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Biomedical subjects

A Pollack

Publications and source records attributed to A Pollack.

At least 19 recordsLinked to original sources

Lack of prostate cancer radiosensitization by androgen deprivation.

PURPOSE: The majority of clinical trials have shown that high-grade prostate cancer patients treated with androgen deprivation (AD) plus radiation (RT) have a survival advantage over those treated with RT alone. One possible mechanism for such a favorable interaction is that AD sensitizes cells to radiation. Animal model studies have provided suggestive evidence that AD sensitizes cells to radiation, but this mechanism is difficult to confirm conclusively in vivo. This question was investigated in LNCaP cells grown in vitro. METHODS AND MATERIALS: LNCaP cells were cultured in vitro in Dulbecco's modified Eagle's medium (DMEM)-F12 medium, containing 10% fetal bovine serum (complete medium [CM]). AD was achieved by culture in charcoal-stripped serum (SS)-containing medium. Replacement of androgen was done by adding the synthetic androgen R1881 at 1 x 10(-10) M to SS. Apoptosis was measured with a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Clonogenic survival was used to determine overall cell death, and the results were corrected for differences in plating efficiency from the various growth conditions. RESULTS: LNCaP cells were grown in CM, SS, or SS + R1881 medium, and cell counts obtained at 3, 4, and 5 days. Cell number increased exponentially in CM, whereas no increase in cell number was observed in SS medium. Cell counts from growth in SS + R1881 were intermediate between these extremes. Apoptosis was measured to determine if the combination of AD + RT in vitro resulted in supra-additive cell death, as has been previously described in an in vivo model system. The cells were cultured for 3 days before RT and apoptosis quantified 24 h after RT. There was a consistent supra-additive increase in apoptosis in cells exposed to AD + RT (2 or 8 Gy), as compared to either treatment given individually. In contrast, significant radiosensitization by AD was not observed by clonogenic survival even when the conditions of AD were varied. No radiosensitization was observed upon incubation in SS medium for 3, 4, or 5 days before RT, or extending AD after RT for 6 h before plating or 24 h after plating. CONCLUSION: The results show that in LNCaP prostate tumor cells supra-additive apoptosis does not translate into radiosensitization by clonogenic survival. Because clonogenic survival is a measure of overall cell death, either the level of apoptosis is too small a component of overall cell death or the increases in apoptosis occurred in a subpopulation that would have been killed by other mechanisms. Although the findings indicate that AD does not act by sensitizing prostate cancer cells to RT, the additive cell death and growth inhibitory effects of AD + RT are clinically meaningful.

Androgens↗

Radiotherapy for stage II testicular seminoma.

PURPOSE: To compare the outcome of patients with Stage II seminoma treated with prophylactic mediastinal irradiation, without any supradiaphragmatic irradiation, and with prophylactic left supraclavicular irradiation (PLSCI). METHODS AND MATERIALS: Between 1960 and 1999, 73 men with Stage II seminoma received postorchiectomy radiotherapy. Before 1984, 36 received prophylactic mediastinal irradiation (Series I); between 1984 and 1992, 17 received no supradiaphragmatic irradiation (Series II); and after 1992, 20 received PLSCI (Series III). The outcomes in these series were compared. RESULTS: The abdominal tumor sizes were as follows: Series I, 2 and 5 and 2 and 5 and 2 and 5 and <or=10 cm, n = 5 (p = 0.75). The median duration of follow-up was 14.4, 9.3, and 4.5 years for Series I, II, and III, respectively. The 6-year freedom from relapse was 94%, 71%, and 95% for Series I, II, and III, respectively. The differences between Series I and II (p = 0.014) and between II and III (p = 0.042) were significant. Three patients in Series II had a relapse in their left supraclavicular fossa-a failure pattern abrogated by PLSCI. CONCLUSIONS: PLSCI significantly diminishes the likelihood of relapse for Stage IIA, IIB, and IIC seminoma (mass <or=10 cm).

Abdomen↗

Policy analysis of cervical cancer screening strategies in low-resource settings: clinical benefits and cost-effectiveness.

