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H Knönagel

Publications and source records attributed to H Knönagel.

At least 19 recordsLinked to original sources
PubMed2002

[Urolithiasis and ultrasound diagnosis. Value of ultrasound in diagnosis of urolithiasis].

In Europe and the United States urolithiasis is a very common clinical finding. In primary diagnostic and at follow up sonography plays a central part because of its high accuracy, its easy and noninvasive use as well as its availability and low costs. Although popular, the color Doppler examination is of minor importance in the evaluation of patients with stone disease. Apart from conservative management shock-wave lithotripsy is the first procedure of choice in the treatment of urinary stones. In the follow up of both patients with conservative and patients after interventional treatment sonography is the first line examination.

Female↗
PubMed2001

High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.

Chromosomes, Human, Pair 3↗
PubMed2001

Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade.

The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.

Adenocarcinoma↗
PubMed2000

High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the 19q13 chromosomal region is frequently amplified in bladder cancer. The cyclin E gene (CCNE), coding for a regulatory subunit of cyclin-dependent kinase 2, has been mapped to 19q13. To investigate the role of cyclin E alterations in bladder cancer, a tissue microarray of 2,317 specimens from 1,842 bladder cancer patients was constructed and analyzed for CCNE amplification by fluorescence in situ hybridization and for cyclin-E protein overexpression by immunohistochemistry. Fluorescence in situ hybridization analysis showed amplification in only 30 of the 1,561 evaluable tumors (1.9%). Amplification was significantly associated with stage and grade (P: < 0.0005 each). Immunohistochemically detectable cyclin E expression was strong in 233 (12.4%), weak in 354 (18.9%), and negative in 1, 286 of the 1,873 interpretable tumors. The majority (62.1%) of CCNE-amplified tumors were strongly immunohistochemistry-positive (P: < 0.0001). The frequency of protein expression increased from stage pTa (22.2%) to pT1 (45.5%; P: < 0.0001) but then decreased for stage pT2-4 (29.4%; P: < 0.0001 for pT1 versus pT2-4). Low cyclin E expression was associated with poor overall survival in all patients (P: < 0.0001), but had no prognostic impact independent of stage. It is concluded that cyclin E overexpression is characteristic to a subset of bladder carcinomas, especially at the stage of early invasion. This analysis of the prognostic impact of CCNE gene amplification and protein expression in >1,500 arrayed bladder cancers was accomplished in a period of 2 weeks, illustrating how the tissue microarray technology remarkably facilitates the evaluation of the clinical relevance of molecular alterations in cancer.

Adult↗
PubMed2000

Clinical significance of interobserver differences in the staging and grading of superficial bladder cancer.

OBJECTIVE: To assess the reliability of the histological diagnosis of bladder cancer by assessing the interobserver variability of staging and grading in pTa/pT1 tumours and evaluating the clinical significance of discrepancies. MATERIALS AND METHODS: All sections from 301 superficial bladder carcinomas were reviewed by one pathologist. The prognostic relevance of grade and stage from both the initial and review diagnosis were determined in 128 patients for whom there was long-term follow-up information. RESULTS: There were significant interobserver differences in both the grading and staging of tumours. From a total of 235 tumours that were initially considered pT1, the reviewer classified 35% as pTa, 56% as pT1, 6% as pT1- (at least pT1), and 3% as pT2-4. In 39% of all biopsies there were interobserver differences in tumour grade. The prognostic significance of grade and stage differed between the initial pathology report and the reviewer's diagnosis. The reviewer's staging allowed a better estimate of the risk of subsequent tumour progression than the initial staging. Progression was significantly more common in 49 tumours in which the reviewer agreed with stage pT1 than in 29 tumours that were down-staged from pT1 to pTa (P = 0.0116). However, the initial tumour grade (P = 0.0386) but not the reviewer's grade (P = 0.2645) was significantly linked to progression. CONCLUSIONS: These results show that grading and staging by different pathologists have varying prognostic implications. If possible, biopsies from bladder tumours should be independently evaluated by two different pathologists before radical therapy is administered.

