Publications by authors named "Mikael Anttinen"

10 Publications

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Prospective comparison of F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

Eur J Nucl Med Mol Imaging 2021 Mar 13. Epub 2021 Mar 13.

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

Purpose: To prospectively compare F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).

Methods: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.

Results: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively.

Conclusion: F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.

Clinical Trial Registration: ID: NCT03537391.
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March 2021

Acute and subacute prostate MRI findings after MRI-guided transurethral ultrasound ablation of prostate cancer.

Acta Radiol 2020 Nov 28:284185120976931. Epub 2020 Nov 28.

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

Background: Magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) is an emerging method for treatment of localized prostate cancer (PCa). TULSA-related subacute MRI findings have not been previously characterized.

Purpose: To evaluate acute and subacute MRI findings after TULSA treatment in a treat-and-resect setting.

Material And Methods: Six men with newly diagnosed MRI-visible and biopsy-concordant clinically significant PCa were enrolled and completed the study. Eight lesions classified as PI-RADS 3-5 were focally ablated using TULSA. One- and three-week follow-up MRI scans were performed between TULSA and robot-assisted laparoscopic prostatectomy.

Results: TULSA-related hemorrhage was detected as a subtle T1 hyperintensity and more apparent T2 hypointensity in the MRI. Both prostate volume and non-perfused volume (NPV) markedly increased after TULSA at one week and three weeks after treatment, respectively. Lesion apparent diffusion coefficient values increased one week after treatment and decreased nearing the baseline values at the three-week MRI follow-up.

Conclusion: The optimal timing of MRI follow-up seems to be at the earliest at three weeks after treatment, when the post-procedural edema has decreased and the NPV has matured. Diffusion-weighted imaging has little or no added diagnostic value in the subacute setting.
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November 2020

Palliative MRI-guided transurethral ultrasound ablation for symptomatic locally advanced prostate cancer.

Scand J Urol 2020 Dec 8;54(6):481-486. Epub 2020 Sep 8.

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

Purpose: Locally advanced prostate cancer can cause bladder outlet obstruction, gross hematuria and frequent hospitalization. While these complications are commonly treated by palliative transurethral resection of the prostate, the improvement is often insufficient. The purpose of this study was to evaluate the safety and feasibility of MRI-guided transurethral ultrasound ablation as an alternative palliative treatment option (pTULSA) for men suffering from symptomatic locally advanced prostate cancer.

Methods: This prospective, phase one study included 10 men in need of palliative surgical intervention due to urinary retention and gross hematuria caused by locally advanced prostate cancer. Patients were followed for 1 year at 3-month intervals. Time without catheter, time without hematuria, reduction in hospitalization time, and adverse events were measured.

Results: Ten patients with locally advanced prostate cancer were enrolled, all having continuous catheterization due to urinary retention and nine had gross hematuria before treatment. At 1 week post-pTULSA five patients were catheter-free. At last follow-up catheter-free and gross hematuria-free rates were 70% and 100%, respectively. Average hospitalization time from local complications reduced from 7.3 to 1.4 days in the 6 months before and after pTULSA. No > Grade 2 treatment related adverse events were reported, with all five being urinary tract infections.

Conclusions: pTULSA appears safe and feasible for palliative ablation of locally advanced prostate cancer. The therapy seems to accomplish long-term hematuria control, can relieve bladder outlet obstruction in selected patients, and seems to reduce the burden of hospitalization due to local complications. NCT03350529.
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December 2020

A Prospective Comparison of F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

Eur Urol Oncol 2020 Jul 13. Epub 2020 Jul 13.

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

Background: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa).

Objective: To compare standard staging modalities with newer and potentially more accurate imaging modalities.

Design, Setting, And Participants: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities.

Outcome Measurements And Statistical Analysis: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, Tc-hydroxymethylene diphosphonate (Tc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and F-prostate-specific membrane antigen-1007 (F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging.

Results And Limitations: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions.

Conclusions: Despite the risk of false positive bone lesions, F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa.

Patient Summary: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.
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July 2020

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.
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October 2019

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.
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January 2020

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.
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December 2018

Transurethral ultrasound therapy of the prostate in the presence of calcifications: A simulation study.

