Therapeutic strategies in epithelial ovarian cancer

Ovarian cancer is the most lethal gynecologic malignancy. It appears that the vast majority of what seem to be primary epithelial ovarian and primary peritoneal carcinomas is, in fact, secondary from the fimbria, the most distal part of the fallopian tube. Treatment of epithelial ovarian cancer is based on the combination of cytoreductive surgery and combination chemotherapy using taxane and platinum. Although clear cell type is categorized in indolent type, it is known to show relatively strong resistance to carboplatin and paclitaxel regimen and thus poor prognosis compared to serous adenocarcinoma, especially in advanced stages. Irinotecan plus cisplatin therapy may effective for the clear cell adenocarcinoma. The larger expectation for improved prognosis in ovarian carcinoma is related to the use of the new biological agents. One of the most investigated and promising molecular targeted drugs in ovarian cancer is bevacizumab, a monoclonal antibody directed against VEGF. PARP inhibitor is another one. A few recent studies demonstrated positive results of bevacizumab on progression-free survival in ovarian cancer patients, however, investigation of molecular targeting drugs in patients with ovarian cancer are still underway

Widefield Choroidal Thickness of Eyes with Central Serous Chorioretinopathy Examined by Swept-Source OCT

PURPOSE: To examine widefield (WF) changes in the choroidal thickness of eyes with central serous chorioretinopathy (CSC). DESIGN: An observational study. PARTICIPANTS: Twenty-two patients with treatment naïve unilateral CSC (20 men and two women) and 28 normal eyes of 28 age-matched healthy participants (21 men and seven women). METHODS: We performed enhanced depth imaging (EDI) of swept-source optical coherence tomography (SS-OCT) with a viewing angle of vertical 20 mm × horizontal 23 mm. Moreover, we developed a grid consisting of nine subfields, with diameters of 3 mm, 9 mm, and 18 mm; inner and outer rings enclosed by circles with diameters of 3 mm and 9 mm and 9 mm and 18 mm, respectively, which were divided into four superotemporal, inferotemporal, superonasal, and inferonasal subfields. MAIN OUTCOME MEASURES: WF changes in choroidal thickness. RESULTS: The mean duration from the presumed onset of CSC was 6.8 ± 3.1 months during the examination. Compared with normal eyes, the choroidal thickness of patients with CSC was significantly greater in all subfields (P<0.020 for fellow eyes; P<0.001 for eyes with CSC). Compared with fellow eyes, the choroidal thicknesses of eyes with CSC were significantly greater, except for the outer superotemporal and inferonasal subfields (P<0.001 for all inner subfields; and P<0.001 for outer superonasal and inferotemporal subfields). In areas with dilated vortex veins, choroidal thickening was observed from the vicinity of the vortex vein ampulla to the macula along the courses of the veins. Choroidal thickenings on the dominant side were significantly greater than those on the non-dominant side (P=0.015 for the nasal subfield of the inner ring; P=0.003 and <0.001 for temporal subfields of the inner and outer rings, respectively). CONCLUSIONS: EDI of SS-OCT imaging facilitated the analysis of WF changes in choroidal thickness not only in both controls and patients with CSC. Local factors of the affected vortex vein and systemic risk factors may be involved in the pathogenesis of CSC

Influence of unique layered microstructure on fatigue properties of Ti-48Al-2Cr-2Nb alloys fabricated by electron beam melting

The influence of a unique layered microstructure consisting of duplex-like region and equiaxed γ grain layers (γ bands) on the fatigue properties of Ti-48Al-2Cr-2Nb alloy bars fabricated by electron beam melting (EBM) was investigated at room temperature (RT) and 1023 K focusing on the angle (θ) between the building direction and cylinder (loading) axis. We found for the first time the fatigue strengths of the alloy bars with the layered microstructure depend strongly on the angle θ. Particularly, the fatigue strength of the alloy bars fabricated at θ = 45° is comparable to that of the hot isostatic pressing (HIP) treated cast alloys, even without HIP treatment. We also found the alloy bars fabricated at θ = 0° and 45° exhibit high fatigue strengths in the low-cycle fatigue life region at 1023 K similar to θ = 45° alloy bars at RT. These high fatigue strengths are caused by inhibition of the brittle main crack initiation by stress relaxation due to shear deformation at the γ bands and large plasticity of the alloys. These findings indicate that the alloys fabricated by EBM at θ = 45° with the unique layered microstructure have a great potential for aerospace and automobile applications.Cho K., Kobayashi R., Oh J.Y., et al. Influence of unique layered microstructure on fatigue properties of Ti-48Al-2Cr-2Nb alloys fabricated by electron beam melting. Intermetallics 95, 1 (2018); https://doi.org/https://doi.org/10.1016/j.intermet.2018.01.009

Natural Course of Pachychoroid Pigment Epitheliopathy

PURPOSE: To investigate the natural course of pachychoroid pigment epitheliopathy (PPE). DESIGN: A retrospective cohort study. SUBJECTS: From the Kyoto central serous chorioretinopathy (CSC) cohort consisting of 548 patients with CSC as of September 2020, we included consecutive unilateral patients with acute or chronic CSC between January 2013 and December 2016. METHODS: All patients underwent complete ophthalmic examination, including multimodal imaging such as fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography/indocyanine green angiography and/or optimal coherence tomography angiography. The fellow eyes of eyes diagnosed with CSC were screened for PPE, and their natural course was evaluated. We also evaluated the association of ARMS2 rs10490924, CFH rs800292, TNFRSF10A rs13278062, and GATA5 rs6061548 genotypes with the natural course. MAIN OUTCOME MEASURES: Incidence of CSC, pachychoroid neovasculopathy, and pachychoroid geographic atrophy (GA). RESULTS: In total, 165 patients with unilateral CSC (mean age, 55.7 ± 12.6 years; female, 22.4%) were included from the Kyoto CSC cohort. Among them, 148 (89.7%) were diagnosed as having PPE in their non-CSC eye. Survival analysis revealed that 16.8% of PPE eyes developed CSC during the 6-year follow up, whereas non-PPE eyes did not. Although genetic factors did not have significant association with CSC development (P > 0.05, log-rank test), choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness (SFCT) were significantly associated with CSC incidence (P = 0.001, log-rank test). Survival analysis showed that eyes without CVH and eyes with SFCT < 300 μm did not develop CSC during the 6-year follow-up. Pachychoroid neovasculopathy developed in only 1 eye with PPE during a follow-up of 46.4 months. Pachychoroid GA did not develop in any of the studied eyes. CONCLUSIONS: This study revealed a natural history of PPE in a relatively large Japanese cohort. Choroidal vascular hyperpermeability and SFCT were significant risk factors for the development of CSC in PPE eyes. Although the current results cannot be generalized for all eyes with PPE, these findings present an important clinical implication

Pachychoroid neovasculopathy and age-related macular degeneration.

Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19. 5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5. 1 × 10[−5]) and showed a greater subfoveal choroidal thickness (p = 3. 4 × 10[−14]). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0. 029), CFH rs800292 (p = 0. 013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10[−3]). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studie

Effectiveness of Reduced-fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

[Purpose] To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC). [Design] Retrospective cohort study. [Participants] A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded. [Methods] All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed. [Main Outcome Measures] The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate). [Results] A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients’ backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P < 0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (–0.06 vs. –0.008, P = 0.07, 12 months; –0.06 vs. –0.03, P = 0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24–7.89; P < 0.001). [Conclusions] The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting