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.

Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study.

BACKGROUND: Improvement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence. METHODS/DESIGN: Multicentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat. DISCUSSION: Where the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We present a recently started multicentre randomized controlled trial that will investigate the role of secondary cytoreductive surgery followed by chemotherapy will improve progression free survival in selected patients with first recurrence of platinum-sensitive epithelial ovarian cancer.

The number of metastatic sites for stage IIIA endometrial carcinoma, endometrioid cell type, is a strong negative prognostic factor.

UNLABELLED: The aim of this study was to look at the impact of the number of sites with tumour involvement on outcome for patients with stage IIIA endometrioid-type endometrial carcinoma. PATIENTS AND METHODS: 141 patients stage IIIA were included. A central histopathological review was performed. Patients staged solely on the presence of a positive peritoneal washing were excluded. Follow-up ranged from 2 to 217 months with a median of 43 months. Endpoints of the study were locoregional recurrence rates, distant metastasis-free survival (DMFS), disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: In multivariate analyses the number of involved sites showed to be the only independent significant variable for DMFS, DFS, and DSS with a Hazard Ratio of 2.1, 2.2, and 2.2, respectively. The DSS was significantly related to the number of involved sites, with a 5-year DSS of 70.4% for one site, 42.8% for two sites, and 43.9% for three sites, respectively (p=0.001). CONCLUSION: The number of involved sites outside the corpus uterine for stage IIIA seems to be a strong negative prognostic factor for stage IIIA endometrial carcinoma.

Restless genital syndrome before and after clitoridectomy for spontaneous orgasms: a case report.

INTRODUCTION: Females despairing of restless genital syndrome (ReGS) may request clitoridectomy for treatment of unwanted genital sensations. Aim. The aim of this study was to report persistence of ReGS despite clitoridectomy. METHODS: Following a clitoridectomy for spontaneous orgasms, a 77-year-old woman was referred to our clinic for persistent unwanted genital sensations and feelings of imminent orgasm. An in-depth interview, routine and hormonal investigations, electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain and pelvis were performed. The localizations of genital sensations were investigated by manual examination of the ramus inferior of the pubic bone (RIPB) and by sensory testing of the skin of the genital area with a cotton swab. MAIN OUTCOME MEASURES: The main outcome measures included sensitivity of dorsal nerve of the clitoris in RIPB and MRI-pelvis. RESULTS: Genital dysesthesias, paresthesias, intolerance (allodynia) for tight clothes, aggravation of symptoms during sitting, restless legs, and overactive bladder were diagnosed. Laboratory assessments, and EEG and MRI of the brain were in agreement with aging, but all results were within the normal range. MRI of the pelvis disclosed varices of the uterus and of the left ovarian vein, and a visible scar in the region of the clitoris. Sensory testing of the genital area showed various points of static mechanical hyperesthesia at the left dermatome of the pudendal nerve. Manual examination of the RIPB also elicited the genital sensations at the left side of the vagina at about the 3 o'clock position. CONCLUSIONS: This patient fulfilled all clinical criteria of ReGS that is believed to be caused by neuropathy of the left pudendal nerve. Clitoridectomy abolished spontaneous orgasms for a great part but not completely, and it did not diminish the typical dysesthesias, paresthesias, and feelings of imminent orgasms that typically belong to ReGS. Clitoridectomy is no optional treatment of ReGS. There is a need for publications of ReGS in general medical journals.

Differences in screening history, tumour characteristics and survival between women with screen-detected versus not screen-detected cervical cancer in the east of The Netherlands, 1992-2001.

OBJECTIVE: In The Netherlands, despite a national screening programme since 1996, invasive cervical cancers have been detected in screened and non-screened women. The aim of this study was to determine differences between Pap-smear history, tumour characteristics and survival of patients with a tumour detected by the screening programme (SP) or outside the screening programme (OSP) in the region of the Comprehensive Cancer Centre Stedendriehoek Twente in the period 1992-2001. STUDY DESIGN: In this period, 263 cervical cancer cases in women aged 30-60 were selected from the regional cancer registry. Patient and tumour characteristics, treatment and follow-up data were extracted. Also, detection modality of the tumour and Pap score of the smear which led to the diagnosis ('diagnostic smear') and the 'previous smear' were registered. RESULTS: Thirty-five percent were SP tumours and 65% were OSP tumours. SP tumours had a lower stage (FIGO I) than OSP tumours: 84% versus 57%. The OSP group exhibited a twofold increase in risk of death (p<0.05) compared to the SP group. Subsequently 61 women (23%) and 46 (17%) women had an abnormal Pap smear (Pap II or higher) 5 and 3 years before the 'diagnostic smear', respectively. Furthermore, 37 women (14%) and 23 women (9%) had a normal smear 5 and 3 years before diagnosis, respectively. CONCLUSION: SP tumours have a lower stage and a better prognosis, probably due to the fact that the screening programme detects the slow growing tumours which in general have a better prognosis. Furthermore, detection and treatment of patients with suspicious smears have been suboptimal and attention should therefore be paid to prompt follow-up of suspicious smears.

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.

