Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix.

High-grade neuroendocrine cervical cancers (NETc) are exceedingly rare, highly aggressive tumors. We analyzed 64 NETc tumor samples by whole-exome sequencing (WES). Human papillomavirus DNA was detected in 65.6% (42/64) of the tumors. Recurrent mutations were identified in PIK3CA, KMT2D/MLL2, K-RAS, ARID1A, NOTCH2, and RPL10. The top mutated genes included RB1, ARID1A, PTEN, KMT2D/MLL2, and WDFY3, a gene not yet implicated in NETc. Somatic CNV analysis identified two copy number gains (3q27.1 and 19q13.12) and five copy number losses (1p36.21/5q31.3/6p22.2/9q21.11/11p15.5). Also, gene fusions affecting the ACLY-CRHR1 and PVT1-MYC genes were identified in one of the eight samples subjected to RNA sequencing. To resolve evolutionary history, multiregion WES in NETc admixed with adenocarcinoma cells was performed (i.e., mixed-NETc). Phylogenetic analysis of mixed-NETc demonstrated that adenocarcinoma and neuroendocrine elements derive from a common precursor with mutations typical of adenocarcinomas. Over one-third (22/64) of NETc demonstrated a mutator phenotype of C > T at CpG consistent with deficiencies in MBD4, a member of the base excision repair (BER) pathway. Mutations in the PI3K/AMPK pathways were identified in 49/64 samples. We used two patient-derived-xenografts (PDX) (i.e., NET19 and NET21) to evaluate the activity of pan-HER (afatinib), PIK3CA (copanlisib), and ATR (elimusertib) inhibitors, alone and in combination. PDXs harboring alterations in the ERBB2/PI3K/AKT/mTOR/ATR pathway were sensitive to afatinib, copanlisib, and elimusertib (P < 0.001 vs. controls). However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.

Sentinel node mapping in high-intermediate and high-risk endometrial cancer: Analysis of 5-year oncologic outcomes.

OBJECTIVE: To assess 5-year oncologic outcomes of apparent early-stage high-intermediate and high-risk endometrial cancer undergoing sentinel node mapping versus systematic lymphadenectomy. METHODS: This is a multi-institutional retrospective, propensity-matched study evaluating data of high-intermediate and high-risk endometrial cancer (according to ESGO/ESTRO/ESP guidelines) undergoing sentinel node mapping versus systematic pelvic lymphadenectomy (with and without para-aortic lymphadenectomy). Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: Overall, the charts of 242 patients with high-intermediate and high-risk endometrial cancer were retrieved. Data on 73 (30.1%) patients undergoing hysterectomy plus sentinel node mapping were analyzed. Forty-two (57.5%) and 31 (42.5%) patients were classified in the high-intermediate and high-risk groups, respectively. Unilateral sentinel node mapping was achieved in all patients. Bilateral mapping was achieved in 67 (91.7%) patients. Three (4.1%) patients had site-specific lymphadenectomy (two pelvic areas only and one pelvic plus para-aortic area), while adjunctive nodal dissection was omitted in the hemipelvis of the other three (4.1%) patients. Sentinel nodes were detected in the para-aortic area in eight (10.9%) patients. Twenty-four (32.8%) patients were diagnosed with nodal disease. A propensity-score matching was used to compare the aforementioned group of patients undergoing sentinel node mapping with a group of patients undergoing lymphadenectomy. Seventy patient pairs were selected (70 having sentinel node mapping vs. 70 having lymphadenectomy). Patients undergoing sentinel node mapping experienced similar 5-year disease-free survival (HR: 1.233; 95%CI: 0.6217 to 2.444; p = 0.547, log-rank test) and 5-year overall survival (HR: 1.505; 95%CI: 0.6752 to 3.355; p = 0.256, log-rank test) than patients undergoing lymphadenectomy. CONCLUSIONS: Sentinel node mapping does not negatively impact 5-year outcomes of high-intermediate and high-risk endometrial cancer. Further prospective studies are warranted.