CONTEXT: Cervical cancer is a leading cause of cancer-related death among women in developing countries. In such low-resource settings, cytology-based screening is difficult to implement, and less complex strategies may offer additional options. OBJECTIVE: To assess the cost-effectiveness of several cervical cancer screening strategies using population-specific data. DESIGN AND SETTING: Cost-effectiveness analysis using a mathematical model and a hypothetical cohort of previously unscreened 30-year-old black South African women. Screening tests included direct visual inspection (DVI) of the cervix, cytologic methods, and testing for high-risk types of human papillomavirus (HPV) DNA. Strategies differed by number of clinical visits, screening frequency, and response to a positive test result. Data sources included a South African screening study, national surveys and fee schedules, and published literature. MAIN OUTCOME MEASURES: Years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (cost per YLS). RESULTS: When analyzing all strategies performed as a single lifetime screen at age 35 years compared with no screening, HPV testing followed by treatment of screen-positive women at a second visit, cost $39/YLS (27% cancer incidence reduction); DVI, coupled with immediate treatment of screen-positive women at the first visit was next most effective (26% cancer incidence reduction) and was cost saving; cytology, followed by treatment of screen-positive women at a second visit was least effective (19% cancer incidence reduction) at a cost of $81/YLS. For any given screening frequency, when strategies were compared incrementally, HPV DNA testing generally was more effective but also more costly than DVI, and always was more effective and less costly than cytology. When comparing all strategies simultaneously across screening frequencies, DVI was the nondominated strategy up to a frequency of every 3 years (incremental cost-effectiveness ratio, $460/YLS), and HPV testing every 3 years (incremental cost-effectiveness ratio, $11 500/YLS) was the most effective strategy. CONCLUSION: Cervical cancer screening strategies that incorporate DVI or HPV DNA testing and eliminate colposcopy may offer attractive alternatives to cytology-based screening programs in low-resource settings.

Adult↗

Clinical staging of prostate cancer: reproducibility and clarification of issues.

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer adopted in 1992 is based on tumor-node-metastasis (TNM) designations. It has been widely accepted for use in local and advanced disease. The purpose of this study was to assess reproducibility of staging among observers and to help clarify staging issues. Twelve prostate cancer cases were sent to 20 physicians with special expertise in prostate cancer including eight urologists, eight radiation oncologists, and four medical oncologists. Physicians were asked to assign a stage based on the 1992 AJCC clinical staging. The most frequently reported stage assigned to each case was taken to be the consensus. Agreement was the percentage of physicians who reported that particular stage. Seventy-five percent of the physicians responded. The overall agreement for assignment of T stage was 63.9%. Differences were found by specialty for inclusion of available information in designating a T stage. The overall agreement for N stage was 73.8%. The most common designation was Nx regardless of availability of a computed tomography scan. The overall agreement for M stage was 76.6%. Without a bone scan the most common designation was Mx regardless of Gleason grade or prostate-specific antigen (PSA). A frequent comment was that PSA was more indicative of disease extent than current clinical staging. The reproducibility of the 1992 clinical AJCC staging is poor even among experts in the field. This problem arises primarily from disagreement regarding which studies are included in assigning a stage. Some of these difficulties are addressed in the 1997 revision. However, the clinical staging does not address the true biological significance of disease in many instances.

Humans↗

Treatment planning using a dose-volume feasibility search algorithm.

PURPOSE: An approach to treatment plan optimization is presented that inputs dose--volume constraints and utilizes a feasibility search algorithm that seeks a set of beam weights so that the calculated dose distributions satisfy the dose--volume constraints. In contrast to a search for the "best" plan, this approach can quickly determine feasibility and point out the most restrictive of the predetermined constraints. METHODS AND MATERIALS: The cyclic subgradient projection (CSP) algorithm was modified to incorporate dose--volume constraints in a treatment plan optimization schema. The algorithm was applied to determine beam weights for several representative three-dimensional treatment plans. RESULTS: Using the modified CSP algorithm, we found that either a feasible solution to the dose--volume constraint problem was found or the program determined, after a predetermined set of iterations was performed, that no feasible solution existed for the particular set of dose--volume constraints. If no feasible solution existed, we relaxed several of the dose--volume constraints and were able to achieve a feasible solution. CONCLUSION: Feasibility search algorithms can be used in radiation treatment planning to generate a treatment plan that meets the dose--volume constraints established by the radiation oncologist. In the absence of a feasible solution, these algorithms can provide information to the radiation oncologist as to how the dose--volume constraints may be modified to achieve a feasible solution.

