BACKGROUND: "Intestinal-type" mucinous carcinoma of the vulva is extremely rare with very few cases reported in the literature. CASE REPORT: The authors report two patients who had diagnosis of intestinal-type mucinous adenocarcinoma of the vulva after excisional biopsy. In both cases, restaging was perfomed with total body computed tomography (CT) scan, gastroscopy, and colonoscopy that showed no other site of disease. A radical vulvectomy with bilateral systematic inguinal lymphadenectomy was performed, and in both cases no residual disease was found. A patient developed metastatic (liver, bone marrow) colonic cancer 36 months after primary surgery, received multiple lines of chemotherapy, and died of disseminated disease 18 months after diagnosis. The other patient was found to have dysplastic polyp in the sigmoid colon, and is alive without disease at 39 months after primary diagnosis. CONCLUSION: Intestinal-type mucinous carcinoma of the vulva has a poor prognosis. Strict endoscopic follow-up of the colon is mandatory in such cases, considering the high propensity of associated gastrointestinal (GI) tumors.

Objectives The aim of this study was to assess the accuracy of transvaginal sonography (TVS) in the preoperative staging of endometrial carcinoma, because accurate preoperative staging of the disease would assist in planning the optimal course of treatment. We investigated the ability to distinguish between cases with < 50% and > 50% myometrial invasion (FIGO Stage Ia -Ib vs. Stage Ic), and tumor extension to the cervical stroma (Stage IIb) according to the old FIGO classification. Methods 140 women with pathologically-proven of endometrial cancer, referred to our institution between 2007 and 2010, were included in this study. All underwent TVS examination about seven days before the surgical staging. Histological findings of myometrial and cervical stroma invasion were used as the reference standard. Results The histological subtypes comprised 75% endometrioid adenocarcinoma, 9% serous papillary, 6% endometrioid villoglandular, 4% villoglandular, 3% adenosquamous and 3% clear cells; there were 60% well differentiate, 15% moderately differentiate and 25% poorly differentiate cancers. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for TSV in the evaluation of < 50% myometrial infiltration were 82%, 77%, 79%, 80% and 48%; of > 50% myometrial infiltration were 86%, 90%, 86%, 90%, and 57%; for cervical invasion were 80%, 100%, 100%, 89% and 63% respectively. Conclusions The transvaginal sonography shows good accuracy in the staging of endometrial carcinoma. Our results support a potential role of TVS for the prediction of strome cervix infiltration of endometrial cancer.

This study evaluates the efficacy and toxicity of dose-dense weekly paclitaxel and carboplatin as neoadjuvant chemotherapy in locally advanced cervical cancer (LACC). We collected 23 cases of LACC treated with weekly paclitaxel and carboplatin for nine cycles: 20 patients had complete or partial response to chemotherapy and were submitted to surgery, 3 with poor response received chemoradiation therapy. Pathologic examination showed complete response in four patients, myometrial invasion <50% in nine and >50% in seven patients, parametrial involvement in two, vaginal metastasis in one and lymphovascular space invasion, with positive margins, in another case. Despite seven patients had radiological evidence of lymph nodes involvement at diagnosis, only one had nodal metastases. Five patients showed grade 3-4 of hematologic toxicity.

Background: To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. Methods: Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR from seven world-wide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. Results: Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (OR=1.32, 95%CI: 0.97-1.80), residual disease after primary cytoreduction (OR=1.69, 95%CI: 1.26-2.27), progression-free interval (OR=2.27, 95%CI: 1.71-3.01), ECOG performance status (OR=2.23, 95%CI: 1.45-3.44), CA125 (OR=1.85, 95%CI: 1.41-2.44) and ascites at recurrence(OR=2.79, 95%CI: 1.88-4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low risk group, in which the proportion of complete cytoreduction was 53.4% compared to 20.1% in the high risk group (OR=4.55, 95%CI: 3.43-6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiveroperating characteristics for predicting complete SCR was 0.68 (95%CI: 0.60-0.79). Conclusions: This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with recurrent ovarian cancer should have SCR as part of their management.

