Old Issues and New Perspectives on Endometrial Cancer Therapy: How Molecular Characteristics Are Changing the Therapeutic Pathway.

The Cancer Genome Atlas (TCGA) has radically changed the history of endometrial cancer by outlining a new classification, based on its molecular characteristics. In the field of oncology, we are approaching the new era of molecular biology, particularly regarding endometrial cancer, with the increasing importance of targeted therapy. This paper is a review of phase III randomized controlled trials published in English between January 2019 and December 2023, comparing drugs of interest with standard adjuvant treatment and molecular subtypes in endometrial cancer. The use of immunotherapy alone or in combination with chemotherapy as therapy in patients with recurrent or advanced primary or metastatic endometrial cancer significantly improves the prognosis of these patients. The results show greater efficacy of all proposed treatments for mismatch repair deficiency (dMMR/MSI-H) patients compared to mismatch repair proficiency (pMMR) patients. Progression-free survival (PFS) and overall survival (OS) are better in dMMR patients in all studies analysed. Immunotherapy has the potential to revolutionize the gynaecological cancer treatment landscape, offering a new pathway and new hope for endometrial cancer patients, improving their outcomes in the future. Given the exciting results obtained in dMMR/MSI-H patients, MMR status should be investigated in every patient with advanced endometrial cancer at the time of diagnosis.

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.

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.

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.

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.

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.

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.

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.

Tailoring parametrectomy for early cervical cancer (Stage IA-IIA FIGO): a review on surgical, oncologic outcome and sexual function.

INTRODUCTION: Cervical cancer is currently one of the most common cancers afflicting the female population worldwide and in industrialized countries the presence of screening and a specific diagnostic and therapeutic process has favored early diagnosis of cervical cancer. In literature have found that reducing the radicality on the parametria in early cervical cancer (ECC), reduces complications without impacting oncological outcomes, but the data in the literature are not yet clear. EVIDENCE ACQUISITION: Searching on PubMed, we included 1473 articles from January 1974 to 2020. We identified all the studies that compared different type of radical hysterectomy in the primary surgical treatment of ECC. 16 articles were elected for the review. EVIDENCE SYNTHESIS: Modified radical hysterectomy (Piver II/Querleu-Morrow Type B) in ECC, if compared to CRH (Piver III/Querleu-Morrow Type C2), is not associated with worse cancer outcome and patient survival, but it is associated with a minor operating time, lower blood loss and minor bladder dysfunction. Nerve sparing radical hysterectomy approach (NSRH/Querleu-Morrow Type C1) compared to CRH (Piver III/Type C2) in the ECC, with our data we can confirm a non-inferiority regarding the oncological outcome. CONCLUSIONS: Reduced radicality on the parametrium offers positive effects on the quality of life (sexual life and bladder function) of patients without impacting on survival, oncological outcome.

Sentinel lymph node in cervical cancer: a literature review on the use of conservative surgery techniques.

INTRODUCTION: Sentinel lymph node detection is a surgical procedure that allow to avoid systematic lymphadenectomy in those tumors in early stage where lymph node spread is not sure. If the sentinel lymph node is not involved by tumor in 98-99% of case other lymph nodes are clean. The reason why less radical surgery is chosen is linked to the lower postoperative morbidity rate, the risk of lower limb lymphedema decreases. The aim of this review was to summarize what is the state of art of using the sentinel lymph node dissection (SLD) technique and what are the future goals to improve the safety and the reliability. EVIDENCE ACQUISITION: We have conducted a review of the literature of the past 10 years to understand the attitudes of oncologist gynecologists in the world to the conservative treatment of cervical cancer. We only selected articles from 2010 onwards, which meet the inclusion criteria. EVIDENCE SYNTHESIS: The detection rate varies from 83% to 100%. The bilateral detection rate, on the other hand, varies from 42% to 100%. The false negative rate ranges from 4% to 12%. Sensitivity varies from 20.7% (considering the frozen section) to 100%. CONCLUSIONS: Indocyanine green is the most reliable and performing tracer for the search of the sentinel lymph node; that the false intraoperative negative rate is too high to be sure not to subject the patient to an incorrect therapeutic procedure; data concerning the safety and survival of conservative lymphadenectomy (SLND) compared to systematic lymphadenectomy are still lacking in the literature and therefore we are awaiting the results of the two ongoing randomized clinical trials that will allow us to have more significant scientific data.

Effectiveness of CO2 laser on urogenital syndrome in women with a previous gynecological neoplasia: a multicentric study.

