Kenneth B. Cummings

Superficial Bladder Cancer: Progression and Recurrence

The tumors in 249 patients presenting initially with stages Ta and T1 bladder cancer were analyzed for tumor progression and recurrence. Only transurethral resection and/or fulguration was used before the first recurrence. Patients who received intravesical chemotherapy after the first tumor recurrence were excluded from an analysis of progression. Progression according to stages Ta and T1, and grades I, II and III was 4, 30, 2, 11 and 45 per cent, respectively. All differences were statistically significant. Progression also correlated with nontumor dysplasia and size. High tumor grade, lamina propria invasion, atypia elsewhere in the bladder, positive urinary cytology, tumor multiplicity and large tumors were associated with shorter intervals free of disease.

Long-term Fate of 90 Patients with Superficial Bladder Cancer Randomly Assigned to Receive or not to Receive Thiotepa

We assigned randomly 90 patients treated previously for superficial transitional cell carcinoma to conventional followup or prophylactic treatment. This followup study details the late incidence of recurrence (29 of 45 patients in the prophylactic group and 34 of 45 controls), the progression of tumor grade and stage, the deaths and causes (24 patients), and the influence of initial stage, grade, carcinoma in situ and positive cytology on the outcome of treatment.

High-dose ketoconazole in advanced hormone-refractory prostate cancer: Endocrinologic and clinical effects

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.

Mitomycin C intravesical therapy in noninvasive bladder cancer after failure on thiotepa.

Mitomycin C 40 mg in 40 ml water was administered intravesically every week for 8 consecutive weeks to 60 patients with superficial bladder cancer. All patients had failed treatment with intravesical thiotepa and had evaluable disease. An objective response of 50% or greater reduction in measured tumor mucosal involvement was obtained in 68% of patients. Forty‐two percent of the patients achieved a complete response, and this included 50% of patients with Grade III disease and 70% of patients with a Tl tumor. Median response duration in complete responders was 12.2 months with a range of 3.5 to 24.3+ months. Fifty‐five percent of patients are still responding. Therapy was generally well tolerated, and in contrast to thiotepa, myelosuppression was not the dose‐limiting effect. One third of all patients experienced symptoms of local irritation, and skin reactions were seen in 12% of patients. Cancer 53:1025‐1028, 1984.

Carcinoma of the bladder: predictors.

The natural history of carcinoma of the bladder is unpredictable. In some patients, invasive (potentially lethal) carcinomas represent their initial clinical presentation, whereas in others, a protracted clinical course characterized by multiple recurrent tumors is witnessed. This latter population of patients is the most vexing to the urologist. The prediction of the patients “state of risk” from the tumor has historically been based on clinical pathologic staging employing grade and stage. Predictive clinical evidence for the development of invasive (potentially lethal) carcinoma has been gleaned from observations of the rapidity and pattern of tumor recurrence (single vs. multiple), tumor characteristics (grade, shape, and presence of lymphatic or venous invasion) and the presence of carcinoma in situ at preselected endoscopically normal biopsy sites. Currently available “objective” predictors such as blood group isoantigen deletion from bladder urothelium of patients with invasive bladder carcinoma are provocative. Presently, this technique cannot pinpoint when tumor invasion will occur in a particular patient. However, the application of this methodology in a prospective study (including examination of preselected endoscopically normal mucosal biopsies) is well as resected tumor tissue may prove valuable. At the ultrastructure level as studied with the electron microscope and immunofluorescent probes, alterations in the plasma membrane have been defined that are associated with malignant transformation and abnormal growth patterns (potentially predictive of tumor invasion). Certain Of these techniques appropriately applied to a population at high risk may ultimately assist the surgeon in timing extirpative surgery.

In vitro modulation of antioxidant enzymes in normal and malignant renal epithelium

SummaryThe activities of three antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase, were monitored in isolated human renal adenocarcinoma tissues and in cultured human renal adenocarcinoma cells. The results were compared to the activities of these enzymes in the proposed cell of origin, isolated human proximal tubular tissues, and cultured proximal tubular epithelial cells. Strong modulation of these enzymes by culture conditions was observed in normal cells but not in carcinoma cells. Low levels of cellular lipid peroxidation, as assessed by levels of malondialdehyde (MDA), were observed in adenocarcinoma cells under the culture conditions tested with one exception: greatly elevated MDA was observed in renal adenocarcinoma cells growth on plastic in serum-free, chemically defined medium. This increased lipid peroxidation correlated with a loss of cell viability under these conditions.

