An umbrella review of the surgical performance of Harmonic ultrasonic devices and impact on patient outcomes.

BACKGROUND: For thirty years, the Harmonic scalpel has been used for precise dissection, sealing and transection. There are numerous meta-analyses on individual surgical procedures with Harmonic, but no overarching review covering all the areas. This umbrella review seeks to summarize the clinical results from the use of Harmonic across surgical fields and broadly quantify its effects on patient outcomes. METHODS: MEDLINE, EMBASE, and Cochrane Databases were searched for meta-analyses (MAs) of randomized controlled trials (RCTs) comparing Harmonic devices to conventional techniques or advanced bipolar (ABP) devices. For each procedure type, the most comprehensive MAs were evaluated. RCTs not already analysed in a MA were also included. Operating time, length of stay, intraoperative blood loss, drainage volume, pain, and overall complications were evaluated, and the methodological quality and certainty of evidence were assessed. RESULTS: Twenty-four systematic literature reviews were identified on colectomy, hemorrhoidectomy, gastrectomy, mastectomy, flap harvesting, cholecystectomy, thyroidectomy, tonsillectomy, and neck dissection. There were also 83 RCTs included. In every MA evaluated, Harmonic devices were associated with either statistically significant or numerical improvements in every outcome compared with conventional techniques; most MAs reported a reduction in operating time of ≥ 25 min. Harmonic versus ABP device MAs in colectomy and thyroidectomy showed no significant differences in outcomes. CONCLUSION: Across surgical procedures, Harmonic devices demonstrated improved patient outcomes for operating time, length of stay, intraoperative bleeding, drainage volume, pain, and overall complications compared to conventional techniques. Additional studies are required to assess differences between Harmonic and ABP devices.

Intraoperative Measures to Reduce the Risk of COVID-19 Transmission During Minimally Invasive Procedures: A Systematic Review and Critical Appraisal of Societies' Recommendations.

BACKGROUND: The coronavirus 2019 pandemic and the hypothetical risk of virus transmission through aerosolized CO2 or surgical smoke produced during minimally invasive surgery (MIS) procedures have prompted societies to issue recommendations on measures to reduce this risk. The aim of this systematic review is to identify, summarize and critically appraise recommendations from surgical societies on intraoperative measures to reduce the risk of severe acute respiratory syndrome coronavirus 2 transmission to the operative room (OR) staff during MIS. METHODS: Medline, Embase, and Google Scholar databases were searched using a search strategy or free terms. The search was supplemented with searches of additional relevant records on coronavirus 2019 resource websites from Surgical Associations and Societies. Recommendations published by surgical societies that reported on the intraoperative methods to reduce the risk of severe acute respiratory syndrome coronavirus 2 transmission to the OR staff during MIS were also reviewed for inclusion. Expert opinion articles were excluded. A preliminary synthesis was performed of the extracted data to categorize and itemize the different types of recommendations. The results were then summarized in a narrative synthesis. RESULTS: Thirty-three recommendation were included in the study. Most recommendations were targeted to general surgery (13) and gynecology (8). Areas covered by the documents were recommendations on performance of laparoscopic/robotic surgery versus open approach (28 documents), selection of surgical staff (13), management of pneumoperitoneum (33), use of energy devices (20), and management of surgical smoke and pneumoperitoneum desufflation (33) with varying degree of consensus on the specific recommendations among the documents. CONCLUSIONS: While some of the early recommendations advised against the use of MIS, they were not strictly based on the available scientific evidence. After further consideration of the literature and of the well-known benefits of laparoscopy to the patient, later recommendations shifted to encouraging the use of MIS as long as adequate precautions could be taken to protect the safety of the OR staff. The release and implementation of recommendations should be based on evidence-based practices that allows health care systems to provide safe surgical and medical assistance.

A device category economic model of electrosurgery technologies across procedure types: a U.S. hospital budget impact analysis.