Use of Sensor Array Analysis to Detect Ovarian Cancer through Breath, Urine, and Blood: A Case-Control Study.

Ovarian cancer (OC) is the eighth most common cancer in women. Since screening programs do not exist, it is often diagnosed in advanced stages. Today, the detection of OC is based on clinical examination, transvaginal ultrasound (US), and serum biomarker (Carbohydrate Antigen 125 (CA 125) and Human Epididymis Protein 4 (HE4)) dosage, with a sensitivity of 88% and 95%, respectively, and a specificity of 84% for US and 76% for biomarkers. These methods are clearly not enough, and OC in its early stages is often missed. Many scientists have recently focused their attention on volatile organic compounds (VOCs). These are gaseous molecules, found in the breath, that could provide interesting information on several diseases, including solid tumors. To detect VOCs, an electronic nose was invented by a group of researchers. A similar device, the e-tongue, was later created to detect specific molecules in liquids. For the first time in the literature, we investigated the potential use of the electronic nose and the electronic tongue to detect ovarian cancer not just from breath but also from urine, blood, and plasma samples.

The Role of TAP/RS Block in Minor Gynecologic Laparoscopic Surgery: A Randomized Clinical Trial.

OBJECTIVES: The aim of the study was to compare, in patients undergoing minor gynecological laparoscopic procedures, the effects of ultrasound (US)-guided transversus abdominis plane (TAP) + rectus sheath (RS) block versus no TAP/RS block in terms of post-surgical pain control using the numeric pain rating scale (NRS) and the degree of patient satisfaction, according to the main goals of Early Recovery After Surgery (ERAS) programs. The primary outcome is to value the postoperative abdominal pain using NRS in both groups. Secondary outcomes are to evaluate blood values, presence of postoperative nausea and vomiting (PONV), postoperative ileus, level of patient expected satisfaction, time of discharge, length of stay (LOS), and the amounts of additional analgesics required. DESIGN: In this prospective randomized controlled trial, patients were randomly assigned to loco-regional anesthesia (LRA) group, who received TAP and RS block under US guidance, or no loco-regional anesthesia (N-LRA) group. Enrolled patients were randomized 1:1 to either receive bilateral TAP/RS block with ropivacaine or sham treatment (patches were applied on the abdominal wall of the patients under general anesthesia). PARTICIPANTS: All patients aged between 18 and 75 years, with ASA (American Society of Anesthesiologists) physical status 1-2, undergoing laparoscopic minor gynecological surgery, were enrolled. SETTING: The study was conducted to the University of Campus Bio-Medico Hospital of Rome. METHODS: Half an hour before surgery, all patients received gabapentin 300 mg per os. Once the patient underwent general anesthesia, US-guided bilateral TAP/RS block was performed by the anesthesiology team, while the uterine manipulator was positioned by a gynecology resident (not involved in the study). In the operative room, all patients received the same standardized anesthetic regimen. Postoperative abdominal pain was assessed at rest, after palpation, during movement, and after a cough by evaluating the patient at 6, 12, 18, 24, 36, 48, and 72 h after surgery, using the NRS from 0 to 10 in both groups. The amount of drug used for analgesia in the first 48 h after surgery was recorded. Moreover, hemoglobin, white blood cells, and c-reactive protein levels were recorded at 24, 48, and 72 h. The presence of PONV and the postoperative ileus was recorded throughout convalescence. The expected level of patient satisfaction at discharge and finally the LOS were assessed. LIMITATIONS: The major weakness of this study is that 60 mL of 0.5% ropivacaine was administered to each patient, without considering weight differences, yet contemporary literature rarely suggests volume/dose titration in fascial blocks. RESULTS: A total of 104 women, undergoing gynecological minor laparoscopic surgery, were enrolled and assigned to LRA group (53 pts) and N-LRA group (51 pts). Postoperative pain was significantly reduced in patients who received TAP/RS block. A reduction in the intake of non-steroidal anti-inflammatory drugs after surgery was registered in LRA group (p < 0.01). Moreover, a significant reduction of LOS (45.97 ± 9.87 vs. 65.08 ± 17.32 h; p < 0.01) and PONV was observed in the LRA group, as well as a better level of patient satisfaction at discharge (9.43 ± 0.94 vs. 8.26 ± 1.19; p < 0.01), compared to the N-LRA group. CONCLUSIONS: US-guided TAP and RS block significantly reduces postoperative pain after minor gynecologic laparoscopic surgery and improves patients' post-operative recovery.

