PubMed Health⌕ Search

Biomedical subjects

H B Carter

Publications and source records attributed to H B Carter.

At least 19 recordsLinked to original sources
PubMed2000

Today men with prostate cancer have larger prostates.

OBJECTIVES: To examine the relationship between prostate size and the method of cancer detection in men with organ-confined prostate cancer, and compare prostate size in men with and without cancer. METHODS: Prostate volume was evaluated in 720 men who had undergone radical prostatectomy for Stage T1c or Stage T2 cancer. Men with Stage T2 cancer were divided into those treated before 1989 (when widespread prostate-specific antigen [PSA] testing began), or not. Gland volume was also examined in 265 men participating in the Baltimore Longitudinal Study of Aging who had no clinical evidence of cancer. Volumes were compared using linear regression to allow for age. RESULTS: Prostate volume in men with Stage T1c cancer was statistically significantly larger than in men with Stage T2 cancer diagnosed in the pre-PSA era after adjusting for age (P = 0.0001), and statistically significantly larger than in men without cancer above age 47 years based on 95% confidence intervals. Prostate volumes in men with Stage T2 cancer diagnosed in the pre-PSA era and in men without cancer were not statistically significantly different. CONCLUSIONS: Prostate volume in men with PSA-detected, organ-confined cancer is larger than in men with palpable organ-confined cancer diagnosed in either the pre-PSA era or PSA era. These discrepancies may reflect a diagnostic bias due to the effect of benign prostatic hyperplasia on serum PSA that results in the selection of men with larger prostates for biopsy.

Adult↗
PubMed2000

Comparative efficiency of prostate-specific antigen screening strategies for prostate cancer detection.

CONTEXT: Despite widespread use of serum prostate-specific antigen (PSA) testing to detect prostate cancer, the relative effectiveness of different PSA screening strategies is unknown. OBJECTIVE: To compare prostate cancer mortality, PSA testing rates, and biopsy rates using various PSA screening strategies, including the standard strategy of annually testing men aged 50 through 75 years. DESIGN AND SETTING: A Monte-Carlo simulation based on a Markov model was used to simulate the natural history of prostate cancer using different starting ages, testing intervals, and PSA thresholds for prostate biopsy. Age-specific PSA levels and prostate biopsy detection probabilities were determined from population data and surgical series. MAIN OUTCOME MEASURES: Numbers of prevented prostate cancer deaths, PSA tests, and prostate biopsies per 1000 men aged 40 through 80 years, compared among 7 different strategies vs no screening. RESULTS: Compared with annual PSA testing beginning at age 50 years, the strategy of PSA testing at ages 40 and 45 years followed by biennial testing beginning at age 50 years was estimated to simultaneously reduce prostate cancer mortality and number of PSA tests and biopsies performed per 1000 men. Specifically, compared with no screening, the standard strategy prevents 3.2 deaths, with an additional 10,500 PSA tests and 600 prostate biopsies, while the earlier but less frequent strategy prevents 3.3 deaths, with an additional 7500 PSA tests and 450 prostate biopsies. Strategies that lowered the PSA threshold for prostate biopsy to below 4.0 ng/mL or strategies that used age-specific PSA levels were not more efficient than use of a PSA threshold of 4.0 ng/mL. These 2 findings remained true under all sensitivity analyses performed to test assumptions of the model. CONCLUSION: Recognizing that the efficacy of PSA screening is unproved, the standard strategy of annual PSA screening beginning at age 50 years appears to be less effective and more resource intensive compared with a strategy that begins earlier but screens biennially instead of annually. JAMA. 2000;284:1399-1405.

Adult↗
PubMed2000

Cancer cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer as vaccines for the treatment of genitourinary malignancies.

