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Biomedical subjects

G R Prout

Publications and source records attributed to G R Prout.

At least 19 recordsLinked to original sources
PubMed1992

The usefulness of serum acid phosphatase in monitoring patients with advanced prostate carcinoma.

The usefulness of serum acid phosphatase (SAP) in monitoring patients with advanced prostate carcinoma has been questioned. We reviewed a series of 59 patients with stage D2 prostate carcinoma. All patients had extended follow-up through at least one clinical relapse, or death. Responses to a variety of therapies were characterized as absent, subjective, or objective. All patients with an elevated pre-treatment SAP that fell to normal following therapy had prolonged survivals and improved prognoses. Conversely, all patients with an elevated SAP which did not normalize following therapy had poorer survivals. Among 36 objective responses to therapy, the SAP was elevated prior to or simultaneous with disease progression in 33 (93% sensitivity). In each ease where the pretreatment SAP normalized following therapy, any subsequent elevation in SAP above normal was always associated with clinical evidence of disease progression (100% specificity). Changes in SAP following therapy correlate well with both disease regression and disease progression in patients with advanced prostatic carcinoma.

Alkaline Phosphatase↗
PubMed1992

Treated history of noninvasive grade 1 transitional cell carcinoma. The National Bladder Cancer Group.

A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone.

Adult↗
PubMed1992

13-cis-retinoic acid in chemoprevention of superficial bladder cancer. The National Bladder Cancer Group.

Animal studies indicate that 13-cis-retinoic acid (CRA) inhibits bladder tumor growth and is effective in treating patients with serious dermatologic disorders. A trial of CRA in patients at high risk for recurrent Ta, T1 tumors was initiated at an experimental dose of 0.5 mg/kg/d in three divided doses, increasing to 1 mg/kg/d at four weeks. Treatment of twenty eligible patients lasted for six months with an additional 24 month follow-up period. One patient was later excluded due to toxicity resulting in an early dose reduction. Eight patients stopped treatment before three months; of these five, had recurrences within three months, one developed pulmonary metastasis, and one developed a T2G3 tumor. Four patients stopped treatment between three and six months; three of them had recurrences before one year and one had no evidence of disease at seven years. Seven patients completed the course; of these three had recurrences within six months, and three more had recurrences at 8, 15, and 45 months, respectively. Toxicity was nearly universal; cheilosis, conjunctivitis, pruritus, joint and eye pain, flashing lights, and erythrocyte sedimentation rate (ESR) over 60 were all noted. The lack of positive results and the frequency and severity of toxicity led to termination of the study.

Carcinoma, Transitional Cell↗
PubMed1991

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.

Adult↗
PubMed1991

Interval report of a phase I-II study utilizing multiple modalities in the treatment of invasive bladder cancer. A bladder-sparing trial.

Clinicians at the Massachusetts General Hospital have used two cycles of methotrexate, cisplatin, and vinblastine (MCV) before radiotherapy and cisplatin in 53 patients with muscle-invasive bladder cancer. Eleven patients did not complete the protocol, but overall, the toxicity was not formidable. Of the total patients accessioned, 34 are alive. Of the 34 patients in the series who completed the full treatment protocol, the estimated survival rate at 54 months is 77%. This interim analysis suggests that the treatment is achieving at least limited success in saving lives and bladders.

Adult↗
PubMed1990

Bladder cancer. Advances in laboratory innovations and clinical management, with emphasis on innovations allowing bladder-sparing approaches for patients with invasive tumors.

