Publications by authors named "Boström P"

235 Publications

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

Eur J Nucl Med Mol Imaging 2020 03 26;47(3):665-673. Epub 2019 Dec 26.

Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.

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 Ga-PSMA-11 PET/MRI.

Methods: Nine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A Ga-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 Ga-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 Ga-PSMA PET.

Trial Registration: NCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-019-04635-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081750PMC
March 2020

Vasectomy and the risk of prostate cancer in a Finnish nationwide population-based cohort.

Cancer Epidemiol 2020 02 21;64:101631. Epub 2019 Nov 21.

Department of Urology, Turku University Hospital, Turku, Finland, Department of Urology, University of Turku, Turku, Finland Kiinamyllynkatu 4-8, 20100, Turku, Finland. Electronic address:

Introduction & Objectives: There are conflicting reports on the association of vasectomy and the risk of prostate cancer (PCa). Our objective was to evaluate the association between vasectomy and PCa from a nationwide cohort in Finland.

Materials & Methods: Sterilization registry of Finland and the Finnish Cancer Registry data were utilized to identify all men who underwent vasectomy between years 1987-2014 in Finland. Standard incidence ratio (SIR) for PCa as well as all-cause standardized mortality ratios (SMR) were calculated.

Results: We identified 38,124 men with vasectomy with a total of 429,937 person-years follow-up data. The median age at vasectomy was 39.7 years (interquartile range [IQR] 35.9-44.0), after vasectomy PCa was diagnosed in 413 men (122 cases 0-10 years, 219 cases 10-20 years and 72 cases >20 years from vasectomy). SIR for PCa for the vasectomy cohort was 1.15 (95% CI: 1.04-1.27). By the end of follow-up, 19 men had died from PCa, while the expected number was 20.5 (SMR 0.93 [95%CI: 0.56-1.44]). The overall mortality was decreased (SMR 0.54 [95%CI: 0.51-0.58]) among men with vasectomy.

Conclusion: We found a small statistically significant increase in PCa incidence after vasectomy, but in contrast the mortality of vasectomized men was significantly reduced. This may be due to higher likelihood of vasectomized men to undergo prostate-specific antigen testing, having healthier general lifestyle and other biological factors e.g. high reproductive fitness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canep.2019.101631DOI Listing
February 2020

Qualitative and Quantitative Reporting of a Unique Biparametric MRI: Towards Biparametric MRI-Based Nomograms for Prediction of Prostate Biopsy Outcome in Men With a Clinical Suspicion of Prostate Cancer (IMPROD and MULTI-IMPROD Trials).

J Magn Reson Imaging 2020 05 21;51(5):1556-1567. Epub 2019 Nov 21.

Department of Diagnostic Radiology, University of Turku, Turku, Finland.

Background: Multiparametric MRI of the prostate has been shown to improve the risk stratification of men with an elevated prostate-specific antigen (PSA). However, long acquisition time, high cost, and inter-center/reader variability of a routine prostate multiparametric MRI limit its wider adoption.

Purpose: To develop and validate nomograms based on unique rapid biparametric MRI (bpMRI) qualitative and quantitative derived variables for prediction of clinically significant cancer (SPCa).

Study Type: Retrospective analyses of single (IMPROD, NCT01864135) and multiinstitution trials (MULTI-IMPROD, NCT02241122).

Population: 161 and 338 prospectively enrolled men who completed the IMPROD and MULTI-IMPROD trials, respectively.

Field Strength/sequence: IMPROD bpMRI: 3T/1.5T, T -weighted imaging, three separate diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm ; 2) b values 0, 1500 s/mm ; 3) values 0, 2000 s/mm .

Assessment: The primary endpoint of the combined trial analysis was the diagnostic accuracy of the combination of IMPROD bpMRI and clinical variables for detection of SPCa.

Statistical Tests: Logistic regression models were developed using IMPROD trial data and validated using MULTI-IMPROD trial data. The model's performance was expressed as the area under the curve (AUC) values for the detection of SPCa, defined as ISUP Gleason Grade Group ≥2.

Results: A model incorporating clinical variables had an AUC (95% confidence interval) of 0.83 (0.77-0.89) and 0.80 (0.75-0.85) in the development and validation cohorts, respectively. The corresponding values for a model using IMPROD bpMRI findings were 0.93 (0.89-0.97), and 0.88 (0.84-0.92), respectively. Further addition of the quantitative DWI-based score did not improve AUC values (P < 0.05).

Data Conclusion: A prediction model using qualitative IMPROD bpMRI findings demonstrated high accuracy for predicting SPCa in men with an elevated PSA. Online risk calculator: http://petiv.utu.fi/multiimprod/ Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1556-1567.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.26975DOI Listing
May 2020

Repeatability of radiomics and machine learning for DWI: Short-term repeatability study of 112 patients with prostate cancer.

Magn Reson Med 2020 06 8;83(6):2293-2309. Epub 2019 Nov 8.

Department of Diagnostic Radiology, University of Turku, Turku, Finland.

Purpose: To evaluate repeatability of prostate DWI-derived radiomics and machine learning methods for prostate cancer (PCa) characterization.

