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Biomedical subjects

M S Soloway

Publications and source records attributed to M S Soloway.

At least 217 records · Page 12Linked to original sources

Urothelial susceptibility to tumor cell implantation: comparison of cauterization with N-methyl-N-nitrosourea.

To determine whether or not transitional cell carcinoma cells will preferentially implant and grow on an altered urothelial surface, cauterization and instillation of N-methyl-N-nitrosourea (MNU) were used to alter the murine bladder urothelium. Transplantable tumor cells (2.09 X 10(6) ) were placed into the bladders of 53 mice. Tumor cell implantation occurred in only 6 per cent of the mice with a normal bladder, whereas tumors were present in 28 per cent of mice pretreated with intravesical MNU and in 67 per cent of mice which had a portion of the bladder cauterized prior to insertion of tumor cells (p less than 0.005). This study not only establishes the optimal technique for implantation in this experimental model, but also suggests that seeding may be a contributory factor in the high recurrence rate following endoscopic treatment of bladder tumors in man.

Animals↗

Chemoimmunotherapy of implanted murine bladder cancer.

The unaltered incidence of recurrence of superficial bladder tumor after discontinuation of intravesical chemotherapy has prompted a search for effective adjuvant therapy. The technique of cauterization and implantation of tumor cells was performed in C3H/He mice to simulate the early stage of bladder cancer to evaluate a regimen of intravesical mitomycin C followed by the systemic immunopotentiator, levamisole. Mice received either normal saline (control), mitomycin C (MMC), levamisole (Leva), or MMC plus Leva. Chemotherapy was given intravesically on days 6 and 13. Immunotherapy was given intraperitoneally on days 7 and 14. All mice were sacrificed on day 21. In the treatment groups, the incidences of bladder tumor varied from 50 to 63 per cent whereas that of the control group was 91 per cent. An increase in spleen weight was observed in the treatment groups of Leva and MMC plus Leva as well as the control group but not observed in the group receiving MMC. Our study suggests that although Leva did not reduce the tumor incidence, an immunostimulator might be of benefit when used in conjunction with MMC.

Animals↗

Invasive bladder cancer: support for screening.

Of 297 patients with bladder cancer treated between 1975 and 1981, 90 (30 per cent) had histologic documentation of muscle invasion, 82 of whom (91 per cent) had invasion into the muscle at the time of presentation. Of these 82 patients 51 (62 per cent) had tumor localized to the bladder after clinical staging. Of 36 patients undergoing radical cystectomy 9 (25 per cent) had microscopic pelvic lymph node involvement. Nine patients underwent urinary diversion alone and 31 presented with perivesical or pelvic nodal tumor extension, or distant metastases. Only 8 of the 90 patients (9 per cent) had prior superficial bladder cancer. The mean survival for patients with stage B to C disease at diagnosis was 23 months and for those with stage D tumor it was 11 months. This experience indicates that the majority of patients with advanced bladder cancer are not identified at a stage when definitive therapy offers an excellent prognosis. More resources must be devoted to earlier detection.

Adult↗

Subsequent tumor analysis of 36 patients who have received intravesical mitomycin C for superficial bladder cancer.

We studied 36 patients with stages O and A (Tis, Ta and T1) bladder cancer who had received 8 weekly doses of 30 or 40 mg. mitomycin C as definitive therapy. Of this group 16 had failed thiotepa therapy and 13 had grade III tumors (6 multifocal carcinoma in situ). The complete response rate at 12 weeks was 45 per cent (negative biopsy and cytology), while an additional 33 per cent had a partial response. Response did not correlate with tumor grade or stage. Patients who had failed thiotepa therapy were less likely to have a complete response, although the over-all response rate was identical to patients who had either not received prior chemotherapy or were not clear thiotepa failures. Followup of these patients indicates that the complete responders were benefited by this regimen since the subsequent recurrence rate was reduced when compared prior to initiation of mitomycin C. Most of these patients received monthly maintenance therapy.

Adult↗

Should the followup of patients with bladder cancer include routine excretory urography?

