HCV treatment failure patients; data were collected regarding the incidence of decompensated cirrhosis, HCC, or liver-related mortality and stratified by SVR status. Two investigators independently extracted data on patient populations, study methods, and results by using standardized forms. The agreement between investigators in data extraction was greater than 95%. Data analysis was performed separately for studies that enrolled only HCV patients with advanced fibrosis. Results: We identified 26 appropriate studies for meta-analysis. Among treatment failure patients with advanced fibrosis, rates of liver-related mortality (2.73%/year; 95% confidence interval [CI], 1.38-4.080), HCC (3.22%/year, 95% CI, 2.02-4.42), and hepatic decompensation (2.92%/year; 95% CI, 1.61-4.22) were substantial. Patients with SVR are significantly less likely than patients who experienced treatment failure to develop liver-related mortality (relative risk [RR], 0.23; 95% CI, 0.10-0.52), HCC (RR, 0.21; 95% CI, 0.16-0.27), or hepatic decompensation (RR, 0.16; 95% CI, 0.04-0.59). Conclusions: HCV patients with advanced fibrosis who do not undergo an SVR have substantial liver-related morbidity and mortality. Achieving SVR is associated with substantially lower liver-related morbidity and mortality. © 2010 AGA Institute.
Volume 9, Issue 5, May 2011, Pages 400-409.e1
Alex Straumann | Sébastien Conus | Lukas P. Degen | Cornelia Frei | Christian Bussmann | Christoph H. Beglinger | Alain M. Schoepfer | Hans Uwe Símon
Backround & Aims: Topical corticosteroids are effective in inducing clinical and histologic remission in patients with eosinophilic esophagitis (EoE). However, the best long-term management strategy for this chronic inflammatory disease has not been determined. Methods: In a randomized, double-blind, placebo-controlled, 50-week trial, we evaluated in 28 patients the efficacy of twice-daily swallowed budesonide (0.25 mg each) to maintain quiescent EoE in remission. Pretreatment and posttreatment activity was assessed clinically, endoscopically, histologically, immunohistologically, and by endosonography. The primary end point was the therapy's ability to maintain EoE in histologic remission. Secondary end points were efficacy in symptom control, prevention of tissue remodeling, and safety. Results: In patients given low-dose budesonide, the load of esophageal eosinophils increased from 0.4 to 31.8 eosinophils/high-power field (P = .017). In patients given placebo, the load increased from 0.7 to 65.0 eosinophils/high-power field (P = .0001); this increase was significantly greater than in patients given budesonide (P = .024). The symptom scores developed in a similar manner in the 2 groups. Budesonide, but not placebo, reduced noneosinophilic markers of inflammation, epithelial cell apoptosis, and remodeling events. Compared with control individuals, patients had significantly thickened esophageal walls, based on endosonography (3.05 vs 2.18 mm; P < .0001). Budesonide therapy was associated with a significant reduction in mucosal thickness (0.75-0.45 mm; P = .025), but epithelial thickness remained stable (261.22 vs 277.23 μm; P = .576). No serious adverse events occurred. Conclusions: Low-dose budesonide is more effective than placebo in maintaining EoE in histologic and clinical remission. Signs of esophageal remodeling showed a trend toward normalization. Long-term administration of topical corticosteroids was well tolerated without induction of epithelial atrophy. © 2011 AGA Institute.
