The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Self-expanding metal stents versus antrectomy for the palliative treatment of obstructive adenocarcinoma of the gastric antrum Prótesis metálicas autoexpandibles versus antrectomía en el tratamiento paliativo del adenocarcinoma obstructivo del antro gástrico

Background: gastric cancer patients are first diagnosed with an unresectable tumor in up to 40% of cases. Gastric outlet obstruction causes nausea, vomiting, dehydration and malnutrition. The aim of the study was to compare self-expanding metal stents to antrectomy and Roux-en Y gastrojejunostomy for palliation of obstructive adenocarcinoma of the gastric antrum. Methods: retrospective study in patients with obstructing cancer of the gastric antrum. Patients were divided into two groups: group A, underwent endoscopic placement of self-expanding metal stents and group B underwent surgical treatment with antrectomy and Roux-en Y gastrojejunostomy. Collected Data included: age, gender, performance status (Karnofsky's score), body mass index, histopathology, clinical stage (TNM classification), technical and clinical success of the procedure, time to oral intake, in-hospital stay, re-intervention rate, and complications related to the treatment and survival. Results: a total of 39 patients with gastric adenocarcinoma were included, 21 male and 18 female. Nineteen patients were assigned to group A and 20 patients to group B. There were no statistically significant differences between groups in regards to age, body mass index, Karnofsky's score and clinical stage. The technical and clinical success was similar for both groups. There was a statistically significant difference between groups favoring Self-expanding metal stent in time to oral intake (1 ± 0 vs. 4.9 ± 0.6 days, p = 0.0001) and in-hospital stay (0.94 ± 1.18 vs. 7.8 ± 7.7 days, p = 0.0005). We did not find statistically significant differences with regards to long-term survival. Conclusions: in patients with malignant gastric outlet obstruction due to gastric cancer, endoscopic palliation with self-expanding metal stents provide a shorter interval to oral intake, shorter in-hospital stay and lower rate of complications.<br>Introducción: los pacientes con cáncer gástrico tienen un tumor irresecable hasta en el 40% de los casos. La obstrucción de salida gástrica ocasiona vómito, deshidratación y desnutrición. El objetivo de este estudio fue comparar las prótesis metálicas autoexpandibles con la antrectomia en el tratamiento paliativo del adenocarcinoma obstructivo del antro gástrico. Método: estudio restrospectivo en pacientes con adenocarcinoma obstructivo del antro gástrico. Los pacientes fueron divididos en dos grupos: grupo A) sujetos que fueron tratados mediante prótesis metálica autoexpandible y grupo B) aquellos que fueron tratados mediante antrectomía y gastroyeyunoanastomosis en Y de Roux. Las variables recogidas fueron: edad, género, índice de masa corporal, histopatología, estadio clínico (TNM), estado general (escala de Karnofsky), días de estancia intrahospitalaria, necesidad de re-intervención, complicaciones relacionada con el tratamiento y sobrevida. Resultados: fueron incluidos 39 pacientes, 21 hombres y 18 mujeres. Diecinueve pacientes correspondieron al grupo A y 20 al grupo B. No hubo diferencias estadísticamente significativas con respecto a la edad, índice de masa corporal, calificación de Karnofsky y estadio clínico. El éxito técnico y clínico fue similar en ambos grupos. Hubo diferencia estadísticamente significativa entre ambos grupos, favoreciendo a las prótesis metálicas autoexpandibles en tiempo de inicio de la vía oral (1 ± 0 vs. 4,9 ± 0,6 días, p = 0,0001) y estancia intrahospitalaria (0,94 ± 1,18 vs. 7,8 ± 7,7 días, p = 0,0005). No encontramos diferencia estadísticamente significativa con respecto a la sobrevida entre los dos grupos. Conclusiones: en pacientes con obstrucción gástrica secundaria a cáncer gástrico avanzado, el tratamiento con prótesis metálicas autoexpandibles proporciona un intervalo mas corto para el inicio de la vía oral, una estancia intrahospitalaria mas corta y una frecuencia de complicaciones menor

Somatic Mutational Landscape in Mexican Patients: <i>CDH1</i> Mutations and chr20q13.33 Amplifications Are Associated with Diffuse-Type Gastric Adenocarcinoma

The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets