Charis Spiliadi

Changes in Liver Histology Accompanying Massive Weight Loss after Gastroplasty for Morbid Obesity

Background: Nonalcoholic steatohepatitis (NASH) is common in morbid obesity. Our goal was to evaluate the alterations in liver histology and biochemistry before and after weight loss in 51 morbidly obese patients following Masons vertical banded gastroplasty. Methods: Two biopsies were performed (on entry and after an average of 18 months), while 16 of these subjects had a third biopsy 17 months after the second. Results: On entry, steatosis and steatohepatitis (mostly grade 3) were present in 98.0% and fibrosis (mostly stage 2) in 94.1% of the subjects. After an excess weight loss of 66%, steatosis and steatohepatitis improved significantly (P<0.001). Although a significant overall decrease in fibrosis occurred (P=0.002), 21 patients (41.1%) did not change and only 6 patients (11.7%) increased in fibrosis. None developed cirrhosis. The decrease in steatohepatitis was significantly correlated (P=0.011) with the reduction of BMI. Fasting serum glucose, lipids, lipoproteins, transaminases, gamma-glutamyl transpeptidase, alkaline phosphatase and fibrinogen were also significantly improved at the time of the second biopsy. The third biopsy performed in 16 of the subjects showed further significant improvement in liver histology. Conclusion: NASH improved significantly with massive weight loss in non-diabetic, non-alcoholic, morbidly obese subjects, while fibrosis improved in nearly half of the patients.

Effectiveness of two quadruple, tetracycline‐ or clarithromycin‐containing, second‐line, Helicobacter pylori eradication therapies

There are no guidelines on second‐line therapies for Helicobacter pylori eradication failures of omeprazole–clarithromycin–amoxicillin triple therapy.

Hypergastrinemia Is Associated with Increased Risk of Distal Colon Adenomas

Background/Aims:Helicobacter pylori infection is a recognized cause of hypergastrinemia, but the association of blood gastrin levels with colonic adenomas (CAs) is controversial. The aim of this study is to investigate if hypergastrinemia, H. pylori infection and/or cagA protein are risk factors for CAs. Methods: In this prospective case-control study, fasting serum samples from 78 consecutive patients with CAs and 78 demographically matched colonoscopy-negative controls were assayed for anti-H. pylori immunoglobulin G, cagA protein and serum gastrin levels. Multivariate analysis was performed to identify risk factors for colon adenomas. Results: Though prevalence of H. pylori antibodies was not significantly different, the prevalence of cagA protein was significantly higher in patients with adenomas (42.3%) as compared with controls (25.6%, p < 0.03). Mediangastrin levels were significantly higher in patients with CAs (55, 20–975 pg/ml) than in controls (45.2, 23–529 pg/ml) (p < 0.001). Hypergastrinemia (>110 pg/ml) was commoner in patients with CAs than in controls (29.5 vs. 11.5%, p = 0.006) and was the only independent risk factor for adenomas (odds ratio 3.2, 95% CI 1.4–7.5) by multivariate analysis, but not H. pylori infection or cagA positivity. There was a significant association of hypergastrinemia and distal distribution of adenomas (p < 0.002). Conclusions: Our study shows that hypergastrinemia is a risk factor for CAs, especially of the distal colon.

Predictive factors and prevalence of follicular gastritis in adults with peptic ulcer and nonulcer dyspepsia

Follicular gastritis is an importanthistological entity, because it may progress to overtgastric MALT lymphoma. However, there is no universalagreement on whether there is any correlation offollicular gastritis with histological features of theantral mucosa or on the prevalence of folliculargastritis. To shed further light on these issues, westudied antral biopsies obtained from 735 adultpatients, who had participated in six consecutiveclinical trials. They included 348 patients withduodenal ulcer, 82 with gastric ulcer, and 305 withnonulcer dyspepsia. The Sydney classification system ofgastritis was used, using a score of 0-3 to grade degreeand activity of inflammation, gland atrophy, intestinalmetaplasia, and H. pylori colonization density.Follicular gastritis was defined as prominent lymphoid follicles with no lymphoepithelial lesion. Noneof the H. pylori-negative patients (N = 159) hadfollicular gastritis. Among H. pylori-positive patients,80/340 (23.5%) with duodenal ulcer, 5/77 (6.5%) withgastric ulcer, and 20/159 (12.6% ) with nonulcerdyspepsia had follicular gastritis (P < 0.001).Multivariate discriminant analysis selected thefollowing four significant predictor variables for follicular gastritis (Wilks λ =0.91, x2 = 70.6, df = 4, P < 0.001):gastritis sum score, atrophic gastritis, age of thepatient, and disease. The prevalence of folliculargastritis was linearly correlated (y = 24.55 – 0.98x, r =–0.62, F1,11 = 6.12, P = 0.03) with theage groups of the 576 H. pylori-positive patientsstudied. In conclusion, follicular gastritis is highlycorrelated with H. pylori-caused severe, activegastritis. It is mostly prevalent in the young H.pylori-infected patients with duodenal ulcer.

