Transitional cell carcinoma of the bladder mimicking recurrent paget's disease of the vulva: report of two cases, with one occurring in a myocutaneous flap.

BACKGROUND: Transitional cell carcinoma of the bladder may spread superficially along and beyond the urogenital epithelium, mimicking vulvar Paget's disease. CASES: These two cases illustrate unusual aspects of transitional cell carcinoma of the bladder and vulvar Paget's disease. Both patients had a history of breast cancer and previously had multiple operations for recurrent vulvar Paget's disease; one patient had a radical vulvectomy with transverse rectus abdominal muscle flap reconstruction. Both had a history of recurrent transitional cell carcinoma of the bladder. Both presented with recalcitrant transitional cell carcinoma of the bladder and clinically recurrent vulvar Paget's disease. Pathologic evaluation, however, revealed pagetoid spread of carcinoma in situ (CIS) throughout the urothelium, with an invasive component in the cervix and extension of the CIS into the rectum in one patient. CONCLUSION: If the history of the patient includes transitional cell carcinoma of the bladder and vulvar Paget's disease, histologic evaluation is needed for accurate diagnosis and proper treatment.

Use of spiral computerized tomography in lieu of angiography for preoperative assessment of living renal donors.

PURPOSE: We evaluate whether spiral computerized tomography (CT) can be used in lieu of renal angiography for preoperative assessment of living renal donors, with special attention to multiplicity of renal vasculature. MATERIALS AND METHODS: A total of 47 living renal donor candidates were evaluated with spiral CT and all but 2 underwent donor nephrectomy. Patients were divided into early and late groups because there was a learning curve with spiral CT. In the early group 18 donors underwent renal angiography as well as spiral CT and 10 underwent nephrectomy after spiral CT only. In the late group 5 had dual radiographic evaluation for ambiguities in spiral CT interpretation and 12 underwent nephrectomy after spiral CT only. Spiral CT was performed and interpreted blind to angiographic results, and vice versa. RESULTS: Spiral CT identified 50 of 52 renal arteries (96%) found at surgery overall and 23 of 25 (92%) found at surgery after spiral CT only. Two accessory arteries were missed in the 10 early group donors evaluated with spiral CT only, yielding an early negative predictive value of 80%. Renal angiography identified another accessory artery missed by spiral CT in the early group. All 3 missed vessels were identified retrospectively. No arteries found at surgery were missed in the late group (negative predictive value 100%), although there were 2 false-positive results detected by spiral CT relative to renal angiography in 1 candidate renal unit. Overall accuracy to predict early renal artery division relative to surgical findings was 93% for spiral CT and 91% for renal angiography. However, early renal artery division was clinically significant for only 1 of 11 vessels found at surgery. Spiral CT demonstrated 4 anomalous venous returns and renal angiography identified none. However, spiral CT missed 2 accessory veins and identified only 1 of 2 fibromuscular dysplasia cases. Total cost for spiral CT and renal angiography was $886 and $2,905, respectively. CONCLUSIONS: Spiral CT is a reasonably good alternative to renal angiography for living renal donor assessment but there is a profound learning curve for performance and interpretation. Renal angiography is still the gold standard with respect to the identification of arterial multiplicity and fibromuscular dysplasia, and it should be used adjunctively in cases with spiral CT ambiguity. Neither spiral CT nor renal angiography is ideal for the assessment of early renal artery division which is seldom an issue. The benefits of spiral CT over renal angiography are potentially lower morbidity, improved donor convenience and reduced cost.

Deoxyribonucleic acid ploidy and serum prostate specific antigen predict outcome following salvage prostatectomy for radiation refractory prostate cancer.

