- Columbia, Maryland, United States
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Research Interests: Epidemiology, Gastroenterology, Cancer, Medicine, Humans, and 15 moreFemale, Male, Connecticut, Clinical Sciences, Aged, Middle Aged, Carcinoma, Adult, Age Factors, European Continental Ancestry Group, Neurosciences, Adenocarcinoma, cystadenocarcinoma, Family Characteristics, and Neoplasm metastasis
SUMMARY-This study conArms the major finding of Ederer and Mers-heimer that, among surgically treated patients with cancer of the lung, women have a more favorable prognosis, particularly when there is no evidence of spread beyond the... more
SUMMARY-This study conArms the major finding of Ederer and Mers-heimer that, among surgically treated patients with cancer of the lung, women have a more favorable prognosis, particularly when there is no evidence of spread beyond the lung. When adjustment was made for "normal mortality expectation " through the use of the relative survival rate, liHle correlation was found between age at diagnosis and survival. A marked difference was found between male and female patients with respect to histologic type. Adenocarcinomas and alveolar cell tumors accounted for a larger proportion of cases in women. Among patients with adenocarcinomas and alveolar cell tumors, survival rates were substantially higher in women-in localized cases as well as for all stages combined. Among patients with epidermoid carcinomas, survival rates in men and women were similar. Lobectomy was employed more frequently in treatment of women. This was associat~d with more frequent occurrence of adenocarci...
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ABSTRACT
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Research Interests: Cancer, Prostate Cancer, Medicine, Humans, African American, and 15 moreMale, Aged, Middle Aged, Carcinoma, Neoplasm Invasiveness, Adult, Prognosis, Age Factors, European Continental Ancestry Group, Health Services Accessibility, Neoplasm staging, Prostate carcinoma, Prostatectomy, High risk, and mass Screening
To determine what factors correlated with the failure of the survivors of childhood cancer to acknowledge their diagnosis. A follow-up interview with 1928 adults who survived childhood cancer to evaluate the late effects of cancer and its... more
To determine what factors correlated with the failure of the survivors of childhood cancer to acknowledge their diagnosis. A follow-up interview with 1928 adults who survived childhood cancer to evaluate the late effects of cancer and its treatment. Cancer was diagnosed in these survivors between 1945 and 1974 before they reached age 20: subjects had to have survived for at least 5 years and to have reached age 21. Fourteen percent of the survivors of malignancies at sites other than the central nervous system said that they had not had cancer. This proportion differed according to the survivors' race, the type of tumor and its treatment, the level of their father's education, the year of diagnosis, and the center where the tumor was diagnosed. Among survivors who knew that they had cancer previously, however, most (81%) correctly identified the type of treatment they had received. Physicians should be aware that a substantial proportion of long-term survivors of childhood cancer may not reveal their past history of cancer and its treatment, and possible clues to the cause of the presenting condition may thus be missed.
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Mesothelioma incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City), Los Angeles County, California, and the SEER Program of the National Cancer Institute were analyzed for... more
Mesothelioma incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City), Los Angeles County, California, and the SEER Program of the National Cancer Institute were analyzed for trends, using original cancer registry diagnoses. Results indicate a significant increase in incidence during 1973-80 for pleural mesothelioma among white males older than 55 at time of diagnosis but not for other age-race-sex-site subgroups. A histopathologic review of New York State and Los Angeles County cases by two independent pathologists, expert in the diagnosis of mesothelioma, lowered the overall estimates but a significant upward trend remained. The observed trend does not appear to be related to changes in diagnostic practice. The results of a five-member panel of expert pathologists will be published in a separate methodology paper.