AIMS: The electrosurgical technology category is used widely, with a diverse spectrum of devices designed for different surgical needs. Historically, hospitals are supplied with electrosurgical devices from several manufacturers, and those devices are often evaluated separately; it may be more efficient to evaluate the category holistically. This study assessed the health economic impact of adopting an electrosurgical device-category from a single manufacturer. METHODS: A budget impact model was developed from a U.S. hospital perspective. The uptake of electrosurgical devices from EES (Ethicon Electrosurgery), including ultrasonic, advanced bipolar, smoke evacuators, and reusable dispersive electrodes were compared with similar MED (Medical Energy Devices) from multiple manufacturers. It was assumed that an average hospital performed 10,000 annual procedures 80% of which involved electrosurgery. Current utilization assumed 100% MED use, including advanced energy, conventional smoke mitigation options (e.g. ventilation, masks), and single-use disposable dispersive electrode devices. Future utilization assumed 100% EES use, including advanced energy devices, smoke evacuators (i.e. 80% uptake), and reusable dispersive electrodes. Surgical specialties included colorectal, bariatric, gynecology, thoracic and general surgery. Systematic reviews, network meta-analyses, and meta-regressions informed operating room (OR) time, hospital stay, and transfusion model inputs. Costs were assigned to model parameters, and price parity was assumed for advanced energy devices. The costs of disposables for dispersive electrodes and smoke-evacuators were included. RESULTS: The base-case analysis, which assessed the adoption of EES instead of MED for an average U.S. hospital predicted an annual savings of $824,760 ($101 per procedure). Savings were attributable to associated reductions with EES in OR time, days of hospital stay, and volume of disposable electrodes. Sensitivity analyses were consistent with these base-case findings. CONCLUSIONS: Category-wide adoption of electrosurgical devices from a single manufacturer demonstrated economic advantages compared with disaggregated product uptake. Future research should focus on informing comparisons of innovative electrosurgical devices.

Economic and clinical outcomes of spinal fusion surgeries with skin closure through skin staples plus waterproof wound dressings versus 2-octyl cyanoacrylate plus polymer mesh tape.

BACKGROUND CONTEXT: Spinal fusion surgeries are one of the most common types of operations performed during inpatient stays in the United States. Successful wound closure, including watertight closure at the skin layer, plays in important role in patient outcomes. PURPOSE: To compare the economic and clinical outcomes of spinal fusion surgeries using one of two sutureless skin closure techniques: skin staples plus waterproof wound dressings (SSWWD) or 2-octyl cyanoacrylate plus polymer mesh tape (2OPMT). STUDY DESIGN/SETTING: Retrospective study using a multi-hospital database. PATIENT SAMPLE: Patients undergoing inpatient spinal fusion surgery for a spine disorder between October 1, 2015 and March 31, 2019. OUTCOME MEASURES: Total costs from the hospital perspective, operating room time (ORT), hospital length of stay (LOS), non-home discharge, infection/wound complications during the 90-day global period (index surgery through 90 days post-discharge), and 30/60/90-day all-cause readmissions. METHODS: Outcomes were compared between study groups using nearest neighbor propensity score matching with exact matching on 45 primary procedure/diagnosis code groupings and generalized estimating equations to account for hospital-level clustering. This study was sponsored by Ethicon, Inc., a Johnson & Johnson company; the authors are employees or consultants of Johnson & Johnson. RESULTS: A total of 11,991 patients met the study criteria (2OPMT=5,961; SSWWD=6,030), of which 3,602 were included in each post-match study comparison group (total=7,204). As compared with the SSWWD group, the 2OPMT group had statistically significant lower median ORT (240 vs. 270 minutes; p=0.002), mean LOS (3.35 [SD=2.6] vs. 3.86 [SD=2.8] days, p=0.031), risks of non-home discharge status (17.63% vs. 23.10%, p=0.035), overall infections/wound complications (1.37% vs. 2.48%, p=0.015), and surgical site infection (1.11% vs. 2.07%, p=0.023). Differences between the study groups in total hospital costs, all-cause readmissions, and other sub-components of the infection/wound complication composite outcome were statistically insignificant (p>0.05). CONCLUSIONS: In this retrospective observational study of patients undergoing elective inpatient spinal fusion surgery, the use of 2OPMT for skin closure was associated with significantly lower ORT, LOS, non-home discharge, and 90-day rates of infections/wound complications as compared with SSWWD.