When irradiated and administered intradermally as vaccines, cancer cells engineered to secrete high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) by gene transfer elicit potent anticancer immune responses in a variety of animal tumor models. Upon vaccination, antigens present in the cancer cells are phagocytosed and processed by skin dendritic cells. These dendritic cells then prime anticancer immune responses by presenting antigenic peptides to T cells. The immune responses generated are capable of eradicating small but lethal cancer cell inocula with minimal toxicity in preclinical animal tumor studies. To develop this vaccination strategy for the treatment of human genitourinary cancers, we have conducted phase I clinical trials using human genitourinary cancer cells as sources of cancer cell antigens. In the first human clinical trial of genetically engineered cancer cell vaccines, a phase I clinical trial of kidney cancer cell vaccines (n = 18), kidney cancer cells were removed at surgery, propagated briefly in vitro, and then genetically modified to secrete high levels of GM-CSF via ex vivo transduction with the retrovirus MFG-GM-CSF. After irradiation, the kidney cancer cells were administered as vaccines to 18 patients with advanced kidney cancers. Vaccine treatment, which caused few side effects, nonetheless appeared to trigger anticancer immune responses manifest as conversion of delayed-type hypersensitivity (DTH) skin responses against irradiated autologous cancer cells after vaccination. Biopsies of vaccine sites yielded findings reminiscent of biopsies from preclinical animal model studies, with evidence of vaccine cell recruitment of dendritic cells, T cells, and eosinophils. One patient with measurable kidney cancer metastases treated at the highest vaccine dose level experienced a partial treatment response. The bioactivity of GM-CSF-secreting autologous cancer cell vaccines was confirmed in a phase I clinical trial for prostate cancer (n = 8). Vaccine cells were prepared from surgically harvested prostate tumors by ex vivo transduction with MFG-GM-CSF in a manner similar to that used for the kidney cancer trial. Vaccine treatment was well tolerated and associated with induction of anticancer immunity as assessed using DTH skin testing. In addition, new antiprostate cancer cell antibodies were detected in serum samples from treated men as a consequence of vaccination. These first clinical trials of GM-CSF-secreting cancer cell vaccines for the treatment of genitourinary cancers have demonstrated both safety and bioactivity, in that very few side effects have been seen and anticancer immune responses have been detected. Future clinical studies will be required to assess vaccine treatment efficacy, refine vaccination dose and schedule, define the appropriate clinical context for the use of such vaccines, and ascertain optimal combinations involving vaccines and other local or systemic anticancer treatments.

Adult↗
PubMed2000

Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer.

Insulin-like growth factors (IGFs) may play a role in prostate growth, hyperplasia, and malignancy. High plasma IGF-I has been associated with increased prostate cancer risk. In a prospective, cohort, case-control study in the Baltimore Longitudinal Study on Aging population, we examined prostate volume by magnetic resonance imaging, and prostate-specific antigen (PSA), IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases (n = 72) or age-matched controls (n = 127) and in 76 additional Baltimore Longitudinal Study on Aging men (normal subjects) with measured prostate volumes and no prostate cancer. We calculated adjusted odds ratios (OR) by logistic regression, relative risks for significant ORs, and receiver operator curves for prostate cancer, using serum measures alone and in combination. Adjusted ORs for the high vs. low tertile were: for IGF-I, 3.1 [confidence interval (CI), 1.1-8.7]; for IGF-II, 0.2 (CI, 0.07-0.6); for IGFBP-3, 0.71 (CI, 0.3-1.7); and for PSA, 12.5 (CI, 3.8-40.9). For significant ORs, relative risk estimates remained significant at 2.0 for IGF-I, 0.3 for IGF-II, and 5.5 for PSA. Receiver operator curves showed PSA to be the most powerful predictor of prostate cancer. Adding IGF-II to PSA improved prediction. IGF-II was significantly and inversely related (r = -0.219; P < 0.01) and PSA was directly and significantly related (r = 0.461; P < 0.0001) to prostate volume, whereas IGF-I and IBFBP-3 were not. High IGF-I and low IGF-II are independently associated with increased risk of prostate cancer, but PSA level is a much stronger predictor of prostate cancer in the ensuing 10 yr than either IGF-I or IGF-II. The absence of a relationship of IGF-I to prostate size is inconsistent with increased ascertainment in men with large prostates as the source of greater prostate cancer risk associated with IGF-I. Our data suggest that IGF-II may inhibit both prostate growth and development of prostate cancer.

