Nuclear DNA ploidy and prostate cancer.
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DNA↗
Biomedical subjects
H Zincke
Publications and source records attributed to H Zincke.
Radical prostatectomy and exenterative procedures for local failure after radiotherapy with curative intent: comparison of outcomes.
During the last 2 decades 62 patients without evidence of distant disease underwent salvage surgery, including radical prostatectomy in 32, anterior exenteration in 23 and total exenteration in 7. Mean followup was 3.7 years, mean radiation dosage was 6,083 cGy. (range 3,060 to 7,400) and interval from irradiation to surgery was 6 to 98 months (mean 48 months). The 5-year nonprogression and cause-specific survivals for radical prostatectomy patients of 82% and 90%, respectively, were significantly (p = 0.0062) better than for patients having exenterative procedures. Despite the more extensive local procedure for larger tumors used in exenteration, the residual cancer rate was higher and local control was not improved. Median time to progression after radical prostatectomy and exenterative procedures was 7.5 and 1.3 years, respectively. Progression and cancer death were related to aneuploid status and, in particular, to hormonal treatment and its timing, with the best results obtained when adjuvant hormonal treatment was used for nonaneuploid tumors. Complications were more frequent than after primary prostate surgery. Salvage exenterative procedures seem to be of questionable benefit because of rapid disease progression. Prostatectomy, if feasible, appears to be an acceptable treatment for these difficult cases.
Aged↗
Hormonal treatment at time of radical retropubic prostatectomy for stage D1 prostate cancer: results of long-term followup.
In this long-term study with a median followup of greater than 10 years 62 patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for stage D1 adenocarcinoma of the prostate were subdivided with respect to nuclear deoxyribonucleic acid ploidy status of the primary cancer and according to whether they received adjuvant early antiandrogen therapy. Patients with diploid cancers who underwent the operation and received adjuvant early endocrine therapy did significantly better than a similar group without early endocrine therapy with respect to disease-free survival (p less than 0.001) and survival from prostate cancer death (p = 0.03). Among patients with nondiploid tumors early endocrine therapy was of some benefit for disease-free survival (p = 0.06) but not for prostate cancer death (p = 0.46).
Adenocarcinoma↗
Pitfalls of "bench surgery" and autotransplantation for renal cell carcinoma.
Under certain circumstances, extracorporeal surgical treatment ("bench surgery") followed by autotransplantation is indicated for renal cell carcinoma. During a 10-year period, 20 patients (16 men and 4 women) underwent bench surgery and attempted autotransplantation for renal cell carcinoma at our institution. The autotransplantation was successful in 16 patients but unsuccessful in 4 because of postoperative renal vascular thrombosis or extensive tumor involvement, which resulted in inadequate renal vein for anastomosis. Of the 16 patients who underwent successful autotransplantations, 4 (25%) subsequently had locally recurrent renal cell carcinoma (a mean of 35 months after initial autotransplantation). Only 6 of the 16 patients who underwent successful autotransplantation were ultimately free of both carcinoma and dialysis. Although an ex vivo surgical procedure can be beneficial for certain patients with renal cell carcinoma, computed tomographic scanning of the autotransplantation site should be performed every 3 to 6 months postoperatively for early detection of local tumor recurrence.
Aged↗
Cyst decompression surgery for autosomal dominant polycystic kidney disease.
A prospective study was undertaken to evaluate the efficacy of surgical cyst decompression for retarding the progression of renal failure and for the management of chronic pain associated with autosomal dominant polycystic kidney disease (ADPKD). Thirty patients with ADPKD and pain (14 patients), renal insufficiency (4 patients), or both (12 patients) underwent unilateral (19 patients) or bilateral (11 patients) cyst reduction surgery. The patients were monitored for 21 +/- 2 months postoperatively. The probability of being painfree was 80% at 1 yr and 62% at 2 yr. Preoperative and 1-to 3-month postoperative serum creatinine levels and GFR (clearance of insulin or (125I) iothalamate) were not significantly different (2.2 +/- 0.3 versus 2.2 +/- 0.3 mg/dL and 49 +/- 8 versus 54 +/- 9 mL/min/1.73 m2, respectively). One-year serum creatinine levels remained unchanged in patients with normal preoperative renal function (1.0 +/- 0.07 versus 1.0 +/- 0.05 mg/dL), whereas those with preoperative progressive renal insufficiency had no difference in the mean slope of reciprocal serum creatinine plots preceding and after surgery (-0.008 +/- 0.001 versus -0.009 +/- 0.002 dL/mg/month). In patients who underwent unilateral surgery, split function isotope scans showed no change in function of the operated kidney when compared with the nonoperated kidney. Surgical cyst decompression provides effective relief of chronic pain without compromising renal function. However, the data in this article do not support the use of this procedure to slow progression of renal insufficiency in ADPKD.
Adult↗
Treatment of primary squamous cell carcinoma of the upper urinary tract.
