Imaging modalities aiding nerve-sparing during radical prostatectomy.

Nerve-sparing robot-assisted radical prostatectomy has decreased the post-surgical complications of prostate surgery, but has not eliminated it. The ability to view the microstructure will enable better surgical decisions and lead to better post-surgical outcomes. An ideal imaging modality should provide rapid image acquisition, be low cost, and be specific to the tissue being examined. This article aims to review the current literature to compare three main techniques: multiphoton microscopy (MPM), optical coherence tomography, and confocal microscopy, to see which of these techniques may be best applied in surgical procedures in the future. Embase and Medline were used as the primary databases. Combinations of various key words were used while researching the literature. These included: "Radical prostatectomy," "nerve-sparing," "nerve mapping," "multiphoton microscopy," "Confocal microscopy," and "Optical Coherence Tomography." Thereafter, the relevant results were selected and used in the review. Although optical coherence tomography is a low cost and compact modality, it lacks cellular resolution, while confocal microscopy offers great cellular resolution but lacks depth. MPM, on the other hand, provides sufficient depth and produces high-resolution images. The limitation of MPM is its lack of portability, however the advent of dual-modality MPM may be a way forward.

A novel Atg5-shRNA mouse model enables temporal control of Autophagy in vivo.

Macroautophagy/autophagy is an evolutionarily conserved catabolic pathway whose modulation has been linked to diverse disease states, including age-associated disorders. Conventional and conditional whole-body knockout mouse models of key autophagy genes display perinatal death and lethal neurotoxicity, respectively, limiting their applications for in vivo studies. Here, we have developed an inducible shRNA mouse model targeting Atg5, allowing us to dynamically inhibit autophagy in vivo, termed ATG5i mice. The lack of brain-associated shRNA expression in this model circumvents the lethal phenotypes associated with complete autophagy knockouts. We show that ATG5i mice recapitulate many of the previously described phenotypes of tissue-specific knockouts. While restoration of autophagy in the liver rescues hepatomegaly and other pathologies associated with autophagy deficiency, this coincides with the development of hepatic fibrosis. These results highlight the need to consider the potential side effects of systemic anti-autophagy therapies.

Utility of early transperineal template-guided prostate biopsy for risk stratification in men undergoing active surveillance for prostate cancer.

OBJECTIVE: To assess the accuracy and utility of routine multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided prostate biopsy (TPB) after enrolment in active surveillance (AS). PATIENTS AND METHODS: From April 2012 to December 2016 consecutive men from our single institution, diagnosed with low- or intermediate-risk prostate cancer on transrectal ultrasonography-guided biopsy, were offered further staging with early mpMRI and TPB within 12 months of diagnosis. Data were collected prospectively. Eligibility criteria comprised: age ≤77 years; Gleason score ≤3 + 4; clinical stage T1-T2; PSA ≤15 ng/mL; and <50% positive biopsy cores. RESULTS: A total of 208 men were enrolled, including 196 with Gleason score 3 + 3 and 12 with Gleason score 3 + 4 disease. The median (range) number of TPB cores was 50 (17-161), with a mean TPB core density of 1.2 cores/cm3 prostate volume. A total of 83 men (39.9%) underwent histopathological upgrading after TPB, including 76 men (38.8%) with Gleason score 3 + 3 disease and seven men (58.3%) with Gleason score 3 + 4 disease. Of these, 26 (31.3%) were found to harbour primary pattern Gleason grade ≥4 disease. In all, 24 (28.9%) upgraded cases had Prostate Imaging Reporting and Data System (PI-RADS) score 1 or 2 lesions on mpMRI, including five men with Gleason score ≥4 + 3 disease. Of these, 14 (58.3%) had a prostate-specific antigen (PSA) density of ≥0.15, including four out of the five men with Gleason ≥4 + 3 disease. Overall there was a change in prostate cancer management in 77 men (37.0%) after TPB. CONCLUSIONS: Early TPB during AS is associated with significant upgrading and a change in treatment plan in over a third of men. If TPB was omitted in men with a PI-RADS score <3 and a PSA density <0.15, 12% of those harbouring more significant disease would have been misclassified.

Lag time for retinoblastoma in the UK revisited: a retrospective analysis.