Baltimore↗
PubMed2000

Is preoperative donation of autologous blood rational for radical retropubic prostatectomy?

PURPOSE: We investigated differences in the rate of homologous blood transfusion and the degree of anemia to determine whether it is rational to have patients donate autologous blood before radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the charts of 221 consecutive men who underwent radical retropubic prostatectomy performed by 1 surgeon in a 14-month period. About half of the patients donated autologous blood preoperatively. We evaluated perioperative hemoglobin, and the rate of autologous and homologous transfusion. RESULTS: The groups did not significantly differ in terms of demographic data, co-morbid conditions, clinical variables or hospitalization. Preoperatively mean hemoglobin plus or minus standard deviation was 13.4 +/- 1 and 14.7 +/- 1 gm./dl. in patients who did and did not donate blood, while homologous transfusion was required in 1 (1%) and 4 (3.5%), respectively (p = 0. 18). At hospital discharge anemia was more prevalent in nondonors. Of the men who did versus did not donate blood hemoglobin was less than 10 and less than 9 gm./dl. in 8.4% versus 34% (p <0.0001), and 12.5% versus 0% (p <0.0004), respectively. CONCLUSIONS: Our retrospective review of a cohort of patients who underwent radical retropubic prostatectomy showed no difference in homologous blood transfusion based on preoperative autologous donation status. Autologous donors had lower hemoglobin preoperatively, a higher rate of transfused units and higher hemoglobin at hospital discharge. Preoperative donation of autologous blood may not decrease the need for homologous transfusion in healthy patients undergoing radical retropubic prostatectomy.

Anemia↗
PubMed1999

Prostate-specific antigen testing of older men.

BACKGROUND: Elevated serum prostate-specific antigen (PSA) levels are predictive of a future diagnosis of prostate cancer. To test the hypothesis that older men with low PSA levels may require less intensive PSA testing because of a reduced prostate cancer detection rate, we evaluated the association between age, baseline PSA level, and prostate cancer detection. METHODS: We conducted a prospective cohort study among participants in a study of aging who had serial PSA measurements taken from age 60 or 65 years until they either were diagnosed with prostate cancer (cancer case subjects) or reached the age of 75 years (subjects without prostate cancer). The time of cancer detection among cancer case subjects was defined as the measurement date on which a PSA level above 4.0 ng/mL was detected (i.e., PSA conversion). Cancer case subjects and subjects without prostate cancer were analyzed according to baseline PSA level and age. RESULTS: All cancer case subjects in the 60-year-old cohort had baseline PSA levels above 0.5 ng/mL, and 14 of 15 cancer cases that would have been detected by a PSA conversion among the 65-year-old cohort were associated with baseline PSA levels of 1.1 ng/mL or more. If PSA testing were discontinued in men aged 65 years with PSA levels of 0.5 ng/mL or less, 100% (95% confidence interval [CI] = 78%-100%) of the cancers would still be detected by age 75 years; if PSA testing were discontinued in men aged 65 years who had PSA levels of 1.0 ng/mL or less, 94% (95% CI = 70%-100%) of the cancers would still be detected by age 75 years. CONCLUSIONS: These data suggest that a decrease in the intensity of screening among older men with low PSA values may not lead to an increase in undetected prostate cancer.

Age Factors↗
PubMed1999

Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer.

