External validation of two MRI-based risk calculators in prostate cancer diagnosis.

BACKGROUND: The diagnosis of (significant) prostate cancer ((s)PC) is impeded by overdiagnosis and unnecessary biopsy. Risk calculators (RC) have been developed to mitigate these issues. Contemporary RCs integrate clinical characteristics with mpMRI findings. OBJECTIVE: To validate two of these models-the MRI-ERSPC-RC-3/4 and the risk model of van Leeuwen. METHODS: 265 men with clinical suspicion of PC were enrolled. Every patient received a prebiopsy mpMRI, which was reported according to PI-RADS v2.1, followed by MRI/TRUS fusion-biopsy. Cancers with ISUP grade ≥ 2 were classified as sPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statistical analysis was performed by comparing discrimination, calibration, and clinical utility RESULTS: There was no significant difference in discrimination between the RCs. The MRI-ERSPC-RC-3/4-RC showed a nearly ideal calibration-slope (0.94; 95% CI 0.68-1.20) than the van Leeuwen model (0.70; 95% CI 0.52-0.88). Within a threshold range up to 9% for a sPC, the MRI-ERSPC-RC-3/4-RC shows a greater net benefit than the van Leeuwen model. From 10 to 15%, the van Leeuwen model showed a higher net benefit compared to the MRI-ERSP-3/4-RC. For a risk threshold of 15%, the van Leeuwen model would avoid 24% vs. 14% compared to the MRI-ERSPC-RC-3/4 model; 6% vs. 5% sPC would be overlooked, respectively. CONCLUSION: Both risk models supply accurate results and reduce the number of biopsies and basically no sPC were overlooked. The van Leeuwen model suggests a better balance between unnecessary biopsies and overlooked sPC at thresholds range of 10-15%. The MRI-ERSPC-RC-3/4 risk model provides better overall calibration.

Paraganglioma of the Seminal Vesicle Case Report and Review of the Literature.

Background: The present case report describes an extremely rare case of a norepinephrine secreting extraadrenal paraganglioma (PGL) located in the seminal vesicle. Case Presentation: A 36-year-old patient had signs of intermittent hypertensive derailments, bradycardia, increased norepinephrine excretion in 24-hour urine, an increased metanephrine plasma concentration, and a positive clonidine suppression test. A suspicious mass was detected in an (18)F-DOPA-PET/CT-scan in the left seminal vesicle. Following adrenergic blockade, a robotically assisted laparoscopic left vesiculectomy with negative soft tissue surgical margins was performed. The patient sustained a couple of few months of voiding difficulties of the lower urinary tract and obstruction of the left upper urinary tract after the surgery, which resolved spontaneously with home medical treatment. Two years after the initial treatment, the patient relapsed, which was confirmed by endocrinologic follow-up tests with increased urine catecholamine, a positive clonidine suppression test, as well as an elevated blood pressure. Staging with (18)F-DOPA-PET/CT-scan confirmed the diagnosis of a recurrent PGL. This was followed by subsequent open surgical removal of the suspicious lesion in the seminal fossa. The patient is still recurrence free 15 months after the second surgery. Complications after the second surgery included an intermittent paresthesia of the left leg lasting 3 to 4 months. No other urologic symptoms such as voiding or erectile dysfunction occurred. Conclusion: DaVinci-assisted laparoscopic vesiculectomy is a viable procedure to treat such cases providing satisfactory results. Relevant for clinical practice are the regular and lifelong follow-up examinations to detect recurrences.

Primary melanoma of the prostate: case report and review of the literature.

