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PubMed2006

Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo.

PURPOSE: We analyzed data from the placebo arm of the MTOPS trial to determine clinical predictors of BPH progression. MATERIALS AND METHODS: A total of 3,047 patients with LUTS were randomized to either placebo, doxazosin (4 to 8 mg), finasteride (5 mg), or a combination of doxazosin and finasteride. Average length of followup was 4.5 years. The primary outcome was time to overall clinical progression of BPH, defined as either a confirmed 4-point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency, or recurrent urinary tract infection. We analyzed BPH progression event data from the 737 men who were randomized to placebo. RESULTS: The rate of overall clinical progression of BPH events in the placebo group was 4.5 per 100 person-years, for a cumulative incidence (among men who had at least 4 years of followup data) of 17%. The risk of BPH progression was significantly greater in patients on placebo with a baseline TPV of 31 ml or greater vs less than 31 ml (p <0.0001), a baseline PSA of 1.6 ng/dl or greater vs PSA less than 1.6 ng/dl (p = 0.0009), a baseline Qmax of less than 10.6 ml per second vs 10.6 ml per second or greater (p = 0.011), a baseline PVR of 39 ml or greater vs less than 39 ml (p = 0.0008) and baseline age 62 years or older vs younger than 62 years (p = 0.0002). CONCLUSIONS: Among men in the placebo arm, baseline TPV, PSA, Qmax, PVR and age were important predictors of the risk of clinical progression of BPH.

Adrenergic alpha-Antagonists↗

PubMed2002

Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials.

PURPOSE: We determine if intravesical bacillus Calmette-Guerin (BCG) reduces the risk of progression after transurethral resection to stage T2 disease or higher in patients with superficial (stage Ta, T1 or carcinoma in situ) bladder cancer. MATERIALS AND METHODS: A meta-analysis was performed of the published results of randomized clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treatment other than BCG. RESULTS: We identified 24 trials with progression information on 4,863 patients. Based on a median followup of 2.5 years and a maximum of 15 years, 260 of 2,658 patients on BCG (9.8%) had progression compared to 304 of 2,205 patients in the control groups (13.8%), a reduction of 27% in the odds of progression on BCG (OR 0.73, p = 0.001). The percent of patients with progression was low (6.4% of 2,880 patients with papillary tumors and 13.9% of 403 patients with carcinoma in situ, reflecting the short followup and relatively low risk patients entered in many of the trials. The size of the treatment effect was similar in patients with papillary tumors and in those with carcinoma in situ. However, only patients receiving maintenance BCG benefited. There was no statistically significant difference in treatment effect for either overall survival or death due to bladder cancer. CONCLUSIONS: Intravesical BCG significantly reduces the risk of progression after transurethral resection in patients with superficial bladder cancer who receive maintenance treatment. Thus, it is the agent of choice for patients with intermediate and high risk papillary tumors and those with carcinoma in situ.

Administration, Intravesical↗

PubMed1994

Can radical prostatectomy alter the progression of poorly differentiated prostate cancer?

A favorable outcome after radical prostatectomy for early stage prostate cancer has sometimes been attributed to the relatively benign natural history of the disease rather than the beneficial effects of treatment. Poorly differentiated tumors, however, are recognized as inherently aggressive and progress rapidly when managed conservatively. We determined the actuarial rate of treatment failure after radical prostatectomy for clinically localized (stages T1 to T3) poorly differentiated cancer, using as an end point an increase in the serum level of prostate specific antigen (PSA) to assess whether treatment altered the rapid progression expected of these cancers. Of 500 patients treated with radical prostatectomy, regardless of grade, the actuarial nonprogression rate was 76 +/- 5% at 5 years and 73 +/- 6% at 10 years. Poorly differentiated cancer, defined as Gleason score 7 or greater in the radical prostatectomy specimen, was present in 268 patients (54%) who had a nonprogression rate at 5 years of 55 +/- 12% compared to 92 +/- 4% for the 232 patients with a well or moderately differentiated (Gleason score less than 7) cancer (p < 0.00005). The extent of the cancer (confined or not confined) was strongly associated with progression (p < 0.00005). Only 76 of the 268 poorly differentiated tumors (28%) were confined to the prostate and the prognosis was excellent. At 5 years 85 +/- 18% of the patients had no evidence of progression, compared to 46 +/- 12% with poorly differentiated cancer extending outside the gland (p < 0.0001). In a multivariate analysis neither the grade nor volume of the tumor influenced the rate of progression when the cancer was confined to the prostate. Impalpable tumors detected by an elevated PSA level were as likely to be poorly differentiated as palpable disease (56% versus 63%) but were significantly more likely to be confined to the prostate (44% versus 24%, p < 0.01). Poorly differentiated cancers usually extend outside of the prostate by the time they are detected, and they progress rapidly. PSA increases the detection of impalpable high grade cancer confined to the gland. When these tumors are detected while still confined, most can be controlled by radical prostatectomy.

Actuarial Analysis↗

PubMed2003

[Homocysteine and progression of carotid atherosclerosis in patients with coronary disease].

BACKGROUND AND OBJECTIVE: Carotid intima-media thickness (IMT) is a marker of generalized atherosclerosis. Sequential evaluation of carotid IMT has permitted to know the factors involved in its progression. However, there are few studies about the influence of homocysteine in such progression. The aim of this work was to know the effect of homocysteine values on the evolution of carotid IMT in patients with coronary disease. PATIENTS AND METHOD: Carotid IMT (baseline and after 4 years of follow-up) was evaluated by a B-mode ultrasonography in 187 patients with coronary disease (166 males and 21 females; age: mean [standard deviation], 60 [7] years); 185 patients were treated with statins from the beginning of the study. RESULTS: Carotid IMT progression was confirmed in 59 patients (31.6%; 95% confidence interval [CI], 25.0-38.7%). Cardiovascular risk factors, basal biochemical parameters and methylenetetrahydrofolate reductase-C677T polymorphism were similar in patients with and without progression except for homocysteine values which were higher in the former (13.3 [5.3]; 95% CI, 12.0-14.6 vs 11.1 [3.5]; 95% CI, 10.5-11.7 (mol/l; p = 0.001). Biochemical changes at the end of the study were similar in both groups. In the multivariate analysis, IMT progression was associated with basal values of homocysteine (odds ratio [OR] 1.19; 95% CI, 1.07-1.31; p = 0.0008), female gender (OR 3.50; 95% CI, 1.17-10.50; p = 0.02), hypertension (OR 2.52; 95% CI, 1.14-5.59; p = 0.02) and basal high-density lipoprotein (HDL)-cholesterol values (OR, 0.94; 95% CI, 0.90-0.98; p = 0.009). CONCLUSIONS: The concentration of homocysteine is associated with the progression of carotid atherosclerosis in patients with coronary heart disease treated with statins.

Arteriosclerosis↗

PubMedDate not supplied

Identification of progressive glaucomatous visual field loss.

In normal individuals, visual field measures are not perfectly repeatable and individual test locations exhibit both short- and long-term sensitivity variations. This physiologic variability is greatly increased in glaucoma and confounds detection of real progressive loss in visual function. Distinguishing progressive glaucomatous visual field loss from test variability therefore represents a complex task. Procedures used for detection of glaucomatous visual field progression may be broadly grouped into four categories: 1) clinical judgment, which consists of simple subjective observation of sequential visual field test results; 2) defect classification systems, whereby specific criteria are used to stratify field loss by discrete score and define progression as score change over time, such as the Advanced Glaucoma Intervention Study scoring system; 3) trend analyses, which follow test parameters sequentially over time to determine the magnitude and significance of patterns within the data, for example linear regression; and 4) event analyses, which identify single events of significant change relative to a reference examination. All of these methods demonstrate distinct benefits and drawbacks, making each useful in specific circumstances, although no single method appears universally ideal. At the present time the best method of detection of progression may be to rely upon confirmation of change at successive examinations and also by correlation of visual field changes with other clinical observations. Alternative analysis methods may become available in the near future to help identify cases of progressive loss.

Confounding Factors, Epidemiologic↗

PubMed1996

Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer.