Vaccination with irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting gene-transduced cancer vaccines induces tumoricidal immune responses. In a Phase I human gene therapy trial, eight immunocompetent prostate cancer (PCA) patients were treated with autologous, GM-CSF-secreting, irradiated tumor vaccines prepared from ex vivo retroviral transduction of surgically harvested cells. Expansion of primary cultures of autologous vaccine cells was successful to meet trial specifications in 8 of 11 cases (73%); the yields of the primary culture cell limited the number of courses of vaccination. Side effects were pruritus, erythema, and swelling at vaccination sites. Vaccine site biopsies manifested infiltrates of dendritic cells and macrophages among prostate tumor vaccine cells. Vaccination activated new T-cell and B-cell immune responses against PCA antigens. T-cell responses, evaluated by assessing delayed-type hypersensitivity (DTH) reactions against untransduced autologous tumor cells, were evident in two of eight patients before vaccination and in seven of eight patients after treatment. Reactive DTH site biopsies manifested infiltrates of effector cells consisting of CD45RO+ T-cells, and degranulating eosinophils consistent with activation of both Th1 and Th2 T-cell responses. A distinctive eosinophilic vasculitis was evident near autologous tumor cells at vaccine sites, and at DTH sites. B-cell responses were also induced. Sera from three of eight vaccinated men contained new antibodies recognizing polypeptides of 26, 31, and 150 kDa in protein extracts from prostate cells. The 150-kDa polypeptide was expressed by LNCaP and PC-3 PCA cells, as well as by normal prostate epithelial cells, but not by prostate stromal cells. No antibodies against prostate-specific antigen were detected. These data suggest that both T-cell and B-cell immune responses to human PCA can be generated by treatment with irradiated, GM-CSF gene-transduced PCA vaccines.

Antigens, Neoplasm↗
PubMed1999

Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease.

OBJECTIVES: To evaluate the relation between age, prostate-specific antigen (PSA) level, and the probability of detecting curable prostate cancer. METHODS: A consecutive surgical series of radical prostatectomies was performed in 492 men with nonpalpable (Stage T1c) disease, who formed the study cohort (mean age 58 years). The cohort was systematically classified into three age groups ([1] 40 to 50 years [n = 69]; [2] 51 to 60 years [n = 227]; [3] 61 to 73 years [n = 196]) and five pretreatment PSA groups ([1] 2.5 to 4.0 ng/mL [n = 36]; [2] 4.1 to 6.0 ng/mL [n = 100]; [3] 6.1 to 8.0 ng/mL [n = 122]; [4] 8.1 to 10.0 ng/mL [n = 76]; [5] greater than 10.0 ng/mL [n = 135]). The percent probability of curable cancer was determined by logistic regression analysis. Curable cancer was defined as organ-confined tumor or a tumor with capsular penetration of low grade (Gleason score less than 7), with negative margins and no involvement of seminal vesicles or lymph nodes. RESULTS: A comparison within age groups and within PSA groups revealed that the probability of curable cancer was more closely associated with age than PSA level. Although the probability of curable cancer was closely related to PSA level across a wide range of PSA values (0.4 to 52 ng/mL), there was only minimal difference (2% to 4%) in the probability of curable cancer within the range of PSA values from 2.5 to 6.0 ng/mL for all ages. CONCLUSIONS: Age is a strong predictor of the probability of curable cancer. Thus, early detection efforts in younger men are more likely to lead to a decrease in prostate cancer mortality. These data suggest that the use of PSA thresholds below 4.0 ng/mL as an indicator of prostate cancer is unlikely to improve the probability of detecting curable cancer.

Adult↗
PubMed1999

Prostate cancer sampled on sextant needle biopsy: significance of cancer on multiple cores from different areas of the prostate.

OBJECTIVES: To determine the relationship between the location of positive sites, when more than one sextant site shows prostate cancer in a given patient, and pathologic stage, tumor volume, and margin status if radical prostatectomy is performed. METHODS: We performed biopsies using a spring-loaded biopsy gun on 343 Stage T1c (nonpalpable) radical prostatectomy specimens from each sextant site. RESULTS: In 56 cases, carcinoma was identified in two separate sextant sites. In 38 cases, the sites were vertical to each other (ie, left apex, left mid); in 8 cases, the sites were diagonal (ie, left apex, right mid); in 5 cases, the sites were horizontal (ie, left apex, right apex); and in 5 cases, they were not contiguous but were separated by an uninvolved sextant site (ie, left apex, left base). Tumors were more likely to be multifocal in cases with diagonally positive biopsies (P <0.0001) and horizontally positive biopsies (P <0.0001) than in those with vertically positive biopsies. No significant differences were found in organ-confined status and margin positivity among cases with different positive biopsy locations. The dominant tumor nodule was larger (mean 2.76 cc) in cases with noncontiguously positive biopsies than in all other groups combined (mean 1.44 cc) (P = 0.017). CONCLUSIONS: When more than one sextant site shows cancer, there are differences in terms of whether the tumors sampled are multifocal versus solitary depending on which sites are positive. However, no significant differences were found in predicting pathologic stage and margin positivity.

