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Biomedical subjects

E G Silva

Publications and source records attributed to E G Silva.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prognostic significance of p53 expression in advanced-stage ovarian serous borderline tumors.

The purpose of this study was to investigate the frequency of p53 overexpression in the primary ovarian tumors of patients with stages II and III serous borderline tumors (SBTs) and to determine the relationship between p53 overexpression and risk of progression/recurrence and survival. Of 112 patients with stages II-IV SBTs, paraffin-embedded tissue from the primary ovarian tumor was available in 68 cases. Immunohistochemical staining for p53 was performed. Clinical information was abstracted from the medical records. The major end points selected for analysis were time to progression/relapse, disease-free survival, overall survival, and cause-specific survival. Univariate and multivariate regression analyses were also performed. The median patient age was 37 years (range, 17-67 years). Twenty-two patients had stage II disease, and 46 had stage III disease. The mean follow-up time was 105 months. Nineteen patients (28%) had either disease progression (1 patient) or relapse (18 patients). Eleven patients died: 10 patients died of their tumor, and 1 patient died of other causes. Thirteen cases (19%) had positive immunostaining for p53. Overexpression of p53 was significantly associated with an increased probability of progression/recurrence (P = 0.005) and a decreased overall survival (P = 0.012). After adjusting for age, International Federation of Gynecology and Obstetrics (FIGO) stage, the presence of residual tumor, and the presence of invasive implants, patients whose tumors overexpressed p53 had a 4-fold increased risk of progression/ recurrence. Similarly, women whose tumor overexpressed p53 had an approximately 6-fold increased risk of death. p53 overexpression in the ovarian tumors of patients with stage II and III SBTs is significantly associated with increased probability of relapse and decreased overall survival. This information should provide better prognostic data to patients and their families and allow us to select patients who might benefit from postoperative treatment.

Adolescent↗
PubMed1998

Serous borderline tumors of the ovary with noninvasive peritoneal implants.

BACKGROUND: The authors conducted this study to update their experience with patients who have ovarian serous borderline tumors with noninvasive peritoneal implants, with the objectives of gaining additional insight into the biologic behavior of these tumors and understanding better the effects of postoperative treatment. METHODS: Seventy-three patients who had ovarian serous borderline tumors with noninvasive peritoneal implants were identified in a retrospective review. Major end points selected for analysis were surgicopathologic response, time to relapse, type of relapse, progression free survival, and overall survival. Univariate and multivariate regression analyses were also performed. RESULTS: The median follow-up time was 10.3 years. Of 20 patients with macroscopic residual disease at completion of initial surgery who subsequently underwent second-look surgery, 3 (15%) had a response to chemotherapy. Twenty-two of 73 patients (30%) either developed progressive disease or had a relapse. The median time from the date of diagnosis to relapse was 7.1 years. Tissue was available from 20 of the 22 patients who had a relapse; 14 (70%) had invasive low grade serous carcinomas, and 6 (30%) had recurrent borderline tumors. Age was the only factor studied that had a significant influence on survival (P = 0.03). In both univariate and multivariate proportional hazards models, age and residual disease were found to be of borderline significance in predicting cancer specific survival. CONCLUSIONS: Approximately 30% of patients who have ovarian serous borderline tumors with noninvasive peritoneal implants will develop progressive or recurrent tumors, most commonly serous carcinomas. The presence of macroscopic residual disease appears to be a predictor of disease free survival. In this study, however, the authors were unable to elucidate the role of postoperative therapy or determine criteria for selecting patients for such therapy.

Adolescent↗
PubMed1998

Ovarian serous borderline tumors with invasive peritoneal implants.

