Identification of first stage labor arrest by electromyography in term nulliparous women after induction of labor

INTRODUCTION: Worldwide induction and cesarean delivery rates have increased rapidly, with consequences for subsequent pregnancies. The majority of intra-partum cesarean deliveries are performed for failure to progress, typically in nulliparous women at term. Current uterine registration techniques fail to identify inefficient contractions leading to first stage labor arrest. An alternative technique, uterine electromyography has been shown to identify inefficient contractions leading to first stage arrest of labor in nulliparous women with spontaneous onset of labor at term. The objective of this study was to determine whether this finding can be reproduced in induction of labor MATERIAL AND METHODS: Uterine activity was measured in 141 nulliparous women with singleton term pregnancies and a fetus in cephalic position during induced labor. Electrical activity of the myometrium during contractions was characterized by its power density spectrum RESULTS: No significant differences were found in contraction characteristics between women with induced labor delivering vaginally with or without oxytocin and women with arrested labor with subsequent cesarean delivery CONCLUSION: Uterine electromyography shows no correlation with progression of labor in induced labor, which is in contrast to spontaneous labor. This article is protected by copyright. All rights reserved

A randomised controlled trial comparing abdominal and vaginal prolapse surgery: effects on urogenital function

OBJECTIVE: To compare the effects of vaginal hysterectomy (combined with anterior and/or posterior colporraphy) and abdominal sacro-colpopexy (with preservation of the uterus) on urogenital function. DESIGN: Randomised trial. SETTING: Three teaching hospitals in The Netherlands. POPULATION: Eighty-two patients undergoing surgical correction of uterine prolapse stages II-IV. METHODS: Participating patients completed the urogenital distress inventory (UDI), before and at six weeks, six months and one year after surgery, to measure discomfort of prolapse and micturition symptoms. Domain scores of the UDI (ranging from 0 to 100, higher scores indicating more discomfort) were compared between groups at all time points. Findings at pelvic examination, number of doctor visits within the first year after surgery because of pelvic floor symptoms and performed or planned surgery of recurrent genital prolapse were also compared. MAIN OUTCOME MEASURE: Domain scores of the UDI at one year after surgery. RESULTS: At one year after surgery, scores on the discomfort/pain domain (mean difference 7.1, 95% confidence interval [CI] 1.1-13.2), overactive bladder domain (mean difference 8.7, 95% CI 0.5-16.9) and obstructive micturition domain (mean difference 10.3, 95% CI 0.6-20.1) of the UDI were significantly higher in the abdominal group than in the vaginal group. Findings at pelvic examination were similar in both groups. Doctor visits because of pelvic floor symptoms were more frequent in the abdominal group than in the vaginal group. Re-operation was performed or planned in 9 of the 41 patients who underwent abdominal surgery and in 1 of the 41 patients who underwent vaginal surgery (odds ratio [OR] = 11.2, 95% CI 1.4-90.0). CONCLUSIONS: Our findings suggest that vaginal hysterectomy with anterior and/or posterior colporraphy is preferable to abdominal sacro-colpopexy with preservation of the uterus as surgical correction in patients with uterine prolapse stages II-I

Vaginal prolapse repair with or without a midurethral sling in women with genital prolapse and occult stress urinary incontinence: a randomized trial

We compared pelvic organ prolapse (POP) repair with and without midurethral sling (MUS) in women with occult stress urinary incontinence (SUI). This was a randomized trial conducted by a consortium of 13 teaching hospitals assessing a parallel cohort of continent women with symptomatic stage II or greater POP. Women with occult SUI were randomly assigned to vaginal prolapse repair with or without MUS. Women without occult SUI received POP surgery. Main outcomes were the absence of SUI at the 12-month follow-up based on the Urogenital Distress Inventory and the need for additional treatment for SUI. We evaluated 231 women, of whom 91 randomized as follows: 43 to POP surgery with and 47 without MUS. A greater number of women in the MUS group reported absence of SUI [86 % vs. 48 %; relative risk (RR) 1.79; 95 % confidence interval (CI) 1.29-2.48]. No women in the MUS group received additional treatment for postoperative SUI; six (13 %) in the control group had a secondary MUS. Women with occult SUI reported more urinary symptoms after POP surgery and more often underwent treatment for postoperative SUI than women without occult SUI. Women with occult SUI had a higher risk of reporting SUI after POP surgery compared with women without occult SUI. Adding a MUS to POP surgery reduced the risk of postoperative SUI and the need for its treatment in women with occult SUI. Of women with occult SUI undergoing POP-only surgery, 13 % needed additional MUS. We found no differences in global impression of improvement and quality of lif

Central radiology assessment of the randomized phase III open-label OVHIPEC-1 trial in ovarian cancer

