Biomedical subjects
Publications and source records attributed to K Steven.
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A patient with rectal cancer and invasion of the urinary bladder without extra-pelvic spread underwent total pelvic exenteration with rectal resection and bladder substitution with the urethro-ileal Kock reservoir. The patient has normal bowel and voiding functions and is without recurrence after two years.
Previous studies of chimeric animals and human tissues have shown the clonal nature of organ development, giving clues as to the normal development of organs and also to abnormal developments, such as atheromatous plaques. The clonal nature of bladder cancer in female patients has been demonstrated, but little has been known of the clonal development of the normal urothelium. Using an X chromosome inactivation analysis of cells microdissected from histologic slides from the female human bladder, macroscopic urothelial patches of monoclonality were detected. These patches are about 120 mm.2 in size, contain about 2 x 10(6) cells each and reflect the presence of coherent cellular families composed of stem cells and their differentiated derivatives. The large size of these patches was surprising when compared with previously reported patch sizes in other organ systems. The patches most probably are composed of the descendants of the original founder cells, which would suggest that only 200 to 300 cells participated in the formation of the urothelium. The limited number of stem cells, each giving rise to millions of cells may provide an explanation for the "field defect" that is often referred to in the pathogenesis of bladder cancer, as different cell patches may possess different predispositions to tumorigenesis.
OBJECTIVE: To compare the health-related quality of life after bladder substitution with that following ileal conduit diversion. PATIENTS AND METHODS: Sixty-seven male patients with bladder cancer completed the questionnaire; 38 had undergone bladder substitution and 29 ileal conduit diversion; the median follow-up was 1.0 year (range 0.5-3.0) and 4.8 years (range 1.1-15.2), respectively. Semi-structured qualitative interviews were conducted and analysed, and the questionnaire was developed based upon these results. RESULTS: Both day- and night-time urinary leakage occurred more frequently following bladder substitution (18% against 10%, and 21% against 3%). Nevertheless, urinary leakage affected conduit patients more severely and they scored higher on a leakage distress scale. Furthermore, 58% of the ileal conduit but only 21% of the bladder substitution patients gave urinary leakage as their main concern (P = 0.04). Ileal conduit patients did not retain their body image as well as those with bladder substitution. The frequency of both sexual and non-sexual physical contacts decreased in the majority of the conduit patients but only in a minority of the bladder substitute patients. Global satisfaction was high and similar in both groups. CONCLUSION: These results show that the health-related quality of life is retained to a higher degree after bladder substitution and supports the use of this procedure as the standard method of diversion after cystectomy for bladder cancer.
We report a case of tumor implantation in the abdominal wall following laparoscopic biopsy of a transitional cell tumor. Tumor seeding is a known risk in patients with transitional cell carcinoma and we recommend that laparoscopic biopsy of urothelial tumors be avoided.
Urine from patients with interstitial cystitis has been reported to be more cytotoxic than urine from healthy subjects when tested in vitro against cells from a normal urothelial cell line. The purpose of the present study was to develop a method to measure urinary cytotoxicity and so make it possible to estimate the toxicity of urine from interstitial cystitis patients. The study included 10 women with interstitial cystitis and 10 healthy controls. Urine specimens were obtained from both groups and urine cytotoxicity was measured by a modified 51Cr-release assay: A range of urine dilutions was added to suspensions of target cells with intracellular bound 51Cr, and cellular death was recorded by measuring the 51Cr-release from the target cells. The transitional cell bladder cell lines T24 and Hu609 and the erythroleukemia K562 cell line were used as target cells. There was no difference in urine cytotoxicity between interstitial cystitis patients and healthy controls. Urine cytotoxicity was increased by dilution in both groups.
Single stage radical cystectomy and pancreaticoduodenectomy (Whipple's procedure) was carried out in a 59-year old man for a benign pancreatic tumour (ancient schwannoma) and multifocal invasive bladder cancer. Urinary diversion was carried out using the urethral Kock reservoir.
A questionnaire study was carried out to compare the health-related quality of life after continent urinary diversion using a Kock pouch with that following ileal conduit diversion. 76 patients completed the questionnaire: 26 patients had a continent and 50 an ileal conduit diversion, median follow-up was 0.9 year (range 0.5-4.4) and 4.9 years (range 2.4-14.7), respectively. The type of operation carried significant relation to the presence of leakage distress associated with urine leakage; 78% among conduit patients versus 50% among continent diversion patients experienced distress. Physical contact between patient and partner was reduced significantly less following continent diversion: 16% against 43% among patients with conduit diversion. Global satisfaction with life was high and similar in the two groups. Continent urinary diversion appears to be superior to conventional ileal conduit diversion.
