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.

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.

Targeting cervical cancer: Is there a role for poly (ADP-ribose) polymerase inhibition?

Patients with metastatic and recurrent cervical cancer (CC) have a poor prognosis with limited palliative treatment options. Increasing understanding of the cellular aberrations inherent to cancer cells has allowed the development of therapies to target biological pathways, an important step toward the individualization of cancer therapy. The poly (ADP-ribose) polymerase (PARP) family of enzymes is important in several DNA repair pathways. Drugs that inhibit these PARP enzymes have been investigated in many types of cancer and their application in the treatment of gynecologic malignancies has rapidly evolved. Although the majority of data for PARPi in gynecologic malignancies has been specifically regarding ovarian cancer, their role in the treatment of uterine and CC is currently being investigated. This review will examine PARP inhibitors in CC, summarizes the critical clinical trials of PARP inhibitors that have been completed, provides an overview of the on-going trials, presents the confirmed conclusions and notes the issues that need to be addressed in future studies.

Intraperitoneal Chemotherapy: A Strategy for the Treatment of Refractory Ascites in Recurrent Endometrial Cancer Patients - Three Case Reports and Review of the Literature.

BACKGROUND: Endometrial cancer currently represents the most frequent gynecologic malignancy in Western countries, and the seventh most common cancer in women. For advanced-stage disease, the recurrence risk is high, and the site of the relapse is heterogeneous with localized or spread peritoneal disease. There are few therapeutic strategies, and the quality of life is poor. CASES PRESENTATION: We present 3 cases of peritoneal-spread recurrences of endometrial cancer in patients with advanced stage at diagnosis. The patients had been subjected to multiple lines of chemotherapy including re-challenging with platinum regimens, pegylated liposomal doxorubicin, and taxane, with progression of disease. These patients came to us with abdominal distension, dyspnea, elevated CA 125, and presence of ascites. After paracentesis with a single administration of intraperitoneal chemotherapy based on carboplatin, all 3 patients showed improvement in their quality of life and breathing as well as reduction of fatigue and anorexia. No complications occurred. CONCLUSION: Although only 3 cases are reported, the exceptional results and the absence of side effects observed strongly warrant future trials to investigate the role intraperitoneal chemotherapy can have both as palliative treatment of refractory ascites and as salvage therapy in advanced endometrial cancer.

Evaluation of Parametrial Status in Locally Advanced Cervical Cancer Patients after Neoadjuvant Chemotherapy: A Prospective Study on Diagnostic Accuracy of Three-Dimensional Transvaginal Ultrasound.

OBJECTIVES: To analyze the diagnostic accuracy of two-dimensional (2D) and three-dimensional transvaginal ultrasound (3D TV-US) for evaluation of parametrial status in locally advanced cervical cancer patients after neoadjuvant chemotherapy (NACT), using histology as the gold standard. METHODS: Consecutive patients with histologically confirmed cervical cancer were staged according to FIGO (International Federation of Gynaecology and Obstetrics) criteria. All IB2-IIIB FIGO stage patients were examined by 2D and 3D TV-US and magnetic resonance imaging (MRI) at the diagnosis time (T0) and after NACT. At T0, the US evaluation of parametrial involvement was compared to MRI before treatment. The results of US and MRI examinations of parametrial status after NACT were compared with the histological specimen. RESULTS: We enroled 51 consecutive patients in the study. Before chemotherapy, clinical examination under anaesthesia identified parametrial involvement in 48 patients, ultrasonography in 46 patients, and MRI in 49 patients. The agreement between US and MRI was 94%. The sensitivity of US for parametrial status was 93.8%, with a positive predictive value of 97.8%, using MRI as the standard. The correlation between US and MRI was statistically significant (p = 0). After chemotherapy, histological examination of surgical specimens identified parametrial involvement in 3 patients. Ultrasonography correctly identified those cases with parametrial infiltration, recording a sensitivity of 100%, specificity of 90.9%, positive predictive value of 50%, and negative predictive value of 100%. The MRI had a sensitivity of 100%, specificity of 45.5%, positive predictive value of 14.3%, and negative predictive value of 100%, respectively. The concordance in the identification of the presence/absence of infiltration between US and MRI with histology was 90% (p = 0.001) and 61%, respectively, after chemotherapy treatment. Particularly, in defining the degree of infiltration, the agreement between US and MRI with histology was 90 and 58%, respectively. CONCLUSION: In locally advanced cervical cancer patients, 2D/3D TV-US can be considered accurate in the evaluation of parametrial infiltration to assess the response to NACT. It could be included as a diagnostic method in the preoperative work-up of cervical cancer.

