Implementation of an Innovative Technology Called the OR Black Box: A Feasibility Study.

Introduction. The operating room (OR) Black Box is an innovative technology that captures and compiles extensive real-time data from the OR, allowing identification and analysis of factors that influence intraoperative procedures and performances - ultimately improving patient safety. Implementation of this kind of technology is still an emerging research area and prone to face challenges. Methods. Observational study running from May 2017 to May 2021 conducted at Copenhagen University Hospital - Rigshospitalet, Denmark, involving 152 OR staff and 306 patients. Feasibility of the OR Black Box was assessed in accordance with Bowen's framework with 8 focus areas. Results. The OR Black Box had a high level of acceptability among stakeholders with 100% participation from management, 93% from OR staff, and 98% from patients. The implementation process improved over time, and an average of 80% of the surgeries conducted were captured. The practical aspects such as numerous formal and informal meetings, ethical and legal approval, recruitment of patients were acceptable, albeit time-consuming. The OR Black Box was adopted without any changes in scheduled surgery program, but capturing hours were adjusted to match the surgery program and relocation of OR staff declining to provide consent was possible. Conclusions. Implementation of the OR Black Box was feasible yet challenging. Management, nearly all staff, and patients embraced the initiative; however, ongoing evaluation, information meetings, and commitment from stakeholders are required and crucial to sustain momentum, continue implementation and expansion. Ideas from this study can be useful in the implementation of similar initiatives.

Role of delayed interval debulking for persistent residual disease after more than 5 cycles of chemotherapy for primary advanced ovarian cancer. An international multicenter study.

BACKGROUND: Standard of care in patients with advanced ovarian cancer (AOC) is upfront surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) is an alternative in selected patients. Most data exist with IDS following 3-4 cycles chemotherapy, however, some patients experience a delay of IDS. So far, the impact of a "delayed" interval debulking surgery (DID) is poorly defined. METHODS: We analyzed data from eight international gynecology-oncology referral centers. Patients were included if they had newly diagnosed AOC and were prone to DID (minimum 5 cycles of NACT) between 2011 and 2017. RESULTS: 308 patients underwent DID. 89.6% had a high-grade serous ovarian cancer. The median number of pre-op NACT was 6 cycles (range 5-9) and 6.1% of patients received additionally bevacizumab. The majority of patients had stage-IV disease (51.3%). Median duration of surgery was 210 min (range 34-561), the median surgical complexity score was 4 (range 1-16). Complete resection was achieved in 60.1%. The median number of post-op chemotherapy cycles was 2 (range 0-5). The rate of severe complications (Clavien-Dindo£3°) was 9.7% and 30 days post-op mortality was 0.3%. The median PFS and OS in patients with complete resection was 19.5 and 49.2 months compared to 14.8 and 33.0 months in patients with incomplete resection (p = 0.001), respectively. We did not observe any survival benefit for patients with cytoreduction to small residuals (1-10 mm) compared to residual disease >1 cm. CONCLUSION: Our data may suggest that offering surgery to patients with persistent disease after 5+ cycles could be associated with favorable outcome if a complete resection is achieved. Patients who had residual disease postoperatively may experience rather peri-operative treatment burden than any benefit from DID.

Survival of selected patients with ovarian cancer treated with fertility-sparing surgery.

RESEARCH QUESTION: How many patients in Denmark were treated with fertility-sparing surgery (FSS) for epithelial ovarian cancer (EOC) and what was their prognosis compared with patients treated with radical surgery (RS)? DESIGN: This study was a retrospective Danish nationwide study, evaluating the effect of FSS compared with RS in patients with EOC, age ≤45 years and International Federation of Gynecology and Obstetrics (FIGO) stage ≤IC3 from 2005 to 2016. RESULTS: A total of 106 patients were included. Of these, 13 were treated with FSS and 93 were treated with RS. Median age was 27 versus 42 years (P < 0.0001). Overall survival did not differ significantly between the two groups. Overall survival rate in the FSS group was 100%, while the overall survival in the RS group was 87%. Disease-specific survival was 100% in the FSS group and 91% in the RS group. CONCLUSIONS: This study shows that patients treated with FSS for FIGO stage I EOC do not have an impaired survival compared with patients treated with RS. Nevertheless, the conclusion must be interpreted with caution due to the limited number of patients and the retrospective nature of the study. Larger studies are needed before conclusions can be drawn.

