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Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin’s gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.

Objective: To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients. Materials and methods: This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers. Results: The study population included 398 (69.5%) and 174 (30.5%) patients having hysterectomy and hysterectomy plus SNM. As the results of the adoption of a propensity-score matched analysis, we selected two homogeneous cohort of patients (150 having hysterectomy only vs. 150 having hysterectomy plus SNM). The SNM group had a longer operative time, but did not correlate with length of hospital stay and estimated blood loss. Overall severe complication rates were similar between groups (0.7% in the hysterectomy group vs. 1.3% in the hysterectomy plus SNM group; p = 0.561). No lymphatic-specific complication occurred. Overall, 12.6% of patients having SNM were diagnosed with disease harboring in their lymph nodes. Adjuvant therapy administration rate was similar between groups. Considering patients having SNM, 4% of patients received adjuvant therapy on the basis of nodal status alone; all the other patients received adjuvant therapy also on the basis of uterine risk factors. Five-year disease-free (p = 0.720) and overall (p = 0.632) survival was not influenced by surgical approach. Conclusions: Hysterectomy (with or without SNM) is a safe and effective method for managing EC patients. Potentially, these data support the omission of side specific lymphadenectomy in case of unsuccessful mapping. Further evidence is warranted in to confirm the role SNM in the era of molecular/genomic profiling.

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

High- and low-risk endometrial carcinoma (EC) differ in whether or not a lymphadenectomy is performed. We aimed to develop MRI-based radio-genomic models able to preoperatively assess lymph-vascular space invasion (LVSI) and discriminate between low- and high-risk EC according to the ESMO-ESGO-ESTRO 2020 guidelines, which include molecular risk classification proposed by “ProMisE”. This is a retrospective, multicentric study that included 64 women with EC who underwent 3T-MRI before a hysterectomy. Radiomics features were extracted from T2WI images and apparent diffusion coefficient maps (ADC) after manual segmentation of the gross tumor volume. We constructed a multiple logistic regression approach from the most relevant radiomic features to distinguish between low- and high-risk classes under the ESMO-ESGO-ESTRO 2020 guidelines. A similar approach was taken to assess LVSI. Model diagnostic performance was assessed via ROC curves, accuracy, sensitivity and specificity on training and test sets. The LVSI predictive model used a single feature from ADC as a predictor; the risk class model used two features as predictors from both ADC and T2WI. The low-risk predictive model showed an AUC of 0.74 with an accuracy, sensitivity, and specificity of 0.74, 0.76, 0.94; the LVSI model showed an AUC of 0.59 with an accuracy, sensitivity, and specificity of 0.60, 0.50, 0.61. MRI-based radio-genomic models are useful for preoperative EC risk stratification and may facilitate therapeutic management.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Endometrial cancer is the most common gynecological disease in developed countries. Although it is considered an indolent disease, advanced and recurrent endometrial carcinomas are characterized by poor prognosis. In the metastatic setting, after the failure of first-line platinum-based chemotherapy, patients have limited therapeutic options. However, endometrial cancer should not be considered as a single entity but as a group of heterogeneous diseases with specific genomic, molecular, and biological features by suggested the analysis of The Cancer Genome Atlas (TCGA). Accumulating data highlighted the effectiveness and safety of the adoption of immune checkpoint inhibitors (ICIs) for several types of solid tumors. In particular, immunotherapy showed promising results in MSI-H/dMMR solid tumors. Endometrial cancer is not an exception. Endometrial cancer has the highest prevalence of MSI across human cancer types, and approximately 30% of primary endometrial cancers are MSI-H/dMMR and 13% to 30% of recurrent endometrial cancers are MSI-H/dMMR. The preliminary results of the KEYNOTE-158, the Australian NCT03015129 and the GARNET trial strongly supported the adoption of ICIs as monotherapy in patients with advanced or recurrent endometrial cancer, after the failure of first-line treatments. Unfortunately, those impressive results are not achieved in patients with MMR proficient disease. Hence, other combinations were tested. In particular, the adoption of ICIs plus tyrosine kinase inhibitors (TKI) showed very compelling results. Recently, the updated results of the KEYNOTE-775 showed that pembrolizumab plus lenvatinib led to significantly longer progression-free and overall survival than chemotherapy among patients with advanced endometrial cancer, irrespective of MMR status. After EMA approval, pembrolizumab plus lenvatinib represents the new standard second-line treatment in endometrial cancer patients, regardless MMR status. Further studies are investigating the ro