BACKGROUND: The objective of the current study was to update the authors' experience with patients with ovarian serous borderline tumors with invasive peritoneal implants to gain additional insight into the biologic behavior of these tumors and a better understanding of the effect of postoperative treatment. METHODS: Thirty-nine patients with ovarian serous borderline tumors with invasive peritoneal implants were identified through a retrospective review. Major endpoints selected for analysis were surgicopathologic response, time to recurrence, type of recurrence, progression free survival, and overall survival. Univariate and multivariate regression analyses also were performed. RESULTS: Median follow-up time was 111 months. Four of 7 evaluable patients who had second-look surgery (57%) had a response to chemotherapy. Twelve of 39 patients (31%) either developed progressive disease or had a recurrence. The median time from date of diagnosis to recurrence was 24 months. In 10 of these 12 patients with a recurrence, tissue was available; 9 had invasive low grade serous carcinoma and 1 had a recurrent borderline tumor. Macroscopic residual disease was the only factor studied that had a significant effect on survival; patients with no macroscopic residual tumor had a significantly better survival than those with any macroscopic residual tumor (P < 0.01). In univariate regression analysis, macroscopic residual disease and the presence of frankly invasive implants were significant predictors of progression free survival. Platinum-based chemotherapy was associated with a significantly shorter progression-free survival. Only macroscopic residual tumor was a significant predictor of survival. CONCLUSIONS: Greater than 30% of patients with ovarian serous borderline tumors with invasive peritoneal implants will develop progressive or recurrent tumor, most commonly serous carcinoma. The presence of macroscopic residual disease appears to be the major predictor of recurrence and survival. However, in this study, the authors were unable to elucidate the role of postoperative therapy or the criteria for selection of patients for such therapy.

Adult↗
PubMed1998

Induction of epithelial neoplasms in the ovaries of guinea pigs by estrogenic stimulation.

OBJECTIVE: We have been searching for an animal model for ovarian epithelial neoplasms. Our previous study suggested that by giving intermediate doses of testosterone to guinea pigs it is possible to induce cystadenomas in the ovaries in 6 to 10 months. METHODS: In this study we investigated the effect of different estrogens including estradiol, diethylstilbestrol (DES), estrone, dienestrol, and hexestrol in 24 guinea pigs. Five guinea pigs received sterile water and were used as controls. RESULTS: Bilateral serous cysts were seen in the ovaries of five guinea pigs that received low (0.25 and 0.35 mg) and intermediate (0.5 and 0.7 mg) doses of estradiol for 2 to 9 months. Surface papillary neoplasms were seen in the ovaries of four guinea pigs that received DES at an intermediate dose (6 mg) and high doses (10 and 12 mg) for 3 to 12 months. The ovaries of the other guinea pigs were unremarkable. Estradiol was measured by radioimmunoassay in three guinea pigs. In the serum it ranged from 450 to 580 pg/ml, and in the ovarian cystadenomas it ranged from 1020 to 6575 pg/ml. CONCLUSIONS: (1) It is possible to induce ovarian neoplasms using estrogenic hormones. (2) The best results are obtained with intermediate doses of estradiol and DES. (3) These two hormones induce different lesions: estradiol is associated with cystic lesions and DES with surface papillary tumors. These observations, together with our previous finding that testosterone induces neoplasms with a predominantly glandular pattern, establish the guinea pig as an excellent animal to study ovarian neoplasms, confirm the significance of hormones in the development of ovarian epithelial tumors, and suggest that the different histologic appearance of ovarian epithelial neoplasms might be related to different hormonal effects.

Animals↗
PubMed1998

Dietary magnesium improves endothelial dependent relaxation of balloon injured arteries in rats.

The purpose of the present study was to examine the importance of magnesium in endothelial function after arterial balloon injury. Male Wistar rats were fed normal, high or low concentrations of magnesium. Three weeks later the animals underwent endothelial injury of the thoracic aorta by a balloon catheter or a sham operation. Biochemical, histological and endothelial function analysis were performed 15 days after the surgical treatment. The animals fed a low magnesium diet presented the lowest level of serum magnesium and the highest ionized blood calcium levels. Histomorphometric analysis revealed no differences among groups neither regarding the magnitude of intimal thickening nor the recovery of endothelial coverage. However, when vasoreactivity responses were compared in the balloon-injured group, those animals fed a high magnesium diet had the better endothelium-dependent vascular relaxation. In conclusion, a higher magnesium level in the diet was beneficial to vessels that underwent endothelial injury by balloon catheter.

Animals↗
PubMed1998

Impaired function of alpha-2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats.

