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Biomedical subjects

M F Sarosdy

Publications and source records attributed to M F Sarosdy.

At least 37 records · Page 2Linked to original sources
PubMed1996

Bropirimine immunotherapy of upper urinary tract carcinoma in situ.

OBJECTIVES: Bropirimine has been shown to be effective in treating approximately 50% of patients with carcinoma in situ (CIS) of the bladder in recent clinical trials. Patients with upper tract CIS were treated with bropirimine to determine whether this oral drug might be effective in that setting. METHODS: Twenty-four patients with negative radiographic findings and positive cytologic evidence for upper tract CIS in one or both ureters received bropirimine (3.0 g/day orally) for 3 consecutive days each week for up to 1 year. Ureteral collection of urine or barbotage for cytologic analysis was performed quarterly thereafter. RESULTS: Ten (48%) of 21 evaluable patients had a negative ureteral cytologic analysis after 12 weeks (5 patients) or 24 weeks (5 patients). Of these 10 patients, 8 continue to have negative cytology for a period of 3 to 30 months (median, more than 9 months). In 2 patients, negative cytology reverted to positive at 6 and 9 months, respectively, during therapy. Twelve (50%) of the 24 patients reported no toxicity. Three patients stopped treatment at 2, 3, and 3 weeks due to pruritic rash, nausea and vomiting, and severe bone pain, respectively. Therapy was stopped in 1 additional patient between 4 and 5 months because of transient liver enzyme elevations, yet this patient has had a continuous negative cytologic analysis for more than 9 months. CONCLUSIONS: Orally administered bropirimine may be effective therapy for CIS of the ureter or renal pelvis, with acceptable toxicity in most patients. Further efforts to better define this activity as well as the possible need for maintenance or intermittent long-term therapy are warranted.

Adjuvants, Immunologic↗
PubMed1996

Oral bropirimine immunotherapy of carcinoma in situ of the bladder: results of a phase II trial.

OBJECTIVES: Bropirimine is an orally administered immunostimulant that has been shown to have activity against carcinoma in situ (CIS) of the bladder. To further assess this potential activity, bropirimine was administered to 42 patients for bladder CIS in a Phase II trial. METHODS: Patients were treated with bropirimine 3.0 g/day by mouth for 3 consecutive days each week up to 1 year. Cystoscopy with biopsies and bladder wash cytology were performed quarterly. RESULTS: Twenty (61%) of 33 evaluable patients converted malignant biopsies and bladder wash cytology to negative, including 6 (50%) of 12 who failed prior bacillus Calmette-Guérin (BCG) immunotherapy, 14 (67%) of 21 who had not received prior BCG therapy, and 12 (80%) of 15 with primary CIS. Median response duration exceeds 21 months. Four of the 20 responders did have a papillary tumor recurrence at 3 to 15 months, all Stage Ta or T1. Mild toxicity (grade I or II) suggestive to interferon induction or administration occurred in one third of patients. Headache, transient hepatic enzyme elevations, skin rash, and arthralgias each occurred in 5% to 14% of the patients, with nausea or emesis in 21%. Grade 1 tachycardia/palpitations or chest pain each were noted in 5%. CONCLUSIONS: Oral bropirimine can induce remission of bladder CIS with acceptable toxicity at 3.0 g/day. Bropirimine may be a valuable alternative to cystectomy for some failures of BCG therapy and may have the potential to replace BCG as front-line therapy because of its ease of administration.

Adjuvants, Immunologic↗
PubMed1996

Additional experience with continent urinary diversion using cutaneous ileocecocystoplasty.

OBJECTIVES: We have used the technique of ileocecocystoplasty with a cutaneous continent catheterizable limb to incorporate native bladder into the urinary reservoir to treat patients with functional and anatomic bladder disorders. This review was performed to evaluate the outcome of the first 8 patients who underwent this procedure. METHODS: A retrospective analysis was performed by chart review and telephone interview. Patients' preoperative and postoperative bladder status and management, satisfaction rating, and renal function are reported. RESULTS: Follow-up of 9 to 64 months (mean, 33.9) in our first 8 patients reveals excellent results in all, including 1 patient who prefers an indwelling catheter due to progressive neuromuscular disability. CONCLUSIONS: Cutaneous ileocecocystoplasty offers urologists and patients continent urinary diversion with minimal morbidity and is a much less extensive procedure than complete bladder replacement.

Adult↗
PubMed1996

Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment.

