Search

Background. The indicators of heart rate variability reflect the vital processes of managing the physiological functions of the body — autonomic balance and functional reserves of its management mechanisms, the adaptive capacity of the body, and stress resistance. At the expressed disturbances of autonomic nervous system homeostasis, the risk of emergence and progression of diseases increases. This is especially true for the elderly, who are characterized by comorbidity. The purpose of the study was to assess the state of adaptive capacity and autonomic regulation of the body in patients with precancerous conditions of the stomach with the thyroid gland pathology. Materials and methods. Seventy-two patients with chronic atrophic gastritis were divided into groups: group I consisted of 34 patients with nodules in the thyroid gland; group II included 23 patients with pathological changes of the thyroid gland and 15 patients of group III had a normal thyroid gland. The heart rate variability was assessed based on the results of PRECISE-diagnostics. To diagnose the functional state of the small intestinal microbiota, a hydrogen breath test was performed. Results. In 81.9 % of patients with chronic atrophic gastritis and thyroid pathology, an imbalance of the sympathetic and parasympathetic parts of the autonomic nervous system with a prevalence of vagotonia including the patients with thyroid nodules (64.7 %) and pathological changes in the thyroid gland (56.5 %) (р < 0.05). A significant violation of the body’s adaptive capacity was found in 63.2 % of patients with chronic atrophic gastritis. The frequency of reduced adaptive capacity of the organism was twice higher in patients with comorbid pathology (p < 0.05). 56.1 % of patients with chronic atrophic gastritis associated with thyroid pathology experienced a decrease in functional reserves of the body. In the spectrum of detected disorders, 68.8 % of patients presented with depletion of functional reserves of the body with increased central control and 31.2 % of patients — hormonal imbalance with a predominance of the humoral link with the inclusion of autonomous control (p < 0.05). The analysis of the stress index showed in half of the examined patients insufficient stress resistance with a probable increase in mean figures to (136.8 ± 7.4) m/s (p < 0.05). Correlations were found between the frequency of detection of excessive bacterial growth syndrome and maladaptation (r = 0.64; p < 0.05), imbalance of the sympathetic and parasympathetic parts of the autonomic nervous system (r = 0.59; p < 0.05). Conclusions. The course of chronic atrophic gastritis associated with thyroid pathology is associated with an imbalance of sympathetic and parasympathetic parts of the autonomic nervous system, depletion of adaptive mechanisms, reduced functional reserves of the body, and stress resistance. At the same time, disorders of the body’s adaptive potential and changes in autonomic balance are associated with the disorders of the small intestinal microbiota, which requires a multidisciplinary approach to the management of patients with comorbid pathology of the stomach and thyroid gland., Актуальність. Показники варіабельності серцевого ритму відображують життєво важливі процеси управління фізіологічними функціями організму — вегетативний баланс і функціональні резерви механізмів його управління, адаптаційні можливості організму та стресостійкість. При виражених порушеннях вегетативного гомеостазу підвищується ризик виникнення та прогресування захворювань. Особливо це стосується людей похилого віку, для яких характерна коморбідність. Мета дослідження: оцінити стан адаптаційних можливостей і вегетативної регуляції організму у хворих на передракові стани шлунка з патологією щитоподібної залози (ЩЗ). Матеріали та методи. 72 хворі на хронічний атрофічний гастрит були розподілені на групи: I групу становили 34 хворі з вузлами у ЩЗ; у II групу ввійшли 23 пацієнти з патологічними змінами ЩЗ і 15 пацієнтів III групи мали нормальну ЩЗ. Оцінку показників варіабельності серцевого ритму проводили за результатами PRECISE-діагностики. Для діагностики функціонального стану тонкокишкової мікробіоти проводили водневий дихальний тест. Результати. У 81,9 % хворих на хронічний атрофічний гастрит, поєднаний із патологією щитоподібної залози, виявлено дисбаланс симпатичної та парасимпатичної ланок вегетативної нервової системи з превалюванням частоти ваготонії за рахунок хворих з вузлами у ЩЗ (64,7 %) та з патологічними змінами ЩЗ (56,5 %) (p

Актуальность. Хронический атрофический гастрит (ХАГ) относится к предраковым заболеваниям желудка, на фоне которого часто наблюдаются кишечная метаплазия и дисплазия, а также чаще, чем у здоровых лиц, может возникать рак желудка. Цель исследования: изучить факторы риска ХАГ и их взаимосвязь с выраженностью морфологических изменений слизистой оболочки желудка. Материалы и методы. Под наблюдением находились 120 пациентов с ХАГ. Все больные проходили эндоскопическое (с функцией NBI), морфологическое обследование и анкетирование с помощью анкеты, которая была разработана для больных с ХАГ с целью изучения факторов риска. Результаты. Были определены значимые факторы развития предраковых изменений слизистой оболочки желудка, среди которых на первый план выступили показатели, которые характеризуют острый (r = 0,593) и хронический стресс (r = 0,544), употребление чрезмерного количества жареных (r = 0,636), копченых (r = 0,512) и маринованных (r = 0,591) продуктов, возраст (r = 0,639), ІІ группа крови (r = 0,651), онконаследственность (r = 0,533), наличие дуоденогастрального рефлюкса (r = 0,524) и патологии щитовидной железы (r = 0,522). По результатам эндоскопического и морфологического исследований выявлено уменьшение частоты Helicobacter pylori-инфицирования по мере роста перестроечных изменений слизистой оболочки желудка (атрофия — метаплазия — дисплазия). Выводы. Установлено возможное влияние таких факторов риска, как стресс, возраст, группа крови, наследственность, употребление чрезмерного количества жареных, копченых и маринованных продуктов, заболевания щитовидной железы и наличие дуоденогастрального рефлюкса на развитие ХАГ.

The article presents the history of colloidal bismuth subcitrate and considers the basic mechanisms of its effects on the gastric mucosa, both cytoprotective and anti-helicobacter. The recent data of the worldwide researches are given on the use of the bismuth subcitrate as a component of antibacterial therapy in order to improve the effectiveness of the eradication, especially under the resistance to the basic drugs. The results of own researches are also shown, they are dedicated to the dynamics of structural adjustment of the gastric mucosa in patients with chronic atrophic gastritis for 3 years after the eradication of H.pylori. The use of first-line therapy with the addition of the drug De-Nol allowed to achieve eradication in 94.3 % of patients and positive microstructural changes of the gastric mucosa.

