Vera Loizzi

The PGC-1α-dependent pathway of mitochondrial biogenesis is upregulated in type I endometrial cancer

PGC-1alpha-dependent pathway of mitochondrial biogenesis was investigated for the first time in type I endometrial cancer and in normal endometrium. In cancer endometrial tissue the citrate synthase activity, the mitochondrial DNA content and the TFAM level were found doubled compared to control endometrial tissue. Moreover, a 1.6- and 1.8-fold increase, respectively, of NRF-1 and PGG-1alpha expression was found. This study demonstrates, for the first time, that the increased mitochondrial biogenesis in type I endometrial cancer is associated to the upregulation of PGC-1alpha signalling pathway.

A rare case of choroidal metastasis presented after conservative management of endometrial cancer

Hematogenous dissemination from endometrial cancer is quite rare. We report a 31-year-old woman who developed choroidal metastasis following conservative management of early-stage endometrial carcinoma. She had received kidney transplantation and was taking steroids and cyclosporine. Three years after hysterectomy for persistent endometrial carcinoma, she developed multiple metastatic disease (to both lungs and right pelvis), and while on treatment with paclitaxel and carboplatin, she complained of a rapid visual deterioration. Ophthalmologic evaluation revealed a metastatic choroidal tumor associated with multiple central nervous system metastases. The patient refused further treatment and died 1 month after diagnosis of choroidal involvement. In conclusion, this is the first reported case of choroidal metastasis from endometrial cancer and highlights the need to consider immunosuppressive treatment as an absolute contraindication to conservative fertility-sparing treatment in gynecological malignancies.

Hysteroscopic evaluation of menopausal women with endometrial thickness of 4 mm or more.

STUDY OBJECTIVE To assess the diagnostic and operative potential of hysteroscopy in postmenopausal patients selected by ultrasound criteria. DESIGN Cohort study (Canadian Task Force classification II-2). SETTING Outpatient ultrasound and hysteroscopy department of a university-affiliated hospital. PATIENTS One hundred fifty-five postmenopausal women with endometrial thickness of 4 mm or more by ultrasound, in menopause for at least 1 year, with or without menopausal complaints. INTERVENTIONS Transvaginal ultrasound and office hysteroscopy with eye-directed biopsy specimens using a 5-mm, continuous-flow, operative hysteroscope. MEASUREMENTS AND MAIN RESULTS Of the 155 women, 129 (83%) were asymptomatic (irregular bleeding). Hysteroscopy showed endometrial pathology in 28% of asymptomatic patients (23 polyps, 5 cases of hyperplasia, 8 submucous myomata) and 76% of symptomatic women (13 polyps, 6 hyperplasia, 1 submucous myoma). Hysteroscopic results compared with histologic diagnosis showed a positive predictive value equal to 97. 1% and 95% in asymptomatic and symptomatic women, respectively, and a negative predictive value equal to 100% in both groups. CONCLUSION Office hysteroscopy with endometrial biopsy samples has a diagnostic and operative role in postmenopausal patients selected based on endometrial thickness on ultrasound, in view of the high prevalence of endometrial pathology in both symptomatic and asymptomatic women.

Groin recurrence in carcinoma of the vulva: management and outcome

The aim of the study was to investigate the management and outcome of inguinal recurrence in vulvar carcinoma patients. A retrospective chart review was conducted on 140 patients with squamous cell carcinoma of the vulva treated between 1994 and 2006. Twenty-one patients were found to have groin recurrence. Median interval between primary treatment of vulvar cancer and groin recurrence was 7 months. Three patients refused any treatment, 3 received chemotherapy, 2 inguino-pelvic radiotherapy and 13 had resection of the groin recurrence. After surgery seven patients received irradiation of the groin and pelvis, and three patients received chemotherapy. One patient died following surgery; 19 patients died of disease with the median survival after diagnosis of inguinal recurrence of 9 months. Only one patient is alive without evidence of disease at 60 months following surgery. In univariate analysis, stage and grade at diagnosis, age and performance status at the recurrent disease, and the extent of residual tumour after resection of groin recurrence were predictors for survival. Groin recurrences from vulvar carcinoma carry a poor prognosis. Multi-modal treatment may result in a palliation of the disease, and a very limited number of patients have long-term survival.

Mitochondrial DNA content and mass increase in progression from normal to hyperplastic to cancer endometrium

BackgroundAn increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1α signalling pathway was previously reported in type I endometrial cancer. The aim of this study has been to evaluate if mtDNA content and the citrate synthase (CS) activity, an enzyme marker of mitochondrial mass, increase in progression from control endometrium to hyperplasia to type I endometrial carcinoma.ResultsGiven that no statistically significant change in mtDNA content and CS activity in endometrium taken from different phases of the menstrual cycle or in menopause was found, these samples were used as control. Our research shows, for the first time, that mtDNA content and citrate synthase activity increase in hyperplastic endometrium compared to control tissues, even if their levels remain lower compared to cancer tissue. In particular, mtDNA content increases seem to precede increases in CS activity. No statistically significant change in mtDNA content and in CS activity was found in relation to different histopathological conditions such as grade, myometrial invasion and stage.ConclusionMtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma.

