Biomedical subjects
Publications and source records attributed to M S Soloway.
A case of osteogenic differentiation in a prostate gland associated with high-dose x-irradiation for adenocarcinoma is reported. Heterologous cancerous elements in adults are extremely unusual in the prostate and their occurrence after treatment has rarely been documented. The relationship of this lesion to the primary glandular neoplasm is discussed.
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The effectiveness of buserelin, a luteinizing hormone-releasing hormone agonist, was tested in 28 patients with Stages C or D adenocarcinoma of the prostate. Of 24 evaluable patients, there were 13 partial responses (54%) by National Prostatic Cancer Project criteria, median duration greater than 6 months. Nine patients had stable disease (38%), median duration greater than 5 months, and only two patients progressed. Performance status improved in 38%, patient-scored pain improved in 46%, and quality of life improved in 57%. Symptoms occurring during treatment consisted of hot flashes, loss of libido, and impotence. A flare of symptoms was observed in only one patient, despite a transient 25% increase in testosterone in 36% of patients. Buserelin is an effective treatment for inducing frequent and meaningful remissions in advanced prostatic cancer.
The use of a tumor colony assay was evaluated for its ability to predict anticancer drug response in an N[4-(5-nitro-2-furyl)-2-thiazolyl] formamide mouse bladder tumor model. One-hour and continuous drug exposure were compared to determine what effect altering drug concentration and time of exposure would have on the predictability of the tumor colony assay in the murine model. Ten anticancer drugs were tested in the murine model, and tumor cells removed from control mice were used for in vitro drug testing. One-hour and continuous drug exposure (using the one-hour drug level) were performed simultaneously and the in vitro and in vivo data compared. Using one-hour drug incubation in the tumor colony assay resulted in a true positive predictive rate of 54 per cent and a true negative predictive rate of 70 per cent. Continuous drug incubation overestimated drug sensitivity resulting in a drop in the predictability of the tumor colony assay. We conclude that using one-hour drug exposure the tumor colony assay is predictive of chemotherapeutic drug response in this murine bladder tumor model.
The flexible nephroscope offers several advantages when used to evaluate the lower urinary tract. Fifty-six men have been endoscoped in an effort to document the ease of urethral passage and visibility with two of these instruments.
Seventy-one radical cystectomies were performed at the University of Tennessee from June, 1976, through December, 1983. The operative mortality rate was 1.5 per cent. The early and late complication rate was 21 and 15 per cent, respectively. Single agent cisplatin was used as adjuvant chemotherapy in patients at high risk for development of metastatic disease and did not alter the poor survival of this group of patients.
Nephrogenic adenoma is an uncommon, benign, apparently metaplastic response of urothelium to chronic infection or irritation. Endoscopically, these lesions easily can be mistaken for malignant tumors, and their scarcity only heightens the possibility of this error. A case report of nephrogenic adenoma accompanied by endoscopic photographs is presented to improve awareness and avoid inappropriate therapy.
The activity of cis-diamminedichloroplatinum(II) was compared to two second generation platinum analogs, cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) and cis-dichlorotransdihydroxybisisopropylamine platinum(IV) in the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced murine bladder tumor model and a tumor colony assay. Murine drug testing revealed that all three drugs were active against the MBT-2 tumor line, although cis-diamminedichloroplatinum(II) was more active than its analogs. All drugs produced enhanced inhibition of clonal growth with increasing drug exposure times. Cis-diamminedichloroplatinum(II) was more active against MBT-2 cells in the plateau growth phase versus the log growth phase after a one hour drug exposure. Similar differential activity depending upon the proliferative state of MBT-2 was not seen with the two platinum analogs. These two platinum analogs have somewhat less activity in vivo and in vitro than cis-diamminedichloroplatinum(II) and would be predicted to be less effective clinically in human bladder cancer than the parent compound.
