The preparation of HEMA-MPC films for ocular drug delivery

There is a need to prolong drug residence time using a biocompatible formulation in the subconjunctival space after surgery to treat glaucoma. Drug releasing discs were prepared with 2-(hydroxyethyl)methacrylate (HEMA) and 2-methacryloyl-oxyethyl phosphorylcholine (MPC). The ratio of bound water (Wb) to free water (Wf) ratio increased from 1:0.3 to 1:6.8 with increasing MPC (0 to 50%, w/w). The optimal balance between water content, SR and mechanical strength were obtained with 10% MPC (w/w) hydrogels. Water-alcohol mixtures were examined to facilitate loading of poorly soluble drugs, and they showed greater hydrogel swelling than either water or alcohol alone. The SR was 1.2 ± 0.02 and 3.3 ± 0.1 for water and water:ethanol (1:1) respectively. HEMA-MPC (10%) discs were loaded with dexamethasone using either water:ethanol (1:1) or methanol alone. Drug release was examined in an outflow rig model that mimics the subconjunctival space in the eye. Dexamethasone loading increased from 0.3 to 1.9 mg/disc when the solvent was changed from water:ethanol (1:1) to methanol with the dexamethasone half-life (t½) increasing from 1.9 to 9.7 days respectively. These encouraging results indicate that HEMA-MPC hydrogels have the potential to sustain the residence time of a drug in the subconjunctival space of the eye

Psa-nadir At 1 Year As A Sound Contemporary Prognostic Factor For Low-dose-rate Iodine-125 Seeds Brachytherapy

Objectives: To identify predictors of outcomes in patients with localized prostate cancer treated with iodine-125 brachytherapy in a longitudinal uncontrolled study. Methods: Between 2000 and 2011, 560 histologically confirmed patients were treated with brachytherapy of whom 305 with ≥24-month follow-up and localized tumor were evaluated after exclusion of those locally advanced and under androgen ablation. Results: Patients' mean age was 63.93 years (44-88), mean pretreatment prostate-specific antigen (PSA) was 6.34 ng/mL (0.67-33.09), overall median follow-up was 75.35 months (24-158.37), biochemical recurrence occurred in 17 patients (5.57 %), cancer-specific survival was 100 %, and overall survival was 98.03 %. At multivariate analyses, only PSA-nadir at 1 year and age were related to disease-free survival: To each unit of PSA-nadir, the risk increases 87.3 %-OR 1.87 (p 70)-OR 4.69 (p = 0.04; 95 % CI 1.39-18.47). Best cutoff for PSA-nadir at one year was 0.285 (AUC = 0.78; p < 0.001; 95 % CI 0.68-0.89). Kaplan-Meier analysis confirmed PSA-nadir (p < 0.001) as prognostic, while D'Amico's classification failed (p = 0.24). No grade 3 or 4 complication was reported, and only 31.4 % of patients had grade 2 urinary or rectal toxicity. PSA bounce ≥0.4 ng/mL occurred in 18.4 % with no impact on biochemical recurrence. Conclusions: Half (50.49 %) of patients in the scenario of localized prostate cancer treated with iodine-125 brachytherapy reach PSA-nadir at 1 year <0.285, recognized as a key independent prognostic factor. Graphical Abstract: [Receiver Operating Characteristic curve analysis for PSA-nadir at 1 year] [Figure not available: see fulltext.] © 2013 Springer-Verlag Berlin Heidelberg.323753759Merrick, G.S., Butler, W.M., Dorsey, A.T., Galbreath, R.W., Blatt, H., Lief, J.H., Rectal function following prostate brachytherapy (2000) Int J Radiat Oncol Biol Phys, 48 (3), pp. 667-674Sylvester, J.E., Grimm, P.D., Wong, J., Galbreath, R.W., Merrick, G., Blasko, J.C., Fifteen-year biochemical relapse-free survival, cause-specific survival, and overall survival following I (125) prostate brachytherapy in clinically localized prostate cancer: Seattle experience (2011) Int J Radiat Oncol Biol Phys, 81 (2), pp. 376-381Vigneri, P., Herati, A.S., Potters, L., The second decade of prostate brachytherapy: evidence and cost based outcomes (2010) Urol Oncol, 28 (1), pp. 86-90Roach III, M., Hanks, G., Thames Jr., H., Schellhammer, P., Shipley, W.U., Sokol, G.H., Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO phoenix consensus conference (2006) Int J Radiat Oncol Biol Phys, 65 (4), pp. 965-974Rivard, M.J., Butler, W.M., Devlin, P.M., Hayes Jr., J.K., Hearn, R.A., Lief, E.P., Meigooni, A.S., Williamson, J.F., American Brachytherapy Society recommends no change for prostate permanent implant dose prescriptions using iodine-125 or palladium-103 (2007) Brachytherapy, 6 (1), pp. 34-37Potters, L., Morgenstern, C., Calugaru, E., Fearn, P., Jassal, A., Presser, J., 12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer (2008) J Urol, 179 (5 SUPPL.), pp. S20-S24Stock, R.G., Cesaretti, J.A., Stone, N.N., Disease-specific survival following the brachytherapy management of prostate cancer (2006) Int J Radiat Oncol Biol Phys, 64 (3), pp. 810-816Stock, R.G., Cesaretti, J.A., Unger, P., Stone, N.N., Distant and local recurrence in patients with biochemical failure after prostate brachytherapy (2008) Brachytherapy, 7 (3), pp. 217-222Ko, E.C., Stone, N.N., Stock, R.G., PSA-nadir of <0.5 ng/mL following brachytherapy for early-stage prostate adenocarcinoma is associated with freedom from prostate-specific antigen failure (2012) Int J Radiat Oncol Biol Phys, 83 (2), pp. 600-607Taira, A.V., Merrick, G.S., Galbreath, R.W., Wallner, K.E., Butler, W.M., Natural history of clinically staged low- and intermediate-risk prostate cancer treated with monotherapeutic permanent interstitial brachytherapy (2010) Int J Radiat Oncol Biol Phys, 76 (2), pp. 349-354Taira, A.V., Merrick, G.S., Butler, W.M., Galbreath, R.W., Lief, J., Adamovich, E., Long-term outcome for clinically localized prostate cancer treated with permanent interstitial brachytherapy (2011) Int J Radiat Oncol Biol Phys, 79 (5), pp. 1336-1342Stone, N.N., Stock, R.G., Unger, P., Intermediate term biochemical-free progression and local control following 125 iodine brachytherapy for prostate cancer (2005) J Urol, 173 (3), pp. 803-807Zelefsky, M.J., Kuban, D.A., Levy, L.B., Potters, L., Beyer, D.C., Blasko, J.C., Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation (2007) Int J Radiat Oncol Biol Phys, 67 (2), pp. 327-333Bowes, D., Crook, J.M., Wallace, K., Evans, A., Toi, A., Finelli, A., Jewett, M.A., Catton, C., Results of a surgically derived nomogram to predict Gleason score upgrading applied to a cohort of patients with "favorable-risk" prostate cancer treated with permanent seed brachytherapy (2012) Urology, 80 (3), pp. 649-655Stokes, S.H., Real, J.D., Adams, P.W., Clements, J.C., Wuertzer, S., Kan, W., Transperineal ultrasound-guided radioactive seed implantation for organ-confined carcinoma of the prostate (1997) Int J Radiat Oncol Biol Phys, 37 (2), pp. 337-341Guarneri, A., Botticella, A., Ragona, R., Filippi, A.R., Munoz, F., Casetta, G., Gontero, P., Ricardi, U., Prostate-specific antigen kinetics after I 125-brachytherapy for prostate adenocarcinoma (2013) World J Urol, 31 (2), pp. 411-415Storey, M.R., Landgren, R.C., Cottone, J.L., Stallings, J.W., Logan, C.W., Fraiser, L.P., Transperineal 125 iodine implantation for treatment of clinically localized prostate cancer: 5-year tumor control and morbidity (1999) Int J Radiat Oncol Biol Phys, 43 (3), pp. 565-567Shapiro, E.Y., Rais-Bahrami, S., Morgenstern, C., Napolitano, B., Richstone, L., Potters, L., Long-term outcomes in younger men following permanent prostate brachytherapy (2009) J Urol., 181 (4), pp. 1665-1671. , Discussion 71Burri, R.J., Ho, A.Y., Forsythe, K., Cesaretti, J.A., Stone, N.N., Stock, R.G., Young men have equivalent biochemical outcomes compared with older men after treatment with brachytherapy for prostate cancer (2010) Int J Radiat Oncol Biol Phys, 77 (5), pp. 1315-1321Merrick, G.S., Wallner, K.E., Galbreath, R.W., Butler, W.M., Brammer, S.G., Allen, Z.A., Biochemical and functional outcomes following brachytherapy with or without supplemental therapies in men < or =50 years of age with clinically organ-confined prostate cancer (2008) Am J Clin Oncol, 31 (6), pp. 539-544Abdel-Wahab, M., Reis, I.M., Hamilton, K., Second primary cancer after radiotherapy for prostate cancer-a SEER analysis of brachytherapy versus external beam radiotherapy (2008) Int J Radiat Oncol Biol Phys, 72 (1), pp. 58-6

