Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Progression”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2002

Genetic analyses of mouse skin tumor progression susceptibility using SENCAR inbred derived strains.

Susceptibility to tumor development varies among individuals in the human population. This variability can also be found among different strains of mice, particularly in the mouse skin chemical carcinogenesis model. The genetic mechanisms underlying mouse skin tumor susceptibility are not fully understood. The SENCAR stock has been found to be the most sensitive mice for skin carcinogenesis studies; however, little is known about the genes underlying tumor susceptibility, particularly, those involved in tumor progression. Experiments with the SSIN/Sprd mice, an inbred strain derived from the outbred SENCAR stock, suggested that papilloma development, tumor promotion, and their conversion into squamous cell carcinomas (SCCs), progression, are regulated by different genes. In the highly sensitive SSIN/Sprd mice, papillomas rarely progress to SCC. Using crosses between the outbred SENCAR and the SSIN/Sprd mice, we previously determined that papilloma progression in the SENCAR stock could be controlled by at least one autosomal dominant gene. However, the outbred nature of the SENCAR stock precluded us from extending those findings. More recently, another inbred strain was developed from the outbred SENCAR stock, the SENCARB/Pt. These mice have similar tumor promotion sensitivity to the SSIN/Sprd but in contrast, have high papilloma progression susceptibility, similar to the outbred original stock. In the present study, we generated F(1), F(2), and backcross hybrids between the SSIN/Sprd and SENCARB/Pt mice to determine a possible model for tumor progression susceptibility and to map the putative tumor susceptibility genes. Our tumor data suggests that papilloma progression susceptibility in the SENCAR mouse skin model could be genetically determined by one susceptibility gene. Our preliminary linkage analysis failed to identify one strong susceptibility locus to confirm this but provided some evidence for at least one possible susceptibility locus in mouse chromosome 14.

Animals↗
PubMed2006

Predictability of disease progression in amyotrophic lateral sclerosis.

The aim of this study was to determine the predictors of disease progression in a group of 832 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS). Disease progression was defined as the time to 20-point change in Appel ALS (AALS) score. The effects of individual prognostic factors on disease progression were assessed with the Kaplan-Meier life-table method. In addition, the prognostic value of each factor was estimated using both univariate and multivariate Cox proportional hazard analyses. The median time to a 20-point change in AALS score in our patient population was 9 months. Age, site of symptom onset, time between first symptom and first examination, total AALS score at first examination, and AALS preslope (rate of disease progression between first symptom and first examination) were significant and independent covariates of disease progression in our population. Identification of predictors of disease progression will facilitate better design of therapeutic trials, permitting the use of disease progression as a primary endpoint and improving baseline stratification of patient populations.

Adult↗
PubMed2004

Genetic aberrations in prostate carcinoma detected by comparative genomic hybridization and microsatellite analysis: association with progression and angiogenesis.

BACKGROUND: In spite of increasing knowledge about the tumor biology of prostate cancer (PC), molecular events involved in tumor progression are not well characterized. There is evidence that a number of genetic alterations play a role in tumor progression and in addition, angiogenesis also contributes. In this study, comparative genomic hybridization (CGH), a sensitive method for detecting regional DNA copy number abnormalities, and microsatellite analysis was used to identify frequent genome changes in PC. Correlation of these data with microvessel density (MVD) and clinical follow-up data was performed to determine genetic alterations that are associated with angiogenesis and subsequent tumor progression. METHODS: Fifty-seven paraffin embedded radical prostatectomy (RP) specimens were microdissected. DNA from the microdissected PC tissue was amplified by degenerate oligonucleoitide primed (DOP)-polymerase chain reaction (PCR), and CGH was performed on the PCR product. Quantitative analyses of the CGH profiles were performed using a t-statistic. Additionally, a microsatellite analysis of chromosome 13q was performed on a subgroup of 31 of the tumors. Using a polyclonal antibody against factor VIII, MVD was determined for all RP specimens. The results of CGH and microsatellite analysis were correlated with the clinical data of the patients and with MVD. RESULTS: Forty-two of the tumors (75%) showed one or more gains while 39 (70%) showed one or more losses per tumor. The most frequent DNA copy number gains were on chromosome 3, 4, 7, 8, 10, 11, 12, 13, and X. The most frequent losses were on chromosomes 2, 5, 6, 8, 10, 13, 15, and 16. Cancer recurrence occurred in 15 patients. The total number of DNA copy number losses was significantly higher in patients with this progression (86%) than without (52%) (P < 0.001). There was no significant difference in the number of gains in patients with or without progression. Contingency table analysis showed a significant correlation between progression and losses in regions of chromosomes 6q and 13q and a gain of chromosome 7q. In multivariate analysis, only loss of chromosome 6 was independently prognostic. The gains that correlated most closely with MVD > 35 were on chromosomes 2q, 7q, and Xq, while the losses most closely associated with MVD > 35 were on chromosomes 8q, 10q, and 13q. However, only the association between loss of chromosome 13q and MVD > 35 was statistically significant. Microsatellite analysis revealed a statistically significant correlation between MVD and instability of locus 171. CONCLUSIONS: This study indicates that the frequency of genetic alterations in PC as detected by CGH correlates with clinical outcome, and that losses of DNA from chromosomes 6q and 13q are important events that correlate with tumor progression, with loss of 13q, especially instability of locus 171, also associated with angiogenesis.