The alpha2-adrenoceptor function in mesenteric arteries of spontaneously hypertensive rats (SHR) was investigated by comparing membrane potential changes in response to adrenergic agonists in preparations from female SHR, Wistar-Kyoto (WKY) and normotensive Wistar rats (NWR). Resting membrane potential was found to be less negative in mesenteric arteries from SHR than in those from NWR and WKY. Apamin induced a decrease in the membrane potential of mesenteric artery rings without endothelium from NWR and WKY, but had no effects in those from SHR. Both UK 14,304 and adrenaline, in the presence of prazosin, induced a hyperpolarization that was significantly lower in de-endothelialized mesenteric rings from SHR than in those from NWR and WKY. In mesenteric rings with endothelium, however, similar hyperpolarization was observed in the three strains. In NWR mesenteric rings with endothelium the hyperpolarization induced by activation of alpha2-adrenoceptors was abolished by apamin, whereas in intact SHR mesenteric rings this hyperpolarization was slightly reduced by apamin and more efficiently reduced by Nomega-nitro-L-arginine. It is concluded that the activity of potassium channels coupled to alpha2-adrenoceptors is altered in the smooth muscle cells of SHR mesenteric arteries, contributing to their less negative membrane potential. On the other hand, the endothelial alpha2-receptors are functioning in mesenteric vessels from SHR and their stimulation induces a hyperpolarization mainly through the release of nitric oxide.

Adrenergic alpha-Agonists↗
PubMed1998

Tumor recurrence in stage I ovarian serous neoplasms of low malignant potential.

Eleven patients treated at the University of Texas M. D. Anderson Cancer Center for recurrent disease after resection of a stage I ovarian serous neoplasm of low malignant potential (SNLMP) are reported. At the time of diagnosis, the age of the patients ranged from 26 to 43 years (mean 33). Seven patients had stage IB tumors and 4 had stage IA tumors. All patients were treated with a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The size of the ovarian tumors ranged from 4 to 15 cm in maximum dimension. Stromal microinvasion was seen in 2 cases, and foci of endosalpingiosis were seen in the peritoneum in 8 cases. Nine patients were treated with radiotherapy and 2 with chemotherapy. The time to recurrent disease ranged from 7 to 39 years (mean 16). Eight tumors recurred in the pelvis or abdomen, 2 in the neck with subsequent abdominal involvement, and 1 in the pleura without abdominal or pelvic involvement. In 10 cases, the recurrent tumors were serous carcinoma, and in 1 case it was a SNLMP. Recurrences were treated with chemotherapy in 10 cases and with hormones in 1 case. Seven patients died of progressive serous carcinoma 2 to 5 years after the recurrence. One patient died of leukemia with recurrent ovarian tumor 10 years after the recurrence was detected. Two patients are alive with progressive disease 1 and 7 years after the recurrence, and 1 patient whose disease recurred as a SNLMP is alive with no evidence of disease 9 years after the recurrence. These 11 patients were compared with 16 patients who had stage I ovarian SNLMPs that did not recur after a minimum follow-up of 15 years. There was no difference in the age of the patients, gravidity, size of the tumors, or several microscopic parameters, including degree of epithelial proliferation, number of mitoses, and nuclear atypia. Microinvasion was found in one case. The only significant difference between the two groups was the low frequency of endosalpingiosis in the cases that had no disease recurrences (12.5% versus 72.7%). In summary, we found no clinical or pathologic features that can unequivocally predict the recurrence of stage I ovarian SNLMPs. Because of the long interval to recurrence, the fact that the recurrent tumors in 10 of 11 patients were serous carcinomas, and the result of the X-chromosome inactivation in one case, the recurrent tumors could represent independent primaries or a slow progression of one clone present in the SNLMPs.

Adult↗
PubMed1997

Prognostic factors in adult granulosa cell tumor of the ovary.