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Research Interests: Genetic Toxicology, Risk, Health, Urban Health, Rural Health, and 7 moreHumans, Colorado, Sex Factors, Time Factors, Neoplasms, Age Factors, and Iowa
Radical retropubic prostatectomy (RRP) pathology from African American (AA) and White men from 1988 to 1999 was examined to determine if the pre-treatment factors PSA, clinical stage, biopsy grade, age at surgery, and year of surgery... more
Radical retropubic prostatectomy (RRP) pathology from African American (AA) and White men from 1988 to 1999 was examined to determine if the pre-treatment factors PSA, clinical stage, biopsy grade, age at surgery, and year of surgery (YOS) were predictive of extracapsular extension (ECE) and positive margins for each ethnic group. Clinical and pathologic data was collected on 179 AA and 548 white men undergoing RRP from 1988 to 1999 at a tertiary military medical facility. Logistic regression with multivariate analysis was used to determine which pre-operative data-points were predictive of pathologic ECE and positive margins for each ethnic group. PSA, biopsy grade, age, and YOS (more recent years had better surgical pathology) were predictive of ECE for AA and white men. PSA, biopsy grade, and YOS were predictive of positive margins for AA men, while PSA and YOS were predictive of positive margins for white men. PSA continues to be a strong predictor of ECE and positive margins for both AA and white men. However, we describe for the first time, YOS being predictive of ECE and positive margins for both AA and White men, using multivariate regression analysis. This is thought to be reflective of the improving public awareness of prostate cancer that has occurred during the PSA-era, resulting in patients participating in screening programs and being diagnosed earlier. Close follow-up of these patients is warranted to determine if the improved pathologic stage of those patients treated more recently translates into improved disease-specific mortality.
Research Interests: Health Education, Logistic Regression, Multivariate Analysis, Prospective studies, Humans, and 15 moreAfrican American, Male, Exploration, Genetic determinism, Aged, Middle Aged, Neoplasm Invasiveness, Ethnic Group, Multivariate Regression, Age Factors, European Continental Ancestry Group, Military Personnel, Adenocarcinoma, Neoplasm staging, and Macho
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Because of their increased risk for second cancers, childhood cancer survivors are people who really should not smoke, but available evidence suggests that they do. We studied the smoking habits of long-term childhood cancer survivors in... more
Because of their increased risk for second cancers, childhood cancer survivors are people who really should not smoke, but available evidence suggests that they do. We studied the smoking habits of long-term childhood cancer survivors in data collected from 1289 adult survivors of childhood cancer and 1930 of their sibling controls. Survivors were diagnosed with cancer between 1945 and 1974 when they were less than 20 years old. Using matched analyses that controlled for the influence of family, survivors were 8% less likely than controls to be current smokers, 13% less likely to be ever-smokers, but 12% less likely to have quit smoking; these differences were not statistically significant. In a logistic regression analysis there was a significant difference by year of diagnosis for current smoking rate ratios (RR); survivors were less likely to be current smokers if diagnosed in recent years (RR = 0.76; 95% confidence intervals = 0.58-0.98, between 1965-74) and quite similar to controls if diagnosed in earlier years (RR = 1.05 between 1945 and 1954). In our group of long-term cancer survivors, the reduction in current smoking came about because survivors were more inclined never to start smoking than controls. Once addicted to tobacco, they were less likely to quit. While the fact that survivors are less likely to start smoking is encouraging, the persistence of smoking habits strongly suggests the need for continuing efforts to prevent smoking in this most vulnerable group.