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) improved investigator-assessed recurrence-free survival and overall survival in patients with stage III ovarian cancer in the phase III OVHIPEC-1 trial. We analyzed whether an open-label design affected the results of the trial by central blinded assessment of recurrence-free survival, and tested whether HIPEC specifically targets the peritoneal surface by analyzing the site of disease recurrence. METHODS: OVHIPEC-1 was an open-label, multicenter, phase III trial that randomized 245 patients after three cycles of neoadjuvant chemotherapy to interval cytoreduction with or without HIPEC using cisplatin (100 mg/m2). Patients received three additional cycles of chemotherapy after surgery. Computed tomography (CT) scans and serum cancer antigen 125 (CA125) measurements were performed during chemotherapy, and during follow-up. Two expert radiologists reviewed all available CT scans. They were blinded for treatment allocation and clinical outcome. Central revision included Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurements and peritoneal cancer index scorings at baseline, during treatment, and during follow-up. Time to centrally-revised recurrence was compared between study arms using Cox proportional hazard models. Subdistribution models compared time to peritoneal recurrence between arms, accounting for competing risks. RESULTS: CT scans for central revision were available for 231 patients (94%) during neoadjuvant treatment and 212 patients (87%) during follow-up. Centrally-assessed median recurrence-free survival was 9.9 months in the surgery group and 13.2 months in the surgery+HIPEC group (HR for disease recurrence or death 0.72, 95% CI 0.55 to 0.94; p=0.015). The improved recurrence-free survival and overall survival associated with HIPEC were irrespective of response to neoadjuvant chemotherapy and baseline peritoneal cancer index. Cumulative incidence of peritoneal recurrence was lower after surgery+HIPEC, but there was no difference in extraperitoneal recurrences. CONCLUSION: Centrally-assessed recurrence-free survival analysis confirms the benefit of adding HIPEC to interval cytoreductive surgery in patients with stage III ovarian cancer, with fewer peritoneal recurrences. These results rule out radiological bias caused by the open-label nature of the study

Cost Effectiveness of Interval Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy in Stage III Ovarian Cancer on the Basis of a Randomized Phase III Trial

PURPOSE In the randomized open-label phase III OVHIPEC trial, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improved recurrence-free and overall survival in patients with stage III ovarian cancer. We studied the cost effectiveness of the addition of HIPEC to interval CRS in patients with ovarian cancer. PATIENTS AND METHODS We constructed a Markov health-state transition model to measure costs and clinical outcomes. Transition probabilities were derived from the OVHIPEC trial by fitting survival distributions. Incremental cost-effectiveness ratio (ICER), expressed as euros per quality-adjusted life-year (QALY), was calculated from a Dutch societal perspective, with a time horizon of 10 years. Univariable and probabilistic sensitivity analyses were conducted to evaluate the decision uncertainty. RESULTS Total health care costs were V70,046 (95% credibility interval [CrI], V64,016 to V76,661) for interval CRS compared with V85,791 (95% CrI, V78,766 to V93,935) for interval CRS plus HIPEC. The mean QALY in the interval CRS group was 2.12 (95% CrI, 1.66 to 2.64 QALYs) and 2.68 (95% CrI, 2.11 to 3.28 QALYs) in the interval CRS plus HIPEC group. The ICER amounted to V28,299/QALY. In univariable sensitivity analysis, the utility of recurrence-free survival and the number of days in the hospital affected the calculated ICER most. CONCLUSION On the basis of the trial data, treatment with interval CRS and HIPEC in patients with stage III ovarian cancer was accompanied by a substantial gain in QALYs. The ICER is below the willingness-to-pay threshold in the Netherlands, indicating interval CRS and HIPEC is cost effective for this patient population. These results lend additional support for reimbursing the costs of treating these patients with interval CRS and HIPEC in countries with comparable health care systems

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

BACKGROUND: Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer. METHODS: In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be feasible. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. The primary end point was recurrence-free survival. Overall survival and the side-effect profile were key secondary end points. RESULTS: In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P=0.76). CONCLUSIONS: Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number, NCT00426257 ; EudraCT number, 2006-003466-34 .)

