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Biomedical subjects

T C Gasser

Publications and source records attributed to T C Gasser.

At least 73 records · Page 4Linked to original sources

Epidermal growth factor receptor expression is associated with rapid tumor cell proliferation in renal cell carcinoma.

Epidermal growth factor receptor (EGF-r) expression and tumor cell proliferation rate have been proposed as potential prognostic parameters in renal cell carcinoma (RCC). In this study, immunohistochemical stains using antibodies to EGF-r and the cell proliferation marker Ki-67 (MIB-1) were used to study the relationship between EGF-r expression, tumor cell proliferation, and prognosis in 50 non-papillary RCC extending beyond the renal capsule (pT3). A high Ki-67 labeling index (LI) was associated with poor patient prognosis (P < .05). Thirty-eight cases (76%) expressed strong cell membrane immunoreactivity for EGF-r. There was a tendency toward a shortened survival for EGF-r-positive tumors (P = .08). Tumor growth fraction (Ki-67 LI) was significantly higher in EGF-r-positive tumors than in EGF-r-negative tumors (P < .05), suggesting that rapid tumor proliferation might be responsible for the poor prognosis associated with EGF-r-positive RCC.

Carcinoma, Renal Cell↗

Chromosome 8p deletions are associated with invasive tumor growth in urinary bladder cancer.

Alterations of chromosome 8, including deletions of 8p, occur frequently in many tumors. In this study, fluorescence in situ hybridization was used to study the relationship between 8p deletions, 8q gains, and phenotype in bladder cancer. Cells from 87 tumors were examined by dual-labeling fluorescence in situ hybridization with a centromere 8 probe (pJM12) and P1 probes for 8p22, 8p12, 8q12, and 8q24. Both 8p22 deletions and 8q24 gains were strongly associated with tumor phenotype. There was a marked difference in 8p22 deletions between noninvasive (pTa) tumors (3/33) and minimally invasive (pT1) tumors (8/19; P = 0.005) whereas there was no significant difference between pT1 and muscle-invasive (pT2-4) tumors (19/35; P = 0.3926). Six tumors with 8p22 deletion were examined at 8p12. Three of these tumors showed no 8p12 deletion, narrowing down the site of a putative tumor suppressor gene distal to 8p12. In one other case, there was a marked increase in 8p12 copy number (> 40 per cell; amplification), suggesting the presence of an oncogene involved in bladder cancer at 8p12. The marked difference in 8p22 deletions between noninvasive (pTa) and minimally invasive (pT1) tumors is consistent with a role of a putative tumor suppressor gene on 8p for development of invasive tumor phenotype.

Chromosome Aberrations↗

[Genomic changes in urinary bladder cancer].

Recent molecular studies on transitional cell carcinomas (TCC) of the urinary bladder suggest two genetically different tumor types with a varying degree of genomic instability-pTa (grade 1 and 2) tumors are usually "genetically stable". These tumors have rarely p53 alterations and contain only few genomic alterations (deletions, DNA sequence copy number gains, amplifications). Genomic changes in these tumors typically include losses of the chromosomes Y and 9 as well as 1q gains. TCC's with invasive growth pattern (pT1-4) are mostly "genetically instable". They have p53 alterations in about 50% of tumors, and often numerous DNA sequence copy number changes including deletions of 2q, 5q, 6q, 8p and 11p as well as gains at 1q, 3p, 3q, 5p, 6p, 8q und 10p. High level amplifications at various sites of the genome are also frequent in these "instable tumors". They may pinpoint the localization of overexpressed oncogenes. Further studies will have to investigate whether genetic analyses can add useful information to the currently used pathological (pTNM) and clinical (superficial/invasive) classifications of urinary bladder cancer.

Carcinoma, Transitional Cell↗

Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy.