BACKGROUND: The clinical course of adult granulosa cell tumor of the ovary is characterized by indolent growth tending toward late recurrence. A variety of clinical and pathologic parameters have previously been evaluated for prognostication with inconclusive results. METHODS: The clinical records and tumor sections of 70 patients with adult granulosa cell tumors of the ovary were reviewed. Patients with recurrent tumors (REC) (n = 19) were compared with patients who remained without disease (NED) (n = 51). RESULTS: Significant differences in stage and tumor size were noted between the two groups; however, after logistic regression analysis, only stage remained statistically significant. Pathologic evaluation revealed that Call-Exner bodies occurred more frequently in tumors of the NED patients. Cellular atypia and high mitotic rates were more frequent in the REC group; however, after logistic regression analysis, only atypia remained statistically significant. When early (< 10 years) and late recurring tumors (> 10 years) were compared, statistically significant differences were again noted: early recurring tumors had fewer Call-Exner bodies, higher mitotic rates, and higher degrees of atypia; late recurring tumors were similar to tumors in the NED patients. CONCLUSIONS: Tumor stage and, to a lesser extent, tumor size are the only clinical parameters of prognostic importance in adult granulosa cell tumors. Cellular atypia and, to lesser extents, mitotic rate and the absence of Call-Exner bodies are the only significant pathologic prognosticators. It is difficult to predict early recurrences and impossible to predict late recurrences using these clinical and pathologic parameters.

Adult↗
PubMed1997

Molecular profile of advanced-stage transitional cell carcinoma of the ovary.

OBJECTIVES: Our purpose was to determine the molecular profile of advanced-stage transitional cell carcinoma in terms of immunostaining for p53, epidermal growth factor receptor and HER-2/neu, deoxyribonucleic acid index, and S-phase fraction and to analyze the prognostic significance of these markers. STUDY DESIGN: Archival paraffin-embedded tissue blocks from 29 advanced stage transitional cell carcinomas were obtained. Selected sections of the primary tumors were immunostained for p53, epidermal growth factor receptor, and HER-2/neu; deoxyribonucleic acid ploidy and S-phase fraction were determined with use of flow cytometry. Clinical information was abstracted from the medical records. Survival times were analyzed according to the life-table methods of Kaplan and Meier, and the statistical significance of the various factors was tested with the log-rank test. The proportional hazards model of Cox was used to identify prognostic factors. RESULTS: Positive immunostaining was observed for p53 in 13 cases (45%), for epidermal growth factor receptor in 14 cases (50%), and for HER-2/neu in 19 cases (65%). Tumors were diploid in 16 cases (55%) and aneuploid in 13 (45%). The S-phase fraction was < or = 15% (mean) in 13 cases (45%) and > 15% in 16 cases (55%). The median survival for the entire group was 52 months. None of the above variables had a significant effect on survival time. CONCLUSION: Neither immunostaining for p53, epidermal growth factor receptor, and HER-2/neu nor deoxyribonucleic acid ploidy nor S-phase fraction allowed us to distinguish transitional cell carcinoma from other more common epithelial ovarian cancers. In addition, no prognostic significance was associated with these biomarkers. A study of larger numbers of cases may be more elucidative.

Adult↗
PubMed1997

Islet cell tumour with vacuolated lipid-rich cytoplasm: a new histological variant of islet cell tumour.

AIMS: A previously unreported clear cell variant of islet cell tumour of the pancreas is described. METHODS AND RESULTS: By light microscopy, the cytoplasm of the clear cells was finely reticulated and vacuolated. Immuno-histochemical and electron microscopy studies confirmed the endocrine nature of the tumour. CONCLUSIONS: The clear cell morphology was due to the accumulation of lipid in the cytoplasm.

Adenoma, Islet Cell↗
PubMed1997

Ovarian serous neoplasms of low malignant potential associated with focal areas of serous carcinoma.

This is a study of 12 cases of Stage III ovarian serous neoplasms of low malignant potential associated with focal areas (< 50%) of serous carcinoma. The purpose of this study was to assess the prognosis of serous tumors that had areas of serous carcinoma but were predominantly of low malignant potential. Eleven serous carcinomas were low grade, and one was high grade. All of the patients underwent surgical resection of the neoplasm and then chemotherapy. Eight patients died of disease after a follow-up of 17 to 94 months (mean, 52 mo). Three patients had no evidence of disease at 60, 69, and 75 months. One patient is alive with progressive disease at 58 months. Serous neoplasms of low malignant potential associated with focal areas (< 50%) of serous carcinoma are aggressive neoplasms that have a prognosis similar to that of serous carcinoma.

Adult↗
PubMed1997

The induction of benign epithelial neoplasms of the ovaries of guinea pigs by testosterone stimulation: a potential animal model.