Prostate cancer is the most common newly diagnosed non-skin cancer and the second leading cause of cancer death in men. It is a unique neoplasm because of the large discrepancy between its clinical incidence and the much higher incidence of latent cancer. Predicting the prognosis of prostate cancer, especially the cancers detected incidentally or by screening, remains a clinically important problem. Immunoreactivity for Onco-antigen 519 (OA-519), a recently described fatty acid synthase (FAS), has been associated with poor prognosis in breast cancers. The authors have previously shown that its detection in prostate cancer correlated with high-grade, large volume, and advanced stage tumors. This study examines the association between OA-519 immunoreactivity in primary prostate cancer and disease progression. The authors used immunohistochemistry with an affinity-purified anti-OA-519 antibody and examined primary prostate cancers (stages A1 to D1) from 99 men with a mean follow-up of 4 years (range = 2 to 9.3). Survival analysis was used to evaluate differences in progression-free survival. OA-519 immunoreactivity was seen in 56 (57%) of the 99 primary prostate cancers examined. OA-519-positive cancers were more likely to progress than the OA-519-negative cancers (P < .04). Univariate survival analysis showed that OA-519 (FAS), histological grade (Gleason score), and clinical stage were significant predictors of disease progression. Multivariate analyses of all cases showed that only histological grade was significant. However, multivariate analysis of the 85 cancers with Gleason scores 2-7 (ie, low to intermediate grade) showed OA-519 (FAS) immunoreactivity to be the only statistically significant predictor of cancer progression (P < .02). Expression of the fatty acid synthase OA-519 by prostate cancers is potentially a clinically useful predictor of disease progression. It appears to be independent of histological grade (Gleason score), at least in cancers with low to intermediate grades. Further studies are needed to evaluate the role of fatty acid synthase in malignancy and the potential therapeutic implications of enzyme blockers.

Aged↗

PubMed2003

DNA cytometric features in biopsies of TaT1 urothelial cell cancer predict recurrence and stage progression more accurately than stage, grade, or treatment modality.

OBJECTIVES: To compare retrospectively the predictive value for recurrence and stage progression of DNA ploidy and S-phase fraction by flow cytometry and highly automated ultrafast image cytometry (ICM) in biopsies of TaT1 urothelial cell carcinomas (UCCs) of the urinary bladder with stage, grade, other pathologic features, and treatment. METHODS: Three experienced pathologists reviewed the stage and grade of 228 UCCs; 193 (85%) consensus cases were analyzed further. We had enough material for single-cell suspensions for both flow cytometry and ICM in 183 cases (94.8%). The 2001 European Society for Analytical Cellular Pathology standards for DNA ICM were followed. The predictive value of DNA features, classic prognosticators (stage, grade, carcinoma in situ, multicentricity), and treatment modality for recurrence and stage progression were analyzed with univariate (Kaplan-Meier) survival and multivariate (Cox model) regression analysis. Ta and T1 cases were analyzed separately. RESULTS: Of the 228 cases, 88 (51.5%) recurred and 13 (7.6%) progressed. On univariate analysis, most of the DNA features studied were statistically significant. Treatment modality and grade were only prognostic for progression (not for recurrence) and only in Ta cases. On multivariate analysis, DNA ICM features performed best; the strongest recurrence predictor for Ta UCC was a DNA index (DI) of 1.0 versus all others, and for T1 UCC, a DI of less than 1.3 versus 1.3 or greater. The best stage progression predictor for Ta UCCs was a DI of 1.0 plus an S-phase fraction of less than 10%, and for T1 UCCs, a DI of less than 1.3 versus 1.3 or greater. With multivariate analysis, sex, age, grade, carcinoma in situ, multicentricity, and treatment modality were excluded once the DNA ICM features were selected. CONCLUSIONS: DNA image cytometric features predict recurrence and stage progression in TaT1 UCC biopsies more accurately than classic prognostic factors, independent of treatment modality.

Aged↗

PubMed1997

HIV-1 disease progression and AIDS-defining disorders in rural Uganda.