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Blinded evaluation of reverse transcriptase-polymerase chain reaction prostate-specific antigen peripheral blood assay for molecular staging of prostate cancer 1 1 The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views...more
The reverse transcriptase-polymerase chain reaction (RT-PCR)-prostate-specific antigen (PSA) assay to detect presumed occult micrometastatic prostate cancer has been controversial, and this molecular staging has been thought to be... more
The reverse transcriptase-polymerase chain reaction (RT-PCR)-prostate-specific antigen (PSA) assay to detect presumed occult micrometastatic prostate cancer has been controversial, and this molecular staging has been thought to be clinically useful by some groups but not others. We used a sensitive nested RT-PCR assay with specific primers derived from the PSA sequence and a very stringent two-step PCR protocol with denaturing temperature of 94 degrees C annealing and extension temperature of 68 degrees C. This method enabled us to detect PSA-expressing LNCaP prostate cancer (PC) cells as low as one cell of 10 million lymphocytes (1/10(7)). Ninety-six patients with PC were studied, including 85 before radical prostatectomy (RP), and 22 controls, including healthy men and women and men with benign prostatic hyperplasia. In 85 patients undergoing RP, a minimum of two independent RT-PCR-PSA assays detected circulating prostate cells preoperatively in 27 patients (31.8%). Of 12 patients with locally advanced or advanced stage cancer, RT-PCR-PSA was positive in 5 (41.7%); of the 22 controls, no patient was RT-PCR-PSA positive. In 10 randomly selected cases, the RT-PCR product was confirmed as PSA by DNA sequencing. Of the 27 patients undergoing RP who were RT-PCR positive, 11 (40.7%) had non-organ-confined disease (pT3a or greater), and of the 58 patients who were RT-PCR negative, 32 (55.2%) had non-organ-confined disease. Patients with RT-PCR positive results also had lower margin positivity (9 of 27, 33.3%) than did patients with RT-PCR negative results (21 of 58, 36.2%). Finally, at a mean follow-up of 25.7 months, 5 (18.5%) of 27 RT-PCR positive patients had recurrence (PSA) compared with 14 (24.1%) of 58 RT-PCR negative patients. On the basis of this blinded study, RT-PCR for PSA-expressing cells in 85 patients before RP is not related to clinical stage, age, race, grade, Gleason sum, serum PSA or prostatic acid phosphatase, tumor volume, or tumor multifocality. RT-PCR positivity did not predict pathologic stage or early PSA recurrence. A standardized RT-PCR assay needs to be developed to account for interlaboratory discrepancies.
Research Interests: Urology, Prostate Cancer, Humans, Female, Male, and 14 moreClinical Sciences, Aged, Middle Aged, Department of Defense, Base Sequence, Prostate Specific Antigen, Radical Prostatectomy, Predictive value of tests, Benign Prostate Hyperplasia, DNA sequence, reverse transcriptase polymerase chain reaction, Neoplasm staging, Prostatic neoplasms, and Peripheral blood
Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. Recent data based upon whole-mounted step-sectioned... more
Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. Recent data based upon whole-mounted step-sectioned radical prostatectomy specimens using a 3-D computer assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was shown to be superior to the traditional sextant biopsy. This pattern includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in a small cohort of patients. We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3% (19/35) were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7% (16/35) of patients were diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the apex and mid portion of the gland are the most important.
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Objective:Radical retropubic prostatectomy (RRP) pathology from African American (AA) and White men from 1988 to 1999 was examined to determine if the pre-treatment factors PSA, clinical stage, biopsy grade, age at surgery, and year of... more
Objective:Radical retropubic prostatectomy (RRP) pathology from African American (AA) and White men from 1988 to 1999 was examined to determine if the pre-treatment factors PSA, clinical stage, biopsy grade, age at surgery, and year of surgery (YOS) were predictive of extracapsular extension (ECE) and positive margins for each ethnic group. Methods:Clinical and pathologic data was collected on 179 AA and 548 white men undergoing RRP from 1988 to 1999 at a tertiary military medical facility. Logistic regression with multivariate analysis was used to determine which pre-operative data-points were predictive of pathologic ECE and positive margins for each ethnic group. Results: PSA, biopsy grade, age, and YOS (more recent years had better surgical pathology) were predictive of ECE for AA and white men. PSA, biopsy grade, and YOS were predictive of positive margins for AA men, while PSA and YOS were predictive of positive margins for white men. PSA continues to be a strong predictor of ...
