A randomized controlled trial investigating rectus sheath catheters following radical cystectomy.

OBJECTIVE: To evaluate whether rectus sheath catheter (RSC) insertion may be an alternative to thoracic epidural (TE). PATIENTS AND METHODS: In a non-blinded, single-centre, non-inferiority study, patients undergoing open radical cystectomy were randomized 1:1 to receive either a TE or surgically placed RSC. The primary endpoint was cumulative opiate use (median oral morphine equivalent [OME]) in the first 72 h postoperatively. Secondary outcomes included visual analogue scale pain scores, measures of postoperative recovery including mobility and time to regular diet, and complications. RESULTS: Ninety-seven patients were randomized (51 TE, 46 RSC). The median OME was 103 (77.5-132.5) mg in the TE arm and 161.75 (117.5-187.5) mg in the RSC arm. A Mann-Whitney U-test confirmed non-inferiority of RSC to TE at a threshold of 15 mg OME (P = 0.002). When comparing pain scores for the first three postoperative days, an early difference was observed that favoured the TE group during post-anaesthesia care unit stay, which was lost after postoperative day 1. Patient satisfaction with analgesia on the third postoperative day was similar in the two arms (P = 0.47). There were no statistically significant differences between arms with respect to the other secondary outcomes. CONCLUSIONS: The outcomes from this prospective randomized trial demonstrated non-inferiority of RSC insertion compared to TE with respect to 72-h opiate use. Patient satisfaction with pain control on postoperative day 3 was the same for each group.

The impact of perioperative complications on favorable outcomes after artificial urinary sphincter implantation for post-prostatectomy incontinence.

OBJECTIVE: To investigate the effect of perioperative complications involving artificial urinary sphincter (AUS) implantation on rates of explantation and continence as well as health-related quality of life (HRQOL). MATERIALS AND METHODS: Inclusion criteria encompassed non-neurogenic, moderate-to-severe stress urinary incontinence (SUI) post radical prostatectomy and primary implantation of an AUS performed by a high-volume surgeon (>100 previous implantations). Reporting complications followed the validated Clavien-Dindo scale and Martin criteria. HRQOL was assessed by the validated IQOL score, continence by the validated ICIQ-SF score. Statistical analysis included Chi (2) test, Mann-Whitney-U test, and multivariate regression models (p<0.05). RESULTS: 105 patients from 5 centers met the inclusion criteria. After a median follow-up of 38 months, explantation rates were 27.6% with a continence rate of 48.4%. In the age-adjusted multivariate analysis, perioperative urinary tract infection was confirmed as an independent predictor of postoperative explantation rates [OR 24.28, 95% CI 2.81-209.77, p=0.004). Salvage implantation (OR 0.114, 95% CI 0.02-0.67, p=0.016) and non-prostatectomy related incontinence (OR 0.104, 95% CI 0.02-0.74, p=0.023) were independent predictors for worse continence outcomes. Low visual analogue scale scores (OR 9.999, 95% CI 1,42-70.25, p=0.021) and ICIQ-SF scores, respectively (OR 0.674, 95% CI 0.51-0.88, p=0.004) were independent predictors for increased HRQOL outcomes. Perioperative complications did not significantly impact on continence and HRQOL outcomes. CONCLUSION: Findings show postoperative infections adversely affect device survival after AUS implantation. However, if explantation can be avoided, the comparative long-term functional results and HRQOL outcomes are similar between patients with or without perioperative complications.

Inhibition of GLI2 with antisense-oligonucleotides: A potential therapy for the treatment of bladder cancer.

The sonic hedgehog (SHH) signaling pathway plays an integral role in the maintenance and progression of bladder cancer (BCa) and SHH inhibition may be an efficacious strategy for BCa treatment. We assessed an in-house human BCa tissue microarray and found that the SHH transcription factors, GLI1 and GLI2, were increased in disease progression. A panel of BCa cell lines show that two invasive lines, UM-UC-3 and 253J-BV, both express these transcription factors but UM-UC-3 produces more SHH ligand and is less responsive in viability to pathway stimulation by recombinant human SHH or smoothened agonist, and less responsive to inhibitors including the smoothened inhibitors cyclopamine and SANT-1. In contrast, 253J-BV was highly responsive to these manipulations. We utilized a GLI1 and GLI2 antisense oligonucleotide (ASO) to bypass pathway mechanics and target the transcription factors directly. UM-UC-3 decreased in viability due to both ASOs but 253J-BV was only affected by GLI2 ASO. We utilized the murine intravesical orthotopic human BCa (mio-hBC) model for the establishment of noninvasive BCa and treated tumors with GLI2 ASO. Tumor size, growth rate, and GLI2 messenger RNA and protein expression were decreased. These results suggest that GLI2 ASO may be a promising new targeted therapy for BCa.

