The anatomy of Trans-Obturator Posterior Anal Sling (TOPAS) and dynamics of potential mechanism of action.

BACKGROUND: The aim of this study was to investigate the course of the transobturator posterior anal sling and its relationship to anatomical structures. METHODS: The transobturator anal sling procedure was performed in four fresh-frozen pelvises. The pelvises were dissected and the structures adjacent to the sling and the course of the sling were identified and measurements obtained. RESULTS: The transobturator posterior anal sling was inserted 2 ± 0.5 cm posteriorly to the anus, and 2.5 ± 0.5 cm caudal to the coccyx under the levator plate at the level of the puborectalis muscle. The tape was 3.5 ± 0.5 cm from the pubic symphysis and 2.3 ± 0.3 cm from the obturator canal at entry into the pelvic cavity. The tape passed 2.3 ± 0.3 cm inferior-medial to the obturator canal. At entry, the sling passed lateral to the ischiopubic ramus through the following structures: gracilis, adductor brevis, obturator externus, obturator membrane, and beneath the obturator internus muscle. The sling traveled 2-3 ± 0.5 cm over the iliococcygeus muscle and perforated the iliococcygeus fibers 0-2 cm medial to arcus tendinous levator ani. The posterior division of the obturator nerve was 2.8 ± 0.7 cm from the tape. The anterior division of the obturator nerve was 3.4 ± 0.8 cm from the tape. The device passed 1.1 ± 0.4 cm from the most medial branch of the obturator vessels. CONCLUSIONS: The transobturator posterior anal sling travels mostly in the avascular area of the ischiorectal fossa and posterior to the puborectalis muscle as intended.

PLANET TOPERS: Planets, Tracing the Transfer, Origin, Preservation, and Evolution of their ReservoirS.

The Interuniversity Attraction Pole (IAP) 'PLANET TOPERS' (Planets: Tracing the Transfer, Origin, Preservation, and Evolution of their Reservoirs) addresses the fundamental understanding of the thermal and compositional evolution of the different reservoirs of planetary bodies (core, mantle, crust, atmosphere, hydrosphere, cryosphere, and space) considering interactions and feedback mechanisms. Here we present the first results after 2 years of project work.

A multicenter, prospective trial to evaluate mesh-augmented sacrospinous hysteropexy for uterovaginal prolapse.

INTRODUCTION AND HYPOTHESIS: Hysterectomy is often part of pelvic organ prolapse repair. However, this may offer no benefit when compared to uterine preservation. We aimed to prospectively evaluate a minimally invasive bilateral sacrospinous hysteropexy using polypropylene mesh. We hypothesized that anatomic success and patient satisfaction can be achieved with this technique. METHODS: Women with uterovaginal prolapse desiring surgery who had completed childbearing were enrolled. Preoperative assessment included standardized prolapse examination and validated symptom and pain scale questionnaires. Women with prior pelvic organ prolapse repair or any contraindication to uterine preservation were excluded. Data including demographic, operative and postoperative information was collected on patients for 1 year following surgery. Continuous variables are summarized as means (standard deviation) and categorical variables are summarized as frequencies and percentages. A mixed-effects model was used to evaluate the changes in questionnaire scores and outcomes at 6 months and 12 months after surgery with random effects accounting for the center effect with adjustment for age. RESULTS: The study group comprised 99 women from three female pelvic medicine and reconstructive surgery (urogynecology) centers. The average age of the participants was 67.0 years (11.32 years), BMI 26.04 kg/m(2) (3.56 kg/m(2)), and the majority were multiparous (98.9%) and menopausal (90.9%). Overall success at 12 months, as measured by composite outcome was 97.7% (with the Ba point as the anatomic landmark) and 96.6% (with the C point as the anatomic landmark). The overall exposure rate was 6.52% and reoperation rate was 7.53%. All subjective questionnaire scores and anatomic outcomes had improved at 12 months. CONCLUSIONS: Sacrospinous hysteropexy using a minimally invasive polypropylene mesh kit is an effective and safe technique for addressing uterovaginal prolapse as an alternative to hysterectomy at the time of pelvic reconstructive surgery.

Tension-free vaginal tape: outcomes among women with primary versus recurrent stress urinary incontinence.

