These data show that the combination of an awareness program with the offer of free diagnostic testing results in the identification of a large number individuals with severe AATD.

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Purpose To investigate the oncologic and reproductive outcome of a conservative treatment with progestin agents in early-stage grade 1 endometrial cancer (G1EC), grade 2 endometrial cancer (G2EC) or complex atypical hyperplasia (CAH) in young premenopausal women. Methods Women treated for early-stage endometrial cancer or atypical hyperplasia of the endometrium with a conservative therapy between 2006 and 2018 were enrolled in this retrospective analysis. Progestin agents were orally administered on a daily basis for 3 months for at least one cycle. Endometrial tissue was obtained by hysteroscopy and Dilatation & Curettage (D&C) being performed before and after end of treatment. Therapeutic response was assessed by pathological examination. Results A total of 14 patients were included. After treatment with progestin agents, 11 of these patients initially showed a complete or partial response. Three patients with early-stage endometrial cancer did not respond. Of the three patients with initially diagnosed atypical hyperplasia, none showed any remaining disease later. Of the eight patients with initially diagnosed endometrial cancer, who had responded to first treatment, three patients were re-diagnosed with endometrial cancer later. One patient with initial endometrial cancer became pregnant but aborted in the 10th week. Conclusion Due to its good efficacy, progestin agents offer a feasible therapeutic option in the fertility-preserving treatment of early-stage endometrial cancer in young premenopausal women. However, recurrence rate remains high. Therefore, a close follow-up is mandatory, also in responders. Patients should be informed of limitations and risks of conservative treatment. Yet after completion of family planning, hysterectomy should be performed.

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N=2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N=522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR=0.87, 95% CI 0.81-0.92, p<0.0001, N=1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR=0.52, 95% CI 0.36-0.74, p=0.0003, N=392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.

The shorter cervical segment after classic radical trachelectomy (RT) imposes a number of pregnancy associated risk factors. In this aspect, large conization (LC) could be an oncologically safe alternative to RT in young women with early stage cervical cancer who want to spare their fertility. Our aim was to evaluate fertility-sparing surgical treatment of early stage cervical cancer after the introduction of LC. Our objectives were to assess surgical, oncological, fertility and obstetric outcomes. We retrospectively investigated oncological and fertility outcomes of patients who underwent LC in a large oncological single University centre between 2009 and 2014. Medical records were reviewed and analysed for surgical, oncological, fertility and obstetric outcomes. Postal questionnaires were collected to further evaluate and validate the fertility and obstetric outcomes. A total of 23 LCs were analysed. Seven patients had to undergo secondary radical hysterectomy after LC due to unclear resection margins. Nine of 16 women tried to conceive, of which all nine became pregnant. Seven patients underwent a prophylactic cerclage between 13 and 16 gestational weeks and seven women delivered 9 children; the majority of women conceived spontaneously. Follow-up time was a median of 3.9 years (2.6–8 years). There was no relapse of cervical cancer in the investigated timeframe. Early stage cervical cancers treated by LC are associated with excellent oncological outcomes. LC appears to be a safe option for eligible women who intend to maintain their fertility.