PREVALENCE OF FATIGUE AND IMPACT ON QUALITY OF LIFE IN CASTRATION-RESISTANT PROSTATE CANCER PATIENTS: the VITAL study.

BACKGROUND: Fatigue is one of the most prevalent symptoms among cancer patients. Specifically, in metastatic castration-resistant prostate cancer (mCRPC) patients, fatigue is the most common adverse event associated with current treatments. The purpose of this study is to describe the prevalence of fatigue and its impact on quality of life (QoL) in patients with CRPC in routine clinical practice. METHODS: This was a cross-sectional, multicentre study. Male chemo-naïve adults with high-risk non-metastatic (M0) CRPC and metastatic (M1) CRPC (mCRPC) were eligible. Fatigue was measured using the Brief Fatigue Inventory (BFI) and QoL was assessed using the Functional Assessment of Cancer Therapy questionnaire for patients with prostate cancer (FACT-P) and the FACT-General (FACT-G) questionnaire. Data were analysed using Mann-Whitney or Kruskal-Wallis tests (non-parametric distribution), a T-test or an ANOVA (parametric distribution) and the Fisher or chi-squared tests (categorical variables). RESULTS: A total of 235 eligible patients were included in the study (74 [31.5%] with M0; and 161 [68.5%] with M1). Fatigue was present in 74%, with 38.5% of patients reporting moderate-to-severe fatigue. Mean FACT-G and FACT-P overall scores were 77.6 ± 16.3 and 108.7 ± 21.4, respectively, with no differences between the CRPC M0 and CRPC M1 subgroups. Fatigue intensity was associated with decreased FACT-G/P scores, with no differences between groups. Among 151 mCRPC patients with available treatment data, those treated with abiraterone-prednisone ≥3 months showed a significant reduction in fatigue intensity (p = 0.043) and interference (p = 0.04) compared to those on traditional hormone therapy (HT). Patients on abiraterone-prednisone ≥3 months showed significantly better FACT-G/P scores than patients on HT (p = 0.046 and 0.018, respectively). CONCLUSION: Our data show a high prevalence and intensity of fatigue and its impact on QoL in chemo-naïve CRPC patients. There is an association between greater fatigue and less QoL, irrespective of the presence or absence of metastasis. Chemo-naïve mCRPC patients receiving more than 3 months of abiraterone acetate plus prednisone showed an improvement of fatigue and QoL when compared to those on traditional HT. TRIAL REGISTRATION: Not applicable since it is not an interventional study.

Ibuprofen nanocrystals developed by 22 factorial design experiment: A new approach for poorly water-soluble drugs.

The reduction of the particle size of drugs of pharmaceutical interest down to the nano-sized range has dramatically changed their physicochemical properties. The greatest disadvantage of nanocrystals is their inherent instability, due to the risk of crystal growth. Thus, the selection of an appropriate stabilizer is crucial to obtain long-term physicochemically stable nanocrystals. High pressure homogenization has enormous advantages, including the possibility of scaling up, lack of organic solvents and the production of small particles diameter with low polydispersity index. The sequential use of high shear homogenization followed by high pressure homogenization, can modulate nanoparticles' size for different administration routes. The present study focuses on the optimization of the production process of two formulations composed of different surfactants produced by High Shear Homogenization followed by hot High Pressure Homogenization. To build up the surface response charts, a 22 full factorial design experiment, based on 2 independent variables, was used to develop optimized formulations. The effects of the production process on the mean particle size and polydispersity index were evaluated. The best ibuprofen nanocrystal formulations were obtained using 0.20% Tween 80 and 1.20% PVP K30 (F1) and 0.20% Tween 80 and 1.20% Span 80 (F2). The estimation of the long-term stability of the aqueous suspensions of ibuprofen nanocrystals was studied using the LUMISizer. The calculated instability index suggests that F1 was more stable when stored at 4 °C and 22 °C, whereas F2 was shown to be more stable when freshly prepared.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

In vitro release of ketoprofen from hydrophilic matrix tablets containing cellulose polymer mixtures.