Adult↗
PubMed1999

Chromosomal imbalances are associated with a high risk of progression in early invasive (pT1) urinary bladder cancer.

Many cytogenetic alterations are known to occur in urinary bladder cancer, but the significance of most of them is poorly understood. To define these chromosomal regions where clinically relevant genes may be located, a series of 54 pT1 urinary bladder carcinomas with clinical follow-up information (median, 52 months; range, 5-167 months) were examined by comparative genomic hybridization. The most frequent alterations included DNA sequence copy number gains at 1q22-24 (33%), 20q11.2-ter (33%), 8q22 and 17q21 (28% each), and 6p22 (15%) as well as deletions at Y (37%), 9p (31%), 9q22-33 and 11p14-ter (28% each), 11q23 (26%), 8p (24%), 13q31 (19%), 2q35-ter (17%), and 2q22-33 (11%). Whereas the histological grade was unrelated to prognosis (P = 0.9752), the risk of tumor progression was significantly associated with the number of deletions per tumor (P = 0.0014). Individual cytogenetic alterations that were linked to subsequent tumor progression included gains of 3p22-24 (P = 0.0112) and 5p (P = 0.0003) as well as losses of 4p11-15 (P = 0.0052), 5q15-23 (P = 0.0410), 6q22-23 (P = 0.0090), 10q24-26 (P = 0.0232), and 18q12-23 (P = 0.0005). Genes with a role for bladder cancer progression may be located at these regions.

Carcinoma↗
PubMed1999

[Value of invasive preoperative imaging in kidney tumors of malignant or uncertain character].

Preoperative staging of malignant renal tumors or undetermined dignity is mainly performed noninvasively using CT or MRI. In cases with vascular invasion or a solitary kidney extensive invasive evaluation of the tumor can influence preoperative planning. We report two cases of oncocytoma and renal cell carcinoma with extensive imaging using DSA or helical CT-cavography.

Adenoma, Oxyphilic↗
PubMed1999

Cyclin D1 overexpression lacks prognostic significance in superficial urinary bladder cancer.

The biological behaviour of urinary bladder neoplasms cannot be adequately predicted by histological criteria alone. Cyclin D1 is a cell-cycle regulating protein known to be overexpressed in a proportion of bladder carcinomas. To evaluate the prognostic significance of cyclin D1 expression and its relationship with tumour phenotype, 392 bladder carcinomas were analysed by immunohistochemistry. Clinical follow-up information was available in 337 patients with superficial bladder tumours (stages pTa/pT1). Cyclin D1 positivity was seen in 176 of 392 carcinomas. Cyclin D1 overexpression was strongly linked to papillary tumour growth, low stage, and low histological grade (p<0.005 each). Multivariate analysis showed that papillary tumour growth was the only parameter which was independently linked to cyclin D1 positivity. There was no significant difference in proliferative activity (Ki67 labelling index) between cyclin D1-negative and -positive tumours. Cyclin D1 positivity was not linked to the risk of recurrence or tumour progression, either in pTa or in pT1 carcinomas. It is concluded that cyclin D1 positivity distinguishes a large subgroup of papillary bladder tumours, but there is no evidence of prognostic significance for increased cyclin D1 expression.

Analysis of Variance↗
PubMed1999

Focal loss of CD44 variant protein expression is related to recurrence in superficial bladder carcinoma.

The majority of papillary transitional cell carcinomas of the bladder are localized tumors at initial diagnosis; identification of those developing recurrence and an aggressive behavior is important. CD44 variant proteins have been implicated in tumor progression and metastasis, and a correlation with adverse prognosis has been demonstrated in a variety of human tumors. Here, the usefulness of conventional CD44 protein immunohistochemistry as a prognostic parameter for recurrence of superficial transitional cell carcinomas was assessed in paraffin sections of 241 tumors with long-term follow-up. A highly significant association was found between focal loss of CD44v3 and -v6 immunostaining and short recurrence-free interval in noninvasive (pTa) transitional cell carcinomas (P = 0.005), but not in minimally invasive (pT1) carcinomas (P = 0.78). Our results indicate the value of conventional CD44 immunohistochemistry as an additional tool for identifying patients at high risk for recurrence of pTa transitional cell carcinomas. They also point to biological differences between noninvasive and minimally invasive transitional cell carcinomas of the bladder.

