Endoscopic three-categorical diagnosis of Helicobacter pylori infection using linked color imaging and deep learning: a single-center prospective study (with video).

BACKGROUND: Helicobacter pylori (H. pylori) eradication is required to reduce incidence related to gastric cancer. Recently, it was found that even after the successful eradication of H. pylori, an increased, i.e., moderate, risk of gastric cancer persists in patients with advanced mucosal atrophy and/or intestinal metaplasia. This study aimed to develop a computer-aided diagnosis (CAD) system to classify the status of H. pylori infection of patients into three categories: uninfected (with no history of H. pylori infection), currently infected, and post-eradication. METHODS: The CAD system was based on linked color imaging (LCI) combined with deep learning (DL). First, a validation dataset was formed for the CAD systems by recording endoscopic movies of 120 subjects. Next, a training dataset of 395 subjects was prepared to enable DL. All endoscopic examinations were recorded using both LCI and white-light imaging (WLI). These endoscopic data were used to develop two different CAD systems, one for LCI (LCI-CAD) and one for WLI (WLI-CAD) images. RESULTS: The diagnostic accuracy of the LCI-CAD system was 84.2% for uninfected, 82.5% for currently infected, and 79.2% for post-eradication status. Comparisons revealed superior accuracy of diagnoses based on LCI-CAD data relative based on WLI-CAD for uninfected, currently infected, and post-eradication cases. Furthermore, the LCI-CAD system demonstrated comparable diagnostic accuracy to that of experienced endoscopists with the validation data set of LCI. CONCLUSIONS: The results of this study suggest the feasibility of an innovative gastric cancer screening program to determine cancer risk in individual subjects based on LCI-CAD.

Kyoto global consensus report on Helicobacter pylori gastritis.

OBJECTIVE: To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. DESIGN: Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. RESULTS: All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. CONCLUSIONS: A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.

Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis.

Recent advances in endoscopic technology allow detailed observation of the gastric mucosa. Today, endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori (H. pylori) infection and evaluate gastric cancer risk. In 2013, the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification, a new grading system for endoscopic gastritis. The Kyoto classification organized endoscopic findings related to H. pylori infection. The Kyoto classification score is the sum of scores for five endoscopic findings (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness with or without regular arrangement of collecting venules) and ranges from 0 to 8. Atrophy, intestinal metaplasia, enlarged folds, and nodularity contribute to gastric cancer risk. Diffuse redness and regular arrangement of collecting venules are related to H. pylori infection status. In subjects without a history of H. pylori eradication, the infection rates in those with Kyoto scores of 0, 1, and ≥ 2 were 1.5%, 45%, and 82%, respectively. A Kyoto classification score of 0 indicates no H. pylori infection. A Kyoto classification score of 2 or more indicates H. pylori infection. Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8, respectively. A Kyoto classification score of 4 or more might indicate gastric cancer risk.

[An update on rickettsiosis]. / L'actualité des rickettsioses.

Rickettsiae are strictly intracellular bacteria belonging to the Rickettsiaceae family. They are transmitted by various arthropods species, which are either vectors or reservoirs for the bacteria. The specific association between Rickettsieae and the vector are extensively studied, moreover Rickettsieae associated diseases are part of a continuously evolving field. Nevertheless, some rickettsiosis, such as epidemic typhus, have been described since the 16th century. Emerging diseases related to these bacteria are being investigated as well as new species, the implication of which is not always clear in human pathology when they are discovered. Some of these diseases are benign, others may be potentially fatal. Clinicians must therefore be aware of them. These issues are reviewed.

Helicobacter pylori Infection, Gastric Cancer and Gastropanel.

Gastric cancer (GC) is one of the most widespread types of cancer worldwide. Helicobacter pylori infection has been clearly correlated with gastric carcinogenesis. At present and in the near future, the most important challenge is and will be the significant reduction of mortality due to GC. That goal can be achieved through the identification of higher-risk patients, such as those with atrophic gastritis, intestinal metaplasia and dysplasia. In this review we intend to discuss the importance of diagnosing H. pylori infection and chronic atrophic gastritis in preventing gastric cancer, using a new non-invasive test called GastroPanel. This test is a classification algorithm including four biochemical parameters pepsinogen I and II (PGI and PGII), gastrin-17 (G17), and anti-Helicobacter pylori antibodies (Ig G anti-Hp) measured in fasting sera, which allows to classify patients as having atrophic or non-atrophic gastritis and to find whether gastritis is associated or not with H. pylori infection. GastroPanel is not a "cancer test", but it can and should be used in the screening and diagnosis of subjects with a high cancer risk; still, a careful diagnostic made by superior digestive endoscopy is compulsory to find possible precancerous or cancerous lesions at an early and curable stage.