Biallelic tumour suppressor loss and DNA repair defects in de novo small-cell prostate carcinoma.

Small-cell prostate carcinoma (SCPC) is an aggressive malignancy that is managed similarly to small-cell lung cancer. SCPC can evolve from prostate adenocarcinoma in response to androgen deprivation therapy, but, in rare cases, is present at initial cancer diagnosis. The molecular aetiology of de novo SCPC is incompletely understood, owing to the scarcity of tumour tissue and the short life-expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology, and the remainder had some admixed adenocarcinoma foci, but all were treated with first-line platinum-based chemotherapy. The median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin-embedded archival tumour tissue. We observed frequent biallelic deletion and/or mutation of the tumour suppressor genes TP53, RB1, and PTEN, similarly to what was found in treatment-related SCPC. Indeed, at the RNA level, pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes, including BRCA1, BRCA2, ATM, and MSH2/6, potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harboured ETS gene rearrangements involving androgen-driven promoters, consistent with the evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape that underlies this unusual pathological variant, and suggest opportunities for targeted therapy strategies in a disease with few treatment options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A prospective randomized pilot study evaluating an ERAS protocol versus a standard protocol for patients treated with radical cystectomy and urinary diversion for bladder cancer.

PURPOSE: There is a lack of evidence demonstrating the benefits of using enhanced recovery after surgery protocols (ERAS). Here, we propose to use a randomized clinical pilot study to demonstrate the benefits and feasibility of implementing ERAS versus standard protocols (SP) in patients undergoing radical cystectomy (RC) and urinary diversion. METHODS: 27 consecutive patients undergoing RC were included in the study. 12 patients were prospectively randomized to follow an ERAS protocol and 15 patients followed an SP. Duration of hospital stay, time to first flatulence and bowel movement, complications and 30 day readmission rates, as well as subjective outcomes such as postoperative pain, nausea, bowel symptoms, quality of life (QoL), and patient experience and satisfaction were evaluated. RESULTS: Patients following ERAS had a significantly shorter: hospital stay, time to flatulence, and time to bowel movement than patients following SP. No major complications were reported. Only one patient in the ERAS group was readmitted for bowel obstruction, and no patients were readmitted in the SP group. Patients under ERAS reported lower postoperative pain scores. Mean Functional Assessment of Cancer Therapy Bladder Cancer score decreased and mean Expanded Prostate Cancer Index Composite, bowel symptom score increased in the SP group at the time of discharge compared to prior to surgery. CONCLUSIONS: This study shows the feasibility of a randomized pilot study assessing ERAS compared to SP post RC. ERAS protocol provided evidence of significant benefits over SP with similar complication rates. This study suggests the need for a clinical trial of assessing ERAS protocols after RC.

The impact of time to metastasis on overall survival in patients with prostate cancer.

PURPOSE: Time to metastasis is often used as a surrogate parameter of treatment success in clinical trials for prostate cancer. However, it has not been shown that there is a clear correlation between time to metastasis and overall survival. Our objective was to evaluate the impact of time to metastasis on OS in patients with prostate cancer. METHODS: Between 2008 and 2015, 269 patients with mPCa were included in this retrospective study with a median follow-up of 7.1 years. Patients were divided into three groups: (1) Presentation with metastasis within three months of initial diagnosis (de-novo-M); (2) patients free of metastasis initially but developed metastasis more than 6 months prior to castration resistance (CSPC-M); (3) patients who developed metastasis within 6 months of becoming castration resistant or after (CRPC-M). RESULTS: There was a significant decrease in OS when metastases were present at diagnosis (median 6.39 years) compared to CRPC-M (19.07) and CSPC-M (18.19 years). De-novo-M and CSPC-M showed a longer OS from occurrence of metastasis to death when compared to CRPC-M, although reaching CRPC earlier. There was no difference in OS between the groups once castration resistance was reached. Time from initial diagnosis to metastasis and to CRPC was correlated with OS and remained important prognosticators in multivariate Cox-regression (p < 0.01 for both). CONCLUSIONS: Time from diagnosis to CRPC (all patients) and time to metastasis (for CRPC-M and CSPC-M patients) are significant prognosticators of overall survival and are therefore valid surrogates in a study setting. Therefore, time to CRPC should be prolonged as long as possible.

Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study.

BACKGROUND: The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrating a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. METHODS: Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts received docetaxel (10 mg/kg) either subcutaneously (SC) or intravenously (IV) and the fourth cohort was treated using the magnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5 µg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using ultrasound. In addition, calipers were used to assess tumor volume. RESULTS: Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemic symptoms of inflammation and infection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that the mean tumor growth rate of our device cohort was significantly lower than SC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in the MADDD treated tumors and a decreased proliferation when compared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight loss) when compared to the device cohort. Finally, MADDD showed minimal expression of CD45 comparable to the control cohort, suggesting no signs of chronic inflammation. CONCLUSIONS: In conclusion, this study showed for the first time that MADDD, clearly suppressed tumor growth in local prostate cancer tumors. This could potentially be a novel clinical treatment approach for localized prostate cancer.

Effectiveness of first-line abiraterone versus enzalutamide among patients ≥80 years of age with metastatic castration-resistant prostate cancer: A retrospective propensity score-weighted comparative cohort study.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) disproportionately affects the elderly. There is limited data assessing the efficacy and tolerability of abiraterone acetate (AA) versus enzalutamide in this population. OBJECTIVE: To compare the clinical efficacy and tolerability of AA versus enzalutamide in patients ≥ 80 years with mCRPC. DESIGN, SETTING AND PARTICIPANTS: A retrospective propensity-weighted comparative cohort study of first-line AA versus enzalutamide among patients with mCRPC aged ≥80 years. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Inverse probability treatment weights based on propensity scores were generated to assess the treatment effect of AA versus enzalutamide on time to PSA progression (TTPP), time to progression (TTP) (first of PSA/radiographic/clinical progression) and overall survival using a weighted Cox proportional hazards model. PSA response rate (PSA RR) was compared between groups using Χ2. RESULTS AND LIMITATIONS: One hundred fifty-three patients received AA, and 125 received enzalutamide. Enzalutamide was associated with higher PSA RR (61.6% vs 43.8%, P < 0.004), and TTP (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.50-0.88, P = 0.01) but not TTPP (HR 0.73, 95% CI 0.53-1.01, P = 0.06). There were significantly more dose reductions with enzalutamide (22.9% vs 44.8%, P > 0.001) but there was no interaction between median proportion of full dose received and TTPP or TTP for either drug. Rates of treatment discontinuation (for reasons other than progression) were also significantly different between AA and enzalutamide (28.8% vs 40.8%, respectively, P = 0.04). The most common reason for dose reductions and discontinuation of enzalutamide was fatigue (30.4% and 5.6%, respectively). CONCLUSIONS: Despite more dose reductions and a higher treatment discontinuation rate, enzalutamide was associated with a higher PSA RR and longer time to progression, than AA. Given that clinical outcomes were not adversely impacted by decreased treatment exposure, dose modification may be a useful treatment strategy to balance toxicity and tolerance.

Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer.