Volume 8, Issue 3, March 2010, Pages 268-274
Millie Long | Hans H. Herfarth | Clare A. Pipkin | Carol Q. Porter | Robert S. Sandler | Michael D. Kappelman
Background & Aims: Patients with inflammatory bowel disease (IBD) might be at increased risk for certain malignancies. We evaluated the risk of non-melanoma skin cancer (NMSC) in patients with IBD and determined how immunosuppressive and biologic medications affect this risk. Methods: We performed retrospective cohort and nested case-control studies by using administrative data from PharMetrics Patient Centric Database. In the cohort study, 26,403 patients with Crohn's disease (CD) and 26,974 patients with ulcerative colitis (UC) were each matched to 3 non-IBD controls. NMSC risk was evaluated by incidence rate ratio (IRR). In the nested case-control study, 387 CD patients and 355 UC patients with NMSC were each matched to 4 IBD patients without NMSC by using incidence density sampling. Conditional logistic regression was used to determine the association between specific IBD medication use and NMSC. Results: In the cohort study, the incidence of NMSC was higher among patients with IBD compared with controls (IRR, 1.64; 95% confidence interval [CI], 1.51-1.78). In the nested-case control study, recent thiopurine use (≤90 days) was associated with NMSC (adjusted odds ratio [OR], 3.56; 95% CI, 2.81-4.50), as was recent biologic use among patients with CD (adjusted OR, 2.07; 95% CI, 1.28-3.33). Persistent thiopurine use (>365 days) was associated with NMSC (adjusted OR, 4.27; 95% CI, 3.08-5.92), as was persistent biologic use among patients with CD (adjusted OR, 2.18; 95% CI, 1.07-4.46). Conclusions: Patients with IBD, especially those who receive thiopurines, are at risk for NMSC. Appropriate counseling and monitoring of such patients with IBD are recommended. © 2010 AGA Institute.
Volume 10, Issue 6, June 2012, Pages 639-645
Tine Jess | Christine Rungoe | Laurent Peyrin-Biroulet
Background & Aims: Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). Studies examining the magnitude of this association have yielded conflicting results. We performed a meta-analysis of population-based cohort studies to determine the risk of CRC in patients with UC. Methods: We used MEDLINE, EMBASE, Cochrane, and CINAHL to perform a systematic literature search. We included 8 studies in the meta-analysis on the basis of strict inclusion and exclusion criteria. We calculated pooled standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for risk of CRC in patients with UC and performed meta-regression analyses of the effect of cohort size, calendar period, observation time, percentage with proctitis, and rates of colectomy on the risk of CRC. Results: An average of 1.6% of patients with UC was diagnosed with CRC during 14 years of follow-up. SIRs ranged from 1.05 to 3.1, with a pooled SIR of 2.4 (95% CI, 2.1-2.7). Men with UC had a greater risk of CRC (SIR, 2.6; 95% CI, 2.2-3.0) than women (SIR, 1.9; 95% CI, 1.5-2.3). Young age was a risk factor for CRC (SIR, 8.6; 95% CI, 3.8-19.5; although this might have resulted from small numbers), as was extensive colitis (SIR, 4.8; 95% CI, 3.9-5.9). In meta-regression analyses, only cohort size was associated with risk of CRC. Conclusions: In population-based cohorts, UC increases the risk of CRC 2.4-fold. Male sex, young age at diagnosis with UC, and extensive colitis increase the risk. © 2012 AGA Institute.
Volume 8, Issue 6, June 2010, Pages 504-508
Lucio Lombardo | Monica Foti | Olga Ruggia | Andrea Chiecchio
Background & Aims: Proton pump inhibitors (PPIs) can cause diarrhea, enteric infections, and alter the gastrointestinal bacterial population by suppressing the gastric acid barrier. Among patients that received long term PPI treatment, we evaluated the incidence of small intestinal bacterial overgrowth (SIBO; assessed by glucose hydrogen breath test [GHBT]), the risk factors for development of PPI-related SIBO and its clinical manifestations, and the eradication rate of SIBO after treatment with rifaximin. Methods: GHBTs were given to 450 consecutive patients (200 with gastroesophageal reflux disease who received PPIs for a median of 36 months; 200 with irritable bowel syndrome [IBS], in absence of PPI treatment for at least 3 years; and 50 healthy control subjects that had not received PPI for at least 10 years). Each subject was given a symptoms questionnaire. Results: SIBO was detected in 50% of patients using PPIs, 24.5% of patients with IBS, and 6% of healthy control subjects; there was a statistically significant difference between patients using PPIs and those with IBS or healthy control subjects (P < .001). The prevalence of SIBO increased after 1 year of treatment with PPI. The eradication rate of SIBO was 87% in the PPI group and 91% in the IBS group. Conclusions: SIBO, assessed by GHBT, occurs significantly more frequently among long term PPI users than patients with IBS or control subjects. High dose therapy with rifaximin eradicated 87%-91% of cases of SIBO in patients who continued PPI therapy. © 2010 AGA Institute.
