Recommendations for a standardised educational program in robot assisted gynaecological surgery: Consensus from the Society of European Robotic Gynaecological Surgery (SERGS).

BACKGROUND: The Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. METHODS: A Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. RESULTS: On review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. CONCLUSIONS: Consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery.

Rare ovarian tumours: Epidemiology, treatment challenges in and outside a network setting.

PURPOSE OF THE REVIEW: More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of <6 per 100,000) and such tumours represent an important challenge for clinicians. RECENT FINDINGS: Rare cancers account for more than one fifth of all new cancer diagnoses, more than any of the single common cancers alone. Reviewing the RARECAREnet database, some of the tumours occur infrequently, whilst others because of their natural history have a high prevalence, and therefore appear to be more common, although their incidence is also rare. Harmonization of medical practice, guidelines and novel trials are needed to identify rare tumours and facilitate the development of new treatments. Ovarian tumours are the focus of this review, but we comment on other rare gynaecological tumours, as the diagnosis and treatment challenges faced are similar. FUTURE: This requires European collaboration, international partnerships, harmonization of treatment and collaboration to overcome the regulatory barriers to conduct international trials. Whilst randomized trials can be done in many tumour types, there are some for which conducting even single arm studies may be challenging. For these tumours alternative study designs, robust collection of data through national registries and audits could lead to improvements in the treatment of rare tumours. In addition, concentring the care of patients with rare tumours into a limited number of centres will help to build expertise, facilitate trials and improve outcomes.

Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not.

Replication of endometriosis-associated single-nucleotide polymorphisms from genome-wide association studies in a Caucasian population.

STUDY QUESTION: Is it possible to replicate the previously identified genetic association of four single-nucleotide polymorphisms (SNPs), rs12700667, rs7798431, rs1250248 and rs7521902, with endometriosis in a Caucasian population? SUMMARY ANSWER: A borderline association was observed for rs1250248 and endometriosis (P = 0.049). However, we could not replicate the other previously identified endometriosis-associated SNPs (rs12700667, rs7798431 and rs7521902) in the same population. WHAT IS KNOWN ALREADY: Endometriosis is considered a complex disease, influenced by several genetic and environmental factors, as well as interactions between them. Previous studies have found genetic associations with endometriosis for SNPs at the 7p15 and 2q35 loci in a Caucasian population. STUDY DESIGN, SIZE, DURATION: Allele frequencies of SNPs were investigated in patients with endometriosis and controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples and peritoneal biopsies were taken from a Caucasian female population consisting of 1129 patients with endometriosis and 831 controls. DNA was extracted for genotyping. The study was performed at a University hospital and research laboratories. MAIN RESULTS AND THE ROLE OF CHANCE: A weak association with endometriosis (all stages) was observed for rs1250248 (P = 0.049). No significant associations were observed for the SNPs rs12700667, rs7798431 and rs7521902. A non-significant trend towards the association of rs1250248 with moderate/severe endometriosis was observed (odds ratio 1.18, 95% confidence interval 0.97-1.44). LIMITATIONS, REASONS FOR CAUTION: The inability to confirm all previous findings may result from differences between populations and type II errors. WIDER IMPLICATIONS OF THE FINDINGS: Our result demonstrates the difficulty of identifying common genetic variants in complex diseases. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Karolinska Institutet and Stockholm City County/Karolinska Institutet (ALF), Stockholm, Sweden, Swedish Medical Research Council (K2007-54X-14212-06-3, K2010-54X-14212-09-3), Stockholm, Sweden, Leuven University Research Council (Onderzoeksraad KU Leuven), the Leuven University Hospitals Clinical Research Foundation (Klinisch onderzoeksfonds) and by the National Scientific Foundation (Fonds voor Wetenschappelijk Onderzoek, FWO). The authors have no conflict of interest.

Ovarian cancer-associated polymorphisms in the BNC2 gene among women with endometriosis.

BACKGROUND: Endometriosis is a common benign gynaecological disease. Epidemiological studies have demonstrated associations between endometriosis and ovarian cancer. Recent genome-wide association studies of ovarian cancer have identified several single nucleotide polymorphisms (SNPs) in the Basonuclin 2 (BNC2) gene. In this study, we investigated these polymorphism in women with endometriosis. METHODS: Six SNPs in and upstream of the BNC2 gene (rs3814113, rs4445329, rs10962656, rs12379183, rs10756819 and rs1339552) were investigated using TaqMan allelic discrimination analysis in a Caucasian population (cases: 798, controls: 351). Allelic frequencies were used as main outcome measure. RESULTS: No associations were observed between the analysed SNPs and endometriosis. CONCLUSIONS: Our results suggest that the analysed polymorphisms in the BNC2 gene are unlikely to contribute to the previously reported risk of ovarian cancer in women with endometriosis.

