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ABSTRACT: INTRODUCTION: Penile fracture is an emergency in urology. Surgical management is recommended, but objective data of postoperative long-term effects, especially regarding voiding and erectile function, vary. AIM: To assess long-term results of patients undergoing surgical therapy for penile fracture. METHODS: Patients presenting with suspicion of penile fracture were included in this study. Diagnosis of penile fracture was made by clinical assessment and surgery performed thereafter. The defect of the tunica albuginea was closed by absorbable suture. In case of concomitant urethral lesion, the defect was repaired simultaneously. Voiding and erectile function were evaluated at long-term follow-up by mail. Patients' status before penile fracture was assessed retroactively. MAIN OUTCOME MEASURES: Erectile function was assessed by the International Index of Erectile Function questionnaire and voiding function by the International Prostate Symptom Score questionnaire. RESULTS: N = 34 patients were included. Penile fracture was suspected in 28/34 (82.4%) patients. Twenty-six of the 28 (92.9%) patients underwent surgery. Only less than half of confirmed fracture patients presented with the classical triad of an audible crack, detumescense, and hematoma. Fourteen of the 26 (53.8%) patients after surgery were available for follow-up. Mean follow-up was 45.6 months (range: 3.6-128.4). In 13/14 (92.9%) patients, penile fracture was confirmed by surgery. At follow-up, 7/13 (53.8%) patients had impaired erectile function, with 3/13 (23.1%) patients needing medical treatment. Four of the 13 (30.8%) patients showed deterioration of voiding including occurrence of urethral fistula. CONCLUSIONS: Penile fracture is an emergency for which surgery should be offered. Clinical suspicion of fracture should be high even with hematoma alone. Concomitant urethral injury is common, particularly with bilateral corporal rupture and/or initial hematuria. Preoperative counseling should include discussion of long-term erectile and voiding dysfunction, penile deformity, and urethral fistula both with and without surgery. Close patient follow-up is required.
Journal of Sexual Medicine 02/2013; · 3.55 Impact Factor
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ABSTRACT: Bladder cancer is the second most common tumor of the genitourinary system. Although transurethral resection is the standard diagnostic and therapeutic procedure, it is not morbidity free. Bladder perforation is the second most common complication and it can lead to severe further complications. We evaluated risk factors for bladder perforation in patients treated with transurethral resection of bladder tumors.
We retrospectively studied the records of 1,284 patients with bladder cancer who underwent transurethral resection of bladder tumors between 1986 and 2006. Data on risk factors for bladder perforation, including age, gender, body mass index, nicotine use, gross hematuria, transurethral catheterization, bladder stones, tumor stage and grade, number of tumors and resection weight, were analyzed with the chi-square or Fisher exact test.
Of the 49 bladder perforations (3.8%) 89.8% were extraperitoneal and 10.2% were intraperitoneal. The risk of bladder perforation was associated with gender (female and male 7.2% and 2.6%, p <0.001), body mass index (less than 25, 25 to 30 and greater than 30 kg/m(2) 5.5%, 3.4% and 0.6%, p = 0.016), tumor stage (pTis, pTa, pT1 and pT2 or greater 3.7%, 2.6%, 4.5% and 6.7%, p = 0.049), infiltration depth (superficial and muscle invasive 3.2% and 6.6%, p = 0.023) and resection weight (less than 2.5 and 20 gm or greater 2.4% and 9.2%, respectively, p = 0.003). Patient age, nicotine use, gross hematuria at diagnosis, transurethral catheterization, bladder stones, number of tumors and tumor grade were not risk factors for bladder perforation.
Aside from tumor characteristics female gender and low body mass index were risk factors for inadvertent bladder perforation during transurethral resection of bladder tumors. Each factor is readily apparent.
The Journal of urology 03/2012; 187(5):1566-70. · 4.02 Impact Factor
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ABSTRACT: The outcome of prostate cancer (CaP) patients treated with radical prostatectomy (RP) might be influenced by family history (FH) in a subset of patients. We analysed the effect of sporadic, familial and hereditary CaP stratified by risk on clinico-pathologic characteristics and biochemical recurrence-free survival (bRFS) following RP.