BACKGROUND: Several systemic therapeutic options exist for metastatic castrate-sensitive prostate cancer (mCSPC). Circulating tumor DNA (ctDNA) can molecularly profile metastatic castration-resistant prostate cancer and can influence decision-making, but remains untested in mCSPC. OBJECTIVE: To determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: We collected plasma cell-free DNA (cfDNA) from 53 patients newly diagnosed with mCSPC and, where possible, during treatment. Targeted sequencing was performed on cfDNA and DNA from diagnostic prostate tissue. RESULTS AND LIMITATIONS: The median ctDNA fraction was 11% (range 0-84%) among untreated patients but was lower (1.0%, range 0-51%) among patients after short-term (median 22d) androgen deprivation therapy (ADT). TP53 mutations and DNA repair defects were identified in 47% and 21% of the cohort, respectively. The concordance for mutation detection in matched samples was 80%. Combined ctDNA and tissue analysis identified potential driver alterations in 94% of patients, whereas ctDNA or prostate biopsy alone was insufficient in 19 cases (36%). Limitations include the use of a narrow gene panel and undersampling of primary disease by prostate biopsy. CONCLUSIONS: ctDNA provides additional information to a prostate biopsy in men with de novo mCSPC, but ADT rapidly reduces ctDNA availability. Primary tissue and ctDNA share relevant somatic alterations, suggesting that either is suitable for molecular subtyping in de novo mCSPC. The optimal approach for biomarker development should utilize both a tissue and liquid biopsy at diagnosis, as neither captures clinically relevant somatic alterations in all patients. PATIENT SUMMARY: In men with advanced prostate cancer, tumor DNA shed into the bloodstream can be measured via a blood test. The information from this test provides complementary information to a prostate needle biopsy and could be used to guide management strategies. Sequencing data were deposited in the European Genome-phenome Archive (EGA) under study identifier EGAS00001003351.

Liquid Biopsy-Analysis of Circulating Tumor DNA (ctDNA) in Bladder Cancer.

Recent advances in DNA profiling techniques have enabled sensitive detection of tumor-associated genomic aberrations in peripheral blood. This type of minimally-invasive molecular interrogation has the potential to guide subsequent treatment selection. The potential utility of ctDNA in bladder cancer (BC) is bolstered by the high somatic mutation rate, meaning that very small numbers of genes or target regions can be informative. First reports indicate that analysis of ctDNA may represent a sensitive method for disease surveillance in patients with different stages of BC. Moreover, recent evidence suggests that ctDNA analysis reveals previously unknown genomic alterations in metastatic patients. Since some of these gene alterations represent therapeutic targets, ctDNA analysis provides an attractive tool to guide individualized therapy in BC.

The role of netrin-1 in metastatic renal cell carcinoma treated with sunitinib.

INTRODUCTION: Clear-cell renal cell carcinoma (ccRCC) is the sixth most common malignancy in men in North America. Since ccRCC is a malignancy dependent on neovascularization, current first line systemic therapies like sunitinib, target the formation of new vessels allowing nutrient deprivation and cell death. However, recent studies have shown that patients develop resistance after approximately 1 year of treatment and show disease progression while on therapy. Therefore, we propose to identify the protein(s) responsible for increased migration with the aim of developing a new therapy that will target the identified protein and potentially slow down the progression of the disease. MATERIAL AND METHODS: Human renal cancer cell lines (Caki-1, Caki-2, ACHN) were treated with increasing doses of sunitinib to develop a sunitinib-conditioned renal cell carcinoma cell line. mRNA microarray and qPCR were performed to compare the differences in gene expression between Caki-1 sunitinib-conditioned and non-conditioned cells. NTN1 was assessed in our in vivo sunitinib-conditioned mouse model using immunostaining. xCELLigence and scratch assays were used to evaluate migration and MTS was used to evaluate cell viability. RESULTS: Human renal cell carcinoma sunitinib-conditioned cell lines showed upregulation of netrin-1 in microarray and q-PCR. Increased migration was demonstrated in Caki-1 sunitinib-conditioned cells when compared to the non-treated ones as well as, increased endothelial cell migration. Silencing of netrin-1 in sunitinib-conditioned Caki-1 cells did not demonstrate a significant reduction in cell migration. CONCLUSION: Netrin-1 is highly upregulated in renal cell carcinoma treated with sunitinib, but has no influence on cell viability or cell migration in metastatic RCC.

Circulating Tumor DNA Reveals Clinically Actionable Somatic Genome of Metastatic Bladder Cancer.