Helicobacter pylori: Helicobacter pylori gastritis--a novel distinct disease entity.

A global consensus report on Helicobacter pylori gastritis has been developed. Topics discussed include whether dyspepsia caused by H. pylori infection is separate from functional dyspepsia or not, the evaluation method for H. pylori-induced gastritis, eradication therapy for H. pylori gastritis to prevent gastric carcinogenesis and management after H. pylori eradication.

Analysis of vacA/cagA genotypes/status in Helicobacter pylori isolates from Iranian children and their association with clinical outcome.

BACKGROUND/AIM: More than 50% of Iranian children are infected with Helicobacterpylori; however, no data exist about the association of vacA/cagA genotype/status with disease outcomes in them. We analyzed association of vacA/cagA genotypes/status of children's isolates with gastric inflammation status as the first step in H. pylori pathogenesis. MATERIALS AND METHODS: Antral biopsies for culture and histopathology were taken from 328 children in 1997-2009. vacA (s, m) alleles and cagA statuses of the isolates were determined by PCR. Histopathology was performed according to the Sydney system; gastritis was scored as normal, mild, moderate, severe, and follicular. RESULTS: A total of 159 culture-positive cases, with no mixed infections, were enrolled in the study. Of them, 60% were cagA-positive; 21.4%, 37.1%, 16.3%, and 25.2% cases were slm1, slm2, s2m1, and s2m2, respectively. Histopathology showed normal (4.4%), mild- chronic (31.4%), moderate-chronic (38.4%), severe-chronic (10.7%), and follicular gastritis (15.1%) cases. Thirty-four (21.4%) of the children had ulcers. Correlation (P < 0.05) was observed between more severe (moderate, severe, follicular) status and both vacAs1 allele and cagA-positive status. No significant relation was observed between genotype/status of vacA/cagA and ulcers (P > 0.05). CONCLUSION: vacAs1 and cagA are associated with more severe gastric inflammation in Iranian children. Association ofvacAs1 and cagA with more severe pathology in Iran may be similar to that of other parts of the world.

Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole.

BACKGROUND AND OBJECTIVES: The acid-inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD. METHODS: A total of 65 patients with GERD (grades A-D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30-mg dose of lansoprazole in the 27 genotyped patients. RESULTS: Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups. CONCLUSIONS: CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.

Analysis of host responses of guinea pigs during Helicobacter pylori infection.

Host responses of guinea pigs infected with Helicobacter pylori were investigated. Passaged H. pylori colonised the stomach for up to 13 weeks after infection, but after 1 month the number of bacteria fell sharply. Specific antibodies, predominantly of the IgG2 subtype, were present from week 3 onwards. Antibodies to urease A and flagella were abundant. Severe inflammation of the gastric mucosa and damage to the stomach epithelium was seen. Infiltrates of mononuclear cells and eosinophils were found near the parietal glands. As infection progressed, inflammation and tissue damage became more localised and more variable between individual animals. These parameters can be used as markers for colonisation of the stomach by H. pylori.

Non-pylori Helicobacter infections in humans.

The spectrum of human non-pylori Helicobacter infections is expanding. Evidence for the presence of bacteria such as H. heilmannii, H. felis, H. rappini, H. cinaedi, H. fennelliae and H. pullorum has been reported. These bacteria are likely to be associated with different clinical disorders. H. heilmannii is the most commonly described non-pylori Helicobacter in humans. Colonization with this bacterium is usually associated with mild gastritis. In some cases, gastric ulcer disease may occur. H. heilmannii are classified as such on the basis of morphological criteria. Recent phenotypical and genotypical data suggest that this is insufficient. Therefore, for a better understanding of the relation between non-pylori Helicobacter species and disease, there is a need for studies focusing on genetic instead of morphological criteria.