Real world data of niraparib in platinum sensitive relapsed ovarian cancer: A multicenter experience of the MITO group.

OBJECTIVE: PARP (poly adenosine diphosphate [ADP]-ribose polymerase) inhibitors are approved as maintenance therapy in platinum sensitive ovarian cancer (OC), in first line and in the recurrent setting, regardless of BRCA mutational status. Real-world data after the introduction of these agents are needed to evaluate whether the benefit observed in phase III randomized clinical trials can be translated into clinical practice. The aim of our study was to provide real-life data on efficacy and safety of niraparib administered as maintenance in platinum sensitive relapsed OC patients (PSROC). METHODS: This retrospective/prospective observational study included relapsed OC patients that received niraparib as maintenance, at the time of platinum sensitive recurrence within the Italian expanded-access program. Clinical data at the time of diagnosis and at the time of recurrence were collected and analyzed. Median progression free survival (PFS) and overall survival (OS) were calculated as the time from start of niraparib treatment to subsequent radiologically confirmed relapse and death or last contact, respectively. RESULTS: Among 304 eligible patients, 260 (85%) had BRCA wild-type tumor and 36. (11.9%) were BRCA mutated. Median PFS was 9.1 months (95% CI: 6.9-11.2) and 10.3 months (95% CI: 7.0-13.5) in the BRCAwt and BRCAmut cohorts, respectively. Furthermore, median OS was 41.7 months (95% CI: 31.6-41.9) and 34.6 months (95% CI: N.E.) in the BRCAwt and BRCAmut cohorts, respectively. CONCLUSION: Data from this large real-life dataset suggested that maintenance with niraparib in the real-life setting of platinum sensitive OC recurrence is effective and well tolerated.

Cardiovascular Effects of Chronic Hormone Therapy: Study on Olympic Female Athletes.

Female physiology is regulated after puberty by the menstrual cycle, whose hormonal fluctuations create a multitude of effects on several systems, including the cardiovascular one. The use of hormone therapy (HT) is quite common in female athletes, and data on cardiovascular effects in this population are lacking. We sought to investigate the effects of HT in highly trained athletes to assess any difference associated with HT on cardiac remodeling, exercise capacity, and clinical correlates. We studied 380 female elite athletes (mean age 25.5 ± 4.8) competing in endurance and mixed sports; 67 athletes (18%) were in chronic HT therapy. All athletes underwent baseline electrocardiography, exercise electrocardiography stress test, transthoracic echocardiogram, and complete blood tests, including lipid profile and inflammation indexes. The echocardiographic study showed a characteristic left ventricular (LV) remodeling, defined by lower LV mass index (86.2 vs 92.5 g/m2, p <0.006), end-diastolic LV diameter (28.3 vs 29.4 mm/m2, p <0.004), and end-diastolic LV volume (61.82 vs 67.09 ml/m2, p <0.010) compared with controls, without changes in systolic function and diastolic relaxation/filling indexes. A lower burden of ventricular arrhythmias on exercise was observed in HT athletes (1.5% vs 8.6% in those without therapy, p = 0.040). Linear regression analysis showed that HT had an independent effect on LV end-diastolic diameter indexed (p = 0.014), LV end-diastolic volume indexed (p = 0.030), and LV mass indexed (p = 0.020). In conclusion, chronic treatment with HT in female athletes is associated with less cardiac remodeling, including a lower LV cavity, volume, and mass, with preserved systolic and diastolic function, and decreased burden of exercise-induced ventricular arrhythmias. HT, therefore, appears to be responsible for a more economic but equally efficient cardiac adaptation to intensive athletic conditioning.

