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Biomedical subjects

M Altaras

Publications and source records attributed to M Altaras.

At least 19 recordsLinked to original sources

Complete hydatidiform mole and a coexistent viable fetus: report of two cases and review of the literature.

OBJECTIVE: The aim of this study was to report the clinical features, management, and outcome of two cases of complete hydatidiform mole with a coexisting viable fetus and to review the literature. PATIENTS: In this article, we report on the well-documented follow-up of 2 cases of twin pregnancies with complete hydatidiform mole and a viable fetus, both of which ended with the delivery of a normal infant at 41 and 26 weeks of gestation. It is of interest that both pregnancies were achieved following induction of ovulation with hMG/hCG. Since 1977, the year in which complete and partial moles were characterized as distinct pathologic entities, 15 cases (including our 2) have been reported. RESULTS: Persistent GTT developed in eight patients (53.3%) and four patients (27.7%) developed metastatic disease. Seventy-five percent patients with persistent GTT were treated with single-agent chemotherapy. The median gestational age of the patients with subsequent persistent GTT was 34.5 weeks compared to 38 weeks in the patients without persistent GTT. CONCLUSION: Complete hydatidiform mole and coexistent fetus is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic tumor. Based on currently available information, it seems that in the presence of a stable pregnancy, normal karyotype, and a normal sonogram it is reasonable to allow the pregnancy to continue.

Adult↗

The value of transvaginal sonography in the preoperative assessment of myometrial invasion in high and low grade endometrial cancer and in comparison to frozen section in grade 1 disease.

OBJECTIVE: To evaluate the diagnostic accuracy of preoperative transvaginal sonography (TVS) in the detection of deep myometrial invasion in endometrial cancer cases classified by the grade of disease, and in comparison to frozen section analysis in grade 1 cases. METHODS: In a prospective study, 91 patients with confirmed endometrial carcinoma underwent preoperative TVS for evaluation of myoinvasion. Sonographic results were categorized as superficial (less than or equal to 1/2 myometrial depth) and deep invasion (greater than 1/2 myometrial depth). TAH-BSO followed by retroperitoneal lymph node sampling were performed in all patients with grade 2-3 tumors. In patients with grade 1 disease, the surgical specimen was intraoperatively evaluated by frozen section, and lymph node sampling was carried out if deep invasion was determined. The preoperative sonographic findings and the frozen section results were compared to the final histopathology report of myoinvasion. RESULTS: In 77 of the 91 (84.6%) patients, the sonographic assessment of the depth of myoinvasion was in accord with the final histopathologic findings. TVS demonstrated a sensitivity of 87.8% and a specificity of 82.7% in detecting deep invasion in the entire study group (grade 1-3), with positive and negative predictive values (PPV, NPV) of 74.3% and 92.3%, respectively. TVS in grade 1 cases (n=47) showed a sensitivity of 77.7%, a specificity of 79%, PPV of 46.6% and NPV of 93.7%. TVS in cases with grade 2-3 tumors (n=44) showed a sensitivity of 90%, specificity of 91.6%, PPV of 90% and NPV of 91.6%. Thus, the accuracy of TVS in grade 2-3 cases was superior to that achieved in grade 1 cases (91% vs 78.7%; p=.002). The myometrial invasion was assessed by frozen section in 41 out of 47 patients with grade 1 disease and demonstrated a sensitivity of 85.7%, a specificity of 100%, PPV of 100% and NPV of 97.1%. The specificity (100%) and accuracy (97.5%) of the frozen section were found to be superior compared to that of the TVS (79% and 78.7%) in detecting deep invasion in grade 1 cases (p=.008, p=.005, respectively). No statistically significant difference was found between the sensitivity of either technique. CONCLUSIONS: TVS appeared to be a more accurate method for preoperative assessment of myoinvasion in grade 2-3 endometrial cancer patients compared to grade 1 patients. In grade 1 cases, this method achieved lower accuracy in detecting deep invasion compared to the frozen section analysis. Based on these data, the value of preoperative TVS results as the sole criterion in the decision to perform extensive surgical procedures in grade 1 endometrial cancer is questionable and warrants further evaluation.

