Eturauhassyövän entsyymikuvantaminen PET-menetelmällä

Eturauhassyövän PET-kuvantamisessa on käytetty eri merkkiaineita. Uusi prostataspesifinen merkkiaine (PSMA) on korvannut lähes kaikki aiemmin käytetyt PET-merkkiaineet. PSMA tarjoaa uusia mahdollisuuksia taudin levinneisyyden selvittelyyn ja uusiutumien toteamiseen hyvin pienillä PSA-arvoilla. Näiden lisäksi PSMA:n sopivia käyttöaiheita ovat esimerkiksi oligometastaattisen taudin tunnistaminen ja systeemihoidon tehon seuranta. Menetelmän haasteena ovat usein esiintyvät hyvin pienet luustokertymät (maxSUV </em

Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

Neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer was introduced several years ago.&nbsp;Despite the evidence supporting its use in clinical practice, only a minority of patients who undergo&nbsp;radical cystectomy receive preoperative chemotherapy. In addition, recommendations and methods&nbsp;to detect patients who would benefit the most from NAC are still unclear. The European Association of&nbsp;Urology (EAU) guidelines panel on muscle-invasive and metastatic bladder cancer recommends the use&nbsp;of cisplatin-based NAC for T2-T4a, cN0 M0 bladder cancer if the patient has a performance status &ge;2 and if the renal function is not impaired, but the American Urological Association, for example, does not&nbsp;have any guideline recommendations on this topic at all. In this review we describe the current literature&nbsp;supporting NAC in association with radical cystectomy in muscle-invasive urothelial carcinoma of the&nbsp;bladder. Evidence acquisition was made searching the Medline database for original articles published&nbsp;before 1st February 2014, with search terms: &ldquo;neoadjuvant chemotherapy&rdquo;, &ldquo;radical cystectomy&rdquo;, and&nbsp;&ldquo;invasive bladder cancer&rdquo;.</p

Survival and mortality of elderly men with localized prostate cancer managed with primary androgen deprivation therapy or by primary observation

Background Androgen deprivation therapy (ADT) remains a primary treatment for localized prostate cancer (PCa) even though there is no evidence that its use is beneficial in the absence of curative treatment. Methods Men aged >= 70 years (n = 16,534) diagnosed with localized PCa from 1985 to 2014 and managed either with primary observation or ADT in the absence of curative treatment were included. The cases were identified from the population-based Finnish Cancer Registry. We estimated the standardized mortality ratios (SMR) for overall mortality by treatment group. We determined the relative risk (RR) of PCa-specific mortality (PCSM) and other-cause mortality between the two treatment groups. Survival was determined using the life table method. Two age groups (70-79 years and >= 80 years) and three calendar time cohorts (1985-1994, 1995-2004, and 2005-2014) were compared following adjustment of propensity score matching between the treatment groups with four covariates (age, year of diagnosis, educational level, and hospital district). Follow-up continued until death or until December 31, 2015. Results Patients in the observation group had lower overall SMRs than those in the ADT group in both age cohorts over the entire study period. PCSM was higher in men aged 70-79 years undergoing primary ADT compared to those managed by observation only (RR: 1.70, 95% confidence interval [CI]: 1.29-2.23 [1985-1994]; RR 1.55, 95% CI: 1.35-1.84 [1995-2004]; and RR 2.71, 95% CI: 2.08-3.53 [2005-2014]); p = 0.005 for periodic trend. A similar trend over time was also observed in men aged > 80 years; (p for age-period interaction = 0.237). Overall survival was also higher among men in their 70's managed by observation compared to those undergoing ADT. Conclusions Primary ADT within four months period from diagnosis is not associated with improved long-term overall survival or decreased PCSM compared to primary conservative management for men with localized PCa. However, this observational study's conclusions should be weighted with confounding factors related to cancer aggressiveness and comorbidities

Uusia työkaluja paikallisesti edenneen ja etäpesäkkeisen eturauhassyövän lääkehoitoon