Impact of COVID-19 Pandemic on the Diagnostic and Therapeutic Management of Endometrial Cancer: A Monocentric Retrospective Comparative Study.

Endometrial cancer represents an ideal target to evaluate the impact of COVID-19 being the most frequent gynecological malignancy in Italy, generally detected at early stages and correlated with favorable oncological outcomes. The present comparative retrospective study carried out at Campus Bio-medico University Foundation in Rome aims to evaluate the impact of the COVID-19 pandemic on the presentation, diagnosis and treatment of EC. All women with a histological diagnosis of non-endometrioid and endometrioid endometrial cancer between 1 March 2018 and 31 October 2022 were included. The number of cases was higher in period 2 (95 vs. 64 cases). Time to diagnosis did not show statistically significant differences but in period 2, 92.06% of the diagnoses were made following abnormal uterine bleeding, while in period 1, only 67.02% were. The waiting time for the intervention was significantly shorter in period 2. Definitive histology, FIGO staging, surgical technique and adjuvant therapy did not show significant differences between the two periods. The study demonstrates that the impact of the COVID-19 pandemic did not have a direct effect on the diagnostic delay, tumor staging and type of therapy but rather on the presentation pattern of endometrial cancer.

Is an episiotomy always necessary during an operative vaginal delivery with vacuum? A longitudinal study.

Objective: The use of episiotomy during operative vaginal birth (OVB) is rather debated among operators and in literature. It is also important to evaluate the indications for which episiotomy is performed. In fact, the consequences of an episiotomy can be invalidating for patients with long-lasting results. The aim of this study is the evaluation of the role of episiotomy during OVB with the vacuum extractor and its correlation with Obstetric Anal Sphincter Injuries (OASIs).Methods: On of 9165 vaginal births, a total of 498 OVB (5.4%) were enrolled in a longitudinal prospective observational study. The incidence of OASIs was evaluated in our population after OVB performed with the vacuum extractor, during which the execution of episiotomy was performed indicated by clinician in charge.Results: OASIs occurred in 4% of the patients (n = 20). Episiotomy was performed in 39% of them (n = 181). OASIs incidence was 6% (n = 17) in the No Episiotomy and 1.8% (n = 3) in Episiotomy group (p<.001). Performance of episiotomy during OVB determined a protective effect against OASIs (p = 0.025 in full cohort and p = 0.013 in the primiparous group). An expulsive phase under one hour was an almost significant protective factor (p = 0.052).Conclusions: The use of episiotomy during OVB was associated with much lower OASIs rates in nulliparous women with a vacuum extraction; OR 0.23 (CI 95% 0.07-0.81) p = 0.037 in nulliparous women and the number necessary to treat was 18 among nulliparous women to prevent 1 OASIs. A further risk factor that emerged from the analysis is a prolonged expulsive period, whereas fundal pressure does not seem to have a statistically significant influence.

Intraoperative Three-Dimensional Transvaginal Ultrasound for Hysteroscopic Metroplasty: a Controlled Study.

This study aims to evaluate the role of intraoperative transvaginal three-dimensional ultrasound (3DUS) during hysteroscopic metroplasty. This is a prospective cohort of consecutive patients with septate uterus undergoing hysteroscopic metroplasty with intraoperative transvaginal 3DUS guidance compared to a historical control group of patients undergoing hysteroscopic metroplasty without 3DUS. We conducted our research in a tertiary care university hospital in Rome, Italy. This study involved nineteen patients undergoing 3DUS-guided hysteroscopic metroplasty for recurrent abortion or infertility compared to 19 age-matched controls undergoing metroplasty without 3DUS guidance. During hysteroscopic metroplasty, 3DUS was performed in the study group when the operator considered the procedure to be completed, according to standards of operative hysteroscopy. If 3DUS diagnosed a residual septum, the procedure was continued until a 3DUS diagnosis of a normal fundus was obtained. The patients were followed with a 3DUS performed 3 months after the procedure. The numbers of complete resections (residual septum absent), suboptimal resections (measurable residual septum of less than 10 mm), and incomplete resections (residual septum > 10 mm) in the intraoperative 3DUS group were compared to the numbers in the control group with no intraoperative 3DUS. At follow-up, measurable residual septa were obtained in 0% of the patients in the 3DUS-guided group versus 26% in the control group (p = 0.04). Residual septa of > 10 mm were obtained in 0% of the 3DUS group versus 10.5% in the control group (p = 0.48). Intraoperative 3DUS reduces the incidence of suboptimal septal resections at hysteroscopic metroplasty.