Methods: A total of 112 patients with diagnosed PCa underwent 2 prostate MRI examinations (Scan1 and Scan2) performed on the same day. DWI was performed using 12 b-values (0-2000 s/mm ), post-processed using kurtosis function, and PCa areas were annotated using whole mount prostatectomy sections. A total of 1694 radiomic features including Sobel, Kirch, Gradient, Zernike Moments, Gabor, Haralick, CoLIAGe, Haar wavelet coefficients, 3D analogue to Laws features, 2D contours, and corner detectors were calculated. Radiomics and 4 feature pruning methods (area under the receiver operator characteristic curve, maximum relevance minimum redundancy, Spearman's ρ, Wilcoxon rank-sum) were evaluated in terms of Scan1-Scan2 repeatability using intraclass correlation coefficient (ICC)(3,1). Classification performance for clinically significant and insignificant PCa with Gleason grade groups 1 versus >1 was evaluated by area under the receiver operator characteristic curve in unseen random 30% data split.

Results: The ICC(3,1) values for conventional radiomics and feature pruning methods were in the range of 0.28-0.90. The machine learning classifications varied between Scan1 and Scan2 with % of same class labels between Scan1 and Scan2 in the range of 61-81%. Surface-to-volume ratio and corner detector-based features were among the most represented features with high repeatability, ICC(3,1) >0.75, consistently high ranking using all 4 feature pruning methods, and classification performance with area under the receiver operator characteristic curve >0.70.

Conclusion: Surface-to-volume ratio and corner detectors for prostate DWI led to good classification of unseen data and performed similarly in Scan1 and Scan2 in contrast to multiple conventional radiomic features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047644PMC
June 2020

Clinical Utility of Mutant Antibody-Based Assays for Determination of Internally Cleaved and Intact Forms of Free Prostate-Specific Antigen.

J Appl Lab Med 2019 05 1;3(6):1014-1021. Epub 2019 Feb 1.

Departments of Biochemistry/Biotechnology, University of Turku, Turku, Finland.

Background: Subforms of prostate-specific antigen (PSA) have been a subject of intensive research, and use of multikallikrein immunoassays can add clinical value to the early detection of prostate cancer, overcoming known limitations of PSA. In this study, we evaluated mutant 4D4 (L3-2) antibody-assisted assay constructs against reference wild-type (wt)-4D4-based assays for determination of intact PSA (iPSA) and nicked PSA (nPSA) in plasma samples.

Methods: Perioperative plasma samples obtained from 105 men who underwent biopsy (73 cancer, 32 noncancer) were analyzed with sandwich immunoassays for total PSA (tPSA), free PSA (fPSA), iPSA (3 constructs), and measured nPSA (2 constructs). Calculated nPSA (CN) was obtained from total fPSA - iPSA.

Results: Mutant-assisted iPSA assays measured lower concentrations than the reference in both patient groups. CN separated the 2 groups with the iPSA using the mutant for capture (I-MC) performing the best ( = 0.008). In prostate volume group > median, only measured nPSA provided significant discrimination [area under the curve (AUC), 0.71; = 0.016] but equally using mutant and wt antibodies. In the whole cohort, all ratios to tPSA performed well (AUC, 0.819-0.870; ≤ 0.0001) with CN based on I-MC scoring highest (AUC, 0.870). Importantly, in the ≤ median volume group, the I-MC/F and CN(I-MC)/T ratios stand out as the best performing parameters (AUC, 0.825 and 0.861; = 0.001 and = 0.0003, respectively).

Conclusions: The new assay construct using the mutant 4D4 (L3-2) as a capture provides clear improvement in separating cancer from noncancer in all subgroups analyzed but especially in patients with prostate volume ≤ median. ClinicalTrials.gov Identifier NCT01864135.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1373/jalm.2018.027797DOI Listing
May 2019

Prostate Cancer Risk Stratification in Men With a Clinical Suspicion of Prostate Cancer Using a Unique Biparametric MRI and Expression of 11 Genes in Apparently Benign Tissue: Evaluation Using Machine-Learning Techniques.

J Magn Reson Imaging 2020 05 6;51(5):1540-1553. Epub 2019 Oct 6.

Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland.

Background: Accurate risk stratification of men with a clinical suspicion of prostate cancer (cSPCa) remains challenging despite the increasing use of MRI.

Purpose: To evaluate the diagnostic accuracy of a unique biparametric MRI protocol (IMPROD bpMRI) combined with clinical and molecular markers in men with cSPCa.

Study Type: Prospective single-institutional clinical trial (NCT01864135).

Subjects: Eighty men with cSPCa.

Field Strength/sequence: 3T, surface array coils. Two T -weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm ; 2) b-values 0,1500 s/mm ; 3) b-values 0, 2000 s/mm .

Assessment: IMPROD bpMRI examinations were qualitatively (IMPROD bpMRI Likert score) and quantitatively (DWI-based Gleason grade score) prospectively reported. Men with IMPROD bpMRI Likert 3-5 had two targeted biopsies followed by 12-core systematic biopsies (SB); those with IMPROD bpMRI Likert 1-2 had only SB. Additionally, 2-core from normal-appearing prostate areas were obtained for the mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 measured by quantitative reverse-transcription polymerase chain reaction.

Statistical Tests: Univariate and multivariate analysis using regularized least-squares, feature selection and tournament leave-pair-out cross-validation (TLPOCV), as well as 10 random splits of the data in training-testing sets, were used to evaluate the mRNA, clinical and IMPROD bpMRI parameters in detecting clinically significant prostate cancer (SPCa) defined as Gleason score ≥ 3 + 4. The evaluation metric was the area under the curve (AUC).

Results: IMPROD bpMRI Likert demonstrated the highest TLPOCV AUC of 0.92. The tested clinical variables had AUC 0.56-0.73, while the mRNA and additional IMPROD bpMRI parameters had AUC 0.50-0.67 and 0.65-0.89 respectively. The combination of clinical and mRNA biomarkers produced TLPOCV AUC of 0.87, the highest TLPOCV performance without including IMPROD bpMRI Likert.

