Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.

BACKGROUND: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia. METHODS AND FINDINGS: This was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age ≥18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA). Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon's judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year. The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome. A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome. Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered. CONCLUSIONS: Noninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting. TRIAL REGISTRATION: The study was registered prospectively in the Dutch Trial Register (NTR 5357; registration date: 11 August 2015; Date of initial participant enrollment: 18 February 2016).

The (cost) effectiveness of procedural sedation and analgesia versus general anaesthesia for hysteroscopic myomectomy, a multicentre randomised controlled trial: PROSECCO trial, a study protocol.

BACKGROUND: In women with abnormal uterine bleeding, fibroids are a frequent finding. In case of heavy menstrual bleeding and presence of submucosal type 0-1 fibroids, hysteroscopic resection is the treatment of first choice, as removal of these fibroids is highly effective. Hysteroscopic myomectomy is currently usually performed in the operating theatre. A considerable reduction in costs and a higher patient satisfaction are expected when procedural sedation and analgesia with propofol (PSA) in an outpatient setting is applied. However, both safety and effectiveness - including the necessity for re-intervention due to incomplete resection - have not yet been evaluated. METHODS: This study is a multicentre randomised controlled trial with a non-inferiority design and will be performed in the Netherlands. Women > 18 years with a maximum of 3 symptomatic type 0 or 1 submucosal fibroids with a maximum diameter of 3.5 cm are eligible to participate in the trial. After informed consent, 205 women will be randomised to either hysteroscopic myomectomy using procedural sedation and analgesia with propofol in an outpatient setting or hysteroscopic myomectomy using general anaesthesia in a clinical setting in the operating theatre. Primary outcome will be the percentage of complete resections, based on transvaginal ultrasonography 6 weeks postoperatively. Secondary outcomes are cost effectiveness, menstrual blood loss (Pictorial blood assessment chart), quality of life, pain, return to daily activities/work, hospitalization, (post) operative complications and re-interventions. Women will be followed up to one year after hysteroscopic myomectomy. DISCUSSION: This study may demonstrate comparable effectiveness of hysteroscopic myomectomy under procedural sedation and analgesia versus general anaesthesia in a safe and patient friendly environment, whilst achieving a significant cost reduction. TRIAL REGISTRATION: Dutch trial register, number NTR5357 . Registered 11th of August 2015.

Age should not be a limiting factor in laparoscopic surgery: a prospective multicenter cohort study on quality of life after laparoscopic hysterectomy.

PURPOSE: A prospective, multicenter cohort study was performed on the implementation of laparoscopic hysterectomy (LH) in the Netherlands. The aim of this study was to evaluate the impact of LH on quality of life (QOL) with respect to age up to 6 months postoperatively. PATIENTS AND METHODS: Women with an indication for LH, either for benign conditions or early-stage low-risk endometrial cancer were included. QOL was measured before and 6 weeks and 6 months after surgery, using the 36-item Short Form Health Survey. Mean QOL values were compared to an unselected, female, Dutch reference population. A longitudinal linear mixed model was applied to assess changes in QOL over time after LH and to determine if in patients ≥65 years of age QOL scores were different. RESULTS: Data on 116 patients were available for analysis. The median age was 54 years at time of surgery (range 34-83) with an interquartile range of 43-65 years. Six months after LH, all QOL values were higher than before surgery and were equal to or higher than those of the reference population. Older women tend to score higher on QOL preoperatively, and these scores remain high postoperatively. CONCLUSION: After LH, QOL improves. Older women report higher QOL values preoperatively and QOL is still high 6 months after the operation. Age does not confer a negative impact on QOL following LH and should not be the reason to refrain from laparoscopic surgery.

Surgical volume and conversion rate in laparoscopic hysterectomy: does volume matter? A multicenter retrospective cohort study.

