Prognostic value of deoxyribonucleic acid content in metastatic renal cell carcinoma

The deoxyribonucleic acid content of tumor specimens from 23 patients with metastatic renal cell carcinoma was analyzed prospectively by flow cytometry and static cytophotometry. Of the primary tumors 10 (43 per cent) were homogeneously diploid or near diploid in 8 samples studied from each tumor and 13 (57 per cent) had an aneuploid deoxyribonucleic acid content in 1 to 8 samples. At the end of followup 9 of 10 patients with diploid or near diploid primary tumors were alive, compared to only 1 of 13 with aneuploid primary tumors. Patients with homogeneously diploid or near diploid tumors survived significantly longer compared to those with aneuploid tumor deoxyribonucleic acid content (p less than 0.001). After excision of solitary diploid or near diploid metastases 4 patients had no evidence of disease. In 3 of these patients the primary tumors were diploid or near diploid, whereas 1 had 1 aneuploid and 7 diploid or near diploid samples in the primary tumor. In 10 other patients 28 metastases revealed concordance in deoxyribonucleic acid content with the primary tumors. Our results indicate that deoxyribonucleic acid content might be a useful prognostic discriminator with implications for the clinical management of patients with metastatic renal cell carcinoma.     

Deoxyribonucleic acid flow cytometry on primary adenocarcinoma of the bladder: an analysis of 36 cases

Deoxyribonucleic acid flow cytometry was applied retrospectively to 36 primary pure adenocarcinomas of the bladder, stages A through D. Six tumors were enteric, 3 mucinous, 11 signet ring, 3 papillary, 5 unspecified and 8 mixed. Eight tumors were urachal in origin and 28 were nonurachal. The deoxyribonucleic acid pattern was diploid in 12 cases, aneuploid in 19, tetraploid in 3 and uncertain in 2. Nineteen patients died of disease after a mean of 27.4 months, 7 were well at a mean of 73.9 months, 8 had died of an unrelated cause and 1 was alive with metastatic disease. Ploidy pattern did not correlate with tumor stage, histological pattern or type of outcome: 6 of 12 patients with diploid and 12 of 22 with nondiploid tumors died of disease. However, if the tumor was urachal 1 of 4 patients with a diploid pattern died of disease, while 3 of 4 with an aneuploid pattern either died or were alive with disease. Our data suggest that deoxyribonucleic acid ploidy pattern apparently is not a significant predictor of outcome for primary adenocarcinoma of the bladder except possibly when the origin is urachal.     

Flow cytometric analysis of primary and metastatic bladder cancer

A total of 22 patients with high grade P2-4N+ transitional cell carcinoma of the bladder underwent flow cytometric analysis of nuclei obtained from paraffin embedded specimens from the primary (bladder) and metastatic (lymph node) sites. Tumor heterogeneity was defined as polyclonal aneuploidy of the primary tumor (not identified in the population studied) or as a difference in the deoxyribonucleic acid index of the primary and metastatic sites of 0.20 or more (8 patients). With these criteria 8 patients (36%) had heterogeneous tumors and 14 (64%) had homogeneous tumors. The median survival of 14 patients with aneuploid and 8 with diploid primary tumors was 17.5 and 8.0 months, respectively (p equals 0.08, Lee-Desu test). When patient survival was compared to the ploidy of the metastatic site, or in patients with diploid primary and metastatic lesions versus deoxyribonucleic acid aneuploidy at either the primary and/or metastatic site, the aneuploid tumors had a longer survival but this difference was not significant (p equals 0.13 and 0.23, respectively). Our study demonstrates the value of flow cytometry to identify primary metastatic tumor heterogeneity. It also suggests that the presence of metastasis may be a more important factor to define the biological potential of transitional cell carcinoma than is deoxyribonucleic acid ploidy.     

Flow cytometric assessment of deoxyribonucleic acid content in renal adenocarcinoma: does ploidy status enhance prognostic stratification over stage alone?

