Vaginal hysterectomy with or without bilateral salpingo-oophorectomy may be an alternative treatment for endometrial cancer patients with medical co-morbidities precluding standard surgical procedures: a systematic review.

OBJECTIVE: Vaginal hysterectomy with bilateral salpingo-oophorectomy may be an alternative strategy for patients with low-risk endometrial cancer and medical co-morbidities precluding laparoscopic or abdominal procedures. The current study evaluates the prevalence of co-existent ovarian malignancy in patients with endometrial cancer and the influence of bilateral salpingo-oophorectomy on survival outcomes in these patients. METHODS: Medline and EMBASE were searched for studies published between January 1, 2000 and November 20, 2017 that investigated (1) the prevalence of co-existing ovarian malignancy (either metastases or primary synchronous ovarian cancer in women with endometrial cancer, and (2) the influence of bilateral salpingo-oophorectomy on recurrence and/or survival rates. RESULTS: Of the pre-menopausal and post-menopausal patients (n=6059), 373 were identified with metastases and 106 were identified with primary synchronous ovarian cancer. Of the post-menopausal patients (n=6016), 362 were identified with metastases and 44 were identified with primary synchronous ovarian cancer. Survival outcomes did not differ for pre-menopausal patients with endometrial cancer with and without bilateral salpingo-oophorectomy (5-year overall survival rates were 89-94.5% and 86-97.8%, respectively). CONCLUSION: Bilateral salpingo-oophorectomy during vaginal hysterectomy seems to have a limited impact on disease outcome in patients with endometrial cancer. These results support the view that vaginal hysterectomy alone or with bilateral salpingo-oophorectomy may be an option for patients with endometrial cancer who are not ideal surgical candidates.

Borderline tumours of the ovary: Common practice in the Netherlands.

OBJECTIVES: Discordance between frozen section diagnosis and the definite histopathological diagnosis and the fact that the frozen section result is not always unambiguous, may contribute to differences in clinical practice regarding perioperative treatment and follow-up of borderline ovarian tumours (BOTs) patients amongst gynaecologic oncologists, which may lead to over- and undertreatment. The aim of the study was to map the Dutch gynaecologists' preferred treatment and follow-up strategy in case of BOTs. METHODS: A questionnaire was sent to all Dutch gynaecologists involved in ovarian surgery with perioperative frozen section analysis, and the outcomes were assessed using descriptive statistics. RESULTS: Nearly half of the respondents (41.0%) would not perform a staging procedure in case of a BOT. In case of an ambiguous frozen section diagnosis, tending towards invasive carcinoma, a considerable number (sBOT 56.4%; mBOT 30.8%) would perform a lymph node sampling as part of the staging procedure. A relaparotomy/relaparoscopy, to perform a lymph node sampling in case of a serous or mucinous carcinoma after a BOT frozen section diagnosis, would be performed by 97.4% and 48.7% of the respondents, respectively. CONCLUSIONS: A considerable number of gynaecologists would perform a staging procedure that is recommended for ovarian cancer in case of an ambiguous BOT frozen section diagnosis, especially for serous tumours. In addition, nearly all gynaecologists would perform a second procedure including a lymph node sampling in case of a serous invasive carcinoma after a BOT frozen section diagnosis, which applies to half of the gynaecologists in case of a mucinous carcinoma.

Cost-effectiveness of laparoscopy as diagnostic tool before primary cytoreductive surgery in ovarian cancer.

