Kenneth I. Wishnow

Renal cell carcinoma. A clinicopathologic and dna flow cytometric analysis of 103 cases

Renal cell carcinoma is unpredictable in outcome, although the best predictor is tumor stage, followed by histologic grade. The authors retrospectively assessed the clinicopathologic features and DNA ploidy of 103 cases of renal cell carcinoma, the latter determined by flow cytometry of formalin‐fixed, paraffin‐embedded tissue. The study group comprised 63 men and 40 women (age, 28–80 years; mean, 57 years). Robson stage at diagnosis was Stage I in 52 patients, Stage II in 21, and Stage III in 30. Statistically significant variables in predicting outcome were Robson stage (P < 0.0001), DNA ploidy (P = 0.0008), mitotic rate (MR, P < 0.0001), worst nuclear grade (WNG, P = 0.0009), predominant nuclear grade (P = 0.019), and sex (P = 0.044). Tumor size, cell type, and architectural pattern were also assessed but did not prove to be significant. Statistically significant associations occurred between DNA ploidy and WNG (P < 0.0001), stage (P = 0.0037), and MR (P = 0.015); between WNG and MR (P < 0.0001) and stage (P = 0.0007); and between stage and MR (P = 0.002). Cox proportional hazards regression analysis of all significant variables showed Robson stage, tumor ploidy, and MR to be independent, significant predictors of outcome. If ploidy data had not been available, WNG would have been independently significant. The authors conclude that DNA ploidy analysis provides significant predictive information on renal cell carcinoma.

Extended resection for locally advanced colorectal carcinoma

We reviewed the medical records of 101 patients who underwent extended resection for locally advanced colorectal carcinoma between 1965 and 1989. Preoperative symptoms related to the genitourinary system were present in 46 patients. Malignant invasion of genitourinary structures by colorectal carcinoma was found in 43 of these 46 patients (93%). In contrast, 51% of the patients without such symptoms had malignant invasion of contiguous structures. Preoperative intravenous pyelography, computerized tomographic scans, and cystoscopy correctly predicted the presence or absence of malignant invasion in 89%, 83%, and 87% of patients, respectively. Tumor-positive resection margins had a negative impact on survival (mean survival: 11.4 months). The 5-year actuarial survival rate for the patients who underwent a curative extended resection (margins tumor negative) was 54%. A thorough preoperative evaluation can identify a significant number of patients with colorectal cancer extending into adjacent organs and structures. Such evaluation is vital for operative planning and patient preparation, since an appropriate extended resection can produce long-term local control and patient survival.

Mucinous adenocarcinoma of the prostate: histochemical and immunohistochemical studies.

Twelve patients with primary mucinous adenocarcinoma of the prostate were included in a clinicopathologic study; criteria included a total tumor volume more than 25% mucinous and single or clustered tumor cells floating in mucin lakes. Patient ages were 57 to 81 years; tumor stages were C (three), D (five), and unknown (four). Bone was the most frequent metastatic site (usually osteoblastic), followed by lymph nodes and lungs. Serum levels of prostatic acid phosphatase and prostate-specific antigen were frequently elevated (five of 10 and three of three measured, respectively). All mucinous adenocarcinomas also contained other histologic patterns: microglandular (four), cribriform (three), comedo (two), solid (two), and hypernephroid (one). Mucinous components composed less than 50% of three tumors, 50% and 75% of six, and more than 75% of three. No tumor contained signet-ring cells. Immunoperoxidase staining was positive for prostatic acid phosphatase and prostate-specific antigen and negative for carcinoembryonic antigen. Treatment was radiation, estrogen, orchiectomy, or a combination. In two of four patients, serum prostatic acid phosphatase levels normalized after therapy. Seven patients died of disease (mean follow-up, 56 months), and five patients are alive with disease (mean, 32.2 months). The proportion of mucinous component did not affect prognosis.

