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Biomedical subjects

T C Gasser

Publications and source records attributed to T C Gasser.

At least 55 records · Page 3Linked to original sources

Reasons for discontinuing intracavernous injection therapy with prostaglandin E1 (alprostadil).

OBJECTIVES: To clarify the reasons why experience with self-injection therapy for erectile dysfunction shows high dropout rates. METHODS: We studied 86 patients 36 to 76 years old who had been on home treatment for at least 3 months. Sixty-nine patients (80%) were continuing to use injections, and 17 (20%) had discontinued the treatment. Patients were evaluated by interview and clinical examination. RESULTS: Patients still in the program used one injection every 2 weeks, and those who had given up treatment had used one injection in 3 weeks (P = 0.31). They were in the program for 39+/-27 and 16+/-22 months (P = 0.002), respectively, and had used 50 (95% confidence interval [CI] 21 to 91) versus 12 (95% CI 4 to 20) injections, respectively (P<0.0001). Injections producing unsatisfactory penile rigidity, prolonged erections, hematoma at injection site, corporal fibrosis, secondary penile deviation, and mean estimated duration of a pharmacoinduced erection showed no significant differences. Patient satisfaction (P = 0.02), estimated partner satisfaction (P = 0.02), increase in self-esteem (P = 0.01), and negligible effort in performing injections (P = 0.001) all showed significantly better results for those still in the program. CONCLUSIONS: Reasons for dropout from self-injection therapy are not based on objective side effects and discomfort. Patients leaving the program are less motivated, less satisfied with the quality of pharmacoinduced sexuality, consider the effort to perform injections to be substantial, and have not achieved improved self-esteem.

Adult↗

Variable response to intracavernous prostaglandin E1 testing for erectile dysfunction.

OBJECTIVES: Anxiety and apprehension may negatively influence the erectile response to the first intracavernous injection with vasoactive agents. This may result in too many false-positive diagnoses of vascular insufficiency if the first injection ever made in a patient is used for color Doppler duplex sonography (CDS) evaluation. METHODS: One hundred sixty-eight consecutive patients (aged 18 to 75 years) with erectile dysfunction underwent a standardized evaluation, including the intracavernous injection test (ICIT) stimulated with 10 microg prostaglandin E1. Responses were recorded on a four-point scale: no response = 0, tumescence = 1, rigidity sufficient for intercourse = 2, full erection = 3. ICIT was repeated after 10 days and combined with CDS. The clinically assessed response to ICIT was correlated with end-diastolic flow velocity. RESULTS: Of 168 patients, 114 (68%) responded equally to the first and second ICIT, but 45 (27%) had an improved response, from tumescence to full erection in the second test (P <0.0001); in 9 (5%), the response deteriorated. The overall mean response was 1.6 (95% confidence interval 1.5 to 1.7) and 1.9 (95% confidence interval 1.7 to 2.0) (P <0.0001) for the first and second test, respectively. Of 168 patients, 89 (53%) responded with erections sufficient for intercourse when tested the first time and 104 (62%) did so after the second injection. CONCLUSIONS: Erectile response to diagnostic intracavernous injection of prostaglandin E1 significantly improved in the second compared with the first test. Therefore, cautious interpretation of CDS is advised when patients are injected for the first time because too many false-positive tests may result.

Adolescent↗

Patterns of metastasis in muscle-invasive bladder cancer (pT2-4): An autopsy study on 367 patients.