Specific Regions, Rather than the Entire Peritoneal Carcinosis Index, are Predictive of Complete Resection and Survival in Advanced Epithelial Ovarian Cancer.

BACKGROUND: Advanced epithelial ovarian cancer (EOC) often involves the peritoneum. Because complete resection of tumor and carcinosis is the most important prognostic factor, the peritoneal carcinosis index (PCI) has been evaluated in EOC. We hypothesize that specific PCI regions comprising the small intestine with mesentery (regions 9-12) and the hepatoduodenal ligament (region 2) are more predictive of complete resection (R = 0) and survival than the entire PCI. MATERIALS AND METHODS: We analyzed prospectively collected nationwide data from 507 patients with International Federation of Gynecology and Obstetrics stage IIIB to IVB EOC who underwent primary surgery with complete cytoreductive intent. The PCI as a predictor of incomplete resection (R > 0) was evaluated with logistic regression and receiver operating caracteristic curves. Survival analysis was performed with Kaplan-Meier curves and Cox regression. RESULTS: Median (range) PCI was 10 (0-33) in R = 0 patients and 24 (1-39) in R > 0 patients; P < 0.0001. The PCI of regions 9 to 12 (odds ratio [OR]:1.38 (1.29-1.47; 95% confidence interval [CI]) and 2 + 9 to 12 (OR: 1.31 [1.24-1.38; 95% CI]) were more predictive of residual tumor than the entire PCI (OR: 1.10 [1.08-1.12; 95% CI]). Similarly, in receiver operating characteristic curve analyses of R greater than 0 versus R = 0, the area under the curve was higher in regions 9 to 12 (78%) and regions 2 + 9 to 12 (79%) than for the total PCI (75%).Median overall survival was 56.8 months (48.3-65.4; 95% CI) after R = 0 and 26.7 months (21.4-32.0; 95% CI) after R greater than 0 (P < 0.0001). Overall survival was 53.8 months for patients with PCI less than median (14) versus 25.7 in patients with PCI greater than median.The PCI in regions 9 to 12 (hazard ratio [HR]: 1.10 [1.07-1.13; 95% CI]) and 2 + 9 to 12 (HR: 1.08 [1.06-1.11; 95% CI]) was associated with a poorer prognosis than the entire PCI (HR: 1.03 [1.02-1.04; 95% CI]). CONCLUSIONS: Selected PCI regions corresponding to the small intestine and hepatoduodenal ligament are more predictive of complete resection and survival than the entire PCI. This confirms that in the majority of the cases, an early intraoperative examination of those selected PCI regions - and not the entire PCI - will reveal whether R = 0 is achievable.

The Importance of Appendectomy in Surgery for Mucinous Adenocarcinoma of the Ovary.

