Biomedical subjects

M F Sarosdy

Publications and source records attributed to M F Sarosdy.

At least 55 records · Page 3Linked to original sources

PubMed1992

Comparative antitumor effects of hormonal ablation, estrogen agonist, estrogen cytotoxic derivative, and antiestrogen in the PAIII rat prostatic adenocarcinoma.

The effects of hormonal ablation, estrogen, estrogen-derived cytotoxic agent, and estrogen antagonist therapies used clinically were evaluated on in vitro colony formation, in vivo growth, and lymphatic and pulmonary metastasis of the PAIII tumor. Ventral prostatic and seminal vesicle weights were evaluated in the same animals to assess androgen-related responses. Estradiol, estramustine phosphate, and testosterone had no effects on PAIII colony formation in vitro. Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII-bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs. Of these treatments, only hypophysectomy had significant (P less than 0.05) inhibitory effects on primary PAIII growth and lymphatic and pulmonary metastasis. LY117018 [6-hydroxy-2-(p-hydroxyphenyl)benzo(b)thien-3-yl-p-2-(l-pyrrolidin yl)ethoxy phenyl ketone] has antiestrogenic activity but produces no significant agonist responses. LY117018 had no effect upon PAIII colony formation in vitro. Following s.c. implantation of PAIII cells, LY117018 (2.0, 10.0, or 20.0 mg/kg s.c.) had no effect on primary tumor growth in the tail. In vitro LY117018 administration produced marked antimetastatic effects. In a dose-dependent manner, LY117018 inhibited PAIII metastasis to the gluteal (97%) and iliac lymph nodes (88%) (P less than 0.05 for both). LY117018 also maximally inhibited pulmonary metastasis by 86% (P less than 0.05). Maximal regression of 42% for ventral prostatic and 35% for seminal vesicle weights were also seen after LY117018 administration (P less than 0.05 for both). Co-administration of estradiol benzoate had no antagonistic effect upon the antitumor responses produced by LY117018. The mechanism of action of LY117018 is not known. The failure of estradiol benzoate to affect PAIII growth and metastasis supports the contention that the responses to LY117018 are not attributable to simple antagonism of estrogen action. LY117018 may be exerting its antitumor effects through autocrine, paracrine, or endocrine mechanisms. LY117018 represents a class of agents with potential utility in treating metastatic cancer of the prostate.

Adenocarcinoma↗

PubMed1992

Continent urinary diversion using cutaneous ileocecocystoplasty.

We have employed a technique of continent urinary diversion that uses ileocecocystoplasty to incorporate native bladder into the urinary reservoir. This allows creation of a reservoir in selected patients using less complicated surgery than complete replacement of the bladder and avoids ureteral-intestinal anastomoses. Early results are promising for this simplified means of continent diversion.

Adult↗

PubMed1992

Management of stage T1 superficial bladder cancer with intravesical bacillus Calmette-Guerin therapy.

We reviewed our results with 86 patients who had a pretreatment history of a stage T1 tumor. All patients were treated with transurethral resection of all visible tumor followed by intravesical bacillus Calmette-Guerin (BCG) and many patients received additional maintenance therapy. Local recurrences were treated with repeat transurethral resection followed by additional BCG. Median followup was 59 months, with a range of 9 to 149 months. Overall, 78 of 86 patients (91%) were free of tumor recurrence with BCG therapy. This result includes 69% of the patients who responded to the initial transurethral resection and intravesical BCG, and 22% who ceased having tumors after additional treatments for local recurrences. Only 7% of the patients had progression to stage T2 tumors after BCG therapy. Grade of the stage T1 tumor, concurrent carcinoma in situ and tumor multiplicity before BCG did not predict tumor recurrence or progression. Of patients with recurrences after BCG therapy, those with stage T1 tumors had a higher rate of progression compared to those with stage Ta tumors but the difference was not statistically significant (p = 0.086). These data clearly support the efficacy of transurethral resection plus intravesical BCG immunotherapy in the treatment of stage T1 tumors as well as in the prevention of disease progression.

Administration, Intravesical↗

PubMed1992

Phase 1 trial of oral bropirimine in superficial bladder cancer.

A total of 34 patients with measurable superficial transitional cell cancer of the bladder entered into a phase 1, nonrandomized, noncomparative trial to assess the toxicity of the oral interferon inducer bropirimine. Of the patients 26 were also evaluable for response. The toxicity of bropirimine was minimal. At the 3-month evaluation 6 patients had experienced complete regression of tumor and had negative cytology studies, and 2 had partial responses. The majority of complete responses were in patients with carcinoma in situ only, with most responses seen at higher dose levels. One patient with papillary tumor and carcinoma in situ had a complete response. Some early responses appear to be durable. Most importantly, a high rate of complete response was noted at higher dose levels among patients who had failed prior therapy with bacillus Calmette-Guerin. Further clinical trials of bropirimine in bladder cancer appear warranted.