Data Conclusion: The qualitative IMPROD bpMRI Likert score demonstrated the highest accuracy for SPCa detection compared with the tested clinical variables and mRNA biomarkers.

Level Of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1540-1553.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.26945DOI Listing
May 2020

rs77559646 Is Associated With First-line Docetaxel Treatment Response in Metastatic Castration-resistant Prostate Cancer.

Anticancer Res 2019 Oct;39(10):5353-5359

Institute of Biomedicine, University of Turku, Turku, Finland

Background: Identification of genetic prognostic biomarkers, such as germline variants, are urgently needed to choose optimal treatment for metastatic castration-resistant prostate cancer (mCRPC).

Patients And Methods: The prognostic value of anoctamin 7 (ANO7) rs77559646 on docetaxel response was tested in a prospective PROSTY randomized trial and a retrospective Auria Biobank set. The variant rs77559646 was genotyped and its association with progression-free survival (PFS) and overall survival (OS) was tested.

Results: In comparison with the non-carriers, the variant carriers had longer PFS (p=0.005) and OS (p=0.003) in the PROSTY cohort. In the retrospective cohort, there was a borderline association with PFS (p=0.09), but not in OS (p=0.9). In both cohorts, Cox regression multivariate models revealed that rs77559646 was an independent prognostic factor for favourable PFS.

Conclusion: The rs77559646 was shown to be a prognostic germline biomarker for better response to docetaxel treatments. To our knowledge, this is the first time that a non-coding germline variant has been associated with chemotherapy of mCRPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.13728DOI Listing
October 2019

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

Scand J Urol 2019 Oct 26;53(5):295-302. Epub 2019 Sep 26.

Department of Urology, Turku University Hospital, Turku, Finland.

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. 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. 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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2019.1660707DOI Listing
October 2019

Prediction of complication related death after radical cystectomy for bladder cancer with machine learning methodology.

Scand J Urol 2019 Oct 25;53(5):325-331. Epub 2019 Sep 25.

Department of Urology, Turku University Hospital and University of Turku, Turku, Finland.

To create a pre-operatively usable tool to identify patients at high risk of early death (within 90 days post-operatively) after radical cystectomy and to assess potential risk factors for post-operative and surgery related mortality. Material consists of 1099 consecutive radical cystectomy (RC) patients operated at 16 different hospitals in Finland 2005-2014. Machine learning methodology was utilized. For model building and testing, the data was randomly divided into training data ( 733, 66.7%) and independent testing data ( 366, 33.3%). To predict the risk of early death after RC from baseline variables, a binary classifier was constructed using logistic regression with lasso regularization. Finally, a user-friendly risk table was constructed for practical use. The model resulted in an area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI = 0.59-0.87). The strongest risk factors were: American Society of Anesthesiologists physical status classification (ASA), congestive heart failure (CHF), age adjusted Charlson comorbidity index (ACCI) and chronic pulmonary disease. This study with a novel methodological approach adds CHF and chronic pulmonary disease to previously known independent prognostic risk factors for early death after RC. Importantly, the risk prediction tool uses purely pre-operative data and can be used before surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2019.1665579DOI Listing
October 2019

Prebiopsy IMPROD Biparametric Magnetic Resonance Imaging Combined with Prostate-Specific Antigen Density in the Diagnosis of Prostate Cancer: An External Validation Study.

Eur Urol Oncol 2020 10 6;3(5):648-656. Epub 2019 Sep 6.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

Background: Biparametric magnetic resonance imaging (bpMRI) combined with prostate-specific antigen density (PSAd) may be an effective strategy for selecting men for prostate biopsy. It has been shown that performing biopsy only for men with bpMRI Likert scores of 4-5 or PSAd ≥0.15 ng/ml/cm is the most efficient strategy.

Objective: To externally validate previously published biopsy strategies using two prospective bpMRI trial cohorts.

Design, Setting, And Participants: After IMPROD bpMRI, 499 men had systematic transrectal prostate biopsies and men with IMPROD bpMRI Likert scores of 3-5 had an additional two to four targeted biopsies.

Outcome Measurements And Statistical Analysis: Various IMPROD bpMRI Likert score and PSAd thresholds were assessed using detection rates for significant prostate cancer (sPCa; Gleason score ≥3 + 4), predictive values, and proportion of biopsies avoided. Net benefits and decision curve analyses (DCA) were compared with the aim of finding an optimal strategy for sPCa detection. Combined biopsies were used for reference.

Results And Limitations: The negative predictive value (NPV) for sPCa in IMPROD bpMRI Likert 3-5 and 4-5 score groups was 93% and 92%, respectively, while the corresponding positive predictive value (PPV) was 57% and 72%, respectively. In DCA, the optimal combination was IMPROD bpMRI Likert score 4-5 or Likert 3 with PSAd ≥0.20 ng/ml/cm, which had NPV of 93% and PPV of 67%. Using this combination, 35% of the study patients would have avoided biopsies and 13 sPCas (6%, 13/229, of all sPCas diagnosed) would have been missed.

Conclusions: IMPROD bpMRI demonstrated a good NPV for sPCa. PSAd improved the NPV mainly among men with equivocal suspicion on IMPROD bpMRI. However, the additional value of PSAd was marginal: the NPV and PPV for IMPROD bpMRI Likert 4-5 score group were 92% and 72%, respectively, while the corresponding values for the best combination strategy were 93% and 67%.