Burden Of Focal Cryoablation Versus Brachytherapy Versus Active Surveillance In The Treatment Of Very Low-risk Prostate Cancer: A Preliminary Head-to-head Comprehensive Assessment

Focal cryoablation (FC), brachytherapy (B) and active surveillance (AS) were offered to patients diagnosed with very low-risk prostate cancer (VLRPC) in an equal access protocol. Comprehensive validated self-report questionnaires accessed patients' erectile (IIEF-5) and voiding (IPSS) functions, Beck scales measured anxiety (BAI), hopelessness (BHS) and depression (BDI), SF-36 reflected patients' quality of life added to the emotional thermometers including five visual analogue scales (distress, anxiety, depression, anger and need for help). Kruskal-Wallis or ANOVA tests and Spearman's correlations were obtained among groups and studied variables. Thirty patients were included, median follow-up 18 months (15-21). Those on AS (n = 11) were older, presented higher hopelessness (BHS) and lower general health perceptions (SF-36) scores than patients opting for FC (n = 10) and B (n = 9), P = 0.0014, P = 0.0268 and P = 0.0168 respectively. Patients on B had higher IPSS scores compared to those under FC and AC, P = 0.0223. For all 30 included patients, Spearman's correlation (rs) was very strong between BHS and general health perceptions (rs = -0.800, P &lt; 0.0001), and weak/moderate between age and BHS (rs = 0.405, P = 0.026) and age and general health perceptions (rs = -0.564, P = 0.001). The sample power was &gt;60%. To be considered in patients' counselling and care, current study supports the hypothesis that even VLRPC when untreated undermines psychosocial domains