Identification of New Helicobacter pylori Subpopulations in Native Americans and Mestizos From Peru.

Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA +/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.

[Prevalence of histological types of gastric polyps in adult patients from a public hospital in Lima-Peru (2007 - 2016)]. / Prevalencia de tipos histológicos de pólipos gástricos en pacientes adultos de un hospital público de Lima-Perú, en el periodo 2007 al 2016.

OBJECTIVES: Establish the prevalence of gastric polyps detected by upper gastrointestinal endoscopy in patients older than 18 years old during the period from 2007 - 2016 in Cayetano Heredia Hospital. MATERIALS AND METHODS: Retrospective cross-sectional study, performed with data from the gastric biopsies reports of patients that have undergone upper gastrointestinal endoscopy between January 2007 and July 2016. Demographic data, endoscopic characteristics of the polyps and associated histological changes of the surrounding gastric mucosa were evaluated, which were subjected to statistical analysis using STATA v14.2. RESULTS: In a population of 16 552 endoscopies, 407 gastric polyps biopsies were found. These results give a prevalence of 2.5% .Gastric polyps were detected predominantly in women (62.38%). The median age was 61 years (52-71 years). The most frequent histological type was the fundic gland polyp (FGP) (44.85%), followed by the hyperplastic (38.48%) and adenomatous (15.23%) polyp. The most frequent location was in the fundus / corpus (48.65%, p = 0.001). The presence of Hp was detected in 30.6% of the biopsies with polyps. CONCLUSION: The prevalence of gastric polyps is similar to other regions of the world; PGF and hyperplastic are the most frequent. Adenomatous polyps showed a greater relationship with and metaplasia and dysplasia.

Prevalencia de tipos histológicos de pólipos gástricos en pacientes adultos de un hospital público de Lima-Perú, en el periodo 2007 al 2016 / Prevalence of histological types of gastric polyps in adult patients from a public hospital in Lima-Peru (2007 - 2016)

Objetivos: Determinar la prevalencia de pólipos gástricos detectados mediante endoscopía digestiva alta, en pacientes mayores de 18 años del Hospital Cayetano Heredia, en el periodo 2007-2016. Materiales y métodos: Estudio retrospectivo de corte transversal, realizado con datos de biopsias gástricas de pacientes sometidos a endoscopía digestiva alta entre enero de 2007 y julio de 2016. Se evaluó cambios histológicos asociados, datos demográficos y características endoscópicas, las cuales fueron sometidas a análisis estadístico mediante STATA v14.2. Resultados: En una población de 16 552 endoscopías realizadas, se encontró 407 biopsias compatibles con pólipos gástricos, lo cual da una prevalencia de 2,5%. Los pólipos gástricos fueron más frecuentes en mujeres (62,38%). La mediana de edad fue de 61 años (52-71 años). El tipo histológico más frecuente fue el pólipo glandular fúndico (PGF) (44,85%), seguido de pólipo hiperplásico (38,48%) y adenomatoso (15,23%). La localización más frecuente fue en fondo/cuerpo (48,65%, p=0,001) Se detectó la presencia de Helicobacter pylori (Hp) en el 30,6% de las biopsias compatibles con pólipos. Conclusión: La prevalencia de pólipos gástricos es similar con otras regiones del mundo; los PGF e hiperplásicos son los más frecuentes. Los pólipos adenomatosos estuvieron en mayor relación a cambios como metaplasia y displasia.

Objectives: Establish the prevalence of gastric polyps detected by upper gastrointestinal endoscopy in patients older than 18 years old during the period from 2007 - 2016 in Cayetano Heredia Hospital. Materials and methods: Retrospective cross- sectional study, performed with data from the gastric biopsies reports of patients that have undergone upper gastrointestinal endoscopy between January 2007 and July 2016. Demographic data, endoscopic characteristics of the polyps and associated histological changes of the surrounding gastric mucosa were evaluated, which were subjected to statistical analysis using STATA v14.2. Results: In a population of 16 552 endoscopies, 407 gastric polyps biopsies were found. These results give a prevalence of 2.5% .Gastric polyps were detected predominantly in women (62.38%). The median age was 61 years (52-71 years). The most frequent histological type was the fundic gland polyp (FGP) (44.85%), followed by the hyperplastic (38.48%) and adenomatous (15.23%) polyp. The most frequent location was in the fundus / corpus (48.65%, p = 0.001). The presence of Hp was detected in 30.6% of the biopsies with polyps. Conclusion: The prevalence of gastric polyps is similar to other regions of the world; PGF and hyperplastic are the most frequent. Adenomatous polyps showed a greater relationship with and metaplasia and dysplasia.

