Indications for urethrectomy.

This review article addresses the pertinent issues regarding management of the urethra in the setting of transitional cell carcinoma of the bladder. This topic is often a subject of considerable confusion among urologic surgeons and is timely in this era of routine orthotopic diversion. The risk of urethral recurrence in the retained urethra is approximately 10%. Of the potential risk factors that may predispose the retained anterior urethra to metachronous transitional cell carcinoma, involvement of the prostatic urethra, glands, or stroma is the most significant. In this circumstance, if a cutaneous diversion is performed, urethrectomy is indicated. Conversely, for orthotopic diversion, involvement of the prostatic urethra with transitional cell carcinoma is not a contraindication to proceeding. Orthotopic diversion should be aborted, and cutaneous diversion and urethrectomy should be performed, only if intraoperative frozen section of the prostatic urethra margin is positive. In a woman, en bloc urethrectomy should be included with cystectomy if cutaneous diversion is planned. Although tumor involvement of the female bladder neck is a risk factor for urethral disease, prospective studies suggest that intraoperative frozen section evaluation of the proximal urethra is more accurate and can be used to exclude orthotopic diversion at cystectomy. Using these and other guidelines, management of the urethra should be straightforward and less concerning for the urologic surgeon.

p53 protein and gene alterations in pathological stage C prostate carcinoma.

PURPOSE: We determined the extent of p53 immunoreactivity in pathological stage C prostate cancer as well as its correlation to tumor grade, substage, recurrence and proliferation rate. To define better the temporal relationship of p53 nuclear reactivity in prostate cancer p53 immunoreactivity was evaluated in all associated prostatic intraepithelial neoplasia lesions. MATERIALS AND METHODS: Using immunohistochemistry p53 status and proliferation rate were determined in 96 tumors from patients with pathological stage C prostate cancer. Single strand conformational polymorphism in exons 5 to 8 was used in a subset of specimens to assess the association of p53 nuclear accumulation with mutations in the p53 gene. RESULTS: p53 Nuclear reactivity was demonstrated in 10 tumors (10.4%), including 6 with high and 4 with low level nuclear reactivity. Of the tumors 86 (89.6%) had no evidence of p53 immunoreactivity. Each of the 6 tumors with high level p53 reactivity had associated areas of prostatic intraepithelial neoplasia that also showed p53 nuclear reactivity. Furthermore, pathological stage C substage (C1, 2 or 3) was significantly associated with p53 nuclear reactivity (p = 0.04). Proliferation rates were correlated with p53 nuclear reactivity (p = 0.09), while there was no association with tumor grade or recurrence. p53 Gene alterations were noted in 2 of the 3 p53 positive tumors versus no alterations in the p53 gene of 3 p53 negative tumors. CONCLUSIONS: p53 Nuclear accumulation is uncommon in pathological stage C prostate cancer and its presence in premalignant prostatic intraepithelial neoplasia lesions suggests that it may be an early event in a subset of prostate cancers.

New technique of vaginal reconstruction following anterior exenteration.

Vaginal reconstruction is important in sexually active females undergoing anterior exenteration for malignant disease. We describe a technique for vaginal reconstruction used in two women who underwent radical cystectomy that required en bloc removal of the anterior vaginal wall. A polyglycolic acid mesh with a pedicle graft of greater omentum creates the anterior 270 degrees and the apex of the neovagina. The technique is simple and adds to the urologist's armamentarium of reconstructive procedures that improve quality of life following exenterative surgery.

Urethral recurrence in patients with orthotopic ileal neobladders.

