Biomedical subjects
Publications and source records attributed to C Cuello.
Gastric juice samples from patients of a rural area of the Colombian Andes at high risk to gastric cancer were tested for mutagenesis with Salmonella typhimurium strains TA100 and TA1538. Direct mutagenic effect was found in samples with detectable amounts of nitrite. This effect was not accountable by nitrite alone. Nitrite-negative samples from the same area and samples from the low-risk area of Cali were negative using the same mutagenesis assay.
Based on the experience with gastric biopsies in a rural population of Colombia with very high rates of gastric cancer, a description of the dysplasias of the gastric mucosa is given. It recognizes two main types of dysplasias: hyperplastic and adenomatous. Different degrees of atypism are recognized within each category. A comparison with other classifications of gastric dysplasias is offered. A positive correlation of dysplasia with gastric juice nitrite is found and offered as an adjuvant to the evaluation of patients with this type of condition.
Three cases of polycystic hydatid disease (PHD) from Colombia are reported and 11 others from the region are reviewed. When cysts from two patients were fed to a dog and an ocelot about 250 mature and gravid specimens of Echinococcus vogeli and two poorly developed strobilae, respectively, were recovered. These human cases constitute the first record of the larval stage of E. vogeli, previously known only from the strobilar stage in the type host, the bush dog (Speothos venaticus). Based on the morphological characteristics of the protoscolex rostellar hooks from other PHD cases (6 Colombian, 1 Ecuadorian, and 1 Panamanian), it was concluded that all were also due to E. vogeli, rather than to E. oligarthrus as had been previously suggested. Although E. oligarthrus is or may be present in the same areas, so far no human infection due to this parasite has been confirmed. Of the 14 cases reported, 13 were pathologically proven to be PHD. Clinically, eight had an undiagnosed tumor-like mass in or near the liver, one had a subcutaneous mass in the anterior sixth intercostal space, and in two the cysts were in the chest. Two were autopsy findings. In contrast to E. multilocularis, the cysts produced by E. vogeli were found to be relatively large and filled with fluid; brood capsules and protoscolices were numerous. Focal necrosis was commonly observed but large necrotic cavities were not seen. The main natural intermediate host is the paca (Cuniculus paca); man probably obtains the infection by contamination from feces of infected hunting dogs.
Samples of gastric contents from 2 groups of patients from a region of high risk for gastric cancer were analyzed for pH, nitrite, nitrate, thiocyanate, and chloride. In each group, the patients could be divided into 2 subgroups: those with a gastric pH of less than 5 and those with a gastric pH of greater than 5. Above pH 5, nitrite was correlated with nitrate. The pH greater than 5 subgroups had significantly higher (P less than 0.01) nitrite content (20- to 100-fold). Some high- and low-nitrite samples were also analyzed for macro and trace metal ions, but differences were not significant. This is the first report in which patients with diagnosed gastric pathology related to a precancerous state were shown to have high levels of a putative carcinogen precursor. The results were compatible with our original hypothesis of intragastric nitrite formation by bacterial reduction of nitrate and concomitant synthesis of carcinogenic N-nitroso compounds.
The gastric juice of patients with atrophic gastritis from the high-risk gastric cancer region of Nariño, Colombia, was analyzed for nitrate, nitrite, and thiocyanate content. Patients whose gastric juice pH is greater than 5 have significant elevation of nitrite values. The possible role of nitrite in gastric carcinogenesis is discussed.
A detailed histologic study was made of uterine cervices from 441 autopsy specimens from the population of Cali, Colombia. Women in this city have one of the highest registered incidence rates of cancer of the uterine cervix. The following prevalence (in percent) of lesions in adult women was found: cervicitis, 79; reserve cell hyperplasia, 14; squamous metaplasia, 41; dysplasia, 9. Contrary to expectations, no increase in prevalence of these lesions was found with age, lower socioeconomic status, or number of pregnancies. A similar study of a sample of hysterectomies performed for uterine prolapse showed approximately the same results. The findings suggest that promotional factors are more important than initiator factors in uterine cervical carcinogenesis.
A double-blind study of atypia in colorectal adenomatous polyps was done with autopsy material from Cali, Colombia (low colon risk), São Paulo, Brazil (intermediate risk), and New Orleans, Louisiana (high risk). An interobserver reproducibility of 82% was obtained. The prevalence of atypia in polyps increased with the cancer risk and also with the size of polyps, but some exceptions to the rule were found. The frequency of atypia increased steadily with age in Cali, but it plateaued after age 50 in the higher risk populations.