Data of 8041 German patients treated with RP between 1994 and 2008 in Germany were analysed. We evaluated the impact of FH stratified by D'Amico's risk classification on pathologic characteristics using Cochran-Mantel-Haenszel tests. The impact of FH stratified by risk on bRFS was analysed in a proportional hazards regression.
Five thousand seven hundred and fifty six (71.6%) had sporadic, 1779 (22.1%) familial and 506 (6.3%) hereditary CaP. Adjusted for risk group, FH was associated with age of onset <65 years (p<0.001) but not with pathological characteristics or bRFS. The subgroup of patients with high risk and hereditary CaP numerically had the lowest bRFS rate at 5 (52.9%) and 10 (30.7%) years. However, this observation was statistically insignificant (p = 0.267). Familial and hereditary CaP patients were 1-2 years younger than sporadic cases at CaP diagnosis.
Sporadic, familial and hereditary CaP have the same pathologic characteristics and bRFS rate following RP. Patients with a positive family history are diagnosed earlier than sporadic patients. Stratification in subgroups by risk group did not add further information.
European journal of cancer (Oxford, England: 1990) 11/2011; 48(9):1312-7. · 4.12 Impact Factor
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Lingyi Lu,
Geraldine Cancel-Tassin,
Antoine Valeri,
Olivier Cussenot,
Ethan M Lange,
Kathleen A Cooney,
James M Farnham,
Nicola J Camp,
Lisa A Cannon-Albright,
Teuvo L J Tammela, [......],
Dallas R English,
William D Foulkes,
Lovise Maehle,
Pal Moller,
Michael D Badzioch,
Steve Edwards,
Michelle Guy,
Ros Eeles,
Douglas Easton,
William B Isaacs
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ABSTRACT: In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members.
In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups.
Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology.
These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer.
The Prostate 07/2011; 72(4):410-26. · 3.48 Impact Factor
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ABSTRACT: Fusion of the 5'-untranslated region of androgen-regulated TMPRSS2 promoter with ETS transcription factor family members is found frequently in prostate cancers, and recent work suggests that the most common TMPRSS2-ERG fusion is associated with an aggressive clinical phenotype compared with fusion-negative prostate cancer. Thus far, analysis of the fusion has been limited to sporadic cases of prostate cancer. In the current study, we explore for an enrichment of TMPRSS2-ERG fusion in familial prostate cancer. TMPRSS2-ERG fusion was identified using a break-apart fluorescence in situ hybridization assay on tissue microarrays. Presence of TMPRSS2-ERG fusion was associated with higher Gleason scores (P = 0.027). Of 75 patients with established history of prostate cancer, we detected the TMPRSS2-ERG fusion in 44 (59%) patients. Almost three quarters (73%) of fusion-positive patients accumulated within 16 specific families whereas only 27% were single fusion-positive cases within one family. Based on reported prevalence rates, we calculated a sibling recurrence risk ratio of up to 18.9. A subset (63%) of families with uniformly TMPRSS2-ERG-positive prostate cancer underwent a genome-wide linkage scan at 500 markers. This revealed several loci located on chromosomes #9, #18, and X that were suggestive of linkage to the TMPRSS2-ERG fusion-positive prostate cancer phenotype with linkage-of-disease scores up to 2.16 and nonparametric linkage scores up to 2.77. This suggests the presence of an inherited susceptibility to developing the TMPRSS2-ERG fusion. Given the association of TMPRSS2-ERG fusion and aggressive prostate cancer, close surveillance of relatives of patients with established fusion-positive prostate cancer or a family history of prostate cancer in general would be warranted.
Cancer Research 02/2009; 69(2):640-6. · 7.86 Impact Factor
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Daniel J Schaid,
Shannon K McDonnell,
Katherine E Zarfas,
Julie M Cunningham,
Scott Hebbring,
Stephen N Thibodeau,
Rosalind A Eeles,
Douglas F Easton,
William D Foulkes,
Jacques Simard, [......],
Monica Emanuelsson,
Elisabeth Stenman,
Björn-Anders Jonsson,
Henrik Grönberg,
Nicola J Camp,
James Farnham,
Lisa A Cannon-Albright,
William J Catalona,
Brian K Suarez,
Kimberly A Roehl
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ABSTRACT: While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1-14.3 (LOD = 2.4), and 20p11.21-q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13-22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives.
