The value of TOP2A, EZH2 and paxillin expression as markers of aggressive breast cancer: relationship with other prognostic factors.

INTRODUCTION: The immunocytochemical expression of topoisomerase II alpha (TOP2A), enhancer of zeste homologue 2 (EZH2) and paxillin has recently gained increasing attention. Although previous studies have commented on the clinical usefulness of these markers, their role remains controversial. AIM: The purpose of the study was to investigate the expression of TOP2A, EZH2 and paxillin in relation to classic prognostic parameters and their significance as prognostic markers in imprints of resected breast carcinomas. METHODS: Imprint smears from 55 patients who underwent surgical treatment for primary carcinoma in our department between 2005 and 2006 were studied immunocytochemically with the use of TOP2A, EZH2 and paxillin antibodies. RESULTS: The expression of TOP2A correlated with higher histologic grade, tumor size and negative PR expression. High intensity staining for EZH2 expression was associated with higher histologic grade, negative ER and PR expression and positive Ki-67 expression. The expression of paxillin showed no correlation with estrogen/progesterone and HER2 expression nor with tumor grade and stage. CONCLUSION: Our data indicate that TOP2A and EZH2 expression are related to a more aggressive tumor phenotype. The expression of paxillin failed to correlate with any of the studied clinicopathologic factors. Further studies are needed to verify these results.

Management of a pregnancy complicated by yolk sac tumor.

BACKGROUND: The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach. CASE: A 35-year-old pregnant woman with a yolk sac tumor underwent left salpingo-oophorectomy at 25 weeks of gestation. Chemotherapy was deferred to the end of the pregnancy owing to concerns for potential fetal risks. Alpha-feto protein level was used to monitor the underlying disease activity. The patient underwent exploratory laparotomy with cesarean section followed by total hysterectomy, omentectomy, right salpingooophorectomy, pelvic, and para-aortic lymphadenectomies at 32 weeks of gestation. She received four postoperative courses of chemotherapy (cisplatin, etoposide, and peplomycin). Currently, mother and child are doing well 6 months after the last chemotherapy cycle. CONCLUSION: In a case of yolk sac tumor in the second trimester of pregnancy, radical surgery combined with elective caesarian section followed by chemotherapy could achieve remission and rescue of fetus. However, the treatment needs to be individualized as there is lack of evidence.

Intraoperative assessment of epithelial and non-epithelial ovarian tumors: a 7-year review.

OBJECTIVE: To determine the accuracy of frozen section diagnosis of ovarian tumors and to discuss discrepant diagnostic cases. METHODS: 932 ovarian tumors were submitted for frozen section examination. Cases with a significant diagnostic discrepancy between the intraoperative and the final histological diagnosis were reviewed. RESULTS: The sensitivity of frozen section diagnosis for benign, borderline and malignant epithelial tumors was 98.82%, 98.97% and 87.66% and the specificity 98.01%, 97.06% and 100%, respectively. There were 27 cases with diagnostic discrepancy. All non teratomatous sex cord/stromal and germ cell tumors were correctly diagnosed while a diagnostic discrepancy was observed in teratomatous tumors. CONCLUSION: Frozen section diagnosis is a reliable method for the surgical management of an ovarian mass. Nevertheless, care should be taken for large tumors measuring > 20 cm in diameter, particularly when the intraoperative diagnosis reveals an epithelial borderline tumor or a teratomatous tumor with an extensive neural component.

Extrauterine pregnancy resulting from late spontaneous rupture of an unscarred gravid uterus: case report.

PURPOSE: Rupture of the unscarred grand uterus is a rare obstetric event associated with major perinatal mortality and a high incidence of maternal mortality and morbidity, particularly peripartum hysterectomy. METHODS & RESULTS: We present the case of a primigravida woman who was admitted at 38 weeks of gestation complaining of intermittent abdominal pain and vaginal bleeding. Although initial evaluation suggested that both mother and fetus were doing well, continuous assessment resulted in cesarean section due to variable decelerations and increasing abdominal pain. An unexpected abdominal pregnancy was discovered resulting from a complete uterine rupture. A healthy infant was delivered and hysterectomy was performed. CONCLUSION: Although extrauterine advanced abdominal pregnancy resulting from late uterine rupture is associated with high maternal and perinatal mortality, a high index of suspicion, close surveillance and ultrasonography can achieve good outcome for both mother and infant. We strongly believe, that this case report contributes to the insight and further knowledge of this rare pregnancy complication.