Carcinoma, Transitional Cell↗
PubMed1999

Polysomies but not Y chromosome losses have prognostic significance in pTa/pT1 urinary bladder cancer.

A disturbed cellular DNA content is of potential diagnostic and prognostic relevance in urinary bladder cancer. To evaluate the prognostic significance of individual chromosomal aberrations in superficial bladder cancer, specimens of 105 tumors (67 pTa, 38 pT1) were examined by fluorescence in situ hybridization (FISH). FISH allows quantitation of chromosomes on a cell by cell level. Centromere probes for the chromosomes Y, 1, and 17 were used. There was a strong association between polysomies of the chromosomes 1 (found in 46% of tumors) and 17 (40% of tumors, P < .0001). Polysomies (1 and 17) were significantly more frequent in pT1 than in pTa tumors (P < .0001 each). In pTa tumors, polysomies of both chromosomes were linked to a high risk of recurrences; polysomy 17 was associated with an increased risk of progression (P < .05 each). There was no significant association between polysomies and an unfavorable prognosis in pT1 carcinomas. Previous studies had suggested a prognostic role of Y losses in bladder cancer. However, Y losses were not linked to recurrences or tumor progression in pTa or pT1 tumors of 67 male patients. These data show that marked genetic differences exist between pTa and pT1 carcinomas. They also indicate that polysomies of different chromosomes may have prognostic relevance in pTa urinary bladder cancer.

Adult↗
PubMed1995

Optimization of prostate carcinoma staging: comparison of imaging and clinical methods.

PURPOSE: The diagnostic value of endorectal coil MRI, body coil MRI, transrectal ultrasound, digital rectal examination and PSA levels were prospectively analysed in order to define the most accurate preoperative staging method. METHODS: 33 patients with prostate carcinoma, who underwent subsequent prostatectomy, were enrolled in the study and examined on a 1.5T system using the body coil as well as the endorectal surface coil before and after the administration of contrast material. The results were compared to digital rectal examination, prostate specific antigen levels and endorectal ultrasound. RESULTS: Staging accuracy of endorectal coil MRI was 87.9% with a sensitivity of 88.9% and specificity of 86.7%. For body coil MRI, the staging accuracy was 75.7%, the sensitivity 66.7% and the specificity 87.9%, for transrectal ultrasound 69.6%, 41.7% and 100% and for the digital rectal examination 56.6%, 33.3% and 100%, respectively. Prediction was improved by combining results of endorectal coil MRI with PSA values. CONCLUSION: Endorectal ultrasound and digital rectal examination both had a tendency to underestimate the extent of the lesion. Endorectal coil MRI proved to be the best preoperative staging method. In combination with PSA values, diagnostic accuracy could be further improved. Therefore, local staging of prostate cancer could be based on these two parameters alone.

Aged↗
PubMed1995

Placebo controlled double-blind study to test the efficacy of the aromatase inhibitor atamestane in patients with benign prostatic hyperplasia not requiring operation. The Schering 90.062 Study Group.

PURPOSE: We tested the theoretical concept that a selective decrease in estrogens has a beneficial therapeutic effect on established benign prostatic hyperplasia. MATERIALS AND METHODS: In a double-blind study 160 patients from 14 centers were randomized between 2 groups to receive either placebo or the aromatase inhibitor atamestane (1-methyl-androsin-1,4 diene-3 17-dione, 400 mg. daily for 48 weeks). RESULTS: The aromatase inhibitor decreased the mean estradiol level by approximately 40% and estrone by 60%. The testosterone concentration increased by more than 40% and dihydrotestosterone increased to 30%. Analysis of clinical parameters showed no difference between placebo and atamestane. CONCLUSIONS: The counter regulatory increase in androgens may counterbalance any positive effect of the decrease in estrogens to preserve intraprostatic homeostasis.

