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Results for “prognostic stratification”

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PubMed2026

Crucial role of telomere maintenance-related genes in survival prediction and subtype identification in colorectal cancer.

BACKGROUND: Telomere maintenance-related genes (TMRGs) are implicated in Colorectal cancer (CRC) development, but their prognostic value and clinical relevance remain insufficiently explored. This study aims to develop a TMRG-based prognostic model and elucidate its clinical utility in CRC management. METHODS: The Cancer Genome Atlas database was utilized to download RNA-seq data from 638 CRC and 51 control samples. Differential expressed genes were screened and intersected with 2086 TMRGs, resulting in the identification of 976 TMRGs. Through univariate and multivariate Cox regression analysis, a prognostic model comprising three telomere maintenance-related biomarkers (PDE1B, TFAP2B, and HSPA1A) was developed and validated using an external dataset. By integrating the model risk score with clinical features, a nomogram was constructed to predict the survival outcomes of CRC patients. Additionally, an in-depth investigation of the immuno-infiltration, functional variation and drug sensitivity analysis were performed in two risk subgroups defined by the prognostic model. Finally, the functional significance of PDE1B in CRC cell lines was investigated through MTT assays, cell colony formation assays, transwell assays and flow cytometry. RESULTS: A total of 976 DE-TMRGs were enriched in telomere/DNA replication pathways. A three-gene signature (PDE1B, TFAP2B, and HSPA1A) stratified patients into high- and low-risk groups with divergent survival (AUC >0.60, validated externally). High-risk patients had advanced N/M stages, elevated M0/M2 macrophages, reduced CD4+ memory T cells, and upregulated immune checkpoints. Nomogram integrating risk score, age, and N/M stage accurately predicted 1-/3-/5-year survival. Low-risk patients showed greater 5-fluorouracil sensitivity. PDE1B expression was significantly reduced in CRC tissues and correlated with advanced stages. Functional assays confirmed PDE1B overexpression suppressed proliferation, migration, invasion, and induced apoptosis in CRC cells. CONCLUSION: This study identifies a moderately predictive telomere maintenance-related gene signature as an independent prognostic predictor in CRC. The risk stratification model effectively discriminates patients with distinct survival patterns, tumor microenvironments, and therapeutic responses, while the integrated nomogram offers additional reference information for survival analysis, albeit with only moderate predictive accuracy. These findings indicate telomere maintenance-related gene signature could serve as a preliminary auxiliary risk stratification tool for postoperative CRC patients, PDE1B may also serve as a potential epithelial tumor-suppressor target for future preclinical studies.

PDE1B↗

PubMed1998

Stepwise strategy on the cost of risk stratification after acute myocardial infarction: a retrospective simulation study.

Stratification of postinfarction patients at high risk of mortality and/or other adverse events can be improved by combining several prognostic markers. As the clinical impact of risk stratification has only recently emerged in prospective trials, there are a lack of data regarding the cost-effectiveness of multimarker strategies. This study performed a comprehensive search of a postinfarction database and simulated different risk stratification strategies involving left ventricular ejection fraction, signal-averaged electrocardiography, Holter monitoring, and heart rate variability, The parameters were assessed before discharge in 417 survivors of acute myocardial infarction followed-up for 1 year. Cardiac mortality was used as the clinical endpoint. A statistical computer model of a stepwise strategy using every feasible sequence of the four tests was used and, based on prices derived from European and American centers, the cost estimates of all possible combinations were compared. During the 1 year after myocardial infarction there were 24 cardiac deaths (5.8%). In all the population, 6% had all four tests positive (cardiac mortality 20%); 25% had at least three tests positive (cardiac mortality 12.5%); 58% had at least two tests positive (cardiac mortality 8.3%); and 92% presented with at least one test positive (cardiac mortality 6.3%). The cost of performing all the tests ranged between $398 and $1,887 for each patient. However, by selecting patients according to a step wise strategy, the costs ranged from $96 (> or = 1 test positive) to $510 (for the least expensive sequences of four tests positive). For each of the centers considered, the costs resulting from the risk stratification protocol were determined by the number of variables combined and sequences of tests adopted. Thus, a step wise strategy using the combination of all four parameters, starting with analysis of Holter variables and finishing with signal-averaged electrocardiography, appears to be the most appropriate and the least expensive approach for selecting patients at high risk of cardiac death.

