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.

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.

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.

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.

Obturator Prosthesis Rehabilitation after Maxillectomy: Functional and Aesthetical Analysis in 25 Patients.

The number of patients undergoing a surgical resection of the maxilla for oncological reasons is constantly increasing, the most common complication of which remains the communication between oral and nasal cavities. On the basis of data arising from the literature regarding the treatment options of maxillary oncological post-surgical defects, obturator prosthesis remains the most used worldwide. We studied 25 patients (with at least 1-year follow up) rehabilitated by obturator prosthesis after maxillary resection leading to oro-nasal communication, providing data on the objective/subjective evaluation of such rehabilitation and mastication performance measured by a two-color chewing gum test. The type of defect was classified according to the classification system proposed by Aramany. Among the patients in our study, 72% rated a higher score for either stability and retention than for aesthetic appearance, as confirmed by the Kapur score rated by clinicians. The two-color chewing gum test shows similar results as only one patient had insufficient chewing function. Interestingly, we found no correlation between the masticatory function and residual denture, confirming that the maxillary obturator remains a predictable solution in such patients regardless of the anatomical alterations following surgery.

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.

Diode Laser Photocoagulation of Oral Venous Malformations in Patients on Anticoagulant Therapy Without Drug Discontinuation.

The diode laser is widely used for the treatment of venous malformations of the oral cavity nowadays. Anticoagulant therapy is usually modified or suspended in patients needing oral surgery, especially for vascular lesion treatment. We report a case series of venous malformations in patients on anticoagulant therapy treated by diode laser photocoagulation without drug discontinuation.

The impact of CO2 laser for treatment of Bartholin's gland cyst or abscess on female sexual function: a pilot study.

The aim of this study is to evaluate the sexual functionality before and after treatment of Bartholin's gland diseases (BGD) with CO2 laser and to compare our results to patients who underwent surgical cold knife and to a healthy control group (HCG). Consecutive patients (n = 15) affected by BG cyst or abscess who underwent CO2 laser treatment were evaluated. Patients were asked to complete the Italian translation of the Female Sexual Functioning Index (FSFI) before and 4 weeks after treatment. Results after CO2 laser were compared with two control groups: patients affected by BG cyst (n = 15) or abscess treated with surgical cold knife treatment and a HCG (n = 18). A statistically significant advantage of CO2 laser versus cold knife treatment in terms of lubrication, pain and global score were recorded. Both the single scores of five domains and total score of FSFI were globally higher after any treatment compared to before (CO2 and cold knife) of BGD. According to our data, CO2 laser therapy is often well tolerated by patients and correlated with a favorable sexual health recovery.

Ultrasonography reappraisal of tubal patency in assisted reproduction technology patients: comparison between 2D and 3D-sonohysterosalpingography. A pilot study.

BACKGROUND: The aim of this study was to compare 2D and 3D-sonohysterosalpingography (2D-3D-HyFoSy) with previous diagnostic laparoscopy in the diagnosis of tubal patency, and compare each procedure in terms of procedure's time, perceived pain and complication rate. METHODS: We prospectively recruited infertile women, previously submitted to laparoscopy and randomly allocated into 2D-HyFoSy (group I) and 3D-HyFoSy (group II). We analyzed the results in term of sensitivity, specificity, positive predictive value and negative predictive value in tubal patency evaluation of both procedures in comparison with laparoscopy. RESULTS: We enrolled 50 women, 25 in group I and 25 in group II. 2D-HyFoSy findings obtained in group I, were concordant with laparoscopy in 81% of cases, with a sensitivity of 80% and a specificity of 92%. In group II, a correspondence was present in 88% of examinations, with a sensitivity and specificity of 98% and 91.4% respectively. 3D-HyFoSy was found to be faster and less painful than 2D (P<0.001). CONCLUSIONS: In the diagnosis of tubal occlusion, in the high-risk population, it seems advisable to us using the 3D-HyFoSy as the first-level examination, while, in low-risk patients, if the tubes appear obstructed in 2D-HyFoSy, the 3D-HyFoSy should be indicated before submitting patients to operative laparoscopy.

Fertility management for malignant ovarian germ cell tumors patients.

Malignant Germ Cell Tumors have primarily affecting adolescents and young adults. In advanced disease, greater than 70% of patients can be cured with standard chemotherapy regimens and fertility-sparing surgery appears to be safe with excellent survival after long-term follow-up. Due to their rarity, follow up and fertility management is largely based on trials of epithelial ovarian cancer or on few small studies. We report a review of the literature studies about the assessment, the monitoring and the treatment of fertility for Malignant Germ Cell Tumors as pratical guidelines for management of fertility in these patients.

Bartholin gland cancer.

INTRODUCTION: Bartholin gland carcinoma is an extremely rare condition. Because of its, phase III trials have not been carried out, there exists no unanimous consensus on treatment and guidelines are missing. METHODS: All studies reporting cases of Bartholin cancer were collected and screened for the evaluations. Baseline characteristics of studies were extracted and were queried in a database. RESULTS: A total number of 133 manuscripts collected were available for the review process, representing a total number of 275 reported cases. The histological type of Bartholin gland cancer was specified in 90.4% cases: 30.7% cases were squamous cell carcinoma, 29.6% adenoid cystic carcinoma, 25% adenocarcinomas. At multivariate analysis adenocarcinoma histotype and positive lymph node were statistical correlated with worse prognosis. CONCLUSION: Bartholin gland cancer remains a challenge for gynecologic oncologists. To better understand and treat this disease, centralization to referral centers and design of multi institutional trials is crucial.

HPV-related vulvar diseases and perspectives of p16INK4a immunochemistry: a review of the literature.