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Human herpesvirus-6 (HHV-6), a ubiquitous virus that causes exanthem subitum and occasional cases of infectious mononucleosis, hepatitis and other viral syndromes, has also been associated with acute lymphocytic leukemia (ALL) in... more
Human herpesvirus-6 (HHV-6), a ubiquitous virus that causes exanthem subitum and occasional cases of infectious mononucleosis, hepatitis and other viral syndromes, has also been associated with acute lymphocytic leukemia (ALL) in children. To further investigate this association, we obtained sera from 50 patients with ALL and 50 age-sex matched controls. Antibodies to HHV-6 were determined using ELISA and indirect immunofluorescent antibody (IFA) tests. No significant difference between antibody titers in the cases and controls was observed. Since seroepidemiologic studies have demonstrated higher HHV-6 antibody titers in young children than in adults, this serologic study suggests that the previous association reported for HHV-6 and ALL was a result of the age of the population rather than a relationship between the virus and the disease.
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Expression of tumor suppressor gene, MASPIN, is associated with inhibition of tumor cell invasion and metastasis. Loss of or decreased expression of Maspin is found frequently in breast and prostate cancer cells. The objective of this... more
Expression of tumor suppressor gene, MASPIN, is associated with inhibition of tumor cell invasion and metastasis. Loss of or decreased expression of Maspin is found frequently in breast and prostate cancer cells. The objective of this study is to investigate Maspin expression in prostate tumor specimens and explore the mechanisms of hormonal regulation of Maspin expression in prostate tumors. Immunohistochemical staining of Maspin expression was performed on surgical whole-mounted prostate specimens. The expression of Maspin was scored on individual tumors. Correlation of Maspin expression with clinicopathological features was analyzed for statistical significance. Androgen ablation-induced Maspin expression was analyzed by Maspin promoter luciferase reporter assay and quantitative reverse transcription-PCR analysis of endogenous Maspin expression in LNCaP cells in vitro and in animal model. Comprehensive evaluation of Maspin expression profile in multiple tumor foci from whole moun...
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Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D)... more
Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-...
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To assess the ability of pretreatment and post-treatment prostate-specific antigen (PSA) measurements, clinical tumor stage, tumor grade, Gleason sum, race, age, and radiation dose to predict the recurrence of prostate cancer following... more
To assess the ability of pretreatment and post-treatment prostate-specific antigen (PSA) measurements, clinical tumor stage, tumor grade, Gleason sum, race, age, and radiation dose to predict the recurrence of prostate cancer following external beam radiation therapy (XRT) since the introduction of PSA as a tumor marker at one tertiary care center. The recurrence of prostate cancer among 371 evaluable patients of 389 patients treated with XRT at Walter Reed Army Medical Center was analyzed using Kaplan-Meier survival methodology and Cox multivariable regression models. Serologic (PSA) recurrence was determined using three consecutive rises in PSA after a nadir value. Clinical recurrence was defined as local recurrence (palpable or positive biopsy) and/or distant (radiographically evident) recurrence. Mean and median follow-up is 40.2 and 39.4 months, respectively (range 3.0 to 89.5), and minimum follow-up is 18 months for patients who were alive at the time of analysis. No patient r...
Research Interests: Urology, Treatment Outcome, Prostate Cancer, Multivariate Analysis, Humans, and 15 moreCox Regression, Male, Clinical Sciences, Aged, Middle Aged, Radiation Dose, Time Dependent, Multivariate Regression, Hormone Therapy, Department of Defense, Prostate Specific Antigen, Predictive value of tests, Local Recurrence, Disease Free Survival, and Prostatic neoplasms
To predict the risk of extracapsular extension and postoperative recurrence before radical prostatectomy (RP) for prostate cancer. We performed multivariate Cox regression analysis on preoperative variables in 260 clinically localized... more
To predict the risk of extracapsular extension and postoperative recurrence before radical prostatectomy (RP) for prostate cancer. We performed multivariate Cox regression analysis on preoperative variables in 260 clinically localized prostate cancer patients who underwent RP. With these data, we constructed a relative risk of recurrence (Rr) equation and an equation to predict the probability of extracapsular extension (PECE) before RP. Rr is calculated as exp[(0.47 x race + 0.14 x PSAST) + (0.13 x worst biopsy Gleason sum) + (1.03 x stage T1c) + (1.55 x stage T2b,c)], where PSAST indicates a sigmoidal transformation of prostate-specific antigen. PECE is calculated as 1/[1 + exp(-Z)], where Z = -2.47 + 0.15 (PSAST) + 0.31 (worst biopsy Gleason sum) + 0.18 (race) + 0.16 (stage T1c) + 0.38 (stage T2b,c). These two equations can be used preoperatively to predict the probability of extracapsular disease and the risk of prostate-specific antigen recurrence in patients undergoing RP.