Volume 10, Issue 12, December 2012, Pages 1342-1359.e2
Donna L. White | Fasiha Kanwal | Hashem B. El- Serag
Background & Aims:Nonalcoholic fatty liver disease (NAFLD) has been implicated as a cause of hepatocellular carcinoma (HCC). We performed a systematic review of epidemiology studies to confirm the association between these disorders.Methods:We searched PubMed for original reports published from January 1992 to December 2011 that evaluated the association between NAFLD, nonalcoholic steatohepatitis (NASH), cryptogenic cirrhosis presumed to be NASH-related, and the risk of HCC. Studies were categorized as offering potential direct evidence (eg, cohort studies) or indirect evidence (eg, case-control, cross-sectional, or case-series studies) for an association. We analyzed data from a total of 17 cohort studies (3 population based, 9 clinic based [6 limited to patients with cirrhosis], and 5 natural history), 18 case-control and cross-sectional studies, and 26 case series.Results:NAFLD or NASH cohorts with few or no cases of cirrhosis cases had a minimal risk for HCC (cumulative HCC mortality of 0%-3% for study periods up to 20 y). Cohorts with NASH and cirrhosis had a consistently higher risk (cumulative incidence ranging from 2.4% over 7 y to 12.8% over 3 y). However, the risk for HCC was substantially lower in these cohorts than for cohorts with hepatitis C-related cirrhosis. Factors that increased risk among cohorts with NASH and cirrhosis could not be determined, because most studies were not sufficiently powered for multivariate analysis.Conclusions:This systematic review shows that despite several limitations, there is epidemiologic evidence to support an association between NAFLD or NASH and an increased risk of HCC; risk seems to be limited to individuals with cirrhosis. © 2012 AGA Institute.
Volume 8, Issue 2, February 2010, Pages 192-199
Ashwani Kumar Singal | Amanpal Singh | Sathya R. Jaganmohan | Praveen Guturu | Rajasekhara R. Mummadi | Yongfang Kuo | Gagan K. Sood
Background & Aims: The effects of antiviral therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis are unclear. We performed a systematic review and meta-analysis to assess HCC risk reduction in patients with HCV-related cirrhosis who have received antiviral therapy. Methods: Twenty studies (4700 patients) were analyzed that compared untreated patients with those given interferon (IFN) alone or ribavirin. Risk ratios (RRs) determined effect size using a random effects model. Results: Pooled data showed reduced HCC risk in the treatment group (RR, 0.43; 95% confidence interval [CI], 0.33-0.56), although the data were heterogenous (χ2 = 59.10). Meta-regression analysis showed that studies with follow-up durations of more than 5 years contributed to heterogeneity. Analysis of 14 studies (n = 3310) reporting sustained virologic response (SVR) rates with antiviral treatment showed reduced HCC risk in patients with an SVR, compared with nonresponders (RR, 0.35; 95% CI, 0.26-0.46); the maximum benefits were observed in patients treated with ribavirin-based regimens (RR, 0.25; 95% CI, 0.14-0.46). Meta-analysis of 4 studies assessing the role of maintenance IFN in nonresponders did not show HCC risk reduction (RR, 0.58; 95% CI, 0.33-1.03). No publication bias was detected by the Egger test analysis (P > 0.1). Conclusions: The risk of HCC is reduced among patients with HCV who achieve an SVR with antiviral therapy. Maintenance therapy with IFN does not reduce HCC risk among patients who do not respond to initial therapy. View this article's video abstract at www.cghjournal.org. © 2010 AGA Institute.