BACKGROUND: The majority of people infected with HIV-1 live in Africa, yet little is known about the natural history of the disease in that continent. We studied survival times, disease progression, and AIDS-defining disorders, according to the proposed WHO staging system, in a population-based, rural cohort in Uganda. METHODS: In 1990 we recruited a random sample of people already infected with HIV-1 (as prevalent cases) detected during the initial survey round of a general-population study to form a natural-history cohort. Individuals from the general-population cohort who seroconverted between 1990 and 1995 (incident cases) were also invited to enroll. Participants were seen routinely every 3 months and when they were III. FINDINGS: By the end of 1995, 93 prevalent cases and 86 incident cases had been enrolled. Four patients in the prevalent group were in stage 4 (AIDS) at the initial visit. During the next 5 years, 37 prevalent cases progressed to AIDS. Seven incident cases progressed to AIDS and the cumulative progression to AIDS at 1, 3, and 5 years after seroconversion was 2%, 6%, and 22%, respectively. The cumulative probability of AIDS at 4 years from entering stages 1, 2, and 3 was 11%, 33%, and 58%, respectively. There were 47 deaths among prevalent cases and seven among incident cases during follow-up. The cumulative mortality 4 years after patients entered stages 1, 2, 3, and 4 was 9%, 33%, 56%, and 86%, respectively. The median survival after the onset of AIDS was 9.3 months. INTERPRETATION: Our results are important for the setting of priorities and rationalisation of treatment availability in countries with poor resources. We found that progression rates to AIDS are similar to those in developed countries for homosexual cohorts and greater than for cohorts infected by other modes of transmission. However, we have found that the rates of all-cause mortality are much higher and the progression times to death are shorter than in developed countries.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Incidence and progression of lens opacities in the Barbados Eye Studies.

OBJECTIVE: To provide 4-year cumulative incidence and progression rates of age-related lens opacities in a population > or =40 years of age, which is mainly of African origin. DESIGN: Cohort study that reexamined surviving members of the population-based Barbados Eye Study 4 years after baseline. PARTICIPANTS: Three thousand four hundred twenty-seven members of the Barbados Eye Study cohort (85% of those eligible). MAIN OUTCOME MEASURES: The Lens Opacities Classification System II (LOCS II) was used at the slit lamp. Cumulative incidence was defined as the development of any nuclear, cortical or posterior subcapsular (PSC) opacities (LOCS II scores > or =2) among persons without that opacity type at baseline. Cumulative progression was defined by at least two-step increases in scores among persons with preexisting lens opacities. RESULTS: The incidence of cortical opacities was about five times greater in black than white participants (age-gender adjusted relative risk = 4.7; 95% confidence interval: 1.9-11.4). In the black population, the 4-year incidence rates were 22.2% (20.4%-24.0%) for any cortical, 9.2% (8.2%-10.4%) for any nuclear, and 3.3% (2.7%-4.0%) for any PSC opacities; rates increased greatly with age. Four-year progression rates were 12.5% for cortical, 3.6% for nuclear, and 23.0% for PSC opacities, without consistent pattern by age. Women had a greater risk of cortical and nuclear opacities (P<0.05) than men and greater progression of nuclear opacities. The presence of PSC opacities at baseline seemed to at least double the incidence and progression rates of other opacities. In persons initially opacity free, single cortical opacities were the predominant type to develop at followup. Visual acuity loss frequently accompanied incident opacities. CONCLUSIONS: This longitudinal study provides new population-based data on the natural history of lens opacities. Incidence and progression of opacities, especially of cortical opacities, were high. After 4 years of followup, 1 in 4 to 5 participants developed cortical opacities, 1 in 11 developed nuclear opacities, and 1 in 30 developed PSC opacities. The information obtained attests to the public health impact of age-related cataract, as well as its extent, in this and similar black populations.

Adult↗

PubMed1996

Incidence and progression of nuclear opacities in the Longitudinal Study of Cataract.

