Bernardo Ruiz

Helicobacter pylori and gastric carcinoma: Serum antibody prevalence in populations with contrasting cancer risks

This investigation examined the correlation between Helicobacter pylori (HP) infection, as reflected in immunoglobulin G serum antibodies, and the risk of gastric cancer. Serum samples were obtained from populations with contrasting gastric cancer risks. the highest prevalence of HP infection, 93%, was observed in the adult population at highest gastric cancer risk, the residents of Pasto, Colombia. in the lower risk Colombian city of Cali, a 63% overall prevalence rate was found. Both children and adults were sampled in New Orleans, Louisiana, where gastric cancer rates are high for blacks but not for whites. the prevalence of HP infection was significantly higher in black than in white adults, 70% versus 43%, P = 0.0001. A higher prevalence was also detected in black compared with white children, 49% versus 32%, P = 0.01; however, an even greater disparity was noted when comparing children from two hospitals, regardless of race, which serve different socioeconomic groups. A prevalence rate of 54% was found at Charity Hospital compared with 24% (P = 0.0001) at Childrens Hospital. Our findings indicate that socioeconomic conditions, known to influence gastric cancer risk, are also important determinants of HP infection.

Pathology and classification of ovarian tumors.

*This article is a US Government work and, as such, is in the public domain of the United States of America. Knowledge of the embryology and microscopic anatomy of the ovary is fundamental to the understanding of the various cancer types that originate in this organ. A complete description of the embryology and anatomy of the ovary is beyond the scope of this monograph; however, comprehensive reviews are available for those who seek more detail. The current discussion focuses on key developmental events and anatomic features that shed light on the natural history of ovarian cancers. At approximately five weeks of gestation, thickenings of the lining of the posterior embryonic body cavity, the coelomic epithelium, form the genital ridges. Continued proliferation of the coelomic epithelium into the underlying primitive connective tissue, known as the mesenchyme, leads to the formation of the primordial indifferent gonads. Cells from adjacent transient embryonic structures, known as mesonephros, concurrently invade the mesenchyme, and the primordial germ cells arrive after a long journey that starts at their place of origin in the yolk sac and takes the cells along the distal embryonic intestine and the posterior wall of the embryonic body cavity. The different tumor types that arise in the ovary are linked to the different cell types that are present at this stage of development: coelomic epithelial, mesenchymal, mesonephric, and germ cells. Ovaries and testes develop in similar fashion until approximately the fourth month of embryonic life. This finding explains the origin of tumors that are commonly associated with testicular tissue but appear in the ovaries and vice versa. At two months gestation, the primitive gonad is recognized as an ovary because of the lack of development of the well-defined testicular sex cords. Instead, mesonephric cells and germ cells remain closely associated, forming illdefined ovarian sex cords embedded in the primitive mesenchyme. The coelomic epithelium remains at the periphery, enwrapping the developing ovary. In the adult, the ovaries are flat, nodular, oval structures that measure between 3 and 5 cm in their greatest dimension and weigh between 2 and 4 g. They are suspended by peritoneal folds and ligaments on either side of the uterus and attached to the back of the broad ligament of the uterus, behind and below the uterine tubes. A single layer of cells, the surface epithelium, which is derived from the coelomic epithelium, lines their external surface. A dense, fibrous tissue, the stroma, which is derived from the mesenchyme, makes up most of their internal substance. The germ cells, also known as oocytes, are located near the periphery of the stroma. The granulosa cells, specialized cells of probable mesonephric origin that are derived from the sex cords, surround the germinal cells that form the follicles. The stroma immediately surrounding the follicles differentiates into plum elongated cells known as theca cells. When stimulated, theca 2631

Helicobacter pylori genotypes may determine gastric histopathology.

The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.

CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance

Emerging evidence indicates the presence of tumor-initiating cells (TIC) or cancer stem cells in osteosarcoma. However, no study has shown specific markers to identify osteosarcoma TICs with in vivo tumor formation ability. Additionally, there has been a lack of investigations gauging the contribution of osteosarcoma TICs to metastatic and drug-resistant properties. In this study, we have identified mouse and human osteosarcoma TICs using mesenchymal stem cell markers CD117 and Stro-1. These markers were preferentially expressed in spheres and doxorubicin-resistant cells. Both mouse and human cells expressing these markers were sorted and analyzed for their abilities of tumor formation with as few as 200 cells, self-renewability, multipotency, drug resistance, metastatic potential, and enrichment of a metastasis-associated marker (CXCR4) and a drug resistance marker (ABCG2). CD117(+)Stro-1(+) cells efficiently formed serially transplantable tumors, whereas CD117(-)Stro-1(-) cells rarely initiated tumors. On orthotopic injections, CD117(+)Stro-1(+ )cell-derived tumors metastasized at a high frequency. Further, CD117(+)Stro-1(+) cells showed high invasive and drug-resistant properties and were efficiently enriched for CXCR4 (20-90%) and ABCG2 (60-90%). These results suggest possible mechanisms for the high metastatic and drug-resistant properties of osteosarcoma TICs. In summary, CD117 and Stro-1 identify osteosarcoma TICs associated with the most lethal characteristics of the disease-metastasis and drug resistance-and these markers offer candidates for TIC-targeted drug delivery aimed at eradicating osteosarcoma.

Review article: antioxidant micronutrients and gastric cancer

A review of the literature reveals a very consistent association between gastric cancer risk and low intake of fruits and vegetables. This observation has been documented in many countries with different epidemiological techniques: interpopulation correlations, case-control studies and follow up of several cohorts. Low serum levels of beta-carotene and alpha-tocopherol, but not vitamin C, have been reported in patients with gastric dysplasia. Helicobacter pylori infection has been associated with lower concentrations of vitamin C in the gastric juice. Detailed studies in Colombia and New Orleans have shown a gradient towards lower concentration in the gastric juice and lower ratios of gastric juice to serum concentration of vitamin C in the following comparisons: i) lower vs. higher gastric cancer risk; ii) mild vs. advanced gastric precancerous histopathologic lesions; iii) mild vs. advanced degree of atrophy; iv) mild vs. advanced damage to the surface gastric epithelium; v) lower vs. higher gastric pH. Such a gradient is not observed for serum levels of vitamin C. The role of infection with H. pylori in the metabolism of ascorbic acid is discussed, as well as the possible role of ascorbic acid in inhibiting cell damage by reactive oxygen species.

Morphometric evaluation of gastric antral atrophy: improvement after cure of Helicobacter pylori infection

OBJECTIVE:Our purpose was to find out if morphometric techniques can document long term changes in gastric antral atrophy after curing Helicobacter pylori infection with or without dietary supplementation with antioxidant micronutrients.METHODS:Study subjects were 132 adult volunteers from a Colombian region with high gastric cancer rates. Participants were randomly assigned to ascorbic acid, β-carotene, and anti-H. pylori treatment, following a factorial design. Gastric biopsies were obtained at baseline and after 72 months of intervention. Atrophy was evaluated by a standard visual analog scale and by morphometry.RESULTS:Statistically significant changes in antral atrophy were detected with morphometric techniques after intervention in subjects who received anti-H. pylori treatment. A nonsignificant trend was also observed with visual scores. This effect was greater among those who were free of infection at the end of the trial. After accounting for the effect of anti-H. pylori treatment, no significant effect was noted for dietary supplementation with ascorbic acid and/or β-carotene.CONCLUSIONS:We conclude that gastric atrophy improves significantly after long term control of H. pylori infection. This effect can be demonstrated both by conventional histological grading and by morphometry.

Incidence of esophageal and gastric cancers among Hispanics, non-Hispanic whites and non-Hispanic blacks in the United States: subsite and histology differences.