PURPOSE: We identified the risk of urethral recurrence following cystectomy for transitions cell bladder carcinoma, stratified by pathological characteristics of the bladder tumor and type of urinary diversion. MATERIALS AND METHODS: The pathological characteristics and clinical courses of 174 men with a Kock ileal neobladder and 262 with a cutaneous urinary diversion were analyzed for time to urethral recurrence. RESULTS: Urethral recurrence was identified in 34 patients at a median of 1.6 years after cystectomy, for an overall 7.9% 5-year risk of recurrence. Carcinoma in situ (p = 0.71) and multifocality (p = 0.17) did not independently confer an increased risk of recurrence. Prostatic urethral involvement, particularly stromal invasion, significantly increased the probability of recurrence (p < 0.001). Patients with a Kock ileal neobladder had a significantly lower probability of recurrence compared to those with cutaneous diversion (p = 0.015), even when associated with prostatic urethral involvement. CONCLUSIONS: Patients with a Kock ileal neobladder have a lower risk of urethral recurrence than those with cutaneous urinary diversion, even when associated with a high risk pathological condition predicting increased risk of urethral recurrence.

Transitional cell carcinoma involving the prostate with a proposed staging classification for stromal invasion.

PURPOSE: We investigated the effect on survival of transitional cell carcinoma of the prostatic urethra, ducts and stroma, and determined the difference between prostatic stromal involvement occurring via direct extension through the bladder wall versus stromal invasion arising intraurethrally. MATERIALS AND METHODS: Between August 1971 and December 1989, 489 men underwent radical cystoprostatectomy for transitional cell carcinoma, including 143 (29.2%) identified with prostate involvement by transitional cell carcinoma, in the cystectomy specimen. Patients were separated into 2 groups: 1-19 in whom the primary bladder tumor extended full thickness through the bladder wall to invade the prostate (classified as P4a) and 2-124 in whom prostate involvement arose from within the prostatic urethra. RESULTS: Five-year recurrence-free and overall survival rates were 25 and 21%, respectively, in group 1 versus 64 and 55%, respectively, in group 2. In the 124 patients in group 2 survival rates were similar for those with prostatic urethral tumors or carcinoma in situ and ductal tumors (no stromal invasion). Five-year overall survival rates without and with stromal invasion were 71 and 36%, respectively (p < 0.0001). Transitional cell carcinoma of the prostatic urethra or ducts does not alter survival predicted by primary bladder stage alone. Prostatic stromal invasion arising intraurethrally significantly decreases survival, which varies based on primary bladder stage (64.6% in stage P1, 30.8% in stages P2/P3a and 13.6% in stage P3b, p = 0.0001). P1 bladder tumors with prostatic stromal invasion arising intraurethrally had a significantly higher survival rate than P4a tumors (64.6 versus 21%, p = 0.0001). P3b bladder tumors with stromal invasion had a survival rate similar to that of P4a tumors (p = 0.78). CONCLUSIONS: Prostatic urethral or ductal transitional cell carcinoma does not alter survival determined by primary bladder stage alone and it should not be classified as P4a. Prostatic stromal involvement arising intraurethrally significantly decreases survival predicted by primary bladder stage alone. P1 bladder tumors with prostatic stromal invasion arising intraurethrally have a significantly higher survival rate than P4a tumors and they should be separately classified as P1str. Muscle invasive (P2/P3a) bladder tumors with stromal invasion have a higher survival rate than P4a tumors (no statistical significance) and they should be designated separately (that is P2str). P3b bladder tumors with prostatic stromal invasion arising intraurethrally are indistinguishable from P4a tumors.

The Kock ileal neobladder: updated experience in 295 male patients.

PURPOSE: Since 1986 orthotopic lower urinary tract reconstruction using the Kock ileal neobladder has been our diversion of choice in patients undergoing cystectomy. We report on the first 295 male patients undergoing this procedure from May 1986 through December 1993. MATERIALS AND METHODS: Complications were assessed, tabulated, subdivided into early (3 months or less postoperatively) and late types, and further categorized with respect to relationship to neobladder construction. Continence was individually evaluated via a detailed patient questionnaire. RESULTS: The pouch related early and late complication rates were 7.2 and 11.6%, respectively, and pouch related abdominal reoperation rates were 0.0 and 1.4%, respectively. Analysis of late pouch related complications revealed 4.1% stone formation and 2.4% afferent nipple stenosis rates, and only 1 case (0.3%) of ileal urethral anastomotic stricture. Of the patients 87 and 86% reported good or satisfactory daytime and nighttime continence, respectively. With regard to age, while overall continence was similar, a significantly greater percentage of patients younger than 70 years experience good daytime and nighttime continence relative to the older counterparts. Of the patients 5% perform regular intermittent catheterization and 2.7% required an artificial urinary sphincter due to unacceptable continence. CONCLUSIONS: The Kock orthotopic ileal neobladder can be constructed with minimal morbidity and extraordinary functional results. We strongly advocate its use when possible.