PURPOSE: We evaluated the ability of an immunoassay for nuclear matrix protein 22 (NMP22 test kit) to predict the subsequent disease status of patients with transitional cell carcinoma of the urinary tract at approximately 10 days after transurethral resection of bladder tumor. MATERIALS AND METHODS: A total of 90 patients with transitional cell carcinoma provided voided urine samples at least 5 days postoperatively. NMP22 was determined using a commercial test kit. At initial cystoscopic examination 3 to 6 months later the disease status was recorded, and the NMP22 values before and after transurethral resection of bladder tumor were compared. RESULTS: Of 125 followup cystoscopic examinations (60 patients had 1, 26 had 2, 3 had 3 and 1 had 4 recurrences) transitional cell carcinoma was pathologically confirmed in 33. No malignancy was present at 79 examinations (if tumor was seen endoscopically, pathological evaluation indicated atypia, dysplasia or no abnormality). NMP22 values in these 2 populations were significantly different (malignancy median 20.81 units per ml. and no malignancy median 5.72 units per ml., Mann-Whitney U test for differences between 2 medians p = 0.00005). Of the 33 recurrences 23 (70%) had NMP22 values greater than the reference range (10 units per ml.). Additionally, NMP22 identified all 6 subjects (100%) who had invasive disease 3 to 6 months later. Of 72 patients with NMP22 less than 10 units per ml. 62 (86%) had no malignancy at subsequent cystoscopy. CONCLUSIONS: NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.

Biomarkers, Tumor↗
PubMed1996

In vivo antitumor activity of bropirimine against PAIII and Dunning MAT-LyLu rodent prostate cancers.

PURPOSE: To evaluate bropirimine for in vivo activity in rodent prostate cancer. MATERIALS AND METHODS: Subcutaneously injected PAIII and Dunning MAT-LyLu rodent prostate cancer cells caused solid tumors and death in controls. Bropirimine was given on varying schedules at 250 mg./kg. by gavage, and tumor volume and survival were recorded. RESULTS: Bropirimine prevented growth when given on the day of tumor injection and caused 95% of advanced tumors to regress completely in the PAIII model. Bropirimine caused significant growth inhibition and prolongation of survival in the MAT-LyLu model. CONCLUSIONS: Bropirimine has statistically significant in vivo activity against both of these rodent prostate cancer cell lines.

Adenocarcinoma↗
PubMed1996

Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract.

PURPOSE: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.

Aged↗
PubMed1995

Raloxifene (LY156758) produces antimetastatic responses and extends survival in the PAIII rat prostatic adenocarcinoma model.

The benzothiophene antiestrogen, raloxifene (LY156758), has selective estrogen pharmacological antagonist activity in rats. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this agent on the lymphatic and pulmonary metastasis and survival in tumor-bearing male Lobund-Wistar (LW) rats. Raloxifene was inactive against colony formation of PAIII cells in vitro. Similarly, following subcutaneous (s.c.) implantation of 10(6) PAIII cells in the tail, s.c. administration of raloxifene (2.0, 10.0, or 20.0 mg/kg/day) for 30 days failed to demonstrate cytoreductive activity against primary tumor growth in the tail. However, in these same animals, raloxifene administration produced significant (P < 0.05) inhibition of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 89% and 81% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by raloxifene treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (P < 0.05) reduced by raloxifene administration in a dose-related manner (maximal reduction = 97% from control values). In these animals, maximal regression of 20% for ventral prostate and 21% for seminal vesicle were also seen after raloxifene administration (P < 0.05 for both). Coadministration of E2B and raloxifene had no consistent antagonistic effect upon the antitumor responses produced by raloxifene. Raloxifene (40.0 mg/kg/day for 28 days) produced marked decreases in PAIII metastasis in the lymphatic and pulmonary components. Continued administration of the compound produced significant (P < 0.05) extension of survival of PAIII-bearing rats. Further studies are needed to define the maximal antitumor efficacy and the mechanism of action of raloxifene in urogenital solid tumor animal models. These data support the contention that raloxifene represents a class of active antimetastatic agents with potential efficacy in the treatment of hormone-insensitive human prostatic cancer.

Adenocarcinoma↗
PubMed1995

Renal cell carcinoma metastatic to the gallbladder or prostate: two case reports.

Although metastatic renal cell carcinoma (RCC) is not uncommon, dissemination to the gallbladder or prostate is very rare. We present 1 case of RCC with synchronous metastasis to the gallbladder and 1 case of RCC with metachronous metastasis to the prostate. These cases illustrate the propensity of RCC for unpredictable presentation and unusual sites of metastases. The first case also illustrates the benefit of adjuvant nephrectomy with excision of a solitary metastasis. Patterns of RCC metastases and flow cytometric analysis of RCC are discussed.

Aged↗
PubMed1995

Intestinal obstruction and bilateral ureteral injuries after laparoscopic oophorectomy in a patient with severe endometriosis.