BACKGROUND: Metastatic status is an essential determinant of prognosis of patients with muscle-invasive bladder cancer treated by cystectomy, and preoperative metastases detection is crucial for treatment selection in these patients. To better understand the metastatic behavior of bladder tumors, autopsies of patients with muscle-invasive bladder carcinomas (pT2-4) were evaluated. METHODS: Protocols and histologic sections from autopsies of 367 patients with pT2-4 bladder cancer were reviewed. RESULTS: Metastases were found in 251 of 367 patients (68%). The most frequent sites of metastases were regional lymph nodes (90%), liver (47%), lung (45%), bone (32%), peritoneum (19%), pleura (16%), kidney (14%), adrenal gland (14%), and the intestine (13%). There was no difference in the frequency and location of metastases between 308 transitional cell carcinomas and 38 squamous cell carcinomas. The frequency of metastases increased with local tumor extension (patients with cystectomy: pT2, 36%; pT3a, 45%; pT3b, 69%; pT4, 79%; p < 0.0001). For all pT classifications, the frequency of metastases was slightly higher in patients treated by cystectomy (metastases in 45% of 29 pT2 and 89% of 28 pT4 tumors) than in patients without cystectomy (36% of pT2 and 79% of pT4 tumors). CONCLUSIONS: These results argue against relevant clinical differences between histologic tumor types. The high frequency of metastases in patients having undergone cystectomy indicates that metastasis often occurs before the time of diagnosis. This emphasizes the need for a better prediction of the metastatic capability of these tumors at the time of diagnosis.

Adult↗

Life-threatening spontaneous retroperitoneal bleeding: a rare complication of oral anticoagulation.

In a patient on oral anticogulation with sudden onset of loin pain, the possibility of spontaneous bleeding in the retroperitoneum must be considered in the differential diagnosis of renal colic. This rare pathology can be life-threatening, and rapid diagnosis with ultrasound and computerized tomography of the abdomen must be made. If the patient is hemodynamically stable, a conservative approach is justified. Otherwise, emergency nephrectomy may be needed. As patients become older and indications for anticoagulant therapy become more common, we will probably have to face more of these rare bleeding complications in the future. We report such a case.

Administration, Oral↗

Intratumoral heterogeneity of von Hippel-Lindau gene deletions in renal cell carcinoma detected by fluorescence in situ hybridization.

Although chromosome 3p deletions are considered an initial event in clear cell renal cell carcinoma (RCC), the reported prevalence of 3p deletions is highly variable. Because molecular analyses may be influenced by intratumoral heterogeneity, this study was performed to evaluate the genetic heterogeneity of the von Hippel-Lindau (VHL) gene (on 3p25.5) in RCC. Fifty-three clear cell and papillary RCCs were examined by dual-labeling fluorescence in situ hybridization with probes for the VHL gene and chromosome 3 centromere. The results were compared with histopathological phenotype, proliferative activity (Ki-67 labeling index) and 8p/17p deletions (both suggested to be linked to RCC progression). A clear-cut VHL deletion (in more than 40% of cells) was detectable in 69% of clear cell RCCs but was not detectable in nine papillary RCCs. A considerable genetic heterogeneity of VHL deletions was seen in clear cell RCCs including VHL-deleted subpopulations with different chromosome 3 counts within individual tumors as well as populations with and without VHL deletions. 8p22 and 17p13 deletions (each of which were detected in 18% of clear cell RCCs) were both linked to VHL deletions. However, 8p and 17p deletions were not associated with tumor grade, stage, or Ki-67 labeling index. The data indicate that some clear cell RCCs may develop independently of VHL alterations.

Carcinoma, Renal Cell↗

EGF-r gene copy number changes in renal cell carcinoma detected by fluorescence in situ hybridization.

Expression of epidermal growth factor receptor (EGF-r) is a frequent event in renal cell carcinoma (RCC). To investigate the role of EGF-r gene copy number changes related to EGF-r overexpression, 50 RCC specimens were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry. Dual-labelling FISH with a repetitive pericentromeric probe for chromosome 7 and a probe for the EGF-r gene (at 7p13) was performed to analyse the EGF-r copy number in relation to chromosome 7 copy number on a cell-by-cell basis. Polysomy 7 was frequent in all histological types of RCC. Chromosome 7 polysomy was found in 26 of 35 clear cell (74 per cent), nine of nine papillary, and three of three chromophobe RCCs. EGF-r gene copy number was closely associated with the chromosome 7 copy number on a cell-by-cell basis. No EGF-r gene amplifications were found. EGF-r positivity was found in 37 of 50 cases (74 per cent) by immunohistochemistry. EGF-r positivity was more common in clear cell (81 per cent) than in papillary tumours (40 per cent; P = 0.029). Neither chromosome 7 nor EGF-r gene copy number was associated with EGF-r expression, indicating that an increased gene dosage is not a mechanism of EGF-r overexpression in RCC.