This retrospective study was done to determine if patients who present with bladder tumors should be followed with routine excretory urograms to detect subsequent upper tract tumors at an early stage. The charts of 337 patients who have been followed for up to 9 years were reviewed. Excluding 1 patient with invasive transitional cell carcinoma of the distal ureter, no documented renal pelvic or ureteral tumor was discovered in any of the followup data. This finding is in contradistinction to patients who present with upper tract tumors and who are known to have a 44 to 54 per cent incidence of bladder tumor either pre-dating or post-dating the upper tract tumor. We conclude that routine excretory urography is neither cost-effective nor necessary for the followup of patients who present with bladder tumors.

Follow-Up Studies↗

Thiotepa-induced myelosuppression: review of 670 bladder instillations.

Intravesical chemotherapy is an integral part of the therapeutic strategy for patients with superficial bladder cancer. Despite the introduction of new agents thiotepa currently is used most owing to its low cost and moderate effectiveness. Myelosuppression is a side effect caused by absorption of the drug through the bladder mucosa. A review of 670 instillations of thiotepa in 72 patients at our medical center revealed a decrease in the white blood or platelet count below normal in 18 per cent of the patients (3.9 per cent of the instillations). In no case did this decrease lead to any problem other than a delay in therapy.

Adult↗

A comparison of estramustine phosphate versus cis-platinum alone versus estramustine phosphate plus cis-platinum in patients with advanced hormone refractory prostate cancer who had had extensive irradiation to the pelvis or lumbosacral area.

Single and combination chemotherapy was compared in a clinical trial for men with advanced, metastatic prostate cancer who had received prior pelvic irradiation and had had progression of disease despite hormonal therapy. The 149 patients were randomized to receive estramustine phosphate or cis-platinum alone or in combination. Of the 149 patients 25 (17 per cent) were excluded from the study but 124 were evaluated for response and survival. Entry variables were distributed similarly among patients in each treatment arm. There were no complete or partial responders but there were nearly twice as many patients whose disease was stabilized (33 per cent) on the combination regimen compared to estramustine phosphate (18 per cent) and about a third more than for cis-platinum (21 per cent). Analysis of survival revealed some advantage for patients on combination therapy. Major toxicities for all treatments were nausea and vomiting (62 to 88 per cent) and accompanying anorexia (72 to 95 per cent). Azotemia developed in 45 per cent of the patients receiving combination therapy. In addition an elevation in serum creatinine occurred in 22 per cent of the patients receiving combination therapy and in 17 per cent of those receiving cis-platinum alone. Myelosuppression occurred infrequently.

Aged↗

Serial spot hydroxyproline/creatinine ratios in metastatic prostatic cancer.

Analysis of urinary hydroxyproline levels offers a marker to monitor osseous involvement in patients with metastatic malignancies. Such a marker is needed in patients with prostatic cancer when bone metastases predominate. Thirty-two men with stage D2 prostatic cancer were monitored by bone scan, acid and alkaline phosphatase values, and urinary hydroxyproline, beginning from 4 to 36 months after initiation of hormonal manipulation and/or systemic chemotherapy. In patients with disease progression determined by bone scan serial urinary hydroxyproline values progressively increased and were significantly elevated compared to urinary values obtained from patients with a stable or improving scan (p less than 0.001). Simultaneous alkaline phosphatase determinations showed less significant differences between patient groups. Acid phosphatase did not reliably indicate osseous response to therapy. These data suggest that urinary hydroxyproline values are predictive as an early objective sign of osseous response in patients receiving therapy for stage D2 prostatic cancer.

Acid Phosphatase↗

Carcinoma of the female urethra: reassessment of modes of therapy.

Of 15 women with primary urethral carcinoma 2 had tumors confined to the urethra and were managed successfully by an operation. Of the 9 patients with tumor extending to the surrounding structures 6 (67 per cent) died of complications related to inadequate control of the primary tumor. The last 4 patients had stage D1 disease or greater at initial diagnosis and died of distant metastases. Our current approach for patients with locally advanced disease is combined brachytherapy and operation in an effort to eradicate the primary tumor, since morbidity and mortality result from failure to control the local tumor.