A total of 70 patients received intravesical mitomycin C for treatment of superficial bladder cancer. The drug was instilled weekly for 8 weeks. Thirty-nine patients (56 per cent) had failed thiotepa therapy and 25 had high grade tumors. Of the patients 27 (39 per cent) had complete eradication of tumor at the initial 3-month evaluation and an additional 27 had a partial response. The response did not vary with initial tumor grade or stage. Followup averaged 28 months for the 70 patients. A muscle invasive tumor developed during followup in 7 per cent of the patients with an initial complete response, 15 per cent with a partial response and 25 per cent of the initial failures. To date 5 patients (7 per cent) have died of bladder cancer. Intravesical mitomycin C is an effective modality for treatment of superficial bladder cancer. Patients achieving a complete response are at little risk for progressive disease.
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The National Bladder Cancer Group undertook a study to determine the effectiveness and toxicity of mitomycin in patients who failed on thiotepa. A total of 117 patients with residual superficial transitional cell bladder cancer (Ta, T1, Tis) who had previously failed on intravesical thiotepa were treated with 40 mg of mitomycin instilled intravesically weekly for eight weeks. Four to six weeks after the last treatment, tumor response was evaluated by cystoscopy, biopsy of the site of the index lesion, and cytology. In 57 patients (48.7%), visible tumor had been ablated. Results of cystoscopy, biopsy, and cytology were negative in 32 (27.4%) patients. Eleven patients (9.4%) had no visible tumor and negative cytology unconfirmed by biopsy. In 14 patients (12%) who had complete destruction of the tumor at cystoscopy, and biopsy specimen was negative for tumor, cytology was positive, indicating a partial response. Six patients (5.1%) withdrew from the study before the first evaluation because of local toxicity (cystitis).
Seventy per cent to 80 per cent of patients with bladder cancer will have their initial tumor confined to the mucosa (Stage Ta or Tcis, carcinoma in situ) or lamina propria (Stage T1), and at least 50 per cent of them will have a true recurrence or new recurrence despite resection of their initial tumor. If the tumor is of low grade and confined to the mucosa, intravesical chemotherapy might be considered either as treatment if the neoplasm is too extensive to resect completely or if multiple prior endoscopic resections have failed, or, alternatively, as prophylaxis against a subsequent tumor after complete endoscopic removal of the existing neoplasm. Thiotepa, until recently the most commonly used agent, completely eradicates all obvious tumor in approximately 30 per cent of patients, and it is effective in preventing subsequent tumor. Myelosuppression occurs in up to 20 per cent of patients receiving this agent, so careful monitoring of the white blood cell and platelet counts is mandatory. Mitomycin has low risk of myelosuppression and is effective in both the treatment and prophylaxis of superficial bladder cancer; the complete response rate is the same whether patients had an initial low-grade papillary or high-grade tumor (carcinoma in situ). Doxorubicin hydrochloride and bacillus Calmette-Guérin (BCG) are other agents that have been used for intravesical therapy. Chemical cystitis, the primary side effect of doxorubicin, has caused discontinuation of treatment in 15 per cent to 20 per cent of patients. The efficacy of doxorubicin varies among those reporting its use. BCG has been shown to be effective in both treatment and prophylaxis, with response rates similar to those reported for mitomycin; however, a comparative trial has not been performed. There is a need to standardize the potency of each BCG vial and to determine fully the necessity of concomitant intradermal administration.
Although intravesical mitomycin C (MMC) is effective in the treatment of superficial bladder cancer, its expense is a major factor limiting its use. These authors have analyzed the antitumor activity and stability of MMC following 2-hour intravesical instillation in consideration of recycling the drug or using a smaller dose over a longer retention time. The first voided urine samples from 11 patients who received 40 mg MMC intravesically were measured for MMC content by high performance liquid chromatography (HPLC). An average of 50% of the parent drug was recovered. MMC from the urine samples inhibited the growth of a transplantable murine transitional cell carcinoma as effectively as stock drug. Moreover, MMC is relatively stable in human urine at body temperature. These findings suggest that recovery and reuse of the intravesically administered drug is possible and if sterility and appropriate concentrations can be established for the initial and subsequent doses, the drug may be able to be recycled.