Grading Helicobacter pylori gastritis in dyspeptic patients.

Helicobacter pylori-like organisms (Hp) and polymorphonuclear leucocytes (PMNs) in 2614 gastroduodenal biopsies from 602 patients with dyspepsia, in Al Ain, United Arab Emirates, between October 1990 and October 1992, were histologically graded to determine the prevalence of Hp gastritis and their utilization in the evaluation of treatment efficacy in these patients. Symptoms of functional dyspepsia included, in order of frequency, abdominal pain or discomfort, flatulence, burning sensation, regurgitation, fullness, nausea, vomiting, bloating and belching. The biopsies were paraffin embedded, sectioned and stained with hematoxylin and eosin (H and E) to grade the inflammation. In addition to H and E, several special stains including modified Giemsa (MG), Wharthin-Starry silver and cold Ziehl-Neelsen stains were utilized to clearly identify Hp organisms. Giemsa method was found to be superior to other special stains in visualizing the Hp organisms in paraffin sections, and was utilized in every case. Two immunohistochemical markers for B cells (CD20) and T cells (CD45RO) were utilized for labeling lymphocytes infiltrating the lamina propria of the gastroduodenal biopsies in formalin-fixed paraffin-embedded sections. H and E and MG stained sections were utilized to count PMNs and Hp, and were graded 0, 1, 2, and 3, corresponding to none, mild, moderate, and severe grades of the Sydney system for classification of gastritis, respectively. Of the total initial 2318 endoscopic biopsies, 98.8% of the patients had suitable biopsies for histologic evaluation. Unsuitable biopsies were recovered from patients with gastric carcinoma. Inflammation was seen in 98.5% of 595 patients with suitable biopsies. In 74.5% of these patients the inflammation was active; 37.5, 32.5 and 4.5% had mild, moderate and severe active inflammation, respectively. In the remaining 24% of the 595 patients, the gastritis was chronic without activity or atrophic changes. As many as 73.6% of the patients with suitable biopsies were Hp positive; 39.8, 29.1 and 4.7% had grades 1, 2 and 3 Hp, respectively. Intestinal metaplasia was found in 28.9% of the 602 patients, and was seen more often in Hp positive than Hp negative patients (34.5 vs 14%, P < 0.005, for d.f. = 1; chi 2 = 10.35). Of the Hp positive patients, 172 and 46 patients attended the first and second follow-up endoscopy visits, respectively. The triple treatment was composed of one dose of tinidazole (2gm), doxycycline, 200 mg initial dose and 100 mg daily for two weeks, and bismuth subcitrate (Gist-Brocades nv, Delft, The Netherlands), 2 tablets twice daily for 4 weeks. After triple drug treatment, eradication of Hp was accomplished, histologically, in 38.4 and 45.7% of the patients on first and second follow-up visits, respectively. Thus, the Sydney system-based grading scale provides an objective histological evaluation of Hp gastritis for accurate prevalence studies, and may prove to be of value in estimating treatment efficacy.

[Therapeutic relevance of the classification of gastritis]. / Therapeutische Relevanz der Gastritis-Klassifikation.

The histological gastritis classification according to the Sydney system is a standardisation of different classification systems used so far. It is based on the principles of etiology, topography and course of the disease, as well as morphological changes of the gastric mucosa in gastritis. Histological examination represents the practical gold standard of Helicobacter pylori detection and can be used on routinely formaldehyde-fixed biopsy material and hematoxylin-eosin stained slides. Histology is therefore also of practical diagnostic value for the control of the eradication therapy of Helicobacter pylori. The sensitivity of histological Helicobacter detection is on average higher than that of other methods including microbiology. Nevertheless, additional bacterial cultures are useful in cases of therapy resistant Helicobacter pylori infections. For routine diagnosis histological Helicobacter pylori detection is often combined with the so-called rapid urease test, which can be used in the endoscopy outpatient department, frequently offering an interim diagnosis of Helicobacter pylori infection. Furthermore, histological examination enables not only exact gastritis classification with Helicobacter pylori detection, but also the diagnosis of precancerous lesions and gastric carcinomas, as well as primary gastric lymphomas. Biopsy material for histological examination can be taken during the routinely necessary gastroscopic examination of patients with gastric symptoms without much additional burden.

