Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association

Published by WB Saunders
Online ISSN: 1542-3565
Publications
Article
Immune responses to Helicobacter pylori are important in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In this retrospective case study, we investigated whether certain alleles and haplotypes of major histocompatibility complex genes are associated with gastric MALT lymphoma and the efficacy of H pylori eradication therapy on the lymphoma. Blood samples were obtained from 18 patients with H pylori-positive gastric MALT lymphoma (5 men and 13 women; age range, 51-80 years), 30 patients with H pylori-positive non-ulcer dyspepsia (17 men and 13 women; age range, 37-77 years), and 30 patients with H pylori-negative non-ulcer dyspepsia (12 men and 18 women; age range, 37-77 years). HLA-DQA1 and DQB1 allele typing was performed by use of a polymerase chain reaction sequence-specific oligonucleotide procedure. All patients with MALT lymphoma were treated with H pylori eradication therapy and followed up by repeated endoscopy and biopsy. We found a significant increase in alleles HLA-DQA1*0103 and HLA-DQB1*0601, and a haplotype DQA1*0103-DQB1*0601, in MALT lymphoma patients when compared with non-ulcer dyspepsia patients who were either H pylori-positive or not and with a healthy control population. After H pylori eradication, the lymphomas regressed completely in all 10 patients who possessed the DQA1*0103-DQB1*0601 haplotype but in only 4 of the 8 without this haplotype (P = .023). DQA1*0103-DQB1*0601 haplotype-positive gastric MALT lymphoma is likely to respond to therapy by eradication of H pylori.
 
Article
Fundic gland polyps (FGPs), the most common type of gastric polyps, have been associated with prolonged proton pump inhibitor therapy and an increased risk of colon cancer. The presence of FGPs has been inversely correlated with Helicobacter pylori infection. We evaluated the prevalence of H pylori-associated gastritis, colonic polyps, and carcinomas in subjects with and without FGPs. We analyzed data collected from community-based endoscopy centers in 36 states (plus Washington DC and Puerto Rico) on patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy between April 2007 and March 2008. Of the 103,385 patients who underwent EGD during this time period, gastric biopsy samples were collected from 78,801 and colonic biopsies from 26,017. Slides of samples from Helicobacter-infected FGPs and FGPs with dysplasia were reviewed. FGPs were detected in 6081 patients (67.8% women). Helicobacter infection was present in less than 0.5% patients with FGPs and 13.0% of those without FGPs (odds ratio [OR], 29.05; 95% confidence interval [CI], 20.4-41.4; P < .0001). Colonic adenomas were detected in 42.3% of women with FGPs and 33.8% of those without (OR, 1.43; 95% CI, 1.26-1.63; P < .001); there was no significant difference in colonic adenomas between men with and without FGPs. Women had a higher prevalence of FGPs. FGPs were associated with gastroesophageal reflux disease symptoms, gastric heterotopia, hyperplastic colonic polyps (only in men), and colonic adenomas (only in women, especially those over 60 years of age). The presence of FGPs was inversely correlated with H pylori infection, active gastritis, and gastric neoplasia.
 
Article
We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 μg/L at diagnosis. We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. The mean survival times after diagnosis were 13.2 ± 7.3 y and 12.5 ± 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 μg/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 μg/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 μg/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 μg/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 μg/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with serum levels of ferritin greater than 1000 μg/L.
 
Article
The long-term outcomes of endoscopic papillary balloon dilation (EPBD) for bile duct stone removal are not well known. A total of 1000 patients with bile duct stones were treated with EPBD. After assessing immediate outcomes, patients were followed up for late biliary complications. Complete bile duct clearance was achieved with EPBD alone in 963 patients (96.3%) in a mean of 1.5 endoscopic sessions. Post-EPBD pancreatitis developed in 48 patients (4.8%), including 1 patient graded as severe. The long-term outcome was evaluated in 837 patients with a mean follow-up period of 4.4 years. Biliary complications were seen in 104 patients (12.4%), and they were less frequent in the cholecystectomy (CCx) after EPBD group than in the gallbladder (GB) left in situ with stones, GB left in situ without stones, and CCx before EPBD groups (2.8% vs 22.6%, 9.2%, and 13.5%, respectively). Stone recurrence was seen in 74 patients (8.8%)--2.4%, 15.6%, 5.9%, and 10.8% in the CCx after EPBD, GB left in situ with stones, GB left in situ without stones, and CCx before EPBD groups, respectively. Lithotripsy and gallbladder status were identified as risk factors for stone recurrence. Cholecystitis occurred in 13 patients (4.5%) in the GB left in situ with stones group. EPBD was effective in treating bile duct stones that were not accompanied by an unacceptably high risk of pancreatitis. Patients with calculous gallbladder had the highest risk for late complications, and cholecystectomy is recommended after removal of their bile duct stones.
 
Article
Upper-gastrointestinal bleeding (UGIB) in the elderly is associated with high morbidity and mortality. The aims of this study were to determine the prognostic factors of UGIB in a large cohort of elders. From March 2005 to February 2006, we conducted a prospective multicenter study in 53 French hospitals that consecutively enrolled 3287 patients for UGIB. A total of 1041 patients (47.8% women) were older than 74 years. Their epidemiologic characteristics and prognosis were compared with the 2246 younger patients (26.8% women). Elders more frequently took drugs causing UGIB: 65% versus 32% for younger patients (P < 10(-6)). Peptic ulcers, erosive gastritis, and esophagitis accounted for 63.6% of UGIB causes in elders versus 39.7% in younger patients (P < 10(-4)). Conversely, esogastric varices and gastropathy were responsible for 11% of UGIB in elders versus 44% in younger patients (P < 10(-6)). The rebleeding rate, morbidity, and in-hospital mortality were not statistically different between elders and younger patients: 11.8% versus 9.7% (P = .07), 22.6% versus 21.6% (P = .5), and 8.9% versus 8.2% (P = .5), respectively. Transfusion requirements, need for surgery, and length of stay were significantly different between elders and younger patients: 73% versus 57.5% (P < 10(-6)), 4% versus 2.5% (P < .02), 10.6 +/- 15.6 versus 8.5 +/- 12.4 days (P < 10(-6)), respectively. Whatever the etiology (peptic lesions or portal hypertension) in-hospital mortality was the same: 6.5% versus 7.3% and 10.9% versus 11.3%, respectively. Elders can do as well as younger patients with acute UGIB. Although the reasons are not completely clear, they may be related to differences in treatment.
 