OBJECTIVE: The aim of this study was to assess the importance of appendectomy during surgery for mucinous ovarian cancer. It can be difficult to distinguish between primary ovarian and primary appendiceal cancers clinically, histologically, and immunohistochemically. Removal of the appendix may facilitate differential diagnosis, improve staging, and possibly increase 5-year survival but may also be associated with increased postsurgical morbidity. In the largest population published to date, we analyze and discuss these matters. METHODS: Prospectively gathered data on 269 patients with confirmed mucinous ovarian adenocarcinoma from a national database were analyzed. The impact of appendectomy and metastases to the appendix on 5-year and overall survival was analyzed. RESULTS: Appendectomy was performed in 172 cases (64%), and in 10 cases (4%), pathologic evaluation of the removed appendix revealed metastases from ovarian cancer. Three of the cases were macroscopically normal, and metastases were discovered only during microscopic evaluation. Patients with metastatic disease to the appendix had significantly worse 5-year survival (22%) compared with patients without metastases (73%) (χ = 31.998, P < 0.0001). Equally, 5-year survival was significantly higher in patients who had been adequately staged with hysterectomy, omentectomy, bilateral salpingo-oophorectomy, and appendectomy (74% vs 52%, χ = 7.322, P = 0.007). In multivariate analysis, increase in revised 2013 International Federation of Gynecology and Obstetrics classification stage (IA reference) was significantly associated with worsened prognosis (hazard ratio, 1.13; P < 0.0001). Equally, each stepwise increase in performance status score was related to a poorer prognosis with hazard ratio of 1.63 (P < 0.0001). Metastases to the appendix and staging did not remain significant factors of survival in multivariate analysis. CONCLUSIONS: Univariate analysis suggests that metastatic disease to the appendix and failure to perform complete staging including appendectomy are related to a worsened prognosis. A normal-looking appendix does not exclude metastatic disease, and because appendectomy is easily performed and does not increase morbidity, it should be performed during surgery for suspected mucinous ovarian cancer.

Robot-assisted surgery in gynecological oncology: current status and controversies on patient benefits, cost and surgeon conditions - a systematic review.

INTRODUCTION: Robot-assisted surgery has become more widespread in gynecological oncology. The purpose of this systematic review is to present current knowledge on robot-assisted surgery, and to clarify and discuss controversies that have arisen alongside the development and deployment. MATERIAL AND METHODS: A database search in PubMed and EMBASE was performed up until 4 March 2016. The search strategy was developed in collaboration with an information specialist, and by application of the PRISMA guidelines. Human participants and English language were the only restrictive filters applied. Selection was performed by screening of titles and abstracts, and by full text scrutiny. From 2001 to 2016, a total of 76 references were included. RESULTS: Robot-assisted surgery in gynecological oncology has increased, and current knowledge supports that the oncological safety is similar, compared with previous surgical methods. Controversies arise because current knowledge does not clearly document the benefit of robot-assisted surgery, on perioperative outcome compared with the increased costs of the acquisition and application. CONCLUSIONS: The rapid development in robot-assisted surgery calls for long-term detailed prospective cohorts or randomized controlled trials. The costs associated with acquisition, application, and maintenance have an unfavorable impact on cost-benefit evaluations, especially when compared with laparoscopy. Future developments in robot-assisted surgery will hopefully lead to competition in the market, which will decrease costs.

Restaging and Survival Analysis of 4036 Ovarian Cancer Patients According to the 2013 FIGO Classification for Ovarian, Fallopian Tube, and Primary Peritoneal Cancer.

OBJECTIVE: With the 2013 International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and primary peritoneal cancer, the number of substages changed from 10 to 14. Any classification of a malignancy should easily assign patients to prognostic groups, refer patients to individualized treatments, and allow benchmarking and comparison of patients and results between centers. The stage should reflect survival in particular. The objective of the study was to validate these requirements of the revised FIGO staging on a high number of ovarian cancer patients. MATERIALS AND METHODS: Demographic, surgical, histological, and survival data from 4036 ovarian cancer patients were used in the analysis. Five-year survival rates (5YSR) and hazard ratios for the old and revised FIGO staging were calculated using Kaplan-Meier curves and Cox regression. RESULTS: A total of 1532 patients were assigned to new stages. Stages IA and IC1 had similar survival (5YSR, 87%); and stages IB, IC2, and IC3 had similar survival (5YSR, 75%-80%). Stage IIC was omitted, resulting in similar survival in stages IIA and IIB (5YSR, 61% and 65%). Of 1660 patients in stage IIIC, 79 were restaged: In 16 cases, IIIC was down-staged to IIIA1, as they had only been stage IIIC owing to lymph node metastases; and in 63 cases, IIIC was down-staged to IIIB, as they had lymph node metastases and abdominal tumor of less than 2 cm. The 5YSR in stage IIIC was unchanged (22%). Stage IV (5YSR, 14% ) was restaged as IVA (13%) and IVB (13%). Both were different from IIIC; P < 0.0001. CONCLUSION: With introduction of new substages, staging becomes more demanding. Second, as fewer patients are allocated to each substage, statistical power is diminished, resulting in uncertainty in the results. Despite this, and most importantly, the revised coding adequately reflects survival, as there was a clear graphical and statistical tendency for poorer survival with increasing stage.

Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells.

Some women suffering from leukemia require bone marrow transplantation to be cured. Bone marrow transplantation is associated with a high risk of sterility, and some patients are offered fertility preservation by cryopreservation of the ovarian cortex. Transplantation of the ovarian cortex to women cured of leukemia who became menopausal is currently not performed because of the risk of introducing the disease. In this study, individual pieces of ovarian cortex intended for reimplantation from 25 patients with leukemia were transplanted to each of 25 nude mice for 20 weeks. The ovarian cortex was examined before and after transplantation by histology and immunohistochemistry, and RT-quantitative PCR (in the 7 patients with a known marker). Seventeen patients had the ovarian cortex retrieved when they were in complete remission. Before transplantation, 4 of 7 pieces (2 from patients in complete remission) of ovarian cortex had a positive RT-quantitative PCR. After transplantation, none of the mice revealed any sign of disease, neither in the pieces of ovarian cortex transplanted nor in any of the murine organs evaluated. Thus, the ovaries from patients in complete remission do not appear to contain viable malignant cells contrasting ovarian tissue retrieved before treatment.

The safety of transplanting cryopreserved ovarian tissue in cancer patients: a review of the literature.

BACKGROUND: Transplantation of frozen/thawed ovarian tissue from patients with a malignant condition is associated with a risk of re-introduction of the disease as the tissue usually is removed before anti-cancer therapy and may thus contain malignant cells. We review studies investigating the presence of malignant cells in cryopreserved ovarian tissue from patients with malignant disease and based on the strength of the evidence, recommendations for transplantations are proposed. MATERIALS AND METHODS: A systematic review of the literature. All peer reviewed studies evaluating the presence of malignant cells in cryopreserved human ovarian tissue were included. Data were searched in Pubmed and Embase with no language restrictions. RESULTS: The majority of the reviewed papers were casuistic reports and few of the included papers were specifically designed to search for malignant cells. Ovarian tissue from 422 patients has been subject to testing for malignant cells by imaging, histology, immunohistochemistry, molecular biology, animal- or clinical transplantation. In 31 (7 %) of the cases the applied test raised suspicion of malignant cell infiltration. No transplantation-related relapse of cancer has been reported after 33 transplantations of frozen/thawed ovarian cortex. CONCLUSION: The quality and strength of the evidence is generally low and prospective studies are needed. The risk of re-introducing a malignant condition when transplanting ovarian tissue depends on the particular disease. Based on the available data, the risk was estimated: Leukaemia: HIGH. Gastrointestinal cancers: MODERATE. Breast cancer, sarcomas of the bone and connective tissue, gynaecological cancers, Hodgkin's and Non-Hodgkin's Lymphoma: LOW.

Reproductive and Endocrine Outcomes in a Cohort of Danish Women following Auto-Transplantation of Frozen/Thawed Ovarian Tissue from a Single Center.