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. Both tumour cell proliferation and neuroendocrine differentiation have been suggested as additional prognostic parameters, neuroendocrine differentiation being considered to enhance tumour cell proliferation. This study investigated the prognostic value of tumour cell proliferation [Ki67 labelling index (LI), MIB 1] and neuroendocrine differentiation and their relationship to each other. One hundred and thirty-seven paraffin-embedded radical prostatectomy specimens were examined. Neuroendocrine differentiation was found in 58 per cent of cases, but was not associated with pTN stage, Gleason score, Ki67 LI, or tumour progression. Ki67 LI was not significantly associated with pTN stage or with Gleason score. High grade (P = 0.0005), advanced local stage (P = 0.0004), positive lymph nodes (P = 0.02), and high Ki67 LI (P = 0.0203) were predictors of tumour progression if univariate analysis was performed, but Cox stepwise regression showed that only advanced local stage (P = 0.0025) and Ki67 LI (P = 0.0105) were independent predictors of tumour progression, the relative risk being 3.6 and 2.5, respectively. It is concluded that Ki67 is an important prognostic marker in prostate cancer with a potential for routine application.

Aged↗

Quinolone prophylaxis in transurethral surgery.

In transurethral surgery, there is much controversy about the benefit of antimicrobial prophylaxis. Any urinary tract infection should be treated before proceeding with a transurethral operation. There is growing evidence that antimicrobial prophylaxis is also beneficial in cases with preoperatively sterile urine. A single dose or short-term prophylaxis appears to be sufficient. As newer fluoroquinolones reach very high tissue concentrations, have a suitable antimicrobial spectrum to cover most uropathogens and can be administered orally, these new drugs represent an attractive choice for prophylaxis in transurethral surgery.

Anti-Infective Agents↗

Prognostic significance of Bcl-2 in clinically localized prostate cancer.

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. To study the prognostic significance of Bcl-2 and p53 overexpression in prostate cancer, 137 consecutive radical prostatectomy specimens were examined by immunohistochemistry. Both Bcl-2 and p53 were associated with malignant phenotype. Bcl-2 expression was more frequent in pT3 tumors (31% positive) than in pT2 tumors (5% positive, P = 0.001). p53 overexpression (found in 8%) was associated with high Gleason score (P = 0.03) and increased tumor growth fraction (Ki67 labeling index (LI); P = 0.017). Survival analysis showed that Bcl-2 expression (P = 0.03), high Ki67 LI (P = 0.018), high grade (P = 0.0037), advanced local stage (P = 0.0005), and positive lymph nodes (P = 0.026) were predictors of progression. The combined analysis of Ki67 LI and Bcl-2 allowed the distinction of three groups with different clinical outcome. Prognosis was best in Bcl-2-negative tumors with low Ki67 LI, worst in Bcl-2-positive tumors with high Ki67 LI, and intermediate in the remaining tumors (P = 0.03). These data suggest that altered expression of both Bcl-2 and p53 play a role in prostate cancer progression. Combined analysis of factors regulating both apoptosis and cell proliferation may be relevant in prostate cancer.

Aged↗

Oral fleroxacin prophylaxis in transurethral surgery.

PURPOSE: A prospective trial was done to test the efficacy of antimicrobial prophylaxis in patients undergoing transurethral surgery. MATERIALS AND METHODS: A total of 75 adults with preoperatively sterile urine was randomized to receive either 400 mg. oral fleroxacin once daily or placebo as long as the catheter was in place. Urine cultures were obtained preoperatively and after removal of the catheter just before hospital discharge. Growth of 10(4)/ml. or more bacteria was considered a positive urine culture. RESULTS: Postoperative urinary tract infection rates were significantly lower in the fleroxacin group (3%) than in the placebo group (23%). Our study demonstrated the benefit of antimicrobial prophylaxis in preventing urinary tract infection after transurethral surgery, including resection of the prostate, in patients with sterile urine. CONCLUSIONS: The oral administration of 1 daily tablet of fleroxacin for the duration of catheterization is a safe, efficacious and clinically feasible regimen.

Administration, Oral↗

[Prevention using quinolones in transurethral surgery].

Much controversy exists as to the benefit of antimicrobial prophylaxis in transurethral surgery. Any urinary tract infection should be treated before proceeding with a transurethral operation. There is growing evidence that antimicrobial prophylaxis is also beneficial in the case of preoperatively sterile urine. A single dose or short-term prophylaxis appears to be sufficient. As newer fluoroquinolones reach very high tissue concentrations, possess a suitable antimicrobial spectrum to cover most uropathogens and may also be administered orally, these new drugs represent an attractive choice for prophylaxis in transurethral surgery.

4-Quinolones↗

[Hematuria].

