A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Socio-economic factors and medical conditions affecting regular stomach cancer screening in Korea: a retrospective longitudinal study using national public health data for 11 years.

OBJECTIVE: This study aimed to explore socio-economic factors and medical conditions that affect regular stomach cancer (SC) screening among Korean adults. STUDY DESIGN: This was a retrospective observational study. METHODS: Study subjects were 5545 adults aged ≥40 years who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey and were followed up to year 2017 based on data linking to the Korean National Health Insurance Service and Korean Health Insurance Review and Assessment. Socio-economic factors included sex, age, residential area, education, occupation, marital status, disability, public and private health insurance, service through local public health organizations, history of cancer except for SC, and family history of SC. Medical factors included six gastric lesions with the possibility of facilitating SC screening, including benign gastric neoplasm, chronic atrophic gastritis, gastric polyp, Helicobacter pylori infection, intestinal metaplasia, and peptic ulcers. The outcome was adherence to SC screening, which was divided into non-adherence, irregular adherence, and regular adherence. RESULTS: After adjusting for the effects of socio-economic factors, multivariate ordinal logistic regression revealed that participants with a history of four types of gastric lesions were more likely to regularly participate in SC screening: chronic atrophic gastritis (odds ratio [OR] 1.567; 95% confidence interval [CI] = 1.276-1.923), gastric polyps (OR 1.565; 95% CI = 1.223-2.003), H. pylori infection (OR 1.637; 95% CI = 1.338-2.003), and peptic ulcer (OR 2.226; 95% CI 1.750-2.831). CONCLUSIONS: To improve participation in SC screening, it is necessary to implement personalized strategies for individuals at risk for gastric cancer in addition to population-based strategies for vulnerable groups.

Assessment of tumor microenvironment in gastric adenocarcinoma.

Gastric cancer (GC), despite the current possibilities of early diagnosis and curative treatment, remains a major public health problem, being one of the main causes of cancer, due to its detection in advanced stages. Screening programs applied in Western countries led to low incidence rates in these countries. Helicobacter pylori bacterial infection is considered to be the highest risk factor for the onset of GC because it causes chronic inflammation of the gastric mucosa and damages hydrochloric acid secretory glands, eventually leading to atrophic gastritis, which has a potential to progress to GC. In our study, we aimed at assessing the tumor microenvironment in gastric adenocarcinomas as approximately 90% of GCs are adenocarcinomas. Our study showed that the tumor microenvironment has an extremely complex morphological structure, totally different from the microscopic structure of the gastric wall, consisting of stromal cells, lymphocytes, plasma cells, macrophages, blood vessels, collagen fibers, extracellular connective matrix, other cells. The tumor microenvironment presents phenotypic, cellular and molecular heterogeneity; therefore, the microscopic aspect differs from one tumor to another and even from one region to another in the same tumor. Poorly or moderately differentiated adenocarcinomas show a more intense desmoplastic reaction than well-differentiated ones. Alpha-smooth muscle actin (α-SMA)-positive stromal cells (tumor-associated fibroblasts) and tumor macrophages were the most numerous cells of the tumor microenvironment. The tumor microenvironment is the result of cooperation between tumor cells, cancer-associated fibroblasts, immune system cells and blood vessels. It allows tumor cells to multiply, grow and metastasize.

Histologic and Cost-Benefit Analysis of Laparoscopic Sleeve Gastrectomy Specimens Performed for Morbid Obesity.

CONTEXT.­: Laparoscopic sleeve gastrectomy (LSG) has quickly become the bariatric surgical procedure of choice for patients with obesity who have failed medical management. Laparoscopic sleeve gastrectomy results in a gastric remnant that is routinely subject to pathologic examination. OBJECTIVE.­: To perform a histologic and cost-benefit analysis of gastric remnants post-LSG. DESIGN.­: All LSG cases performed at University Health Network, Toronto, Ontario, Canada, between 2010 and 2019 were reviewed. Specimens that underwent routine histopathologic assessment and ancillary immunohistochemical analysis were analyzed. Baseline patient characteristics and surgical outcomes were obtained from our internal database. The total cost of specimen gross preparation, examination, sampling, and producing and reporting a hematoxylin-eosin slide was calculated. RESULTS.­: A total of 572 patients underwent LSG during the study period and had their specimens examined histologically. A mean of 4.87 blocks generating 4 hematoxylin-eosin slides was produced. The most common histologic findings reported in LSG specimens ranged from no pathologic abnormalities identified together with proton pump inhibitor-related change. A minority of cases demonstrated clinically actionable histologic findings, of which Helicobacter pylori infection was the most common. The total cost for the complete pathologic analysis of these cases amounted to CaD $66 383.10 (US $47 080.21) with a mean of CaD $116.05 (US $82.40) per case. A total of CaD $62 622.75 (US $44 413.30) was spent on full examination of cases that had no further postoperative clinical impact. CONCLUSIONS.­: There is a broad spectrum of pathologic findings in LSG specimens, ranging from clinically nonactionable to more clinically actionable. The vast majority of histologic findings had no clinical impact, with only a minority of cases being clinically significant. This study therefore recommends that LSG specimens be subject to gross pathologic examination in the vast majority of cases. However, sections should be submitted for microscopic analysis if grossly evident lesions are present and if there is a clinical/known history of clinically actionable findings.