Neoadjuvant Chemotherapy: An Alternative Option of Treatment for Locally Advanced Cervical Cancer

Although the incidence of cervical cancer has declined in both North America and Europe, it still represents the second most common cancer in women and the fifth most common malignancy worldwide. Most patients in the developed countries present with disease either confined to the cervix or with limited extension beyond it. Historically, the standard treatment was usually radiotherapy or radical hysterectomy with node dissection. In 1999, five randomized clinical trials performed by the Gynecologic Oncology Group, the Radiation Therapy Oncology Group and the Southwest Oncology Group have demonstrated a significant outcome advantage when cisplatin-based chemotherapy was administered during radiation in patients with cervical cancer. In the current review, we will analyze the role of neoadjuvant chemotherapy followed by radiotherapy and surgery as an alternative option treatment to the standard chemoradiation for locally advanced cervical cancer (stage Ib2 or larger).

Cisplatin and Vinorelbine Chemotherapy in Recurrent Vulvar Carcinoma

Purpose: To evaluate the activity and toxicity of the combination of cisplatin and vinorelbine in patients with recurrent carcinoma of the vulva that has not been previously treated with chemotherapy. Patients and Methods: Sixteen women with a median age of 65 years (range 43–79) with recurrent vulvar carcinoma were enrolled in the study. Nine patients had local recurrent disease (perineum, vagina and/or vulva), whereas 7 had disease in the groin; 9 patients had received prior radiotherapy. Cisplatin was administered intravenously on day 1 and vinorelbine was given on day 1 immediately after cisplatin and on day 8. Results: A total of 68 cycles of chemotherapy were administered. Fifteen women were assessed for response. Objective responses were recorded in 6 patients (40%) – with 4 patients (27%) achieving a complete response and 2 (13%) achieving a partial response –, whereas 4 patients (27%) had stable disease and 5 had progressive disease. The median progression-free survival was 10 months (range 3–17), whereas the overall survival from the beginning of the chemotherapy was 19 months (range 1–30). Due to the small number of patients, no significant correlation with site of recurrence could be found. Conclusion: The combination of cisplatin and vinorelbine is a well-tolerated and active regimen in the treatment of patients with recurrent vulvar carcinoma.

Two Cases of Endometrial Cancer Diagnosis Associated with Bone Metastasis

Background: Endometrial adenocarcinoma is commonly seen in postmenopausal women and uterine bleeding is the first sign in 90% of the cases. Bone metastasis as the presenting feature is extremely rare. We report two endometrial cancer patients with metastasis to the tibia and cervical vertebra at the time of primary disease. Cases: Two patients were diagnosed with stage IVB endometrial cancer with involvement of the tibia and cervical column, respectively. The first case was treated with 8 cycles of platinum, doxorubicin, and cyclophosphamide, but she died 3 months after the completion of chemotherapy as a result of progressive disease. The second case received surgery followed by chemotherapy with cisplatin and doxorubicin, but she died 2 months later. Conclusions: These cases highlight the rare and unusual presentation of endometrial cancer. For this reason a review of the literature is also provided for all cases with evidence of bone metastasis at presentation of the disease, and as a recurrence.

The value of ultrasonographic examination of the uterine cervix in predicting post-term pregnancy.

Abstract Object: To assess whether transvaginal ultrasound is helpful in predicting the post-term onset of labor (≥ 1 weeks). Setting: Antenatal clinic of a University hospital and referral center. Subject and mehods: One hundred and twenty singleton uncomplicated pregnancies in primiparous women were enrolled at 37 weeks of gestation. Ultrasound examination of the cervical length by a transvaginal probe was performed at recruitment and at weekly intervals until 40 completed weeks. Subjects were divided into Group A (those with spontaneous onset of labor ≤ 1 completed weeks) and Group B (those not in labor by that date). Results: Eighty women delivered ≤ 41 completed weeks, forty were not in labor by that date. The cervix was significantly shorter at 39 and 40 weeks in group A, but no particular cervical length was predictive of post-term delivery. Discussion: There is a significant difference in cervical length in women delivering at term compared with those due to have a post-term delivery. This difference is significant from 39 weeks of gestation onwards. We speculate that targeted transvaginal ultrasound may be useful in predicting the post-term onset of labor and possibly in assisting its active management.

Carcinosarcoma of the ovary: analysis of 13 cases and review of the literature.

Objectives: The aim of this study was to evaluate our experience with patients affected by ovarian carcinosarcoma. Patients and Methods: During a 16-year period, data on 13 patients with ovarian carcinosarcoma were collected. They were obtained from hospital charts and follow-up visits. Survival curves were estimated by the Kaplan-Meier method and compared using the log-rank test. All tests were two-tailed with p values <0.05 considered significant. Results: Our study was conducted on 13 patients with ovarian carcinosarcoma referred to our unit, during an observation time of about 16 years (March 1994 to October 2010). An improved survival was observed in patients treated with optimal cytoreductive surgery with residual tumors <2 cm (30 vs. 5 months; p = 0.042). All patients underwent adjuvant chemotherapy based on the combination of cisplatin, epirubicin and ifosfamide (PEI) and taxol and carboplatin (TAX-CBDCA) regimen. Overall survival of the patient population was 17 months. Conclusions: Similarly to data published in the literature, we observed that malignant mixed mullerian ovarian tumors are very aggressive and are usually diagnosed at an advanced age and at an advanced stage of disease. Therefore, due to the rarity of the tumor we would like to add our series to those already published in the literature, although our treatment recommendations are actually based upon retrospective studies with a small patient population.