The creation of new blood vessels from existing ones, which is a mechanism called "angiogenesis", is essential in cancer to supply cancerous growth. Moreover, the development and the progression of the tumor and its metastases are the result of an efficient vascular response. Cancer cells release and activate different angiogenic growth factors and their receptors in the tumor microenvironment to promote the angiogenic process. The most important pro-angiogenic factor is the "Vascular Endothelial Growth Factor" (VEGF) because of its mitogen activity on vascular endothelium. Bevacizumab is a monoclonal antibody that obstructs the binding of circulating vascular endothelial growth factor to its receptors and has been approved for the treatment of primary and recurrent ovarian cancer but also for many other solid tumors.

Objective: To objectively assess anorectal dysfunction following nerve-sparing radical hysterectomy in stage I-II cervical carcinoma patients. Material and Methods: Between 2008 and 2012, 21 patients with primary cervical cancer stage FIGO I-II were enrolled in this prospective study. All women underwent nerve-sparing radical hysterectomy. Anorectal manometry was performed preoperatively and 6 months after surgery. A paired Student t test was used to assess the statistical difference between the manometric evaluations. A p value <0.05 was considered statistically significant. Results: Twenty-one patients were available for follow-up. Maximal and mean anal resting and squeezing pressures were unaffected by the surgical procedure, rectoanal inhibitory reflex and length of the high anal pressure zone did not change after the operation. The minimal volume to elicit rectal sensation, urge to defecate and maximal tolerable volume did not change significantly in the postoperative period, although they decreased in 2 and increased in 3 patients. In addition, rectal compliance did not change after surgery. Furthermore, no significant differences were found between patients who were or were not treated with adjuvant radiotherapy. Conclusions: Our findings suggest that nerve-sparing radical hysterectomy for cervical cancer does not seem to be associated with long-term anorectal dysfunction

Vulvar cancer rapresents 5% of gynaecological malignancies. Aimof this study is to identify factors that influence the survival of these patients. 122 patients were analyzed with a follow-up of 60.74 months. The characteristics analyzed were: age at diagnosis, type of surgical treatment, FIGO stage, histological type, grade, surgical margins, adjuvant therapy, interval diagnosis-relapse, site of recurrence. The statistical analysis showed that the prognostic factors are: FIGO stage, relapse free interval, the site of recurrence, positive lymph nodes and surgical margins in the histological examination. While age at diagnosis, grading and type of surgery seem not to influence the survival of patiens with vulvar cancer.

Background: Carboplatin plus paclitaxel administered every 3 weeks is standard first-line chemotherapy for patients with advanced ovarian cancer. A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial. The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks. Methods: We did a multicentre, randomised, phase 3 study at 67 institutions in Italy and France. Women with FIGO stage IC-IV ovarian cancer, an ECOG performance status of 2 or lower, and who had never received chemotherapy were randomly allocated in a 1:1 ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175 mg/m2) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m2) every week for 18 weeks. Randomisation was done by computer-based minimisation, stratified by centre, residual disease after surgery, and ECOG performance status. The study was not blinded. Coprimary endpoints were progression-free survival and quality of life (assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI] score), and analysis was by modified intention to treat. This report presents the final analysis. The study is registered with ClinicalTrials.gov, number NCT00660842. Findings: 822 patients were enrolled into the study between Nov 20, 2008, and March 1, 2012; 12 withdrew their consent immediately after randomisation and were excluded, and 810 were eligible for analysis. 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule. After median follow-up of 22·3 months (IQR 16·2-30·9), 449 progression-free survival events were recorded. Median progression-free survival was 17·3 months (95% CI 15·2-20·2) in patients assigned to treatment every 3 weeks, versus 18·3 months (16·8-20·9) in women allocated to the weekly schedule (hazard ratio 0·96, 95% CI 0·80-1·16; p=0·66). FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p<0·0001); with treatment every 3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores remained stable. Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3-4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen. Interpretation: A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer. Funding: None. © 2014 Elsevier Ltd.

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 &lt;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 cyto-reductive surgery with residual tumors &lt;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. Copyright (C) 2011 S. Karger AG, Basel

Carcinosarcoma is a well-recognized tumor even if it is an uncommon entity. Neoplasms usually occur in the oral cavity, pharynx, esophagus, larynx and skin, and have been rarely documented in the female genital tract. This case reports a patient with a diagnosis of vulvar carcinosarcoma that has been treated with radical vulvectomy and a left inguinal lymphadenectomy but she died two months later of progressive disease. Because of the extreme rarity and severe prognosis of the tumor, we believe that this is a useful addition to the literature and might serves as a reminder to physicians that a multidisciplinary approach for management should be undertaken for treatment.