Chromosome Aberrations↗
PubMed1999

Cytokine expression in B-CLL in relation to disease progression and in vitro activation.

Earlier, we reported an association between low in vitro and in vivo IL-1 and IL-6 production, decreased IL-1beta and IL-10 mRNA expression and B cell chronic lymphocytic leukemia (B-CLL) disease progression. We have now further investigated cytokine mRNA transcription in B-CLL cells and cytokine serum levels in B-CLL patients. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification of tumor necrosis factor (TNFalpha), IFNgamma, IL-6 and BCGF was equally often seen in non-progressive and progressive patients. However, 4 out of 23 non-progressive cases expressed mRNA for IL-12 while no IL-12 expression was seen in 15 progressive patients. No IL-12 was found in sera or supernatants from in vitro stimulated B-CLL cells, whereas TNFalpha and IL-10 were detected in sera from 51 and 31 of 65 B-CLL patients, respectively. TNFalpha values were significantly high in sera from patients in stages III and IV with disease progression. TNFalpha and IL-10 were also detected in culture supernatants from in vitro stimulated B-CLL cells, whereas IFNgamma was undetectable in these cultures and rarely positive in serum. Although further investigations are required, our data and that from previous reports indicate that B-CLL-derived cytokines are involved in B-CLL disease progression.

Adult↗
PubMed2000

Comparison of progression of macrovascular diseases after kidney or pancreas and kidney transplantation in diabetic patients with end-stage renal disease.

AIMS/HYPOTHESIS: The aim of the study was to examine the effect of pancreas-kidney transplantation on the progression of macrovascular diseases in Type I diabetic patients with end-stage renal disease. METHODS: The progression of cerebrovascular disease, coronary heart disease and peripheral vascular disease in uraemic patients with Type I (insulin-dependent) diabetes mellitus and who had had simultaneous pancreas-kidney transplantation was compared with that of recipients of a kidney transplant alone. Between 1986 and 1998 a total of 11 uraemic diabetic patients received a simultaneous pancreas-kidney transplantation and 10 diabetic patients a kidney transplant alone. All transplants functioned for at least 24 months, the mean observation period was 69 +/- 37 compared with 70 +/- 33 months in both patient groups. Macroangiopathic diseases were classified in four stages as described earlier. RESULTS: In the group with simultaneous pancreas-kidney transplantation progression of cerebrovascular and coronary heart disease was observed in four patients (36%) and progression of peripheral vascular disease in five subjects (45%). In the cohort with kidney transplant alone four patients (40%) showed progression of cerebrovascular and coronary heart disease and five progression of peripheral vascular disease (50%); the difference is not significant. Mean values of HbA1c (5.8 +/- 0.2 vs 7.5 +/- 0.6%, p < 0.001) and serum triglycerides (1.2 +/- 0.4 vs 2.0 +/- 1.0 mmol/l, p < 0.05) were significantly lower in the patients with pancreas-kidney transplantation than in the patient group with kidney transplant alone. Serum cholesterol concentrations and blood pressures were similar in both cohorts. CONCLUSION/INTERPRETATION: From our results we concluded that pancreas-kidney transplantation reduces risk factors for the development of macroangiopathy but fails to halt progression of macrovascular diseases similar to Type I diabetic patients with kidney transplant alone.

Adult↗
PubMed2005

Progression of parkinsonism in multiple system atrophy.