Histological Examination in Obtaining a Diagnosis in Patients with Lymphadenopathy in Lima, Peru.

The differential diagnosis for lymphadenopathy is wide and clinical presentations overlap, making obtaining an accurate diagnosis challenging. We sought to characterize the clinical and radiological characteristics, histological findings, and diagnoses for a cohort of patients with lymphadenopathy of unknown etiology. 121 Peruvian adults with lymphadenopathy underwent lymph node biopsy for microbiological and histopathological evaluation. Mean patient age was 41 years (Interquartile Range 26-52), 56% were males, and 39% were HIV positive. Patients reported fever (31%), weight loss (23%), and headache (22%); HIV infection was associated with fever (P < 0.05) and gastrointestinal symptoms (P < 0.05). Abnormalities were reported in 40% of chest X-rays (N = 101). Physicians suspected TB in 92 patients (76%), lymphoma in 19 patients (16%), and other malignancy in seven patients (5.8%). Histological diagnoses (N = 117) included tuberculosis (34%), hyperplasia (27%), lymphoma (13%), and nonlymphoma malignancy (14%). Hyperplasia was more common (P < 0.001) and lymphoma less common (P = 0.005) among HIV-positive than HIV-negative patients. There was a trend toward reduced frequency of caseous necrosis in samples from HIV-positive than HIV-negative TB patients (67 versus 93%, P = 0.055). The spectrum of diagnoses was broad, and clinical and radiological features correlated poorly with diagnosis. On the basis of clinical features, physicians over-diagnosed TB, and under-diagnosed malignancy. Although this may not be inappropriate in resource-limited settings where TB is the most frequent easily treatable cause of lymphadenopathy, diagnostic delays can be detrimental to patients with malignancy. It is important that patients with lymphadenopathy undergo a full diagnostic work-up including sampling for histological evaluation to obtain an accurate diagnosis.

[Validation of the rapid urease test for the detection of Helicobacter pylori in a Peruvian hospital]. / Validación del test rápido de la ureasa para la detección del Helicobacter pylori en el Hospital Nacional Cayetano Heredia, Lima, Perú.

OBJECTIVE: To validate a rapid urease test (RUT) in Cayetano Heredia Hospital (HCH) in Lima, Peru. MATERIALS AND METHODS: This is a prospective observational study that included 181 patients over 18 years old with dyspeptic symptoms. All of them underwent upper gastrointestinal endoscopy at the Department of Gastroenterology at HCH. They had not received, during the last four weeks, proton pump inhibitors (PPIs), bismuth or antibiotics. Two biopsies of antrum were taken, one to perform the TRU (Sensibacter pylori test®) and the other one for pathology, in order to determine by both methods the presence of H. pylori infection. TRU's results were compared with pathology ́s (gold standard). RESULTS: 181 patients, average age 52.8±13.5 years, were evaluated. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) at 20 minutes were 86.8%, 98.5%, 81.5% and 99% and at 24 hours 97.3%, 99.5%, 95.7% y 99.1% respectively. CONCLUSION: The rapid urease test is a reliable, accessible and easy to apply test for the diagnosis of H. pylori infection.

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies.

Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project ("TCGA"). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a continuous biomarker panel that combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation levels of IRF4, ELMO1, CLIP4 and MSC.We observed an inverse association between the GDMI and histological progression to gastric cancer, when comparing gastritis patients without metaplasia (mean = 5.74, 95% CI, 4.97-6.50), gastritis patients with metaplasia (mean = 4.81, 95% CI, 3.77-5.84), and gastric cancer cases (mean = 3.38, 95% CI, 2.82-3.94), respectively (p < 0.0001). Promoter methylation of IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001), is also associated with increasing severity from gastritis with no metaplasia to gastritis with metaplasia and gastric cancer.Our findings suggest that IRF4, ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful molecular tools for gastric cancer risk stratification in endoscopic biopsies.