OBJECTIVE: To evaluate the cost-effectiveness of a diagnostic laparoscopy prior to primary cytoreductive surgery to prevent futile primary cytoreductive surgery (i.e. leaving >1cm residual disease) in patients suspected of advanced stage ovarian cancer. METHODS: An economic analysis was conducted alongside a randomized controlled trial in which patients suspected of advanced stage ovarian cancer who qualified for primary cytoreductive surgery were randomized to either laparoscopy or primary cytoreductive surgery. Direct medical costs from a health care perspective over a 6-month time horizon were analyzed. Health outcomes were expressed in quality-adjusted life-years (QALYs) and utility was based on patient's response to the EQ-5D questionnaires. We primarily focused on direct medical costs based on Dutch standard prices. RESULTS: We studied 201 patients, of whom 102 were randomized to laparoscopy and 99 to primary cytoreductive surgery. No significant difference in QALYs (utility=0.01; 95% CI 0.006 to 0.02) was observed. Laparoscopy reduced the number of futile laparotomies from 39% to 10%, while its costs were € 1400 per intervention, making the overall costs of both strategies comparable (difference € -80 per patient (95% CI -470 to 300)). Findings were consistent across various sensitivity analyses. CONCLUSION: In patients with suspected advanced stage ovarian cancer, a diagnostic laparoscopy reduced the number of futile laparotomies, without increasing total direct medical health care costs, or adversely affecting complications or quality of life.

Laparoscopy to Predict the Result of Primary Cytoreductive Surgery in Patients With Advanced Ovarian Cancer: A Randomized Controlled Trial.

Purpose To investigate whether initial diagnostic laparoscopy can prevent futile primary cytoreductive surgery (PCS) by identifying patients with advanced-stage ovarian cancer in whom > 1 cm of residual disease will be left after PCS. Patients and Methods This multicenter, randomized controlled trial was undertaken within eight gynecologic cancer centers in the Netherlands. Patients with suspected advanced-stage ovarian cancer who qualified for PCS were eligible. Participating patients were randomly assigned to either laparoscopy or PCS. Laparoscopy was used to guide selection of primary treatment: either primary surgery or neoadjuvant chemotherapy followed by interval surgery. The primary outcome was futile laparotomy, defined as a PCS with residual disease of > 1 cm. Primary analyses were performed according to the intention-to-treat principle. Results Between May 2011 and February 2015, 201 participants were included, of whom 102 were assigned to diagnostic laparoscopy and 99 to primary surgery. In the laparoscopy group, 63 (62%) of 102 patients underwent PCS versus 93 (94%) of 99 patients in the primary surgery group. Futile laparotomy occurred in 10 (10%) of 102 patients in the laparoscopy group versus 39 (39%) of 99 patients in the primary surgery group (relative risk, 0.25; 95% CI, 0.13 to 0.47; P < .001). In the laparoscopy group, three (3%) of 102 patients underwent both primary and interval surgery compared with 28 (28%) of 99 patients in the primary surgery group ( P < .001). Conclusion Diagnostic laparoscopy reduced the number of futile laparotomies in patients with suspected advanced-stage ovarian cancer. In women with a plan for PCS, these data suggest that performance of diagnostic laparoscopy first is reasonable and that if cytoreduction to < 1 cm of residual disease seems feasible, to proceed with PCS.

Staging procedures in patients with mucinous borderline tumors of the ovary do not reveal peritoneal or omental disease.

OBJECTIVES: Staging in case of a borderline tumor of the ovary (BOT) is a controversial issue. Upstaging is not uncommon, but this occurs especially with presumed stage I serous borderline tumors. There are only a few documented cases of BOTs of non-serous histology that were not confined to the ovary. The aim of this study was to assess the incidence of non-invasive and invasive implants in the omentum and other (extra)pelvic peritoneal surfaces in patients with a mucinous BOT (mBOT). METHODS: A retrospective cohort study was performed in three hospitals in the Netherlands. All patients with a histopathological diagnosis of mBOT diagnosed from January 1st 1990 to December 1st 2015 were identified and included when the inclusion criteria were met. RESULTS: In total, 74 patients were included. Of these 74 patients, 46 (62.2%) underwent a staging procedure. In 12 (26.1%) patients, only omental tissue was obtained, in 32 (69.6%) patients, omental tissue and peritoneal biopsies were obtained and in two (4.3%) patients, only peritoneal biopsies were obtained. No implants were seen upon microscopic examination in any of the patients. Two patients (3%) developed a recurrence. CONCLUSIONS: Because no extra-ovarian disease was found, staging procedures in the case of an mBOT may be omitted. However, the actual perioperative decision for staging or not should be taken in the context of a frozen section diagnosis, which is not always accurate and straightforward. Recurrence with malignant disease is rare after mBOT. The value of post-treatment surveillance seems limited after bilateral salpingo-oophorectomy.

Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study.

BACKGROUND: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT) in combination with interval debulking surgery (IDS) is performed. Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS). In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer. METHODS: Multicentre randomized controlled trial, including all gynaecologic oncologic centres in the Netherlands and their affiliated hospitals. Patients are eligible when they are planned for PDS after conventional staging. Participants are randomized between direct PDS or additional diagnostic laparoscopy. Depending on the result of laparoscopy patients are treated by PDS within three weeks, followed by six courses of platinum based chemotherapy or with NACT and IDS 3-4 weeks after three courses of chemotherapy, followed by another three courses of chemotherapy. Primary outcome measure is the proportion of PDS's leaving more than one centimetre tumour residual in each arm. In total 200 patients will be randomized. Data will be analysed according to intention to treat. DISCUSSION: Patients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis. However, there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high. Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool to predict the outcome of PDS. Despite the absence of strong evidence and despite the possible complications, laparoscopy is already implemented in many countries. We propose a randomized multicentre trial to provide evidence on the effectiveness of laparoscopy before primary surgery for advanced stage ovarian cancer patients. TRIAL REGISTRATION: Netherlands Trial Register number NTR2644.

Laparoscopic hysterectomy is preferred over laparotomy in early endometrial cancer patients, however not cost effective in the very obese.

BACKGROUND: Total laparoscopic hysterectomy (TLH) is safe and cost effective in early stage endometrial cancer when compared to total abdominal hysterectomy (TAH). In non-randomised data it is often hypothesised that older and obese patients benefit most from TLH. Aim of this study is to analyse whether data support this assumption to advice patients, clinicians and policy makers. METHODS: Data of 283 patients enrolled in a randomised controlled trial comparing TAH versus TLH in early stage endometrial cancer were re-analysed. Randomisation by sequential number generation was done centrally, with stratification by trial centre. Using multivariate analysis, predictors of major complications and conversions to laparotomy were assessed. For the cost effectiveness analysis, subgroups of patients were constructed based on age and body mass index (BMI). For each subgroup, costs per major complication-free patient were estimated, using incremental cost effect ratios (extra costs per additional effect). RESULTS: Older (odds ratio (OR): 1.05; 1.01-1.09) and obese (OR: 1.05; 1.01-1.10) patients had a higher risk to develop complications, for both groups. In obese (OR: 1.17; 1.09-1.25) patients and patients with a previous laparotomy (OR: 3.45; 1.19-10.04) a higher risk of conversion to laparotomy was found. For patients>70 years of age and patients with a BMI over 35 kg/m2, incremental costs per major complication-free patients were €16 and €54 for TLH compared to TAH, respectively. CONCLUSION: In general, TLH should be recommended as the standard surgical procedure in early stage endometrial cancer, also in patients>70 years of age. In obese patients with a BMI>35 kg/m2 TLH is not cost effective because of the high conversion rate. A careful consideration of laparoscopic treatment is needed for this subgroup. Surgeon experience level may influence this choice.

Cost effectiveness of laparoscopy versus laparotomy in early stage endometrial cancer: a randomised trial.

OBJECTIVE: To determine the cost effectiveness of total laparoscopic hysterectomy (TLH) versus total abdominal hysterectomy (TAH) in early stage endometrial cancer alongside a multicenter randomised controlled trial (RCT). METHODS: An economic analysis was conducted in 279 patients (TLH n=185; TAH n=94) with early stage endometrial cancer from a societal perspective, including all relevant costs over a three month time horizon. Health outcomes were expressed in terms of major complication-free rate and in terms of utility based on women's response to the EQ-5D. Comparisons of costs per major complication-free patient gained and costs with utility gain and costs were made, using incremental cost effectiveness ratios. RESULTS: The mean major complication-free rate and median utility scores were comparable between TLH and TAH at three months. TLH is more costly intraoperatively (Δ$1.129) and less costly postoperatively in-hospital (Δ$-1.350) compared to TAH. Incremental costs per major complication-free patient were $-52. Higher cost ($249) were generated while no gains in utility (-0.02) were observed for TLH compared to TAH. Analysing utility at six weeks, incremental costs per additional point on the EQ-5D scale were $1.617. CONCLUSION: TLH is cost effective compared to TAH, based on major complication-free rate as measure of effect. Along with future cost saving strategies in laparoscopy, TLH is assumed to be cost effective for both effect measures. Therefore and due to comparable safety, TLH should be recommended as a standard-of-care surgical procedure in early endometrial cancer.