Human Genetics 12/2006; 120(4):471-85. · 5.07 Impact Factor
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Scott J Hebbring,
Henna Fredriksson,
Kirsten A White,
Christiane Maier,
Charles Ewing,
Shannon K McDonnell,
Steven J Jacobsen,
James Cerhan,
Daniel J Schaid,
Tarja Ikonen, [......],
Teuvo L J Tammela, Kathleen Herkommer,
Thomas Paiss,
Walther Vogel,
Marta Gielzak,
Jurga Sauvageot,
Johanna Schleutker,
Kathleen A Cooney,
William Isaacs,
Stephen N Thibodeau
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ABSTRACT: The Nijmegen breakage syndrome 1 (NBS1) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer. Numerous mutations have been identified in NBS1, including the founder mutation 657del5. In this study, a number of analyses were done to determine whether mutations in NBS1 are associated with an increased risk for prostate cancer. The frequency of the 657del5 mutation in both familial prostate cancer cases (1,819 affected men among 909 families) and sporadic prostate cancer cases (1,218 affected men) collected from five centers participating in the International Consortium for Prostate Cancer Genetics were compared with that found in 697 normal controls. Seven individuals were identified to carry the mutation among the 3,037 cases screened: four in the familial group (three from one family and one from another) and three in the sporadic cases. The carrier frequency was 0.22% (2 of 909) for the probands and 0.25% (3 of 1,218) for the sporadic cases of prostate cancer. The 657del5 mutation was not detected in either the 293 unaffected members of the prostate cancer families or in the 697 control samples tested. The entire NBS1 gene was also sequenced in 20 of the youngest affected individuals from the Finnish group of familial cases to identify the presence of possible mutations in this high-risk group. One rare (D95N) and one common (E185Q) missense alteration was identified. More detailed analyses of the E185Q polymorphism, along with a third rare variant (R215W), failed to show an association with prostate cancer. Because the 657del5 mutation was absent from the control population, we are unable to determine if this alteration predisposes to prostate cancer. However, our data does suggest that mutations within NBS1, and in particular, 657del5, do not significantly contribute to the overall prostate cancer burden within our patient samples.
Cancer Epidemiology Biomarkers & Prevention 06/2006; 15(5):935-8. · 4.12 Impact Factor
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ABSTRACT: The MSR1 gene at 8p22 has been suggested as a candidate gene for hereditary prostate cancer because germline variants have been found to be associated with the disease. Aside from a single nonsense mutation (R293X) that was found repeatedly at low frequencies in several samples, little evidence has been gained by follow-up studies to confirm the gene's relevance for prostate cancer. Prompted by reasonable support for a linkage to 8p22, we sought to determine the mutation spectrum of MSR1 in our family sample. Screening of 139 probands (representing 139 prostate cancer families) revealed 15 novel and a total of 20 sequence variants within the 10 coding exons and their intronic proximities. Aside from the known mutation c.877C>T (R293X) present in two of our families, we identified a second nonsense allele (c.251C>G; S84X) and a splice-site mutation (c.818-1G>A) that results in mRNA instability (each in a single pedigree). The novel missense alleles were c.703C>T (H235Y), c.856C>T (P286S), c.905C>T (P302L), c.1193C>G (A398G), and c.1289A>G (K430R). Of the eight variants that affect the encoded protein (splice site, nonsense, and missense), only R293X as well as the polymorphism c.823C>G (P275A) were additionally present at remarkable frequencies in further samples of sporadic prostate cancer and controls. Of note, carriers of R293X were equally frequent in 367 sporadic prostate cancer cases (1.9%) and in 197 controls (2.0%). To our knowledge, our study is the first to demonstrate further loss of function variants of MSR1 apart from R293X. Nevertheless, the low frequencies of deleterious alleles, in addition to an apparently moderate penetrance, does not support MSR1 as a major susceptibility gene in this family sample.
Human Mutation 01/2006; 27(1):98-102. · 5.69 Impact Factor
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ABSTRACT: Several linkage studies have provided evidence for a prostate cancer aggressiveness gene on chromosome 7q. This report details the results of the first mutation screen and association study of EZH2 (located at 7q35) as a potential candidate gene for the development of aggressive prostate cancer.
