A prospective multicentric study of risk-reducing salpingo-oophorectomy in BRCA mutation patients.

BACKGROUND AND AIM OF THE WORK: BRCA1/2 are tumour-suppressor genes involved in DNA homologous recombination and ovarian cancer development.  The study evaluated the risk of tumor cancer in women presenting the BRCA mutations. METHODS: Risk-reducing surgery (RRS) was performed in 100 patients carrying BRCA1 (aged between 30-73 years, median age was 51 years) and BRCA 2 mutation (aged between 36-70 years, median age was 53 years). Fifty-eight patients had previous history of breast cancer. RESULTS: Between the 100 patients, 82 women underwent risk-reducing salpingo-oophorectomy (RRSO) through a laparoscopic minimally invasive approach, 7 (7 %) underwent laparoscopic RRSO and contextual hysterectomy, 1 woman (1 %) underwent RRSO through a laparotomic approach and 10 women (10 %) laparotomic RRSO and hysterectomy. During 5 (5 %) laparoscopic RRSO, prophylactic bilateral mastectomy was also performed. Early and late complication occurred in 3 patients (3 %). Two patients (2 %) were found to have occult Serous Tubal Intraepithelial Carcinoma (STIC) and three patients (3 %) occult cancer. CONCLUSIONS: RRSO is safe and feasible in BRCA mutation carriers. The procedure is effective for genetic prevention of ovarian cancer.

Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22).

BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published. METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®). RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found. CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics. CLINICAL TRIAL REGISTRATION: This study is registered under NCT02408536 on ClinicalTrials.gov .

Prognostic factors in clear cell carcinoma of endometrium: analysis of 55 cases.

BACKGROUND AND AIM OF THE WORK: The purpose of this study was to evaluate the clinical and pathologic prognostic factors associated with survival in patients with clear cell carcinoma (CCC) of the endometrium. METHODS: A retrospective review of fifty-five patients with endometrial clear cell carcinoma were collected. RESULTS: The median overall and disease-free survivals were 40 and 20 months, respectively. A univariate analysis was performed with respect to stage of disease, age, lymph nodes status, myometrium invasion, lymph vascular space invasion and adjuvant therapy. Stage was found to be the only important prognostic factor related to survival. In fact, early stage had a median survival of 77 months compared to 34 months in the advanced disease (p<0.04). These differences remained significant after adjusting for single stage (stage III versus IV).    Conclusions: Endometrial CCC is a rare histotype. Advanced stage disease is considered a poor prognostic factor. Recurrences are high even in early stage. Randomized clinical trials are needed.

PARP inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective.

Epithelial ovarian cancer (EOC) has a poor prognosis. Since the introduction of paclitaxel as antineoplastic agent >20 years ago, only a few phase III randomized trials have shown challenging data regarding different therapeutic options for facing its aggressive clinical course and granting active therapies to patients. Different studies have shown the utility of poly(ADP-ribose) polymerase (PARP) inhibitors in women with EOC with or without BRCA mutations, both germline and somatic. Three PARP inhibitors, olaparib, rucaparib and niraparib, have been recently approved by the Food and Drug Administration for clinical use in EOC patients, though with different clinical indications and profiles of toxicity, while two other molecules, veliparib and talazoparib, are still under clinical investigation. The aim of the present paper is to evaluate the current status of PARP inhibitors in terms of molecular activity, pharmacodynamic properties and clinical applications.

A phase II study: dose-dense carboplatin and paclitaxel as neoadjuvant chemotherapy in locally advanced cervical 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.

Biological Pathways Involved in Tumor Angiogenesis and Bevacizumab Based Anti-Angiogenic Therapy with Special References to Ovarian Cancer.

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.

Uterine Rupture after Laparoscopic Myomectomy in Two Cases: Real Complication or Malpractice?

We describe two cases of uterine rupture in pregnancy after laparoscopic myomectomy and analyze all the aetiological factors involved in this circumstance according to the recent literature, focusing above all on the surgical procedures and the characteristics of the excised myomas. The two cases of uterine rupture in pregnancy following laparoscopic myomectomy occurred at 36 and 18 weeks of gestation, respectively. Both women had undergone laparoscopic multiple myomectomy and uterine rupture occurred along the isthmic myomectomy scars, despite the fact that compliance with all the recent technical surgical recommendations for the previous laparoscopic multiple myomectomy had been fully observed. In our cases we identified the isthmic localization, size of the excised myomas (≥4 cm), and individual characteristics of the healing process as possible risk factors for "a real complication." Larger studies and robust case-control analyses are needed to draw reliable conclusions; special care should be paid when performing laparoscopic myomectomy in women planning a later pregnancy.

US-color Doppler early diagnosis of uterine rupture with protrusion of umbilical cord.

OBJECTIVE: to analyze a case of uterine rupture in a pregnant woman that had a previous laparoscopic myomectomy. METHODS: pregnant woman at 34 weeks gestation came to our emergency room for abdominal pain. She had undergone a previous laparoscopic multiple myomectomy. Patient was evaluated in our Department, that is a tertiary center, by a team of experienced ultrasonographers. RESULTS: at a first clinical examination, the findings were a deep abdominal pain, dysuria and a positive Giordano's sign on the right. 2D ultrasound showed an alive intrauterine foetus, normal anterior fundal placenta and mild reduction of amniotic fluid. It revealed also a maternal right pyelectasis. A further meticulous ultrasound evaluation plus color Doppler revealed on the left side of the uterus the presence of a small vascularised area with venous and arterial flow that seemed to be in continuity with umbilical cord and that had its ultrasound characteristics. Emergency laparotomy was performed and confirmed the hypothesis of uterine rupture. DISCUSSION: uterine rupture seems to occur more frequently as a consequence of a laparoscopic myomectomy and the classic signs and symptoms are fetal distress, loss of uterine contractility, abdominal pain, hemorrhage and shock, so the early US suspect of uterine rupture was extremely important in the decision to perform an emergency caesarean section. CONCLUSION: the correlation between clinical examination and ultrasound-Doppler findings has been essential to recognise an obstetrical emergency and to perform prompt surgery.