Administration, Oral↗

PubMed1992

Inhibition of PAIII rat prostatic adenocarcinoma growth and metastasis by a new diarylsulfonylurea antitumor agent, LY181984.

LY181984 is a compound in a series of orally active diarylsulfonylureas with broad spectrum in vivo activity against syngeneic rodent and human xenograft tumor models. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this antitumor agent on the lymphatic and pulmonary metastasis of the tumor in male Lobund Wistar rats. LY181984 was inactive against the proliferation of PAIII cells in vitro. Following subcutaneous implantation of 10(6) PAIII cells in the tail, oral administration of LY181984 (25.0, 50.0, or 100.0 mg./kg./day) for 30 days had no significant effects on body weight gain. LY181984 treatment produced significant (p less than 0.05) dose-dependent inhibition of primary tumor growth in the tail (max. inhibition = 46% from untreated control levels). In these same animals, LY181984 administration produced significant (p less than 0.05) dose-dependent inhibiton of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 79% and 80% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by oral LY181984 treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (p less than 0.05) reduced by LY181984 administration in a dose-dependent manner (maximal reduction = 78% from control values). While the non-toxic doses (less than 100.0 mg./kg./day for 28 days) of LY181984 produced marked decreases in tumor growth and metastasis, administration of the compound had no effect on the survival of PAIII-bearing rats. These data support the contention that LY181984 represents a new class of orally active antitumor and antimetastatic agents with potential efficacy in the treatment of hormone-insensitive prostatic cancer. Further studies are needed to define maximal efficacy of LY181984 and other sulfonylurea agents in urogenital solid tumor animal models.

Adenocarcinoma↗

PubMed1992

Systematic transrectal ultrasound guided prostate biopsy after negative digitally directed prostate biopsy.

The diagnostic accuracy of digitally directed prostate biopsies was evaluated by performing systematic ultrasound guided biopsies on 44 patients who had previously had a negative prostate biopsy by systematic digitally directed technique. All 44 patients still had palpable abnormalities. Core biopsies (2 to 4) were obtained from each lateral lobe of the prostate with 2 additional cores directed at hypoechoic lesions. Only 4 of the 44 ultrasound directed biopsies (9.1%) were positive for cancer. These results confirm the postulate that random systematic digitally directed biopsy is highly accurate in making the diagnosis of prostate cancer. They also suggest that performing biopsies in a systematic pattern is more important than the method used to guide the biopsy needle.

Biopsy↗

PubMed1992

A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

PURPOSE: A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS: As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION: Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.

Adult↗

PubMed1992

Management of the male urethra after cystectomy for bladder cancer.

All patients with locally advanced transitional-cell carcinoma of the bladder should undergo thorough precystectomy assessment of the prostatic urothelium for evidence of malignancy. Those with carcinoma or carcinoma in situ should not be considered candidates for orthotopic continent diversion, and urethrectomy should be recommended. Regardless of risk status, all patients with a urethral remnant after cystectomy should have semiannual urethral washings performed for cytologic analysis. Any positive result should be followed by urethrectomy. By identifying and modifying the treatment plan for those patients who are clearly at increased risk of developing a urethral recurrence, it should be possible to reduce the morbidity and anxiety that urethral recurrence can entail. More importantly, the risk of noncompliance in follow-up with disastrous results is reduced, and both the patient and the physician can be assured that the best management for urothelial malignancy has been offered, not simply isolated treatment of the primary bladder carcinoma.

Carcinoma, Transitional Cell↗

PubMed1992

Principles of intravesical chemotherapy and immunotherapy.

By tailoring the use and selection of an intravesical agent to the individual patient, it should be possible to reduce toxicity and avoid overtreatment. Similarly, patients with more alarming disease processes can be treated sooner if the need for that more aggressive or toxic therapy is recognized early. Finally, it is important to recognize that patients who fail initial therapy with BCG have a good probability of responding to additional BCG and that there are promising investigational immunotherapies available for those who fail adequate courses of BCG.

Administration, Intravesical↗

PubMed1991

A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder.