Eturauhassyöpä on miehillä tavallisimmin todettu syöpä ja miesten toiseksi yleisin syöpäkuolemien aiheuttaja Suomessa. Levinneen eturauhassyövän lääkehoidossa keskeistä on androgeenireseptorin toiminnan estäminen syöpäsoluissa. Useampi androgeenivaikutusta estävä lääke on hiljattain osoittautunut kolmannen vaiheen lääketutkimuksissa tehokkaaksi levinneen eturauhassyövän hoidossa. Nykyisistä hoitomuodoista etsitään parhaillaan entistä tehokkaampia yhdistelmiä ja optimaalista käyttöjärjestystä. Kastraatioresistenssin selättämiseksi tarvittaneen vielä lääkemolekyylejä, joiden vaikutusmekanismi poikkeaa aikaisemmin kehitetyistä molekyyleistä.</p

Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with 68Ga-PSMA-11 PET/MRI in men with treatment-naïve prostate cancer

PURPOSE: Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression. Therefore, we hypothesised that ADT improves the performance of PSMA-PET imaging in primary staging of prostate cancer. The purpose of the study was to demonstrate the time course effect of ADT on PSMA uptake in different types of metastatic lesions evaluated with 68Ga-PSMA-11 PET/MRI.METHODS: Nine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A 68Ga-PSMA-11 PET/MRI was performed once before and 3 times post-ADT (degarelix, Firmagon). Change of maximum standardised uptake values (SUVmax) in prostate, lymph nodes, bone metastases, and physiologically PSMA-avid organs were evaluated in a time frame of 1-8 weeks.RESULTS: All patients reached castration levels within 10 days, and 50% decrease in prostate-specific antigen (PSA) concentration was observed 14 days post-ADT. A heterogeneous increase in PSMA uptake was observed 3 to 4 weeks post-ADT. This phenomenon was definitively more evident in bone metastases: 13 (57%) of the metastasis, with a mean (range) SUVmax increase of 77% (8-238%). In one patient, already having bone metastases at baseline, three new bone metastases were observed post-ADT. Of lesions with reduced SUVmax, none disappeared.CONCLUSIONS: Both in patient and region level, increase in PSMA uptake post-ADT is heterogenous and is seen most evidently in bone metastases. Preliminary results on a small cohort of patients suggest the clinical impact of ADT on improving the performance of 68Ga-PSMA PET in staging seems to be minor. However, the optimal imaging time point might be 3 to 4 weeks post-ADT. Since none of the metastases with decreasing SUVmax disappeared, it seems that short-term usage of ADT does not interfere with the interpretation of 68Ga-PSMA PET.TRIAL REGISTRATION: NCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.</p

Coral restoration - A systematic review of current methods, successes, failures and future directions.

Coral reef ecosystems have suffered an unprecedented loss of habitat-forming hard corals in recent decades. While marine conservation has historically focused on passive habitat protection, demand for and interest in active restoration has been growing in recent decades. However, a disconnect between coral restoration practitioners, coral reef managers and scientists has resulted in a disjointed field where it is difficult to gain an overview of existing knowledge. To address this, we aimed to synthesise the available knowledge in a comprehensive global review of coral restoration methods, incorporating data from the peer-reviewed scientific literature, complemented with grey literature and through a survey of coral restoration practitioners. We found that coral restoration case studies are dominated by short-term projects, with 60% of all projects reporting less than 18 months of monitoring of the restored sites. Similarly, most projects are relatively small in spatial scale, with a median size of restored area of 100 m2. A diverse range of species are represented in the dataset, with 229 different species from 72 coral genera. Overall, coral restoration projects focused primarily on fast-growing branching corals (59% of studies), and report survival between 60 and 70%. To date, the relatively young field of coral restoration has been plagued by similar 'growing pains' as ecological restoration in other ecosystems. These include 1) a lack of clear and achievable objectives, 2) a lack of appropriate and standardised monitoring and reporting and, 3) poorly designed projects in relation to stated objectives. Mitigating these will be crucial to successfully scale up projects, and to retain public trust in restoration as a tool for resilience based management. Finally, while it is clear that practitioners have developed effective methods to successfully grow corals at small scales, it is critical not to view restoration as a replacement for meaningful action on climate change

Critical evaluation of the subcutaneous engraftments of hormone naïve primary prostate cancer

