Rafael Medrano-Guzmán

Stomach microbiota composition varies between patients with non-atrophic gastritis and patients with intestinal type of gastric cancer

We aimed to characterize microbiota of the gastric mucosa as it progress to intestinal type of cancer. Study included five patients each of non-atrophic gastritis (NAG), intestinal metaplasia (IM) and intestinal-type gastric cancer (GC). Gastric tissue was obtained and DNA extracted for microbiota analyses using the microarray G3 PhyloChip. Bacterial diversity ranged from 8 to 57, and steadily decreased from NAG to IM to GC (p = 0.004). A significant microbiota difference was observed between NAG and GC based on Unifrac-presence/absence and weighted-Unifrac-abundance metrics of 283 taxa (p < 0.05). HC-AN analyses based on presence/absence of 238 taxa revealed that GC and NAG grouped apart, whereas IM overlapped with both. An ordinated analyses based on weighted-Unifrac distance given abundance of 44 taxa showing significance across categories revealed significant microbiota separation between NAG and GC. This study is the first to show a gradual shift in gastric microbiota profile from NAG to IM to GC.

Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients

Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3–V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.

Polymorphisms in HLA-DQ genes, together with age, sex, and Helicobacter pylori infection, as potential biomarkers for the early diagnosis of gastric cancer

Polymorphisms in inflammation‐related genes are factors associated with the development of gastroduodenal diseases in Helicobacter pylori‐infected individuals.

Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study

BackgroundGastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer.MethodsWe included 201 healthy controls and 162 patients with distal gastric cancer who underwent primary surgical resection between 2009 and 2012 in Mexico City. The clinical and pathological data of patients were recorded by questionnaire, and the cancer subtype was classified as intestinal or diffuse. Pathological staging of cancer was based on the tumor–node–metastasis staging system of the International Union Against Cancer. Concentrations of IL-1β, IL-6, TNF-α, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-γ, and TGF-β in plasma were measured using enzyme-linked immunosorbent assay.ResultsLevels of IL-1β, IL-6, IFN-γ, and IL-10 were significantly higher and that of MCP-1 was lower in gastric cancer patients compared with controls. No differences in IL-8 or TNF-α levels were observed between gastric cancer and controls. IFN-γ and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1β and IL-6 were higher and TGF-β lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1β and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients. Receiver-operating characteristic analysis showed that for diagnosis of GC, IL-6 had high specificity (0.97) and low sensitivity (0.39), IL-10 had moderate specificity (0.82) and low sensitivity (0.48), and IL-1β and IFN-γ showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively).ConclusionsIncreased levels of IL-6, IFN-γ, and IL-10 might be useful as diagnostic biomarkers for GC; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. IL-1β, IL-6, MCP-1, and TGF-β differentiate intestinal from diffuse GC. IFN-γ and IL-10 might be useful for diagnosis of early stage GC, and IL-1β, IL-8, and MCP-1 for late stages of the disease.

Evaluación por inmunohistoquímica de la expresión del HER2 en cáncer gástrico. Estudio clínico-patológico de 93 casos

BACKGROUND Gastric cancer in Mexico is ranked third in both males and females. Most patients present clinically with advanced disease and treatment options are sparse. HER2 overexpression in gastric cancer is related to poor outcome. Immunohistochemical testing for HER2 is becoming the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab. OBJECTIVES To determine the frequency of HER2 overexpression in patients with gastric cancer in the Hospital de Oncología del Centro Médico Nacional, Siglo XXI and its association with other histopathological findings. MATERIAL AND METHODS Patients with gastric cancer who underwent surgery between March 12, 2006-August 31, 2011, were enrolled in this retrospective study. Diagnosis was confirmed by review of slides and immunohistochemistry with anti-HER2 antibody was performed. Scoring was done by Hoffman scoring system. Medical records were evaluated. RESULTS Ninety-three patients were included in the study, with 43 (46.2%) male and 50 (53.7%) female patients. The median age was 64 years. HER2-positive tumours were identified in 6 patients (6.45%) and located most frequently in the proximal stomach. There was no difference in HER2 overexpression in relation to age, gender or histologic type. CONCLUSION In our study, about 7% of patients with gastric cancer were HER2-positive on immunohistochemistry.

Correction to: Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study

After publication of the original article [1] the authors found the following author names were incorrect and needed to be amended:

Factores pronóstico de sobrevida en adenocarcinoma gástrico avanzado resecable

BACKGROUND Patients under 45 years with gastric cancer are associated with a poor prognosis. Recent studies report that the 5-year survival is better in younger patients after curative resection. OBJECTIVE To determine if prognostic factors such as age under 45 years old, anaemia, weight loss, tumour differentiation, histological sub-type, depth of invasion, and lymph node involvement, reduce the survival of patients with resectable advanced gastric adenocarcinoma undergoing gastrectomy with limited and extended lymphadenectomy. MATERIALS AND METHODS This study included a cohort of consecutive cases treated in the Sarcomas Department of the Oncology Hospital of the Centro Médico Nacional Siglo XXI, of the Instituto Mexicano del Seguro Social, during the period between January 2000 and December 2006. RESULTS Of the total of 588 patients evaluated, 112 (19%) were under 45 years, 43% classified as Borrmann IV, and 36% as Borrmann III. Metastatic disease was present in 39.3%, localised diffuse in 12.5%; lower resectability 52.7 vs. 61.3% in older than 45 years. At the end of the study 29.5% of patients under 45 years were alive; no recurrence in 26.8%, with an overall survival of 58.6±4.3 months, compared with 18.3% of patients alive over 45 years, 17.9% disease-free, and with overall survival 35.2±4.3 months resectable disease. CONCLUSIONS Patients under 45 years have a better survival after a two-year disease-free period.