Indications for Urethrectomy in an Era of Continent Urinary Diversion

Interest in performing a continent urinary diversion and in preserving sexual potency after radical cystectomy for transitional cell carcinoma of the bladder has emphasized the need to identify accurately those men who are at high risk for urethral recurrences. We reviewed the records of 200 men who underwent radical cystectomy between 1969 and 1976. In 76 men urethrectomy and cystectomy were combined. Of these patients 6 had known urethral tumors and the incidence of unsuspected urethral malignancy was 2.9%. A total of 124 men had initial cystectomy only and were monitored up to 16 years (mean 67 months). Of these patients 6 (4.8%) underwent subsequent urethrectomy for malignant disease 6 to 40 months (median 23.5 months) after cystoprostatectomy. This group included 1 of 69 patients (1.5%) who presented with a solitary tumor not encroaching on the bladder neck, 1 of 22 (4.5%) with either carcinoma in situ or multifocal tumors not involving the prostate and none of the 9 with tumor at the bladder neck alone, which suggests that these patients may be satisfactory candidates for continent urinary diversion and may avoid the added risk to potency associated with urethrectomy. However, urethral recurrences were found in 4 of 24 patients (17%) who presented with disease extending into the prostate, including 3 of 10 (30%) with stromal invasion. These results emphasize the importance of assessing the prostatic urethra and ducts carefully before deciding to eliminate urethrectomy.

Identifying patients with low risk clinical stage I nonseminomatous testicular tumors who should be treated by surveillance

We examined the records of 82 patients with clinical Stage I nonseminomatous germ cell tumors of the testis who, after radical orchiectomy, were treated by surveillance at M.D. Anderson Cancer Center between October, 1981, and March, 1987. Our purpose was to determine whether or not patients with a low risk of relapse can be identified at the time of the initial staging evaluation. In 30 of 82 patients (Group 1), embryonal carcinoma constituted less than 80 percent of the tumor, no vessel invasion was present, and the preorchiectomy serum AFP level was less than 80 ng/dL. No relapses occurred in this group. Fifty-two patients (Group 2) had more than 80 percent embryonal carcinoma or vessel invasion or a serum AFP level higher than 80 ng/dL. Relapse occurred in 24 (46%) of these patients. The difference in the rate of relapse between patients in Group 1 and Group 2 was statistically significant (P less than 0.00001). A separate analysis of teratoma as a predictor of nonrelapse showed that the orchiectomy specimens of 30 of the 82 patients contained more than 50 percent teratoma. Only 1 relapse occurred among 25 patients with more than 50 percent teratoma and no vessel invasion. Our data show that there is a subgroup of patients with clinical Stage I nonseminomatous germ cell tumor who have a very low rate of relapse. We believe these patients can be effectively treated by surveillance and should be spared the morbidity of an unnecessary retroperitoneal lymph node dissection.

Stage B ( P 2 3A N0) transitional cell carcinoma of bladder highly curable by radical cystectomy

Seventy-one patients with pathologic Stage B (P2/3a/N0) transitional cell carcinoma (TCC) of the bladder underwent radical cystectomy alone without preoperative radiotherapy or perioperative chemotherapy between 1983 and 1987 and have been followed a median of fifty months. The five-year actuarial survival and disease-free survival rates were 82 percent and 77 percent, respectively, and only 13 patients (18%) have relapsed. Histologic parameters were evaluated as to prognostic impact; none correlated with disease-free survival rates although the presence of vessel involvement portended a worse disease-free survival rate (68% versus 80%). During this same period, an additional 15 patients underwent radical cystectomy for pathologic Stage B disease but received adjuvant chemotherapy on the basis of vessel invasion. Their disease-free survival rate at five years was 80 percent, comparable to the disease-free survival rate for patients with vessel invasion treated by surgery alone (68%). Although the role of systemic chemotherapy in the management of invasive bladder cancer remains under investigation, it would appear that patients with Stage B TCC are best treated with radical cystectomy alone. Continued analysis of modern surgical results grouped by current pathologic staging criteria is needed to identify patients who have a relatively low risk of relapse and thus little need for additional therapeutic intervention. These results demonstrate that Stage P2/3a/N0 TCC of the bladder is highly curable by surgery.