Prospective evaluation of a whole-blood antibody test (FlexPack HP) for in-office diagnosis of Helicobacter pylori infection in untreated patients.

Objectives Rapid, reliable in‐office tests are needed for applying the adopted screen‐and‐treat strategy in Helicobacter pylori‐positive young dyspeptic patients. Design We have evaluated the performance characteristics of a whole‐blood antibody (WBA) test for the detection of H. pylori infection under in‐office conditions. Methods In a prospective double‐blind study, 183 untreated patients referred to a tertiary centre for endoscopy because of dyspepsia were studied. Patients were defined as H. pylori‐positive if two out of three tests (histology, rapid urease test, Gram staining of biopsy smears) were positive, and H. pylori‐negative if all three tests were negative. An in‐office test detecting IgG antibodies to H. pylori (FlexPack HP, Abbott Diagnostics) was used with capillary blood and compared with an ELISA detecting IgG (quantitative) and IgA (qualitative) H. pylori serum antibodies. Results Of the 183 patients, 139 were defined as H. pylori‐positive. The in‐office test had 79% sensitivity, 95% specificity, 98% positive and 59% negative predictive value. The respective values for IgG serum antibodies were 94, 70, 91 and 79% and those for IgA antibodies were 86, 82, 94 and 64%. About 50% of the false‐negative in‐office tests had a serum IgG antibody titre > 100 units. Co‐evaluation of our data with published reports suggested that both the median sensitivity and negative predictive value of the kit are significantly inferior when performed with whole‐blood (five studies) compared with serum (nine studies) (82 versus 92% and 82 versus 93% respectively, P< 0.035). Conclusions Improvement of the performance characteristics of FlexPack HP in‐office test is needed. However, the test may be a useful tool for identifying H. pylori‐positive patients in younger age groups who could be managed without upper gastrointestinal endoscopy. Eur J Gastroenterol Hepatol 12:727‐731

Cell turnover of serrated adenomas

Serrated adenomas of the colon are characterized by epithelial neoplasia combining the architectural features of hyperplastic polyps and the cytological features of adenomas. Cell turnover, which is related to the malignant potential of these polyps, has not been thoroughly investigated. The aim of this study was to investigate epithelial cell proliferation, apoptosis, and oncoprotein expression in serrated adenomas. Twenty‐five hyperplastic polyps, 25 serrated adenomas, and 25 tubulovillous adenomas resected from the colons of 75 patients were studied by immunohistochemical staining using monoclonal antibodies against MIB‐1, Bcl‐2, Bax, p53, and the TUNEL method for the detection of apoptosis. In serrated adenomas, the proliferation rate was significantly lower than in tubulovillous adenomas in both the lower and the upper parts of the crypts, and higher than that of hyperplastic polyps. Apoptosis was also significantly lower in serrated than in tubulovillous adenomas, but higher than in hyperplastic polyps. p53 oncoprotein expression was significantly greater in both serrated and tubulovillous adenomas than in hyperplastic polyps. bcl‐2 protein expression was higher only in tubulovillous adenomas. Bax index was significantly different between tubullovillous and serrated adenomas, but the lowest values were observed in hyperplastic polyps. Serrated adenomas are highly proliferative polyps. They should be considered a biologically different entity from hyperplastic polyps. The intermediate features between serrated adenomas, hyperplastic polyps, and tubulovillous adenomas using the antibodies analysed in this study could have implications for the rate or the mechanism of development of malignancy in this type of polyp. Copyright