In the present decade important progress has been made in the understanding of the biology and management of bladder cancer. Experimental laboratory models and new investigative tools have revealed potentially important prognostic markers and have led to an improved understanding of the histogenesis of the disease. Advances in the management of superficial bladder cancer (intravesical chemotherapy or immunotherapy, improved urinary cytology, laser technology, flexible fiberoptic cystoscopy, and photodynamic therapy) have, in some subgroups, improved tumor control while decreasing patient complications. For invasive bladder cancer (invasive of bladder muscle or beyond) improved techniques of cystectomy and radiotherapy have reduced the complications of treatment and may have contributed small but important improvements in cure. A major improvement in the last decade has occurred in objective remission rates with chemotherapy for patients with metastatic bladder cancer. From 20% to 40% of patients achieve a complete remission, and 10% to 20% may survive for more than 3 years. Randomized Phase III trials are currently in progress and must be completed to define the true role of multidrug chemotherapy in patients with metastatic disease and to validate data from the regimens of cyclophosphamide, methotrexate, and vincristine (CMV) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) before any of these approaches to treatment can be considered of proven benefit. Preliminary data from the Massachusetts General Hospital are presented of a potentially effective approach to select patients with invasive tumor for successful bladder preservation. In this approach transurethral debulking surgery is combined with upfront CMV chemotherapy plus cisplatin and 4000 cGy. If tumor is found on cystoscopic reevaluation with biopsy and cytology immediately following cisplatin and 4000 cGy, cystectomy is performed; if not, consolidation by a radiation boost to 6480 cGy plus cisplatin is given. The approach is fairly well tolerated, allows cystectomy without undue complications, has yielded a 88% complete response rate in patients selected for bladder preservation, and resulted in 90% of patients free of distant metastases with follow-up ranging from 6 to 30 months. A randomized Phase III trial with and without neoadjuvant MCV chemotherapy for selective bladder preservation is now under way and accruing well.

Actuarial Analysis↗
PubMed1990

Multi-drug resistance of a doxorubicin-resistant bladder cancer cell line.

A bladder tumor cell line resistant to doxorubicin (MGH-U1R) has been established previously by culturing a human transitional cell carcinoma cell line (MGH-U1) in increasing concentrations of the drug. MGH-U1R is 40 times more resistant to doxorubicin than MGH-U1. In the present study, MGH-U1R was evaluated for its multi-drug resistance or pleiotropism by testing against other chemotherapeutic agents. MGH-U1R was found to be 188 times more resistant to vinblastine and 13 times more resistant to etoposide than MGH-U1, while remained sensitive to bleomycin. Taken together with earlier evidence that the resistance of MGH-U1R to doxorubicin can be reversed by a calcium-channel blocker verapamil, and the measured over-expression of the mdr1 gene in these cells, MGH-U1R has the characteristic multiple drug resistance properties similar to other established doxorubicin resistant carcinoma cell lines. MGH-U1R may be a useful model for the development of strategies in overcoming drug-resistance in the treatment of transitional cell carcinoma.

Bleomycin↗
PubMed1990

Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy.

Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.

Aged↗
PubMed1990

The effect of verapamil on a multi-drug resistant bladder carcinoma cell line and its potential as an intravesical chemotherapeutic agent.

A human bladder transitional cell carcinoma cell line, MGH-U1R, exhibits reproducible resistance to doxorubicin. We examined the effects on survival of this cell line caused by verapamil, which has been shown to reverse multi-drug resistance in vitro in other neoplastic cell lines. Both MGH-U1R and MGH-U1, the non-resistant parent cell line, were treated with varying concentrations of doxorubicin alone, verapamil alone, or both drugs simultaneously, all for one hour. Cells were then grown in drug-free medium for 10 days, stained, and counted. Standard survival curves were calculated. Verapamil alone had no significant cytotoxicity. Verapamil at concentrations of 16 micrograms./ml. and 32 micrograms./ml. decreased the IC50 of doxorubicin for MGH-U1R by a factor of 2.5. Using H3-verapamil, we also examined the systemic and local absorption of this drug resulting from intravesical verapamil administration in rabbits. All animals were treated for one hour, and multiple serum samples were drawn during treatment. Verapamil was found in high concentrations in the mucosa, less in the adventitia, and was absent in venous blood. Verapamil effectively reverses resistance to doxorubicin of MGH-U1R in vitro. The intravesical use of verapamil appears to be safe, and may prove to be a useful adjunct in the intravesical therapy of some bladder tumors.