Barbed and conventional sutures in spinal surgery patients: an economic and clinical outcomes comparison.

OBJECTIVE: To compare economic and clinical outcomes of barbed sutures versus conventional sutures alone in wound closure for patients undergoing spinal surgery. METHOD: A retrospective study using the Premier Healthcare Database. The database was searched for patients who underwent elective inpatient spinal surgery (fusion or laminectomy) for a spinal disorder between 1 January 2014 and 30 June 2018 (first=index admission). Using billing records for medical supplies used during the index admission, patients were classified into mutually-exclusive groups: patients with any use of STRATAFIX (Ethicon, US) knotless tissue control devices (barbed sutures group); or patients with use of conventional sutures alone (conventional sutures group). Outcomes included the index admission's length of stay, total and subcategories of hospital costs, non-home discharge, operating room time (ORT, minutes), wound complications and readmissions within ≤90 days. Propensity score matching and generalised estimating equations were used to compare outcomes between the study groups. RESULTS: After matching, 3705 patients were allocated to each group (mean age=61.5 years [standard deviation, SD±12.9]; 54% were females). Compared with the conventional suture group, the barbed suture group had significantly lower mean ORT (239±117 minutes, versus 263±79 minutes conventional sutures, p=0.015). Operating room costs were also siginificantly lower in the barbed suture group ($6673±$3976 versus $7100±$2700 conventional sutures, p=0.020). Differences were statistically insignificant for other outcomes (all p>0.05). Subanalysis of patients undergoing fusions of ≥2 vertebral joints yielded consistent results. CONCLUSION: In this study, wound closure incorporating barbed sutures was associated with lower ORT and operating room costs, with no significant difference in wound complications or readmissions, when compared with conventional sutures alone.

Tension-free Vaginal Tape-Obturator for Treatment of Pure Urodynamic Stress Urinary Incontinence: Efficacy and Adverse Effects at 10-year Follow-up.

BACKGROUND: Inside-out transobturator tape (tension-free vaginal tape-obturator [TVT-O]) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence (SUI). However, data reporting long-term outcomes are lacking. OBJECTIVE: To assess the efficacy and safety of TVT-O 10 yr after implantation for the treatment of female pure SUI. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, prospective study was conducted in five tertiary referral centers in three countries. All consecutive women with urodynamically proven pure SUI treated by TVT-O were included. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. INTERVENTION: TVT-O implantation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data regarding subjective outcomes (International Consultation on Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement, and patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Univariable analysis was performed to investigate outcomes. RESULTS AND LIMITATIONS: One hundred sixty-eight women had TVT-O implantation. At 10-yr follow-up, 160 patients (95%) were available for the evaluation. We did not find any significant change of the surgical outcomes during this time. At 10 yr after surgery, 155 of 160 patients (97%) declared themselves cured (p=0.7). Similarly, at 10-yr evaluation, 148 of 160 patients (92%) were objectively cured. No significant deterioration of objective cure rates was observed over time (p=0.4). The history of failure of previous anti-incontinence procedures (hazard ratio: 5.34; 95% CI, 2.61-11.9; p=0.009) was the only predictor of recurrence of SUI. The onset of de novo overactive bladder was reported by 23 of 160 patients (14%) at 10-yr follow-up. No other late complications were reported. CONCLUSIONS: The 10-yr results of this study showed that TVT-O is a highly effective and safe option for the treatment of SUI. PATIENT SUMMARY: At long-term follow up, tension-free vaginal tape-obturator is highly effective and safe for the treatment of stress urinary incontinence.

A randomized, controlled clinical trial of an intravesical pressure-attenuation balloon system for the treatment of stress urinary incontinence in females.