Does Hormone Replacement Therapy Impact the Prognosis in Endometrial Cancer Survivors? A Systematic Review.

PURPOSE: The objective of this study was to evaluate the impact of hormone replacement therapy (HRT) on the prognosis in endometrial cancer (EC) survivors. METHODS: The research was conducted using the following electronic databases: MEDLINE (PubMed), Web of Science, ClinicalTrial.gov, and Cochrane Library. We performed a review of studies published from January 1986 to January 2019. We selected studies that included EC patients submitted to surgery with curative intent and postoperative use of HRT. RESULT: Seven of 1,332 abstracts considered were eligible: 4 retrospective series, 1 prospective study, 1 randomized controlled trial, and 1 population study. Globally in the observed studies there was not a significant increase in the recurrence rate, measured by the relative risk, in the EC survivors using HRT compared with the controls in tumour stages I and II. The bias was that HRT was prescribed only to low-risk patients, who were young and had a low stage of disease. CONCLUSION: This systematic review shows that HRT use had no negative effect on prognosis in EC survivors in tumour stages I and II.

The EOLO (End-of-Life Ovarian Cancer) Study: Approach to Ovarian Cancer Patients at the End of Life.

BACKGROUND: Chemotherapy at the end of life is a complex and challenging problem in medical oncology. Patients affected by ovarian cancer (OC) often experience a chronicization and slow progression of their disease, and chemotherapy is proposed until the end of life. METHODS: We retrospectively analyzed data from patients affected by OC treated at our department and having died in the period between 2007 and 2017 and evaluated the frequency of antineoplastic treatments until the end of life, the chemotherapy-related toxicity, mortality, and the most frequent palliative care measure adopted. RESULTS: A total of 110 OC deaths, after a median overall patient survival of 52.8 months (range 4-232), were analyzed. 77.3% of the patients presented with FIGO stage IIIC OC at diagnosis and 12.7% with FIGO stage IV OC. 89% of the histological types were serous papillary. The median age was 55 years (range 31-82) at diagnosis and 60 years (range 33-84) at death. Of the 110 patients analyzed, 85 (77%) had undergone chemotherapy over the last 3 months of life and 38% had chemotherapy even during the last month of life. The overwhelming majority of patients (81%) needed supportive therapies. Despite the treatments received, the majority of the patients died at home, 19% died in hospital, and only 4.5% died in hospice. The quality of life of these patients decreased dramatically in the last 30 days, but best supportive care improved the symptoms. CONCLUSIONS: End-of-life chemotherapy for OC patients is a thorny problem. More studies and a multidisciplinary approach are needed to better treat these patients.

Implementation of the Four-Category Classification of Cesarean Section Urgency in Clinical Practice. A Prospective Study.

PURPOSE: This study is aimed at investigating the clinical efficacy of the 4-category classification of urgent cesarean section. METHODS: Women giving birth from September 2012 to December 2014 were prospectively investigated. Urgency C-section categories were color-coded: red - maternal/fetal life threat; yellow - maternal/fetal compromise, not life-threatening; and green - early delivery necessary. Results were audited. RESULTS: A total of 4,754 women gave birth in the period considered, 1,313 (27.6%) with C-section of which 867 were urgent. The code was red in 0.98% of women, and 91.5% of newborns were delivered ≤30'; yellow in 5.1%; and green in 11.7%. The mean decision-to-delivery interval (DDI) ± SD was 19.6 ± 9.5 min, 36.6 ± 15.3 (p < 0.01), and 80.3 ± 52.8 (p < 0.01), respectively; and mean umbilical pH was 7.24 ± 0.10, 7.29 ± 0.08 (p < 0.05), and 7.33 ± 0.04 (p < 0.01) in the red, yellow, and green groups, respectively. Two (4.2%) red and 4 (2.2%) yellow newborns were acidotic. Mean DDI ± SD decreased from 21.7 ± 9.7 min in the period September 2012 to February 2013 to 17.4 ± 9.7 min in the period February to December 2014 (p = NS). CONCLUSIONS: Four-category classification led to achieving the target time in >90% of category 1 emergency C-sections, and stratified newborns with significantly different acidosis levels.

Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

Novel Insights into Molecular Mechanisms of Endometrial Diseases.

Endometrial diseases are the most common gynecological pathologies in Western Countries [...].

Vulvodynia: A practical guide in treatment strategies.

Vulvodynia is a debilitating condition characterized by chronic vulvar pain, with a detrimental impact on the patient's overall quality of life. Its etiology is multifactorial, but still in the process of being clearly outlined. Vulvodynia is not a single entity. It is a heterogeneous condition characterized by multiple triggers, making it challenging to define a reference standard for its treatment. In this manuscript we selected all articles including the following key criteria: "vulvodynia". The primary outcomes observed included the resolution of chronic pelvic pain, dyspareunia and sexual satisfaction, psychological well-being, and overall quality of life. Most pharmacologic treatments require further evidence to be recommended. On the other hand, non-pharmacologic approaches such as psychotherapy, physical therapy, and surgery have received stronger support. This review summarizes pros and cons of adopting available treatments. Multimodal approaches should be introduced to improve patient outcomes. Further investigations are warranted to improve patients' quality of life.

The contribution of the 1H-MRS lipid signal to cervical cancer prognosis: a preliminary study.

BACKGROUND: The aim of this study was to investigate the role of the lipid peak derived from 1H magnetic resonance (MR) spectroscopy in assessing cervical cancer prognosis, particularly in assessing response to neoadjuvant chemotherapy (NACT) of locally advanced cervical cancer (LACC). METHODS: We enrolled 17 patients with histologically proven cervical cancer who underwent 3-T MR imaging at baseline. In addition to conventional imaging sequences for pelvic assessment, the protocol included a single-voxel point-resolved spectroscopy (PRESS) sequence, with repetition time of 1,500 ms and echo times of 28 and 144 ms. Spectra were analysed using the LCModel fitting routine, thus extracting multiple metabolites, including lipids (Lip) and total choline (tCho). Patients with LACC were treated with NACT and reassessed by MRI at term. Based on tumour volume reduction, patients were classified as good responder (GR; tumour volume reduction > 50%) and poor responder or nonresponder (PR-or-NR; tumour volume reduction ≤ 50%). RESULTS: Of 17 patients, 11 were LACC. Of these 11, only 6 had both completed NACT and had good-quality 1H-MR spectra; 3 GR and 3 PR-or-NR. A significant difference in lipid values was observed in the two groups of patients, particularly with higher Lip values and higher Lip/tCho ratio in PR-NR patients (p =0.040). A significant difference was also observed in choline distribution (tCho), with higher values in GR patients (p = 0.040). CONCLUSIONS: Assessment of lipid peak at 1H-MR spectroscopy could be an additional quantitative parameter in predicting the response to NACT in patients with LACC.

Assessing the role of low volume disease in endometrial cancer.

The role of retroperitoneal staging in endometrial cancer is still unclear. Although the prognostic value of lymphadenectomy has been demonstrated no data support the therapeutic value of nodal dissection. Sentinel node mapping represents an evolution of lymphadenectomy. Sentinel node mapping allows a more accurate identification of low-volume diseases (i.e., micrometastasis and isolated tumor cells) that are not always detectable via conventional histopathological evaluation. Adjuvant therapy might play a role in patients with low-volume disease. However, the presence of isolated tumor cells alone seems to not impact outcomes of endometrioid endometrial cancer patients. Hence, the choice to deliver adjuvant therapies has to be tailored based on uterine factors only. The introduction of molecular and genomic profiling would be useful in selecting appropriate surgical and adjuvant treatments. The molecular-integrated risk profile should be integrated in clinical practice to overcome the need of retroperitoneal staging (in case of non-bulky nodes) in patients at low risk.