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Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

Objective: To investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. Methods: This is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. Results: Charts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p < 0.001, log-rank test) and SNM (p = 0.038, log-rank test) correlated with a lower risk of developing surgery-related events. Independently, open abdominal surgery was associated with an increased risk of developing lymphatic morbidity (OR: 37.4 (95%CI: 4.38, 319.5); p = 0.001). Conclusion: The adoption of the laparoscopic approach and SNM technique were associated with lower 90-day complication rates than open surgery in high-risk endometrial cancer undergoing staging surgery.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the “copy number high” group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous

Objective: Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). Methods: This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. Results: Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p = 0.416, log-rank test) and overall survival (p = 0.940, log-rank test) than patients undergoing SLN alone. Conclusions: Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

Olaparib is currently approved in maintenance treatment of advanced ovarian cancer after response to first-line chemotherapy for breast related cancer antigens (BRCA) mutated patients. The use of this agent is based on data from SOLO1 study that observed a decreased risk of disease progression or death and a median progression-free survival about 36 months longer in case of therapy with olaparib. However, this trial recruited only patients with advanced stage ovarian cancer. The aim of this review is to retrace the available data in order to clarify the potential efficacy and feasibility of olaparib administration in newly diagnosed epithelial ovarian cancer also in early stages.

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Objective: Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. Methods: This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. Results: Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. Conclusion: Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

Surgery is the mainstay of treatment in the management of early-stage cervical cancer. Until the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, minimally invasive radical hysterectomy was the recommended approach to treat patients with early-stage disease. The results of the LACC trial questioned the adoption of minimally invasive surgery in cervical cancer. In comparison with the open approach, minimally invasive surgery correlated with worse disease-free and cancer-specific survival. Similarly, other retrospective studies highlighted this correlation, thus corroborating the results of the LACC trials. In the present review, we evaluated current evidence and further prospective of the adoption of minimally invasive radical hysterectomy in cervical cancer. Moreover, we sought to assess some unsolved issues regarding the role of minimally invasive surgery in early-stage cervical cancer patients.

Objective: Only 10–15% of serous borderline ovarian tumors (BOTs) with extra-ovarian disease have invasive implants, and conservative treatments have been rarely reported. The MITO14 is a multi-institutional retrospective study conducted with the aim of systematically collecting data from consecutive BOT patients. The present analysis reports the oncological and reproductive outcomes of women with serous BOT and invasive implants registered into the MITO14 database and conservatively treated between August 2002 and May 2019. Methods: Thirteen patients (FIGO2014 stage II–III serous BOT with invasive implants) were recruited. Primary and secondary endpoints were, respectively, recurrence and death rates, and pregnancy and live birth rates. Only patients undergoing fertility-sparing surgery (FSS) were included, while patients were excluded in case of: age > 45 years; second tumor(s) requiring therapy interfering with the treatment of BOT. Results: Median follow-up time from primary cytoreduction was 146 months (range 27–213 months). Eleven patients (84.6%) experienced at least one recurrence (median time to first relapse 17 months, range 4–190 months), all of these undergoing secondary surgery (FSS in 7). Five patients attempted to conceive: 3 achieved at least one pregnancy and 2 gave birth at least to a healthy child. At the end of the observation period, all patients were alive with no evidence of disease. Conclusions: Fertility-sparing treatment should be considered in a context of serous BOT with invasive implants. Despite the high rate of recurrence, FSS provides good chances of reproductive success without a negative impact on overall survival.

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.