Volume 8, Issue 5, May 2010, Pages 471-473
Michael S. Silverman | Ian D. Davis | Dylan R. Pillai
Background & Aims: Clostridium difficile infection (CDI) can relapse in patients with significant comorbidities. A subset of these patients becomes dependent on oral vancomycin therapy for prolonged periods with only temporary clinical improvement. These patients incur significant morbidity from recurrent diarrhea and financial costs from chronic antibiotic therapy. Methods: We sought to investigate whether self- or family-administered fecal transplantation by low volume enema could be used to definitively treat refractory CDI. Results: We report a case series (n = 7) where 100% clinical success was achieved in treating these individuals with up to 14 months of follow-up. Conclusions: Fecal transplantation by low volume enema is an effective and safe option for patients with chronic relapsing CDI, refractory to other therapies. Making this approach available in health care settings has the potential to dramatically increase the number of patients who could benefit from this therapy. © 2010 AGA Institute.
Volume 8, Issue 2, February 2010, Pages 105-110
Angelo Zullo | Cesare Cesare Hassan | Francesca Cristofari | Alessandro Andriani | Vincenzo De Francesco | Enzo Ierardi | Silverio Tomao | Manfred S. Stolte | Sergio M. Morini | Dino Vaira
Background & Aims: Different remission rates of gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma have been reported after Helicobacter pylori eradication. We assessed the long-term remission and relapse rates of early stage MALT lymphoma in patients treated only by H pylori eradication and identified factors that might predict outcome. Methods: This systematic review analyzed data from 32 studies, including 1408 patients. Results: The MALT lymphoma remission rate was 77.5% (95% confidence interval, 75.3-79.7), and was significantly higher in patients with stage I than stage II1 lymphoma (78.4% vs 55.6%; P = .0003) and in Asian than in Western groups (84.1% vs 73.8%; P = .0001). Neoplasia confined to the submucosa regressed more frequently than that with deeper invasion (82.2% vs 54.5%; P = .0001); patients with lymphoma localized to the distal stomach experienced regression more frequently than those with lymphoma of the proximal stomach (91.8% vs 75.7%; P = .0037). The remission rate was higher among patients without the API2-MALT1 translocation than in those with this translocation (78% vs 22.2%; P = .0001). In an analysis of data from 994 patients, 7.2% experienced lymphoma relapse during 3253 patient-years of follow-up evaluation, with a yearly recurrence rate of 2.2%. Infection and lymphoma were cured by additional eradication therapy in all patients with H pylori recurrence (16.7%). Five (0.05%) of the patients initially cured of lymphoma developed high-grade lymphoma within 6 to 25 months of therapy. Conclusions: H pylori eradication is effective in treating approximately 75% of patients with early stage gastric lymphoma. Long-term follow-up evaluation of these patients is needed to detect early lymphoma relapse or progression. © 2010 AGA Institute.
Volume 8, Issue 9, September 2010, Pages 806-811
Koen P. De Jong | Chung Yung Nio | John J. Hermans | Marcel Gw W Dijkgraaf | Dirk Joan J Gouma | Casper HJ J Van Eijck | Eddy van Heel | Gunter Klass | Paul Fockens | Marco J. Bruno
Background & Aims: The prevalence of pancreatic cysts is not known, but asymptomatic pancreatic cysts are diagnosed with increasing frequency. We investigated the prevalence of pancreatic cysts in individuals who were screened by magnetic resonance imaging (MRI) as part of a preventive medical examination. Methods: Data from consecutive persons who underwent abdominal MRI (n = 2803; 1821 men; mean age, 51.1 ± 10.8 y) at an institute of preventive medical care were included from a prospective database. All individuals had completed an application form including questions about possible abdominal complaints and prior surgery. MRI reports were reviewed for the presence of pancreatic cysts. Original image sets of all positive MRI reports and a representative sample of the negative series were re-assessed by a blinded, independent radiologist. Results: Pancreatic cysts were reported in 66 persons (2.4%; 95% confidence interval, 1.9-3.0); prevalence correlated with increasing age (P < .001). There was no difference in prevalence between sexes (P = .769). There was no correlation between abdominal complaints and the presence of pancreatic cysts (P = .542). Four cysts (6%) were larger than 2 cm and 3 (5%) were larger than 3 cm. Review of the original image sets by the independent radiologist did not significantly change these findings. Conclusions: The prevalence of pancreatic cysts in a large consecutive series of individuals who underwent an MRI at a preventive medical examination was 2.4%. Prevalence increased with age, but did not differ between sexes. Only a minority of cysts were larger than 2 cm. © 2010 AGA Institute.
