Hormone replacement therapy in gynecological cancer survivors and BRCA mutation carriers: a MITO group survey.

OBJECTIVE: Early iatrogenic menopause in gynecological cancer survivors and BRCA mutation (BRCAm) carriers undergoing risk-reducing salpingo-oophorectomy (RRSO) is a major health concern. Hormone replacement therapy (HRT) is the most effective remedy, but remains underused in clinical practice. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group promoted a national survey to investigate the knowledge and attitudes of healthcare professionals regarding the prescription of HRT. METHODS: The survey consisted of a self-administered, multiple-choice 45-item questionnaire, available online to all MITO members for 2 months starting from January 2022. RESULTS: A total of 61 participants completed the questionnaire (47 out of 180 MITO centers; compliance: 26.1%). Most respondents were female (73.8%), younger than 50 years (65.6%), and gynecologic oncologists (55.7%), working in public general hospitals (49.2%). An 84.4% of specialists actively discuss HRT with patients and 51.0% of patients ask the specialist for an opinion on HRT. The rate of specialists globally in favor of prescribing HRT was 22.9% for ovarian cancer, 49.1% for cervical cancer, and 8.2% for endometrial cancer patients. Most respondents (70.5%) believe HRT is safe for BRCA-mutated patients after RRSO. Nearly 70% of physicians prescribe systemic HRT, while 23.8% prefer local HRT. Most specialists recommend HRT for as long as there is a benefit and generally for up to 5 years. CONCLUSION: Real-world data suggest that many healthcare professionals still do not easily prescribe HRT for gynecological cancer survivors and BRCA mutation carriers after RRSO. Further efforts are required to implement the use of HRT in clinical practice and to support both clinicians in recommending HRT and patients in accepting it.

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.

Primary neuroendocrine neoplasms of the vulva: A review of the MITO rare cancer group.

Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients' age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

Iodized Salt May Not Be Sufficient to Guarantee an Adequate Iodine Intake in Pregnant Women.

Adequate iodine intake is of crucial importance in pregnancy to meet the thyroid hormone needs of both mother and fetus. In the present study, undertaken as a part of the surveillance actions following the introduction in Italy of a national salt iodination program in 2005, the iodine intake was investigated in 123 pregnant women and 49 control women living in the same area of central Italy. All the participants were screened for urinary iodine concentration (UIC), serum level of thyrotropin, free-thyroxine, free-triiodothyronine, and thyroid volume. Moreover, they were provided with a questionnaire on the use of iodine-containing salt or supplements. Control women had a median UIC of 102 µg/L, consistent with an iodine sufficiency, while in pregnant women the median UIC value was 108 µg/L, lower than the endorsed UIC of 150 µg/L. In addition, pregnant women showed a significantly increased median thyroid volume compared to controls. Interestingly, the median UIC did not differ between pregnant women not using iodine-containing salt or supplements and those regularly consuming iodized salt alone, while pregnant women with a daily intake of iodine-containing supplements had an adequate median UIC (168 µg/L). In conclusion, the data reported here showed that pregnant women and their fetuses are still exposed to the detrimental effects of iodine deficiency and that the consumption of iodine-containing supplements should be recommended in pregnancy.

The efficacy of preoperative low-residue diet on postoperative ileus following cesarean section.

