PARP inhibition: a promising therapeutic target in ovarian cancer

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer

Early Diagnosis of Congenital Uterine Anomalies: Is the Three Dimensional Ultrasound Approach the Suitable Choice? 3D in Uterine Anomalies

Purposes: Congenital uterine anomalies (CUA) are benign conditions associated with relatively serious complications affecting the reproductive life. Due to their infrequency CUA are often misdiagnosed, exposing the patient to possible future complications. Case description: We report the cases of three women affected by an unknown CUA, which underwent three different diagnostic and surgical approaches. Conclusions: A correct and early diagnosis of CUA is mandatory to allow a correct clinical and therapeutic management. In our opinion we might avoid the use of MRI considered as the second line technique after 2D-US, keeping in mind that in CUA the diagnostic value of 3D-US has the same accuracy as MRI

A Small Molecule SMAC Mimic LBW242 Potentiates TRAIL- and Anticancer Drug-Mediated Cell Death of Ovarian Cancer Cells

BACKGROUND: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (SMAC) has been described to sensitize for apoptosis. We have explored the pro-apoptotic activity of LBW242, a mimic of SMAC/DIABLO, on ovarian cancer cell lines (A2780 cells and its chemoresistant derivative A2780/ADR, SKOV3 and HEY cells) and in primary ovarian cancer cells. The effects of LBW242 on ovarian cancer cell lines and primary ovarian cancer cells was determined by cell proliferation, apoptosis and biochemical assays. PRINCIPAL FINDINGS: LBW242 added alone elicited only a moderate pro-apoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or anticancer drugs in inducing apoptosis of both ovarian cancer cell lines and primary ovarian cancer cells. Mechanistic studies show that LBW242-induced apoptosis in ovarian cancer cells is associated with activation of caspase-8. In line with this mechanism, c-FLIP overexpression inhibits LBW242-mediated apoptosis. CONCLUSION: LBW242 sensitizes ovarian cancer cells to the antitumor effects of TRAIL and anticancer drugs commonly used in clinic. These observations suggest that the SMAC/DIABLO mimic LBW242 could be of value for the development of experimental strategies for treatment of ovarian cancer

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer

Vulvar malignancy in neurofibromatosis syndrome

Type 1 neurofibromatosis (NF1) is a dominantly inherited neurologic disorder that affects primarily the skin, bones, and peripheral nervous system. It may be associated with a variety of clinical manifestations including cafe-au-lait spots, skinfold freckling, Lisch nodules, and visceral neurofibromas. Individuals affected by NF1 harbor an increased risk for both benign and malignant tumors. Malignant transformation is usually observed in the form of neurosarcoma. Rarely, NF1 affects the genital tract, and isolated vulvar localization is extremely rare. Here is reported a rare case of a solitary neurosarcoma of the vulva in a 43-year-old woman affected by NF1 syndrome treated with surgical excision. The purpose of this case is to underline the possibility of association between NF1 and genital tract sarcoma and to suggest an accurate evaluation of rapid growth vulvar mass in this setting

Bartholin gland cancer

INTRODUCTION: Bartholin gland carcinoma is an extremely rare condition. Because of its, phase III trials have not been carried out, there exists no unanimous consensus on treatment and guidelines are missing. METHODS: All studies reporting cases of Bartholin cancer were collected and screened for the evaluations. Baseline characteristics of studies were extracted and were queried in a database. RESULTS: A total number of 133 manuscripts collected were available for the review process, representing a total number of 275 reported cases. The histological type of Bartholin gland cancer was specified in 90.4% cases: 30.7% cases were squamous cell carcinoma, 29.6% adenoid cystic carcinoma, 25% adenocarcinomas. At multivariate analysis adenocarcinoma histotype and positive lymph node were statistical correlated with worse prognosis. CONCLUSION: Bartholin gland cancer remains a challenge for gynecologic oncologists. To better understand and treat this disease, centralization to referral centers and design of multi institutional trials is crucial

Obturator Prosthesis Rehabilitation after Maxillectomy: Functional and Aesthetical Analysis in 25 Patients

The number of patients undergoing a surgical resection of the maxilla for oncological reasons is constantly increasing, the most common complication of which remains the communication between oral and nasal cavities. On the basis of data arising from the literature regarding the treatment options of maxillary oncological post-surgical defects, obturator prosthesis remains the most used worldwide. We studied 25 patients (with at least 1-year follow up) rehabilitated by obturator prosthesis after maxillary resection leading to oro-nasal communication, providing data on the objective/subjective evaluation of such rehabilitation and mastication performance measured by a two-color chewing gum test. The type of defect was classified according to the classification system proposed by Aramany. Among the patients in our study, 72% rated a higher score for either stability and retention than for aesthetic appearance, as confirmed by the Kapur score rated by clinicians. The two-color chewing gum test shows similar results as only one patient had insufficient chewing function. Interestingly, we found no correlation between the masticatory function and residual denture, confirming that the maxillary obturator remains a predictable solution in such patients regardless of the anatomical alterations following surgery

CO2 Laser Treatment for Bartholin Gland Abscess: Ultrasound Evaluation of Risk Recurrence

Study Objective: To evaluate the efficacy of CO2 laser treatment and parameters correlated with recurrence in patients with Bartholin gland abscesses treated using this approach. Design: Prospective study (Canadian Task Force classification II-2). Setting: University hospital. Patients: One hundred forty-seven patients who met eligibility criteria. Intervention: Preoperative ultrasound evaluation of Bartholin gland lesions and CO2 laser treatment. Measurements and Main Results: All patients received CO2 laser therapy, with median operative time 15 minutes (range, 12-35 minutes). Median postoperative stay was 1 hours (range, 1-4 hours). Estimated 3-year relapse-free rate was 88.56%. Lesion wall thickness 0.5-1.5 mm, multilocular lesion, and hyperechogenic lesion were correlated with recurrence. Conclusion: CO2 laser of Bartholin gland abscesses could be a valid option. Ultrasound characteristics of Bartholin gland lesions could predict lesion recurrence rate. © 2013 AAGL