Research Interests: Military Medicine, Risk, Survival Analysis, Humans, Male, and 14 moreFollow-up studies, Aged, Middle Aged, Neoplasm Invasiveness, Public health systems and services research, Prognosis, Reproducibility of Results, Disease Progression, Prostate Specific Antigen, Proportional Hazards Models, Predictive value of tests, Neoplasm staging, Prostatic neoplasms, and Prostatectomy
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Prostate-specific antigen (PSA) test has become a widely used screening test in prostate cancer (CaP). However, low specificity of serum PSA leads to many false-positive and false-negative results and clinical uncertainty. Development of... more
Prostate-specific antigen (PSA) test has become a widely used screening test in prostate cancer (CaP). However, low specificity of serum PSA leads to many false-positive and false-negative results and clinical uncertainty. Development of CaP-specific diagnostic and prognostic markers is needed. Detection of circulating PSA-expressing cells (CPECs) in blood and bone marrow of CaP patients has potential in molecular diagnosis and prognosis. Our novel observations of the frequent presence of CPECs in CaP patients with organ-confined disease by reverse transcription (RT)-PCR-PSA assay in epithelial cells enriched from peripheral blood (ERT-PCR/PSA) have led us to test the hypothesis that CPECs have diagnostic potential for CaP. Epithelial cells from peripheral blood of radical prostatectomy patients or prostate biopsy patients were isolated using antiepithelial cell antibody, Ber-EP4-coated magnetic beads, and total RNA specimens from these cells were analyzed for PSA expression by RT-P...
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To determine the incidence of choriocarcinoma in the United States, the authors examined data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-1982, the National Center for Health Statistics, and the Centers for... more
To determine the incidence of choriocarcinoma in the United States, the authors examined data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-1982, the National Center for Health Statistics, and the Centers for Disease Control. They calculated an overall incidence of one per 24,096 pregnancies or one per 19,920 livebirths. Among whites, who comprised the majority of cases, the incidence was estimated to be one per 22,623 livebirths. After adjustment for age and birth effects, whites demonstrated the lowest rates, with blacks and other races at 2.1- and 1.8 fold elevated risk, respectively. The incidence among whites increased dramatically with maternal age, with women aged 40-44 years at an 8.6-fold excess risk compared with those aged 20-24 years. In addition, teenagers who gave birth were at higher risk. Possible reasons for these incidence patterns are discussed.
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Clinical reports of small numbers of pediatric brain tumor patients observed for brief periods suggest that long-term survivors continue to have major handicaps into adulthood. To quantify these late effects we interviewed 342 adults (or... more
Clinical reports of small numbers of pediatric brain tumor patients observed for brief periods suggest that long-term survivors continue to have major handicaps into adulthood. To quantify these late effects we interviewed 342 adults (or their proxies) who had CNS tumors diagnosed before the age of 20 between 1945 and 1974, survived at least 5 years, and reached 21 years of age. Survivors were 32 years old on average at follow-up. When compared with 479 matched siblings as controls. CNS tumor survivors were more likely to have died or to have become mentally incompetent sometime during the follow-up period. They were more likely to be at risk for such adverse outcomes as unemployment (odds ratio [OR], 10.8; 95% confidence interval [CI], 4.6 to 25.7], to have a health condition that affected their ability to work (OR, 5.9; CI, 3.7 to 9.4), to be unable to drive (OR, 28.8; CI, 6.9 to 119.9), or to describe their current health as poor (OR, 7.8; CI, 1.7 to 35.7). Unfavorable outcomes w...