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Biomedical subjects

G R Prout

Publications and source records attributed to G R Prout.

At least 55 records · Page 3Linked to original sources

Invasive bladder carcinoma. The importance of initial transurethral surgery and other significant prognostic factors for improved survival with full-dose irradiation.

This review covers recent observations (all retrospective) on useful prognostic indicators in patients treated by radiation for this heterogeneous disease, including presenting clinical characteristics, extent of conservative surgery, radiographic studies, and pathologic subtypes. Although imperfect and incomplete, this review offers some criteria to identify which patients will do well and which quite poorly if treated by bladder-preserving full-dose radiation therapy. Such criteria should help clinicians recommending full-dose radiation therapy, radical cystectomy, or innovative combinations of chemotherapy, radiation, and surgery.

Actuarial Analysis↗

A refined method for assessing 99mTc-MDP whole body retention in prostate cancer patients.

Whole body retention (WBR) of 99mTc labeled methylene diphosphonate (MDP) has been shown to significantly differentiate various clinical stages of prostate cancer. Whole body measurements, when performed at 5 min and 24 h after i.v. administration of 99mTc-MDP, allows for the calculations of percentage whole body retention (% WBR) after one day. The latter can be expressed relative to either the anterior or posterior projection, or in combination as the geometric mean value. In an attempt to better describe the clinical course of prostate cancer patients with bone metastases we have refined the % WBR calculations to include a normalization factor. The latter consists of the mean 24-h value of WBR's as obtained from 10 prostate cancer patients without bony metastases as determined by bone scintigram. These values were determined for each projection to be: anterior = 26.5 +/- 4.7%, posterior = 37.5 +/- 7.4%, and geometric mean = 31.5 +/- 5.7%. The % WBR is then divided by the normalization factor of choice and expressed as (% WBR)N. These data are used to better express 99mTc MDP 24-h whole body retentions when following the clinical course of patients with metastatic carcinoma of the prostate. Caution should be exercised when interpreting these data when metabolic bone pathology is present. A false negative (% WBR)N value will result if an infiltration of the 99mTc-MDP occurs during administration.

False Negative Reactions↗

The outcome of conservative treatment of carcinoma in situ of the bladder.

We treated 52 patients with carcinoma in situ by transurethral resection, thiotepa and other intravesical chemotherapeutic agents. All patients underwent standard initial and subsequent evaluative procedures and the average followup was 62 months. Half of the patients had a history of stage Ta and/or T1 transitional cell carcinoma. The remainder had carcinoma in situ when first diagnosed (10 had carcinoma in situ only). Of 12 patients treated by transurethral resection alone 1 reached 60 months without radical cystectomy or disease progression. There were 18 patients who had a complete response following chemotherapy, 11 had a partial response (positive cytology) and 11 failed (persistent carcinoma in situ). Patients with a history of transitional cell carcinoma had a statistically significantly greater probability of achieving a complete response. Despite other types of treatments only 2 of 22 patients (partial response and failure) achieved a lasting complete response. Persistent partial response and failure resulted in progressive transitional cell carcinoma (stage T2 or greater, prostatic involvement and metastases) and only 1 of these survived for more than 5 years without cystectomy. None of our patients received bacillus Calmette-Guerin because it was not available during the time most of the patients were treated. While the lives and bladders in some patients may be spared by its use, failure to achieve a complete response indicates impending disaster and cystectomy should be considered seriously.

Administration, Intravesical↗

Total bone uptake in management of metastatic carcinoma of the prostate.

The status of patients with skeletal metastases from prostatic carcinoma was determined from a quantitative uptake and retention measurement of the bone scanning radiopharmaceutical 99mtechnetium-methylene diphosphonate. Whole body counts were performed 5 minutes and 24 hours after intravenous administration of 99mtechnetium-methylene diphosphonate, and were expressed as the percentage uptake by the skeleton at 24 hours. Skeletal uptake determinations were done in 29 patients with prostatic cancer (17 with osseous metastases) who were evaluated at 3 to 6-month intervals. Group 1 consisted of patients who responded to therapy and achieved remission, group 2 included patients with relapse or progressive disease, group 3 consisted of those with metastases who were in remission for longer than 6 months and group 4 included those without evidence of any bony metastases. The baseline mean +/- standard deviation 24-hour skeletal uptake values were 46.1 +/- 12.0 per cent in group 1, 34.3 +/- 13.9 per cent in group 2, 27.0 +/- 5.9 per cent in group 3 and 28.9 +/- 5.5 per cent in group 4. At 3 to 6 months the values in group 1 (responders) decreased by 18 per cent, while those in group 2 (relapse or progression) increased by 19 per cent and those in group 3 (remission) increased by 1.5 per cent. The quantitative 24-hour skeletal uptake test was performed easily, reproducible and at least as useful as concurrent chemical blood tests and subjective bone scan interpretations.

