NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori.

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

Polymorphisms PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in a high risk population.

Genetic variants are considered risk factors for gastric cancer. To date, 61 polymorphisms have been identified as associated with this disease. The aim of the present study was to analyze the association of some of those polymorphisms with GC in Chile. We performed a case-control study including 310 gastric cancer cases and 311 controls to assess the association of 36 single-nucleotide polymorphisms genotyped by Global Screening Array (GSA). Three polymorphisms was significantly associated: PSCA rs2294008 (allele model, OR = 1.49, 95%CI 1.17-1.88, P = 1.08 × 10-3), IL-4 rs2243250 (allele model, OR = 1.28, 95%CI 1.01-1.62, P = 0.04), and MUC1 rs4072037 (allele model, OR = 0.78, 95%CI 0.61-0.99, P = 0.04).PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in Chile. It suggests that those polymorphisms could be used as biomarkers to assess the genetic risk for this cancer outside of the previously studied populations, not only for East Asians and Caucasians populations.

Polymorphisms in RAS/RAF/MEK/ERK Pathway Are Associated with Gastric Cancer.

The RAS/RAF/MEK/ERK pathway regulates certain cellular functions, including cell proliferation, differentiation, survival, and apoptosis. Dysregulation of this pathway leads to the occurrence and progression of cancers mainly by somatic mutations. This study aimed to assess if polymorphisms of the RAS/RAF/MEK/ERK pathway are associated with gastric cancer. A case-control study of 242 gastric cancer patients and 242 controls was performed to assess the association of 27 single nucleotide polymorphisms (SNPs) in the RAS/RAF/MEK/ERK pathway genes with gastric cancer. Analyses performed under the additive model (allele) showed four significantly associated SNPs: RAF1 rs3729931 (Odds ratio (OR) = 1.54, 95%, confidence interval (CI): 1.20⁻1.98, p-value = 7.95 × 10-4), HRAS rs45604736 (OR = 1.60, 95% CI: 1.16⁻2.22, p-value = 4.68 × 10-3), MAPK1 rs2283792 (OR = 1.45, 95% CI: 1.12⁻1.87, p-value = 4.91 × 10-3), and MAPK1 rs9610417 (OR = 0.60, 95% CI: 0.42⁻0.87, p-value = 6.64 × 10-3). Functional annotation suggested that those variants or their proxy variants may have a functional effect. In conclusion, this study suggests that RAF1 rs3729931, HRAS rs45604736, MAPK1 rs2283792, and MAPK1 rs9610417 are associated with gastric cancer.

Polymorphisms in TWIST1 and ZEB1 Are Associated with Prognosis of Gastric Cancer Patients.

BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) program has been linked as a driver of metastatic dissemination by conferring migratory and invasive capacity to cancer cells. Gastric cancer (GC) patients with tumors expressing altered levels of EMT markers have low survival. This study aimed to assess if polymorphisms of CDH1, TWIST1, SNAIL2, ZEB1 and ZEB2 genes are associated with survival in GC patients. PATIENTS AND METHODS: A total of 153 individuals with diagnosis of GC were recruited in Santiago, Chile. All patients were genotyped using Infinium Global Screening Array (GSA). Twenty Tag SNPs of the studied genes were retrieved. RESULTS: Three SNPs were associated with survival: rs2526614 (TWIST1) (genotype CA + AA, adjusted HR=0.58, 95%CI=0.37-0.93), rs6953766 (TWIST1) (genotype GG, crude HR=2.02, 95%CI=1.06-3.82, adjusted HR=2.14, 95%CI=1.07-4.25), and rs431073 (ZEB1) (genotype AC + CC, crude HR=1.62, 95%CI=1.01-2.59, adjusted HR=1.96, 95%CI=1.18-3.25). CONCLUSION: To the best of our knowledge, this is the first study proposing a role of these SNPs in cancer prognosis. Their use as prognostic markers of GC survival warrants further investigation.

IL-8-251T>A (rs4073) Polymorphism Is Associated with Prognosis in Gastric Cancer Patients.

BACKGROUND/AIM: Inflammation is a key process in gastric carcinogenesis. Cytokines are mediators of inflammation and are involved in metastasis and tumorigenicity. We previously assessed the role of cytokine gene polymorphisms in gastric cancer risk in Chile. In the present study, we aimed to analyze whether these polymorphisms are associated with overall survival (OS) in gastric cancer (GC) patients. PATIENTS AND METHODS: A total of 153 individuals with GC diagnosis were followed-up for at least 2 years. Hazard ratios (HR) were estimated from Cox regression models using SNPs as predictor variables. The following SNPs were genotyped for study using a TaqMan assay: rs16944 (IL1B -511C>T); rs4073 (IL8 -251 T>A); rs2275913 (IL-17 -197G>A); rs1800872 (IL10 -592 C>A); rs1800896 (IL10 -1082A>G); rs28372698 (IL32). RESULTS: Interleukin-8 rs4073 (IL-8 -251T>A) showed association with OS under the dominant model (TA + AA) only when adjusted by clinicopathological variables (HR=1.64, 95%CI=1.05-2.55, p=0.030, q-value=0.18), but not with the univariate model (HR=1.51, 95%CI=0.98-2.31, p=0.062, q-value=0.37). No significant differences were observed after adjusting for population stratification (PC1 and PC2 from Principal Component Analysis using genotypes from Infinium Global Screening Array). After stratification by clinicopathological variables, the association with shorter overall survival was higher among patients with diffuse-type tumors (HR=2.24, 95%CI=1.16-4.45) and patients with tumor size >5 cm (HR=1.79, 95%CI=1.08-2.97). CONCLUSION: These results suggest a role of IL-8 rs4073 in cancer prognosis. Its use as a prognostic marker of GC survival warrants further investigation.