Background. Until now, the issue of the correlation between the cytokine balance and the progression of structural changes in the gastric mucosa remain completely uncertain. At the same time, the determination of the role of cytokine ba­lance as a component of gastric carcinogenesis will make it possible to substantiate new approaches to managing patients with atrophic gastritis. The purpose was to assess the level of pro- and anti-inflammatory cytokines, vascular endothelial growth factor (VEGF) at the stages of progression of structural changes in the gastric mucosa of patients with atrophic gastritis. Materials and methods. The study included 79 individuals with atrophic gastritis who underwent narrow band imaging endoscopic examination. The patients were divided into groups taking into account the revealed structural changes in the gastric mucosa: group I — 7 people with gastric mucosal atrophy without intestinal metaplasia (IM); group II — 16 individuals with gastric mucosal atrophy with IM limited by the antrum; group III — 45 people with diffuse IM against the background of gastric mucosal atrophy; group IV — 10 individuals with gastric mucosal dysplasia. In all patients, we assessed the level of interleukins (IL-8, IL-10, IL-18), tumor necrosis factor alpha (TNF-α), VEGF. Results. In patients of group IV, the concentration of IL-8 in the blood serum was 18.6 (11.3; 23.9) pg/ml that was significantly higher than in group I (by 5.0 times, p, Актуальність. До сьогодні питання взаємодії цитокінового балансу та прогресування структурних змін слизової оболонки шлунка (СОШ) залишаються остаточно не визначеними. Водночас визначення ролі цитокінового балансу як складової шлункового канцерогенезу дозволить обґрунтувати нові підходи до тактики ведення пацієнтів з атрофічним гастритом. Мета: оцінити рівень про- та протизапальних цитокінів, васкулоендотеліального фактора росту на етапах прогресування структурних змін СОШ у хворих на атрофічний гастрит. Матеріали та методи. У дослідження включено 79 хворих на атрофічний гастрит, яким проведено ендоскопічне дослідження в режимі NBI. Хворі були розподілені на групи з урахуванням виявлених структурних змін у СОШ: І група — 8 пацієнтів з атрофією СОШ без кишкової метаплазії (КМ); ІІ група — 16 хворих з атрофією СОШ із КМ, обмеженою антральним відділом шлунка; ІІІ група — 45 осіб з дифузною КМ на фоні атрофії СОШ; IV група — 10 пацієнтів з дисплазією СОШ. Усім хворим оцінювали рівень інтерлейкінів (ІЛ-8, ІЛ-10, ІЛ-18), фактора некрозу пухлини альфа (TNF-α), васкулоендотеліального фактора росту (VEGF). Результати. У хворих IV групи концентрація ІЛ-8 в сироватці крові становила 18,6 (11,3; 23,9) пг/мл і була вірогідно вище порівняно з пацієнтами І групи (в 5,0 раза; р

Актуальность. Коморбидная патология остается распространенной, но недостаточно изученной проблемой. В настоящее время частота и характер соединенной патологии у больных с хроническим метапластическим атрофическим гастритом (ХМАГ) окончательно не выяснены, как и роль щитовидной железы (ЩЖ) в этиопатогенезе данного заболевания. Цель: оценить состояние коморбидности у больных с ХМАГ и изучить частоту и характер структурных изменений ЩЖ у данной категории больных, исследовать литературные данные по этой проблеме. Материалы и методы. В обследование включен 41 больной с ХМАГ в возрасте (60,1 ± 2,4) года, среди которых было 29 женщин и 12 мужчин. Больным проводилась гастроскопия (с NBI-режимом и забором биопсийного материала), ультразвуковое исследование ЩЖ, анкетирование с помощью Сumulative Illness Rating Scale (CIRS), а также по историям болезни изучались коморбидные заболевания желудочно-кишечного тракта (ЖКТ). Результаты. У 82,9 % больных с ХМАГ выявлены ультразвуковые диффузные изменения ЩЖ, причем у 48,8 % обследованных они выявлялись впервые, а у 37,8 % пациентов данные изменения сочетались с наличием узлов в ЩЖ. К тому же у 9,8 % больных выявлены ультразвуковые признаки аутоиммунного тиреоидита. У 97,6 % пациентов с ХМАГ наблюдалась полиморбидная патология, причем у 92,7 % больных — со стороны 3 систем и больше и только у 4,9 % — со стороны 2 систем. Установлена положительная корреляционная связь между возрастом больных и суммарным количеством баллов, набранных с помощью опросника коморбидности CIRS (r = 0,412, p = 0,04). По данным СIRS, наиболее часто у пациентов с ХМАГ сочеталась патология верхнего и нижнего отделов ЖКТ (97,7 и 53,7 % соответственно), патология костно-мышечного аппарата и кожных покровов (68,3 %), патология глаз, ушей, горла, носа и гортани (56,1 %), сосудистая патология (56,1 %), заболевания сердца (51,2 %) и эндокринно-метаболическая патология (34,1 %). Выводы. У 82,9 % больных с ХМАГ выявлены ультразвуковые структурные изменения ЩЖ. Перспективным направлением дальнейшего исследования, на наш взгляд, было бы изучение аутоиммунных процессов в желудке и ЩЖ (установление возможных взаимосвязей между аутоиммунным тиреоидитом и аутоиммунным гастритом), а также особенностей течения данных коморбидных заболеваний. Необходимо уделить внимание ХМАГ не только как заболеванию, которое является фактором риска развития рака желудка, но и как возможному маркеру наличия сопутствующей патологии щитовидной железы.

