Emanuela Mancini

Emerging biological treatments for uterine cervical carcinoma.

Cervical cancer is the third most common cancer worldwide, and the development of new diagnosis, prognostic, and treatment strategies is a major interest for public health. Cisplatin, in combination with external beam irradiation for locally advanced disease, or as monotherapy for recurrent/metastatic disease, has been the cornerstone of treatment for more than two decades. Other investigated cytotoxic therapies include paclitaxel, ifosfamide and topotecan, as single agents or in combination, revealing unsatisfactory results. In recent years, much effort has been made towards evaluating new drugs and developing innovative therapies to treat cervical cancer. Among the most investigated molecular targets are epidermal growth factor receptor and vascular endothelial growth factor (VEGF) signaling pathways, both playing a critical role in cervical cancer development. Studies with bevacizumab or VEGF receptor tyrosine kinase have given encouraging results in terms of clinical efficacy, without adding significant toxicity. A great number of other molecular agents targeting critical pathways in cervical malignant transformation are being evaluated in preclinical and clinical trials, reporting preliminary promising data. In the current review, we discuss novel therapeutic strategies which are being investigated for the treatment of advanced cervical cancer.

Laparoscopic Debulking Surgery in the Management of Advanced Ovarian Cancer After Neoadjuvant Chemotherapy.

Objective The purpose of this study was to evaluate the feasibility and morbidity of total laparoscopic debulking surgery in the treatment of advanced ovarian cancer after neoadjuvant chemotherapy. Methods/Materials We performed a retrospective review of laparoscopic approach in patients with histologically confirmed epithelial ovarian cancer (International Federation of GynaecologyObstetrics stages IIIC-IV) who received 3 courses of neoadjuvant chemotherapy, from January 2010 to December 2014, at the Gynaecologic Oncologic Unit, “Regina Elena” National Cancer Institute, Rome, Italy. Results A total of 30 patients were included. The median age was 50 years (range, 26–73 years), median body mass index was 24.5 kg/m2 (range, 19–39 kg/m2). All patients had good clinical response to 3 cycles of neoadjuvant chemotherapy. All women underwent a complete debulking surgery with no residual disease. The median operating time was 152 minutes (range, 70–335 minutes), the median blood loss was 70 mL (range, 50–200 mL). The median number of removed pelvic lymph nodes was 15 (range, 13–25). There was 1 (3.3%) intraoperative complication and 2 (6.6%) postoperative short-term complications. The median length of hospital stay was 4 days (range, 3–13 days). The median follow-up was 15 months (range, 2–54 months). Twenty-six patients are free from recurrence at the time of this report. Conclusions Laparoscopic cytoreduction in patients with advanced ovarian cancer after neoadjuvant chemotherapy, when performed by skilled surgeons, seems feasible and may decrease the impact of aggressive surgery on high-morbidity patients, such as on women after chemotherapy.

Robotic Hysterectomy in Severely Obese Patients With Endometrial Cancer: A Multicenter Study

STUDY OBJECTIVE The aim of this study was to evaluate the surgical and oncologic outcomes of robotic hysterectomy with or without or less pelvic and aortic lymphadenectomy in severely obese patients (body mass index [BMI] ≥ 40 kg/m(2)) with endometrial cancer. MATERIAL AND METHODS Between August 2010 and November 2014, patients with histologically confirmed endometrial cancer and BMI ≥40 kg/m(2) were deemed eligible for the study and underwent RH with or without pelvic and aortic lymphadenectomy. RESULTS Seventy patients were divided into 3 groups according to their BMI: group A, BMI between 40 and 45 kg/m(2) (50 patients); group B, BMI between 45 and 50 kg/m(2) (10 patients); and group C, BMI above 50 kg/m(2) (10 patients). No significant statistical differences were found between the 3 groups in terms of operation time, blood loss, hospital stay, and oncologic results. Pelvic lymphadenectomy was performed in 42%, 30%, and 20% of patients in groups A, B, and C, respectively. An intraoperative complication occurred in 1 patient in group A, early postoperative complications in 4 patients in group A and in 1 patient in group C, and a late postoperative complication occurred in 1 patient in group A. No conversions to laparotomy were necessary; however, 3 patients underwent conversions to laparoscopy in group A and 1 patient in both groups B and C. CONCLUSION Our study showed that robotic surgery in severely obese patients with endometrial cancer is safe and feasible. Moreover, it seems that an increase in BMI does not change the surgical and oncologic outcomes. However, randomized controlled trials are needed to confirm these results.

Fasting as possible complementary approach for polycystic ovary syndrome: hope or hype?

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women.

Surgical and Oncological Outcome of Robotic Surgery Compared With Laparoscopic and Abdominal Surgery in the Management of Locally Advanced Cervical Cancer After Neoadjuvant Chemotherapy.