Histological assessment of gastric pseudopyloric metaplasia: Intra- and inter-observer consistency.

BACKGROUND: The histological spectrum of oxyntic mucosal atrophy (a major determinant of gastric cancer risk) includes pseudopyloric metaplasia (PPM), which histological assessment has been regarded as unreliable. PPM consistently expresses Trefoil-Factor 2 (TFF2), which is histochemically detecteble (TFF2-IHC). AIMS: Intra- and inter-observer consistency in assessing PPM was examined using both hematoxylin & eosin (H&E) and TFF2-IHC. MATERIALS AND METHODS: Seventy-four oxyntic biopsy samples obtained from autoimmune gastritis were considered. Two serial histological sections obtained from the paraffin-embedded tissue-samples were stained with H&E and TFF2-IHC. Three pathologists (Alpha, Beta, Gamma) independently scored PPM by both staining and the Intra- and inter-observer consistency (H&E versus TFF2-IHC) was calculated using k-statistics and/or Spearman's coefficient. RESULTS: Based on H&E-stain versus TFF2-IHC, intra-observer consistency in PPM assessement was ranked as consistently "good" (k-values: Alpha=0.79; Beta=0.78; Gamma=0.75). Based on H&E, the overall PPM inter-observer consistency among the 3 observers was ranked as "good" (k=0.77) (the inter-observer consistency for pairs of observers was as follows: Alpha versus Beta k=0.88; Alpha versus Gamma k=0.87; Beta versus Gamma k=0.80). Based on TFF2-IHC, the overall PPM inter-observer agreement was ranked as "excellent" (k=0.91) (the inter-observer consistency for pairs of observers was as follows: Alpha versus Beta k=1; Alpha versus Gamma k=0.91; Beta versus Gamma k=0.91). CONCLUSION: Relying on either H&E staining or TFF2-IHC, pathologists assess PPM consistently.

Use of endoscopic assessment of gastric atrophy for gastric cancer risk stratification to reduce the need for gastric mapping.

Background/Aims: Stratification for gastric cancer risk typically involves histologic grading of gastric biopsies. This study aimed to compare endoscopic assessment of gastric atrophy and histologic gastric mapping for gastric cancer risk stratification in a region with relatively high risk of gastric cancer.Methods: Endoscopic and histologic gastric cancer risk stratification were compared in Vietnamese patients with functional dyspepsia. Endoscopic gastric atrophy was graded according to the Kimura-Takemoto classification. High-risk histologic lesions were defined as gastric dysplasia, Operative Link on Gastritis Assessment (OLGA) gastritis stage III/IV, intestinal metaplasia in both the antrum and the corpus or incomplete intestinal subtype at any site. Two experienced pathologists, blinded to endoscopic information, jointly examined all specimens and reached a consensus. The presence of high-risk histologic lesions was compared among patients with different endoscopic grades of gastric atrophy.Results: There were 280 subjects (mean age, 46.1 ± 10 years, and male, 50%). The numbers of patients with moderate/severe grade of endoscopic gastric atrophy and high-risk histologic lesions were 126 (45.0%) and 46 (16.4%), respectively. The sensitivity, specificity, positive and negative likelihood ratios of moderate/severe endoscopic atrophic grade for detecting high-risk histologic lesions were 93% (95% CI 86%-100%), 65% (95% CI 58%-71%), 2.64 (95% CI 2.18 - 3.18) and 0.10 (95% CI 0.03 - 0.30), respectively.Conclusions: Gastric cancer risk assessment using endoscopic or histologic methods provided similar results such that the absence or a mild grade of endoscopic gastric atrophy would preclude the need for histologic mapping.