Objectives: To analyze the clinicopathological characteristics and prognostic factors associated with survival in patients with central nervous system (CNS) metastases from epithelial ovarian cancer. Methods: Twenty patients with CNS involvement from ovarian carcinoma were evaluated in this retrospective study; their features and survivals were analyzed using Kaplan-Meier and log-rank test methods. Results: The incidence of CNS metastases was 5%, among 400 patients with ovarian cancer treated in our single institution. The median age at diagnosis of the ovarian cancer was 55 years. The median interval to the brain involvement and the median survival were 33 and 18 months, respectively. Prognostic factors associated with survival were the International Federation of Gynecology and Obstetrics stage, the surgical resection, the multimodal treatment, and the response after the therapy of the brain metastases. Conclusions: Brain involvement from ovarian cancer is uncommon but is increasing in incidence. Although the prognosis is usually poor, a multimodal approach can result in a long-term remission of the metastases and in an improvement of the overall survival.

Objective: To identify differences in the management and outcome of patients with central nervous system metastases from epithelial ovarian cancer. Methods: The clinical and pathologic characteristics, treatment, and outcome of 23 patients with brain metastases from epithelial ovarian cancer who were treated during 19821994 were compared with those of 20 patients treated during 1995-2010 at the same center. Results: No differences were found in terms of primary tumor characteristics, time interval from ovarian cancer diagnosis to brain involvement diagnosis, sites of metastasis, and presence of extracranial disease. The main difference between the 2 groups was the therapeutic approach. During 1982-1994, most patients received radiotherapy only, whereas most patients during 1995-2010 underwent surgical resection followed by radiotherapy and/or chemotherapy. The duration of survival during 1982-1994 was 5 months, which was significantly shorter than the duration of survival (18 months) during 1995-2010. Conclusion: An aggressive multimodal treatment approach might prolong the survival of patients with brain involvement from ovarian cancer. (C) 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Paclitaxel is a member of the taxane agents that has demonstrated efficacy in ovarian cancer, both in first- and in second-line therapy. Counted among the side-effects of this drug are neurological disorders. In the present study, a rare case of a non-neuropathic ocular disorder, known as cystoid macular edema (CME), due to paclitaxel in patients treated for ovarian cancer is described. Macular edema, or CME, is a common cause of visual impairment that has been classically demonstrated by fluorescein angiograms, showing capillary leakage. CME without fluorescein leakage is rare, and its most common causes are juvenile X-linked retinoschisis, Goldmann-Favre syndrome, and niacin toxicity. At the present time, the mechanism associated with the form of CME that does not exhibit any signs of fluorescein leakage has not been elucidated due to an absence of histopathological studies. Several mechanisms have been proposed, although it is considered to occur due to disruption of the normal blood-retinal barrier by molecules with a molecular weight lower than that of fluorescein, which leads to fluid accumulation in the intracellular space. It is well known that taxane agents cause fluid retention, represented by edema, weight gain, and third-space fluid collection (pericardial, pleural, ascites), and this appears to be associated with their cumulative dose. The present case study confirms that macular edema associated with paclitaxel use exhibits spontaneous resolution following discontinuation of the causative agent. Taxane-associated maculopathy has been scarcely reported in the literature, but the gynecological oncologist should be alert to its possible development, and an ophthalmologic evaluation should be offered to all patients using paclitaxel

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.

Although uterine prolapse and carcinoma of the uterine cervix are not rare event, their association is very uncommon. An 86-year-old patient gravida 8, para 5 was admitted for vaginal bleeding from a uterine prolapse of 20 years of duration. On physical examination, a complete third-degree prolapsed uterus with an ulcerated lesion of 12 cm in maximum diameter involving both the anterior and posterior lips of the cervix was observed. Because of the poor performance status and high American Society of Anesthesiology scoring, the patient was admitted for a vaginal hysterectomy with upper vaginectomy in spinal anesthesia. However, she died of pulmonary embolism 20 days after surgery. A case of a cervical cancer with a complete uterine prolapse of 20 years of duration is reported. We believe that this case typically rare to see in a developed country might be a useful addition to the few published reports.