Article
Ulcerative colitis (UC) is associated with an increased risk for colorectal cancer (CRC) and possibly also increased risk for cancers outside the intestinal tract. We followed-up a population-based cohort of 1160 patients with UC diagnosed in Copenhagen County between 1962 and 1987 for up to 36 years to analyze the overall and site-specific cancer risk. Observed vs. expected cancers were presented as standardized morbidity ratio (SMR) with 95% exact confidence intervals (CI) calculated by using individual person-years at risk and sex- and age-specific incidence rates for the Danish background population in 1995. The cohort was followed-up for a median of 19 years, or 22,290 person-years. A total of 124 malignancies were observed compared with 139.85 expected (SMR, .89; 95% CI, .74-1.07). The observed number of CRCs was almost exactly equal to expected: 13 cases vs. 12.42 (SMR, 1.05; 95% CI, .56-1.79). The cumulative probability of CRC was .4% by 10 years, 1.1% by 20 years, and 2.1% by 30 years of disease. Among men, melanoma was increased (SMR, 3.45; 95% CI, 1.38-7.10); otherwise, no increased risk for cancer could be detected. No hepatobiliary cancers and no increased risk for lymphoma or leukemia were found. Neither the overall cancer risk, nor the CRC risk, were increased in this population-based cohort after a median of 19 years of follow-up evaluation. An active surgical approach in medical treatment failures and long-term use of 5-aminosalicylic acid (5-ASA) as relapse prevention may explain this remarkable result.
 
Article
Obesity is associated with Barrett's esophagus (BE) and with changes in circulating levels of adipokines (leptin and adiponectin) and cytokines. Although studies have reported that adipokines and inflammatory cytokines are necessary for the development of BE, their role is controversial. We performed a case-control study; cases (n=141) were patients who underwent esophagogastroduodenoscopy and were found to have BE, based on endoscopy and histology, and controls (n=139) were primary care patients eligible for screening colonoscopies who agreed to undergo esophagogastroduodenoscopy. We examined the association between BE and circulating levels of adipokines and cytokines (interleukin [IL]1β, 6, 8, 10, and 12p70; tumor necrosis factor [TNF]α; and interferon [IFN]γ). Cases and controls were compared, calculating odds ratios (ORs) and 95% confidence intervals (CIs) and using unadjusted and multiple logistic regression, adjusting for age, sex, race, waist-hip ratio, use of proton pump inhibitors and non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The adjusted ORs for BE were 2.62 (95% CI, 1.0-6.8), 5.18 (95% CI, 1.7-15.7), and 8.02 (95% CI, 2.79-23.07) for the highest quintile vs the lowest quintile of levels of IL12p70, IL8, and leptin, respectively, but the OR not significant for IL6 (2.39; 95% CI, 0.84-6.79). The adjusted OR for BE was 0.14 for highest quintile of IL10 compared with lowest quintile (95% CI, 0.05-0.35) and 0.03 for IL1β ≥median vs none detected (95% CI, 0.006-0.13). Higher levels of IL8 and leptin and lower levels of IL10 and IL1β were associated with the presence of long- (≥3 cm) and short-segment BE. There were no differences between cases and controls in levels of IFNγ, TNFα, adiponectin, or insulin. Based on a case-control study, BE is associated with circulating inflammatory cytokines and leptin and low levels of anti-inflammatory cytokines. These findings could partly explain the effect of obesity on BE.
 
Article
Unremitting gastric acid and pepsin hypersecretion causes serious persistent and relapsing lesions, but the natural history with medical treatment alone has not been well-defined. The aims of this study were to heal and prevent relapse of acid/peptic lesions during acid suppression and to analyze benefits and risks during long-term lansoprazole treatment. Sixty-seven patients (49 with Zollinger-Ellison syndrome [ZES], 18 without), with basal acid output (BAO) >15 mmol/h or >5 mmol/h if post-antrectomy (n = 9, all ZES), were treated with individually optimized doses of lansoprazole (7.5-450 mg/day; median, 75 mg/day) to reduce BAO to <5 mmol/h or <1 mmol/h post-antrectomy and underwent endoscopy every 3-6 months for up to 13 years (median, 6.25 years). Before treatment, 94% had duodenal ulcer, 64% had esophagitis, 60% had 1 or more bleeding episodes, 13% had perforated ulcers, 90% had pain, 60% had heartburn, and 40%-48% had diarrhea, vomiting, and/or weight loss. Forty-seven patients (70%) remained symptom- and lesion-free, whereas 13 (20%) had mild, transient relapses, and 7 (10%) had more complicated relapses. Overall, symptoms were reduced 90+%; ulcer or esophagitis relapsed in 4.8% of patients/year, unrelated to Helicobacter pylori , whereas complications declined to <2%/y. Post-antrectomy ZES patients had 3.6-fold higher relapse rates than unoperated ZES patients (67% vs 18%, respectively). With BAO >5 mmol/h in intact patients, relative risk of relapse was 4.1, confidence interval 2.1-8.1, P < .001. Twenty patients died, 3 as a result of ZES (2 metastatic gastrinomas). With individually optimized medical suppression of acid secretion, 90% of patients had good to excellent long-term outcomes without surgery, with an annualized total relapse rate of <5%.
 
Article
Background & aims: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. Methods: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). Results: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects. Conclusions: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.
 
Article
Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13 C-aminopyrine breath test ( 13 C-ABT) and 13 C-galactose breath test ( 13 C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease. We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13 C-GBT and 13 C-ABT, and the results were expressed as a percentage of the administered dose of 13 C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13 C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis. On average, 13 C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13 C-ABT results from 30 to 120 minutes. 13 C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13 C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13 C-GBT and 13 C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis. In patients with chronic liver disease, both 13 C-GBT and 13 C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.
 
Article
Malnutrition persists in most patients with chronic pancreatitis despite an adequate clinical response to oral pancreatic enzyme substitution therapy. Our aims were to analyze the accuracy of the 13C-mixed triglyceride breath test as a tool for evaluating the effect of enzyme therapy on fat digestion in chronic pancreatitis, and to analyze the impact of modifying the therapy according to the breath test on patients' nutritional status. The accuracy of the breath test for monitoring the effect of therapy was evaluated prospectively in 29 patients with maldigestion secondary to chronic pancreatitis by using the coefficient of fat absorption as the gold standard. Therapy was modified to obtain a normal breath test result in a further 20 chronic pancreatitis patients with malnutrition despite an adequate clinical response to the enzyme therapy; the impact of this therapeutic modification on patients' nutritional status was evaluated. The coefficient of fat absorption and breath test results were similar when assessing fat absorption before and during treatment. Modification of the enzyme therapy to normalize fat absorption as assessed by the breath test in the second group of 20 patients was associated with a significant increase of body weight (P < .001), and serum concentrations of retinol binding protein (P < .001) and prealbumin (P < .001). The 13C-mixed triglyceride breath test is an accurate method to evaluate the effect of enzyme therapy on fat digestion. This method is simpler than the standard fecal fat test to assess therapy in patients with pancreatic exocrine insufficiency. Normalizing fat absorption improves nutrition in these patients.
 