INTRODUCTION: Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16INK4a immunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap. METHODS: A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, Clincaltrials.gov and Scopus. The key search terms were HPV, VIN, p16INK4a immunochemistry and p53. RESULTS: We found that nuclear and cytoplasmic immunostaining for p16INK4a was intense and diffuse in HPV-associated lesions and weak and focal in normal vulvar epithelium, nondysplastic lesions, lichen sclerosus and keratinizing vulvar squamous cell carcinoma. p53 nuclear immunostaining was always negative in HPV-related disease. CONCLUSIONS: Our findings indicated that p16INK4a or p16INK4a/p53 immunoreactivity, along with histological diagnosis, could be a convenient means to adequately classify VIN and its connection to HPV infection. Therefore, the clear recognition of HPV-associated VIN would lead to an appropriate strategy of treatment and follow-up.

Beyond circulating microRNA biomarkers: Urinary microRNAs in ovarian and breast cancer.

Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.

Trends in Mortality After Primary Cytoreductive Surgery for Ovarian Cancer: A Systematic Review and Metaregression of Randomized Clinical Trials and Observational Studies.

BACKGROUND: Primary cytoreductive surgery (PDS) followed by platinum-based chemotherapy is the cornerstone of treatment and the absence of residual tumor after PDS is universally considered the most important prognostic factor. The aim of the present analysis was to evaluate trend and predictors of 30-day mortality in patients undergoing primary cytoreduction for ovarian cancer. METHODS: Literature was searched for records reporting 30-day mortality after PDS. All cohorts were rated for quality. Simple and multiple Poisson regression models were used to quantify the association between 30-day mortality and the following: overall or severe complications, proportion of patients with stage IV disease, median age, year of publication, and weighted surgical complexity index. Using the multiple regression model, we calculated the risk of perioperative mortality at different levels for statistically significant covariates of interest. RESULTS: Simple regression identified median age and proportion of patients with stage IV disease as statistically significant predictors of 30-day mortality. When included in the multiple Poisson regression model, both remained statistically significant, with an incidence rate ratio of 1.087 for median age and 1.017 for stage IV disease. Disease stage was a strong predictor, with the risk estimated to increase from 2.8% (95% confidence interval 2.02-3.66) for stage III to 16.1% (95% confidence interval 6.18-25.93) for stage IV, for a cohort with a median age of 65 years. CONCLUSIONS: Metaregression demonstrated that increased age and advanced clinical stage were independently associated with an increased risk of mortality, and the combined effects of both factors greatly increased the risk.

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.

Vulvar malignancy in neurofibromatosis syndrome.

Type 1 neurofibromatosis (NF1) is a dominantly inherited neurologic disorder that affects primarily the skin, bones, and peripheral nervous system. It may be associated with a variety of clinical manifestations including cafe-au-lait spots, skinfold freckling, Lisch nodules, and visceral neurofibromas. Individuals affected by NF1 harbor an increased risk for both benign and malignant tumors. Malignant transformation is usually observed in the form of neurosarcoma. Rarely, NF1 affects the genital tract, and isolated vulvar localization is extremely rare. Here is reported a rare case of a solitary neurosarcoma of the vulva in a 43-year-old woman affected by NF1 syndrome treated with surgical excision. The purpose of this case is to underline the possibility of association between NF1 and genital tract sarcoma and to suggest an accurate evaluation of rapid growth vulvar mass in this setting.

CO2 laser treatment for Bartholin gland abscess: ultrasound evaluation of risk recurrence.

STUDY OBJECTIVE: To evaluate the efficacy of CO2 laser treatment and parameters correlated with recurrence in patients with Bartholin gland abscesses treated using this approach. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: One hundred forty-seven patients who met eligibility criteria. INTERVENTION: Preoperative ultrasound evaluation of Bartholin gland lesions and CO2 laser treatment. MEASUREMENTS AND MAIN RESULTS: All patients received CO2 laser therapy, with median operative time 15 minutes (range, 12-35 minutes). Median postoperative stay was 1 hours (range, 1-4 hours). Estimated 3-year relapse-free rate was 88.56%. Lesion wall thickness 0.5-1.5 mm, multilocular lesion, and hyperechogenic lesion were correlated with recurrence. CONCLUSION: CO2 laser of Bartholin gland abscesses could be a valid option. Ultrasound characteristics of Bartholin gland lesions could predict lesion recurrence rate.

A small molecule SMAC mimic LBW242 potentiates TRAIL- and anticancer drug-mediated cell death of ovarian cancer cells.

BACKGROUND: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (SMAC) has been described to sensitize for apoptosis. We have explored the pro-apoptotic activity of LBW242, a mimic of SMAC/DIABLO, on ovarian cancer cell lines (A2780 cells and its chemoresistant derivative A2780/ADR, SKOV3 and HEY cells) and in primary ovarian cancer cells. The effects of LBW242 on ovarian cancer cell lines and primary ovarian cancer cells was determined by cell proliferation, apoptosis and biochemical assays. PRINCIPAL FINDINGS: LBW242 added alone elicited only a moderate pro-apoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or anticancer drugs in inducing apoptosis of both ovarian cancer cell lines and primary ovarian cancer cells. Mechanistic studies show that LBW242-induced apoptosis in ovarian cancer cells is associated with activation of caspase-8. In line with this mechanism, c-FLIP overexpression inhibits LBW242-mediated apoptosis. CONCLUSION: LBW242 sensitizes ovarian cancer cells to the antitumor effects of TRAIL and anticancer drugs commonly used in clinic. These observations suggest that the SMAC/DIABLO mimic LBW242 could be of value for the development of experimental strategies for treatment of ovarian cancer.