Carcinoma, Renal Cell↗

[Cytogenetic changes in prostatic carcinoma].

Development and progression of tumors is driven by a malfunction of specific genes. Although prostate cancer is one of the most frequent tumors, little is known about the genes involved. Cytogenetic and molecular examinations have shown that chromosomal deletions most frequently involve 7q, 8p, 10q, 13q, 16q, 17p and the Y chromosome. These loci may carry tumor suppressor genes with relevance for prostate cancer. DNA sequence copy number gains were most frequently observed at chromosomes 7, 8q, and 11q. These regions may carry currently unknown oncogenes. There is increasing evidence for a clinical relevance of genetic alterations. Polysomies of several chromosomes were shown to be associated with poor prognosis of prostate cancer patients. Androgen receptor amplification can be found in hormone-refractory carcinomas which may respond to total androgen blockage. For the future it is hoped that the identification of the genes involved in prostate cancer and the determination of their function could allow for significant improvements of treatment strategies for prostate cancer patients.

Biomarkers, Tumor↗

Patterns of chromosomal imbalances in advanced urinary bladder cancer detected by comparative genomic hybridization.

To identify genetic changes linked to bladder cancer progression we analyzed 90 invasive transitional cell carcinomas (37 pT1 and 53 pT2-4) by comparative genomic hybridization. The most frequent alterations included 1q+ (37%), 5p+ (24%), 6q- (19%), 8p-(29%), 8q+ (37%), 9p- (31%), 9q- (23%), 11p-(24%), 11q- (22%), 17q+ (29%), and 20q+ (28%). Interestingly, there were three groups of alterations that frequently occurred together (9p- and 11q13+/ 20q+ and 11q13+ or 17q+/1q+ and 3p+ or 11q-). These loci might carry genes that interact with each other in specific molecular pathways. There were remarkable genetic similarities between minimally and deeply invasive tumors of different histological grades, including a similar number of aberrations per tumor and an equal frequency of most individual alterations. However, deletions of 5q, 6q, and 15q and gains of 5p, 7p, and Xq were significantly more frequent in pT2-4 than in pT1 carcinomas. These loci may harbor genes that are important for bladder cancer progression.

Chromosome Aberrations↗

Ki67 labeling index in core needle biopsies independently predicts tumor-specific survival in prostate cancer.

A better knowledge of the biological aggressiveness of individual tumors could facilitate the selection of treatment in prostate cancer patients. This study assesses the influence of histological and molecular features in core needle biopsy specimens of prostate cancer on tumor-specific survival. Formalin-fixed core needle biopsy specimens from 111 consecutive patients (mean follow-up, 5.0 years) were immunohistochemically examined for their proliferative activity (Ki67 labeling index [LI]) and expression of p53 and Bcl-2. Overexpression of p53 was found in 16% of the biopsy specimens and was mainly restricted to poorly differentiated tumors. Bcl-2 positivity was found in 20% of tumors. The median Ki67 LI was 7.5%. There was a strong relationship between Ki67 LI and Gleason grade, with a continuous increase in the proliferative activity from low-grade to high-grade tumors (P = .0006). Univariate tumor-specific survival analysis showed that high Gleason score (P = .0018), high percentage of biopsy tumor involvement (P = .0227), high Ki67 LI (P = .0007), and p53 positivity (P = .0024) were predictors of tumor-related death. A high Ki67 LI emerged as the only independent predictor of tumor-specific survival in multiparametric analysis. These results indicate that core needle biopsy specimens of the prostate not only are useful for diagnosis of malignancy but also can provide valuable prognostic information. Immunohistochemical examinations of molecular features may be a helpful adjunct for a better pretherapeutic assessment of prostate cancer aggressiveness and therefore contribute to an improved initial patient management.

Aged↗

Focal neuroendocrine differentiation lacks prognostic significance in prostate core needle biopsies.