Article
The aim of this study was to examine the risk of pancreatitis in patients with celiac disease (CD) from a general population cohort. By using Swedish national registers, we identified 14,239 individuals with a diagnosis of CD (1964-2003) and 69,381 reference individuals matched for age, sex, calendar year, and county of residence at the time of diagnosis. Cox regression estimated the hazard ratios (HRs) for a subsequent diagnosis of pancreatitis. We restricted analyses to individuals with more than 1 year of follow-up and no diagnosis of pancreatitis before or within 1 year after study entry. Conditional logistic regression estimated the association of pancreatitis with subsequent CD. CD was associated with an increased risk of subsequent pancreatitis of any type (HR, 3.3; 95% confidence interval [CI], 2.6-4.4; P < .001; on the basis of 95 positive events in individuals with CD vs 163 positive events in reference individuals) and chronic pancreatitis (HR, 19.8; 95% CI, 9.2-42.8; P < .001; on the basis of 37 and 13 positive events, respectively). Adjustment for socioeconomic index, diabetes mellitus, alcohol-related disorders, or gallstone disease had no notable effect on the risk estimates. The risk increase for pancreatitis was only found among individuals with CD diagnosed in adulthood. Pancreatitis of any type (odds ratio, 3.2; 95% CI, 2.5-4.3; P < .001) and chronic pancreatitis (odds ratio, 7.3; 95% CI, 4.0-13.5; P < .001) were associated with subsequent CD. This study suggests that individuals with CD are at increased risk of pancreatitis.
 
Article
Helicobacter pylori is an important causative factor in gastric carcinogenesis. However, its role in extragastric gastrointestinal malignancies, such as esophageal cancer, is controversial. The aim of this study was to explore the relationship of H. pylori infection and H. pylori cagA-positive strain with this malignancy by performing meta-analysis of all relevant studies. Extensive MEDLINE English language medical literature searches for human studies were performed through February 2007 with suitable keywords. Pooled estimates were obtained by using fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test. In adenocarcinoma patients there were inverse significant relationships with both the H. pylori prevalence (pooled odds ratio [OR], 0.52; 95% confidence interval [CI], 0.37-0.73; P < .001) and the prevalence of H. pylori cagA-positive strain (pooled OR, 0.51; 95% CI, 0.31-0.82; P = .006). Similarly in patients with Barrett's esophagus there were inverse significant relationships (pooled OR, 0.64; 95% CI, 0.43-0.94; P = .025 and pooled OR, 0.39; 95% CI, 0.21-0.76; P = .005, respectively). In patients with squamous cell carcinoma there were no significant relationships with both H. pylori prevalence (pooled OR, 0.85; 95% CI, 0.55-1.33; P = .48) and the prevalence of H. pylori cagA-positive strains (pooled OR, 1.22; 95% CI, 0.7-2.13; P = .48). The results showed an inverse statistically significant relationship of H. pylori infection with both esophageal adenocarcinoma and Barrett's esophagus, which might suggest a protective role of the infection in these entities. On the contrary, no statistically significant relationship with squamous cell carcinoma was found.
 
Article
The increasing incidence of hepatocellular carcinoma (HCC) in the United States has significant health and economic consequences. Ultrasound (US) surveillance is recommended for patients with cirrhosis because of their high risk of HCC and improving treatment outcomes for small tumors. We assessed the costs, clinical benefits, and cost effectiveness of US surveillance and alternative strategies for HCC in cirrhosis using a computer-based state transition model with parameters derived from available literature. Our model compared a policy of no surveillance with 6 surveillance strategies in cirrhotic patients ages 50 years and older in the United States: (1) annual US, (2) semiannual US, (3) semiannual US with alpha-fetoprotein, (4) annual computed tomography (CT), (5) semiannual CT, and (6) annual magnetic resonance imaging. The number of screening tests needed to detect one small HCC, cost per treated HCC, lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios were calculated. Semiannual US surveillance for HCC in cirrhosis increased quality-adjusted life expectancy by 8.6 months on average, but extended it nearly 3.5 years in patients with small treated tumors. Semiannual US surveillance had an incremental cost-effectiveness ratio of $30,700 per quality-adjusted life year (QALY) gained, and was more cost effective than the alternative surveillance strategies using a threshold of $50,000 per QALY gained. The incremental cost-effectiveness ratios for the combined alpha-fetoprotein/US and annual CT strategies exceeded $50,000/QALY unless the sensitivity and specificity of US decreased to less than 65% and 60%, respectively. Semiannual US surveillance for HCC in cirrhotic patients improves clinical outcomes at a reasonable cost.
 
Article
Little is known about differences in the prevalence of severe iron overload at death in whites and blacks. We evaluated data and samples from 16,152 autopsies (8484 whites, 7668 blacks) performed at a single university hospital. Cases of severe multi-organ iron overload were identified by review of autopsy protocols and Perls-stained tissue specimens, analysis of hepatocyte and Kupffer cell iron levels, and measurement of liver tissue iron concentrations. We analyzed autopsy data from 10,345 adults (age > or =21 years), 1337 children (1-20 years), and 4470 infants (<1 year). Iron overload without reports of excessive exogenous iron was observed in 18 adults; the prevalence in whites and blacks was 0.0019 and 0.0015, respectively (P = .6494). Twenty-nine adults and 2 children had iron overload with reports of excessive exogenous iron. In adults, the prevalences of iron overload with reports of excessive exogenous iron in whites and blacks were 0.0040 and 0.0013, respectively (P = .0107). Among adults, the prevalence of cirrhosis was 6-fold greater in those with iron overload. In adults with severe iron overload, 67% without reports of excessive exogenous iron and 14% with reports of excessive exogenous iron died of hepatic failure or cardiomyopathy caused by siderosis. The overall prevalence of deaths caused by severe iron overload in whites and blacks was 0.0021 and 0.0009, respectively (P = .0842). The prevalence of severe iron overload without reports of excessive exogenous iron did not differ significantly between whites and blacks. The prevalence of iron overload with reports of excessive exogenous iron was greater in whites. Hepatic failure and cardiomyopathy were common causes of death in severe iron overload cases.
 
