Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial.

Importance: Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven. Objective: To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. Design, Setting, and Participants: A double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized. Interventions: Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. Main Outcomes and Measures: The co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). Results: Of 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group. Conclusions and Relevance: Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001403426.

Laparoscopic myomectomy: clinical outcomes and comparative evidence.

Laparoscopic myomectomy is a common surgical treatment for symptomatic uterine leiomyomas. Proponents of the laparoscopic approach to myomectomy propose that the advantages include shorter length of hospital stay and recovery time. Others suggest longer operative time, greater blood loss, increased risk of recurrence, risk of uterine rupture in future pregnancies, and potential dissemination of cells with use of morcellation. This review outlines techniques for performance of laparoscopic myomectomy and critically appraises the available evidence for operative data, short-term and long-term complications, and reproductive outcomes.

Laparoscopic vessel sealing technologies.

Laparoscopic vessel sealing devices have revolutionized modern laparoscopy. These devices fall into 2 major categories: advanced bipolar and ultrasonic instruments. The range of tissue effects available with these technologies is more limited than with conventional monopolar electrosurgery; however, both advanced bipolar and ultrasonic devices efficiently seal vessels (≤7-mm and ≤5-mm diameter, respectively), and most also have built-in tissue transection capabilities. These technologies have been the subject of a range of comparative studies on their relative advantages and disadvantages, and, to date, neither advanced bipolar or ultrasonic devices has been proven to be superior.

Comparative studies of energy sources in gynecologic laparoscopy.

Energy sources incorporating "vessel sealing" capabilities are being increasingly used in gynecologic laparoscopic surgery although conventional monopolar and bipolar electrosurgery remain popular. The preference for one device over another is based on a combination of factors, including the surgeon's subjective experience, availability, and cost. Although comparative clinical studies and meta-analyses of laparoscopic energy sources have reported small but statistically significant differences in volumes of blood loss, the clinical significance of such small volumes is questionable. The overall usefulness of the various energy sources available will depend on a number of factors including vessel burst pressure and seal time, lateral thermal spread, and smoke production. Animal studies and laboratory-based trials are useful in providing a controlled environment to investigate such parameters. At present, there is insufficient evidence to support the use of one energy source over another.

Laparoscopic subtotal hysterectomy: evidence and techniques.

Laparoscopic subtotal/supracervical hysterectomy (LSH) is a surgical option when hysterectomy is indicated. Proponents of LSH suggest possible advantages including reduced recovery time, decreased risk of pelvic organ prolapse, and decreased risk of organ damage, in particular to the urinary tract. Opponents of LSH have suggested that the future risk of cervical malignancy, the possibility of ongoing cyclical bleeding, limited morbidity due to total laparoscopic hysterectomy, and similar clinical outcomes render this approach unnecessary. One study compared LSH with laparoscopically assisted vaginal hysterectomy in a randomized controlled trial that reported psychologic and sexual outcomes; however, no clinical data were published. The present review outlines techniques for subtotal hysterectomy and critically appraises the available evidence for outcomes including operative data, short- and long-term complications, and functional outcomes.

Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial.

OBJECTIVE: To estimate whether botulinum toxin type A is more effective than placebo at reducing pain and pelvic floor pressure in women with chronic pelvic pain and pelvic floor muscle spasm. METHODS: This study was a double-blinded, randomized, placebo-controlled trial. All participants presented with chronic pelvic pain of more than 2 years duration and evidence of pelvic floor muscle spasm. Thirty women had 80 units of botulinum toxin type A injected into the pelvic floor muscles, and 30 women received saline. Dysmenorrhea, dyspareunia, dyschezia, and nonmenstrual pelvic pain were assessed by visual analog scale (VAS) at baseline and then monthly for 6 months. Pelvic floor pressures were measured by vaginal manometry. RESULTS: There was significant change from baseline in the botulinum toxin type A group for dyspareunia (VAS score 66 versus 12; chi2 = 25.78, P < .001) and nonmenstrual pelvic pain (VAS score 51 versus 22; chi2 = 16.98, P = .009). In the placebo group only dyspareunia was significantly reduced from baseline (64 versus 27; chi2 = 2.98, P = .043). There was a significant reduction in pelvic floor pressure (centimeters of H2O) in the botulinum toxin type A group from baseline (49 versus 32; chi2 = 39.53, P < .001), with the placebo group also having lower pelvic floor muscle pressures (44 versus 39; chi2 = 19.85, P = .003). CONCLUSION: Objective reduction of pelvic floor spasm reduces some types of pelvic pain. Botulinum toxin type A reduces pressure in the pelvic floor muscles more than placebo. Botulinum toxin type A may be a useful agent in women with pelvic floor muscle spasm and chronic pelvic pain who do not respond to conservative physical therapy. CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Registry, http://www.actr.org.au/, ACTRN012605000515695 LEVEL OF EVIDENCE: I.