AIMS: Evaluate the efficacy, safety, and tolerability of a novel pressure-attenuation balloon for the treatment of female stress urinary incontinence (SUI) using a prospective, randomized, single-blind, multi-center design, evaluated at 3 months. METHODS: Sixty-three females with SUI were randomized 2:1 to treatment with a balloon (N = 41) or sham procedure (N = 22). The sham (control) entailed the same procedure without the deployment of a balloon. Endpoints were evaluated at 3 months and included a composite endpoint that required both ≥10 point increase in the 22-item Incontinence Quality of Life Survey (I-QOL) and ≥50% decrease in provocative pad weight. Additional endpoints included incontinence episode frequency, and PGII assessment. RESULTS: In an ITT analysis, 63% of women in the treatment group achieved the composite endpoint, compared to 31% in the Control Group (P = 0.0200). In a per protocol analysis, 81% of women in the treatment arm had a 50% decrease in pad weight test vs. 45% in the Control Group (P = 0.0143); 41.6% of the treatment patients were dry on pad weight test (≤1gram) vs. 0% in the Control Group (P < 0.001), and 58% of treated patients reported improvement on a PGII assessment versus 25% of women in the Control Group (P = 0.025). Adverse events in the treatment group included dysuria (14.6%), gross hematuria (9.8%), and UTI (7.3%). CONCLUSIONS: This minimally invasive treatment for female SUI with an intravesical pressure-attenuation balloon was safe and effective. The concept of pressure attenuation as a therapy for SUI is valid and feasible for those patients that can tolerate the balloon.

Effect of local infiltration analgesia on post-operative pain following TVT-O: a double-blind, placebo-controlled randomized study.

PURPOSE: To evaluate the effect of a protocol of local anesthesia and epinephrine associated with sedo-analgesia on post-TVT-O pain in comparison with infiltration of saline and epinephrine. METHODS: Forty-two patients undergoing TVT-O were randomized into two groups to receive periurethral infiltration with epinephrine only (group A, n = 21) or with epinephrine plus 1 % lidocaine hydrochloride (group B, n = 21). Post-operative pain was assessed using a visual analog scale (VAS) from 0 (absence of pain) to 10 (maximum pain possible), 1, 6, 12 and 24 h after the procedure. The total amount of analgesia was recorded and the proportion of women reporting a pain VAS score ≥4, 1 h after the procedure was calculated. ANOVA for repeated measures and Bonferroni correction, the Student's t test for independent samples, the Mann-Whitney U test, the Fisher exact test, or the χ (2) test for parametric was used. RESULTS: Pain level was significantly lower in group B 1 (p = 0.01) and 6 h (p = 0.05) after surgery, but not 12 and 24 h after the procedure. No significant difference was observed in the proportion of women requesting analgesia and in the total dosage of analgesics between the two groups. A significant higher proportion of women in group A reported a pain VAS score higher than four 1 h after surgery in comparison with patients in group B. CONCLUSIONS: This randomized study seems to indicate that systematic infiltration before TVT-O positioning with local anesthetic may reduce immediate post-operative pain.

Effects of an oral contraceptive containing estradiol valerate and dienogest on circulating androgen levels and acne in young patients with PCOS: an observational preliminary study.

This study shows the effect of a 1 year treatment with an estradiol valerate/dienogest pill in 36 women suffering from polycystic ovaries and mild or moderate acne. At beginning of the study, 24 patients (66.7%) had grade 1-2 (mild) acne and 12 patients (33.3%) had grade 3 (moderate) acne. After 12 cycles of therapy, we found an improvement of acne in 19 (52.8%) patients and a worsening of acne in 3 (8.4%) patients. The percentage of patients recovered was statistically significant (p < 0.01). SHBG levels were significantly higher after 6 and 12 months of therapy (p < 0.001), while total testosterone levels were lower in all patients at 6 and 12 months although this trend did not reach statistical significance. In conclusion, the present study suggests that the E2V/DNG pill could exert a positive influence on acne and hyperandrogenism. Since this is an observational study on a very limited population number, additional randomized controlled studies on larger populations are needed also to determine the effects of this contraceptive over longer periods of use.

Short-term effects of an oral contraceptive containing oestradiol valerate and dienogest on bone metabolism and bone mineral density: an observational, preliminary study.