PURPOSE: We assessed clinical and pathological variables for the ability to predict improved outcome following salvage prostatectomy for radiation refractory prostate cancer. We identify factors that might assist in selection of candidates for this procedure. MATERIALS AND METHODS: Between 1966 and 1996, 108 patients (mean age 64.7 years) underwent salvage radical retropubic prostatectomy for radiation refractory prostate cancer. Preoperative serum prostate specific antigen (PSA), available in 70 patients treated since 1987, was less than 4 in 19, 4 to 10 in 31 and greater than 10 ng./ml. in 20. Serum PSA before radiotherapy was available in 37 patients. Serum PSA before radiotherapy and salvage surgery, tumor grade, deoxyribonucleic acid (DNA) ploidy and margin status were analyzed for the ability to predict cancer specific and progression-free survival (local, systemic and PSA 0.2 ng./ml. or greater). Complication rates were compared between early (before 1990) and late (1990 to 1996) salvage prostatectomy groups. RESULTS: Overall cancer specific and progression-free survival at 10 years was 70 and 44%, respectively. The pathological stage was pT2N0 in 39%, pT3-4N0 in 42% and pTxN+ in 19% of cases. DNA ploidy was predominately nondiploid, that is diploid in 25%, tetraploid in 64% and aneuploid in 11% of tumors. Although preoperative serum PSA was not predictive of pathological stage, patients with preoperative PSA less than 10 ng./ml. had better progression-free survival than those with higher levels (p = 0.05). DNA ploidy was the strongest predictor of cancer specific (p = 0.002) and progression-free (p = 0.002) survival. Controlling for grade and PSA using the Cox proportional hazards model, DNA ploidy remained a significant predictor of prostate cancer death (p <0.001) and disease progression (p <0.001). Complication rates improved somewhat in more recently treated patients but incontinence and bladder neck contracture rates remained significant. CONCLUSIONS: DNA ploidy and preoperative serum PSA appear to be the most important predictors of outcome following salvage prostatectomy for radiation refractory prostate cancer. Preoperative consideration of these factors may be helpful in selecting candidates for this procedure.

Influence of prostate-specific antigen testing on the spectrum of patients with prostate cancer undergoing radical prostatectomy at a large referral practice.

OBJECTIVE: To analyze trends in the clinical stage and pathologic outcome of patients with prostate cancer who underwent radical prostatectomy at a large referral practice during the prostate-specific antigen (PSA) testing era. MATERIAL AND METHODS: Between January 1987 and June 1995, 5,568 patients with prostate cancer (4,774 with clinically localized disease of stage T2c or less) underwent pelvic lymphadenectomy and radical retropubic prostatectomy at our institution. Patient age, preoperative serum PSA level, clinical stage, pathologic stage, Gleason score, and tumor ploidy were assessed. Outcome was based on clinical and PSA (increases in PSA level of 0.2 ng/mL or more) progression-free survival. RESULTS: Patient age (65 to 63 years old; P<0.001) and serum PSA level (median, 8.4 to 6.8 ng/mL; P<0.001) decreased during the study period. The percentage of patients with clinical stage T1c prostate cancer increased from 2.1% in 1987 to 36.4% in 1995 (P<0.001), and clinical stage T3 cancer decreased from 25.3% to 6.5% (P<0.001). Nondiploid tumors decreased from 38.3% to 24.6% (P<0.001), and the proportion of patients with pathologically organ-confined disease increased from 54.9% to 74.3% (P<0.001). More cT1c than cT2 tumors were diploid (80% versus 72%; P<0.001), had a Gleason score of 7 or less (75% versus 65%; P<0.001), and were confined to the prostate (75% versus 57%; P<0.001). Five-year progression-free survival was 85% and 76% for patients with clinical stage T1c and T2, respectively (P<0.001). CONCLUSION: Since the advent of PSA testing, patients referred to our institution for radical prostatectomy have shown a significant migration to lower-stage, less-nondiploid, more often organ-confined prostate cancer at the time of initial assessment. Cancer-free survival associated with PSA-detected cancer (cT1c) is superior to that with palpable tumors (cT2). Whether these trends translate into improved long-term cancer-specific survival remains to be confirmed with longer follow-up.

Primary surgical therapy for clinical stage T3 adenocarcinoma of the prostate.

Radical prostatectomy has not been a widely accepted treatment option in patients with clinical stage T3 prostate cancer due to the potential for incomplete excision of tumor and the high incidence of lymph node metastases. In addition, the morbidity of surgical therapy in these patients has been questioned. As a result, alternative treatment modalities, including androgen ablative therapy and radiotherapy, are often used in patients with locally advanced disease. However, in terms of local disease control and long-term disease-free survival rates, most alternative treatments have serious limitations in clinical stage T3 tumors. We recently reported our extended experience with radical prostatectomy and adjuvant therapy in a large group of patients with clinical stage T3 disease and this article updates that experience. Although 31% of patients in our series had node-positive disease, 25% had pathologically organ-confined tumors likely to be cured by surgical therapy alone. Cancer-specific survival rates at 5, 10, and 15 years were 93%, 84%, and 74%, respectively, and operative morbidity paralleled that of patients with clinically localized disease. Our experience suggests that excellent long-term survival with low treatment-related morbidity can be achieved with radical prostatectomy and adjuvant therapy in patients with clinical stage T3 prostate cancer.

