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  • 1
    Abstract: Background: By targeting the prostate-specific membrane antigen (PSMA) on prostate cancer (PCa) cells PSMA-PET/CT shows great potential in locating the site of biochemical recurrence even at low PSA (Prostate-specific antigen)-levels. Accurate imaging of PCa recurrent lymph node metastases (LNM) is crucial for metastases directed therapies such as salvage-lymph node dissection (salvage-LND). Objective: To evaluate the diagnostic accuracy of PSMA-PET/CT for detection of affected lymph-node regions at salvage-LND for nodal recurrence of PCa. Design, setting and participants: 30 patients with the suspicion of exclusively nodal PCa-relapse after primary therapy underwent a template pelvic and/or retroperitoneal salvage-LND after whole body 68-Ga-PSMA-PET/CT. The diagnostic accuracy of PET/CT was evaluated in comparison to the histopathology of 965 resected lymph nodes (LN) dissected from 68 main regions (pelvic left/right, retroperitoneal) and 289 subregions (common iliac, external iliac, obturator, internal iliac, presacral, aortic-bifurcation, aortal, caval). LNM and tumor deposits in LNM were measured bidimensionally in the histopathology. PSMA-expression was analyzed by immunohistochemistry in LNM. Results: LNM were present in 11.4% of the resected LN (110/965) resulting in 45 positive main regions and 85 positive subregions. PET/CT was true positive in 41 main regions and 69 subregions. Three PET-negative main regions and 16 PET-negative subregions finally contained LNM, the majority of these false negative subregions (13/16) were in neighboring regions of true-positive subregions. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were: main region-based 93.2%, 100%, 100%, 88.9% and 95.6%, subregion-based 81.2%, 99.5%, 98.6%, 92.7 and 94.1%. Median short diameters of tumor deposits in LNM resected from false-negative subregions (1.3 mm) were significantly smaller than in LNM removed from true-positive subregions (5.5 mm, p〈0.0001). Based on anatomical subregions containing just one LNM, the necessary short diameter of tumor deposits in LNM required to reach a detection rate of 50% and 90% was estimated to be 〉/= 2.3 mm and 〉/= 4.5 mm, respectively. Conclusion: In men with biochemical PCa-relapse and positive PSMA-PET/CT, PET/CT detects metastatic affected anatomical regions with high accuracy at a main region and at a subregion-level. If the decision for salvage-LND is prompted by a positive PSMA-PET/CT, the size of metastases is crucial for accurate detection of affected regions. All LNM showed a clear PSMA-expression in the immunohistochemistry. Further studies need to investigate how to translate the high anatomical correlation observed between PET/CT and surgical findings into optimal approaches for target salvage-LND.
    Type of Publication: Journal article published
    PubMed ID: 28529650
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  • 2
    Abstract: PURPOSE/BACKGROUND: [(18)F]fluoroethylcholine ((18)FECH) has been shown to be a valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT is a promising technique for staging and restaging of PCa. We explore the value of GRPr-PET using the (68)Ga-labeled GRPr antagonist RM2 in a selected population of patients with biochemically recurrent PCa and a negative/inconclusive (18)FECH-PET/CT. MATERIAL AND METHODS: In this retrospective study 16 men with biochemical PCa relapse and negative (n = 14) or inconclusive (n = 2) (18)FECH-PET/CT underwent whole-body (68)Ga-RM2-PET/CT. Mean time from (18)FECH-PET/CT to (68)Ga-RM2-PET/CT was 6.1 +/- 6.8 months. Primary therapies in these patients were radical prostatectomy (n = 13; 81.3%) or radiotherapy (n = 3; 18.7%). 14/16 patients (87.5%) had already undergone salvage therapies because of biochemical relapse prior to (68)Ga-RM2-PET/CT imaging. Mean +/- SD PSA at (68)Ga-RM2-PET/CT was 19.4 +/- 53.5 ng/ml (range 1.06-226.4 ng/ml). RESULTS: (68)Ga-RM2-PET/CT showed at least one region with focal pathological uptake in 10/16 patients (62.5%), being suggestive of local relapse (n = 4), lymph node metastases (LNM; n = 4), bone metastases (n = 1) and lung metastasis with hilar LNM (n = 1). Seven of ten positive (68)Ga-RM2 scans were positively confirmed by surgical resection and histology of the lesions (n = 2), by response to site-directed therapies (n = 2) or by further imaging (n = 3). Patients with a positive (68)Ga-RM2-scan showed a significantly higher median PSA (6.8 ng/ml, IQR 10.2 ng/ml) value than those with a negative scan (1.5 ng/ml, IQR 3.1 ng/ml; p = 0.016). Gleason scores or concomitant antihormonal therapy had no apparent impact on the detection of recurrent disease. CONCLUSION: Even in this highly selected population of patients with known biochemical recurrence but negative or inconclusive (18)FECH-PET/CT, a (68)Ga-RM2-PET/CT was helpful to localize PCa recurrence in the majority of the cases. Thus, (68)Ga-RM2-PET/CT deserves further investigation as a promising imaging modality for imaging PCa recurrence.