Complications of the afferent antireflux valve mechanism in the Kock ileal reservoir.

PURPOSE: Since 1982 the Kock ileal reservoir has been the primary form of urinary diversion in patients requiring lower urinary tract reconstruction at our institution. The intussuscepted afferent nipple valve of the Kock ileal reservoir is designed to prevent reflux and protect the upper urinary tract. Problems associated specifically with the afferent antireflux valve have been few. We defined and characterized all complications associated with the Kock pouch antireflux nipple valve. MATERIALS AND METHODS: From November 1984 through July 1992, 802 patients underwent construction of a continent Kock ileal reservoir. All complications associated with the afferent antireflux valve in this group and their management were identified. RESULTS: Overall, 79 of 802 patients (9.8%) had a total of 84 complications of the afferent antireflux valve (10.4%), including formation of stones on staples securing the afferent nipple valve in 42 cases (5.2%), stenosis of the afferent valve in 35 (4.3%) and prolapse of the valve in 7 (0.9%). A total of 81 patients required surgical intervention to correct the afferent valve complication: 56 (7.0%) were treated endoscopically and 25 (3.1%) required open surgical revision. CONCLUSIONS: We report an overall complication rate of 10.4% associated with the afferent antireflux nipple valve in the Kock ileal reservoir. Most complications can be treated endoscopically without difficulty on an outpatient basis with the use of local sedation. With these results, and only a 3% incidence of open surgical correction of all afferent nipple problems, we encourage the continued use of the intussuscepted afferent nipple valve whenever continent urinary diversion is performed.

Orthotopic urinary diversion: the Kock ileal neobladder.

Orthotopic urinary diversion via the Kock ileal neobladder is the preferred form of bladder reconstruction in men and, now, in women undergoing cystectomy at the University of Southern California. Through June of 1993, 266 men were diverted in this fashion. There were 3 perioperative mortalities (1.1%); early complications occurred in 47 men (17.7%), whereas 35 (15.0%) experienced late complications. Approximately 85% of the men enjoy good or satisfactory continence day and night, with a large majority having a normal voiding pattern. Through May of 1993, 14 women were similarly diverted; 2 patients (14.2%) experienced early complications, whereas 1 patient (7.1%) had a late complication. The continence and voiding pattern appear to be even better in this small group of women as compared with the men. Orthotopic Kock continent urinary diversion yields an extraordinary functional result that can be accomplished with minimal complication and high patient satisfaction.

Bilateral emphysematous pyelonephritis: a case report and review of the literature.

Emphysematous pyelonephritis is a rare, rapidly progressive, life-threatening infection of the renal parenchyma. It most commonly is unilateral, is found almost exclusively in diabetics, is associated with gas-forming coliform bacteria, and is characterized by the presence of gas within the renal parenchyma. Early aggressive therapy (combined medical and surgical) is the hallmark of successful treatment. A high index of suspicion coupled with radiographic imaging is essential to make a timely diagnosis and guide therapeutic intervention. Bilateral emphysematous pyelonephritis is an even more rare phenomena, with only 14 reported cases in the English literature and is associated with a high patient mortality. We herein present an additional case and review the literature as it pertains to bilateral emphysematous pyelonephritis. Appropriate care requires aggressive combined medical and surgical therapy in an attempt to preserve renal function without increased mortality.

Indications for lower urinary tract reconstruction in women after cystectomy for bladder cancer: a pathological review of female cystectomy specimens.