ObjectiveWe examined subsite- and histology-specific esophageal and gastric cancer incidence patterns among Hispanics/Latinos and compared them with non-Hispanic whites and non-Hispanic blacks.MethodsData on newly diagnosed esophageal and gastric cancers for 1998–2002 were obtained from 37 population-based central cancer registries, representing 66% of the Hispanic population in the United States. Age-adjusted incidence rates (2000 US) were computed by race/ethnicity, sex, anatomic subsite, and histology. The differences in incidence rates between Hispanics and non-Hispanics were examined using the two-tailed z-statistic.ResultsSquamous cell carcinoma accounted for 50% and 57% of esophageal cancers among Hispanic men and women, respectively, while adenocarcinoma accounted for 43% among Hispanic men and 35% among Hispanic women. The incidence rate of squamous cell carcinoma was 48% higher among Hispanic men (2.94 per 100,000) than non-Hispanic white men (1.99 per 100,000) but about 70% lower among Hispanics than non-Hispanic blacks, for both men and women. In contrast, the incidence rates of esophageal adenocarcinoma were lower among Hispanics than non-Hispanic whites (58% lower for men and 33% for women) but higher than non-Hispanic blacks (70% higher for men and 64% for women). Cardia adenocarcinoma accounted for 10–15% of gastric cancers among Hispanics, and the incidence rate among Hispanic men (2.42 per 100,000) was 33% lower than the rate of non-Hispanic white men (3.62 per 100,000) but 37% higher than that of non-Hispanic black men. The rate among Hispanic women (0.86 per 100,000), however, was 20% higher than that of non-Hispanic white women (0.72 per 100,000) and 51% higher than for non-Hispanic black women. Gastric non-cardia cancer accounted for approximately 50% of gastric cancers among Hispanics (8.32 per 100,000 for men and 4.90 per 100,000 for women), and the rates were almost two times higher than for non-Hispanic whites (2.95 per 100,000 for men and 1.72 per 100,000 for women) but about the same as the non-Hispanic blacks.ConclusionSubsite- and histology-specific incidence rates of esophageal and gastric cancers among Hispanics/Latinos differ from non-Hispanics. The incidence rates of gastric non-cardia cancer are almost two times higher among Hispanics than non-Hispanic whites, both men and women. The rates of gastric cardia cancer are lower among Hispanics than non-Hispanic whites for men but higher for women. The rates of esophageal and gastric cardia adenocarcinomas are higher among Hispanics than non-Hispanic blacks.

Serum pepsinogens as markers of response to therapy for Helicobacter pylori gastritis.

We have investigated the effect of therapy forHelicobacter pylori gastritis on serum concentrations of pepsinogen I and II in 43 patients. In the 22 patients in whom therapy resulted in dramatic decrease in gastritis scores and in clearance of the bacteria, there was a highly significant (P=0.0001) fall in mean serum pepsinogen II from 13.3±0.8 to 7.9±0.7 μg/liter, and a less pronounced fall in pepsinogen I from 89.0±5.9 to 78.5±0.4 μg/liter (P=0.01). These changes resulted in a significant (P=0.01) increase in the pepsinogen I/II ratio. In contrast, nonsignificant declines of 3.5% and 11.6% were observed in mean pepsinogen I and II levels in the 21 patients whose gastritis failed to resolve histologically and whose infection did not clear. These findings suggest that serum pepsinogen levels, especially pepsinogen II, are a new tool that may be found to be clinically useful in evaluation of treatment outcome in patients withH. pylori-associated gastritis.

Helicobacter pylori-associated gastritis and the ascorbic acid concentration in gastric juice.

Patients infected with Helicobacter pylori have abnormally low ascorbic acid concentration in gastric juice. Low vitamin C intake and Helicobacter pylori infection have been related to an increased risk of gastric carcinoma. This report examines the association between ascorbic acid and Helicobacter pylori in patients referred for upper gastrointestinal endoscopy. Elevated gastric pH and the damage to the gastric surface epithelium were inversely associated with the ascorbic acid concentration in gastric juice. We postulate that these two factors mediate the ascorbic acid-decreasing effect of Helicobacter pylori. Patients with nonpremalignant conditions (normal gastric histology, diffuse antral gastritis, or duodenal ulcer) had lower gastric pH, less damage to the gastric epithelium, and higher levels of ascorbic acid in gastric juice than patients with atrophic gastritis, intestinal metaplasia, or dysplasia.

Excess risk of subsequent primary cancers among colorectal carcinoma survivors, 1975–2001

Studies of persons with colorectal cancer have reported increased risk of subsequent primary cancers. Results have not been consistent, however, and there is little information about such risk in specific races and ethnic populations.