The effect of cellulose ether polymer mixtures, containing both hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC K15M or K100M), on ketoprofen (KTP) release from matrix tablets was investigated. In order to evaluate the compatibility between the matrix components, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) experiments were performed. The results evidence the absence of significant intermolecular interactions that could eventually lead to an incompatibility between the drug and the different excipients. Formulations containing mixtures of polymers with both low and high viscosity grades were prepared by a direct compression method, by varying the polymer/polymer (w/w) ratio while keeping the drug amount incorporated in the solid dispersion constant (200 mg). The hardness values of different matrices were found within the range 113.8 to 154.9 N. HPLC analysis showed a drug content recovery between 99.3 and 102.1%, indicating that no KTP degradation occurred during the preparation process. All formulations attained a high hydration degree after the first hour, which is essential to allow the gel layer formation prior to tablet dissolution. Independent-model dissolution parameters such as t(10%) and t(50%) dissolution times, dissolution efficiency (DE), mean dissolution time (MDT), and area under curve (AUC) were calculated for all formulations. Zero-order, first-order, Higuchi, and Korsmeyer-Peppas kinetic models were employed to interpret the dissolution profiles: a predominantly Fickian diffusion release mechanism was obtained - with Korsmeyer-Peppas exponent values ranging from 0.216 to 0.555. The incorporation of HPC was thus found to play an essential role as a release modifier from HPMC containing tablets.

Advances in urologic oncology "OncoUrology Forum Special Edition": The best of 2020.

OBJECTIVE: To provide latest findings of Urologic Oncology on prostate, kidney, and bladder cancer, and analyze its impact on clinical practice as well as future schemes in the medium- and long-term. METHODS: This document reviews the abstracts on Uro-Oncology presented at the 2020 Congresses (EUA, AUA, ASCO, ESMO and ASTRO), the publications with the highest impact and especially the new lines of development and progress in Uro-Oncology evaluated by the OncoForum committee. RESULTS: The use of prostate-specific membrane antigen (PSMA) radioligands in the diagnosis of prostate cancer may have great potential and utility in the coming years due to their improved sensitivity and specificity. The genetic characterization of the tumor is important at both, germline and somatic levels, due to the significant role of BRCA2 mutations regarding risk. The cohort multiple randomised controlled trial is the most suitable study design at the genitourinary cancer level. The application of big data will lead to process improvements, savings in healthcare costs, and an empowerment of real-life studies through ease of data comparison, management, and storage. CONCLUSIONS: The use of new diagnostic techniques with PSMA ligands will provide a more comprehensive diagnostic modality, increase the number of studies about tumor genetic profiling, and enhance their quality. The practical application of artificial intelligence will improve the treatment genitourinary cancer.

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors.

OBJECTIVE: To identify predictors of immune-related adverse events (IRAEs) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Assess associations between outcomes and the development of IRAEs. METHODS: Retrospective analysis of patients with NSCLC treated with ICIs between 2016 and 2020 in the Pulmonology Department of our hospital. Patients with and without IRAEs were compared. A logistic regression analysis was performed to determine predictors of IRAEs. Progression-free survival (PFS) and overall survival (OS) curves were calculated using the Kaplan-Meier method, and the long-rank test was used to assess survival differences between groups. Univariate and multivariate Cox proportional-hazards regression models were used to identify factors associated with PFS and OS. The value considered statistically significant was p≤0.05. RESULTS: A total of 184 patients (77.7% men, mean age 66.9±9.5 years) treated with ICIs were analyzed. During follow-up, 49 (26.6%) patients developed IRAEs and 149 (81.0%) died. According to the multivariate logistic regression analysis, treatment with statins (OR:3.15; p = 0.007), previous systemic corticosteroid therapy (OR:3.99; p = 0.001), disease controlled as response to ICI (OR:5.93; p < 0.001) and higher hemoglobin values (OR:1.28; p = 0.040) were independent predictors for the development of IRAEs. Patients who developed IRAEs had significantly longer medians of PFS (41.0 vs 9.0 weeks, p < 0.001) and OS (89.0 vs 28.0 weeks; p < 0.001). CONCLUSIONS: Patients treated with statins, pre-ICI systemic corticosteroids, higher baseline hemoglobin value and controlled disease as initial response to ICI had a higher risk of developing IRAEs. The development of IRAEs was associated with better outcomes.