In 10 families with linkage of chromosome 7q31-33 to aggressive prostate cancer, we sequenced the promoter region and all 20 exons of EZH2. We genotyped 11 variants in 287 prostate cancer probands and 96 controls. Association between the disease and the variants/haplotypes was evaluated taking into account clinical data and disease recurrence.
The individual variation sites did not show significant differences in the allele frequencies between cases and controls. In contrast, one haplotype had a higher frequency in controls, and another haplotype was significantly more frequent in cases with low grade tumors (GI/II) and progression free survival (NED).
We have possibly identified haplotypes which mark alleles that have a beneficial effect on the development of prostate cancer. Moreover, our results suggest that genetic variations of the EZH2 gene are not responsible for the linkage of 7q to aggressive prostate cancer.
The Prostate 12/2005; 65(3):252-9. · 3.48 Impact Factor
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ABSTRACT: Multiple lines of evidence have implicated the CAV-1 gene in prostate cancer progression. CAV-1 is located within the prostate cancer aggressiveness locus at 7q31-33, and was identified as being overexpressed in prostate tumors. Mutation screening was performed as well as a case-control study to examine if polymorphisms in CAV-1 are associated with prostate cancer aggressiveness in a German population.
We sequenced the CAV-1 promoter region and its open reading frame in prostate cancer families with linkage to chromosome 7q31-33. Additionally, 105 unrelated familial prostate cancer probands, 190 sporadic cases, and 191 controls were genotyped at four intronic single nucleotide polymorphisms. Resulting haplotypes were tested for association using age at diagnosis, tumor grade, TNM stage, and follow up information to stratify for aggressive disease.
No mutation was found in the CAV-1 coding region or in the promoter. One of the 11 observed haplotypes showed an increased frequency in cases with high tumor stage (P = 0.03).
This is the first report providing evidence for CAV-1 being involved in predisposition to aggressive prostate cancer. The association of a potential risk haplotype agrees well with a role of CAV-1 in tumor progression but needs further confirmation.
The Prostate 11/2005; 65(2):171-7. · 3.48 Impact Factor
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Jianfeng Xu,
Latchezar Dimitrov,
Bao-Li Chang,
Tamara S Adams,
Aubrey R Turner,
Deborah A Meyers,
Rosalind A Eeles,
Douglas F Easton,
William D Foulkes,
Jacques Simard, [......],
Thomas Paiss,
Fredrik Wiklund,
Monica Emanuelsson,
Elisabeth Stenman,
Bjorn-Anders Jonsson,
Henrik Gronberg,
Nicola J Camp,
James Farnham,
Lisa A Cannon-Albright,
Daniela Seminara
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ABSTRACT: Evidence of the existence of major prostate cancer (PC)-susceptibility genes has been provided by multiple segregation analyses. Although genomewide screens have been performed in over a dozen independent studies, few chromosomal regions have been consistently identified as regions of interest. One of the major difficulties is genetic heterogeneity, possibly due to multiple, incompletely penetrant PC-susceptibility genes. In this study, we explored two approaches to overcome this difficulty, in an analysis of a large number of families with PC in the International Consortium for Prostate Cancer Genetics (ICPCG). One approach was to combine linkage data from a total of 1,233 families to increase the statistical power for detecting linkage. Using parametric (dominant and recessive) and nonparametric analyses, we identified five regions with "suggestive" linkage (LOD score >1.86): 5q12, 8p21, 15q11, 17q21, and 22q12. The second approach was to focus on subsets of families that are more likely to segregate highly penetrant mutations, including families with large numbers of affected individuals or early age at diagnosis. Stronger evidence of linkage in several regions was identified, including a "significant" linkage at 22q12, with a LOD score of 3.57, and five suggestive linkages (1q25, 8q13, 13q14, 16p13, and 17q21) in 269 families with at least five affected members. In addition, four additional suggestive linkages (3p24, 5q35, 11q22, and Xq12) were found in 606 families with mean age at diagnosis of < or = 65 years. Although it is difficult to determine the true statistical significance of these findings, a conservative interpretation of these results would be that if major PC-susceptibility genes do exist, they are most likely located in the regions generating suggestive or significant linkage signals in this large study.