Introduction: Diet may influence various aspects of human health. In fact, it is well known that diet can favour or not the development of various human pathologies, like diabetes, hypertension, and hypercholesterolaemia. Interestingly, diet has an influence in cancer development too (e.g., this relation has been studied for pancreatic, colonic, gastric, and breast cancers). Between the mechanisms that could explain this relation, there is epigenetic. In fact, thanks to epigenetic reprogramming, certain substances introduced with diet could affect gene expression, especially of those genes involved in cells' proliferation and growth. In recent years, some studies have been published about the role that diet could have on chemotherapy outcome. Especially, various studies have analysed the effects of fasting and ketogenic diet (KD) during chemotherapy. The aim of this study is to summarize scientific evidences about diet and its effects on chemotherapy on humans and to better understand if these approaches deserve to be further investigated and might be suitable and beneficial during cancer treatment. Materials and Methods: We performed an electronic literature search of the PubMed database, using the combination of following terms: "fasting"or "ketogenic"with "chemotherapy,""cancer treatment."We included studies on humans about fasting and KD during chemotherapy, excluding reviews, case series including <10 patients, studies conducted on animals or limited to radiotherapy treatment, and studies that were mostly about molecular mechanisms. Results/Discussion In our analysis we included 4 studies (1 randomized controlled trial, 1 retrospective study, and 2 prospective pilot studies) about KD and 4 studies (1 prospective cohort study, 1 case series report, and 2 randomized trials) about fasting during oncological treatments. Authors suggested an improvement of quality of life (QoL) and fatigue in patients under chemotherapy, especially in the 8 days after chemotherap

Purpose: Intravenous (IV) chemotherapy has been compared with intraperitoneal (IP) chemotherapy in randomized clinical trials in advanced ovarian cancer (OC). The aim of this meta-analysis was to evaluate efficacy and toxicity of IV and IP and identify differences in outcomes. Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and the proportion of patients with grade ≥2 acute toxicity. Results: Four randomized clinical trials representing 2461 patients were identified. The hazard ratio (HR) of PFS was 0.88 (95% CI 0.80–0.98; p = 0.01, I 2 = 24%) in favor of IP chemotherapy. IP chemotherapy was also associated with significant OS improvement compared with IV chemotherapy, with HR of 0.79 (95% CI 0.67–0.92; p = 0.003, I 2 = 0%). Globally, grade ≥2 toxicities were reduced with IV chemotherapy. Conclusion: This meta-analysis shows the superiority of IP chemotherapy over IV infusion in terms of clinical outcomes but toxicity rates. Its precise role in the management of advanced OC remains to be determined.

The aim of this study is to evaluate the sexual functionality before and after treatment of Bartholin’s gland diseases (BGD) with CO 2 laser and to compare our results to patients who underwent surgical cold knife and to a healthy control group (HCG). Consecutive patients (n = 15) affected by BG cyst or abscess who underwent CO 2 laser treatment were evaluated. Patients were asked to complete the Italian translation of the Female Sexual Functioning Index (FSFI) before and 4 weeks after treatment. Results after CO 2 laser were compared with two control groups: patients affected by BG cyst (n = 15) or abscess treated with surgical cold knife treatment and a HCG (n = 18). A statistically significant advantage of CO 2 laser versus cold knife treatment in terms of lubrication, pain and global score were recorded. Both the single scores of five domains and total score of FSFI were globally higher after any treatment compared to before (CO 2 and cold knife) of BGD. According to our data, CO 2 laser therapy is often well tolerated by patients and correlated with a favorable sexual health recovery.

Vulvodynia is a women's health problem that may affect as many as 15% of women who seek gynecological care, and yet little attention is given to this condition and it is frequently dismissed as psychosomatic. Thus, vulvodynia still remains a major health problem in Western countries, leading to significant morbidity and a reduced quality of life for many women. This condition carries large costs incurred as a result of both medical treatment and lost productivity. Vulvodynia is becoming a universal priority in the prevention, care, education, and research areas of pain and its consequences and it remains one of the poorly understood complex chronic pain syndromes, representing a multifactorial clinical syndrome of unexplained vulvar pain and sexual dysfunction.

Objectives In ovarian cancer (OC), approximately 70% will relapse within 12 months from diagnosis; inflammation plays an important role in cancer initiating and progression; thus, a combination of neutrophil-to-lymphocyte ratio (NLR) and fibrinogen (F-NLR) has been proposed as prognostic marker in several tumors. The aim of our study was to investigate the correlation between NLR, fibrinogen, and F-NLR and survival in OC population. Methods Patients with diagnosis of OC admitted to our institute between 2011 and 2016 were included. Data about pretreatment complete blood count were collected. Neutrophil-to-lymphocyte ratio was defined as the absolute neutrophil count divided by the absolute lymphocyte count; the F-NLR score was 0 for low NLR and fibrinogen, 1 for low NLR and high fibrinogen, or, conversely, 2 for both high markers. We correlated this index with progression-free survival. Results A total of 94 patients were enrolled. Median age at diagnosis was 55 (34-83) years; more than 80% of patients presented International Federation of Gynecology and Obstetrics stage III-IV at diagnosis, and 72 (77%) presented high-grade serous histology. Primary debulking surgery was performed in 57 women (60%), whereas 37 (40%) underwent interval debulking surgery. Mean serum NLR was 5.25 ± 5.37, and mean serum fibrinogen value was 4.19 ± 0.97 g/L. The median follow-up time was 27 months (range, 8-60 months). All patients with F-NLR value of 2 presented advanced disease compared with 64% of those with F-NLR of 0 (P < 0.031); these patients more frequently required neoadjuvant chemotherapy (P < 0.003) and more often had platinum-resistant disease (P < 0.022). Patients with high F-NLR presented worse progression-free survival than did patients with low F-NLR (12 vs 42 months, respectively, P = 0.023). Conclusions Combining NLR and fibrinogen levels could be used as a factor for prediction of prognosis and response to treatment in patients affected with OC.