Platinum-based chemotherapy for advanced transitional cell carcinoma of the upper urinary tract.

OBJECTIVE: To report the results of platinum-based chemotherapy used at one medical center in patients with advanced transitional cell carcinomas (TCCs) of the upper urinary tract. MATERIAL AND METHODS: Between July 1981 and February 1993, 28 patients (mean age, 59.3 years) with advanced TCC of the upper urinary tract received cisplatin-based chemotherapy. Of the 28 patients, 14 received a median of 4 cycles of cisplatin, methotrexate, and vinblastine sulfate, 8 received a median of 4.5 cycles of methotrexate, vinblastine, doxorubicin hydrochloride, and cisplatin, 5 received a median of 5 cycles of etoposide and cisplatin, and 1 was treated with 7 cycles of only cisplatin. Overall survival estimates were constructed from nonparametric analysis with the Kaplan-Meier method. RESULTS: The overall response rate (partial and complete) to chemotherapy was 54%. The most responsive metastatic sites were the lung and lymph nodes-78 and 47% overall response rate, respectively. The estimated median duration of survival for the entire study group was 14 months. In the study population, only three patients were long-term survivors. A significant survival advantage was noted only in the few patients (with limited metastatic tumor volume) who had a complete response to therapy. Initial dose reductions in chemotherapy because of decreased baseline renal function were necessary in 79% of the patients. CONCLUSION: Removal of the primary lesion in the presence of metastatic or locally advanced disease does not apparently improve chemotherapy response rates or patient survival. In addition, many patients do not receive optimal dosing of systemic chemotherapy after nephrectomy. Therefore, by avoiding dose modifications, the overall response rates and survival may conceivably be improved. A diagnostic biopsy or nephron-sparing surgical procedure and neoadjuvant systemic therapy may be considered in patients with advanced TCC at the time of initial assessment in order to allow optimal dosing of chemotherapy.

[Detailed evaluation of sexual function after radical prostatectomy: is patient satisfaction correlated with the quality of erections?]. / Evaluation détaillée de la fonction sexuelle après prostatectomie radicale: la satisfaction des patients est-elle corrélée à la qualité des érections?

INTRODUCTION: Post radical prostatectomy potency rates, quantified on the basis of physician survey, have ranged up to 80%. Physician derived potency data, however, may not be representative of true post-prostatectomy potency rates or more importantly may not accurately portray patients' post-operative sexual satisfaction. We conducted a pilot study combining physician derived and patient derived subjective data with objective measures of erectile function. MATERIALS AND METHODS: Eleven men, mean age of 59 years, who were treated with nerve sparing radical retropubic prostatectomy formed the study group. Initially, the patients responded to a physician directed telephone survey on sexual status. Potency was then objectively assessed utilizing Rigiscan testing on two consecutive evenings. Lastly, the patients completed a validated short questionnaire directed to obtain a patients' subjective perception of sexual function. RESULTS: All the patients responded to the first part of the study by informing the physician that they were sexually active or potent after radical prostatectomy. Of these 11 patients, however, only 2 (18%) were mostly satisfied with their sex life according to the quality of life questionnaire. Rigiscan testing revealed that 8 of the 11 patients had nocturnal erections which were adequate for vaginal penetration. Of the 5 patients who stated that they were mostly dissatisfied with their sexual functioning, 3 had objective evidence of adequate erectile ability as documented by Rigiscan. Three of the four patients who were ambivalent with respect to their sexual function also demonstrated objective evidence of normal erectile activity. CONCLUSION: Although a patient may inform his care provider that he is sexually active or potent, he may not be satisfied with his present level of sexual functioning. In addition, we observed that some dissatisfied patients do have normal Rigiscan patterns indicating that a percentage of patients who are not happy with their level of sexual function after radical prostatectomy may have a psychogenic component to their problem.

Free, complexed, and total serum prostate-specific antigen concentrations and their proportions in predicting stage, grade, and deoxyribonucleic acid ploidy in patients with adenocarcinoma of the prostate.

