Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol.

INTRODUCTION: Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. METHODS AND ANALYSIS: In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. ETHICS AND DISSEMINATION: This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov: NCT04026230, Eudra-CT: 2016-004774-17, protocol code: ESTO2, protocol date 10 September 2020 and version 6.

Improved renal cancer prognosis among users of drugs targeting renin-angiotensin system.

PURPOSE: We explored renal cell cancer (RCC) survival among users of antihypertensive medication as hypertension is proposed to be a risk factor for RCC and ACE-inhibitors and angiotensin receptor blockers (ARBs) have been associated with improved prognosis of RCC. METHODS: Finnish cohort of 13,873 participants with RCC diagnosed between 1995-2012 was formed from three national databases. RCC cases were identified from Finnish Cancer Registry, medication usage from national prescription database and co-morbidities from Care Registry of Healthcare. Logistic regression was used to calculate odds ratios for metastatic tumor extent at the time of diagnosis. Risk of RCC specific death after diagnosis was analyzed using Cox regression adjusted for tumor clinical characteristics. RESULTS: A total of 5,179 participants died of RCC during the follow-up. No risk association was found for metastatic tumor extent for any drug group. ACE-inhibitors, but no other drug group were associated with decreased risk of RCC specific death overall (HR 0.88, 95% CI 0.82-0.95) compared to non-users. In time-dependent analysis high-dose use of ACE-inhibitors (392 Defined Daily Dose (DDD)/year), HR 0.54, 95% CI 0.45-0.66) and ARBs (786.1 DDD/year, HR 0.66, 95% CI 0.50-0.87) associated with improved RCC survival. No information of TNM-classification or tobacco smoking was available. CONCLUSION: ACE-inhibitors and ARBs in high dose associated with improved RCC specific survival. This may reflect overall benefit of treating hypertension with medication targeting renin-angiotensin system (RAS) system among RCC patients. Further studies are needed to explore the role of RAS in RCC.

Update of the position paper on arterial hypertension and erectile dysfunction.

: Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensive drugs on the penile tissue. Available information points toward divergent effects of antihypertensive drugs on erectile function, with diuretics and beta-blockers possessing the worst profile and angiotensin receptor blockers and nebivolol the best profile.

Expression of LHCG receptors in the human penis.

The aim of this study is to investigate the expression of the luteinizing hormone/choriogonadotropin (LHCG) receptor in the human penis to see, if the luteinizing hormone (LH) effects are possible in the spongious and cavernous tissue of the penis. The number of men with erection disturbances increases significantly simultaneously with the elevated LH concentrations between 40 and 70 years. It is possible that the elevated LH concentrations may influence locally the erectile mechanisms. The precondition for this is the expression of LHCG receptors in the penis. Penile tissue was obtained from three patients undergoing total or partial penectomy due to a rectal cancer with secondary penile metastasis or squamous cell carcinoma of the penis. Immunohistochemistry was used for the detection of the LHCG receptor. Positive immunoreaction for LHCG receptors was discovered in the endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis, also in the endothelial cells of the capillary walls in all patients. Our results show that LHCG receptor is expressed in the spongious and cavernous tissue of the human penis. This finding suggests that LH can affect the spongious and cavernous tissue in human and play a significant role in the development of erectile dysfunction among the aging men.

Risk of urothelial cancer death among people using antihypertensive drugs-a cohort study from Finland.

