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.

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.

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.

Laparoscopic treatment of small-bowel obstruction following laparoscopic lymphadenectomy.

Laparoscopic pelvic lymph node dissection followed by radical perineal prostatectomy has become the treatment of choice for selected patients at our institution with clinically localized adenocarcinoma of the prostate. We describe 2 cases in which bowel obstruction caused by incarceration of a loop of small bowel into a trocar site was managed with laparoscopic techniques.

Relationship between contraction and relaxation in human and rabbit corpus cavernosum.

Although alterations in corporeal smooth muscle tone undoubtedly play an important role in the etiology of erectile dysfunction, the relationship between the degree of corporeal smooth muscle contraction and the magnitude of the observed relaxation response has never been quantitated. Thus, in vitro studies were conducted to examine the relationship between alpha 1-adrenergic contractility, and relaxations elicited by the clinically and physiologically relevant vasorelaxants, nitroglycerin, nitroprusside, and prostaglandin E1. Corporeal tissues strips were isolated from impotent and potent men, as well as sexually mature rabbits, and precontracted over a wide range of phenylephrine doses, prior to exposure of each tissue to the same dose of vasorelaxant. Plots of percent contraction versus percent relaxation revealed that the relationship between contraction and relaxation was accurately described by a first order linear equation, and characterized by an inverse relationship in all tissues studied, for all vasorelaxants examined. Statistical analysis indicated that the slope of the regression line was significantly greater than unity in all corporeal tissues obtained from patients with organic impotence; however, corporeal tissues obtained from patients with documented erections and from sexually mature rabbits had significantly lower slopes that were indistinguishable from unity. The existence of an inverse relationship between contraction and relaxation, even in the absence of organic disease, emphasizes the importance of the level of basal corporeal smooth muscle tone per se. These studies provide further evidence implicating heightened adrenergic tone as a significant etiologic factor in erectile dysfunction.

Combined laparoscopic pelvic lymph node dissection and modified belt radical perineal prostatectomy for localized prostatic adenocarcinoma.

OBJECTIVE: Despite many known advantages, the radical perineal prostatectomy (RPP) had fallen out of favor because of the need for a second incision for the regional lymph node dissection. Laparoscopic lymphadenectomy, however, provides an accurate and minimally invasive alternative to open lymph node dissection. Herein are reported the practical advantages of combining laparoscopic lymph node dissection (LPLND) with RPP. METHODS: Forty-nine patients with clinically localized carcinoma of the prostate were considered candidates for RPP using a modified Belt technique. Thirty-five patients underwent attempted LPLND and 31 of these patients subsequently underwent RPP; 14 patients underwent RPP alone. Variables examined included total operative time, transfusion requirement, length of hospital stay, continence, and potency. RESULTS: The mean operative time for LPLND combined with RPP in 31 patients, including time for repositioning, was 4.5 hours (range 3.0 to 7.0 hours). Only 26 percent of the patients who underwent the combined approach required blood transfusions of which 75 percent received autologous units. Mean length of stay was six days, and laparoscopy did not contribute significantly to postoperative morbidity. Eighty-four percent of the patients are completely continent. Of 27 potent patients who underwent nerve-sparing surgery, 22 percent are potent and an additional 30 percent are sexually active with intracavernous pharmacotherapy. There were no perioperative deaths, 2 major complications, and 5 minor complications. CONCLUSIONS: Laparoscopic techniques now permit the urologist to utilize the perineal approach, and its many advantages, to radical prostatic extirpation without the need for a formal abdominal incision. The minimal blood loss and low morbidity associated with laparoscopic pelvic lymphadenectomy combined with the radical perineal prostatectomy make this procedure an attractive alternative to the open retropubic approach for clinically localized prostatic adenocarcinoma.

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.

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.

Management of recurrent penile cancer following partial or total penectomy.

The initial management of localized penile carcinoma determines the probability of recurrence. Although potentially disfiguring, the management of recurrent carcinoma of the penis requires aggressive surgical resection of both the primary lesion and nodal sites to effect the best chance for long-term survival.

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.

[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.

Legal issues associated with PCP abuse--the role of the forensic expert.

These cases illustrate some of the complex issues associated with PCP-related litigation. The concept that malice is implied when an experienced drug user commits a crime while under the influence of the drug is not held in most states, at the present time. The authors have now reviewed in detail four cases of unexpected death following the use of neck holds in PCP-intoxicated individuals. In all of the cases, multiple carotid compression holds had been attempted, according to the history. Skin abrasions, hemorrhage into the soft tissues of the neck, and fractures of the hyoid bone and thyroid cartilage provide structural evidence of the application of substantial force to the neck. On autopsy, there has been no evidence of lethal injuries to the bronchial tree, brain, or heart. Drugs related to PCP are known to alter the carotid sinus reflex. Mechanical stimulation of the carotid sinus in the neck normally results in a slowing of heart rate and a decrease in blood pressure. Carotid sinus stimulation, coupled with the effects of PCP on blood vessels, might result in a marked fall in the blood pressure that could lead, ultimately, to death. Individuals intoxicated with PCP may be at a higher risk to complications of carotid compression neck holds. Hence, additional cases would be expected to become medicolegal issues.

Phencyclidine deaths.

The potential for a pharmacologic "overdose" and the cause of death associated with phencyclidine abuse is discussed. Nineteen deaths associated exclusively with phencyclidine intoxication have been documented. In 13 cases the immediate cause of death was asphyxia by drowning or trauma with lower levels of phencyclidine present suggesting behavioral toxicity. In two cases, the presence of phencyclidine in high concentrations constituted the only finding, and the probable cause of death was primary respiratory depression accompanied by seizure activity. A secondary drug effect or concurrent disease process may have contributed to the death of the remaining four individuals.

Phencyclidine use among youth: history, epidemiology, and acute and chronic intoxication.

Phencyclidine use appears to be in a growth phase nationally. Factors contributing to the increasing popularity include the user's ability to control the dosage, an understanding of the immediate effects, and its availability. Those most at risk appear to be young Caucasian males. Phencyclidine-related problems are often like tips of icebergs, the underlying causes of which are hidden from public view. The problems often surface in the form of speech difficulties, memory loss, thinking disorders, personality changes, paranoia, severe depression, violence, accidents, suicides and homicides. Of particular concern to law enforcement personnel is the upsurge in phencyclidine-related violent crimes and carrying of weapons by users to protect themselves from their imagined persecutors. The evidence currently available supports the assumption that if there is a solution to the problem of phencyclidine abuse, that solution is prevention. Therefore, medical personnel and others within the helping professions must be alerted to the fact that phencyclidine is not just another drug problem. The findings from users we have already studied strongly suggest that phencyclidine is not an "upper" or a "downer," but perhaps an "insideouter", with longer term implications.

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.

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.

Phencyclidine--states of acute intoxication and fatalities.

Phencyclidine is now one of the most frequently used main ingredients of "street drug" preparations. Its effects are highly dose dependent and three varieties of acute intoxication have been seen clinically associated with different dosages and routes of administration. Most persons using phencyclidine smoke it sprinkled on parsley in low doses. The presence of horizontal and vertical nystagmus associated with hypertension in a patient who is agitated or comatose are diagnostic of a phencyclidine intoxicated state. Sensory isolation and intravenous administration of diazepam in the event of seizure activity have proved effective in the treatment of acute intoxicated states. Phencyclidine has pronounced behavioral toxicity and several deaths due to this agent have now been documented. It is unknown whether seizure activity or respiratory depression is the primary cause of death in pharmacological overdoses.