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.

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.

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.

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.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

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.

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 Role of 2D/3D Ultrasound to Assess the Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer.

INTRODUCTION: Different imaging techniques were introduced to improve preoperative clinical staging of locally advanced cervical cancer (LACC) with transvaginal ultrasound (TV-US) or transrectal ultrasound (TR-US) representing a promising staging technique in the evaluation of the local extension of the disease for invasive tumors. The aim of this study was to evaluate the response to neoadjuvant chemotherapy (NACT) in LACC by 2D/3D ultrasound examination. MATERIALS AND METHODS: We prospectively enrolled patients affected by histologically and clinically confirmed LACC. All patients were scheduled for 3 cycles of platinum-based NACT followed by radical surgery. The ultrasound examination was performed at every cycle and within 10 days before surgery. The parameters evaluated were: the volume (automatically computed by the VOCAL software) and the mass vascularization. RESULTS: From March 2010 to March 2019, 157 women were recruited. Among these patients, 12 of them were excluded: 6 for the presence of distant metastases, 4 for rare histology, and 2 for severe comorbidities not allowing the protocol treatment. Seventeen patients after NACT were excluded because they were not amenable to radical surgery. Thus, 128 were considered for the final analysis of whom 106 (83%) were considered responders to NACT by histology. The sensibility and specificity of ultrasound with regard to the response to chemotherapy compared to histological specimen were 94 and 82%, respectively, with an accuracy of 92%. The positive predictive value and negative predictive value were 96 and 75%, respectively. Finally, we found that nonetheless there was a trend towards a continuous response to chemotherapy among patients who were considered responders to NACT at pathological examination; the major volume and vascularization index (VI) reduction were observed during the first 2 cycles (74, 71% and 47, 63%, respectively). On the contrary, non-responders showed an initial reduction of the VI (4.86 consisting of 33%, 95% CI 0.79-8.92, p = 0.013), but no significant modification in tumour volume along NACT. CONCLUSION: 2D/3D ultrasound is useful in assessing early response to NACT in patients with LACC.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Lymphadenectomy in Ovarian Cancer: Is It Still Justified?

PURPOSE OF REVIEW: The aim of this review is to determine, in the light of recent evidences, the role of lymphadenectomy in ovarian cancer. RECENT FINDINGS: The lymphadenectomy in ovarian neoplasms (LION) trial reports no better outcomes and higher complication and mortality rates associated with lymphadenectomy. Even if performed by expert hands, lymphadenectomy has a cost in terms of longer operative time, blood loss, higher rates of transfusions, and intensive unit care. If on the one hand retroperitoneal staging is not correlated to survival benefits both in early and advanced ovarian cancer, on the other hand it is associated with an increased surgery-related morbidity. Surgical treatment of isolated nodal recurrences seems to be feasible and associated with survival benefits.

Efficacy of ulipristal acetate (UPA) for the treatment of expulsion uterine myomas: report of two cases.

Expulsion leiomyoma can represent an emergency condition and may lead to severe vaginal hemorrhage with anemia and urgent hysterectomy. Among medical treatments used for leiomyoma, Selective progesterone receptor modulators (SPRM) and, in particular, Ulipristal Acetate (UPA) have been proved to be effective in the management of bleeding and myoma size reduction. However, to our knowledge, there are no cases reported in literature on the use of UPA used as 'emergency' medical therapy in patients with severe anemia and vaginal bleeding due to expulsion leiomyoma. In this paper we would report two cases of patients affected by expulsion myoma successfully treated with UPA with immediate resolution of vaginal bleeding and subsequent elective conservative treatment.

Effects of Neoadjuvant Chemotherapy Plus Radical Surgery as Front Line Treatment Strategy in Patients Affected by FIGO Stage III Cervical Cancer.

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.

Dose-Dense Neoadjuvant Chemotherapy plus Radical Surgery in Locally Advanced Cervical Cancer: A Phase II Study.

