Leslie M. Rainwater

Stage D1 Prostatic Adenocarcinoma: Significance of Nuclear DNA Ploidy Patterns Studied by Flow Cytometry

Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 91 samples of prostatic adenocarcinoma from patients with stage D1 disease (metastatic deposits in pelvic lymph nodes). All patients had undergone radical retropubic prostatectomy and bilateral pelvic lymphadenectomy. Clinical follow-up ranged from 5 to 19 years. Nuclei were extracted from paraffin-embedded archival material. Isolated nuclei were stained with propidium iodide. The DNA ploidy pattern was diploid (normal) in 42% of tumors, tetraploid in 45%, and distinctly aneuploid in 13%. Only 15% of DNA diploid tumors progressed locally or systemically, whereas 75% of tumors with an abnormal DNA ploidy pattern (tetraploid or aneuploid) subsequently progressed ( P P

Well Differentiated Clear Cell Renal Carcinoma: Significance of Nuclear Deoxyribonucleic Acid Patterns Studied by Flow Cytometry

Nuclear deoxyribonucleic acid ploidy was determined in 206 samples of well differentiated clear cell renal carcinoma via a previously described technique on paraffin-embedded archival material. Grade 2 tumors had a higher incidence of abnormal deoxyribonucleic acid patterns than grade 1 tumors. Of stage 1 well differentiated clear cell renal tumors 60 per cent had a normal deoxyribonucleic acid histogram pattern, whereas 67 per cent of higher stage tumors had an abnormal pattern. The existence of abnormal nuclear deoxyribonucleic acid histogram patterns in the primary tumor tissue had a significant correlation with subsequent development of metastatic disease, independent of tumor grade and stage. The 10-year actuarial survival rate was 62 per cent for patients with normal deoxyribonucleic acid histograms and 37 per cent for patients with abnormal patterns. These results demonstrate that nuclear deoxyribonucleic acid ploidy measured by flow cytometry is an important variable in the classification and determination of prognosis for patients with clear cell renal carcinoma.

Prostate specific antigen values after radical retropubic prostatectomy for adenocarcinoma of the prostate : impact of adjuvant treatment (hormonal and radiation)

Prostate specific antigen (PSA) levels were obtained before and after radical retropubic prostatectomy in 192 patients: 78 (41%) had pathological stage B2 cancer or less, 83 (43%) had stage C or C+ and 31 (16%) had stage D1 disease. Of those with stages B2 or less, C, C+ and D1 disease 82, 86, 65 and 90%, respectively, had postoperative PSA values of 0.2 ng./ml. or less (when first evaluated 30 or more days postoperatively). At 1 year postoperatively 94% of the stages C and C+ cancer patients treated with adjuvant radiation had PSA levels of 0.2 ng./ml. or less, which was significantly different from those not treated adjuvantly (p = 0.02). This effect of adjuvant radiation on PSA was temporary in the small number of patients with longer followup. Adjuvant orchiectomy for stage D1 lesions resulted in female PSA levels in virtually all cases. This decrease may be misleading and may reflect a direct hormonal effect rather than a decrease in tumor volume. Positive surgical margins did not significantly affect postoperative PSA levels, possibly because of the frequent use of adjuvant treatment.

Radical Prostatectomy After Radiation Therapy for Cancer of the Prostate: Feasibility and Prognosis