IVF outcome in women with endometriosis in relation to tumour necrosis factor and anti-Müllerian hormone.

This study reports on anti-Müllerian hormone (AMH) in serum and follicular fluid (FF) in relation to inflammatory parameters in women with and without endometriosis undergoing IVF. Serum and FF samples were obtained from 72 women, with (n = 34) and without (n = 38) endometriosis, undergoing IVF. The concentrations of AMH, FSH, tumour necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and several interleukins were analysed. Women with endometriosis had significantly lower AMH in serum and FF (serum: 6.38 versus 12.8 pM; P < 0.01, FF: 14.0 versus 19.6 pM; P < 0.05). TNF was increased in FF (40.0 versus 30.8 pg/ml, P < 0.05) from women with endometriosis and significantly higher concentrations of IL-15 and GM-CSF were detected in FF (both P < 0.05). During IVF, women with endometriosis responded well to FSH but had lower fertilization rates. Women with endometriosis have elevated concentrations of several cytokines in FF. They respond adequately to exogenous FSH but may have impaired oocyte quality, reflected in lower fertilization rates, presumably resulting from an inflammatory process in the ovaries. Further studies are needed to elucidate the role of AMH in predicting ovarian reserve in women with endometriosis.

Olive baboon (Papio anubis anubis) as a model for intrauterine research.

BACKGROUND: The Olive baboon is a popular animal model for reproductive and surgical research. The Institute of Primate Research, Nairobi, Kenya, has been using the animal for reproductive research for many years. In the baboon, compared with other smaller non-human primates, it is possible to insert uterine probes such as, catheters, curettes and other linear instruments (to cannulate cervix for uterine procedures like flushing, endometrium biopsy, embryo transfer, etc.). METHODS: However we noticed in a few animals this was difficult and problematic, particularly in some stages of the menstrual cycle, in retroverted uteri, in extensive adhesions or in some anatomically unique animals and we have developed a technique called 'Chai technique' for this purpose. RESULTS AND CONCLUSIONS: The Chai technique is unique to the baboon and not possible in human. It does not seem to cause injuries as frequently as uterine perforation and, in our experience, has been surprisingly successful.

Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon.

BACKGROUND: Inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha), are important in the pathogenesis of endometriosis. We assessed the efficacy of anti-TNF monoclonal antibody (mAb, c5N), known to prevent induced endometriosis in baboons, in reducing established endometriosis in baboons. METHODS: This prospective, randomized, blinded, controlled study was conducted in baboons at the Institute of Primate Research (IPR), Nairobi, Kenya. Endometriosis was induced in 18 adult female baboons (Papio anubis) with regular menstrual cycles and a normal pelvis; the extent of endometriosis was documented by videolaparoscopy 25 days later. The baboons were then randomly assigned to receive a single infusion of either placebo (n=7, 5 ml/kg) or c5N (n=11, 5 mg/kg). Follow-up laparoscopy was performed 25 days later to document any differences in the number, surface area and estimated volume of lesions between the two groups and between the first and the second laparoscopies in each group. Representative biopsies of at least one endometriotic lesion per baboon were obtained at the final laparoscopy. RESULTS: Significant reductions in total surface area, estimated total volume of endometriotic lesions and both number and surface area of red lesions were observed after treatment with c5N, but not after placebo treatment, when compared to the initial laparoscopy. Conversely, a significant increase in the number of typical and red lesions was observed after placebo treatment when compared to the initial laparoscopy. Neither c5N nor placebo treatment affected the menstrual cycle. CONCLUSION: In baboons with induced endometriosis, anti-TNF-mAb (c5N) treatment significantly reduced the extent of endometriosis, mainly due to reducing both the number and surface area of red lesions. These findings suggest that anti-TNF-mAb therapy may have therapeutic potential for active peritoneal endometriosis.

The effect of endometriosis, cycle stage, lymphocyte suppression and pregnancy on CA-125 levels in peritoneal fluid and serum in baboons.