Are frozen-section examinations of ureteral margins required for all patients undergoing radical cystectomy for bladder cancer?

Unsuspected malignant disease was discovered by frozen-section examination of the ureteral margins in 8 of 403 patients (2%) undergoing cystectomy for treatment of bladder cancer. Once malignant disease was demonstrated, a short segment of the proximal ureter was resected in 6 patients; in 5 instances dysplastic changes remained at the second margin, which was anastomosed to the bowel. No clinically recognized tumor developed at this site in any of the 8 patients. In an additional 26 instances (19 patients), dysplastic changes were known to be present in the ureteral margin at the time of ureteroenteric anastomoses. Again, no recognizable tumor has developed at the anastomotic site after a median follow-up of six years. We conclude that frozen-section examinations of the ureteral margins prior to constructing the ureteroenteric anastomosis are not indicated for the patient undergoing routine cystectomy for bladder cancer, but should be reserved for patients who are at increased risk for carcinoma in situ (those with multifocal bladder carcinoma in situ or transitional cell carcinoma of the prostatic ducts).

Seminal vesicle involvement by in situ and invasive transitional cell carcinoma of the bladder.

We report six cases of seminal vesicle involvement by transitional cell carcinoma of the bladder among 187 consecutive cystoprostatectomy specimens. Two of these six cases showed mucosal spread without stromal invasion (type A); the remaining four cases presented a direct extension (type B) from muscle-invasive carcinomas of the bladder. Type A involvement of the seminal vesicle was associated with a long history of superficial bladder cancer with similar mucosal spread to the prostatic ducts, acini, and ejaculatory ducts. One type A case showed extensive pagetoid spread of transitional cell carcinoma to the urethral meatus and collecting ducts of the kidney. Because the clinical significance of mucosal spread or direct invasion of seminal vesicles is not clear, pathologists and urologists need to be aware of these phenomena. More cases should be analyzed to determine further clinicopathologic implications

Long-term serum creatinine valuesafter radical nephrectomy

Both pre- and postnephrectomy levels of serum creatinine were measured in 52 consecutive patients who underwent radical nephrectomy for localized renal cell carcinoma between 1971 and 1976. At the time of follow-up, 17 patients were alive and 35 had died, 14 of renal cell carcinoma and 21 of other causes. Follow-up lasted a minimum of 115.5 months (mean 151.1 months, median 141.1, range 115.5-211.3 months) for 16 of the 17 patients who were alive. In this group only 2 patients had elevations in the serum creatinine level above 1.6 mg/dL-1.9 mg/dL and 2.4 mg/dL, respectively. The patient whose value was 2.4 mg/dL was a diabetic who required insulin. No serious renal failure, renal disease, or tumors in the contralateral kidney occurred among the total group of 52 patients. These data indicate that renal function remains adequate in patients who have a normal contralateral kidney and are treated by radical nephrectomy.

Regeneration of the canine urinary bladder mucosa after complete surgical denudation.

To study the site of origin of epithelial regeneration in the urinary bladder after surgical denudation, we completely obliterated the bladder mucosa in 17 dogs, using the neodymium: YAG laser. Bladder-mapping studies showed that the regenerating cells arose from the epithelium of the terminal ureters and urethra. Experimental construction of isolated bladder pouches confirmed these findings and demonstrated that urine flow was not essential for reepithelialization. These results are relevant to the treatment of patients with multifocal carcinoma in situ of the bladder. Although the entire bladder can be denuded successfully, the studies demonstrate that the procedure might fail if the sources of epithelial regrowth, the distal ureters and urethra, contain untreated carcinoma in situ.