A total of 30 patients underwent an operation (radical prostatectomy in 27 and cystoprostatectomy in 3) for prostate cancer. In 17 patients radiotherapy with curative intent (range 5,700 to 7,500 cGy., mean 6,130 cGy.) had failed locally at 7 to 150 months (mean 48.8 months) later; 13 underwent the operation 2 months or less after planned radiotherapy (4,000 to 7,000 cGy., mean 5,431 cGy.). Followup was 1 to 16 years (mean 6.7 years). There was no perioperative death. The most significant complications were vesical neck contracture (17 per cent), lymphedema (10 per cent) and incontinence (10 per cent). Pathological staging revealed 8 patients with stage D1 disease. Of tumor grade, stage, adjuvant hormonal treatment and ploidy pattern only the last was associated with progression and survival. An increasing number of patients with local, albeit often symptomatic, radiation failure may present during the next years and they must be treated. Salvage prostatectomy is feasible and its associated morbidity seems to be acceptable; alternative (nonoperative) treatment modalities have proved not to be effective. Deoxyribonucleic acid ploidy pattern can provide valuable prognostic information in this difficult patient population for decision-making regarding radical surgery and adjuvant hormonal treatment.

Flow Cytometry of Renal Oncocytoma: Common Occurrence of Deoxyribonucleic Acid Polyploidy and Aneuploidy

Flow cytometry was performed on 51 typical specimens of renal oncocytoma. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Of the 51 available tissue blocks 86 per cent were evaluable and 50 per cent of these samples showed a deoxyribonucleic acid (DNA) histogram that was approximately the same as normal renal parenchyma. Of the oncocytoma samples 39 per cent showed a marked increase (more than 10 per cent of the nuclei) in the tetraploid DNA peak, while 11 per cent showed a distinct DNA aneuploid peak. Among 21 evaluable grade 2 oncocytic renal tumors 33 per cent showed a normal DNA histogram, 43 per cent showed a marked increase in the DNA tetraploid peak and 24 per cent showed a DNA aneuploid peak. The common presence of polyploid nuclei containing double quantities of chromosomal DNA may correlate with the long-standing pathological observation that oncocytic tumors often contain a distinct population of large nuclei. Indeed, 86 per cent concurrence was seen between the detection of an abnormal DNA content by flow cytometry and the histopathological presence of large abnormal nuclei in these specimens. Since renal oncocytomas (grade 1 oncocytic tumors) rarely, if ever, metastasize and are relatively noninvasive locally, their markedly abnormal flow cytometry patterns are of considerable interest. Moreover, DNA polyploidy has not been identified previously in renal tumors. The biological significance and mechanism of DNA polyploidy, and the relationship of DNA polyploidy and DNA aneuploidy to the pathogenesis of oncocytic renal tumors require further laboratory investigation. The clinical use of flow cytometry to classify and to predict the behavior of renal tumors will be complicated, since renal oncocytomas commonly have polyploid and aneuploid DNA histograms.

Prostate-Specific Antigen Testing in Untreated and Treated Prostatic Adenocarcinoma

The isolation and purification of prostate-specific antigen (PSA) and the development of a radioimmunoassay for this antigen represent major advancements for the detection of adenocarcinoma of the prostate and the monitoring of response to therapy in patients with this disease. Both monoclonal and polyclonal assays for PSA are available. In attempts to correlate pathologic tumor stage and PSA levels, tumors of higher stage (pathologic stages C1, C2, D1, and D2) have been associated with elevated PSA levels. Increased PSA levels have also been found in patients with benign prostatic diseases (benign prostatic hypertrophy and prostatitis). PSA has been shown to be an excellent marker after radical prostatectomy and for monitoring of radiation therapy. Patients with a persistently elevated PSA level for more than 6 months postoperatively should be assessed for residual or recurrent local or systemic disease. Thus far, routine use of PSA testing as a mass screening modality for prostatic cancer has not been considered cost-effective.

Renal cell carcinoma in young andold patients Comparison of prognostic pathologic variables (cell type, tumor grade and stage, and DNA ploidy pattern) and their impact on disease outcome

A group of 41 young patients (age less than or equal to 40 years; mean, 35.7 years) and a group of 34 old patients (age greater than or equal to 80 years; mean, 82.4 years) who underwent operation for renal cell carcinoma between 1970 and 1986 were compared. Sex, grade, and DNA ploidy pattern distributions were similar between the groups. Granular cell and papillary cancers with lower stages at presentation were more common among the young. In patients with high-stage disease, 73 percent of the older group but none of the younger had DNA diploid tumors. Low-stage clear cell carcinoma caused cancer death only in the young. Stage I nondiploid clear cell carcinomas were associated with death (33%) only in the young. Overall, death rates seem similar for both groups but among the young most (63%) occurred with low-stage disease and a nondiploid pattern only; among the old, 88 percent occurred with high-stage disease and independent of DNA ploidy pattern.