The efficacy and feasibility of fractional CO2 laser therapy for the treatment of urinary incontinence: a multicentric case-control study.

BACKGROUND: Female urinary incontinence is a significant public health problem. Conservative treatments require high patient compliance, while surgery often leads to more complications and recovery time. Our aim is to evaluate the efficacy of microablative fractional CO2 laser (CO2-laser) therapy in women with urinary incontinence (UI). METHODS: This is a retrospective analysis of prospectively collected data on women with stress urinary incontinence (SUI) and mixed urinary incontinence (MUI) with predominant SUI subjected to four sessions of CO2-laser therapy performed once a month, between February 2017 and October 2017, with a 12-month follow-up. The subjective Visual Analogue Scale (VAS) 0-10 was used to score and variables were evaluated at baseline and at one, six and 12 months after initiation of therapy. Finally, results were compared to a control group. RESULTS: The cohort consisted of 42 women. The proportion of patients with vaginal atrophy among those younger than 55 years was substantially lower (3/23; 13%) than among those older than 55 years (15/19; 78.9%). CO2 laser treatment was associated with a significant improvement in VAS scores recorded one-month, six-months, and one-year, after conclusion of therapy (P<0.001). VAS scores improved significantly in patients with either SUI (26/42; 61.9%) or mixed UI (16/42; 38.1%). No major post treatment complications were registered. Women with vaginal atrophy demonstrated significantly better results (P<0.001). CONCLUSIONS: Results confirm the efficacy and a good safety profile, for CO2 laser treatment in SUI, mostly in women with postmenopausal vaginal atrophy and should be considered as a treatment option for female patients with concomitant SUI and vaginal atrophy.

Hysterectomy alone vs. hysterectomy plus sentinel node mapping in endometrial cancer: Perioperative and long-term results from a propensity-score based study.

OBJECTIVE: To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients. MATERIALS AND METHODS: This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers. RESULTS: The study population included 398 (69.5%) and 174 (30.5%) patients having hysterectomy and hysterectomy plus SNM. As the results of the adoption of a propensity-score matched analysis, we selected two homogeneous cohort of patients (150 having hysterectomy only vs. 150 having hysterectomy plus SNM). The SNM group had a longer operative time, but did not correlate with length of hospital stay and estimated blood loss. Overall severe complication rates were similar between groups (0.7% in the hysterectomy group vs. 1.3% in the hysterectomy plus SNM group; p = 0.561). No lymphatic-specific complication occurred. Overall, 12.6% of patients having SNM were diagnosed with disease harboring in their lymph nodes. Adjuvant therapy administration rate was similar between groups. Considering patients having SNM, 4% of patients received adjuvant therapy on the basis of nodal status alone; all the other patients received adjuvant therapy also on the basis of uterine risk factors. Five-year disease-free (p = 0.720) and overall (p = 0.632) survival was not influenced by surgical approach. CONCLUSIONS: Hysterectomy (with or without SNM) is a safe and effective method for managing EC patients. Potentially, these data support the omission of side specific lymphadenectomy in case of unsuccessful mapping. Further evidence is warranted in to confirm the role SNM in the era of molecular/genomic profiling.

The use of sealing hemostat patch (HEMOPATCH®) in laparotomic myomectomy: a prospective case-control study.