Flow cytometry was used to analyze deparaffinized primary renal cell carcinoma specimens from 106 patients to evaluate deoxyribonucleic acid ploidy as a predictor of disease progression and survival. Of these specimens 62 (58%) demonstrated aneuploid stem lines: 30 (48%) of these were tetraploid aneuploid while 32 were nontetraploid aneuploid. Two or more specimens were analyzed from a single primary tumor in 17 patients and heterogeneity of ploidy status was observed in 5 (30%). Specimens of the primary tumor, and regional and/or distant metastases from 11 patients were analyzed; 5 (45%) demonstrated discordance between the ploidy of the primary and the metastatic site. A significant correlation was noted between the presence of aneuploid stem lines and high stage disease (p equals 0.004) but there was no significant correlation between ploidy status and tumor grade. Although there was a significant difference (p equals 0.037) in the incidence of disease progression in patients with diploid tumors (13%) versus those with aneuploid tumors (35%) in the total population, and Kaplan-Meier disease-specific survival curves demonstrated a survival advantage for patients with diploid tumors in the total population, no clear survival advantage was demonstrated for evaluable patients with diploid tumors when controlled for tumor, nodes and metastases stage. In conclusion, the heterogeneity of ploidy status in primary renal cell carcinoma, the high incidence of disease progression in patients with diploid primary tumors and the lack of a clearly demonstrable stage-independent impact of ploidy on prognosis currently would not support widespread clinical application of ploidy status of the primary tumor in the management of individual patients with renal cell carcinoma.     

In situ management of renal tumors: renal cell carcinoma and transitional cell carcinoma

In the last 8 years 15 patients with malignant neoplasms in functionally solitary kidneys underwent in situ excision of the tumor with preservation of renal parenchyma. Of 10 patients with renal cell carcinoma 8 underwent partial nephrectomy, 1 had a central wedge resection and 1 had enucleation of 3 tumors. After followup of 6 months to 4.7 years 6 patients are free of disease. One patient died of metastatic cancer and 1 of cardiovascular disease. Of 5 patients with transitional cell carcinoma of the kidney (including 2 with parenchymal invasion) 2 underwent partial nephrectomy and 3 underwent extensive resection of renal pelvic lesions. After followup of 6 months to 7 years 2 patients are alive, 2 died of metastatic disease and 1 died of metastatic bladder carcinoma. Only 1 of the 5 patients had locally recurrent tumor. These data demonstrate the efficacy of in situ management of renal tumors in selected patients with solitary kidneys or compromised renal function.     

Infarction-nephrectomy for metastatic renal carcinoma. Southwest oncology group study

Thirty patients with metastatic renal cell cancer were treated by renal infarction, followed by delayed nephrectomy. All cases were collected over an eighteen-month period, with a minimum follow-up of one year. There were no complete remissions and only one partial remission, which lasted twenty-one months before progression of disease. Three patients had stable disease for at least six months, but eventually all patients showed evidence of progression. After tumor progression was documented patients were treated with intramuscular medroxyprogesterone acetate (Depo-Provera) 800 mg per week. No patient responded to this therapy. Overall, a 28 per cent one-year survival and a seven-month median survival were realized, which is similar to other series in which no therapy or palliative nephrectomy was performed. We conclude that infarction and nephrectomy is not an effective modality in the treatment of metastatic renal cell carcinoma. In addition, medroxyprogesterone was not shown to be significantly active against renal cancer in this study.     

乳腺癌原发灶及腋淋巴结FCM分析对预后的评价

作者采用流式细胞仪（ＦＣＭ）对５８例乳腺癌患者的原发灶及腋淋巴结共１１６份新鲜组织进行ＤＮＡ含量、倍体及Ｓ－期细胞百分率（ＳＰＦ）分析。经过５年随访,发现复发及转移（简称复发）２３例,其中２１例已死亡。结合各种因素进行分析,发现异倍体及高ＳＰＦ有较高的复发率,特别当病期较晚或腋淋巴结有转移时。作者还发现原发灶ＦＣＭ的分析结果比腋淋巴结的分析结果对预后有更大的价值。作者总结了二倍体肿瘤复发的可能原因,并提出了加强异倍体肿瘤术后治疗的建议。     

Metastatic parathyroid carcinoma: dilemmas in management.

