[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.

Fibronectin expression on surgical specimens correlated with the response to intravesical bacillus Calmette-Guerin therapy.

Attachment of bacillus Calmette-Guerin (BCG) organisms to the bladder during intravesical therapy is thought to be mediated exclusively by the glycoprotein fibronectin, which is expressed variably on epithelial surfaces and on basement membranes. We examined the relationship between the degree of fibronectin expressed on surgical specimens obtained from 50 candidates for BCG therapy and the subsequent clinical response. Immunoperoxidase staining for fibronectin was performed on tumor, nonadjacent normal mucosa and basement membrane tissues, and the intensity of the staining was scored on a scale of 0 to 3+ (control 2+). In the absence of recurrence at quarterly surveillance cystoscopy, a course of Tice BCG therapy consisted of 6 weekly and 12 monthly instillations. Recurrence of noninvasive tumor prompted a second BCG course. Followup ranged from 24 to 66 months (median 40 months). Of the 50 patients (11 with carcinoma in situ) disease progression occurred in 9 (none with carcinoma in situ). Compared to the results for tumors or for basement membranes, the degree of fibronectin expression on normal mucosa was well correlated with the clinical response (r = 0.59, p < 0.001 by Kendall Tau B). Routine assessment of fibronectin expression on the normal mucosa associated with superficial bladder cancer may be useful for predicting the clinical response to BCG therapy.

A new porphyrin photosensitizer (PH1008) in model membranes, normal cells, and bladder cancer cells.

Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N-dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent.

Clinical and immunological response to nifedipine for the treatment of interstitial cystitis.

Nifedipine is a calcium channel antagonist known to inhibit smooth muscle contraction and cell-mediated immunity. The clinical and local immune response to nifedipine was investigated in an open trial with 10 female interstitial cystitis patients, whose disease was diagnosed according to the consensus criteria developed in 1987 at a National Institutes of Health workshop. To evaluate the symptoms and clinical response of the patients objectively we scored the symptoms of frequency, urgency, nocturia, dysuria and suprapubic pain on a scale of 0 to 2. Nifedipine was administered as a single daily dose determined by a dose-titration test. Urinary interleukin-2 inhibitor activity, a marker of cell-mediated inflammation, was measured using a murine interleukin-2 dependent cell line. Before nifedipine therapy the symptom scores (total of the 5 symptoms) ranged between 5 and 9, and after 2 months they ranged between 0 and 6. Of the 9 patients followed for at least 4 months only 1 failed to have a significant clinical improvement, 5 showed at least a 50% decrease in symptom scores and 3 were asymptomatic. Drug side effects were minimal. Urinary interleukin-2 inhibitor activity before nifedipine therapy confirmed the presence of cell-mediated inflammation. After 4 months of therapy interleukin-2 inhibitor activity was normal in 7 of 9 patients regardless of the severity of symptoms, which indicated that nifedipine exerted an immunosuppressive effect. Although our data suggest that nifedipine is an efficacious, well tolerated, convenient oral medication for the treatment of interstitial cystitis, the true value of nifedipine for patients with this disease must be determined by a prospective, randomized trial of nifedipine versus placebo.

Interleukin-2 immunotherapy followed by resection of residual renal cell carcinoma.

We administered 10 (E5) units per kg. interleukin-2, 3 times daily, with or without lymphokine-activated killer cells, to 10 patients with metastatic renal cell carcinoma. All patients had metastases to the lung, and 3 of 5 patients who had previously undergone nephrectomy had metastases to the renal fossa. Of the 9 patients who completed at least 1 course of therapy 3 had complete regression of disease outside the abdomen, including 2 who were rendered disease-free after subsequent cytoreductive surgery (nephrectomy in 1 and resection of the renal fossa recurrence in 1). Viable tumor comprised less than 1% of each surgical specimen. Our results support the view that initial treatment with interleukin-2 immunotherapy, followed by abdominal cytoreductive surgery if the peripheral metastases have regressed, may be preferable to the practice of performing abdominal cytoreductive surgery before administering interleukin-2 immunotherapy for patients with widely metastatic renal cell carcinoma.

Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high-dose interleukin-2 immunotherapy.

High-dose interleukin-2 (IL-2) immunotherapy can cause hypotension, respiratory distress, interstitial edema, and thrombocytopenia, similar to endotoxic shock. We have observed that IL-2 has no direct effect on coagulation factors in vitro, but it has been observed to alter the coagulant properties of vascular endothelium. Accordingly, we investigated the possibility that IL-2 infusions initiate plasma fibrinolysis and disseminated intravascular coagulation (DIC). We studied the clinical course, platelet count, and coagulation profile in response to IL-2 infusion in seven patients, two with metastatic melanoma and five with metastatic renal cell carcinoma. Every patient experienced hemodynamic instability and thrombocytopenia, and one patient suffered an unusual complication, mesenteric thrombosis. No patient had appreciable changes in the prothrombin time or the partial thromboplastin time, nor did factors V or VIII decline in the two patients observed. In four patients examined, we found decreased titers of Hageman factor (factor XII), high molecular weight kininogen, prekallikrein, and plasma thromboplastin antecedent, as if these had been consumed by reactions of the intrinsic pathway of thrombin formation. Circulating D-dimer fragments were found in the plasma of every patient at some point during each infusion cycle, and we observed decreased titers of plasminogen in the four patients just mentioned, suggesting that IL-2 infusions initiated fibrinolysis. Taken together, the clotting factor derangements and related toxicity phenomena cannot be ascribed firmly to DIC. Activation of the intrinsic (contact) system of coagulation, however, may provide one link between the vascular endothelial surface alterations caused by IL-2 infusions and the development of the systemic toxicity that resembles septic shock.

Synchronous, primary bilateral lymphoma of testes.

Lymphoma of the testicle is the most common testicular neoplasm in men over sixty years of age, but usually represents a secondary manifestation of systemic disease. This case report describes the rare phenomenon of a synchronous, primary bilateral lymphoma of the testes (Stage Ie) occurring in a sixty-eight-year-old man.

Measurement and partial characterization of an interleukin-2 inhibitor (IL-2-IN) in human urine.

We observed a human urine-derived protein complex (IL-2-IN) which competitively inhibits interleukin-2 (IL-2) dependent murine lymphocyte proliferation. Measurements of urinary IL-2-IN have been used to stratify the immune response of patients to bacteria in the bladder. Partial characterization of IL-2-IN indicates that it is a heat-stable, 75 kDa complex comprised of interleukin-2 bound to another protein(s). Although the IL-2-IN complex is stable in physiologic buffers, the complex can be disrupted using acidic or low-ionic strength buffers, thereby liberating IL-2. IL-2-IN activity is susceptible to bacterial and endogenous urinary proteolysis. The IL-2 bound in the IL-2-IN complex cannot be detected using a double monoclonal antibody radioimmunoassay for IL-2. Unlike other IL-2 binding proteins, the IL-2 binding protein of the IL-2-IN complex is not a soluble interleukin-2 receptor. A modification of the bioassay for interleukin-2 activity is the method of choice for the detection and quantification of urinary IL-2-IN.

Urinary interleukins in patients receiving intravesical Bacillus Calmette-Guerin therapy for superficial bladder cancer.

Intravesical administration of Bacillus Calmette-Guerin (BCG) causes a localized cell-mediated immune response. The intensity of this inflammatory response may be gauged by measuring the levels of both interleukin-2 (IL-2) and an inhibitor of interleukin-2 (IL-2-IN) activity in the urine during the hours after a BCG instillation. The levels of urinary IL-2 and IL-2-IN in the sixth week of BCG therapy predicted the subsequent clinical course in a group of 25 patients (P less than 0.01). Measurement of urinary IL-2 and IL-2-IN activity may be used to identify accurately those patients likely to develop a tumor recurrence, thereby sparing them the risk associated with inadequately treated bladder cancer. Since IL-2 and IL-2-IN are competitive with respect to biologic activity, and since relatively high urinary levels of either IL-2 or IL-2-IN activity correlated with a favorable clinical course, the authors conclude that the presence of bioactive IL-2 in urine is not required for the prevention of recurrent superficial bladder cancer.