    Type of Publication: Journal article published
    PubMed ID: 28417160
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  • 3
    Abstract: PURPOSE: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared (68)Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material. METHODOLOGY: Seven patients with histopathologically proven primary PCa underwent (68)Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sorensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion. RESULTS: PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57+/-22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (+/-0.18), 0.45 (+/-0.17) and 0.48 (+/-0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max). CONCLUSION: In a slice by slice analysis with histopathology, (68)Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa.
    Type of Publication: Journal article published
    PubMed ID: 28042330
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  • 4
    ISSN: 1432-1041
    Keywords: Key words Bladder cancer ; Fluorescent photodetection ; Photodynamic diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In an open study, the local and systemic side effects and pharmacokinetics of 5-aminolevulinic acid (5-ALA) and the fluorescent metabolite protoporphyrin IX (PPIX) were investigated after intravesical administration for the fluorescent photodetection of superficial bladder carcinoma. Patients and methods: In 20 patients with confirmed bladder carcinoma, 5-ALA was introduced into the bladder 2 h (15 patients) and 4 h (5 patients) before an elective endoscopic resection. The 5-ALA and PPIX levels in the plasma were determined before and up to 10 h after application, and in the urine 2 h or 4 h after application. Results: The plasma level of 5-ALA rose rapidly, the maximal concentration (340 ng/ml) being reached in 0.55 h (2 h) or 0.62 h (4 h). The elimination half-life of 5-ALA amounted to 0.74 h (2 h) or 0.79 h (4 h). In five of the patients, there was a measurable plasma concentration which ranged from the detection limit of 4.3 ng/ml to 14 ng/ml between 2 h and 5 h after application, and then fell below the detection limit after 9 h. Absorption of 5-ALA by the bladder was low, i.e. less than 1% of the total amount applied. During a period of observation of 96 h, no 5-ALA-specific side effects appeared. Conclusion: Because of the small quantity of 5-ALA resorbed following its intravesical administration, only minimal concentrations of PPIX that are responsible for producing side effects can be metabolised in the plasma. Therefore, no systemic side effects are to be expected after the intravesical administration of 5-ALA.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1433-0563
    Keywords: Key words Infertility • ICSI • TESE • Reproductive medicine ; Schlüsselwörter Infertilität • ICSI • TESE • Reproduktionsmedizin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach den ersten Erfolgen der in-vitro Fertilisation 1978 wurden die verschiedenen Techniken der ovariellen Stimulation, der Eizellengewinnung und der Embryonenkultivierung entscheidend verbessert. Die Entwicklung von Mikroinjektionstechniken war ein Meilenstein in der Reproduktionsmedizin. Sogar in Fällen ausgeprägter Verminderung der Samenqualität konnten Schwangerschaftsraten von ungefähr 20 % pro Behandlung nach der Anwendung der intrazytoplasmatischer Spermieninjektion (ICSI) erreicht werden. Wesentliche Eckpunkte bei dem Einsatz von reproduktionsmedizinischen Maßnahmen (ART) ist die Altersgrenze der Frau sowie das vorzeitige Erlöschen der Ovarialfunktion und die Möglichkeit beim Mann Spermatozoen zu gewinnen. Deshalb ist ein interdisziplinäres Vorgehen Voraussetzung, um den komplexen Problemen eines betroffen Paares gerecht zu werden. Es gibt Hinweise, daß Kinder, die nach Mikroinjektionstechniken geboren wurden, ein höheres Risiko für chromosomale Veränderungen haben. Trotz allem scheinen die Prozentsätze von schweren Fehlbildungen nach reproduktionsmedizinischen Maßnahmen im Vergleich zur Normalbevölkerung gleich zu sein. Eine Abschätzung des möglichen Risikos und der Erfolgsaussichten sowie die gründliche Beratung des betroffenen Paares muß vor Einleitung invasiver reproduktionsmedizinischer Verfahren erfolgen.