Molecular analysis of B-cell clonality in Helicobacter Pylori gastritis

The aim of our study was to identify PCR-detectable clonal B-cell population in Helicobacter pylori gastritis and assess their relation to the Wotherspoon-Isaacson (W-I) grade for gastric lymphoid infiltrates. Amplified DNA was obtained from thirty four H. pylori positive gastritis dyspeptic patients and thirty four H. pylori negative matched controls. Clonal bands were observed in 6 (2/17 W-I Grade 1, 2/13 W-I Grade 2, and 2/4 W-I Grade 3 lesions) and polyclonal smears in 24 cases (15 W-I Grade 1, 7 W-I Grade 2, and 2 W-I Grade 3). Four additional W-I Grade 2 samples with clonal bands were associated with background polyclonal smear and were not reproducible. Clonal bands were not recorded in controls. B-cell clonality was not related to W-I grades. We conclude that certain H. pylori positive gastritis patients show PCR-detectable monoclonality, which is independent of the W-I grade of gastritis and cannot be taken as evidence of an existing neoplastic lesion.

Performance of two immunosorbent assay kits for the detection of serum immunoglobulin G to Helicobacter pylori in untreated Greek patients

Background: The performance of serological methods used to detect Helicobacter pylori varies with the ethnicity and prevalence of the infection in the community. We have prospectively evaluated the performance of two commercially available serum enzyme immunoassays (EIA) detecting H. pylori immunoglobulin G (IgG) antibodies in the sera of untreated Greek patients. Methods: One-hundred-and-thirty consecutive untreated dyspeptic patients underwent endoscopy with biopsies from the gastric body ( n = 2) and antrum ( n = 2). Serum samples were also obtained from each patient. Serum H. pylori IgG antibody titres were determined with two EIA kits (Pyloriset EIA-G and Milenia H. pylori IgG). Sensitivities, specificities and optimal cut-off values of serum EIAs were determined for the population under investigation by using receiver operating characteristic (ROC) curve analysis and histology as gold standard. Results: Ninety-seven patients were defined H. pylori -positive and 33 negative by histology. ROC curve analysis for the Pyloriset kit yielded 86% (95% CI, 78%-92%) sensitivity and 85% (68%-95%) specificity at an optimal cut-off value of S 358 units/ml. The respective values for the Milenia kit were 86% (78%-92%) and 82% (65%-93%) at an optimal cut-off value of S 51 units/ml. The suggested cut-off values of the manufacturers for Pyloriset and Milenia kits are S 300 and S 44 EIA units, respectively, which yield 2% and 4% higher sensitivity, but 9% lower specificity for both EIA kits. Conclusions: Both serum EIA kits performed well in our study. Our data show that EIA cut-off values should be optimized for the population under investigation.

Evaluation of a Single-Step Serological Assay for Laboratory Diagnosis of Helicobacter pylori Infection

Abstract.A rapid, single-step, in-laboratory qualitative test for the detection of IgG antibodies to Helicobacter pylori in serum (TestPack Plus; Abbott Laboratories, Germany) was evaluated. This test may be used as an alternative to enzyme immunoassays (EIAs). Of 153 adult patients, 110 were defined as Helicobacter pylori positive and 43 as Helicobacter pylori negative by the gold standard, a combination of three tests. The performance characteristics of the TestPack Plus, i.e. sensitivity, specificity, and positive and negative predictive values, were not significantly different from the corresponding values obtained with an EIA used for comparative purposes, the Pyloriset EIA-G test (Orion Diagnostica, Finland). The high positive predictive value (93%) of the TestPack Plus single-step serological test makes it a valuable tool for rapid in-laboratory screening purposes, especially in countries with a high prevalence of Helicobacter pylori infection.

Molecular Analysis of B-Cell Clonality in Helicobacter Pylori Gastritis

The aim of our study was to identify PCR-detectable clonal B-cell population in Helicobacter pylori gastritis and assess their relation to the Wotherspoon-Isaacson (W-I) grade for gastric lymphoid infiltrates. Amplified DNA was obtained from thirty four H. pylori positive gastritis dyspeptic patients and thirty four H. pylori negative matched controls. Clonal bands were observed in 6 (2/17 W-I Grade 1, 2/13 W-I Grade 2, and 2/4 W-I Grade 3 lesions) and polyclonal smears in 24 cases (15 W-I Grade 1, 7 W-I Grade 2, and 2 W-I Grade 3). Four additional W-I Grade 2 samples with clonal bands were associated with background polyclonal smear and were not reproducible. Clonal bands were not recorded in controls. B-cell clonality was not related to W-I grades. We conclude that certain H. pylori positive gastritis patients show PCR-detectable monoclonality, which is independent of the W-I grade of gastritis and cannot be taken as evidence of an existing neoplastic lesion.