OBJECTIVES: To evaluate the effects of a combined oral contraceptive (COC) containing dienogest/oestradiol valerate (DNG/E2V) on bone mineral density (BMD) and on serum and urinary bone turnover markers in young, healthy, fertile women. METHODS: At baseline and after three and six months of intake of the aforementioned COC, serum and urinary calcium, osteocalcin, urinary pyridinoline (PYD), and deoxypyridinoline (D-PYD) of 30 women aged 21 to 34 years were measured. At baseline and after six months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: Urinary levels of PYD and D-PYD were significantly lower at three and six months in comparison with basal values (p < 0.05). Serum calcium levels showed an increasing trend, which reached statistical significance after six months in comparison with basal values while urinary levels of calcium did not vary significantly. Serum osteocalcin levels were somewhat, but not significantly, lower during pill use in comparison with basal values. After six months, spinal BMD values did not differ significantly from basal values. CONCLUSIONS: The DNG/E2V COC has no short-term adverse effect on bone turnover markers. No significant change in BMD was observed after six months of use of that pill.

The use of an oral contraceptive containing estradiol valerate and dienogest before office operative hysteroscopy: a feasibility study.

To investigate the impact of a 3 months preoperative administration of an oral contraceptive, containing dienogest (DNG) and estradiol valerate (E2V) on the outcome of office operative hysteroscopy (OOH). One-hundred and forty-two patients diagnosed at office hysteroscopy as having an asynchronous endometrium associated with either a broad-base sessile endometrial polyp (>1.5, <2.5 cm) or a uterine septum (>1/3 uterine cavity) or scheduled for tubal sterilization were enrolled into a prospective case-control study at University "Federico II" of Naples. 86/142 patients accepted the preoperative hormonal treatment (Group A), while 56/142 refused, thus becoming controls (Group B). Group A underwent OOH during the 10th-20th days of the third cycle of treatment. In Group B OOH was performed at enrolment, together with the diagnostic procedure. The study outcomes were: endometrial pattern, success rate, operating time, degree of surgical difficulty and pain score. An overall improvement of the endometrium was reported in 100% of cases in Group A. A statistically significant difference in success rate could not be demonstrated between two groups. Operative procedures were performed significantly quicker and easier in Group A than Group B (p < 0.001 and p < 0.05, respectively). The mean Visual Analog Scale (VAS) score was significantly lower in Group A (p < 0.001). A short pretreatment with combined oral contraceptive (COC) containing E2V/DNG seems to have a favorable impact on endometrium which in turn may result in an improvement of the overall outcomes of OOH.

Effects of a modified technique for TVT-O positioning on postoperative pain: single-blind randomized study.

INTRODUCTION AND HYPOTHESIS: One of the most frequent and distressing complications of the tension-free vaginal tape obturator (TVT-O) procedure for stress urinary incontinence (SUI) is groin pain, which may be related to the surgical technique or to the tape. The aim of this study was to evaluate the impact of a more limited dissection and a more medial trocar trajectory in TVT-O positioning on postoperative pain. METHODS: Seventy-two SUI patients were randomized to undergo TVT-O either with the traditional technique (group A) or a modified procedure (reduced paraurethral dissection and a more medial trocar trajectory) (group B). Visual analog scale pain scores 12 h, 24 h, and 1 month after the procedure, number of analgesic vials, objective cure rate, and patient functional and quality of life scores 6 months after the procedure were evaluated. Data were analyzed by the Student's t test for parametric variables, the Mann-Whitney U and Wilcoxon tests for nonparametric variables, and Fisher's exact test for categorical variables. RESULTS: Pain scores were significantly lower in group B compared with group A 24 h after surgery (P = 0.01). Pain scores significantly decreased from 12-24 h postoperatively to 1 month follow-up in both groups (P < 0.001). No significant differences were observed in the number of analgesic vials administered, cure rates, and questionnaire scores between the two groups. CONCLUSIONS: More limited dissection and a more medial trocar trajectory of TVT-O seem to reduce postoperative groin pain at 24 h after the procedure, but not the analgesic requirement.

TVT-Secur for the treatment of female stress urinary incontinence: a 24-month follow-up retrospective study.