Intravoxel Incoherent Motion (IVIM) MR Quantification in Locally Advanced Cervical Cancer (LACC): Preliminary Study on Assessment of Tumor Aggressiveness and Response to Neoadjuvant Chemotherapy.

The aim of this study was to determine whether quantitative parameters obtained from intravoxel incoherent motion (IVIM) model at baseline magnetic resonance imaging (MRI) correlate with histological parameters and response to neoadjuvant chemotherapy in patients with locally advanced cervical cancer (LACC). METHODS: Twenty patients with biopsy-proven cervical cancer, staged as LACC on baseline MRI and addressed for neoadjuvant chemotherapy were enrolled. At treatment completion, tumor response was assessed with a follow-up MRI evaluated using the revised response evaluation criteria in solid tumors (RECIST; version 1.1), and patients were considered good responders (GR) if they had complete response or partial remission, and poor responders/non-responders (PR/NR) if they had stable or progressive disease. MRI protocol included conventional diffusion-weighted imaging (DWI; b = 0 and 1000 s/mm2) and IVIM acquisition using eight b-values (range: 0-1500 s/mm2). MR-images were analyzed using a dedicated software to obtain quantitative parameters: diffusion (D), pseudo-diffusion (D*), and perfusion fraction (fp) from the IVIM model; apparent diffusion coefficient (ADC) from conventional DWI. Histologic subtype, grading, and tumor-infiltrating lymphocytes (TILs) were assessed in each LACC. RESULTS: D showed significantly higher values in GR patients (p = 0.001) and in moderate/high TILs (p = 0.018). Fp showed significantly higher values in squamous cell tumors (p = 0.006). CONCLUSIONS: D extracted from the IVIM model could represent a promising tool to identify tumor aggressiveness and predict response to therapy.

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

Value of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and Sentinel Lymph Node Biopsy in Endometrial Cancer Patients: A Prospective Study.

The aim of this study is to define the role of preoperative positron emission tomography/computed tomography (PET/CT) scan and sentinel lymph node (SLN) biopsy for nodal metastasis detection in Endometrial Cancer (EC) patients. From January 2014 to August 2016 patients affected by EC scheduled for surgery underwent PET/CT scan and SLN mapping with indocyanine-green. Patients with suspicious lymph nodes at FDG-PET/CT underwent selective pelvic lymphadenectomy. In case of undetectable SLN, no further lymphadenectomy was performed if PET/CT scan was negative. Basic descriptive statistics were used to describe outcomes. A total of 83 patients were enrolled in the study. PET/CT scan was suggestive of nodal involvement in 15 patients. SLN were detected bilaterally in 78% of patients. Detection rate was influenced by patients' BMI and surgical learning curve. Five patients were node-positive: all of these had hypermetabolic nodes on PET/CT scan; in one patient SLN was not detected. Ten out of 15 patients with suspicious nodes on PET/CT scan were node-negative. After a median follow up of 24 months all patients are alive. Four patients experienced recurrent disease. No nodal relapse was recorded. Lymphatic mapping with sentinel node biopsy is able to reduce morbidity associated with pelvic lymphadenectomy. Sentinel node assessment is a feasible and appealing procedure and should be performed in a specialized center. Detection rate strongly improves with learning curve, while is reduced in morbidly obese patients. PET/CT scan shows high sensitivity but moderate specificity for nodal metastasis and may help to avoid nodal dissection in patients with sentinel node mapping failure.

Fertility-sparing surgery for women with stage I cervical cancer of 4 cm or larger: a systematic review.