Background: Hormone replacement therapy (HRT) has been tested in women with BRCA1 and BRCA2 mutations who underwent risk-reducing salpingo-oophorectomy (RRSO), but its effect on breast cancer (BC) risk has never been appraised using meta-analysis comparison. We performed the first meta-analysis aimed to clarify whether HRT after RRSO could negatively impact on BC risk in women carriers of BRCA1 and BRCA2 mutations. Methods and material: Pubmed and Scopus databases were searched to retrieve articles written in the English language. Trials comparing RRSO with or without HRT were identified and only those trials with available BC events were included. BC risk was the main endpoint. Results: Three trials with 1100 patients were included. There was not a significantly higher BC risk in BRCA1 and BRCA2 mutation carriers receiving HRT after RRSO (HR = 0.98; 95% CI 0.63–1.52). There was a slightly but not significantly, benefit in BC risk reduction in favor of estrogen alone HRT versus estrogen plus progesterone HRT formulation (OR = 0.53; 95% CI 0.25–1.15). Conclusion: HRT use after RRSO in BRCA 1 and BRCA2 mutation carries does not affect BC risk. Comparison of the different HRT types suggests that estrogen alone should be related to lowest BC risk.

Background: Cutaneous relapse from endometrial cancer is a rare event, and often is part of a plurimetastatic disease with poor prognosis. Besides palliative chemotherapy, no consensus is present in literature about the specific treatment of skin metastases, in particular in order to improve symptoms. Objectives: In this paper the authors present a case of multi-metastatic endometrial cancer patient with also cutaneous metastasis, treated with palliative systemic therapy and electrochemotherapy. In particular the authors will describe the clinical, dermatoscopic, and pathological features of cutaneous metastases and their management. A literature review on cutaneous metastasis from endometrial cancer is also presented. Materials and Methods: A PubMed research was made using the terms "endometrial carcinoma", "skin", "cutaneous", "metastasis", and "spread". Discussion: The present case of unusual localization of skin metastases from endometrial cancer is the second described in the literature. The other known cases of cutaneous metastasis from endometrial cancer are summarized and reviewed. Electrochemotherapy can be proposed as an effective and safe loco-regional therapy for skin metastases, especially in case of multiple lesions. To the present authors' knowledge this is the first case of cutaneous metastases from endometrial cancer treated with electrochemotherapy.

Endometrial cancer is one of the most frequent female cancers in women. Around 3-14% of endometrial cancers are diagnosed in young women wishing to preserve their fertility. Incidence of endometrial cancer in this age group is increasing, for which fertility-sparing therapy is increasingly need to be used to preserve quality of life in these patients. Progestin-based treatment is the most common type of fertility-sparing therapy. The aim of this review is to assess and analyse most recent findings concerning fertility-sparing progestin therapy for young women with primary and recurrent endometrial cancer. Diagnosis, treatment, follow-up, and oncologic and reproductive outcomes are investigated. Fertility-sparing progestin therapy is highly effective in selected young women with primary and recurrent endometrial cancer. Patients careful selection as to be mandatory to achieve the best outcomes without compromising survival. Because of the not negligible recurrence rate after conservative treatment, close surveillance is required and prophylactic hysterectomy has to be performed in patients completing family planning. Pregnancy outcomes are very encouraging, thanks to assisted reproductive technologies. Medroxyprogesterone acetate and megestrol acetate are the ideal progestins employed for fertility-sparing therapy, but further studies should be made to establish the optimal dose and treatment timing in this setting.