We studied the effects of different hormones on the epithelial cells of the ovaries of 11 guinea pigs. Three received testosterone, two received estrone, three megestrol, and three chorionic gonadotropin. Three control guinea pigs received sterile water. Benign epithelial cysts larger than 1.5 mm were found in six guinea pigs, three who received testosterone, one who received megestrol, and two who received chorionic gonadotropin. In one of the three guinea pigs who received testosterone, 2.5-cm bilateral cysts were grossly identified. Papillary excrescences were found on the ovarian surface in four guinea pigs, three who received testosterone and one who received megestrol. The proliferating epithelial cells also formed benign glands in the ovarian stroma in two guinea pigs who received testosterone, the most exuberant epithelial proliferations, including large bilateral cystadenomas, papillary excrescence that formed a small papillary neoplasm, and glands in the ovarian stroma that formed adenomatous areas, were seen in the guinea pig who received an intermediate dose of testosterone for the longest time. By radioimmunoassay, the serum level of testosterone was 22 ng/dL in one of the controls and 10,000, 12,000, and 15,000 ng/dL in the three guinea pigs who received testosterone. In the guinea pig with the most exuberant epithelial proliferation, the level of testosterone in the uterus was similar to that in the serum (13,860 ng/mg), but in the wall of the ovarian epithelial cyst, it was three times higher than it was in the serum (44,000 ng/mg). Our study shows that testosterone stimulates the growth of epithelial cells in the ovaries of guinea pigs, resulting in benign cysts, small adenomas in the ovarian parenchyma, and papillomas on the ovarian surface. The study also shows that guinea pigs can be used as an animal model for epithelial tumors of the human ovary.

Animals↗
PubMed1996

Transitional cell neoplasms of the ovary and urinary bladder: a comparative immunohistochemical analysis.

Walthard cell nests, the Brenner tumor (benign, proliferating, low malignant potential, and malignant), and primary ovarian transitional cell carcinoma are considered to be primary female genital tract proliferations of transitional-type (urothelial) epithelium on conventional light microscopic grounds. In order to further investigate the similarities (or dissimilarities) of proliferations of female genital tract transitional epithelium and urothelium, we compared transitional cell proliferations (TCPs) of the female genital tract (n = 25) and urinary bladder (n = 15) using antibodies to carcinoembryonic antigen (CEA; clone 0062), carbohydrate determinant 19-9 (CA19-9; clone 1116-NS-19-9), cytokeratin 7 (CK-7; clone OV-TL 12/30), and cytokeratin 20 (CK-20; clone Ks 20.8), four monoclonal antibodies that have been shown to stain transitional cell urothelial proliferations. Both groups of tumors exhibited significant staining for CEA, CA19-9, and CK-7, and the difference in numbers of cases staining was not significant. CA19-9 was present in 15 of 25 female genital tract TCPs as compared with 12 of 15 bladder TCPs; CEA was present in 17 of 25 female genital tract TCPs and nine of 15 comparable bladder TCPs. CK-7 was present in all cases studied with the exception of one Walthard cell nest and a malignant Brenner tumor that was not immunoreactive with the other antibodies tested. In contrast, 13 of 15 bladder TCPs were CK-20 positive, whereas only one of 25 female genital tract TCPs was positive (< 5% of cells). Walthard cell nests and benign Brenner tumors were more likely to be CA19-9 positive than were Brenner tumors of low malignant potential, malignant Brenner tumors, and primary transitional cell carcinoma of the ovary. We conclude that despite their apparent morphologic and immunologic similarity to TCPs of the urinary bladder (particularly at the histologically low-grade end of the transitional cells spectrum), Walthard cell nests and ovarian Brenner tumors constitute an immunophenotypically distinct form of TCP.

Antibodies, Monoclonal↗
PubMed1996

Effect of treatment with cholecalciferol on the membrane potential and contractility of aortae from spontaneously hypertensive rats.

1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) was supplemented with 12.5 micrograms cholecalciferol per 100 g body weight daily, by gavage, for 4 weeks. 2. The amplitude of the contractile responses of aortic rings from SHR to potassium and adrenaline, which was smaller than in NWR aortae, was increased after treatment with cholecalciferol. No further changes were observed in the responses of NWR and SHR aortae in the presence of 100 nM apamin. 3. The membrane potentials of aortae from SHR, which were higher than those of aortae from NWR, decreased after treatment with cholecalciferol. Further depolarization was observed in aortic rings from NWR, but not in aortic rings from SHR, after their preincubation with 100 nM apamin. 4. It is concluded that cholecalciferol normalizes the membrane potential and contractility of aortae from SHR, probably through an effect on lipid composition and structure of the plasma membrane.

