Association between Helicobacter pylori infection, mismatch repair, HER2 and tumor-infiltrating lymphocytes in gastric cancer.

BACKGROUND: The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information. AIM: To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC. METHODS: Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 immune cells, and dMMR and HER2-status were determined by immunohistochemistry (IHC). H. pylori infection was evaluated by routine histology and quantitative PCR (qPCR) in a subset of samples. RESULTS: dMMR was found in 34.4%, HER2+ in 5% and H. pylori-positive in 55.7% of samples. High IT-TIL was associated with grade-3 (P = 0.038), while ST-TIL with grade-1 (P < 0.001), intestinal-histology (P < 0.001) and no-recurrence (P = 0.003). dMMR was associated with high TIL levels in the ST (P = 0.019) and IB (P = 0.01) compartments, and ST-CD3 (P = 0.049) and ST-CD8 (P = 0.05) densities. HER2- was associated with high IT-CD8 (P = 0.009). H. pylori-negative was associated with high IT-TIL levels (P = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments (P = 0.002-0.047) and CD8 density in the IT and ST compartments (P = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 (P = 0.003) and CD8/CD3 (P = 0.001 in IT and P = 0.002 in ST) and high IT-CD3 (P = 0.021), ST-CD3 (P = 0.003) and CD3/CD163 (P = 0.002). CONCLUSION: TIL levels were related to dMMR and H. pylori-negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

The relationship between tumour infiltrating lymphocytes, Epstein-Barr virus and Helicobacter pylori infection in gastric cancer.

Objective: Epstein-Barr virus (EBV) and Helicobacter pylori (HP) infections have been extensively recognised as gastric cancer (GC) triggers, and recent publications suggest they could behave as predictive markers for immune-modulating therapies. Tumour-infiltrating lymphocytes (TILs) have also been identified as a predictive biomarker for immunotherapy in different malignancies. This study aimed to investigate the association between EBV and HP infection with TIL levels in GC. Methods: TIL evaluation in haematoxylin-eosin was performed by a pathologist and density of CD3, CD8 and CD163 positive (immunohistochemistry staining) immune cells was calculated with the use of digital pathology software. EBV infection was detected by in situ hybridisation (ISH) and by quantitative polymerase chain reaction (qPCR). Methylation status of EBV-related genes was detected by PCR and a methylome analysis was performed by the Illumina Infinium MethylationEPIC BeadChip. HP status was detected by qPCR. Results: We included 98 resected GC Peruvian cases in our evaluation. Median TIL percentage was 30. The proportion of EBV+ detected by ISH was 24.1%, of EBV+ detected by qPCR was 41.8%, while 70% showed methylation of EBV-related genes, and 58.21% of cases were HP+. Younger age (p = 0.024), early stages (p = 0.001), HP+ (p = 0.036) and low CD8 density (p = 0.046) were associated with longer overall survival (OS). High TIL level was associated with intestinal subtype (p < 0.001), with grade 2 (p < 0.001), with EBV qPCR+ (p = 0.001), and with methylation of EBV-related genes (p = 0.007). Cases with high TIL level and cases that are EBV positive share eight genes with similarly methylated status in the metabolomic analysis. High CD8 density was associated with EBV PCR+ (p = 0.012) and HP- (0.005). Conclusion: Lower CD8 density and HP+ predict longer OS. High TIL level is associated with EBV+ and methylation of EBV-related genes, while lower CD8 density is associated with HP+ GC.

Helicobacter Pylori Detected in Tap Water of Peruvian Patients with Gastric Cancer.

OBJECTIVE: To evaluate the correlation between the presence of H. pylori in paired samples of tap water and gastric cancer (GC) lesion in Lima city (Peru). MATERIAL AND METHODS: Gastric tissue and tap-water samples were prospectively collected from 82 Gastric Cancer who lived in Lima. HspA and ureA genes were evaluated by qPCR in the samples.  Results: The median age of patients with GC was 63 years, 52.4% were men and stage-II in 36.6%. A home-living time> 10 years was reported in 84.1% of patients. Boiling water treatment was indicated in 85.4% of cases. H. pylori was detected in 69.5% of gastric tissues and in 12.2% of analyzed tap-water. There was no differences in gastric infection rates among those with or without water contamination (70% vs. 69.4%, p=0.971). Conclusion & Impact: H. pylori was found in tap-water samples, however, detection rates were lower than in gastric cancer samples. Other sources of infection transmission should be investigated.

Prevalence of Helicobacter pylori Infection, Its Virulent Genotypes, and Epstein-Barr Virus in Peruvian Patients With Chronic Gastritis and Gastric Cancer.

PURPOSE: Helicobacter pylori (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection. PATIENTS AND METHODS: A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction. RESULTS: Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The cagA gene was detected in 79.9%; vacAs1 and vacAm1 alleles in 41.6% and 60.7%, respectively; and concurrent expression of vacAs1 and vacAm1 in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC (P < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate (P < .001) and multivariate (P = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status. CONCLUSION: Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.

