Kastraation luustovaikutukset eturauhassyöpäpotilailla

Levinneen eturauhassyövän hoitona käytetään yleisesti kirurgista tai kemiallista kastraatiota. Kastraation tavallisia haittavaikutuksia ovat hikoilu, kuumat aallot ja punoitus kasvoissa, painon ja rasvan lisääntyminen, lihasmassan vähentyminen, impotenssi ja anemia. Kastraatio vaikuttaa luustoon hormonitasapainon muutosten kautta ja altistaa osteoporoosille. Kastraation on osoitettu selvästi lisäävän osteoporoosin ja murtumien riskiä eturauhassyöpää sairastavilla miehillä. Osteoporoosin mahdollisuus ja lihasvoiman heikkeneminen tulee ottaa huomioon jo hoitoa aloittaessa. Kastraatiohoitoon joutuville potilaille tulee antaa huolellinen ohjeistus liikunnan lisäämisestä ja elämäntapamuutoksista. Kalsiumin ja D-vitamiinin riittävästä saannista tulee huolehtia. Euroopan urologiyhdistyksen suosituksen mukaisesti luuston tiheysmittaus tulisi suorittaa ennen pitkäkestoisen kastraatiohoidon aloitusta. Osteoporoosin komplikaatioita voidaan ehkäistä lääkehoidolla, jota suositellaan pääsääntöisesti pienienergiaisen murtuman sairastaneille, luuston tiheysmittauksen perusteella todetun osteoporoosin hoitoon sekä kliinisen harkinnan mukaan myös muille suuren murtumariskin potilaille

Value of Ga-68-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [F-18]fluoromethylcholine PET-CT and multiparametric MRI-a phase I/II study

Objectives The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [Ga-68]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [F-18]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI).Methods This phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology, 2016). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the "index lesion." All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [Ga-68]Ga-RM2 and [F-18]FCH PET-CT findings were correlated with mpMRI and histopathologic results.Results Of the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [Ga-68]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [F-18]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [Ga-68]Ga-RM2 PET-CT was higher compared to that of [F-18]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [Ga-68]Ga-RM2 PET-CT and [F-18]FCH PET-CT in the intermediate-risk group (p = 0.01) and [Ga-68]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [Ga-68]Ga-RM2 and [F-18]FCH PET-CT in the intraprostatic malignant lesions ([Ga-68]Ga-RM2: mean SUVmax: 5.98 +/- 4.13, median: 4.75; [F-18]FCH: mean SUVmax: 6.08 +/- 2.74, median: 5.5; p = 0.13).Conclusions [Ga-68]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [Ga-68]Ga-RM2 PET-CT and [F-18]FCH PET-CT in the intermediate-risk group and [Ga-68]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks.</p

Validation of IMPROD biparametric MRI in men with clinically suspected prostate cancer: A prospective multi-institutional trial

Background: Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption.Methods and findings: The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score >= 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings.Conclusions: IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial.</p

Validation of IMPROD biparametric MRI in men with clinically suspected prostate cancer : A prospective multi-institutional trial

Background Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption. Methods and findings The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score >= 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings. Conclusions IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial.Peer reviewe

Impact of structural changes on energy efficiency of Finnish pulp and paper industry

A key challenge in prevention of global warming is how to increase energy efficiency, to be able to deal with increased fossil CO2 emissions from rising energy usage. Increasing energy efficiency will decrease energy usage and is in a key role in emission mitigation. The focus is the pulp and paper industry, which is energy-intensive. Development of industrial energy efficiency has been studied before but the role of industrial transformation is still mostly unknown. The knowledge must be improved, to be able to predict future developments in the most effective way. In this research, impact of various production unit closures and start-ups on energy efficiency of the Finnish pulp and paper industry were studied utilizing statistical analysis. Results indicate that about 20% of the Finnish pulp and paper industry energy efficiency improvement between 2011 and 2017 is caused by the major structural changes. The rest, 80% of the progress, was mainly due to improved technology and more optimal operational modes. Additional findings suggest that modern mill start-ups have a significantly greater potential to reduce energy consumption than old mill closures.Peer reviewe

