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Biomedical subjects

L Baert

Publications and source records attributed to L Baert.

At least 55 records · Page 3Linked to original sources

Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide.

PURPOSE: We define the risk of bladder cancer in multiple sclerosis related to the use of indwelling catheters and cyclophosphamide administered as an immunomodulating agent. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,351 patients with multiple sclerosis referred to the National Center for Multiple Sclerosis. RESULTS: Of the 2,351 patients 2 women and 5 men (0.29%) had bladder cancer. Of the 850 chronically catheterized patients the incidence was 0.7%. One patient with cancer performed intermittent catheterization for a rate of 0.23% in this group. In a subgroup of 70 patients treated with cyclophosphamide 5 chronically catheterized patients (5.7%) had bladder cancer. Hematuria was the most common presenting symptom. These data were compared with those in the literature on bladder cancer in spinal cord injury. CONCLUSIONS: These data suggest a possible synergistic role of cyclophosphamide and chronic catheterization in the induction of secondary bladder cancer. Regular cystoscopy is warranted in these patients to allow early detection of bladder tumors. Nitric oxide metabolism may be an important factor in the carcinogenesis of this type of bladder cancer.

Adjuvants, Immunologic↗

Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years.

OBJECTIVES: To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer. METHODS: A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis. RESULTS: In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated. CONCLUSIONS: Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.

Aged↗

Histology may depend on the presence of partial monosomy or partial trisomy 3 in renal cell carcinoma.

Rearrangements of 3q were found in 10% of a series of 230 cases of renal cell carcinoma (RCC). Together with observations from the literature, these structural changes can be concluded to involve two different regions, 3q21 and 3q11-12, and are usually present as unbalanced translocations. In some of these cases of RCC with the translocation, the normal chromosome 3 may reduplicate, giving rise to a partial trisomy 3q instead of a partial monosomy 3. In those cases, however, histology shows chromophilic-papillary RCC instead of clear cell-nonpapillary. Hence, besides the still unresolved underlying molecular changes causing RCC, histology may in part depend on the presence of partial monosomy or partial trisomy 3.

Adenocarcinoma, Papillary↗

Management of carcinoma of the bladder.

Carcinoma of the bladder (CaB) is a common tumor of the genitourinary tract. In the United States in 1997, CaB was second in frequency of occurrence and third in mortality among genitourinary tumors. This tumor has a well-documented history of environmental and industrial causative factors. The strongest etiologic risk factors include the use of tobacco, which is thought to be responsible for half of the CaB diagnosed in men in the United States, and some arylamines. In the past 30 years, there has been major improvement in the survival of patients with this disease. Multiple factors were responsible for this accomplishment and they include: 1) better understanding of the natural history of CaB, 2) development of immunohistochemical analysis helpful in defining prognostic factors, 3) improved imaging and nonimaging diagnostic modalities helpful in making earlier diagnosis and better defining the true anatomical extent of the tumor, 4) development of more effective therapy for carcinoma in situ, 5) major improvement in surgical techniques resulting in better treatment outcomes, and 6) the wide use of adjuvant chemotherapy. Major stress has been placed on the quality of life of patients treated for CaB. Quality of life was improved by optimizing surgical, radiation, and medical treatment techniques. The two most important factors producing this quality-of-life improvement include: 1) the use of organ-preserving therapy in properly selected patients that involves the use of a multimodality therapeutic approach with transurethral resection, radiation therapy, and chemotherapy; and 2) the ability to treat selected men and women with radical cystectomy followed by orthotopic reconstruction that allows patients nearly physiologic voiding. Current research efforts are directed toward better patient selection for appropriate therapy which is expected to increase patient survival and improve quality of life. Of particular importance in the selection of this optimal therapy in patients with CaB is a wide application in the clinical practice of important recent advances in molecular genetics.

Carcinoma↗

Fluorescence detection of flat transitional cell carcinoma after intravesical instillation of aminolevulinic acid.