PURPOSE: In an attempt to identify women who may be appropriate candidates for orthotopic lower urinary tract reconstruction, archival cystectomy specimens from female patients undergoing cystectomy for primary bladder cancer were reviewed. These pathological findings should provide a better understanding of tumor involvement at the bladder neck (vesicourethral junction) and urethra in women with transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Cystectomy specimens of 67 consecutive women undergoing surgery for biopsy proved transitional cell carcinoma of the bladder between July 1982 and July 1990 were pathologically reviewed. RESULTS: Histological evidence of tumor (carcinoma in situ or gross carcinoma) involving the urethra was present in 9 patients (13%). Tumor was confined to the proximal and mid urethra, and the distal urethra was not involved. All patients with carcinoma involving the urethra had concomitant evidence of carcinoma involving the bladder neck. A total of 17 patients (25%) had tumor involvement of the bladder neck and those with an uninvolved bladder neck also had an uninvolved urethra. The association between the presence of tumor in the bladder neck and urethra was highly significant (p < or = 0.00012). Tumor involving the bladder neck and urethra tended to be more commonly associated with high grade and stage tumors, and node-positive disease. CONCLUSIONS: Although the fate of the retained urethra following cystectomy for bladder cancer in women is unknown, these results show that women with transitional cell carcinoma of the bladder without evidence of tumor involving the bladder neck are at low risk for urethral malignancy. These patients may be offered lower urinary tract reconstruction that includes preservation of and diversion through the urethra (orthotopic diversion). Urethral surveillance will be necessary, as it is in men after orthotopic urinary diversion.

Accumulation of nuclear p53 and tumor progression in bladder cancer.

BACKGROUND: We have previously demonstrated a strong association between nuclear accumulation of p53 protein, as determined by immunohistochemical analysis, and mutations in the p53 gene. The purpose of this study was to determine the relation between nuclear accumulation of p53 and tumor progression in transitional-cell carcinoma of the bladder. METHODS: Histologic specimens of transitional-cell carcinoma of the bladder (stages Pa, noninvasive disease, to P4, disease with direct extension into adjacent organs or structures) from 243 patients who were treated by radical cystectomy were examined for the immunohistochemical detection of p53 protein. Nuclear p53 reactivity was then analyzed in relation to time to recurrence and overall survival. RESULTS: The detection of nuclear p53 was significantly associated with an increased risk of recurrence of bladder cancer (P < 0.001) and with decreased overall survival (P < 0.001). In patients with cancer confined to the bladder, the rates of recurrence for stage P1, P2, and P3a tumors that had no detectable nuclear p53 reactivity at five years were 7, 12, and 11 percent, respectively, as compared with 62, 56, and 80 percent, respectively, for tumors that had p53 immunoreactivity. Similar results were obtained when the presence or absence of p53 in the nuclei of the tumor cells was studied in relation to overall survival. In a multivariable analysis stratified according to grade, pathological stage, and lymph-node status, nuclear p53 status was an independent predictor (and in cancer confined to the bladder, the only independent predictor) of recurrence and overall survival (P < 0.001). CONCLUSIONS: In patients with transitional-cell carcinoma confined to the bladder, an accumulation of p53 in the tumor-cell nuclei detected by immunohistochemical methods predicts a significantly increased risk of recurrence and death, independently of tumor grade, stage, and lymph-node status. Patients with transitional-cell carcinoma confirmed to the bladder that demonstrates nuclear p53 reactivity should be considered for protocols of adjuvant treatment.

Glycophorin A on normal and leukemia cells detected by monoclonal antibodies, including a new monoclonal antibody reactive with glycophorins A and B.

