Urological Complications in Radical Surgery for Cervical Cancer: A Comparative Meta-Analysis before and after LACC Trial.

BACKGROUND: After the LACC trial publication in 2018, the minimally invasive approach (MIS) has severely decreased in favor of open surgery: MIS radical hysterectomy was associated with worse oncological outcomes than open surgery, but urological complications were never extensively explored in pre- versus post-LACC eras, even if they had a great impact on post-operative QoL. The purpose of this meta-analysis is to compare functional and organic urological complication rates before and after LACC trial. METHODS: An independent search of the literature was conducted 4 years before and after the LACC trial and 50 studies were included. RESULTS: The overall rate of urologic complications was higher in pre-LACC studies while no differences were found for organic urological complications. Conversely, the overall risk of dysfunctional urological complications showed a higher rate in the pre-LACC era. This is probably related to a sudden shift to open surgery, with potential lower thermal damage to the urinary tract autonomic nervous fibers. CONCLUSIONS: This meta-analysis showed that the incidence of urological complications in radical cervical cancer surgery was higher before the LACC trial, potentially due to the shift to open surgery. Nevertheless, further studies are needed to shed light on the connection between minimally invasive surgery and urological damage.

Percutaneous-assisted laparoscopy for ovarian tissue cryopreservation: a single-center experience.

PURPOSE: To compare surgical and post-operative outcomes of patients submitted to traditional laparoscopy and percutaneous-assisted laparoscopy for ovarian tissue explant for cryopreservation. METHODS: This is a single-center retrospective comparative study conducted in IRCCS "Regina Elena" National Cancer Institute of Rome. Patients submitted to laparoscopic excision of ovarian tissue, before starting chemotherapy were enrolled. We compared the classic laparoscopic approach vs percutaneous-assisted laparoscopy, using the Percuvance grasping forceps. RESULTS: Fifty-nine young oncologic women were enrolled; 38 underwent a conventional laparoscopy (LAP), 21 received a percutaneous laparoscopy (PERC). The baseline characteristics were similar in both groups, furthermore no differences were found in terms of peri-operative complications, median estimated blood loss (p = 0.4), operative time (p = 0.2), recovery times (p = 0.1), median time to chemotherapy (p = 0.7), median area of collected samples (p = 0.9). The postoperative pain evaluated by VAS-score, was significantly lower in the PERC group vs LAP group, both the day of surgery (range 0-4 vs 0-2; p = 0.02) and after 1 (range 0-3 vs 0-2; p = 0.002) and 2 days (range 0-3 vs 0-1; p = 0.0001). Moreover, better aesthetic results were detected in the PERC group, 2 months after surgery (median 9 vs 10, range 7-10 vs 9-10; p = 0.0001). CONCLUSIONS: Percutaneous-assisted laparoscopy has proven to be an effective and safe procedure for the excision of ovarian tissue for cryopreservation, in young oncologic patients that want to preserve their fertility. The percutaneous procedure appears superior to conventional laparoscopy in terms of aesthetic outcomes and post-operative pain reduction. CLINICAL TRIAL ID: NCT05134090, 24th Nov 2021, retrospectively registered.

Orally Administered Combination of Hyaluronic Acid, Chondroitin Sulfate, Curcumin, and Quercetin in the Prevention of Postcoital Recurrent Urinary Tract Infections: Analysis of 98 Women in Reproductive Age After 6 Months of Treatment.

OBJECTIVE: The aim of this study is to assess the efficacy of orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin for the prevention of postcoital recurrent urinary tract infection (UTI) in reproductive age women. METHODS: Ninety-eight consecutive patients in reproductive age affected by UTI were considered for the study. All 98 patients received a combination of HA, CS, curcumin, and quercetin two tablets per diem for the first month and one tablet every day for the next 5 months. We investigate recurrence of UTI with the Urinary Tract Infection Symptoms Assessment and the Pelvic Pain and Urinary Urgency Frequency. The quality of life and sexual function were valued using 36-Item Short Form Survey, Female Sexual Function Index, and the Female Sexual Distress Scale questionnaires. The same investigations were performed at the first visit and after 6 months of treatment. RESULTS: The symptoms associated with UTI significantly decreased after 6 months of treatment, in particular dysuria episodes diminished and number of voiding decreased (P < 0.0001). During the treatment period, only seven patients (7.1%) experienced a UTI recurrence, confirmed by positive urine culture with bacteriuria of greater than 10 colony forming units/mL. The Pelvic Pain and Urinary Urgency Frequency, Female Sexual Function Index, Female Sexual Distress Scale, and 36-Item Short Form Survey showed a statistically significant improvement after 6 months. CONCLUSIONS: Oral administration of a combination of HA, CS, curcumin, and quercetin is a valid and well-tolerated nonantibiotic treatment for prevention of postcoital UTI in reproductive age women.

Usefulness of Ospemifene in the treatment of urgency in menopausal patients affected by mixed urinary incontinence underwent mid-urethral slings surgery.