PURPOSE: The biological behavior of prostate cancer is highly variable and cannot sufficiently be predicted by histological criteria alone. New prognostic factors are needed in core needle biopsies before initial treatment decisions. We investigate the prognostic significance of focal neuroendocrine differentiation in core needle biopsies of prostate cancer. MATERIALS AND METHODS: Core needle biopsies from 105 untreated patients (mean age 71 years) were immunohistochemically examined for focal neuroendocrine differentiation using an antibody against chromogranin A. Tumor cell proliferation was assessed with Ki-67 labeling index using MIB 1 antibody. The cause of death was determined by examination of records including autopsy reports. RESULTS: Focal neuroendocrine differentiation was found in 25% of the tumors. There was no association between the presence of focal neuroendocrine differentiation and Gleason score or Ki-67 labeling index. Tumor specific survival analysis revealed that high Gleason score and high Ki-67 labeling index were predictors of tumor specific death, whereas focal neuroendocrine differentiation failed to provide prognostic information. There was a significant increase in frequency and density of neuroendocrine differentiation between initial core needle biopsies and later specimens of secondary hormone resistant prostate cancer in 15 patients. CONCLUSIONS: In contrast to high Gleason score and high Ki-67 labeling index, focal neuroendocrine differentiation is not a prognostic factor in core needle biopsies of prostate cancer. Focal neuroendocrine differentiation seems to appear more frequently and intensively in hormone resistant prostate cancer, supporting a role of neuroendocrine cells in the development of hormone refractory disease.

Aged↗

[Transurethral thermotherapy of the prostate--a very promising treatment method for benign prostatic hyperplasia].

Transurethral resection of the prostate remains the most common method for the treatment of benign prostatic hyperplasia (BPH). Due to unsatisfactory results in about 18% of the patients new methods to treat BPH have been developed. We evaluated 45 patients 6 and 12 months after transurethral microwave thermotherapy using the Prostatron device with Prostasoft 2.5 software. There was a significant improvement of the urinary symptoms and of the quality of life index from 18 to 9.5 and from 3.2 to 1.6 points, respectively. Urinary flow rate improved from 8.8 to 12.1 ml/sec and residual urine was reduced from 101 to 52 ml. The treatment was well tolerated and side effects were minimal. High-energy transurethral microwave thermotherapy is an effective and safe minimal invasive alternative to treat BPH in selected patients. As no anesthesia is required transurethral microwave thermotherapy can also be offered to high risk and elderly patients.

Aged↗

Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization.

Little is known about the genetic changes underlying invasive tumor growth in bladder cancer. Because alterations that are linked to invasive tumor growth may be detectable in minimally invasive (stage pT1) but not in noninvasive (stage pTa) tumors, we searched for genetic differences between 28 pTa and 28 papillary pT1 bladder tumors by comparative genomic hybridization. Losses of 9q (54%), 9p (39%), and Y (28%) and gains of 1q (14%) were most prevalent in pTa tumors. These changes may play a role in the initiation of noninvasive papillary bladder cancer. The total number of aberrations was higher in pT1 tumors (6.5 +/- 5.4) than in pTa tumors (2.3 +/- 2.1; P = 0.0003), suggesting an increased genetic instability at stage pT1. Specific alterations, which were significantly more frequent in pT1 than in pTa tumors (P < or = 0.05), included deletions at 2q (36% of pT1 tumors), 8p (32%), and 11p (21%) and gains at 1q (54%), 8q (32%), 3p, 3q, 5p, 6p, and 10p (18% each). These loci are candidates for carrying genes involved in invasive tumor growth in bladder cancer. High-level amplifications at 1q22-24, 3p24-25, 6p22, 8p12, 8q21-22, 10p12.1-14, 11q13, 12q15-21, 13q31-33, Xp11-13, and Xq21-22.2 may pinpoint the location of oncogenes with relevance for bladder cancer.

Chromosome Aberrations↗

[Results of microsurgical reconstruction after vasectomy].