Forty-six patients with primary squamous cell carcinoma of the upper urinary tract treated over a 44-year period were studied. The lack of characteristic presentation caused delay in diagnosis. Associated urinary calculi were found in only five (11%) of the patients. Almost all of the tumors were histologically high grade; at surgery, 84% of the tumors were locally advanced or metastatic. Prognosis is poor independent of treatment; the overall 24-month survival rate was 22%. Comparison with a previous study of renal pelvic transitional cell carcinoma indicates that these two forms of urothelial neoplasm are biologically different.
Adult↗
Renal cell carcinoma in young and old 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.
Adult↗
Transurethral resection versus needle biopsy prior to radical prostatectomy for stage C prostate cancer. Influence on progression and survival.
Previous reports have claimed that transurethral resection of the prostate (TURP) preceding definitive radiation therapy for patients with Stage C prostate cancer promotes the risk of distant metastasis and increases the mortality rate. A total of 490 patients with pathologic Stage C adenocarcinoma of the prostate treated by radical prostatectomy were studied. Median time to follow-up was 4.6 years. Comparison was made between patients who had TURP within the six months preceding prostatectomy (n = 54) and those who had needle biopsy (n = 437) prior to operation. No significant differences were noted in local recurrence of disease, systemic progression of disease, disease-free interval, and overall and cause-specific survival, even after adjustment for clinical (adjuvant treatment) and pathologic prognostic variables. Our data suggest that for patients with pathologic Stage C prostate cancer treated by radical surgery, preoperative TURP is not associated with unfavorable outcome.
Aged↗
Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome.
Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice.
Adenocarcinoma↗
The incidence of multicentricity in renal cell carcinoma.
We established the frequency of cancer multicentricity in kidneys removed for renal cell carcinoma by examining 100 intact, formalin preserved kidneys with a diameter of less than 80 mm. (1987 to 1989). The mean diameter of the predominant tumors was 51 mm. (range 15 to 80 mm). After the capsules were removed the kidneys were serially sectioned at 3 mm. intervals, and cortical and intraparenchymal nodules were removed for histological examination. A total of 3 kidneys had multiple tumors found previously on routine pathological examination. In addition, we discovered another 11 nodules in 10 other kidneys. Four nodules had histological features consistent with carcinoma. The size of the nodules ranged from 2 to 5 mm. The rest of the nodules consisted of 3 adenomas, 1 adrenal rest, 1 oncocytoma coexisting with an adenoma and 1 carcinoma permeating through the lymphatic vessels. The mean size of the predominant tumors in the kidneys bearing multiple nodules was 49 mm. Therefore, we observed a 13% incidence of small renal nodules and a 7% multicentricity of renal cell carcinoma in kidneys from patients who underwent nephrectomy.
Carcinoma, Renal Cell↗
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.
Adenocarcinoma↗
The role of pathologic variables and hormonal treatment after radical prostatectomy for stage D1 disease.
Pathologic Stage D1 disease proves to be present in nearly 20% of patients who undergo radical prostatectomy for presumably clinically localized adenocarcinoma of the prostate. Disease outcome in patients who have undergone radical prostatectomy is significantly related to nuclear DNA ploidy pattern of the primary tumor and immediate adjuvant hormonal treatment, which prevents progression in all patients with a DNA diploid tumor pattern (40%). Although adjuvant hormonal treatments decrease progression significantly in patients with nondiploid tumors (60%), its impact on cancer death rate is less certain. This group of patients should be studied prospectively with innovative treatment programs.
Adenocarcinoma↗
Cause-specific survival advantage shown for hormone therapy for diploid prostate tumors.
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Androgens↗
Stage B prostate adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis.
Over a 16-year period (1966 to 1981), 349 patients underwent radical retropubic prostatectomy for pathologic stage B adenocarcinoma of the prostate. Nuclear DNA content was measured by flow cytometry on available archival material of 283 patients. Two hundred sixty-one patients (92%) had high-quality histograms. The ploidy distribution was as follows: DNA diploid, 177 (68%); DNA tetraploid, 74 (28%); and DNA aneuploid, 10 (4%). The average follow-up was 9.4 years. At the time of follow-up, 53 patients (20%) within the study group had developed tumor progression: 22 local, 23 systemic, and 8 both. The ploidy distribution of the population that developed tumor progression was 27 DNA diploid (51%), 16 DNA tetraploid (30%), and 10 DNA aneuploid (19%). This ploidy distribution is significantly different from that found for the nonprogression group with stage B disease. Overall, 31% of patients with DNA nondiploid tumors had tumors that progressed compared with 15% of patients with DNA diploid tumors. All (100%) DNA aneuploid tumors progressed. The DNA ploidy distribution of all pathologic stage B prostate cancers differs significantly from that found in more advanced stages (C and D1) previously reported for the same time interval. However, the ploidy distribution of stage B tumors that progressed closely resembles that of the stage C and D1 tumors. These results further support the working hypothesis that nuclear DNA content has marked prognostic significance for patients with adenocarcinoma of the prostate. It seems to us that analysis of ploidy by flow or static cytometry will become an essential tool for treating patients with localized prostate cancer.