Volume 8, Issue 2, February 2010, Pages 213-219.e4
Stefano Crippa | Carlos F. Fernández-del Castillo | Roberto Salvia | Dianne M. Finkelstein | Claudio Bassi | Ismael Domínguez | Alona Muzikansky | Sarah P. Thayer | Massimo Falconi | Mari Mino-Kenudson | Paola Capelli | Gregory Yves Lauwers | Stefano Partelli | Paolo Paolo Pederzoli | Andrew Louis Warshaw
Background & Aims: Mucin-producing neoplasms (MPNs) of the pancreas include mucinous cystic neoplasms (MCNs) and main-duct, branch-duct, and combined intraductal papillary mucinous neoplasms (IPMNs). MCNs and branch-duct IPMNs are frequently confused; it is unclear whether main-duct, combined, and branch-duct IPMNs are a different spectrum of the same disease. We evaluated their clinical and epidemiologic characteristics. Methods: Patients who underwent resection for histologically confirmed MPNs were identified (N = 557); specimens were reviewed and eventually reclassified. Results: One hundred sixty-eight patients (30%) had MCNs, 159 (28.5%) had branch-duct IPMNs, 149 (27%) had combined IPMNs, and 81 (14.5%) had main-duct IPMNs. Patients with MCNs were significantly younger and almost exclusively women; 44% of patients with main-duct or combined IPMNs and 57% of those with branch-duct IPMNs were women. MCNs were single lesions located in the distal pancreas (95%); 11% were invasive. IPMNs were more frequently found in the proximal pancreas; invasive cancer was found in 11%, 42%, and 48% of branch-duct, combined, and main-duct IPMNs, respectively (P = .001). Patients with invasive MCN and those with combined and main-duct IPMNs were older than those with noninvasive tumors. The 5-year disease-specific survival rate approached 100% for patients with noninvasive MPNs. The rates for those with invasive cancer were 58%, 56%, 51%, and 64% for invasive MCNs, branch-duct IPMNs, main-duct IPMNs, and combined IPMNs, respectively. Conclusions: MPNs comprise 3 different neoplasms: MCNs, branch-duct IPMNs, and main-duct IPMNs, including the combined type. These tumors have specific clinical, epidemiologic, and morphologic features that allow a reasonable degree of accuracy in preoperative diagnosis. © 2010 AGA Institute.
Volume 10, Issue 2, February 2012, Pages 166-173.e1
Aldo J. Montaño-Loza | Judith Meza-Junco | Carla MM M Prado | Jessica R L Lieffers | V. Elaine Baracos | Vincent Gordon Bain | Michael B. Sawyer
Background & Aims: Sarcopenia, defined as a low level of muscle mass, occurs in patients with cirrhosis. We assessed its incidence among cirrhotic patients undergoing evaluation for liver transplantation to investigate associations between sarcopenia and mortality and prognosis. Methods: We studied 112 patients with cirrhosis (78 men; mean age, 54 ± 1 years) who were consecutively evaluated for liver transplantation and had a computed tomography scan at the level of the third lumbar (L3) vertebrae to determine the L3 skeletal muscle index; sarcopenia was defined by using previously published, sex-specific cutoffs. Results: Of the patients studied, 45 (40%) had sarcopenia. Univariate Cox analysis associated mortality with ascites (hazard ratio [HR], 2.12; P =.04), encephalopathy (HR, 1.99; P =.04), level of bilirubin (HR, 1.007; P < .01), international normalized ratio (HR, 7.69; P < .001), level of creatinine (HR, 1.01; P =.005), level of albumin (HR, 94; P =.008), serum level of sodium (HR, 89; P < .001), Model for End-Stage Liver Disease (MELD) score (HR, 1.14; P < .01), Child-Pugh score (HR, 2.84; P < .001), and sarcopenia (HR, 2.18; P =.006). By multivariate Cox analysis, only Child-Pugh (HR, 1.85; P =.04) and MELD scores (HR, 1.08; P =.001) and sarcopenia (HR, 2.21; P =.008) were independently associated with mortality. The median survival time for patients with sarcopenia was 19 ± 6 months, compared with 34 ± 11 months among nonsarcopenia patients (P =.005). There was a low level of correlation between L3 skeletal muscle index and MELD (r = -0.07; P =.5) and Child-Pugh scores (r = -0.14; P =.1). Conclusions: Sarcopenia is associated with mortality in patients with cirrhosis. It does not correlate with the degree of liver dysfunction evaluated by using conventional scoring systems. Scoring systems should include evaluation of sarcopenia to better assess mortality among patients with cirrhosis. © 2012 AGA Institute.