    Notes: Summary Since the first child was born after in-vitro fertilization in 1978, different techniques of ovarian stimulation, oocyte retrieval and embryo culture have improved significantly. The development of microinjection techniques was a mile stone in reproductive medicine. Even in cases of severe impairment of semen quality, using the Intracytoplasmic Sperm Injection (ICSI), pregnancy rates of approximately 20 % per treatment cycle can be achieved. However for using artificial reproductive techniques (ART) the female age is a major limiting factor as well as the development of premature ovarian failure (POF). Crucial for the male is the question whether or not sperm cells can be retrieved. Today an interdisciplinary approach is recommended to take care of the afflicted couple in order to address the complex problem of infertility. There is evidence that children born after microinjection techniques bare a higher risk for chromosomal aberrations compared to the normal population. However rates of major malformations seem to be identical in both groups. An evaluation of the potential risks and efforts and an extensive counseling of the infertile couple has to be taken before initiating invasive ART.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Urological research 14 (1986), S. 241-246 
    ISSN: 1434-0879
    Keywords: Seminal fluid ; Biochemical analysis ; Citrate ; Fructose ; Carnitine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The measurement of biochemical markers in human seminal plasma is important in the evaluation of male infertility. We recommend the measurement of one representative substance for each organ involved in seminal fluid production as a routine diagnostic tool: The initial fructose level for seminal vesicular function, citrate or acid phosphatase for the prostate gland and free carnitine as an index of epididymal function. A biochemical analysis of seminal fluid enables us to detect disturbances of the male adnexal organs and may lead to more exact therapy.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1335
    Keywords: Whole blood cell cultures ; Cytokine production ; Urogenital carcinomas ; Immune competence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The production of the cytokines interferon γ (IFN γ), interleukin-1 α (IL-1 α) and tumor necrosis factor α (TNF α) was investigated in the mitogen-stimulated whole blood cell culture media from 51 patients with urinary bladder carcinomas, 52 patients with renal carcinomas, 31 patients with prostatic carcinomas and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive enzymo-immunological assay. In the blood cell culture supernatants of the patients with urinary bladder carcinomas significancy lower levels of IFN γ (P≤0.001), IL-2 (P≤0.001) and TNFα (P≤0.05) were found as compared to the controls. Blood cells of patients with renal carcinomas had lower production of IFN γ (P≤0.01), IL-2 (P≤0.001) and IL-1α (P≤0.01), whereas the values of the total group of patients with prostatic carcinomas were not significantly different from those of the controls. Lymphocyte and monocyte counts were almost identical in the control and all tumor patient groups. When the patients with renal carcinomas and prostatic carcinomas were analyzed according to their different clinical stages we could show a gradual depression of the IFN-γ levels, which was related to tumor burden.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 14 (1998), S. 66-75 
    ISSN: 1434-808X
    Keywords: Schlüsselwörter Azoospermie ; Infertilität ; Vasovasostomie ; Epididymovasostomie ; TURED
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Bei etwa 5 % der infertilen Männer liegt ein Verschluß der Samenwege vor. Da eine operative Korrektur einer Obstruktion der Samenwege eine der wenigen kausalen Therapieformen der männlichen Infertilität darstellt, ist die Diagnose dieses Erkrankungsbilds von wesentlicher Bedeutung. Neben der Lokalisation der Obstruktion durch Ejakulatuntersuchungen stellen die körperliche Untersuchung, Hormonanalyse, Hodenbiopsie und die Sonographie die wichtigsten diagnostischen Maßnahmen vor einer operativen Korrektur dar. In Abhängigkeit von der Lokalisation des Verschlusses erfolgt bei einer Obstruktion der proximalen Samenwege eine mikrochirurgische Reanastomosierung, bei einem zentralen Samenwegverschluß eine transurethrale Elektroresektion der Obstruktion. Die Ergebnisse der verschiedenen operativen Verfahren sind bezüglich Durchgängigkeits- und Schwangerschaftsraten zu differenzieren und betragen 35–95 % bzw. 15–60 % und liegen damit deutlich über den Ergebnissen reproduktionstechnischer Verfahren.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 14 (1998), S. 148-153 
    ISSN: 1434-808X
    Keywords: Schlüsselwörter Infertilität ; körperliche Untersuchung ; Ultraschalluntersuchung ; Hoden
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Trotz der Entwicklung neuer assistierter reproduktionsmedizinischer Techniken darf auf eine umfassende andrologische Untersuchung nicht verzichtet werden, um dem infertilen Paar eine optimale Therapie anbieten zu können. Neben einer detaillierten Anamneseerhebung ist die körperliche Untersuchung des Mannes in einer ungewollt kinderlos gebliebenen Partnerschaft die Basis für alle weiteren diagnostischen und therapeutischen Maßnahmen. Der Ultraschall ist heute bei der urologisch-andrologischen Untersuchung so bedeutend geworden, daß er die „dritte Hand“ des Untersuchers genannt wird. Alle Genitalorgane – Hoden, Nebenhoden, Prostata, Bläschendrüsen und Penis – sind sonographisch hervorragend abzubilden und krankhafte Veränderungen mit einer hohen Treffsicherheit zu diagnostizieren.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 14 (1998), S. 249-250 
    ISSN: 1434-808X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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