Computer Simulation↗

PubMed1992

Mucinous carcinoma of the ovary. Pathologic prognostic factors.

Thirty-four ovarian mucinous carcinomas defined by nuclear stratification in excess of three layers (noninvasive mucinous carcinoma, NIMC) or stromal invasion (invasive mucinous carcinoma, IMC) were examined to define prognostic indicators. Twenty-two patients had NIMC (Stage I, 15; Stage II, 1; Stage III, 5; and Stage IV, 1). Twelve patients had IMC (Stage I, one; Stage II, one; and Stage III, ten). Fifteen patients died, ten with IMC and five with NIMC (mean survival, 16.7 months). Nineteen patients survived, two with IMC and 17 with NIMC (mean follow-up, 12 years). Ten of the 12 patients with IMC who died had Stage III disease. Five of the 22 patients with NIMC who died included four with Stage III and one with Stage I disease. Among patients who died, those with IMC tended to have a shorter mean survival than those with NIMC. No differences among groups were identified with respect to nuclear grade, mitotic activity, percentage of tumor displaying more than three cell layers, or amount of invasion. In ovarian mucinous carcinoma, clinical stage and stromal invasion are the most important prognostic variables, and they are interrelated. Stage I NIMC rarely pursues an aggressive course.

Adenocarcinoma, Mucinous↗

PubMed2007

Prognostic impact of peakVO2-changes in stable CHF on chronic beta-blocker treatment.

BACKGROUND: Peak oxygen uptake (pVO2) is used for risk stratification in chronic heart failure (CHF), but little is known about the prognostic impact of pVO2-changes in patients on chronic beta-blocker (BBL) therapy. We therefore prospectively evaluated individual pVO2-changes at a 6-month interval in patients all receiving BBL. METHODS: 194 patients with stable CHF on stable medication were included (V1) and underwent clinical evaluation and exercise testing. Testing was repeated (V2) at 5.7+/-1.5 months after V1 and patients were followed >12 months after V2. Death or hospitalisation due to cardiac reasons was the predefined EP (EPP, end-point positive; n=62; EPN, end-point negative; n=113). RESULTS: Initial characteristics did not differ between EPP and EPN. Multivariate cox regression analysis revealed that change of pVO2 (EPP: -0.6+/-2.6 ml/kg min; EPN: +2.5+/-3.3 ml/kg min; p<0.001) was independent to pVO2, LVEF, NTproBNP and NYHA at V2 for prediction of the combined end-point during follow-up. An increase of pVO2 by 10% was identified as an adequate cut-off value for risk stratification and ROC-analysis showed the significant incremental prognostic value of the determination of pVO2 changes in combination with pVO2. CONCLUSIONS: Serial measurements of pVO2 yield additional information for risk stratification in clinically homogenous CHF patients receiving BBL. This is the first study demonstrating this fact within a narrow predefined interval with all patients on BBL.

Adult↗

PubMed2026

Large-scale multiethnic electronic health record resource for diabetes complications research: the North West London Diabetes Cohort (NWLDC) - cohort profile.

PURPOSE: The North West London Diabetes Cohort is established to provide systematic characterisation of a large diabetes population as a foundation for complications research and prognostic modelling. Many predictive modelling studies neglect the essential descriptive characterisation of underlying cohorts, focusing narrowly on model accuracy. This cohort profile addresses this gap by comprehensively describing the demographic composition, clinical characteristics and complication incidence patterns. The notably diverse, multiethnic population enables examination of ethnic disparities and supports future development of reliable prognostic models and evidence-based prevention strategies for diabetes complications. PARTICIPANTS: At baseline, 337 271 patients with diabetes were identified. It includes 279 067 patients with type 2 diabetes, 17 638 with type 1 diabetes, 33 590 with gestational diabetes and 6916 with unspecified diabetes. The earliest diabetes diagnosis dates to January 1932, with data updated to 27 May 2025. FINDINGS TO DATE: This cohort profile describes baseline characteristics of patients with comprehensive data collected on demographics (age, sex, Deprivation Index, ethnicity), clinical measures (glycated haemoglobin, body mass index, blood pressure, lipids and estimated glomerular filtration rate) and 14 major diabetes complications tracked longitudinally. Key findings for patients with type 2 diabetes reveal diabetic retinopathy as the most common complication (74.6 per 1000 person-years), followed by hypertension (51.0) and kidney disease (31.4). Cumulative incidence analyses using the Aalen-Johansen estimator, which accounts for mortality as a competing risk, demonstrated significant ethnic disparities, with black, Asian, mixed and other ethnic groups showing elevated risk compared with white patients. Time-varying Cox models identified strong clustering between cardiovascular and renal complications, confirming a cardiometabolic-renal syndrome. Mental health conditions (depression and anxiety) were prevalent throughout the disease timeline, occurring both before and after diabetes diagnosis. FUTURE PLANS: This cohort will be used as a platform for developing and validating prognostic models for diabetes complications, enabling risk stratification and targeted interventions. Future work will incorporate medication data to refine diabetes type classification, examine the effectiveness of antidiabetic medications in preventing different complications and address demographic differences in prognostic model performance and prediction accuracy. To better characterise lifestyle, further interrogation of electronic health record data will examine recording of advice given, including dietary advice, referral to weight management schemes and presence of alcohol consumption codes.