Kastraation luustovaikutukset eturauhassyöpäpotilailla

Levinneen eturauhassyövän hoitona käytetään yleisesti kirurgista tai kemiallista kastraatiota. Kastraation tavallisia haittavaikutuksia ovat hikoilu, kuumat aallot ja punoitus kasvoissa, painon ja rasvan lisääntyminen, lihasmassan vähentyminen, impotenssi ja anemia. Kastraatio vaikuttaa luustoon hormonitasapainon muutosten kautta ja altistaa osteoporoosille. Kastraation on osoitettu selvästi lisäävän osteoporoosin ja murtumien riskiä eturauhassyöpää sairastavilla miehillä. Osteoporoosin mahdollisuus ja lihasvoiman heikkeneminen tulee ottaa huomioon jo hoitoa aloittaessa. Kastraatiohoitoon joutuville potilaille tulee antaa huolellinen ohjeistus liikunnan lisäämisestä ja elämäntapamuutoksista. Kalsiumin ja D-vitamiinin riittävästä saannista tulee huolehtia. Euroopan urologiyhdistyksen suosituksen mukaisesti luuston tiheysmittaus tulisi suorittaa ennen pitkäkestoisen kastraatiohoidon aloitusta. Osteoporoosin komplikaatioita voidaan ehkäistä lääkehoidolla, jota suositellaan pääsääntöisesti pienienergiaisen murtuman sairastaneille, luuston tiheysmittauksen perusteella todetun osteoporoosin hoitoon sekä kliinisen harkinnan mukaan myös muille suuren murtumariskin potilaille

Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model

<div><p><b>Background and purpose —</b> Selective androgen receptor modulators (SARMs) have been developed to have systemic anabolic effects on bones and muscles without the adverse effects of steroidal androgens. One unexplored therapeutic option is the targeted application of SARMs for the enhancement of local new bone formation. We evaluated the osteogenic efficacy of a locally released SARM (ORM-11984).</p><p><b>Methods —</b> ORM-11984 was mixed with a copolymer of L-lactide and ɛ-caprolactone (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM-11984 from the matrix. A bone marrow ablation model was used in female Sprague-Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12 weeks, the volume of intramedullary new bone and the perimeter of bone-implant contact were measured by micro-computed tomography and histomorphometry.</p><p><b>Results —</b> Contrary to our hypothesis, there was a negative correlation between the amount of new bone around the implant and the dose of ORM-11984. There was only a mild (and not statistically significant) enhancement of bone formation in ablated bones subjected to the lowest dose of the SARM (10%).</p><p><b>Interpretation —</b> This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM. This result highlights the complexity of androgenic effects on bones and also suggests that there are biological limits to the targeted local application of SARMs.</p></div

In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548

PURPOSE: A novel [(68)Ga]-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 peptide (BAY86-7548) having high affinity to bombesin receptor subtype II to detect primary and metastatic prostate carcinoma using positron emission tomography/computed tomography (PET/CT) was synthesized and evaluated for prostate cancer. EXPERIMENTAL DESIGN: In this first human study with BAY86-7548, 14 men scheduled for radical prostatectomy (n = 11) or with biochemical recurrence after surgery or hormonal therapy (n = 3) were enrolled. The patients received an intravenous injection of BAY86-7548 followed by over 60-minute dynamic imaging of prostate gland (n = 10) and/or subsequent whole-body imaging (n = 14). The visual assessment of PET/CT images included evaluation of intraprostatic (12 subsextants) and pelvic nodal uptake of BAY86-7548 in 11 surgical patients and detection of potential metastatic foci in all patients. In patients with biochemical recurrence, results were compared with those of either [(11)C]-acetate (n = 2) or [(18)F]-fluoromethylcholine (n = 1) PET/CT. RESULTS: We found a sensitivity, specificity, and accuracy of 88%, 81% and 83%, respectively, for detection of primary PCa and sensitivity of 70% for metastatic lymph nodes using histology as gold standard. BAY86-7548 correctly detected local recurrence in prostate bed and showed nodal relapse in accordance with [(11)C]-acetate PET/CT in 2 patients with biochemical relapse. In the third hormone refractory patient, BAY86-7548 failed to show multiple bone metastases evident on [(18)F]-fluoromethylcholine PET/CT. CONCLUSION: BAY86-7548 PET/CT is a promising molecular imaging technique for detecting intraprostatic prostate cancer