The aim of this study was to assess the effectiveness and safety of Ospemifene in the improvement of urgency component in women affected by mixed urinary incontinence (MUI) who underwent surgery with mid-urethral sling (MUS). Eighty-one patients with MUI underwent surgical intervention with MUS were enrolled. After surgical intervention 38 patients received Ospemifene 60 mg one tablet daily per os for 12 weeks. Physical examination, 3-day voiding diary, urodynamic testing were performed at the start and the follow-up after 12 weeks in the Trans-Obturator-Tape (TOT)-Alone group and TOT-Ospemifene. Patients completed the Overactive Bladder Symptom and Health-Related Quality of Life Short-Form (OAB-Q SF), International Consultation on Incontinence Questionnaire (ICIQ-UI-SF), and King' s Health Questionnaire (KHQ). A significant difference between the two groups was observed in peak flow (ml/s), in first voiding desire (ml), in maximum cystometric capacity (ml), and in detrusor pressure at peak flow (cmH2O) at urodynamic evaluation. A significative difference between the two groups at voiding diary was observed in the mean number of voids, urgent micturition episodes/24 h, urge urinary incontinence, and in nocturia events. The OAB-Q symptoms and OAB-Q (HRQL) scores after 12 weeks showed a significative difference between the two groups. Ospemifene is an effective potential therapy after MUSs in women with MUI improving urgency symptoms and quality of life.

Long-term experience of vaginal vault prolapse prevention at hysterectomy time by modified McCall culdoplasty or Shull suspension: Clinical, sexual and quality of life assessment after surgical intervention.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of modified McCall culdoplasty or Shull suspension in preventing vaginal vault prolapse after vaginal hysterectomy and the long-term impact on quality of life and sexual function. STUDY DESIGN: Retrospective analysis in 414 patients underwent vaginal hysterectomy for pelvic organ prolapse (POP) and vaginal suspension through modified McCall culdoplasty (group A) or Shull suspension (group B) was evaluated. Clinical features and concomitant surgical procedures were assessed. Surgical data and perioperative and postoperative complications have also been analyzed. Clinical characteristics, urinary symptoms, POP-Q score classification, Quality of Life and Sexual Function were evaluated at baseline and at median follow up with P-QoL, ICIQ-UI-SF, PISQ-12, FSFI, FSDS questionnaires. RESULTS: The median follow up was 8.9 year (5.1-14.2 years). 200 women in group A and 214 in group B were evaluated. Vaginal vault prolapse occurred in 2 patients in group A and in 2 patients in group B. POP-Q score for all compartments showed a significant (p < 0.001) decrease for both groups without significant differences between the 2 groups. The total vaginal length (TVL) was reduced in greater proportion in McCall group (p < 0.001). P-QoL and ICIQ-UI-SF questionnaires documented an improvement for both groups (p < 0.001). The number of patients who regularly practice sexual activity increased in both groups, but patients in group B experienced a better quality of sexual life evaluated with PISQ-12 and FSFI. CONCLUSIONS: Both surgical techniques showed effectiveness and safety in preventing vaginal vault prolapse in women who underwent vaginal hysterectomy, with a significant improvement in quality of life and sexuality. Shull technique demonstrated greater improvement in sexual function.

Overactive bladder syndrome treatment with ospemifene in menopausal patients with vulvovaginal atrophy: improvement of sexuality?

The aim of this study was to assess the effectiveness of ospemifene in the improvement of sexual function in postmenopausal women with vulvovaginal atrophy (VVA) affected by overactive bladder syndrome (OAB) or urge urinary incontinence (UUI). One hundred five postmenopausal patients with VVA affected by OAB and/or UUI were enrolled for the study. All patients received ospemifene 60 mg for 12 weeks. Clinical examination, 3-d voiding diary and the vaginal health index (VHI) were performed at baseline and at 12 weeks. Patients completed the OAB-Q SF, FSFI, FSDS, and SF-36 questionnaires. The patient's satisfaction was also calculated. After 12 weeks, the reduction of urinary symptoms was observed. The OAB-Q symptoms, OAB-Q (HRQL) score were (55.34 ± 13.54 vs. 23.22 ± 9.76; p < .0001) and (22.45 ± 9.78 vs. 70.56 ± 15.49; p < .0001), before and after treatment. SF-36 questionnaire showed a significant improvement (p < .0001). VHI score increased and the women who regularly practice sexual activity increased after treatment. The total FSFI score increased significantly and the FSDS score changed after 12 weeks (p < .0001). The PGI-I after 12 weeks showed a total success rate of 90.5%. Ospemifene is an effective potential therapy for postmenopausal women with VVA affected by OAB or UUI improving sexual function and quality of life.

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

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

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

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

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

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

Management of HPV-related cervical disease: role of p16INK4a immunochemistry. Review of the literature.

This systematic review of 43 studies aims to evaluate the absolute and relative sensitivity and specificity of p16INK4a with regard to uterine cervix lesions, describing innovations and techniques for the detection of high-grade cervical dysplasia and allowing correct treatment. Studies were identified in the PubMed database up to March 2015. The keywords hrHPV, p16INK4a gene, and uterine cervical disease (MeSH terms) were used. Only English-language articles were included. We considered retrospective and prospective studies that assessed p16INK4a or p16INK4a/Ki67 staining, with or without HPV-DNA testing (HC2/PCR) as a comparator test, in cytological/histological specimens for which the diagnosis of ASCUS, LSIL or HSIL was verified with a reference standard. The primary outcome for cervical lesions was evaluation of the absolute p16INK4a immunoreactivity; the secondary outcome was evaluation of the relative p16INK4a immunoreactivity versus HPV testing in those studies where comparator tests were available. p16INK4a was more specific than HPV-DNA test (median values of 56.1% vs. 52.25% in CIN grade ≥2 lesions; 82.5% vs. 53% in negative and CIN grade ≥1 lesions). The main limitation of this study is linked to both qualitative and quantitative p16INK4a levels of expression, while the second limitation is the lack of standardized scales. p16INK4a and HPV-DNA used together increased the sensitivity and negative predictive value for CIN detection. p16INK4a can be considered a biomarker of CIN2 or CIN3, indicating a high risk of relapse or evolution to invasive carcinoma. Also p16INK4a-negative CIN should be considered and further research should be performed.

Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.

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

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