Carcinoma in situ (CIS) of the bladder is a confounding disease that is difficult to recognize endoscopically because it is a flat cancer. Many studies have suggested its relationship with subsequent invasive disease. Early recognition of CIS therefore is essential in offering the patient the most appropriate treatment and the highest cure rate. Because white light cystoscopic examination is not sufficient to reveal areas of dysplasia or CIS, random biopsies are recommended. The authors evaluate whether amino levulinic acid (ALA) fluorescence detection could be helpful in diagnosing CIS and if the specificity could be enhanced by reducing the ALA dose. Sixteen patients with papillary bladder cancer, and CIS and dysplasia were given low-dose ALA. Fluorescence detection of the metabolized ALA was performed 3 hours later, with the naked eye, after blue light illumination. Carcinoma in situ or dysplasia was found in 50 biopsies. The sensitivity for detecting CIS was 94% with a specificity of 54%. Carcinoma in situ can be diagnosed with a very high accuracy through fluorescence detection after ALA instillation. Fluorescence detection can be achieved with the naked eye and does not necessitate either complex equipment or specially trained personnel.

Administration, Intravesical↗

A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer.

OBJECTIVES: To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer. METHODS: A total of 1,453 patients with either confirmed metastatic disease (M1), or T3/T4 non-metastatic disease with elevated prostate-specific antigen (M0) were recruited into one of two identical, multicentre, randomised studies to compare 'Casodex' 150 mg/day with castration. The protocols allowed for combined analysis. RESULTS: At a median follow-up period of approximately 100 weeks for both studies, 'Casodex' 150 mg was found to be less effective than castration in patients with metastatic disease (M1) at entry (hazard ratio of 1.30 for time to death) with a difference in median survival of 6 weeks. In symptomatic M1 patients, 'Casodex' was associated with a statistically significant improvement in subjective response (70%) compared with castration (58%). Analysis of a validated quality-of-life questionnaire proved an advantage for 'Casodex' in sexual interest and physical capacity. 'Casodex' had a substantially lower incidence of hot flushes compared to castration (6-13% compared with 39-44%) and the most commonly reported adverse events were those expected for a potent antiandrogen. However, in patients with M0 disease at entry, the data are still immature with only 13% of M0 patients having died. An initial analysis of this immature data has suggested that the results in these patients may be different to those obtained in patients with M1 disease. A further survival analysis in patients with M0 disease is therefore planned when the data are more mature. CONCLUSIONS: 'Casodex' 150 mg is less effective than castration in patients with M1 disease. However, 'Casodex' has shown a benefit in terms of quality of life and subjective response when compared to castration and has an acceptable tolerability profile. Thus 'Casodex' 150 mg monotherapy is an option for patients with M1 prostate cancer for whom surgical or medical castration is not indicated or is not acceptable.

Aged↗

Prediction of urinary continence following radical prostatectomy.

The aim of this study was to assess the incidence of incontinence after radical prostatectomy and to identify the various factors that can predict urinary continence after radical prostatectomy. Urinary continence following a radical prostatectomy was evaluated in 175 consecutive patients who underwent surgery. Immediately after catheter withdrawal, on the 15th postoperative day, 66% of the patients were incontinent. Varying degrees of incontinence persisted in 53% of the cohort at 1 month postoperatively. Thirty-three, 12, 8 and 2% of the patients remained incontinent at respectively 3, 6, 9 and 12 months of follow-up. A number of possible pre- and peroperative factors which might predict the continence status were examined are related to it at subsequent intervals after the surgical intervention. Preservation of the neurovascular bundles, prior transurethral resection of the prostate, preoperative micturition disorders and age were significant contributors in the prediction of urinary incontinence after radical prostatectomy.

Aged↗

A cystine lower pole renal calculus treated with holmium: YAG laser using a flexible 9,5F transurethral ureteroscope.

We report a case of a 1.5 cm cystine staghorn calculus of the right lower pole in a 32 year female known cystinuric patient. With a 200 microns Holmium laser probe through a 9,5 F flexible ureteroscope the calculus was fragmented in small particles. An internal ureteral stent was inserted at the end of the procedure. All but one small residual fragments were evacuated spontaneously after removal of the stent. This case shows that flexible ureteroscopy combined with the Holmium laser is a safe and efficient procedure to treat medium size renal cystine calculi. It can be repeated in case of recurrence with minimal trauma to the urologic tract.