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

Role of cytokine gene polymorphisms in gastric cancer risk in Chile.

AIM: To assess the role of pro- and anti-inflammatory polymorphisms in gastric cancer susceptibility. PATIENTS AND METHODS: We genotyped 12 polymorphisms in eight cytokine genes (Interleukin-1ß -IL1B-, IL8, IL17A, IL17F, IL32, tumor necrosis factor-α -TNF-, IL1RN, IL10) in a case-control study of 147 patients with gastric cancer and 172 controls. RESULTS: Single polymorphism analysis revealed an association between the IL10 -592C>A single nucleotide polymorphism and cases with moderately- or well-differentiated tumors [AA vs. GG, odds ratio (OR)=3.01; 95% confidence interval (CI)=1.08-8.50]. We further analyzed gene-gene interactions using a combined attribute network implemented in multifactor dimensionality reduction software. The analysis revealed an interaction between IL8 -251A>T and IL32 rs28372698 SNPs among cases with moderately- or well-differentiated tumors. Homozygosity for both IL8 -251T and IL32 T alleles increases the odds for developing gastric cancer up to 2.63-fold (OR=2.63; 95% CI=1.15-6.03). This association was higher compared to the homozygosity for the IL8-251 T allele alone (OR=1.11; 95% CI=0.51-2.43) or the IL32 T allele alone (OR=1.21; 95% CI=0.54-2.72). CONCLUSION: These findings suggest that IL10 -592C>A increases the odds for developing gastric cancer. An interaction between IL8 -251A>T and IL32 rs28372698 SNPs is also proposed.

Melanoma maligno primario atípico de esófago y su manejo quirúrgico: a propósito de un caso clínico / Atypical primary malignant melanoma of esophagus and the surgical management: Case report

Resumen Introducción El melanoma maligno primario de esófago es un tumor raro y muy agresivo. De manejo controversial, el tratamiento quirúrgico es el que predomina en enfermedad localizada. Caso clínico Presentamos el caso de una mujer joven con melanoma maligno primario de esófago de presentación atípica y su manejo quirúrgico utilizando la técnica de Akiyama.

Introduction The Primary Malignant Melanoma of Esophagus is an uncommon and very agressive tumor. With controversial management, it predominates the surgical treatment in localized disease. Clinical case We present the case of a young women with Primary Malignant Melanoma of Esophagus with atypical presentation and its surgical management using the Akiyama technique.

[Peliosis hepatis: report of one case]. / Peliosis hepática focal: Caso clínico radiológico.

Peliosis hepatis is a rare vascular condition of the liver characterized by the presence of cystic blood-fi lled cavities distributed randomly throughout the liver parenchyma. We report a 46 year old female, with dyspepsia. An abdominal Doppler ultrasound showed a hyper vascularized solid liver nodule of 5 cm diameter. Magnetic resonance imaging and CT scan showed the same hyper vascularized nodule. With the possible diagnoses of primary hepatocellular carcinoma or focal nodular hyperplasia, the patient was subjected to an excision of hepatic segment VI, where the nodule was located. The pathological diagnosis of the surgical piece was a peliosis hepatis.

Peliosis hepática focal: Caso clínico radiológico / Peliosis hepatis: Report of one case

Peliosis hepatis is a rare vascular condition of the liver characterized by the presence of cystic blood-fi lled cavities distributed randomly throughout the liver parenchyma. We report a 46 year old female, with dyspepsia. An abdominal Doppler ultrasound showed a hyper vascularized solid liver nodule of 5 cm diameter. Magnetic resonance imaging and CT scan showed the same hyper vascularized nodule. With the possible diagnoses of primary hepatocellular carcinoma or focal nodular hyperplasia, the patient was subjected to an excision of hepatic segment VI, where the nodule was located. The pathological diagnosis of the surgical piece was a peliosis hepatis.

Resultados inmediatos y sobrevida alejada en cáncer gástrico: estudio de 108 pacientes sometidos a gastrectomía total radical D2 con criterio R0 / Immediate results and late survival of radical gastrectomy in 108 patients with resectable gastric cancer

El cáncer gástrico constituye en Chile la primera causa de muerte por cáncer en el hombre y la resección quirúrgica el único tratamiento que puede revertir el curso de la enfermedad. De un total de 195 pacientes operados de cáncer gástrico entre los años 1992 y 2001, se seleccionaron en un trabajo prospectivo los 108 casos sometidos a gastrectomía total con linfadenectomía D2 y resección R0, con los objetivos de evaluar la morbimortalidad postoperatoria, la sobrevida a cinco años y los factores pronósticos asociados. La mortalidad postoperatoria fue de un 0,9 por ciento y las complicaciones se presentaron en el 17,5 por ciento (fístulas 5,5 por ciento y abscesos subfrénicos 4,6 por ciento). La sobrevida global a 1 año fue 87,6 por ciento, a 3 años 61,1 por ciento y a 5 años 48,9 por ciento; para los cánceres precoces la sobrevida a cinco años fue 87,5 por ciento y para los avanzados 47 por ciento. En el análisis univariado los factores pronósticos significativos fueron el T, precoz versus avanzado y el compromiso linfonodal. En el análisis multivariado el único factor pronóstico significativo fue el compromiso linfonodal.

Pancreatitis aguda / Acute pancreatitis

La pancreatitis aguda es una entidad frecuente en nuestro medio. La enfermedad biliar es la causa principal en el desencadenamiento de ella. La evolución de la pancreatitis aguda puede adquirir diferentes formas clínicas que se relacionan con el pronóstico. Se proponen factores pronósticos de la enfermedad tanto desde el punto de vista clínico, de laboratorio y de imagenología. Se analizan los tratamientos actuales y conductas terapéuticas