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J C Araya

Publications and source records attributed to J C Araya.

At least 19 recordsLinked to original sources

Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis.

BACKGROUND & AIMS: Cancer of the gallbladder is the number one cause of cancer mortality in Chilean women. Incidence rates for this tumor vary widely on a worldwide basis, being approximately 30 times higher in high-risk than in low-risk populations, suggesting that environmental factors such as infectious microorganisms, carcinogens, and nutrition play a role in its pathogenesis. Because several Helicobacter sp. colonize the livers of animals and induce hepatitis, the aim of this study was to determine whether Helicobacter infection was associated with cholecystitis in humans. METHODS: Bile or resected gallbladder tissue from 46 Chileans with chronic cholecystitis undergoing cholecystectomy were cultured for Helicobacter sp. and subjected to polymerase chain reaction (PCR) analysis using Helicobacter-specific 16S ribosomal RNA primers. RESULTS: Recovery of Helicobacter sp. from frozen specimens was unsuccessful. However, by PCR analysis, 13 of 23 bile samples and 9 of 23 gallbladder tissues were positive for Helicobacter. Eight of the Helicobacter-specific PCR amplicons were sequenced and subjected to phylogenetic analysis. Five sequences represented strains of H. bilis, two strains of "Flexispira rappini" (ATCC 49317), and one strain of H. pullorum. CONCLUSIONS: These data support an association of bile-resistant Helicobacter sp. with gallbladder disease. Further studies are needed to ascertain whether similar Helicobacter sp. play a causative role in the development of gallbladder cancer.

Adult

Tumor specific Epstein-Barr virus infection is not associated with leiomyosarcoma in human immunodeficiency virus negative individuals.

BACKGROUND: Recent studies have suggested that the Epstein-Barr virus (EBV) is associated with leiomyosarcoma in children with human immunodeficiency virus (HIV) and in organ transplant recipients. To determine whether EBV is associated with leiomyosarcoma in HIV negative patients, the authors examined resected leiomyosarcomas for EBV and HIV. METHODS: Twenty-four leiomyosarcomas were studied and their diagnosis confirmed on pathologic review. From these specimens DNA was isolated. Tumor samples were analyzed for EBV and HIV using a polymerase chain reaction (PCR) technique followed by gel electrophoresis and Southern blot analysis. DNA from an EBV-infected human Burkitt's lymphoma cell line and peripheral blood from an HIV positive patient were used as positive controls for the presence of EBV and HIV, respectively. Immunohistochemistry was performed using an antibody to Epstein-Barr nuclear antigen. RESULTS: HIV was not present in any of the patients analyzed. EBV DNA was detected in tumor tissue; however, 80 cycles of PCR were used before EBV sequences were detected. Therefore, the data indicate that tumor tissue was not infected with EBV. The positive results observed after 80 cycles of PCR were likely due to infiltrating lymphocytes. Immunohistochemistry confirmed the lack of active or latent EBV infection in tumor cells. CONCLUSIONS: The results indicate that EBV is not associated with sporadic leiomyosarcoma in HIV negative patients. Therefore, the biology of leiomyosarcoma associated with HIV may be substantially different from the more common sporadic form.

Adult

Double immunostaining for p53 and molecular chaperone hsp72/73 in gastric carcinoma.

AIMS: To examine the relation between the expression of p53 protein and the chaperone heat shock protein (hsp)72/73 in a population at high risk for gastric carcinoma, using single and double immunohistochemistry, and to compare the expression of these two proteins with clinicopathological features. METHODS: Monoclonal antibodies were used to investigate the expression of p53 protein and hsp72/73 in 46 human gastric carcinomas. A double immunohistochemical technique was used in cases that showed p53/hsp72/73 coexpression. RESULTS: p53 immunoreactivity was present in 11 tumours (24%), and hsp72/73 immunostaining was observed in 22 cases (48%). p53 expression was observed as nuclear staining in tumoral cells. hsp72/73 expression was demonstrated mainly as cytoplasmic staining, but six tumours also showed focal weak nuclear staining. Seven cases showed p53 and hsp72/73 coexpression with immunoreactivity for both proteins in the same neoplastic cells, three of them with focal areas of nuclear coexpression. p53 expression was seen more frequently in cases that showed a high intensity (+ + +) of hsp72/73 staining. No significant association was observed between the expression of the two proteins and clinicopathological features. CONCLUSIONS: More than half of our cases may have some impairment in p53 protein growth suppressive function, as a result of p53 gene alterations or complex formation. The positive correlation between p53 expression and intensity of hsp72/73 supports the postulate of a p53 regulating function for the chaperone hsp72/73. A high intensity of hsp72/73 immunohistochemical staining could be used as an indirect marker of p53 gene abnormalities.