Background: To analyse the association between antihypertensive (anti-HT) drug use and risk of urothelial cancer (UC) death. UC occurs as bladder cancer (BCa) and upper tract urothelial carcinomas (UTUCs). Hypertension is a suggested risk factor for BCa and may impair disease prognosis. However, it's unclear if use of anti-HT drugs could improve the prognosis of UC.Materials and methods: This study evaluated the association between use of anti-HT drugs and UC survival among 14,065 participants diagnosed with BCa and 1080 with UTUC during 1995-2012 in Finland. It analyzed data using the multivariable adjusted conditional Cox regression model.Results: Angiotensin-receptor (ATR) blocker use before BCa diagnosis was associated with slightly decreased risk of BCa death (HR = .81, CI = .71-0.93). The association was dose-dependent and it decreased in association with elevated intensity of ATR-blocker use. Post-diagnostic use of ATR-blockers was similarly associated with better survival compared to non-users (HR = .81, CI = .71-0.92. Interestingly, use of calcium-channel blockers also associated with better survival and the risk of BCa death decreased with increasing intensity of use (HR = .67, CI = .52-0.86 for highest intensity).Conclusions: This large population-based cohort suggests decreased risk of BCa death among ATR-blocker and calcium-channel blocker users. The risk association among ATR-blockers and calcium-channel blockers was dose-dependent suggesting a causal explanation. Similar risk associations are not observed for other anti-HT drug users, which may suggest a direct effect of ATR blocker or calcium-channel blocker use. Further studies are needed to elucidate the potential anticancer mechanism.

Increasing kidney cancer incidence and survival in Estonia: role of age and stage.

BACKGROUND: Kidney cancer rates in Estonia are high. The study aimed to examine long-term trends in kidney cancer incidence, mortality and survival in Estonia, with special focus on age, birth cohorts, morphology and TNM stage. MATERIAL AND METHODS: Estonian Cancer Registry provided data on all incident cases of kidney cancer (ICD-10 C64), diagnosed in adults (age ≥15 years) in Estonia during 1995 - 2014. Relative survival ratios (RSR) were calculated and excess hazard ratios of dying were estimated with gender, age, period of diagnosis and TNM stage as independent variables. Joinpoint regression modeling was used to calculate estimated annual percentage change for incidence (1970-2014) and mortality (1995-2016) trends. Age-specific incidence rates were presented by birth cohort and period of diagnosis. RESULTS: Incidence increased significantly in both sexes, with the steepest rise seen for localized cancer. Cohort effects were pronounced particularly in men, while period effects were seen from the mid-1980s to mid-1990s in both sexes. Age-standardized five-year RSR for total kidney cancer increased by 13 percentage units (from 53% to 65%) over the study period; the increase was larger for renal cell carcinoma (from 63% to 78%). Survival increases of about five percentage units were seen for stages I/II and III. Age and gender were not associated with excess risk of dying from renal cell carcinoma after adjusting for stage. CONCLUSION: Estonia is currently among countries with the highest incidence of kidney cancer. The results suggest a combined effect of changing risk profiles in successive birth cohorts and increasing diagnostic activity around 1990. Large survival increase can mostly be attributed to earlier detection, but improved diagnosis and treatment have probably influenced stage-specific survival. High proportion of tumors with unspecified morphology and those with unknown stage among the elderly warrants further investigation of diagnostic and treatment practices.

Bladder Cancer Survival of Men Receiving 5α-Reductase Inhibitors.

PURPOSE: Androgens may have a role in bladder carcinogenesis. We studied whether 5α-reductase inhibitors were associated with bladder cancer specific mortality in a population based cohort of men with bladder cancer. MATERIALS AND METHODS: The study cohort consisted of 10,720 Finnish men with bladder cancer newly diagnosed in 1997 to 2012 who were identified in a national cancer registry. Median followup was 4.17 years after bladder cancer diagnosis. We analyzed the HR and 95% CI of the risk of bladder cancer death by 5α-reductase inhibitor administration using Cox regression adjusted for age, gender, comorbidities, primary bladder cancer treatment and tumor extent at diagnosis. Lag time analyses were performed to assess the long-term risk association. Simultaneous administration α-blockers was considered to estimate possible confounding by indication. RESULTS: Administering 5α-reductase inhibitors before bladder cancer diagnosis was associated with a lower risk of bladder cancer death (HR 0.84, 95% CI 0.73-0.97). The risk decrease became stronger with years of use. Conversely prediagnostic administration of α-blockers was not associated with bladder cancer survival (HR 1.02, 95% CI 0.91-1.13). Similarly 5α-reductase inhibitor administration after diagnosis was associated with a decreased risk of bladder cancer death (HR 0.77, 95% CI 0.68-0.88). Bladder cancer survival was not associated with α-blockers (HR 0.98, 95% CI 0.90-1.07). The risk decrease due to 5α-reductase inhibitors persisted up to 5 years. CONCLUSIONS: Patients who receive 5α-reductase inhibitors have improved disease specific survival after bladder cancer diagnosis compared to those who do not receive them while α-blockers were not associated with survival. This supports the benefits of 5α-reductase inhibitors in bladder cancer.