OBJECTIVE: To evaluate the outcomes of tension-free vaginal tape in the treatment of primary versus recurrent genuine stress urinary incontinence. METHODS: A retrospective, multicenter study of 245 consecutive women who were treated with tension-free vaginal tape for genuine stress urinary incontinence (157 for primary and 88 for recurrent genuine stress urinary incontinence) over a 27-month period was performed. Concurrent surgical repairs were performed as required. Subjective and objective outcome data were assessed from routine postoperative visits. Office and hospital records were reviewed to determine patient characteristics, intraoperative findings, and surgical outcomes. RESULTS: Women with recurrent genuine stress urinary incontinence were older (mean age 64.6 versus 59.4 years, P =.004) than those with primary incontinence; they were less likely to have an intact uterus (22.7% versus 66.9%, P <.001), and were more likely to have intrinsic sphincter deficiency (70.5% versus 47.1%, P <.001). The mean duration of follow-up was 38 (+/-16) weeks. Cure rates among patients with recurrent versus primary genuine stress urinary incontinence were similar (85% and 87%, respectively, P =.23). Complication rates were similarly low in both groups (4.5% versus 7.6% for recurrent and primary genuine stress urinary incontinence, respectively, P =.35). Postoperative voiding dysfunction occurred at low rates in both groups. CONCLUSION: Tension-free vaginal tape is a highly effective treatment among patients with recurrent stress incontinence, with outcomes comparable with those among patients with primary incontinence.

Release of tension-free vaginal tape for the treatment of refractory postoperative voiding dysfunction.

OBJECTIVE: To report our experience with surgical release of tension-free vaginal tape (TVT) for the treatment of persistent post-TVT voiding dysfunction. METHODS: A total of 1175 women underwent TVT placement for treatment of genuine stress urinary incontinence and/or intrinsic sphincter deficiency over a 2-year period. Additional procedures and vaginal repairs were performed as indicated. Among these patients, 23 women (1.9%) had persistent voiding dysfunction (urinary retention, incomplete bladder emptying, or severe urgency or urge incontinence) refractory to conservative management. This cohort underwent a simple vaginal TVT release procedure, performed on an outpatient basis. Preoperative characteristics, intraoperative, and postoperative details were assessed by review of operative notes, medical records, and office notes. Continence status was assessed using subjective and objective information. RESULTS: Mean age was 67 years (range 46-86 years), and the mean interval between TVT placement and release was 17.3 weeks (range 2-69 weeks; median 8.6 weeks). For the release procedure, there were no intraoperative complications, and all patients were discharged on the day of surgery. All cases of impaired emptying were completely resolved, and all cases of irritative symptoms were resolved (30%) or improved (70%) by 6 weeks. Fourteen (61%) patients remained continent 6 weeks after the release procedure, six (26%) were improved over baseline, and three patients (13%) had recurrence of stress incontinence. CONCLUSION: Refractory voiding dysfunction after TVT is a relatively uncommon situation and can be successfully managed with a simple midline release procedure. In most cases, the release procedure does not compromise overall improvement in symptoms of stress incontinence.

Phase I trial of outpatient weekly docetaxel, carboplatin and concurrent thoracic radiation therapy for stage III unresectable non-small-cell lung cancer: a Vanderbilt cancer center affiliate network (VCCAN) trial.

PURPOSE: Docetaxel, an active agent for non-small cell lung cancer (NSCLC), has demonstrated activity as a radiosensitizer in numerous pre-clinical studies. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly Docetaxel, Carboplatin with concurrent thoracic radiation therapy (TRT) in patients with unresectable stage III NSCLC. PATIENTS AND METHODS: In this phase I clinical trial, Docetaxel was administered weekly as a 1-h intravenous infusion for 6 weeks with a starting dose of 20 mg/m(2). Docetaxel doses were escalated by 10 mg/m(2) increments in successive cohorts of three patients. DLT was defined as grade >or=3 nonhematologic and hematologic toxicity according to RTOG toxicity criteria. Once the DLT of Docetaxel alone was reached, weekly Carboplatin (AUC 2) was added at a DLT-2 dose of Docetaxel (two dose levels below that of dose limiting toxicity). Docetaxel doses were again escalated at 10 mg/m(2) increments in successive cohorts of three new patients to define further DLT and MTD of Docetaxel/Carboplatin with TRT. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). RESULTS: Fifteen patients were entered onto this study with Docetaxel alone through three dose escalations (from 20 to 40 mg/m(2) weekly). The DLT of weekly Docetaxel/TRT was esophagitis and the MTD was 30 mg/m(2) per week for 6 weeks. Nine more patients were added with the Docetaxel/Carboplatin/TRT regimen. The DLT of weekly Docetaxel/Carboplatin with TRT was esophagitis and the MTD of Docetaxel was 20 mg/m(2) per week with weekly Carboplatin (AUC 2). There were 2 complete responses and 13 partial responses in 25 evaluable patients (RR 60%). CONCLUSIONS: This combination regimen has activity with manageable toxicity in patients with stage III NSCLC. A phase II study is planned to define activity.