Adult↗

Identification of an enriched CD4+ CD8alpha++ CD8beta+ T-cell subset among tumor-infiltrating lymphocytes in human renal cell carcinoma.

Three-color immunofluorescence flow-cytometric analysis of freshly isolated tumor-infiltrating lymphocytes (TIL) from patients with primary renal cell carcinoma (RCC) revealed a unique, not previously described TIL subset with a CD3+ CD4+ CD8alpha++ CD8beta+ phenotype. This subset represented at least 5% of CD3+ TIL in 15 of 21 patients with clear cell RCC, whereas it was not or only marginally represented in patients with papillary RCC or sarcomatoid RCC. In one-third of the patients with clear cell RCC, more than 20% of CD3+ TIL and in one patient more than half of the CD3+ TIL displayed this phenotype. The occurrence of this subset was not associated with pathological stage, tumor diameter, nuclear grade, cytogenetic abnormalities or vascular invasion in this patient cohort. When present, the CD3+ CD4+ CD8alpha++ CD8beta+ subset was detected in similar proportions in tumor tissue and tumor capsula, and it was also detected in adjacent non-tumoral renal tissue, albeit in much lower proportions. Despite strong cell surface expression of various activation markers (CD69, CD54 and HLA-DR), CD3+ CD4+ CD8alpha++ CD8beta+ cells displayed no ex vivo cytolytic activity in an anti-CD3-redirected cytotoxicity assay. In contrast with CD3+ CD4+ CD8- cells from the same tumor sample, they were markedly deficient in IL-2R alpha up-regulation following anti-CD3 triggering. The possibility that these cells represent either anergic cells or a highly specialized effector population with a discrete, as yet undescribed function is discussed.

Antigens, CD↗

Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup.

PURPOSE: We described the long-term outcome of intravesical capsaicin instillations in patients with urinary incontinence and compared its efficacy in 2 similar populations of patients with multiple sclerosis in a dual center study. MATERIALS AND METHODS: During 5 years 79 patients with intractable urinary incontinence have been treated with intravesical capsaicin. The majority of patients had spinal cord disease due to multiple sclerosis but 4 were neurologically normal. Cystometry was performed before and 4 to 6 weeks after intravesical instillation of 1 to 2 mmol./l. of capsaicin in 30% ethanol in saline. Instillations of vehicle (30% ethanol in saline) alone were carried out in 5 patients. RESULTS: In patients with phasic detrusor hyperreflexia complete continence was achieved in 44%, satisfactory improvement occurred in 36% and treatment failed in 20%. Clinical benefit from a single instillation lasted 3 to 6 months and was repeated in some patients with similar improvement. Capsaicin was ineffective in patients with poor bladder compliance and in neurologically normal patients with sensory urgency and detrusor instability. There was no clinical or urodynamic improvement in patients treated with vehicle alone. There have been no long-term complications. CONCLUSIONS: Our study shows that repeated instillations of intravesical capsaicin are effective in treatment of patients with detrusor hyperreflexia due to spinal cord disease and that effectiveness of the treatment persists at least 3 to 5 years.

Administration, Intravesical↗

Anal tenesmus caused by seminal vesicle cyst.

Congenital cysts of the seminal vesicles with ipsilateral renal aplasia or dysplasia are rare but have been well described in the literature. We report the first case where anal tenesmus was the only presenting symptom. Another unique feature was the combination of this anomaly with a duplication of the inferior vena cava.

Adult↗

Chromosome analysis in angiomyolipoma.

Cytogenetic data on angiomyolipomas are scarce. We report a series of 10 cases from nine patients without clinical history of tuberous sclerosis. We found chromosome abnormalities in two, and in both cases the chromosomal changes were only numerical ones, i.e., trisomy 7 and trisomy 8.

Adult↗

From time dependent intermittent selfcatheterisation to volume dependent selfcatheterisation in multiple sclerosis using the PCI 5000 Bladdermanager.