OBJECTIVE: To investigate current evidence on oncological, fertility and obstetric outcomes of patients with stage I cervical cancer of 4 cm or larger undergoing fertility-sparing surgery (FSS). METHODS: Systematic review of studies including women affected by stage I cervical cancer ≥4 cm who underwent FSS. Main outcome measures: disease-free survival (DFS), overall survival (OS), pregnancy rate, live birth rate, premature delivery rate. RESULTS: Fifteen studies met all eligibility criteria for this systematic review, involving 48 patients affected by cervical cancer ≥4 cm who completed FSS. Three patients (6.3%) experienced a recurrence and one of them (2.1%) died of disease. The 5-year DFS rate was 92.4%. The 5-year OS rate was 97.6%. A significantly shorter 5-year DFS was reported for high-risk patients (G3, non-squamous histotype, diameter ≥5 cm) compared with low-risk (74.7% vs. 100%; log-rank test, p=0.024). Data about fertility outcomes were available for 12 patients. Five patients out of 12 (41.7%) attempted to conceive with an estimated pregnancy rate of 80%, a live birth rate of 83.3% and a premature delivery rate of 20%. CONCLUSION: Women with high tumor grade, aggressive histology and tumor size ≥5 cm have a higher risk of recurrence. Oncologic outcomes are encouraging among low-risk patients; however, the lack of high-quality studies makes it difficult to draw any firm conclusions. Prospective multicentric clinical trials with a proper selection of inclusion/exclusion criteria should be conducted in women with low-risk factors, strong desire to preserve their fertility and high likelihood to conceive.

Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: The Role of Immune-related Factors.

BACKGROUND/AIM: Treatment of locally advanced cervical cancer (LACC) consists of concomitant chemoradiation or neoadjuvant chemotherapy (NACT) plus radical surgery (RS). This study analyzed the prognostic role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), tumor infiltrating lymphocytes (TILs), and PD-L1 expression in LACC patients, treated with NACT+RS. PATIENTS AND METHODS: We prospectively analyzed 37 LACC patients treated from December 2016 to September 2019. Patients were submitted to pelvic examination, biopsy and imaging. RESULTS: In 65% of cases, a nodal involvement was present at pre-treatment MRI. All cancers showed the presence of stromal TILs and PD-L1 staining of inflammatory cells. No significant correlations were found between clinicopathological parameters and the number of TILs and PDL-1 at baseline. After NACT, 29 patients (78%) were submitted to RS; 28% of patients showed pathological complete response, 62% partial response and 10% stable disease. Seven (24%) patients reported a positive node. Patients with high levels of stromal TILs and low NLR and PLR showed a significantly better response to NACT. No significant correlation was observed between PD-L1 expression and response to NACT. CONCLUSION: The number of TILs, the expression of PDL1, and NLR and PLR ratios correlate significantly with the response of LACC patients to NACT.

Relationship between cervical excisional treatment for cervical intraepithelial neoplasia and obstetrical outcome.

INTRODUCTION: The aim of our systematic review was the assessment of effects of excisional treatments for the management of cervical intraepithelial neoplasia (CIN) on preterm delivery (PD), lower birth weight (LBW), preterm premature rupture of membrane (PPROM) and obstetrical outcomes. EVIDENCE ACQUISITION: A structured search was carried out in PubMed-Medline, Embase, and Cochrane Controlled Trials Register databases through November 30, 2019. The search included a combination of the following terms: "loop electrosurgical excision procedure (LEEP)," "large loop excision of transformation zone (LLETZ)," "cold-knife conization (CKC)," "laser cervical conization (CLC)," "preterm delivery" and "neonatal outcome." EVIDENCE SYNTHESIS: Thirty-two of 561 publications considered were included: 28 retrospective series, 2 prospective studies and 2 multicenter trials. Globally in several studies there was a significant increase in PD, measured by the relative risk, in the women underwent a surgical procedure for the CIN. In their majority, the studies were retrospective and therefore a high risk of bias. CONCLUSIONS: This systematic review shows that the surgical treatment of the CIN was associated with an increased risk of PD, LBW and pPROM before 37 pregnancy weeks compared to untreated women, especially in a CKC and LLETZ procedure. Moreover, the increase of the of PD was associated with cone size, cervical length, repeated treatment and a short conization-to-pregnancy interval.