Analysis of surgical outcomes and learning curve of surgical parameters for robotic hysterectomy: a comparison between multiport versus single-site.

Introduction: The primary goal is to analyze the learning curve of surgical parameters (docking, operation and console time) between multiport and single-site robotic hysterectomy techniques, performed by expert laparoscopic surgeons.Material and methods: The trial is a retrospective analysis of 229 patients enrolled between 2010 and 2018 who underwent robotic hysterectomies with bilateral salpingo-oophorectomies (HBSO) for gynecological diseases.Results: Surgical parameters, learning curve and surgical outcomes were analyzed in order to evaluate the transition from multiport to single-site programs, performed by non-expert surgeons using the multiport technique. All surgical times (total, docking and console time) were shorter in the multiport robotic hysterectomy group, while the intraoperative complication rate was lower in the robotic single-site hysterectomy group (p = 0.007). The learning curve of operative, console and docking time significantly decreased more in the robotic-single site hysterectomy group, than in the multiport robotic hysterectomy group over time (p value < 0.001).Conclusions: The direct transition from the laparoscopy program to the single-site approach is feasible and effective in HBSO performed by expert laparoscopic surgeons. The learning curve of robotic single-site hysterectomy shows that the proficiency in this technique requires more cases than the multiport robotic hysterectomy cases and needs more time to fit the surgical step to the single-site platform.

Cytokines and chemokines levels in primary HPV infection: a pilot study.

The purpose of the study was to compare cytokines (CK) and chemokines concentrations in blood and cervico-vaginal samples between human papillomavirus (HPV)-positive and HPV-negative women, who had no previous history of HPV infection. A case-control study compares the activity and the concentration of CK/chemokines between 19 HPV-positive and 22 HPV-negative women matched by age. Plasma and cervico-vaginal levels of CK and chemokines were measured using cytofluorimetric analysis and expressed as mean of percentages. Plasma rates of interleukin (IL)-6 were significantly greater in HPV-negative women (mean value of 5.20±4.79 pg/ml) in comparison with HPV-positive women (mean value of 2.57±3.09 pg/ml) (p = 0.001). On the contrary, plasma levels of Eotaxin and hMCP-1 were significantly higher in HPV-positive women, with a mean value of 13.87±4.54 pg/ml (p = 0.022) and 53.53±19.51 pg/ml (p = 0.005), respectively. Differences in cervico-vaginal CK/chemokines concentrations were statistically not significant. Difference in plasma concentrations of IL-6, Eotaxin, IL-1ß and hMCP-1 was statistically significant even by analyzing HPV-16/18 and multiple HPV genotypes infections. Primary HPV infection shows a characteristic pattern of plasma CK/chemokines concentration as opposed to HPV-negative subjects and persistent HPV infection. Keywords: chemokines; cytokines; HPV primary infection; plasma pattern.

Single-site Versus Multiport Robotic Hysterectomy in Benign Gynecologic Diseases: A Retrospective Evaluation of Surgical Outcomes and Cost Analysis.

OBJECTIVE: To compare the surgical outcomes and costs of robotic-assisted hysterectomy with the single-site (RSSH) or multiport approach (RH). DESIGN: A retrospective analysis of a prospectively collected database (Canadian Task Force classification II1). SETTING: A university hospital. PATIENTS: Consecutive women who underwent robotic-assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy for the treatment of benign gynecologic diseases. INTERVENTIONS: Data on surgical approach, surgical outcomes, and costs were collected in a prospective database and retrospectively analyzed. MEASUREMENTS AND MAIN RESULTS: The total operative time, console time, docking time, estimated blood loss, conversion rate, and surgical complications rate were compared between the 2 study groups. Cost analysis was performed. One hundred four patients underwent total robotic-assisted hysterectomy and bilateral salpingo-oophorectomy (45 RSSH and 59 RH). There was no significant difference in the indications for surgery and in the characteristics of the patients between the 2 study groups. There was no significant difference between the single-site and multiport approach in console time, surgical complication rate, conversion rate, and postoperative pain. The docking time was lower in the RH group (p = .0001). The estimated blood loss and length of hospitalization were lower in the RSSH group (p = .0008 and p = .009, respectively). The cost analysis showed significant differences in favor of RSSH. CONCLUSION: RSSH should be preferred to RH when hysterectomy is performed for benign disease because it could be at least as equally effective and safe with a potential cost reduction. However, because of the high cost and absence of clear advantages, the robotic approach should be considered only for selected patients.