The incidence of parathyroid carcinoma in patients surgically treated for primary hyperparathyroidism at the University of Michigan Hospital was 0.4% during an 18-year period. The courses of the five patients with metastatic disease are described. Histologic reevaluation and assessment of the DNA ploidy pattern were performed in each case. Localization studies preceded all reexplorations. The number of operative procedures in each patient ranged from two to 10. Two patients are living with recurrent disease and one has been disease free for 42 months. Two patients died after 2 and 12 years, respectively. Three patients had aneuploid tumors; one had a diploid tumor. One patient had both aneuploid and diploid cell populations. Dilemmas in diagnosis, localization, and medical and surgical management were encountered in patients with metastatic carcinoma. The chosen treatment should be evaluated individually in each case because of the variability in aggressiveness of this malignancy. Surgical resection proved most effective in some of these patients for both local and distant recurrences. Bisphosphonates and gallium nitrate have been reported to be effective in controlling hypercalcemia. Only the former had some effect in one of our patients.     

Transitional cell carcinoma of the renal pelvis and ureter: prognostic relevance of nuclear deoxyribonucleic acid ploidy studied by slide cytometry: an 8-year survival time study.

In 72 patients with urothelial carcinoma of the renal pelvis or ureter the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Followup ranged from 1 to 8 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumors and clinical course. Malignancy grade 1 tumors showed DNA frequency peaks in the diploid range, while tumors assessed as malignancy grade 2 showed heterogeneous DNA distribution patterns. Malignancy grade 3 tumors exhibited 71% aneuploid and 29% tetraploid DNA values. The proliferation rate of the tumor cells was statistically significantly higher in malignancy grades 2 and 3 than in malignancy grade 1. The prognosis for grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups (patients with grades 1 and 3 tumors) DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy although they exhibit the same histomorphological degree of differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive) tumors. There was also a positive correlation between T category and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage T1 tumors, 56% with stage T2 tumors and almost 85% with stage T3, N+ tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei had no metastases and no local tumor progression for up to 8 years, whereas patients with aneuploid tumor cell nuclei suffered metastasis and local tumor progression within 24 to 36 months. The patients died of the tumor 36 months after primary diagnosis on the average. The determination of DNA ploidy, tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry affords valuable clues as to prognosis.     

Immunotherapy with interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer with in situ primary cancers: a pilot study.

A total of 12 patients with stage 4 renal cell carcinoma and primary renal tumors in situ was entered into a pilot study using treatment with interleukin-2 and alpha-interferon followed by radical nephrectomy. Of the patients 11 underwent nephrectomy after an initial course of immunotherapy. Ten patients were able to receive a second course of immunotherapy given after nephrectomy. One patient achieved a complete response of lung and mediastinal metastases without any change in the primary renal tumor but after nephrectomy the patient remained in complete remission for greater than 11 months. A total of 3 patients achieved a partial response at some extrarenal sites but they had progression elsewhere. Toxicity was similar to previous experience with this immunotherapy regimen. Therefore, we demonstrated that metastatic tumor regression is possible with primary renal tumors in situ and that aggressive interleukin-2-based immunotherapy can be tolerated in the presence of a large renal tumor.     

Deoxyribonucleic acid cytometry and histological findings before and after 125iodine implantation of primary prostate cancer.

Deoxyribonucleic acid (DNA) flow cytometry and light microscopy were performed in pre-radiotherapy and post-radiotherapy biopsies obtained from the primary tumor in 31 patients with prostate cancer. Radiotherapy was applied by means of transperineal 125iodine (125I) implantation. Of the patients 21 had pretreatment biopsies and in 19 of these biopsies also were performed 1 and/or 1 1/2 years after the 125I implantation. Posttreatment biopsies were available for DNA flow cytometry in 12 additional patients without pretreatment DNA flow cytometry assessment. Of the 21 pretreatment biopsies 7 were diploid, 6 tetraploid and 8 aneuploid. All 31 posttreatment biopsies were either tetraploid (21) or aneuploid (10). All 6 pretreatment diploid tumors became tetraploid after radiotherapy. At 1 and/or 1 1/2 years after 125I implantation residual tumors were found in 28 of 31 prostatic glands. The high frequency of nondiploid DNA stemlines 1 or more years after 125I implantation and the high rate of residual tumor leave some doubt about the radiocurability of prostate cancer by the chosen radiotherapy technique.     