Acid Phosphatase↗

The success of radiation therapy in controlling prostatic cancer within the treated field.

An important question is the ultimate (i.e. with "infinite" time of follow-up) local tumor regrowth rate for patients treated for specified stages of clinically localized prostatic cancer. Using combined data from patients irradiated at Stanford University from 1956 through 1983, and patients irradiated at the Massachusetts General Hospital from 1973 through 1979, we approached this question by an evaluation of the cumulative frequency of local tumor regrowth. These curves, relating cumulative incidence of local regrowth against time, approached an asymptote. These results indicate that following 6,800 to 7,500 cGy external beam irradiation, permanent local control of cancer of the prostate occurs in 85% to 90% of patients with stage T2 (B) tumors and in 60% to 70% of patients with stage T3 and T4 (C) tumors. Further analysis of the patients with T3 and T4 tumors may identify subgroups in whom more aggressive initial therapy is indicated.

Follow-Up Studies↗

A possible specific chromosome change in transitional cell carcinoma of the bladder.

Chromosome changes were ascertained in nine tumor samples from seven untreated patients with transitional cell carcinoma of the urinary bladder. All tumors analyzed showed abnormal karyotypes. In one tumor, a single numerical abnormality (+7) was the sole detectable change. From 1 to 19 structurally abnormal chromosomes could be identified in the remaining 8 tumors. The same abnormality, an isochromosome of the short arm of chromosome #5, was found in five tumors from four patients. We have previously described the presence of this marker chromosome in three of nine cases of transitional cell carcinoma of the bladder. We therefore conclude that i(5p) constitutes the most consistent nonrandom chromosome abnormality in this malignancy. Other chromosomes most frequently involved in structural changes in the present series of tumors were chromosomes #1, #6, #11, and #13.

Aged↗

Chromosome changes in germ cell tumors of the testis.

Chromosome analysis was performed on short-term cultures established from samples of six tumors of the testis. Histologically, four tumors were embryonal cell carcinomas (three primary, one metastatic) and two of mixed histology with predominance of teratoma. The modal chromosome number was hypotriploid in four tumors, triploid in one, and hypertriploid in another. All tumors contained structurally abnormal chromosomes, ranging in number from 1 to 10 in different cases. A small metacentric marker chromosome, identified as an isochromosome of the short arm of chromosome #12 [i(12p)], was present in all tumors analyzed. Unlike other marker chromosomes, this one was invariably present in at least two copies per metaphase in all cases; all other chromosome markers were present in single copy in all tumors. Together with the previous reports on the presence of i(12p) in seminoma and teratoma of the testis, our findings suggest that this karyotypic abnormality is characteristic for all histologic varieties of germ cell tumors of the testis.

Adult↗

Rearrangement of chromosome 3 in renal cell carcinoma.

Rearrangements involving chromosome #3 were detected in 8 of 12 nonfamilial renal cell carcinomas. These results suggest that rearrangement of chromosome #3 is associated with the genesis and progression of a subclass of human renal cell carcinoma.

Adult↗

The treated histories of patients with Ta grade 1 transitional-cell carcinoma of the bladder.

One hundred sixty patients with grade 1 transitional-cell carcinoma of the bladder were evaluated and treated at the Massachusetts General Hospital, Boston. The mean follow-up period was 57 months. There were 92 new patients and 68 patients who had a history of transitional-cell carcinoma. Fifty-three patients (33%) never had another transitional-cell carcinoma. Sixty-eight (43%) of the remaining 107 patients had recurrent Ta grade 1 transitional-cell carcinoma. In 32 patients (20%) disease progressed in grade, in seven patients (4%) invasive transitional-cell carcinoma developed, five patients underwent cystectomy, and one patient died of transitional-cell carcinoma. High-risk factors included positive results of cytologic studies after therapy and three or more recurrences. Multiple therapies were used, but it is impossible to determine if anything other than transurethral resection altered the course in these patients. The data suggest that patients with low-risk factors and Ta grade 1 tumors might be followed up with a quarterly cytologic examination and cystoscopy once or twice a year, unless a change in symptoms occurs.

Adult↗

Preoperative irradiation, lymphadenectomy, and 125iodine implantation for patients with localized carcinoma of the prostate.