Patient Summary: We investigated a rapid prostate magnetic resonance imaging protocol (IMPROD bpMRI) combined with prostate-specific antigen (PSA) density for detection of significant prostate cancer. Our results show that IMPROD bpMRI is a good diagnostic tool, but the additional value provided by PSA density is marginal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euo.2019.08.008DOI Listing
October 2020

Decreased forced expiratory volume in first second is associated with erectile dysfunction in apparently healthy men. A preliminary study.

Int J Impot Res 2020 Jul 5;32(4):420-425. Epub 2019 Sep 5.

Central Satakunta Health Federation of Municipalities, Harjavalta, Finland.

Although it has been evaluated that even 76% of men with chronic obstructive pulmonary disease suffer from erectile dysfunction, the association has been poorly characterised. The aim of the study was to describe the association between forced expiratory volume in first second and erectile dysfunction in apparently healthy men. All together 331 men aged 45-70 years old were randomly drawn from a cross-sectional population-based study conducted in 2005 in Finland. Decreased forced expiratory volume was defined by performing mini-spirometry and erectile dysfunction by International Index of Erectile Function short form questionnaire. After adjustment for age and depressive symptoms predicted forced expiratory volume (FEV < 65%) was associated with 2.66 (95% CI, 1.18-5.99) increased risk of moderate to severe erectile dysfunction (International Index of Erectile Function short form score < 17). Therefore, the authors highlight the importance of erectile and sexual health evaluation and treatment, if necessary, in men with decreased lung function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41443-019-0184-1DOI Listing
July 2020

Histopathological evaluation of prostate specimens after thermal ablation may be confounded by the presence of thermally-fixed cells.

Int J Hyperthermia 2019 ;36(1):915-925

Department of Urology, Turku University Hospital , Turku , Finland.

Prostate cancer can be eradicated with heat exposure. However, high and rapid temperature elevations may cause thermofixation giving the appearance of viable tissue. The purpose was to characterize the immunoprofile and evaluate the viability of prostate regions with suspected thermofixation. A prospective, ethics-approved and registered study (NCT03350529) enrolled six patients with MRI-visible, biopsy-concordant prostate cancer to undergo lesion-targeted MRI-guided transurethral ultrasound ablation (TULSA) followed by radical prostatectomy at 3 weeks, to evaluate the accuracy and efficacy of TULSA with whole-mount histology as a reference standard. If ambiguity about complete necrosis within the ablated region remained after hematoxylin-eosin staining, viability was assessed by immunohistochemistry. Treatment day MRI-thermometry and 3-week contrast-enhanced MRI post-TULSA were examined to assess ablation success and correlation with histopathology. One patient presented with an apparently viable subregion inside the ablated area, surrounded by necrosis on H&E staining, located where temperature was highest on MRI-thermometry and tissues completely devascularized on MRI. Immunoprofile of the apparently viable tissue revealed changes in staining patterns suggesting thermofixation; the most significant evidence was the negative cytokeratin 8 staining detected with Cam5.2 antibody. A comprehensive literature review supports these observations of thermofixation with similar findings in prostate and other tissues. Thermally-fixed cells can sustain morphology on H&E staining. Misinterpretation of treatment failure may occur, if this phenomenon is not recognized and immunohistochemistry performed. Based on the previous literature and the current study, Cam5.2 staining for cytokeratin 8 appears to be a practical and reliable tool for distinguishing thermally-fixed from viable cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02656736.2019.1652773DOI Listing
January 2020

Reply to Mengxin Lu, Yi Zhang, Yu Xiao's Letter to the Editor, re: Kimmo Kettunen, Peter J. Boström, Tarja Lamminen, et al. Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells. Eur Urol 2019;76:430-4.

Eur Urol 2019 11 13;76(5):e137-e138. Epub 2019 Aug 13.

Institute of Biomedicine, University of Turku, and Department of Pathology, Turku University Hospital, Turku, Finland. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2019.07.049DOI Listing
November 2019

Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils.

Immunity 2019 09 8;51(3):561-572.e5. Epub 2019 Aug 8.

MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland. Electronic address:

Lymphatic vessels form a critical component in the regulation of human health and disease. While their functional significance is increasingly being recognized, the comprehensive heterogeneity of lymphatics remains uncharacterized. Here, we report the profiling of 33,000 lymphatic endothelial cells (LECs) in human lymph nodes (LNs) by single-cell RNA sequencing. Unbiased clustering revealed six major types of human LECs. LECs lining the subcapsular sinus (SCS) of LNs abundantly expressed neutrophil chemoattractants, whereas LECs lining the medullary sinus (MS) expressed a C-type lectin CD209. Binding of a carbohydrate Lewis X (CD15) to CD209 mediated neutrophil binding to the MS. The neutrophil-selective homing by MS LECs may retain neutrophils in the LN medulla and allow lymph-borne pathogens to clear, preventing their spread through LNs in humans. Our study provides a comprehensive characterization of LEC heterogeneity and unveils a previously undefined role for medullary LECs in human immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2019.06.027DOI Listing
September 2019

Randomised Trial of Adjuvant Radiotherapy Following Radical Prostatectomy Versus Radical Prostatectomy Alone in Prostate Cancer Patients with Positive Margins or Extracapsular Extension.

Eur Urol 2019 11 30;76(5):586-595. Epub 2019 Jul 30.

Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland; Docrates Cancer Center, Helsinki, Finland; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland. Electronic address:

Background: It remains unclear whether patients with positive surgical margins or extracapsular extension benefit from adjuvant radiotherapy following radical prostatectomy.

