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Biomedical subjects

A Pollack

Publications and source records attributed to A Pollack.

At least 37 records · Page 2Linked to original sources
PubMed2000

External beam radiotherapy dose response characteristics of 1127 men with prostate cancer treated in the PSA era.

PURPOSE: To characterize the relationship of radiotherapy dose to prostate cancer patient outcome, with an emphasis on the influence of pretreatment prognostic variables. METHODS AND MATERIALS: The 1127 Stage T1-T4 prostate cancer patients examined were treated consecutively with definitive external beam radiotherapy at the University of Texas-M.D. Anderson Cancer Center from 1987 to 1997. All had a pretreatment prostate-specific antigen (PSA) level. Treatment failure was defined as two consecutive PSA elevations on follow-up. There were 994 patients treated with a four-field box throughout to 60-70 Gy after a small reduction at 46 Gy and 161 treated with a six-field conformal boost after 46 Gy to 74-78 Gy. No patient received neoadjuvant or adjuvant androgen ablation. Median follow-up was 51.8 months. RESULTS: Patients were divided into three radiotherapy dose groups consisting of </=67 Gy (n = 500), >67-77 Gy (n = 495), and >77 Gy (n = 132). Relative to other prognostic factors, there were fewer patients treated to the highest dose level with a pretreatment PSA (PSAB) </=4 or >20 ng/ml, Stage T3/T4 disease, or a Gleason score of 2-6. Actuarial 4-year freedom from biochemical failure (bNED) rates for the entire cohort were 54%, 71%, and 77% (p < 0.0001) for the low-, intermediate-, and high-dose groups. PSAB, palpable stage, and Gleason score were also highly significant. In Cox proportional hazards regression, dose (p < 0. 0001 as a continuous or categorical variable) was an independent predictor of bNED, as were the other prognostic factors. Pairwise univariate comparisons showed that an increase in dose from </=67 Gy to >67-77 Gy was associated with improved bNED rates for all PSAB (</=10 and >10), stage (T1/T2 and T3/T4), and Gleason score (2-6 and 7-10) subgroups tested. In contrast, the only prognostic group that benefited from raising dose from >67-77 Gy to >77 Gy was patients with a PSAB >10 ng/ml; although trends were noted for Stage T1/T2 and Gleason 2-6 patients. Patients with the combined features of a PSAB >10 ng/ml and Stage T1/T2 disease had 4-year bNED rates of 61% and 93% at the intermediate- and high-dose levels. A strongly significant linear association between dose (60-78 Gy) and 4-year actuarial bNED was demonstrated for patients with these intermediate-risk features. CONCLUSION: Prostate cancer dose response to external beam radiotherapy should be considered in the context of pretreatment prognostic factors. Our data indicate that, for favorable patients with a PSAB of </=10 ng/ml, intermediate doses of >67-77 Gy provide the same rate of control as higher doses. However, longer follow-up may reveal a benefit to dose escalation >77 Gy, even in this favorable subset. Substantial and clinically relevant enhancements in bNED were seen at all dose levels for moderate-risk patients, such as those having a PSAB >10 ng/ml and Stage T1/T2 disease. Sustained bNED was not realized for high-risk patients, even using 78 Gy; these patients may be best treated with higher doses, whole pelvic irradiation, and/or androgen ablation plus radiation.

Aged↗
PubMed2000

Simultaneous estimation of T(G2+M), T(S), and T(pot) using single sample dynamic tumor data from bivariate DNA-thymidine analogue cytometry.

BACKGROUND: Estimating the duration of S phase (T(S) ) and the potential doubling time (T(pot) ) from a single time measurement of the movement of cells using bivariate cytometry is common. However, these estimates require an assumption of the duration of G2 + M (T(G2+M) ). Inspection of the measured dynamic quantities, relative movement [RM(t)], fractions of labeled divided and undivided cells (f(lu)(t) and f(ld)(t)) suggests that T(G2+M), T(S), and T(pot) can be determined simultaneously. METHODS: An equation connecting the growth of the cell population, time, and the dynamic quantities was determined. The equation cannot be solved analytically, but accurate approximations can be used to find T(pot). From this result, the value of T(G2+M) can be determined from f(ld)(t), and T(S) can be determined from RM(t). RESULTS: Kinetic parameters obtained from single time estimates using the new method compared to those obtained from the analysis of multiple time-point measurements of MCa-K and MCa-4 murine tumors are shown to be in close agreement. Moreover, estimates of T(G2+M) in MCa-4 tumors, treated with paclitaxel, provide extra information on the changes in T(G2+M). When applied to the rat R3327-G prostate tumor model following androgen ablation, a correlation analysis of the T(pot) values obtained by the new and previous single time-point methods demonstrates that the rank order from shortest to longest T(pot) values are largely preserved. CONCLUSIONS: The new procedure makes direct estimation of T(G2+M) possible from single time-dynamic measurements. The results from previous studies on T(S) and T(pot) are largely unchanged, but extra information is now available.

