Andreas Karameris

Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease

A close relationship has been found between Helicobacter pylori and peptic ulcer disease. Furthermore, eradication of H. pylori is associated with low recurrence rates. The aim of the present study was to examine whether eradication of H. pylori has any impact on the complications of ulcers, such as bleeding. Thirty-one patients hospitalized for duodenal ulcer bleeding, undergoing conservative treatment and with a previous history of bleeding, comprised the group studied. All patients had emergency endoscopy, and tests for H. pylori proved to be positive in all. After discharge, patients were given omeprazole 20 mg daily for 4 weeks for ulcer healing, which was achieved in all patients (100%). After this, patients were randomized to receive either omeprazole 20 mg t.i.d. alone (group O, n = 15) or the combination of omeprazole 20 mg t.i.d. + amoxicillin 500 mg q.i.d. (group O + A, n = 16) for 2 weeks. Endoscopy was performed 4 weeks after treatment ended to check for eradication of H. pylori and again when rebleeding or symptomatic relapse occurred. Groups O and O + A were similar in age, sex, smoking habits, and NSAID use. The follow-up period was 12 months for both groups. Eradication was achieved in 2 of 15 (13.3%) patients in group O and in 13 of 16 (81.3%) patients in group O + A (p < .001). Five patients rebled during follow-up. All of them belonged to group O and were patients in whom eradication had failed. In contrast, none of group O + A had rebleeding (p = 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of Helicobacter pylori CagA status to gastric cell proliferation and apoptosis.

Despite the fact that the association ofHelicobacterpylori with an increased risk of gastriccancer is well documented, the exact mechanisms of thisassociation have not been elucidated. Our aim was to shed some light on these mechanisms by studyingThe relationship of H. pylori CagA status to gastriccell proliferation and apoptosis, since both play animportant role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fiftypatients [32 men, 18 women, median age 39.5 years (range18-67)], referred for upper gastrointestinal endoscopy,from whom antral biopsies were taken. On biopsy specimens gastritis was estimated byscoring the severity of inflammatory infiltrate, and thepresence of atrophy and intestinal metaplasia were alsonoted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelialapoptotic index (AI) was measured by special stainingfor apoptosis, and CagA status was determinedserologically by immunoblotting the sera of patientsagainst H. pylori antigens. Thirty-eight (76%) of the50 patients were H. pylori (positive) and 12 (24%) H.pylori (negative). Among the 38 H. pylori (+) patients,28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the H. pylori CagA(+) and CagA(-) groups,the PI values [median (ranges)] were 5 (4-7) and 3.7(3.5-5.5), respectively (P < 0.05). In addition thedifference in PI between the H. pylori CagA(+) and H. pylori (-) groups was highly significant (P< 0.001). Concerning apoptosis, in the H. pyloriCagA(+) and CagA(-) groups, the values for AI were 1(1-30) and 5.5 (1-35), respectively (P < 0.05). In addition, the difference in AI between theH. pylori CagA(-) and H. pylori (-) groups, wassignificant (P < 0.05). We conclude that H. pyloriCagA(+) strains induce increased gastric cellproliferation, which is not accompanied by a parallel increasein apoptosis. This might explain the increased risk forgastric carcinoma that is associated with infection byH. pylori CagA(+) strains.

Pulmonary Autotaxin Expression Contributes to the Pathogenesis of Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic form of diffuse lung disease occurring mainly in older adults. Increased lysophosphatidic acid (LPA) concentrations have been reported in the alveolar space of both idiopathic pulmonary fibrosis patients and a corresponding animal model, whereas the genetic deletion or pharmacological inhibition of LPA receptor 1 attenuated the development of the modeled disease, suggesting a direct involvement of LPA in disease pathogenesis. In this report, increased concentrations of autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular LPA production, were detected in both murine and human fibrotic lungs. The genetic deletion of ATX from bronchial epithelial cells or macrophages attenuated disease severity, establishing ATX as a novel player in IPF pathogenesis. Furthermore, the pharmacological inhibition of ATX attenuated the development of the modeled disease, suggesting that ATX is a possible therapeutic target in IPF.

Helicobacter pylori infection and gastric juice vitamin C levels : impact of eradication

H. pylori has recently been recognized as a novel risk factor of gastric cancer, but its precise role in gastric carcinogenesis is as yet unknown. The aim of the present study was to assess the relationship betweenH. pylori infection and vitamin C levels in gastric juice and also to examine whether eradication ofH. pylori could have any impact on these levels. Gastric juice and plasma vitamin C levels were measured in 88 dyspeptic patients who had an upper gastrointestinal endoscopy. In the subgroup ofH. pylori-positive patients, eradication was attempted with triple therapy. This subgroup was studied on two occasions, ie, before and after treatment. There were 58H. pylori-positive and 30 -negative patients. Gastric juice vitamin C levels inH. pylori-positive patients were statistically lower (P<0.001) than the levels in theH. pylori-negative patients. Triple therapy achieved eradication in 45 patients (77.6%) of the 58H. pylori-positive patients. BeforeH. pylori was eradicated in these 45 patients gastric juice vitamin C levels were significantly (P<0.001) lower than those after eradication, the latter being no different than the group of 30H. pylori-negative patients. There was a significant (P<0.001) improvement of gastritis after eradication, which paralleled the elevation of gastric juice vitamin C levels. No difference was noted in plasma vitamin C levels betweenH. pylori-negative and -positive patients or in the latter before and afterH. pylori treatment. In 13 of the 58H. pylori-positive patients where eradication was not successful there was no difference in gastric juice vitamin C levels before and after eradication and the same was observed for the degree of gastritis. It is concluded thatH. pylori-infected patients have lower gastric juice vitamin C levels in comparison toH. pylori-negative patients.H. pylori eradication restores gastric juice vitamin C levels, which may prove potentially important in the prevention of gastric cancer.