High-dose melphalan and autologous stem cell transplantation as consolidation treatment in patients with chemosensitive ovarian cancer: results of a single-institution randomized trial.

The role of high-dose chemotherapy (HDCT) in epithelial ovarian cancer (EOC) remains controversial. This study was initiated to compare the efficacy and tolerability of HDCT as a consolidation approach in women with chemosensitive advanced EOC (FIGO stages IIC-IV). Patients who had achieved their first clinical complete remission after six cycles of conventional paclitaxel and carboplatin combination chemotherapy were randomly assigned to receive or not high-dose melphalan. The primary objective was to compare time to disease progression (TTP). A total of 80 patients were enrolled onto the trial. Patients who were randomized to receive HDCT were initially treated with cyclophosphamide 4 g/m(2) for PBPC mobilization. HDCT consisted of melphalan 200 mg/m(2). Of the 37 patients who were allocated to HDCT, 11 (29.7%) did not receive melphalan either due to patient refusal (n=5) or due to failure of PBPC mobilization (n=6). In an intent-to-treat analysis, there were no significant differences between the two arms in TTP (P=0.059) as well as in overall survival (OS) (P=0.38).

Prognostic factors in patients treated with taxane-based chemotherapy for recurrent or metastatic endometrial cancer: proposal for a new prognostic model.

OBJECTIVE: Taxane-based chemotherapy has been recently introduced as an effective therapeutic option in recurrent or metastatic endometrial carcinoma (RMEC). The aim of the study was to determine the prognostic factors in RMEC after taxane-based chemotherapy. METHODS: One hundred ten patients who received paclitaxel-containing regimen for RMEC were retrospectively evaluated. Potential prognostic factors for overall survival were identified with the Kaplan-Meier method in univariate and the Cox regression model in multivariate analysis. RESULTS: Performance status (PS) and relapse within the field of previous external radiation were independent prognostic factors for overall survival (p=0.007 and p=0.026 respectively). Non-endometriod histology was associated with a shorter median survival compared to endometriod adenocarcinoma (14.46 vs. 17.57 months, p=0.093), but histology was not an independent prognostic factor (HR=1.43, 95% CI: 0.82-2.48, p=0.21). Stratification according to PS and relapse within the irradiation field identified three risk groups with distinctly different prognosis (median survival 27.36, 16.71, and 11.33 months for the group of favorable, intermediate, and unfavorable prognosis respectively, p<0.001). Within the favorable prognosis group, 34% of patients had a probability of 5-year survival. CONCLUSION: PS at diagnosis and relapse within the irradiated area may constitute a valid prognostic model in RMEC patients who receive taxane-based chemotherapy and are able to identify long-term survivors.

The role of three-dimensional (3D) sonography and 3D power Doppler in the preoperative assessment of borderline ovarian tumors.

PURPOSE OF INVESTIGATION: To determine the value of three-dimensional (3D) sonography and 3D power Doppler in distinguishing borderline ovarian tumors from benign cysts and malignant tumors. METHODS: One hundred and seventy-two women with a mean age of 37 years (range 28-45) and diagnosis of a confirmed pelvic mass were referred for preoperative evaluation with 3D sonography and 3D power Doppler. Sonographic criteria used for the diagnosis of borderline tumors were based on a system that included morphological characteristics, histological evaluation and power Doppler imaging. RESULTS: Ten lesions were histopathologically diagnosed as borderline ovarian tumors, 42 as malignant and 120 as benign. Three-dimensional sonography revealed 120 ovarian tumors which scored below 7 (benign), according to Kurjak's scale, 12 tumors which scored between 7-8 and 40 tumors between 9-13 (malignant). CONCLUSIONS: Preoperative assessment of borderline tumors by 3D imaging may promote improved patient care and introduce laparoscopic management as an alternative surgical approach.

Anthracycline-based adjuvant chemotherapy in early-stage uterine sarcomas: long-term results of a single institution experience.