PURPOSE: To estimate incidence and progression rates of nuclear opacities in the Longitudinal Study of Cataract, an epidemiologic study of the natural history of all types of lens opacities. METHODS: The Lens Opacities Classification System III was used to assess longitudinal changes between baseline and follow-up lens photographs for the 764 Longitudinal Study of Cataract participants. Baseline data, collected until December 1988 as part of a case-control study, included color slit, retroillumination, and Scheimpflug photographs. The same data were collected by the longitudinal Study of Cataract at four subsequent visits at yearly intervals. RESULTS: Among patients free of nuclear opacities at baseline, the incidence of new opacities was 6% after 2 years and 8% after 5 years of follow-up. The progression of pre-existing nuclear opacities was much higher. After 2 years, nuclear opacities had progressed in more than one third of the patients with pre-existing opacities; after 5 years, almost half had progressed. Older age was significantly related to higher incidence of new nuclear opacities, but not to progression of pre-existing opacities. Patients with other opacity types had higher nuclear incidence and progression rates. CONCLUSIONS: In this clinic-based, older-patient population, new nuclear opacities developed in less than one tenth of the patients after 5 years of follow-up. In contrast, almost one half of the patients with pre-existing opacities had worsened after 5 years. These estimated rates can be used to plan intervention or other studies of nuclear changes in similar populations.

Aged↗

PubMed1999

The role of pubertal progress in the development of depression in early adolescence.

BACKGROUND: Lack of longitudinal studies on the relationship between pubertal progress and changes in depression during adolescence. METHODS: Changes in the Anxious/Depressed scores of the Child Behavior Checklist and Youth Self-Report were predicted from pubertal progress. Subjects were young adolescents from the Dutch general population, aged 10-12 years at T1 and 12-14 years at T2. From the 1327 parent reports, 207 showed a change that exceeded the cut-off for inclusion in the analyses. From the 1414 self-reports, 476 exceeded the cut-off. RESULTS: Apart from increase, decrease in depression was common. Pubertal progress was inversely related to the parent reports of boys' depression only. CONCLUSION: Self-perceptions of depressive symptoms change independently from pubertal progress, whereas changes observable to parents are inversely related to it in boys. LIMITATIONS: Progress was not measured across the whole pubertal development. CLINICAL RELEVANCE: One can expect parents to observe a decrease in boys' depression in the period when most pubertal progress is made. More attention should be paid to decreases in depressive symptomatology.

Adolescent↗

PubMed2003

A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase.

BACKGROUND: Detectable serum hepatitis C virus (HCV) RNA in HCV patients with persistently normal alanine transaminase (PNALT) has been found to be associated with significant liver damage. AIMS: The primary outcome of this study was to compare the histological progression of fibrosis in patients with PNALT and elevated alanine transaminase (ALT). METHODS: Forty patients with PNALT (Group 1) and 41 patients with elevated ALT (Group 2) were recruited into this study. Only patients with fibrosis of F0 to F2 were recruited into this study. RESULTS: The median time to second liver biopsies was 6.3 (range 2.0-11.1) years. Nine patients (22.5%) in Group 1 and 17 patients (41.5%) from Group 2 had progression of fibrosis. There was a trend towards a significantly higher cumulative probability of fibrosis progression in Group 2 (P=0.06). In patients with an initial F0 to F1 fibrosis, there was a significant difference in cumulative probability of fibrosis progression between Groups 1 and 2 (22.6% (7/31) vs. 43.3% (13/31), respectively, P=0.02). CONCLUSIONS: Anti-HCV patients with PNALT with an initial fibrosis of F0 or F1 were less likely to develop progression of fibrosis than those with elevated ALT, although patients with PNALT may have histologically and clinically progressive disease.

Adult↗

PubMed2003

Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis.

BACKGROUND/AIMS: This study aimed at evaluating the effect of ursodeoxycholic acid (UDCA) treatment on histologic progression in primary biliary cirrhosis (PBC). METHODS: Using combined individual histologic findings from four clinical trials, we selected the patients in whom paired liver-biopsy specimens were available with a time interval of about 36 months between biopsies. A total of 367 patients were selected (UDCA: 200 vs. placebo: 167). RESULTS: Overall, there was no significant difference in the progression of the histologic stage between the two groups. By contrast, in the subgroup of patients with initial stages I-II (n=177) there was a significant decrease in the histologic stage progression in the UDCA group relative to the placebo group (P<0.03). Overall, there was a significant delay in the progression of periportal necroinflammatory lesions (P=0.03), and an improvement in the degree of ductular proliferation (P=0.02) in the UDCA group compared with the placebo group. There was no significant difference in the progression of other specific lesions. CONCLUSIONS: A 2-year UDCA treatment reduces periportal necroinflammation and improves ductular proliferation, and when initiated at the earlier stages I-II of the disease also delays the progression of histologic stage. These data support the early initiation of the drug to prevent these histologic features of PBC.