Because of the increasing number of divorces surgical refertilisation by vasovasostomy has become increasingly important. Of 33 patients operated in the last decade, 32 could be reached for follow-up. The patency-rate was 86% and the pregnancy-rate 28%. Possible explanations for this discrepancy are discussed. The time lag between vasectomy and vasovasostomy was the most important prognostic factor. There was no difference in the results between one-layer and two-layer anastomosis. With an interdisciplinary approach the same patency rate as described in the literature was achieved.

Adult↗

p53 protein expression but not mdm-2 protein expression is associated with rapid tumor cell proliferation and prognosis in renal cell carcinoma.

The clinical course of renal cell carcinoma (RCC) is highly variable. Overexpression of the p53 protein has been suggested as a possible prognostic parameter in RCC. Overexpression of the mdm-2 oncogene product has been shown to interact with the p53 function. To investigate the immunohistochemical overexpression of mdm-2 protein in comparison with that of p53 protein in RCC, 50 nonpapillary pT3 RCCs were immunostained for p53 protein (DO-7) and mdm-2 (IF2). Tumor growth fraction (Ki-67 labeling index; MIB-1) was determined by immunohistochemistry. p53 positivity was detected in 16% of tumors. mdm-2 overexpression was seen in 30% of RCCs. There was a significant association between p53 and mdm-2 immunostaining (P = 0.0006), suggesting that mdm-2 protein may contribute to p53 protein stabilization in RCC. p53 overexpression was associated with a high Ki-67 LI (P = 0.0002), suggesting that p53 overexpression is involved in growth control in RCC. Survival analysis showed that Ki-67 LI (P = 0.04) and p53 overexpression were associated with poor prognosis (P = 0.0021), whereas mdm-2 overexpression was not related to patient outcome (P = 0.73). A Cox regression analysis revealed tumor stage (P < 0.001) and p53 overexpression (P < 0.05) to be independent prognostic parameters. It is concluded that p53 but not mdm-2 may be of practical relevance in predicting patient prognosis in RCC.

Carcinoma, Renal Cell↗

DNA aberrations in urinary bladder cancer detected by flow cytometry and FISH.

Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%; P < 0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as "superficial bladder cancer." The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for > or = 4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.

Carcinoma, Transitional Cell↗

Mumps orchitis: report of a mini-epidemic.

PURPOSE: The incidence of mumps orchitis has declined dramatically since the introduction of vaccination. While in the past cases of mumps have only been seen occasionally at our institution, recently there has been a sharp increase in the number of confirmed cases. MATERIALS AND METHODS: Between June 1995 and April 1996, 11 patients with severe mumps orchitis were hospitalized at our clinic. Medical history, therapeutic measures and clinical outcome were recorded for each patient. RESULTS: All patients showed marked scrotal swelling with a temperature above 38.5 C. Serum C-reactive protein was significantly elevated (mean 140 mg./l.). The vaccination status of 1 of the 11 patients (9%) was unknown. Medical records from the remaining 10 patients indicated that they had not been vaccinated. Nine patients (82%) had a typical mumps parotitis preceding the orchitis. In 2 patients the clinical diagnosis of parotitis was uncertain but mumps serology was positive. None of the patients showed other manifestations of mumps. Antibodies to the mumps virus (IgG and IgM) were determined in 6 patients and positive in all cases. The average interval between parotitis and onset of orchitis was 10 days. All patients were hospitalized for an average of 6 days. Treatment included bed rest with local cooling, scrotal support and systemic treatment with nonsteroidal anti-inflammatory drugs. Ciprofloxacin or clavulanic acid/amoxicillin was administered as bacterial orchitis could not be excluded at initial presentation. The mean time to cessation of fever was 3.6 days (range 3 to 5). Antibiotics were administered for an average of 8.8 days (range 7 to 13) and anti-inflammatory drugs were given an average of 8.6 days (range 7 to 11). One patient required scrotal exploration. CONCLUSIONS: Since the introduction of a vaccine against the mumps virus there is a diminished risk for mumps and its complications. However, in case of scrotal swelling mumps orchitis should still be considered. Despite vaccination mumps has not been erradicated. Therefore, continued vaccination should be considered an important step in minimizing clinical outbreaks and working towards a possible eradication of this disease in the future.

Adolescent↗