Gastric cancer is the third leading cause of cancer-related mortality and the leading infection associated cancer worldwide. In the US, there are estimated 27,510 new cases and 11,140 gastric-cancer related deaths in 2019.1 Gastric adenocarcinoma (GA) is the most common form of gastric cancer. Histologically, by the Lauren classification, GA can be divided to two types: intestinal GA and diffuse GA.2 The Cancer Genome Atlas (TCGA) initiative has identified 4 molecular subtypes of gastric cancers: genomically stable (diffuse), chromosomally stable (intestinal), microsatellite instability, and Epstein-Barr virus subtypes.3 GA is also classified based on anatomic location into cardia (CGA) or non-cardia GA (NCGA). NCGA include those arising from the antrum, incisura, body, and/or fundus.4 Intestinal-type NCGA (hereafter simply referred to as “NCGA”) results from the complex interaction between genetic, environmental, and microbial determinants, which drive the stepwise progression through a series of discrete histopathologic stages, the “Correa cascade”, from non-atrophic gastritis to gastric preneoplasia (chronic atrophic gastritis (AG), gastric intestinal metaplasia (GIM)) and dysplasia, prior to malignant transformation to invasive adenocarcinoma in a minority of patients (1–3%). Helicobacter pylori (H. pylori) is the dominant factor in this cascade with an attributable risk of 75–88% but additional pathways are recognized.5, 6 Most factors which account for the prevalence of GIM and its progression to neoplasia lack definitive evidence. Despite the established association of GIM with increased risk of incident NCGA, currently it’s not possible to predict who will develop gastric neoplasia. Furthermore, whether the endoscopic surveillance of GIM to detect early NCGA compared to no surveillance may improve patient-related outcomes, has not been established, particularly in low incidence countries like the US. Whether selected surveillance of GIM for identifiable high-risk groups within, such as racial/ethnic minorities and immigrants, is similarly unclear. These critical knowledge gaps formed the rationale behind the American Gastroenterological Association’s (AGA) Clinical Practice Guideline Committee’s constructing evidence-based guidelines to inform the management of patients who are diagnosed with GIM based on gastric biopsies performed in routine clinical practice. The technical review team systematically summarized and synthesized the literature to inform pre-defined clinical questions proposed by the AGA guideline panel using standard systematic review methodology. With guidance from the guideline committee, we developed a comprehensive list of direct and indirect evidence needed to inform the guideline questions. The direct evidence included randomized and non-randomized comparative studies that assessed the benefits and/or harms of endoscopic surveillance in patients with GIM. The indirect evidence included the prevalence of GIM, the incidence of intestinal-type NCGA in individuals with GIM, and specified risk factors and biomarkers associated with the development of NCGA in patients with GIM: family history of gastric cancer, racial/ethnic background, immigration status, smoking history, pernicious anemia and/or autoimmune atrophic gastritis, GIM topographic extent, GIM histological subtype, and predictive biomarkers (e.g., H. pylori and its virulence factors (e.g. cagA and vacA), and the pepsinogens). Our systematic literature search did not identify studies that provide direct evidence to inform our clinical questions, although we were able to identify many studies that informed our questions indirectly. It was evident that there was inconsistent and incomplete methodology among the studies and many publications were missing essential demographic, clinical, endoscopic and/or pathology data. These data elements are necessary to allow a thorough assessment of the events reported and to determine the certainty of that evidence. The lack of direct evidence and the lack of certainty in the indirect evidence limited the guideline’s panel ability to make strong recommendations for a common clinical condition. To stimulate the field to improve clinical outcomes, best practices are intended to guide future research and overcome the limitations of the available evidence. The aim of this guidance document is to highlight the methodological limitations that the technical review and guideline team encountered in the literature review and provide guidance for future design of high quality studies on GIM as a premalignant finding that is associated with development of gastric cancer. We have provided a general checklist that will facilitate standardization of future studies to advance the science of GIM with rigorous evidence to inform clinical care. For completeness, we include measures that are important yet were outside the scope of the AGA GIM technical reviews and guidelines (e.g., endoscopy imaging).

Background & Aims Adult zymogen-producing (zymogenic) chief cells (ZCs) in the mammalian gastric gland base are believed to arise from descending mucous neck cells, which arise from stem cells. Gastric injury, such as from Helicobacter pylori infection in patients with chronic atrophic gastritis, can cause metaplasia, characterized by gastric cell expression of markers of wound-healing; these cells are called spasmolytic polypeptide-expressing metaplasia (SPEM) cells. We investigated differentiation and proliferation patterns of neck cells, ZCs, and SPEM cells in mice. Methods C57BL/6 mice were given intraperitoneal injections of high-dose tamoxifen to induce SPEM or gavaged with H pylori (PMSS1) to induce chronic gastric injury. Mice were then given pulses of 5-bromo-2ʹ-deoxyuridine (BrdU) in their drinking water, followed by chase periods without BrdU, or combined with intraperitoneal injections of 5-ethynyl-2ʹ-deoxyuridine. We collected gastric tissues and performed immunofluorescence and immunohistochemical analyses to study gastric cell proliferation, differentiation, and turnover. Results After 8 weeks of continuous BrdU administration, fewer than 10% of homeostatic ZCs incorporated BrdU, whereas 88% of neck cells were labeled. In pulse-chase experiments, various chase periods decreased neck cell label but did not increase labeling of ZCs. When mice were given BrdU at the same time as tamoxifen, more than 90% of cells were labeled in all gastric lineages. After 3 months' recovery (no tamoxifen), ZCs became the predominant BrdU-labeled population, whereas other cells, including neck cells, were mostly negative. When we tracked the labeled cells in such mice over time, we observed that the proportion of BrdU-positive ZCs remained greater than 60% up to 11 months. In mice whose ZCs were the principal BrdU-positive population, acute injury by tamoxifen or chronic injury by H pylori infection resulted in SPEM cells becoming the principal BrdU-positive population. After withdrawal of tamoxifen, BrdU-positive ZCs reappeared. Conclusions We studied mice in homeostasis or with tamoxifen- or H pylori–induced SPEM. Our findings indicated that mucous neck cells do not contribute substantially to generation of ZCs during homeostasis and that ZCs maintain their own census, likely through infrequent self-replication. After metaplasia-inducing injury, ZCs can become SPEM cells, and then redifferentiate into ZCs on injury resolution.

Background & Aims Chronic atrophic gastritis can lead to gastric metaplasia and increase risk of gastric adenocarcinoma. Metaplasia is a precancerous lesion associated with an increased risk for carcinogenesis, but the mechanism(s) by which inflammation induces metaplasia are poorly understood. We investigated transcriptional programs in mucous neck cells and chief cells as they progress to metaplasia mice with chronic gastritis. Methods We analyzed previously generated single-cell RNA-sequencing (scRNA-seq) data of gastric corpus epithelium to define transcriptomes of individual epithelial cells from healthy BALB/c mice (controls) and TxA23 mice, which have chronically inflamed stomachs with metaplasia. Chronic gastritis was induced in B6 mice by Helicobacter pylori infection. Gastric tissues from mice and human patients were analyzed by immunofluorescence to verify findings at the protein level. Pseudotime trajectory analysis of scRNA-seq data was used to predict differentiation of normal gastric epithelium to metaplastic epithelium in chronically inflamed stomachs. Results Analyses of gastric epithelial transcriptomes revealed that gastrokine 3 (Gkn3) mRNA is a specific marker of mouse gastric corpus metaplasia (spasmolytic polypeptide expressing metaplasia, SPEM). Gkn3 mRNA was undetectable in healthy gastric corpus; its expression in chronically inflamed stomachs (from TxA23 mice and mice with Helicobacter pylori infection) identified more metaplastic cells throughout the corpus than previously recognized. Staining of healthy and diseased human gastric tissue samples paralleled these results. Although mucous neck cells and chief cells from healthy stomachs each had distinct transcriptomes, in chronically inflamed stomachs, these cells had distinct transcription patterns that converged upon a pre-metaplastic pattern, which lacked the metaplasia-associated transcripts. Finally, pseudotime trajectory analysis confirmed the convergence of mucous neck cells and chief cells into a pre-metaplastic phenotype that ultimately progressed to metaplasia. Conclusions In analyses of tissues from chronically inflamed stomachs of mice and humans, we expanded the definition of gastric metaplasia to include Gkn3 mRNA and GKN3-positive cells in the corpus, allowing a more accurate assessment of SPEM. Under conditions of chronic inflammation, chief cells and mucous neck cells are plastic and converge into a pre-metaplastic cell type that progresses to metaplasia.