A 4-month-old girl was admitted to hospital with extensive ulceration and erosion of the left eyelid where 17 days earlier the skin had been broken when hit by a ball. Despite antibiotic therapy the lesion expanded to involve the orbit. Biopsy of the eyelid on the 4th day in hospital, and examination of the eye and attached tissues removed on the 6th, failed to detect amebae until after the infant's death due to a blood transfusion 2 weeks later. Re-examination of the tissues revealed abundant amebae with characteristic morphology of Entamoeba histolytica in subcutaneous tissues of the biopsy and in the loose exudate and necrotic tissues attached to the eye at all levels from lids to base.
A case control study of patients discharged from hospitals revealed fourfold differences in geographic variation in stomach cancer risk within the Department of Narino (Colombia). Data from gastroscopic surveys of population groups, samples of water supplies, and urine and saliva in Narino also indicated a generally positive correlation among the following parameters: 1) gastric cancer risk, 2) prevalence of chronic atrophic gastritis and intestinal metaplasia, 3) nitrate content of well waters, and 4) nitrate excretion by the population. Urinary excretion reflected the ingestion of nitrates, and this implied a higher average intake of nitrates in the populations at high risk for stomach cancer. The Narino data could be construed as presumptive epidemiologic evidence for the role of nitrate availability in the etiology of stomach cancer.
Endoscopic surveys in the Department of Narino (Colombia) showed that natives of areas of very high risks for stomach cancer have a higher prevalence of atrophic gastritis and intestinal metaplasia than do persons born in other parts of Narino. In these surveys, diets were compared between individuals with and without evidence of these suspect precursor lesions of stomach cancer and between individuals born in the areas designated as high and low risk for stomach cancer. The composite evidence from the comparisons indicated lettuce to be negatively associated with stomach cancer and raised the possibility to a positive association for corn. The relationship of these findings to other epidemiologic evidence and the implications for applying the epidemiology of stomach cancer to the epidemiology of precursor lesions were examined.
The premalignant process in the gastric mucosa was studied by gastroscopic surveys of Colombian populations, and the prevalence of superficial gastritis, chronic atrophic gastritis, and intestinal metaplasia was calculated for population samples having a very high gastric cancer risk (Nariño), very low risk (Cartagena), and intermediate risk (Cali). The prevalence of individuals with normal mucosa in successive age groups was used to estimate "depletion" curves, which were taken as indicators of the dynamics of the premalignant process in each community. Differences corresponding to the geographic variation in stomach cancer risk were found: In the high-risk areas of Nariño, around 75% of the population developed some type of gastritis by 45 years of age, whereas in the low- and intermediate-risk population of Cartagena and Cali, the proportion of such lesions did not exceed 50% at age 45 or thereafter. The effect of environmental factors in early life seemed to be important in determining the prevalence of lesions in each population.
An overview of the epidemiologic and pathologic significance of premalignant lesions of the stomach is presented, with correlations between cancer risk, prevalence of atrophic gastritis and environmental factors such as nitrate and food items. The protective role of lettuce and fresh vegetables is discussed. The diffuse type of gastric cancer appears to be less environmentally linked than the intestinal type, and it is hypothesized that the pathogenetic process may begin during the first decade of life. An analysis of precursor lesions and gastric cancer in various geographic regions of Columbia, South America is presented to illustrate these relationships.
It is postulated that one major subtype of gastric carcinoma ("intestinal type") is the end- result of a series of mutations and cell transformation begun in the first decade of life. The mutagen could be a nitroso compound synthesised in the upper gastrointestinal tract by the action of nitrite (i.e., from food or saliva) on naturally occurring nitrogen compounds. Under normal conditions these nitroso compounds do not reach the gastric epithelial cell, presumably because their synthesis is inhibited by antioxidants present in food or because of their inability to pass the mucous barrier. The barrier may be overcome by abrasives or irritants such as hard grains, food with high sodium-chloride concentration, or surfactants. Once the first mutation occurs, the glandular gastric epithelium is gradually changed to intestinal-type epithelium, the mucous barrier altered, and the pH elevated. Under these conditions, bacteria proliferate in the gastric cavity and facilitate the conversion of nitrates to nitrites, thereby increasing the nitrite pool and the probability of formation of mutagenic-carcinogenic nitroso compounds. This process of gastric atrophy and intestinal metaplasia goes on for 30 to 50 years until some of the individuals affected have the final mutation or cell transformation which allows the cell to become autonomous and invade other tissues.
The incidence of large-bowel cancer in Cali, Colombia, for 1962-71 shows the upper socioeconomic classes to be a higher risk. This is the first report of a socioeconomic gradient in risk for this site. The gradients were most marked for cancer of the ascending through rectosigmoid colon and were minimal for cancer of the cecum and rectum. The Cali experience presents several parallels with information derived from comparisons of developed and developing countries and also appears consistent with recent information on the possible role of dietary factors in bowel cancer.
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