Ovarian tissue cryopreservation (OTC) is a method of fertility preservation in girls and young women prior to gonadotoxic treatment. It is a safe and promising method to restore fertility. The initial recovery of endocrine function is high, but the longevity of the grafted tissue varies. In this single-center, combined retro- and prospective cohort study, we report the reproductive outcome and hormonal recovery following ovarian tissue transplantation (OTT) and evaluate possible predictors of the chance of pregnancy. The study includes 40 women from eastern Denmark undergoing 53 OTTs between 2003 and 2021. Permission to obtain retrospective data was given by the Danish Patient Safety Authorities and prospective data-collection by informed consent. Initial recovery of endocrine function was seen in 18/19 women with POI, and ongoing function of the grafted tissue in 7/14 two years from OTT. Live birth rate (LBR) was 41%, with 20 children to 39 women trying to conceive. Women who conceived had higher AFC at the time of OTC than women who did not (p ± 0.04). Repeated transplantations were not successful in terms of delivery. Half of all pregnancies were achieved by ART, but PRs were lower after ART than by spontaneous conception. LBRs after OTT are encouraging. Chance of pregnancy after OTT is correlated to ovarian reserve at OTC. Repeated transplantations were not successful in terms of unfulfilled pregnancy wish.

Cryopreservation of ovarian tissue for a decade in Denmark: a view of the technique.

This paper presents the Danish 10-year experience (1999-2009) with cryopreservation (n=386) and autotransplantation of ovarian tissue (n=18). Before applying the technique to humans, the method was thoroughly tested and validated. The cryoprotectant solution was chosen after histological evaluation of mouse and human ovarian tissue after freezing with four different combinations of cryoprotectants. Viability was confirmed by transplantation of frozen-thawed human ovarian tissue (n=49) to oophorectomized Nude mice. Viability after transport of fresh tissue 4-5h prior to freezing had previously been validated. Overnight transport of fresh ovarian tissue prior to cryopreservation was evaluated when human ovarian tissue was kept on ice for 20h and then cryopreserved. The thawed ovarian tissue was transplanted to an oophorectomized Nude mouse and histology confirmed viability. In Denmark 12 women have received a total of 18 autotransplantations of ovarian tissue. All women resumed ovarian function and three healthy babies were born to two women. In both women, the tissue was transported on ice for 4-5h prior to cryopreservation. Ovarian tissue cryopreservation is an important method for fertility preservation; however, before applying the method clinically, each laboratory should perform thorough validation of their technique.

Use of cryopreserved ovarian tissue in the Danish fertility preservation cohort.

OBJECTIVE: To evaluate the use of cryopreserved ovarian tissue in the Danish fertility preservation cohort. DESIGN: Retrospective cohort study. SETTING: University hospitals and fertility clinics. PATIENT(S): Ovarian tissue cryopreservation (OTC) was performed for 1,186 Danish girls and women from 1999-2020, of whom 117 subsequently underwent ovarian tissue transplantation (OTT). Subgroup 1 included 759 patients with a follow-up period of >5 years. Out of these, OTT rates were further analyzed for those patients who were alive and aged >24 years in July 2020 (subgroup 2; n = 554). INTERVENTION(S): OTC and OTT. MAIN OUTCOME MEASURE(S): OTT, death, donation of tissue. RESULT(S): In subgroup 1, 14% of the patients had undergone OTT, 18% had died, 9% had donated their tissue for research, and 59% still had their tissue stored. In subgroup 2, 19% had undergone OTT and for most diagnoses the OTT rates ranged from 15% to 22% with benign hematologic diseases having the highest OTT rate (35%). On the basis of the entire cohort, stratified age analysis indicated that women aged ≥30 years at OTC were more likely to return for OTT than women aged 18-29 years at OTC; mean storage times were 3.7 and 3.6 years, respectively. Only 4% of the girls aged <18 years at OTC had undergone OTT. CONCLUSION(S): The OTT rates depended on the diagnosis, age at OTC, and follow-up time. Specific criteria are needed for reporting and comparing OTT rates. Six out of 10 patients still had their cryopreserved tissue stored and longer follow-up is needed, especially for younger girls.

Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles.

BACKGROUND: The aim of the present study was to determine the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B and steroids in normal human small antral follicles and to relate them to follicular size. METHODS: A group of 103 women having one ovary removed for fertility preservation by cryopreservation prior to gonadotoxic treatment served as a source of a total of 272 human small antral follicles. Prior to cryopreservation of the ovarian cortex, fluid from small antral follicles were collected. On the basis of the follicular volume, the diameter was calculated and follicles with diameters from 3 to 12 mm were included. RESULTS: Concentrations of AMH decreased significantly (P < 0.0005) from 1124 +/- 158 ng/ml (mean +/- SEM) in follicles with a diameter of 3 mm to a concentration of 392 +/- 98 ng/ml in 9 mm follicles, followed by a reduction to below 100 ng/ml in 12 mm follicles. The concentrations of inhibin-B rose from 57 +/- 10 ng/ml (mean +/- SEM) in 3 mm follicles to 142 +/- 10 ng/ml in 12 mm follicles (P < 0.0005) with a peak concentration of almost 200 ng/ml in 9-10 mm follicles. Relating hormone concentrations with age showed that even follicles from girls younger than 10 years showed the same range of AMH concentrations as those from older girls or women. CONCLUSIONS: The intrafollicular concentrations of AMH become progressively lower with increasing follicle diameters. In contrast, concentrations of inhibin-B increased with increasing follicle diameter with peak values at around 9 mm in diameter. This suggests that AMH and inhibin-B undertake important intrafollicular functions around the time of normal follicular selection in the mid-follicular phase of the menstrual cycle.

Concentration of anti-Müllerian hormone and inhibin-B in relation to steroids and age in follicular fluid from small antral human follicles.

CONTEXT: Ovaries surgically removed for fertility preservation served as a source of follicle fluid from human small antral follicles. OBJECTIVE: The objective of the study was to measure intrafollicular concentrations of anti-Müllerian Hormone (AMH), inhibin-B, progesterone, androstenedione, testosterone, estradiol, and IGF binding protein-4. SETTING: The study was conducted at a university hospital. PATIENTS: Patients included 43 women having one ovary removed prior to receiving gonadotoxic treatment due to malignant disease. INTERVENTIONS: Fluid from 100 follicles (diameter of 3-9 mm) were included. MAIN OUTCOME MEASURES: Intrafollicular concentrations of the measured hormones, their possible intercorrelation, and correlation with age were measured. RESULTS: Concentrations of AMH were unrelated to follicular fluid concentrations of androstenedione and testosterone. There was a significant negative correlation between estradiol, inhibin-B, progesterone, and AMH. In four age groups spanning 11-37 yr, levels of AMH, estradiol, androstenedione, testosterone and inhibin-B remained constant, whereas progesterone showed significant variations. IGF binding protein-4 was unrelated to any other measured hormone. CONCLUSIONS: This study was unable to confirm a stimulatory effect of androgens on AMH secretion but did enforce a close intimate correlation between AMH and estradiol expressions in the developing human follicle. The insignificant variation of the AMH concentration with age, even in prepubertal girls, suggests that AMH expression is unrelated to menstrual cycle FSH cyclicity.

Ovarian function after removal of an entire ovary for cryopreservation of pieces of cortex prior to gonadotoxic treatment: a follow-up study.