Adult

Curative resection in potentially resectable tumours of the gallbladder.

OBJECTIVE: To study the value of surgical treatment in patients with potentially resectable gallbladder cancer. DESIGN: Prospective non-randomised study. SETTING: University hospital, Chile. SUBJECTS: 109 Patients with gallbladder cancers, most of which were detected in the cholecystectomy specimen. INTERVENTIONS: 53 Patients underwent reoperation with the aim of doing a lymphadenectomy and resecting the gallbladder bed. MAIN OUTCOME MEASURES: Morbidity and short and long term mortality RESULTS: Residual tumour after cholecystectomy was mainly observed in patients with serosal and adipose tissue infiltration. Lymph nodes and liver invasion were associated with recurrence. Survival analysis was focused on the group with subserosal infiltration because it is the largest subgroup in this study and prognosis is intermediate. Patients who underwent curative resection had a significantly better survival than those treated by simple cholecystectomy (p = 0.005). CONCLUSIONS: Extended cholecystectomy improved the prognosis of patients whose cancers were restricted to the subserosal layer. Additional treatments are necessary to improve the results obtained with operation alone.

Adult

DNA ploidy pattern and tumor suppressor gene p53 expression in gallbladder carcinoma.

The relationship between p53 gene expression and DNA content in advanced gallbladder carcinoma was studied. Fifty-three cases of advanced gallbladder carcinoma (45 primary tumors and 8 metastases) were analyzed, p53 protein expression was determined by immunohistochemistry, DNA content was measured by cytophotometric techniques. Study subjects included 45 (85%) female and 8 male patients, with an overall mean age of 58.6 years. Positive staining for p53 protein was observed in 27 (51%) cases. In subserosal tumors, the expression was significantly less than that in tumors that reached the serosa (P = 0.01). Twenty-nine (55%) cases were diploid and 24 were aneuploid. Sixty-seven % of primary tumors were diploid, whereas 87% of metastases showed an aneuploid DNA content. Both diploid and aneuploid tumors were positive for the p53 protein in the same proportion, and p53 was also expressed equally in both primary and secondary tumors. In advanced gallbladder carcinoma, the expression of the p53 gene was earlier than the accumulation of abnormal quantities of chromosomal DNA in the tumor cells. The determination of these events as markers in preneoplastic lesions is warranted in gallbladder carcinogenesis.

Adenocarcinoma

[Immunohistochemical expression of p53 oncoprotein in large bowel adenomas and carcinomas].

BACKGROUND: Colorectal carcinoma is the sixth cause of death in Chile. Half of malignant tumors in humans have genetic alterations in protoncogenes, tumor suppressing genes or both. One of the most frequent alterations is that involving p53 tumor suppressor gene. AIM: To study, using immunohistochemical methods, alterations in p53 gene expression in colorectal carcinomas and adenomas. MATERIAL AND METHODS: A random sample of 28 large bowel adenomas and 44 carcinomas was studied. Determination of p53 protein was made with an immunohistochemical method using monoclonal antibodies. Patients were followed for a mean of 36 months (range 1 to 100 months). RESULTS: p53 immunostaining was obtained in one adenoma (3.5%) and in 18 carcinomas (41%, p = 0.01). There were no differences in survival during follow up, between cancer patients that expressed or did not express p53 protein. CONCLUSIONS: About half of colorectal tumors have immunohistochemical expression of p53 protein, as published abroad. We did not find a prognostic value for this protein in our sample.

Adenocarcinoma

Comparison of mutagenic activity of bile between Chilean and Japanese female patients having cholelithiasis.

The mutagenic activity of bile was compared between Chilean and Japanese female patients having cholelithiasis by the Ames assay using Salmonella typhimurium tester strain TA98 in the presence of S9 mix with blue rayon adsorption technique. A reason for conducting the present investigation is that Chile and Japan have the highest mortality rates for the gallbladder cancer (GBC) in the world. Of 24 bile samples collected in Chile, 20 (83.3%) samples showed mutagenicity. In the case of Japanese bile, 21 (80.8%) of 26 and 5 (19.2%) of 26 cases were mutagenic in samples from high- and low-risk areas for GBC, respectively. Therefore, both the Chilean and the Japanese samples collected in high-risk areas showed higher mutagenic rates than the Japanese ones in a low-risk area, with a statistical significance (p < 0.001), chi-square test). The average number of revertant colonies were 128 +/- 92 (mean +/- SD), 62 +/- 14 and 66 +/- 13, respectively, when the blue rayon extracts of 200 microliters bile were applied to the Ames test. Thus, Chilean bile had a tendency to show a higher mutagenic activity than Japanese.

