Leopoldo E. Ladaga

Ex Situ Study of the Effectiveness of Enucleation In Patients with Renal Cell Carcinoma

We wished to identify the efficacy of enucleation (excavation) in the treatment of renal cell carcinoma. Surgical specimens from 26 patients with polar or peripheral lesions, 50 per cent of which were found incidentally by computerized tomography scan, were considered amenable to this form of treatment and were studied by ex situ enucleation after standard radical nephrectomy. Eleven patients were determined to have unsuccessful enucleation after histopathological study demonstrated capsular invasion, vascular invasion, residual tumor in the bed or multicentric tumors. Preoperative computerized tomography assessment did not accurately predict success of enucleation. The presence of a fibrous pseudocapsule of compressed renal parenchyma, which might facilitate a dissection plane and successful enucleation, did not correlate with tumor size. Microscopic examination of pseudocapsular integrity frequently revealed areas of thinning, disruption and penetration by neoplasm. When parenchymal preservation is necessary in the treatment of renal cell carcinoma, as wide a margin of adjacent renal parenchyma as possible should be excised with the tumor. In this study enucleation alone was associated with a significant risk of incomplete excision and, therefore, potential for treatment failure. We do not recommend enucleation in the presence of a normal contralateral kidney.

Cytogenetic evaluation of 20 cultured primary prostatic tumors

We report the cytogenetic evaluation of 20 cultured cell strains derived from primary prostatic adenocarcinomas obtained from radical prostatectomies. The majority of the strains contained cells with only normal male karyotypes (46,XY), but cytogenetically abnormal clonal populations were found in five strains. Two of those strains contained aberrations involving the Y chromosome, one with a -Y and one with a +Y. Three strains (one of which also had the XYY karyotype) exhibited cells with double-minute chromosomes and four strains contained near tetraploid cells.

OUTCOMES AFTER INTRAVESICAL BACILLUS CALMETTE-GUERIN ARE NOT AFFECTED BY SUBSTAGING OF HIGH GRADE T1 TRANSITIONAL CELL CARCINOMA

PURPOSE Substaging of T1 bladder tumors into T1a and T1b based on invasion of the tumor superficial to and beyond the muscularis mucosa has been assigned prognostic significance. We determined whether outcomes after intravesical bacillus Calmette-Guerin (BCG) differ between stage T1a and T1b subcategories. MATERIALS AND METHODS Retrospective pathological evaluation of the initial transurethral resection specimens of stage T1 bladder tumors was performed by 2 pathologists. Grade 1, 2 or 3 and stage T1a or T1b were assigned to each case. Followup was from the date of transurethral resection to date of death or the last visit. Kaplan-Meier probability and log rank test were used to evaluate recurrence and progression. RESULTS Substaging was performed in 49 of the 55 patients (89%) with stage T1 disease. Disease was stage T1a in 32 (65%), stage T1b in 17 (35%), grade 3 in 45 (92%) and grade 2 in 4 (8%) cases. Maximum followup was 147 months (median 71) and 28 cases had a minimum of 5 years of followup. Recurrence was noted in 33 cases (67.3%), including 22 stage T1a (69%) and 11 stage T1b (65%), at a median followup of 11.3 and 8.6 months, respectively. Progression to a higher stage of disease was recorded in 12 cases (24.4%), including 7 (22%) stage T1a and 5 (29%) stage T1b, at a median followup of 108 and 120 months, respectively. The difference between T1a and T1b subcategories was not statistically significant in regard to recurrence-free (p = 0.7203) and progression-free (p = 0.574) outcomes. CONCLUSIONS Substaging of T1 tumors did not affect response to BCG in regard to recurrence or progression. Therefore, intravesical BCG is effective for stages T1a and T1b disease.

Cytogenetic analysis of four primary prostatic cultures

Primary cell cultures were established from tissue specimens obtained from patients undergoing transurethral resection of the prostate. Cytogenetic analysis of these cultures revealed a normal male chromosomal complement from one and a 45,X karyotype from another patient with benign prostatic hyperplasia. In addition, a normal male chromosomal complement was observed from a moderately differentiated prostatic carcinoma, and a grossly abnormal karyotype was observed from a poorly differentiated adenocarcinoma of the prostate. This latter specimen contained a modal chromosome number of 84 with several consistent marker chromosomes including homogeneous staining regions and double minutes, and no normal chromosomes 3, 5, 10, 15 or Y. Primary prostatic cell cultures exhibit epithelial-specific keratin intermediate filament proteins, and, in conjunction with cytogenetic analysis, provide a model for the study of human prostate cancer.

Malignant hypertension in children secondary to chronic pyelonephritis: laboratory and radiologic indications for partial or total nephrectomy.