Objective: To compare the effectiveness and tolerability of adjuvant radiotherapy following radical prostatectomy.

Design, Setting, And Participants: This was a randomised, open-label, parallel-group trial. A total of 250 patients were enrolled between April 2004 and October 2012 in eight Finnish hospitals, with pT2 with positive margins or pT3a, pN0, M0 cancer without seminal vesicle invasion.

Intervention: A total of 126 patients received adjuvant radiotherapy at 66.6Gy.

Outcome Measurements And Statistical Analysis: The primary endpoint was biochemical recurrence-free survival, which we analysed using the Kaplan-Meier method and Cox proportional hazard regression. Overall survival, cancer-specific survival, local recurrence, and adverse events were secondary endpoints.

Results And Limitations: The median follow-up time for patients who were alive when the follow-up ended was 9.3yr in the adjuvant group and 8.6yr in the observation group. The 10-yr survival for biochemical recurrence was 82% in the adjuvant group and 61% in the observation group (hazard ratio [HR] 0.26 [95% confidence interval {CI} 0.14-0.48], p<0.001), and for overall survival 92% and 87%, respectively (HR 0.69 [95% CI 0.29-1.60], p=0.4). Two and four metastatic cancers occurred, respectively. Out of the 43 patients with biochemical recurrence in the observation group, 37 patients received salvage radiotherapy. In the adjuvant group, 56% experienced grade 3 adverse events, versus 40% in the observation group (p=0.016). Only one grade 4 adverse event occurred (adjuvant group). A limitation of this study was the number of patients.

Conclusions: Adjuvant radiotherapy following radical prostatectomy is generally well tolerated and prolongs biochemical recurrence-free survival compared with radical prostatectomy alone in patients with positive margins or extracapsular extension.

Patient Summary: Radiotherapy given immediately after prostate cancer surgery prolongs prostate-specific antigen progression-free survival, but causes more adverse events, when compared with surgery alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2019.07.001DOI Listing
November 2019

Radiomics and machine learning of multisequence multiparametric prostate MRI: Towards improved non-invasive prostate cancer characterization.

PLoS One 2019 8;14(7):e0217702. Epub 2019 Jul 8.

Dept. of Diagnostic Radiology, University of Turku, Turku, Finland.

Purpose: To develop and validate a classifier system for prediction of prostate cancer (PCa) Gleason score (GS) using radiomics and texture features of T2-weighted imaging (T2w), diffusion weighted imaging (DWI) acquired using high b values, and T2-mapping (T2).

Methods: T2w, DWI (12 b values, 0-2000 s/mm2), and T2 data sets of 62 patients with histologically confirmed PCa were acquired at 3T using surface array coils. The DWI data sets were post-processed using monoexponential and kurtosis models, while T2w was standardized to a common scale. Local statistics and 8 different radiomics/texture descriptors were utilized at different configurations to extract a total of 7105 unique per-tumor features. Regularized logistic regression with implicit feature selection and leave pair out cross validation was used to discriminate tumors with 3+3 vs >3+3 GS.

Results: In total, 100 PCa lesions were analysed, of those 20 and 80 had GS of 3+3 and >3+3, respectively. The best model performance was obtained by selecting the top 1% features of T2w, ADCm and K with ROC AUC of 0.88 (95% CI of 0.82-0.95). Features from T2 mapping provided little added value. The most useful texture features were based on the gray-level co-occurrence matrix, Gabor transform, and Zernike moments.

Conclusion: Texture feature analysis of DWI, post-processed using monoexponential and kurtosis models, and T2w demonstrated good classification performance for GS of PCa. In multisequence setting, the optimal radiomics based texture extraction methods and parameters differed between different image types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217702PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613688PMC
February 2020

Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells.

Eur Urol 2019 10 28;76(4):430-434. Epub 2019 Jun 28.

Institute of Biomedicine, University of Turku, and Department of Pathology, Turku University Hospital, Turku, Finland. Electronic address:

Many patients with muscle-invasive bladder cancer (BC) are either ineligible for or do not benefit from cisplatin-based chemotherapy, and there is an unmet need to estimate individuals' drug sensitivities. We investigated the suitability of conditionally reprogrammed (CR) cells for the characterization of BC properties and their feasibility for personalized drug sensitivity screening. The CR cultures were established from six BC tumors with varying histology and stage. Four cultures were successfully propagated for genomic, transcriptomic, and protein expression profiling and compared to the parental tumors. Two out of four CR cultures (urothelial carcinoma and small cell neuroendocrine carcinoma [SmCC]) corresponded well to their parental tumors and underwent drug sensitivity screening to identify novel drugs for the respective tumors. Both cultures were sensitive to standard BC chemotherapy agents (eg cisplatin and gemcitabine) and to conventional drugs such as taxanes and inhibitors of topoisomerase and proteasome. The SmCC cells were also sensitive to statins (eg, atorvastatin and pitavastatin). In summary, after confirming their representativeness and origin, we conclude that CR cells are a feasible platform for personalized drug sensitivity testing and might thus add to the approaches used to personalize BC treatment strategies. PATIENT SUMMARY: We investigated the conditional reprogramming method for generating patient-derived bladder cancer cell cultures and studied their feasibility for planning personalized treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2019.06.016DOI Listing
October 2019

"I want to know what it is used for": Clients' perspectives on completing a routine outcome measure (ROM) while undergoing psychotherapy.

Psychother Res 2020 03 14;30(3):337-347. Epub 2019 Jun 14.

Department of Psychology, University of Gothenburg, Gothenburg, Sweden.

