Age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours.

BACKGROUND AND PURPOSE: Brain metastases originating from gynaecological tumours are a rare phenomenon, but have an increasing incidence due to better targeted therapies. This study aimed to identify factors that predict survival in these patients, which can be used in creating a robust prognostic tool for shared decision making. MATERIALS AND METHODS: We identified a consecutive cohort of 73 patients treated for gynaecological brain metastases in two tertiary institutions. Baseline demographics, pathology and serum CA-125 were included in a multivariable Cox proportional hazards model. RESULTS: Median overall survival in our cohort was 14.4 months, with a one-year survival of 56.4% and a two-year survival of 39.1%. Thirty-eight patients (52.1%) had ovarian carcinoma as the primary malignancy. The following factors were significantly associated with survival: age (HR 1.05 per year), CA-125 (HR 1.02 par 50 U/ml), and uterine and vulvar primary tumours (when compared to ovarian carcinoma, with HRs 3.07 and 8.70). A post-hoc analysis with primary tumour site reclassified into ovary versus non-ovary showed a HR of 0.50 for ovarian primary tumour type. CONCLUSION: We have found that age, pathology and CA-125 are prognostic factors for survival in patients with brain metastases from gynaecological tumours. Our findings may provide a foundation for future development of prediction models, for the benefit of both patients and physicians.

[The surgical learning curve]. / De chirurgische leercurve.

Surgical perfection takes years of training and a learning curve to optimize outcomes. This creates an ethical dilemma: although healthcare systems benefit from training new surgeons, the learning curve may cause suboptimal outcomes for the first patients a resident operates on. Can collective interest for the betterment of healthcare be combined with the wellbeing of the individual patient? We argue that this is possible under controlled circumstances. Residency programmes can optimize the learning curve of the trainee by active and extensive supervision: the 'See one, do one' mentality is outdated, even in relatively simple procedures. Residents can improve their skills by using hands-on training on animals or cadavers, or by re-watching their own procedures. It is possible that despite all preventative measures, the effect of the learning curve on surgical outcomes is inevitable and necessary where new surgeons are trained within regular healthcare systems. Ultimately, practice makes perfect.

A novel cell-processing method 'AgarCytos' in conjunction with OCT3/4 and PLAP to detect intratubular germ cell neoplasia in non-obstructive azoospermia using remnants of testicular sperm extraction specimens.

STUDY QUESTION: Can we diagnose intratubular germ cell neoplasia (IGCN) using the immunohistochemical markers placental-like alkaline phosphatase (PLAP) and OCT3/4 using a novel cell-processing method 'AgarCytos', applied to the remnants of testicular sperm extraction (TESE) specimens and what is the prevalence of a testicular germ cell (pre)malignancy in men with a non-obstructive azoospermia (NOA) undergoing TESE for fertility treatment? SUMMARY ANSWER: IGCN can be successfully detected by immunohistochemical evaluation of AgarCytos, made of the remnants of TESE biopsies. The observed prevalence of a germ cell (pre)malignancy in this specific population was found to be 4.4%. WHAT IS KNOWN ALREADY: Infertile men are at higher risk for testicular cancer than the general population. IGCN can be detected by immunohistochemistry using PLAP and OCT3/4 in standard testicular biopsies and, with less accuracy, in semen. STUDY DESIGN, SIZE, DURATION: Between January 2011 and April 2012 a prospective cohort study was conducted at a Dutch tertiary care academic training hospital. All males with NOA (n = 182) undergoing a urological work-up followed by a diagnostic TESE for fertility treatment (n = 251) were included. PARTICIPANTS, SETTING, METHODS: After cryopreservation of sperm, if present, an AgarCyto was made of the remnants of the TESE biopsies. Sections were stained with haematoxylin-eosin for pathological examination as well as PLAP and OCT3/4 for immunohistochemistry to detect IGCN. MAIN RESULTS AND THE ROLE OF CHANCE: Eight men (4.4%) were diagnosed with a germ cell (pre)malignancy: six of them had seminoma, two without and four with concomitant IGCN, and two of them had IGCN only. Microscopic evaluation including immunohistochemical analysis of the AgarCytos diagnosed three (1.6%) more cases of a germ cell (pre)malignancy compared with scrotal ultrasound alone (one case of bilateral seminoma with concomitant IGCN and two cases of IGCN alone). No false-positive cytology results were found upon conventional histological evaluation. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is lack of a simultaneously taken standard testicular biopsy, to compare the results of our novel diagnostic method with. Nevertheless, in all but one of our cases orchidectomy followed and the diagnosis was confirmed by histology. In the remaining case repeat TESE showed similar results. WIDER IMPLICATIONS OF THE FINDINGS: Simultaneous screening for IGCN is highly recommended to men with NOA undergoing TESE, because of the increased incidence of germ cell (pre)malignancies in this specific population. The principal advantage of our new method is that all available testicular tissue can be used for both sperm recovery and pathological evaluation, increasing the yield of spermatozoa as well as the chance to find (pre)malignant cells. In those cases where the disease is still in a premalignant stage, early diagnosis will allow for timely treatment and reduction of morbidity and mortality in this group of patients. STUDY FUNDING/COMPETING INTEREST(S): This study was (partially) funded by Merck Serono (the Netherlands). There are no conflicting interests to disclose. TRIAL REGISTRATION NUMBER: N/A.