Article
First-degree relatives of gastric cancer patients are at risk for developing precancerous conditions. The aim of this study was to investigate the potential of biomarkers pepsinogen I (PGI), pepsinogen II (PGII), their ratio (PG I:II), as well as gastrin 17 for screening of precancerous conditions and corpus predominant gastritis. First-degree relatives of gastric cancer patients underwent endoscopy. Three biopsy specimens from the antrum and 3 from the corpus were evaluated according to the Sydney classification. Serum was taken for the measurement of fasting PGI, PGII, and gastrin 17 by enzyme-linked immunosorbent assay kits. A total of 481 patients were examined (age, 47.8 +/- 6.7 y). With the extension of gastritis, PGII was increased up to 2.5 times (6.6 +/- 2.8 microg/mL in normal mucosa, 9.5 +/- 6.7 microg/mL in antral gastritis, and 16.9 +/- 12.4 microg/mL in corpus-predominant gastritis; P < .01), PGI increased slightly (88.3 +/- 29.4 microg/mL in normal mucosa and 111.2 +/- 71.4 microg/mL in corpus-predominant gastritis), and gastrin 17 was increased substantially in corpus-predominant gastritis (15.3 +/- 19.5 pmol/mL vs 3.8 +/- 5.7 pmol/mL in normal mucosa). By using a cut-off value of 7.5 microg/mL for PGII, any type of gastritis from normal mucosa can be diagnosed with a sensitivity and specificity of 80%. The sensitivity and specificity of the PG I:II ratio (< or =3) and gastrin 17 (>17 pmol/mL) together were 9.4% and 99% for screening corpus-predominant gastritis and 14.8% and 97.8%, respectively, for screening intestinal metaplasia in the corpus. PGII is a suitable marker for screening any gastritis from normal mucosa, but neither PGI, the PG I:II ratio, gastrin 17, nor their combination were able to select those with precancerous conditions and corpus-predominant gastritis among the first-degree relatives of gastric cancer patients.
 
Article
The long-term immunogenicity and efficacy of hepatitis B virus (HBV) vaccination remain to be defined. We aimed to examine the long-term immunogenicity and efficacy of HBV vaccination with 3 different regimens over 18 years of follow-up. A total of 318 Chinese subjects receiving 3 different regimens of HBV vaccination (2-dose recombinant vs. 3-dose recombinant vs. 3-dose plasma-derived vaccines) without receiving a booster dose were recruited. The HBV serologic markers, including hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc), were determined at yearly follow-up. After 18 years, 88 subjects were still being followed up. Compared with subjects receiving the 2-dose regimen, subjects receiving the 3 dose regimens had a significantly higher geometric mean titer of anti-HBs and a higher proportion had anti-HBs titers > or =10 mIU/mL during the 18 years of follow-up. There were no differences in these 2 parameters between subjects receiving the 3-dose recombinant and subjects receiving the 3-dose plasma-derived vaccines. A total of 88 anamnestic responses were documented in 70 subjects (8 with initial anti-HBs titers <100 mIU/mL at 12 months and 7 with anti-HBs titers <10 mIU/mL before the anamnestic responses). No subject became positive for HBsAg. Three subjects had benign breakthrough HBV infection without leading to chronicity indicated by isolated anti-HBc positivity. There was less long-term immunogenicity associated with the 2-dose regimen when compared with the 3-dose regimens of HBV vaccination. Because of the highly effective anamnestic responses, a booster dose was not necessary at least up to 18 years after the primary vaccination.
 
Article
BACKGROUND & AIMS: There are no accurate and reliable tools for diagnosis of early-stage pancreatic ductal adenocarcinoma (PDA) or small metastatic lesions. It is also a challenge to differentiate PDA from focal mass-forming pancreatitis (FMP). There is controversy over the efficacy of 18-fluorodeoxyglucose positron-emission tomography (FDG-PET) in diagnosis of PDA. We investigated whether FDG-PET provides information that, combined with data from other imaging techniques, can aide in decision making for patients with suspected PDA. METHODS: We performed a retrospective analysis of data collected from 232 consecutive patients with suspected PDA at Kobe University Hospital from January 2006 through June 2012. All patients underwent a diagnostic imaging protocol that included multi-detector row computed tomography (MDCT), super-paramagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), and FDG-PET. Based on endoscopic ultrasonography, fine-needle aspiration biopsy, or endoscopic retrograde cholangiopancreatography analyses, 218 patients had PDA (89 underwent resection and 129 did not) and 14 had FMP (8 had focal mass-forming chronic pancreatitis [FMCP] and 6 had focal mass-forming autoimmune pancreatitis [(FMAIP]). RESULTS: FDG-PET detected 50% of stage 0 and I, 91.9% of stage II, 100% of stage III, and 96.8% of stage IV tumors. Detection was significantly affected by tumor size (P =.024) and T stage (P =.023) in resected tumors. MDCT and SPIO-MRI detected significantly more liver metastases than FDG-PET. Few para-aortic lymph node or peritoneal metastases were detected by FDG-PET. FDG-PET correctly identified 11 of the 14 patients with FMP (5/8 with FMCP and 6/6 with FMAIP). CONCLUSIONS: FDG-PET is not effective in detecting early-stage PDA and small metastases, or in differentiating PDA from FMP. Combining FDG-PET with current diagnostic techniques for PDA did not provide any decisive information, so it should not be included in this analysis.
 
Article
The safety and efficacy of maintenance therapy with the anti-tumor necrosis factor certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous versus interrupted maintenance therapy with subcutaneous certolizumab pegol in patients with Crohn's disease. Patients who responded to induction therapy at week 6 of the PEGylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial were assigned randomly to groups given certolizumab pegol (continuous) or placebo (drug-interruption) during weeks 6 to 26. Patients who completed PRECiSE 2 were eligible to enter PRECiSE 3, an ongoing, prospective, open-label extension trial in which patients have received certolizumab pegol (400 mg) every 4 weeks for 54 weeks to date, and were not offered the option to increase their dose. Disease activity was measured by the Harvey-Bradshaw Index. Harvey-Bradshaw Index responses at week 26 for the continuous and drug-interruption groups were 56.3% and 37.6%, respectively; corresponding remission rates were 47.9% and 32.4%, respectively. Of patients responding at week 26, response rates at week 80 after the start of PRECiSE 2 in the continuous and drug-interruption groups were 66.1% and 63.3%, respectively; among patients in remission at week 26, week 80 remission rates were 62.1% and 63.2%, respectively. More patients in the drug-interruption group developed antibodies against certolizumab pegol (and had lower plasma concentrations of certolizumab pegol) than the continuously treated group. Certolizumab pegol effectively maintains remission of Crohn's disease for up to 18 months. Continuous therapy is more effective than interrupted therapy.
 