Abstract Severe renin-mediated hypertension was noted in 2 children as a result of selective renal damage from vesicoureteral reflux during the early years of life. In each case the reflux had been corrected successfully long before hypertension developed. In 1 case the late damage involved only 1 kidney and nephrectomy resulted in immediate relief of the hypertension. In the second case, even though both kidneys showed segmental scarring from calicectasis and chronic pyelonephritis, removal of the atrophied lower pole of 1 kidney made hypertension amenable to medical treatment and reduced excessive renin output to a fraction of the original high levels. The mechanism of renin-mediated hypertension in kidneys with segmental scars of chronic pyelonephritis is believed to be ischemia of the relatively normal renal cortex in proximity to areas of interstitial fibrosis, within which are tortuous interlobular and smaller arterioles with severe intimai thickening. Hypertrophy of normal renal segments occurs in young patients with segmental chronic pyelonephritis. To accommodate this enlargement the original calix develops an extension or elongation readily distinguishable from other dilated calices.

Comparison of transrectal fine-needleaspiration cytology and core needle biopsy in diagnosis of prostate cancer

One hundred sixty-nine transrectal fine-needle aspirations of the prostate gland were performed in 166 patients over a two-year period. The results were compared with simultaneous core needle biopsy performed in all but 4 patients. Forty-seven (28%) aspirations were either unsatisfactory or inconclusive. Of the remaining 122 (72%) patients in whom a cytologic diagnosis could be made, core biopsy was available in 120. Aspiration cytology was 87 percent sensitive and 96 percent specific with an overall agreement of 93 percent with core biopsy. No major complications occurred. We conclude that fine-needle aspiration of the prostate is accurate, safe, and cost-effective, and greater application of this technique is encouraged.

Are three substages of clinical B prostate carcinoma useful in predicting disease-free survival?

The B1 nodule, a 1.5 cm area of induration surrounded on at least two sides by prostatic tissue of normal consistency, was defined by Jewett in 1968 as the stage of prostatic cancer best suited for treatment and cure by radical prostatectomy (RP). The area of prostatic induration suitable for RP was subsequently extended to less than one lobe (Stage B1); this extension of induration was supported by the study of Walsh and Jewett in 1980 showing a 51 percent survival free-of-disease at fifteen-year follow-up. Subsequently, clinical staging systems evolved which substaged clinical B into three categories of induration: B1N = less than 1.5 cm nodule, B1 = greater than 1.5 cm but less than one lobe, and B2 = one lobe or both lobes. To determine if digital assessment of these progressively greater degrees of induration would translate into different intervals to first progression, whether local or distant, we reviewed prostate diagrams and descriptions of all Stage B patients treated by Iodine-125 interstitial implant and external beam radiation therapy between 1974 and 1985 at our institution. Forty-six patients had B1 nodules, 78 patients B1 (less than one lobe), and 52 patients B2 (one lobe or greater). Mean follow-up was fifty-five months. We found B1N, which was also associated with well-differentiated grade and a normal acid phosphatase, to have the longest interval to progression.

Pathological findings after preoperative irradiation for carcinoma of the urinary bladder.

Pathological descriptions of specimens obtained in 17 patients with urinary bladder carcinoma both at biopsy before preoperative irradiation and after surgery are presented. No positive lymph nodes were found in 16 patients who had lymphadenectomy at the time of surgery. No tumor was found postoperatively in 58.8% of patients and 82.3% had a reduction in tumor stage.

Monoclonal Antibodies to Human Prostate and Bladder Tumor-Associated Antigens

Monoclonal antibodies to human prostate adenocarcinoma membrane antigens were produced by fusion of P3X63/Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized against the prostate cancer cell line DU145. The hybrids were screened for antibody production using glutaraldehyde-fixed cells in a solid-phase radioimmunoassay. Antibody-binding specificity was also checked by quantitative adsorption, membrane immunofluorescence, and complement-dependent cytotoxicity assays. A hybridoma clone (83.21) was isolated that secreted antibodies which preferentially bound to several prostate and bladder cancer cell lines but did not bind to a variety of other normal and malignant human cell lines. This antibody also reacted with a cytomegalovirus-transformed human embryonic lung cell line but not to normal human embryonic lung cells. Quantitative adsorption studies demonstrated that the 83.21 monoclonal antibody was strongly reactive to membrane preparations from human prostate adenocarcinoma tissue and a liver metastasis of prostate carcinoma. Little or no binding activity was observed against two other prostate carcinomas, bening prostatic hyperplasia, normal prostate, or normal liver. Binding studies indicate that the 83.21 monoclonal antibody does not bind to alpha-fetoprotein, carcinoembryonic antigen, prostatic acid phosphatase, human leukocyte antigen, beta 2-microglobulin, HLA-Dr antigens, fibronectin, or prostate antigen. The data indicate that we have isolated a monoclonal antibody that binds to an antigen(s) expressed by several urogenital carcinoma cell lines as well as human prostate tumor tissue and that the antibody is not directed against well-known human tumor cell markers.