The Diagnostic Tests for Detection of Helicobacter pylori Infection.

Helicobacter pylori causes one of the most common infections in human populations. The role of this bacterium in chronic gastritis, gastric ulcer, gastric cancer, as well as extra-digestive diseases such as ischemic heart disease and chronic obstructive pulmonary diseases, is well known. Prevention and control of these diseases can occur by early diagnosis and eradication of H. pylori infection. At present, different methods have been established to detect H. pylori infection. The biopsy-based tests, which are known as invasive methods, such as rapid urease test and histology, have the highest specificity among the others. Similarly, culture of biopsy samples is used for diagnosis of H. pylori infection. It has a high specificity value, and also allows us to perform antibiotic sensitivity testing. On the contrary, polymerase chain reaction and other molecular methods have good sensitivity and specificity, and can be used for detection of H. pylori infection, its virulence factors, and eradication success after treatment. While serological tests are more appropriate for epidemiological studies, their main weakness for clinical use is low specificity. Overall, specificity and sensitivity, cost, usefulness, and limitation of tests should be considered for selection of detection methods of H. pylori in each country.

Impact of delayed care on surgical management of patients with gastric cancer in a low-resource setting.

BACKGROUND: Gastric cancer is the fifth most common cancer in Eastern Africa. Diagnostic delays in low-resource countries result in advanced disease presentation. We describe perioperative management of gastric cancer in Rwanda. METHODS: A retrospective review of records at three hospitals was performed to identify gastric adenocarcinoma cases from January 2012 to June 2016. Multiple perioperative and tumor-related variables were collected. Descriptive and bivariate analyses were performed. RESULTS: The final analysis included 229 patients with gastric cancer. Median age was 58 years (interquartile range [IQR] 49-65) and 49.6% were female (n = 114). Patients reported symptoms (ie, weight loss, epigastric pain) for a median time of 12 months (IQR 7.5-24). On presentation, 18.8% ( n = 43) had gastric outlet obstruction; 13.5% ( n = 31) had a palpable mass. Fifty-one percent ( n = 117) underwent an operation; of these, 74% ( n = 86) received gastrojejunostomy or were inoperable; and 29% ( n = 34) underwent curative resection. Palliative care referrals were made for 9% ( n = 20). Pathology reports were available for 190 patients (83.0%). Only 11.3% ( n = 26) had Helicobacter pylori ( H. pylori) testing of which 65.4% tested positive ( n = 17). CONCLUSIONS: A majority of patients presented with advanced disease. Very few patients had a curative resection. Significant advances in diagnosis and treatment are needed to improve the care of gastric cancer patients in Rwanda.

Selective staining of gastric biopsies for H. pylori does not affect detection rates or turnaround time and improves cost compared to reflexive staining.

AIMS: To evaluate how reflexive versus selective H. pylori stains affect detection rates, turnaround time (TAT), and cost savings in a real life practice environment following an institutional policy change. METHODS: The aforementioned parameters were evaluated in all cases in the year preceding and the year following an institutional policy change from reflexive to selective staining. RESULTS: 1497 patients comprised the reflexive stain (RS) group of which 228 (15.2%) were H. pylori positive. 1629 patients comprised the selective stain (SS) group of which 237 (14.5%) were H. pylori positive. There was no significant difference in H. pylori detection rates between the RS and SS groups (OR=0.95, 95% CI=0.78-1.15, p=0.59). TATs were similarly equivalent with a mean of 52.4h for the RS cohort and 53.7h for the SS cohort (p=0.344), both of which included a resident preview day. We calculated an average laboratory cost savings of $11.68 per case, which saved our department over $15,000 (37%) in the year following the policy change. CONCLUSIONS: Our results support a policy of selective staining for H. pylori as opposed to reflexive staining and go on to show that laboratories that change their policy can expect to generate cost savings without compromising detection rates or TAT.

Low Yield and High Cost of Gastric and Duodenal Biopsies for Investigation of Symptoms of Abdominal Pain During Routine Esophagogastroduodenoscopy.