BACKGROUND: Progression of parkinsonian motor impairment is usually rapid and relentless in multiple system atrophy (MSA). However, it may also be subject to considerable variation. Prospective natural history studies using validated rating scales are required to accurately determine the progression of parkinsonism in MSA. OBJECTIVE: To assess the progression of parkinsonism in patients with the Parkinson variant of MSA. METHODS: Parkinsonian motor impairment was assessed on regular therapy at two time points (mean follow-up 11.8 months, SD 1.4) using the Hoehn and Yahr scale (H&Y), the Schwab and England ADL scale (SES) and the motor examination section of the UPDRS (UPDRS-III) in 38 patients with clinically probable MSA-P. RESULTS: We examined 38 patients with probable MSA-P (mean age 63.2 years, SD 7.4; mean disease duration 4.1 years, SD 3.0). The mean difference of UPDRS-III between baseline and follow-up was 10.8 (95% CI 8.6-12.9), consistent with an average annual 28.3 % increase of UPDRS-III baseline scores. Several variables were associated with faster progression of parkinsonism including low baseline global motor disability as assessed by H&Y and SES, low baseline UPDRS-III score, and short disease duration. UPDRS-III progression was unrelated to gender, age at symptom onset, and age at baseline visit. CONCLUSION: This is the first observational study on UPDRS rates of decline in MSA. The observed 28.6% annual increase of UPDRS-III scores illustrates the rapid progression of motor impairment in MSA. Furthermore, motor progression appeared to be accelerated during the early disease stages. Our data allow sample size calculations that may be helpful for the planning of future therapeutic trials.

Age of Onset↗
PubMed2004

Bayes' theorem applied to perimetric progression detection in glaucoma: from specificity to positive predictive value.

PURPOSE: To estimate the specificity of a clinical evaluation of a series of visual fields and to calculate the positive predictive value of progression. METHODS: The specificity of a clinical evaluation of a series of visual fields was estimated using nonparametric ranking and probability calculus. The positive predictive value of progression was calculated using Bayes' theorem. The literature suggests a prior probability of progression of typically 0.10 in the case of one visual field per year. Three different prior probability values were used: 0.05, 0.10, and 0.20. Calculations were performed for a sensitivity of 0.50, 0.80, and 1.00. RESULTS: Specificity of a clinical evaluation of a series of visual fields was calculated as 0.83 for four fields (two baseline fields, one follow-up field with suspected progression, and one confirmation of the suspected progression), 0.90 for five fields, and 0.95 for six fields. Positive predictive values ranged from 0.14 to 0.83. Positive predictive value was approximately 0.5 for a prior probability of 0.10, a sensitivity of 0.80, and a specificity of 0.90. CONCLUSIONS: Realistic series of visual fields that are apparently progressive have a positive predictive value of typically 0.5, i.e., half of them are stable. In the case of a high prior probability (uncontrolled glaucoma or long interval between successive fields), four fields may suffice to diagnose progression, whereas at least six fields are required if the prior probability is low.

Bayes Theorem↗
PubMed2006

Progressive disease in patients with cancer presenting to an emergency room with acute symptoms predicts short-term mortality.

GOALS: Patients with symptomatic, advanced cancer continue to be referred late or not at all for hospice or palliative care. We conducted a retrospective cohort study to determine whether evidence of cancer progression is an independent predictor of short-term mortality in acutely symptomatic cancer patients. PATIENTS AND METHODS: We reviewed the records of 396 patients who visited the emergency center at a comprehensive cancer center in January 2000. Records were reviewed for clinical characteristics, including symptoms, type and extent of cancer, and whether the patient's cancer was stable or progressing (uncontrolled) at the time of the emergency center visit. Cox regression analysis was used to assess survival at 90 and 180 days, after controlling for patient characteristics. MAIN RESULTS: Patients who died within 14, 90, or 180 days were more likely to have disease progression than those who did not. Dyspnea on emergency center presentation and disease progression were independent predictors of death within 90 or 180 days, after controlling for patient age, symptoms, signs, and the presence of metastases. The odds ratios for death within 90 and 180 days were 3.97 and 4.34, respectively (95% confidence intervals: 1.44, 10.94 and 1.87, 10.09). CONCLUSION: Cancer disease progression is a clinical measure of increased risk of short-term mortality in acutely symptomatic cancer patients. Future studies should examine whether the use of this characteristic enhances identification of patients who could benefit from timely referral to hospice or palliative care. Symptomatic cancer patients presenting to a cancer center emergency room were more likely to die within 14, 90, or 180 days if they had evidence of recent progression of their cancer. Among patients with disease progression, 47% died within 90 days and 61% within 180 days.