Purpose: Targeted agents and immunotherapies promise to transform the treatment of metastatic bladder cancer, but therapy selection will depend on practical tumor molecular stratification. Circulating tumor DNA (ctDNA) is established in several solid malignancies as a minimally invasive tool to profile the tumor genome in real-time, but is critically underexplored in bladder cancer.Experimental Design: We applied a combination of whole-exome sequencing and targeted sequencing across 50 bladder cancer driver genes to plasma cell-free DNA (cfDNA) from 51 patients with aggressive bladder cancer, including 37 with metastatic disease.Results: The majority of patients with metastasis, but only 14% of patients with localized disease, had ctDNA proportions above 2% of total cfDNA (median 16.5%, range 3.9%-72.6%). Twelve percent of estimable samples had evidence of genome hypermutation. We reveal an aggressive mutational landscape in metastatic bladder cancer with 95% of patients harboring deleterious alterations to TP53, RB1, or MDM2, and 70% harboring a mutation or disrupting rearrangement affecting chromatin modifiers such as ARID1A Targetable alterations in MAPK/ERK or PI3K/AKT/mTOR pathways were robustly detected, including amplification of ERBB2 (20% of patients) and activating hotspot mutations in PIK3CA (20%), with the latter mutually exclusive to truncating mutations in TSC1 A novel FGFR3 gene fusion was identified in consecutive samples from one patient.Conclusions: Our study demonstrates that ctDNA provides a practical and cost-effective snapshot of driver gene status in metastatic bladder cancer. The identification of a wide spectrum of clinically informative somatic alterations nominates ctDNA as a tool to dissect disease pathogenesis and guide therapy selection in patients with metastatic bladder cancer. Clin Cancer Res; 23(21); 6487-97. ©2017 AACR.

Treatment Outcomes and Tumor Loss of Heterozygosity in Germline DNA Repair-deficient Prostate Cancer.

BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA). DESIGN, SETTING, AND PARTICIPANTS: We recruited 319 mCRPC patients and performed targeted germline sequencing of 22 DNA repair genes. In patients with deleterious germline mutations, plasma cell-free DNA was also sequenced. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-specific antigen response and progression were assessed in relation to initial androgen deprivation therapy (ADT) and subsequent therapy for mCRPC using Kaplan-Meier analysis. RESULTS AND LIMITATIONS: Of the 319 patients, 24 (7.5%) had deleterious germline mutations, with BRCA2 (n=16) being the most frequent. Patients (n=22) with mutations in genes linked to homologous recombination were heterogeneous at initial presentation but, after starting ADT, progressed to mCRPC with a median time of 11.8 mo (95% confidence interval [CI] 5.1-18.4). The median time to prostate-specific antigen progression on first-line AR-targeted therapy in the mCRPC setting was 3.3 mo (95% CI 2.7-3.9). Ten out of 11 evaluable patients with germline BRCA2 mutations had somatic deletion of the intact allele in ctDNA. A limitation of this study is absence of a formal control cohort for comparison of clinical outcomes. CONCLUSIONS: Patients with mCRPC who have germline DNA repair defects exhibit attenuated responses to AR-targeted therapy. Biallelic gene loss was robustly detected in ctDNA, suggesting that this patient subset could be prioritized for therapies exploiting defective DNA repair using a liquid biopsy. PATIENT SUMMARY: Patients with metastatic prostate cancer and germline DNA repair defects exhibit a poor response to standard hormonal therapies, but may be prioritized for potentially more effective therapies using a blood test.

The impact of perioperative complications on favorable outcomes after artificial urinary sphincter implantation for post-prostatectomy incontinence

ABSTRACT Objective To investigate the effect of perioperative complications involving artificial urinary sphincter (AUS) implantation on rates of explantation and continence as well as health-related quality of life (HRQOL). Materials and methods Inclusion criteria encompassed non-neurogenic, moderate-to-severe stress urinary incontinence (SUI) post radical prostatectomy and primary implantation of an AUS performed by a high-volume surgeon (>100 previous implantations). Reporting complications followed the validated Clavien-Dindo scale and Martin criteria. HRQOL was assessed by the validated IQOL score, continence by the validated ICIQ-SF score. Statistical analysis included Chi (2) test, Mann-Whitney-U test, and multivariate regression models (p <0.05). Results 105 patients from 5 centers met the inclusion criteria. After a median follow-up of 38 months, explantation rates were 27.6% with a continence rate of 48.4%. In the age-adjusted multivariate analysis, perioperative urinary tract infection was confirmed as an independent predictor of postoperative explantation rates [OR 24.28, 95% CI 2.81-209.77, p=0.004). Salvage implantation (OR 0.114, 95% CI 0.02-0.67, p=0.016) and non-prostatectomy related incontinence (OR 0.104, 95% CI 0.02-0.74, p=0.023) were independent predictors for worse continence outcomes. Low visual analogue scale scores (OR 9.999, 95% CI 1,42-70.25, p=0.021) and ICIQ-SF scores, respectively (OR 0.674, 95% CI 0.51-0.88, p=0.004) were independent predictors for increased HRQOL outcomes. Perioperative complications did not significantly impact on continence and HRQOL outcomes. Conclusion Findings show postoperative infections adversely affect device survival after AUS implantation. However, if explantation can be avoided, the comparative long-term functional results and HRQOL outcomes are similar between patients with or without perioperative complications.