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer EDITORIAL COMMENT

The majority of patients with ovarian cancer (OC) receive an initial diagnosis of advanced disease that has spread from the ovaries to the peritoneal surface. The most effective treatment for patients with advanced disease is cytoreductive surgery followed by systemic chemotherapy. As an alternative, interval cytoreductive surgery is performed after 3 cycles of chemotherapy. Following these treatments, the primary site of disease recurrence is the peritoneal surface. Delivery of chemotherapy by the intraperitoneal (IP) route enhances drug delivery at the peritoneal surface and eliminates residual microscopic peritoneal disease more efficiently than intravenous administration. Previous trials have shown that after primary cytoreductive surgery combined use of intravenous and IP chemotherapy results in longer overall survival among patients with stage III OC compared with intravenous administration alone. Combined intravenous/IP chemotherapy has several drawbacks that have hampered its adoption in many countries. These include catheter-related problems, increased demands on the patient, and gastrointestinal and renal adverse effects. Most of these drawbacks can be circumvented by delivery of the IP chemotherapy at the end of surgery. Delivery of IP chemotherapy during surgery under hyperthermic conditions—termed hyperthermic IP chemotherapy (HIPEC)—increases the penetration of chemotherapy at the peritoneal surface. Although addition of HIPEC to interval cytoreductive surgery is feasible in women with OC, efficacy data from randomized trials are lacking. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of interval cytoreductive surgery with HIPEC as compared with interval cytoreductive surgery without HIPEC in patients with stage III epithelial OC. Subjects were patients receiving neoadjuvant chemotherapy who had at least stable disease after 3 cycles of carboplatin (area under the curve of 5–6 mg/mL per minute) and paclitaxel (175 mg/m2 of body surface area). Of these patients, 245 were randomized: 122 to the surgery-plus-HIPEC group and 123 to the surgery-without-HIPEC group. Randomization was performed at the time of surgery in cases in which surgery that would result in complete cytoreduction (no visible disease) or optimal cytoreduction (≥1 residual tumors measuring ≤10 mm in diameter) was deemed to be feasible. Patients received an additional 3 cycles of carboplatin and paclitaxel postoperatively. Recurrence-free survival was the primary study end point. Key secondary end points were overall survival and the side effect profile. Data for recurrence-free and overall survival were analyzed according to intention to treat. Among patients who underwent cytoreductive surgery, disease recurrence or death occurred in 89% (110/123) of patients in the surgery-without-HIPEC group and 81% (99/122) of patients in the surgery-plus-HIPEC group; the hazard ratio for disease recurrence or death was 0.66, with a 95% confidence interval of 0.50 to 0.87, P = 0.003. The median recurrence-free survival was 3.5 months longer in the surgery-plus-HIPEC group than in the surgery-without-HIPEC group (14.2 vs 10.7 months). At a median follow-up of 4.7 years, 62% (76/123) of patients in the surgery-without-HIPEC group and 50% (61/122) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% confidence interval, 0.48–0.94; P = 0.02). There were no significant differences in the incidence of adverse events of any grade between the 2 groups (25% in the surgery-withoutHIPEC group and 27% in the surgery-plus-HIPEC group, P = 0.76)

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

The majority of patients with ovarian cancer (OC) receive an initial diagnosis of advanced disease that has spread from the ovaries to the peritoneal surface. The most effective treatment for patients with advanced disease is cytoreductive surgery followed by systemic chemotherapy. As an alternative, interval cytoreductive surgery is performed after 3 cycles of chemotherapy. Following these treatments, the primary site of disease recurrence is the peritoneal surface. Delivery of chemotherapy by the intraperitoneal (IP) route enhances drug delivery at the peritoneal surface and eliminates residual microscopic peritoneal disease more efficiently than intravenous administration. Previous trials have shown that after primary cytoreductive surgery combined use of intravenous and IP chemotherapy results in longer overall survival among patients with stage III OC compared with intravenous administration alone. Combined intravenous/IP chemotherapy has several drawbacks that have hampered its adoption in many countries. These include catheter-related problems, increased demands on the patient, and gastrointestinal and renal adverse effects. Most of these drawbacks can be circumvented by delivery of the IP chemotherapy at the end of surgery. Delivery of IP chemotherapy during surgery under hyperthermic conditions—termed hyperthermic IP chemotherapy (HIPEC)—increases the penetration of chemotherapy at the peritoneal surface. Although addition of HIPEC to interval cytoreductive surgery is feasible in women with OC, efficacy data from randomized trials are lacking. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of interval cytoreductive surgery with HIPEC as compared with interval cytoreductive surgery without HIPEC in patients with stage III epithelial OC. Subjects were patients receiving neoadjuvant chemotherapy who had at least stable disease after 3 cycles of carboplatin (area under the curve of 5–6 mg/mL per minute) and paclitaxel (175 mg/m2 of body surface area). Of these patients, 245 were randomized: 122 to the surgery-plus-HIPEC group and 123 to the surgery-without-HIPEC group. Randomization was performed at the time of surgery in cases in which surgery that would result in complete cytoreduction (no visible disease) or optimal cytoreduction (≥1 residual tumors measuring ≤10 mm in diameter) was deemed to be feasible. Patients received an additional 3 cycles of carboplatin and paclitaxel postoperatively. Recurrence-free survival was the primary study end point. Key secondary end points were overall survival and the side effect profile. Data for recurrence-free and overall survival were analyzed according to intention to treat. Among patients who underwent cytoreductive surgery, disease recurrence or death occurred in 89% (110/123) of patients in the surgery-without-HIPEC group and 81% (99/122) of patients in the surgery-plus-HIPEC group; the hazard ratio for disease recurrence or death was 0.66, with a 95% confidence interval of 0.50 to 0.87, P = 0.003. The median recurrence-free survival was 3.5 months longer in the surgery-plus-HIPEC group than in the surgery-without-HIPEC group (14.2 vs 10.7 months). At a median follow-up of 4.7 years, 62% (76/123) of patients in the surgery-without-HIPEC group and 50% (61/122) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% confidence interval, 0.48–0.94; P = 0.02). There were no significant differences in the incidence of adverse events of any grade between the 2 groups (25% in the surgery-withoutHIPEC group and 27% in the surgery-plus-HIPEC group, P = 0.76). These data indicate that among patients with stage III epithelial OC addition of HIPEC to interval cytoreductive surgery provides longer recurrence-free survival and overall survival compared with surgery alone and no higher rates of adverse effects