In literature it has been reported that concentrations of serum pepsinogens increase during administration of proton pump inhibitors (PPI). However, the magnitude of these changes is still to be assessed. The aim of this study was to evaluate the changes in levels of pepsinogen I (PG-1) and pepsinogen II (PG-2) on the background of therapy with omeprazole which has been administered before breakfast in double standard dose (40 mg). The regimen of PPI administration completely corresponds to conventional PPI-test. There were two groups of patients: 1st one (gastroesophageal reflux desiase) — 10 women and 9 men, mean age (52.37 ± 3.25) years; 2nd one (functional dyspepsia) — 11 women and 8 men, mean age (48.37 ± 3.56) years. It was found that in 1st group PGI rises from (141.90 ± 7.99) mcg/l to (177.61 ± 7.81) mcg/l, in 2nd group — from (115.02 ± 10.16) mcg/l to (152.37 ± 12.33) mcg/l (p < 0.05). PG-2 level changes in the same. In 1st group PG-2 rises from (21.65 ± 3.13) mcg/l to (32.64 ± 3.42) mcg/l, in 2nd group — from (14.84 ± 1.64) mcg/l to (23.55 ± 2.37) mcg/l (p < 0.05). In 6 cases absolute increase of PGI (ΔPG-2) didn’t reach threshold of 7.0 mcg/l considered by us as level of insufficient acid inhibition. Two of these patients had atrophic gastritis (PG-1 < 50 mcg/l; ratio PG-/PG-2 < 3.0), rest 4 patients didn’t have atrophic gastritis but in half cases they hadn’t adequate answer to PPI administration. There was a significant correlation between increase of PG-1 level and disappearance of reflux complaints evaluated by dynamics in RS-cluster of GSRS-questionnaire.

Background & Aims An association between gastric cancer and the rs2294008 (C>T) polymorphism in the prostate stem cell antigen ( PSCA ) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals. Methods We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori -infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori -negative relatives, and 100 population controls. Additionally, a population-based study of chronic atrophic gastritis provided 533 cases and 1054 controls. We then genotyped 2 population-based, case-control studies of upper gastrointestinal cancer: the first included 312 gastric cancer cases and 383 controls; the second included 309 gastric cancer cases, 159 esophageal cancer cases, and 211 controls. Odds ratios were computed from logistic models and adjusted for confounding variables. Results Carriage of the risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1–1.9) and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3–2.8). The association was strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2–10.7). An inverse association was observed between carriage of the risk allele and gastric cardia cancer (OR, 0.5; 95% CI: 0.3–0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI: 0.3–0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2–0.9). Conclusions The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.

Background & Aims: A cascade of precursor lesions (eg, atrophic gastritis, intestinal metaplasia, and dysplasia) precedes most gastric adenocarcinomas. Quantification of gastric cancer risk in patients with premalignant gastric lesions is unclear, however. Consequently, endoscopic surveillance is controversial, especially in Western populations. Methods: To analyze current surveillance practice and gastric cancer risk in patients with premalignant gastric lesions, all patients with a first diagnosis between 1991 and 2004 were identified in the Dutch nationwide histopathology reizistry (PALGA); follow-up data were evaluated until December 2005. Results: In total, 22,365 (24%) patients were diagnosed with atrophic gastritis, 61,707 (67%) with intestinal metaplasia, 7616 (8%) with mild-to-moderate dysplasia, and 562 (0.6%) with severe dysplasia. Patients with a diagnosis of atrophic gastritis, intestinal metaplasia, or mild-to-moderate dysplasia received re-evaluation in 26%, 28%, and 38% of cases, respectively, compared with 61% after a diagnosis of severe dysplasia (P

Background & Aims: The MUC1 mucin is expressed on the cell surface of epithelial cells lining the gastric mucosa. Epidemiologic studies suggest that functional allelic variations in the MUC1 gene may play a role in human susceptibility to Helicobacter pylori-associated pathologies, including gastric adenocarcinoma. We have evaluated the impact of Muc1 expression on the colonization and pathogenesis of gastric Helicobacter infections. Methods: Wild-type and Muc1-deficient mice were infected with H pylori and colonization and gastritis levels determined. Primary gastric cells were used to examine the impact of Muc1 expression on bacterial adherence. Results: Mice lacking Muc1 were colonized by 5-fold more H pylori within 1 day of infection, and this difference was maintained for at least 2 months postinfection. Mice heterozygous for the null Muc1 allele developed intermediate bacterial colonization. Although wild-type mice developed only a mild gastritis when infected for 2 months with H pylori, Muc1−/− mice developed an atrophic gastritis marked by loss of parietal cells. We demonstrate H pylori adhesion to purified MUC1 and significantly increased adhesion to cultured murine Muc1 null gastric epithelial cells, suggesting that Muc1 acts as a decoy limiting binding to the cell surface. Conclusions: Muc1 provides a protective barrier, which limits both acute and chronic colonization by H pylori, as well as playing a major role in limiting the inflammation induced by Helicobacter infection. We propose that Muc1 restricts access of H pylori to the epithelial surface, hence reducing exposure of the host to proinflammatory bacterial products.

Background & Aims: To screen the genetic variants in cyclooxygenase-2 (COX-2), and evaluate their effects on COX-2 expression and risk of gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, Shangdong Province, an area of China, a high-risk area of GC. Methods: Genotypes were determined by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography analysis in 248 GC cases and 1523 subjects with precancerous gastric lesions. COX-2 expression was detected by immunohistochemical analysis of biopsy specimens of 593 subjects selected at random from 1523 subjects. COX-2 transcriptional activity was examined by luciferase reporter gene assay. Results: We found an increased risk of GC in subjects with 1195 AA genotype (adjusted odds ratio [OR], 2.33; 95% confidence interval [CI]: 1.45–3.75). Stratified analysis indicated that an elevated risk of GC was observed in subjects carrying the AA genotype and Helicobacter pylori infection (OR, 3.88; 95% CI: 1.46 –10.34) or smoking (OR, 7.02; 95% CI: 2.19 –22.48), and a high expression of COX-2 was found in subjects with AA genotype (OR, 1.84; 95% CI: 1.09 – 3.10) compared with GG genotype. The prevalence of COX-2 expression positivity varied markedly by histologic status, and the OR (OR, 5.35; 95% CI: 2.64 –10.8) was significantly increased for dysplasia compared with superficial gastritis/chronic atrophic gastritis. Furthermore, tissue homogenate with H pylori infection could significantly stimulate COX-2 promoter activity driven by 1195A compared with the 1195G containing counterparts. Conclusions: These findings suggest that COX-2 polymorphisms may play an important role, at least in part, in developing GC in this high-risk population.