OBJECTIVE: To evaluate the efficacy of preoperative low-residue diet on postoperative ileus in women undergoing elective cesarean section (CS). METHODS: This is a surgeon-blind, randomized controlled trial enrolling pregnant women at ≥39 weeks of gestation undergoing elective CS. Patients were preoperatively randomized to receive either low-residue diet (arm A) or free diet (arm B) starting from three days before surgery. The primary outcome was the postoperative ileus. The secondary outcomes were the postoperative pain (assessed through VAS scale), the quality of the surgical field (scored using a 5-point scale, from poor to excellent), postoperative complications, and the length of hospital stay. Perioperative data were collected and compared between groups. RESULTS: A total of 166 patients were enrolled and randomized in arm A (n = 83) and arm B (n = 83). Postoperative ileus over 24 h was significantly shorter in arm A, compared to arm B (19.3% vs 36.2%). The surgical evaluation of small intestine was scored ≥3 in 96.4% of arm A patients versus 80.7% in arm B, while evaluation of large intestine, respectively, in 97.7% and 81.9%. Postoperative pain after 12 h from CS was significantly lower in arm A (VAS, 3.4 ± 1.7) compared to arm B (VAS, 4.1 ± 1.8). There were no significant differences as regards postoperative pain at 24 and 48 h, nausea/vomit, surgical complications, and hospital stay. CONCLUSIONS: Implementation of a preoperative low-residue diet for women scheduled for elective CS would reduce postoperative ileus and pain. Further large-scale studies are required before translating these research findings into routine obstetrical practice.

Chemo-surgical approach in vulvar leiomyosarcoma: A case report.

INTRODUCTION: Primary sarcoma of the vulva is an extremely rare entity, representing only 1%-3% of all vulvar malignant neoplasms. Among sarcomas, leiomyosarcoma (LMS) is the most prevalent histologic variant. Due to the rarity of LMS, guidelines are lacking and phase III trials have not been carried out, so clinical management is based on local clinical practice and physician experience. CASE PRESENTATION: Here, we described a case of primary LMS of the vulva and its successful management, with the adoption of neoadjuvant chemotherapy and surgery. We report a case of a 74-year-old woman with 12.5 cm vulvar LMS. The patient received three cycles of neoadjuvant chemotherapy with a partial response. Radical vulvectomy with vulvar reconstruction with V-F flap was carried out. Surgical margins were negative. Three additional cycles of adjuvant chemotherapy were delivered. RESULTS: One year after treatment, the patient was disease-free. CONCLUSION: There are no approved therapeutic protocols for this rare neoplasia. Surgery is the mainstay of treatment. However, it is not always feasible, so neoadjuvant chemotherapy was delivered for downstaging the vulvar lesion. We suppose that neoadjuvant chemotherapy has optimized the possibilities of radical surgery. Despite the anectodical nature of this case presentation, neoadjuvant chemotherapy seems a valid therapeutic option for managing patients with bulky vulvar sarcoma. Further large collaborative studies are warranted to identify the best therapeutic option for these patients.

Role of Circulating Biomarkers in Platinum-Resistant Ovarian Cancer.

Ovarian cancer (OC) is the second most common cause of death in women with gynecological cancer. Considering the poor prognosis, particularly in the case of platinum-resistant (PtR) disease, a huge effort was made to define new biomarkers able to help physicians in approaching and treating these challenging patients. Currently, most data can be obtained from tumor biopsy samples, but this is not always available and implies a surgical procedure. On the other hand, circulating biomarkers are detected with non-invasive methods, although this might require expensive techniques. Given the fervent hope in their value, here we focused on the most studied circulating biomarkers that could play a role in PtR OC.

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.

Recurrent mantle cell lymphoma in the uterine cervix: a case report.

BACKGROUND: Mantle cell lymphoma is one of several subtypes of non-Hodgkin lymphoma. Cervical relapse of non-Hodgkin lymphoma is a very rare condition that has a variable and nonspecific presentation and may resemble other neoplastic or inflammatory conditions. CASE PRESENTATION: Our patient was a 58-year-old Caucasian woman who experienced relapse of mantle cell lymphoma with cervical localization. She complained of postmenopausal vaginal bleeding, bladder pressure, and rapid growth of a cervical lesion. An irregular tumor mass of the cervix was visualized during gynecological examination, with findings highly suggestive of locally advanced cervical cancer. Surprisingly, the biopsies showed an extra nodal relapse of mantle cell lymphoma in the cervix. The rarity of this presentation and the scarcity of clinical studies make this type of recurrence very aggressive and difficult to treat. CONCLUSIONS: Obtaining a definitive histological diagnosis by biopsy or surgical resection and starting appropriate therapy are essential for recovery and treatment of these patients, even if the prognosis is poor.