Article
Background & aims: We investigated the usefulness of dual-phase F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) to differentiate benign from malignant intraductal papillary mucinous neoplasms (IPMNs) and to evaluate branch-duct IPMNs. Methods: We used FDG-PET/CT to evaluate IPMNs in 48 consecutive patients who underwent surgical resection from May 2004 to March 2012. IPMNs were classified as benign (n = 16) or malignant (n = 32) on the basis of histology analysis. The ability of FDG-PET/CT to identify branch-duct IPMNs was compared with that of the International Consensus Guidelines. Results: The maximum standardized uptake value (SUVmax) was higher for early-phase malignant IPMNs than that for benign IPMNs (3.5 ± 2.2 vs 1.5 ± 0.4, P < .001). When the SUVmax cutoff value was set at 2.0, early-phase malignant IPMNs were identified with 88% sensitivity, specificity, and accuracy. The retention index values for malignant and benign IPMNs were 19.6 ± 17.8 and -2.6 ± 12.9, respectively. When the SUVmax cutoff was set to 2.0 and the retention index value to -10.0, early-phase malignant IPMNs were identified with 88% sensitivity, 94% specificity, and 90% accuracy. In identification of branch-duct IPMNs, when the SUVmax cutoff was set to 2.0, the sensitivity, specificity, and accuracy values were 79%, 92%, and 84%, respectively. By using a maximum main pancreatic duct diameter ≥7 mm, the Guidelines identified branch-duct IPMNs with greater specificity than FDG-PET/CT. The Guidelines criteria of maximum cyst size ≥30 mm and the presence of intramural nodules identified branch-duct IPMNs with almost equal sensitivity to FDG-PET/CT. Conclusions: Dual-phase FDG-PET/CT is useful for preoperative identification of malignant IPMN and for evaluating branch-duct IPMN.
 
Article
Nonalcoholic fatty liver disease (NAFLD) is extremely common among morbidly obese patients. We assessed the usefulness of plasma caspase-generated cytokeratin 18 (CK-18) fragments as a novel marker for NAFLD in a bariatric cohort. The cohort consisted of 99 consecutive patients who underwent liver biopsy at the time of bariatric surgery. CK-18 levels were measured by using an enzyme-linked immunosorbent assay before and 6 months after surgery. Patients were subdivided into 4 histologic groups: not NAFLD (normal liver biopsy), nonalcoholic fatty liver (NAFL), borderline diagnosis, and definitive nonalcoholic steatohepatitis (NASH). CK-18 levels were significantly higher in subjects with NASH compared with those with not NAFLD, NAFL, or borderline diagnosis (median [25th quartile, 75th quartile], 389 U/L [275, 839] vs 196 U/L [158, 245], vs 217 U/L [154, 228], or vs 200 U/L [176, 274], respectively; P < .0001). CK-18 levels were significantly higher in subjects with moderate to severe fibrosis versus those with no or mild fibrosis (334.5 U/L [240.5, 896] vs 207 U/L [175, 275], respectively; P = .007). A significant decrease in CK-18 levels was observed in most patients 6 months postoperatively. The area under the receiver operating characteristic curve for NASH diagnosis was estimated to be 0.88 (95% confidence interval, 0.77-0.99). The values with the best combination of sensitivity and specificity were 252 U/L (sensitivity, 82%; specificity, 77%) and 275 U/L (sensitivity, 77%; specificity, 100%). These results support the potential utility of this test for diagnosis and staging of NAFLD before bariatric surgery.
 
Article
Histologic techniques are used to distinguish autoimmune pancreatitis (AIP) from pancreatic malignancies and to confirm the etiology of pancreatitis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a well-established technique used in the diagnosis of pancreatic cancer. However, it is unclear whether specimens obtained from pancreatic lesions by EUS-FNA are adequate for the histologic diagnosis of AIP, because the evaluation of tissue architecture and immunostaining assays usually require larger samples. We evaluated samples collected by EUS-FNA with a conventional 19-gauge needle by histologic analysis, looking for features of AIP. We analyzed data from 44 patients who were diagnosed with AIP and underwent EUS-FNA with a 19-gauge needle from January 2004 to September 2010. The FNA specimens were reviewed by histologic analysis; AIP was diagnosed based on the presence of lymphoplasmacytic sclerosing pancreatitis or immunoglobulin (Ig)G4-positive plasma cells in the infiltrate. The specimen amount was inadequate from 3 patients. Among the remaining 41 patients, histopathologic analysis revealed lymphoplasmacytic sclerosing pancreatitis in 17 samples and IgG4-positive plasma cells in 5 (3 samples were positive for both); no samples had granulocytic epithelial lesions. Therefore, 19 patients (43%) were diagnosed with AIP based on histologic analysis. One patient had temporary abdominal pain. EUS-FNA, with a 19-gauge needle, is a safe and reliable procedure for obtaining pancreatic samples for the histologic analysis of AIP. Although it does not have a high diagnostic yield, it might be useful in patients without typical features of AIP because it would allow patients to avoid surgery.
 
Article
Keratin-8 (KRT8)-null mice develop spontaneous colitis and predisposition to liver injury. Human studies show that some KRT8 variants predispose to end-stage liver disease and progression and suggest that such variants might associate with UC or CD. We asked whether mutations in KRT8 or KRT19, the major intestinal keratins, are associated with UC/CD. Exonic regions of the KRT8/KRT19 genes were polymerase chain reaction-amplified using genomic DNA from 2 independent groups. Group I included 91 unrelated patients with CD, 93 unrelated patients with UC, and 70 unrelated/unaffected volunteers. KRT8 variants were also tested with pyrosequencing in Group II that included 682 independent nuclear families with both parents and at least 1 CD/UC-affected offspring and 273 unaffected controls. Both cohorts were enriched for familial IBD. In Group I, KRT19 variants were identified in CD/UC patients within the promoter and exons 1+2, with similar mutation frequencies in the control/CD/UC groups. In contrast, 16 of 184 CD+UC patients harbored KRT8 heterozygous variants involving Gly62-to-Cys and Arg341-to-His and a novel Arg341-to-Cys, which were noted in 4 volunteers (Arg341-to-His) and correlated with extensive UC (P = .005). One family with unaffected parents had 3 pediatric-affected siblings with severe disease, 2 of whom are compound heterozygous (Gly62-to-Cys/Arg341-to-His). However, there was no significant departure from random transmission of the 3 alleles in Group II IBD families. KRT8 and KRT19 variants are not overtransmitted or associated with familial IBD, although a potential role in sporadic IBD cannot be excluded. A novel but rare keratin-8 Arg341-to-Cys is identified in IBD patients.
 
Article
Elsewhere in this issue Julian Walters and his colleagues report a major advance in our understanding of the pathogenesis of chronic diarrhea associated with idiopathic bile acid malabsorption.1 The story is a fascinating one and unites long standing and very recent discoveries in physiology, biochemistry, and molecular biology.
 