BACKGROUND: Serum CA-125 during the mid-follicular phase has been reported to be a clinically useful and reproducible marker in the diagnosis of advanced endometriosis in women. This study was undertaken to document the effect of the menstrual cycle, pregnancy and lymphocyte suppression on CA-125 levels in peritoneal fluid (PF) and serum in baboons with a normal pelvis and baboons with endometriosis. METHODS: CA-125 levels were measured in 264 serum samples that were serially obtained during one menstrual cycle from 10 animals with and without endometriosis. In addition, CA-125 levels were determined in 204 archived samples (serum, n = 112 and PF, n = 92) obtained from 32 female baboons with or without endometriosis. The CA-125 assays were performed by radioimmunoassay using kits from Centocor (Malvern, PA, USA). RESULTS: Serum CA-125 levels were at their highest during menstruation and decreased progressively during the follicular and luteal phase. PF CA-125 levels were increased during the follicular phase in baboons with a normal pelvis, but no cyclic changes were observed in animals with endometriosis. Serum CA-125 levels were unaffected by induction, lymphocyte suppression or pregnancy. Induction of endometriosis resulted in increased PF CA-125 levels, whereas lymphocyte suppression or pregnancy had no effect. CONCLUSION: In baboons, serum CA-125 originates mainly from eutopic endometrium whereas the main source of PF CA-125 seems to be the peritoneum or ectopic endometrium. The baboon appears to be a valid model to further study the relationship between endometriosis and CA-125.

A survey of chronic renal failure in Jamaica.

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conducted at six Jamaican healthcare facilities between July 1998 and December 1999 and included 605 patients with CRF. Men with CRF (57% of patients, mean age of 56.7 years) were significantly older than women (mean age 53.2 years). Hypertension was the most commonly associated medical condition (60.8% of patients) followed by diabetes mellitus (31.4% of patients). The estimated crude point prevalence of CRF in persons 20 years and over at the end of 1999 was 327 per million population. More than one-third of patients with CRF (39%) were receiving renal replacement therapy, the most common modality being haemodialysis, and only 1.8% of patients had received kidney transplantation. The prevalence of chronic renal failure was not increased in areas known to have high soil cadmium levels. Chronic renal failure is a significant public health problem in Jamaica and is placing an increasing financial burden on the healthcare sector.

A survey of chronic renal failure in Jamaica

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conducted at six Jamaican healthcare facilities between July 1998 and December 1999 and included 605 patients with CRF. Men with CRF (57 of patients, mean age of 56.7 years) were significantly older than women (mean age 53.2 years). Hypertension was the most commonly associated medical condition (60.8 of patients) followed by diabetes mellitus (31.4 of patients). The estimated crude point prevalence of CRF in persons 20 years and over at the end of 1999 was 327 per million population. More than one-third of patients with CRF (39) were receiving renal replacement therapy, the most common modality being haemodialysis, and only 1.8 of patients had received kidney transplantation. The prevalence of chronic renal failure was not increased in areas known to have high soil cadmium levels. Chronic renal failure is a significant public health problem in Jamaica and is placing an increasing financial burden on the healthcare sector

Persistent gestational trophoblastic disease presenting as left hemiparesis in a Jamaican teenager.

A 19-year-old woman, who delivered a macerated stillborn at 32 weeks' gestation and had persistent postpartum vaginal bleeding, presented with a left hemiparesis three and a half months after delivery. A clinical diagnosis of persistent gestational trophoblastic disease (GTD) was made, based on quantitative serum beta-hCG of more than 200,000 IU/ml, cannon ball metastases on chest X-ray and two ring enhancing lesions, metastases, in the right parietal lobe on Computed Axial Tomography (CAT) scan of the brain. Despite combination chemotherapy, with methotrexate, cyclophosphamide and actinomycin D, her condition worsened and she died.

Persistent gestational trophoblastic disease presenting as left hemiparesis in a Jamaican teenager

A 19-year-old woman, who delivered a macerated stillborn at 32 weeks' gestation and had persistent postpartum vaginal bleeding, presented with a left hemiparesis three and a half months after delivery. A clinical diagnosis of persistent gestational trophoblastic disease (GTD) was made, based on quantitative serum beta-hCG of more than 200,000 IU/ml, cannon ball metastases on chest X-ray and two ring enhancing lesions, metastases, in the right parietal lobe on Computed Axial Tomography (CAT) scan of the brain. Despite combination chemotherapy, with methotrexate, cyclophosphamide and actinomycin D, her condition worsened and she died.

Cryptococcosis in the West Indies

Crptococcosis with meningitis is reported in seven patients, six from Jamaica and one from Belize. All seven had headache, six had fever and five had confusion/coma. Despite biochemical findings of meningitis in the cerebrospinal fluid of five patients, Cryptococcosis was diagnosed antemortem in only three. Two patients treated with oral flucytosine survived. Awareness that Cryptococcosis occurs in the West Indies may assist in early diagnosis which is crucial to successful treatment (AU)

Cryptococcal eye disease.

A survey is given of the clinical picture of an infection with Cryptococcus neoformans. The symptoms and therapy are reviewed and the case history of a 13 year old boy suffering from this fungus infection is discussed.