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Biomedical subjects

G Alund

Publications and source records attributed to G Alund.

At least 19 recordsLinked to original sources
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

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↗
PubMed1992

Significance of cavernosography in standardized cavernosometry.

Ninety-five patients with erectile dysfunction underwent standardized cavernosometry and cavernosography. In a first stage, the investigation was performed in each patient without and in a second stage with 60 mg papaverine injected intracavernously. A pathological maintenance flow rate between 20 and 120 ml/min decreased by 55% on average. The induction flow is of considerable variability and of poor diagnostic value. For quantification of venous leakage, the maintenance flow rate is of great importance and in correlation with the time of pressure decrease. Our results with a sensitivity of 59% suggest that cavernosography as the only screening method for venous leakage is not sufficient. In most of the cases, cavernosography is indicated only in consideration of venous leakage surgery.

Blood Flow Velocity↗
PubMed1992

Venous leakage--a new therapeutical concept.

According to our opinion, so-called venous leakage is no venous disease but a result of impaired cavernous tissue. Since in over 90% of all patients with venous leakage also arterial disease was discovered and since ultrastructural degenerative processes in the cavernous bodies were detected, we consider traditional corrective venous surgery as unphysiological and illogical. We suggest arterial revascularization combined with a mechanical penis banding as a new therapeutical concept.

Arterial Occlusive Diseases↗
PubMed1991

[Venous leakage--a new therapeutic concept].

According to our opinion, so-called venous leakage is not a venous disease but a result of impaired cavernous tissue. Since in over 90% of all patients with venous leakage arterial disease has also been discovered, and since in addition ultrastructural degenerative processes have also been detected in the cavernous bodies, we consider the traditional treatment in the form of venous surgery unphysiological and illogical. We suggests arterial revascularization combined with mechanical penis banding as a new therapeutic concept.

Erectile Dysfunction↗
PubMed1990

[Organ-preserving therapy in kidney tumors].

Renal cell carcinoma in solitary kidneys or both kidneys requires renal sparing tumour resection to avoid renal failure. This paper presents the course of 16 patients with 17 solid renal tumours. The results achieved with this approach in T1-2 N0 M0 tumours are similar to those of radical nephrectomy.

Humans↗
PubMed1989

[Do shock waves damage the kidney? Morphologic and functional changes of the kidney following exposure to shock waves].

The introduction of extracorporeal shockwave lithotripsy (ESWL) as a routine procedure has brought about a dramatic change in the therapy of urolithiasis. More than 500,000 patients have been treated successfully. Although a tissue damaging effect of the shock wave on the kidney was regarded as non-existent, phenomena such as hematuria during ESWL treatment and subsequent subcapsular hematomas suggest the possibility of damage in the region of the renal parenchyma by the shockwave itself. To investigate this possibility canine kidneys were examined histologically at different intervals after shockwave exposure. Extensive histological changes such as hemorrhage and sometimes direct tubular damage were found, with scar formation after three months. These changes are limited to the areas exposed to ESWL treatment.

Animals↗
PubMed1989

Management of ureteral stones by extracorporeal shock wave lithotripsy. 3 years of experience.

From April 1985 to March 1987 181 patients with ureteral stones were treated by means of extracorporeal shock wave lithotripsy (ESWL). Management for proximal calculi changed from in situ ESWL treatment (group n = 27) or placement of a ureteral catheter below calculi (group II, n = 30) to retrograde stone manipulation into renal pelvis (group IV, n = 52) or ESWL treatment under intraoperative irrigation of saline in cases where repositioning failed (group III, n = 50). The best stone-free rate for upper ureteral stones was obtained in group IV with 96% after 6 weeks, presenting also the shortest hospital stay (4.2 days) and lowest quota of postoperative auxiliary procedures (2%). Stones, not being dislodged into renal pelvis (49%), could be treated successfully in 86% by irrigation with saline during ESWL (group III). The stone-free rate decreased in patients with in situ treatment (group I: 67%) or ureteral catheter placement (group II: 83%). Treatment of these stones increased the need of postoperative ancillary procedures to approximately 30%. For distal ureteral stones ESWL and preoperative Zeiss placement achieved a stone-free rate of 95%.

Adult↗
PubMed1989

[The staghorn calculus: anatrophic nephrolithotomy versus percutaneous litholapxy and extracorporeal shockwave therapy versus extracorporeal shockwave lithotripsy monotherapy. A report of over 6 years' experience].

From 1982 to December 1987, 71 with incomplete (C4 by Rocco) and 37 with complete (C5 by Rocco) staghorn calculi underwent anatrophic nephrolithotomy (AN; n = 29), or combined percutaneous nephrostolithotomy and ESWL (PCNL + ESWL; n = 21), or ESWL monotherapy without or with preoperative JJ stenting (n = 37/21). The patients with incomplete staghorn calculi (C4) and preoperative ureteral stenting were free of stones after 6 months in 15 of 17 cases (88%), which is comparable to our results with AN (90%) and combined PCNL + ESWL (85%). ESWL without JJ stenting were free of stones in only 52%. The treatment of infected C4 calculi with JJ stenting was especially successful (92%). Complete staghorn calculi (C5) represented the best results after AN (78%) and combined PCNL + ESWL (75%), in contrast to ESWL without JJ stenting (44%). Four patients with C5 calculi were treated with ESWL and preoperative stenting, three of them were free of stones after 6 months. For incomplete staghorn calculi (C4), ESWL monotherapy with JJ stenting seems to be a justifiable noninvasive method which offers excellent results in stone elimination (88%), with lower costs than AN or PCNL + ESWL. More invasive procedures should be reserved for complete staghorn calculi.

Combined Modality Therapy↗