Biopsy, Needle↗
PubMed1999

The significance of prior benign needle biopsies in men subsequently diagnosed with prostate cancer.

PURPOSE: We determine the relationship between a history of benign needle biopsies, and the volume and location of cancer. MATERIALS AND METHODS: We evaluated 395 men who underwent radical prostatectomy for stage T1c (nonpalpable) prostate cancer. RESULTS: Of the men 74 had 1 or more prior benign needle biopsies. Prior benign biopsy correlated with tumor in the anterior or lateral portion of the radical prostatectomy specimen (p = 0.044) and prostate weight (p = 0.002). The likelihood of prior benign biopsy was 32.5% for men with a 75 gm. or greater prostate compared to 15.2% for those with a less than 75 gm. prostate. Although prior benign biopsy correlated with "very limited" tumor in the prostate (less than 0.2 cc, no Gleason pattern 4 or 5 and organ confined disease) (p = 0.005), only 28.4% of patients with prior benign biopsy had "very limited" tumor. In a multivariate analysis prior benign biopsy correlated only with anterior or lateral distribution and enlarged prostate size. Of the prior benign biopsy cases 12% had positive margins, average tumor volume was 1.15 cc and 27% had nonorgan confined disease. These figures were not different from those in cases with cancer on the first biopsy. In prior benign biopsy cases although PSA velocity predicted tumor volume and "very limited" tumor, a specific clinically useful cutoff value was not present. Needle biopsy grade and number of positive cores were not predictive of tumor volume or "very limited" cancer. CONCLUSIONS: Prior benign biopsy in men subsequently diagnosed with prostate cancer does not indicate indolent tumor. Benign biopsies are more likely in larger prostate glands and when cancer is in the anterior and lateral regions of the gland, suggesting the need for different biopsy strategies to improve cancer detection.

Biopsy, Needle↗
PubMed1998

Isolated vasculitis of the seminal vesicle.

We present 2 cases of histologically identified necrotizing vasculitis found in the seminal vesicles of radical prostatectomy specimens containing prostatic adenocarcinoma. In neither case did the patient suffer from symptoms nor show signs of systemic vasculitis. In 1 case, the vasculitis correlated clinically with dense adhesions noted at surgery that simulated extraprostatic tumor extension. Isolated vasculitis of the seminal vesicle is similar to reports of isolated vasculitis limited to other organs, in that local clinical findings may or may not be present, but the patient is free of systemic disease. Careful clinical follow-up is warranted to exclude the subsequent development of systemic vasculitis in these patients.

Aged↗
PubMed1998

Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings.

PURPOSE: Approximately 25% of radical prostatectomies performed for stage T1c disease show potentially insignificant prostate cancer. We previously reported the use of serum prostate specific antigen (PSA) density and needle biopsy findings to predict potentially insignificant cancer. We now evaluate whether using free/total serum PSA levels along with needle biopsy findings can better predict tumor significance. MATERIALS AND METHODS: We studied 163 radical prostatectomy specimens of stage T1c prostate cancer in which free/total serum PSA levels were determined. Free/total serum PSA levels were measured with Tandem-MP PSA assays. Insignificant prostate cancers were organ confined with tumor volumes less than 0.5 cc and Gleason score less than 7. Advanced tumors were either Gleason score 7 or greater, established extraprostatic extension with positive margins, or positive seminal vesicles or lymph nodes. Other cases were considered as moderate tumor. Moderate and advanced tumors were considered significant. RESULTS: Of the tumors 30.7% were insignificant, 49.7% moderate and 19.6% advanced. The best model to predict preoperatively insignificant tumor was a free/total PSA of 0.15 or greater and favorable needle biopsy findings (less than 3 cores involved, none of the cores with greater than 50% tumor involvement and Gleason score less than 7). Using this model of the 18 tumors predicted to be insignificant 17 were insignificant for a positive predictive value of 94.4%. Of the 145 cases that were predicted to be significant 112 were correctly predicted for a negative predictive value of 77.2%. There was only 1 tumor predicted to be insignificant which was classified as moderate. No tumor predicted to be insignificant was advanced. CONCLUSIONS: In conjunction with needle biopsy findings, free/total PSA levels accurately predict insignificant tumor in stage T1c disease.