BACKGROUND: Ovarian function was studied in Danish patients who had ovarian tissue cryopreserved, and the patients' experiences with the procedure were investigated. METHODS: There were 92 women who had an entire ovary removed for cryopreservation 18-75 months earlier. Reasons included: breast cancer (n = 31; 34%), Hodgkin's lymphoma (n = 23; 25%), bone marrow transplantation (BMT) (n = 19; 21%) and others (n = 19; 21%). Patients completed a questionnaire, and transvaginal ultrasonic antral follicle count and serum analysis for follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were performed in 73 women. RESULTS: In total, 11% of the BMT patients had normal ovarian function. Hodgkin's patients who only received ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) (n = 12) and 60% of the breast cancer patients showed little evidence of ovarian damage. Regular menstruation was shown to be a good indicator of ovarian function. The cryopreservation procedure rarely complicated cancer treatment (5%) and 84% felt comforted because they had potentially secured their fertility. CONCLUSIONS: Cryopreservation of ovarian tissue should be considered in young female patients with Hodgkin's lymphoma receiving more aggressive treatment than ABVD and in patients scheduled for BMT. The recommendation for breast cancer patient should be individualized. The cryopreservation process did not delay cancer treatment.

Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue.

BACKGROUND: Cryopreservation of the ovarian cortex with subsequent autotransplantation has, on an experimental basis, been performed to preserve fertility in women being treated for a malignant disease. The present study reports ovarian activity and pregnancies following autotransplantation of frozen/thawed ovarian tissue. METHODS: One complete ovary was cryopreserved from each of six patients who were 26-35 years old prior to treatment. Tissue from three of the patients was transported 4-5 h on ice prior to cryopreservation. After a period of 17-32 months, orthotopic autotransplantation was performed replacing 20-60% of the tissue. Two patients received additional heterotopic transplants. RESULTS: In all cases, the tissue restored menstrual cyclicity 14-20 weeks following transplantation. Four of the six women conceived following assisted reproduction: two women (who had the tissue transported 4-5 h prior to cryopreservation) each, based on the orthotopic transplanted tissue, delivered one healthy child (February 2007 and January 2008); one woman miscarriaged in gestational Week 7; and the other had a positive hCG test but no clinical pregnancy. The remaining two women did not become pregnant. CONCLUSIONS: Two additional healthy children have been born as a result of the ovarian cryopreservation procedure. In both cases, the ovarian tissue was transported 4-5 h prior to freezing demonstrating that hospitals may offer cryopreservation without having the necessary expertise locally.

[Treatment of primary and recurrent ovarian cancer].

With 550 new cases/year ovarian cancer constitutes 3% of all cancers among women. The unspecific symptoms cause delayed diagnosis and hence poor survival rates. Screening initiatives have been disappointing. In order to accelerate diagnosis and correct surgical management, patients are referred to centralized, specialized units. The primary treatment comprises surgical total cytoreduction followed by platinum-based chemotherapy. Newer biological agents are added when randomized trials have shown a benefit. Recurrence is managed by chemotherapy alone or repeated radical surgery followed by chemotherapy.

The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer.

AIM: To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. PATIENTS AND METHODS: A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. RESULTS: There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. CONCLUSION: In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node resection is associated with improved survival in stage IA and IC1. Chemotherapy should only be offered where randomized controlled studies have shown a benefit.

Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer.

AIM: Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea. METHODS: Women (n=59, mean age 42.6 years [(range 23.3-52.5]) with eBC were recruited before any treatment. Pretreatment ovarian reserve markers (anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status at 2 years. RESULTS: Pretreatment AMH was significantly lower in women with amenorrhoea at 2 years (4.0 ± 0.9 pmol/L versus 17.2 ± 2.5, P<0.0001), but FSH and inhibin B did not differ between groups. By logistic regression, pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of ovarian status at 2 years (P=0.005; odds ratio 0.013). We combined these data with a similar cohort (combined n=75); receiver-operator characteristic analysis for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82-0.97)). A cross-validated classification tree analysis resulted in a binary classification schema with sensitivity 98.2% and specificity 80.0% for correct classification of amenorrhoea. CONCLUSION: Pretreatment AMH is a useful predictor of long term post chemotherapy loss of ovarian function in women with eBC, adding significantly to the only previously established individualising predictor, i.e. age. AMH measurement may assist decision-making regarding treatment options and fertility preservation procedures.