Within mental health care, the use of routine outcome measure (ROMs) has increased. So far, clients' perspectives on ROMs in the context of long-term psychotherapy remain largely unexplored. The present study aimed to explore clients' perspectives on completing the CORE-OM throughout psychotherapy. Eight clients attending a psychiatric outpatient clinic in Sweden were interviewed and the data were analyzed according to the principles of interpretative phenomenological analysis. The results included three main themes. The clients described an which gave room for interpretations regarding possible consequences of the results. The theme describes the clients' reflections about the CORE-OM, both as a measure and as a means for communication requiring continuous feedback. The indicated that completing the questionnaire was useful for clients by evoking feelings and increasing awareness of inner states ROMs should be used with great care in the treatment process and openness about the purpose of the instrument might increase the validity of the results. The use of ROMs as both an outcome measure on group level and a therapeutic tool is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10503307.2019.1630780DOI Listing
March 2020

Symptoms and diagnostic delays in bladder cancer with high risk of recurrence: results from a prospective FinnBladder 9 trial.

World J Urol 2020 Apr 8;38(4):1001-1007. Epub 2019 Jun 8.

Department of Urology, Turku University Hospital, Turku, Finland.

Purpose: To investigate the symptoms and delays in the clinical pathway of bladder cancer (BC).

Methods: This is a substudy of a prospective, randomized, multicenter phase III study (FinnBladder 9, NCT01675219) where the efficacy of photodynamic diagnosis and 6 weekly optimized mitomycin C instillations are studied in pTa bladder cancer with high risk for recurrence. The data of presenting symptoms and critical time points were prospectively collected, and the effect of factors on delays was analyzed.

Results: At the time of analysis, 245 patients were randomized. Analysis included 131 patients with primary bladder cancer and their complete data. Sixty-nine percent had smoking history and 67% presented with macroscopic hematuria. Median patient delay (from symptoms to health-care contact) was 7 days. The median general practice delay (from health-care contact to urology referral) was 8 days. Median time from urology referral to cystoscopy was 23 days and from cystoscopy to TUR-BT 21 days. Total time used in the clinical pathway (from symptom to TUR-BT) was 78 days. Current and former smokers had non-significantly shorter patient-related and general practice delays compared to never smokers. TUR-BT delay was significantly shorter in patients with malignant cytology (16 days) compared to patients with benign cytology (21 days, p = 0.03).

Conclusions: Patient-derived delay was short and most of the delay occurred in the referral centers. The majority had macroscopic hematuria as the initial symptom. Surprisingly, current and past smokers were more prone to contact the health-care system compared to never smokers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00345-019-02841-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154016PMC
April 2020

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

PLoS Med 2019 06 3;16(6):e1002813. Epub 2019 Jun 3.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

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.

Trial Registration: ClinicalTrials.gov NCT02241122.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1002813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546206PMC
June 2019

Neoadjuvant Chemotherapy Does Not Increase the Morbidity of Radical Cystectomy: A 10-year Retrospective Nationwide Study.

Eur Urol Oncol 2018 12 14;1(6):525-530. Epub 2018 Jul 14.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

Background: Neoadjuvant chemotherapy (NAC) is underutilized in the treatment of bladder cancer (BC).

Objective: To investigate the effect of NAC on the risk of surgical complications for radical cystectomy (RC) in a population-based setting.

Design, Setting, And Participants: All radical cystectomies performed in Finland during 2005-2014 were included in the study. Data were collected retrospectively using a web-based data collection platform. Complications were recorded for 90 d using the Clavien classification. Patients treated with NAC were compared to patients receiving RC alone using three cohorts and approaches: the entire cohort, a neoadjuvant period cohort, and a matched cohort.

Outcome Measurements And Statistical Analysis: For all three cohorts, odds ratios (ORs) were estimated using simple binary logistic regression. In addition, a multivariable stratified logistic model with propensity score was used. For the matched cohort analysis, both univariate and adjusted analyses were carried out.

Results And Limitations: During 2005-2014, 1427 RCs were performed in Finland, of which 1385 were included in the analyses. NAC was introduced in 2008, and 231 patients (16%) were assigned to NAC and 214 (15%) received two or more cycles of chemotherapy. Within 90 d, 61% of patients experienced complications and mortality was 4% (1.9% in the NAC group, and 4.4% in the RC-alone group). In simple binary logistic regression, NAC patients had significantly fewer complications, but this was not observed in multivariable or propensity score analyses. In the matched cohort analyses, no differences in complication rates could be observed. None of the analyses demonstrated higher complication rates in the NAC group.

Conclusions: Our retrospective study reports on nationwide use of NAC for BC and demonstrates that NAC does not increase RC morbidity.

Patient Summary: Chemotherapy given before radical surgery does not increase severe postoperative complications in the treatment of bladder cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euo.2018.06.014DOI Listing
December 2018

Correlation between F-1-amino-3-fluorocyclobutane-1-carboxylic acid (F-fluciclovine) uptake and expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter 1 (LAT1) in primary prostate cancer.

EJNMMI Res 2019 May 31;9(1):50. Epub 2019 May 31.

Turku PET Centre, Turku, Finland.

Purpose: To evaluate the expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter1 (LAT1) in prostate cancer (PCa) and their impact on uptake of F-1-amino-3-fluorocyclobutane-1-carboxylic acid (F-fluciclovine) which is approved for the detection of recurrent PCa.