PURPOSE OF INVESTIGATION: Uterine sarcomas are rare neoplasms characterized by a high rate of local recurrences and distant metastases. The role of chemotherapy in early-stage completely resected disease remains controversial. METHODS: Thirty-one patients with Stage I or II uterine sarcomas, referred to our center for adjuvant chemotherapy, received anthracycline-based regimens. Seventeen (54.8%) patients received ifosfamide, etoposide and epirubicin, six (19.4%) were treated with doxorubicin and carboplatin, three (9.6%) were administered doxorubicin and ifosfamide, while five (16.1%) patients received various anthracycline-based regimens. RESULTS: With a median follow-up of 82 months disease recurred in 12 (38.7%) patients. Five-year survival probability is estimated at 54%. Both median overall survival and time to progression for all patients have not been reached yet. Patients who received ifosfamide-containing regimens had a statistically significant benefit in overall survival (p < or = 0.05) when compared with those treated with non-ifosfamide-containing regimens. CONCLUSION: Our data suggest a potential role for anthracycline- and ifosfamide-containing chemotherapy in the adjuvant setting for early-stage uterine sarcomas.

Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix.

PURPOSE: Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent cancer of the cervix, and the combination of these two agents has shown activity and possible synergism in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent cervical cancer to evaluate its activity. PATIENTS AND METHODS: Thirty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m2 administered intravenously over a 3-hour period followed by cisplatin 75 mg/m2 administered intravenously with granulocyte colony-stimulating factor support. The chemotherapy was administered every 3 weeks for a maximum of six courses. RESULTS: Sixteen patients (47%; 95% confidence interval, 30% to 65%) achieved an objective response, including five complete responses and 11 partial responses. Responses occurred in 28% of patients with disease within the radiation field only and in 57% of patients with disease involving other sites. The median duration of response was 5.5 months, and the median times to progression and survival for all patients were 5 and 9 months, respectively. Grade 3 or 4 toxicities included anemia in 18% of patients and granulocytopenia in 15% of patients. Fifty-three percent of patients developed some degree of neurotoxicity; 21% of cases were grade 2 or worse. CONCLUSION: The combination of paclitaxel with cisplatin seems relatively well tolerated and moderately active in patients with metastatic or recurrent cervical cancer. The significant incidence of neurotoxicity is of concern, and alternative methods of administration of the two agents could be evaluated. Then, further study of this combination, alone or with the addition of other active agents, is warranted.

Maternal mortality in Greece (1980-1996).

OBJECTIVE: To use data from the National Statistical Service of Greece to examine trends in maternal mortality and risk factors for maternal deaths. STUDY DESIGN: Maternal mortality in Greece has been studied from years 1980 to 1996 in total, by cause of death, by residency (urban/rural) and by maternal age. The maternal mortality ratio (MMR) has been defined as the number of deaths per 100,000 live births. RESULTS: From years 1980 to 1996, there have been 136 maternal deaths (MMR: 7). The number of deaths has significantly decreased during this period and six major causes of death have been identified, resulting in 80% of maternal deaths. A simulation of maternal mortality between urban and rural areas has been achieved during the last decade. Also, maternal mortality rises dramatically with age. CONCLUSIONS: Although overall rates of maternal mortality in Greece have been significantly decreased over the last years, an improved recording of maternal deaths is necessary for identifying preventable factors and developing effective interventions.

Retroperitoneal endometriosis causing cyclical ureteral obstruction.

We report a case of retroperitoneal endometriosis involving the periureteral tissues of the left ureter. The patient suffered from cyclical symptoms of left ureteral obstruction during menstruation. Endometriosis of the ureter is not common and in this case the preoperative diagnosis presented difficulties due to the absence of any pathological findings during the clinicolaboratory evaluation of the patient before or after menstruation. The patient was managed with surgical resection of the affected ureteral segment and subsequent end-to-end anastomosis of the left ureter. A brief review of the subject is also presented.

How to avoid suboptimal management of cervical carcinoma by simple hysterectomy.

OBJECTIVE: To determine the reasons leading to an inappropriate simple hysterectomy in the presence of carcinoma of the cervix and to evaluate factors related to survival. METHODS: All preoperative information was abstracted from 63 cervical cancer patients cleared by simple hysterectomy from 1980-1993. Cervical cancer screening history as well as the indication for hysterectomy were analyzed. The 5-year survival was calculated and correlated with the tumour histological subtype and presumed stage of disease. RESULTS: The most common preoperative symptom was abnormal uterine bleeding (73%). The absence of preoperative cytology, an inadequately evaluated abnormal Pap smear and the failure to differentiate from endometrial carcinoma were the main causes leading to an inappropriate simple hysterectomy. The cumulative 5-year survival was 63.5% and was correlated with the presumed stage of disease and the histological subtype. CONCLUSION: Only with close adherence to the cervical cancer screening guidelines and appropriate evaluation of presenting symptoms can we avoid inappropriate management of cervical carcinoma with simple hysterectomy.