Adult↗

Increased frequency of TP53 mutations in BRCA1 and BRCA2 ovarian tumours.

We screened 81 ovarian tumours (30 BRCA1 associated, 18 BRCA2 associated, and 33 sporadic) for somatic TP53 mutations using both DNA analysis and immunostaining. TP53 mutations were significantly more frequent in tumours with mutations in BRCA1 (70% by immunostaining and 60% by DNA analysis) and BRCA2 (67% and 50%) compared to sporadic controls (39% and 30%) (P = 0.009). A higher proportion of tumours with BRCA1 and BRCA2 mutations were poorly differentiated, and TP53 mutant tumours in all categories were also more likely to be poorly differentiated. The poor differentiation of tumours with BRCA1 and BRCA2 mutations may be directly related to the role of these genes in DNA repair, and the need to overcome cell cycle checkpoints, often through loss of TP53. These results are consistent with the model of BRCA-induced tumorigenesis in which loss of checkpoint control is necessary for tumour development.

Alleles↗

Adenocarcinoma arising from the gastrointestinal epithelium in benign cystic teratoma of the ovary.

Malignant transformation of benign cystic teratoma of the ovary is rare, with an incidence of 1.8%. The commonest malignant neoplasm to develop is squamous carcinoma (80%). Adenocarcinoma occurs with less frequency, and only one of which has ever been cited to be of gastrointestinal origin. A 38-year-old female underwent TAH-BSO due to a large right ovarian tumor. Microscopically and immunohistochemically, the tumor was defined as mucinous adenocarcinoma originating from gastrointestinal epithelium in benign cystic teratoma.

Adenocarcinoma, Mucinous↗

Expression of cytokeratin-20 in endometrial carcinoma.

OBJECTIVE: Cytokeratins are constituents of the intermediate filaments of epithelial cells which are expressed in various combinations depending on the epithelial type and the degree of differentiation. The recently identified cytokeratin-20 (CK-20) was found with immunohistochemical methods to be expressed in gastrointestinal epithelium, uroepithelial cells, and Merkel cells. Clues were also found for low expression of CK-20 in endometrial carcinoma cells. The aim of this study was to examine whether CK-20 expression can be measured in endometrial carcinoma with the more sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) methods and therefore used as a potential diagnostic tumor biomarker for endometrial carcinoma. METHODS: In the present study we have used RT-PCR methods to determine expression of CK-20 in endometrial epithelial cells. Endometrial specimens were collected from 18 patients with endometrial carcinoma and 22 patients that underwent hysterectomy due to benign diseases. The specimens were prepared for both RT-PCR and immunohistochemical analysis. RNA, of the various cell pellets, was extracted and RT-PCR was performed with CK-20 and CK-19 primers (CK-19 was used as a marker for normal epithelial cells). Immunohistochemistry was carried out with the avidin-biotin-peroxidase complex method on formalin-fixed paraffin sections using CK-20 antibody. RESULTS: CK-20 amplification band (370 bp) was obtained with mRNA extracted from endometrial carcinoma cells of 17 of the patients with endometrial carcinoma (sensitivity, 94.4%). CK-20 was negative in 21 patients with benign endometrial disease (specificity, 91.3%). No positive results were obtained with the immunohistochemical methods. CONCLUSION: These results indicate that RT-PCR of CK-20, because of its high sensitivity, is a potential biomarker for detecting endometrial carcinoma.

Adult↗

Aztreonam plus piperacillin--empiric treatment of neutropenic fever in gynecology-oncology patients receiving cisplatin-based chemotherapy.