Background & Aims: The identification of precursor lesions has a great impact on the understanding of tumorigenesis. Precursor lesions of endocrine tumors are known to occur in the setting of the MEN1 syndrome. The aim of this study was to test the hypothesis that MEN1-associated duodenal gastrinomas originate from diffuse preneoplastic gastrin cell changes. Precursor lesions may precede the development of duodenal gastrinomas because, in contrast to sporadic gastrinomas, these tumors are usually multiple. Methods: The distribution of endocrine cells in the nontumorous duodenal tissue was analyzed qualitatively and quantitatively for 25 patients operated on for a duodenal gastrinoma. MEN1 status was assessed clinically and by polymerase chain reaction-based mutational analysis. Results: Fourteen of 25 patients with gastrinoma had proliferative, hyperplastic lesions consisting of gastrin cells in the nontumorous duodenal mucosa, similar to the gastric enterochromaffin-like cell lesions observed in chronic atrophic gastritis. All patients with Zollinger-Ellison syndrome with proven MEN1 had such proliferative gastrin cell lesions, and all patients with Zollinger-Ellison syndrome without precursor lesions were MEN1 negative. Conclusions: Duodenal gastrinomas in MEN1, but not sporadic duodenal gastrinomas, are associated with proliferative gastrin cell changes within the nontumorous mucosa. It is likely that these lesions precede the development of MEN1-associated duodenal gastrinomas.

Background & Aims: Interleukin-1 beta (IL-1β) polymorphisms are associated with increased risk of gastric cancer in whites. This study aimed to examine effects of these polymorphisms on gastric acid secretion, atrophic gastritis, and risk of peptic ulcer in Japan. Methods: We determined IL-1B -511/-31 and IL-1RN genotypes and measured gastric juice pH, serum pepsinogen (PG) I and II levels, and gastritis and atrophy scores in Helicobacter pylori –positive patients with gastritis only, gastric ulcers, or duodenal ulcers (DUs), and H. pylori –negative controls. Results: In the H. pylori –positive group, subjects with the proinflammatory IL-1B -511 T/T genotype had the highest atrophy and gastritis scores, the highest median gastric juice pH, and the lowest median serum PG I/PG II ratios. Although gastric juice pH significantly increased and serum PG I and PG I/PG II ratios significantly decreased in the IL-1B -511 T/T genotype group with age, no such age-dependent changes were observed in the C/C genotype group. Changes in the C/T genotype group were intermediate. In the H. pylori –negative group, the IL-1 loci had no effect on any of the physiologic or morphologic parameters. Carriage of IL-1RN allele 2 significantly protected against DU disease while the IL-1B -511 T/T genotype significantly protected against DU recurrence in patients older than 60 years. Conclusions: Proinflammatory IL-1β polymorphisms are associated with hypochlorhydria and atrophic gastritis in Japan. The effects are dependent on H. pylori infection and become more significant with advancing age. This may explain the high incidence of gastric cancer in Japan and also the age-dependent decrease in DU recurrence in infected subjects. GASTROENTEROLOGY 2002;123:92-105

Background & Aims The gastric cancer–causing pathogen Helicobacter pylori up-regulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress–induced apoptosis and DNA damage. A subpopulation of SMOX high cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects. Methods SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H pylori –infected Egfr wa5 mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. A phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsy specimens from Colombian and Honduran cohorts were analyzed by immunohistochemistry. Results SMOX expression and DNA damage were decreased, and apoptosis increased in H pylori –infected Egfr wa5 mice. H pylori –infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damage high apoptosis low cells. Phosphoproteomic analysis showed increased EGFR and erythroblastic leukemia-associated viral oncogene B (ERBB)2 signaling. Immunoblot analysis showed the presence of a phosphorylated (p)EGFR–ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damage high apoptosis low cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR–ERBB2, and pERBB2 were increased predominantly in tissues showing gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR–ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress. Conclusions In an analysis of gastric tissues from mice and patients, we identified a molecular signature (based on levels of pEGFR, pERBB2, and SMOX) for the initiation of gastric carcinogenesis.

Background & Aims: Helicobacter pylori –infected gastric mucosa evolves through stages of chronic gastritis, intestinal metaplasia (IM), glandular atrophy (GA), and dysplasia before carcinoma develops. We studied if H. pylori eradication would alter the course of premalignant histologic changes in the stomach. Methods: Volunteers from the Yantai County in China underwent upper endoscopy with biopsy specimens obtained from the antrum and corpus. H. pylori –infected subjects were randomized to receive either a 1-week course of omeprazole, amoxicillin, and clarithromycin (OAC) or placebo. At 1 year, endoscopies with biopsies were repeated. Results: A total of 587 H. pylori –infected subjects were randomized to OAC (n = 295) and placebo (n = 292). At 1 year, H. pylori was eradicated in 226 subjects assigned to OAC. In the placebo group, 245 patients remained H. pylori infected. Analysis of paired samples obtained from the same patients showed that acute and chronic gastritis decreased in both the antrum and corpus after H. pylori eradication ( P P = 0.014). In the H. pylori –infected group, antral biopsy specimens had more pronounced acute gastritis ( P = 0.01), whereas corpus specimens showed increased acute and chronic gastritis ( P P = 0.052). When histologic changes were compared between the 2 groups, decrease in acute and chronic gastritis was more frequent after H. pylori eradication ( P H. pylori –infected group, increase in GA was seen in the corpus ( P = 0.01). Conclusions: At 1 year, H. pylori eradication is beneficial in preventing progression of pathologic changes of the gastric mucosa. GASTROENTEROLOGY 2000;119:7-14

Background & Aims: Helicobactor pylori mostly colonizes the gastric mucus that contains salivary antibodies. We studied the role of saliva in the induction and maintenance of gastric immunity conferred by oral vaccination against H. pylori. Methods: C57BL/6 mice underwent a sialoadenectomy before and after intragastric immunization using whole-cell sonicates of H. pylori and cholera toxin as an adjuvant. At 1 and 6 months after oral inoculation, we assessed the density of the H. pylori colonizing the stomach, specific antibodies in gastric secretion and sera, and the constituents of cellular infiltrates in the tissue. Results: A sialoadenectomy before, but not after, immunization abrogated protection by the vaccination at 1 month after inoculation. Protected mice had more neutrophils, plasma cells, and lymphocytes, but fewer eosinophils, in the gastric tissue than nonprotected mice. Protected mice had a greater increase of immunoglobulin (Ig) G1 specific to H. pylori than IgG2a in sera. At 6 months after inoculation, oral immunization was less effective in mice who had a sialoadenectomy than in control immunized mice. The antibody titers in both gastric secretion and in sera did not correlate with the density of bacteria colonizing the stomach. Conclusions: It is suggested that, in intragastric immunization against H. pylori, saliva is necessary for both the induction and maintenance of optimal immunity in the stomach. Effective immunity was associated with an increased number of neutrophils and lymphocytes in gastric tissue.