Prostate cancer incidence, mortality and survival trends in Estonia, 1995-2014.

OBJECTIVE: The aim of this study was to analyze long-term trends in prostate cancer (PCa) incidence, mortality and survival in Estonia, with specific focus on age and stage. MATERIALS AND METHODS: Data on PCa incident cases and deaths in 1995-2014 were obtained from the Estonian Cancer Registry and the Causes of Death Registry, respectively. Joinpoint regression was used to estimate the annual percentage change for incidence and mortality trends. Relative survival ratios (RSRs) were calculated for four 5 year periods. Incidence and survival were analyzed by age and stage. RESULTS: The average annual number of new PCa cases in Estonia increased more than three-fold from 1995-1999 to 2010-2014. The age-standardized overall incidence and the incidence of localized cancer increased steeply until 2011, then leveled off. The incidence of locally/regionally spread or distant PCa remained stable. A significant increase in PCa mortality was seen only in men aged 65 years and older. The overall 5 year RSR increased from 58% to 90% over the study period. Survival increased considerably for all stages. CONCLUSIONS: The dramatic rise in the incidence of PCa in Estonia since the late 1990s was limited to localized cancers. This, together with rapid increases in survival, is probably due predominantly to extensive opportunistic prostate-specific antigen testing of middle-aged and elderly men. The ongoing increase in PCa mortality among older men warrants validation of causes of death to avoid possible overestimation. Evaluation of diagnostic and treatment strategies could identify possibilities for improving outcomes of non-localized PCa.

Components of metabolic syndrome and prognosis of renal cell cancer.

OBJECTIVE: This study analyzes risk associations between metabolic syndrome (MetS) components and the extent and prognosis of renal cell cancer (RCC). The independent effect of each MetS component is unclear, but they may affect RCC prognosis. MATERIALS AND METHODS: The study included 13,873 RCC patients (7720 men, 6153 women) diagnosed in Finland in 1995-2012. Data on MetS components (hypertension, dyslipidemia, diabetes and obesity) were obtained as recorded diagnoses or drug purchases related to these conditions. Risk of advanced RCC at diagnosis was estimated by logistic regression. Cox proportional hazard regression was used to evaluate risk associations for RCC death by MetS components after diagnosis. Components were analyzed as time-dependent variables, and included in analyses simultaneously to evaluate their independent effects. RESULTS: During follow-up (median 1.92, SD 4.35 years) 5179 participants died of RCC. Risk of advanced RCC at diagnosis was associated with hypertension [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.74-90] and dyslipidemia (OR 0.52, 95% CI 0.48-0.57). After adjustment for tumor extent, hypertension remained associated with increased risk of RCC death (hazard ratio 1.44, 95% CI 1.35-1.54]. Other MetS components were not independently associated with RCC death when taking hypertension into account. Study limitations include the non-randomized design and lack of smoking status. CONCLUSIONS: The lower risk of advanced disease among hypertensive participants may reflect the higher proportion of incidental renal tumors found through more frequent physician contacts. Nevertheless, hypertension was independently associated with worse RCC survival, whereas other MetS components had no clear prognostic role.

Muraglitazar-eluting bioabsorbable vascular stent inhibits neointimal hyperplasia in porcine iliac arteries.

