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Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. Here we describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from non-neoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and H&E microscopy for detection of glioma infiltration (κ=0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct.

OBJECTIVES To describe pelvic organ prolapse surgical success rates using a variety of definitions with differing requirements for anatomic, symptomatic, or re-treatment outcomes. METHODS Eighteen different surgical success definitions were evaluated in participants who underwent abdominal sacrocolpopexy within the Colpopexy and Urinary Reduction Efforts trial. The participants’ assessments of overall improvement and rating of treatment success were compared between surgical success and failure for each of the definitions studied. The Wilcoxon rank sum test was used to identify significant differences in outcomes between success and failure. RESULTS Treatment success varied widely depending on definition used (19.2–97.2%). Approximately 71% of the participants considered their surgery “very successful,” and 85.2% considered themselves “much better” than before surgery. Definitions of success requiring all anatomic support to be proximal to the hymen had the lowest treatment success (19.2–57.6%). Approximately 94% achieved surgical success when it was defined as the absence of prolapse beyond the hymen. Subjective cure (absence of bulge symptoms) occurred in 92.1% while absence of re-treatment occurred in 97.2% of participants. Subjective cure was associated with significant improvements in the patient’s assessment of both treatment success and overall improvement, more so than any other definition considered (P<.001 and <.001, respectively). Similarly, the greatest difference in symptom burden and health-related quality of life as measured by the Pelvic Organ Prolapse Distress Inventory and Pelvic Organ Prolapse Impact Questionnaire scores between treatment successes and failures was noted when success was defined as subjective cure (P<.001). CONCLUSION The definition of success substantially affects treatment success rates after pelvic organ pro-lapse surgery. The absence of vaginal bulge symptoms postoperatively has a significant relationship with a patient’s assessment of overall improvement, while anatomic success alone does not.

IMPORTANCE Over 300,000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly performed transvaginal surgeries to correct apical prolapse. Little is known about their comparative efficacy and safety, and it is unknown whether perioperative behavioral therapy with pelvic floor muscle training (BPMT) improves outcomes of prolapse surgery. OBJECTIVE To compare outcomes between 1) SSLF and ULS and 2) perioperative BPMT and usual perioperative care in women undergoing surgery for vaginal prolapse and stress urinary incontinence. DESIGN, SETTING AND PARTICIPANTS Multi-center, 2×2 factorial randomized trial of 374 women undergoing surgery to treat both apical vaginal prolapse and stress urinary incontinence was conducted between 2008 and 2013 at 9 U.S. medical centers. Two-year follow-up rate was 84.5%. INTERVENTIONS Surgical intervention: Transvaginal surgery including mid-urethral sling with randomization to SSLF (n = 186) or ULS (n=188); Behavioral intervention: Randomization to perioperative BPMT (n = 186) or usual care (n=188). MAIN OUTCOME MEASURES The primary outcome for the surgical intervention (surgical success) was defined as: 1) no apical descent greater than one-third into vaginal canal or anterior or posterior vaginal wall beyond the hymen (anatomic success); 2) no bothersome vaginal bulge symptoms and 3) no retreatment for prolapse at 2 years. For the behavioral intervention, primary outcome at 6 months was urinary symptom scores (Urinary Distress Inventory; range 0–300, higher scores worse), and primary outcomes at 2 years were prolapse symptom scores (Pelvic Organ Prolapse Distress Inventory; range 0–300, higher scores worse) and anatomic success. RESULTS At 2 years, surgical group was not significantly associated with surgical success rates [ULS 59.2% (93/154) vs. SSLF 60.5% (92/152), OR 0.9 (95% CI 0.6, 1.5)] or serious adverse event rates [ULS 16.5% (31/188) vs. SSLF 16.7% (31/186), OR 0.9 (95% CI 0.5, 1.6)]. BPMT was not associated with greater improvements in urinary scores at 6 months [treatment difference −6.7 (95% CI −19.7, 6.2)], prolapse scores at 24 months [treatment difference −8.0 (95% CI −22.1, 6.1)] or anatomic success at 24 months. CONCLUSIONS AND RELEVANCE Two years after vaginal surgery for prolapse and stress urinary incontinence, neither ULS nor SSLF was significantly superior to the other for anatomic, functional, and or adverse event outcomes. Perioperative BPMT did not improve urinary symptoms at 6 months or prolapse outcomes at 2 years.

BACKGROUND Women without stress urinary incontinence undergoing vaginal surgery for pelvicorgan prolapse are at risk for postoperative urinary incontinence. A midurethral sling may be placed at the time of prolapse repair to reduce this risk. METHODS We performed a multicenter trial involving women without symptoms of stress incontinence and with anterior prolapse (of stage 2 or higher on a Pelvic Organ Prolapse Quantification system examination) who were planning to undergo vaginal prolapse surgery. Women were randomly assigned to receive either a midurethral sling or sham incisions during surgery. One primary end point was urinary incontinence or treatment for this condition at 3 months. The second primary end point was the presence of incontinence at 12 months, allowing for subsequent treatment for incontinence. RESULTS Of the 337 women who underwent randomization, 327 (97%) completed follow-up at 1 year. At 3 months, the rate of urinary incontinence (or treatment) was 23.6% in the sling group and 49.4% in the sham group (P<0.001). At 12 months, urinary incontinence (allowing for subsequent treatment of incontinence) was present in 27.3% and 43.0% of patients in the sling and sham groups, respectively (P = 0.002). The number needed to treat with a sling to prevent one case of urinary incontinence at 12 months was 6.3. The rate of bladder perforation was higher in the sling group than in the sham group (6.7% vs. 0%), as were rates of urinary tract infection (31.0% vs. 18.3%), major bleeding complications (3.1% vs. 0%), and incomplete bladder emptying 6 weeks after surgery (3.7% vs. 0%) (P≤0.05 for all comparisons). CONCLUSIONS A prophylactic midurethral sling inserted during vaginal prolapse surgery resulted in a lower rate of urinary incontinence at 3 and 12 months but higher rates of adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health; OPUS ClinicalTrials.gov number, NCT00460434.)