BACKGROUND: Esophagogastroduodenoscopy (EGD) referrals for symptoms of abdominal pain are common. Current guidelines for dyspepsia recommend biopsies of gastric mucosa for Helicobacter pylori in all patients referred for EGD. Our study aimed to determine the clinical yield and cost-effectiveness of gastric and duodenal biopsy in EGDs performed for abdominal pain. METHODS: Three hundred and ninety-one outpatient EGDs performed at a single academic tertiary care center were studied. For each procedure, endoscopic as well as pathologic findings from the stomach and duodenum were then recorded. Charge of biopsy was calculated using the increased charges for professional fees, forceps, and pathology fees when a biopsy was performed. RESULTS: Gastric biopsies were obtained on 304 EGDs performed with 13 (4.2%) patients diagnosed with H. pylori. In patients with abnormal gastric mucosa on EGD, 11 of 167 (6.5%) were positive for H. pylori compared to 2 of 137 (1.4%) with normal appearing mucosa (p = 0.02). Charge per diagnosis of H. pylori for normal mucosa was calculated to be $43,073. Duodenal biopsies were performed in 263 cases. Celiac disease was diagnosed in 4 of 263 cases (1.5%). Of patients with abnormal duodenal mucosa on EGD, 1 of 36 (2.7%) were positive for celiac disease compared to 3 of 227 (1.3%) with normal mucosa (p = 0.57). Charge per diagnosis of celiac disease for normal mucosa was calculated to be $47,580. CONCLUSION: Routine biopsy during EGD for symptoms of abdominal pain has low yield with high costs. Practice of routine biopsies of normal appearing tissue and the present guidelines should be reconsidered in the investigation of abdominal pain with EGD.

Prospective identification of Helicobacter pylori in routine gastric biopsies without reflex ancillary stains is cost-efficient for our health care system.

Despite the recommendation of expert gastrointestinal pathologists, private and academic centers (including our own) have continued to use ancillary stains for identification of Helicobacter pylori. For a 1-month period, gastric biopsies were prospectively evaluated for H pylori using routine hematoxylin and eosin (H&E) and a reflex Diff-Quik stain. During this time, 379 gastric biopsies were collected on 326 patients. H pylori organisms were prospectively identified in 23 (7%) patients, all of whom had superficial dense lymphoplasmacytic inflammation expanding the lamina propria. An additional 2 patients with neutrophilic inflammation were found to have H pylori by immunohistochemical staining. One patient diagnosed as having normal gastric mucosa was retrospectively found to have inflammation with rare H pylori organisms originally overlooked on both H&E and Diff-Quik but later identified on immunostain (0.5%). No patients with chemical gastritis (16%) or chronic inflammation (27%) were found to have H pylori. During the study month, 9 immunostains for H pylori were performed in addition to the 379 Diff-Quik. After discontinuation of reflex Diff-Quik, approximately 20 immunostains are performed for H pylori each month, which decreases technical time spent for processing gastric biopsies and reduces cost to the health care system. In our population with a low prevalence of H pylori, reflex staining for organisms is not cost-effective. The organisms can be seen on routine H&E; when suspicious superficial or active inflammation is present without visible organisms, immunohistochemical stains will confirm presence or absence within a day. Discontinuation of up-front ancillary studies is cost-effective without compromising patient care.

[Helicobacter pylori gastritis: assessment of OLGA and OLGIM staging systems]. / Gastrites chroniques à hélicobacter pylori: évaluation des systèmes OLGA et OLGIM.

Helicobacter pylori (H pylori) gastritis presents a risk of cancer related to atrophy and intestinal metaplasia. Two recent classifications OLGA (Operative Link on Gastritis Assessment) and OLGIM (Operative Link on Gastritic Intestinal Metaplasia assessment) have been proposed to identify high-risk forms (stages III and IV). The aim of this study is to evaluate the OLGA and OLGIM staging systems in H pylori gastritis. A descriptive study of 100 cases of chronic H pylori gastritis was performed. The revaluation of Sydney System parameters of atrophy and intestinal metaplasia, of gastric antrum and corpus, allowed identifying respectively the stages of OLGA and OLGIM systems. The progressive risk of our H pylori gastritis was 6% according to OLGA staging and 7% according to OLGIM staging. Significant correlation was revealed between age and OLGA staging. High-risk gastritis according to OLGIM staging was significantly associated with moderate to severe atrophy. High-risk forms according to OLGA staging were associated in 80% of the cases to intestinal metaplasia. OLGA and OLGIM systems showed a highly significant positive correlation between them with a mismatch at 5% for H pylori gastritis. The OLGA and OLGIM staging systems in addition to Sydney System, allow selection of high risk forms of chronic gastritis requiring accurate observation.