Advances in urologic oncology "OncoForum": The best of 2019. / Avances en uro-oncología «OncoForum¼: lo mejor del 2019.

OBJECTIVE: Review the latest evidence on urologic oncology on kidney, bladder and prostate tumors. METHODS: Abstracts on kidney, bladder and prostate cancer presented at the 2019 congresses (EAU, AUA, ASCO and ESMO) and the publications with the greatest impact in this period, with the highest evaluation by the OncoForum committee, are reviewed. RESULTS: In patients with metastatic kidney cancer, regimens including immunotherapy (nivolumab + ipilimumab, pembrolizumab) have been shown to be superior to sunitinib in terms of survival. In patients with non-muscle invasive bladder cancer, pembrolizumab has been shown to be an effective alternative in those refractory to bacillus Calmette-Guérin, while in patients with metastatic urothelial cancer, third-line enfortumab vedotin achieved a significant response rate (44%). In patients with localized prostate cancer (PCa), ultrafractionated external radiotherapy did not show any greater acute toxicity than fractionated or hypofractionated radiotherapy. The benefit of enzalutamide and apalutamide associated with castration has been confirmed in M1 PCa patients, regardless of disease volume. In patients with castration-resistant M0 PCa, treatment with enzalutamide, apalutamide or darolutamide has been associated with a delay in the occurrence of metastasis and prolonged survival. Cabazitaxel has demonstrated a survival benefit in patients with metastatic CRPC, while olaparib showed anti-tumor activity after chemotherapy in those tumors with mutations in DNA repair genes. CONCLUSIONS: These data show the implementation of immunotherapy as a novel alternative against renal and bladder cancer. The arrival of new agents for advanced urothelial carcinoma should be highlighted, and the efficacy of enzalutamide and apalutamide in de novo metastatic prostate cancer is established. In metastatic CRPC, cabazitaxel and olaparib (targeting mutations) are promising therapeutic options.

Androgen deprivation therapy in patients with localized disease: Comparison with curative intent treatments and time to castration resistance. Results of the Spanish Prostate Cancer Registry. / Terapia de privación de andrógenos en pacientes con enfermedad localizada: comparación de las opciones de tratamiento y tiempo hasta la resistencia a la castración. Resultados del Registro Español de Cáncer de Próstata.

BACKGROUND: The effect of primary androgen deprivation therapy (ADT) in patients with localized prostate cancer (PCa) has not been well documented. The objective of the present study was to analyze the outcome of tumors treated with ADT as primary therapy in the Spanish Prostate Cancer Registry (19.4% of the series). PATIENTS AND METHODS: Patients were classified in three groups: 1) with low/intermediate risk clinically localized tumors; 2) with high risk and locally advanced (T3-4) tumors; 3) with metastatic tumors. Time to castration resistance and overall cancer-specific survival were analyzed. In non-metastatic tumors, survivals in patients treated with ADT were compared with data from patients who underwent local treatments from the Spanish Prostate Cancer Registry. RESULTS: 703 cases were analyzed. There were significant differences in the time to castration resistance, which was lower in the group of metastatic tumors. During follow-up, there were 179 deaths (25.5%) of which 89 (12.6%) were due to PCa. After 3 years of ADT, only 14.6% of patients in group 1 had died (1% due to PCa), 20.5% in group 2 and 46.8% in group 3 (9.2% and 31.3% due to PCa, respectively). Cancer-specific survival was significantly worse in group 1 using ADT than radical prostatectomy or radiotherapy. In high-risk and locally advanced tumors, ADT also had a lower cancer-specific survival than local treatments. CONCLUSION: A longer time until the castration resistance was observed in patients with well- and intermediate-risk localized tumors treated with ADT. Patients with metastatic tumors showed the shortest time to castration resistance.