Volume 8, Issue 3, March 2010, Pages 275-279
Linda Rabeneck | Lawrence F. Paszat | Refik Saskin
Background & Aims: The incidence of colorectal cancer (CRC) is reduced for at least 10 years after a negative colonoscopy, compared with the general population. However, CRCs do occur in individuals after a negative colonoscopy. We investigated whether the colonoscopy volume and specialty of the endoscopists who perform the exam are associated with CRC after a negative complete colonoscopy. Methods: A cohort of Ontario residents, 50-80 years old, who had a negative complete colonoscopy between January 1, 1992, and December 31, 1997, was identified by using linked administrative databases. Cohort members had no history of CRC or inflammatory bowel disease or a recent colonic resection. Each individual was followed through December 31, 2006, and those with a new diagnosis of CRC were identified. Multivariable analysis was used to evaluate the association of patient, endoscopist, and procedure setting characteristics with incident CRC. Results: A cohort of 110,402 individuals with a negative complete colonoscopy was identified; the majority (86%) had their procedures performed in hospitals. During the 15-year follow-up period, 1596 (14.5%) developed CRC. There was no association between endoscopist colonoscopy volume and incident CRC. Among persons who had their colonoscopies at a hospital, those who had their procedures performed by a non-gastroenterologist were at significantly increased risk for developing subsequent CRC. Conclusions: Endoscopist specialty is an important determinant of the effectiveness of colonoscopy in usual clinical practice. After a negative colonoscopy, those who have had their procedures performed by a gastroenterologist are less likely to develop CRC. © 2010 AGA Institute.
Volume 9, Issue 1, January 2011, Pages 30-35
Mario Cottone | Anna Kohn | Marco Daperno | Alessandro Armuzzi | Luisa Guidi | Renata D'Incà | Fabrizio Bossa | Erika Angelucci | Livia Biancone | Paolo Gionchetti | Sandro Ardizzone | Claudio Papi | Walter Fries | Silvio Danese | Gabriele Riegler | Maria Cappello | Fabiana Castiglione | Vito Annese | Ambrogio Orlando
Background & Aims: Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis factor (TNF) inhibitors in these patients. Methods: We collected data from patients with IBD treated with infliximab (n = 2475) and adalimumab (n = 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn's disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 years old or younger who were treated with both biologics and 190 patients older than 65 years who were treated with other drugs. The primary end points were severe infection, cancer, or death. Results: Among patients more than 65 years old who received infliximab and adalimumab, 11% developed severe infections, 3% developed neoplasms, and 10% died. No variable was associated with severe infection or death. Among control patients more than 65 years old, 0.5% developed severe infections, 2% developed cancer, and 2% died. Among control patients less than 65 years old, 2.6% developed severe infections, none developed tumors, and 1% died. Conclusions: Patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age that did not receive these therapeutics. The effects of anti-TNF agents in older patients with IBD should be more thoroughly investigated, because these patients have higher mortality related to hospitalization than younger patients. © 2011 AGA Institute.