Background: The objective of this study was to evaluate feasibility, safety and clinical outcome of long-term therapy with topotecan (Hycamtin) in recurrent or persistent ovarian cancer. Patients and Methods: A retrospective chart review was conducted on all patients treated with topotecan (TPT) at the Department of Obstetrics and Gynecology, University of Bari, Italy between 1999 and 2007. Pertinent clinicopathologic information, response and toxicity following treatment with TPT were collected. TPT was given at a dosage ranging between 1.5 and 1.0 mg/m(2) every three to four weeks. All patients were evaluated for toxicity acording to the CTC and response according to the RECIST response criteria. Time to progression (TTP) was calculated from initiation of TPT treatment and start of the next chemotherapy regimen. Results: A total of 30 patients received TPT for at least eight cycles for recurrent ovarian (22), fallopian tube (3) or primary peritoneal carcinoma (5). A total of 432 cycles of chemotherapy were given, with an average of 14.4 cycles per patient (range 8-22). Dose reduction was necessary in 20 patients (66%). About half of the patients required blood transfusions and growth factors. Non hematologic toxicity was mild and manageable. Responses were observed in 16/30 patients (53%), the remaining having SD. Median time to treatment progression was 28 months (range 9-88). Conclusion: Long-term treatment with topotecan in recurrent/persistent ovarian cancer is feasible with limited evidence of cumulative toxicity. The results of this retrospective analysis suggest a potential role for late response and survival benefit for those patients without disease progression who continue topotecan therapy beyond six cycles of treatment.

Objective: Pelvic lymph nodes are the most common site of extrauterine spread in clinical early-stage endometrial cancer. International Federation of Gynecology and Obstetrics has mandated surgical evaluation of lymph nodes in endometrial cancer since 1988; however, the clinical impact of lymphadenectomy has never been addressed. Design: We reported a retrospective analysis in order to evaluate whether pelvic systematic lymph dissection improves overall and progression-free survival compared with no lymphadenectomy. Method: From 1991 through 2008, patients with endometrial carcinoma were evaluated using a log-rank statistic and a Cox multivariable regression analysis. All statistical tests were two-sided. Results: Of the 410 patients with a diagnosis of endometrial carcinoma, 390 underwent primary surgery. Of those who underwent surgery, 285 had endometrioid histology. One hundred and ninety (190) patients had surgery with no lymphadenectomy, whereas 95 had surgery with lymphadenectomy. Only 4 women revealed positive nodes. Median number of removed nodes was 14 in the lymphadenectomy group. The 5-year survival rate of 90% and 86% was achieved, respectively, for lymphadenectomy and no lymphadenectomy ( p¼0.501). Conclusions: Although systematic pelvic lymphadenectomy significantly improved surgical staging of women with clinical early-stage endometrial carcinoma by detecting a higher rate of patients with positive nodes, it did not improve overall survival.

Objectives: Aim of this study was to evaluate the effect of adjuvant therapy on the recurrence and on the overall survival in patients with early stage endometrioid adenocarcinoma of endometrium and lymphovascular space invasion (LVSI) treated with primary surgery. Methods: 48 patients with endometrioid adenocarcinoma of endometrium and LVSI were evaluated in this retrospective study. The Log-Rank test was used for statistical analyses and the Kaplan-Meyer method was used for time-to-event analysis. Results: 14 (29%) received radiotherapy as adjuvant therapy, whereas 34 (71%) did not received any adjuvant therapy. Between the patients who underwent adjuvant therapy, 4 (28%) developed a recurrence, the median time to recurrence was 26 months (8-53) and the median survival after recurrence was 56 months (29-120). 12(50%) patients who had not received any therapy relapsed, the median time to recurrence was 12 months (4-38) and the median survival after recurrence was 30 months (14-93). The analysis demonstrated that adjuvant therapy is not associated neither to a decreased in the occurrence of relapse (p=0,2), neither to an increase in survival (p=0,1). Conclusion: The administration of adjuvant radiotherapy in patients with recurrent endometrioid adenocarcinoma of early stage endometrial cancer and LVSI does not affect neither the occurrence of relapse, neither the overall survival.

BACKGROUND: An increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1alpha 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. RESULTS: Given 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. CONCLUSION: MtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma.

Type I endometrial cancer (EC) is the most common form of EC, displaying less aggressive behavior than type II. The development of type I endometrial cancer is considered a multistep process, with slow progression from normal endometrium to hyperplasia, the premalignant form, and endometrial cancer as a result of an unopposed estrogenic stimulation. The role of mitochondria in type I EC tumor progression and prognosis is currently emerging. This review aims to explore mitochondrial alterations in this cancer and in endometrial hyperplasia focusing on mitochondrial DNA mutations, respiratory complex I deficiency, and the activation of mitochondrial quality control systems. A deeper understanding of altered mitochondrial pathways in type I EC could provide novel opportunities to discover new diagnostic and prognostic markers as well as potential therapeutic targets.