Biopsy, Needle↗
PubMed1997

Recommended prostate-specific antigen testing intervals for the detection of curable prostate cancer.

OBJECTIVE: To evaluate prostate-specific antigen (PSA) testing intervals that maintain the detection of curable cancer and reduce unnecessary testing. DESIGN AND PATIENTS: Historical prospective study of serial PSA measurements at 2- and 4-year intervals from frozen serum samples of 40 men who eventually developed prostate cancer and 272 men without prostate cancer who were participants in a prospective aging study (Gerontology Research Center of the National Institute on Aging, the Baltimore Longitudinal Study of Aging) and the case series of 389 consecutive men treated surgically for nonpalpable prostate cancer. MAIN OUTCOME MEASURES: Probability of a PSA conversion to 4.1 to 5.0 ng/mL and to greater than 5.0 ng/mL at 2 and 4 years and probability of detecting curable prostate cancer by age and PSA level. RESULTS: When the pretreatment PSA level was less than or equal to 4.0 ng/mL, nonpalpable prostate cancers were highly likely (34/36, 94%) to be curable (organ-confined or capsular penetration with Gleason score < 7 and negative margins), and the majority (25/36, 69%) were small cancers (confined tumor < or = 0.5 cm3 with no Gleason pattern 4 or 5). When the pretreatment PSA level was greater than 4.0 ng/mL and less than or equal to 5.0 ng/mL, cancers were highly likely to be curable (32/36, 89%), and a minority were small cancers (12/36, 33%). When the pretreatment PSA level was greater than 5.0 ng/mL, 96 (30%) of 317 cancers were noncurable. The PSA conversion (for cancer cases) to a level at which cure is less likely (> 5.0 ng/mL) is rare (0%) after 2 or 4 years when the initial PSA is less than 2.0 ng/mL. PSA conversion to a range at which cancers are likely to be curable and less likely to be small (4.1-5.0 ng/mL) is rare after 2 years (0%-4%) when the baseline PSA level is less than 2.0 ng/mL but common when the baseline PSA level is between 2.1 and 3.0 ng/mL (27%) or 3.1 and 4.0 ng/mL (36%). CONCLUSIONS: These data suggest that for men with no cancer suspected on digital rectal examination, a PSA level of 4.0 to 5.0 ng/mL is an acceptable range for maintaining the detection of curable prostate cancer and a 2-year PSA testing interval is not likely to miss a curable prostate cancer when the initial PSA level is less than 2.0 ng/mL. Recognizing that 70% of a screened population between the ages of 50 years and 70 years have PSA levels less than 2.0 ng/mL, elimination of annual PSA testing for these men would result in large health care cost savings.

Aged↗
PubMed1997

Prediction of significant cancer in men with stage T1c adenocarcinoma of the prostate.

Widespread prostate specific antigen (PSA) testing results in detection of prostate cancer 4-6 years earlier than possible with digital rectal examination. Twenty to thirty percent of prostate cancers detected with PSA testing (non-palpable disease) are small tumors (< 0.5cc) that may be unimportant in some men. Pre-treatment criteria that include PSA density and prostate biopsy findings provide the means to assess the significance of prostate cancer after diagnosis. This information is useful when counseling men regarding management options for non-palpable, PSA detected prostate cancer.

Adenocarcinoma↗