Adenocarcinoma↗
PubMed2000

Evaluation of alternative methods of cervical cancer screening for resource-poor settings.

BACKGROUND: Noncytologic methods of screening for cervical carcinoma and its precursor lesions are needed for resource-poor settings in which cervical carcinoma continues to be an important cause of morbidity and mortality. METHODS: Two thousand nine hundred forty-four women ages 35-65 years were recruited from Cape Town, South Africa and screened using a combination of a Papanicolaou (Pap) smear, human papillomavirus (HPV) DNA testing, direct visual inspection after the application of a 5% acetic acid solution (DVI), and cervicography. Cervicography was considered primarily as a method with which to quality control the DVI examinations. Women with squamous intraepithelial lesions (SIL) or carcinoma on Pap smear, positive DVI examination (acetowhite lesion or cervical ulcer/growth), high levels of high risk HPV DNA (relative light units [RLU] > 10x positive control), or positive Cervigramtrade mark were referred for colposcopy and cervical biopsy. RESULTS: Pap smears were positive in 8.1% of all women screened and identified 65 (78%) of all cases of biopsy confirmed high grade disease (high grade SIL or invasive carcinoma). DVI and cervicography were classified as positive in 18.1% and 10.5%, respectively, of women screened and identified 58 (67%) and 46 (58%) of all cases of high grade disease, respectively. The results of HPV DNA testing varied depending on the cutoff value used to define a positive result. At the standard cutoff level (RLU > 1x positive control), 16.2% of women screened were classified as high risk HPV DNA positive, as were 63 women with high grade disease (73%). CONCLUSIONS: DVI and HPV DNA testing identified similar numbers of high grade SIL (cervical intraepithelial neoplasia Grade 2,3) and invasive carcinoma cases as Pap smears. However, both classify considerably more women without cervical disease as being test positive.

Adult↗
PubMed2000

Human papillomavirus DNA testing for cervical cancer screening in low-resource settings.

BACKGROUND: In many low-resource settings, there are barriers to cytologic screening for cervical cancer. This study evaluates human papillomavirus (HPV) DNA testing as an alternative screening method. METHODS: Cervical samples from 2944 previously unscreened South African women aged 35-65 years were tested for high-risk types of HPV with the use of the Hybrid Capture I (HCI) assay. Women also had a Pap smear, direct visual inspection of the cervix, and Cervicography(TM). Women positive on any screening test were referred for colposcopy. Samples from women with biopsy-confirmed, low-grade squamous intraepithelial lesions (SILs) (n = 95), high-grade SILs (n = 74), or invasive cervical cancer (n = 12) and a random sample of women with no cervical disease (n = 243) were retested for HPV DNA with the use of the more sensitive Hybrid Capture II (HCII) assay. All P values are two-sided. RESULTS: High-risk HPV DNA was detected in 73.3% and 88.4% of 86 women with high-grade SIL or invasive cancer and in 12.2% of 2680 and 18.1% of 243 women without evidence of cervical disease, with the use of the HCI and HCII assays, respectively. HPV DNA testing with the HCII assay was more sensitive than cytology for detecting high-grade SIL and invasive cancer (McNemar's test, P =.04), and testing with the HCI assay was of equivalent sensitivity (P =.61). Cytology had a statistically significantly better specificity (96.8%) than either the HCI assay (87.8%) or the HCII assay (81.9%) (P<.01). Receiver operating characteristic curves identified test cutoff values that allow HPV DNA testing to identify 57% of women with high-grade SIL or cancer, while classifying less than 5% of women with no cervical disease as HPV DNA positive. CONCLUSIONS: HPV DNA testing has a sensitivity equivalent to, or better than, that of cytology. Since HPV DNA testing programs may be easier to implement than cytologic screening, HPV testing should be considered for primary cervical cancer screening in low-resource settings.

Adult↗
PubMed2000

HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer.

