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Biomedical subjects

I Roa

Publications and source records attributed to I Roa.

At least 19 recordsLinked to original sources

[CD44 (HCAM) expression in subserous gallbladder carcinoma].

BACKGROUND: HCAM or CD44 is a multifunctional cell adhesion molecule, related to cell-cell, cell-extracellular matrix interactions and involved in tumor invasion. AIM: To study the importance of CD44 expression in subserous gallbladder carcinoma. MATERIAL AND METHODS: One hundred five samples (93 female) of subserous gallbladder carcinoma and 33 non tumoral gallbladder were studied. CD44 was stained using the streptavidine-biotin technique, using human anti CD44 antibodies. Eighty subjects with carcinoma were followed for a period up to 105 months. RESULTS: Mean age of patients was 62.6 years old, all tumors were adenocarcinoma, all were silent and 13% were well differentiated. CD44 was expressed in all controls and in 91%, the expression was normal. In 57% of cancer samples, CD44 expression was abnormal, in 50% it was less expressed and in 24%, it was not expressed. No differences in CD44 expression was observed between mucosa from control samples and mucosa adjacent to the tumor or superficial or deep tumoral areas. Global five years survival was 40%. No significant differences in survival were observed in those tumors with a lower of absent CD44 expression. Six patients with a higher expression died before 18 months of follow up. CONCLUSIONS: Nearly 50% of subserous gallbladder carcinomas show an abnormal CD44 expression.

Adenocarcinoma↗

[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↗

Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population.

We examined 169 cases of gastric adenocarcinoma for microsatellite instability (MSI), using a panel of 8 microsatellite markers. Of these cases, 142 were from the United States, a country of relatively low risk for gastric cancer. Comparing microdissected tumors to normal cells from the same patient, we classified tumors as being microsatellite-stable (MSS) or having a low frequency of MSI (MSI-L, up to 30% of markers different in the tumor) or a high frequency of MSI (MSI-H, 30% or more of markers different). Among our American cases, we identified 26 (18.2%) showing MSI-H and 15 (10.6%) showing MSI-L. Twenty cases were from Korean patients, and they showed no significant differences in proportions of MSI-H and MSI-L from the American cases. MSI-H tumors in the American patients were characterized by elevated frequencies of band shifts in repeat sequences of the BAX (50%), transforming growth factor-beta receptor type II (TGFbetaRII, 68.9%), beta(2)-microglobulin (21.4%) and E2F4 (51.7%) genes. Alterations in E2F4 in MSI-H tumors were always integral multiples of 3 nucleotides lost or gained, which would not cause a frameshift mutation, and within the range of normal polymorphisms for this sequence. North American patients (n = 127) with MSI-H and MSI-L tumors had a longer median survival of 541 days and 587 days, respectively, compared to 265 days for patients with MSS tumors (p = 0.027). This survival difference may result from a significantly greater tendency for metastases in the MSS group (p = 0.031).

Humans↗

[P53 gene mutation in gallbladder cancer].

BACKGROUND: Gallbladder cancer frequency and mortality renders it one of the most important neoplastic diseases in Chile. P53 tumor suppressor gene has been studied in most types of cancer, but there is scarce information about it in gallbladder cancer. AIM: To study the frequency of P53 gene mutation in gallbladder cancer in the ninth region of Chile. MATERIAL AND METHODS: In 25 pathological samples of gallbladder cancer, the direct amplification and sequencing of p53 gene exons 5,6,7,8-8 was possible. RESULTS: Seventeen punctual mutations were observed in 13 cases (52%). There were 10 transitions, 5 transversions, one insertion (codon 194) and one deletion (codon 186). Eight cases had mutations in exon 5, six had mutations in exon 6, two had mutations in exon 7 and one had mutations in exons 8-9. In 14 of 25 cases, gene p53 protein was positive. When immunohistochemical expression of gene p53 protein was positive in more than 20% of cells, there was a high correlation between genetic alterations and immunohistochemical expression of the protein, with a specificity, sensitivity, positive and negative predictive values over 80%. CONCLUSIONS: P53 gene mutation is observed in a high proportion of gallbladder cancers at it can be accurately detected with conventional immunohistochemical techniques. The importance of this gene in the genesis of this carcinoma should be determined studying preneoplastic lesions and early carcinomas.

Adenocarcinoma↗

[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↗

[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↗

[Bcl-2 gene protein expression in salivary gland tumors].