Squamous cell carcinoma of the renal pelvis: nuclear deoxyribonucleic acid ploidy studied by flow cytometry

From 1944 to 1987, 28 patients with squamous cell carcinoma of the upper urinary tract were treated and also had tumor specimens that were fully evaluable by flow cytometric nuclear deoxyribonucleic acid ploidy analysis: 22 had squamous cell carcinoma of the intrarenal collecting system, 4 had tumors of the ureter, and 2 had tumors of the renal pelvis and ureter. Eight patients (29%) had deoxyribonucleic acid diploid, 11 (39%) tetraploid and 9 (32%) aneuploid ploidy patterns. Ploidy pattern significantly correlated with histological grade and tumor stage. Almost all tumors were histologically of high grade; among the patients with high grade tumors ploidy analysis separated fair and poor prognosis groups. Pathological stage was the dominant clinical variable. A total of 14 patients (50%) had advanced stage disease and all died within 12 months of diagnosis. Nearly all of these patients showed abnormal ploidy patterns and ploidy analysis was not useful prognostically for this group. In contrast, all 3 patients with squamous cell carcinoma of the renal pelvis who were long-term survivors had deoxyribonucleic acid diploid tumors. However, there is no clear statistical evidence from this study that ploidy analysis provides important prognostic information independent of stage and grade for patients with squamous cell carcinoma of the renal pelvis.     

Primary adenocarcinoma of the bladder: favorable prognostic significance of deoxyribonucleic acid diploidy measured by flow cytometry

Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy.     

Prognostic significance of tumor deoxyribonucleic acid content in surgically resected small-cell carcinoma of lung.

The prognostic role of deoxyribonucleic acid flow cytometry was investigated in 53 cases of surgically resected small-cell lung cancer. Deoxyribonucleic acid aneuploidy was detected in 26 patients (49.1%), the remaining tumors being either diploid or tetraploid. Patients with aneuploid tumors had a significantly reduced 2-year survival (38.5%) when compared with patients with diploid or tetraploid tumors (70.3%; p less than 0.05). This finding was independent of tumor stage on multiple logistic regression analysis. Diploid or tetraploid deoxyribonucleic acid content was associated with a particularly good 2-year survival (85%) in N0 or N1 disease. Tumor deoxyribonucleic acid ploidy should be taken into account in planning of management and assessment of prognosis in small-cell lung cancer.     

The prognostic value of deoxyribonucleic acid flow cytometric analysis in stage D2 prostatic carcinoma

This study was designed to compare the prognostic potential of tumor grade and ploidy status in patients with stage D2 prostate cancer. Two outcome groups were selected on the basis of survival after orchiectomy: a bad outcome group consisting of 66 patients who died of the disease within 12 months and a good outcome group comprising 37 patients who survived beyond 5 years. Tumors were classified histologically as well (17%), moderately (17%) or poorly (66%) differentiated. Tumor grade was a significant predictor of outcome, with 76% of poorly differentiated tumors in the bad outcome group and 65% of well differentiated tumors in the good outcome group (p less than 0.005). Deoxyribonucleic acid (DNA) ploidy analysis was performed on formalin fixed, paraffin embedded samples of the primary tumor to yield 97 final tracings that were classified using set criteria for DNA ploidy status. Over-all, 54% of the tumors were nondiploid (33% aneuploid and 21% tetraploid) and the remaining 46% were diploid. DNA ploidy status was a significant indicator of outcome (p less than 0.001), with 64% of diploid tumors in the good outcome group and 88% of the nondiploid tumors in the poor outcome group. Tetraploid tumors behaved no differently from other nondiploid tumors. We conclude that DNA ploidy status and tumor grading are significant independent predictors of outcome after orchiectomy and when combined yield important additional prognostic information.     

Primary renal carcinoid tumor

A case of primary renal carcinoid tumor in a sixty-seven-year-old man is presented. Radical nephrectomy removed the primary disease, but hepatic metastases developed and the patient subsequently died. Review of the literature disclosed 8 other cases of primary renal carcinoid. Three of these had metastatic spread.     