Fifty-four patients with clinically and surgically localized prostatic carcinoma were treated with low-dose preoperative irradiation (1,050 cGy), pelvic lymphadenectomy, and interstitial 125Iodine implantation. The follow-up range is 2 to 9 years with a median follow-up of 5 years. Overall local tumor control is 92%. Actuarial 5-year survival is 86% and the actuarial disease-free survival at 5 years is 73%. Patients with poorly differentiated tumors have a significantly worse actuarial survival (62%) at 5 years than patients with well (95%) or moderately well differentiated tumors (93%), p = 0.04. Disease-free survival at 5 years was influenced by grade: well (100%), moderate (60%), and poor (48%), p = 0.03. Multivariate regression analysis indicates that only the degree of differentiation (p = 0.05) significantly impacts on survival. Both degree of differentiation (p = 0.04) and nodal status (p = 0.03) significantly influence disease-free survival. Potency has been maintained in 71% of patients potent at the time of implantation. Late reactions have been acceptable to date: bladder outlet obstruction (13%), mild proctitis (13%), cystourethritis (6%), incontinence (2%), and prostatic calculi (2%).

Adenocarcinoma↗

Chromosome anomalies suggestive of malignant transformation in bilateral renal oncocytoma.

A patient with bilateral renal oncocytoma is presented, and the clinical, radiological and pathological characteristics of this uncommon, clinically benign renal tumor are discussed briefly. Chromosomal analysis studies revealed the following clonal abnormalities: trisomy of chromosome 7, and monosomy of chromosomes 3 and 14, and the X chromosome. A possible clonal abnormality of chromosome 10 and 3 nonclonal anomalies also were identified. The same anomalies were present in both tumors. These karyotypic anomalies are compatible with malignant transformation of the cells of these tumors and, since benign tumors rarely are associated with demonstrable cytogenetic changes, they suggest that oncocytoma, although clinically benign, may have malignant potential.

Adenoma↗

Cytogenetic studies of tumor tissue from patients with nonfamilial renal cell carcinoma.

A method combining an enzymatic technique and short term culture was applied to 27 tumor tissues from 22 patients with nonfamilial renal cell carcinoma in order to establish the chromosome changes in these tumors. Chromosome analyses were successfully carried out in quinacrine mustard-Hoechst 33258 and G-banded preparations of 14 tumors from 12 patients, including 2 cases in which established cell lines were obtained after 43 and 64 days in culture and maintained for 25 and 30 passages in an in vitro system, respectively. The modal chromosome numbers ranged from 38-46 in 11 samples, involving chromosomes in structural and numerical changes and 72 chromosomes in one case, with the remaining 2 samples showing a variety of chromosome numbers. Banding analysis revealed 45 clonal aberrations in 11 tumor samples from 10 patients and nonclonal aberrations in the remaining 3 samples from 2 of the patients. Rearrangements of chromosome 3 were observed in 12 tumors, with the breakpoints on this chromosome almost totally clustered from p11 to p21. In one case both primary and metastatic tumors were studied, and an isochromosome for the long arm of chromosome 1 was observed as clonal in origin in the metastatic tissue. Two cases showed nonclonal changes. The remaining case had one clonal abnormality, i.e., deletion of 6q. Of the remaining 33 clones, chromosomes 1, 2, 6, 11, and 17 were frequently involved. These results suggest that renal cell carcinoma may be cytogenetically classified into 3 categories: (a) tumors with changes of chromosome 3: (b) tumors with other clonal aberrations; and (c) tumors without clonal changes. Rearrangements of chromosome 3 may be possibly associated with the genesis and/or progression of renal cell carcinoma.

Adult↗

Vascular invasion as a prognosticator of metastatic disease in nonseminomatous germ cell tumors of the testis. Importance in "surveillance only" protocols.

Forty-five nonseminomatous germ cell carcinomas of the testis were evaluated retrospectively to define the biologic features associated with the occurrence of metastatic disease. A statistical analysis of several pertinent clinical and pathologic factors was performed. The factors evaluated included: duration of symptoms before diagnosis, serum level of alpha-fetoprotein, serum or urinary level of human chorionic gonadotropin, testicular weight, extent of local tumor (pathologic T stage), and vascular invasion at the primary site. In each case, metastases were documented by a retroperitoneal node dissection, other biopsies, or by chest films. In 29 tumors with vascular invasion, 25 patients were seen with metastatic disease. In 16 tumors without vascular invasion, 3 patients demonstrated metastasis. The presence or absence of vascular invasion was strongly correlated with concomitant lymph node involvement or subsequent appearance of other metastatic disease (chi-square = 17.19). Additionally, vascular invasion in bifactoral++ analysis with tumor size and pathologic T stage proved a significant prognosticator even in low-staged (chi-square = 8.48) and small tumors (chi-square = 8.13). The implications of these findings, both as an adjunct to the staging of nonseminomatous germ cell tumors and in the management of clinical Stage I lesions, are discussed.