A Strategy for Helicobacter Immunohistochemistry Utilization in Pediatric Practice: Insights From Morphologic and Cost-Benefit Analyses.

OBJECTIVES: Recent studies in adults have examined the utility of immunohistochemistry (IHC) in detecting Helicobacter in gastric biopsy specimens and reached differing conclusions. Dedicated cost-benefit analysis of Helicobacter IHC in pediatric gastric biopsy specimens has not been performed. METHODS: From 1,955 pediatric gastric biopsies in a 1-year period, we identified 63 Helicobacter -positive and 120 Helicobacter -negative biopsy specimens. All cases were scored according to the Updated Sydney System for the severity of inflammation. RESULTS: We observed that pediatric Helicobacter infection was significantly associated with germinal center formation, active inflammation, oxyntic mucosa with moderate to severe chronic inflammation, and antral mucosa with any chronic inflammation, exclusive of mild and superficial chronic inflammation. At least one associated pattern was seen in each Helicobacter -positive biopsy specimen. In comparison with adults, pediatric Helicobacter -positive biopsy specimens are more likely to lack acute inflammation and more likely to show moderate to marked chronic inflammation. CONCLUSIONS: We recommend performing Helicobacter IHC on pediatric gastric biopsy specimens with any of the above inflammatory patterns. This approach can sensitively identify pediatric patients with Helicobacter gastritis, limit IHC staining to approximately 30% of all gastric biopsy specimens, and reduce costs by up to $55,306.90 per 1,000 biopsy specimens.

Vertical sleeve gastrectomy specimens have a high prevalence of unexpected histopathologic findings requiring additional clinical management.

BACKGROUND: Laparoscopic vertical sleeve gastrectomy is used with increasing frequency as a therapeutic option for morbid obesity. Before the procedure, patients undergo a rigorous preoperative evaluation including double contrast upper gastrointestinal radiographic series at our institution. Patients undergoing sleeve gastrectomy are presumed to have no significant gastric pathology. OBJECTIVES: To investigate the prevalence of histopathologic findings requiring clinical follow-up in sleeve gastrectomy specimens. SETTING: University Hospital, United States. METHODS: Retrospective review was conducted of all primary vertical sleeve gastrectomy specimens performed for morbid obesity at our institution from July 2008 until August 2012 (N = 248). RESULTS: Unanticipated findings warranting clinical follow-up were identified in 8.4% of cases and included cases of H. pylori gastritis, autoimmune gastritis with microcarcinoid formation, necrotizing vasculitis, and intestinal metaplasia. H. pylori was identified in 5.2% of all cases and in 33.3% of cases of gastritis. Neoplasms were identified at laparoscopy in 2 additional cases (0.8%). CONCLUSIONS: Surgeons and pathologists should be aware of the high prevalence of diagnoses requiring clinical follow-up in vertical sleeve gastrectomy specimens.

Upfront special staining for Helicobacter pylori in gastric biopsy specimens is not indicated.

OBJECTIVES: The practice of routine upfront use of special stains in biopsy specimens with minimal or no inflammation has not been evaluated. This study was conducted to determine the value of special stains for Helicobacter pylori in gastric biopsy specimens showing variable degrees of inflammation and to evaluate the practice of upfront ancillary staining of all mucosal biopsy specimens. METHODS: Immunohistochemical or Diff-Quik stains were done on sections of 570 gastric biopsy specimens. The rates of positivity for H pylori were calculated in each category based on the degree of inflammation and classified as normal, minimal, mild, moderate, or severe. RESULTS: H pylori was not detected in 386 (67.7%) biopsy specimens that were classified as normal (6.0%) or with minimal inflammation (28.2%) or mild inactive gastritis (33.5%). The organism was identified by Diff-Quik or immunohistochemical stain in 76 (89.4%) of 85 with moderate active gastritis and 30 (93.8%) of 32 biopsy specimens showing severe active gastritis. CONCLUSIONS: Upfront staining of gastric biopsy specimens is not cost-effective since a significant proportion of the gastric biopsy specimens were normal or showed minimal inflammation; in none of these biopsy specimens was the organism found. Special stains should be performed only in selected biopsy specimens that reveal any degree of chronic active gastritis or moderate inactive gastritis.