Cervical intraepithelial neoplasia in the young female. Diagnosis and management.

The prevalence of HPV and CIN in young women has increased in recent years. During a 5-year period (1996-2000), 78 sexually active young females, aged 15-20 years, were referred to the Colposcopic Unit of the 1st Department of Obstetrics and Gynecology of the University of Athens in the major University-appointed hospital in Greece, because of an abnormal cytology or a suspicious cervical abnormality in the presence of negative cytology. Colposcopic examinations were found to be within normal limits in 12/78 (15.4%) of cases. Cervical pathology was related in 22 cases (28.2%) to HPV infection, 23 (29.5%) cases to CIN 1, 18 (23.1%) cases to CIN II and 3 (3.8%) to CIN III. No relation between oral contraceptive use and cigarette smoking with HPV infection was found. Our findings strongly confirm the necessity of obtaining cervicovaginal smears on all sexually active gynecologic and obstetric teenage patients.

Malignant rhabdoid tumor of the clitoris in an elderly patient: report of a case.

Malignant rhabdoid tumors of the vulva are rare neoplasms which most of the time show aggressive behavior and a dismal prognosis. We report a case of malignant rhabdoid tumor of the clitoris occurring in an elderly patient. Due to the similarities that these neoplasms show with other low-differentiated tumors, immunohistochemical and ultrastructural assessment should always be conducted so that accurate diagnosis is achieved. Individualized extensive surgical treatment might decrease relapsing disease.

Cervical intraepithelial neoplasia in young women.

The aim of the study was to determine the incidence and outcome of cervical intraepithelial neoplasia (CIN) in Greek young women. A retrospective analysis was conducted of women aged 16 - 20 years with a histological diagnosis of CIN during the years 1999-2005. Management was individualised for each case. The rates of regression, persistence and progression were measured. A total of 80 adolescents were identified. Some 54 patients (67.5%) had CIN1 and 26 (32.5%) had CIN2/3. Regression of the CIN1 lesions expressed as negative cytological or histological follow-up was observed in 74% and 93% of the patients at 12 and 24 months, respectively. The majority of adolescents (92%) with CIN2/3 underwent conisation and in 79% of them, histology of the specimen confirmed the initial diagnosis. CIN1 lesions will most likely regress over a 2-year period following diagnosis in women aged 16 - 20 years. Nevertheless, close monitoring is mandatory, as 10 - 15% of these lesions will either persist or progress to high-grade CIN. Management for adolescents with high-grade CIN lesions should be individualised according to a variety of parameters and adjusted to the patients' safety.

The impact of age in the outcome of patients with advanced or recurrent cervical cancer after platinum-based chemotherapy.

OBJECTIVES: Cervical cancer is a disease of middle-aged and elderly but still there are young women diagnosed with advanced disease that is incurable with local treatment and is treated with platinum-based combination chemotherapy. It is unknown whether these young patients have a poorer outcome compared to older patients or whether elderly patients have inferior outcome than younger patients when treated with combination chemotherapy. METHODS: We compared the outcome between young (<35), elderly (>70) and middle-aged (35-70) women who were treated with platinum-based combination chemotherapy for advanced, recurrent or persistent disease. RESULTS: Two hundred and eighteen patients were included in our database. The baseline clinical and disease characteristics were not different between age groups but anemia and thrombocytosis were more frequent in younger patients. Median survival for all patients was 13.4 (95%CI 11-15.8) months while survival of patients<35 years of age was 9 months (95% CI 5.8-12), of patients older than 70 was 10 months (95% CI 6.9-13) of patients 35 to 70 years of age was 14.5 months (95% CI 11-18) (p=0.004). Multiple factors were significant for survival in univariate analysis but only weight loss, pain score and relapse inside an irradiated filed were significant predictors of outcome in multivariate analysis. CONCLUSIONS: Very young (<35) and elderly (>70) patients have a worse prognosis after treatment with combination chemotherapy for advanced or recurrent cervical cancer. Nevertheless, this difference is not significant when adjusted for other prognostic factors.