The use of portable, patient controlled, ultrasound device for the measurement of the bladder volume (PCI 5000, Bladdermanager) in the management of neurogenic bladder dysfunction in Multiple Sclerosis is presented. Twenty-three patients were transferred from time dependent intermittent catheterisation to volume dependent intermittent catheterisation using this device. Evaluation of the accuracy of the measurements showed an accuracy of 91.05%. The efficacy per catheterisation improved significantly from 260.8 cc +/- 154 cc to 297.5 cc +/- 138 cc. The frequency of incontinence measured during 48 h decreased on the entire group from 69 to 39. Six patients could delete one catheterisation a day. Functional Independence Measurements (FIM score) did not show an increase of the level of assistance needed, using this device.

Adult↗

Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma.

We investigated the phenotype and functional capacities of tumour-infiltrating lymphocytes (TIL), freshly isolated from primary renal cell carcinoma (RCC) specimens (n = 20). Three-colour flow cytometry immunophenotyping revealed that RCC TIL consist mainly of CD3+ T cells, with a clear predominance of CD4- CD8+ over CD4+ CD8- T cells, and a marked population of CD4+ CD8+ T cells. Natural killer (NK) cells were also strongly represented (> 25% in 15 of 20 tumour samples), while B cells constituted a minor TIL subset (< 5% in 18 of 20 tumour samples). More importantly, the T and NK cells within the tumour displayed a significantly higher expression of the early activation marker CD69 than their counterparts in adjacent normal renal tissue and in peripheral blood. Expression of CD54 and of HLA-DR was also elevated on CD3+ TIL, and HLA-DR expression was further vigorously up-regulated following ex vivo stimulation with anti-CD3, all suggesting enhanced immune activity within the tumour microenvironment. CD3+ CD4+ TIL displayed a normal capacity to up-regulate CD25 expression and to secrete both Th1-type (IL-2, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)) and Th2-type (IL-4, IL-5 and IL-10) cytokines upon triggering with anti-CD3. Furthermore, cytokine production was susceptible to modulation by CD28 costimulation. CD3+ CD8+ TIL, on the other hand, consistently demonstrated a poor up-regulation of CD25 upon triggering with anti-CD3, and displayed poor ex vivo cytolytic activity in an anti-CD3-redirected 4-h cytotoxicity assay against murine P815 cells. Collectively, our findings indicate that the CD3+ CD4+ TIL in RCC have normal functional capacities, whereas the proportionally major CD3+ CD8+ TIL are functionally impaired. The relevance of these findings to the in vivo local immune response in RCC is discussed.

Adult↗

Treatment of metastatic carcinoma of the prostate.

Disseminated carcinoma of the prostate (CaP) is a common manifestation of this disease. Metastatic CaP in the United States is seen in about 45,000 patients each year at diagnosis. At least the same number of patients who have had prior definitive treatment with surgery or radiotherapy develop evidence of metastatic disease. Hormonal management is the most important and well established treatment for patients with prostatic metastases. Orchiectomy remains the most efficient and most cost effective therapy in a rapid ablation of testicular androgens. Due to a well known psychological reaction to castration which is seen in many patients, diethylstilbestrol (DES) is a good alternative and cost effective therapy. The mode of action of DES is to suppress LH production and to slowly, indirectly, decrease serum testosterone level. In recent years, total androgen blockade (TAB) has become a widely accepted treatment option. This treatment has been shown in several clinical trials to be effective and well tolerated by the patients. A major problem with a routine use of TAB is a relatively high cost of this therapy. In a European prospective randomized trial, goserelin acetate-flutamide combination significantly increased time to progression when compared with orchiectomy alone. Patients with localized and symptomatic metastases are best treated with radiotherapy. Those with multiple sites of involvement are best treated with strontium-89 which results in a good palliation in a majority of patients. Nearly all hormonally treated patients, with metastatic CaP, eventually show tumor progression. Presently available chemotherapy is of a low effectiveness and should not be used for these patients outside of controlled clinical trials. Current research is directed to identify effective therapy for hormone refractory patients. Immunotherapy and gene therapy may be useful future therapeutic options.

Androgen Antagonists↗