Antibiotic therapy must be instituted promptly and on an empiric basis in neutropenic patients. We evaluated the efficacy of a combined antibiotic regimen of monobactam (aztreonam) and antipseudomonal penicillin (piperacillin) in treating neutropenic fever episodes in gynecologic-oncology patients receiving cisplatin-based chemotherapy. A retrospective analysis of response to this regimen was performed. The rationale of this combination is the lack of nephrotoxicity and ototoxicity in patients who are or were previously treated with other nephrotoxic/ototoxic agents like cisplatin. A total of 19 courses of this regimen was administered to 13 patients with neutropenic fever following a complete fever work-up. Aztreonam (1-2gr q8h) plus piperacillin (4gr q8h) were administered intravenously for 6-8 days. Blood cultures were positive in four febrile episodes, and urine cultures were positive in seven. Gram negative organisms accounted for all positive cultures. The cultured organism showed in-vitro sensitivity to at least one of the drugs in all positive isolates. Clinical response with defervescence was noted during therapy in 18/19 courses (94.7%). Although the two drugs share a common bactericidal mechanism they were found to be highly active in this subgroup of patients. A double blind prospective evaluation of this empiric combination is warranted.

Adult↗

A second primary malignancy in a cohort of patients with epithelial ovarian cancer--characteristics of diagnosis.

As the life expectancy of cancer patients has been extended because of earlier diagnosis and improved therapeutic modalities, second primary tumors are being diagnosed more frequently. We have examined the clinical characteristics of 38 second primary tumors in a cohort of patients diagnosed with epithelial ovarian cancer in our department over a 6-year period. The most frequent neoplasm associations were in decreasing order of occurrence: ovary-breast, ovary-endometrium, and ovary-gastro-intestinal tract. Most heterochronous second primary tumors have been diagnosed following patient symptoms and not during routine follow-up of patients with a known primary cancer. Family history was obtained for 30/38 patients (19 with full pedigrees and 11 with partial information). Two of these 30 patients (6.6%) had one affected first degree relative-one with ovarian cancer and one with breast cancer. With an increased risk of developing a second malignancy after having a previous tumor, closer surveillance of patients posttreatment for cancer is warranted.

Adult↗

A 30s PAS stain for frozen section analysis of surgical margins of vulvectomy in Paget's disease.

Application of a modified periodic-acid Schiff's procedure (PAS) technique in frozen section analysis of surgical margins of vulvectomy specimen in Paget's disease is described. The reaction obtained using a microwave procedure takes only 30 seconds. This method was found to be useful in identifying Paget cells on the margins thought to be free of disease by conventional histological evaluation.

Aged↗

Sonographic and Doppler flow characteristics of ovarian tumors of low-malignant potential.

OBJECTIVE: To outline the sonographic and color Doppler flow imaging characteristics of ovarian tumors of low-malignant potential (OCLMP). METHODS: Fourteen women with ovarian tumors of low-malignant potential were compared with 26 women with ovarian cystadenomas and 23 with ovarian carcinomas. RESULTS: Sonographically, more complex structures and echogenic lesions were found in the OCLMP and malignant tumors than in the cystadenomas, and the difference was statistically significant. Color blood flow imaging revealed a similar resistant index (RI) in the OCLMP (0.487 +/- 0.07) and cystadenomas (0.489 +/- 0.09) when compared with statistically significant lower RI in the ovarian carcinomas (0.391 +/- 0.05) (P < 0.001). CONCLUSIONS: Among young women, the combination of a complex ovarian mass with turbid fluid and echogenic lesions whose color Doppler flow imaging registers in the low range (RI < 0.5) should raise the suspicion of an ovarian tumor of low-malignant potential.

Adult↗

Transvaginal color Doppler ultrasound in the assessment of invasive cervical carcinoma.

OBJECTIVE: To assess the validity of transvaginal color Doppler flow in the prediction of malignancy in the uterine cervix. STUDY DESIGN: Sixteen women with cervical pathology (14 with invasive carcinoma and 2 with cervical intraepithelial neoplasia III) were examined using transvaginal sonography as well as transvaginal color Doppler with measurements of the resistance index of tumor blood flow. Twenty-four women with histologically proven normal cervices served as a control group. RESULTS: Resistance index (RI) was significantly lower in the study group [0.493; 0.475-0.511 (mean + 95% CI)] than in control group [0.643; 0.627-0.659] (P < 0.0001) (t'). There was no statistically significant difference between the carcinoma group and the CIN III cases (P = 0.067) (t'). Only two cases with cervical carcinoma showed dense vascularity with color Doppler. A RI cutoff less than or equal to 0.573 showed a sensitivity of 81% with a specificity of 93%, a positive predictive value of 93%, and a negative predictive value of 81%. CONCLUSION: Color Doppler flow evaluation of RI in cervix vessels may aid in the early diagnosis and management of cervical carcinoma and in differentiating benign from malignant tumors. The validity of this technique as a screening program for diagnosis is limited.