Urinary cytology is increasingly accepted as a diagnostic tool in the detection and follow-up of patients with bladder cancer. Its potential value has been reduced, however, by the relative inexperience of most pathologists in the examination of urinary specimens, and by the lack of cellular criteria specifically reflecting the morphology of low-grade papillary and flat lesions of bladder epithelium. The cytologic features of urothelial lesions, including papillary transitional cell carcinomas and flat urothelial dysplasias have been studied in both experimental systems and clinical situations and their application to a selected patient population is presented. Overall, the cytohistologic correlation for patients with bladder cancer was 92%. Positive cells reflecting the morphology of the tumor occurred in 62% of patients with grade I transitional cell carcinomas, and cells suspicious for malignancy were identified in an additional 14% of these individuals. Using the criteria presented, a positive cytology can correlate with a papillary grade I bladder tumor, and should not necessarily indicate the presence of another neoplasm. Dysplastic cells in cytologic specimens are often identified in patients having urothelial dysplasia as the most serious bladder lesion, but the cytologic diagnosis of dysplasia may represent an under-interpretation of a low-grade papillary bladder tumor. The cells of urothelial neoplasms, including low-grade transitional cell carcinomas and dysplasias, differ morphologically both from normal and reactive/reparative elements, and can be detected in cytologic samples. The changes are often subtle and require experience and a cautious approach for accurate interpretation.
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 T1 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.
Hydroxyproline is excreted in urine as a breakdown product of normal bone turnover: A dialyzable (D) fraction (90% of total) reflects active bone destruction and a nondialyzable (ND) fraction reflects bone growth/regrowth. In metastatic prostate cancer where blastic osseous metastases predominate, disease progression on bone scan correlated with elevation of both total hydroxyproline excretion (7.84 + 1.28, P less than 0.001) and the ND urinary level (0.94 +/- 0.20, P less than 0.01). In patients with a serially stable/improving scan, urinary excretion of each fraction (2.18 + 0.27 and 0.27 +/- 0.01) was similar to that of men with no evidence of disease. For Stage D2 prostate cancer, these two markers satisfactorily monitor osseous activity in the intervals between serial bone scintigraphy.
Carcinoma of the male urethra is infrequent. To date approximately 600 cases have been reported. We reviewed 16 cases of carcinoma of the male urethra seen at the University of Tennessee and the Memphis Veterans Administration Hospital. The mean patient age was sixty-three years (range 38 to 84). The most common presentation was a palpable mass followed by symptoms of urinary obstruction. Five urethral carcinomas arose distal to the suspensory ligament of the penis while 11 were of bulbar or bulbomembranous origin. The histology was squamous cell carcinoma in 8 patients (50%), mixed squamous and transitional cell carcinoma in 5 (31%), transitional cell carcinoma in 2 (13%), and adenocarcinoma in 1 (6%). The mean patient survival was fifteen months following diagnosis of a proximal urethral tumor and seventy-seven months for tumors arising distally. Neoplasms of the distal urethra can be surgically managed successfully even if regional lymph nodes are involved. The prognosis for proximal urethra tumors remains poor and is best treated by a combination of surgery and radiotherapy.
Estramustine phosphate, a combination steroid and alkylating agent, has been used for treatment of cancer of the prostate since 1969. We treated 32 patients with Stages C and D prostate cancer with this compound. Using the National Prostatic Cancer Project criteria of response, no patient achieved complete or partial objective response. Sixty-two per cent of the patients without prior hormonal manipulation and 12 per cent of those who were progressing following hormonal therapy met the criteria for a stable response. Both Stage C patients, 50 per cent of D1 and 28 per cent of D2 patients achieved disease stabilization for a mean duration of 14.8 months. There was no correlation between tumor grade and response to treatment. Fifty per cent of the patients whose elevated acid phosphatase declined remain stable, whereas 80 per cent in whom the acid phosphatase did not decline have progressed. Estramustine is effective in patients without prior hormonal manipulation. In those refractory to hormones, the prognosis is poor yet data exist to support the superiority of estramustine phosphate over conventional therapy.