Percutaneous afferent neuromodulation for the refractory overactive bladder: results of a multicenter study.

PURPOSE: More than 20 million Americans have an overactive bladder, the predominant symptoms being frequency, urgency, urge incontinence and pelvic pain. While the etiology is not completely understood, most investigators believe the causes to be many and the pelvic floor to be intimately related. Whatever the etiology, traditional therapies, including dietary manipulation, bladder drill, medications and physical therapy, are often poorly tolerated and/or ineffective. We report a prospective, multicenter clinical trial that was undertaken to determine the safety and efficacy of percutaneous peripheral afferent nerve stimulation for treatment of refractive overactive bladder and/or pelvic floor dysfunction. MATERIALS AND METHODS: A total of 53 patients with overactive bladders, in whom all traditional therapy failed, were enrolled in 1 of 5 sites within the United States. Patients received weekly percutaneous electrical stimulations via a 34 gauge needle placed near the tibial nerve 3 finger breadths above the ankle. Urodynamic studies, detailed voiding diaries, quality of life surveys, and incontinence impact questionnaires were completed before, during and after the study. RESULTS: Of the patients with a mean age of 57.4 years 89% (47 of 53) completed the 12-week study. A total of 71% of patients were classified as treatment successes by the investigators and were started on long-term treatment. On average patients noticed a 25% reduction in mean daytime and 21% reduction in mean nighttime voiding frequencies (p <0.05). Urge incontinence was reduced by an average of 35% (p <0.05). Statistically significant improvements were noted in selective pain and quality of life indexes. No significant adverse events related to treatment were noted in any patients. CONCLUSIONS: Percutaneous peripheral afferent nerve stimulation offers a safe, minimally invasive and effective treatment for managing refractive overactive bladder and/or pelvic floor dysfunction.

Patient satisfaction with laparoscopic Burch retropubic urethropexy.

OBJECTIVE: To assess six-month and three- to four-year patient-oriented outcomes after laparoscopic Burch retropubic urethropexy. STUDY DESIGN: Twenty-two women with urodynamically proven genuine stress incontinence with urethral hypermobility underwent laparoscopic Burch retropubic urethropexy. Preoperatively, all 22 women completed a questionnaire concerning their incontinence. Postoperative measures of symptoms of incontinence, impact of incontinence on daily activities and patient satisfaction were assessed at six months and three to four years postoperatively. In those women who were followed, the questionnaire data at the three-time points (preoperative, six months and three to four years) were compared. RESULTS: Thirteen women (59%) completed postoperative questionnaires at six months and three to four years. When compared to preoperative data, there was a significant improvement in symptoms of stress incontinence at six months (P = .0005) and at three to four years (P = .002). There was also a significant reduction in limitations on daily activities at six months (P = .0005) and at three to four years (P = .0005) as compared to preoperative data. Twelve of the 13 women considered their surgery successful at six months and at three to four years. CONCLUSION: After laparoscopic Burch retropubic urethropexy, there was a significant improvement in patient-oriented outcomes, including complaints of incontinence and functional status.

A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study).