Humans↗

PubMed2005

Follicular thyroid carcinoma: the role of histology and staging systems in predicting survival.

OBJECTIVE: To evaluate the risk factors including tumor histomorphology for survival specific to follicular thyroid carcinoma (FTC) and to apply commonly employed staging systems in predicting survival for patients with FTC. SUMMARY BACKGROUND DATA: FTC is usually analyzed collectively with papillary thyroid carcinoma (PTC) in risk group analysis. Risk factors and risk group analysis are important in the management of patients with FTC, although current published therapeutic guidelines call for total thyroidectomy followed by radioactive iodine (I) ablation for all FTC patients. METHODS: Over a 40-year period, 156 patients surgically treated for FTC with an average follow-up of 14.4 years were retrospectively studied after histologic reclassification according to the type and degree of invasiveness of the tumor. Potential risk factors for survival were calculated using multivariate analysis, and the prognostic accuracy of AMES risk group stratification, UICC/AJCC pTNM staging, Degroot classification, and MACIS scoring schemes in predicting survival was compared. RESULTS: Seventeen (11%) patients had distant metastases at presentation, and bilateral thyroid resection was performed for 131 (84%) patients. Seventeen (11%) patients died of recurrent or metastatic disease. The overall and cancer-specific survival (CSS) rates at 10 years were 79% and 88%, respectively. None of the patients with minimally invasive (n = 49) or angioinvasive (n = 23) carcinomas died compared with 17 of 84 patients with widely invasive carcinomas (P = 0.0007). Using the Cox proportional hazards model, old age, the presence of distant metastases, and incomplete tumor excision were independent prognostic factors for survival. For patients who underwent curative treatment, old age and widely invasive carcinoma were risk factors for poor survival. All staging systems studied accurately predicted CSS, and the pTNM UICC/AJCC staging system yielded the best prognostic information. CONCLUSIONS: Commonly adopted staging systems can be applied specifically to patients with FTC. The distinction of FTC in minimally invasive and widely invasive carcinoma based on the extent of invasiveness rather than vascular invasion is important in identifying low-risk FTC patients for a more conservative management.

Adenocarcinoma, Follicular↗

PubMed2001

Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program.

To reliably estimate the prognoses of patients with hepatocellular carcinoma (HCC), both liver function and tumor-related factors should be accounted for. However, there are few worldwide staging systems that assess prognostic value in the context of selecting individual patients for randomized stratification in therapeutic and clinical trials. We investigated the value of known prognostic systems and verified the usefulness of the new scoring system proposed by the Cancer of the Liver Italian Program (CLIP), as determined from 662 Japanese patients. A retrospective analysis of the HCC diagnoses at 4 Japanese institutions from 1990 and 1998 was performed. Overall survival was the only end point used in the analysis. Discriminatory ability and predictive power of the CLIP score were compared with those of Okuda stage and AJCC TNM stage. Compared with the Okuda and AJCC staging systems, the CLIP score's enhanced discriminatory capacity, which was tested by the linear trend test and Harrels' c-index, revealed a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. Moreover, the likelihood ratio test showed that the CLIP score had additional homogeneity of survival within each score above that of the Okuda stage or the AJCC stage. This was true for 3 subgroups of patients who received surgery, transcatheter arterial chemoembolizations, and percutaneous ethanol injections. Collectively, these findings indicate that the CLIP score has the highest stratification ability with regard to prognosis in patients with HCC. The CLIP score could be used internationally to stratify randomization groups in therapeutic and clinical trials.