Paratesticular fibrous pseudotumor in young males presenting with histological features of IgG4-related disease: two case reports.

INTRODUCTION: Paratesticular fibrous pseudotumors represent benign new growths confined to intrascrotal structures. Both pathogenesis and clinical management are little understood due to the rarity of the lesion, with less than 200 cases reported to date. Recently, paratesticular fibrous pseudotumors have been postulated to be immunoglobulin G4-related, pathogenetically. Here we report two cases of patients with paratesticular fibrous pseudotumor to highlight the clinical features of this rare disease and we report the immunohistochemical examinations to support the theory of paratesticular fibrous pseudotumor being an immunoglobulin G4-related disease. CASE PRESENTATIONS: A 28-year-old white man presented with a painless intrascrotal mass. After a clinical examination, a malignant growth was suspected. His ultrasound results revealed a well-demarcated hypoechoic lesion of 1.5cm in diameter at the spermatic cord. Our patient underwent local excision. His follow-up has been uneventful for 12 years. The second case was an 18-year-old white man who presented with a painless scrotal mass suspicious of testicular tumor. A magnetic resonance imaging scan revealed a 3cm mass at the spermatic cord with very low signal density on T2-weighted imaging and a low and inhomogeneous uptake of gadolinium contrast agent on T1-weighted, fat-suppressed imaging. Following local excision, our patient has been well for 18 months.On histological examination, both of the lesions consisted of collagen-rich hyalinized fibrotic tissue with storiform features. There were lymphofollicular infiltrates and, sporadically, also venulitis. The immunoglobulin G4 staining (in case 2) showed an infiltrate of 10 to 15 positive cells per high-power field on average, corresponding to a proportion of 40% in evaluable hot spots. The two patients with paratesticular fibrous pseudotumor presented within a time span of 15 years. During that time, 400 patients with testicular germ cell tumors had been treated in our institution. CONCLUSIONS: The specific histological features documented in our case lend support to the theory of paratesticular fibrous pseudotumor being an immunoglobulin G4-related sclerosing disorder. Paratesticular fibrous pseudotumors usually occur in young adulthood. Clinically, paratesticular fibrous pseudotumor can mimic testicular malignancy. Ultrasonographic findings are largely unspecific, however, scrotal magnetic resonance imaging may aid in discriminating the lesion from malignant tumors. Local excision, whenever technically feasible, is the preferred treatment of paratesticular fibrous pseudotumor.

Evidence for acute vascular toxicity of cisplatin-based chemotherapy in patients with germ cell tumour.

BACKGROUND: Acute early vascular toxicity of chemotherapy for germ cell tumour (GCT) is poorly understood. To explore the pathogenesis of this complication we evaluated laboratory parameters associated with vascular disease. PATIENTS AND METHODS: In 33 GCT patients the following parameters were investigated with routine laboratory methods before and after chemotherapy: von Willebrand factor antigen (vWF:AG), collagen binding capacity (vWF:CB), lipoprotein (a), homocysteine, plasminogen activator inhibitor I, total cholesterol, high density lipoprotein, low density lipoprotein, troponine I. Statistical evaluation involved descriptive analysis and the Wilcoxon signed rank test. RESULTS: Levels of vWF:AG and vWF:CB increased significantly upon therapy (p=0.002). All other parameters remained unchanged. Upon late measurement, vWF:AG and vWF:CB were normalised. CONCLUSION: As von Willebrand factor is released from endothelial cells upon damage, we postulate that early vascular toxicity of chemotherapy is caused by direct damage of the vascular endothelium. Long-term vascular complications of chemotherapy appear to be different, pathogenetically.