Polycystic Ovary Syndrome and Alteration of Vocal Function: A Systematic Review and Meta-Analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common hormonal disorder among young women, correlated with hyperandrogenism. Among the symptoms of PCOS, vocal alterations are quite unknown. Dysphonia may be related to hyperandrogenism, and there is no consensus about its prevalence and the severity of vocal disorders, which can cause noticeable discomfort. METHODS: A systematic review of the literature was conducted. Four studies on PCOS that evaluated the phonatory system were included for a total of 174 patients (96 PCOS, 78 controls), and a meta-analysis on comparable data was performed. RESULTS: Four studies evaluated parameters related to vocal symptomatology, altered audiometric examination, and findings at the laryngoscopy in patients affected by PCOS versus controls. Although the individual studies showed increased incidence of alterations and a tendency to develop speech fatigue in women with PCOS, when the results of studies were pulled in meta-analysis, the overall difference was not statistically significant. The studies themselves were very different from each other; therefore, it is hard to draw any firm conclusions. DISCUSSION: The aim of this study was to assess the prevalence of vocal alterations, the correlation with hyperandrogenism, the quality of life, and the voice changes after starting a therapy for PCOS. The present meta-analysis failed to find any difference in terms of PCOS and control cohort. However, the lack of high-quality studies makes it difficult to draw firm conclusions. New and larger studies or big population program data are therefore warranted.

Spotlight on Compounded Bioidentical Hormones.

BACKGROUND: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. OBJECTIVES: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. METHODS: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, PubMed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. OUTCOMES: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. CONCLUSION AND OUTLOOK: These formulations might provide effective options to best tailor therapies to each patient.

The performance of the node reporting and data system 1.0 (Node-RADS) and DWI-MRI in staging patients with cervical carcinoma according to the new FIGO classification (2018).

PURPOSE: To evaluate the diagnostic accuracy of the Node-RADS score and the utility of apparent diffusion coefficient (ADC) values in predicting metastatic lymph nodes (LNs) involvement in cervical cancer (CC) patients using magnetic resonance imaging (MRI). The applicability of the Node RADS score across three readers with different years of experience in pelvic imaging was also assessed. MATERIAL AND METHODS: Among 140 patients, 68 underwent staging MRI, neoadjuvant chemotherapy and radical surgery, forming the study cohort. Node-RADS scores of the main pelvic stations were retrospectively determined to assess LN metastatic likelihood and compared with the histological findings. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of LNs classified as Node-RADS ≥ 3 were measured and compared with histological reports, considered as gold standard. RESULTS: Sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and accuracy were calculated for different Node-RADS thresholds. Node RADS ≥ 3 showed a sensitivity of 92.8% and specificity of 72.5%. Node RADS ≥ 4 yielded a sensitivity of 71.4% and specificity of 100%, while Node RADS 5 yielded 42.9% and 100%, respectively. The diagnostic performance of mean ADC, cADC and rADC values from 78 LNs with Node-RADS score ≥ 3 was assessed, with ADC demonstrating the highest area under the curve (AUC 0.820), compared to cADC and rADC values. CONCLUSION: The Node-RADS score provides a standardized LNs assessment, enhancing diagnostic accuracy in CC patients. Its ease of use and high inter-observer concordance support its clinical utility. ADC measurement of LNs shows promise as an additional tool for optimizing patient diagnostic evaluation.

The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma.

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 role of ICIs and TKIs in the first line and are testing new combinations (e.g. ICIs plus PARP inhibitors).

Ten-year outcomes following laparoscopic and open abdominal radical hysterectomy for "low-risk" early-stage cervical cancer: A propensity-score based analysis.

OBJECTIVE: Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. METHODS: This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. RESULTS: Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100-310) vs. 184 (range, 150-240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100-1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). CONCLUSIONS: Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients.