BACKGROUND: Many women diagnosed with gynecological cancers undergo adjuvant therapy, which may lead to transient or permanent menopause that ultimately leads to urogenital syndrome and vulvovaginal atrophy. Studies advise against the use of estrogen in women with a history of hormone-dependent cancer. One alternative is vaginal microablative fractional CO2 laser, which promotes tissue regeneration through the production of collagen and elastic fibers. OBJECTIVE: To evaluate the effectiveness of CO2 laser in the treatment of urogenital syndrome-in particular, symptomatic vulvovaginal atrophy in women who have survived gynecological cancers. METHODS: A retrospective study was carried out, including all patients with a history of gynecological cancers and vulvovaginal atrophy who underwent CO2 laser treatment between November 2012 and February 2018 in four Italian centers. The study was approved by the local ethics committee of each participating institution. The inclusion criteria were women aged between 18 and 75; Eastern Cooperative Oncology Group performance status <2; and history of breast, ovarian, cervical, or uterus cancer. Patients had to have vulvovaginal atrophy and at least one of the following symptoms of urogenital syndrome: vaginal dryness, dyspareunia, vaginal introitus pain, burning, or itching. Three applications were administered at baseline, 30 days, and 60 days. All patients were evaluated before the first laser session, at each session, and 4 weeks after the last session. In particular, patients were asked to indicate the intensity of symptoms before the first session and 4 weeks after the last session, using Visual Analog Scale (VAS) scoring from 0 ('no discomfort') to 10 ('maximum discomfort'). RESULTS: A total of 1213 patients underwent CO2 laser treatment and of these, 1048 were excluded because they did not meet the inclusion criteria in the analysis. Finally, a total of 165 patients were included in the study. The mean age at the time of treatment was 53 years (range 31-73). Dryness improved by 66%, dyspareunia improved by 59%, burning improved by 66%, pain at introitus improved by 54%, and itching improved by 54%. The side effects were evaluated as pain greater than VAS score 6 during and after the treatment period. No side effects were seen in any sessions. CONCLUSIONS: Fractional microablative CO2 laser therapy offers an effective strategy in the management of the symptoms of genitourinary syndrome in post-menopausal women and in survivors of gynecological cancer.

Efficacy of fractional CO2 laser treatment in postmenopausal women with genitourinary syndrome: a multicenter study.

OBJECTIVE: Genitourinary syndrome of menopause (GSM), especially vulvovaginal atrophy (VVA), is one of the most common conditions among women in either natural (4%-47%) or medically induced (23.4%-61.5%) menopause. The aims of this study are to assess the efficacy and effectiveness of CO2 laser in postmenopausal women with clinical signs and symptoms of GSM, in particular VVA, and to evaluate both possible early and late side effects related to this kind of treatment. METHODS: This retrospective, multicenter study was conducted after collecting data from a pre-existing database. We performed three to four CO2 laser treatments on all the women enrolled in this protocol. We used a fractional CO2 laser system (SmartXide VLR, Deka m.e.l.a., Florence, Italy) with a VulvoVaginal Laser Reshaping (VLR) scanning system and appropriate handpieces for the vaginal area. All women before and after the treatment were assessed. The pre- and post-treatment averages of the symptoms, the standard deviation, and the P values were calculated. RESULTS: Six hundred forty-five women who met the inclusion criteria were considered. In all the parameters examined (dyspareunia, vaginal orifice pain, dryness/atrophy, itching, burning, pH) statistically significant data were found between the pretreatment and the post-treatment (dryness: before = 8.30, after = 2.97 [P < 0.0001], dyspareunia: before = 8.70, after = 3.51 [P < 0.0001]; burning: before = 6.12, after = 1.78 [P < 0.0001]; vaginal orifice pain: before = 8.07, after = 2.94 [P < 0.0001]; itching: before = 6.09, after = 1.32 [P < 0.0001]). CONCLUSIONS: Our results show the effectiveness and a good degree of tolerance of treatment with the CO2 laser system in postmenopausal women with GSM.

Ovarian cancer relapse: From the latest scientific evidence to the best practice.

Ovarian cancer (OC) is the fifth most common cause of cancer death in women worldwide. Despite treatment options have continued to improve in recent years, the recurrence rate is still high; in fact around 80% of patients relapses within 18 months. Recently, the scientific landscape is agree in asserting that the ovarian cancer is not a single disease but the outcome of patients depends from the molecular and biological characterization of tumor tissue. In this scenario, molecular targeted therapy given alone or in combination with chemotherapy is showing significant results. We review the different options for the treatment of ovarian cancer recurrence, including the role of surgery, in order to try outlining a possible treatment algorithm evaluating the recent scientific literature and the most important trials.

Role of human epididymis protein 4 (HE4) in detecting recurrence in CA125 negative ovarian cancer patients.

OBJECTIVE: There are no current guidelines regarding evaluation of patients with normal CA125 at initial diagnosis during routine surveillance after completion of treatment. Thus, the purpose of this study was to evaluate the role of human epididymis protein 4 (HE4) in the detection of recurrence in patients with ovarian cancer and a negative CA125 at diagnosis. METHODS: All patients with ovarian cancer with a negative CA125 referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were included in the study. Inclusion criteria were: age between 18 and 70 years old, diagnosis of epithelial ovarian cancer, optimal primary surgery (residual tumor <1 cm), and normal CA125 at initial diagnosis. Patients with other malignancies or chronic diseases were excluded from the study. Statistical analysis was based on the calculation of percentages, means, medians, and ranges of the values. RESULTS: A total of eight patients were included in the study. The median age was 53 years (range 40-75). All patients had a normal CA125 at initial diagnosis while seven (87.5%) patients had abnormal HE4 levels at diagnosis. The International Federation of Gynecology and Obstetrics (FIGO) stages at enrollment varied from IC to IIIC (IB (1), IC (3), IIC (1), IIIC (3)). The most common histologic subtype was serous (62.5%). Seven patients recurred and had abnormal HE4 and normal CA125 values. The median HE4 at recurrence was 107 pmol/L. The median disease-free interval was 55 months (range 5-108) and all the patients underwent optimal cytoreductive surgery. CONCLUSIONS: HE4 levels may serve as a marker for recurrence in patients with a normal CA125 at initial diagnosis. Future studies are needed to evaluate the role of HE4 levels in earlier detection of recurrent ovarian cancer.