Non-ulcer dyspepsia and Helicobacter pylori infection--morphological analysis according to the Sydney system--changes before and after treatment.

Non-ulcer dyspepsia (NUD) means the presence of upper abdominal pain and discomfort and also nausea, vomiting, flatulence, heartburn and belching. It is estimated, that about 20-30% of all patients refer to a doctor because of dyspeptic symptoms. Helicobacter pylori (Hp) infections are diagnosed in about 60% of persons with NUD and in 80-100% of patients with clinical, endoscopic and histological diagnosis of gastritis. The authors decided to investigate a correlation between gastritis and Hp infection and a relationship between the influence of antibacterial therapy and Hp eradication from gastric mucus and to observe gastric mucosa condition. We examined 73 patients (range age 16-73): 40 females and 33 males. We employed the Sydney System for evaluation of gastric mucosa condition. The patients were divided into two groups: Hp-positive 50 persons and Hp-negative-23 persons. Hp infected subjects were treated with antibacterial drugs (bismuth + metronidazol + amoxycillin or bismuth + metronidazol + tetracycline) and Hp-negative only with bismuth. Hp eradication was obtained in 72.7% of patients treated with bismuth + metronidazol + amoxycillin and 76.4% of persons treated with bismuth + metronidazol + tetracycline. A statistically significant difference between these two kinds of antibacterial therapy was not noted. Both methods are equally effective. We observed also and improvement of the histological state of antrum and corpus gastric mucosa after therapy in comparison to changes before treatment. We noticed a decrease of dyspeptic complaint in 89.2% of Hp infected persons in whom Hp had been eradicated. Among Hp-negative 23 patients gastric mucosa was normal in 30% and chronic gastritis was found in 70% of subjects. Based upon the present results it seems very important and suitable to detect Hp organisms in gastric mucus of all dyspeptic patients who are endoscopically examined and biopsied at the same time. We would suggest to do an urease test and to take histological samples together with full endoscopic examination according to the Sydney System guidelines.

Ultrastructural study of the gastric mucosa and Helicobacter pylori in duodenal ulcer patients.

OBJECTIVE: To investigate the relationship between Helicobacter pylori and gastric mucosa in control and duodenal ulcer patients at the electron microscopic level. METHODS: Three antral biopsies were taken from each of 20 normal control volunteers and 30 duodenal ulcer patients presented to the gastroenterology unit at Jordan University Hospital for upper endoscopic examination. Each specimen was fixed and processed for electron microscopic study. RESULTS: Two types of Helicobacter pylori were observed and identified by their morphology at electron microscopy. The first one was characterized by double external smooth membranes and homogeneous cytoplasmic contents, and the second type with a characteristic ring-shaped intracytoplasmic vacuole. Electron microscopic examination of normal controls showed normal gastric mucosa and a small number of Helicobacter pylori in 12 out of 20 controls. However, in duodenal ulcer patients, 5 different patterns of interaction between the Helicobacter pylori and gastric mucosa were observed in relation to the severity of the disease. In duodenal ulcer patients, various types of epithelial damage was seen accompanied with a decrease or absence of mucous secretion and with more colonization of bacteria. CONCLUSION: The morphology and pathogenesis of Helicobacter pylori was described in duodenal ulcer patients, and 5 different patterns of contact between Helicobacter pylori and surface epithelium were recognized causing variable degrees of microvillous atrophy and reduced mucous secretion. The vacuolated type of Helicobacter pylori was more adherent to the damaged epithelium and there was a direct relationship between the epithelial damage and bacterial load. In the normal controls, no epithelial damage and scanty bacteria were observed. The various types of epithelial changes of gastric mucosa has initiated more research at electron microscopic level on the immune mechanism of the gastric mucosa to determine the underlying cause of the varying severity of the disease.

[Morphology of gastritis and Helicobacter pylori infection]. / Morfoloska slika gastritisa i infekcije Helicobacterom pylori.