Aged↗
PubMed1993

[Experience with video transurethral resection].

During 14 months more than 300 endoscopic interventions were performed by video-control only: 160 TUR of prostate, 37 TUR of bladder-tumours, 7 ureteroscopies, 17 manipulations with bladder stones and stents, 9 sight-urethrotomies, 72 diagnostic cystoscopies, 2 percutaneous nephrolithotripsies and 12 laparoscopic interventions. Technical requirement is a light and rotatable camera, preferably a monitor mounted over the patient and a self-adjusting light-source. The advantages are better identification of tissue, the use where there is limited mobility of the patient's hip joint and the possibility of demonstration and documentation. The urologist's face is protected against blood contact (HIV-prophylaxis), and he is taking care of his spine. It is the best way of instruction for the learning urologist and even a good training for laparoscopic surgery.

Cystoscopes↗
PubMed1993

[Spontaneous recanalization after vasectomy].

Two cases of spontaneous recanalisation could be reoperated. The recanalisation was proved histologically. The reasons were analysed. The own technique is presented: resection of at least two centimeters of the vas, ligature, electrocoagulation, proximally turning-up fixation of the end, distally immersing the end in a tobacco-pouch.

Adult↗
PubMed1992

[Value of intravenous urography versus ultrasound in preoperative assessment of prostatic hyperplasia].

Even 60 years after its first clinical application intravenous urography (IVU) is still an essential part of basic diagnostic measures in benign hyperplasia of the prostate (BPH). We compared the value of the IVU to the ultrasound examination in the preoperative evaluation prospectively in 79 patients. Out of a total of 16 pathological findings (20%), only 5 findings (6.3%) could be proved in the IVU. If there was no clinical relevance, however, no treatment was necessary; neither did the pathological findings influence the strategy of surgery. Indirect signs of a tumour in 3 IVU's could be identified ultrasonically as parapelvic or cortical cysts, respectively. In addition to reliable and reproducible estimates of prostatic size, ultrasonography provides information on the residual volume, dilatation of the upper urinary tract, renal masses or stone disease. We recommend ultrasound examination as a helpful method in the preoperative evaluation of BPH. IVU should be considered only for answering specific and clinically relevant questions.

Aged↗
PubMed1992

Endocrine treatment prior to radical retropubic prostatectomy in patients with T3 prostate cancer: a retrospective study of 22 patients.

Twenty-two patients with locally advanced prostatic carcinoma stage T3, N0, M0 have been treated with LH-RH agonists during a mean time of 5 months prior to radical retropubic prostatectomy. Although tumors appeared to be confined to the organ in 68% of the patients after endocrine treatment, pathological examination of the surgical specimens showed in 89% evidence of extraprostatic disease, which questions the clinical impression of 'downstaging'. A disparity between the tumor grade of the biopsy and that of the operative specimen as well as an increased size of tumor-involved lymph nodes despite endocrine treatment led us to speculate that a certain proportion of patients will bear the risk of disease progression during preoperative androgen deprivation. Furthermore, there was local recurrence early in the postoperative course and at the high rate of 39%.

Aged↗
PubMed1992

[Problems with the intraurethral spiral].

In the last decade numerous attempts have been undertaken in non-surgical treatment of benign prostatic hyperplasia in order to enable the patient to void his bladder under control, without residual urine and without surgical resection. For the time being, attempts with drug therapy, as well as the more invasive methods with thermic or dilating effect on the prostatogenic infravesical obstruction are based on empiric studies. For many patients transurethral or suprapubic long-term catheterisation is, after all, the only solution. In this respect the "urologic spiral" represents a conservative alternative. In 1980 Fabian was the first to report on the successful clinical application of the intraprostatic "partial catheter" in 2 patients. 4 years later Fabian's remarkably good results in 48 patients are promising. However, what strikes first as an efficient innovation may also have its shortcomings and complications, as it was our experience in the first applications.

Aged↗