Background & Aims: Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. Methods: H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. Results: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. Conclusions: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects. GASTROENTEROLOGY 2000;118:22-30

The gastric transitional zones are the junctional zones between the different types of mucosa: antral-body, body-cardia, and antrum-duodenum. In this article, the importance of the transitional zone in determining disease outcome, specifically duodenal ulcer, gastric ulcer, and possibly gastric cancer, is reviewed. Both gastric ulcers and duodenal ulcers are located immediately adjacent to the transitional zones. The transitional zones are dynamic rather than static areas. Local acid levels determine the behavior of Helicobacter pylori at the antral-body transitional zone and, as a consequence, the geographic distribution of gastritis in the stomach and the formation of duodenal ulcer and gastric ulcer. This review also explains that diffuse antral gastritis and multifocal atrophic gastritis are part of the same disease and not separate entities.

Background & Aims: Infection with Helicobacter pylori uniformly leads to a chronic superficial gastritis that may progress to atrophic gastritis, a premalignant process. A mouse model of Helicobacter felis infection was used to study possible genetic determinants of the response to infection. Methods: Three inbred mouse strains with known secretory phospholipase A 2 (sPLA 2 ) genotypes [BALB/c (+/+), C3H/HeJ (+/+), and C57BL/6 (−/−)] were orally infected with H. felis and examined longitudinally using routine histology, immunocytochemistry, electron microscopy, proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling, and Northern and Western blot studies. Results: Only the C57BL/6 strain showed increased gastric fundic proliferation and apoptosis in response to infection. In addition, the C57BL/6 mouse showed a marked loss of parietal and chief cells, along with a marked expansion of an aberrant gastric mucous cell lineage that stained positive for spasmolytic polypeptide. In contrast, no significant change in these cell types was observed in BALB/c and C3H/HeJ strains. Increased expression of sPLA 2 was observed in BALB/c and C3H/HeJ after H. felis infection, whereas sPLA 2 expression was absent in C57BL/6 mice. Conclusions: H. felis infection leads to increased apoptosis and altered cellular differentiation in the C57BL/6 mouse, a strain that lacks gastric sPLA 2 expression. Because sPLA 2 has been identified recently as the MOM1 (modifier of MIN) locus that influences polyp formation in the colon, these studies suggest that sPLA 2 may also influence the gastric epithelial response to Helicobacter infection. GASTROENTEROLOGY 1998;114:675-689

Much of what is currently accepted on the natural history of Helicobacter pylori-induced gastritis and its relationship with gastric adenocarcinoma rests on the assumption that atrophic gastritis can be correctly identified and reproducibly recognized. Recently, several studies have indicated that pathologists have a low level of agreement on this topic, and the terms "gastric atrophy" and "atrophic gastritis" remain imprecisely defined and, therefore, poorly understood. Furthermore, the genesis and progression of the atrophic changes taking place in the gastric mucosa of some, but not all, subjects infected with H. pylori are incompletely characterized. This review has three aims: (1) to briefly reexamine our current knowledge of the mechanisms involved in the injury and repair of gastric glands; (2) to present a hypothesis on the development of gastric atrophy; and (3) to propose a new, stringent definition of gastric atrophy that may be usefully applied in the clinical research arena.

Several lines of evidence support an association between Helicobacter pylori infection and gastric cancer. The natural history of H. pylori-associated gastritis is inexorable progression ultimately leading to gastric atrophy. In general, this process requires between 20 and 40 years to complete. Atrophic gastritis is widely considered to be a precursor lesion of the intestinal type of gastric cancer. Moreover, areas with a high prevalence of H. pylori infection also have a high prevalence of gastric cancer. Strong evidence from three prospective studies shows the risk of gastric cancer to be increased fourfold in H. pylori-positive persons. Several retrospective studies have also confirmed that H. pylori infection is associated with development of gastric cancer, especially in the younger generation, early gastric cancer, and noncardiac gastric cancer. H. pylori alone is not likely responsible for gastric cancer. Rather, it may provide a suitable environment, including chronic gastritis and intestinal metaplasia, for neoplastic change. Recognition of an association between H. pylori infection and gastric cancer has led to a major shift in emphasis on the cause of the disease. Research into H. pylori has focused attention on the importance of chronic inflammation and impaired host defense mechanisms as factors in the development of gastric cancer. H. pylori infection leads to changes in many factors that are important to the pathogenesis of gastric cancer, including vitamin C content of gastric juice, reactive oxygen metabolites, and epithelial cell proliferation. Eradication of the organism may reverse these changes. Therefore, eradication of H. pylori in infected persons might be a route to preventing gastric cancer, although many questions still remain as to the effectiveness of this strategy.

The article presents data on the study of the nature of endoscopic changes of gastric mucosa in patients with atrophic gastritis with varying severity of structural damage. It is shown that endoscopic manifestations of atrophic gastritis are heterogeneous and are characterized, in addition to atrophic changes, by changes in mucosal relief (nodularity, tuberosity), focal hyperplasia, polyps, xanthomas. These changes correlate with the presence of intestinal metaplasia and dysplasia of the gastric mucosa. Incidence of atrophic-hyperplastic gastritis is significantly higher in patients with precancerous changes of the gastric mucosa.It is shown that the use of anti-foaming agent simethicone improves diagnostic efficiency of EGDS, helping to identify premalignant disease and gastric cancer., В статье представлены данные об изучении характера эндоскопических изменений слизистой оболочки желудка у больных с атрофическим гастритом с различной выраженностью структурных нарушений. Показано, что эндоскопические проявления атрофического гастрита являются неоднородными и характеризуются, помимо атрофических изменений, наличием изменений рельефа слизистой оболочки (узловатость, бугристость), очаговых гиперплазий, полипов, ксантом. Указанные изменения коррелируют с наличием кишечной метаплазии и дисплазии слизистой желудка. Частота атрофически-гиперпластических гастритов достоверно выше у пациентов с наличием предраковых изменений слизистой желудка.Показано, что применение пеногасителя симетикона повышает диагностическую эффективность эзофагогастродуоденоскопии, способствуя выявлению предраковой патологии и рака желудка., У статті наведено дані з вивчення характеру ендоскопічних змін слизової шлунка у хворих на атрофічний гастрит із різним ступенем структурних порушень. Показано, що ендоскопічні прояви атрофічного гастриту є неоднорідними і характеризуються, окрім атрофічних змін, наявністю змін рельєфу слизової (вузлуватість, бугристість), вогнищевих гіперплазій, поліпів, ксантом. Указані зміни корелюють із наявністю кишкової метаплазії і дисплазії слизової шлунка. Частота атрофічно-гіперпластичного варіанту гастрита вірогідно вища у хворих із наявністю передракових змін слизової шлунка.Показано, що застосування піногасника симетикону підвищує діагностичну ефективність езофагогастродуоденоскопії, сприяє виявленню передракової патології і раку шлунка.