Effect of interferon alpha, interferon beta, and interferon gamma on the in vitro growth of human renal adenocarcinoma cells

Interferon-α, interferon-β, and interferon-γ differ in their antiproliferative effects for several cell lines. Interferons were thus assessed for their activity in inhibiting proliferation of three renal cell carcinoma cell lines. The malignant epithelial phenotype of each of these cell lines was confirmed by electron microscopy, histology, karyotype and tumorigenicity. When compared on an anti-viral unit basis, naturally produced interferon-β was more effective than natural interferon-α for all cell lines and clones. Proliferation of each of the cell lines was inhibited by interferon-γ. In all cases, removal of interferons from culture media resulted in resumption of the rate of cell growth after a variable delay of 6–10 days. If the antiproliferative effects of interferons predominate in mediating tumor regression, clinical response may depend upon the type of interferon to which the tumor is exposed.

Perineal liposarcoma: diagnosis and management.

Perineal liposarcoma is excessively rare. Its clinical and pathological behavior can only be predicted by comparison with the behavior of liposarcoma in other parts of the body. We describe the management of a man who presented with symptoms related to bladder outlet obstruction and was found to have a prostatic mass on digital examination of the rectum. A needle biopsy was performed and the tissue was histologically consistent with sarcoma of the prostate. Computerized tomography suggested that the mass extended through the urogenital diaphragm and was contiguous with the corpus spongiosum and corpora cavernosa of the penis. Complete surgical extirpation was achieved through a perineal approach, although local extension of the growth beneath the internal anal sphincter and the urogenital diaphragm necessitated reconstruction of these structures. The surgical margins were free of tumor. We advocate local surgical extirpation rather than pelvic exenteration in these cases.

Antiproliferative activity of recombinant interferons alpha and beta for human renal carcinoma cells: Supra-additive activity with elevated temperature or vinblastine

SummaryWe are investigating IFN activity for human renal cell carcinoma (RCC) in conjunction with other forms of therapy in vitro. Our investigations employed IFN alpha and beta generated by recombinant DNA technology. We employed IFN species in conjunction with vinblastine or elevated temperature of incubation for RCC cells. Recombinant IFNs alpha and beta were provided by Triton/Cetus IFN program. RCC cells grown at 37°C with 1,000 IU/ml IFN alpha for seven days produced significant inhibition in growth kinetics (p<0.01). Incubation at 39.5 °C significantly augmented inhibition producing cytotoxicity without altering growth kinetics in controls (p<0.01). Treatment of cells with IFN beta (5 ng/ml) 24 hours prior to treatment with vinblastine (0.25 μg/ml×1 h) resulted in supra-additive inhibition of growth kinetics as determined by isobole analysis (p<0.001). Concomitant treatment with IFN and vinblastine or IFN treatment 24 hours after vinblastine treatment augmented inhibition to a lesser extent. Our results suggest supra-additive biological activity of recombinant IFN at increased temperature, or with vinblastine.

Sheathed Catheter System for Fluoroscopically Guided Retrograde Catheterization, and Brush and Forceps Biopsy of the Upper Urinary Tract

A sheathed (coaxial) ureteral catheter has been designed for use in fluoroscopically guided retrograde procedures. Once the catheter has been inserted into the ureter the inner section is removed, leaving a semiflexible sheath as a conduit for biopsy forceps, curved catheters and other instruments. The sheath facilitates ureteral stenting, forceps biopsy of the renal pelvis and brush biopsy of all calices. The sheath also helps in percutaneous stone extraction by allowing retrograde passage and removal of balloon catheters with the patient in the prone position. Cystoscopy is needed initially to insert the catheter but not to pass instruments through the sheath. Thus, procedures can be completed in a standard fluoroscopy room.