Hematuria is an important symptom to be taken seriously and to be investigated quickly and thoroughly. One can distinguish between gross and microscopic hematuria as well as between initial, total and terminal hematuria. The most common cause of hematuria is bladder infection. However, because of the grave consequences bladder cancer has to be excluded. Family doctors have many tools to investigate the urine, i.e. urinary sticks, microscopic urine analysis, urine culture as well as sonography of the urinary bladder. If suspicion of bladder cancer arises further investigations by an urologist using cystoscopy, intravenous or retrograde pyelogram and sonography must be considered. Treatment of bladder cancer consists in transurethral resection of the tumor, local or systemic chemotherapy or radical cystectomy.

Algorithms↗

Heterogeneity of chromosome 17 and erbB-2 gene copy number in primary and metastatic bladder cancer.

To study the relationship of tumor genomic heterogeneity with bladder cancer phenotype and p53 gene alterations, 138 primary bladder tumors were examined by dual labeling fluorescence in situ hybridization (FISH) using probes for chromosome 17 centromere (p17H8) and p53 (17p13.1). The number of different aneusomic populations > 5% (and monosomic populations > 20%) of cells served as a marker for heterogeneity. Nuclear p53 overexpression and Ki67 labeling index (Ki67 LI) were determined by immunohistochemistry. The number of aneusomic populations was 0 in 53 tumors, 1 in 18, 2 in 47, 3 in 9, and > 3 in 11 tumors. Presence of aneusomy was associated with tumor grade and stage (P < 0.0001 each). Ki67 LI was low in disomic tumors (11.0 +/- 7.7), higher in tumors with 1-3 aneusomic populations (17.4 +/- 11.3), and highest in tumors with > 3 aneusomic populations (25.8 +/- 10.9; P = 0.02 for > 3 vs. 1-3 populations). Aneusomy and heterogeneity were associated with p53 alterations. Aneusomy was seen in 35% of tumors with neither p53 expression nor p53 deletion but in 97% of tumors with both p53 deletion and expression. Nine of 11 tumors with > 3 aneusomic populations exhibited both p53 deletion and overexpression. To study genomic heterogeneity in tumor progression, two recurrences and three metastases of a tumor with known erbB-2 amplification were examined for centromere 17 and erbB-2 copy number. A considerable heterogeneity in centromere 17 and erbB-2 gene copy number was found in both recurrences and metastases, indicating a marked genomic instability in these metastatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell↗

Y chromosome loss detected by FISH in bladder cancer.

To examine the significance of Y chromosome losses in bladder cancer, fluorescence in situ hybridization (FISH) was used to determine its prevalence and associations with known parameters of malignancy. Cells were dissociated from formalin-fixed paraffin-embedded bladder tumors from 68 male patients and from 11 post-mortem bladder washes of male patients with a negative bladder cancer history, and were examined by FISH using centromeric probes for chromosomes X, Y, 7, 9, and 17. Nullisomy for chromosome Y was seen in 23 of 68 tumors (34%), monosomy in 28 of 68 tumors (41%), and polysomy in 17 of 68 tumors (25%). There was no association between chromosome Y loss and tumor grade, stage, tumor growth fraction (Ki67 LI), p53 immunostaining, and presence of p53 deletions. Patient age was higher for tumors with a Y loss (73.5 +/- 12.0 years) than for tumors without Y loss (66.6 +/- 10.8 years; p = 0.0207). In one normal bladder wash, a distinct subpopulation (38% of cells) with Y nullisomy was seen. These data suggest that Y loss is a frequent event that can occur early in bladder cancer, although there is no evidence for a role of Y loss in tumor progression.

Age Factors↗

Ureteral amyloid deposits of beta 2-microglobulin origin in both kidney recipients of 1 donor.

We report on 2 renal transplant recipients with ureteral amyloid deposits, each of whom received 1 kidney from the same donor. Ureteral stenosis developed in both cases. Immunohistochemistry revealed beta 2-microglobulin derived AB amyloid within the stenotic parts of the ureters, which to our knowledge has not been described previously at that site. Usually AB amyloid is found in patients on long-term hemodialysis. Amyloid transfer by transplantation as a possible cause for ureteral stenosis was excluded because the donor had had normal renal function and autopsy showed no evidence of amyloidosis. It is more likely that the secondary deposit of AB amyloid in the transplanted ureters was facilitated by preexisting ischemic ureteral damage.