Background/Aims: Because the precancerous significance of gastric epithelial dysplasia (GED) is still under debate, this study attempts to ascertain whether a prospective follow-up of GED can contribute to clarifying its clinical and pathological relationships with gastric cancer (GC). Methods: One hundred twelve patients with mild (G1), moderate (G2), and severe (G3) GED or diagnosed as indefinite for dysplasia were prospectively followed up with a standardized endoscopic and bioptic protocol. Results: Evaluation of GED outcome refers only to 93 patients with a follow-up period longer than 12 months. Regression of dysplasia was documented in 36%, 27%, and 0% of G1, G2, and G3 GED cases, respectively. Progression to more severe dysplasia or evolution into GC was detected in 21%, 33%, and 57% of G1, G2, and G3 GED cases, respectively. Evolution into GC was documented for all grades of dysplasia and correlated significantly with high-grade atrophic gastritis. A high prevalence of early GC (86.9%) was also observed. Conclusions: GED is a preinvasive lesion, and carcinomatous evolution increases proportionally with its histological grade. Bioptical follow-up is mandatory for all histological grades of GED and significantly increases the likelihood of GC being detected in its early stages.

Gastrointestinal epithelia contain a powerful protease inhibitor called pancreatic secretory trypsin inhibitor (PSTI). Gastric mucus obtained from patients with atrophic gastritis or gastric ulceration shows changes suggestive of excessive proteolytic digestion. Therefore, the aim of this study was to examine whether mucosal PSTI levels are affected by gastritis and/or ulceration.Mucosal PSTI levels were measured in 12 patients with normal gastric histology and 26 patients with gastritis and/or gastric ulceration.In control subjects, mean gastric PSTI concentrations were 990 ng/mg protein (95% confidence interval, 819-1195) in the antrum and 445 ng/mg protein (95% confidence interval, 395-502) in the body. Immunostaining for PSTI was strongly positive in the pyloric glands of the antrum and in the foveolar/surface and mucus neck cells of the gastric body. Tissue levels of PSTI were reduced by 40% in biopsy specimens showing superficial gastritis (P = 0.035) and by 75% in biopsy specimens showing atrophic gastritis and/or gastric ulceration (P0.001). Immunostaining was also reduced in specimens showing atrophic gastritis.The decrease in tissue PSTI levels associated with gastric atrophy probably represents a permanent reduction in one of the mucosal defense mechanisms. This may lead to the maintenance and even expansion of the gastritic process with time.

Background/Aims: Bacterial overgrowth of the small intestine commonly occurs in association with hypochlorhydria caused by atrophic gastritis or during treatment with omeprazole. The purpose of this study was to determine the clinical significance of bacterial overgrowth on small intestinal absorption and permeability and to evaluate the reliability of noninvasive breath tests to detect bacterial overgrowth in subjects with hypochlorhydria. Methods: Seventeen healthy, elderly subjects with atrophic gastritis or omeprazole treatment (40 mg/day) and documented bacterial overgrowth were studied. Results: There was no evidence of fat malabsorption (72-hour fecal fat) or clinically significant carbohydrate malabsorption (25 g d-xylose and fecal pH) in any subject. The ratio of lactulose to mannitol excreted was normal in both atrophic gastritis and omeprazole-treated groups. Three subjects in each group had abnormally high α 1 -antitrypsin clearances. Lactulose (10 g) and glucose (80 g) hydrogen breath tests were only abnormal in 1 out of 17 subjects, whereas the 1 g [ 14 C]d-xylose test was abnormal in 6 out of 17 subjects. Conclusions: Bacterial overgrowth caused by atrophic gastritis or omeprazole treatment is typically not associated with clinically significant fat or carbohydrate malabsorption. Noninvasive breath tests for bacterial overgrowth are not reliable in subjects with hypochlorhydria.

Background & Aims Although defects in tight junction (TJ) epithelial paracellular barrier function are believed to be a primary cause of inflammation, the mechanisms responsible remain largely unknown. Methods We generated knockout mice of stomach-type claudin-18, a major component of TJs in the stomach. Results Cldn18 −/− mice were afflicted with atrophic gastritis that started on postnatal day 3. This coincided with a decrease in intragastric pH due to H + secretion from parietal cells and concomitant up-regulation of the cytokines, interleukin-1β, cyclooxygenase-2, and KC, resulting in spasmolytic polypeptide-expressing metaplasia (SPEM). Oral administration of hydrochloric acid on postnatal day 1 induced the expression of these cytokines in Cldn18 −/− infant stomach, but not in Cldn18 +/+ mice. A paracellular H + leak in Cldn18 −/− stomach was detected by electrophysiology and H + titration, and freeze-fracture electron microscopy showed structural defects in the TJs, in which the tightly packed claudin-18 (stomach-type)-based TJ strands were lost, leaving a loose meshwork of strands consisting of other claudin species. Conclusions These findings provide evidence that claudin-18 normally forms a paracellular barrier against H + in the stomach and that its deficiency causes paracellular H + leak, a persistent up-regulation of proinflammatory cytokines, chronic recruitment of neutrophils, and the subsequent development of SPEM in atrophic gastritis.