Effectiveness of aromatase inhibitors in the treatment of advanced endometrial adenocarcinoma.

PURPOSE: Type I endometrial cancer is a common tumor of the female genital tract. Since in post-menopausal women aromatase enzyme can stimulate the endometrial tissue neoplastic growth, the use of aromatase inhibitors may have a therapeutic effect, especially in patients not eligible for surgery. METHODS: A systematic review has been performed, with a very specific scope, i.e., the use of aromatase inhibitors in the treatment of advanced or recurrent endometrial cancer, as a single agent or in combination with others drugs. RESULTS: On the basis of the 117 records retrieved from the bibliographic search, the rationale for the use of aromatase inhibitors in endometrial cancer therapy is discussed. Six papers fall within the scope of our systematic review and their results are thoroughly analyzed. Moreover, we report our experience on the clinical effectiveness of anastrozole in the post-chemotherapy treatment of a patient affected by advanced-stage endometrial cancer. CONCLUSION: In general, aromatase inhibitors seem to have limited clinical benefit in the treatment of advanced and recurrent endometrial cancer, although further clinical trials are necessary to investigate more in depth their role. In our case, we experienced a positive feedback in terms of control of an advanced-stage disease.

The Mucosal Innate Immune Response in Primary Human Papillomavirus Infection: A Pilot Study.

OBJECTIVES: The purpose of the study was to evaluate the mucosal immune response in women affected by primary human papillomavirus (HPV) infection, in comparison with HPV-negative women with no previous history of HPV. METHODS: A case-control study comparing the activity of myeloperoxidase (MPO) and lactoferrin (LF) between 19 HPV-positive and 19 HPV-negative women matched for age. Plasmatic and cervicovaginal levels of polymorphonuclear neutrophils (PMN) exhibiting MPO and LF receptors were measured using cytofluorimetric analysis and expressed as mean of percentages. RESULTS: Cervicovaginal levels of MPO-/LF- PMN were lower among HPV-negative women, with a mean rate of 18.81% (SD, 21.38), as opposed to a mean rate of 35.56% (SD, 21.02) (P = 0.020) in HPV-positive women. A similar significant difference was not proven in plasma. The mean rates of plasmatic levels of MPO-/LF- PMN were 36.21% (SD, 16.87) and 36.93% (SD, 10.54) (P = 0.875) in cases and controls, respectively. All patients were evaluated 1 year later, and only 6 cases became negative. CONCLUSIONS: The presence of MPO-/LF- PMN has been considered as a marker of lower rate of apoptosis of HPV-infected cells. This could explain why HPV-positive women are less capable to deal with a primary infection.

Obstetric risk factors and time trends of neurodevelopmental outcome at 2 years in very-low-birthweight infants: a single institution study.

AIM: To assess the time trends of neonatal survival and infant neurodevelopmental outcome in very-low-birthweight children at 24 months corrected age over a 20-year period. METHOD: The study cohort comprised 857 infants (439 males and 418 females) weighing less than 1500g at birth or delivered before 32 weeks gestational age in the period 1989 to 2008. Neurological examination and cognitive assessment of the infants (Bayley Scales of Infant Development and Griffiths Mental Developmental Scale) were performed at 24 months corrected age. RESULTS: The prevalence of neonatal survival with normal neurodevelopmental outcome increased from 55.3% (104/188) in 1989 to 1993, to 61.4% in 1994-1998 (116/189), 68.3% in 1999 to 2003 (138/202), and 84.5% in 2004 to 2008 (235/278) (annual increase=1%, 95% CI 2.1-4.1; p<0.001). In logistic models, the increase in the rate of normal neurodevelopmental outcome during the periods studied was consistent across the categories of birthweight (≤1000g as opposed to >1000g), gestational age (≤28wks as opposed to >28wks), and clinical characteristics (pre-eclampsia/growth restriction as opposed to spontaneous prematurity/rupture of membranes). INTERPRETATION: The increased rate of normal neurodevelopmental outcome at 2 years among very-low-birthweight infants is independent of obstetric risk factors.

Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS).

The association between vulvodynia and interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic, debilitating disease of unknown etiology, may involve sex hormone-dependent mechanisms regulating vulvo-vaginal health. We aimed to prospectively investigate the effects of 12 weeks of local estrogen therapy (LET) on urinary/bladder and sexual symptoms in premenopausal women with IC/BPS. Thirty-four women (mean age: 36.1 ± 8.4) diagnosed with IC/BPS were treated vulvo-vaginally three-times/week with estriol 0.5 mg cream and tested by validated questionnaires (ICSI/ICPI, pain urgency frequency [PUF], female sexual function index [FSFI]) and by cotton swab testing, vaginal health index (VHI) and maturation index (MI) before and after treatment. Vulvodynia was present in 94.1% of IC/BPS women. A significant positive effect of LET was evident on urinary and sexual function (p < 0.001, for both) following 12 weeks, as well as an improvement of the VHI (p < 0.001) and the MI (p < 0.04). The results of this open study indicate that 12 weeks of local estriol cream at vaginal and vestibular level may ameliorate urinary/bladder pain symptoms, as well as may improve domains of sexual function. The association between vulvar pain and bladder pain could, therefore, be related to a vaginal environment carrying signs of hypoestrogenism, but further studies are needed to clarify this issue.

Barbed suture in minimally invasive hysterectomy: a systematic review and meta-analysis.

PURPOSE: Total laparoscopic or robotic hysterectomy represents one of the most performed gynecological procedures nowadays. Minimally invasive procedures seem to increase the risk of vaginal cuff dehiscence (VCD). Barbed suture is a new class of suture introduced to aid surgeons during laparoscopic suturing, with the aim to reduce operative time, blood loss, and vaginal dehiscence. METHODS: We identified all articles that report a series of laparoscopic or robotic-assisted hysterectomy using barbed suture compared to conventional suture for vaginal cuff closure. The main outcome measures were vaginal cuff suturing time, vaginal bleeding, and vaginal dehiscence with or without small bowel evisceration. Suturing time was meta-analyzed as the standardized mean difference, which is the difference in means of two arms divided by pooled standard deviation with 95 % confidence intervals. For vaginal bleeding and dehiscence risk difference were calculated for each study and then meta-analyzed. Fixed models were considered if heterogeneity was low (I (2) < 50 %), otherwise random models were preferred. RESULTS: We show that minor bleeding (RD = 0, 95 % CI 0.03-0.03; p value = 0.907) and VCD (RD = -0.01, 95 % CI 0.02-0.00; p value = 0.119) are comparable in minimally invasive hysterectomy with or without the use of barbed suture. The major bleeding (RD = -0.03; 95 % CI 0.05-0.00; p value = 0.047) appears borderline significant, but the difference between the two types of sutures is not high and the upper limit of 95 % IC is equal to 0 so they were considered comparable. Instead, meta-analysis on vaginal cuff suturing time demonstrates that suturing time is reduced with the use of barbed suture (SMD = -0.96, 95 % CI 1.26-0.70; p value <0.001). CONCLUSIONS: Barbed suture is safe and well tolerated as traditional sutures and is associated with reduced operative time of laparoscopic vaginal vault closure.

Neutrophil to lymphocytes ratio in deep infiltrating endometriosis as a new toll for clinical management.

Several mechanisms, including altered local and systemic immune system, apoptosis, and new angiogenesis, are responsible for the development and progression of endometriosis. Over the years many markers have been studied, like CA 125 and, recently, neutrophil-to-lymphocyte ratio (NLR). This tool is cost-effectiveness and non-invasiveness as a marker of systemic inflammatory diseases. The aim of this study is to assess the role of NLR in the real-life management of patients with endometriosis in order to evaluate the possible association between this value and symptoms. We performed a retrospective analysis of 199 premenopausal women affected by endometriosis, from January 2013 to December 2020, evaluating the characteristics of disease, the symptoms and the NLR. Analyzing the neutrophiles, the mean ± SD value was 6.1 ± 4.5 × 103/ul, while for lymphocytes mean ± SD value was 1.8 ± 0.7.NLR was categorized according to its median value (> 2.62 vs ≤ 2.62). The comparison between NLR values and CA 125, endometriosis stage, dysmenorrhea and presence of chronic pelvic pain, adjusting for previous therapy did not find a significant association. An interesting result, although not significant, was the association between NLR and chronic pelvic pain (OR = 1.9). In the sub-group of patients without previous therapy this association is even stronger (OR = 4.8, 95% CI 0.5-50.2, p = 0.190). The link between NLR and chronic pelvic pain can provide a further hint to the clinician even when taking symptoms into account to develop a particular therapeutic treatment related to the various expressions of NLR. Finally, NLR may enable the creation of customized follow-up protocols that divide patients into high- and low-risk categories for endometriosis recurrence.