The overall frequency of ureteral injury during laparoscopic adnexectomy for endometriosis is unknown, and intestinal obstruction after laparoscopy is rare. Our patient had two postoperative complications: small bowel obstruction and bilateral ureteral injuries discovered 2 and 39 days, respectively, after outpatient laparoscopic adhesiolysis and bilateral salpingo-oophorectomy for severe endometriosis. Pelvic examination and vaginal sonography revealed a large unilocular cystic mass. Laparoscopy showed a fixed large endometrioma firmly attached to pelvic peritoneum and intestines in the pelvic cavity, and significant adhesions in the upper part of a midline incision from prior abdominal hysterectomy. These midabdominal adhesions were not released. The patient underwent laparoscopic bilateral adnexectomy as an outpatient. Two days later she was admitted with small bowel obstruction. Thirty-nine days later, diagnostic evaluation revealed urinary ascites with right ureteral stricture at the uterine artery level, and complete ligation and resection of the left ureter at the pelvic brim near the infundibulopelvic ligament stump. She underwent left ureteral implantation with psoas hitch and right ureterolysis. Follow-up cystogram and intravenous pyelography at 6 and 20 weeks revealed complete recovery. In cases of severe endometriosis with significant ureteral and intestinal involvement, laparotomy may have to be considered.

Adult↗
PubMed1995

Results of a multicenter trial using the BTA test to monitor for and diagnose recurrent bladder cancer.

OBJECTIVES: We compare the Bard BTA (bladder tumor antigen) test to voided cytology studies in patients undergoing surveillance cystoscopy for recurrent bladder cancer. MATERIALS AND METHODS: A prospective, blinded, multicenter trial was performed. RESULTS: A total of 499 patients underwent 1,014 cystoscopic examinations and tumor was identified in 151. The bladder tumor antigen test was more sensitive than cytology studies in detecting recurrent cancer (p < 0.001), being positive in 61 cases versus 25 for cytology. The trial in healthy volunteers and nonurological patients estimates bladder tumor antigen test specificity to be 95.9%. CONCLUSIONS: The bladder tumor antigen test is a simple, rapid and inexpensive adjunct to cystoscopy, and the results are equivalent or superior to those of voided cytology as performed in this trial.

Adult↗
PubMed1995

The lack of predictive value of prostate specific antigen density in the detection of prostate cancer in patients with normal rectal examinations and intermediate prostate specific antigen levels.

PURPOSE: The management of patients with a normal digital rectal examination and a prostate specific antigen (PSA) level of 4.0 to 10.0 ng./ml. remains controversial. To improve the specificity of cancer detection in this group, PSA density has been recommended with biopsies based on a PSA density of 0.15 or more. To evaluate PSA density as a discriminator of prostate cancer we enrolled patients in a prospective study. MATERIALS AND METHODS: A prospective evaluation was done of 44 consecutive patients with a palpably normal digital rectal examination and a serum PSA level of 4.0 to 10.0 ng./ml. enrolled during a 13-month period. All patients underwent transrectal ultrasound with sextant biopsies regardless of calculated PSA density. RESULTS: Overall, 8 of 44 men (18%) had prostate cancer. There was no significant difference in the mean PSA density between the patients with positive and negative biopsies (mean 0.12 and 0.15, respectively, p = 0.258). Also, there was no significant association between PSA or PSA density and a positive biopsy in multivariate analysis (p = 0.863). Receiver operating characteristic curves for PSA and PSA density failed to demonstrate any superior benefit for PSA density in this patient population. A PSA density of 0.15 was an unreliable indicator of cancer (sensitivity 12.5%, specificity 61.1% and positive predictive value 6.7%). CONCLUSIONS: In our study, PSA density did not discriminate between patients with positive and negative biopsies, and in fact most cancers would not have been detected if a PSA density of 0.15 or more had been used as the sole indication for biopsy. Therefore, we recommend systematic biopsies in these patients independent of calculated PSA density.

Aged↗
PubMed1995

Percutaneous aortic stent placement for life threatening aortic rupture due to metastatic germ cell tumor.

Patients with testicular carcinoma frequently present with advanced disease and symptoms resulting from metastatic lesions. We report an unusual case of successful emergency management of a massive rupturing aortic pseudoaneurysm midway through systemic chemotherapy for stage III germ cell tumor by percutaneous trans-luminal placement of an aortic bypass stent-graft. Unstable hemorrhage was controlled, allowing our patient to complete chemotherapy and undergo elective retroperitoneal lymph node dissection with resection of the pseudoaneurysm and residual disease after normalization of tumor markers. Final pathological evaluation revealed only fibrosis in the resected tissue. Followup angiography demonstrated a patent stent-graft and the patient was without evidence of disease 1 year after retroperitoneal lymph node dissection.

Adult↗
PubMed1995

Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer.

