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Biomedical subjects

Kenneth Steven

Publications and source records attributed to Kenneth Steven.

9 recordsLinked to original sources
PubMed2006

Transitional cell bladder tumor: predicting recurrence and progression by analysis of microsatellite loss of heterozygosity in urine sediment and tumor tissue.

Transitional cell bladder tumors (TCT) is prone to recurrence (60-80%) after tumor resection. Up to 25% of these patients will progress, so it is important to find reliable predictive markers. We analyzed for loss of heterozygosity (LOH) with respect to 13 microsatellites located on 10 different chromosomal arms. This analysis was performed on the urine sediment and tumor tissue from 59 patients with bladder TCT and on the urine and normal-looking mucosa from 25 patients with a history of bladder TCT but no evidence of disease at the time of the study inclusion. The median follow-up period was 23.1 months (range, 2-48 months) for the 59 patients with bladder TCT and 25 months (range, 4-57 months) for the 25 patients without evidence of ongoing active disease. Correlation between LOH and eventual recurrence, progression, and mortality was investigated. In patients with noninvasive TCT, correlation between 11p tumor tissue LOH and recurrence was found. Similarly, 8p LOH in both urine sediment and tumor tissue correlated with progression. Finally, in the group of patients with a history of bladder TCT, normal tissue 8p and/or 11p LOH correlated with recurrence.

Aged↗
PubMed2004

Microbial flora in ileal and colonic neobladders.

OBJECTIVE: To describe bacterial colonization in patients with ileal and colonic neobladders. METHODS: Twenty-three patients with right colon neobladders, 30 with ileal neobladders, 11 who had undergone radical prostatectomy, and 6 healthy controls were included. Culture of clean-catch, midstream urine specimens was done weekly for 3 weeks, and this was repeated after 6 months. Residual urine was measured, and the patients were interviewed about leakage. All patients and controls were antibiotic free during the study except for 13 of the ileal neobladder patients, who were treated with trimethoprim 100mg daily. RESULTS: Urine cultures from controls and prostatectomy patients were negative for bacteria, whereas 67% of the specimens from patients with neobladders, not on antibiotic therapy, were culture positive, and half of these contained uropathogenic species, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacterial colonization (including uropathogenic strains) was strongly correlated with residual urine (p<0.005), but not with leakage. Anaerobic strains were found more frequently (p=0.04) in urine from ileal neobladders than in urine from colonic neobladders. The 13 patients with ileal neobladders and on prophylactic antibiotic therapy carried bacteriuria in 80% of the samples, the majority being anaerobic strains. Uropathogenic strains, mainly Enterecoccus faecalis was revealed in 30% of the samples. CONCLUSIONS: The lower urinary tract of patients with ileal or colonic neobladders is heavily colonized with potentially uropathogenic and anaerobic bacteria. Complete bladder emptying reduces the bacterial burden. Anaerobic colonization is increased in neobladders reconstructed from ileum. Prophylactic antibiotic therapy does not seem to reduce the bacterial burden, but interferes with the bacterial composition.

Aged↗
PubMed2004

Microsatellite analysis of urine sediment versus urine cytology for diagnosing transitional cell tumors of the urinary bladder.

The aim was to evaluate microsatellite analysis of urine sediment (MAUS) as an alternative method to urine cytology for routine diagnosis of patients with transitional cell tumors (TCT) of the urinary bladder. Urine cytology has the advantage of being non-invasive, fast and cheap, but is of limited value because of its low sensitivity. MAUS has previously been found to be a successful alternative method. However, the experimental set-up of such investigations implied exclusion of samples with unfavorable characteristics and use of a large number of markers. In the present study, MAUS was tested on all samples routinely available and a small panel of markers was selected. The urine sediments of 66 TCT patients and 24 controls were analyzed by MAUS with 16 fluorescent markers and by urine cytology. All samples were analyzed, including the ones of later micturition, with gross hematuria, leukocyturia or absence of visible sediment. In patients with tumors of low grade (grades I-II), MAUS was significantly more sensitive than urine cytology. The two methods were of equivalent diagnostic power in high-grade (grades III-IV), high-stage (pT1-pT4) tumors. A panel of the six most informative markers for MAUS was selected. Although MAUS has an advantage over routine cytology in low-grade, low-stage tumors, an overall sensitivity of 45% is not sufficient for routine clinical use.

Adult↗
PubMed2003

Relative importance of sources of symptom-induced distress in urinary bladder cancer survivors.

OBJECTIVE: The influence of specific symptoms on emotions and social activities in the individual patient varies. Little is known about this variation in urinary bladder cancer survivors (in other words, about the relative importance of sources of symptom-induced distress). METHODS: We attempted to enroll 404 surgical patients treated with cystectomy and a conduit or reservoir in four Swedish towns (Stockholm, Orebro, Jönköping, Linköping), 101 surgical patients treated with cystectomy and orthotopic neobladder at the Herlev Hospital in Copenhagen, Denmark, and 71 patients treated with radical radiotherapy for bladder cancer, as well as 581 men and women controls in Stockholm and Copenhagen. An anonymous postal questionnaire was used to collect the information. RESULTS: A total of 503 out of 576 (87%) treated patients and 422 out of 581 (73%) controls participated but 59 patients were excluded. The primary source of self-assessed distress among cystectomised patients was compromised sexual function; reduced intercourse frequency caused great distress in 19% of the conduit patients, 20% of the reservoir patients and 19% of the bladder substitute patients. The primary source of self-assessed distress in patients treated with radical radiotherapy was symptoms from the bowel; 17% reported great distress due to diarrhoea, 16% due to abdominal pain, 14% due to defecation urgency and 14% due to faecal leakage. The highest proportion of subjects being distressed was 93% (substantial: 43%, moderate: 29% and little: 21%) for treated upper or lower urinary retention (indwelling catheter or nephrostomy). CONCLUSION: The distress caused by a specific symptom varies considerably and the prevalence of symptoms causing great distress differs between treatments in bladder cancer survivors. It is possible that patient care and clinical research can be made more effective by focusing on important sources of symptom-induced distress.