Magnetic resonance imaging-radiomics in endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Endometrial carcinoma is the most common gynecological tumor in developed countries. Clinicopathological factors and molecular subtypes are used to stratify the risk of recurrence and to tailor adjuvant treatment. The present study aimed to assess the role of radiomics analysis in pre-operatively predicting molecular or clinicopathological prognostic factors in patients with endometrial carcinoma. METHODS: Literature was searched for publications reporting radiomics analysis in assessing diagnostic performance of MRI for different outcomes. Diagnostic accuracy performance of risk prediction models was pooled using the metandi command in Stata. RESULTS: A search of MEDLINE (PubMed) resulted in 153 relevant articles. Fifteen articles met the inclusion criteria, for a total of 3608 patients. MRI showed pooled sensitivity and specificity 0.785 and 0.814, respectively, in predicting high-grade endometrial carcinoma, deep myometrial invasion (pooled sensitivity and specificity 0.743 and 0.816, respectively), lymphovascular space invasion (pooled sensitivity and specificity 0.656 and 0.753, respectively), and nodal metastasis (pooled sensitivity and specificity 0.831 and 0.736, respectively). CONCLUSIONS: Pre-operative MRI-radiomics analyses in patients with endometrial carcinoma is a good predictor of tumor grading, deep myometrial invasion, lymphovascular space invasion, and nodal metastasis.

Endometrial carcinosarcoma.

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.

Gestational choriocarcinoma.

Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.

Fertility-sparing treatment for serous borderline ovarian tumors with extra-ovarian invasive implants: Analysis from the MITO14 study database.

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.

Evaluating long-term outcomes of three approaches to retroperitoneal staging in endometrial cancer.

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.

Clear cell carcinoma of the endometrium.

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.

Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer.

BACKGROUND: Cervical cancer survivors report the worst quality of life (QoL) among all cancer survivors and this is mainly due to their younger age and the long-term treatment sequelae. AIM: The purpose of this study is to assess the long-term QoL and sexual function of locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemotherapy (NACT) and radical hysterectomy (RH) instead of the standard chemoradiotherapy. METHODS: This is a retrospective case-control study including LACC patients (FIGO stage IIB-IVA) treated with the NACT-RH strategy and a control group of healthy women undergoing hysterectomy for uterine fibromatosis in the same period. OUTCOMES: Main outcome measures were the EORTC QLQ-C30 and EORTC QLQ-CX24 for quality of life and Female Sexual Function Index (FSFI) for sexual function. RESULTS: Overall, 96 patients were included: 48 LACC and 48 controls. The mean age at diagnosis was 45.5 ± 9.0 and 47.0 ± 7.8, respectively (P = .38). Compared to controls, LACC patients reported lower mean scores for the global health status (69.4 ± 22.6 vs 81.2 ± 24.3; Mean Difference (MD): -11.80 [95% CI: -21.19, -2.41]; P = .016), QLQ-C30 functional scale (80.1 ± 22.6 vs 92.4 ± 14.9; MD: -12.30 [95% CI: -19.96, -4.64]; P = .002), QLQ-Cx24 functional scale (55.5 ± 25.0 vs 80.4 ± 22.4; MD: -24.00 [95% CI: -34.40, -15.40]; P < .001), and the total FSFI (19.3 ± 9.6 vs 26.2 ± 9.9; MD: -6.90 [95% CI: -10.80, -3.00]; P < .001). On the other hand, LACC patients reported higher mean scores on the QLQ-C30 (16.9 ± 22.1 vs 8.4 ± 16.6; MD: 8.50 [95% CI: 0.68, 16.32]; P = .03) and QLQ-CX24 (26.0 ± 28.8 vs 15.0 ± 11.7; MD: 11.00 [95% CI: -2.21, 19.79]; P = .01) symptoms scales. CLINICAL IMPLICATIONS: The confirmed poor quality of life even in surgically treated LACC survivors underlines the importance of tailoring parametrectomy based on lymph node status and developing personalized strategies. STRENGTHS AND LIMITATIONS: The study assessed the long-term QoL and sexual function in the specific subpopulation of LACC patients treated with NACT-RH. Main limitations include the small sample size and the retrospective design. CONCLUSION: LACC long-term survivors treated with NACT-RH experience poor QoL and sexual dysfunction. Palaia I, Santangelo G, Caruso G, et al. Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer. J Sex Med 2022;19:613-619.

Age-Adjusted Charlson Comorbidity Index Predicts Survival in Endometrial Cancer Patients.