Aromatase inhibitors in the pharmacotherapy of endometriosis.

INTRODUCTION: Endometriosis is a benign chronic inflammatory disease responsible for debilitating pain and decreased quality of life. The traditional treatment is based on estroprogestins, progestins, GnRH analogs, and surgery. Recently, aromatase inhibitors (AIs) demonstrated good efficacy in controlling symptoms and size of endometriotic implants, mostly because they suppress extraovarian estrogen synthesis, which can enhance the hypoestrogenic state ameliorating symptoms of endometriosis. AREAS COVERED: Phase I, II, III and IV trials, on the use of AIs used for the treatment of endometriosis, have been retrieved. The pharmacokinetics and pharmacodynamics of third-generation non-steroidal AIs have also been investigated. A MEDLINE search has been performed using the following MeSH keywords: 'endometriosis,' aromatase inhibitors,' 'therapy,' and 'treatment'. The timeframe was from 2010 up to November 2022 including reviews, systematic reviews, reports, case series, and retrospective or prospective trials. EXPERT OPINION: AIs have shown good clinical efficacy in combination with hormonal therapy in disease control, and they represent a promising second-line therapy in selected patients, yet more research is needed on alternative drug delivery systems and better control of adverse effects. In postmenopausal women in which surgery is contraindicated, AIs represent an excellent treatment option. Their application in routine clinical practice remains limited by adverse effects.

Endometriosis pain and epithelial neutrophil activating peptide-78 levels.

Endometriosis is a chronic gynecological disorder involved in the pathogenesis of chronic pelvic pain, based on a probable up regulation of the inflammatory system. The objective of the study is to investigate the peritoneal and serum levels of ENA-78 with the severity of endometriosis symptoms (dysmenorrhea, chronic pelvic pain and dyspareunia) using the visual analogue scale (VAS). This is a prospective case-control study that included 53 symptomatic women with evidence of endometriosis and 53 age-matched controls who underwent elective laparoscopic surgery for benign diseases. The concentration of ENA-78 was assessed in blood and peritoneal fluid samples in the follicular phase. In peritoneal fluid and plasma, the concentration of ENA-78 was significantly higher in cases than in controls (p < 0.001). A significant correlation was observed between peritoneal fluid ENA-78 levels and the severity of dysmenorrhea (Spearman Rho = 0.237; p = 0.014), and chronic pelvic pain (Spearman Rho = 0.220; p = 0.022) in endometriosis patients. Plasma levels ENA-78 showed a significant correlation with the severity (VAS score) of chronic pelvic pain (Spearman Rho = 0.270, p = 0.005 for cases), though a weak correlation was evident between plasma levels of ENA-78 and severity of dysmenorrhea (Spearman Rho = 0.083, p = 0.399 for cases). In conclusion, chronic pelvic pain in endometriosis is caused by changes of local and systemic activated chemokine patterns. These modifications involve the relationship between pro-inflammatory, angiogenic and angiostatic chemokines that modulate the severity of endometriosis associated symptoms.

Veliparib for the treatment of ovarian cancer.

INTRODUCTION: Ovarian cancer represents the sixth most commonly diagnosed cancer among women, with an incidence of 6.1 cases per 100.000 women and a cumulative lifetime risk of 0.5%. Treatment is based on debulking surgery and platinum-based chemotherapy, with the potential combination with taxane. However, the recently available data on the genetic basis and aetiology of ovarian cancer has led to the development of new anticancer drugs. Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising new classes of targeted agents currently under investigation for the treatment of ovarian cancer. Veliparib is a small molecule that inhibits both PARP-1 and PARP-2 and was originally shown to be efficacious in BRCA-associated tumors. AREAS COVERED: This manuscript reviews the Phase I and II studies investigating the use of veliparib in ovarian cancer. This article also provides and discusses the pharmacokinetics and pharmacodynamics of veliparib. EXPERT OPINION: It is still being discussed whether PARP inhibitors should be used in a front-line or relapsed setting, alone or in combination with cytotoxic chemotherapy or as maintenance treatment. In terms of veliparib, further investigations are needed to explore its full potential in ovarian cancer. It is hoped that the ongoing phase 3 trials will help to further elucidate it potential as a treatment option.