Introduction: The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of platinum resistant (PR) recurrent ovarian cancer (ROC) with particular attention to Phase III and ongoing trials. Areas covered: Since platinum free interval (PFI) represents the most important predictive factor for response to platinum re-treatment in ROC, non-platinum regimens are conventionally considered the most appropriate approaches. Impressive progress has been made in recent decades, resulting in the identification of most effective cytotoxic agents and in the development of new target strategies. However, the efficacy of most of these drugs for the treatment of PR disease is still limited. Expert opinion: The most favorable benefit for the treatment of PR disease, has been described by the AURELIA trial that showed a 3.3 months increase in progression free survival (PFS) when bevacizumab was combined with non-platinum single agent chemotherapy in bevacizumab-naïve patients. Nevertheless, the use of novel agents is associated to important costs for just little gains in survival. Thus, in our opinion the economic evaluation, such as the incorporation of quality of life into the clinical studies is crucial for the development of future trials for PR-ROC.

Background Vulvar cancer is a rare disease accounting for approximately 5% of female genital tract tumors worldwide. Currently surgery represents the mainstay alone or sometimes, in combination with chemo-radiotherapy, for locally advanced tumors and recurrent disease. However, significant physical and sexual impairment mostly due to anatomical distortion of external genitalia are a consequence of radical surgical treatment. Postoperative reconstruction after demolitive surgeries improves aesthetic and functional results, guarantees an adequate coverage of large tumors and assures safe surgical margin. The present study aimed to analyze feasibility and complication rates of fascio-cutaneous flap after excision for vulvovaginal malignancies. Methods PubMed (MEDLINE), Web of Science, and CINAHL were searched for records of validated vulvovaginal reconstructive techniques after demolitive surgery for vulvar cancer. All cohorts were rated for quality using a scoring method taking into account the design of the study, the sample size and quality of report of surgical data and complications. Results A total of 24 studies met all eligibility criteria for this systematic review. All the studies were realized between 1996 and 2015. The overall sample size was 443 patients. Two major group of flap according to type of movement were identified: Advancement Flap (V-Y Gluteal Fold Flap; Medial Thigh Flap) and Transpositional Flap (Lotus Petal Flap; Gluteal Thigh Flap; Gluteal Fold Flap and Anterolateral Thigh Flap). The overall complications rates reported for advancement (26.7% among 165 patients on 11 series) and transposition flaps (22.3% among 278 patients on 13 series) were comparable. Conclusions A tailored procedure, based on patients' characteristics, size and location of the defect is still the goal of a successful reconstructive surgery. Proper planning of the surgical procedures, knowledge of the different surgical options and technical skills are required in order to

Objective: The aim of this study was to assess the efficacy and tolerability of trabectedin given every 10 days as a single agent in recurrent ovarian cancer after 3 prior regimens. Method: Trabectedin 0.6 mg/m2 was administered as a 3-h infusion every 10 days on a 21-day cycle. The study population was compared to patients treated with weekly paclitaxel 80 mg/m2 intravenously on days 1, 8, 15, and 22 every 4 weeks. Results: We identified 34 patients previously submitted to at least 3 lines of chemotherapy who received single-agent trabectedin between 2010 and 2015. They were matched with a historical series of 34 patients who received weekly paclitaxel. No significant differences in response rate were found. Median progression-free survival was 4 months; 5 months in the trabectedin group and 4 months in the paclitaxel group. Overall survival (OS) was 13 months for the trabectedin group and 7 months for the paclitaxel group (p = 0.015). Patients who received platinum after trabectedin had a significant OS increase compared to those who received platinum after paclitaxel (18 vs. 9 months, respectively; p = 0.009). The most frequent drug-related grade 3/4 toxicities were reversible hepatic toxicity, neutropenia, anemia, thrombocytopenia, and gastrointestinal toxicity. Conclusion: Single-agent trabectedin every 10 days is an active treatment with a manageable toxicity profile in heavily pretreated advanced relapsed ovarian cancer patients.

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.