OBJECTIVES: To explore current delays in diagnosis of retinoblastoma (Rb) and effect on outcome with comparison to a study from the 1990s. SETTING: Primary, secondary, tertiary care: majority from South of England. PARTICIPANTS: A retrospective analysis of 93 new referrals of sporadic (non-familial) Rb to a specialist Rb unit in London, UK from January 2006 to February 2014. PRIMARY AND SECONDARY OUTCOMES: International Intraocular Retinoblastoma Classification, lag times including parental delay and healthcare professional delay, patients requiring enucleation and requirement of adjuvant chemotherapy postenucleation (high-risk Rb). RESULTS: During the study period, 29% presented via accident and emergency (A&E). The median referral time from symptom onset to visiting primary care (PC) was 28 days and PC to ophthalmologist 3 days (range 0-181 days). The median time from local ophthalmologist to the Rb Unit was 6 days (0-33). No significant correlation was found between delay and International Classification of Retinoblastoma grade (p>0.05) or between postenucleation adjuvant chemotherapy and enucleation groups (p>0.05). Less enucleations (60%) are being performed compared with the previous study (81%) (p=0.0015). CONCLUSIONS: Parents are attending A&E more compared with the 1990s and this may reflect the effect of public awareness campaigns. More eyes are being salvaged despite a similar number of children requiring adjuvant chemotherapy. High-risk Rb and Group E eyes do not correlate with increased lag time in the UK. Other determinants such as tumour biology may be more relevant.

Branch retinal vein occlusion: treatment modalities: an update of the literature.

BACKGROUND: Retinal vein occlusion is the second most common retinal vascular disorder after diabetic retinopathy and is considered to be an important cause of visual loss. In this review, our purpose is to update the literature about the treatment alternatives for branch retinal vein occlusion. METHODS: Eligible papers were identified by a comprehensive literature search of PubMed, using the terms "branch retinal vein occlusion," "therapy," "intervention," "treatment," "vitrectomy," "sheathotomy," "laser," "anti-VEGF," "pegaptanib," "bevacizumab," "ranibizumab," "triamcinolone," "dexamethasone," "corticosteroids," "non-steroids," "diclofenac," "hemodilution," "fibrinolysis," "tPA," and "BRVO." Additional papers were also selected from reference lists of papers identified by the electronic database search. RESULTS: Treatment modalities were analyzed. CONCLUSIONS: There are several treatment modalities for branch retinal vein occlusion and specifically for its complications, such as macular edema, vitreous hemorrhage, retinal neovascularization, and retinal detachment, including anti-aggregative therapy and fibrinolysis, isovolemic hemodilution, vitrectomy with or without sheathotomy, peripheral scatter and macular grid retinal laser therapy, non-steroid agents, intravitreal steroids, and intravitreal anti-vascular endothelial growth factors (anti-VEGFs).

Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications. An update of the literature.

BACKGROUND/PURPOSE: Retinal vein occlusion is the second most common retinal vascular disorder after diabetic retinopathy and is considered to be an important cause of visual loss. In this review, the purpose is to make an update of the literature about the classification, epidemiology, pathogenesis, risk factors, clinical features, and complications of branch retinal vein occlusion (BRVO). METHODS: Eligible articles were identified using a comprehensive literature search of MEDLINE, using the terms "branch retinal vein occlusion," "pathogenesis," "epidemiology," "risk factors," "clinical features," "diagnosis," and "complications." Additional articles were also selected from reference lists of articles identified by the electronic database search. RESULTS: Classification, epidemiology, pathogenesis, risk factors, clinical features, and complications are analyzed. CONCLUSIONS: Branch retinal vein occlusion has an incidence of 0.5% to 1.2%. Several risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, thrombophilia and hypercoagulation, systemic and inflammatory diseases, medications, and ocular conditions, have found to be associated with BRVO. The symptoms depended on the site and severity of the occlusion. The average reduction in visual acuity for ischemic BRVO is 20/50 and for nonischemic BRVO is 20/60. Acute BRVO can be detected by fundoscopy, where flame hemorrhages, dot and blot hemorrhages, cotton wool spots, hard exudates, retinal edema, and dilated tortuous veins can be observed. Chronic BRVO would be more subtle and characterized by the appearance of venous collateral formation and vascular sheathing, in addition to complications previously mentioned. Areas of ischemia can be evaluated using fluorescein angiography. The extent of macular edema and the presence of retinal detachment can be detected by fundoscopic examination or fluorescein angiography, although optical coherence tomography is considered to be the best method. As far as complications, the most common is macular edema, followed by retinal neovascularization, vitreous hemorrhage, or retinal detachment.

Diagnosis and treatment of coats' disease: a review of the literature.

Coats' disease is an idiopathic, ophthalmic condition characterized by retinal telangiectasis, intraretinal and subretinal exudation, which can lead to retinal detachment. It is mostly unilateral, progressive and affects mainly males during childhood, although adult cases have also been described. In this review, we make an update of the literature about Coats' disease, emphasizing on diagnosis and treatment, including the most recent treatment modalities, i.e. anti-vascular endothelial growth factor agents.

Steroid synthesis by primary human keratinocytes; implications for skin disease.

Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3ßHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-(3)H]-pregnenolone through each steroid intermediate to [7-(3)H]-cortisol in cultured PHK. Trilostane (a 3ßHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra-adrenal cortisol synthesis, which could be a fundamental pathway in skin biology with implications in psoriasis and atopic dermatitis.