Objective: To evaluate clinicopathologic features and to investigate the outcome of patients with ovarian Sertoli-Leydig cell tumors (SLCTs). Methods: Data concerning 21 patients treated in 11 MITO centers were retrospectively reviewed. Results: Median age was 37 (range 16-76). FIGO stage was: 17 (81%) IA, 1 (4.8%) IC, 1 (4.8%) IIB and 2 (9.5%) IIIC. Five patients (23.8%) had G1 tumor, ten (47.6%) had G2, and six (28.6%) had G3. Fertility-sparing operation was performed in 11 patients, while hysterectomy with bilateral salpingo-oophorectomy was executed in 10 patients; five patients received adjuvant chemotherapy (G2-3). Seven patients (33.3%) relapsed with a median time to recurrence of 14 months. Six recurrent patients had G2-3 disease, while one had G1. Four patients had stage IA disease, one IC and 2 stage IIIC. Patients with stage IA disease did not receive adjuvant chemotherapy. Two patients had pelvic recurrence, 4 abdominal (one with lymph nodal involvement), one on the contralateral ovary and the trocar access. Five patients underwent salvage surgery plus chemotherapy, while one received only salvage chemotherapy and one palliation. Five patients died of disease, four had received first treatment not in a MITO center. 5 year overall survival was 100% for patients with G1 disease and 77.8% for G2-3. 5 year overall survival was 92.3% for stage I and 33.3% for stage > I. Conclusions: The prognosis of patients with grade 1 SLCT is excellent without adjuvant chemotherapy. Patients with advanced stage or grade 2-3 tumors appear to benefit from postoperative chemotherapy

Mitochondrial DNA (mtDNA) mutations have been described in almost all types of cancer. However, their exact role and timing of occurrence during tumor development and progression are still a matter of debate. A Vogelstein-like model of progression is well established for endometrial carcinoma (EC), however, mtDNA has been scarcely investigated in these tumors despite the fact that mitochondrial biogenesis increase has been shown to be a hallmark of type I EC. Here, we screened a panel of 23 type I EC tissues and matched typical hyperplasia for mutations in mtDNA and in four oncosupressors/oncogenes, namely PTEN, KRAS, CTNNB1 and TP53. Overall, mtDNA mutations were identified in 69% of cases, while mutational events in nuclear genes occurred in 56% of the cases, indicating that mtDNA mutations may precede the genetic instability of these genes canonically involved in progression from hyperplasia to tumor. Protein expression analysis revealed an increase in mitochondrial biogenesis and activation of oxidative stress response mechanisms in tumor tissues, but not in hyperplasia, in correlation with the occurrence of pathogenic mtDNA mutations. Our results point out an involvement of mtDNA mutations in EC progression and explain the increase in mitochondrial biogenesis of type I EC. Last, since mtDNA mutations occur after hyperplasia, their potential role in contributing to genetic instability may be envisioned.

PREDICTORS OF SURVIVAL IN PATIENTS WITH RECURRENT OVARIAN CANCER UNDERGOING SECONDARY CYTOREDUCTIVE SURGERY BASED ON AN INTERNATIONAL COLLABORATIVE ANALYSIS R.-Y. Zang1, P. Harter2, D.S. Chi3, J. Sehouli4, R. Jiang1, C.G. Tropé5, A. Ayhan6, G. Cormio7, Y. Xing8, K. Wollschlaeger9, E.I. Braicu4, C.A. Rabbitt3, H. Oksefjell5, W.-J. Tian1, C. Fotopoulou4, J. Pfisterer10, A. du Bois2, J.S. Berek11 1Ovarian Cancer Program, Department of Gynecologic Oncology, Fudan University Cancer Hospital, Shanghai, China, 2Department of Gynecology & Gynecologic Oncology, HSK, Dr. Horst Schmidt Klinik, Wiesbaden, Germany, 3Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 4Department of Gynecology, Charité Medical University of Berlin, Berlin, Germany, 5Division of Gynecology and Obstetrics, Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway, 6Department of Obstetrics and Gynecology, Baskent University Faculty of Medicine, Ankara, Turkey, 7Department of Gynecology, Obstetrics and Neonatology, University of Bari, Bari, Italy, 8Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 9Department of Gynecology and Obstetrics, University of Magdeburg, Magdeburg, 10Department of Gynecology and Obstetrics, Hospital Solingen, Solingen, Germany, 11Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, USA Background: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. Methods: Individual data of 1,100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analyzed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared to 27.0 months in those with residual disease of 0.1-1cm and 15.6 months in those with residual disease of >1cm, respectively (P< 0.0001). Progression-free interval (< 23.1 months vs. >=23.1 months, hazard ratio (HR),1.72; score: 2), ascites at recurrence (present vs. absent, HR, 1.27; score: 1), extent of recurrence (multiple vs. localized disease, HR, 1.38; score: 1) as well as residual disease after SCR (R1 vs. R0, HR, 1.90, score: 2; R2 vs. R0, HR,3.0, score: 4) entered into the risk model. Conclusion: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer.