Helicobacter pylori infection almost invariably results in chronic gastritis. The Sydney System (1990) emphasised the importance of combining topographical, morphological and etiological aspects in attempt to make clinical useful diagnosis of chronic gastritis. The aims of revised Sydney System in Houston (1994), Texas, were to improve terminology of chronic gastritis emphasising distinction between nonatrophic and atrophic gastritis, and in addition to determinate special forms of gastritis. The special forms of gastritis were described and diagnostic criteria were provided. Principles and grading of histological division of Sydney System were only slightly modified, grading being improved by the provision of a visual scale. Endoscopy and histological findings of 1062 patients from University Hospital Merkur were compared to evaluate the value of endoscopic division of Sydney System, and the modified grading proposed by Houston classification. There was no correlation between endoscopic and histological findings. Localisation of inflammatory cells was either 1) superficial or 2) diffuse in the mucosa, respectively. In Helicobacter pylori positive patients the most common finding was chronic active gastritis, and in Helicobacter pylori negative superficial and inactive chronic gastritis.

Molecular techniques for studying the epidemiology of infection by Helicobacter pylori.

The efficacy of one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell protein patterns for fingerprinting isolates of Helicobacter pylori was assessed by means of computerized numerical analysis. Virtually all strains were found to have unique, stable, and reproducible protein profiles. The application of this technique to a collection of isolates from eight patients showed clearly that each harboured a distinct strain that was present before treatment and persisted after treatment. This suggests that relapse was due to recrudescence of the same strain rather than re-infection with a different strain. Minor differences in protein banding profiles within sets of isolates from the same patient were evident, and this was confirmed by means of both two-dimensional PAGE protein patterns and restriction endonuclease analysis of DNA on the same strains.

[A new international classification of gastritis]. / Novaia mezhdunarodnaia klassifikatsiia gastrita.

New, published in 1989-90, international classifications of gastritis take into consideration its topography, the degree of morphological changes and etiology. This approximates the morphological diagnosis of gastritis to the nosological one. The most frequent cause of the gastritis is pyloric Helicobacter. Their presence should be indicated in the morphological diagnosis as this predetermines the therapeutic policy.

[The clinical and morphofunctional characteristics of different types of stomach ulcer]. / Klinicheskie i morfofunktsional'nye osobennosti razlichnykh tipov iazvy zheludka.

AIM: The study of a complex of anamnestic, clinicoendoscopic and functional-morphological characteristics in type I and II (according to Johnson) gastric ulcer. MATERIALS AND METHODS: Esophagogastroduodenoscopy, gastric secretion tests, determination of blood group and Rh factor were performed in 91 patients (52 patients with ulcer type I and 39 with ulcer type II). RESULTS: Ulcers type I have arisen in the presence of long-term chronic gastritis. They were associated with marked changes in the mucosa of gastric body, its atrophy and intestinal metaplasia, persistent recurrences in the same gastric zone. Ulcers type II are characterized by hereditary loading, 0(I) blood group, combination with gastroduodenal erosions, season occurrence, trend to migration and recurrence in different gastric or duodenal zones, HCl hypersecretion, high occurrence of Helicobacter pylori infection. CONCLUSION: It is thought valid to include types of gastric ulcer in current classification of ulcer.

Gastroesophageal cancer: focus on epidemiology, classification, and staging.

Gastroesophageal cancer (GEC), comprising proximal esophagogastric junction (EGJ) and distal gastric cancer (GC), is a significant public health concern. The epidemiology of these tumors has significantly changed over the past several decades especially in developed countries. There is a recognized decrease in incidence and mortality of distal GC and an increase in incidence and mortality of proximal EGJ cancer. The changing epidemiology is thought to be mainly due to changing trends of risk factors such as lower incidence of Helicobacter pylori infection and increasing incidence of obesity and gastroesophageal reflux. Histologically, EGJ cancers are adenocarcinoma (AC), while distal esophagus may be squamous cell carcinoma (SCC) or AC. Distal GC is predominantly AC. Following anatomical and histological distinction, tumors are staged with endoscopic ultrasound (EUS), computerized tomography (CT), and often positron emission tomography (PET) with or without diagnostic laparoscopic and peritoneal washing. Accurate staging of tumors, with emphasis on excluding occult metastasis, is imperative to avoid unnecessary surgical resection. Therefore, it is crucial to understand how these tumors are classified, the associated epidemiology, and the current standards of staging prior to selecting the appropriate course of therapy. In this review we will discuss the epidemiology, classification, and staging of locally advanced GEC.