BACKGROUND: In carcinoma of the bladder, both intravesical chemotherapy and immunotherapy can induce tumor regression and reduce the rate of recurrence, but the relative merits of these two therapies are unclear. We conducted a multi-institutional study to address this question. METHODS: Patients with rapidly recurrent (stage Ta and T1) or in situ transitional-cell carcinoma of the bladder were randomly assigned to receive either doxorubicin administered intravesically or bacille Calmette-Guérin (BCG) administered both intravesically and percutaneously. The 262 eligible patients were followed for a median of 65 months. Complete responses to treatment of carcinoma in situ were confirmed by biopsy and cytologic analysis of the urine. RESULTS: For patients with Ta and T1 tumors without carcinoma in situ, the estimated probability of being disease free at five years was 17 percent after doxorubicin, as compared with 37 percent after immunotherapy with BCG (P = 0.015). The median times to treatment failure (termination of treatment, due to persistence, recurrence, or progression of disease) were 10.4 and 22.5 months, respectively. For patients with carcinoma in situ the complete-response probability estimates (i.e., the estimated probability of documented disappearance of disease) were 34 percent for doxorubicin (23 of 67 patients) and 70 percent for BCG (45 of 64 patients) (P less than 0.001); the median times to treatment failure were 5.1 and 39 months, respectively. The probability of being disease-free at five years survival among the patients with carcinoma in situ was 18 percent after treatment with doxorubicin and 45 percent after BCG therapy. Patients treated with BCG had a higher incidence of toxic systemic effects and a larger number of local irritative symptoms than patients treated with doxorubicin, but few of these adverse reactions were severe. CONCLUSIONS: As compared with intravesical doxorubicin, immunotherapy with BCG provides improved protection against the recurrence of superficial bladder cancer.

Administration, Cutaneous↗

PubMed1991

Complications of the Heitz-Boyer urinary diversion: case report of late development of malignancy.

We report on 3 patients with bladder exstrophy followed for more than 15 years after having undergone Heitz-Boyer urinary diversion. One patient had adenocarcinoma at the ureterocolonic anastomoses 16 years after diversion. To our knowledge this is the first reported case of a malignancy developing after a Heitz-Boyer procedure. The other 2 patients had significant problems with urinary incontinence and recurrent urinary tract infections. Initial success with this form of urinary diversion can be followed by significant long-term complications.

Adenocarcinoma↗

PubMed1991

Prospective randomized comparison of intravesical with percutaneous bacillus Calmette-Guerin versus intravesical bacillus Calmette-Guerin in superficial bladder cancer.

Conflicting reports of the necessity for percutaneous bacillus Calmette-Guerin (BCG) administration with intravesical BCG prompted us to evaluate its benefit in a randomized prospective comparison of intravesical versus intravesical with percutaneous BCG therapy. Intravesical Tice BCG was given in a dose of 50 mg. with or without percutaneous BCG weekly for 6 weeks, at 8, 10 and 12 weeks, at 6 months and every 6 months thereafter. Tumor recurrence was documented in 13 of 30 patients (43%) receiving only intravesical BCG and in 15 of 36 patients (42%) receiving intravesical plus percutaneous BCG. The addition of percutaneous BCG to intravesical therapy did not increase treatment efficacy in this study.

Administration, Intravesical↗

PubMed1990

A randomized prospective comparison of oral versus intravesical and percutaneous bacillus Calmette-Guerin for superficial bladder cancer.

Reports of a dramatic decrease in tumor recurrence and regression of muscle invasive disease with oral bacillus Calmette-Guerin prompted us to conduct a randomized prospective comparison of oral bacillus Calmette-Guerin with the standard intravesical plus percutaneous therapy. Oral therapy consisted of 200 mg. Tice bacillus Calmette-Guerin 3 times each week. Intravesical and percutaneous Tice bacillus Calmette-Guerin at a dose of 50 mg. was given weekly for 6 weeks, at 8, 10 and 12 weeks, then at 6 months and every 6 months thereafter. Minimal side effects confirmed the safety of oral bacillus Calmette-Guerin. Tumor recurrence was documented in 21 of 33 oral bacillus Calmette-Guerin patients (64%) and 18 of 55 (33%) who received intravesical plus percutaneous therapy (p less than 0.002, chi-square test). We were unable to demonstrate any antitumor activity of oral bacillus Calmette-Guerin in this study.

Administration, Intravesical↗

PubMed1990

Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer.

Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. Complications from bacillus Calmette-Guerin therapy are usually minor but serious and even fatal reactions can occur. Five recent cases illustrate the gravity of bacillus Calmette-Guerin sepsis. One man with severe debility and the organic brain syndrome died acutely with a fever of 40 C. Two men had frank sepsis that progressed to multiorgan failure and death. Sepsis progressed despite the use of isoniazid, rifampin and streptomycin. Two men who had equally progressive sepsis with intravesical bacillus Calmette-Guerin survived with the use of cycloserine for the first 72 hours of treatment. Triple antituberculous antibiotics, including cycloserine, may be lifesaving. Sepsis resulted from intravenous absorption through inflamed or disrupted urothelium. Bacillus Calmette-Guerin treatment should not be administered in the presence of severe cystitis or after grossly traumatic catheterization.

Administration, Intravesical↗

PubMed1989

Correlation of clonogenic growth with histologic diagnosis after resection of residual tissue following chemotherapy for nonseminomatous testis cancer.

Patients who undergo chemotherapy for metastatic nonseminomatous germ cell cancer of the testis often undergo subsequent resection of residual tissue. We performed a retrospective review of 11 consecutive patients who had their resected residual tissue cultured in a soft agar clonogenic assay to determine if there were any biological data that could be obtained in this setting. Twelve assays were performed on the 11 patients. Some colony formation occurred in 10 of the 12 assays, including 4 of 5 assays in which cancer was found and 6 of 7 in which no cancer was found. The rate of colony formation, however, was significantly less for the noncancerous tissues than for the ones with cancer noted (p = 0.019). Three of the patients with cancer are dead, while all of those with benign tissue remain free of disease, with follow-up ranging from three to six years. Our data suggest that clonogenic growth from resected tissue after chemotherapy has the potential to supplement histologic findings, possibly as a predictor of the future biologic behavior of a patient's disease process.

Antineoplastic Agents↗

PubMed1989

Long-term results of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer.

Between January 1978 and February 1984, 120 patients with superficial bladder tumors and/or carcinoma in situ were enrolled in previously reported therapeutic trials of bacillus Calmette-Guerin. Of all treated patients 78 per cent responded to initial therapy, with a followup of 13 to 120 months (median 67 months). Of the 18 patients who failed 10 were treated with repeat, intensified courses. Nine patients who had recurrent tumors within 3 to 30 months after initiation of bacillus Calmette-Guerin therapy (median 6 months) eventually ceased having recurrence. Status free of disease in the 9 patients ranged from 25 to 90 months since the last recurrence (median 64 months). With retreatment of some of the early failures, the initial success rate of 78 per cent was increased to 89 per cent. These data support the concept that intravesical immunotherapy with bacillus Calmette-Guerin should be repeated in patients who initially appear not to respond. The data also suggest that bacillus Calmette-Guerin induces a durable beneficial response rather than simply delays eventual tumor recurrence.

Administration, Intravesical↗

PubMed1989

Combination immunotherapy of murine transitional cell cancer using BCG and an interferon-inducing pyrimidinone.

The immunomodulator ABPP (2-amino-5-iodo-6-phenyl-4(3H) pyrimidinone) is an interferon inducer and has been shown to have in vivo activity against the murine bladder tumor MBT-2. Two experiments were performed to determine if ABPP might enhance the in vivo anti-tumor activity of Bacillus Calmette-Guerin (BCG). First, in vivo stimulation of cell-mediated cytotoxicity by BCG and ABPP was measured in C3H mice using a chromium-release assay. An earlier, greater, and longer-lasting increase in cytotoxicity was caused by ABPP than by BCG. Based on the differing times to peak cytotoxic stimulation, groups of 15 mice each were pretreated intraperitoneally at different times prior to inoculation with MBT-2. Compared to saline, ABPP alone did not increase survival, while BCG alone did increase survival (p less than 0.01), and the combination of BCG and ABPP yielded the highest survival (p less than 0.001). These results indicate that 1) ABPP affects the immune system differently than BCG, and 2) while ABPP may have less single-agent activity against MBT-2 than BCG, ABPP may serve to potentiate the activity of BCG.

Animals↗

PubMed1989

A prospective double-blind trial of intracorporeal papaverine versus prostaglandin E1 in the treatment of impotence.

A randomized prospective, double-blind clinical trial was performed comparing intracorporeal injections of papaverine (30 mg. per ml.) with prostaglandin E1 (10 mcg. per ml.) as pharmacological treatment of impotence. A total of 15 men completed the study, receiving papaverine and prostaglandin E1 in a crossover design. Over-all, 9 of 15 evaluable patients had a full erection with either 1 or both drugs: 3 secondary to papaverine only, 2 to prostaglandin E1 only, and 4 to both drugs. No major complications were observed. We conclude that intracorporeal prostaglandin E1 may be used successfully to stimulate pharmacological erections and that it might be useful in patients not responding to intracorporeal papaverine.

Adult↗