PURPOSE: Uterine myomas are the most common gynecological disease. In these cases, a myomectomy is performed traditionally laparotomically. However, alternatives have been widely used, including laparoscopic, endoscopic, and robotic surgery. During these techniques, diffuse parenchymatous bleeding remains one of the main intraoperative and postoperative complications and sometimes requires unplanned hysterectomies. Recently, hemostatic agents and sealants have been used to prevent excessive blood loss during surgical repair. METHODS: We propose a prospective case-control study on the use of a sealing hemostat patch (HEMOPATCH®) on uterine sutures in laparotomic myomectomy. In the period between July 2016 and April 2017, 46 patients with symptomatic uterine fibromatosis underwent surgery. They were divided into two groups of 23 patients, with different treatments in the hemostatic phase of oozing bleeding. HEMOPATCH® is applied in group A, and spray electrocoagulation is applied in group B. RESULTS: In group A, we achieve faster hemostasis (p < 0.05), than in group B. We report a significantly lower C-reactive protein value on the second and third days after surgery for group A compared to group B. CONCLUSIONS: HEMOPATCH®, during laparotomic myomectomy, is a valid alternative solution for obtaining rapid hemostasis and consequently intraoperative and postoperative bleeding. Furthermore, we suggest that a lower inflammatory peritoneal state is probably correlated with the barrier effect of the patch on the suture.

C-reactive protein "at first sight": Standard postoperative trend in gynecological surgery and a comparative analysis with white blood cell levels.

OBJECTIVE: There is a lack of information about the normal trend of C-reactive protein (CRP) blood levels in the postoperative days after gynecological benign surgery. We investigated the impact of different surgical techniques on CRP trend. We performed a comparative analysis between a CRP and white blood cell (WBC) trend in postoperative monitoring. METHODS: We studied 207 surgical patients for benign gynecological pathology. We analyzed CRP and WBC levels after surgery in the total number of women and separately by approaches. RESULTS: CRP mean log scores showed a typical behavior. Moreover, results from chi-square test underline that the proportion of women with this result is independent from the type of surgery they underwent. Log score mean values of CPR differed between all groups and between times. No difference in the mean number of white cells between the second and the third day was found, as observed for CRP. CONCLUSIONS: Our study shows a trend reference model in postoperative monitoring of patients with benign gynecological surgery. The comparative analysis between the CRP and WBC trend in the postoperative days provided us data demonstrating the superiority of CRP in postsurgical patient outcomes monitoring.

Role of Protopine and Nuciferine in the Management of Nocturia, Urgency, and Dysuria in Pre- and Postmenopausal Women: A Prospective Pilot Study.

