9 research outputs found
Natural history of benign prostatic hyperplasia: Appropriate case definition and estimation of its prevalence in the community
There is no consensus about a case definition of benign prostatic hyperplasia (BPH). In the present study, BPH prevalence rates were determined using various case definitions based on a combination of clinical parameters used to describe the properties of BPH: symptoms of prostatism, prostate volume increase, and bladder outflow obstruction. The aim of this study—in a community-based population of 502 men (55–74 years of age) without prostate cancer—was to determine the relative impact on prevalence rates of the inclusion of these different parameters (and of different cutoff values for these parameters) in a case definition of BPH. There is agreement that age is the dominant determinant of BPH. However, of 28 different case definitions that were formulated only eight gave a statistically significant increase in the prevalence of BPH with age. The highest overall prevalence of 19% (95% confidence interval [CI], 15–23%) occurred using the definition that combines a prostate volume >30 cm3 and an International Prostate Symptom Score (IPSS) >7. The lowest prevalence rate of 4.3% (95% CI, 2-6%) occurred using the definition that combines a prostate volume >30 cm3, an IPSS >7, a maximum flow rate 50 mL Thus, prevalence rates depend very much on the parameters used in a case definition. Follow-up will establish which men will eventually request a workup and treatment for BPH and will help determine the best clinical definition of BPH
Prostate specific antigen in a community-based sample of men without prostate cancer: Correlations with prostate volume, age, body mass index, and symptoms of prostatism
The correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community‐based population. A sample of 502 men aged 55 through 74 years was evaluated, excluding those with a serum PSA above 10 ng/ml, those with biopsy proven prostate cancer, and those who had previously undergone a prostate operation. PSA and PSAD did not correlate with the body mass index. Weak correlations were found betwe
FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma
Fibroblast growth factor receptor 3 (FGFR3) and P53 mutations are
frequently observed in bladder cancer. We here describe the distribution
of FGFR3 mutations and P53 overexpression in 260 primary urothelial cell
carcinomas. FGFR3 mutations were observed in 59% and P53 overexpression in
25%. Interestingly, FGFR3 and P53 alterations were mutually exclusive,
because they coincided in only 5.7% of tumors. Consequently, we propose
that they characterize two alternative genetic pathways in urothelial cell
carcinoma pathogenesis. The genetic alterations were reflected in the
pathology and the clinical outcome, i.e., FGFR3 mutations were found in
low-stage/-grade tumors and were associated with a favorable disease
course, whereas P53 alterations were tied to adverse disease parameters
Combined microsatellite and FGFR3 mutation analysis enables a highly sensitive detection of urothelial cell carcinoma in voided urine
PURPOSE: Fibroblast growth factor receptor 3 (FGFR3) mutations were
reported recently at a high frequency in low-grade urothelial cell
carcinoma (UCC). We investigated the feasibility of combining
microsatellite analysis (MA) and the FGFR3 status for the detection of UCC
in voided urine. EXPERIMENTAL DESIGN: In a prospective setting, 59 UCC
tissues and matched urine samples were obtained, and subjected to MA (23
markers) and FGFR3 mutation analysis (exons 7, 10, and 15). In each case,
a clinical record with tumor and urine features was provided. Fifteen
patients with a negative cystoscopy during follow-up served as controls.
RESULTS: A mutation in the FGFR3 gene was found in 26 (44%) UCCs of which
22 concerned solitary pTaG1/2 lesions. These mutations were absent in the
15 G3 tumors. For the 6 cases with leukocyturia, 46 microsatellite
alterations were found in the tumor. Only 1 of these was also detected in
the urine. This was 125 of 357 for the 53 cases without leukocyte
contamination. The sensitivity of MA on voided urine was lower for
FGFR3-positive UCC (15 of 21; 71%) as compared with FGFR3 wild-type UCC
(29 of 32; 91%). By including the FGFR3 mutation, the sensitivity of
molecular cytology increased to 89% and was superior to the sensitivity of
morphological cytology (25%) for every clinical subdivision. The
specificity was 14 of 15 (93%) for the two (molecular and morphological)
cytological approaches. CONCLUSIONS: Molecular urine cytology by MA and
FGFR3 mutation analysis enables a highly sensitive and specific detection
of UCC. The similarity of molecular profiles in tumor and urine
corroborate their clonal relation
Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors
Testicular germ-cell tumors (TGCTs) of adolescents and adults originate
from intratubular germ cell neoplasia (ITGCN), which is composed of the
malignant counterparts of embryonal germ cells. ITGCN cells are
characterized, among others, by the presence of stem cell factor receptor
c-KIT. Once established, ITGCN will always progress to invasiveness.