Article
Celiac disease is considered rare in North America. However, an increasing incidence and widening clinical spectrum have been reported in many countries, and serologic screening suggests a higher prevalence of minimally symptomatic disease. This study reports temporal trends in the incidence of celiac disease in Olmsted County, Minnesota. All county residents diagnosed with celiac disease between 1950 and 2001 were identified through the Rochester Epidemiology Project. Incidence rates were calculated assuming a Poisson distribution, and changes in incidence by calendar year, age, and gender were assessed by using Poisson regression. Altogether, 82 new cases of celiac disease were identified during the 50-year period. There was a marked female predominance (P < 0.005), and the incidence rates increased with age (P < 0.001) and calendar period (P < 0.001). The overall annual incidence of celiac disease was 2.1 per 100,000 (95% confidence interval [CI], 1.7-2.6) but increased from 0.9 per 100,000 (CI, 0.5-1.2) in 1950-1989 to 3.3 per 100,000 (95% CI, 2.2-4.4) in the 1990s. The incidence was 9.1 per 100,000 (95% CI, 5.2-13.0) in the final 2 years of the study. Serology prompted biopsy in a substantial proportion of recent diagnoses. Clinical features also changed over time, with less diarrhea and weight loss at presentation. Celiac disease has increased recently in this well-characterized population. Milder clinical features and use of serology suggest an increased detection rate, although a true increase in incidence may have also occurred. Celiac disease is not rare in North America.
 
Article
K-ras mutation is frequently detected in pancreatic juice of patients with pancreatic small cystic lesions, as well as those with pancreatic cancer. Those cystic lesions are often found by chance with modern radiologic imaging modalities. In this study, we prospectively examined the prognosis of patients with pancreatic cystic lesions, focusing on pancreatic cancer development. A total of 197 patients with pancreatic cystic lesions, 80 with intraductal papillary mucinous neoplasm (IPMN) and 117 with non-IPMN cysts, were followed up for 3.8 years on average. Blood tests and imaging diagnosis were performed twice a year. The observed incidence of pancreatic cancer was compared with the expected incidence calculated on the basis of age- and gender-matched mortality of pancreatic cancer in the general Japanese population. Pancreatic cancer developed in 7 patients during the observation period (0.95% per year), infiltrating ductal carcinoma in 5 and intraductal papillary mucinous carcinoma in 2. Three of the ductal cancer cases had pancreatic non-IPMN cyst as preexisting lesion. At least 2 of the carcinomas arose in regions remote from preexisting lesions. The observed incidence of pancreatic cancer was 22.5 times higher (95% confidence interval, 11.0-45.3) than expected mortality from this cancer among general population. Patients with pancreatic cystic lesions are at a considerably high risk for pancreatic cancer, with a standardized incidence rate of 22.5. Cancer might develop in regions remote from the preexisting cystic lesion, suggesting diffuse pathologic changes predisposing to malignant transformation in the entire pancreas harboring cystic lesions.
 
Article
BACKGROUND & AIMS: Treatments for inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) have changed over time, with unclear effects on prognosis. We assessed overall and cause-specific mortality in a Danish cohort of patients with IBD during a 30-year time period. METHODS: We compared data from 36,080 patients with UC and 15,361 with CD, who were diagnosed in Denmark from 1982-2010, and compared them with data from 2,858,096 matched individuals from the general population (controls). Overall and cause-specific mortality were estimated by Cox regression analysis, adjusted for age, sex, disease duration, and known comorbidities before IBD diagnosis. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Mortality greatly increased in the first year after individuals were diagnosed with IBD; intermediate-term and long-term mortalities increased by approximately 10% among individuals with UC and 50% among those with CD, compared with the general population. Compared with the time period of 1982-1989, mortalities decreased among patients diagnosed with UC from 1990-1999 (HR, 0.96; 95% CI, 0.90-1.02) and from 2000-2010 (HR, 0.88; 95% CI, 0.82-0.95). These reductions were mainly due to decreased mortality from colorectal cancer, gastrointestinal disorders, and suicide. For individuals with CD, mortality did not change among these time periods because of long-term increases in mortality from infections, cancer, respiratory diseases, and gastrointestinal diseases. CONCLUSIONS: In a Danish cohort, mortality from UC decreased from 1982 to 2010, largely because of reduced mortalities from gastrointestinal disorders and colorectal cancer. People with CD had 50% greater mortality than the general population, and this value did not change during this time period.
 
Article
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. 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). 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. 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.
 
Article
ANVUGIB is a common reason for hospital admission and has been traditionally associated with a mortality rate of 5%-10%. There have been numerous innovations in the prevention and management of ANVUGIB in recent years, although the effect of these innovations on ANVUGIB incidence and outcomes is unknown. We used the Statistics Canada's Health Person Oriented Information Database [corrected], which contains data characterizing every inpatient hospital admission in Canada between 1993 and 2003. We identified admissions consistent with nonvariceal upper gastrointestinal bleeding using both a broad and narrow ICD-9/ICD-10-based definition. Data were extracted concerning patient demographics, incidence of surgery for complications of upper gastrointestinal bleeding, and overall mortality. Between 1993 and 2003, ANVUGIB incidence decreased from 77.1 cases to 53.2 per 100,000/y for the broad definition, and from 52.4 to 34.3 cases per 100,000/y for the narrow definition. ANVUGIB incidence rose slightly in 2000, coincident with the introduction of COX-2 inhibitors. The proportion of ANVUGIB subjects requiring surgical intervention declined over the 10 years from 7.1% to 4.5%, although the rate of decline did not increase after the introduction of intravenous proton pump inhibitors (IV PPIs). The mortality rate remained steady at approximately 3.5%. The incidence of ANVUGIB and the need for operative intervention has been steadily declining since 1993. ANVUGIB-associated mortality remained constant, although at a rate lower than traditionally reported. The impact of IV PPIs on mortality and operative intervention on a population-wide basis is likely minimal.
 
Article
Data on safety and long-term follow-up evaluation of population-based cohorts of inflammatory bowel disease (IBD) patients treated with infliximab are sparse. The aim of this article is to describe the use of infliximab in a national Danish population-based IBD cohort during 1999-2005. Medical records of all infliximab-treated IBD patients were scrutinized to abstract information on patient demographics, treatment efficacy, and adverse events. A total of 651 patients (619 with Crohn's disease, 15 with ulcerative colitis, and 17 with colonic IBD type unclassified) received infliximab during 1999-2005. A total of 3351 infusions were administered, with a median of 3 infusions per patient. A positive clinical response was observed in 82.7% (95% confidence interval, 79.9-85.5) of patients. Infusion reactions were observed after 146 of 3351 infusions (4.4%). Significantly fewer infusion reactions were seen in patients also receiving azathioprine or methotrexate (63 of 2079; 3.0%), compared with patients not receiving azathioprine or methotrexate (83 of 1272; 6.5%) (P < .0001). Severe adverse events were observed after 112 of 3351 infusions (3.3%) in a total of 95 patients (14.6%). Four patients developed cancer versus 5.9 expected (standardized incidence ratio, 0.7; 95 confidence interval, 0.2-1.7) and 13 patients died versus 6.9 expected (standardized mortality ratio, 1.9; 95% confidence interval, 1.0-3.2). Two deaths caused by infections were possibly related to infliximab. Infliximab seemed effective in IBD and generally was well tolerated. However, rare but severe adverse events occurred, and patients receiving infliximab therefore should be selected carefully and monitored closely. No lymphomas and no increased risk of cancer were observed.
 