Clinical and technical evaluation of the ACS:OV serum assay and comparison with three other CA125-detecting assays.

BACKGROUND: In this study the clinical and technical performance of the CA125- detecting Bayer ACS:OV immunoluminometric serum assay was compared with three other well-established CA125-detecting assays. METHODS: A total of 1112 serum samples was included in this evaluation: 462 from apparently healthy women, 153 from patients with benign ovarian disease, 163 from patients with malignant ovarian disease, 10 from patients with borderline ovarian malignancies and 78 samples from 12 ovarian cancer patients during monitoring of disease. Serum samples from women with malignant endometrial (n = 68) and colon (n = 32) diseases were also included. Moreover, serum samples from women with benign uterine disease and endometriosis (n = 136) plus 10 serum samples from men (n = 7) and women (n = 3) with human anti-mouse antibodies (HAMA) after immunoscintigraphy were included. All samples were tested in duplicate with the Bayer ACS:OV, the Centocor CA125 II, the Abbott IMx CA125 and the Roche (formerly Boehringer Mannheim) Enzymun-Test CA125 II assays. RESULTS: The clinical performance of the Bayer ACS:OV assay, assessed in various patient groups, was similar to that of the two other automated assays. In serum from patients with benign diseases the highest values were found in patients with benign ovarian tumours. In the ovarian cancer patients followed during the course of disease we found similar marker patterns with all four assays. In contrast to the Roche Enzymun-CA125 II assay and to a lesser extent the Centocor CA125 II assay, the Bayer ACS:OV assay was less sensitive to interference from HAMA. CONCLUSION: The Bayer ACS:OV assay is a precise and reliable test for the quantification of CA125 in serum.

Steroid cell tumour not otherwise specified during pregnancy: a case report and diagnostic work-up for virilisation in a pregnant patient.

Steroid cell tumours not otherwise specified are rare ovarian tumours, which can cause foetal and maternal virilisation. This is the first case report that describes a steroid cell tumour not otherwise specified during pregnancy. Differential diagnosis, a diagnostic work-up and treatment are discussed.

Outcome of Endometrial Cancer Stage IIIA with Adnexa or Serosal Involvement Only.

Objective. The aim of this study is to look at possible differences in outcome between serosa and adnexal involvement stage IIIA endometrial carcinoma. Methods. 67 patients with stage IIIA endometrial carcinoma were included, 46 with adnexal involvement and 21 with serosa. A central histopathological review was performed. Results. The 7-year locoregional failure rate was (LRFR) 2.2% for adnexal involvement and 16.0% for involvement of the serosa (P = .0522). The 7-year distant metastasis-free survival was 72.7% for adnexal involvement and 58.7% for serosa (P = .3994). The 7-year disease-specific survival (DSS) was 71.8% for patients with adnexal involvement and 75.4% for patients with serosa. Conclusion. Endometrial carcinoma stage IIIA with involvement of the adnexa or serosa showed to have a comparable disease-specific survival. Locoregional control was worse for serosa involvement compared to adnexa.

The differential diagnostic potential of a panel of tumor markers (CA 125, CA 15-3, and CA 72-4 antigens) in patients with a pelvic mass.

OBJECTIVE: The purpose of this study was to assess the differential diagnostic potential of a combination of CA 125, CA 15-3, and CA 72-4 antigens in the definition of malignant disease, especially ovarian carcinoma in patients with a pelvic mass. STUDY DESIGN: A total of 412 patients were evaluated in a multicenter, retrospective study. RESULTS: Two hundred twenty-six malignant, 171 benign pelvic tumors (of which 129 were benign ovarian tumors), and 15 borderline tumors were evaluated. One hundred thirty-three patients had ovarian carcinoma. In 76 cases (55%), the International Federation of Gynecology and Obstetrics stage was III or IV. Borderline tumors (n = 15) were excluded from the statistical calculations. CA 125 antigen was the most sensitive marker for ovarian carcinoma (81%). The highest specificity and positive predictive value was obtained with CA 15-3 antigen (95% and 92%, respectively). Considering a concomitant elevation of all 3 markers as positive, a positive predictive value of 97% was found. However, only 28% of the patients in the total group and 41% of the patients with ovarian carcinoma had a concomitant elevation of all 3 markers. The combination of all 3 markers with levels below the cut-off resulted in a (false-positive) positive predictive value for malignancy between 12% and 36%. With the use of logistic regression analysis, we found a correct prediction in 73% of the cases. CA 15-3 antigen makes the most significant (P <.0001) contribution to the logistic model in the prediction of malignancy in the total group, with all pelvic masses with an odds ratio of 3.86. CONCLUSION: The combination of a simultaneous elevated level of CA 125, CA 15-3, and CA 72-4 antigens was predictive for malignant disease in almost all cases. However, such concomitant elevation was found in few of the malignant masses. Logistic regression analysis revealed that CA 15-3 antigen makes the most significant contribution to a model for the prediction of malignancy in the total group. The logistic model gave a correct prediction in 73% to 83%. The present tumor marker panel seems inferior to combinations with other test modalities, which include ultrasonography and/or physical examination and/or menopausal status or age.