Med Phys 2018 Nov 1;45(11):4793-4805. Epub 2018 Oct 1.

Department of Radiology, Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland.

Purpose: Transurethral ultrasound therapy is an investigational treatment modality which could potentially be used for the localized treatment of prostate cancer. One of the limiting factors of this therapy is prostatic calcifications. These attenuate and reflect ultrasound and thus reduce the efficacy of the heating. The aim of this study is to investigate how prostatic calcifications affect therapeutic efficacy, and to identify the best sonication strategy when calcifications are present.

Methods: Realistic computational models were used on clinical patient data in order to simulate different therapeutic situations with naturally occurring calcifications as well as artificial calcifications of different sizes (1-10 mm) and distances (5-15 mm). Furthermore, different sonication strategies were tested in order to deliver therapy to the untreated tissue regions behind the calcifications.

Results: The presence of calcifications in front of the ultrasound field was found to increase the peak pressure by 100% on average while the maximum temperature only rose by 9% during a 20-s sonication. Losses in ultrasound energy were due to the relatively large acoustic impedance mismatch between the prostate tissue and the calcifications (1.63 vs 3.20 MRayl) and high attenuation coefficient (0.78 vs 2.64 dB/MHz /cm), which together left untreated tissue regions behind the calcifications. In addition, elevated temperatures were seen in the region between the transducer and the calcifications. Lower sonication frequencies (1-4 MHz) were not able to penetrate through the calcifications effectively, but longer sonication durations (20-60 s) with selective transducer elements were effective in treating the tissue regions behind the calcifications.

Conclusions: Prostatic calcifications limit the reach of therapeutic ultrasound treatment due to reflections and attenuation. The tissue regions behind the calcifications can possibly be treated using longer sonication durations combined with proper transducer element selection. However, caution should be taken with calcifications located close to sensitive organs such as the urethra, bladder neck, or rectal wall.
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November 2018

[The many causes of chronic pain in the groin].

Duodecim 2014 ;130(19):1940-3

Mikkelin keskussairaala.

One or more causes may be revealed underlying chronic pain in the groin. Knowledge of the complex anatomy of the groin may provide hints about the cause of the pain. In addition to clinical studies, imaging studies are often needed, with X-ray, ultrasonography and in particular MR imaging of the pelvis being the most important ones. The latter provides the best information on the structures of the groin region and the surrounding soft tissues. We present two rare causes of pain in the groin, the diagnosis of which was delayed due to insufficient imaging.
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January 2015

Histopathological evidence for an association of inflammation with ductal pin-like lesions but not with ductal adenocarcinoma in the prostate of the noble rat.

Prostate 2008 May;68(7):728-39

Institute of Biomedicine, Department of Anatomy, University of Turku, Turku, Finland.

Background: Chronic inflammation may contribute to the development of prostate cancer. The goal of this study was to determine the possible association of prostatic inflammation, prostatic intraepithelial neoplasia (PIN)-like lesion, and prostate cancer, and to assess the androgen and estrogen dependency of the early steps of carcinogenesis.

Methods: Noble rats were treated with testosterone and estradiol implants for 13, 18, or 26 weeks. Hormone dependency of the lesions was studied in a subset of animals by removing hormone implants for 3 weeks after 15 weeks treatment time.

Results: After treatment for 13 weeks, acute and chronic inflammation was found in the dorsolateral prostate lobes and both inflammation and PIN-like lesions were present in the periurethal area of the prostate in all animals (n = 8). Following hormone exposure for 18 and 26 weeks, inflammation in the prostate remained, and adenocarcinomas in the periurethal prostate area with no adjacent inflammation were observed in all 18 animals studied. When both hormone implants were removed after 15 weeks, PIN-like lesions progressed further to adenocarcinoma only in two of seven animals. When only the estradiol implants were removed, three of five animals developed adenocarcinomas.

Conclusions: Even though adenocarcinomas were not morphologically associated with inflammation, PIN-like lesions preceding adenocarcinoma were found in close association with inflammation, pointing towards a possible initiator role of inflammation in the early steps of prostatic carcinogenesis. Further, these results indicate that both androgens and estrogens together play a significant role in the induction of inflammation and prostatic cancer in this model.
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May 2008