Acute Disease↗
PubMed2007

Part 2. Automated change detection and characterization applied to serial MR of brain tumors may detect progression earlier than human experts.

An algorithm was developed which compares serial MRI brain examinations of brain tumor patients and judges them as either "stable" or "progressing". A set of 88 serial MR cases were obtained, consisting of cases which were stable and remained stable for at least 8 months, cases which were stable but progressed in less than 8 months, and cases which were progressing. The algorithm was run and its output was compared to the original clinical interpretation. Of the exam pairs which were judged stable and which remained stable at least 8 months after the later examination, the algorithm diagnosed 45/46 as stable. For exam pairs judged to be progressing, the algorithm judged 15/17 to be progressing. Of the exam pairs which were judged stable, but which went on to progress less than 8 months after the later of the pair, 16/25 were judged by the algorithm to be progressing.

Algorithms↗
PubMed2005

A retrospective study on the influence of apolipoprotein e and serum lipids in progressive renal failure.

BACKGROUND: Progression of renal failure is associated with altered lipoprotein metabolism. Apolipoprotein E polymorphism is an important genetic marker for dyslipidemia. The main purpose of this retrospective study was to examine the influence of apolipoprotein E polymorphism and serum lipids level on the progression rate in a group of patients with kidney diseases of diverse etiology. METHODS: Progression rate, with regard to apolipoprotein E polymorphism and initial serum creatinine value, median (162 micromol/l), was determined by reviewing the charts of 385 patients on renal replacement therapy with a median follow-up time of 4.85 years. RESULTS: Progression rate was negatively correlated to serum cholesterol in the group with type 2 diabetes (p= 0.001). In addition, the urine albumin excretion rate (UAER) was higher in type 2 diabetics carrying the epsilon2 allele (2.1 g/l) as compared to non-epsilon2 allele carriers (1.2 g/l) (p=0.009). Although serum cholesterol in patients with autosomal dominant polycystic kidney disease (ADPKD) carrying the apolipoprotein epsilon4 allele was 5.87 +/- 1.0 mmol/l, which was significantly higher compared to non-epsilon4 carriers, 4.97 +/- 1.1 mmol/l (p=0.026), progression rate was similar in the two groups, 4.4 +/- 0.8 micromol/l/year. An increase in the relative frequency of the apolipoprotein epsilon4 allele was found in patients with ADPKD (0.29), as compared to (0.16) in the rest of the diagnostic groups (p=0.0023). In addition, in the whole study population a positive correlation was found between progression rate and underlying disease (p < 0.005), UAER (p < 0.005) and blood pressure (p < 0.005). CONCLUSIONS: The results of the present study indicate that the decline of renal function in patients with diabetes type 2 may not be associated with levels of plasma cholesterol, but with triglyceride lipoproteins, considered remnant lipoproteins. Any association between cholesterol and apolipoprotein epsilon4 allele with progression in ADPKD may not necessarily be straightforward since this disease is influenced by other genetic and unidentified factors.

Adolescent↗
PubMed2005

Halting the progression of atherosclerosis with intensive lipid lowering: results from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial.

Intravascular ultrasonography is a catheter-based technique used to provide 3-dimensional views of the vessel lumen as well as the size and distribution of atherosclerotic plaques. This imaging technique was used in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study, an 18-month, randomized, controlled, multicenter trial comparing the effects of intensive versus moderate lipid-lowering therapy on plaque progression in patients requiring coronary angiography. A total of 253 patients were randomized to atorvastatin 80 mg/day (intensive lipid lowering) and 249 patients were randomized to pravastatin 40 mg/day (moderate lipid lowering). Low-density lipoprotein (LDL) cholesterol levels decreased from a baseline mean of 150 mg/dL (3.9 mmol/L) in both groups to 79 mg/dL (2.0 mmol/L) in the atorvastatin group and 110 mg/dL (2.9 mmol/L) in the pravastatin group. High-sensitivity C-reactive protein (hs-CRP) levels decreased by 36.4% in the atorvastatin group versus 5.2% in the pravastatin group (P <0.001). For the primary end point of percent change in total atheroma volume, a significantly lower rate of progression from baseline was observed with atorvastatin (-0.4%) than with pravastatin (2.7%) (P = 0.02). Linear regression analysis showed an inverse relation between lipid reduction and plaque progression for both groups; however, at any given level of LDL cholesterol, the progression rate was lower with atorvastatin compared with pravastatin. Both regimens were well tolerated. The results show that intensive lipid lowering with atorvastatin 80 mg/day for 18 months halted the progression of coronary atherosclerosis, whereas more moderate lipid lowering with pravastatin 40 mg/day was associated with progression. The differences in the progression rate are likely to be a result of greater reduction in atherogenic lipoproteins and hs-CRP with intensive therapy.