OBJECTIVE: Comorbidity scores are increasingly used to reduce potential confounding in oncologic research. This is of paramount importance in endometrial cancer (EC) since it is characterized by quite indolent behavior. Here, we aim to evaluate the impact of various comorbidities and concurrent medications used on survival outcomes, adopting the age-adjusted Charlson comorbidity index (A-CCI). DESIGN: This is an observational study. Charts of 257 EC patients were retrieved. METHODS: We retrospectively evaluated data of patients who underwent surgical treatment for EC. A-CCI was calculated by summing the weighted comorbidities and age of each patient. A binomial value was assigned to different comorbidities and different drugs. Oncologic outcomes were evaluated using Cox proportional hazard models adjusted for age. RESULTS: A-CCI ≥3 correlated with more aggressive tumor features (47.6% vs. 26.8%, p = 0.001), higher risk of recurrence (29.7% vs. 11.6%, p = 0.001), death (20.7% vs. 7.1%, p = 0.002), and death due to disease (16.6% vs. 6.3%, p = 0.012). Considering comorbidities and drugs at parsimonious multivariable analysis model: cardiac disease, liver disease, and proton pump inhibitors (PPIs) use were independent predictors of disease-free survival. Cardiac disease, autoimmune disease, and PPIs use were independent predictors of overall survival. Diabetes was the only independent predictor for cause-specific survival. LIMITATIONS: The major limitation of the present study is its retrospective nature and the relatively small sample size that limit the possibility to have firm conclusions. CONCLUSION: Patients with EC are characterized by a high burden of comorbidities. Comorbidities are associated directly with survival outcomes. Further attention is needed to improve the active management of comorbidities soon after EC treatments. Interventional studies are needed to improve patients' outcomes.

Correlation between preoperative imaging biomarkers and histological prognostic factors in endometrial cancer: A prospective study.

PURPOSE: We compared transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration, cervical involvement, and for measuring tumor volume in endometrial cancer patients. We also correlated tumor volume to worse histological prognostic factors. METHODS: We recruited women with a histological diagnosis of endometrial cancer between March 2019 and March 2021. Inclusion criteria were: age ≥ 18 years, written informed consent, biopsy-proven endometrial cancer, absence of previous neoadjuvant chemo- or radiotherapy treatment, patient suitable for primary surgery. Exclusion criteria were: advanced disease stage and other coexisting malignant tumors. TVUS and MRI were used, in the absence of any contraindication. We compared the preoperative imaging results with final histopathology. RESULTS: The accuracy of TVUS and MRI in evaluating myometrial infiltration, cervical invasion and tumor volume were comparable. A tumor volume ≥2 ml showed a positive correlation with worse histological prognostic factors, such as high tumor grade, diffuse lymphvascular space involvement (LVSI) and deep myometrial invasion (p < 0.05). CONCLUSION: TVUS should be used as first-line imaging modality, being more available, cost-effective, and more acceptable by patients. A careful local staging of endometrial cancer patients before surgery is fundamental in order to improve tailored treatment and minimize costs.

Hepatobiliary Disease Resection in Patients with Advanced Epithelial Ovarian Cancer: Prognostic Role and Optimal Cytoreduction.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety in terms of prognostic significance and perioperative morbidity and mortality of cytoreduction in patients affected by advance ovarian cancer and hepato-biliary metastasis. METHODS: Patients with a least one hepatobiliary metastasis who have undergone surgical treatment with curative intent of were considered for the study. Perioperative complications were evaluated and graded with Accordion severity Classification. Five-year PFS and OS were estimated using the Kaplan-Meier curve. RESULTS: Sixty-seven (20.9%) patients had at least one metastasis to the liver, biliary tract, or porta hepatis. Forty-four (65.7%) and 23 (34.3%) patients underwent respectively high and intermediate complexity surgery according. Complete cytoreduction was achieved in 48 (71.6%) patients with hepato-biliary disease. In two patients (2.9%) severe complications related to hepatobiliary surgery were reported. The median PFS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) was 19 months [95% confidence interval (CI) 16.2-21.8] and 8 months (95% CI 6.1-9.9). The median OS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) 45 months (95% CI 21.2-68.8 months) and 23 months (95% CI 13.9-32.03). CONCLUSIONS: Hepatobiliary involvement is often associated with high tumor load and could require high complex multivisceral surgery. In selected patients complete cytoreduction could offer survival benefits. Morbidity related to hepatobiliary procedures is acceptable. Careful evaluation of patients and multidisciplinary approach in referral centers is mandatory.