Adult↗

PubMed1999

Epidermal grafts for treatment of stable and progressive vitiligo.

BACKGROUND: Previous reports have shown the effectiveness of epidermal grafts for patients with stable vitiligo. OBJECTIVE: Our purpose was to evaluate the effectiveness and complications of epidermal grafts in patients with stable and progressive vitiligo and to compare the results in both groups. METHODS: Epidermal grafting with suction blisters was performed in 40 patients with vitiligo (26 stable and 14 progressive). The grafted sites and donor sites were examined for repigmentation for longer than 3 months, up to 2.5 years. RESULTS: Complete repigmentation was observed in 19 patients with stable (73.1%) and 10 with progressive vitiligo (71.4%). Of the 29 patients who experienced complete repigmentation, we noted recurrences in 2 patients with stable disease (10.5%) and 4 with progressive disease (40%). CONCLUSION: Although patients with progressive vitiligo showed more frequent recurrence than those with stable disease, epidermal grafting may be an effective treatment not only for stable vitiligo but also for progressive vitiligo.

Adolescent↗

PubMed2004

[Predictors of progression and death in patients with advanced HIV infection in the era of highly active antiretroviral therapy].

INTRODUCTION: To assess the factors associated with progression of infection and death in HIV-positive patients with severe immunodepression in the era of highly active antiretroviral therapy (HAART). METHODS: We studied 146 HIV-infected patients with < 100 x 10(6)/L CD4+ lymphocytes and positive cytomegalovirus (CMV) serology enrolled between December 1997 and October 1998 and prospectively followed a median of 12.1 months. The main outcome measures were progression of HIV infection, defined as the appearance of a new AIDS-defining disease (CDC category C) or death. HIV viral load, lymphocyte count (CD4+ and CD8+), HAART administration and other clinical variables were evaluated at baseline. CMV viremia (determined by PCR) and HAART efficacy were recorded during follow-up. RESULTS: Progression was observed in 40% of patients and 17% died. Factors associated with progression or death were CD4+ lymphocyte count less than 50 x 10(6)/L, CD8+ lymphocyte count less than 500 x 10(6)/L, HIV viral load more than 300,000 copies RNA/mL, CMV viremia, and absence or inefficacy of HAART. In the multivariate model, absence of HAART and low CD4+ and CD8+ counts remained statistically associated with progression, but the only variable associated with death was CMV viremia. CONCLUSIONS: In patients with advanced HIV infection, CD4+ and CD8+ cell count and HAART were the most important factors related to progression, and CMV viremia was the strongest predictor of death.

AIDS-Related Opportunistic Infections↗

PubMed2003

Relapse or progression after hematopoietic cell transplantation using nonmyeloablative conditioning: effect of interventions on outcome.

OBJECTIVE: This study analyzes the effect of interventions aimed at reinducing remissions in patients with relapse or progression of malignant disease following allogeneic hematopoietic cell transplantation (HCT) using nonmyeloablative conditioning. METHODS: We performed a retrospective analysis of 81 instances of relapse or progression occurring among 224 patients given HCT as treatment of their hematologic malignancies. All patients received conditioning with 2 Gy total-body irradiation with or without fludarabine and with postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. RESULTS: Overall survival of patients after relapse or progression was 36%. Fifteen of the 81 patients were given no interventions. Three of these 15 (20%) patients are alive with disease while 12 died with disease progression. Sixty-six patients (81%) received interventions, including withdrawal of immunosuppression (n=32), donor lymphocyte infusions (n=13), or chemotherapy (n=21). Twenty of the 66 (30%) are alive, 5 in complete remission, 4 in partial remission, 1 with stable and 10 with progressive disease. The overall response rate to intervention was 27%. Forty-six (70%) of the patients given interventions died, mainly due to relapse/progression. Patients not receiving interventions had a 1-year survival estimate of 15% compared to 41% in patients given interventions. Factors associated with survival in patients given intervention were disease response (p=0.002), disease category (p=0.001), and time to relapse from transplantation (p=0.0005). CONCLUSIONS: While the overall prognosis of patients relapsing or progressing after nonmyeloablative HCT is poor, interventions such as the combined use of immunotherapy and chemotherapy can improve patient survival.