PURPOSE: To evaluate the biocompatibility of a new muraglitazar-eluting polylactide copolymer stent and investigate its ability to prevent the formation of intimal hyperplasia. MATERIALS AND METHODS: Ten self-expandable muraglitazar-eluting poly-96 L/4D-lactic acid (PLA96) stents and 10 self-expandable control PLA96 stents were implanted into porcine common iliac arteries. After 28 days follow-up, all stent-implanted iliac arteries were harvested and prepared for quantitative histomorphometric analysis. RESULTS: Angiographic analysis revealed that one control PLA96 stent had occluded and one had migrated. Histomorphometric analysis demonstrated that, with the control PLA96 stent, the luminal diameter and area were decreased versus the muraglitazar-eluting PLA96 stents (means ± standard error of the mean, 3.58 mm ± 0.34 vs 4.16 mm ± 0.14 and 9.83 mm(2) ± 2.41 vs 13.75 mm(2) ± 0.93, respectively). The control PLA96 stent induced more intimal hyperplasia than the bioactive muraglitazar-eluting PLA96 stent (557 µm ± 122 vs 361 µm ± 32). Vascular injury scores demonstrated only mild vascular trauma for both stents (muraglitazar-eluting, 0.68 ± 0.07; control, 0.75 ± 0.08). Inflammation scores also showed mild inflammation for both stents (muraglitazar-eluting, 1.05 ± 0.17; control, 1.23 ± 0.19). CONCLUSIONS: This new muraglitazar-eluting PLA96 stent was shown to be biocompatible with a tendency for better patency and less intimal hyperplasia compared with the control PLA96 stents.

Dexamethasone-eluting vascular stents.

Percutaneous transluminal angioplasty (PTA) with stenting is widely used in the treatment of vascular disorders, but restenosis remains a significant problem. Drug-eluting stents (DES) have been developed as an attempt to reduce the intimal response leading to restenosis. Drugs used in DES include mainly immunosuppressive and anti-proliferative compounds. Glucocorticoids are also an interesting possibility for those purposes because they have anti-proliferative effects in vascular smooth muscle cells and down-regulate the production of cytokines and growth factors driving inflammation and fibrosis. In this MiniReview, feasibility and safety of drug-eluting metal and biodegradable vascular stents are discussed with special emphasis on dexamethasone-eluting stents.

The effect of pH on the degradation of biodegradable poly(L-lactide-co-glycolide) 80/20 urethral stent material in vitro.

PURPOSE: To investigate in vitro whether pH ranging between 6 and 9 has an effect on the degradation of stent fibers made of poly(l-lactide-co-glycolide) (PLGA) 80/20. MATERIALS AND METHODS: The fibers were divided into three groups and immersed in sodium phosphate-buffered saline (Na-PBS) solution with three different pH values: 6, 7.4, and 9. The mechanical and thermal properties were studied, and scanning electron microscopy (SEM) images were taken at specific time points of hydrolysis. RESULTS: The tensile testing showed that the strength of the fibers decreased through hydrolysis and was lost at 8 weeks in all groups. The T(m) and T(g) of the PLGA fibers did not indicate any significant differences between the different groups. In SEM images taken at 4 weeks, there were no significant differences between the fibers immersed in Na-PBS solutions of different pH values. However, at 8 weeks the surface of the fiber immersed in saline with a pH of 6 seemed coarser than that of those immersed in neutral (pH 7.4) or alkaline (pH 9) Na-PBS. CONCLUSION: The studied pH values did not influence the degradation behavior of the PLGA 80/20 fibers. Therefore, rabbits can be used as model animals for human biodegradable urological devices even though the pH of their urine is different.

Preclinical evaluation of new indomethacin-eluting biodegradable urethral stent.