Urinary interleukin-2 inhibition in patients with cystitis.

An inhibitor of interleukin-2 activity (IL-2-IN) is present in the urine of most patients during the acute phase of untreated bacterial cystitis (UTI). We measured urinary IL-2-IN activity in 30 adults with uncomplicated UTIs and followed the patients for an additional 6 months. Urinary IL-2-IN activity ranged between 0 and 1.97 units/mg urine creatinine (U/mg u.c.). Relatively low levels of IL-2-IN (less than 0.5 U/mg u.c.) correlated with a prior history of recurrent UTIs (p less than 0.01), and also were predictive of a subsequent UTI during the 6 month follow-up, regardless of the prior medical history (p less than 0.01). Measurement of urinary IL-2-IN during the untreated phase of a UTI may prove helpful for directing antibiotic prophylaxis against subsequent UTIs.

Measurement of serum interleukin-2 activity.

The accurate measurement of serum interleukin-2 activity is crucial for assessing the efficacy and toxicity of systemic immunotherapy with recombinant interleukin-2. Incubation of serum at 56 degrees C for 30 minutes facilitates the bioassay for interleukin-2 activity by destroying the interleukin-2 inhibitory activity native to human serum. As this report will demonstrate, however, 30% to 50% of interleukin-2 activity in serum taken from patients or normal volunteers was destroyed by heating at 56 degrees C. No loss of recombinant interleukin-2 activity occurred during heating in serum-free media. The percentage of interleukin-2 activity lost at 56 degrees C varied from patient to patient and also varied with the time of exposure. Native serum interleukin-2 inhibitory activity can be removed, and interleukin-2 activity can be assessed accurately in serial dilutions of the serum beyond 1:64.

Interleukin-2 self-association.

The self-association of human recombinant interleukin-2 (IL-2) from E. coli was explored. Self-association, with an apparent Kd of 0.6 micromolar, has pronounced effects on (1) the surface exposure of Trp-121, deduced from quenching studies employing potassium iodide and acrylamide, (2) the apparent quantum yield of Trp-121, the fluorescence of Trp-121 in IL-2 aggregates is 4-fold lower than in IL-2 "monomers", and (3) IL-2-mediated phospholipid vesicle fusion/aggregation.

Endocrine therapy for bladder outlet obstruction from carcinoma of the prostate.

The optimum treatment of bladder outlet obstruction from prostatic cancer is controversial. Although transurethral resection of the prostate may provide immediate relief of the obstruction, there are attendant surgical and anesthetic risks, as well as accumulating clinical evidence to suggest that transurethral resection of the prostate may cause tumor dissemination and diminish patient survival. Orchiectomy, which can be performed safely with local anesthesia, provides definitive endocrine therapy and has been used at our institution in preference to transurethral resection to relieve bladder outlet obstruction from carcinoma of the prostate. There were 35 patients between 51 and 96 years old in urinary retention from carcinoma of the prostate. Patients were treated with orchiectomy and suprapubic or urethral catheter drainage, and subsequently were given voiding trials. If a patient failed to void satisfactorily within 60 days transurethral resection of the prostate was performed. Over-all, 24 of 35 patients (68.6 per cent) were relieved of bladder outlet obstruction by orchiectomy alone. Neither tumor stage nor grade correlated significantly with the response to orchiectomy. We conclude that transurethral resection of the prostate may be held in reserve for patients who do not respond to endocrine therapy or those who do not wish to risk sexual impotence.