Assessment of p21, p53 expression, and Ki-67 proliferative activities in the gastric mucosa of children with Helicobacter pylori gastritis.

BACKGROUND: Helicobacter pylori that is generally acquired in childhood and infects the gastric mucosa is considered to be responsible for many pathobiological changes that are linked to the pathogenesis of gastric cancer. Although the majority of studies on the subject have been carried out in adults, there are a limited number of studies on children that reflect the early period of infection and may be of greater significance. AIM: We aimed to determine the role of H. pylori infection and/or gastritis in several histopathological changes, p53, p21, and cell proliferation-associated Ki-67 antigen expression in the gastric mucosa. MATERIALS AND METHODS: We studied 60 patients with a mean age of 7.5 ± 4.5 years at referral. On the basis of endoscopic appearance and the evaluation of the gastric antral specimens, the patients were divided into three groups: patients without gastritis, patients with H. pylori-positive gastritis, and patients with H. pylori-negative gastritis. To determine the expression of p53, Ki-67, and p21 in gastric biopsy specimens, immunohistochemical stains were performed. RESULTS: The incidence of neutrophil activity, which was one of our histopathologic parameters, was significantly higher in the H. pylori-positive gastritis group than the other two groups. The presence of lymphoid aggregate was more frequent in H. pylori ± gastritis groups than the nongastritis group. p53 expression was found to be significantly higher in the H. pylori-positive gastritis group than the nongastritis group. Ki-67 and p21 expressions were significantly more frequent in the H. pylori-positive gastritis group than the other two groups. When we evaluated the density of H. pylori, as the density of bacteria increases, we found that the expressions of p53, p21, and Ki-67 increased significantly. CONCLUSION: Expression of the studied precancerous markers in significant amounts indicates the importance of childhood H. pylori infection in the constitution of gastric cancer in adulthood.

Assessment of the relationship between Helicobacter pylori infection, endoscopic appearance and histological changes of the gastric mucosa in children with gastritis (a single center experience).

BACKGROUND: Helicobacter pylori infection is an important cause of gastritis in childhood, its role in the pathogenesis of peptic ulcer disease in adults and children being generally known. In some cases, there are therapeutic management issues, because they do not heal or they often relapse, although treatment regimens are applied as recommended. Our aim was to analyze the relationship between endoscopic appearance and histological changes of the gastric mucosa in children with gastritis associated with H. pylori infection, in which persistent infection after treatment was found. MATERIALS AND METHODS: It was a prospective study on 1332 children assessed in our Service (Ist Pediatric Clinic, Tirgu Mures, Romania), between January 2008 and January 2013, for gastritis with various etiologies. There were 609 cases of gastritis-associated with H. pylori infection. RESULTS: The average age of patients was 13.21 years; the higher incidence was noted in 13-18-year-old group, female gender and rural areas provenience; a number of 544 patients diagnosed with gastritis with H. pylori were reassessed subsequently; after treatment, gastritis has healed and the infection was eradicated in 88.23% cases after a month, while in 64 patients infection persisted. After a second regimen, endoscopic-histological modifications persisted in 31 (5.69%) cases; 1.28% cases remained positive for longer. CONCLUSIONS: H. pylori infection was associated with high age group, as well as with endoscopic modifications; also, the presence of H. pylori was correlated with histopathologic diagnostic. We try to emphasize the importance of assessing bacterial resistance to antibiotics, studying of bacterial genome and genetic susceptibility of human subjects.

Eradication of Helicobacter pylori infection by the probiotic strains Lactobacillus johnsonii MH-68 and L. salivarius ssp. salicinius AP-32.

BACKGROUND: The current therapy for Helicobacter pylori infection includes antimicrobial agents and proton pump inhibitors. We have examined the ability of Lactobacillus spp. to inhibit H. pylori infection. MATERIALS AND METHODS: Probiotic strains isolated from samples of adult feces, infant feces, breast milk, and vaginal swab collected from healthy volunteers in Taiwan and commercially available strains were screened for antagonism toward H. pylori. Inhibition liquid culture assay was used to screen potential anti-H. pylori activity. Then, we performed agar plate inhibition assay, and assays to determine the capacity of probiotics for adhesion, and inhibition and killing of H. pylori, and measured the levels of IL-8 and IL-10. Using animal models, we studied regulation of gastric acid and histopathological changes accompanying anti-H. pylori activity. RESULTS: We found that six of the tested strains suppressed urease activity of H. pylori: Lactobacillus acidophilus TYCA08, L. acidophilus TYCA15, L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32 were more effective than the others. In vivo, L. johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 alone or in combination, reduced the H. pylori load in the gastric mucosa, and also reduced inflammatory chemokine expression and lymphocyte infiltration. CONCLUSIONS: Lactobacillus johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 effectively suppress H. pylori viability, and when used as probiotics, they may help decrease the occurrence of gastritis, and even reduce the risk of H. pylori infection.