Adenocarcinoma↗
Nuclear deoxyribonucleic acid ploidy and serum prostate specific antigen in operable prostatic adenocarcinoma.
A total of 71 patients with prostate carcinoma who underwent radical retropubic prostatectomy had preoperative measurement of serum prostate specific antigen levels and subsequent nuclear deoxyribonucleic acid ploidy analysis of the resected tumors. Prostate specific antigen levels were determined by a commercially available prostate specific antigen radioimmunometric assay (normal range 0 to 4.0 ng./ml.). The paraffin-embedded blocks of the prostate specimens were analyzed by flow cytometry for nuclear deoxyribonucleic acid content using Hedley's technique and propidium iodide staining. A strong association was found between nuclear deoxyribonucleic acid ploidy patterns and preoperative prostate specific antigen values. All patients with tetraploid and aneuploid tumors had elevated preoperative prostate specific antigen values. By contrast, all patients with preoperative antigen values of less than 4 ng./ml. had diploid tumors (p less than 0.0034). Prostate specific antigen levels were proportional to the estimated volume of the primary tumor (p less than 0.0065). However, even after statistical adjustment for tumor volume the preoperative prostate specific antigen value was still significantly and independently correlated with deoxyribonucleic acid ploidy pattern (p less than 0.007). However, only 35% of the patients with diploid tumors had antigen levels within the normal range. Conversely, 65% of the patients with diploid neoplasms had abnormally high antigen levels preoperatively. These results suggest that patients with localized biopsy proved prostate carcinoma and normal preoperative prostate specific antigen values are most likely to have diploid tumors; based on a 95% confidence level, the true proportion of patients with normal prostate specific antigen values who also have a deoxyribonucleic acid diploid tumor is 85 to 100%. Since localized deoxyribonucleic acid diploid tumors are known to be associated with a favorable prognosis for patients with prostate carcinoma treated by radical prostatectomy, a preoperative serum prostate specific antigen level within the normal range may help to predict disease outcome.
Adenocarcinoma↗
Progression and survival after renal-conserving surgery for renal cell carcinoma: experience in 104 patients and extended followup.
Of 104 patients who underwent a conservative operation for renal cell carcinoma 42 underwent partial nephrectomy, 60 underwent enucleation and 2 underwent a combination of these procedures. A total of 14 patients required an extracorporeal operation with autotransplantation. Forty patients had bilateral renal cell carcinoma (20 were synchronous and 20 were asynchronous) and 39 had either a solitary kidney or a poorly functioning contralateral renal unit. An operation was performed in the presence of a normal contralateral unit in 20 patients. The maximal duration of followup was 20 years (mean 4.9 years): 43, 17 and 7 patients were followed for 5 or more, 10 or more and 15 or more years, respectively. The 5-year cause-specific survival rates were 88.6 +/- 5.6, 91.6 +/- 4.7 and 88.9 +/- 3.8%, respectively, for the enucleation group, partial nephrectomy group and all patients combined. The percentages of patients free of local recurrence at 5 years for the enucleation and partial nephrectomy groups were 94.6 +/- 3.9 and 93.3 +/- 4.7%, respectively. The 14 patients who required an ex vivo approach had larger, higher stage and higher grade tumors, and a poorer outcome (5-year cause-specific survival rate and local rate free of recurrence were 54.9 +/- 17.2 and 85.7 +/- 13.2%, respectively). None of the 20 patients with a normal contralateral unit had progression. The local survival rate free of disease and cause-specific survival rate were not significantly different for the simple enucleation and partial nephrectomy groups. Even longer followup is needed to assess more clearly the definitive role of simple enucleation in the treatment of renal cell carcinoma and the clinical relevance of possible positive margins in a patient population that usually is older.
Carcinoma, Renal Cell↗
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.
Adenocarcinoma↗
Long-term outcome of renal transplantation in autosomal dominant polycystic kidney disease.
This study was performed to determine the long-term outcome of renal transplantation in 54 patients with end-stage renal failure secondary to autosomal dominant polycystic kidney disease (ADPKD) and in 107 patients with renal diseases other than ADPKD or diabetes mellitus matched by gender, age, year of transplantation, and source of the allograft. The overall patient survival and patient survival with a functioning first renal allograft were similar in both groups. Infection and cardiovascular accidents were the leading causes of early and late death in both groups. No cause of death was greatly overrepresented in the ADPKD group. Serious complications from extrarenal manifestations of ADPKD following renal transplantation included a ruptured intracranial aneurysm in one patient, a dissection of the ascending thoracic aorta in one patient, and infected hepatic cysts in two patients. Neoplasia (other than skin or cervical) occurred in four ADPKD patients and in one control patient and included one lymphoma in each group. Two ADPKD and one control patient had monoclonal gammopathies of undetermined significance. No complications related to the retention of native kidneys were detected in 12 ADPKD patients with a mean follow-up of 3 years. Cysts were observed in the renal allografts of some patients in both groups at autopsy and in a prospective computed tomography (CT) study of the allograft. However, we failed to detect a significant difference in the occurrence and number of the cysts between ADPKD and control patients.
Adult↗