Approximately 2.5-5% of patients with a TGCT will develop bilateral
disease and require complete castration, resulting in infertility, a need
for lifelong androgen replacement, and psychological stress. To date, the
only way to predict a contralateral tumor is surgical biopsy of the
contralateral testis to demonstrate ITGCN. We did a retrospective study of
224 unilateral and 61 proven bilateral TGCTs (from 46 patients, in three
independently collected series in Europe) for the presence of activating
c-KIT codon 816 mutations. A c-KIT codon 816 mutation was found in three
unilateral TGCT (1.3%), and in 57 bilateral TGCTs (93%; P < 0.0001). In
the two wild-type bilateral tumors for which ITGCN was available, the
preinvasive cells contained the mutation. The mutations were somatic in
origin and identical in both tumors. We conclude that somatic activating
codon 816 c-KIT mutations are associated with development of bilateral
TGCT. Detection of c-KIT codon 816 mutations in unilateral TGCT identifies
patients at risk for bilateral disease. These patients may undergo
tailored treatment to prevent the development of bilateral disease, with
retention of testicular hormonal function
High-dose-rate brachytherapy and external-beam radiotherapy for hormone-naïve low- and intermediate-risk prostate cancer: A 7-year experience
Purpose: To report clinical outcomes and early and late complications in 264 hormone-naïve patients with low- and intermediate-risk prostate cancer treated with high-dose-rate brachytherapy (HDR-BT) in combination with external-beam radiotherapy (EBRT). Methods and Materials: Between February 2000 and July 2007, 264 patients underwent HDR-BT in combination with EBRT as a treatment for their low- to intermediate-risk prostate cancer. The HDR-BT was performed using ultrasound-based implantation. The total HDR-BT dose was 18 Gy in 3 fractions within 24 h, with a 6-h minimum interval. The EBRT started 2 weeks after HDR-BT and was delivered in 25 fractions of 1.8 Gy to 45 Gy within 5 weeks. Results: After a mean follow-up of 74.5 months, 4 patients (1.5%) showed prostate-specific antigen progression according to the American Society for Radiation Oncology definition and 8 patients (3%) according to the Phoenix definition. A biopsy-proven local recurrence was registered in 1 patient (0.4%), and clinical progression (bone metastases) was documented in 2 patients (0.7%). Seven-year actuarial freedom from biochemical failure was 97%, and 7-year disease-specific survival and overall survival were 100% and 91%, respectively. Toxicities were comparable to other series. Conclusions: Treatment with interstitial HDR-BT plus EBRT shows a low incidence of late complications and a favorable oncologic outcome after 7 years follow-up
Toxicity and quality of life after high-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer
Background and purpose The use of HDR brachytherapy (HDR-BT) as monotherapy for prostate cancer (PC) is increasing worldwide with good tumour control rates and acceptable toxicity. We report our results on toxicity and quality of life (QoL) after HDR-BT monotherapy for PC patients. Materials and methods 166 low- and intermediate-risk localized PC patients were treated with HDR-BT to a total dose of 38 Gy in four fractions. Genitourinary (GU) and gastrointestinal (GI) toxicities were prospectively assessed using EORTC-RTOG questionnaires and physicians charts. QoL was evaluated using EORTC QLQ-PR25 questionnaires. Results Three months after treatment, acute GU and GI toxicities were reported in 10.8% and 7.2%. Acute toxicity resolved within two months in the majority of patients (61%). Late grade ≥2 GU and GI toxicity were reported in 19.7% and 3.3% of patients 12 months after HDR-BT. Mean QLQ-PR25 scores showed clinically relevant changes from baseline for urinary symptoms and sexual functioning. With a mean follow-up of 35 months, biochemical failure was observed in 2.4%. Overall survival at 60 months was 93.6% and cancer-specific survival was 100%. Conclusions HDR-BT monotherapy for localized PC showed excellent clinical outcome and acceptable acute and late toxicity. Urinary symptoms and sexual function QoL decreased after treatment
Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice
BACKGROUND: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment.METHODS: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes.RESULTS: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). CONCLUSIONS: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.</p