Animals↗
PubMed1996

Merkel cell carcinoma of the skin: imaging and clinical features in 93 cases.

Clinical, pathological and imaging data for 93 patients with Merkel cell carcinoma were reviewed. Median survival duration from the date of diagnosis was estimated using the Kaplan-Meier product-limit method. Survival durations of patients with no metastastic disease, with regional lymph node metastasis only and with distant metastases were compared using the Cox-Mantel log-rank test. The median age for patients with Merkel cell carcinoma was 70 years (range 35-91 years). The tumour occurred in 71 men and 22 women. The most common primary site was the head and neck region (64 patients), followed by the extremities (21 patients) and the trunk (10 patients). Median survival duration for the whole group was 33 months (range 2-140 months). Imaging studies of the primary sites were available for 10 patients and of metastatic sites for seven patients. Sonograms of the primary skin lesions showed single or multicentric hypoechoic nodules arising from the dermis and growing into the subcutaneous tissues. CT scans showed single or multiple minimally enhancing soft tissue nodules, in two instances associated with lytic bone erosion. The metastatic lesions were moderately hypoechoic on sonography and target-shaped with or without ring-enhancement on CT. Imaging studies have a limited role in diagnosis of the clinically evident primary skin lesions, but may be helpful in the assessment of the depth of the invasion and are crucial in the evaluation of regional and distant metastatic disease. If regional adenopathy is found then CT of the chest, abdomen and pelvis may be in order.

Adult↗
PubMed1996

Dual effect of clonidine on mesenteric artery adrenoceptors: agonistic (alpha-2) and antagonistic (alpha-1).

The effect of clonidine on the mesenteric vascular bed and the isolated mesenteric artery was examined in preparations in which tonus was induced by norepinephrine or endothelin. In preparations precontracted by norepinephrine, clonidine caused a relaxation which was not inhibited by the alpha-2 antagonists yohimbine and idazoxan or by the K+ channel blockers apamine, tetraethylammonium and glibenclamide. In preparations precontracted with endothelin, clonidine increased the depolarization and induced a contraction. Both these effects were inhibited by prazosin. In isolated mesenteric arteries, norepinephrine cause a significant depolarization that was inhibited by clonidine or prazosin. On the other hand, clonidine caused a hyperpolarization which was inhibited by idazoxan or yohimbine, but not by prazosin. This hyperpolarization was also abolished by apamine, tetraethylammonium and glibenclamide. It is concluded that clonidine acts on alpha-1 adrenoceptors as a partial agonist, causing relaxation of the mesenteric artery precontracted with norepinephrine or contraction of preparations precontracted with endothelin. Moreover, clonidine can open K+ channels and hyperpolarize the plasma membrane of mesenteric artery by acting on alpha-2 adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1996

Leuprolide acetate in advanced ovarian serous tumor of low malignant potential. A case report.

BACKGROUND: Patients with advanced ovarian tumors of low malignant potential have no defined systemic therapy. Leuprolide acetate and other gonadotropin-releasing hormone analogues have definitive activity in ovarian epithelial carcinomas. On the basis of these considerations, we used leuprolide acetate to treat a young woman with an advanced ovarian tumor of low malignant potential. CASE: In a case of a long-term survivor of high-risk advanced-stage ovarian serous tumor of low malignant potential, suboptimal primary cytoreductive surgery was performed; at that time it was found that the tumor had directly invaded the outer uterine wall and rectosigmoid colon serosa and had metastasized to the pelvic lymph nodes. Postoperative adjunctive hormonal treatment with leuprolide acetate was administered and resulted in a complete clinical and serologic response. The patient remained disease free 68 months after the initial diagnosis. Her only symptoms were minimal hot flashes and vaginal dryness. CONCLUSION: Leuprolide acetate may be active in the treatment of ovarian tumors of low malignant potential. It should be considered frontline systemic therapy for this disease.

Adult↗