Influence of tumor cell DNA ploidy on the natural history of rectal cancer

We have examined tumor cell DNA content as a possible variable in the behavior of early rectal cancer treated by local excision. Flow cytometry assays of tumor cell DNA content were carried out on specimens of archived, paraffin-embedded tissue specimens from 30 patients (11 male and 19 female) whose early rectal cancers were treated by curative local excision more than 60 months previously. The cancers invaded to the muscularis mucosae in 2 patients (1 with aneuploid disease and 1 with diploid disease), into the submucosa in 15 patients (7 with aneuploid disease and 8 with diploid disease), and the muscularis propria in 13 patients (8 with aneuploid disease and 5 with diploid disease). A total of 16 patients had aneuploid disease and 14 had diploid disease. Local recurrence of cancer developed in 12 patients. Of these 12 patients, 10 (83 percent) had aneuploid disease. By contrast, of the 18 patients who remained free of disease, 12 (67 percent) had diploid disease. Seven of the 12 patients with recurrence died. Six of these seven (86 percent) had aneuploid disease. The aggressive clinical behavior of the tumors with aneuploid DNA content was not otherwise predictable by standard histologic features. Aggressive tumor behavior appears to correlate closely with aneuploidy in locally treated rectal cancers, as opposed to a lack of correlation in our patients treated with major resection. The fact that these cancers are being treated by local excision may allow the prognostic impact of DNA content to reflect the natural history of cancer.     

The current management of bilateral Wilms tumor

The good prognosis of synchronous bilateral Wilms tumor seems inappropriate for the magnitude of the disease process. Our experience with 11 cases demonstrates the unusual tumor response to chemotherapy and limited preservative surgery. Although 2 patients died 2 with metastatic disease have responded to chemotherapy and are alive at 5 and 8 years after treatment. In addition, 1 patient has survived with biopsy only and no definitive surgery. Although all surgical options have been used, ranging from biopsy alone to bench surgery with autotransplantation to bilateral nephrectomy, our experience demonstrates the effectiveness of a conservative approach with initial biopsy, chemotherapy and subsequent partial nephrectomy if needed. Our survival data and the histological examination of the tumors after chemotherapy suggest a strong relationship of bilateral Wilms tumor to the nodular renal blastema-nephroblastomatosis complex, and a mechanism to explain the excellent tumor response to chemotherapy.     

Management of locally recurrent renal cell carcinoma after partial nephrectomy

While partial nephrectomy can provide effective treatment for selected patients with renal cell carcinoma, postoperative local tumor recurs in approximately 10 per cent of the cases. We describe 4 patients in whom tumor recurred in a solitary renal remnant after partial nephrectomy for renal cell carcinoma 1 to 6 years previously. The original tumor was pathological stage I in 2 patients and stage III in 2. Neither of the patients with stage I renal cell carcinoma had metastatic disease when locally recurrent carcinoma was noted. A second partial nephrectomy was done in these patients and they are alive 1 and 10 years later. Both patients with stage III renal cell carcinoma also had metastatic disease when locally recurrent carcinoma was noted. One patient died 1 year later and the other is alive 1 year later. Patients who undergo partial nephrectomy for renal cell carcinoma should be followed closely to allow for early detection of local tumor recurrence. When this occurs, secondary surgical treatment may be possible with complete tumor excision and the opportunity for extended survival.     

Experience of the parenchyma saving procedure in the surgical management of renal cell carcinoma

The result of renal conserving procedures for the surgical management of renal cell carcinoma experienced in 10 patients was reported. All except two were afflicted with tumor involvement in both kidneys (four cases) or in the solitary functioning kidney (four cases). The tumor stage was I in 8 and IV in 2 patients. One of the stage IV patients died of metastatic disease 8 months postoperatively. Of the 9 patients, 8 remained free of cancer in the follow-up period, while one who received an enucleative surgery and whose pseudocapsule of the tumor was missing had a local recurrence. Four of the 5 tumors having no pseudocapsule or having an invasion in the pseudocapsule were grade 2 or 3. The renal conserving surgery is believed to yield an excellent control in low grade and low stage tumors. Partial nephrectomy, rather than simple enucleation, remains to be a preferred surgical treatment in parenchyma-sparing operation, although the enucleative surgery may have a good indication for multiple and central encapsulated tumors.