The role of human epididymis protein 4 as a biomarker in gynecologic malignancies.

INTRODUCTION: The serum levels of glycoprotein human epididymis protein 4 (HE4) have been widely investigated in patients with ovarian cancer as a tumor marker to differentiate benign gynecological tumors from ovarian cancers (OC). A few studies demonstrated the promising role of HE4 in endometrial cancer (EC) too. The aim of this review is to provide an outline of published studies investigating HE4 in the diagnosis of gynecologic malignancies, focusing on its role in OC and EC. EVIDENCE ACQUISITION: We conducted a systematic review of literature from January 1952 to June 2018 on the role of HE4 in OC and EC focusing on the diagnostic power in terms of sensitivity and specificity. EVIDENCE SYNTHESIS: We identified 49 articles with an overall sample size of 12,631 patients in OC group and five studies with an overall sample size of 1221 patients in EC group. We stated that HE4 had a pooled sensitivity of 78% and specificity of 86% in the detection of borderline or malignant OC and a pooled sensitivity of 78.8% and specificity of 100% in EC diagnosis. CONCLUSIONS: This systematic review confirms the importance of HE4 in the diagnosis of epithelial ovarian cancer and its promising role in endometrial cancer (endometrioid histology).

The role of macroplastique implantation in the management of occult urinary stress incontinence.

OBJECTIVE: Pelvic floor disorders, in particular pelvic organ prolapse (POP) and stress urinary incontinence (SUI), are common in women. There is a described higher risk to develop postoperative SUI also in preoperatively continent women: this happens because in 30% of women the relief of the urethral obstruction caused by prolapse, unmasks a pre-existing compromised urethral function and thus an "occult" or potential SUI. The aims of this study were to evaluate the role of Macroplastique® implant, TVT-O or surgery alone in the management of occult urinary stress incontinence during prolapse surgery in terms of success rate and adverse events. STUDY DESIGN: We enrolled 47 consecutive patients scheduled to vaginal prolapse surgery who did not report symptoms of stress incontinence. We collected surgical data, success and complication rates. Moreover we compared all the data with retrospective ones regarding surgery plus concomitant TVT-O (39 pts) and surgery alone (41 pts). RESULTS: At 12-months follow-up, we reported a success rate of 87,2% in the "macroplastique group", comparable to the "surgery plus TVT-O group", with a statistically significant difference in comparison to the "surgery alone" group. "Surgery + TVT-O" group reported a higher rate of major complications (p<0,01) in comparison to the other groups. CONCLUSIONS: Postoperative SUI prevention at the time of prolapse repair remains a challenging issue. In selected patients, Macroplastique may play an interesting role having a good success rate and a low complication rate and for these reasons it may be proposed as A concomitant procedure during POP surgery.

Implementing the Risk of Endometrial Malignancy Algorithm (REM) adding obesity as a predictive factor: Results of REM-B in a single-center survey.

OBJECTIVE: In 2013, our group assessed a risk stratification tool of endometrial cancer (EC), called REM (Risk of Endometrial Malignancy). A well known risk factor for EC is body mass index (BMI). In fact, (BMI > 30 and <35 kg/m2) and severe obesity (BMI > 35 kg/m2) were associated with a 2.6-fold and a 4.7-fold increase in EC risk, respectively. Therefore, in the present study we aim to improve the performance of REM, including BMI and developing a new scoring system, called REM-B (Risk of Endometrial Malignancy score associated to BMI), to classify patients into high risk or low risk groups for EC. STUDY DESIGN: Women, between 45 and 80 years, diagnosed with ultrasound endometrial abnormalities and scheduled to have surgery were enrolled on a prospective study at Department of Gynaecologic Oncology of Campus Bio-Medico of Rome. Preoperative clinical, ultrasound and laboratory features were taken into account. RESULTS: A total of 675 patients (88 with EC and 587 with benign endometrial disease) were divided in training set (TS) and verification set (VS). Age, symptom, BMI, HE4 levels and ultrasound endometrial thickness were found statistically significant and included into multivariate logistic regression model in order to determine the probability to have EC. REM-B showed an overall sensitivity of 94.7% (versus 92% of REM) and a specificity of 97.4% (versus 96% of REM). CONCLUSIONS: Our data support the use of REM-B to triage patients into low and high risk of EC, even if an external validation of model is needed.