Adolescent↗

Polyserositis as an unusual sign of methotrexate toxicity.

We present a 46-year-old patient who underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy for persistent trophoblastic disease. Single-agent chemotherapy with alternate methotrexate 1 mg/kg/day and leucovorin 0.1 mg/kg for 8 days was instituted on the first postoperative day. Various adverse symptomatology developed, culminating in a unique side effect, polyserositis. To the best of our knowledge, the wide spectrum of side effects, the short time lapse after onset of chemotherapy, and their severity are uncommon in a patient receiving her first chemotherapeutic treatment with MTX.

Antimetabolites, Antineoplastic↗

Transvaginal sonographic measurements of postmenopausal ovarian volume as a possible detection of ovarian neoplasia.

BACKGROUND: The purpose of our study was to determine whether ovarian volume, as measured by transvaginal ultrasound and plotted on the nomogram of normal postmenopausal ovarian volume, could assist in the diagnosis of ovarian neoplasia. METHODS: A retrospective study was undertaken, in which the ovaries of 85 postmenopausal women were examined by transvaginal ultrasonography prior to laparotomy. Three dimensions of each ovary were measured and ovarian volume was calculated. The results were plotted on the nomogram of normal postmenopausal ovarian volume. RESULTS: Eighty-five ovarian tumors were diagnosed. The range of the mean ovarian volume varied between 98.15 cm3 to 161.81 cm3 from perimenopausal age to > 15 postmenopausal years, as compared to 2.2 +/- 1.4 - 8.6 +/- 2.8 cm in the normal postmenopausal women. The deviation from the normal volume was more striking in the malignant tumors group (100%) than in the benign group (86%). When plotted on the nomogram, these values showed significant deviation (above 2 s.d.) from the norm for each group of neoplasms in every menopausal age. CONCLUSIONS: Sonographic detection of abnormal postmenopausal ovarian volume and the demonstration of the deviation from the ovarian volume nomogram, could assist the physician in early diagnosis of ovarian neoplasia. Ovarian volume measurements can serve as the primary method leading to diagnosis of ovarian cancer.

Age Factors↗

Low molecular heparin (Enoxaparin) as an alternative treatment of acute deep venous thrombosis in gynecologic oncology patients.

While heparin has been the standard treatment in established deep vein thrombosis (DVT), it carries associated potential hazards of hemorrhage and induction of thrombocytopenia. Enoxaparin (Rhone-Poulenc Rorer Pharm. Inc., France) is a low molecular weight heparin which has antithrombotic properties, and has been demonstrated effective in prophylaxis of DVT, apparently without severe treatment related bleeding complications. Six patients with genital malignancies, presenting with Doppler sonography confirmed deep venous thrombosis, were treated with Enoxaparin. A uniform dosage of 2 mg/kg/day in two divided doses was administered subcutaneously for 10 days during hospitalization and then continued on an out-patient basis. The clinical symptoms of venous thromboses diminished in all six patients. Enoxaparin represents an effective treatment of DVT, with the potential advantage of a lessening hemorrhagic complications. With administration of low molecular heparin, the activated partial thromboplastin time (aPTT) is not dramatically altered, making laboratory monitoring unnecessary. Our clinical findings demonstrate an easily applied therapy for gynecologic oncology patients, which is potentially safer to use, less costly, and less dependent on laboratory monitoring than the normal regimen.

Adult↗

Characterization of the prenylated protein methyltransferase in human endometrial carcinoma.