Animals↗
PubMed1990

Historical and modern role of cystoscopy and bladder mucosal biopsy in detecting bladder cancer in a high-risk population.

The use of cystoscopy and bladder biopsy to screen cohorts of persons with no history of bladder carcinoma would be unsatisfactory because of the low prevalence of the disease, even in the highest risk occupations. Cystoscopy/biopsy should follow noninvasive modern-day techniques that can be used for screening at reasonable cost and no risk to the workers involved. Dipstick testing for hematuria, urinary cytology, flow cytometry, quantitative fluorescence image analysis, and other emerging technologies are far more useful as screening methods. Examples of bladder tumors and benign lesions are included to demonstrate the heterogeneity of bladder carcinoma and the difficulties the urologist faces in deciding which lesions may be malignant. Positive preliminary tests increase the sensitivity and specificity of the diagnostic examination.

Biopsy↗
PubMed1990

Detection of exfoliated bladder cancer cells by monoclonal antibodies to tumor-associated cell surface antigens.

Monoclonal antibodies (Mabs) to human tumor antigens have potential for tumor detection and treatment. For bladder carcinoma, the detection of exfoliated tumor cells in urinary specimens may be accomplished with Mabs reacting to tumor cell-surface components. This method may be useful for screening and monitoring carcinogen-exposed workers. A Mab generated by our laboratory, 3G2-C6, reacts with high affinity to a cell-surface component expressed by bladder tumor cells. The potential utility of this Mab in detecting exfoliated tumor cells was evaluated in bladder wash specimens. The Mab method detected positive cells in 87% (56/64) of specimens from patients with bladder cancer, including a great majority with grade 1 tumor and carcinoma in situ, superior to the routine cytology done on the same specimens. Cells in specimens from patients with urinary calculi, chronic cystitis, and history of bladder cancer also reacted with the Mab, suggesting that other stimuli can induce antigen expression. The Mab method can also be performed on urine samples, thus allowing evaluation of the ability of the Mab to identify premalignant, malignant, and other abnormal exfoliated cells in urine. The Mab method represents a unique opportunity to develop noninvasive detection of bladder cancer and to monitor and screen bladder cancer high-risk groups.

Antibodies, Monoclonal↗
PubMed1989

Long-term experience with flutamide in patients with prostatic carcinoma.

Fifty-two patients with previously untreated metastatic carcinoma of the prostate were treated with flutamide 250 mg tid. Response was classified according to objective and subjective criteria, and duration of response and total survival were chosen as endpoints. Disease manifestations at presentation and tumor burden were studied to determine their relationship, if any, to treatment response and outcome. Total survival was longest in 26 patients who had objective responses (mean 50 months). Patients who failed to respond (n = 13) and those who had subjective responses (n = 13) survived an average of eleven and 17.2 months, respectively. Tumor burden was correlated with response to treatment and total survival; those judged to have a minimum tumor burden had objective responses and survived an average of sixty months. Sixteen other patients who had been previously treated with diethylstilbestrol were also studied. Nine of these had cardiovascular complications while taking diethylstilbestrol, and tolerated flutamide without further complications. Those in remission stayed in remission, and sexual potency returned to 5 patients.

Adenocarcinoma↗
PubMed1989

Renal cortical tumors. Cytogenetic characterization.

The authors examined three cortical tumors (adenomas) of the kidney and found a consistent chromosome pattern. A combination of chromosome abnormalities (+7, +7, +17, -Y) was shared by these tumors. In contrast, none of them showed alterations of chromosome 3p and 5q, the most common changes in renal cell carcinomas. The chromosome abnormalities in these patients may define a subgroup of renal tumors, so-called adenomas, that cannot be distinguished easily from adenocarcinomas in histopathologic examination.

Adenoma↗