Assessment of Helicobacter pylori eradication in patients on NSAID treatment.

BACKGROUND: In this post-hoc analysis of a randomized, double blind, placebo controlled trial, we measured the sensitivity and specificity of Helicobacter pylori IgG-antibody titer changes, hematoxylin and eosin (H&E) stains, immunohistochemical (IHC) stains and culture results in NSAID using patients, following H. pylori eradication therapy or placebo. METHODS: 347 NSAID using patients who were H. pylori positive on serological testing for H. pylori IgG-antibodies were randomized for H. pylori eradication therapy or placebo. Three months after randomization, gastric mucosal biopsies were taken for H. pylori culture and histological examination. At 3 and 12 months, blood samples were taken for repeated serological testing. The gold standard for H. pylori infection was based on a positive culture or both a positive histological examination and a positive serological test. Sensitivity, specificity and receiver operating curves (ROC) were calculated. RESULTS: H. pylori eradication therapy was successful in 91% of patients. Culture provided an overall sensitivity of 82%, and 73% after eradication, with a specificity of 100%. Histological examination with either H&E or IHC stains provided sensitivities and specificities between 93% and 100%. Adding IHC to H&E stains did not improve these results. The ROC curve for percent change in H. pylori IgG-antibody titers had good diagnostic power in identifying H. pylori negative patients, with an area under the ROC curve of 0.70 (95 % CI 0.59 to 0.79, P = 0.085) at 3 months and 0.83 (95% CI 0.76 to 0.89, P < 0.0001) at 12 months. A cut-off point of at least 21% decrease in H. pylori IgG-antibody titers at 3 months and 58% at 12 months provided a sensitivity of 64% and 87% and a specificity of 81% and 74% respectively, for successful eradication of H. pylori. CONCLUSIONS: In NSAID using patients, following H. pylori eradication therapy or placebo, histological examination of gastric mucosal tissue biopsies provided good sensitivity and specificity ratios for evaluating success of H. pylori eradication therapy. A percentual H. pylori IgG-antibody titer change has better sensitivity and specificity than an absolute titer change or a predefined H. pylori IgG-antibody titer cut-off point for evaluating success of H. pylori eradication therapy.

Assessment of desmosomal components (desmoglein 1-3, plakoglobin) in cardia mucosa in relation to gastroesophageal reflux disease and Helicobacter pylori infection.

Gastroesophageal reflux disease is associated with impaired epithelial barrier function and abnormal expression of proteins forming cell-cell contacts by tight junctions and desmosomes in distal esophageal squamous mucosa. Although gastroesophageal reflux disease and Helicobacter pylori are both associated with chronic inflammation of the adjacent cardia mucosa, it is not known whether these lead to derangements of the desmosomal complexes. Here, we assessed the expression of 4 proteins (plakoglobin and desmoglein 1, 2, and 3) forming epithelial desmosomal complexes by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in biopsies from 67 patients with gastroesophageal reflux disease and 23 gastroesophageal reflux disease-negative controls. Plakoglobin and desmoglein 2 were ubiquitously expressed in all samples, whereas desmoglein 1 and 3 were not expressed in cardia mucosa. Gastroesophageal reflux disease was specifically associated with elevated transcript levels of desmoglein 2 and plakoglobin. These were significantly increased from 2.0- to 2.7-fold in patients with gastroesophageal reflux disease compared with controls (P < .01), and significantly increased immunohistochemical scores for both proteins were observed (P < .05) as well. The combined presence of gastroesophageal reflux disease and Helicobacter pylori infection had no additional effect on desmosomal gene expression. Taken together, the up-regulation of plakoglobin and desmoglein 2 in cardia mucosa of patients with gastroesophageal reflux disease supports the concept that the "transition zone" between distal esophagus and proximal stomach is affected by gastroesophageal reflux disease as well, and architectural and molecular changes in the desmosomal compartment contribute to the pathogenesis of gastroesophageal reflux disease in the cardia mucosa.