OBJECTIVE: To assess the efficacy and toxicity profile of dose-dense cisplatin-based neoadjuvant chemotherapy (NACT) followed by radical surgery in patients affected by locally advanced cervical cancer. METHODS: Patients affected by carcinoma of the uterine cervix FIGO (International Federation of Obstetrics and Gynecology) stage IB2-IIIB were enrolled into the study. The treatment schedule consisted of 5 cycles of intravenous paclitaxel 60 mg/m(2) plus cisplatin 60 mg/m(2) every 10 days; patients were then submitted to radical hysterectomy and pelvic lymphadenectomy. RESULTS: From January 2011 to March 2013, 22 patients were enrolled. Median age was 47 (26-83) years. FIGO stages included 1 IIA, 15 IIB, 1 IIIA, and 5 IIIB. Ninety-one percent of patients completed all the 5 planned cycles of NACT. Three patients experienced allergic reactions to paclitaxel. Grade 3-4 hematological toxicity was observed in 18% of cases. In 3 cases, grade 3-4 extra-hematological adverse and life-threatening events were reported (1 ototoxicity, 1 transient ischemic attack, and 1 myocardial infarction). No treatment-related death occurred. The operability rate was 86.4%. The overall response rate was 52.6%: 5 patients (26.3%) experienced clinical complete response, and 5 (26.3%) showed a clinical partial response. Stable disease was observed in 47.4% of patients, with no progressive disease recorded. Pathological response was observed in 57.9% of cases. Six out of 19 (31.6%) patients were submitted to adjuvant treatment. CONCLUSION: Dose-dense cisplatin-based NACT showed a response rate in approximately half of patients. However, in consideration of the reported extra-hematological toxicity, further studies on and new strategies with dose-dense platinum-based NACT are required to improve outcome in cervical cancer patients.

Predictors of postoperative morbidity after cytoreduction for advanced ovarian cancer: Analysis and management of complications in upper abdominal surgery.

OBJECTIVE: To evaluate the complication rate and its impact in patients who have undergone upper abdominal surgery for treatment of advanced ovarian cancer. METHODS: Patients who have undergone upper abdominal surgery including diaphragm surgery, splenectomy, distal pancreatectomy, gastric resection, liver resection and biliary surgery were considered for the study. Perioperative complications were evaluated and graded according to Clavien-Dindo. RESULTS: One hundred and twenty one patients were included. Two hundred and twelve surgical procedures were performed. Thirty-six patients reported at least one complication, but 61.1% of these the complication was mild. Median hospital stay for patients with and without complication was 7 vs. 13days respectively (p<0.001). There was a significant correlation between post-operative hospital stay and the total number of surgical procedures (R=0.445, p<0.001). At multivariate analysis, diaphragmatic resection and pancreatic resection were associated with a significant increase of postoperative hospital stay, furthermore diaphragmatic resection (p=0.004), hepatic resection (p=0.004), pancreatectomy (p=0.011) and biliary surgery (p=0.049) were independent predictors of severe (G3-G4) complication. CONCLUSIONS: Rate of complications of patients submitted to upper abdominal surgery for ovarian cancer is acceptable. Prediction of severe complications is the goal for its optimal management. Extensive procedures should be avoided with those patients in which optimal residual tumor could not be reached.

Fertility-sparing surgery in early-stage cervical cancer patients: oncologic and reproductive outcomes.

OBJECTIVE: The aim of this study was to evaluate the safety, feasibility, and effectiveness of conservative management of early-stage cervical cancer (eCC) in young women willing to preserve their childbearing potential. METHODS: Data of 22 consecutive young women (aged <40 years) undergoing conservative management of eCC were prospectively collected. Conservative management consists of cervical conization plus laparoscopic pelvic lymphadenectomy. RESULTS: Median age was 32.5 years (range, 27-40 years). Twenty-one women (95%) were nulliparous. Histology included adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma in 11 (50%), 10 (45%), and 1 (5%) patients, respectively. Six (27%) and 16 patients (73%) were affected by stage IA2 and IB1, respectively. The mean number of pelvic lymph node removed was 26 (SD, 8.6). After primary treatment, 3 patients required radical surgery due to the presence of metastatic nodes detected at the time of diagnostic lymphadenectomy. In addition, 1 patient (5%), after the successful execution of conservative treatment, asked for hysterectomy. After a mean follow-up of 48.8 (SD, 32.8) months, no recurrence was diagnosed among patients undergoing ultraconservative treatment, whereas 2 out of 3 patients with positive pelvic nodes who had radical hysterectomy developed recurrent disease. Considering the whole cohort, 5-year disease-free and overall survival rates were 85.9% and 93.7%, respectively. Looking at reproductive outcomes, 15 of 18 patients (4 patients had hysterectomy) attempted to conceive, and 8 (53%) women had spontaneous pregnancies CONCLUSIONS: Conservative management for eCC seems to be associated with long-term oncologic effectiveness, preserving reproductive function. Further large prospective studies are warranted to improve patients' care.