OBJECTIVES: Nearly half of men with clinically localized prostate cancer are understaged. We evaluated whether knowledge of preoperative free prostate-specific antigen (f-PSA), complexed (c-PSA), and total (t-PSA) concentrations or the ratios thereof (f-PSA/t-PSA, c-PSA/t-PSA, and f-PSA/c-PSA) could improve upon the staging of prostate cancer when compared with standard PSA testing (t-PSA). In addition, we examined their associations with tumor grade and deoxyribonucleic acid (DNA) ploidy. METHODS: Two hundred ninety patients with prostate cancer, 178 (61%) of whom were treated with radical prostatectomy, formed the study group. RESULTS: Although there were significant differences in the f-PSA concentrations with respect to clinical stage, considerable overlap in PSA levels among the clinical substages was observed. Statistically significant differences but weak correlations were observed between the individual f-PSA, c-PSA, and t-PSA concentrations with regard to pathologic stage (organ-confined versus extraprostatic) and grade. No significant relationship, however, was observed with the three ratios. Higher PSA values were not always associated with a pathologic stage of pT3 or greater, and lower levels did not ensure that a tumor was organ-confined. Only a slight association was observed between c-PSA and t-PSA levels and DNA ploidy. No significant relationship was observed between the f-PSA levels as well as the three ratios with regard to DNA ploidy. A statistically significant improvement in predicting pathologic stage was observed when combining knowledge of preoperative t-PSA concentration with the c-PSA/t-PSA ratio. However, the area under the receiver operator characteristic curves was only slightly increased; as such this combination was of limited clinical utility. CONCLUSIONS: Statistically significant but weak correlations were observed between the molecular forms of PSA and stage, grade, and DNA ploidy. The significant overlap in f-PSA and c-PSA values among all stages, grades, and ploidy values precluded any useful predictive information for the individual patient. As such, preoperative knowledge of f-PSA and c-PSA values and the three ratios provided no additional diagnostic information over standard PSA (t-PSA) values alone.

Analysis of risk factors for progression in patients with pathologically confined prostate cancers after radical retropubic prostatectomy.

PURPOSE: Up to 26% of patients with pathologically organ confined prostate cancer will experience clinical progression after radical prostatectomy. We attempted to identify patients at greatest risk for future clinical failure despite a favorable pathological outcome. MATERIALS AND METHODS: The study group included 904 patients treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for disease confined to the prostate gland. Preoperative serum prostate specific antigen (PSA), clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients further according to risk of progression. RESULTS: Preoperative PSA concentration, clinical stage, grade and DNA ploidy were significant univariate predictors of progression (p < 0.0001), whereas pathological stage was not (p = 0.2). Multivariate analysis identified pathological grade (p < 0.0001), preoperative serum PSA concentration (p = 0.0006) and DNA ploidy (p = 0.0089) as independent predictors of progression. The prognostic scoring system separated the patients into 5 distinct groups. Patients with the lowest score had a 92% progression-free survival rate at 5 years, compared to only 39% of those with the highest scores. CONCLUSIONS: Patients believed to be at higher risk for cancer progression despite having organ confined disease might be targeted for adjuvant therapy and closer surveillance, while those at low risk may be followed less often.

Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery.

PURPOSE: We investigated the outcome of nephron sparing surgery in patients with low grade and low stage (Robson stage II or less) renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 185 patients treated with nephron sparing surgery and 209 matched for patient age and sex, and tumor stage and grade who were treated with radical nephrectomy. Kaplan-Meier survival curves were constructed for progression and survival end points. Multivariate analysis was performed to determine the tumor characteristics independently correlated with progression and cancer death. RESULTS: No significant difference was observed with respect to progression-free, crude or cancer specific survival between the nephron sparing surgery and radical nephrectomy groups. Less than 5% of the patients treated with conservative nephron sparing surgery had local recurrence. Tumor size was a strong independent predictor of outcome, whereas Robson stage was not. Patients treated with radical nephrectomy had a significant cancer specific and progression-free survival advantage when controlling for tumor diameter and grade. However, no difference was observed in patients with primary tumor diameters of 4 cm. or less. CONCLUSIONS: Robson staging is inaccurate in predicting tumor behavior. Patients with tumors larger than 4 cm. and a normal contralateral kidney may be best served by radical nephrectomy rather than elective nephron sparing surgery. However, nephron sparing surgery may result in an outcome similar to that of radical nephrectomy for low grade, low stage renal cell carcinomas of 4 cm. or smaller.

Risk factors for progression in patients with prostate cancer treated with radical prostatectomy.