Energy sources for gynecologic laparoscopic surgery: a review of the literature.

IMPORTANCE: A range of energy sources are used in gynecologic laparoscopy. These energy sources include monopolar electrosurgery, bipolar electrosurgery (including "advanced bipolar" devices that incorporate tissue feedback monitoring), and various types of laser and ultrasonic technologies. Gynecologists using these tools should be aware of the potential benefits and potential dangers of these instruments. OBJECTIVE: This review provides an overview of the biophysics of these energy sources, their tissue effects, and the complications that may arise. It aims to highlight any potential advantages or disadvantages of various energy sources, as reported by clinical and laboratory studies. EVIDENCE ACQUISITION: Literature relating to energy sources used in gynecologic laparoscopy was reviewed. RESULTS: While laboratory-based studies have reported differences between various energy sources, these differences may not be clinically significant. The choice of instrumentation may depend on the nature of the surgical task being performed, but other factors, such as the surgeon's training/experience, cost, and industry marketing, may also influence the decision. CONCLUSIONS: TAn awareness of the pros and cons of each energy modality and their relative efficacy profiles is paramount. RELEVANCE: It is important that surgeons have an understanding of the biophysics of these technologies in order to understand their limitations and potential dangers and to utilize the most appropriate energy source(s) in the appropriate clinical setting, in order to both minimize the risk of inadvertent injuries during gynecologic laparoscopy and to maximize cost-efficient delivery of health care.

Clinical and quality-of-life outcomes after fertility-sparing laparoscopic surgery with bowel resection for severe endometriosis.

STUDY OBJECTIVE: To describe the effect of fertility-sparing laparoscopic excision of endometriosis and bowel resection on clinical and quality-of-life outcomes. DESIGN: Prospective observational cohort study (Canadian Task Force classification II-2). SETTING: Australian tertiary referral center for the surgical treatment of endometriosis. PATIENTS: Seven consecutive patients with known endometriosis involving the bowel. INTERVENTION: Laparoscopic resection of all endometriosis, including laparoscopic bowel resection with end-to-end anastomosis with or without temporary ileostomy. MEASUREMENTS AND MAIN RESULTS: Preoperative and 12-month postoperative data were collected by use of visual analogue scores for dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and dyschezia. Validated research tools (SF12, EuroQOL, and Sexual Activity Questionnaire) also assessed quality of life. Reduction in median pain scores at baseline was demonstrated and at 12 months after operation for dysmenorrhea 71 (interquartile range 43-85) versus 5 (0-10); p=.028, nonmenstrual pelvic pain 74 (48-85) versus 11 (0-18); p=.046, dyspareunia 66 (0-98) versus 5 (0-8); p=.080, and dyschezia 48 (20-64) versus 20 (0-40); p=.173. All measures of quality of life were improved at 12 months after surgery, although not reaching statistical significance because of the small sample size. All three women wishing to conceive after operation have been successful, resulting in three live births at term. There were few complications associated with this surgery. CONCLUSION: Fertility-sparing laparoscopic excision of endometriosis with bowel resection results in improvements in all aspects of pain and quality of life. Results appear to parallel published data for conservative resection of endometriosis not involving bowel. For women with severe endometriosis involving bowel, this surgical treatment provides a viable alternative to pelvic clearance and successfully maintains fertility.

Inhibitors of de novo nucleotide biosynthesis as drugs.

Potent inhibitors of enzymes catalyzing reactions in the de novo pathways for biosynthesis of purine and pyrimidine nucleotides are synthetic or natural-product analogues of pathway intermediates or, more recently, inhibitors rationally designed from a knowledge of the catalytic mechanism. Such inhibitors may be effective drugs against cancer, inflammatory disorders, or various infections. For human cancer, the purine pathway may be a better target for inhibition than the pyrimidine pathway, where toxic side effects are more apparent. Drugs such as methotrexate and 6-mercaptopurine have multiple sites of action, making it difficult to quantitatively predict their effects upon cells. Rational design of inhibitors based upon the X-ray structure of the target enzyme has the prospect of yielding drugs with only one site of action in human cells. Such a drug is VX-497, a potent inhibitor of the purine enzyme, IMP dehydrogenase.