Adolescent↗

A simplified technique for quantifying 24-h whole body retention of 99mTc-labeled methylene diphosphonate (MDP).

A simple technique for measuring 24-h whole-body retention (24-h WBR) of 99mTc-labeled methylene diphosphonate (MDP) is described. We chose a standard thyroid probe-scaler system (Picker-Magna Scanner) as our counting instrument and characterized it relative to: photon saturability; optimum counting time post administration; patient positioning; and results with prostate cancer patients with positive/negative scintigram diagnoses for bone metastases. Whole body retention values of 99mTc at 24 h were easily measured with our instrumentation. Initially whole body count rates were determined at 5-min post injection and, again at 24 h. Data accumulated prior to the 5-min time period were inaccurate due to a higher sensitivity for the activity in the early circulation. Also, initial count rates obtained from patients injected with (740 MBq) (20 mCi) 99mTc-MDP usually required a correction due to detector saturation. The data observed at 24 h, representing skeletal tracer uptake, required no such correction. Patient positioning was rigorously controlled for the two time intervals to insure constant geometry. The 24 h-WBR values measured for prostate cancer patients with positive bone scintigrams was significantly different from those patients with negative scintigrams (58.8 +/- 8.7% and 29.2 +/- 9.6% respectively). Measurement of the 24 h-WBR has great potential for following various pathologies in the clinical setting.

Bone Neoplasms↗

Validation of the tumor, nodes and metastasis classification of renal cell carcinoma.

A retrospective analysis of 252 patients with renal cell carcinoma was performed with the tumor, nodes and metastasis system of cancer staging. Each patient received a clinical and a pathological classification. Patient survival was calculated for each pT stage. All patients with stage pT1 disease (100 per cent) were alive at 5 years, as were 91 per cent of those with stage pT2 tumors. Higher T stages showed poorer survival; 58 per cent of the patients with stage pT3 and only 25 per cent with stage pT4 tumors were alive at 5 years. Invasion into the inferior vena cava (pT3c) had an adverse effect on survival, which was statistically significant compared to patients in the pT3a and pT3b subgroups. The type of surgical procedure performed had no influence on ultimate survival, nor did the use of adjuvant radiation therapy. The tumor, nodes and metastasis system clearly documents that the survival of patients with renal cell carcinoma depends on the local extent of the primary tumor, determined at the time of surgical exploration.

Adult↗

Full-dose irradiation for patients with invasive bladder carcinoma: clinical and histological factors prognostic of improved survival.

We reviewed the outcome of 55 patients treated from 1974 to 1982 by full-dose radiation therapy (6,400 to 6,800 rad) to identify factors associated with tumor radioresponsiveness and patient cure. All patients had histological proof of muscle invasion by tumor. Of the patients 8 (14 per cent) had clinical stage T2, 29 (53 per cent) stage T3 and 18 (33 per cent) stage T4 disease. Thirteen patients are alive, all but 2 without evidence of cancer. Survivors include 1 of 9 patients who underwent salvage cystectomy for a local recurrence. The actuarial 5-year survival rate for the entire group was 28 per cent, with a corrected survival of 33 per cent. Median survival was 2.3 years. Corrected survival for patients with stages T2 and T3 disease was 45 per cent versus 9 per cent for those with stage T4 cancer (p equals 0.009). Within the group with stages T2 and T3 cancer (all with proof of muscle invasion) the most striking prognostic factor was papillary surface histological findings, with local control by radiation therapy alone of 63 per cent versus 20 per cent in the group with solid or flat tumors (p equals 0.01), and corrected 5-year survival of 62 per cent (papillary) versus 0 per cent (flat or solid) (p equals 0.002). Other significant prognostic factors for 5-year survival in this group were extent of transurethral resection (54 per cent complete versus 17 per cent incomplete, p equals 0.009) and ureteral obstruction on excretory urography (47 per cent without versus 14 per cent with, p equals 0.01). Our results suggest that full-dose radiation therapy can be offered to patients with muscle-invading bladder cancer, with a relatively higher probability of success in those with less advanced tumors by clinical stage, papillary surface histological findings and no ureteral obstruction, and in whom a complete transurethral resection is possible.

Aged↗