Objectives To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. Methods A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. Results A total of 103 EOC patients with a â ¥ 6 month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60 days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage Iâ II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed â ¥ 3 years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43 months, 95% CI 31â 58) compared to those with residual tumor (median OS: 33 months, 95% CI 28â 46; p < 0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. Conclusions This is the only large multicentre study published so far on TCS in EOC with â ¥ 6 month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

Introduction: Brenner tumor of the ovary represents an uncommon neoplasm. It constitutes about 1.5% of all ovarian tumors with a peak of incidence in the fifth decade. The vast majority of Brenner tumors is benign, while only 1% is malignant and associated with a poor prognosis. Diagnosis could be made only with histological examination, and surgery is the mainstay of treatment. Materials and methods: Here we present the case of a patient affected by a malignant Brenner tumor of the ovary, with metastases to brain, lung and liver and by a concomitant low grade endometroid adenocarcinoma of the uterus. A postoperative platinum based chemotherapy (CHT) was planned. The adjuvant treatment was discontinued for hematologic and liver toxicity and the patient died one month later due to a cardiorespiratory arrest. Results and discussion: For what concerns adjuvant therapy, it is supposed that chemotherapy is profitable in the survival of these patients, but what agents would really provide an objective response in the presence of metastatic disease is not standardized. Conclusion: Because of the rarity and the limited good quality research reports, multicentric prospective trials are needed to improve preoperative diagnosis of MBTs and investigate the best treatment.

Background: During the last decades many successful efforts have been made in order to increase life expectancy in ovarian cancer (OC) patients. However, just a few studies have investigated the impact of OC on quality of life (QoL) and sexual function in OC cases during treatment. Objective: The aim of this study was to evaluate the QoL and sexual function of OC patients during chemotherapy (CT). Patients and Methods: Forty-nine subjects were enrolled and filled in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OV28, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) questionnaires. The results were evaluated globally and consequently stratified into several groups: single surgery versus multiple surgeries, age ≤48 years versus >48 years, and first-line CT versus multiple lines of CT. Results: Menopause-related symptoms, body image and attitude toward the disease were significantly worse during first-line CT (p = 0.018, p = 0.029 and p = 0.006, respectively). Sexual outcomes resulted in better scores in younger patients in all questionnaires (FSFI: p = 0.001; FSDS: p = 0.048; specific EORTC QLQ-OV28 items: p = 0.022). Scores concerning body image, attitude toward the disease and CT-associated symptoms resulted worse in patients after the first surgery (p = 0.017, p = 0.002 and p = 0.012, respectively). Conclusion: Our study confirms that OC has a detrimental impact on QoL and intimacy, particularly in younger patients, during the first course of CT and after the first cytoreductive surgery.

Ovarian cancer is a most lethal gynecologic tumor. The mainstay treatment is cytoreductive surgery followed by platinumbased chemotherapy. However, a high percentage of patients recur, thus needing multiple treatments with a frequently poor prognosis. In the last two decades, research has focused on the potential of target therapies to improve the survival of patients affected by ovarian cancer. Bevacizumab is one of the most studied target therapies, and it is approved for first- and second-line treatment of advanced epithelial ovarian, fallopian tube, and primary peritoneal tumors. Despite its widespread use with favorable results, controversy regarding patient selection and the best schedule, dosage, and timing of bevacizumab still exists. This review summarizes the state of the art on the use of bevacizumab for ovarian cancer in front-line, recurrence, and neoadjuvant settings. This study focuses on the results of pivotal trials, emerging data, ongoing research, and still unanswered questions about the most adequate dosage of bevacizumab and its potential activity after disease progression or rechallenge in previously treated patients.

Objective: The aim of this study was to evaluate the feasibility and safety of type B radical hysterectomy (RH) in the management of patients affected by locally advanced cervical cancer with favorable prognostic factors (tumor diameter <40 mm, negative nodes, or lymphovascular space involvement) and clinical response to neoadjuvant chemotherapy (NACT). Methods: The data of women undergoing platinum-based NACT followed by RH plus bilateral systematic pelvic lymphadenectomy were collected. Patients undergoing type B RH (Group A) were compared with those undergoing type C RH (Group B); a propensity-matched comparison (1:1) was carried out to minimize selection biases. Postoperative complications were reported and 5-year survival outcomes were assessed using the Kaplan–Meier model. Results: Thirty-six node-negative patients undergoing type B RH (Group A) were compared with 36 propensity-matched patients undergoing type C RH (Group B). The bladder dysfunction rate was significantly lower in Group A compared with Group B (13.9 vs. 69.4 %; p < 0.0001), and no statistically significant difference in 5-year overall survival (OS) and disease-free survival (DFS) between groups was reported (OS 93.0 vs. 96.7 %, p = 0.42; DFS 88.6 and 85.5 %, p = 0.77). Conclusions: Type B RH after NACT in well-selected patients is a safe procedure that upholds the results of type C, reducing operative time and late postoperative morbidity, without detrimental effect on survival. Further prospective trials are warranted to confirm our results on a large scale.