Miastenia gravis de tipo bulbar en niños: un caso de difícil diagnóstico / Bulbar Myasthenia Gravis in children: a case of difficult diagnosis

La miastenia gravis (MG) es un trastorno autoinmune caracterizado por debilidad y fatigabilidad de los músculos esqueléticos debida a la disfunción de la unión neuromuscular. Se presenta el caso de una adolescente de 11 años de edad, con diagnóstico de miastenia gravis de tipo bulbar. La paciente presentó dos crisis de MG previamente diagnosticadas de manera equivocada como crisis asmáticas. Recibió tratamiento con inmunoglobulina humana, corticoides, piridostigmina y timectomía. Se discute la evolución clínica y riesgos atribuibles a situaciones sociales que pueden retrasar el diagnóstico y su manejo efectivo.

Myasthenia gravis (MG) is an autoimmune disorder characterized by weakness and fatigability of the skeletal muscles due to dysfunction of the neuromuscular junction. We report the case of an 11-year-old girl diagnosed with bulbar myasthenia gravis. The patient had two previous crises of myasthenia gravis erroneously diagnosed as asthma attacks. She received treatment with human immunoglobulin, corticosteroids, pyridostigmine and thymectomy. We discuss the clinical course and the risks attributable to social situations that can delay the diagnosis and its effective management.

Validación del test rápido de la ureasa para la detección del Helicobacter pylori en el Hospital Nacional Cayetano Heredia, Lima, Perú / Validation of the rapid urease test for the detection of Helicobacter pylori in a Peruvian hospital

Objetivos: Validar un test rápido de la ureasa (TRU) en el Hospital Cayetano Heredia (HCH) de Lima, Perú Materiales y métodos: Estudio observacional prospectivo. Se incluyó 181 pacientes mayores de 18 años de edad con síntomas dispépticos, que fueron sometidos a endoscopía digestiva alta en el Servicio de Gastroenterología del HCH y que no hubiesen recibido durante las últimas cuatro semanas inhibidores de la bomba de protones (IBPs), bismuto o antibióticos. Se tomó dos biopsias de antro una para hacer el TRU (Sensibacter pylori test®) y otra para anatomía patológica con el fin de determinar la presencia de la infección por H. pylori por ambos métodos. Finalmente se comparó el resultado de la anatomía patológica (patrón de oro) con el de TRU. Resultados: Se evaluó 181 pacientes, la edad promedio fue 52,8±13,5 años. La sensibilidad, especificidad, valor predictivo negativo (VPN), valor predictivo positivo (VPP) a los 20 minutos fueron de 86,8%, 98,5%, 81,5% y 99% y a las 24 horas 97,3%, 99,5%, 95,7% y 99,1% respectivamente. Conclusión: El TRU es un test confiable, accesible y de fácil aplicación para hacer el diagnóstico de la infección por H. pylori.

Objective: To validate a rapid urease test (RUT) in Cayetano Heredia Hospital (HCH) in Lima, Peru. Materials and methods: This is a prospective observational study that included 181 patients over 18 years old with dyspeptic symptoms. All of them underwent upper gastrointestinal endoscopy at the Department of Gastroenterology at HCH. They had not received, during the last four weeks, proton pump inhibitors (PPIs), bismuth or antibiotics. Two biopsies of antrum were taken, one to perform the TRU (Sensibacter pylori test®) and the other one for pathology, in order to determine by both methods the presence of H. pylori infection. TRU’s results were compared with pathology´s (gold standard). Results: 181 patients, average age 52.8±13.5 years, were evaluated. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) at 20 minutes were 86.8%, 98.5%, 81.5% and 99% and at 24 hours 97.3%, 99.5%, 95.7% y 99.1% respectively. Conclusion: The rapid urease test is a reliable, accessible and easy to apply test for the diagnosis of H. pylori infection.

Soil-Transmitted Helminth Infections Are Associated With an Increase in Human Papillomavirus Prevalence and a T-Helper Type 2 Cytokine Signature in Cervical Fluids.