Amyloidosis↗

[Primary detection of malignant mesothelioma of the tunica vaginalis testis using the BMA-120 monoclonal antibody].

Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor, with only 40 cases previously described in the literature. Treatment consists of inguinal orchiectomy with close-follow up [1]. Asbestose exposure, trauma and hydrocele have been implicated as risk factors. We describe a histopathological examination with the BMA antibody (Behring, Marburg, Germany) and the Lu-5 antibody (Hoffmann-La Roche, Basel, Switzerland). Furthermore, we describe the patient's history and the management according to preceding reports in the literature.

Aged↗

Influence of urological irrigation fluids on urothelial bacterial adherence.

The influence of various urological irrigation solutions on bacterial growth and adherence to urothelium was investigated in in vitro and guinea pig models. The irrigation solutions glycine 1.5%, glycine 1.5% and ethanol 1%, glycerol 3%, mannose 6%, sorbitol 2.7% and mannitol 0.54% all inhibited bacterial growth compared with normal saline. In guinea pigs, the influence on bacterial adherence of four irrigation solutions (glycine 1.5%, glycine 1.5% and ethanol 1%, mannose 6%, povidone-iodine) was investigated using two different strains of E. coli. After cauterizing one side of the bladder and inoculation with 2.7 x 10(8) colony forming units under high or low pressure, the bladder was irrigated with the irrigation solutions. There was a stronger adherence of E. coli O6 (with type I pili) than of E. coli ATCC 25922 (without type I pili) to bladder urothelium, particularly to the injured side. There was no significant difference between the high- and low-pressure groups. None of the various irrigation solutions was clearly superior. As mannose 6% effectively inhibited type I pili and also had some antibacterial activity it may reduce urinary tract infection if used as irrigation solution.

Animals↗

Absence of urethral strictures with suprapubic urinary drainage during extracorporeal circulation.

Postoperative urethral strictures following extracorporeal circulation in open heart surgery are not uncommon. The etiology is not clear. Ischemia and pressure of the Foley catheter may cause a lesion that eventually leads to urethral stricture. We retrospectively analyzed 300 patients who had undergone open heart surgery. In 1 group the bladder was drained by a Foley catheter during extracorporeal circulation, while another group underwent suprapubic drainage. Strictures developed in 10 of 152 patients (6.6%) with an indwelling catheter. Conversely, no strictures occurred in the 148 patients treated with suprapubic urinary drainage. The use of suprapubic drainage during extracorporeal circulation greatly decreases the risk of postoperative urethral strictures.

Adolescent↗

The Hydroflex penile prosthesis: a test case for the introduction of new urological technology.

The AMS Hydroflex* penile prosthesis was introduced for commercial distribution in 1985 but 5 years later this device was no longer available on the United States market. In an attempt to understand why this device, which initially enjoyed substantial popularity, was abruptly withdrawn from the market, patients who underwent implantation at the University of Wisconsin were interviewed and a critical analysis of the Food and Drug Administration approval process of medical devices was performed. An AMS Hydroflex penile prosthesis was implanted in 17 patients (mean age 57.7 years, range 27 to 84 years). The followup period ranged from 37 to 73 months with a mean of 58 months, and 3 patients died within that time. Of the remaining patients 10 (71%) were satisfied with the device in the first months after implantation but only 6 (43%) were satisfied at the time of followup, 9 (64%) were more satisfied with sexual relationships after receiving the prosthesis and 7 (50%) found the prosthesis simple to operate. Mechanical failure was noticed by 11 patients (79%), of whom 5 (45%) underwent further surgery. Classification of medical devices started with the enactment of the Medical Device Amendment to the Federal Food, Drug and Cosmetic Act, May 28, 1976. All medical devices that were in commercial distribution at that time were classified in 3 regulatory control categories depending upon the degree of regulation necessary to assure safety and effectiveness of each device. Before May 28, 1976 no approved application was necessary for marketing medical devices, and the Food and Drug Administration has variable amounts of information about safety and effectiveness of the different devices marketed prior to that date. Since May 1976 approved applications have been mandated for new or significantly changed devices. The specific process by which the Hydroflex prosthesis, as well as other medical devices, is approved is critically reviewed.

Adult↗