Article
We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis. Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. Results: In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians. rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated.
 
Article
The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endoluminal surgery for gastrointestinal neoplasm in the colorectum, are reported. ESD was performed on 186 consecutive patients with 200 colorectal epithelial neoplasms who had preoperative diagnoses of mucosal or slight submucosally invasive neoplasms. In addition, these could be of large size, with submucosal fibrosis, or located on an intestinal fold. The therapeutic efficacy and safety were assessed. The targeted lesions consisted of 102 adenomas, 72 noninvasive carcinomas, and 26 invasive carcinomas. Seven lesions (3.5%) were histologically considered to be at substantial risk for nodal metastasis after ESD. The rate of en bloc resection was 91.5% (183/200), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 70.5% (141/200). Two lesions (1%) required emergency colonoscopies as a result of hematochezia after ESD. Eleven (5.5%) immediate perforations that occurred during ESD were successfully managed conservatively, but 1 (0.5%) delayed perforation required laparotomy. Two multiple-piece resections of 111 tumors (1.8%), which were successfully followed by colonoscopy (median follow-up, 18 months; range, 12-60 months), were found as locally recurrent tumors 2 and 21 months after ESD. No lymph node or distant metastasis was detected in 77 patients with noninvasive or invasive carcinoma (median follow-up, 24 months; range, 6-74 months). ESD is applicable in the colorectum with promising results. However, when considering the risks and benefits, piecemeal endoscopic resection or colorectal resection might be more appropriate for some subgroups of large flat neoplasms or those with submucosal fibrosis.
 
Article
Most studies of trends in diverticular disease have focused on diverticulitis or on a composite outcome of diverticulitis and bleeding. We aimed to quantify and compare the prevalence of hospitalization for diverticular bleeding and diverticulitis overall and by sex and race. We analyzed data from the Nationwide Inpatient Sample from 2000 through 2010. We identified adult patients with a discharge diagnosis of diverticular bleeding or diverticulitis. Using yearly US Intercensal data, we calculated age-, sex-, and race- specific rates, as well as age-adjusted prevalence rates. The prevalence of hospitalization per 100,000 persons for diverticular bleeding decreased over the 10 year (y) period from 32.5 to 27.1 (-5.4; 95% confidence interval (CI), -5.1 to -5.7). The prevalence of hospitalization for diverticulitis peaked in 2008 (74.1/100,000 in 2000, 96.0/100,000 in 2008 and 91.9/100,000 in 2010). The prevalence of diverticulitis was higher in women than men, whereas women and men had similar rates of diverticular bleeding. The prevalence of diverticular bleeding was highest in Blacks (34.4/100,000 in 2010); whereas the prevalence of diverticulitis was highest in Whites (75.5/100,000 in 2010). Over the past 10 y, the prevalence of hospitalization for diverticulitis increased and then plateaued while that of diverticular bleeding decreased. The prevalence according to sex and race differed for diverticulitis and diverticular bleeding. These findings indicate different mechanisms of pathogenesis for these disorders. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
 
Article
The incidence of primary hepatocellular carcinoma (HCC) is greater in black Americans compared with white Americans. The aim of this study was to better define racial disparity in HCC patients in the United States. We compared HCC risk factors in 158 black and 701 white HCC patients > or = 11 years of age in the Nationwide Inpatient Sample for 2000. Black HCC patients were younger than white patients (mean age, 54.1 +/- 17.1 vs. 65.1 +/- 13.7 y; P < .002). Sixty-two percent of black HCC patients were age 60 or younger, whereas 68% of white HCC patients were age 61 or older. Hepatitis C virus (HCV) (25.4%), diabetes (22.1%), alcohol (15.1%), cryptogenic cirrhosis (8.6%), and hepatitis B virus (HBV) (7.3%) were the most prevalent risk factors for HCC overall. HBV (22.8% vs 3.9%, P < .0001; adjusted odds ratio [OR], 5.3; 95% confidence interval [CI], 3.0-9.2), HCV (34.8% vs 23.3%, P = .0003; OR, 1.3; 95% CI .9-1.9), concurrent HBV and HCV (8.2% vs 1.7%, P < .0001; OR, 4.5; 95% CI, 1.9-10.4), HBV plus diabetes (2.5% vs .3%, P = .002; OR, 14.1; 95% CI, 2.2-88.2), and HCV plus diabetes (8.9% vs 4.4%, P < .02; OR, 2.3; 95% CI, 1.2-4.6) were more common in black HCC patients. There was no racial difference in the frequency of alcoholic and cryptogenic liver diseases and diabetes. Higher rates of HBV, HCV, concurrent HBV and HCV, and viral hepatitis associated with diabetes might explain the greater burden of HCC in black Americans.
 
Article
The Board of Editors of Gastroenterology identified 6 topics in basic gastroenterology research in which exciting advancements have been made during the past year. These topics are (1) NOD2 variants in Crohn's disease, (2) Heliobacter pylori and CagA and VacA pathogenesis, (3) beta-catenin function in normal colonic epithelia and colon cancer, (4) DNA methylation in colonic cancer, (5) the HCV replicon, and (6) the use of small interfering RNA in somatic cell genetics. Basic research in gastroenterology has been characterized during the past year by the rapid translation from fundamental research into pathophysiological systems. New technological advances are being applied to difficult areas of gastrointestinal research. Well-defined patient populations are critical to extend the knowledge derived from the human genome to gastrointestinal diseases.
 
Article
The increasing incidence of microscopic colitis has been partly attributed to detection bias. We aimed to ascertain recent incidence trends and the overall prevalence of microscopic colitis in a population-based study. Using data from the Rochester Epidemiology Project, we identified residents of Olmsted County, Minnesota who were diagnosed with collagenous colitis or lymphocytic colitis from January 1, 2002 through December 31, 2010 based on biopsy results and the presence of diarrhea (n=182; mean age at diagnosis, 65.8 y; 76.4% female). Poisson regression analyses were performed to evaluate associations between incidence and age, sex, and calendar period. The age- and sex-adjusted incidence of microscopic colitis was 21.0 cases/100,000 person-y (95% confidence interval [CI], 18.0-24.1 cases/100,000 person-y). The incidence of lymphocytic colitis was 12.0/100,000 person-y (95% CI, 9.6-14.3/100,000 person-y) and collagenous colitis was 9.1/100,000 person-y (95% CI, 7.0-11.1/100,000 person-y). The incidence of microscopic colitis and its subtypes remained stable over the study period (P=.63). Increasing age (P<.001) and female sex (P<.001) were associated with increasing incidence. On December 31, 2010, the prevalence of microscopic colitis was 219 cases/100,000 persons (90.4 per 100,000 persons for collagenous colitis and 128.6 per 100,000 persons for lymphocytic colitis). The incidence of microscopic colitis in Olmsted County residents has stabilized and remains associated with female sex and increasing age.
 