PURPOSE: To evaluate the effect of an indomethacin-eluting biodegradable urethral stent on the production of inflammatory cytokines in vitro and the degradation and biocompatibility of the new stent in vivo. MATERIALS AND METHODS: The effects of an indomethacin and indomethacin-eluting biodegradable stent on monocyte chemoattractant protein (MCP)-1, RANTES (regulated on activation, normal T-cell expressed and secreted), and transforming growth factor-ß were measured in THP-1 cells by enzyme-linked immunosorbent assay. Stents (copolymer of L-lactide and glycolide acid) that were coated with 50L/50D polylactic acid and two different concentrations of indomethacin were inserted into the rabbit urethra. Stents without the drug were used as controls. Scanning electron microscopy (SEM) was used to assess the degradation of the stents. Biocompatibility was evaluated using histologic analyses of the urethral specimen. The measurements were performed at 3 weeks and 3 months. RESULTS: Indomethacin and indomethacin-releasing stent material inhibited MCP-1 and RANTES production in activated THP-1 macrophages. SEM analysis revealed that indomethacin coating had no effect on the degradation process of the stents and less epithelial polyposis had developed in the indomethacin stent group. In histologic analyses at 3 weeks, indomethacin-eluting stents caused more calcification but no significant differences in other tissue reactions. At 3 months, the indomethacin-eluting stents caused less inflammatory reaction and calcification compared with the control stents. CONCLUSION: Indomethacin-eluting property can be safely added to biodegradable stents without major influence on the degradation time. The development of epithelial polyposis in the urethra can be potentially reduced by the new indomethacin-eluting urethral stents.

Biocompatibility of new drug-eluting biodegradable urethral stent materials.

OBJECTIVES: To investigate the effects of biodegradable stent material (poly-96L/4D-lactic acid [PLA]) on the production of cytokines and other inflammatory mediators in vitro and the biocompatibility of new drug-eluting biodegradable urethral stent materials in vivo. Indomethacin, dexamethasone, and simvastatin were used in the materials. METHODS: The effects of the biodegradable stent material on cytokines and other inflammatory mediators were measured using the Human Cytokine Antibody Array and enzyme-linked immunosorbent assay in THP-1 cells, with bacterial lipopolysaccharide as a positive control. To assess the biocompatibility of the stent materials, we used muscle implantation. Biodegradable stent materials without drug-eluting properties and silicone and latex were used as controls. The measurements were done at 3 weeks and 3 months. RESULTS: The PLA stent material induced production of inflammatory mediators, especially interleukin-8, tumor necrosis factor-alpha, and transforming growth factor-beta, in vitro. The increase in the production of these mediators with the PLA stent material was smaller than in the cells treated with lipopolysaccharide. In vivo, the effects of the biodegradable materials did not differ at 3 weeks, although, at 3 months, dexamethasone had induced more tissue reactions than had the other materials. At 3 months, fibrosis and chronic inflammatory changes were decreased in the biodegradable material groups compared with the positive control. CONCLUSIONS: PLA stent material increased the production of cytokines and other inflammatory mediators less than did positive controls in vitro. The in vivo biocompatibility of the drug-eluting biodegradable materials was better than that of the positive controls. Drug-eluting biodegradable urethral stents could potentially offer a new treatment modality in the future.

Biodegradable braided poly(lactic-co-glycolic acid) urethral stent combined with dutasteride in the treatment of acute urinary retention due to benign prostatic enlargement: a pilot study.

OBJECTIVE: To evaluate, in a pilot study, the efficacy and safety of combining a braided poly(lactic-co-glycolic acid) (PLGA, a copolymer of l-lactide and glycolide) urethral stent and dutasteride in the treatment of acute urinary retention (AUR) due to benign prostatic enlargement (BPE). PATIENTS AND METHODS: Ten men with AUR due to BPE were treated as outpatients. A biodegradable braided PLGA urethral stent was inserted into the prostatic urethra, using a specially designed insertion device under visual control. Dutasteride treatment was started and the patients were followed up for 3 months after insertion of the stents. RESULTS: In all patients the stents were placed successfully with the new insertion device. All men were able to void after inserting the stent. At 1 month five patients voided freely with a low residual urine volume (<150 mL), two voided but had a high residual urine volume and a suprapubic catheter was placed, and three needed a suprapubic or an indwelling catheter before 1 month, due to AUR or comorbidities. At 3 months five patients were voiding with no problems. CONCLUSIONS: We have developed a new and effective insertion device for biodegradable braided prostatic stents. The new braided-pattern stent overcomes the earlier problems of migration and sudden breakage into large particles associated with biodegradable spiral stents. However, the mechanical properties of the new stent need to be improved and tested in a longer follow-up. We consider that this new biodegradable braided-pattern urethral stent could provide a new option in the future treatment of AUR.