The impact of time from biopsy to radical prostatectomy on Gleason score undergrading and other related factors. / Impacto del tiempo desde la biopsia a la prostatectomía radical en la infragradación del grado de Gleason y análisis de factores relacionados.

INTRODUCTION: Gleason score biopsy undergrading (GSBU) can have an impact on the management and prognosis of patients with prostate cancer. We analyze the possible impact of time and other clinical and analytical factors in the appearance of GSBU in our series. PATIENTS AND METHOD: Ambispective, multicenter study of 1955 patients with localized prostate cancer undergoing radical prostatectomy between 2005 and 2018. Descriptive statistics and hypothesis testing are reported by univariate and multivariate analyses. RESULTS: Mean age 63.69 (44-80) years, median PSA 8.70 ng / ml (1.23-99). GSBU was observed in 34.7% of the entire cohort. In 72.8% of the cases, the GSBU occurred in one consecutive Gleason score, with the progression from 3 + 3 to 3 + 4 being the most frequent (289 patients, 47.6%). Performing radical prostatectomy 90-180 days before or after the biopsy does not have an impact on its undergrading in any of the groups. In the univariate and multivariate analysis, the presence of tumor or pathological rectal examination in both lobes, the tumor load ≥50% of cylinders and a DPSA ≥0.20, showed independent discriminative capacity to select patients who presented GSBU. CONCLUSIONS: The time from biopsy to radical prostatectomy did not show impact on GSBU. The number of affected cylinders, bilateral tumor and DPSA are easily accessible parameters that can help us select patients with greater probability of presenting GSBU.

Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer.

BACKGROUND: The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment. METHODS: Patients with T1c-T2 clinical stage with prostate-specific antigen (PSA) >20 ng ml(-1) and/or Gleason score >or=7 (4+3) and T3 were included. Treatment consisted of three cycles of D 36 mg m(-2) on days 1, 8 and 15 every 28 days concomitant with CAB, followed by radical prostatectomy (RP). RESULTS: A total of 57 patients were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and T3, 16 (28%) patients. Gleason score was >or=7 (4+3) in 44 (77%) patients and PSA >20 ng ml(-1) in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%) patients completing neoadjuvant therapy together with RP. The rate of pCR was 6% (three patients). Three (6%) additional patients had microscopic residual tumour (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%) patients presented PSA relapse. CONCLUSION: Short-term neoadjuvant D and CAB induced a 6% pCR rate, which is close to what would be expected with ADT alone. The combination was generally well tolerated.

Comparison of ELISA and HPLC-MS methods for the determination of exenatide in biological and biotechnology-based formulation matrices.

The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.

Three-year interim results of overall and progression-free survival in a cohort of patients with prostate cancer (GESCAP group). / Resultados preliminares de supervivencia global y libre de progresión a tresaños en una cohorte de pacientes diagnosticados de cáncer de próstata (grupo GESCAP).

AIMS: To describe the 3-year progression-free survival (PFS), overall survival (OS) and disease-specific mortality in the prospective prostate cancer GESCAP cohort, as well as the progression to castration resistance in patients on hormone therapy. MATERIAL AND METHODS: Prospective, observational, epidemiological, multicentre study. Of the 4087 patients recruited, 3843 were evaluable. The variables analysed were the risk group (localized, locally advanced, lymph involvement, metastatic), age, prostate-specific antigen (PSA) levels, Gleason score and initial treatment. Kaplan Meier survival analysis, the log-rank test and the Cox model were used to evaluate the survival data. RESULTS: Three-year PFS was 81.4% and OS was 92.4%. During the 3 years of follow-up, 303 patients died (7.9%), 110 of them (36.3%) due to disease-related causes. The probability of castration resistance for all patients on hormone therapy (n=715) was 14.2%: 5%, 9.9%, 26.1% and 44.4% in localized, locally advanced, lymph involvement and metastatic cancer, respectively (log-rank P<.0001). Patients with metastases had poorer outcomes with respect to PFS, OS, disease-specific mortality and castration resistance. In the multivariate analysis, the Gleason score, PSA and presence of metastases were associated with shorter OS and PFS. CONCLUSIONS: Our study showed stratification of risk, with a more unfavourable prognosis for patients with metastases. Patients with locally advanced disease differed with respect to those with localized disease due to their higher risk as regards disease-specific mortality. (Controlled-trials.com ISRCTN19893319).