Significant differences of lymphocytes isolated from ascites of patients with ovarian cancer compared to blood and tumor lymphocytes. Association of CD3+CD56+ cells with platinum resistance.

OBJECTIVES: Tumor infiltrating lymphocytes (TILs) and T regulatory cells (Tregs) have been associated with prognosis in ovarian cancer, but their prognostic significance in ascites has not been studied. We performed a prospective study of T lymphocytes isolated from ascites from patients with ovarian carcinoma and we compared them with the respective populations in blood and tumors. METHODS: Mononuclear cells from ascites (n=71) and blood were isolated by Ficoll, while tumor lymphocytes (n=20) were obtained upon mechanical dissociation. Phenotypic analysis was performed with flow cytometry. Ascites from 10 patients with cirrhosis was used as control. RESULTS: Tregs containing CD4(+)CD25(+) cells, NK-T containing CD3(+)CD56(+) cells and CD69 and HLADR expression of CD4 and CD8 lymphocytes were significantly increased in tumor ascites compared to blood and control ascites. A selective accumulation of these populations in the ascites of cancer patients, was suggested by the significantly higher ascites/blood (A/B) ratios in cancer patients but not controls. Cancer cell content in ascites was correlated with CD4(+)CD25(+), CD4(+)CD69(+), CD4(+)HLADR(+) and CD8(+)CD69(+) cells. There was no correlation of lymphocyte populations between ascites and samples from peritoneal metastases. Higher tumor grade was associated with increased A/B CD4(+)CD25(+) ratio and reduced CD3(+)CD56(+) cells, while platinum resistance was associated with reduced A/B CD3(+)CD56(+) ratio. CONCLUSIONS: There are significant differences of CD3(+)CD56(+) and CD25(+)CD4(+) lymphocytes and increase in lymphocyte activation between blood, ascites and peritoneal metastases from patients with ovarian cancer. The selective accumulation of CD3(+)CD56(+) population in ascites may be a predictive factor for platinum resistance.

Can local application of imiquimod cream be an alternative mode of therapy for patients with high-grade intraepithelial lesions of the vagina?

The aim of the present study was to assess the local application of imiquimod cream 5% as an alternative mode of therapy for high-grade vaginal intraepithelial neoplasia (VAIN 2/3). Positive human papillomavirus (HPV) patients with multifocal high-grade VAIN (2/3) not involving the vaginal vault in hysterectomized patients took part in this study. The treatment consisted of vaginal application of the cream under colposcopic guidance. Following management, biopsies were obtained from the previously recorded lesions. p53 expression was recorded prior and after therapy. Seven patients with VAIN 2/3 took part in this study. Six patients (86%) were positive for high-risk HPV type while three (43%) women who were positive for p53 nuclei prior to therapy were found to be negative following treatment. After treatment, 86% of the patients were found to have either HPV infection or low-grade VAIN. During follow-up, two patients (28.5%) were managed by vaginectomy, one for persistent and one for recurrent high-grade VAIN. Currently, from the five patients that are followed, three have simple HPV infection and two, VAIN 1. Imiquimod cream 5% might represent an alternative although not permanent method of management in young, HPV-positive women with multifocal high-grade lesions of the vagina (VAIN 2/3).

The role of liquid-based cytology associated with curettage in the investigation of endometrial lesions from postmenopausal women.

OBJECTIVE: This study investigates the role of liquid-based cytology with ThinPrep technique, in the detection of endometrial lesions, using direct endometrial sampling from postmenopausal women with the Endogyn endometrial device. METHODS: It was performed on 491 postmenopausal women referred to our clinic for abnormal bleeding or other symptoms and/or a thickness of endometrium >5 mm on ultrasound. Endometrial sampling, dilatation and curettage (D&C) and hysterectomy were performed on all patients. For the diagnosis, the WHO classification scheme was used. RESULTS: According to our findings a sensitivity of 98.08%, specificity of 100%, positive predictive value of 100%, negative predictive value of 100% and overall accuracy of 98.98% were observed in both endometrial sampling and in D&C. CONCLUSIONS: Endometrial sampling is complementary to D&C for the diagnosis of endometrial lesions and it is necessary for it to be performed before D&C and/or hysterectomy.