BACKGROUND: An ecological correlation between invasive cervical cancer incidence and burden of soil-transmitted helminths (STH) is hypothesized to explain the excess in detectable human papillomavirus (HPV) infection in Latin America, via a global T-helper type 2 (Th2)-biased mucosal immune response secondary to STH infection. METHODS: The association between current STH infection and HPV prevalence was compared in regions of Peru where STH is or is not endemic. Adjusted prevalence ratios (PRs) with robust variance were estimated as an effect measure of STH infection on HPV prevalence in each study site. Soluble immune marker profiles in STH-infected and STH-uninfected women were compared using Spearman rank correlation with the Sidak correction. RESULTS: Among women in the helminth-endemic region of the Peruvian Amazon, those with STH infection women had a 60% higher prevalence of HPV, compared with those without STH infection (PR, 1.6; 95% confidence interval, 1.0-2.7). Non-STH parasitic/protozoal infections in the non-STH-endemic population of Peru were not associated with HPV prevalence. In Iquitos, A Th2 immune profile was observed in cervical fluid from helminth-infected women but not helminth-uninfected women. CONCLUSIONS: A proportion of the increased HPV prevalence at older ages observed in Latin America may be due to a population-level difference in the efficiency of immunological control of HPV across the lifespan due to endemic STH infection.

Correlación entre síntomas gastrointestinales funcionales y la histopatología de la mucosa gástrica, incluyendo la infección por Helicobacter pylori, en Lima, Perú.

OBJECTIVE: This study aims to investigate the relationship between functional gastrointestinal disorders and histopathology characteristics, including H. pylori infection, of gastric mucosa, at Cayetano Heredia National Hospital, Lima-Peru, in 2013. MATERIALS AND METHODS: 112 patients were interviewed prospectively between June and July 2013 in the gastroenterology service. Dyspepsia, irritable bowel syndrome, and postprandial distress syndrome were characterized using the Rome III Survey. RESULTS: Pathology results were determined by gastric biopsies obtained by endoscopy. Of the patients interviewed, biopsy results were obtained for 101. 22.8% had atrophy, 24.8% had intestinal metaplasia, 57.4% presented with H pylori. CONCLUSIONS: Using chi-square analysis, no statistically significant relationship could be identified between clinical presentation and biopsy results.

Correlación entre síntomas gastrointestinales funcionales y la histopatología de la mucosa gástrica, incluyendo la infección por Helicobacter pylori, en Lima, Perú / Correlation between functional gastrointestinal disorders and gastric mucosa histopathology findings, including Helicobacter pylori infection, in Lima, Peru

This study aims to investigate the relationship between functional gastrointestinal disorders and histopathology characteristics, including H. pylori infection, of gastric mucosa, at Cayetano Heredia National Hospital, Lima-Peru, in 2013. Materials and methods: 112 patients were interviewed prospectively between June and July 2013 in the gastroenterology service. Dyspepsia, irritable bowel syndrome, and postprandial distress syndrome were characterized using the Rome III Survey. Results: Pathology results were determined by gastric biopsies obtained by endoscopy. Of the patients interviewed, biopsy results were obtained for 101. 22.8% had atrophy, 24.8% had intestinal metaplasia, 57.4% presented with H pylori. Conclusions: Using chisquare analysis, no statistically significant relationship could be identified between clinical presentation and biopsy results...

El objetivo de este estudio fue investigar la correlación que existe entre la presencia de síntomas gastrointestinales y los hallazgos histopatológicos de la biopsia gástrica incluyendo la presencia de la infección por Helicobacter pylori. Materiales y métodos: Este estudio prospectivo comprendió a 112 pacientes que se incluyeron entre junio y julio de 2013 en el Servicio de Gastroenterología del Hospital Nacional Cayetano Heredia, Lima-Perú a los que se les hizo endoscopía y biopsia gástrica. Los síntomas de dispepsia, síndrome de intestino irritable y síndrome de distrés post prandial fueron obtenidos usando las encuestas de Roma III. Resultados: De los pacientes a los que se les hizo la encuesta sólo en 101 se les evaluó la biopsia. 22,8% tuvo atrofia, 24,8% presentó metaplasia intestinal, y en 57,4% se reportó la infección por Helicobacter pylori. Conclusiones: Usando el análisis con chi-cuadrado no se pudo establecer ninguna correlación estadísticamente significativa entre la presentación clínica y los resultados de las biopsias...

