Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority.

The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9–12, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.

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Comprehensive molecular characterization of gastric adenocarcinoma

H. pylori is one of the most common bacterial infections in human beings, and its discovery 20 years ago altered the diagnosis and treatment of gastroduodenal disease. This review considers current knowledge about the epidemiology and transmission of H. pylori, as well as the role of this infectious agent in the pathogenesis of upper gastrointestinal tract disease. Diagnostic approaches, indications for therapy, and measures of therapeutic efficacy are reviewed.

Helicobacter pylori infection.

Background: Guidelines on the management of Helicobacter pylori , which cover indications for management and treatment strategies, were produced in 2000. Aims: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer. Results: Eradication of H pylori infection is recommended in ( a ) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; ( b ) patients with atrophic gastritis; ( c ) first degree relatives of patients with gastric cancer; ( d ) patients with unexplained iron deficiency anaemia; and ( e ) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a “test and treat” strategy if other causes are excluded. Eradication of H pylori infection ( a ) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and ( b ) may prevent peptic ulcer in patients who are naive users of non-steroidal anti-inflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility. Conclusion: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development.

https://gut.bmj.com/content/gutjnl/56/6/772.full.pdf

Current concepts in the management of Helicobacter pylori infection - The Maastricht III Consensus Report

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

https://gut.bmj.com/content/gutjnl/66/1/6.full.pdf

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Management of Helicobacter pylori infection is evolving and in this 4th edition of the Maastricht consensus report aspects related to the clinical role of H pylori were looked at again in 2010. In the 4th Maastricht/Florence Consensus Conference 44 experts from 24 countries took active part and examined key clinical aspects in three subdivided workshops: (1) Indications and contraindications for diagnosis and treatment, focusing on dyspepsia, non-steroidal anti-inflammatory drugs or aspirin use, gastro-oesophageal reflux disease and extraintestinal manifestations of the infection. (2) Diagnostic tests and treatment of infection. (3) Prevention of gastric cancer and other complications. The results of the individual workshops were submitted to a final consensus voting to all participants. Recommendations are provided on the basis of the best current evidence and plausibility to guide doctors involved in the management of this infection associated with various clinical conditions.

/pdf/management-of-helicobacter-pylori-infection-the-maastricht-49ckggvuif.pdf

Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report

Background Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. Methods We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. Results Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metap...

Helicobacter pylori infection and the development of gastric cancer

A 25-year-old woman presented with a 15-month history of catamenial hemoptysis. The patient reported recurrent episodes of hemoptysis lasting 4–5 days, beginning on the day prior to or the first day of her menstrual cycle and resolving spontaneously. The patient was completely asymptomatic between menses. Her past medical history was significant for a spontaneous abortion and chronic hepatitis C treated with interferon. Her physical examination, including gynecologic examination, was unremarkable. The results of the laboratory examinations including complete blood count, liver function tests and urinalysis were within the normal range. Additional evaluation revealed a bleeding time of 2 min, a coagulation time of 9.5 min, and a sputum culture that grew normal flora. Her chest roentgenogram revealed a faint consolidation in the left lower lung field. Subsequent chest computed tomography revealed a 2-cm infiltrate in the anterior basal segment of the left lower lobe, most consistent with hemorrhage within the lung. Fiberoptic bronchoscopy was performed during a symptomatic period which revealed bleeding from a bronchus in the anterior basal segment of the left lower lobe. A bronchial washing was performed with 7 ml of saline. There was no bronchoscopic evidence of endobronchial or mucosal lesions. The bronchial washing was centrifuged at 700 g for 5 min, and a smear of the sediment was fixed with a fixative spray and stained by the Papanicolaou method. Cytologic examination of the sample showed clusters of columnar and cuboidal epithelial cells consistent with endometrial epithelium (fig. 1). Bronchial washings, obtained at the same time, were negative for acid-fast bacilli and fungi. Following the bronchoscopic examination, the patient had two additional episodes of catamenial hemoptysis followed by resolution of her symptoms. She has remained asymptomatic for 6 months. The final diagnosis was pulmonary endometriosis. The roentgenographic work-up of parenchymal pulmonary endometriosis often has a low diagnostic yield, as chest roentgenograms are unremarkable in the majority of cases [1]. In the minority of cases where the chest roentgenogram is abnormal, the findings are sometimes nonspecific and nondiagnostic, such as the findings in our case. Furthermore, histologic confirmation of the diagnosis is often challenging. Therefore, a definitive diagnosis of parenchymal pulmonary endometriosis may be difficult to make. A review of the literature revealed 79 reported cases of parenchymal pulmonary endometriosis. A histologic diagnosis was confirmed in 24 cases. In 50 of the 79 cases, the diagnosis of parenchymal pulmonary endometriosis was made on the basis of clinical history alone. Cytologic examination of sputum, bronchial secretions, or bronchial washings was performed in 21 of the 79 reported cases, and cell clusters consistent with endometrial origin were found in 4 of these cases [2–4]. In our case, fiberoptic bronchoscopy was useful in the diagnosis as a bronchial washing revealed cytologic evidence of an endometrial etiology. Cytologic examination of sputum or bronchial washings has not been used frequently in the diagnosis of parenchymal pulmonary endometriosis. However, considering that histologic confirmation is often difficult and roentgenographic examination is often of minimal diagnostic value, we were impressed by the effectiveness of cytologic examination of bronchial washings in the present case and consider it useful in confirming the diagnosis of parenchymal pulmonary endometriosis.

Michio Yamakido

Papers

Helicobacter pylori infection and the development of gastric cancer

A case of parenchymal pulmonary endometriosis, diagnosed by cytologic examination of bronchial washing.