Algorithms↗

Addition of radiation therapy to androgen ablation improves outcome for subclinically node-positive prostate cancer.

OBJECTIVES: To determine the outcome for node-positive prostate cancer treated by early androgen ablation with or without prostatic radiation. METHODS: Two hundred fifty-five men with lymphadenectomy-proven pelvic nodal metastases treated with early androgen ablation alone (n = 183) or with combined ablation and radiation (n = 72) between 1984 and 1998 were retrospectively reviewed for disease outcome and survival. Post-treatment disease status was based on the prostate-specific antigen levels or on the clinical and radiographic status for patients treated before 1987. Univariate and multivariate statistics were used to determine the prognostic factors and assess the influence of radiation treatment. RESULTS: With a median follow-up of 9.4 years, the 5, 10, and 13-year overall survival rate for those treated with early ablation alone was 83%, 46%, and 21%, respectively. The freedom from relapse or rising prostate-specific antigen rate for these patients was 41%, 25%, and 19% at 5, 10, and 13 years, respectively. Distant metastasis and local recurrence occurred with a 10-year actuarial incidence of 44% and 51%, respectively. With a median follow-up of 6.2 years, the 5 and 10-year overall survival rate for those treated with radiation and ablation was 92% and 67%, respectively. The freedom from relapse or rising prostate-specific antigen rate in these men was 91% and 80% at 5 and 10 years, respectively. The superior outcome for combined ablation and radiation was substantial and statistically significant in the univariate and multivariate analyses. CONCLUSIONS: Early androgen ablation alone has little curative potential for node-positive prostate cancer. The addition of prostatic radiation to ablation resulted in substantial and significant improvement in disease control and patient survival.

Adult↗

Infectious aneurysm clipping by an MRI/MRA wand-guided protocol. A case report and technical note.

Infectious aneurysms are potentially deadly sequelae of multiple etiologies, typically associated with subacute bacterial endocarditis (SBE). Since these aneurysms tend to be distal, there are no consistent landmarks by which to localize them, in contrast to more typical aneurysms that occur on the circle of Willis or proximal, large cerebral vessel bifurcations. In addition, they tend to be extremely friable and may be obscured by blood if intracranial hemorrhage (ICH) has already occurred. These factors make clipping these aneurysms technically difficult, and searching for easily ruptured aneurysms without standard landmarks adds risk to the procedure. In this report, we describe the case of a 9-year-old boy with SBE and subsequent ICH secondary to a mycotic aneurysm. This aneurysm was localized to within millimeters by the MRI protocol described herein. The aneurysm was excised and the patient recovered without incident. Thus, MRI/MRA-guided frameless stereotaxy may be useful for localizing distal mycotic aneurysms, improving patient outcome by decreasing morbidity and mortality.

Aneurysm, Infected↗

Adenoviral-mediated p53 transgene expression sensitizes both wild-type and null p53 prostate cancer cells in vitro to radiation.