BACKGROUND: A multicenter, retrospective, cohort study was conducted in the Netherlands. The aim was to evaluate whether surgical volume of laparoscopic hysterectomies (LHs) performed by proven skilled gynecologists had an impact on the conversion rate from laparoscopy to laparotomy. METHODS: In 14 hospitals, all LHs performed by 19 proven skilled gynecologists between 2007 and 2010 were included in the analysis. Surgical volume, conversion rate and type of conversion (reactive or strategic) were retrospectively assessed. To estimate the impact of surgical volume on the conversion rate, logistic regressions were performed. These regressions were adjusted for patient's age, Body Mass Index (BMI), ASA classification, previous abdominal surgery and the indication (malignant versus benign) for the LH. RESULTS: During the study period, 19 proven skilled gynecologists performed a total of 1051 LHs. Forty percent of the gynecologists performed over 20 LHs per year (median 17.3, range 5.4-49.5). Conversion to laparotomy occurred in 5.0% of all LHs (53 of 1051); 38 (3.6%) were strategic and 15 (1.4%) were reactive conversions. Performing over 20 LHs per year was significantly associated with a lower overall conversion rate (ORadjusted 0.43, 95% CI 0.24-0.77), a lower strategic conversion rate (ORadjusted 0.32, 95% CI 0.16-0.65), but not with a lower reactive conversion rate (ORadjusted 0.96, 95% CI 0.33-2.79). CONCLUSION: A higher annual surgical volume of LHs by proven skilled gynecologists is inversely related to the conversion rate to laparotomy, and results in a lower strategic conversion rate.

Implementing an advanced laparoscopic procedure by monitoring with a visiting surgeon.

STUDY OBJECTIVE: To investigate the feasibility of safely implementing a total laparoscopic hysterectomy (LH) in established gynecologists' practices with on-site coaching and monitoring of the learning curve by an experienced visiting surgeon. DESIGN: Multicenter prospective feasibility and implementation study (Canadian Task Force classification II-2). SETTING: Eleven general gynecologists in 8 hospitals (1 university hospital and 7 regional hospitals) participated. PATIENTS: Laparoscopic hysterectomy was performed in 83 patients during the learning curve, and in 83 patients after the learning curve. INTERVENTIONS: During the learning curve, an experienced visiting laparoscopist was available for coaching during each LH. A competence score was marked on an Objective Structured Assessment of Technical Skills (OSATS) form. Complications were recorded intraoperatively and postoperatively for 6 weeks after surgery in all patients. MEASUREMENTS AND MAIN RESULTS: Nine of 11 gynecologists reached the competence score of at least 28 points during the study, from January 2005 to January 2007. A major complication occurred in 3 of 83 LH procedures (4%) performed during the learning curve, and in 5 of 83 LH procedures (6%) performed after the learning curve (p = .72). CONCLUSION: The concept of a visiting surgeon for on-site coaching and monitoring of established gynecologists during the learning curve of an advanced laparoscopic procedure using Objectively Structured Assessment of Technical Skills is feasible. According to the observed complication rate during and after the learning curve, on-site coaching is a useful tool when implementing a new laparoscopic technique in established gynecologists' practices.

Aromatase, cyclooxygenase 2, HER-2/neu, and p53 as prognostic factors in endometrioid endometrial cancer.

The prognostic value of aromatase, cyclooxygenase 2 (COX-2), HER-2/neu, and p53 expression was determined in endometrioid endometrial cancer. Tissue microarrays were constructed comprising samples from 315 endometrioid endometrial cancer patients. Expression of aromatase, COX-2, HER-2/neu, and p53 was determined by immunostaining and related to classical clinicohistopathologic parameters, in addition to recurrence of disease and survival. Median follow-up time for all patients was 5.0 years. Patients were classified as Fédération Internationale de Gynécologie Obstétrique stage I (59.0%), stage II (17.1%), stage III (19.4%), and stage IV (4.1%). Sixty-five patients (20.6%) developed recurrent disease, and 38 (12.1%) died because of endometrial cancer. Aromatase, COX-2, HER-2/neu, and p53 expression was observed in 133 (42.2%), 107 (34.0%), 17 (5.4%), and 21 (6.7%) tumor cases, respectively. Aromatase expression in tumor cells was related to aromatase expression in stromal cells (P < 0.0001) and to HER-2/neu expression in tumor cells (P = 0.019). Aromatase expression in tumor as well as stromal cells was related to a low stage of disease (P = 0.02 and P = 0.001, respectively), whereas aromatase expression in stromal cells was also related to a low tumor grade (P = 0.021). P53 expression was related to a high stage and a high grade (P = 0.006 and P < 0.0001, respectively). In multivariate analysis, p53 overexpression was independently related to death because of the disease (P = 0.043; odds ratio 3.0; 95% confidence interval, 1.0-8.7). For COX-2, HER-2/neu, and aromatase, no relation with any other histopathologic parameter or survival was found. In conclusion, aromatase and p53 expression are related to tumor grade and stage of disease, whereas p53 is an independent prognostic factor in endometrioid endometrial cancer.