Transforming growth factor alpha-Pseudomonas exotoxin-40 (TP40) is a hybrid fusion protein that selectively binds to cancer cells that express the epidermal growth factor receptor. TP40 is then internalized and kills these cells by virtue of its Pseudomonas exotoxin-derived domains. We studied the safety and short-term antitumor activity of intravesical TP40 in 43 patients with refractory superficial bladder cancer. These patients had resected Ta/T1 disease (n = 19), visible Ta or T1 lesions (n = 11), or carcinoma in situ (n = 13). Patients were treated with increasing dose levels of TP40 at 0.15, 0.3, 0.6, 1.2, 2.4, 4.8, or 9.6 mg/week for 6 weeks and evaluated by comparing pretreatment and posttreatment cystoscopic examinations, cytology, and histopathology. All TP40 doses were well tolerated. No evidence of antitumor activity was seen in any of the patients with Ta or T1 lesions. However, 8 of 9 patients with evaluable carcinoma in situ were judged by histopathology of multiple biopsy specimens to exhibit clinical improvement following TP40 therapy. In most of these responsive patients, cystoscopic examination supported the histopathological findings, although cytology of urine and bladder washings persistently demonstrated malignant cells. Therefore, TP40 appears to be a well-tolerated biological agent that may prove to have utility in treating carcinoma in situ of the bladder.

Aged↗
PubMed1994

Hormonal therapy for metastatic prostate cancer: issues of timing and total androgen ablation.

This review summarize results of hormonal management in patients with metastatic prostate cancer in terms of both timing and amount of androgen blockade. The standard of delayed hormonal therapy resulted from data of the Veterans Administration Cooperative Urologic Research Group showing high toxicity in patients treated with estrogen therapy. Reanalysis of those data using cancer-specific deaths showed improved cancer-specific survival with early hormonal therapy. A large and growing body of clinical data also suggests a superior benefit to early hormonal therapy. The concept of total androgen (adrenal and testicular) ablation was supported by reports that show a survival advantage using a combined blockade over luteinizing hormone-releasing hormone agonist alone. A National Cancer Institute study showed particularly impressive disease-free and overall survival in a subset of patients with low volume disease and good performance status. However, caution should be exercise in view of differing Canadian and European data. This review provides guidelines for treatment, but ultimately the timing and amount of androgen deprivation must be tailored to the individual patient. Ongoing and future prospective studies hold the promise of answers to these difficult and unresolved questions.

Adrenalectomy↗
PubMed1993

In vitro sensitivity testing of human bladder cancers and cell lines to TP-40, a hybrid protein with selective targeting and cytotoxicity.

TP-40 is a hybrid fusion protein produced by recombinant technology and consists of a molecule of transforming growth factor-alpha (TGF-alpha) fused to the Pseudomonas exotoxin PE-40. A panel of human and murine bladder cancer cell lines was found to be universally sensitive in vitro to TP-40 in a clonogenic assay. All lines expressed receptor for epidermal growth factor (EGF), though none demonstrated gene amplification for the EGF receptor. The sensitivity to TP-40 may be blocked by preexposure to EGF. Six human bladder tumors taken directly from patients were all sensitive in vitro to TP-40; these included well-differentiated tumors. TP-40 may prove to be effective as an intravesical agent in bladder cancer via selective targeting to cells that express EGF receptors, as do the majority of human bladder cancers.

ADP Ribose Transferases↗
PubMed1993

Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study.

PURPOSE: This multicenter, randomized phase III clinical trial evaluated the efficacy of etoposide plus carboplatin (EC) versus etoposide plus cisplatin (EP) in good-risk germ cell tumor (GCT) patients. PATIENTS AND METHODS: Between October 1986 and December 1990, 270 patients with good-risk GCTs were randomized to receive four cycles of either EP or EC. The etoposide dose in all patients was 100 mg/m2 on days 1 through 5. EP patients received cisplatin at 20 mg/m2 on days 1 through 5 and therapy was recycled at 21-day intervals. For EC patients, the carboplatin dose was 500 mg/m2 on day 1 of each cycle and the EC recycling interval was 28 days. RESULTS: Two hundred sixty-five patients were assessable: 131 patients treated with EC and 134 treated with EP. One hundred fifteen of 131 assessable patients (88%) treated with EC achieved a complete response (CR) versus 121 of 134 patients (90%) treated with EP (P = .32). Sixteen patients (12%) treated with EC relapsed from CR versus four patients (3%) treated with EP. Therefore, 32 patients (24%) who received carboplatin experienced an event (incomplete response [IR] or relapse) compared with 17 of 134 patients (13%) who received cisplatin (P = .02). At a median follow-up of 22.4 months, event-free and relapse-free survival were inferior for patients treated with EC (P = .02 and P = .005, respectively). No difference in overall survival was evident (P = .52). CONCLUSION: Two-drug therapy with EC using this dose and schedule was inferior to therapy with EP. Cisplatin remains as the standard platinum analog in the treatment of patients with good-risk GCTs. Carboplatin should be restricted to investigational trials in GCT.

Adolescent↗