Adult

Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression.

BACKGROUND & AIMS: Scarce biological information exists about the importance of preneoplastic lesions in gallbladder cancer. The aim of this study was to estimate the time required for the sequence of dysplasia (DY) to carcinoma of the gallbladder. METHODS: Eighty-four cases of DY, 60 cases of early carcinomas (ECs), 181 cases of advanced carcinomas (ACs), and 121 cases of metastatic (ME) gallbladder cancer were analyzed. Age was used as the main parameter. Statistical analysis was performed using analysis of variance and multiple regression analysis. RESULTS: Among all cases, the mean age of female patients was lower than the mean age of male patients (P = 0.001). A significant difference in mean age between sexes by specific type of lesion was also observed (P < 0.001). The mean age was 46.3 years (SD, 16) in the DY group, 57.5 years (SD, 16.7) in the EC group, 59 (SD, 13.7) in the AC group, and 61.1 (SD, 12.1) in the ME group. Multiple regression analysis showed statistically significant differences (r = 0.386; P < 0.001) in the mean age of patients with dysplastic lesions compared with the carcinoma group. CONCLUSIONS: According to these observations, the period required to progress from dysplasia to advanced gallbladder carcinoma would be around 15 years, observing a continuum in the progression of the lesions.

Adult

[Hepatocellular carcinoma. General aspects of diagnosis and treatment].

Hepatocellular carcinoma is the most frequent form of primary hepatic cancer and has a high dissemination capacity. About 90% of tumors develop over a pre-existing cirrhosis but they also may occur in a normal liver. It has a higher frequency among males and 80% of tumors have clinical manifestations. It is associated to hepatitis B and C virus infection, alcoholism, cirrhosis of any etiology, consumption of aflatoxin Bl, oriental race and familial history. Patients are staged using classifications proposed by Okuda, Child-Pugh and the performance status test. Alpha feto protein is useful for diagnosis and follow up Abdominal ultrasound, hepatic scintiscan, angiography with lipiodol, CAT scan and nuclear magnetic resonance have a high diagnostic yield. Non surgical therapeutic alternatives include intratumoral alcoholization, chemoembolization and other such as tamoxifen and monoclonal antibodies. Surgical treatment is based on hepatic resection, whose magnitude depends on hepatic function. Hepatic transplantation is a new therapeutic alternative for patients in whom resection is not feasible and have a single small tumor without metastases.

Biomarkers, Tumor

[Gallbladder cancer. Case-control study].

Gallbladder cancer is the principal oncological cause of death in chilean women and cholelithiasis is a well recognized risk factor. Aiming to unravel other risk factors for gallbladder cancer, we compared 50 patients subjected to cholecystectomy in whom a gallbladder cancer was found with 50 age and sex matched operated controls without cancer. Subjects were clinically assessed and interrogated about demographic, obstetrical features and feeding features. Multiples and early pregnancies were factors significantly associated to the development of gallbladder cancer. Twenty subjects (44%) with cancer knew that they had cholelithiasis and 41 patients in each group were symptomatic. It is concluded that pregnancy may be a risk factor for gallbladder cancer probably due to the lithogenic effect of its hormonal changes. Also, early cholecystectomy in symptomatic individuals may be an effective preventive measure.

Adult

[Proliferating cell nuclear antigen in cervical cancer and precursor lesions].

The aim of this study was to study the degree of cellular proliferation quantifying the immunohistochemical expression of the proliferating cell nuclear antigen. We assessed paraffin embedded samples of 25 infiltrating epidermoid cervical carcinomas, 76 precursor lesions (34 of low and 42 of high grade), 29 normal and 13 metaplastic epidermoid epithelia. Mean values of proliferating cell nuclear antigen expression were 13.7% in normal epithelia, 15.7% in epidermoid metaplasia, 37.1% in low grade precursor lesions (35.3% in condilomas and 38.8% in mild dysplasia), 48.7% in high grade lesions (47.9% in moderate dysplasias, 50.5% in severe dysplasias and 50% in carcinoma in situ) and 54.7% in infiltrating carcinoma. There were differences in proliferating cell nuclear antigen expression nd mitotic index between low grade precursor lesions and high grade lesions and infiltrating carcinoma. No correlation was observed between mitotic index and proliferating cell nuclear antigen expression. We conclude that infiltrating epidermoid cervical carcinoma and its precursor lesions have a high level of proliferative activity, demonstrated by a high percentage of cells in active phases of the cellular cycle.