Adenocarcinoma↗

Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer.

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.

Aged↗

Bladder cancer. Management of an increasingly common tumor.

The incidence of bladder cancer is slowly rising, which may be due in part to the increasing use of chemicals in every phase of our modern society. Improvements in detection will, it is hoped, allow earlier diagnosis, at a stage when it is highly likely that the entire tumor can be removed. Intravesical chemotherapy reduces the number and frequency of subsequent tumors and may be able to control the neoplastic process sufficiently to prevent progression and the need for cystectomy and/or radiation therapy. Unfortunately, advances in management of superficial tumors have not been matched for invasive tumors. Despite improvements in preoperative and postoperative care, introduction of the linear accelerator, and use of chemotherapy, about 50% of patients with stage B, C, or D bladder cancer die of the disease. Most patients with invasive tumors do not come to the attention of a physician until the tumor has progressed to this stage. Thus, a major task is to identify those harboring bladder cancer earlier, when the disease can be successfully managed.

Endoscopy↗

Use of tumor colony assay in clinical oncology.

We have evaluated the usefulness of the tumor colony assay in predicting chemotherapeutic drug response in our cancer patient population. We found that a wide variety of human tumors will produce clonal growth in this in vitro assay. Low growth rates in many of the common human tumors, however, severely restrict the utility of this assay in a large number of cancer patients. A retrospective analysis using the assay to predict anticancer drug response revealed a true-positive predictive rate of 63% and a true-negative predictive rate of 96%. We conclude that if growth stimulants can be developed to enhance clonal growth without altering the predictability of the assay, the tumor colony assay could prove to be extremely useful in selecting appropriate chemotherapy for individual cancer patients.

Adenocarcinoma↗

Use of the tumour colony assay in the evaluation of patients with bladder cancer.

In this study we examined the ability of tumour specimens derived from bladder barbotage to produce cluster/colony formation in a tumour colony assay. In 114 bladder washings from 65 patients and 15 control subjects, we found that cluster and colony formation was highest from bladder washings obtained from patients with biopsy proven bladder cancer who were not on intravesical chemotherapy. Growth rates were extremely low, restricting the usefulness of the in vitro assay in its present form. This study suggests that improvements in the growth rates in the tumour colony assay will be necessary before this system can have real value in monitoring transitional cell carcinoma of the bladder.

Agar↗

Histopathologic evaluation of response to treatment of human tumors grown in the nude mouse.

The histopathologic changes following chemotherapy treatment of a number of human tumors grown in nude mice were evaluated. On the basis of the histopathologic profile, three response levels were recognized--a mild response, a moderate response and a severe response. Severe response was characterized by arrest of cell division and profound nuclear-cytoplasmic degenerative changes. Regrowth of effectively treated tumors originated in clusters of cells most probably representing resistant tumor cell clones. Histopathologic changes represent a sensitive indicator of the response of nude mouse grown human tumors to anticancer agents. Availability and correct interpretation of the post-treatment histopathologic picture is of importance in selecting the proper combination treatment which would maximize tumor response.

Animals↗

Total, dialyzable, and nondialyzable postabsorptive hydroxyproline. Values in patients with cancer.

The postabsorptive urinary total (T), dialyzable (D), and nondialyzable (ND) hydroxyproline (HYPRO) tests were evaluated to determine whether the patterns of excretion varied according to the predominance of osteoblastic v osteolytic bone involvement in 58 patients with neoplastic disease. In patients with osteolytic lesions from multiple myeloma, elevated T and D levels with normal ND HYPRO values were observed, along with elevated D/ND ratios. In prostate cancer, the T, D, and ND values were all elevated and the D/ND ratio was normal. Patients with Hodgkin's disease had elevated T, D, and ND HYPRO levels, and the D/ND ratio was in the range of patients with prostate cancer. The data suggest that these collagen markers may be useful in the long-term evaluation of these neoplasms in patients.

Bone Neoplasms↗