'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate.

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.

Interstitial cystitis is associated with intraurothelial Tamm-Horsfall protein.

A defective barrier between the urine and urothelium has been suggested as an etiology for interstitial cystitis. With immunohistochemical techniques we assayed the bladder biopsies of 14 interstitial cystitis patients and 10 normal controls for intraurothelial Tamm-Horsfall protein to assess indirectly the in vivo permeability of the urothelium. Eight pathological controls, including bladder biopsies from 3 patients with inflammation owing to infection or catheterization and biopsies of 5 transitional cell carcinomas of the bladder, also were assayed. Superficial intraurothelial Tamm-Horsfall protein was identified in the biopsies from 10 of 14 interstitial cystitis patients (71 per cent) but only 1 of 10 controls (10 per cent) (p less than 0.01). Tamm-Horsfall protein was not identified in biopsies from the pathological controls. In 6 of 7 cases when more than 1 biopsy was available for analysis the findings were identical in each specimen. There was a direct correlation between the density of detrusor mast cells and the demonstration of intraurothelial Tamm-Horsfall protein. Seven of the 9 evaluable interstitial cystitis patients with intraurothelial Tamm-Horsfall protein but only 1 of 4 without intraurothelial Tamm-Horsfall protein experienced a favorable response to intravesicle oxychlorosene sodium (p greater than 0.05). These data suggest that abnormal permeability of the urothelium is associated with and a possible cause of interstitial cystitis and that the demonstration of intraurothelial Tamm-Horsfall protein in bladder biopsy specimens may prove to be useful as a diagnostic test for interstitial cystitis.

Tumor grade and stage as prognostic variables in upper tract urothelial tumors.

Clinical and pathologic data of 54 patients with clinically localized transitional cell tumors of the upper urinary tract were reviewed to determine the significance of tumor grade and stage on patient survival. There were 43 tumors of the renal pelvis (one bilateral) and 11 tumors of the ureter. The primary tumor was staged by the new TNM classification into low stage (Ta: limited to mucosa; T1: lamina propria invasion) and high stage (T2: muscularis invasion; T3; invasion beyond the muscularis). Tumors were low stage (Ta/T1) in 28 cases (51.8%) and advanced (T2/T3) in 26 cases (48.2%). Twenty-five of 54 (46.3%) of the patients had low grade (Grades 1 and 2) and 29 of 54 (53.7%) had high grade (Grades 3 and 4) tumors. Median survival for all patients from date of diagnosis was 31 months, with a 5-year survival rate of 45.8%. Grade (low/high) matched stage (low/high) in 45 of 54 patients (83%). Median survival for patients with low grade tumors was 66.8 months compared to 14.1 months in patients with high grade tumors. Median survival for low stage tumors was 91.1 months and for high stage tumors was 12.9 months. These differences in survival related to both tumor stage (P = 0.001) and grade (P = 0.004) were statistically significant by log-rank test. Fourteen of the 54 patients (25.9%) developed local recurrence and 29 (53.7%) developed distant metastases. The lung was the most common site of metastasis. Eighteen patients (33.3%) had or developed transitional cell carcinoma of the bladder, which preceded the diagnosis of transitional cell carcinoma of the upper tract in seven cases and developed subsequently in 11 cases. Primary tumor stage by the new TNM classification is a better predictor of prognosis than tumor grade, although both variables are strongly predictive of patient course and survival. The advantages of the new TNM classification are discussed.

Epidermal growth factor and prostatic carcinoma: an immunohistochemical study.

Associations between epidermal growth factor (EGF) and carcinoma of the prostate (CAP) have not been systematically investigated. We used indirect immunohistochemical techniques to demonstrate cytoplasmic EGF in paraffin-embedded sections of the following primary prostatic tissues: benign prostatic hyperplasia (BPH) (N = 10), BPH adjacent to CAP (N = 42), clinically localized CAP (N = 45), untreated metastatic CAP (N = 10), and metastatic CAP after varying periods of androgen deprivation (N = 10). In six of the latter 10 cases biopsies of the primary tumor obtained before androgen deprivation therapy were also available for study. Three of the BPH specimens (6%) and 44 of the CAP specimens (68%) stained. Forty per cent of the localized tumors stained but all untreated and treated metastatic tumors stained (p less than 0.01). There were direct but statistically insignificant correlations between the demonstration of EGF and both the Gleason score of localized and untreated metastatic tumors and the pathologic stage of localized tumors. The proportion of malignant cells stained in EGF positive tumors was similar regardless of Gleason score, pathologic stage or the presence or absence of metastases. However, the proportion of cells stained was greater in five of six specimens obtained during hormonal deprivation compared to specimens of the same tumor obtained before treatment. These data suggest that some prostatic cancers interact with EGF and that the interaction may be influenced by the androgenic milieu.

Polyglycolic acid mesh in repair of renal injury.

To evaluate the use of a polyglycolic acid (PGA) mesh graft for partial nephrectomy, we replaced the upper pole of the left kidney in 12 New Zealand white rabbits with a free omental fat graft and the lower pole with PGA mesh. The mesh stopped the bleeding immediately during the operation. At forty-eight hours, the fibers were still intact, with an organized clot on the surface of the mesh. Between two weeks and two months, the fibers had begun to be digested by histiocytes, with formation of giant cells and fibroblastic proliferation with collagen deposition around the mesh. At three months, there was complete resorption of the PGA mesh and formation of a new fibrous capsule. There was no renal reaction and no difference between the PGA mesh and the omental fat graft. We believe that PGA mesh can be helpful in repairing injured kidneys by securing hemostasis and serving as a scaffold for the formation of a new capsule.