Preoperative frailty assessment in patients undergoing gynecologic oncology surgery: A systematic review.

OBJECTIVE: The aim of the present article was to discuss currently available evidence on the impact of frailty assessment on adverse postoperative outcomes and survival in patients undergoing surgery for gynecological cancer. METHODS: Systematic search of Medline (PubMed) and Embase databases until September 30, 2020. Key inclusion criteria were: (1) randomized or observational studies; (2) patients undergoing non-emergent surgery for gynecological malignancies; (3) preoperative frailty assessment. RESULTS: Through the process of evidence acquisition, twelve studies including 85,672 patients were selected and six tools were evaluable: 30-item frailty index, 40-item frailty index, modified frailty index (mFI), John Hopkins Adjusted Clinical Groups index, Fried frailty criteria, Driver's tool. The prevalence of frailty varied roughly from 6.1% to 60% across different series included. The mFI was the most adopted and predictive instrument. Pooled results underlined that frail patients were more likely to develop 30-day postoperative complications (OR:4.16; 95%CI 1.49-11.65; p:0.007), non-home discharge (OR:4.41; 95%CI: 4.09-4.76; p < 0.001), ICU admission (OR:3.99;3.76-4.24; p < 0.001) than the non-frail counterpart. Additionally, frail patients experienced worse oncologic outcomes (disease-free and overall survivals) than non-frail patients. CONCLUSION: The present systematic review demonstrated that preoperative frailty assessment among gynecologic oncology patients is essential to predict adverse outcomes and tailor a personalized treatment. The mFI appeared as the most used and feasible tool in daily practice, suggesting that tailored therapeutic strategies should be considered for patients with 3 or more frailty-defining items.

Spotlight on the role of human papillomavirus vaccines.

In high income setting, the massive implementation of screening programs has reduced the incidence of cervical cancer, dramatically. However, cervical cancer still remains a major health concern, being one of the most common cause of death for cancer among women. The adoption of primary prevention through vaccination against HPV aims to reduce the prevalence of HPV-related lesions and cervical cancer. Accumulating data highlighted the cost-effectiveness of introducing HPV vaccination for adolescent and young adults. In the present review, we critically evaluated the role of vaccination against HPV, focusing much more on the role of vaccination in specific cluster of subjects (eg, post-treatment and older adults). Additionally, we evaluated the available evidence on the role of vaccination in HIV-positive subjects and in women receiving solid organs transplantation. We observed that although vaccination might be considered effective in those cluster of subjects; further evidence is needed to assess the cost-effectiveness of vaccination in these settings.

Modified fragility index and surgical complexity score are able to predict postoperative morbidity and mortality after cytoreductive surgery for advanced ovarian cancer.

OBJECTIVE: The aim of this study was to assess the impact of surgical complexity on postoperative complications and mortality, according to patient's frailty (mFI) following surgery for ovarian cancer. METHODS: Patients undergoing cytoreductive surgery for ovarian cancer from 2008 to 2018 were identified from our database. A surgical complexity score from 1 to 3 was used to assess the extent of surgery (simple to complex, respectively). mFI with 11 variables, based on mapping the Canadian Study of Health and Aging Frailty Index to the NSQIP comorbidities was evaluated. Data were analyzed using Fisher exact test, independent sample t-test, and logistic regression. RESULTS: Of 263 patients identified, 33% reported at least one postoperative complication and 6% had severe complications. BMI ≥ 30 (p = 0.04) increased mFI (p = 0.04) and high-complexity surgery (p < 0.001) were independent predictors of severe complications (G3-G5). Patients with high frailty index score (mFI ≥ 3) who underwent intermediate or high-complexity surgery were at higher risk of severe complications ranging from 29.4% to 50. CONCLUSIONS: The combined evaluation of mFI and surgical complexity expected may identify patients at higher risk for severe morbidity allowing to stratify patients who are less likely to tolerate a surgical extensive treatment.

Fertility-sparing treatment in advanced-stage serous borderline ovarian tumors. An analysis from the MITO14 study database.

OBJECTIVES: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs). METHODS: A multi-institutional retrospective study was conducted within the MITO Group. RESULTS: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. CONCLUSIONS: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.

Sentinel node mapping vs. sentinel node mapping plus back-up lymphadenectomy in high-risk endometrial cancer patients: Results from a multi-institutional study.

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.