A new hemagglutinating monoclonal antibody, MoAb31, detected glycophorins A and B in Western blots. Results with enzyme-modified erythrocytes indicated the MoAb31 determinants were sialic acid dependent, and resided on glycophorin A on the trypsin-resistant, ficin-sensitive segment, and on glycophorin B on the ficin-sensitive segment. Another new monoclonal antibody, MoAb36, detected the Wrb antigen, located on the non-glycosylated segment of glycophorin A near its insertion into the lipid bilayer. Immunofluorescent staining of normal hematopoietic and leukemia cells with these and other monoclonal antibodies to glycophorin A demonstrated glycophorin A on erythroid cells only. Cytofluorograph analysis showed the majority of cells of the erythroleukemia cell lines K562 and HEL expressed glycophorin A, as indicated by reactivity with the monoclonal glycophorin A antibodies R10, R18, 6A7 and 10F7. However, reactivity with monoclonal antibodies to glycosylated determinants (MoAb31 and R1.3) and to the non-glycosylated segment near the membrane insertion (MoAb36, and R7.1) was reduced or absent. Expression of "missing" glycophorin A antigens on K562 and HEL could not be induced using a variety of chemical and biologically active modifiers. We conclude that glycophorin A of erythroleukemia cell lines K562 and HEL differs from glycophorin A at the surface of normal, mature erythrocytes with respect to reactivity with monoclonal glycophorin A antibodies.

Comparison of human and siamang ABH and MN blood groups using monoclonal antibodies.

Comparison of human and siamang ABHIi and MNSs blood groups using monoclonal antibodies and enzyme-modified erythrocytes showed a different organization of ABHIi in the siamang, and a greatly altered expression of the sialoglycoproteins that express MNSs. While several monoclonal antibodies to human MNSs sialoglycoproteins failed to agglutinate siamang erythrocytes, MoAb145, a monoclonal antibody that reacts with the MN sialoglycoprotein, agglutinated siamang erythrocytes to almost the same titer as human red blood cells. These studies suggest the potential usefulness of monoclonal antibodies in seroprimatology.

Altered cell surface antigen expression in bladder carcinoma detected by a new hemagglutinating monoclonal antibody.

A hemagglutinating monoclonal IgM antibody (MoAb145) was produced against a high incidence red blood cell membrane antigen. By the specific red cell adherence test, the antibody also reacted with human bladder epithelium; in addition, expression of the MoAb145 antigen was lost in some cases of transitional cell carcinoma of the bladder, in a manner similar to the ABH blood group. Hemagglutination studies with a panel of erythrocytes lacking specific high incidence red blood cell membrane antigens indicated that MoAb145 did not recognize ABH specificity but rather a determinant absent from rare MN variant erythrocytes, including En(a-) erythrocytes, which lack glycophorin-alpha. Failure of MoAb145 to stain, by indirect immunofluorescence, the erythroleukemia cell line K562, which expresses glycophorin-alpha and the MN blood group, and failure to inhibit MoAb145 hemagglutination with an erythrocyte sialoglycoprotein fraction that contained MN blood group activity suggests that MoAb145 does not recognize either glycophorin-alpha or the MN blood group, but rather another membrane determinant, which is altered in En(a-) erythrocytes. This study demonstrates a new epitope detected by MoAb145 that is shared between human erythrocyte membranes and bladder epithelia, and is affected by neoplastic transformation in transitional cell carcinoma of the bladder.

Identification and quantitation of the protein content of blood group antibody eluates prepared by the rapid acid-stromal method. Use in committed erythroid progenitor cell assays.

Anti-D sensitized red cells were converted to stroma, either by digitonin or hypotonic lysis, and eluates prepared by the modified rapid acid-stromal method. SDS-PAGE and both rocket- and crossed-immunoelectrophoresis showed that, of the total protein content of the eluates, 11 to 25 percent was IgG, 18 to 45 percent was globin, and 34 to 71 percent was red cell membrane protein. Eluates were free of albumin, transferrin, and other non-IgG serum proteins; they did not contain proteolytic activity, and eluates were noninhibitory to the growth of committed erythroid progenitors. The rapid acid-stromal method produced high-titered blood group antibody eluates free of contaminating immune or nonimmune activity which were suitable for assay of blood group antigen expression by hemopoietic stem cells and committed progenitors.