Edad media de la erupción dental en una población escolar analizada por dos métodos / Mean age of dental eruption in a school-age population analyzed by 2 methods

Introducción: Ya que la erupción dental es el resultado de una serie de eventos fisiológicos, es importante conocer con precisión la edad promedio de exfoliación y erupción de cada órgano dentario, lo que resulta de utilidad para establecer criterios de diagnóstico, prevención y tratamiento. El objetivo de este trabajo fue comparar los métodos de estudio transversal y longitudinal en la estimación de la edad media de la erupción dental. Métodos: Se estudió una muestra de 524 individuos (273 niñas y 251 niños) de 5-9 años de edad en el Estado de México. Se observaron los dientes permanentes presentes: primer molar superior, incisivos central y lateral, y primer molar inferior. Para el método longitudinal, se realizó el seguimiento de los niños durante 3 años, hasta registrar el brote dental. Para el método transversal, se registró la observación de los dientes presentes durante el segundo año de seguimiento. Se utilizó abatelenguas, espejo dental y luz natural. Resultados: En ambos métodos, la erupción dental se presentó primero en el sexo femenino. La edad media de erupción dental entre los dos métodos no mostró diferencia estadística en el 88% de los dientes. Conclusiones: La medición de la edad de erupción dental a través del método transversal proporciona datos confiables con relación al método longitudinal.

Background: Because dental eruption is the result of a series of physiological events, it is important to acknowledge precisely the mean age of exfoliation and eruption of each dental organ. This is useful to establish diagnostic, preventive and treatment criteria. The aim of this study was to compare the cross-sectional and cohort methods toward estimating the average age of dental eruption. Methods: The study sample was comprised of 524 school-age children from the State of Mexico (273 females and 251 males). Only permanent teeth were surveyed: the first upper molar and central and lateral incisors and the first lower molar. The cohort was observed during a 3-year period until the tooth budded. Dental mirror, tongue depressor and day light were used. Cross-sectional method consisted of permanent teeth observed after the first year. Results: In both methods, teeth budded first in females. The average ages of dental eruption according to both methods did not show statistical difference in 88% of the teeth. Conclusions: Measurement of the age of dental eruption through cross-sectional method provides reliable data in relation to the cohort method.

[Mean age of dental eruption in a school-age population analyzed by 2 methods]. / Edad media de la erupción dental en una población escolar analizada por dos métodos.

BACKGROUND: Because dental eruption is the result of a series of physiological events, it is important to acknowledge precisely the mean age of exfoliation and eruption of each dental organ. This is useful to establish diagnostic, preventive and treatment criteria. The aim of this study was to compare the cross-sectional and cohort methods toward estimating the average age of dental eruption. METHODS: The study sample was comprised of 524 school-age children from the State of Mexico (273 females and 251 males). Only permanent teeth were surveyed: the first upper molar and central and lateral incisors and the first lower molar. The cohort was observed during a 3-year period until the tooth budded. Dental mirror, tongue depressor and day light were used. Cross-sectional method consisted of permanent teeth observed after the first year. RESULTS: In both methods, teeth budded first in females. The average ages of dental eruption according to both methods did not show statistical difference in 88% of the teeth. CONCLUSIONS: Measurement of the age of dental eruption through cross-sectional method provides reliable data in relation to the cohort method.

[Metastatic primary gastric adenocarcinoma in amigdala]. / Adenocarcinoma metastásico de amígdala de primario gástrico.

We report the case of a 79 years old female patient, with a one year history of dysphagia, presence of a tumor in the right palatine tonsil and cervical lymph node involvement. A biopsy of the palatine tonsil tumor informed as an adenocarcinoma was performed followed by a gastroscopy that reported a lesion in gastric body and antrum whose histologycal diagnosis was a moderately differentiated tubular adenocarcinoma. The patient received chemotherapy with 5FU. We present this case due to the unusual presentation of metastasis to the palatine tonsil and also for being the first manifestation of a gastric cancer.

Adenocarcinoma Metastásico de Amígdala de Primario Gástrico / Metastatic primary gastric adenocarcinoma in amigdala

Reportamos el caso de una paciente mujer de 79 años, con historia de 1 año de enfermedad caracterizado por disfagia y tumoración en amígdala derecha y adenopatía cervical. Se le realiza biopsia de tumoración amigdalina que fue diagnosticada como Adenocarcinoma, realizándose posteriormente una gastroscopia encontrándose una lesión en cuerpo y antro con estudio histopatológico de Adenocarcinoma Tubular infiltrante moderadamente diferenciado. La paciente recibió posteriormente quimioterapia con 5FU. Presentamos el caso debido a lo inusual que es encontrar metástasis amigdalina, siendo ésta además la primera manifestación de un cáncer gástrico.

We report the case of a 79 years old female patient, with a one year history of dysphagia, presence of a tumor in the right palatine tonsil and cervical lymph node involvement. A biopsy of the palatine tonsil tumor informed as an adenocarcinoma was performed followed by a gastroscopy that reported a lesion in gastric body and antrum whose histologycal diagnosis was a moderately differentiated tubular adenocarcinoma. The patient received chemotherapy with 5FU. We present this case due to the unusual presentation of metastasis to the palatine tonsil and also for being the first manifestation of a gastric cancer.