Adjuvant therapy after radical prostatectomy should ideally be limited to those patients at greatest risk for cancer recurrence, but identification of these patients remains a challenge. Although tumor volume has traditionally been regarded as the most important prognostic factor in patients with localized prostate cancer, a recent multivariate analysis has shown that tumor is not an independent predictor. Moreover, accurate measurement of tumor volume is extremely difficult. Preoperative serum prostate-specific antigen (PSA) levels have been identified as a significant independent predictor of progression. Disease-free survival is significantly better in patients with DNA-diploid prostate cancers than in those with nondiploid tumors. Histological grade is also a powerful predictor of disease progression. As a basis for selecting candidates for adjuvant therapy, clinical staging is too inaccurate and pathological staging too subjective. A recent Mayo Clinic study assessed the value of widely available clinical and laboratory parameters in predicting treatment failure after radical prostatectomy in 904 patients with pathologically organ-confined prostate cancer. Multivariate analysis identified Gleason score, preoperative serum PSA concentration, and DNA ploidy as independent predictors for progression. These risk factors were used to develop a scoring system that allows patients to be classified according to their risk of progression. Patients in the highest risk categories might be targeted for adjuvant therapy and closer surveillance, whereas those at lower risk might be followed less frequently.

Prostate specific antigen detected prostate cancer (clinical stage T1c): an interim analysis.

PURPOSE: The majority of impalpable prostate cancers (state T1c) are biologically significant. We report the interim results in 257 patients with stage T1c prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: Prostate specific antigen progression-free survival was assessed by the Kaplan-Meier method. Multivariate analyses were performed to determine which clinical and pathological variables independently correlated with progression. Comparisons among the various clinical substages (T1a to T2b/c) were calculated. RESULTS: Of the patients with stage T1c cancers 51% had stage pT2c or less and 91% had clinically significant tumors on the basis of pathological grade, deoxyribonucleic acid ploidy and tumor volume. High preoperative prostate specific antigen, poorly differentiated tumors and nondiploid status were strong independent predictors of progression. The 5-year survival rate free of progression was 84%. Patients with clinical stage T1c cancers had a significant progression-free survival advantage compared to those with clinical stage T2b/c disease (p = 0.0005). CONCLUSIONS: Impalpable tumors should not be regarded as insignificant or innocuous on the basis of pathological analysis. Disease-free survival in the stage T1c group was similar to that in the clinical stages T1a to T2a group but significantly better than that in the T2b/c group.

Extended experience with radical prostatectomy for clinical stage T3 prostate cancer: outcome and contemporary morbidity.

PURPOSE: Radical prostatectomy for clinical stage T3 prostate cancer has not been widely accepted due to the potential for incomplete excision of the local tumor and high incidence of lymph node metastases. In addition, contemporary morbidity is unknown. We report the long-term results in 812 patients with clinical stage T3 prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: Between 1966 and 1992, 812 patients with clinical stage T3 prostate cancer underwent radical prostatectomy of whom 479 (60%) received adjuvant therapy. RESULTS: Mean patient age was 65 years (range 40 to 78). Mean followup was 4.5 years (range up to 24). Disease was stage pT2c or less in 17% of patients, pT3a to c in 49% and node-positive in 33%. Of the primary tumors pathological Gleason score was 7 or greater in 62%. Crude and cancer-specific survival rates at 5, 10 and 15 years were 86%, 70% and 51%, and 90%, 80% and 69%, respectively. Operative morbidity paralleled that of patients with clinically localized disease (T2c or less). CONCLUSIONS: An excellent survival rate with low treatment related morbidity can be achieved by performing primary radical prostatectomy with adjuvant therapy in the patient with clinical stage T3 prostate cancer.

Critical evaluation of salvage surgery for radio-recurrent/resistant prostate cancer.

PURPOSE: A positive post-irradiation prostatic biopsy associated with an increasing prostate specific antigen level but no palpable evidence of local progression may identify a subgroup of patients who could be cured by salvage surgical therapy. MATERIALS AND METHODS: Between 1967 and 1992, 132 patients underwent salvage surgery, including radical retropubic prostatectomy in 79, anterior exenteration in 38, total exenteration in 5 and bilateral pelvic lymphadenectomy only in 10. RESULTS: The 10-year cancer-specific survival rate in the prostatectomy group was 72%. Local control was equivalent among the surgical groups. Radical retropubic prostatectomy patients with negative surgical margins and nonaneuploid tumors demonstrated a significant survival advantage. Adjuvant hormonal therapy improved the disease-free survival rate in patients with nonaneuploid tumors. CONCLUSIONS: Radical retropubic prostatectomy can achieve excellent survival with low morbidity in select patients. Patients with clinical stage T2 or less disease and with prostate specific antigen detected cancers (52% and 75%, respectively) had pathological stage T2 disease. Thus, by using modern diagnostic techniques patients can be identified who may be cured with salvage surgery.