The American Journal of Human Genetics 08/2005; 77(2):219-29. · 10.60 Impact Factor
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ABSTRACT: Prostate cancer is a complex disease with a substantial genetic contribution involved in the disease risk. Several genomewide linkage studies conducted so far have demonstrated a strong heterogeneity of susceptibility. In order to assess candidate regions that are particularly relevant for the German population, we performed a genomewide linkage search on 139 prostate cancer families. A nonparametric method (Zlr scores), using GENEHUNTERPLUS, was applied at 500 markers (panel P1400, deCODE), with an average spacing of 7.25 cM. In the entire family collection, linkage was most evident at 8p22 (Zlr=2.47, P=0.0068), close to the previously identified susceptibility gene MSR1. Further local maxima with Zlr>2 (P<0.025) were observed at 1q, 5q and 15q. In a subgroup of 47 families, which matched the Johns Hopkins criteria of hereditary prostate cancer, suggestive linkage was found on 1p31 (Zlr=3.37, P=0.00038), a previously not described candidate region. The remaining 92 pedigrees, with no strong disease history, revealed a maximum Zlr=3.15 (P=0.00082) at 8q13, possibly indicating a gene with reduced penetrance or recessive inheritance. Our results suggest pronounced locus heterogeneity of prostate cancer susceptibility in Germany. In the present study population, the MSR1 gene could play a significant role. Other conspicuous loci, like 1p31 and 8q13, need further investigation in order to verify their relevance and to identify candidate genes.
European Journal of HumanGenetics 03/2005; 13(3):352-60. · 4.40 Impact Factor
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ABSTRACT: January 1986 and September 2003 cystectomy and formation of an ileal neobladder were performed in 86 female patients. In this retrospective study we focused on the impact of orthotopic reconstruction on female sexuality.
To assess female sexuality the standardized self-reporting instrument female sexual function index was mailed to 44 patients who were 70 years or younger at cystectomy with a recurrence-free followup of greater than 1 year, no pelvic irradiation and no concomitant diseases impairing sexual functions. The questionnaire analyzes 6 domains (desire, arousal, lubrication, orgasm, satisfaction and pain) with 19 items. It was returned by 29 patients (65.9%) with a median age of 65.0 years. The indication for cystectomy was benign disease in 8 cases and malignancy in 21.
Factors influencing female sexuality were age younger than 60 years, benign disease, partnership at surgery and current partnership. Clean intermittent catheterization, urinary stress incontinence and hormonal therapy did not affect the results. The 11 of 17 patients who remained sexually active after cystectomy even had slight improvement in all female sexual function items. Six patients ceased to be sexually active postoperatively due to erectile dysfunction or partner death. One patient with interstitial cystitis became sexually active following cystectomy due to the loss of pelvic pain. Another 12 patients remained sexually inactive postoperatively.
All aspects of female sexuality may remain unchanged following cystectomy and ileal neobladder formation as long as sexual activity is not ceased due to other reasons. Even fertility can be preserved when the internal genitalia do not have to be removed.
The Journal of Urology 12/2004; 172(6 Pt 1):2353-7. · 3.75 Impact Factor
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ABSTRACT: Radical prostatectomy is a standard therapy for patients with prostate cancer diagnosed by prostatic needle biopsy, prostate cytology, transurethral resection of the prostate or prostatectomy. In a small group of patients no tumour can be found in the radical prostatectomy specimen. These cases are classified as stage pT0. The aim of this study was to evaluate the clinical presentation of this entity and their prognosis.
In a nation-wide database the clinical data of 3609 patients with prostate cancer were collected. 28 patients (0.8%) were staged as pT0 in the radical prostatectomy specimen. The data included age, prostate specific antigen (PSA), and pathological report at diagnosis, histology of the radical prostatectomy specimen and follow-up data.