CONTEXT: More than half of the women diagnosed as having cervical cancer in the United States have not been screened within the last 3 years, despite many having had contact with the health care system. In many other regions of the world, there is only limited access to cervical cancer screening. OBJECTIVE: To determine whether testing of self-collected vaginal swabs for human papillomavirus (HPV) DNA can be used to screen for cervical disease in women aged 35 years and older. DESIGN: Cross-sectional observational study comparing Papanicolaou smears with HPV DNA testing of self-collected vaginal swabs. SETTING: Outpatient clinics in a periurban settlement outside of Cape Town, South Africa, between January 1998 and April 1999. PARTICIPANTS: Screening was performed on 1415 previously unscreened black South African women aged 35 to 65 years. INTERVENTION: Women self-collected a vaginal swab for HPV testing in the clinic and were then screened using 4 different tests: Papanicolaou smear, direct visual inspection of the cervix after the application of 5% acetic acid, cervicography, and HPV DNA testing of a clinician-obtained cervical sample. Women with abnormal results on any of the screening tests were referred for colposcopy. MAIN OUTCOME MEASURE: Biopsy-confirmed high-grade cervical squamous intraepithelial lesions or invasive cancer. RESULTS: High-grade squamous intraepithelial lesions were identified in 47 (3.4%) of 1365 women adequately assessed, and there were 9 cases of invasive cancer. Of women with high-grade disease, 66.1% (95% confidence interval [CI], 52.1%-77.8%) had high risk for HPV detected in self-collected vaginal samples, and 67.9% (95% CI, 53.9%-79.4%) had an abnormal Papanicolaou smear (P = .78). The false-positive rates for HPV DNA testing of self-collected vaginal samples and Papanicolaou smears were 17.1% (95% CI, 15.1%-19.3%) and 12.3% (95% CI, 10.5%-14.2%), respectively (P<.001). A high-risk type of HPV DNA was detected in 83.9% (95% CI, 71.2%-91.9%) of women with high-grade disease and 15.5% (95% CI, 13.6%-17.7%) of women with no evidence of cervical disease using a clinician-obtained cervical sample. CONCLUSIONS: These results indicate that HPV testing of self-collected vaginal swabs is less specific than but as sensitive as Papanicolaou smears for detecting high-grade cervical disease in women aged 35 years and older, and HPV testing offers an important new way to increase screening in settings where cytology is not readily performed.

Adult↗
PubMed2000

The early supra-additive apoptotic response of R3327-G prostate tumors to androgen ablation and radiation is not sustained with multiple fractions.

PURPOSE: The treatment of R3327-G tumor-bearing rats with androgen ablation (AA) via castration results in a supra-additive increase in apoptosis when 2-8 Gy gamma-irradiation (RT) is given as a single dose 3-14 days afterwards. We report here the dose response and effect of multiple fractions on this supra-additive apoptotic response. MATERIALS AND METHODS: Dunning R3327-G tumors were grown in the flanks of Copenhagen rats and the experiments were initiated at a tumor volume of 1.0-1.5 cc. Androgen ablation was achieved by castration 3 days prior to gamma-irradiation. Apoptosis was measured with a terminal deoxynucleotidyl transferase dUTP-biotin nick end-labeling assay 6-h after RT, unless otherwise specified. RESULTS: The dose response of the supra-additive apoptotic response was assessed by irradiating castrated animals with single doses of 2, 4, 8, or 16 Gy (n = 5 per group); tumor cell apoptosis at 6-h following irradiation was 2.4%+/-0.7% (+/- SEM), 4.2%+/-0.8%, 6.5%+/-1.4%, and 1.6%+/-0.3%, respectively. The RT only and AA only controls had < 1% apoptosis. The effect of fractionated RT on apoptosis was investigated to determine if the supra-additive apoptotic response was sustained with repeated 2-8 Gy fractions. When tumor-bearing animals were treated with repeated daily 2-Gy fractions, there was a reduction in the level of the supra-additive apoptotic response. After five 2-Gy fractions at 24-h intervals, apoptosis in the combined treated tumors was at levels seen in the AA controls. This raised the possibility that more than 24 h are required for recovery of the high supra-additive apoptotic levels seen after one fraction. When the interfraction interval was extended to 96 h, there was no significant increase in apoptosis over the additive effect of AA and RT. Although there was a decline in supra-additive apoptosis with repeated fractions, a dose response for tumor growth delay was evident for RT alone using 2.5-Gy fractions. Moreover, the combination of AA + fractionated RT resulted in a supra-additive enhancement in tumor growth delay to 5 cc. CONCLUSION: The early supra-additive apoptotic response from AA and single fraction radiation is not seen at high single fraction doses and is not sustained with repeated fractions. Therefore, the classical apoptotic response that occurs within 24 h of irradiation is not likely to be the main mechanism responsible for any clinical benefit seen with this combination.

Animals↗
PubMed2000

Optic nerve head blood flow measurements in non-arteritic anterior ischaemic optic neuropathy.

PURPOSE: To determine whether a decrease in blood flow, measured by the Heidelberg retiinal flowmeter, can characterise a disc at risk and predict the occurrence of non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: Blood flow, volume and velocity were measured in the optic nerve heads of 14 unaffected fellow eyes of patients with unilateral NAION, and compared with those of the affected eyes and of the eyes of 7 age-matched healthy controls. RESULTS: The affected eyes were found to differ from the unaffected eyes in all three haemodynamic parameters. Flow (measured in arbitrary units) is the most important parameter to be taken into consideration. Blood flow was significantly lower in affected than in unaffected eyes (upper rim, p < 0.05; lower rim, p < 0.025). It was also significantly lower in the unaffected eyes than in the healthy control eyes (p < 0.005, upper and lower rims), and in the affected eyes than in the control eyes (p < 0.00005, upper and lower rims). CONCLUSION: Decreased blood flow in the optic nerve head may indicate a risk for NAION and be considered a characteristic of the disc at risk.