Factors related to early castration resistance in metastatic prostate cancer. Results from the National Prostate Cancer Registry in Spain. / Factores relacionados con la resistencia a la castración precoz en el cáncer de próstata metastásico. Resultados del Registro nacional de cáncer de próstata en España.

INTRODUCTION: The objective of the study was to determine the factors independently related with the development of castration resistance (CR) in prostate cancer (PC) in the medium term. MATERIAL AND METHODS: 155 patients diagnosed with metastatic PC with a follow-up of up to 39 months. Data taken from the National PC Registry. The evaluated variables were age, PSA, nadir PSA, Gleason, perineural invasion, TNM stages, and ADT type (intermittent/continuous). RESULTS: Mean follow-up 26,2±13,4 months. 47.1% developed early CR, with mean time until onset of 12,2±8,7 months. Univariate analysis the mean PSA was correlated with CR (290±905,1 ng/mL in non CR, 519,1±1437,2 ng/mL in CR, P<.001), mean age (73,3±8,3 years in non CR, 69,1±9,3 in CR P=.01), mean PSA nadir (15,5±57,3ng/mL in non CR, 15,9±23,7 ng/mL in CR, p<0,001), Gleason (in ≥8, HR:2,11. 95% CI: 1.22-3.65, p=0.006), and T stage (in T3-T4, HR: 2.85. 95% CI: 1.57-5.19, P<.001). Multivariate analysis the independent variables associated to CR are age (HR: 0.96. 95% CI: 0.94-0.99, P=.01), PSA nadir (HR: 1.65. 95% CI: 1,43-1,91, P<.001), and T3-T4 stage (HR: 2.11. 95% CI: 1.10-4.04, P=.02). CONCLUSIONS: PSA nadir and T3-T4 tumor stage at diagnosis are associated to an increased risk of developing CR. In addition, age at diagnosis is shown as a variable that decreases risk. Therefore, an older age would be associated with lower risk probability of CR in the medium term.

[Insignificant prostate cancer. Analysis our series]. / Cancer de próstata insignificante. Análisis de nuestra serie.

The objective of this study is to analyse the specimen of radical prostatectomy of patients who had, prior to the surgery insignificant prostate cancer biopsies. The end point is demonstrate the possibility of an active surveillance as a therapeutic option for prostate cancer in selected is the possibility of an active surveillance as therapeutic for the prostate cancer, in selected individuals if we are able to find diagnostic algorisms to predict the real insignificant tumours. The selected group of patients for the study has a PSA less or equal 10, one positive core of prostatic transrectal ultrasound biopsy with a Gleason score less than 7. This group of patients is considerate as having a potential insignificant tumour. We will consider prostatectomy's specimens and the Gleason sore is less than 7 and the tumoral volume is les or equal to 5%. Of 394 patients with prostate cancer and homogeneous criterias for our study, we have selected 53 patients according to the criteria of insignificant tumour in the biopsy. Our results showed that only 22 of 53 (41.5%) patients were identified as having an insignificant prostate cancer in the RP specimens. Moreover 92.2% of this tumours were organ-confined. In conclusion we are able to say that tumours of low-risk and low tumoral volume in the biopsy, do not correlate always to insignificant tumours in PR specimens, but we have observed that the majority are organ-confined tumours. Finally, the diagnostic's algorisms dies not to predict tumours that may safely treated with active monitoring.

Developments in urologic oncology "OncoForum": The best of 2017. / Avances en uro-oncología «OncoForum¼: lo mejor del 2017.

OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2017 in the main annual meetings. METHODS: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. RESULTS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib compared to placebo showed a benefit in patients at higher risk of recurrence. In cisplatin-ineligible advanced urothelial cancer, pembrolizumab elicits clinically meaningful, durable responses. Among patients with localized prostate cancer, treatment for disease progression was less frequent (absolute difference, 26.2 percentage pontis) and adverse events was more frequent with surgery than with observation. Among patients with locally advanced or merastatic prostate cancer, androgen-deprivation therapy plus abiraterone and prednisolone resulted in fewer deaths and fewer treatment-failure events (P<.001). Among patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate, enzalutamide median radiographic progression free survival was 8,1 months and enzalutamide median overall survival was not reached. CONCLUSIONS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib showed a benefit across subgroups including patients at higher risk of recurrence. Among patients with localized prostate cancer, surgery was not associated with significantly lower all-cause or porstate-cancer mortality than observation. Among patients with locally advanced or merastatic prostate cancer, androgen-deprivation therapy plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than androgen-deprivation therapy alone. In patients with metastatic castration-resistant prostate cancer previously treated with abiraterone enzalutamide remained active.

Radium-223 for the treatment of metastatic castration-resistant prostate cancer: A window of opportunity. / Radio-223 en el tratamiento del cáncer de próstata resistente a la castración metastásico: una ventana de oportunidad.

CONTEXT: The elimination of bone metastases, restoration and/or preservation of bone morphology and prevention and/or delay of skeletal events are a fundamental objective in the management of metastatic castration-resistant prostate cancer (mCRPC). Radium-223 is the first targeted alpha therapy with effects on bone that has been shown to increase survival in these patients, besides providing other bone-related benefits. OBJECTIVE: To analyze the impact of bone metastasis on mCRPC, and the benefits and the window of opportunity provided by radium-223 in the treatment of patients with mCRPC in the current treatment era. EVIDENCE ACQUISITION: A bibliographic search of PubMed and Spanish and international congresses on radium-223 and other first-line treatments for mCRPC was performed. Recent guidelines and recommendations by experts were also consulted. SUMMARY OF THE EVIDENCE: Evidence for the mechanism of action of radium-223 widen its effects to the tumor bone environment. Survival of patients treated with radium-223 is higher in those with mild symptoms as opposed to those with moderate-severe symptoms. The presence of visceral metastases even in the early stages of mCRPC supports starting radium-223 therapy before the symptoms become clinically relevant. A 3-year study has confirmed its good safety profile. Changes in tALP and LDH may be useful markers for monitoring the treatment with radium-223, but they are not predictors of overall survival. CONCLUSION: Radium-223 is a valuable therapeutic alternative in the treatment of patients with mCRPC in early stages of the disease, with a good safety profile. Its benefits extend to the bone environment.

Actual incidence of prostate cancer in healthcare areas of the autonomous community of Castilla-Leon during 2014. CAPCYL registry data. / Incidencia real de cáncer de próstata en las áreas sanitarias de la comunidad autónoma de Castilla y León durante el año 2014. Datos del registro CAPCYL.

OBJECTIVE: To determine the actual incidence of prostate cancer (PC) in the healthcare areas of Castilla-Leon in 2014. MATERIAL AND METHODS: A multicentre study was conducted with the participation of 7 of the 9 healthcare areas of Castilla-Leon. We collected retrospective data that included 87.8% of the target population (men diagnosed with PC with histopathological confirmation in 2014). We calculated the raw and age-adjusted incidence rates based on the direct method and consulted the community and national epidemiological data in the Spanish National Institute of Statistics. RESULTS: A total of 1198 new cases of PC were diagnosed, with a raw incidence rate in the community of 109.54 cases per 100,000 men. The adjusted rates for the Spanish and European populations were 115.41 and 110.07, respectively. The age group with the highest diagnostic concentration was the 60-70-year group, with 41.97% of the diagnoses. The group with the highest incidence was the 70-80-year group, with 438.87 cases per 100,000 inhabitants. There were differences in the raw and age-adjusted incidence rates and in the age at diagnosis among the various included healthcare areas. CONCLUSIONS: The community raw incidence rate was higher than most existing data. We observed significant differences among the various geographical areas, which could be explained mainly by the age distribution and the opportunistic screening policies for each area.