Introduction: Endometrial cancer (EC) is the most common gynaecological cancer. Despite significant progress in the multimodality treatment approach, the prognosis remains poor for patients with advanced disease. Thus, there is the necessity of more effective strategies.The microtubule-stabilizing agent ixabepilone is the first drug in this new class of agents that has been approved for metastatic breast cancer treatment. Based on empiric data and on the clinical efficacy demonstrated in breast cancer, several clinical trials were proposed to define its role in EC.The aim of this review is to determine whether ixabepilone improved the clinical outcome in patients with locally advanced, recurrent or metastatic EC.Areas covered: Preclinical and clinical studies of ixabepilone in endometrial cancer were analyzed and discussed. Data were obtained by searching for English peer-reviewed articles on PubMed, phase I and II studies registered on clincaltrials.gov, and related abstracts recently presented at major international congresses.Expert opinion: Advanced or recurrent EC still represents a challenge and an unmet need in the panorama of gynaecological malignancies. Ixabepilones future therapeutic role in EC remains ill defined. Nevertheless, despite its limited efficacy in EC, clinicians treating gynaecological tumours should be aware of its main aspects.

Background: To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian cancer. Results: Bevacizumab was associated with significant improvement of PFS and OS compared with standard treatment with HRs of 0.53 (95% CI 0.44 - 0.63; p < 0.00001) and 0.87 (95% CI, 0.77 to 0.99; p = 0.03), respectively. Bevacizumab increased the incidence of G3/G4 hypertension (RR 19.01, 95% CI 7.77 - 46.55; p < 0.00001), proteinuria (RR 17.31, 95% CI 5.42 - 55.25; p < 0.00001), arterial thromboembolic events (ATE) (RR 4.99, 95% CI 1.29 - 19.27; p = 0.02) and bleeding (RR 3.14, 95% CI 1.35 - 7.32; p = 0.008). Materials and Methods: Three randomized phase III trials representing 1502 patients were identified. Pooled hazard ratio (HR), odd ratio (OR), risk ratio (RR) with 95% confidence interval (CI) were calculated using fixed or random effects model. Conclusions: Adding bevacizumab to standard chemotherapy improved ORR, PFS and OS, and it had a higher, but manageable, incidence of toxicities graded 3 to 4.

Background: To assess the clinical efficacy and prognostic outcome of neoadjuvant chemotherapy (NACT) plus radical surgery (RS) as front line treatment in patients with FIGO stage III cervical cancer (CC). Methods: In this retrospective study, 52 FIGO stage III CC patients treated from 2005 to 2015 were included. All patients received platinum-based chemotherapy. Patients reporting clinical response or stable disease after NACT underwent to RS and bilateral systematic pelvic lymphadenectomy with or without aortic lymphadenectomy or anterior exenteration. Patients with progressive disease underwent palliative management. Results: After NACT, clinical response was observed in 23 patients (44 %): 4 (7.7 %) complete and 19 (36.5 %) partial responses, respectively. Also, 15 patients (28.8 %) had stable disease and 14 (26.9 %) showed disease progression. RS was performed in 40 cases (76.9 %): respectively, 28 (70 %) and 7 (17.5 %) underwent type C2 and D radical hysterectomy, while 5 patients (12.5 %) underwent anterior exenteration. At pathological evaluation, 23 patients (57.5 %) had positive pelvic nodes and 4 (10 %) also had positive aortic nodes. In 6 patients (15 %), moderate-severe (G3–G5) complications occurred. A total of 27 patients (67.5 %) received adjuvant therapy: 16 patients (40 %) received chemotherapy, 10 (25 %) received chemoradiation and 1 (2.5 %) received radiotherapy. Disease relapse occurred in 24 cases (60 %). After follow-up period of 60 months, the median OS of the whole population included was 37 months. Among the 40 surgically treated patients, median OS and DFS were 48 and 23 months, respectively. Conclusions: NACT plus RS represent a valid alternative with acceptable morbidity for patients with stage III CC.