Urethral in situ biocompatibility of new drug-eluting biodegradable stents: an experimental study in the rabbit.

OBJECTIVE: To assess the effect of drug-eluting properties on the degradation process and the biocompatibility of biodegradable drug-eluting urethral stents. MATERIALS AND METHODS: Braided biodegradable 80 L/20D-PLGA (copolymer of polylactide and polyglycolide) stents with drug-eluting properties were used as the test material. The drugs analysed were indomethacin, dexamethasone and ciprofloxacine. 80 L/20D-PLGA stents without a drug coating served as controls. In all, 16 male rabbits were used and divided into four groups. The stents were inserted under general anaesthesia into the posterior urethra. After 1 month, the rabbits were killed and the urethra removed for histological and optic microscopy analyses. RESULTS: Control stents and the dexamethasone-eluting stents degraded totally during the follow-up period. Conversely, in both indomethacin- and ciprofloxacine-eluting stent groups, the degradation process was significantly delayed and they induced an increase in epithelial hyperplasia. Histological analysis showed that all the stents induced eosinophilia, but there were no significant differences in the intensity of acute or chronic inflammatory reactions and fibrosis. CONCLUSIONS: A drug-eluting capacity can be added to biodegradable stents. The addition of a drug influences the biodegradation time of PLGA urethral stents. Further studies are needed, to find the proper concentrations and releasing profiles of the drugs to achieve the desired bioactivity and biocompatibility properties.

A new biodegradable braided self-expandable PLGA prostatic stent: an experimental study in the rabbit.

PURPOSE: The biodegradable PLGA (a copolymer of L-lactide and glycolide) urethral stent with a spiral configuration has been used clinically for the prevention of postoperative urinary retention after different types of thermal therapy for benign prostatic hyperplasia. A new braiding pattern for this stent has recently been developed by our group. The aim here was to investigate the in situ degradation and biocompatibility of the new braided stent in the rabbit urethra. MATERIALS AND METHODS: PLGA stents with a one-over-one braiding pattern and steel stents served as controls that were inserted into the posterior urethras of 24 male rabbits using a special delivery instrument. The animals were sacrificed after 1 week, 1 month, 2 months, or 4 months, and light microscopy and histologic analyses were performed. RESULTS: The delivery instrument worked well and cystoscopy was not needed in the insertion process. The braided PLGA stents degraded smoothly in 1 to 2 months. The metallic stents induced more epithelial hyperplasia and epithelial changes than the biodegradable stents at all time points analyzed. These differences increased during follow-up. CONCLUSION: The degradation process was well controlled and the biodegradable stents were more biocompatible than the metallic stents. The new stent can be inserted into the posterior urethra without cystoscopic aid.

Tissue biocompatibility of new biodegradable drug-eluting stent materials.

Drug-eluting stents are a recent innovation for endovascular and endourethral purposes. The aim of this study was to assess the biocompatibility of new biodegradable drug-eluting stent materials in vivo. Rods made of SR-PLDLA (self-reinforced poly-96L,4D: -lactic acid) covered with P(50L/50D)LA and rods made of 96L/4D SR-PLA and covered with P(50L/50D)LA including indomethacin 3.3 microg/mm(2)or dexamethasone 1.5 microg/mm(2), were inserted into the dorsal muscles of 20 rabbits serving as test animals. Rods made of silicone and organotin-positive polyvinylchloride were used as negative and positive controls. The animals were sacrificed after 1 week, 1 month, 2 months or 4 months. Histological changes attributable to the operative trauma were seen in all specimens at 1 week and 1 month. At 2 months both dexamethasone and indomethacin induced less fibrosis than the plain SR-PLDLA covered with P(50L/50D)LA without drug. At 4 months dexamethasone induced both chronic inflammatory changes and foreign body reaction, whereas the reactions in the indomethacin and drug-free plain SR-PLDLA groups were insignificant. The new biodegradable drug-eluting stent materials are highly biocompatible. Drug-eluting biodegradable stents may offer a promising new treatment modality for vascular and urethral diseases. However, further studies are needed to demonstrate their feasibility and efficacy.