BACKGROUND: Salivary gland tumors have heterogeneous pathological features. Oncogene Bcl-2 product expression inhibits apoptosis and therefore is important for tumor proliferation. AIM: To assess the immunohistochemical gene Bcl-2 protein expression in salivary gland tumors. MATERIAL AND METHODS: Twenty seven salivary gland tumors were selected from the archives of the Pathology Department of Temuco Regional Hospital. There were 20 pleiomorphic adenomas, 4 cystic adenoid carcinomas and three mucoepidermoid carcinomas. Immunohistochemical gene Bcl-2 protein expression was determined in paraffin included pathological slices. RESULTS: All pleiomorphic adenomas expressed the protein, specially in tubulo ductal structures, solid and trabecular areas. All cystic adenoid carcinomas expressed the protein in myoepithelial cells. Two mucoepidermoid carcinomas were positive, only in the epidermoid areas. CONCLUSIONS: immunohistochemical gene Bcl-2 protein was expressed in virtually all benign and malignant salivary gland tumors. This observation suggest an important role of this protein in the development of these tumors.

Adenoma, Pleomorphic↗

[Chronic sclerosing non-specific sialadenitis of the submandibular gland (Küttner tumor). Report of one case].

Chronic sclerosing unspecific sialadenitis or Küttner tumor, is an infrequent inflammatory lesion of submandibular gland. We report a 60 years old male presenting with a slowly growing, painless, bilateral submandibular tumor of two years of evolution. Pathological examinations showed marked atrophy of glandular parenchyma with increased fibrous connective tissue and an intense lymphocytic infiltration with lymphoid follicle formation. Lymphocyte population study with kappa, lambda, CD20 and CD45RO antibodies was similar to that observed in reactive lymph nodes. There was no over expression of Bcl-2 gene protein, involved in the phenomenon of apoptosis of glandular tissue, that could explain the pathogenesis of atrophy. This protein was positive only in lymphoid cells and glandular conducts. An immune etiology, with replacement of glandular tissue by lymphoid and fibrous connective tissue is suggested.

Chronic Disease↗

[Microbiological study of gallbladder bile in a high risk zone for gallbladder cancer].

BACKGROUND: Gallbladder cancer is frequent in Chile and there is sparse information about the association between this type of cancer and the presence of bacteria in the gallbladder bile. AIM: To determine the presence of aerobic bacteria in gallbladder bile in patients with and without gallbladder cancer. MATERIAL AND METHODS: A microbiological analysis of bile and pathological study was performed in 608 gallbladders, obtained during to cholecystectomies performed to 513 women and 95 men aged 44 years old as a mean. RESULTS: Pathological study showed a chronic cholecystitis in 468 cases (77%), an acute cholecystitis in 140 (33%), cancer in 24 (3.9%) and dysplasia in 5 cases (0.8%). A positive culture was obtained in 22.5% of women and 28.5% of males. Twenty seven percent of women over 30 years old had positive cultures compared with 10% of younger women (p < 0.001). Thirty two percent of acute cholecystitis had positive cultures, compared with 24% of chronic cholecystitis (p = 0.03). E Coli was isolated in 51% of positive cases, Streptococci-Enterococci in 24%, Enterobacter sp in 9%, Klebsiella and Proteus in lower proportions. Salmonella sp was isolated in 4 cases, being all women with chronic cholecystitis. Thirteen of 29 cases with cancer or dysplasia had positive cultures (45%), compared with 25% of patients with inflammatory gallbladder diseases (p = 0.02). Streptococci-Enterococci were isolated in 7 cases and Enterobacter sp in three. CONCLUSIONS: The presence of Salmonella sp in gallbladder bile was not frequent in the studied patients. Its role in the pathogenesis of gallbladder cancer must be reassessed.

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↗

p53 tumour suppressor gene protein expression in early and advanced gallbladder carcinoma.

AIMS: Gallbladder carcinoma is one of the most frequent malignant tumours occurring in Chile and the mortality rate in both sexes ranks among one of the highest in the world. Mutation of p53 tumour suppressor gene has been demonstrated in many tumours. Our aim was to determine protein expression of p53 gene in early and advanced gallbladder carcinoma. METHODS AND RESULTS: Protein expression of gene p53 was studied by immunohistochemical means in 191 gallbladder carcinomas (157 primary tumours, 34 metastases) and 25 controls. In 86 out of 191 cases (45%), protein expression of gene p53 was observed. Differences related to sex, age, or race were not observed. All gallbladder controls were negative. Twenty-five per cent of well-differentiated tumours were p53 positive, while moderate or poorly differentiated carcinomas reached 50% (P = 0.04). p53 expression was observed in 23.5% of early carcinomas and in 48.2% of advanced carcinomas (P = 0.01). No differences between primary tumours and metastasis were demonstrated. CONCLUSIONS: Protein expression of p53 tumour suppressor gene is observed in 45% of gallbladder carcinomas. The absence of expression in controls and in normal mucosa adjacent to tumours suggests its utility in differentiating atypical gallbladder epithelia from neoplastic lesions.

Carcinoma↗

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↗