PURPOSE: To evaluate the mid-term efficacy and safety of the TVT-Secur device in the treatment of stress urinary incontinence. STUDY DESIGN: Retrospective study evaluating 68 women affected by stress urinary incontinence treated with TVT-Secur procedure with hammock approach who attended the 24-month follow-up visit. Stress test, urodynamics, patient functional and quality of life questionnaires, visual analog scale pain score, and post-operative complications were evaluated. Data distribution was evaluated using the Shapiro-Wilk's test. Data were analyzed by the Student's t test for parametric variables, the Wilcoxon test for non-parametric variables, and the Chi-squared test for categorized variables. RESULTS: Objective cure rate 24 months after surgery was 80.8 %. Incontinence-quality of life and patient global impression of severity scores showed significant improvement. The only intra-operative complications were a vaginal wall tear and a case of severe bleeding, while post-operative complications were de novo urgency in five cases (7.3 %), one acute urinary retention (1.4 %), and one tape exposure (1.4 %). The study is limited by the retrospective design and the heterogeneity of patients. CONCLUSIONS: TVT-Secur seems to be an effective and safe procedure for stress urinary incontinence.

Case report: a most peculiar family with spontaneous, recurrent ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) mostly occurs as a complication of induction of ovulation. However, rarely, it may occur spontaneously at the beginning of a natural pregnancy and in the absence of any assisted reproductive treatment. Spontaneous OHSS has been reported in pregnant women affected by hypothyroidism, polycystic ovary syndrome, gonadotropin-producing pituitary adenoma, but also in normal pregnancies. The aetiology of this condition is still unclear. We hereby report on a case of spontaneous, familial, recurrent OHSS in a 26-year-old primipara whose first-degree cousin, paternal grandmother and a number of other members of her father's family had suffered from a similar condition. This case seems to support the concept of a genetic predisposition for spontaneous OHSS thereby suggesting the need for preventive and therapeutic strategies.

Metalloproteinases, vascular endothelial growth factor, and angiopoietin 1 and 2 in eutopic and ectopic endometrium.

OBJECTIVE: To evaluate the expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and 2 (ANGPT1/ANGPT2), and matrix metalloproteinases 1, 2, and 9 (MMP-1, MMP-2, MMP-9) in eutopic and ectopic endometrium. DESIGN: Experimental retrospective study. SETTING: University hospital. PATIENT(S): Eutopic and ectopic endometrium samples from 30 women with endometriosis and endometrium biopsy samples from 30 healthy women. INTERVENTION(S): Biopsies of ovarian endometriomas and eutopic endometrium. MAIN OUTCOME MEASURE(S): Immunohistochemical staining to evaluate the expression of VEGF, ANGPT1, ANGPT2, MMP-1, MMP-2, and MMP-9, and real-time polymerase chain reaction analysis to quantify mRNA expression. RESULT(S): Patients with endometriosis had higher levels of angiogenic factors and metalloproteinases in endometriotic cysts than in eutopic endometrium. These substances were also overexpressed in eutopic endometrium of patients with endometriosis when compared with normal controls. CONCLUSION(S): Overexpression of angiogenic factors and metalloproteinases may be the characteristic feature of endometrium with greater potential to transform into endometriotic lesions in the peritoneal cavity. Structural and/or functional differences of eutopic endometrium could have a role in the pathogenesis of endometriosis secondary to the backward passage of endometrial cells into the peritoneal cavity. Whether these local factors may induce, promote, and/or regulate this transformation remains to be determined.

Atypical squamous cells and low squamous intraepithelial lesions in postmenopausal women: implications for management.

