Focusing and imaging with increased numerical apertures through multimode fibers with micro-fabricated optics

The use of individual multimode optical fibers in endoscopy applications has the potential to provide highly miniaturized and noninvasive probes for microscopy and optical micromanipulation. A few different strategies have been proposed recently, but they all suffer from intrinsically low resolution related to the low numerical aperture of multimode fibers. Here, we show that two-photon polymerization allows for direct fabrication of micro-optics components on the fiber end, resulting in an increase of the numerical aperture to a value that is close to 1. Coupling light into the fiber through a spatial light modulator, we were able to optically scan a submicrometer spot (300 nm FWHM) over an extended region, facing the opposite fiber end. Fluorescence imaging with improved resolution is also demonstrated.Comment: 5 pages, 3 figure

Surgery on breast cancer in pregnancy

Pregnancy-associated breast cancer (PABC) is defined as breast cancer develops either during or within 1 year after pregnancy, it is a rare disease arising in 1:3,000 to 1:10,000 pregnant women. Prognosis of this tumor is influenced by local or systemic treatment, which might be conditioned by gestational age and limited by the concern on potential adverse impact on fetus. The aim of this literature review is to analyze the main topics regarding surgical treatment of patients diagnosed with breast cancer in pregnancy: anesthesia and maternal-fetal monitoring, type of breast surgery, immediate breast reconstruction after radical surgery and management of the axilla. Some important topics remain controversial since the relative rarity of PABC precludes the feasibility of large studies leading to a lack of literature data. Multi-institutional collaboration is warranted to collect women with PABC, in order to best define surgical treatment in view of associated maternal and fetal risks

Efficacy and fertility outcomes of levonorgestrel-releasing intra-uterine system treatment for patients with atypical complex hyperplasia or endometrial cancer: A retrospective study

Objective: To investigate the efficacy of levonorgestrel-releasing intra-uterine system (LNG-IUS) treatment in patients affected by atypical complex hyperplasia/endometrial cancer (ACH/EC) wishing to preserve their fertility and to present fertility outcomes of those patients who actively tried to conceive. Methods: Data of consecutive women with ACH/EC who underwent fertility-sparing treatment using LNG-IUS were retrospectively evaluated. Results: Overall, 48 patients and the mean (\ub1standard deviation) length of follow-up was 82.6\ub147.2 months. Among patients with ACH, 25/28 (89.3%) had a complete response (CR), 2/28 (7.1%) had a partial response (PR) and 1/28 (3.6%) had a progressive disease (PD). Mean (\ub1standard deviation) time to CR was 6.7\ub14.0 months. Among patients with G1 EC, 13/16 (81.3%) had a CR, 1/16 (6.3%) had a PR and 2/16 (12.5%) had a PD. Mean (\ub1standard deviation) time to CR was 5.0\ub12.9 months. Among patients with G2 EC, 3/4 (75.0%) had a CR and 1/4 (25.0%) had a PD. Mean (\ub1standard deviation) time to CR was 4.0\ub10 months. Only 19 (39.6%) patients who had CR actually attempted to conceive. Eleven (57.9%) women tried to conceive naturally while 8 (42.1%) women underwent an in vitro fertilization (IVF). Fourteen (73.7%) patients wishing to conceive achieved a pregnancy (6 spontaneously and 8 through IVF). Conclusions: Fertility-sparing treatment of patient with ACH/EC with LNG-IUS achieves high regression rates and good fertility outcomes. Future larger multi-institutional studies should be designed to confirm these preliminary findings

Serum proprotein convertase subtilisin/Kexin type 9 and vascular disease in type 2 diabetic patients

BackgroundProprotein Convertase Subtilisin/Kexin type 9 (PCSK9) levels have been suggested as novel atherosclerotic biomarker. PCSK9 plays important roles in the pathogenesis of atherosclerosis by regulating the degradation of low-density lipoprotein receptor as well as different inflammatory pathways. Considering the important prognostic role of arterial stiffness in cardiovascular disease (CVD), the aim of the study is to investigate the correlation between PCSK9 levels and arterial stiffness in a cohort of diabetic patients, without previous CV events. MethodsThis cross-sectional analysis enrolled 401 Caucasian patients with type II diabetes mellitus (T2DM). PCSK9 levels were measured by ELISA test, arterial stiffness was estimated by measuring carotid-femoral pulse wave velocity (PWV). ResultsPatients were divided in three tertiles according to increasing value of PCSK9. From the I to the III tertiles, there was a significant increase in high sensitivity C-reactive protein (hs-CRP), fibrinogen and white blood cells (WBC) and a reduction in estimated glomerular filtration rate (e-GFR). Patients with higher levels of PCSK9 presented increased systolic, diastolic blood pressure, pulse pressure and PWV. PWV was significantly and directly correlated with PCSK9, fibrinogen, age, BMI and PP, and indirectly correlated with diet, lifestyle and e-GFR. Serum PCSK9 was the major predictor of PWV, justifying a 16.9% of its variation. ConclusionOur study demonstrates a close association between circulating PCSK9 levels and PWV in T2DM subjects without previous CV events even after adjusting for well-known CV risk factor and pharmacological medications. Serum PCSK9 could be a useful biomarker for CV risk stratification in diabetic subjects

A multicentre retrospective cohort study of ovarian germ cell tumours: evidence for chemotherapy de-escalation and alignment of paediatric and adult practice

Background Adult guidelines recommend BEP (bleomycin, etoposide, cisplatin) for all ovarian germ cell tumours, causing debilitating toxicities in young patients who will survive long term. Paediatricians successfully reduce toxicities by using lower bleomycin doses and substituting carboplatin for cisplatin, while testicular and paediatric immature teratomas (ITs) are safely managed with surgery alone. Aim The aim was to determine whether reduced-toxicity treatment could rationally be extended to patients older than 18 years. Methods Multicentre cohort study was carried out in four large UK cancer centres over 12 years. Results One hundred thirty-eight patients were enrolled. Overall survival was 93%, and event-free survival (EFS) was 72%. Neoadjuvant/adjuvant chemotherapy (82% BEP) caused 27 potentially chronic toxicities, and one patient subsequently died from acute lymphoblastic leukaemia. There was no difference in histology, stage or grade in patients ≤/>18 years, and EFS was not different in these age groups (≤18:28% and >18:28%; log-rank P = 0.96). Histological subtype powerfully predicted EFS (log-rank P = 4.9 × 10−7). Neoadjuvant/adjuvant chemotherapy reduced future relapse/progression in dysgerminoma (n = 37, chemo:0% vs. no chemo:20%), yolk sac tumour (n = 23, 26.3% vs.75%) and mixed germ cell tumour (n = 32, 40%vs.70%) but not in IT (n = 42, 33% vs.15%). Additionally, we observed no radiological responses to chemotherapy in ITs, pathological IT grade did not predict EFS (univariate hazard ratio 0.82, 95% confidence interval: 0.57–1.19, P = 0.94) and there were no deaths in this subtype. Conclusion Survival was excellent but chemotherapy toxicities were severe, implying significant overtreatment. Our data support the extension of reduced-toxicity, paediatric regimens to adults. Our practice-changing findings that IT was chemotherapy resistant and pathological grade uninformative strongly endorse exclusive surgical management of ovarian ITs at all ages

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects