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Biomedical subjects

A Pollack

Publications and source records attributed to A Pollack.

At least 145 records · Page 8Linked to original sources
PubMed1995

Aldose reductase (EC 1.1.1.21) activity and reduced-glutathione content in lenses of diabetic sand rats (Psammomys obesus) fed with acarbose.

The effects of acarbose on cataract development, lens aldose reductase (EC 1.1.1.21) activity and lenticular reduced-glutathione content in diabetic sand rats (Psammomys obesus) were determined. Diabetic sand rats (diet-induced) were fed on diets with or without acarbose (0.4 g/kg) for 39 d. Daily plasma glucose, cataract incidence, aldose reductase and glutathione content were evaluated. After 19 d on acarbose, daily plasma glucose profile was significantly reduced compared with that of sand rats not receiving acarbose. Cataract incidence was markedly lower in sand rats treated with acarbose. After 20 d, cataracts had developed in 90% of the animals fed without acarbose, whereas none was observed in sand rats fed with acarbose. After 37 d acarbose treatment the incidence of cataracts reached only 30%. Compared with untreated animals, lens aldose reductase activity was significantly lower in sand rats fed with acarbose for 39 d (7.6 (SE 0.78) v. 3.5 (SE 0.55) mumol NADPH/mg protein per min respectively, P < 0.001). Concomitantly, significantly higher lenticular protein and reduced-glutathione contents (90 (SE 23) v. 240 (SE 23.5) micrograms/mg tissue respectively, P < 0.001 and 369 (SE 48.6) v. 645 (SE 71.1) micrograms/mg tissue respectively, P < 0.001) were found. These results suggest that decreasing hyperglycaemia, accompanied by lower aldose reductase activity obtained by acarbose, led to a significant preventive effect on cataract development in sand rats.

Acarbose↗
PubMed1995

Right ventricular mass measurement by electron beam computed tomography. Validation with autopsy data.

RATIONALE AND OBJECTIVES: Validation of right ventricular mass quantitation by electron beam computed tomography in humans has not been performed. The ability of electron beam computed tomography to accurately determine the septal component of the right ventricle also has not been determined. This article addresses both issues. METHODS: Twenty human adult hearts obtained at autopsy were scanned by electron beam computed tomography in a short-axis projection. Planimetry of the right ventricular free wall and septal components of each slice was performed and summed to determine right ventricular mass. These measurements were compared against comparable measurements obtained by autopsy weights of the hearts. RESULTS: Right ventricular free wall weights by electron beam computed tomography (53.9 +/- 18.4 g) correlated well (slope = .92, r = .92, standard error of the estimate = 7.4 g, P < .001) with autopsy weights (55.8 +/- 18.4 g). Right ventricular septal weights by electron beam computed tomography (6.1 +/- 2.3 g) correlated poorly (slope = .04, r = .11, standard error of the estimate = 2.4 g, P = .65) with autopsy weights (13.9 +/- 6.3 g). CONCLUSIONS: Electron beam computed tomography quantitation of right ventricular mass is accurate in humans if only the free wall and not the septal component is utilized.

Aged↗
PubMed1995

The relationship of local control to distant metastasis in muscle invasive bladder cancer.

PURPOSE: We examined the relationship of local failure to distant metastasis in patients with muscle invasive bladder cancer. MATERIALS AND METHODS: This retrospective review included 240 patients treated with radical cystectomy with or without multiagent chemotherapy at our institution between 1984 and 1990 for clinical stage T2 to T4 transitional cell carcinoma of the bladder. The distribution of patients by clinical stage was 89 T2, 77 T3a, 51 T3b and 23 T4. Median followup was 55 months. RESULTS: The actuarial 5-year local control, freedom from distant metastasis and overall survival rates were 80%, 68% and 52%, respectively. There was a profoundly significant relationship between local failure and distant metastasis with distant metastasis in 56% of those with local failure. The actuarial 5-year freedom from distant metastasis rate for those with local control was 77% compared to 29% for those with local failure (p < 0.0001, log rank test). This relationship held when the group was subdivided by stage and when only cases of complete cystectomy were analyzed. The significance of this finding in light of the possible contribution of potential prognostic factors was examined. Univariate analyses revealed late clinical stage, abnormal pretreatment serum creatinine levels, the administration of chemotherapy, late pathological stage and lymph node involvement to correlate significantly with distant metastasis rates. Multivariate analyses using Cox proportional hazards models with freedom from distant metastasis as the end point revealed pathological stage, local failure and lymph node involvement to be the only significant covariates. CONCLUSIONS: Since local failure highly correlated with distant failure, treatment planning to optimize local control should be of foremost concern for those at high risk of failure by this mode (for example patients with T3b/4 disease). New treatment strategies, such as the use of preoperative radiotherapy as an adjunct to chemotherapy and radical surgery, should be considered in this high risk population.

Actuarial Analysis↗
PubMed1994

Preoperative radiotherapy for muscle-invasive bladder carcinoma. Long term follow-up and prognostic factors for 338 patients.

BACKGROUND: This study was performed to determine the importance of various potential prognostic factors in a large cohort of patients with transitional cell carcinoma of the bladder who were treated relatively uniformly at a single institution. METHODS: Between 1960 and 1983, 338 patients with muscle-invasive bladder carcinoma received preoperative radiotherapy (50 Gy in 25 fractions) followed 4-6 weeks later with radical cystectomy. Lymph node sampling was performed only when suspicious adenopathy was encountered. Ninety-eight percent of the patients completed the treatment as planned. The median followup for those living was 90 months. RESULTS: Actuarial 5-year pelvic control, disease free, and overall survival rates were 84, 51, and 44%, respectively, for all patients, and 88, 58, and 50%, respectively, for those who treatment completed. The overwhelming majority of failures were from distant metastases (43% at 5 years). The pathologic complete response rate was 42%, and downstaging was seen in 65% of the patients. Univariate actuarial analyses revealed clinical stage, clinical perivesical extension, tumor size, pretreatment hemoglobin level, pretreatment blood urea nitrogen (BUN) concentration, results of intravenous pyelography, sex, age, pathologic response, and pathologic complete response, correlated with disease outcome. A Cox proportional hazards model showed pathologic response (P < 0.0001), clinical stage (P = 0.01), hemoglobin level (P < 0.02), pathologic complete response (P < 0.05), and BUN concentration (P < 0.05), were correlated significantly with pelvic control. When only pretreatment factors were analyzed, clinical stage, hemoglobin level, and BUN concentration remained the only factors predictive of pelvic control. Similar results were obtained when overall survival was used as the endpoint, except that pathologic complete response and BUN concentration were replaced by sex as significant covariates. A Cox proportional hazards model using disease free status as the endpoint revealed pathologic response and tumor size to be independent predictors of patient outcome. Restricting this analysis only to pretreatment factors showed that pretreatment hemoglobin and tumor size were the only factors correlated with disease free status. CONCLUSIONS: The most significant prognostic factor was pathologic response, which correlated highly with all disease endpoints investigated. The most consistently significant pretreatment factors were hemoglobin level and clinical stage, although tumor size, sex, and BUN concentration also were independent predictors of patient outcome. These factors should be considered in patients receiving radiotherapy for bladder preservation.

Carcinoma, Transitional Cell↗
PubMed1994

Muscle-invasive bladder cancer treated with external beam radiotherapy: prognostic factors.

PURPOSE: To determine the relationship of several potential prognostic factors to the outcome measures of pelvic control, freedom from metastases, and overall survival for bladder cancer patients treated with definitive external beam radiotherapy. METHODS AND MATERIALS: The records of 135 patients treated with high-dose, planned continuous-course, external beam radiotherapy for muscle-invasive transitional cell bladder cancer were reviewed. These patients were treated to an average total dose of 6588 +/- 475 cGy with an average fractional dose of 207 +/- 18 cGy using megavoltage. Median potential follow-up for all patients, including those who died, was 249 months. RESULTS: The actuarial results at 5 year were 31% pelvic control, 58% freedom from metastases, and 26% overall survival. In the univariate analyses, several factors were correlated with disease outcome including clinical stage, tumor morphology, gross total transurethral resection (TURBT), findings at bimanual exam after TURBT, clinical perivesical extension, age, and clinical complete response at first follow-up cystoscopy (Clinical-CR). A Cox proportional hazards model revealed that only Clinical-CR was independently predictive of pelvic control. In terms of freedom from metastases, only Clinical-CR and clinical stage were significantly associated with outcome in the multivariate analysis. When the multivariate analysis was restricted to T2 and T3 tumors only, then clinical perivesical extension replaced stage as being associated with freedom from metastases. The only factors significantly related to overall survival in the Cox proportional hazards model were Clinical-CR, age, and complete TURBT; stage was of borderline significance when only pretreatment factors were considered. CONCLUSIONS: Clearly, the most important prognostic factor was Clinical-CR. The pretreatment factors of stage, clinical perivesical extension, and gross total TURBT also correlated with outcome, but, to a lesser degree. For patients medically unfit for radical cystectomy radiotherapy is a viable option, particularly for selected patients. Patients with T4 tumors are poor candidates for definitive radiotherapy and should be treated palliatively if they cannot tolerate systemic therapy.

Aged↗
PubMed1994

Serum prostate-specific antigen after radiation therapy for clinically localized prostate cancer: prognostic implications.

PURPOSE: Serum prostate-specific antigen (PSA) levels following definitive radiation for prostate cancer are increasingly recognized as the most sensitive means to monitor disease status. However, beyond general agreement that patients fare poorly when posttreatment PSA levels fail to normalize, many questions relative to postirradiation PSA remain unanswered. This study evaluates the potential prognostic value of postirradiation PSA in a large cohort of patients followed with serial PSA determinations. METHODS AND MATERIALS: We analyzed disease outcome in 427 patients with clinical stages T1 (122 men), T2 (147 men), T3 (152 men), and T4 (six men) prostate cancer receiving definitive external radiation as sole therapy and followed for times ranging from 9-73 months (median 30 months) with a total of 2260 posttreatment PSA values. RESULTS: Excluding three patients who died due to intercurrent illness without a posttreatment PSA, postirradiation PSA fell in 416 of 424 men (98%). Prostate-specific antigen levels continued to fall for up to 12 months but there was no evidence of significant declines beyond that. The time to nadir PSA was: 3 months, 60 patients; 6 months, 68 patients, 9 months 148 patients; 12 months, 144 patients. Time to nadir was not a significant determinant of outcome. Prostate-specific antigen levels at 3 and 6 months and the nadir level were individually highly correlated with outcome. In multivariate analyses of posttreatment values, only the nadir value was independently significant, with increasing relapse rates as its value was higher. It retained significance when pretreatment PSA level was included in the model. Nadir values ranged from undetectable (52 patients) to 20.3 ng/ml with a median of 1.1 ng/ml. Nadir values down to 1 ng/ml were prognostic; below 1 ng/ml (182 patients) the nadir value no longer yielded prognostic information additional to that inherent in the pretreatment value. Only patients with nadir levels < 1 ng/ml fared well (5-year incidence of relapse or rising PSA 17%); however, if the pretreatment level exceeded 30 ng/ml, then even a nadir level < 1 ng/ml was associated with a 40% failure rate at 5 years. CONCLUSION: The nadir PSA value after radiation is a significant posttreatment determinant of outcome and was second only to the pretreatment value. Surprisingly low nadir values were prognostically significant. Only patients whose nadir falls below 1 ng/ml can be said to have achieved a biochemical complete remission. However, even such low nadir values do not portend durable disease control for patients with high pretreatment PSA levels.

Aged↗
PubMed1994

Influence of initial presentation on treatment outcome of clinically localized prostate cancer treated by definitive radiation therapy.

PURPOSE: The increasing proportion of early stage prostate cancer diagnosed by various early detection methods together with reports espousing watchful waiting as a management option raise the possibility that patients may be selected for surveillance according to their initial presentation. METHODS AND MATERIALS: The outcome for 427 men with clinical stages T1 to T4 localized prostate cancer treated with radiation therapy was evaluated according to their presentation: elevated prostate-specific antigen (PSA) level; abnormal digital rectal examination; or, urologic symptomatology. RESULTS: With a median follow-up of 30 months, there were no significant differences in disease outcome according to initial presentation. The actuarial incidence of relapse at 5 years was: PSA-detected (54 patients), 24%; digital rectal-detected (173 patients) 29%; and, symptom-detected (200 patients) 31% (p = 0.79). Likewise, there were no significant differences in the incidence of postradiation rising PSA profiles among the three groups. The actuarial incidence of relapse and/or rising PSA at 5 years was: PSA-detected 35%; digital rectal-detected 42%; symptom-detected, 48% (p = 0.72). On the other hand, T-stage, Gleason grade, pretreatment PSA, pretreatment acid phosphatase, and transurethral resection in T3/T4 disease were each highly correlated with outcome. In multivariate proportional hazards regression pretreatment PSA (p = 0.0003), Gleason grade (p = 0.045), and transurethral resection in T3/T4 disease (p = 0.0562) correlated with outcome, but initial presentation did not (p = 0.25). CONCLUSION: The absence of a prognostic gradient, good to bad, from PSA-detected through digital rectal-detected to symptom-detected cancer suggests that the initial presentation of patients with localized prostate cancer is not a valid basis for selecting watchful waiting vs. initial treatment.

Aged↗
PubMed1994

Prostate specific antigen doubling time and disease relapse after radiotherapy for prostate cancer.

BACKGROUND: Serum prostate specific antigen (PSA) correlates with prostate tumor volume. Therefore, PSA-doubling time (PSA-DT) in patients with a rising PSA profile after radiotherapy should be predictive of the time to clinical disease relapse. The purpose of this study was to characterize the relationship between PSA-DT and the time to disease relapse after the onset of a rising PSA (PSA-TTR) in 427 men treated in the PSA-era with high dose radiotherapy for Stages T1-4 adenocarcinoma of the prostate. METHOD: There were 119 patients with a rising PSA profile after radiotherapy, and of these, there was sufficient information to calculate PSA-DT using nonlinear least squares regression in 100. There were 44 patients in this cohort who had documented disease relapse. The median patient follow-up was 38 months. RESULTS: The average PSA-DT was 13.5 plus or minus 11.6 mo (+/- standard deviation). PSA-DT values correlated with tumor grade, pretreatment PSA, and stage. PSA-DT was also strongly related to the outcome measures of local relapse, distant metastases, and any disease relapse. The shorter the PSA-DT, the greater the risk of disease relapse. The average PSA-TTR was 10.1 plus or minus 8.2. The only prognostic factor that correlated with PSA-TTR was tumor grade. A linear regression analysis of normalized PSA-DT and PSA-TTR revealed a significant correlation in which a PSA-DT of 11 months predicted for disease relapse 24 months later. Because several factors including physician and patient preferences could alter this relationship, a comparison was made between the actuarial PSA rise time for patients treated in the PSA-era and actuarial clinical disease relapse using a cohort of similarly treated men from the pre-PSA-era (n = 798). The results showed the lead time to be over 40 months in the majority of patients and that this lead time was much shorter in those with high grade tumors. CONCLUSIONS: PSA-DT is a strong prognostic factor for patients with biochemical evidence of failure after radiotherapy. A short PSA-DT predicts for more rapid progression to symptoms. The timing of the progression from a rising PSA to clinical disease relapse is probably longer than expected and is estimated to be 40 months on average.

Adenocarcinoma↗
PubMed1994

Thymoma. A retrospective study of 87 cases.

BACKGROUND: The authors retrospectively analyzed 87 patients with malignant thymoma treated at M.D. Anderson Cancer Center between 1951 and 1990. The analysis examined the clinical stages, histologic types, and treatment modalities and attempted to determine if chemotherapy had an impact on survival. METHODS: The patients were divided into three groups by their year of treatment and treatment modality. Patients treated between 1951 and 1975 were in Group I; patients treated between 1976 and 1980 were in Group II; and patients treated between 1981 and 1990 were in Group III. Most of the patients (18 [72%] in Group I; 16 [62%] in Group II; and 18 [50%] in Group III) had surgical resection alone or with radiotherapy. Patients with advanced-stage disease in Group I received single-agent chemotherapy, whereas patients with advanced-stage disease in Group II received a different, combination chemotherapy regimen, and those in Group III were treated primarily with cisplatin- and doxorubicin-based combination chemotherapy, e.g., the cyclophosphamide doxorubicin, and cisplatin with or without prednisone. The 17 patients treated with cisplatin with or without prednisone were separately evaluated for survival according to their response. RESULTS: Twenty-eight patients (5 [20%] in Group I; 6 [23%] in Group II; and 17 [47%] in Group III) received chemotherapy alone or after surgery or radiotherapy. The cisplatin with or without prednisone regimen was used in 17 Group III patients for initial treatment or for relapse. The overall response rate among the patients receiving the cisplatin with or without prednisone regimen was 64%; 6 (35%) had a complete response, and 5 (29%) had a partial response. Thirty-one (36%) of the 87 total patients had 45 recurrent tumors; the lung (29%), pleura (22%), and mediastinum (18%) were the most common sites of recurrence, whereas bone was the most common distant metastatic site. The 5-year survival rate was 70% in patients with Stage I disease, 71% in patients with Stage II or III disease, and 46% in patients with Stage IV disease. The 10-year survival rate was 70% in patients with Stage I disease, 47% in patients with Stage II or III disease, and 21% in patients with Stage IV disease. Statistical analysis indicated a significant difference among the survival rates of patients with noninvasive Stage I, invasive Stage II plus III (P = 0.033), and Stage II plus III and IV tumors (P = 0.056), but not between patients with Stage II or III tumors. Patients with a major response to the cisplatin with or without prednisone regimen had a significant survival improvement compared to those with no response (P = 0.002, log-rank test). CONCLUSIONS: Because thymoma is a chemosensitive tumor and frequently recurs in patients with Stage II or greater disease, chemotherapy carries a potential survival benefit and should be incorporated into the multimodality approach to prolong disease-free survival.

Adolescent↗
PubMed1994

Near-diploidy: a new prognostic factor for clinically localized prostate cancer treated with external beam radiation therapy.

BACKGROUND: DNA ploidy is a significant prognostic factor in patients with prostate cancer. Using DNA/nuclear protein flow cytometry, a subpopulation of tumors with near-diploid DNA is identifiable. The prognostic significance of near-diploidy was examined. METHODS: Paraffin-embedded formalin fixed prostate tumor tissue from patients treated at M. D. Anderson Cancer Center with external beam radiation therapy was processed for DNA/nuclear protein flow cytometry. All patients had pretreatment and follow-up serum prostate specific antigen (PSA) levels. Seventy-six specimens were suitable for flow cytometric analysis. Tumors were classified as either diploid (n = 30), near-diploid (n = 24), or nondiploid (n = 22, tetraploid and aneuploid). Median follow-up time was 36 months. RESULTS: Diploid tumors were associated with a significantly better actuarial outcome at 4 years, compared with near-diploid tumors, using either biochemical relapse (rising PSA) or a composite end point of a rising PSA or clinical relapse (16% versus 52% relapse, P < 0.05, log-rank). Moreover, patients who had nondiploid tumors had the worst prognosis (77% relapse, composite end point). No significant difference was observed between diploid and near-diploid neoplasms regarding actuarial local control, freedom from metastasis, freedom from clinical relapse, or overall survival time. A Cox proportional hazards model, using the composite end point of a rising PSA or relapse, was performed with ploidy categorized as diploid, near-diploid, and nondiploid; pretreatment PSA, DNA ploidy, and tumor grade were found to be independent prognostic factors. When ploidy was categorized as diploid or near-diploid (nondiploid tumors excluded), pretreatment serum PSA and DNA ploidy were independent predictors of outcome. Ploidy remained an independent prognostic factor even when nondiploid tumors were excluded. CONCLUSIONS: These data show that patients who have near-diploid tumors have an intermediate prognosis between the more favorable diploid tumors and the less favorable nondiploid tumors.

Acid Phosphatase↗
PubMed1994

The T classification of clinically localized prostate cancer. An appraisal based on disease outcome after radiation therapy.

BACKGROUND: This study was performed to evaluate the use of the 1992 International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) T categories for localized prostate cancer treated with radiation therapy and to compare the prognostic power of this system with the Whitmore-Jewett scheme. METHODS: The outcome for 427 men with Stages A2-C or T1a-T4b prostate cancers, followed for a mean of 32 months after treatment, was evaluated for relapse or rising prostate-specific antigen (PSA) levels, disease relapse, metastatic failure, and local recurrence relative to the two staging systems. Univariate and multivariate analysis was used to compare the two staging systems. The T categories were based on digital rectal examination. RESULTS: At 5 years, the actuarial incidence of relapse or rising PSA level was as follows: Stage A2, 29%; Stage B, 41%; Stage C, 62%. The corresponding results according to T category were as follows: T1a, 0%; T1b, 37%; T1c, 23%; T2a, 39%; T2b, 38%; T2c, 42%; T3a, 53%; T3c, 68%; T4b, greater than 75%. Too few patients were in the T3b and T4a categories. The following five-category grouping was significantly superior prognostically to the Whitmore-Jewett system: T1a, T1c, T1b/T2, T3, T4. The actuarial incidences of relapse or rising PSA at 5 years were as follows: T1a, 0%; T1c, 23%; T1b/T2, 41%; T3, 61%; and T4, 75%. No differences were evident within the T2 or T3 categories. CONCLUSIONS: The current UICC/AJCC system appears to be a valid method for categorizing a primary prostate carcinoma. This system defines a greater number of meaningful tumor categories and is prognostically superior to the traditional Whitmore-Jewett scheme.

Actuarial Analysis↗
PubMed1994

Simultaneous cytokinetic measurement of aneuploid tumors and associated diploid cells following continuous labelling with chlorodeoxyuridine.

Cells from a murine tumor, MCa-K, were continuously labelled with the thymidine analogue chlorodeoxyuridine (CldUrd) and analyzed by bivariate flow cytometry in order to measure the growth fraction (GF) and potential doubling time (Tpot) of both the DNA-aneuploid tumor cells and the associated DNA-diploid cells. MCa-K has a DNA index of 1.7, rendering two, partially overlapping, populations observable with labelled and unlabelled cells in each population. The data from these tumors may be divided into three regions of differing DNA content, with one region containing a pure DNA-diploid population, a second region with both cell types, and a third region including only DNA-aneuploid cells. Equations are presented to characterize the fractions of labelled cells in each region as a function of labelling time and cell type, thereby permitting estimation of the proliferative properties of the populations. These equations include the possibility that DNA-aneuploid cells cease cycling both in G1 and in S phase to account for the observed numbers of unlabelled cells with S phase contents. The estimated value of Tpot of the DNA-diploid cells is 126.0 h with a GF of 42%, while that of the DNA-aneuploid cells is 36.9 h with a GF of 69%. It is also estimated that between 2% and 6% of all DNA-aneuploid cells starting DNA synthesis cease cycling, leading to 25% of the cells having an S-phase DNA content being noncycling.

Aneuploidy↗
PubMed1994

The prognostic significance of DNA ploidy in clinically localized prostate cancer treated with radiation therapy.

PURPOSE: To determine the prognostic significance of deoxyribonucleic acid (DNA) ploidy in comparison to pretreatment prostate specific antigen (PSA) and other prognostic factors for patients with adenocarcinoma of the prostate treated with external beam radiotherapy. METHODS AND MATERIALS: Paraffin-embedded prostatic adenocarcinoma material was obtained from patients treated from 1987-1991. Sufficient histologic material for flow cytometric DNA content analysis was obtained from 86 patients and adequate histograms were obtained from 76 of these. The DNA histogram profiles were classified as diploid, tetraploid, or aneuploid. Median patient follow-up was 36 months. RESULTS: There were 54 patients with diploid tumors, and 22 with nondiploid tumors (11 tetraploid and 11 aneuploid). Since the disease outcome for tetraploid and aneuploid tumors was the same, these were pooled (nondiploid tumors). The distribution of diploidy and nondiploidy correlated with pretreatment PSA (p < 0.0005) and grade (p = 0.055), but not with stage, pretreatment prostatic acid phosphatase, transurethral resection, pretreatment serum testosterone, or age. In actuarial univariate analyses, DNA ploidy was a significant predictor of outcome for local failure, distant metastases, any clinical relapse, rising PSA, and rising PSA and/or relapse. Ploidy was not a significant predictor of overall survival, although there were only six deaths. Diploidy predicted for improved outcome, for example, 34.6% incidence of a rising PSA and/or relapse at 4 years compared to 76.9% with nondiploidy (p < 0.0001). An actuarial univariate analysis of other potential prognostic factors using the composite endpoint of rising PSA and/or relapse also revealed pretreatment PSA, grade, pretreatment prostatic acid phosphatase, stage, and serum testosterone to be significant predictors of outcome. In Cox proportional hazards analysis, pretreatment PSA, DNA ploidy, and grade were the only independent prognostic factors for disease outcome using the composite endpoint. CONCLUSION: DNA ploidy is an independent predictor of outcome in patients with Stages T1-T3 prostate cancer treated with definitive external beam radiotherapy.

Adenocarcinoma↗
PubMed1994

Proliferation kinetics of recruited cells in a mouse mammary carcinoma.

Solid tumors contain populations of proliferating (P) and quiescent (Q) cells. Shifting between these populations occurs continuously and cells are recruited from quiescence to proliferate (Q-->P) as a result of exogenously applied or endogenous cell depleting stimuli. Direct measurements of the proliferation kinetics of these Q-->P cells in solid tumors are difficult to make because of the much larger percentage of P-cells. In order to specifically analyze the kinetics of the Q-->P cells, double thymidine analogue labeling was used. This was accomplished by first labeling in vivo all of the P-cells in MCaK tumors using continuous exposure to chlorodeoxyuridine (CldUrd) administered by a minipump over 21 h. About 75% of the aneuploid cells are P-cells based on CldUrd labeling. At different times after the pumps were removed, the tumors were pulse-labeled with iododeoxyuridine (IdUrd) and harvested 6 h later. A 3-color flow cytometry assay was used to simultaneously and independently analyze CldUrd and IdUrd incorporation, as well as DNA content. The Q-->P cells were identified as having only been labeled with IdUrd. The length of their S-phase was calculated from the movement of the Q-->P cells during the 6 h after IdUrd labeling. The results showed the length of S-phase for the recruited cells to be slightly, but significantly, longer than the length of S-phase for the total cells (11 h versus 9 h, respectively). Thus, the recruited cells appear to have slightly slower kinetics than the proliferating cells in the absence of a perturbing stimulus such as radiotherapy or chemotherapy.

Animals↗
PubMed1994

Development of proliferative retinopathy in a gestational diabetes patient following rapid metabolic control.

Rapid glucose control was achieved by insulin therapy in a patient diagnosed to have gestational diabetes at 8 weeks of pregnancy. A decrease of the initially high hemoglobin A1c level (16.2%) to normal values (5.9%) was achieved within 12 weeks. At 31 weeks severe bilateral proliferative diabetic retinopathy developed. To our knowledge this case is the first report of a patient with gestational diabetes who developed de novo proliferative diabetic retinopathy.

Adult↗
PubMed1994

The serum prostate-specific antigen level three months after radiotherapy for prostate cancer: an early indicator of response to treatment.

A total of 347 patients with stages A2-C adenocarcinoma of the prostate treated with external beam radiotherapy and with pretreatment and 3-month prostate-specific antigen (PSA) levels were studied to evaluate the potential prognostic significance of the fall in PSA concentration from its baseline (PSAB) to its 3-month (PSA3) level. PSA levels fell in 333 patients (96%). With two exceptions, the patients whose PSA level did not fall had low PSAB and remained without evidence of disease. Since PSA levels fall virtually always, the fact that a fall occurs is of no prognostic value. When the magnitude of the fall relative to baseline was examined, patients with the largest falls had the worst outcomes. This paradoxical result was explained by the relationship between PSAB and PSA3. Regression analysis showed that the fall in PSA level was approximately proportional to the cube root of the baseline value. Thus, patients with high PSAB had high falls, but a high PSAB was an overwhelming predictor for poor outcome. Hence, PSA fall relative to baseline was not a meaningful prognostic factor. The only factor of prognostic value was the absolute PSA3 value. Patients with PSA3 < or = 2 ng/ml fared well at 4 years (freedom from relapse, 91%; incidence of rising PSA profile, 20%); patients with PSA3 > 2, but < or = 10 ng/ml had an intermediate, individually indeterminate outcome (freedom from relapse, 51%; incidence of rising PSA profile, 58%); patients with PSA3 > 10 ng/ml can be said to have failed treatment (freedom from relapse, 50%; incidence of rising PSA profile, 90%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Early androgen ablation for stage D1 (N1 to N3, M0) prostate cancer: prognostic variables and outcome.

To elucidate the outcome for patients with stage D1 (N1 to N3, M0) prostate cancer we reviewed 179 patients with lymphadenectomy proved pelvic nodal metastases who underwent immediate androgen ablation as the only initial treatment. With a median followup of 43 months, the 5 and 8-year actuarial rates of freedom from disease progression were 55% and 25%, respectively, and the median interval to disease progression was 67 months. The 5 and 8-year survival rates were 85% and 57%, respectively. Median survival after disease progression was 36 months. Local and distant disease progression was equally important. At 5 and 8 years the incidence of local progression was 32% and 51%, respectively, while metastatic rates at the same intervals wer 22% and 44%, respectively. Multivariate regression revealed that tumor grade and transurethral resection in preoperative stage C disease correlated with disease progression. Pretreatment prostate specific antigen (PSA) levels were not predictive of outcome. The fact that transurethral resection predicted for local as well as distant failure suggests that the procedure selects for rather than aggravates adverse disease. Posttreatment PSA levels were a sensitive index of response to treatment and of subsequent outcome. All patients who failed to achieve undetectable PSA levels had relapse by 8 years, whereas those whose levels became undetectable experienced only a 5% incidence of disease progression. These data show that androgen ablation alone is not curative for node positive disease but is associated with significant disease control and good short-term (5-year) survival. The primary tumor is an important source of androgen insensitive cells and comprehensive treatment strategies for this stage of disease require attention to the primary tumor as well as microscopic metastases.

Adenocarcinoma↗