Atherosclerosis↗
PubMed2006

Overexpression of cyclin D1 is associated with elevated levels of MAP kinases, Akt and Pak1 during diethylnitrosamine-induced progressive liver carcinogenesis.

Hepatocellular carcinoma (HCC) is a multi-factorial and multi-step process. However, the molecular mechanisms, which play a pivotal role during progressive development of HCC, are not known. Accordingly Sprague-Dawley rats were administered diethylnitrosamine (DEN) for one to three months in order to understand the molecular alterations during progressive development of liver tumor. In this study involvement of G1/S regulatory proteins, MAP kinases and cell survival factors were analyzed using RT-PCR, western blotting and in vitro kinase assays. The data showed overexpression of cyclin D1 and increased expression and activation of ERK1/2, p38 kinase and JNK1/2 with progression of tumor suggesting that MAP kinases play an important role during tumorigenesis. These molecular alterations were supported by Akt upregulation and increase in the levels of inactive GSK3beta with progression of liver tumor. Further, p21-actived kinase1 (Pak1) was found to be upregulated with tumor progression, which is a novel observation during progressive liver carcinogenesis. These results indicate that elevated levels of all the three MAP kinases (ERK1/2, p38 and JNK1/2), Akt/GSK3beta and Pak1 are associated with cyclin D1 upregulation, which helps in the disruption of the G1/S regulatory point of the cell cycle and leads to abnormal cell proliferation during progressive hepatocarcinogenesis.

Animals↗
PubMed2004

TUR and adjuvant intravesical chemotherapy in T1G3 bladder tumors: recurrence, progression and survival in 137 selected patients followed up to 20 years.

OBJECTIVES: To evaluate a highly selected population of patients affected by T1G3 bladder transitional cell carcinoma (TCCB) treated by transurethral resection (TUR) and adjuvant intravesical chemotherapy. MATERIALS AND METHODS: Between January 1976 and April 1999, 137 patients with T1G3 TCCB were treated by TUR plus intravesical chemotherapy. Particularly, a sequential combination of mitomycin C (MMC) and epirubicin (EPI) was adopted in 91 patients (66.4%). The main exclusion criteria were concomitant or previous Tis, previous T1G3 TCCB, tumor size greater than 3 centimeters and number of tumors more than 3. TUR was repeated if a superficial tumor recurred. Patients went off study if Tis, recurrent T1G3 or invasive tumor were detected during treatment or thereafter. Adjuvant therapy, recurrence and progression were considered in multivariate analysis regarding recurrence, progression and survival respectively. RESULTS: Observation period was up to 240 months with a minimum of 2 years in 112 patients (82%). Seventy patients (51%) recurred. The recurring tumor was again a T1G3 in 22 (16%) patients. Thirteen patients (9.5%) progressed. The 5-year progression-free survival rate was 90%. Median progression-free survival was 149 months. Twenty-two patients (16%) died, 9 (6.6%) of whom due to bladder cancer. Median overall survival was 155 months. The 3- and 5-year disease-free overall survival rates were 89% and 80% respectively. Ten cystectomies (7.3%) were performed. In conclusion, 123 patients (90%) maintained their intact bladder with a mean disease-free overall survival of 104 months. The sequential combination of MMC and EPI adjuvant therapy resulted more effective to be than single drug chemotherapy on recurrence rate (p=0.0021) but had no impact upon progression (p=0.127) and specific survival (p=0.163). Progression (p<0.001) after conservative treatment was the main prognostic factor for survival. CONCLUSION: A conservative approach is an appropriate therapeutic option for the initial management of selected T1G3 bladder tumors.

Adult↗
PubMed2004

Chromosomal high-polysomies predict tumour progression in T1 transitional cell carcinoma of the bladder.