OBJECTIVES: Nocturia was commonly treated with drugs burdened with high costs and numerous side effects; in fact, more than 70% of patients drop out of long-term treatment. Protopine and nuciferine are two alkaloids that have different effects on the neurotransmitter receptors involved in the regulation mechanism of the onset of urinary stimuli. The aim of the study was to evaluate the efficacy in controlling primarily nocturia and secondarily urgency and dysuria after 3 months of treatment with combination therapy of protopine and nuciferine syrup. DESIGN: This is a prospective cohort study in which all patients were diagnosed with overactive bladder syndrome (OAB) and the presence of the following symptoms: nocturia, urgency, and dysuria. Thirty patients were administered 10 mL/die (16.6 mg of nuciferine, 0.09 mg of protopine) of syrup for 3 months. Patients were evaluated at baseline (T0) with the International Consultation on Incontinence Questionnaire (ICIQ), Visual Analogue Scale (VAS) for the evaluation of dysuria, Patient Perception of Intensity of Urgency Scale (PPIUS) and at 3 months (T1) with the Patients' Global Impression of Change (PGI-C) scale, PPIUS, VAS, and ICIQ. PARTICIPANTS: Women with diagnosis of OAB; the presence of nocturia, urgency, and dysuria symptoms agreeing to undergo treatment and compiling informed consent; and the absence of contraindications to the use of active ingredients were included in the study. SETTING: Patients were recruited at T0 during the visit to the Uro-Gynecology clinic of the University of "Campus Bio-Medico" and visited again 3 months (T1) after the initiation of therapy. METHODS: We explored survey data by descriptive statistics: in particular, continuous values (i.e., ICIQ) have been summarized by mean and standard deviation of discrete ordinal values (i.e., VAS, PPIUS, and bladder diary parameters at T0 and T1) by median, minimum, and maximum reported scores. Where we could assume normality in distribution, assessed by the Shapiro-Wilk test and the evaluation of the QQ plot, we compared the observation of T0 and T1 with the paired Student's t test; otherwise, we tested differences in distribution with the paired Mann-Whitney U test. RESULTS: Thirty patients completed a 3-month therapy. The ICIQ and VAS questionnaires for the assessment of dysuria, both, reported an improvement in dysuria at T1 (p < 0.001). The PPIUS questionnaire reported an improvement in urinary urgency at T1 (p < 0.001). The PGI-C scale in T1 indicated an improvement in symptoms: 93% for nocturia, 70% for urinary urgency, and 63% for dysuria. LIMITATIONS: The weaknesses of this study are the small number of patients; as a pilot study, the study design was not randomized with a placebo and without blinding; and the short follow-up. CONCLUSIONS: Protopine and nuciferine can be an interesting alternative to primarily treat and reduce nocturia episodes, in addition to improving OAB-related urgency and dysuria.

Efficacy of termoablative fractional CO2 laser (Monnalisa Touch) in stress urinary incontinence.

PURPOSE: Usually, in stress urinary incontinence (SUI), nonsurgical therapy such as pelvic floor muscle training (PFMT) and lifestyle changes are proposed before surgical treatment. Laser therapy has recently been recommended for the treatment of SUI, helping to reconstruct the collagen that supports the vagina and the pelvic floor. The aim of the study was to evaluate the efficacy of SUI treatment with a CO2 intravaginal laser in patients waiting for anti-incontinence surgery (TVT-O). METHODS: This is a prospective, case-control study. Fifty-two patients have been included in our study and we divided them into two groups: atrophy and no atrophy. We also adopted a control group retrospectively identified from our database of patients undergoing PFMT. The subjective estimation of SUI symptoms before and after treatment was evaluated using the Visual Analog Scale before and after 1, 6, and 12 months of treatment. The objective evaluation with the urodynamic study with the stress test and a 3-day voiding diary to count the number of episodes of incontinence, before and after treatment. RESULTS: The intravaginal CO2 laser improved all the parameters considered for SUI in both groups. Its results were more relevant in the atrophy group, in comparison to the no atrophy group, even if they were both statistically significant. There were no statistically significant differences for all the parameters evaluated for SUI between laser treatment and PFMT in the control group. CONCLUSION: The CO2 laser is well-tolerated, minimally invasive, safe, and showing efficacy for SUI. More studies are needed to consider it as first-instance therapy, like PFMT, or at least, as a bridge therapy to surgery.

The Utility of CO2 Laser Treatment of Pelvic Symptoms in Women with Previous Perineal Trauma during Delivery.

This study aimed to examine the impact of fractional CO2 laser treatment of pelvic symptoms in women who have undergone perineal trauma from vaginal delivery. It was a retrospective, monocentric analysis that encompassed all women assessed for pelvic discomfort or signs of vulvovaginal atrophy following vaginal delivery between 2013 and 2018. The severity of symptoms was assessed using the Visual Analogue Scale (VAS). Twenty-seven patients met the inclusion criteria and were sorted into two groups: (1) women who had undergone episiotomies during labor (n = 11); and (2) women who had experienced spontaneous tears during vaginal delivery (n = 16). For women with episiotomies, each treatment and subsequent evaluation consistently showed a significant reduction in dyspareunia intensity. A similar positive trend was observed regarding pain at the introitus (7.5 vs. 6.5 after the first treatment, p = 0.03; 6.5 vs. 3 after the second treatment, p = 0.01; 3 vs. 1 after the third treatment, p = 0.01). Among women experiencing spontaneous perineal tears during delivery, there was a notable decrease in dyspareunia following all treatments (8 vs. 7 after the first treatment, p = 0.01; 8 vs. 4 after the second treatment, p = 0.02; 3 vs. 1 after the third treatment, p = 0.03). The impact of laser treatment did not exhibit significant differences between women who underwent episiotomies and those who experienced spontaneous perineal tears. In conclusion, fractional CO2 laser can be regarded as a non-pharmacological option for managing pelvic floor symptoms in women who encountered perineal trauma during delivery, independently from the nature, spontaneity, or iatrogenesis of the perineal laceration.