Current opinion on bevacizumab on endometrial cancer treatment.

INTRODUCTION: Advanced or recurrent endometrial cancer is still a challenge for clinicians as it has a poor prognosis despite treatment efforts. Thus, there is an urgent need for new agents with activity in this subset of patients. The increased knowledge of the molecular aspects of endometrial carcinogenesis has led to the development of molecular targeted therapies and in particular anti-angiogenic drugs. One of the most promising of these agents is bevacizumab , a recombinant humanized immunoglobulin monoclonal antibody to VEGF. AREAS COVERED: The objective of this paper is to discuss the role of angiogenesis in endometrial cancer and analyze the rational of bevacizumab use, alone or in combination with other therapies, in endometrial cancer patients. We reviewed the most important preclinical and clinical studies published on this topic up to March 2014. EXPERT OPINION: Bevacizumab in combination with others targeted therapies, chemotherapy or radiotherapy demonstrated promising anti-tumor activity. Despite the good oncological outcomes of these recent clinical experiences, caution must be used in light of significant toxicity reported in this subset of heavily pre-treated patients. The identification of biomarkers able to predict either the efficacy or toxicity of anti-angiogenic drugs is a compelling need.

Oxaliplatin for the treatment of ovarian cancer.

INTRODUCTION: Oxaliplatin is an important drug in treatment of several solid tumors. Ovarian cancer (OC) is sensitive to chemotherapy and the overall response rate with primary therapy is about 75%. Unfortunately, 60 - 70% of patients experience recurrence requiring additional treatments and finally die of progressive disease within 5 years of the initial diagnosis. Currently, a platinum-based combination therapy is recommended in platinum-sensitive disease while a non-platinum single-agent therapy is preferred in platinum-resistant disease that is characterized by a low response rate. AREAS COVERED: In this article, the authors review the Phase II and Phase III studies of oxaliplatin as an OC therapy. Furthermore, the authors discuss the pharmacokinetic and pharmacodynamic features of oxaliplatin. EXPERT OPINION: Platinum emerged as the mainstay of OC treatment in frontline therapy, and platinum compounds remain a critical component of chemotherapy also in relapsed disease. Unfortunately, increasing exposure to carboplatin/cisplatin raises the risk of resistance or hypersensitivity to platinum. Several studies have demonstrated the safety and effectiveness of oxaliplatin, both alone and in combination regimens, in relapsed OC, demonstrating a good tolerability profile. Moreover, the therapeutic spectrum of oxaliplatin might be extended to OC patients who experienced hypersensitivity to carboplatin because of its favorable toxicity profile and at least equal efficacy.

Vaginal cuff closure with absorbable bidirectional barbed suture during total laparoscopic hysterectomy.

OBJECTIVE: Hysterectomy represents one of the most performed procedures in gynecological surgery. The minimally invasive approach increases patients' benefits and reduces hospitalization costs. The aim of this study was to demonstrate the efficacy and safety of double barbed suture in vaginal cuff closure during total laparoscopic hysterectomy. STUDY DESIGN: A retrospective cohort study of 88 consecutive patients treated with total laparoscopic hysterectomy for benign or precancerous conditions was undertaken from January 2010 to December 2011. Vaginal cuff suture was performed with traditional interrupted suture with polycolic acid (Vicryl™) in 40 patients and with bidirectional barbed device, Quill SRS™, in 48 patients. RESULTS: No difference in vaginal cuff dehiscence, major vaginal bleeding or spotting, and infection was evident between the two groups, with significant reduction in operative times for the bidirectional barbed suture group. CONCLUSION: Vaginal cuff suture performed with bidirectional barbed QUILL SRS™ is a safe and well-tolerated procedure that reduces operative times.