Primary chemotherapy for clinical stage II nonseminomatous germ cell testicular tumors: selection criteria and long-term results.

OBJECTIVE: To determine the treatment option for patients with low-volume stage II nonseminomatous germ cell testicular tumors (NSGCTT) that yields the best survival, is associated with the least morbidity, and avoids "double therapy"--that is, chemotherapy and retroperitoneal lymph node dissection (RPLND). DESIGN: We reviewed our institutional experience with 28 patients with stage II NSGCTT who received primary chemotherapy between August 1983 and October 1992. MATERIAL AND METHODS: The 28 study patients (mean age, 28 years; range, 20 to 52) with low-volume stage II NSGCTT were treated with bleomycin, etoposide, and cisplatin. The correlation of response rates with volume of disease and predominant histologic cell type was determined. The duration of survival was measured from the initiation of chemotherapy to the appearance of progressive disease or death or the date of last follow-up visit. RESULTS: Of the 28 patients treated, 27 (96%) achieved a complete response--20 (71%) with only chemotherapy and an additional 7 (25%) with chemotherapy plus surgical treatment. Twenty-seven patients (96%) remained free of disease after a median follow-up of 72 months. The most frequent complication was cisplatin-associated paresthesias or tinnitus which was noted in 13 patients (46%). In 11 of 15 patients (73%), attempts to have children have been successful. CONCLUSION: Excellent long-term survival rates in patients with stage II NSGCTT can be achieved with primary chemotherapy. In this series, 71% of patients were spared RPLND. The need for postchemotherapy RPLND seemed to be related to the initial metastatic tumor volume and possibly the histologic features of the primary tumor. Continued refinement in surgical techniques and chemotherapeutic regimens will necessitate the comparison of these two treatment approaches in a randomized prospective trial.

Cytoreductive surgery for stage IV renal cell carcinoma.

To facilitate the regression of extra renal disease in response to systemic therapy, cytoreductive surgery has been advocated as step 1 in the treatment of stage IV renal cell carcinoma. To determine the effect of surgery on subsequent clinical course, we reviewed the treatment records of 30 patients with known stage IV carcinoma of the kidney who underwent nephrectomy or additional procedures in preparation for systemic therapy. Of 30 patients only 7 (23%) underwent systemic therapy postoperatively. Progression of the disease, surgical morbidity and mortality were the factors preventing 77% of our patients from continuing with treatment. Since regression of extra renal lesions is the goal of systemic therapy, our data suggest that nephrectomy and most other cytoreductive operations in preparation for systemic therapy are not efficient treatment strategies.

Endothelin-1 as a putative modulator of erectile dysfunction: I. Characteristics of contraction of isolated corporal tissue strips.

Normal erectile physiology is heavily dependent on a delicate balance between the effects of endogenous vasoconstricting and vasorelaxing hormones on the tone of the corporal smooth muscle. Recent studies indicate that endothelin-1 (ET-1) is present and physiologically active in the human corpora. The primary goal of the present investigation was to further define the role of ET-1 in corporal physiology and to ascertain whether it might play a role in augmenting corporal tone in vivo, as reported in other vascular tissues. Thus, we conducted pharmacological studies of ET-1-induced steady-state contractions in isolated human corporal smooth muscle strips to determine if there were any detectable age- or diabetes-related alterations in ET-1-induced contractions. For statistical analysis, the patient population was divided into 2 age groups, A (< or = 59 years of age; = 11 patients) and B (> or = 60 years of age; n = 7 patients), and further subdivided into 2 diagnostic categories, diabetic (n = 7 patients) and nondiabetic (n = 11 patients). Construction of cumulative concentration response curves (CRCs) for ET-1-induced contractions revealed characteristically slow onset and long-lasting responses. Endothelin-1 CRC data were computer fit to the logistic equation to derive Emax (calculated maximal response), pEC50 (negative logarithm of the concentration that elicits one-half of the calculated maximal response) and slope factor (n) values. Two-factor analysis of variance revealed no detectable age- or diabetes-related alterations, nor any age-diabetes interaction in any of the logistic parameters. Furthermore, logistic analysis of ET-1 CRC data on 14 isolated corporal tissue strips derived from 3 potent patients with documented spontaneous erections revealed no differences in ET-1 contractility from that observed for patients with organic erectile dysfunction. Importantly, despite an apparent absence of age- or diabetes-related alterations in ET-1-induced steady-state contractions, preliminary studies demonstrated that coadministration of the alpha 1-adrenergic agonist phenylephrine and ET-1 produce much greater contractile responses than those observed in the presence of phenylephrine (PE) alone. Moreover, the magnitude of the augmentation was precisely that predicted by a model for simple additivity of agonist effects. Such observations suggest that the physiological relevance of ET-1 to corporal physiology may be related to its ability to augment the contractile responses of other vasomodulators present in the human corpora, in particular, perhaps modulating the contractile responses to sympathetic activity.