Post-conization cervical stenosis treated with silicone catheter in microinvasive cervical cancer patient: A case report.

INTRODUCTION: Cervical stenosis can represent a hard complication to treat after conization for microinvasive cervical cancer. PRESENTATION OF CASE: A young woman with cervical stenosis post-trachelectomy for a microinvasive cervical cancer came to our Department. We introduced a silicone catheter of 18 French in cervical canal. The catheter was removed after 20 days. The procedure was resolutive. DISCUSSION: Cervical stenosis is one of the most frequent complication of conization. Among the different described techniques proposed in literature, we would here report the successful use of a silicon urethral catheter into the cervical canal. CONCLUSION: This method can be an easy and cheap procedure to take in consideration.

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.

Severe hemoperitoneum due to endometriosis in a non-pregnant woman under dienogest therapy: a case report.

Endometriosis is a chronic, estrogen-dependent, inflammatory disease that mainly affects women of reproductive age and is defined by the presence of endometrial glands and stroma at ectopic sites. Spontaneous hemoperitoneum due to bleeding of pelvic endometriotic foci represents a very rare and severe complication of endometriosis, although most cases described in literature regard pregnant women. We hereby present a case of a severe hemoperitoneum in a non-pregnant, 42 years old woman, under dienogest therapy for deep endometriosis. This life-threatening condition was promptly managed by performing an exploratory laparoscopy where the source of bleeding was found and hemostasis successfully achieved.Bleeding from pelvic endometriotic foci ought to be considered in the differential diagnosis of gynecological causes of acute abdomen and hemoperitoneum, even under medical therapy.

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.

Functions and the Emerging Role of the Foetal Liver into Regenerative Medicine.

During foetal life, the liver plays the important roles of connection and transient hematopoietic function. Foetal liver cells develop in an environment called a hematopoietic stem cell niche composed of several cell types, where stem cells can proliferate and give rise to mature blood cells. Embryologically, at about the third week of gestation, the liver appears, and it grows rapidly from the fifth to 10th week under WNT/ß-Catenin signaling pathway stimulation, which induces hepatic progenitor cells proliferation and differentiation into hepatocytes. Development of new strategies and identification of new cell sources should represent the main aim in liver regenerative medicine and cell therapy. Cells isolated from organs with endodermal origin, like the liver, bile ducts, and pancreas, could be preferable cell sources. Furthermore, stem cells isolated from these organs could be more susceptible to differentiate into mature liver cells after transplantation with respect to stem cells isolated from organs or tissues with a different embryological origin. The foetal liver possesses unique features given the co-existence of cells having endodermal and mesenchymal origin, and it could be highly available source candidate for regenerative medicine in both the liver and pancreas. Taking into account these advantages, the foetal liver can be the highest potential and available cell source for cell therapy regarding liver diseases and diabetes.

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.

Role of intraperitoneal chemotherapy in ovarian cancer in the platinum-taxane-based era: A meta-analysis.

PURPOSE: Intravenous (IV) chemotherapy has been compared with intraperitoneal (IP) chemotherapy in randomized clinical trials in advanced ovarian cancer (OC). The aim of this meta-analysis was to evaluate efficacy and toxicity of IV and IP and identify differences in outcomes. METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and the proportion of patients with grade ≥2 acute toxicity. RESULTS: Four randomized clinical trials representing 2461 patients were identified. The hazard ratio (HR) of PFS was 0.88 (95% CI 0.80-0.98; p = 0.01, I2 = 24%) in favor of IP chemotherapy. IP chemotherapy was also associated with significant OS improvement compared with IV chemotherapy, with HR of 0.79 (95% CI 0.67-0.92; p = 0.003, I2 = 0%). Globally, grade ≥2 toxicities were reduced with IV chemotherapy. CONCLUSION: This meta-analysis shows the superiority of IP chemotherapy over IV infusion in terms of clinical outcomes but toxicity rates. Its precise role in the management of advanced OC remains to be determined.