Background & Aims Transgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to nonhelicobacter microbiota overgrowth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic INS-GAS mice. Methods We compared gastric lesions, levels of messenger RNA, serum inflammatory mediators, antibodies, and gastrin among germfree and H pylori–monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyrosequencing. Results Germfree INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until 9 months old and did not develop GIN through 13 months. H pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic atrophy, marked foveolar hyperplasia, dysplasia, and robust serum and tissue proinflammatory immune responses (particularly males) between 5 and 11 months postinfection (P, National Institutes of Health (U.S.) (Grant R01 AI37750), National Institutes of Health (U.S.) (Grant R01 CA093405), National Institutes of Health (U.S.) (Grant P30 ES02109), National Institutes of Health (U.S.) (Grant P01 CA028842), National Institutes of Health (U.S.) (Grant T32 RR07036)

A seroepidemiologic study of the prevalence of Helicobacter pylori infection in Japan was performed, and the relationship between serum pepsinogen I and II levels (markers of gastritis and gastric atrophy) and H. pylori infection was investigated. Four hundred and eighteen asymptomatic children and adults were studied. The prevalence of anti-H. pylori immunoglobulin G antibody increased with age. For persons born after 1950, the frequency of H. pylori infection increased at approximately 1% per year; for those born before 1950 the prevalence was high (70%-80%) and relatively constant. Serum pepsinogen I and II levels were significantly higher in H. pylori-infected volunteers than in H. pylori-uninfected volunteers [51.6 +/- 3 vs. 42.9 +/- 2 ng/mL (P less than 0.05) for pepsinogen I; 16.0 +/- 1 vs. 7.5 +/- 0.8 ng/mL (P less than 0.001) for pepsinogen II]. The ratio of pepsinogen I to pepsinogen II was significantly lower in H. pylori-infected volunteers (3.5 +/- 0.2) than in uninfected volunteers (6.3 +/- 0.3; P less than 0.001). The apparent decrease in prevalence of H. pylori accompanying the Westernization of Japan may eventually be accompanied by a reduction in the frequency of atrophic gastritis, the precursor lesion of the epidemic form of gastric carcinoma, and ultimately result in a decrease in the incidence of gastric carcinoma in Japan.

Fundic argyrophil cells were studied for a mean period of 68.7 months (range, 11-170) in 18 patients with fundic atrophic gastritis and achlorhydria. Initially, 12 patients had hyperplasia of the argyrophil cells, the severity of which was assessed using a semiquantitative classification based on the number of argyrophil clusters per square millimeter. At the end of the study, the degree of hyperplasia was unchanged in 9 patients, had decreased in 2, and had increased in 1; no significant increase in the number of argyrophil clusters, precarcinoid changes, or carcinoid tumors were observed and the high level of gastrinemia [mean, 4.8 (range, 1.9-8.1) times the upper limit for normal) did not change significantly. Of the 6 patients with no hyperplasia at the outset of the study, 4 continued without hyperplasia and 2 presented a low-grade hyperplasia at the 20th and 130th month. Gastrinemia increased significantly in the last patient and stayed normal in the other 5. This study argues in favor of the stable appearance of fundic argyrophil cells in patients with atrophic gastritis and stable gastrinemia.

Objective of the study: Since 2013, H. pylori eradication therapy for atrophic gastritis associated with H. pylori became available for coverage by insurance in Japan. For first-line therapy, triple eradication therapy (proton pump inhibitor (PPI) + amoxicillin (AMPC) + clarithromycin (CAM) is available for H. pylori eradication, in Japan. The resistance of H. pylori strains to CAM accounts for the majority of eradication failures, the incidence of which is currently increasing and it affects H. pylori eradication rate in Japan. Another matter is recurrence of H. pylori infection after eradication. H. pylori infection sometimes recurs after successful eradication. The rate of recurrence after successful eradication is reported to be 0.5% to 2.0% in the western countries. In this study, we investigated about the long term transition of primary drug susceptibility ofH. pylori strains to CAM, and the rate of recurrence after successful eradication in Japan.Methods: Three hundred sixty six patients after successful eradication of H. pylori were followed up by culture, histological examination and urea breath tests. In 22 patients in whom H. pylori recurred during follow-up, the susceptibility of the H. pylori strains to clarithromycin was investigated. And in 17 recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR-based restriction fragment length polymorphism (RFLP) analysis. Results: The primary resistance of H. pylori to CAM is increasing, especially in these 6 years, its rate is very high at 35%. Ten of 22 (45.5%) recurrences appeared at 6 months after successful eradication of H. pylori, and after 1 year, the annual recurrence rate of H. pylori infection was 0.29% per patient year. In recurrent cases, 50.0% (5/10) of the strains detected 6 months after successful eradication were found to be susceptible to clarithromycin. And 58.3% (7/12) of the strains detected at 12 months or later were found to be susceptible to clarithromycin. In the 10 patients who showed a recurrence of H. pylori after 12 months, all the patients showed different DNA profiles, and 5 of 7 (71.4%) patients showed different DNA profiles at 6 months after eradication Conclusions: The rate of CAM-resistant H. pylori strains is very high in Japan. Because of that, for the recurrence cases, it occurs with low frequency (0.29% per patient year), drug sensitivity examination may be necessary in Japan.

polymorphism and widely used in the eradication, rabeprazole (RPZ) and esomeprazole (EPZ). Patients and methods: This was a prospective, multi-centered, non-blinded, randomized clinical trial. We conducted tests such as rapid urease test or urea breath test (UBT) in patients confirmed of having gastric/duodenal ulcers or chronic atrophic gastritis by esophagogastroduodenoscopy (EGD) to find the infection status of H. pylori, and 147 positive patients were enrolled. Gastric juice was collected to see the CYP2C19 polymorphism and CAM resistant rate during EGD. Patients were randomized into either RPZ 10 mg bid + AMPC 750 mg bid + CAM 200 mg bid for 7 days group or EPZ 20 mg bid + AMPC 750 mg bid + CAM 200 mg bid for 7 days group. Background factors (age, gender, height, weight, BMI, smoking, alcohol, concomitant drugs, baseline disease) were studied, and eradication was evaluated by UBT at least four weeks after the end of the eradication therapy. Results: The evaluation subject was 147 patients, and a background factors did not have the significant difference between both groups (p>0.05). The eradication rate in RPZ group was 68.4% (52/76) while it of EPZ group was 77.5% (55/71), with no significant difference between groups (p=0.27). Overall CAM resistant rate 15% (22/147). As for the eradication success rate of CAM resistant, the eradication rate in RPZ group was 40.0% (2/5) while it of EPZ group was 52.9% (9/17), with no significant difference between groups (p>0.05). In all, the ratio distribution of CYP2C19 genotype was RM 31%(19/61), intermediate metabolizers (IM) 54 %( 33/61), poor metabolizers (PM) 15%(9/61). Between the two groups, there was no significant difference in the success rate of eradication by each genotype (p>0.05). Conclusions: In the eradication rate of H. pylori by the triple therapy, RPZ and EPZ were comparable. Also, in the examination by clarithromycin resistance and CYP2C19 genotype, the eradication rate of both drugs was equivalent.