Transverse folds in the distal ureter were found on urograms in two adult patients with ureteral obstruction. These folds were associated with but did not cause ureteral obstruction. Histopathological examination of the excised ureter in one patient showed that the folds were made of luminal projections of lamina propria containing prominent bundles of smooth muscle. The folds probably originate as a result of a lower compliance of the distal part of the ureter, which reduces the distension produced by a luminal rise in pressure.
Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X chromosome for three tumors. Single locus alterations were detected in three tumors, while three other tumors revealed changes in two or more loci. In one tumor we found microsatellite instability in all five loci analyzed on chromosome 9. The alterations detected were either minor 2-base pair changes or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis.
A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder tumors from smokers and 13 of 40 (33%) tumors from lifetime nonsmokers. Overall, 13 of the 50 (26%) total point mutations discovered in this and previous work were G:C-->C:G transversions, a relatively rare mutational type in human tumors. In six tumors, identical AGA (Arg)-->ACA (Thr) point mutations at codon 280 were observed, suggesting a mutational hotspot in these tumors. Comparison of the mutational spectra from smokers and nonsmokers revealed no obvious differences in the types or positions of inactivating mutations; however, 5 of 15 tumors containing point mutations from cigarette smokers had double mutations, four of which were tandem mutations on the same allele. No double mutations were found in tumors from nonsmoking patients. None of the mutations in smokers were G:C-->T:A transversions, which would be anticipated for exposure to the suspected cigarette smoke carcinogen 4-aminobiphenyl. The results suggest that, although cigarette smoke exposure may not significantly alter the kinds of mutations sustained in the p53 gene, it may act to increase the extent of DNA damage per mutagenic event.
A model of the mechanics of smooth muscle reservoirs was derived from the stress-strain relation in smooth muscle strips. The model was applied to the intestinal bladder reservoir but may also be applied to natural reservoirs such as the bladder. The relation between reservoir volume and pressure was calculated at different values of smooth muscle tone and was found to accord with clinical results. The muscle tone of the bowel when measuring off the bowel to construct the reservoir was found to have a profound influence on its ultimate volume. Stiffening of a part of the reservoir wall as a result of edema or fibrosis will cause a substantial decrease in functional capacity, both directly as a result of a reduced expansion of the diseased part and indirectly by enhancing the stretching of the adjacent normal wall. The pressure rise produced by a slow peristaltic contraction was calculated to depend both upon the strength of contraction and on the degree of reservoir filling: Almost no pressure rise will occur in the near empty reservoir, while the highest pressure rise was calculated to occur at a volume of about 300 ml. If only a part of the reservoir contracts, more filling is needed before the pressure increases and the maximum pressure will be reached at a substantially higher volume. Localized contractions will stretch the resting reservoir wall and so activate stretch receptors, which may cause a desire to void, resulting in reduced functional capacity.
A theoretical analysis of the mechanics of tubular and detubularised bowel bladders is presented. The results are compared with clinical findings following bladder substitution with the tubular ileocaecal and the detubularised urethral Kock reservoir. The theoretical results are consistent with clinical observations showing that detubularisation increases reservoir capacity substantially, delays the onset and reduces the amplitude of the pressure rise produced by contractions. These findings account for the markedly improved nocturnal continence (80 versus 17% at 2 years), the longer voiding intervals (4 versus 2.5 h at 1 year) and the predisposition to urinary retention (25 versus 0% at 1 year) with detubularised bladder substitution. A simple equation is derived to calculate the capacities of both near-spherical and cylindrical reservoirs. The capacity of the U pouch is calculated to be less than that of the W-shaped, S-shaped and Kock reservoirs. Altering the shape of a reservoir from spherical to ellipsoid is calculated to have only a slight effect on its mechanical characteristics. Consequently the essence of detubularisation is to create a reservoir with high capacity, while shape is of secondary importance.
We report our experience of the treatment of carcinoma in situ (CIS) using intravesical therapy with the Danish Bacillus Calmette-Guérin (BCG) strain 331 (SSI). Forty-two patients received treatment, 11 had primary and 31 secondary CIS. The median follow-up period was 26 months (range 3-68). Patients received 6 weekly instillations (1 course) and non-responders an additional 6 instillations at 2-week intervals (2 courses). The complete response rate was 59% for 1-course patients, 33% for the 2-course patients and 68% for the entire series. Patients were considered treatment failures if they suffered progression to invasive cancer, metastasis or died from transitional cell carcinoma. BCG treatment was more effective in primary than in secondary CIS, with a complete response rate of 80% versus 65% and with no failures versus 35%. Patients with persistent CIS after the first course of BCG had a greater risk of failure than responders: 50% versus 17%. Patients with persistent CIS after the second course had a 75% failure rate. This suggests that cystectomy should be considered for non-responders following a 6-week course and recommended to those not responding to 2 courses. Ten patients had CIS in the prostatic urethra. All responded to BCG treatment; 2 suffered from recurrent CIS 1 associated with invasive urethral tumour. The incidence and severity of side effects were similar to those reported with other strains of BCG. One patient with primary CIS failed to complete the treatment owing to "BCG-itis".