PURPOSE/OBJECTIVE: The effect of adenoviral-mediated p53 transgene expression on the radiation response of two human prostate cancer cell lines, the p53(wild-type) LNCaP and p53(null) PC3 lines, was examined. The objective was to determine if this vector sensitizes cells to radiation independently of their p53 status. METHODS AND MATERIALS: A recombinant adenovirus-5 vector (RPR/INGN 201, Introgen Therapeutics, Houston, TX) containing a CMV promoter and wild-type p53-cDNA (Ad5-p53) was used to facilitate p53 transgene expression. A multiplicity of infection (MOI) of 10-40 viral particles per cell was used, based on Ad5/CMV/lacz infection and staining for the beta-galactosidase reporter gene product. Clonogenic assays were performed to evaluate the degree of sensitization to radiation of viral-transduced cells compared with irradiated nontransduced controls. The relative efficacy of these treatments to induce apoptotic cell death was determined using the TUNEL assay. RESULTS: The delivery of Ad5-p53 (10 MOI) reduced control plating efficiency from 36.5% to 0.86% in the LNCaP cell line and from 75.1% to 4.1% in the PC3 cell line. After correcting for the effect of Ad5-p53 on plating efficiency, the surviving fraction after 2 Gy (SF2) of gamma-irradiation was reduced over 2.5-fold, from 0.187 to 0.072, with transgene p53 expression in the LNCaP cell line. Surviving fraction after 4 Gy (SF4) was reduced over 4.5-fold, from 0.014 to 0.003, after Ad5-p53 treatment. In the PC3 cell line, Ad5-p53 (40 MOI) reduced SF2 over 1.9-fold from 0.708 to 0.367, and SF4 over 6-fold from 0.335 to 0.056. In both the LNCaP and PC3 cell lines, the combination of Ad5-p53 plus radiation (2 Gy) resulted in supra-additive apoptosis (approximately 20% for LNCaP and approximately 15% for PC3 at 50 MOI), above that seen from the addition of the controls; control vector Ad5-pA plus RT (0.15% for LNCaP and 1.44% for PC3), Ad5-p53 alone (28.6% for LNCaP and 21.7% for PC3), RT alone (0% for LNCaP and 0.23% for PC3), or Ad5-pA alone (0.1% for LNCaP and 0.29% for PC3). CONCLUSION: The clonogenic survival and apoptosis data demonstrate that p53 transgene expression sensitizes human prostate adenocarcinoma cells in vitro to irradiation. As this effect was observed in both the p53(wild-type) LNCaP and p53(null) PC3 lines, radiosensitization was independent of p53 status.

Adenoviridae↗

Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer.

PURPOSE: To determine the effect of radiotherapy dose on prostate cancer patient outcome and biopsy positivity in a phase III trial. PATIENTS AND METHODS: A total of 305 stage T1 through T3 patients were randomized to receive 70 Gy or 78 Gy of external-beam radiotherapy between 1993 and 1998. Of these, 301 were assessable; stratification was based on pretreatment prostate-specific antigen level (PSA). Dose was prescribed to the isocenter at 2 Gy per fraction. All patients underwent planning pelvic computed tomography scan to confirm prostate position. Treatment failure was defined as an increasing PSA on three consecutive follow-up visits or the initiation of salvage treatment. Median follow-up was 40 months. RESULTS: One hundred fifty patients were randomized to the 70-Gy arm and 151 to the 78-Gy arm. The difference in freedom from biochemical and/or disease failure (FFF) rates of 69% and 79% for the 70-Gy and 78-Gy groups, respectively, at 5 years was marginally significant (log-rank P: =.058). Multiple-covariate Cox proportional hazards regression showed that the study randomization was an independent correlate of FFF, along with pretreatment PSA, Gleason score, and stage. The patients who benefited most from the 8-Gy dose escalation were those with a pretreatment PSA of more than 10 ng/mL; 5-year FFF rates were 48% and 75% (P: =.011) for the 70-Gy and 78-Gy arms, respectively. There was no difference between the arms ( approximately 80% 5-year FFF) when the pretreatment PSA was < or = 10 ng/mL. CONCLUSION: A modest dose increase of 8 Gy using conformal radiotherapy resulted in a substantial improvement in prostate cancer FFF rates for patients with a pretreatment PSA of more than 10 ng/mL. These findings document that local persistence of prostate cancer in intermediate- to high-risk patients is a major problem when doses of 70 Gy or less are used.

Disease-Free Survival↗

Primary treatment of cystosarcoma phyllodes of the breast.