The diagnosis was made by TURP (transurethral resection of the prostate) in 15, prostatectomy in 2, needle biopsy in 11, and cytology in 2 patients. For patients who underwent TURP or prostatectomy the preoperative staging was T1a in 10 and T1b in 5 cases. 12 patients diagnosed by biopsy or cytology were classified T2a and one patient after biopsy as T2b. 9 patients had a GI- and 19 a GII-tumour, GIII-pattern was not represented. The mean age at diagnosis was 64.7 years (range 53-79 years). The PSA at the time of diagnosis was <4ng/ml in 8 cases; 4-10ng/ml in 16 cases and >10ng/ml in 4 patients. One patient presented with a micrometastasis in a single lymph node. Median follow-up was 62 months (19-150). All patients had undetectable PSA levels following surgery. No patient presented with clinical or biochemical progression. One patient died with no evidence of disease at 133 months after radical prostatectomy.
None of the clinical parameters had a strong association with a pathologically proven T0 situation after radical prostatectomy in this setting. Interestingly no patient had a high-grade tumour. None of the patients classified as pT0 had a biochemical or clinical relapse during follow-up.
European Urology 02/2004; 45(1):36-41. · 8.49 Impact Factor
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ABSTRACT: It has been suggested that chromosome 7q32 contains genes that influence the progression of prostate cancer from latent to invasive disease. In an attempt to confirm this linkage to prostate cancer aggressiveness, 100 German prostate cancer families were genotyped using a panel of eight polymorphic markers on chromosome 7q. We used a multipoint allele sharing method based upon a likelihood ratio test implemented in GENEHUNTERPLUS v1.2 in order to calculate the nonparametric Z(lr) and the associated LOD scores. We applied the aggressiveness of prostate cancer given by the pathological tumour grade of each individual, and the mean age of onset of a family as covariates, and constructed two weighted models. The first (weight(0-1) model) puts weights on families with at least two cases of GIII prostate cancer. The second (weight(0-2) model) also adds weights to families with early and late onset cancer respectively. The unweighted analysis gave no evidence of linkage to chromosome 7q. The Z(lr) scores increased when including the covariates, to 2.60 (P=0.005) using the weight(0-1) and to 3.02 (P=0.001) using the weight(0-2) model for late onset prostate cancer. The associated LOD scores were respectively 1.47 (P=0.009) and 1.98 (P=0.002). The markers that gave most evidence for linkage were exactly in the range of the published prostate cancer aggressiveness region. Our results support a widespread relevance of this locus and suggest that aggressive and late onset prostate cancer is linked to chromosme 7q31-33 in the German population.
European Journal of HumanGenetics 02/2003; 11(1):17-22. · 4.40 Impact Factor
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ABSTRACT: Several prostate cancer (PCa) susceptibility loci have been reported, but attempts to confirm them in independent data sets have produced inconsistent results. It is not yet clear, how much of this variation is due to differences between different populations. HPCX was originally identified in a combined data set of PCa families from the USA and Scandinavia. Considerable differences in the frequency of linked families were observed in this heterogeneous family sample as well as in following studies.
In order to estimate the significance of HPCX in the German population, DNA samples from 104 PCa families were genotyped at six polymorphic markers spanning a region of approximately 14 cM on Xq27-28, which includes the proposed HPCX candidate locus.
In the entire data set, a maximum NPL Z score of 1.20 (P = 0.11) at marker DXS984 was observed. Statistically significant evidence for linkage was obtained in the subset of 63 families with early-onset disease (i.e., < or = 65 years) with a maximum NPL Z score of 2.32 (P = 0.009) at the same location.
Our results confirm the existence of a prostate cancer susceptibility gene on Xq27-28 also in the German population.
The Prostate 06/2002; 52(1):12-9. · 3.48 Impact Factor
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ABSTRACT: A thymidine to cytosine transition (designated A2 variant) in the promoter region of CYP17 has previously been associated with a familial history of prostate cancer in North American families. The purpose of the present study was to determine whether this correlation could be replicated in a European population.
Case-control comparisons were performed by modelling a dominant (A1/A2 + A2/A2 vs. A1/A1) and a recessive (A2/A2 vs. A1/A2 + A1/A1) effect of the promoter modification.
An insignificant overrepresentation of homozygous carriers of the A2 allele (recessive effect) was found in sporadic cases, as compared to controls. However, the A2 variant was not related to familial disease.
Our results do not suggest a role of CYP17 as a high-risk susceptibility gene for familial prostate cancer, nor as a modifier for the disease risk in the European population.
Anticancer research 25(2B):1303-7. · 1.73 Impact Factor