Adolescent↗

PubMed2001

Stromal-epithelial interactions in the progression of ovarian cancer: influence and source of tumor stromal cells.

Stromal cells are essential for the progression of many cancers including ovarian tumors. Stromal cell-epithelial cell interactions are important for tumor development, growth, angiogenesis, and metastasis. In the current study, the effects of normal ovarian bovine stromal cells on ovarian tumor progression was investigated. The hypothesis tested is that ovarian stromal cells will alter the onset and progression of ovarian tumors. Conditioned medium from normal bovine ovarian surface stromal cells was found to stimulate the growth of normal ovarian surface epithelium and had no effect on the growth of human tumor cell lines SKOV3 and OCC1. Human ovarian cancer cell lines, SKOV3 and OCC1, were injected subcutaneously into nude mice to examine tumor progression. Tumor growth in the nude mice was dramatically reduced when normal ovarian surface stromal cells were co-injected with SKOV3 or OCC1 cells. Similar results were obtained with normal bovine or human ovarian stromal cells. In contrast, irrelevant testicular stromal cells and epithelial cells had no effect on tumor growth in the nude mouse. Histological examination of these tumors revealed a characteristic stromal cell component adjacent to epithelial cell colonies. Sections of these tumors were hybridized with species specific genomic probes using fluorescence in situ hybridization to identify cell populations. Epithelial cells were shown to be of human origin (i.e. SKOV3 or OCC1), but stromal cells were found to be primarily murine in origin (i.e. host tissue). No detectable bovine cells were observed in the tumors after one week post-injection. Results suggest that stromal cells are an essential component of ovarian tumors. Interestingly, normal ovarian stromal cells had the ability to inhibit tumor growth, but were not able to survive long-term incubation at the tumor site. The developing tumor appears to recruit host (i.e. murine) stromal cells to invade the tumor and support its growth. In summary, normal ovarian stromal cells can inhibit ovarian tumor progression and the developing tumors recruit adjacent host stroma to become "tumor stroma". The tumor stroma likely develop an altered phenotype that cooperates with the tumorigenic epithelial cells to help promote the progression of ovarian cancer.

Animals↗

PubMed2000

Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis.

OBJECTIVES: This prospective cohort study of patients with coronary artery disease (CAD) sought to determine the impact of social support, anger expression and cynical hostility on progression of coronary atherosclerosis as shown by angiography. BACKGROUND: Low social support, high levels of expressed anger and cynical hostility are correlated to increased CAD morbidity and mortality. However, the impact of these factors, alone or together, on progression of human coronary atherosclerosis is unknown. METHODS: Of 223 patients with CAD documented by standardized angiography at baseline, 162 had a second angiogram after two years. An expert panel who had no knowledge of the patients' characteristics evaluated the films pairwise to determine disease progression. At baseline, all patients were asked to answer three self-report questionnaires: questions concerning emotional social support, the State-Trait-Anger-Expression Inventory (STAXI) and the Cook-Medley cynical hostility scale. Each patient's clinical and laboratory status was followed. RESULTS: Questionnaires and angiographic follow-up data were available for 150 patients. Bivariate analysis of the psychological variables showed a higher risk of progression only for patients who scored high on STAXI anger-out or low on social support. In the multivariate analysis, when adjusting for confounding variables and examining the interaction between psychological variables, only patients with both high anger-out and low social support were at highly increased risk for progression (odds ratio 30, confidence interval [CI] 5.5 to 165.1; RR 3.19). CONCLUSIONS: Patients with CAD and low emotional social support who express anger outwardly are at a highly increased risk of disease progression, independent of medication or other risk factors.

Anger↗