BACKGROUND: Primary melanoma of the prostate has an extremely rare incidence. Only five cases have been reported in the literature and prognosis is poor. The most likely origin of prostatic melanoma is the transitional epithelium of the prostatic urethra. Surgical care for primary melanoma of mucosal sites is less well established than for primary cutaneous melanoma, but excision of the primary is recommended if the patient has no systemic disease. CASE PRESENTATION: Here, we describe a case of primary malignant melanoma of the prostate. A 37-year-old male patient with history of both chemo- and radiation therapy for Hodgkin's disease was admitted to the University Hospital Heidelberg on suspicion of pleomorphic sarcoma of the bladder. In-house diagnostic work-up revealed a malignant melanoma of the prostate. We then performed radical prostatectomy with extended lymphadenectomy. Despite presumably curative surgery, the patient suffered from early relapse of disease with pulmonary metastasis. Systemic chemotherapy and subsequent immuno-oncologic treatment was thereafter initiated. CONCLUSION: Since prostatic melanoma is a rare disease and a melanoma metastasis of unknown primary is the differential diagnosis, a multidisciplinary approach including early imaging to rule out possible metastases and to search for another potentially existing primary is advisable. To prevent complications related to local tumor progression and to receive tissue for mutational analysis, we recommend complete surgical resection to reduce the tumor mass. Novel immune and targeted oncologic therapies can lead to an improved survival in some cases and support of clinical trials is needed.

The Impact of Magnetic Resonance Imaging on Prediction of Extraprostatic Extension and Prostatectomy Outcome in Patients with Low-, Intermediate- and High-Risk Prostate Cancer: Try to Find a Standard.

PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (mpMRI) and to predict extracapsular extension (ECE), seminal vesicle (SV) infiltration, and a negative surgical margin (SM) status at radical prostatectomy (RP) for different prostate cancer (PC) risk groups. PATIENTS AND METHODS: In the study, 805 men underwent 3 tesla mpMRI without endorectal coil before MRI/transrectal ultrasonography-fusion guided prostate biopsy. MRIs were analyzed using the prostate imaging reporting and data system. The cohort was classified into risk groups according to National Comprehensive Cancer Network (NCCN) criteria. Of 132 men who subsequently underwent RP, pathologic stage and SM status at RP were used as reference. Retrospectively, we investigated a European Society of Urogenital Radiology (ESUR) score for ECE and SV-infiltration. Statistical analyses included regression analyses, receiver operating characteristics (ROC), and Youden Index to assess an ESUR-score cutoff. RESULTS: Area under the curve in ROC curve analyses was 0.82 for ESUR-ECE score to detect pT(3a)-disease and 0.77 for ESUR-SV score for pT(3b). Using a cutoff of 4 for ECE and of 2 for SV, the positive predictive value of the ECE-score for harboring pT(3) was 50.0%, 90.0%, and 88.8% for the low-, intermediate- and high-risk cohort. Retrospectively, the use of the ESUR-ECE score preoperatively would have changed the initial surgical plan, according to NCCN criteria, in 31.1% of patients. In the high-risk subgroup, 9/35 (25.7%) patients were correctly assessed as not harboring pT(3) by imaging (ECE score <4), and would have allowed secure robot-assisted radical prostatectomy and nerve-sparing surgery (NSS). When T3 suspicion on preoperative MRI would be taken into account, intraoperative frozen-sections (IFS) might avoid positive SM in 12/18 high-risk patients and an oncologic secure NSS in 8/20 intermediate-risk patients. CONCLUSION: Prediction of pT(3) disease is crucial to plan NSS and to achieve negative SM in RP. Standardized ECE scoring on mpMRI is an independent predictor of pT(3) and may help to plan RP with oncologic security, even in high-risk patients. In addition, it allows more accurate selection of a subgroup of patients for systematic and MRI-guided IFS.

Volumetry may predict early renal function after nephron sparing surgery in solitary kidney patients.