Objective The primary aim is to evaluate the surgical and oncological outcome of robotic radical hysterectomy (RRH) plus pelvic lymphadenectomy in locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). The secondary aim is to compare the surgical and oncological results of RRH after NACT with a historical cohort of patients undergoing laparoscopic radical hysterectomy or abdominal radical hysterectomy plus pelvic lymphadenectomy for LACC after NACT. Methods We enrolled a total of 41 patients in this study with LACC undergoing RRH, who achieved a clinical partial or complete response to NACT. The surgical and oncological outcomes of 2 historical groups were compared: the laparoscopic group (41 patients) with the laparotomic group (43 patients). Results The median estimated blood loss, operative time, and length of hospital stay were statistically significant and in favor of the robotic group. No conversion to laparotomy in the robotic group was necessary. There were no significant differences between the 3-year overall survival and disease-free survival rates in the minimally invasive groups; nevertheless, the robotic group showed the same recurrence rate of laparoscopic in a short-interval follow-up. Conclusions The robotic approach could be considered a feasible and safe alternative to other surgical options. Multicenter randomized clinical trials with longer follow-ups are necessary to evaluate the overall oncologic outcomes of this procedure.

Robotic single site versus robotic multiport hysterectomy in early endometrial cancer: a case control study

Objective To compare surgical outcomes and cost of robotic single-site hysterectomy (RSSH) versus robotic multiport hysterectomy (RMPH) in early stage endometrial cancer. Methods This is a retrospective case-control study, comparing perioperative outcomes and costs of RSSH and RMPH in early stage endometrial cancer patients. RSSH were matched 1:2 according to age, body mass index, comorbidity, the International Federation of Gynecology and Obstetric (FIGO) stage, type of radical surgery, histologic type, and grading. Mean hospital cost per discharge was calculated summarizing the cost of daily hospital room charges, operating room, cost of supplies and length of hospital stay. Results A total of 23 women who underwent RSSH were matched with 46 historic controls treated by RMPH in the same institute, with the same surgical team. No significant differences were found in terms of age, histologic type, stage, and grading. Operative time was similar: 102.5 minutes in RMPH and 110 in RSSH (p=0.889). Blood loss was lower in RSSH than in RMPH (respectively, 50 mL vs. 100 mL, p=0.001). Hospital stay was 3 days in RMPH and 2 days in RSSH (p=0.001). No intraoperative complications occurred in both groups. Early postoperative complications were 2.2% in RMPH and 4.3% in RSSH. Overall cost was higher in RMPH than in RSSH (respectively,

Circulating cell-free DNA content as blood based biomarker in endometrial cancer

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Serum DNA integrity index as a potential molecular biomarker in endometrial cancer

5,181.06). Conclusion Our retrospective study suggests the safety and feasibility of RSSH for staging early endometrial cancer without major differences from the RMPH in terms of surgical outcomes, but with lower hospital costs. Certainly, further studies are eagerly warranted to confirm our findings.

Robotic single site radical hysterectomy plus pelvic lymphadenectomy in gynecological cancers

Background Altered circulating cell-free DNA (cfDNA) levels are related to cancer development and aggressiveness. Up to now, very few studies have been performed for evaluating cfDNA content in endometrial cancer (EC). Methods First, we measured cfDNA release in blood serum of EC cancer patients collected before surgery and before the beginning of any treatment by SYBR Gold assay and correlated it with tumor aggressiveness. We also assessed the relative mitochondrial cell-free DNA (cfmtDNA) content by qRT-PCR. Next, we correlated cfDNA levels with BMI, age, hypertension and inflammation markers. Results CfDNA levels are higher in G2 and G3 compared with G1 EC sera. A significant modulation of cfDNA content was detected in sera from patients with BMI>30 compared with those with BMI<30. We observed a further and significant alteration in cfDNA level in hypertensive patients with G2-G3, but not in G1 EC. Analysis of preoperative neutrophil-to-lymphocyte (NLR) and monocyte-to-lymphocyte (MLR) ratios suggests a contribution of the host response in the altered cfDNA levels in EC. Conclusions Our data indicate that assessment of total and mitochondrial cfDNA levels in blood sera and the relative NLR and MLR in blood obtained from preoperative patients may help clinical management and prognosis in EC.

Single-access laparoscopic approach in the surgical treatment of endometrial cancer: A single-institution experience and review of literature

BackgroundCirculating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive “liquid biopsy” biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients. The aim of our study was to evaluate the possible role of cfDNA and its integrity index as a complementary tool for endometrial cancer (EC) management.MethodsAlu-quantitative real-time PCR (qPCR) analysis wasprformed on 60 serum samples from preoperative EC patients randomly recruited. Both cfDNA content and DNA integrity index were measured by qPCR-Alu115 (representing total cfDNA) and qPCR-Alu247 (corresponding to high molecular weight DNA) and correlated with clinicopathologic characteristics. Lymphovascular space invasion (LVSI) was detected by hematoxylin and eosin staining. In case of doubt, LVSI status was further evaluate by immunohistochemistry using anti-CD31 and anti-CD34 antibodies.ResultsTotal cfDNA content significantly increases in high grade EC. A significant decrease of DNA integrity index was detected in the subset of hypertensive and obese high grade EC. Serum DNA integrity was higher in samples with LVSI. The ordinal regression analysis predicted a significant correlation between decreased integrity index values and hypertension specifically in tumors presenting LVSI.ConclusionsOur study supports the utility of serum DNA integrity index as a noninvasive molecular biomarker in EC. We show that a correlation analysis between cfDNA quantitative and qualitative content and clinicopathologic features, such as blood pressure level, body mass index (BMI) and LVSI status, could represent a potential predictive signature to help stratification approaches in EC.