Carcinoma, Squamous Cell

[Gallbladder cancer: immunohistochemical expression of the protein related to estrogen receptor (p29) and of the protein induced by estrogen (pS2)].

The high frequency of gallbladder cancer in women suggests a role for estrogens in its development. The aim of this study was to study the immunohistochemical expression of p29 estrogen receptor associated protein and pS2 estrogen induced protein in 111 pathological samples of gallbladder carcinoma, coming from 88 women and 23 men, 30 metastases of gallbladder cancer, coming from 25 women and 5 men and in 25 non-tumoral gallbladders. In the latter, p29 protein was positive in 12 samples (48%) and pS2 in 15 cases (60%). p29 was positive in 40% and pS2 in 32% of tumors. p29 expressed with higher frequency in metastases than in primary tumors (57 and 31% respectively, p < 0.02). Early tumors had a significantly lower expression of p29 than advanced tumors or than metastases. Both proteins expressed in 18% of samples (synchronic expression) whereas one of both proteins did so in 60% of cases (asynchronic expression). We conclude that most gallbladder cancer samples express proteins associated to estrogen receptor or induced by estrogens.

Adenocarcinoma

[Laparoscopic cholecystectomy makes difficult the analysis of gallbladder mucosa. Morphometric study].

Laparoscopic gallbladder surgery damages gallbladder mucosa, impeding an adequate histological examination. We studied gallbladder samples coming from 56 conventional and 44 laparoscopic cholecystectomies performed in patients with chronic cholecystitis without signs of acute inflammation. The length of each examined sample and the length of the portion where superficial epithelia was not found was measured. No differences in sample length was found between both types of cholecystectomy. However; the segment with superficial mucosa was significantly shorter in the samples coming from laparoscopic surgery. Seventeen samples did not contain mucosa at all and 14 of these (82%) came from laparoscopic procedures. Eighty six percent of samples coming from laparoscopic surgery were considered inadequate for histological study compared to 36% of samples coming from conventional cholecystectomy. It is concluded that laparoscopic cholecystectomy hampers the study of gallbladder mucosa and may have an impact on the diagnosis of neoplastic gallbladder lesions.

Cholecystectomy

[Proliferating cell nuclear antigen (PCNA) in patients with malabsorption syndrome: comparative study with morphometric parameters].

The study of small bowel mucosa is routine in the study of patients with malabsorption. We report 16 children aged from 8 months to 6 years old (2 with giardiasis, 8 with primary malnutrition and 5 with celiac disease) in whom a morphometric and PCNA immunostaining was performed in the small intestinal biopsy. Positivity for PCNA was found in the lower portion of the crypts reaching 156 microns of heigh in patients with giardiasis, 103 microns in primary malnutrition and 182 microns in celiac disease (p < 0.01 compared to primary malnutrition). A negative and significant correlation was found between the degree of architectural disorder (expressed the mucosal index) and the proliferative portion of the crypts (expressed as the percentage of PCNA(+) crypts. We propose these methods as complements to the small bowel mucosa histopathological study in the diagnosis of celiac disease, to assess the degree of architectural disorder and the proliferative activity.

Child

[Expression of p29, estrogen receptor related protein in primary breast carcinoma. Methodological, anatomoclinical, and DNA content analysis].

The aim of this work was to assess the immunohistochemical detection of a estrogen receptor related protein (p29) in 48 histological samples of primary mammary carcinoma and its relationship to clinical, morphological and ADN content parameters. p29 protein was positive in 62.5% of samples. Over 50% of samples had a moderate or intense immunohistochemical staining (staining index over 16) and 77% has a heterogeneous expression of p29 protein. Seventy six percent of p29 positive and 53% of p29 negative tumors had a proliferation fraction over 10% (determined by the S fraction with flux cytometry). No relationship between p29 expression and the analyzed anatomoclinical variables was found. These results highlight this immunohistochemical method as an alternative to more complex and difficult biochemical techniques. On the other hand, the good results obtained in formalin fixed tissues allow retrospective studies in mammary carcinoma samples.

Biomarkers, Tumor