Adult↗
PubMed2002

Distressful symptoms and well-being after radical cystectomy and orthotopic bladder substitution compared with a matched control population.

PURPOSE: We compared subjective quality of life, well-being, urinary tract symptoms and distress in patients after radical cystectomy and orthotopic urinary reconstruction with those in a matched control population. MATERIALS AND METHODS: Included in this study were 101 consecutive recurrence-free patients who underwent radical cystectomy and orthotopic bladder substitution with an ileal urethral Kock neobladder at Herlev Hospital with a minimum followup of 1 year. A frequency matched control group comprising 147 individuals was selected from the same geographical region. Information was collected by an anonymous postal questionnaire and analyzed externally in Sweden. RESULTS: The prevalence of low or moderate psychological well-being (32% versus 36%) and subjective quality of life (30% versus 38%), and high or moderate anxiety (23% versus 18%) and depression (26% versus 37%) was similar in patients with an orthotopic neobladder and population controls. Patients with a neobladder felt as attractive as the control population. Of the operated men 94% had erectile dysfunction compared with 48% of controls. Daytime and nighttime urinary frequency was similar in patients and controls (3% and 3%, and 15% and 13%, respectively), while the prevalence of urinary leakage at least once monthly was higher in patients (18% versus 5%). Intermittent self-catheterization was performed by 26% of patients with a neobladder. Urinary tract infection (14% versus 6%) was more common and the prevalence of distressful bowel symptoms (14% versus 9%) was slightly more common in patients than in controls. CONCLUSIONS: Well-being and subjective quality of life in patients after radical cystectomy and orthotopic bladder substitution were similar to those in a matched control population.

Adaptation, Psychological↗
PubMed2002

Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours.

This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma of the bladder. In the first trial, local treatment consisted of cystectomy (DAVECA 8901) and in the other trial the treatment was radiotherapy (DAVECA 8902); 153 eligible patients were randomized. The majority of the patients (89%) completed the protocol. The overall time to progression for all 153 patients was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19.2 months in the group receiving chemotherapy and 16.3 in the group not receiving chemotherapy. The 5-year survival rate was 19% in the group receiving chemotherapy and 24% in the groups not receiving chemotherapy (p = 0.98). Late toxicity grade 3 or 4 of the bladder was recorded in 25% of the patients (actuarial rate). Neoadjuvant chemotherapy with cisplatin and methotrexate did not significantly improve disease-free or overall survival in 153 randomized patients with invasive bladder cancer.

Aged↗
PubMedDate not supplied

New evaluation of plasma DNA microsatellite analysis in patients with TCC of the urinary bladder.

BACKGROUND: To determine the diagnostic value of plasma DNA microsatellite analysis in patients with transitional cell carcinoma (TCC) of the urinary bladder, by redefining plasma LOH from the equivalent analysis in controls. The method was further tested for MSI (microsatellite instability) and compared with tissue DNA analysis. MATERIALS AND METHODS: Sixteen microsatellites were amplified in leukocyte, plasma and tissue DNA from 40 patients and 28 controls, and analysed in a laser-based, capillary electrophoresis system. Plasma LOH was determined from the controls' cut-off values. RESULTS: The difference between plasma LOH frequency in patients (25% (10/40)) and controls (14% (4/28)) was not significant. Nevertheless, it occurred significantly more often in low rather than high-grade tumors (p=0.03) and controls (p=0.04). Plasma MSI was dependent upon the number of PCR cycles. Tissue LOH was present in 78% (31/40) of the patients and in none of the controls. Tissue MSI was uncommon. CONCLUSION: The results of plasma DNA microsatellite analysis in TCC need cautious interpretation.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

Under-representation of bladder transitional cell tumour 9q, 11p and 14q LOH in urine and impact on molecular diagnosis.

BACKGROUND: To investigate whether the recently reported evidence of differences in the overall loss of heterozygosity (LOH) frequency between urine and tumour tissue in patients with transitional cell tumours (TCT) of the urinary bladder involved specific chromosomal sites, and their impact in diagnosis. MATERIALS AND METHODS: Blood, tissue and urine specimens were obtained from 55 patients and 25 controls. Sixteen microsatellites were PCR-amplified and blindly analyzed for LOH through a laser-based capillary electrophoresis system. RESULTS: Significant frequence differences between tumour tissue and urine sediment LOH were found in 9q and 11p in non-invasive disease and 14q in invasive disease. There was no significant difference for all the other chromosomal arms analyzed. CONCLUSION: The contribution in the urine sediment of cells belonging to tumours of the same histological classification differs according to the specific genetic alterations these cells carry. Furthermore, the location regarding these differences could indicate regions involved in tumour exfoliation or apoptosis.

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