Postpartum Posterior Reversible Encephalopathy Syndrome (PRES): Three Case Reports and Literature Review.

Posterior reversible encephalopathy syndrome is a rare complication generally associated with headache and acute changes in blood pressure. Delay in the diagnosis and treatment may result in death or in irreversible neurological sequelae. We present three cases of PRES occurring in young women during puerperium. We report a literature review ranged from January 1990 to June 2015 describing clinical features, diagnostic and medical approach, and maternal outcome.

The age-adjusted Charlson comorbidity index as a predictor of survival in surgically treated vulvar cancer patients.

OBJECTIVE: To evaluate the impact of age-adjusted Charlson comorbidity index (ACCI) in predicting disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) among surgically treated patients with vulvar carcinoma. The secondary aim is to evaluate its impact as a predictor of the pattern of recurrence. METHODS: We retrospectively evaluated data of patients that underwent surgical treatment for vulvar cancer from 1998 to 2016. ACCI at the time of primary surgery was evaluated and patients were classified as low (ACCI 0-1), intermediate (ACCI 2-3), and high risk (>3). DFS, OS and CSS were analyzed using the Kaplan-Meir and the Cox proportional hazard models. Logistic regression model was used to assess predictors of distant and local recurrence. RESULTS: Seventy-eight patients were included in the study. Twelve were classified as low, 36 as intermediate, and 30 as high risk according to their ACCI. Using multivariate analysis, ACCI class was an independent predictor of worse DFS (hazard ratio [HR]=3.04; 95% confidence interval [CI]=1.54-5.99; p<0.001), OS (HR=5.25; 95% CI=1.63-16.89; p=0.005) and CSS (HR=3.79; 95% CI=1.13-12.78; p=0.03). Positive nodal status (odds ratio=8.46; 95% CI=2.13-33.58; p=0.002) was the only parameter correlated with distant recurrence at logistic regression. CONCLUSION: ACCI could be a useful tool in predicting prognosis in surgically treated vulvar cancer patients. Prospective multicenter trials assessing the role of ACCI in vulvar cancer patients are warranted.

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.

Antimüllerian hormone is reduced in the presence of ovarian endometriomas: a systematic review and meta-analysis.

OBJECTIVE: To evaluate if the presence of endometriomas impacts on the ovarian reserve as evaluated with antimüllerian hormone (AMH). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Patients with unoperated endometriomas versus controls without endometriomas. INTERVENTION(S): Electronic databases searched up to June 2017 to identify articles evaluating AMH levels in patients with unoperated endometriomas versus controls without endometriomas. MAIN OUTCOME MEASURE(S): The primary analysis was aimed at evaluation of AMH levels (mean and SD) in patients with and without endometriomas. Secondary analyses were aimed at evaluating AMH levels in patients with ovarian endometriomas compared to patients with either non-endometriosis benign ovarian cysts or healthy ovaries. RESULT(S): Of the 39 studies evaluated in detail, 17 were included, for a total of 968 patients with endometriomas and 1874 without endometriomas. AMH was significantly lower in patients with unoperated endometriomas compared to patients with no endometriomas (mean difference -0.84, with 95% confidence interval [CI] -1.16 to -0.52). At secondary analyses, AMH in patients with endometriomas was significantly lower both versus non-endometriosis benign ovarian cysts (mean difference -0.85, 95% CI -1.37 to -0.32, and versus women with healthy ovaries (mean difference -0.61, 95% CI -0.99 to -0.24). CONCLUSION(S): Ovarian reserve evaluated with AMH is reduced in patients with ovarian endometriomas compared both to patients with other benign ovarian cysts, and to patients with healthy ovaries.