Benign schwannoma in supraclavicular region: a false-positive lymph node recurrence of breast cancer suspected by PET scan.

INTRODUCTION: Positron emission tomography (PET) is the most accurate imaging modalities to detect malignancies. And it helps to take decisions regarding diagnosis, staging, recurrence, and therapeutical management. CASE PRESENTATION: We report a case of a suspected supraclavicular lymph node relapse, diagnosed by PET-CT in a breast cancer patient. The lymph node was surgically removed in outpatient with local anesthesia. Histological findings diagnosed a benign Schwannoma. In this patient PET-CT failed to distinguish benign tumors from metastatic supraclavicular lymph nodes. CONCLUSION: This case confirms the need to investigate histologically suspected supraclavicular lesions, during breast cancer follow up.

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.

An update of laparoscopy in cervical cancer staging: is it a useful procedure?

OBJECTIVE: It was the aim of this study to report on the role of laparoscopic staging in a large series of locally advanced cervical cancer (LACC) patients and its impact on prognosis. METHODS: Consecutive patients with LACC were considered for surgical staging: gynecological examination, cystoscopy and laparoscopy with peritoneal biopsies and peritoneal fluid cytology. RESULTS: Between February 2000 and September 2010, a total of 167 women were evaluated. In 5 patients, laparoscopy could not be performed. One hundred and sixty-two patients had correct laparoscopic staging: 49 International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIA (>4 cm), 67 IIB, 39 III, and 7 IVA. Abdominal spread was found in 33 cases (20%). There was a minor laparoscopy complication rate of 1%. We found a significant difference in the distribution of peritoneal spread for tumor grade and FIGO stage (p = 0.01 and p < 0.0001, respectively), whereas no statistically significant difference for the histological type was found [p = not significant (NS)]. The median follow-up was 80 months (range 4-144). The median overall survival was 65 months. The patients without abdominal spread did not benefit from a significantly longer survival (median overall survival of 59 vs. 70 months; p = NS). CONCLUSIONS: Laparoscopic staging in cervical cancer is a safe and feasible technique but it does not modify the prognosis of LACC patients.

Advances in small molecule maintenance therapies for high-grade serous ovarian cancer.

INTRODUCTION: Ovarian cancer is one of the most lethal gynecological tumors with a lack of effective treatment modalities especially in advanced/recurrent disease. Nevertheless, recently, new small molecules have emerged as an effective approach for the management of ovarian cancer patients, especially in the maintenance setting. AREAS COVERED: This review summarizes the role of small molecules used in the management of high-grade serous ovarian cancer. The authors performed a critical review of current evidence and ongoing studies. Of note, tyrosine kinase inhibitors (TKIs) and poly(ADP-ribose) polymerase (PARP) inhibitors are the most intriguing medications in this setting. EXPERT OPINION: Protein-targeted therapies against tumor tissues have progressed significantly in the last years due to an enhanced knowledge of the biological and molecular processes of carcinogenesis. Treatment with small molecules allows the targeting of specific proteins involved in cancer biology. TKIs seem promising but further data are necessary to assess the pros and cons of adopting this treatment modality. PARP inhibitors represent the new standard of care for ovarian cancer patients harboring either a BRCA mutation or with homologous recombination deficiency (HRD). Interestingly, the accumulation of data has highlighted that PARP inhibitors provide benefits even in patients with HR proficient tumors.