Detection of soluble antigen and DNA of Trypanosoma cruzi in urine is independent of renal injury in the guinea pig model.

The diagnosis of Chagas disease in humans is generally limited to the detection of specific antibodies. Detection of T. cruzi antigens in urine has been reported previously, but is not used in the diagnosis. In this study, soluble T. cruzi antigens and DNA were detected in urine samples and were associated with kidney injury and systemic detection of the parasite. We used 72 guinea pigs infected with T. cruzi Y strain and 18 non-infected guinea pigs. Blood, kidney, heart and urine samples were collected during the acute phase and chronic phase. Urine samples were concentrated by ultrafiltration. Antigens were detected by Western Blot using a polyclonal antibody against trypomastigote excretory-secretory antigen (TESA). T. cruzi DNA was detected by PCR using primers 121/122 and TcZ1/TcZ2. Levels of T. cruzi DNA in blood, heart and kidney were determined by quantitative PCR. T. cruzi antigens (75 kDa, 80 kDa, 120 kDa, 150 kDa) were detected in the acute phase (67.5%) and the chronic phase (45%). Parasite DNA in urine was detected only in the acute phase (45%). Kidney injury was characterized by high levels of proteinuria, kidney injury molecule-1 (KIM-1) and urea, and some histopathological changes such as inflammation, necrosis, fibrosis and scarce parasites. The detection of antigens and DNA in urine was associated with the presence of parasite DNA in blood and heart and with high levels of parasite DNA in blood, but not with the presence of parasite in kidney or kidney injury. These results suggest that the detection of T. cruzi in urine could be improved to be a valuable method for the diagnosis of Chagas disease, particularly in congenital Chagas disease and in immunocompromised patients.

Colonoscopic findings in Peruvian patients with chronic diarrhea.

OBJECTIVE: To report the colonoscopic and pathological findings in patients with chronic diarrhea from a gastroenterology unit during approximately 3 years in a general teaching hospital located in Lima-Peru. MATERIALS AND METHODS: Patients with chronic diarrhea as the motive for colonoscopy from March 2008 to December 2010 were selected from the colonoscopy report computerized database. Colonoscopic findings were registered. Biopsies taken during the procedure were prospectively reviewed. RESULTS: 226 patients were included, of which 162 (71.7%) had a colon biopsy available. The average age of the patients was 53.6±16.36. 85.8% of patients were reported to have a normal colon. 14.8% of patients were found to have a normal colonic mucosa or mucosal edema, 35.8% of patients had lymphocytic colitis and 28.4% had paucicelular colitis. CONCLUSIONS: The majority of colonoscopies were reported with unremarkable macroscopic findings. Lymphocytic colitis was unusually frequent compared to previous reports.

Socioeconomic and nutritional factors account for the association of gastric cancer with Amerindian ancestry in a Latin American admixed population.

Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.

[Stromal tumor of esophagus: case report]. / Tumor estromal de esófago: reporte de caso.

Gastrointestinal stromal cell tumors (GIST) are rare neoplasms of the gastrointestinal tract, although they are the most common mesenchymal neoplasms. The stomach and small intestine are the most frequent site of involvement accounting for approximately 85% of cases. However, esophagus involvement is exceptional (<5%); indeed some large series fail to report it. Surgery resection is the cornerstone of treatment; currently imatinib has demonstrated its utility to reduce local recurrences and tumor mass. We report a 75 years-old male with a medical history of dysphagia who presented upper gastrointestinal bleeding caused by an esophageal GIST. The patient did not undergo surgery because of severe chronic heart failure.

Dimorphic fungal coinfection as a cause of chronic diarrhea and pancolitis.

Histoplasma capsulatum and Paracoccidioides brasiliensis are dimorphic fungi that cause systemic mycosis mostly in tropical South America and some areas of North America. Gastrointestinal involvement is not uncommon among these fungal diseases, but coinfection has not previously been reported. We report a patient with chronic diarrhea and pancolitis caused by paracoccidioidomycosis and histoplasmosis.