Methods: Twenty-five hormone-naïve patients with histologically confirmed PCa underwent PET/CT before prostatectomy. Dynamic imaging was performed immediately after injection of 368 ± 10 MBq of F-fluciclovine and the uptake in PCa was expressed as SUV at six sequential 4-min time frames and as tracer distribution volume (V) using Logan plots over 0-24 min. The expression of ASCT2 and LAT1 was studied with immunohistochemistry (IHC) on a tissue microarray (TMA) containing three cores per carcinoma lesion. The TMA slides were scored independently by two trained readers based on visual intensity of ASCT2/LAT1 expression on a four-tiered scale. The correlations between ASCT2/LAT1 staining intensity, SUVmax/V, and Gleason grade group (GGG) were assessed using Spearman's rank correlation coefficient (ρ).

Results: Forty tumor foci (> 0.5 mm in diameter, max. 3 per patient) were available for TMA. In visual scoring, low, moderate, and high staining intensity of ASCT2 was observed in 4 (10%), 24 (60%), and 12 (30%) tumors, respectively. No tumors showed high LAT1 staining intensity while moderate intensity was found in 10 (25%), 25 (63%) showed low, and the remaining 5 (12%) were negative for staining with LAT1. Tumors with GGG > 2 showed significantly higher uptake of F-fluciclovine and higher LAT1 staining intensity (p < 0.05). The uptake of F-fluciclovine correlated significantly with LAT1 expression (ρ = 0.39, p = 0.01, for SUV at 2 min and ρ = 0.39, p = 0.01 for V). No correlation between ASCT2 expression and F-fluciclovine uptake or GGG was found.

Conclusions: Our findings suggest that LAT1 is moderately associated with the transport of F-fluciclovine in local PCa not exposed to hormonal therapy. Both high and low Gleason grade tumors express ASCT2 while LAT1 expression is less conspicuous and may be absent in some low-grade tumors. Our observations may be of importance when using F-fluciclovine imaging in the planning of focal therapies for PCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13550-019-0518-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544711PMC
May 2019

SORLA regulates endosomal trafficking and oncogenic fitness of HER2.

Nat Commun 2019 05 28;10(1):2340. Epub 2019 May 28.

Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520, Turku, Finland.

The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the cell surface. Here, we find that sortilin-related receptor 1 (SORLA; SORL1) co-precipitates with HER2 in cancer cells and regulates HER2 subcellular distribution by promoting recycling of the endosomal receptor back to the plasma membrane. SORLA protein levels in cancer cell lines and bladder cancers correlates with HER2 levels. Depletion of SORLA triggers HER2 targeting to late endosomal/lysosomal compartments and impairs HER2-driven signalling and in vivo tumour growth. SORLA silencing also disrupts normal lysosome function and sensitizes anti-HER2 therapy sensitive and resistant cancer cells to lysosome-targeting cationic amphiphilic drugs. These findings reveal potentially important SORLA-dependent endosomal trafficking-linked vulnerabilities in HER2-driven cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-10275-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538630PMC
May 2019

Decorin Expression in Human Vulva Carcinoma: Oncosuppressive Effect of Decorin cDNA Transduction on Carcinoma Cells.

J Histochem Cytochem 2019 07 22;67(7):511-522. Epub 2019 Apr 22.

Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.

The extracellular matrix proteoglycan decorin is well-known for its oncosuppressive activity. Here, decorin expression was examined in human vulva carcinoma tissue samples and in primary and commercial cell lines representing this malignant disease. Furthermore, the effect of adenovirus-mediated decorin cDNA (Ad-DCN) transduction on the viability, proliferation, and the expression and activity of the epidermal growth factor receptor (ErbB/HER) family members of the cell lines were investigated. Using in situ hybridization and immunohistochemistry for decorin, it was demonstrated that malignant cells in human vulva carcinoma tissues lack decorin expression. This result was true independently on tumor stage, grade or human papillomavirus status. RT-qPCR analyses showed that the human vulva carcinoma cell lines used in this study were also negative for decorin expression. Transduction of the cell lines with Ad-DCN caused a marked reduction in cell viability, while the proliferation of the cells was not affected. Experiments examining potential mechanisms behind the oncosuppressive effect of Ad-DCN transduction revealed that ErbB2/HER2 expression and activity in carcinoma cells were markedly downregulated. In conclusion, the results of this study showed that human vulva carcinoma cells lack decorin expression, and that Ad-DCN transduction of these cells induces oncosuppressive activity in part via downregulation of ErbB2/HER2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1369/0022155419845373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598130PMC
July 2019

IMPROD biparametric MRI in men with a clinical suspicion of prostate cancer (IMPROD Trial): Sensitivity for prostate cancer detection in correlation with whole-mount prostatectomy sections and implications for focal therapy.

J Magn Reson Imaging 2019 11 22;50(5):1641-1650. Epub 2019 Mar 22.

Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland.

Background: Prostate MRI is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). However, development and validation of methods for focal therapy planning are still lagging.

Purpose: To evaluate the diagnostic accuracy on lesion, region-of-interest (ROI), and voxel level of IMPROD biparametric prostate MRI (bpMRI) for PCa detection in men with a clinical suspicion of PCa who subsequently underwent radical prostatectomy.

Study Type: Prospective single-institution clinical trial (NCT01864135).

Population: Sixty-four men who underwent radical prostatectomy after IMPROD bpMRI performed in prebiopsy settings.

Field Strength/sequence: IMPROD bpMRI consisted of T -weighted imaging (T w) and three separate diffusion-weighted imaging acquisitions with an average acquisition time of 15 minutes.