Background: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. Methods: Individual data of 1100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analysed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared with 27.0 months in those with residual disease of 0.1-1 cm and 15.6 months in those with residual disease of > 1 cm, respectively (P<0.0001). Progression-free interval (≤23.1 months vs >23.1 months, hazard ratio (HR): 1.72; score: 2), ascites at recurrence (present vs absent, HR: 1.27; score: 1), extent of recurrence (multiple vs localised disease, HR: 1.38; score: 1) as well as residual disease after SCR (R1 vs R0, HR: 1.90, score: 2; R2 vs R0, HR: 3.0, score: 4) entered into the risk model. Conclusion: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer. © 2011 Cancer Research UK All rights reserved.

Objectives: It was the aim of this study to evaluate clinicopathological characteristics and prognostic factors of uterine leiomyosarcomas (LMS). Methods: Twenty-eight patients with uterine LMS were evaluated in this retrospective study. Their features and survival were analyzed by Kaplan-Meier and log-rank tests. Results: The median age of the patients was 52 years (range 25-74). Nine patients had a disease with a mitotic count <10/10 high-power fields. Twenty-one patients presented with stage I disease, 1 with stage II and 6 with stage IV. Twelve patients underwent total hysterectomy and bilateral salpingo-oophorectomy, 2 simple hysterectomy, 5 myomectomy and 9 more comprehensive surgical treatments. Adjuvant chemotherapy was administered to 16 patients, whereas chemoradiation was given only to 2 patients. Fifty percent presented with recurrence of the disease. The median overall survival was 46 months. Age, mitotic count, type of surgery, adjuvant therapy, recurrence and clinical response to chemotherapy were not found to affect survival, while the menopausal status and FIGO (International Federation of Gynecology and Obstetrics) stage were found to be prognostic factors. Conclusion: In our series, the menopausal state and FIGO stage were found to be prognostic factors related to survival. Copyright (C) 2011 S. Karger AG, Basel

Clusterin (CLU) is a nearly ubiquitous multifunctional protein synthesized in different functionally divergent isoforms, sCLU and nCLU, playing a crucial role by keeping a balance between cell proliferation and death. Studying in vivo CLU expression we found a higher mRNA expression both in neoplastic and hyperplastic tissues in comparison to normal endometria; in particular, by RT-qPCR we demonstrated an increase of the specific sCLU isoform in the neoplastic and hyperplastic endometrial diseases. On the contrary, no CLU increase was detected at the protein level. The CLU gene transcriptional activity was upregulated in the hyperplastic and neoplastic tissues, indicating the existence of a fine post-trans-criptional regulation of CLU expression possibly responsible for the protein decrease in the malignant disease. A specific CLU immunoreactivity was present in all the endometrial glandular cells in comparison to the other cellular compartments where CLU immunoreactivity was lower or absent. In conclusion, our results suggest the existence of a complex regulatory mechanism of CLU gene expression during the progression from normal to malignant cells, possibly contributing to endometrial carcinogenesis. Moreover, the specific alteration of the sCLU:nCLU ratio associated with the pathological stage, suggests a possible usage of CLU as molecular biomarker for the diagnosis/prognosis of endometrial proliferative diseases.