Morbidity of contemporary radical retropubic prostatectomy for localized prostate cancer.

Complication rates in 1,000 consecutive patients who underwent radical retropubic prostatectomy for clinically localized prostate cancer between November 1989 and January 1992 were assessed and compared to complication rates in a historical group of patients operated on by primarily the same surgeons prior to 1987. In the contemporary series, there were no operative deaths, only 22% of patients required blood transfusion, and only six (0.6%) patients suffered rectal injuries. Early complications, including myocardial infarction, pulmonary embolism, bacteremia, and wound infection, occurred in less than 1% of patients. Vesical neck contracture, the most common late complication, developed in 87 patients (8.7%). At 1 year post-surgery, 80% of patients were completely continent, and fewer than 1% were totally incontinent.

Renal cell carcinoma: considerations for nephron-sparing surgery.

OBJECTIVES: The performance of nephron-sparing surgery in patients with a normally functioning contralateral kidney is controversial. To explore the risk factors that may contribute to the success or failure of nephron-sparing surgery, we examined the radiology and pathology reports of 278 patients who underwent radical nephrectomy for the treatment of clinically localized renal cell carcinoma. METHODS: We collated patient data from the records of 278 patients with Stage III renal cell carcinoma entered into the Eastern Cooperative Oncology Group protocol EST 2886 and compared preoperative clinical staging with postoperative pathologic results. Patients were considered potential candidates for nephron-sparing surgery if their preoperative radiographic studies indicated that the carcinoma was a single polar lesion 5 cm or less in diameter. RESULTS: Of 278 radical nephrectomy specimens, 36 had primary lesions 5 cm or less in diameter. Preoperative radiographic studies showed 14 of 36 would not have been considered eligible for nephron-sparing surgery. Of the remaining 22 potential candidates, pathologic studies showed multifocal lesions in 11, renal vein disease in 4, and nodal disease in 2. Only 5 of 22 patients might have had specimen-confined disease (T3a lesion). CONCLUSIONS: Capsular-penetrating (T3a) renal cell carcinoma is not often appreciated preoperatively and is associated frequently with multifocal lesions, renal vein or nodal disease. Frozen section studies to rule out T3a disease at the time of nephron-sparing surgery may help determine which patients need radical surgery.

Penile gangrene associated with chronic renal failure: report of 7 cases and review of the literature.

Distal penile gangrene associated with renal failure is a rare entity with only 3 cases reported in the literature. Certain physiological abnormalities are commonly found in association with this condition, including secondary hyperparathyroidism, diabetes and peripheral vascular disease. We report our experience with 7 patients who presented with this condition. All patients had end stage renal disease with 5 on hemodialysis, 1 on peritoneal dialysis and 1 with a functioning cadaveric renal transplant. Six patients had diabetes mellitus and all had derangements of the calcium and phosphate metabolism, with the calcium-phosphorus product being greater than 70. Five patients were treated expectantly with resolution of gangrene in 2 and stable disease in 3. Three of the 5 patients managed expectantly and both patients treated with penectomy died of unrelated causes within 3 months. We conclude that there is no advantage to aggressive surgical treatment of penile gangrene associated with renal failure, since the outcome is the same. The overall mortality for this group is high due to associated co-morbid disease regardless of the type of treatment. Furthermore, subtotal parathyroidectomy is not indicated, since spontaneous improvement and mortality rates reported in our series were similar to those of previously reported cases. Expectant management of affected patients affords the best treatment.