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J C Araya

Publications and source records attributed to J C Araya.

At least 19 recordsLinked to original sources

[Findings in surgical reinterventions for cancer of the gallbladder in patients with and without preoperative chemotherapy and radiotherapy].

BACKGROUND: The usefulness of surgery in the treatment of gallbladder cancer has not been clearly established. The benefits of chemo and radiotherapy are similarly dubious. AIM: To report the pathological findings in patients subjected to surgical reinterventions for gallbladder cancer. PATIENTS AND METHODS: We report 54 patients with gallbladder cancer that were subjected to a second surgical intervention for resection of liver segments IVb and V and lymph nodes corresponding to the liver hilar, portal, peripancreatic, celiac artery and periaortic territories. Thirteen of these patients were subjected to preoperative chemo-radiotherapy (4500 Gy and 5-fluouracil 500 mg/m2). RESULTS: Lymph node metastases were found in 25 and 38%, and liver metastases in 25 and 28% of patients with or without chemo-radiotherapy respectively. The most frequent pathological findings attributed to radiation in the liver were fatty infiltration in 75% of cases, vascular transformation in 83% of cases and minimal periportal lymphocyte infiltration in 40% of cases. Lymph nodes were atrophic in 67% of cases and had foci of cortical necrosis in 46% of cases. Three cases had regional lymph node and liver metastases. Most tumor cells were viable. CONCLUSIONS: No differences in the number of lymph node or liver metastases were observed between patients with and without chemo-radiotherapy. No effect of the treatment on residual tumor was observed either.

Chemotherapy, Adjuvant↗

[Incipient gallbladder carcinoma. Clinical and pathological study and prognosis in 196 cases].

BACKGROUND: There is little information about the behavior of early gallbladder carcinoma. AIM: To report the clinical and pathological features of 196 patients with early gallbladder carcinoma. MATERIAL AND METHODS: All patients with gallbladder cancer diagnosed between 1988 and 1997 were reviewed. In 703 of 829 patients, there was information about clinical features and follow up, and were included in this study. All gallbladders were subjected to a complete mapping. When neoplastic cells involved only the mucosa or muscular layer, the tumors were considered as early. RESULTS: One hundred ninety six patients had an early carcinoma (161 women, aged 57.5 years and 35 male, aged 63.4 years). One hundred twenty eight tumors were located in the mucosa and 68 in the muscular layer. Patients with tumors involving the mucosa were younger than those with tumors involving the muscular layer. All tumors were adenocarcinomas, 66% were well differentiated and 32% moderately differentiated. Tumors were not visible macroscopically in 132 cases. Five and 10 years survival was 92%. Subjects of less than 40 years old had a 100% survival at 5 years. A hepatic and lymph node resection was done in 12 patients with tumors infiltrating the muscular layer but in only one, the tumor infiltrated the liver. No difference in survival was observed when a simple cholecystectomy or radical surgery was done. CONCLUSIONS: Nearly 25% of gallbladder carcinomas can be classified as early and its diagnosis requires a directed study. Simple cholecystectomy is curative for this type of gallbladder cancer.

Analysis of Variance↗

[Helicobacter pylori and chronic gastritis: relationship between infection and inflammatory activity in a high risk population for gastric cancer].

BACKGROUND: Helicobacter pylori has been involved in gastric epithelial cell damage and gastric gland loss or atrophy. AIMS: To evaluate role of Helicobacter pylori infection in acute and chronic changes of chronic gastritis in a high gastric cancer-risk population. MATERIAL AND METHODS: 200 patients with chronic gastritis were selected from pathological files of Temuco Hospital. A complete histopathological protocol was fulfilled considering the presence of infection by Helicobacter pylori-like-organism (HLO), acute and chronic inflammatory infiltrate, epithelial cell damage and epithelial cell regeneration. RESULTS: 82% of patients showed infection by HLO. Moreover, this infection reached a frequency of 92.7% in gastric ulcer patients and 94.4% in duodenal ulcer patients. A statistically significant positive correlation was found between HLO infection and polymorphonuclear infiltrate, lymphocytic infiltrate, mucus depletion and epithelial regenerative activity. There was not a statistical correlation between HLO infection and atrophy. Finally, 90% of patients with multifocal atrophic gastritis and 100% of patients with diffuse antral gastritis had HLO infection. CONCLUSIONS: HLO gastric infection frequently caused acute inflammatory changes in gastric mucosa with chronic gastritis. Sometimes these changes were severe, with marked polymorphonuclear migration throughout epithelium and severe epithelial cell damage. Recovery of these changes could be considered as a goal in Helicobacter pylori eradication therapy decision.

Chronic Disease↗

[Gastric cancer and tumor growth regulation. Study of cell proliferation markers and protein complex p53/p21WAF1/CIP1/mdm-2].

BACKGROUND: p53/p21WAF1/CIP1 and mdm-2 proteins play an important role in cell cycle regulation. The study of the pathogenesis of gastric cancer is important to understand how these tumors progress during their natural history. AIM: To study the relationship between the immunohistochemical expression of p53/p21WAF1/CIP1 and mdm-2 and cell proliferation in gastric cancer. MATERIAL AND METHODS: Fifty one gastrectomy specimens with gastric cancer were studied using immunohistochemistry for p53/p21WAF1/CIP1 and mdm-2. Cell proliferation was determined by immunolabelling with PCNA and Ki67 antigens. Mitosis figures were counted in 10 high power microscopic fields. RESULTS: Patients from whom gastric cancer specimens were obtained had a mean age of 59.3 years. Ki67 and mitosis counting showed the highest correlation index with proliferation indexes studied. No correlation was found between the expression of protein complex p53/p21WAF1/CIP1 and mdm-2 and morphological characteristics of gastric tumors. Mdm-2 protein overexpression was the only marker that showed an independent correlation with cell proliferation. Moreover, mdm-2 positive tumors showed the highest proliferation indexes when p53 was not immunohistochemically over-expressed, as determined by PCNA labelling index. CONCLUSIONS: In gastric cancer, a direct correlation between mdm-2 overexpression and cell proliferation was observed. Moreover, the fact that mdm-2 positive tumors showed the highest cell proliferation when p53 was not overexpressed, entitles us to hypothesize that mdm-2 overexpression could play a major role in gastric carcinogenesis.

Biomarkers, Tumor↗

[Carcinoma hepatocellular. Description of verified clinical characteristics in a region of Southern Chile].

BACKGROUND: Hepatocellular carcinoma is the most frequent primary tumor of the liver. It is associated to chronic liver diseases and has a high prevalence in some regions of Africa and Asia. AIM: To describe the clinical characteristics of patients with hepatocellular carcinoma, admitted to two hospitals of the IX region of southern Chile. MATERIAL AND METHODS: Prospective study of 29 consecutive patients admitted to two hospitals in Temuco, Chile. Clinical features, laboratory values and viral markers were analyzed. RESULTS: Eighteen patients were male and ages ranged from 29 to 75 years old. The most frequent presenting symptom was abdominal pain in 21 patients. Seven subjects had a history of alcoholism. Serum bilirubin values ranged from 0.1 to 15.8 mg/dl, alkaline phosphatases ranged from 171 to 3476 U/l, ASAT from 24 to 5400 U/l and alpha feto protein from 1.4 to 350 ng/ml. Two patients had a positive hepatitis B surface antigen and all had negative hepatitis C virus antibodies. Mean tumoral diameter was 9.6 cm and the most common presentation was nodular. Mean survival after the diagnosis was 6.3 months. CONCLUSIONS: These patients with hepatocellular carcinoma have a low frequency of positive viral markers and tumors of large sizes on presentation.

Adult↗

[P53 tumor suppressor gene in digestive neoplasms].

Malignant diseases of the digestive tract cause more than 50% of deaths due to cancer in Chile. There is a high incidence of gastric and gallbladder cancer and an increasing frequency of colorectal cancer. P53 tumor suppressor gene has a great importance in carcinogenesis and its alterations are specially important in digestive tract tumors such as colorectal cancer. There is contradictory evidence about the frequency of p53 gene or protein alterations or their biological significance. There is little information about p53 in Chile and it is mostly limited to immunohistochemical studies. This revision analyzes the frequency of p53 alterations in digestive tract tumors in Chile, using immunohistochemical and molecular biology methods. A special emphasis is given to the prognostic importance of this gene.

Digestive System Neoplasms↗

[p53 gene mutation in cancer of the colon and rectum].