We investigate the impact of the residual kidney volume measured by tumor volumetry on preoperative imaging in predicting post-operative renal function. Nephron sparing surgery (NSS) in renal cell carcinoma (RCC) is the standard treatment for T1 kidney tumors. Resection of kidney tumors in solidary kidneys needs precise preoperative counseling of patients regarding post-operative renal function. Patients planned for renal tumor surgery who underwent prior nephrectomy on the contralateral side were included. We identified 35 patients in our database that underwent NSS in solitary kidneys and met the inclusion criteria. Tumor volumetry was performed on computer tomography (CT) or magnetic resonance imaging (MRI) with the Medical Imaging Interaction Toolkit (MITK). Clinical and pathological data were assessed. Follow-up data included renal function over 3 years. Mean age was 64 ± 8.1 years. Mean tumor volume on imaging was 27.5 ± 48.6 cc. Mean kidney volume was 195.2 ± 62.8 cc and mean residual kidney volume was 173.4 ± 65.3 cc. We found a correlation between renal function (MDRD) and residual kidney volume on imaging 1-week post-surgery (p = 0.038). Mid- and long-term renal function was not associated with residual kidney volume. In conclusion, renal volumetry may predict early renal function after NSS.

Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels.

Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A-Mel-3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters. Fluorescently labeled liposomes with different surface charge were prepared. Accumulation of i.v. injected liposomes was assessed by quantitative intravital fluorescence microscopy of tumor and surrounding host tissue. The histological distribution of liposomes was analyzed by double-fluorescence microscopy 20 min after application of fluorescently labeled lectin as a vascular marker. After i.v. application of anionic and neutral liposomes, we observed an almost homogeneous distribution of liposome-induced fluorescence throughout the chamber preparation without specific targeting to tumor tissue. In contrast, cationic liposomes exhibited a significantly enhanced accumulation in tumor tissue and tumor vasculature up to 3-fold compared to surrounding tissue (p<0.05). The histological distribution of neutral and anionic liposomes revealed extravasation 20 min after i.v. injection, while cationic liposomes displayed a highly selective accumulation on the vascular endothelium. In conclusion, cationic liposomes exhibited a preferential uptake in angiogenic tumor vessels and therefore may provide an efficient tool for the selective delivery of diagnostic or therapeutic agents to angiogenic blood vessels of solid tumors. On the other hand, anionic and neutral liposomes may be used as carriers of drugs to the extravascular compartment of tumors due to their extravasation.

Platelet-endothelial interaction in tumor angiogenesis and microcirculation.

Activated platelets release angiogenic growth factors and have therefore been proposed to contribute to tumor angiogenesis within a potentially prothrombotic tumor microcirculation. The aim of the study was to investigate interactions of platelets with the angiogenic microvascular endothelium of highly vascularized solid tumors during growth and in response to endothelial stimulation in comparison with normal subcutaneous tissue. Experiments were performed in the dorsal skinfold chamber preparation of C57BL/6J mice bearing the Lewis lung carcinoma (LLC-1) or methylcholanthrene-induced fibrosarcoma (BFS-1). Fluorescently labeled rolling and adherent platelets, red blood cell velocity, and vessel diameters were assessed by intravital fluorescence microscopy on days 1, 3, 8, and 14 after tumor cell implantation. Slightly elevated numbers of rolling platelets were observed in the early stages of tumor angiogenesis at day 1 (control, 1.7 +/- 0.6; LLC-1, 3.4 +/- 1.8; BFS-1, 3.0 +/- 0.7 [1/mm/s], P <.05) and day 3 (control, 1.6 +/- 0.6; LLC-1, 4.1 +/- 1.7, P <.05; BFS-1, 2.3 +/- 0.5 [1/mm/s]) after tumor cell implantation. Endothelial stimulation with calcium ionophore A23187 at day 14 after tumor cell implantation resulted in a minor increase to 2.1 +/- 0.4 (LLC-1) and 1.8 +/- 0.8 (BFS-1) rolling platelets (1/mm/s) in tumor microvessels compared with 4.9 +/- 0.9 in controls (P <.05). Platelet adherence was not observed. We therefore conclude that in the 2 experimental tumors under study, (1) slightly increased platelet rolling is a transient phenomenon after tumor cell implantation, and (2) platelet-endothelial interaction in response to endothelial stimulation is reduced in tumor microvessels.