PURPOSE: We conducted a prospective phase II study to determine the response rate, toxicity, and survival rate of concurrent weekly paclitaxel, carboplatin, and hyperfractionated radiation therapy (paclitaxel/carboplatin/HFX RT) followed by 2 cycles of paclitaxel and carboplatin for locally advanced unresectable non-small cell lung cancer (NSCLC). The weekly paclitaxel and carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. METHODS AND MATERIALS: Forty-three patients with unresectable stage IIIA and IIIB NSCLC from the Vanderbilt Cancer Center and Affiliate Network (VCCAN) institutions were entered onto the study from June 1996 until May 1997. Weekly intravenous (IV) paclitaxel (50 mg/m(2)/l-hour) and weekly carboplatin (AUC 2) plus concurrent hyperfractionated chest RT (1.2 Gy/BID/69.6 Gy) were delivered for 6 weeks followed by 2 cycles of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). RESULTS: Forty-two patients were evaluable for response and toxicities. Three patients achieved a complete response (7.2%) and 30 patients achieved a partial response (71.4%), for an overall response rate of 78.6% [95% C.I. (66.2%-91.0%)]. The 1- and 2-year overall and progression-free survival rates of all 43 patients were 61.6% and 35% respectively, with a median survival time of 14.3 months. The median follow-up time was 14 months. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (26%). There was an incidence of 7% grade 3 and 9.5% grade 4 pulmonary toxicities. CONCLUSIONS: Weekly paclitaxel, carboplatin, plus concurrent hyperfractionated RT is a well-tolerated outpatient regimen. The response rate from this regimen is encouraging and appears to be at least equivalent to the more toxic chemoradiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/carboplatin/HFX RT in a phase III study.

A phase I trial of outpatient weekly docetaxel and concurrent radiation therapy for stage III unresectable non small-cell lung cancer: a Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial.

Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical studies, probably due to its role as a cell cycle synchronizer for the G2/M radiosensitive phase of the cell cycle. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of docetaxel with concurrent thoracic radiation therapy (TRT) to patients with unresectable stage III non small-cell lung cancer (NSCLC). Fifteen patients were entered into this study. Docetaxel was administered as a 1-hour intravenous (I.V.) infusion, repeated every week for 6 weeks with starting dose of 20 mg/m2. Doses were escalated in 10 mg/m2 increments in successive cohorts of three new patients, if tolerated. Unacceptable toxicity was defined as grade = 3 nonhematologic or hematologic toxicity according to Eastern Cooperative Oncology Group (ECOG) toxicity criteria. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). At the first dose level (20 mg/m2/week), one patient developed grade 4 hyperglycemia and accrual was expanded to five patients. At the second level (30 mg/m2/week), two out of six patients developed grade 3 esophagitis. At the third level (40 mg/m2/week), two out of four patients developed grade 3 esophagitis and one patient developed grade 3 pulmonary toxicity. The weekly docetaxel MTD with concurrent radiation therapy (RT) was found to be 30 mg/m2. The DLT was esophagitis and pulmonary toxicity. Other toxicities encountered included skin reaction, nausea and vomiting, as well as diarrhea. Additionally, there were no treatment-related mortalities or late-occurring toxicities. Esophagitis was the principal DLT of concurrent weekly docetaxel and thoracic radiation in the outpatient setting. The MTD of concurrent weekly docetaxel with TRT is 30 mg/m2 weekly for 6 weeks. This study is still open to accrual with weekly docetaxel and TRT in locally advanced NSCLC patients.

Ureteral compromise after laparoscopic Burch colpopexy.

Ureteral obstruction occurred in two patients after laparoscopic Burch cystourethropexy. Both women experienced right flank pain and right hydronephrosis. Cystoscopy revealed transmural passage of suture anterior and lateral to the ureteral orifice on the right side. One patient was managed by suprapubic cystoscopy to release the suture; the other was managed by preperitoneal laparoscopy to release suture at the bladder neck. In both patients efflux of urine was seen immediately from the ureteral orifice after suture release. Ultrasound confirmed prompt resolution of hydronephrosis. Cystoscopy with confirmation of patent ureters should be performed after every case of retropubic cystourethropexy. Retrograde rigid cystoscopy may not afford adequate access to remove transmural sutures. Placement of sutures at the bladder neck from medial to lateral may avoid entrapment of the intramural portion of ureter. (J Am Assoc Gynecol Laparosc 6(2):217-219, 1999)

The effect of posterior wall support defects on urodynamic indices in stress urinary incontinence.