Intrafamilial spread of Helicobacter pylori: a genetic analysis.

Background. A high incidence of Helicobacter pylori among family members of children with H. pylori gastritis has previously been documented on biopsy material. The main objective of this study was the genetic clarification of H. pylori strains involved in intrafamilial dispersion.

The association between CagA status and the development of esophagitis after the eradication of helicobacter pylori

BACKGROUND Strains of Helicobacter pylori with the cytotoxine-associated gene A (cagA) are linked to severe forms of gastroduodenal disease. Although eradication of H. pylori may predispose to the development of reflux esophagitis, the effects of CagA status on risk of esophagitis after successful H. pylori treatment are not known. METHODS We studied 50 consecutive patients without esophagitis in whom H. pylori was eradicated successfully. CagA status was determined by immunoblotting sera from patients against H. pylori antigens. Patients underwent upper gastrointestinal endoscopy before eradication and 6, 12, 18, and 24 months after eradication or when reflux symptoms occurred. Biopsy specimens of the antrum and corpus were evaluated for gastritis before H. pylori eradication and at the end of the study. The sum of the scores for acute and chronic inflammation (both measured on a 0 [absent] to 3 [severe] scale) comprised the total gastritis severity score. RESULTS In a multivariate proportional hazards regression analysis, positive CagA serology (hazard ratio [HR] = 10, 95% confidence interval [CI]: 1.3 to 81) and moderate-to-severe corpus gastritis (total severity score > or =4) before eradication (HR = 2.3, 95% CI: 1.2 to 6.1) were independent risk factors for the development of esophagitis after H. pylori eradication. CONCLUSION Patients infected with strains of H. pylori that are cagA-positive are at increased risk of developing esophagitis after eradication of H. pylori.

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.

Increased Expression of Epidermal Growth Factor Receptor (EGF-R) in Patients with Different Forms of Lung Fibrosis

Introduction. Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). Patients and Methods. Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n = 4 and fibrotic, n = 11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. Results. A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. Conclusions. We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization.

Expression of hypoxia-inducible factor (HIF)-1a-vascular endothelial growth factor (VEGF)-inhibitory growth factor (ING)-4- axis in sarcoidosis patients.

BackgroundSarcoidosis is a granulomatous disorder of unknown etiology. The term of immunoangiostasis has been addressed by various studies as potentially involved in the disease pathogenesis. The aim of the study was to investigate the expression of the master regulator of angiogenesis hypoxia inducible factor (HIF)-1a – vascular endothelial growth factor (VEGF)- inhibitor of growth factor 4-(ING4) - axis within sarcoid granuloma.MethodsA total of 37 patients with sarcoidosis stages II-III were recruited in our study. Tissue microarray technology coupled with immunohistochemistry analysis were applied to video-assisted thoracoscopic surgery (VATS) lung biopsy samples collected from 37 sarcoidosis patients and 24 controls underwent surgery for benign lesions of the lung. Computerized image analysis was used to quantify immunohistochemistry results. qRT-PCR was used to assess HIF-1a and ING4 expression in 10 sarcoidosis mediastinal lymph node and 10 control lung samples.ResultsHIF-1a and VEGF-ING4 expression, both in protein and mRNA level, was found to be downregulated and upregulated, respectively, in sarcoidosis samples compared to controls. Immunohistochemistry coupled with computerized image analysis revealed minimal expression of HIF-1a within sarcoid granulomas whereas an abundant staining of ING4 and VEGF in epithelioid cells was also visualized.ConclusionsOur data suggest an impairment of the HIF-1a – VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.

Lower adenoma miss rate with FUSE vs. conventional colonoscopy with proximal retroflexion: a randomized back-to-back trial

Background and study aims Full-spectrum colonoscopy (FSC) promises to increase adenoma detection by providing a wider field of view. The aim of this study was to compare adenoma miss rates of FSC with those of conventional colonoscopy complemented by right-colon re-examination using scope retroflexion (CC/R). Patients and methods At two tertiary endoscopy facilities, patients who were scheduled for colonoscopy for the assessment of symptoms or for colorectal cancer screening/surveillance were randomized (1:1) to undergo same-day, back-to-back colonoscopies (FSC or CC/R first), performed by one of five endoscopists who had documented adenoma detection rates > 35 %. Per-protocol data were analyzed. Results We randomized 220 patients. There were five FSC technical failures (three air pump and two left screen); therefore, 107 and 108 cases were analyzed in the FSC and CC/R index procedure arms, respectively. Withdrawal times were similar for FSC and CC/R (7.7 minutes vs. 7.6 minutes). Overall, we detected 3 cancers and 153 adenomas (FSC = 92; CC/R = 61); 81 were detected in the proximal colon, 3 of which were detected by retroflexed examination. By per-lesion analysis, FSC showed a significantly lower adenoma miss rate compared with CC/R overall (10.9 % [95 % confidence interval (CI) 3.8 to 18.1] vs. 33.7 % [95 %CI 23.4 to 44.1]) and in the proximal colon (13.9 % [95 %CI 2.6 to 25.2] vs. 42.2 % [95 %CI 27.8 to 56.7]). The advanced adenoma miss rate was lower with FSC overall (4.3 % [95 %CI - 4.0 to 12.7] vs. 25.9 % [95 %CI 9.4 to 42.5]). There were no adverse events. Conclusions FSC outperformed conventional colonoscopy with right-colon scope retroflexion in the detection of missed adenomas, both overall and in the proximal colon, even when performed by experienced endoscopists.Trial registered at ClinicalTrials.gov (NCT02117674).