Clusterin (CLU) is a nearly ubiquitous multifunctional protein synthesized in different functionally divergent isoforms, sCLU and nCLU, playing a crucial role by keeping a balance between cell proliferation and death. Studying in vivo CLU expression we found a higher mRNA expression both in neoplastic and hyperplastic tissues in comparison to normal endometria; in particular, by RT-qPCR we demonstrated an increase of the specific sCLU isoform in the neoplastic and hyperplastic endometrial diseases. On the contrary, no CLU increase was detected at the protein level. The CLU gene transcriptional activity was upregulated in the hyperplastic and neoplastic tissues, indicating the existence of a fine post-trans-criptional regulation of CLU expression possibly responsible for the protein decrease in the malignant disease. A specific CLU immunoreactivity was present in all the endometrial glandular cells in comparison to the other cellular compartments where CLU immunoreactivity was lower or absent. In conclusion, our results suggest the existence of a complex regulatory mechanism of CLU gene expression during the progression from normal to malignant cells, possibly contributing to endometrial carcinogenesis. Moreover, the specific alteration of the sCLU:nCLU ratio associated with the pathological stage, suggests a possible usage of CLU as molecular biomarker for the diagnosis/prognosis of endometrial proliferative diseases.

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P &lt; 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.

The aim of this study was to report the clinical features, management, and outcome of complete hydatidiform mole with a coexisting viable fetus. Two cases are reported. In both cases ultrasound examination demonstrated a normally growing live fetus alongside a normal placenta and an additional intrauterine echogenic mass with features of hydatidiform mole. The hCG levels were significantly increased and fetal karyotypes were normal. A cesarean section performed at 28 weeks' gestation in the first case and at 26 weeks' gestation in the second one resulted in the delivery of live normal infant and two adjoining placentas in both cases. Microscopic examination of the abnormal placentas confirmed complete hydatidiform mole. The babies did well and serial maternal serum hCG levels showed a declining trend and were undetectable by a few months after delivery. Continuation of a twin pregnancy with complete hydatidiform mole (CHMF) is an acceptable option. There is, although, an increased risk of developing maternal and fetal complications. Close surveillance of an ongoing pregnancy is compulsory to detect potential early signs of complications.

Objectives: The aim of this study was to assess the accuracy of transvaginal sonography (TVS) in the preoperative staging of endometrial carcinoma, because accurate preoperative staging of the disease would assist in planning the optimal course of treatment. We investigated the ability to distinguish between cases with &lt; 50% and &gt; 50% myometrial invasion (FIGO Stage Ia -Ib vs. Stage Ic), and tumor extension to the cervical stroma (Stage IIb) according to the old FIGO classification. Methods: 140 women with pathologically-proven of endometrial cancer, referred to our istitution between 2007 and 2010, were included in this study. All underwent TVS examination about seven days before the surgical staging. Histological findings of myometrial and cervical stroma invasion were used as the reference standard. Results: The histological subtypes comprised 75% endometrioid adenocarcinoma, 9% serous papillary, 6% endometrioid villoglandular, 4% villoglandular, 3% adenosquamous and 3% clear cells; there were 60% well differentiate, 15% moderately differentiate and 25% poorly differentiate cancers. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for TSV in the evaluation of &lt; 50% myometrial infiltration were 82%,77%, 79%, 80% and 48%; of &gt; 50% myometrial infiltration were 86%, 90%, 86%, 90%, and 57%; for cervical invasion were 80%, 100%, 100%, 89% and 63%, respectively. Conclusion: The transvaginal sonography shows good accuracy in the staging of endometrial carcinoma. Our results support a potential role of TVS for the prediction of strome cervix infiltration of endometrial cancer.

No abstract available

Aims: We present this case to improve medical knowledge about unusual presentation of leiomyomas and about the diagnostical findings of examinations settled down per rectal way. We provide images and stress the importance of differential diagnosis based on imaging. Presentation of the Case: We report a case of a 26 years old nulliparous, with a leiomyoma developed on the posterior upper third of the vagina surgically removed. The patient came to our Unit with dysmenorrhea and menorrhagia and underwent physicalexamination and ultrasound scan. Both exams were executed per transrectal way because of her being a virgo. A Computed Tomography scan has been executed too. All the results pointed out the presence of a round-shaped, well delimitated, solid mass in posterior vaginal wall. Magnetic Resonance confirmed this diagnosis. Discussion: We widely discuss the symptomathologic cortege, the diagnostic iter based on imaging we settled down, the possible differential diagnosis, and surgical therapy performed. Concordance of imaging, negativity of tumor markers and general well-being status of the patient led to the diagnostical hypotesis of vaginal benign neoformation. These data excluded other diagnosis as endometriosis, uterine fibroma, primitive vaginal malignant tumor and metastasis of other-site primitive malignant neoplasia. The patient has been treated by surgical transvaginal excission therapy. Conclusion: US imaging and MR gives us the possibility to recognize a mass and to discern his nature and localization, thus to choose the best therapy in each case. Hystopathology still represent the gold standard in making a diagnosis in gynaecological oncology.