Total laparoscopic hysterectomy versus abdominal hysterectomy in the treatment of patients with early stage endometrial cancer: a randomized multi center study.

BACKGROUND: Traditionally standard treatment for patients with early stage endometrial cancer (EC) is total abdominal hysterectomy and bilateral salpingo oophorectomy (TAH+BSO) with or without lymph node dissection through a vertical midline incision. While TAH is an accepted effective treatment, it is highly invasive, visibly scarring and associated with morbidity. An alternative treatment is the same operation by laparoscopy. Though in several studies total laparoscopic hysterectomy (TLH+ BSO) seems a safe and feasible alternative approach in early stage endometrial cancer patients, there are no randomized data available yet. Furthermore, a randomized controlled trial with surgeons trained in laparoscopy is warranted in order to implement this technique in a safe manner. The aim of this study is to compare the treatment related morbidity, cost-effectiveness and quality of life in early stage endometrial cancer patients treated by laparoscopy versus the standard open approach. METHODS: A multi centre randomized clinical phase 3 trial, including 5 university hospitals and 15 regional hospitals in the Netherlands. Only gynecologists trained in performing a TLH are allowed to participate. INCLUSION CRITERIA: Patients with a clinical stage I endometrioid adenocarcinoma or complex atypical hyperplasia are randomized in a 2:1 allocation to receive TLH or TAH. The main outcome measure is the rate of major complications, as assessed by an independent clinical review board. In total, 275 patients are required to have 80% power at alpha-0.05 to detect a significant difference of 15% complication rate. Secondary outcome measures are 1) costs and cost-effectiveness, 2) minor complications, and 3) quality of life. All data from this multi center study are reported using case record forms. Data regarding quality of life, pain, body Image, sexuality and additional homecare are assessed with self reported questionnaires. DISCUSSION: A randomized multi center study in early stage endometrial cancer patients with inclusion criteria for patients and surgeons is designed and ongoing. Results will be presented at the end of 2009. TRIAL REGISTRATION: Dutch trial register number NTR821.

Lymphvascular space involvement: an independent prognostic factor in endometrial cancer.

PURPOSE OF INVESTIGATION: To evaluate whether lymphvascular space involvement (LVSI) is a risk factor for relapse of disease and lymph node metastasis in endometrial cancer. METHODS: From 1978 till 2003, 609 patients with epithelial endometrial cancer were treated at the Groningen University Medical Center. The association of LVSI and relapse of disease was evaluated in the total group of 609 patients and in a 'low' and 'high' risk stage I endometrial cancer group. In 239 surgically staged patients, the relation of LVSI and lymph node metastasis was investigated. RESULTS: The median age at diagnosis was 63 years (range 27-92 years) with a median follow-up of 58 months (range 0-236 months). More than half of the patients (56%) received adjuvant radiotherapy. LVSI was present in 123 patients (25,6%), and a prognostic factor for relapse of disease (multivariate analysis, P < 0.0001). In the 'low' and 'high' risk stage I endometrial cancer patients an increase of 2.6 times in relapse of disease was observed in the presence of LVSI. LVSI positive tumors were more likely to have metastasized to the pelvic lymph nodes (multivariate analysis, P = 0.001). In patients with proven negative nodes, LVSI was a prognostic factor for relapse of disease (univariate analysis, P = 0.02). CONCLUSION: LVSI is a predictor of nodal disease and an independent prognostic factor for relapse of disease in all stages of endometrial cancer. Patients with stage I endometrial cancer with positive LVSI are at risk for relapse of disease and might therefore benefit from adjuvant therapy. CONTENT: The presence of lymphvascular space involvement (LVSI) in endometrial cancer is significantly and independently associated with an increased risk of pelvic lymph node metastases and/or relapse of disease.