Article
This article summarizes the clinical research advances in gastroenterology and hepatology that were reviewed during the Plenary Session of the American Gastroenterological Association's Annual Meeting in May 2004 in New Orleans, Louisiana. The clinical research advances included the efficacy of infliximab in the treatment of fistulizing Crohn's disease, survival after isolated intestinal transplantation, the role of endoscopic treatment of bleeding peptic ulcers and Barrett's esophagus, the recurrence of cancer after laparoscopic colectomy, the impact of microsatellite instability on the response to adjuvant chemotherapy with 5-fluorouracil (5-FU), the epidemiology of obesity and its response to low-carbohydrate diets, the potential role of gastrointestinal factors in the development of obesity, and, the newly appreciated condition, autoimmune pancreatitis with associated cholangitis. Clinical research advances will impact the management of digestive diseases.
 
Article
This review highlights areas of clinical research in gastroenterology and hepatology that were published during the last year and were summarized during the most recent American Gastroenterological Association Plenary Session. The topics include a comparison of the risk of recurrent bleeding in patients taking clopidogrel versus aspirin plus a proton pump inhibitor, the introduction of rifaximin for the treatment of traveler's diarrhea, and the results of an oral vaccine for cholera tested in a high endemic area where there is also a high prevalence of human immunodeficiency virus infection. In inflammatory bowel disease, the impact of a biomarker of inflammation, C-reactive protein, to the response to a new biologic therapy is identified as potentially important because it might facilitate the selection of patients for these treatments. Results of device, endoscopic, and surgical treatment of obesity are reviewed, including the evidence of significant impact of surgery-induced weight loss on comorbid diseases. In the field of cancer, colonoscopic screening results in more polyps detected, down-staging of cancers identified, and improved cancer survival. A new familial syndrome associated with a serrated adenoma/carcinoma phenotype and variability in microsatellite instability is described. A controlled study demonstrates that a urine-derived substance, ulinastatin, reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Hepatic stellate cells are involved in the fibrogenesis associated with nonalcoholic fatty liver disease. These areas of clinical research demonstrate the breadth of significant advances that will impact on the clinical practice of gastroenterology and hepatology.
 
Article
This review highlights areas of clinical research in gastroenterology and hepatology that were published predominantly in the journal Clinical Gastroenterology and Hepatology during the last year and were summarized during the American Gastroenterological Association Presidential Plenary Session in May 2006. The topics included eosinophilic esophagitis in children, detecting high-grade dysplasia or carcinoma in Barrett's esophagus, advances in management of celiac disease with elemental diet or gluten predigestion, the safety of NSAIDs in inflammatory bowel disease, the role of steroids in development of abscesses, prognosis of colorectal cancer associated with inflammatory bowel disease, screening for familial colorectal cancer in apparently sporadic disease, a new syndrome of familial colorectal cancer, new drugs in the treatment of chronic constipation and obesity, hepatoma risk factors and underserved racial/ethnic groups, and the application of new imaging and biology in diagnosis of gastroenterological disorders.
 
Article
Hepatic encephalopathy (HE) is a major complication of cirrhosis that causes substantial mortality and utilization of resources. We analyzed 5 cycles of the Nationwide Inpatient Sample, conducted between 2005 and 2009, to determine national estimates of incidence, prevalence, inpatient mortality, severity of illness, and resource utilization for inpatients with HE. The yearly inpatient incidence of HE ranged from 20,918 (2005) to 22,931 (2009) (P = .2226), comprising approximately 0.33% of all hospitalizations in the United States. Over the 5-year period of analysis, mortality of inpatients with HE remained relatively stable, at 14.13%-15.61% (P = .062); however, the proportion of patients with major and extreme severity of illness increased (P < .0001). The average length of inpatient stay increased from 8.1 to 8.5 days (P = .019). The average total inpatient charges increased from $46,663 to $63,108 per case (P < .0001). Furthermore, total national charges related to HE increased from $4676.7 million (2005) to $7244.7 million (2009). In multivariate analysis, independent predictors of inpatient mortality included the number of diagnoses per admission (odds ratio [OR] = 1.022; 95% confidence interval [CI], 1.016-1.029 per diagnosis), number of procedures per admission (OR = 1.192 per procedure; 95% CI, 1.177-1.208), and major or extreme severity of illness (OR = 3.16; 95% CI, 2.84-3.50). The most important predictors of cost, charge, and length of stay were admission to a large, urban hospital; use of Medicaid or Medicaid as the payer; major or extreme severity of illness; number of diagnoses at discharge; and procedures per admission (P < .05). Resource utilization increased from 2005 to 2009 for patients discharged from US hospitals with the diagnosis of HE. The inpatient mortality rate, however, remained stable, despite a trend toward more severe disease.
 
Article
We investigated the prevalence of and trends and risk factors for fecal incontinence (FI) in the US among non-institutionalized adults from 2005 to 2010. We analyzed data from 14,759 participants in the US National Health and Nutrition Examination Survey (49% women, 20 y or older), from 2005 to 2010 (the FI Severity Index was added in 2005-2006). FI was defined as accidental leakage of solid or liquid stool or mucus at least once in preceding month. Sampling weights were used to obtain estimates for the national population. Logistic regression was used to identify risk factors for FI. The prevalence of FI among non-institutionalized US adults was 8.39% (95% confidence interval, 7.76-9.05). It was stable throughout study period: 8.26% in 2005-2006, 8.48% in 2007-2008, and 8.41% in 2009-2010. FI resulted in release of liquid stool in most cases (6.16%). Prevalence increased with age, from 2.91% among 20-29 y old participants to 16.16% (14.15%, 18.39%) among participants 70 y and older. Independent risk factors for FI included older age, diabetes mellitus, urinary incontinence, frequent and loose stools, and multiple chronic illnesses. FI was more common among women only when they had urinary incontinence. FI is a common problem among non-institutionalized US adults. Its prevalence remained stable from 2005 through 2010. Diabetes mellitus and chronic diarrhea are modifiable risk factors. Future studies on risk factors for FI should assess for presence of urinary incontinence.
 
Top-cited authors
Michael Camilleri
  • Mayo Foundation for Medical Education and Research
William J Sandborn
  • University of California, San Diego
Suresh Chari
  • Mayo Foundation for Medical Education and Research
Siddharth Singh
  • Mayo Foundation for Medical Education and Research
Jonathan E Clain
  • Mayo Foundation for Medical Education and Research