UNLABELLED: The main prognostic factor generally accepted for tumour progression in T1 transitional cell carcinoma (TCC) of the bladder is histological grade. Despite this fact it is considered inaccurate to make clinical decisions on individuals. It appears that progression from minimally invasive to deeply invasive cancer is concurrent with the acquisition of genomic alterations that increase the malignant potential of cancer cells. The aim of this study is to determine if changes in chromosomes 7, 8, 9 and 17 copy number can be used to predict recurrence and progression in patients with T1 TCC of the urinary bladder. METHODS: Thirty-one T1 TCC samples were analyzed for chromosomal alterations by fluorescence in situ hybridization using centromeric probes for chromosomes 7, 8, 9 and 17. Clinical data were collected from the patients' clinical records and correlated with chromosomal studies. RESULTS: Histological grade was confirmed as a prognostic factor of tumour progression (p=0.01). None of the cytogenetic alterations demonstrated in the studied group could be related to tumour recurrence. The high-polysomies (five or more copies) of chromosomes 8, 9 and 17 showed predictive value (p=0.05, 0.05, 0.03 respectively) for tumour progression since it was observed that patients with high-polysomy of these chromosomes showed more risk of tumour progression towards muscle-invasive disease than those without high-polysomy alteration. CONCLUSION: Our findings suggest a possible prognostic significance of highly aneuploid cells (high-polysomies of chromosomes 8, 9 and 17) in tumour progression of T1 TCC bladder tumours. FISH analysis is a reproducible technique for evaluating cytogenetic alterations and could contribute to the assessment of the individual prognosis of T1 transitional cell carcinoma of the bladder.

Aged↗
PubMed2003

Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.

BACKGROUND & AIMS: Long-standing ulcerative colitis has long been recognized as a risk factor for colorectal cancer, but there is still no universal consensus on the optimal management of ulcerative colitis patients with low-grade dysplasia in flat mucosa. Some authorities favor prompt colectomy, whereas others recommend continued surveillance. The purpose of our study was to determine the frequency with which flat low-grade dysplasia in ulcerative colitis progresses to advanced neoplasia (high-grade dysplasia or colorectal cancer) and whether specific variables could predict such progression. METHODS: We reviewed the medical histories, colonoscopic findings, and surgical and pathology reports of 46 patients with ulcerative colitis diagnosed with flat low-grade dysplasia on a surveillance colonoscopy. The rates of neoplastic progression, as well as the frequency of advanced neoplasia, were tabulated. We correlated progression with several clinical and colonoscopic variables: the number of biopsy samples positive for flat low-grade dysplasia, the duration and anatomic extent of disease, patient age, and medication use. RESULTS: Among these 46 patients, there were 7 cases of colorectal cancer, 5 of which were stage II or higher. Unexpected advanced neoplasia occurred in 4 of 17 (23.5%) patients who underwent colectomy for flat low-grade dysplasia. On an actuarial basis, the rate of neoplastic progression was 53% at 5 years. No clinical features predicted progression to advanced neoplasia. Cancers, including 2 at advanced stages, developed despite frequent follow-up surveillance examinations. CONCLUSIONS: A finding of flat low-grade dysplasia during ulcerative colitis surveillance is a strong predictor of progression to advanced neoplasia. Early colectomy should be recommended for such patients.

Actuarial Analysis↗
PubMed2005

Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression.

We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value.

Adult↗
PubMed2005

Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy.

PURPOSE: To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. METHODS AND MATERIALS: Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. RESULTS: Our data failed to suggest a significant correlation between the site-by-site two-dimensional image intensity on the pre-RIT scan and the likelihood of response at those sites. In contrast, an analysis of pretreatment target volumes did correlate significantly with progression. A collective analysis of disease sites from all 20 patients found that 83% (10/12) sites of "bulky" (maximal diameter > or = 5 cm) disease displayed evidence of progression vs. 28% (26/93) of "nonbulky" disease sites containing gross disease but no area measuring >5 cm (p < 0.001). All patients with at least one site of bulky disease had initial disease progression occur at a bulky site, with a bulky site being the sole first site of progression in approximately 50%. In patients with only nonbulky disease sites, approximately one third progressed initially at an entirely new site of disease. CONCLUSION: We conclude that we can use tumor bulk to establish a statistical hierarchy of likely tumor progression sites and use this pattern to direct the use of additional external beam radiotherapy to augment treatment.

Adult↗
PubMed2005

Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation.

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

Adult↗