Background: Patient-derived xenografts (PDXs) are considered to better recapitulate the histopathological and molecular heterogeneity of human cancer than other preclinical models. Despite technological advances, PDX models from hormone naïve primary prostate cancer are scarce. We performed a detailed analysis of PDX methodology using a robust subcutaneous model and fresh tissues from patients with primary hormone naïve prostate cancer.Methods: Clinical prostate tumor specimens (n=26, Gleason score 6–10) were collected from robotic-assisted laparoscopic radical prostatectomies at Turku University Hospital (Turku, Finland), cut into pieces, and implanted subcutaneously into 84 immunodeficient mice. Engraftments and the adjacent material from prostatic surgical specimens were compared using histology, immunohistochemistry and DNA sequencing.Results: The probability of a successful engraftment correlated with the presence of carcinoma in the implanted tissue. Tumor take rate was 41%. Surprisingly, mouse hormone supplementation inhibited tumor take rate, whereas the degree of mouse immunodeficiency did not have an effect. Histologically, the engrafted tumors closely mimicked their parental tumors, and the Gleason grades and copy number variants of the engraftments were similar to those of their primary tumors. Expression levels of androgen receptor, prostate-specific antigen, and keratins were retained in engraftments, and a detailed genomic analysis revealed high fidelity of the engraftments with their corresponding primary tumors. However, in the second or third passage of tumors, the carcinoma areas were almost completely replaced by benign tissue with frequent degenerative or metaplastic changes.Conclusions: Subcutaneous primary prostate engraftments preserve the phenotypic and genotypic landscape. Thus, they serve a potential model for personalized medicine and preclinical research but their use may be limited to the first passage.</p

Elastic Wave Scattering from a Rough Strip-Like Crack

Ultrasonic nondestructive testing is a widely used method for searching for defects, e.g. cracks, in the nuclear power industry. Even though the method can be considered as wellestablished the theoretical understanding is far from complete, especially when more complicated situations are considered. Consequently, it is advantageous to have access to a good mathematical model of the testing procedure. Such a model can, for instance, be used to perform parametric studies, to develop testing procedures, for qualification purposes, and for education. Furthermore, systematic use of a well tested and validated simulation program will most likely result in a better physical understanding of the process. It should also be emphasized that experimental work is a very expensive alternative to mathematical modeling

Feasibility of MRI-guided transurethral ultrasound for lesion-targeted ablation of prostate cancer

Background: MRI-guided transurethral ultrasound ablation (TULSA) has been evaluated for organ-confined prostate cancer (PCa). The purpose of this study was to assess the safety and toxicity, accuracy and short-term evolution of cell-death after lesion-targeted TULSA.Methods: This prospective, registered, Phase-I treat-and-3-week-resect-study enrolled six patients with MRI-visible-biopsy-concordant PCa. Lesions were targeted using TULSA with radical intent, except near neurovascular bundles (NVB). Robot-assisted-laparoscopic-prostatectomy (RALP) was performed at 3 weeks. Post-TULSA assessments included MRI (1 and 3 weeks), adverse events and quality-of-life (QoL) to 3 weeks, followed by RALP and whole-mount-histology. Treatment accuracy and demarcation of thermal injury were assessed using MRI and histology.Results: Six patients (median age = 70 years, prostate volume = 60 ml, PSA = 8.9 ng/ml) with eight biopsy-confirmed MRI-lesions (PIRADS ≥3) were TULSA-treated without complications (median sonication and MRI-times of 17 and 117 min). Foley-catheter removal was uneventful at 2–3 days. Compared to baseline, no differences in QoL were noted at 3 weeks. During follow-up, MRI-derived non-perfused-volume covered ablated targets and increased 36% by 3 weeks, correlating with necrosis-area on histology. Mean histological demarcation between complete necrosis and outer-limit-of-thermal-injury was 1.7 ± 0.4 mm. Coagulation necrosis extended to capsule except near NVB, where 3 mm safety-margins were applied. RALPs were uncomplicated and histopathology showed no viable cancer within the ablated tumor-containing target.Conclusions: Lesion-targeted TULSA demonstrates accurate and safe ablation of PCa. A significant increase of post-TULSA non-perfused-volume was observed during 3 weeks follow-up concordant with necrosis on histology. TULSA achieved coagulation necrosis of all targeted tissues. A limitation of this treat-and-resect-study-design was conservative treatment near NVB in patients scheduled for RALP.</p