This study was carried out to examine the efficacy of extraperitoneal pelvioscopy in detecting pelvic metastasis in patients scheduled to undergo radical cystectomy without preoperative chemo- or radiotherapy. The results of pelvioscopy were compared with those obtained by laparotomy. 54 consecutive patients underwent pelvioscopy without complications. Three were technically insufficient. Lymphatic tissue was biopsied in 29 (54%). Pelvioscopy demonstrated tumor dissemination in 5 patients (9.3%): 2 had pT4b tumor, 2 pelvic nodal metastases and 1 both. The remaining 49 patients with benign pelvioscopy were scheduled for laparotomy but 7 patients did not undergo the procedure: 3 had extrapelvic metastasis, 1 bronchial carcinoma, 1 aortic aneurysm, 1 refused surgery and 1 had pulmonary insufficiency. Accordingly, 42 patients underwent open exploration which demonstrated pelvic metastasis in 11: 9 had nodal metastasis, 1 a pT4b tumor and 1 both. Consequently the sensitivity of pelvioscopy in detecting pelvic metastasis was calculated at only 31%. This result indicates that extraperitoneal pelvioscopy should be considered a screening procedure rather than an accurate staging procedure for pelvic metastasis.
Seventy-three transitional cell carcinomas of the bladder were analyzed by immunohistochemistry for p53 nuclear accumulation, and the results were compared to mutations detected in the p53 gene by single strand conformational polymorphism analysis (SSCP) and DNA sequence analysis. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections. A highly significant association between the presence of p53 mutations and p53 nuclear reactivity as detected by immunohistochemistry was found (P = 0.0001). Of 32 tumors that demonstrated p53 mutations by SSCP, 27 (84%) showed p53 nuclear reactivity. Of the five cases that did not demonstrate p53 nuclear reactivity, four had mutations in exon 5. However, of 41 tumors with no evidence of p53 mutation by molecular analysis, 12 (29%) showed p53 immunoreactivity. This indicates that immunohistochemical methods may be more sensitive than SSCP in detecting p53 mutations or that discordant cases represent tumors with accumulation of wild type p53 protein, without mutations at the p53 locus. Of the 15 tumors that were found to have mutations at exon 8, 13 demonstrated high-intensity homogeneous p53 nuclear reactivity by immunohistochemistry, and all mutations located at codon 280 demonstrated high-intensity homogeneous immunoreactivity. However, three of three tumors with exon 6 mutations demonstrated low-level p53 immunoreactivity, and four of six tumors with mutations in exon 5 showed no detectable p53 nuclear reactivity. This indicates that the heterogeneity of immunoreactivity observed when analyzing p53 nuclear accumulation may be related to the site of the p53 gene mutation. Information on tumor grade, stage, lymph node status, disease-free interval, and overall survival were available in 54 patients who had undergone cystectomy. A significant association was observed between p53 alterations (detected by immunohistochemistry and SSCP) and histological tumor grade (P = 0.003) and stage (P = 0.01). We conclude that the immunohistochemical detection of p53 nuclear accumulation in formalin-fixed, paraffin-embedded tissue is highly associated with mutations in the p53 gene; this association has now been demonstrated in a large number of tumors. The heterogeneity of p53 nuclear reactivity seems to be related to the site of mutation in the p53 gene. A small proportion of tumors with a p53 gene mutation do not demonstrate immunohistochemically detectable p53 nuclear accumulation. Furthermore, a small but substantial proportion of tumors demonstrate p53 nuclear reactivity but do not show detectable mutations in the p53 gene by SSCP. Finally, both grade and stage of bladder cancer are related to p53 alterations, detected by immunohistochemistry or molecular methods.(ABSTRACT TRUNCATED AT 400 WORDS)
Fifty male patients who had undergone bladder substitution with a urethral Kock pouch after radical cystectomy for bladder cancer, were evaluated in the immediate postoperative period by retrograde pyelography and pouch cystography, and at later follow-up by pouch cystography. Other radiologic procedures (urography, ultrasonography, CT, etc.) were not part of a routine program, but were used when clinically indicated. In 12% a ureteroileal anastomotic leakage was found; the leaks resolved with continued ureteral stenting. Extravasation at the anastomosis between the pouch and the urethra was seen in 55% at the first cystography. It resolved within one month in all cases by simply leaving a catheter in the bladder. On the late cystograms reflux was observed in 6% of patients, whereas stone formation in the pouch was not encountered. A careful radiologic follow-up of patients with urinary diversions is essential to minimize postoperative complications.