Insulin-loaded nanoparticles are prepared by alginate ionotropic pre-gelation followed by chitosan polyelectrolyte complexation.

Alginate nanoparticles were prepared from dilute alginate sol by inducing a pre-gel with calcium counter ions, followed by polyelectrolyte complex coating with chitosan. Particles in the nanometer size range were obtained with 0.05% alginate and 0.9 mM Ca2+. The mean particle size was influenced by time and stirring speed of nanoparticle preparation, by alginate guluronic acid content and chitosan molecular weight and by the initial alginate:chitosan mass ratio. The association efficiency of insulin into alginate nanoparticles, as well as loading capacity were mainly influenced by the alginate:chitosan mass ratio. Under optimized size conditions, the association efficiency and loading capacities were as high as 92% and 14.3%, respectively. Approximately 50% of the protein was partially retained by the nanoparticles in gastric pH environment up to 24 hours while a more extensive release close to 75% was observed under intestinal pH conditions. Mild formulation conditions, optimum particle size range obtained, high insulin entrapment efficiency, and resistance to gastrointestinal release seem to be synergic and promising factors toward development of an oral insulin delivery form.

Prostate carcinoma and stem cells.

Stem cells, as classically defined, are cells with a capacity to self-renew and to generate daughter cells that can differentiate down several cell lineages to form all of the cell types that are found in the mature tissue. Stem cells and tumour cells have many similar features, including infinite lifespan, self-renewal, multidrug resistance, telomerase expression and, in the instance of the prostate, androgen independence. Evidence supports a role for stem cells in the etiology of many types of cancer. The evolution of androgen-independent prostate carcinoma may reflect the emergence of stemlike prostate tumour cells. Because cancer may be a disease of stem cell lineages and Shh-Gli signalling controls the behaviour of precursors and of cells with stem cell properties in the mammalian tissues, prostate cancer might derive from inappropriate expansion of prostatic epithelial stem cell lineages caused by abnormal Shh-Gli function. This review attempts to integrate these recent results.

[Radical prostatectomy with minilaparotomy "minilap" for patients with prostate cancer]. / Técnica de minilaparotomía "minilap" en pacientes sometidos a prostatectomía radical por cáncer de próstata.

INTRODUCTION: prostate cancer is the most frequent tumor in males. The use of PSA contributes to diagnose tumors with low stage. Radical Prostatectomy (R.P.) is the gold standard to treat this tumor; however such is not exempt of risks. Different technical modifications like minimal incisions minilaparotomy "minilap" had contributed to improve results. We review our experience with Minilap on patients underwent a RP. MATERIAL AND METHODS: Between April 1997 and September 2005 carry out 110 RP with Minilap technique. All cases were performed with minimal incision 7-8 cm of length. We use and specific retractor developed in our hospital. Median age at time of surgery was 65 (47-79). Clinical stage in 39 (35.4%) were T1c, 64 (58.3%) T2 and 7 (6.3%) T3. Sixty eight percent were Gleason score < or =6, 34(30.9%) 7 and 1 (0.9%) Gleason 8. RESULTS: In 86 cases (38.5%) pathological stage were pT2, 21 (19%) pT3, 1 (0.9%) pT4 and 2 (1.8%) pT0. Nine patients (8%) had postoperative complications. No re-interventions were necessary and 101 (90%) were discharge without per operatives complications. Mean length of stay was 4 days and 97 (88.8%) of patients were discharge with only five days length of stay. Urinary continence rate with a year like minimal follow up is 92.3% and 40% preserve sexual activity. CONCLUSIONS: Minimal invasive techniques like minilap can be done in regular form with good results and without long learning curve.