Recommendations for the treatment of vulvar cancer in settings with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Due to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed. Methods: The panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care. Results: Consensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations. Conclusion: The development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care.

Early Mini-Invasive Treatment of Persistent Cervical Dysplasia: Clinical Outcome and Psycho-Relational Impact.

Introduction: After the diagnosis of L-SIL, 77. 3% had a persistent infection and anomalous Pap Test results. Many of these patients had highlighted psychological consequences such as anxiety, hypochondria, fear of cancer, and sexual problems. Several studies suggested that the clearance of HR-HPV infection could be accelerated by cervical excisional procedures, especially in L-SIL. In consideration of the psychological implications for HPV infection and related dysplasia in patients with CIN1 at PAP-smear and HR-HPV positivity at least for 6 months, we decided to plan a prospective study where we tried to anticipate excisional cervical using a minimally invasive treatment: thin loop electrosurgical excision procedure (t-LEEP). This study aims to analyze the clearance of HR-HPV after 6 and 12 months, clinical outcomes related to t-LEEP, and the psycho-relational impact at 12 months after t-LEEP. Materials and Methods: We enrolled patients with the diagnosis of L-SIL at PAP-smear and HR-HPV positivity with a persistent CIN 1 (at least for 6 months), confirmed by cervical biopsy. All enrolled patients underwent t-LEEP. We followed prospectively and performed for all patients the HPV DNA test at 6 (T1) and 12 months (T2) and STAI-Y and FSFI scores at T0 and T2. Results: We prospectively enrolled 158 patients, 22 are excluded for the established criteria. Patients with HR-HPV and CIN 1 lesions treated with t-LEEP had an overall clearance of 83.8% at T2. In subgroups analysis at T2, we had a regression: in smoker 71.8%, in contraceptive users 69.5%, in patients aged <25 years 100%, aged 25-30 years 85%, aged 30-35 years 94.4%, aged 35-40 years 92%, and aged ≥40 years 89.1%, in HPV-16 96.4%, in HPV-53 89.5%, in HPV-18 87.5%, in HPV-31 86.6%, and in coinfected 3.5%. STAI-Y and FSFI after t-LEEP (T2) were statistically significant, reducing anxiety status and improving sexual function. Conclusion: Based on these results, the use of t-LEEP in patients with persistent CIN 1 and HPV-HR at least for 6 months could be useful for accelerating HPV-HR clearance, in particular, for a subpopulation patient with an increased risk of progression and/or patients with psychological and sexual consequences of carrying an HR-HPV infection.

Assessing the role of minimally invasive radical hysterectomy for early-stage cervical cancer.

Surgery is the mainstay of treatment in the management of early-stage cervical cancer. Until the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, minimally invasive radical hysterectomy was the recommended approach to treat patients with early-stage disease. The results of the LACC trial questioned the adoption of minimally invasive surgery in cervical cancer. In comparison with the open approach, minimally invasive surgery correlated with worse disease-free and cancer-specific survival. Similarly, other retrospective studies highlighted this correlation, thus corroborating the results of the LACC trials. In the present review, we evaluated current evidence and further prospective of the adoption of minimally invasive radical hysterectomy in cervical cancer. Moreover, we sought to assess some unsolved issues regarding the role of minimally invasive surgery in early-stage cervical cancer patients.