OBJECTIVE: To determine if posterior vaginal wall defects affect urodynamic indices and mask stress urinary incontinence. METHODS: Ninety women with grade 0, 1, 2, or 3 posterior wall defects were evaluated prospectively by complete urodynamics to assess their urinary complaints. None had severe anterior or apical support defects. Urethral pressure profilometry and cough stress test were performed with the posterior wall in the unretracted position and then with the posterior wall retracted using a split speculum. Analysis of covariance was used to compare adjusted mean differences in maximum urethral closure pressure, functional urethral length, and units of leakage volume during the cough stress test in the unretracted and retracted positions among the posterior wall grade groups. RESULTS: In women with grade 3 posterior wall defects, there were significant changes from the unretracted to the retracted position in maximum urethral closure pressure of -7.0 cm H20, (99% confidence interval [CI] -12.4, -1.6), functional urethral length of -0.3 cm (99% CI -0.5, -0.1), and leak volume units of +0.7 (99% CI 0.4, 1.0) during the cough stress test. There were four women with grade 3 posterior wall defects who demonstrated potential stress incontinence when their posterior wall was retracted. CONCLUSION: A grade 3 posterior wall defect may artificially raise maximum urethral closure pressure, increase functional urethral length, and mask urinary stress incontinence during a cough stress test. Women with grade 3 posterior wall defects should be tested with the posterior wall retracted during urodynamic evaluation.

Preliminary analysis of a phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer.

We conducted a prospective phase II study to determine the response rate, toxicity profile, and survival rate among patients with locally advanced unresectable non-small cell lung cancer receiving concurrent weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), carboplatin, and hyperfractionated radiation therapy followed by two cycles of adjuvant paclitaxel and carboplatin. The weekly paclitaxel/carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. Thirty-two patients with unresectable stage IIIA and IIIB non-small cell lung cancer from Vanderbilt Cancer Center Affiliate Network institutions entered the study from June 1996 until February 1997. Weekly intravenous paclitaxel (50 mg/m2 over 1 hour) and weekly carboplatin (area under the concentration-time curve of 2) plus concurrent hyperfractionated chest radiotherapy (1.2 Gy twice daily [69.6 Gy total]) delivered for 6 weeks were followed by two cycles of paclitaxel (200 mg/m2) and carboplatin (area under the concentration-time curve of 6). Among 22 patients evaluable for response, one (4.5%) achieved a complete response and 16 (72.7%) achieved partial response, for an overall response rate of 77%. Among 23 patients evaluable for toxicity, esophagitis was the principal finding: grade 3 or 4 esophagitis occurred in eight patients (35%). Grade 3 and 4 pulmonary toxicities each occurred in 26% of patients. Thus, weekly paclitaxel/carboplatin plus concurrent hyperfractionated radiotherapy is a well-tolerated outpatient regimen with an encouraging response rate that is at least equivalent to more toxic chemoradiation regimens. These findings indicate that further clinical evaluation of weekly paclitaxel/carboplatin/hyperfractionated radiotherapy is warranted in phase III trials.

Grief and the sexual relationship of couples who have experienced a child's death.

In an interview study of the sexual relationship of bereaved parents, 16 of 24 heterosexual couples interviewed after the death of a child reported a break or decline in sexual intercourse. Consistent with social constructivist perspectives, the meanings couples gave to sexual intercourse, the death, and their grief were central in their understanding of the break or decline--e.g., the belief that intercourse was too painful because it was how the child had been made. Meanings were also linked to the continuation or resumption of the intercourse--e.g., that intercourse was life-affirming. Touching, which was defined as sexual by many people interviewed, had consistent meanings across couples--connection, support, and comfort--although couples differed in whether touching increased, decreased, or did not increase enough to satisfy one partner following the death. The meanings that couples used in discussing touching and the decline or break in sexual intercourse were also used in talking about extramarital affairs and grieving during intercourse.

Use of Interceed Absorbable Adhesion Barrier for vaginoplasty.

Vaginal agenesis is a rare condition that can be treated successfully with a variety of nonoperative as well as surgical procedures. The difference between most of the surgical techniques lies in the material used to line the newly created canal. Skin grafts, peritoneum, and amnion have all been reported for this purpose. In the present study, four women with vaginal agenesis underwent surgical construction of an artificial vagina using Interceed Absorbable Adhesion Barrier to cover an inflatable stent placed within the neovagina. There were no intraoperative or postoperative complications, and epithelialization of the neovagina was complete by 3-6 months. All four subjects were satisfied with the results of the surgery and none of the women reported difficulty complying with postoperative care. This modification of the Abbe-McIndoe technique does not require a separate operative procedure to harvest a lining for the neovagina. The use of Interceed may reduce the cost, operative time, and morbidity associated with other vaginoplasty techniques.