BACKGROUND: Cystosarcoma phyllodes is a rare sarcoma of the breast. Although surgical removal is the mainstay of treatment, the extent of surgery required (excision vs. mastectomy) and the need for additional local therapy, such as radiotherapy, are unclear. The current study evaluated the rate of local and distant failure, as well as potential prognostic factors, to better define appropriate treatment strategies. METHODS: One hundred one patients treated primarily for cystosarcoma phyllodes of the breast were evaluated. These tumors were classified histologically into benign (58%), indeterminate (12%), and malignant (30%) based on well defined criteria. Stromal overgrowth (29%) was considered separately. Surgery was comprised of local excision with breast conservation (47%) or mastectomy (53%). Microscopic surgical margins were negative in 99% of cases. Six patients received adjuvant radiotherapy. RESULTS: Overall survival for the 101 patients was 88%, 79%, and 62% at 5, 10, and 15 years, respectively. For patients with nonmalignant (benign or indeterminate) and malignant cystosarcoma phyllodes, the overall survival was 91% and 82%, respectively, at 5 years, and 79% and 42%, respectively, at 10 years. Similar rates were observed based on the presence or absence of stromal overgrowth. Local recurrence occurred in 4 patients, with an actuarial 10-year rate of 8%. Eight patients developed distant metastases, with an actuarial 10-year rate of 13%. Multivariate analysis using Cox proportional hazards regression revealed stromal overgrowth to be the only independent predictor of distant failure. CONCLUSIONS: Local failure in this group of largely margin negative patients with cystosarcoma phyllodes of the breast was low, showing that breast-conserving surgery with appropriate margins is the preferred primary therapy. The current study data do not support the use of adjuvant radiotherapy for patients with adequately resected disease. Patients with stromal overgrowth, particularly when the tumor size was > 5 cm, were found to have a high rate of distant failure; such patients merit consideration of a trial that examines the efficacy of systemic therapy.

Adult↗

Complications from radiotherapy dose escalation in prostate cancer: preliminary results of a randomized trial.

OBJECTIVE: To compare early and late side effects in prostate cancer patients with Stage T1b-T3 disease randomized to receive 70 Gy or 78 Gy. METHODS: There were 189 patients randomized with a minimum follow-up of 2 years, that were available for this analysis. All patients were initially treated with a 4-field box to an isocenter dose of 46 Gy at 2 Gy per fraction. In the 70-Gy arm, treatment was continued to a reduced volume using a 4-field box technique. In the 78-Gy arm, treatment was continued to a reduced volume using a conformal 6-field arrangement. Side effects were graded on a 1-4 scale, adapted from Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. RESULTS: No significant differences in acute rectal or bladder toxicity were seen between the two treatment techniques (p > 0.6 for all comparisons). The 5-year Kaplan-Meier risks of Grade 2 or higher late bladder toxicity were 20% and 9% for 70-Gy and 78-Gy groups, respectively (log rank, p = 0.8). The 5-year risks of Grade 2 or higher late rectal toxicity were 14% and 21% for 70 Gy and 78 Gy, respectively (p = 0.4). Dose-volume histogram analysis of the 78-Gy patients showed a significant correlation between the percentage of rectum irradiated to 70 Gy or greater and the likelihood of developing late rectal complications. Patients with more than 25% of the rectum receiving 70 Gy or greater had a 5-year risk of Grade 2 or higher complications of 37% compared to 13% for patients with 25% or less (p = 0.05). All three Grade 3 complications occurred when greater than 30% of the rectum received 70 Gy or more. CONCLUSION: The overall rate of complications was similar in both treatment arms. However, there is evidence for a significant increase in late rectal complications when more than 25% of the rectum received 70 Gy or greater. This parameter may serve as a benchmark for the design of future three-dimensional conformal trials.

Aged↗

Minisatellite mutation frequency in human sperm following radiotherapy.

Screening pedigrees for inherited minisatellite length changes provides an efficient means of monitoring repeat DNA instability but has given rise to apparently contradictory results regarding the effects of radiation on the human germline. To explore this further in individuals with known radiation doses and to potentially gain information on the timing of mutation induction, we have used an extremely sensitive single molecule approach to quantify the frequencies of mutation at the hypervariable minisatellites B6.7 and CEB1 in the sperm of three seminoma patients following hemipelvic radiotherapy. Scattered radiation doses to the testicles were monitored and pre-treatment sperm DNA was compared with sperm derived from irradiated pre-meiotic, meiotic and post-meiotic cells. We show no evidence for mutation induction in any of the patients and discuss this finding in the context of previous population studies using minisatellites as reporter systems, one of which provided evidence for radiation-induced germline mutation.

Adult↗

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↗

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↗

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↗