Assessment: The diagnostic accuracy of prospectively reported manual cancer delineations and regions increased with 3D dilation were evaluated on the voxel level (volume of 1.17 mm , 1 mm , 125 mm ) as well as the 36 ROI level. Only PCa lesions with a diameter ≥ 5 mm or any Gleason Grade 4 were analyzed. All data and protocols are freely available at: http://petiv.utu.fi/improd STATISTICAL TESTS: Sensitivity, specificity, accuracy.

Results: In total, 99 PCa lesions were identified. Forty (40%, 40/99) had a Gleason score (GS) of >3 + 4. Twenty-eight PCa lesions (28%, 28/99) were missed by IMPROD bpMRI, three (7.5%, 3/40) with GS >3 + 4. 3D dilation of manual cancer delineations in all directions by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve sensitivity approaching 100% on a voxel level.

Data Conclusion: IMPROD bpMRI had a high sensitivity on lesion level for PCa with GS >3 + 4. Increasing 3D lesion delineations by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve high sensitivity on the voxel level. Such information may help in planning ablation therapies.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1641-1650.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.26727DOI Listing
November 2019

Population-based cohort study of the impact on postoperative mortality of anastomotic leakage after anterior resection for rectal cancer.

BJS Open 2019 02 15;3(1):106-111. Epub 2018 Oct 15.

Surgery Unit, Department of Surgical and Perioperative Sciences Umeå University Umeå Sweden.

Background: Anastomotic leakage following anterior resection for rectal cancer may result in death. The aim of this study was to yield an updated, population-based estimate of postoperative mortality and evaluate possible interacting factors.

Methods: This was a retrospective national cohort study of patients who underwent anterior resection between 2007 and 2016. Data were retrieved from a prospectively developed database. Anastomotic leakage constituted exposure, whereas outcome was defined as death within 90 days of surgery. Logistic regression analyses, using directed acyclic graphs to evaluate possible confounders, were performed, including interaction analyses.

Results: Of 6948 patients, 693 (10·0 per cent) experienced anastomotic leakage and 294 (4·2 per cent) underwent reintervention due to leakage. The mortality rate was 1·5 per cent in patients without leakage and 3·9 per cent in those with leakage. In multivariable analysis, leakage was associated with increased mortality only when a reintervention was performed (odds ratio (OR) 5·57, 95 per cent c.i. 3·29 to 9·44). Leaks not necessitating reintervention did not result in increased mortality (OR 0·70, 0·25 to 1·96). There was evidence of interaction between leakage and age on a multiplicative scale ( = 0·007), leading to a substantial mortality increase in elderly patients with leakage.

Conclusion: Anastomotic leakage, in particular severe leakage, led to a significant increase in 90-day mortality, with a more pronounced risk of death in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bjs5.50106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354192PMC
February 2019

Progress towards a Nordic standard for the investigation of hematuria: 2019.

Scand J Urol 2019 Feb 14;53(1):1-6. Epub 2019 Jan 14.

f Department of Clinical Medicine , Aarhus University , Aarhus , Denmarkl.

To describe the management of patients with hematuria in the Nordic countries in relation to bladder cancer epidemiology, especially in the context of introducing fast track pathways with the aim of proposing a common guideline. Epidemiological data on bladder cancer from each country, and the combined cancer registry, Nordcan, were analyzed. The evolution of the different national recommendations and the introduction of fast track pathways were assessed. Patients' demographics, type of hematuria and cancer detection rates were analysed if available. The crude incidence of bladder cancer has increased substantially since the 1960s, while the age standardized incidence has been stable during recent decades. The relative survival has increased in all countries, while the mortality has been stable. For those with microscopic hematuria there has been a clear trend towards less rigorous investigations. In the fast track pathways, introduced in three of five countries, about one in five patients with macroscopic hematuria had a cancer diagnosis. Data show that time to diagnosis has been reduced. The number of patients with bladder cancer is increasing in the Nordic region. The introduction of fast track pathways has been important in improving the management of patients with suspicion of the disease. Our recommendation is to focus on macroscopic hematuria in the fast track pathways. Microhematuria without any symptoms should not be an indication for cystoscopy. However, urinary tract symptoms accompanied by microhematuria can still be investigated according to respective guidelines but not necessarily within fast track pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2018.1555187DOI Listing
February 2019

Cell-type-specific CD73 expression is an independent prognostic factor in bladder cancer.

Carcinogenesis 2019 03;40(1):84-92

MediCity Research Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.

CD73 is an adenosine-producing cell surface enzyme, which exerts strong anti-inflammatory and migration modulating effects in many cell types. We evaluated the potential of CD73 as a biomarker in predicting the outcome of bladder carcinoma. CD73 expression in tumor and stromal cells was analyzed using immunohistochemistry in 270 bladder cancer (BC) patients [166 non-muscle-invasive BC (NMIBC) and 104 muscle-invasive BC (MIBC) tumors]. The correlations of CD73 with clinical and pathological characteristics were evaluated with Pearson's and Fischer's tests. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the association between CD73 expression and outcome. CD73 expression showed substantial variation in basal and suprabasal layers of the cancerous epithelium, stromal fibroblasts, endothelial cells and lymphocytes in different tumor specimens. In log-rank analyses, CD73 expression in cancer cells associated with better survival both in NMIBC and MIBC, whereas CD73 positivity in stromal fibroblasts associated with impaired survival in NMIBC. In multivariable models, CD73 negative epithelial cells in both BC types and CD73 negative endothelial cells in MIBC were independent factors predicting poor outcome. We conclude that in contrast to many other cancer types, high CD73 expression in BC predicts favorable prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgy154DOI Listing
March 2019