OBJECTIVES: To determine whether the use of local Estrogen Replacement Therapy (ERT) affects the adequacy of colposcopic examination; to distinguish abnormal cervical smears secondary to hypoestrogenism from abnormal cervical smears due to true preneoplastic changes; and to suggest an effective management of atypical squamous cells of undeterminated significance (ASCUS) and low grade squamous intraepithelial lesion (L-SIL) in menopausal women. STUDY DESIGN: Two-hundred fifty-four postmenopausal women with abnormal pap smears (L-SIL or ASCUS) underwent colposcopy and HPV DNA testing. All patients with positive colposcopy underwent punch biopsy, and all patients with positive histological findings underwent surgical treatment. Patients with negative colposcopy, both satisfactory [visible Squamo-Columnar Junction (SCJ)] and unsatisfactory, were treated with local estrogenic replacement therapy (ERT) for 3 months, and repeated colposcopy and pap smears. Patients with negative colposcopy and negative pap smears after ERT were included in a 6 months cytological and colposcopic follow-up. Patients with positive colposcopy underwent punch biopsy, if colposcopy was negative and cytology was positive, patients underwent endocervical curettage. RESULTS: One-hundred ninety-five had a diagnosis of ASCUS and 59 a diagnosis of L-SIL. At the first colposcopy, 39 patients showed a lesion and had an appropriate treatment. One-hundred eighty-eight in the ASCUS group and 27 in the L-SIL group had a negative colposcopy and were treated with local ERT. At first colposcopic examination, 37 of the 215 negative colposcopies resulted satisfactory and 178 of the 215 resulted unsatisfactory. After local ERT, 130 of the 178 patients had a satisfactory follow-up colposcopy. After ERT, 25 patients of 215 with initial abnormal CVS and negative colposcopy, required appropriate treatment. After ERT, 190 patients of 215 showed negative colposcopy and at cytologic follow-up showed 23 ASCUS and 167 normal CVS. CONCLUSIONS: A correct diagnosis and an efficient treatment seem to be obtained with a short-time ERT followed by a short-time cytological and colposcopic follow-up. With a single course of local ERT it may be possible to distinguish between benign CVS mimicking atrophy and true preneoplastic changes. Estrogen therapy will often cause enough ectropion of the endocervical cells so that the entire SCJ can be visualized. Moreover, it may reduce the number of endocervical curettage or loop excision or cone procedure for women with inadequate colposcopic examination.

Postmenopausal hypoestrogenism increases vasoconstrictor neuropeptides and decreases vasodilator neuropeptides content in arterial-wall autonomic terminations.

OBJECTIVE: To investigate the effects of postmenopausal hypoestrogenism on the content of autonomic vasoconstrictor (neuropeptide Y) and vasodilator neuropeptides (vasoactive intestinal peptide and substance P) at the arterial level. DESIGN: Prospective, clinical study. SETTING: Department of Gynecology and Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II," Naples, Italy. PATIENT(S): Twenty premenopausal women and 20 postmenopausal women, matched for age and parity. INTERVENTION(S): All patients underwent abdominal hysterectomy with bilateral oophorectomy for benign conditions. During surgery, a sample of uterine artery was obtained. The presence of E2, estrogen receptor alpha (ER alpha), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and S100 (a generic neuronal marker) was evaluated by means of immunohistochemistry and Western-blot analysis. MAIN OUTCOME MEASURE(S): Mean arterial content of E2, ER alpha, VIP, NPY, and SP. RESULT(S): Both immunohistochemical and Western-blot analysis showed that after menopause, the reduction in E2 and ER alpha in the uterine artery wall is associated with a decrease in vasodilator neuropeptides and an increase in vasoconstrictor NPY. A similar immunopositivity for S100 was observed in pre- and postmenopausal samples, which demonstrated similar total neuronal fiber contents. CONCLUSION(S): Postmenopausal hypoestrogenism seems to increase arterial vascular tone through a reduction of vasodilator neuropeptides and an increase in vasoconstrictor peptides in the arterial-wall termination of the autonomous system. These changes in neuropeptide content in the arterial walls might represent a new mechanism underlying the negative effects of menopause on the cardiovascular system.

Longitudinal evaluation of serum leptin and bone mineral density in early postmenopausal women.

OBJECTIVE: To evaluate total and site-specific bone mineral density (BMD) and serum leptin levels in postmenopausal women treated with a calcium supplement and in postmenopausal women receiving estrogen plus progestin therapy. DESIGN: Forty-four women were randomized to receive either calcium supplementation (group A, n = 22) or transdermal 17beta-estradiol at a dose of 50 mug/day in a continuous regimen and nomegestrol at a dose of 5 mg/day for 12 days per month in a sequential regimen (group B, n = 22). All women underwent dual-energy x-ray absorptiometry determination of BMD and blood sampling in the morning at the beginning of the study and after 12 months. Leptin was determined by radioimmunoassay in all samples. RESULTS: After 12 months, serum leptin levels were significantly higher in group A (control) in comparison with group B and baseline values, whereas both total and pelvic BMDs were significantly lower in group A in comparison with group B and baseline values. At baseline, a significant correlation was found between leptin levels, body mass index, and total-body BMD. After 12 months, leptin was still correlated to body mass index in both groups, but the association with BMD was lost. CONCLUSIONS: This study confirms previous evidence of a significant correlation between serum leptin and BMD in early postmenopausal women. Furthermore, this correlation is lost over time during the progression of the postmenopausal period, independently from the administration of estrogen-progestin therapy. Further studies and longer follow-up periods are needed to better understand theses issues.

Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the effects of estrogen-progestin therapy on serum levels of receptor-activating nuclear factor kappabeta ligand (RANKL), osteoprotegerin, osteocalcin, leptin, and ghrelin in a cross-sectional study of 99 healthy postmenopausal women conducted at the Menopause Clinic of our department. DESIGN: In this cross-sectional, observational study, 99 participants were divided into two groups. Group A was composed of 77 postmenopausal women who had never received estrogen-progestin therapy, and group B was composed of 22 postmenopausal women who had received transdermal 17beta-estradiol at a dose of 50 microg/day in a continuous regimen for at least 24 months and nomegestrol at a dose of 5 mg/day for 12 days/month in a sequential regimen. All participants underwent blood sampling in the morning and quantitative ultrasound bone-densitometry measurement of the proximal phalanges of the dominant hand. RESULTS: T score and amplitude-dependent speed of sound were significantly higher in group B than in group A. No significant differences in RANKL, osteoprotegerin, and osteocalcin were observed between the two groups. Serum leptin levels were significantly lower in group B than in group A, whereas ghrelin was significantly higher in group B than in group A. CONCLUSIONS: The data gathered in this preliminary study indicate that estrogen-progestin therapy may protect against postmenopausal bone loss, but this protective effect does not seem to be exerted through action on the RANK-RANKL-osteoprotegerin system. Similarly, although several reports suggest that leptin and ghrelin are involved in bone metabolism, we could not detect any important correlation of these two hormones with bone metabolism or bone status in treated and untreated postmenopausal women. Because of the limited number of treated participants and the study design, the results of this preliminary study must be confirmed in larger, prospective, longitudinal studies.

Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene.

OBJECTIVE: To compare body composition and serum leptin levels in untreated postmenopausal women and postmenopausal women treated with tibolone or raloxifene. DESIGN: This was a prospective, randomized, controlled study. Sixty-eight postmenopausal women were randomized to receive either no treatment (group A, n = 21) or tibolone 2.5 mg/day (group B; n = 23) or raloxifene 60 mg/day (group C; n = 24). All women underwent height, weight, body mass index evaluation and dual energy x-ray absorptiometry determination of body composition at the beginning of the study and after 12 months. Serum leptin levels were determined at the beginning of the study and after 1, 3, 6, and 12 months in all groups. RESULTS: Women in group A showed no significant changes in both fat and lean mass of arms and legs, whereas a significant increase in trunk fat mass, total fat mass, total percentage of body fat, and trunk percentage of fat was detected 1 year after the beginning of the study. After 12 months, the total percentage of fat mass was significantly higher in group A compared with group B, and the trunk percentage of fat mass was significantly higher in group A compared with groups. In subjects in groups B and C, after 1 year, fat mass, both total and at all areas evaluated, did not show any significant change compared with baseline values. In subjects in group B, total lean and lean mass of the trunk and legs increased significantly at the end of the study, whereas no significant changes were observed in lean mass, total and at all areas evaluated in subjects in group C. After 12 months, total lean mass and lean mass of the legs were significantly higher in group B compared with the other groups. In group A, serum leptin levels were significantly increased at the end of the study compared with baseline values. Leptin concentrations were significantly higher in group A compared with groups B and C after 6 and 12 months. No significant change in serum leptin levels in subjects in groups B and C was detected throughout the study. Serum leptin levels showed a positive, significant correlation with all body composition parameters and body mass index in all groups at the beginning and at the end of the study. CONCLUSIONS: The present study confirms that postmenopausal hypoestrogenism leads to increased fat content and serum leptin levels. Raloxifene and tibolone seem to prevent postmenopausal body composition changes without significant modifications of serum leptin levels.