BACKGROUND: Genetic events associated to colorectal carcinoma are well characterized, but there is scanty information about this issue in Chilean subjects. AIM: To determine the frequency and distribution of exons 5, 6, 7, 8 and 9 mutations and the immunohistochemical expression of p53 gene in biopsy samples of colorectal carcinoma. MATERIAL AND METHODS: p53 gene exons 5, 6, 7, 8 and 9 were directly sequenced in 42 biopsy samples of colorectal carcinoma. Immunohistochemical expression of p53 was determined in 35 samples. RESULTS: Thirty one discrete mutations (12 transitions, 11 transversions and 8 insertions) were observed in 21 samples (60%). Nine samples had mutations in exon 5, twelve samples had mutations in exon 6, seven samples had mutations in exon 7 and three samples had mutations in exons 8 and 9. Immunohistochemical expression of p53 protein was observed in 18 of 35 cases. There was a high correlation between the genetic alteration and immunohistochemistry, when p53 was expressed in more the 20% of cells. The positive and negative predictive values of p53 expression were 87 and 80% respectively. There was a non significant lower mortality among patients with mutations in their biopsies. CONCLUSIONS: These results confirm the involvement of p53 gene mutations in colonic carcinogenesis. Immunohistochemical methods for the detection of p53 protein have a high predictive value.

Adenocarcinoma↗

Preoperative chemoradiotherapy in the treatment of gallbladder cancer.

Gallbladder cancer is generally associated with a poor prognosis, with local recurrence being the main pattern of failure. In an attempt to improve on the present status of management, we evaluated a prospective Phase II study involving preoperative 5-fluorouracil and radiation. Among 27 eligible patients with a potentially resectable gallbladder cancer detected after cholecystectomy, 18 were treated with preoperative radiation (4500 cGy; 180 cGy/fraction, 5 days/week) concurrent with a continuous infusion of 5-fluorouracil (350 mg/m2/day, days 1-5 and 21-25). Toxicity included leukopenia (8 patients) and thrombocytopenia (7 patients). Delay in surgery due to hematological toxicity was seen in 6 patients. Of the 18 patients, 15 underwent a reoperation. Resection was performed in 13 (86%). Pathologic findings after reoperation revealed residual tumor in both liver and lymph nodes in 3 patients. At a median follow-up of 24 months, 7 patients are alive. Among the patients who died after curative resection, local recurrence was demonstrated in only 1. This is the first report concerning preoperative chemoradiation in gallbladder cancer. To assess its effect on survival, a prospective randomized trial will be necessary.

Adult↗

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↗

Peritoneal pseudomyxoma in a child with a gallbladder Peutz-Jeghers-like hamartomatous polyp: a case report.

A 2-year, 6-month-old boy with peritoneal pseudomyxoma had a hamartomatous Peutz-Jeghers-like polyp in the gallbladder. The morphological pattern of the polyp was very characteristic of what is usually considered an hamartomatous polyp. The patient presently reported has no clinical characteristics of Peutz-Jeghers syndrome. The peritoneal pseudomyxoma creates differential diagnostic problems with well-differentiated mucinous adenocarcinoma.

Child, Preschool↗

[Tumor invasion in gallbladder cancer. Importance of blood vascular tumor infiltration diagnosis].

BACKGROUND: The infiltration of venous blood vessels in gallbladder carcinoma and its importance as a prognostic factor has not been well studied. Victoria blue stain has been used to identify vascular involvement in gastric and thyroidal carcinomas. AIM: To assess blood vessel infiltration using Victoria blue stain in gallbladder carcinomas. MATERIAL AND METHODS: One hundred forty eight samples of gallbladder carcinomas, coming from 24 men and 123 women aged 60.4 +/- 12.2 years old, were studied. They were stained with Victoria blue stain to quantify blood vessel invasion. RESULTS: Twenty nine percent of tumors had blood vessel infiltration, 61% had lymph vessel and 20% had perineural infiltration. Lymph vessel or perineural involvement was found in 81% and 31% of those tumors with blood vessel infiltration, respectively. Perineural infiltration was associated with lymph or vascular involvement in 93 and 40% of tumors, respectively. None of the early carcinomas had blood vessel infiltration, whereas 33% of advanced tumors had this type of infiltration (p < 0.001). No differences in vascular infiltration were observed according to the differentiation of the tumor. CONCLUSIONS: Blood vessel infiltration was observed only in advanced gallbladder carcinomas and was tightly related to the degree of gallbladder wall infiltration. The presence of perineural infiltration was the best marker of lymph or blood vessel infiltration.

Adenocarcinoma↗

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↗