Safety of laparoscopy versus laparotomy in early-stage endometrial cancer: a randomised trial.

BACKGROUND: The standard surgery for early-stage endometrial cancer is total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy, which is associated with substantial morbidity. Total laparoscopic hysterectomy (TLH) and bilateral salpingo-oophorectomy is less invasive and is assumed to be associated with lower morbidity, particularly in obese women. This study investigated the complication rate of TLH versus TAH in women with early-stage endometrial cancer. METHODS: This randomised trial was done in 21 hospitals in The Netherlands, and 26 gynaecologists with proven sufficient skills in TLH participated. 283 patients with stage I endometrioid adenocarcinoma or complex atypical hyperplasia were randomly allocated (2:1) to the intervention group (TLH, n=187) or control group (TAH, n=96). Randomisation by sequential number generation was done centrally in alternate blocks of six and three participants, with stratification by trial centre. After assignment, the study coordinators, patients, gynaecologists, and members of the panel were not masked to intervention. The primary outcome was major complication rate, assessed by an independent panel. Data were analysed by a modified intention-to-treat analysis, since two patients in both groups were excluded from the main analysis. This trial is registered with the Dutch trial registry, number NTR821. FINDINGS: The proportion of major complications was 14.6% (27 of 185) in the TLH group versus 14.9% (14 of 94) in the TAH group, with a difference of -0.3% (95% CI -9.1 to 8.5; p=0.95). The proportion of patients with an intraoperative major complication (nine of 279 [3.2%]) was lower than the proportion with a postoperative major complication (32 of 279 [11.5%]) and did not differ between TLH (five of 185 [2.7%]) and TAH (four of 94 [4.3%]; p=0.49). The proportion of patients with a minor complication was 13.0% (24 of 185) in the TLH group and 11.7% (11 of 94) in the TAH group (p=0.76). Conversion to laparotomy occurred in 10.8% (20 of 185) of the laparoscopic procedures. TLH was associated with significantly less blood loss (p<0.0001), less use of pain medication (p<0.0001), a shorter hospital stay (p<0.0001), and a faster recovery (p=0.002), but the procedure took longer than TAH (p<0.0001). INTERPRETATION: Our results showed no evidence of a benefit for TLH over TAH in terms of major complications, but TLH (done by skilled surgeons) was beneficial in terms of a shorter hospital stay, less pain, and quicker resumption of daily activities. FUNDING: The Dutch Organization for Health Research and Development (ZonMw), programme efficacy.

Comparison of accuracy measures of two screening tests for gestational diabetes mellitus.

OBJECTIVE: To compare the accuracy measures of the random glucose test and the 50-g glucose challenge test as screening tests for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: In this prospective cohort study, pregnant women without preexisting diabetes in two perinatal centers in the Netherlands underwent a random glucose test and a 50-g glucose challenge test between 24 and 28 weeks of gestation. If one of the screening tests exceeded predefined threshold values, the 75-g oral glucose tolerance test (OGTT) was performed within 1 week. Furthermore, the OGTT was performed in a random sample of women in whom both screening tests were normal. GDM was considered present when the OGTT (reference test) exceeded predefined threshold values. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the two screening tests. The results were corrected for verification bias. RESULTS: We included 1,301 women. The OGTT was performed in 322 women. After correction for verification bias, the random glucose test showed an area under the ROC curve of 0.69 (95% CI 0.61-0.78), whereas the glucose challenge test had an area under the curve of 0.88 (0.83-0.93). There was a significant difference in area under the curve of the two tests of 0.19 (0.11-0.27) in favor of the 50-g glucose challenge test. CONCLUSIONS: In screening for GDM, the 50-g glucose challenge test is more useful than the random glucose test.