Technical Consideration In Radical Retropubic Prostatectomy: Blood Loss AfterLigation of Dorsal Venous Complex

The estimated blood loss and blood transfused in 641 patients undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy were analyzed to compare ligation and nonligation of the deep dorsal venous complex. Group 1 (325 men) had no attempt at deep dorsal vein ligation and group 2 (316) had ligation of the deep dorsal venous complex. Group 2 was subdivided into group 2a-137 men in whom an attempt at a nerve-sparing procedure was made and group 2b-179 in whom no such attempt was made. Estimated intraoperative blood loss was significantly different between the groups: group 1--mean loss 1,262 ml. and group 2--mean loss 1,020 ml. (p less than 0.0001). The amounts of blood transfused intraoperatively were significantly different: group 1-1.73 units and group 2-1.21 units (p less than 0.0002). Intraoperative blood loss was not significantly different between subgroups 2a and 2b but the mean amount of blood transfused intraoperatively was lower in group 2a than in group 2b (0.99 and 1.39 units, respectively p less than 0.02). The greatest amounts of blood lost and transfused were in group 1 (no ligation) and the least amounts were in group 2a (ligation and nerve-sparing), representing highly statistically significant differences (p less than 0.0001).

Wilms Tumors: Relationship of Nuclear Deoxyribonucleic Acid Ploidy to Patient Survival

Nuclear deoxyribonucleic acid ploidy studies with paraffin-embedded archival tumor specimens were performed by flow cytometry on extracted nuclei from 56 Wilms tumors. Before the era of chemotherapy 9 patients had a 33 per cent survival rate at 5 years. No significant correlation between deoxyribonucleic acid ploidy pattern and survival was seen in this early group of patients. Since 1960, 47 patients underwent radical nephrectomy and received chemotherapy. Deoxyribonucleic acid histograms in this group were normal in 13 tumors, while 23 tumors exhibited a tetraploid pattern (greater than 10 per cent nuclei in the G2 peak) and 11 showed an aneuploid pattern. Survival rates according to deoxyribonucleic acid ploidy pattern showed that 100 per cent of the patients with a normal or aneuploid histogram pattern were alive at 2 and 5 years. Patients with a deoxyribonucleic acid tetraploid pattern had a significantly worse survival of 74 and 69 per cent at 2 and 5 years (p less than 0.02 and less than 0.01), respectively. Tumors with a normal or aneuploid histogram pattern for all stages and a deoxyribonucleic acid tetraploid pattern for pathological stage I or II were associated with a 2 and 5-year survival rate of 100 and 97 per cent, respectively. However, patients with stages III and IV tumors with a deoxyribonucleic acid tetraploid pattern had a significantly worse survival of 25 per cent at 2 and 5 years (p less than 0.0001). Measurement of nuclear deoxyribonucleic acid ploidy identifies a patient group who are at high risk for treatment failure, that is stages III and IV tumors with a deoxyribonucleic acid tetraploid pattern.

Transureteroureterostomy with Cutaneous: Ureterostomy: A 25-Year Experience

We reviewed 67 patients who underwent transureteroureterostomy with cutaneous ureterostomy for benign (32) and malignant (35) disease in regard to the indications for and complications of the procedure. The most common complications included urine leakage at the ureteroureterostomy, stomal stenosis and calculus formation. Renal function improved or remained stable in 75% of the patients. Transureteroureterostomy with cutaneous ureterostomy is a viable alternative diversion technique in a select group of patients.