The aim of this phase II multicentric study was to evaluate the efficacy and toxicity of neo-adjuvant chemotherapy with weekly topotecan and cisplatin in locally-advanced squamous cervical cancer. PATIENTS AND METHODS: From November 2008 to January 2011, 92 patients met the inclusion criteria and were enrolled. Eligibility criteria were: squamous or adenosquamous cervical cancer; clinical stages IB2, IIA, IIB; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)≤ 2; neutrophils ≥1500/μL; platelets ≥100,000/μL, normal renal and liver function. Treatment consisted of six courses of weekly topotecan (2mg/m(2)) and cisplatin (40 mg/m(2)). All responsive and stable patients were submitted to radical surgery, while progressed cases underwent definitive radiotherapy±chemotherapy. Primary end-point was evaluation of efficacy and toxicity. All patients are evaluable for toxicity and efficacy. RESULTS: Ninety-six percent of patients completed the six planned courses of chemotherapy, and 95% of courses were administered at a full dose and without interruption or delay. Mean age was 49 years (35-64 years). FIGO Stage distribution was 30 IB2, 13 IIA and 49 IIB. Treatment was well tolerated and no death occurred. G3-G4 haematological toxicity was observed in 28% of patients (5% out of cycles). Support therapies (blood transfusions and/or erythropoietin and/or Granocyte-Colony Stimulating Factor) were given to 24% of patients. Clinical response rate was 77%. The nine progressed cases were irradiated, while the remaining 83 patients were submitted to radical surgery. An overall pathologic response was observed in 67% of patients, with an optimal response rate of 32% and a disease downstage in 57% of patients. Nodal metastases occurred in 36% of patients. Adjuvant therapy (radiotherapy and or chemotherapy) was prescribed in 55% of patients, because of lymph node metastases, parametrial or vaginal involvement or cut-through margins. Median follow-up was 18 months: 76% of patients are alive and free from recurrence, 24% of patients relapsed and 13% died. CONCLUSIONS: Weekly topotecan and cisplatin showed an acceptable toxicity profile; the promising response rate warrants further investigation.

Background: Chemoradiation is the standard treatment for locally-advanced cervical cancer. Neoadjuvant chemotherapy is an alternative, with a 14% absolute improvement in survival, especially when intense and short. Methods: Since 2006, 83 patients were enrolled in this multicentric prospective phase II study. Eligibility criteria: squamous or adenosquamous cervical carcer; stages IB2, IIA, IIB; ECOG PS≤2; neutrophils ≥1,500 /μL; platelets ≥100,000/μL, normal renal and liver function. Treatment consisted of 6 weekly courses of Topotecan (2 mg/m2) and Cisplatin (40 mg/m2). All responsive and stable patients were submitted to radical surgery, while progressed underwent definitive radiotherapy±chemotherapy. Primary endpoint was evaluation of efficacy and toxicity . Results: Mean age was 48 years. Clinical FIGO Stage: 25 IB2; 11 IIA; 47 IIB. Suspicious lymph nodes at MRI were 35%. Ninety-six percent of patients received 6 courses, 98% of cycles were delivered at a full dose, without any delay in 96%. Treatment was well tolerated, no death occurred. G3-G4 bone marrow toxicity was observed in 4% of cycles. Clinical response rate was 81%. Five progressive cases and 3 partial responses with severe co-morbidities were treated with radiotherapy±chemotherapy, the others underwent radical surgery. Overall pathological response rate was 64%, with 25% of optimal responses. Nodal metastases occurred in 37% of patients. Forty-four percent of patients received adjuvant therapy because of negative prognostic factors. Mean follow-up is 20 months, 84% of patients are free from recurrence, 18% relapsed and 4% died. Conclusions: Weekly Topotecan and Cisplatin showed an acceptable toxicity and a promising response rate.