The processing of ras and of other GTP-binding proteins includes a final reversible step in which the carboxy terminal prenylated cysteine is methylated by the enzyme prenylated protein methyltransferase (PPMTase). The significance of this modification and of the role of PPMTase in human tumors has yet to be fully elucidated. Here we characterize the PPMTase of human endometrial carcinomas (tumors in which the frequency of ras gene mutations is relatively high) and compare it to the PPMTase of the normal endometrium. Our results show that in both types of tissues the enzyme is bound to the membranes. It can utilize synthetic substrates such as N-acetyl-S-farnesyl-L-cysteine (Km = 18-20 microM) and is blocked by the PPMTase inhibitor S-farnesylthioacetic acid (Ki = 2 microM). In vitro methylation assays and [alpha-32P]GTP blot-overlay assays showed that the major endogenous PPMTase substrates are small GTP-binding proteins. Methylation of these proteins in vitro is blocked by farnesylthioacetic acid. The kinetic properties of PPMTase from the carcinomas and the normal tissues are very similar. However, levels of PPMTase activity (but not of its endogenous substrates) are higher in the carcinomatous endometrium than in the normal one. The elevated enzyme activity is restricted to the crude mitochondrial fraction (8.0 +/- 0.4 vs. 5.4 +/- 0.1 pmol N-acetyl farnesylcysteine methyl ester formed/min/mg protein by the carcinoma and by the normal endometrial preparations, respectively). As this fraction is enriched in plasma membranes, it appears that the elevated enzyme activity could be related to ras protein methylation; if so, selective methylation blockers might inhibit the growth of endometrial carcinomas.

Endometrial Neoplasms↗

Continuous tamoxifen treatment in asymptomatic, postmenopausal breast cancer patients does not cause aggravation of endometrial pathologies.

Adjuvant tamoxifen therapy for breast cancer patients has been found to be associated with various endometrial pathologic conditions, including endometrial cancer. This preliminary case control study evaluated whether prolonged and continuous exposure to tamoxifen in the menopause may aggravate existing endometrial pathologies. Two vaginal ultrasound evaluations of endometrial thickness and histologic findings of two endometrial biopsies, performed 18 months apart, were evaluated for 25 asymptomatic, postmenopausal breast cancer patients who were continuously treated with tamoxifen. In the first endometrial biopsy, 4 patients (16.0%) were found to have endometrial pathologies: 2 patients had proliferative endometrium, 1 had hyperplastic endometrium, and 1 had an endometrial polyp. In the second endometrial biopsy, none of these patients showed any endometrial pathologies. Another patient (4.0%) with no endometrial pathology in the first visit had endometrial hyperplasia in the second visit. None of the patients developed endometrial cancer, and generally there was no increase in ultrasonographically-measured endometrial widths. The results of this preliminary study may suggest that there is no increased risk of development of endometrial pathologies during an additional 18 months of continuous tamoxifen therapy nor is there aggravation of already existing endometrial pathologies.

Aged↗

The role of color Doppler flow in the management of nonmetastatic gestational trophoblastic disease.

Three patients with findings suggestive of invasive gestational trophoblastic neoplasm and lung metastasis were assessed by color Doppler transvaginal ultrasound, before and during chemotherapy. The sonographic findings were correlated with beta-hCG levels measured at various stages of treatment. Results were compared with blood flow indices found during normal first trimester pregnancies, and those following elective termination of pregnancy. The mean resistance indices were significantly lower in the patients treated with chemotherapy (0.410 +/- 0.04) than in the early pregnancy control group (5-8 weeks gestation; n = 20, resistance index = 0.494 +/- 0.06). The difference between the groups was statistically significant (chi 2; p < 0.05). No pathological flow patterns could be discerned in 10 patients, who after termination of pregnancy had beta-hCG levels below 5 IU/ml. The response of gestational trophoblastic neoplasms to chemotherapy could be reliably assessed by observing the changes in flow resistance, which paralleled the gradual decrements in serial measurements of beta-hCG levels. Thus, the statistically significant results of our study are very encouraging and may indicate that color Doppler flow is a noninvasive, reproducible, useful and highly reliable new diagnostic approach for the diagnosis and management of patients suffering from uterine malignant gestational trophoblastic disease.

Animals↗