Attenuated CagA oncoprotein in Helicobacter pylori from Amerindians in Peruvian Amazon.

Population genetic analyses of bacterial genes whose products interact with host tissues can give new understanding of infection and disease processes. Here we show that strains of the genetically diverse gastric pathogen Helicobacter pylori from Amerindians from the remote Peruvian Amazon contain novel alleles of cagA, a major virulence gene, and reveal distinctive properties of their encoded CagA proteins. CagA is injected into the gastric epithelium where it hijacks pleiotropic signaling pathways, helps Hp exploit its special gastric mucosal niche, and affects the risk that infection will result in overt gastroduodenal diseases including gastric cancer. The Amerindian CagA proteins contain unusual but functional tyrosine phosphorylation motifs and attenuated CRPIA motifs, which affect gastric epithelial proliferation, inflammation, and bacterial pathogenesis. Amerindian CagA proteins induced less production of IL-8 and cancer-associated Mucin 2 than did those of prototype Western or East Asian strains and behaved as dominant negative inhibitors of action of prototype CagA during mixed infection of Mongolian gerbils. We suggest that Amerindian cagA is of relatively low virulence, that this may have been selected in ancestral strains during infection of the people who migrated from Asia into the Americas many thousands of years ago, and that such attenuated CagA proteins could be useful therapeutically.

Tumor estromal de esófago: reporte de caso / Stromal tumor of esophagus: case report

Los tumores del estroma gastrointestinales (GIST) son neoplasias poco frecuentes del tracto digestivo, sin embargo, son los tumores mesenquimales más frecuentes. El estómago y el intestino delgado son los lugares de presentación más comunes representando aproximadamente el 85 por ciento de los casos. Por otro lado la ubicación esofágica es excepcional (<5 por ciento), inclusive existen grandes series donde su frecuencia no se reporta. El manejo quirúrgico es el tratamiento definitivo, sin embargo actualmente con el uso de imatinib se ha podido disminuir la frecuencia de recurrencias y la masa tumoral. Presentamos un paciente varón de 75 años con antecedente de disfagia que presentó hemorragia digestiva alta debido a un GIST de esófago. El paciente no fue sometido a manejo quirúrgico, debido a una severa insuficiencia cardiaca.

Gastrointestinal stromal cell tumors (GIST) are rare neoplasms of the gastrointestinal tract, although they are the most common mesenchymal neoplasms. The stomach and small intestine are the most frequent site of involvement accounting for approximately 85 percent of cases. However, esophagus involvement is exceptional (<5 percent); indeed some large series fail to report it. Surgery resection is the cornerstone of treatment; currently imatinib has demonstrated its utility to reduce local recurrences and tumor mass. We report a 75 years-old male with a medical history of dysphagia who presented upper gastrointestinal bleeding caused by an esophageal GIST. The patient did not undergo surgery because of severe chronic heart failure.

Helicobacter pylori from Peruvian amerindians: traces of human migrations in strains from remote Amazon, and genome sequence of an Amerind strain.

BACKGROUND: The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes. PRINCIPAL FINDINGS: Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia. This suggests descent of Shimaa strains from H. pylori that had infected the people who migrated from Asia into The Americas some 15,000+ years ago. In contrast, European type sequences predominated in strains from Amerindian Lima shantytown residents, but with some 12% Amerindian or East Asian-like admixture, which indicates displacement of ancestral purely Amerindian strains by those of hybrid or European ancestry. The genome of one Shimaa village strain, Shi470, was sequenced completely. Its SNP pattern was more Asian- than European-like genome-wide, indicating a purely Amerind ancestry. Among its unusual features were two cagA virulence genes, each distinct from those known from elsewhere; and a novel allele of gene hp0519, whose encoded protein is postulated to interact with host tissue. More generally, however, the Shi470 genome is similar in gene content and organization to those of strains from industrialized countries. CONCLUSIONS: Our data indicate that Shimaa village H. pylori descend from Asian strains brought to The Americas many millennia ago; and that Amerind strains are less fit than, and were substantially displaced by, hybrid or European strains in less isolated communities. Genome comparisons of H. pylori from Amerindian and other communities should help elucidate evolutionary forces that have shaped pathogen populations in The Americas and worldwide.