Aged↗
PubMed2000

Two-stage cervical cancer screening: an alternative for resource-poor settings.

OBJECTIVE: We sought to introduce 2-stage cervical cancer screening in which 2 screening tests are performed sequentially (the second test is performed only if the first result is positive), followed by treatment if both test results are abnormal. STUDY DESIGN: A total of 1423 women from Cape Town, South Africa, were screened by direct visual inspection, human papillomavirus deoxyribonucleic acid testing, cytologic testing, and cervicography. If an abnormality was identified with any test, women were referred for colposcopy. RESULTS: Direct visual inspection, cytologic testing, human papillomavirus deoxyribonucleic acid testing, and cervicography, when used alone, identified 24, 26, 23, and 23 cases of disease (high-grade squamous intraepithelial lesion or cancer) per 1000 women, respectively, and would classify 182, 71, 137, and 112 women without disease as having abnormal results. Two-stage screening with direct visual inspection first, followed by cytologic testing, human papillomavirus deoxyribonucleic acid testing, or cervicography, would detect 18, 16, and 18 cases per 1000 women, respectively, and would substantially reduce the number of women without disease who were classified as having abnormal results. CONCLUSION: Two-stage screening for cervical cancer provides an attractive alternative to conventional screening for low-resource settings.

Adult↗
PubMed2000

Unusual gingival presentation of post-transplantation lymphoproliferative disorder: a case report and review of the literature.

Post-transplantation lymphoproliferative disorder is a well-documented complication of solid organ or bone marrow transplantation. Histologically, it is characterized by an abnormal proliferation of lymphocytes, which can range from benign B-cell hyperplasia to malignant lymphoma. Non-Hodgkin's lymphoma (NHL) is associated with several risk factors, such as congenital or acquired immunodeficiency states, autoimmune disorders, and infectious agents (eg, Epstein-Barr virus). Primary sites of presentation in the head and neck are Waldeyer's ring, paranasal sinuses, salivary glands, the oral cavity, and the larynx. Clinical appearance of gingival NHL varies but is usually found to be an asymptomatic gingival enlargement or mass resembling a pyogenic granuloma. We present a patient with a gingival ulceration that was subsequently diagnosed as Epstein-Barr virus malignant lymphoma resulting from the immunosuppression needed to prevent graft-versus-host disease after bone marrow transplantation.

Adult↗
PubMed2000

Prognostic factors in prostate cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in prostate cancer and stratified them into categories reflecting the strength of published evidence and taking into account the expert opinions of the Prostate Working Group members. MATERIALS AND METHODS: Factors were ranked according to the previous College of American Pathologists categorical rankings: category I, factors proven to be of prognostic importance and useful in clinical patient management; category II, factors that have been extensively studied biologically and clinically but whose importance remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected pertaining to existing prognostic factors, and (3) improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included preoperative serum prostate-specific antigen level, TNM stage grouping, histologic grade as Gleason score, and surgical margin status. Category II factors included tumor volume, histologic type, and DNA ploidy. Factors in category III included perineural invasion, neuroendocrine differentiation, microvessel density, nuclear roundness, chromatin texture, other karyometric factors, proliferation markers, prostate-specific antigen derivatives, and other factors (oncogenes, tumor suppressor genes, apoptosis genes, etc).

Biomarkers, Tumor↗
PubMed2000

Cyclophosphamide and carboplatin and selective consolidation in advanced seminoma.

This prospective Phase II study assesses the clinical efficacy and complications of a treatment regimen of combination chemotherapy with cyclophosphamide and carboplatin and selective consolidation in advanced seminoma. Of 46 patients who entered the study between December 1992 and October 1998, 46 were evaluable. Thirty-two achieved a complete remission (70%; 95% confidence interval, 56-83%) after chemotherapy alone. Fourteen achieved a complete remission (30%; 95% confidence interval, 18-46%) after chemotherapy plus consolidation. Forty-three of the 46 patients (93%; 95% confidence interval, 82-97%) remained in remission after a median follow-up period of 27.4 months. No patient experienced nephrotoxic, neurotoxic, or ototoxic effects or hemorrhagic cystitis. No patient had neutropenic fever requiring hospitalization. Thirteen % required platelet transfusions, and 9% required transfusions of packed RBCs. For patients with advanced seminoma, treatment with cyclophosphamide and carboplatin and selective consolidation is safe and effective.

Adolescent↗