Adult↗

PubMed1982

[Probability of survival and prognostic factors in chronic obstructive lung disease].

The course of chronic obstructive pulmonary disease (COPD) is described over a 3-7 year period in 201 patients treated by family physicians and in the same hospital. The probability of survival after 3 years is 63% (normal population of same age 85%) and after 5 years 48% (normal 75%) for all patients. These figures are comparable with data in the literature of the last 12 years (42-69% 5-year survival). The patients in our study are 68 years old on average and have an FEV1 of 1.3 liters. The prognosis of COPD is significantly influenced by the following factors: ECG signs of cor pulmonale, clinical signs of heart failure, vital capacity, FEV1 and paCO2. For example, within a 3 year period 63 of 124 patients with heart failure died as compared to only 3 of 57 without. Retrospective analysis shows inhalation therapy by motor-driven nebulizers to have a favourable effect on survival. For IPPB home therapy a favourable effect can only be shown after stratification for the two most significant prognostic factors to exclude therapeutic bias. No effect on survival was noted with long-term steroid therapy. 11% of patients who have never smoked, and those who have stopped smoking, live significantly (p less than 0.002) longer than those who continued to smoke more than 3 cigarettes per day during the observation period.

Aged↗

PubMed2001

Prognostic value of dobutamine stress technetium-99m-sestamibi single-photon emission computed tomography myocardial perfusion imaging: stratification of a high-risk population.

OBJECTIVES: This work was undertaken to define the intrinsic cardiac risk of the patient population referred for dobutamine stress perfusion imaging and to determine whether dobutamine technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography (SPECT) imaging is capable of risk stratification in this population. BACKGROUND: In animal models, dobutamine attenuates the myocardial uptake of (99m)Tc-sestamibi resulting in underestimation of coronary stenoses. Therefore, we hypothesized that the prognostic value of dobutamine stress (99m)Tc-sestamibi SPECT myocardial perfusion imaging might be impaired, owing to reduced detection of coronary stenoses. METHODS: We reviewed the clinical outcome of 308 patients (166 women, 142 men) who underwent dobutamine stress SPECT (99m)Tc-sestamibi imaging at our institution from September 1992 through December 1996. RESULTS: During an average follow-up of 1.9 +/- 1.1 years, there were 33 hard cardiac events (18 myocardial infarctions [MI] and 15 cardiac deaths) corresponding to an annual cardiac event rate of 5.8%/year, which is significantly higher than the event rate for patients referred for exercise SPECT imaging at our institution (2.2%/year). Event rates were higher after an abnormal dobutamine (99m)Tc-sestamibi SPECT study (10.0%/year) than after a normal study (2.3%/year) (p < 0.01), even after adjusting for clinical variables. In the subgroup (n = 29) with dobutamine-induced ST-segment depression and abnormal SPECT imaging, the prognosis was poor, with annual cardiac death and nonfatal MI rates of 7.9% and 13.2%, respectively. CONCLUSIONS: Patients referred for dobutamine perfusion imaging are a high-risk population, and dobutamine stress (99m)Tc-sestamibi SPECT imaging is capable of risk stratification in these patients.

Aged↗

PubMedDate not supplied

Prognostic factors for patients with esophageal cancer treated with radiation therapy in PCS: a preliminary study.

PURPOSE: We investigated the prognostic factors, with special reference to age, for esophageal cancer patients, who did not receive surgery but were treated with radiation in the context of a Patterns of Care Study (PCS) in Japan. PATIENTS AND METHODS: The fifth PCS database format employed in the United States was used to collect information on 455 esophageal cancer patients by external audit. The data of patients who had not received surgery (n=252) were further selected and divided into two age groups, patients 75 years old or older (n=90) and patients younger than 75 years (n=162). Cox's proportional hazards model was used for the statistical analysis, with crude survival as the endpoint. Variables tested were age; Karnofsky performance status (KPS); history of pulmonary disease, cardiovascular disease, and diabetes; AJCC stage; external dose; treatment period; combination with chemotherapy; utilization of brachytherapy, and stratification of institutions. RESULTS: Statistically significant prognostic factors for all patients in the non-surgery group were KPS p=.0001), stage (p=.0001), and utilization of brachytherapy (p=.0102). For younger patients, KPS (p=.0001), stage (p=.0007), external dose (p=.0001), and utilization of brachytherapy (p=.0034) were significant, and for the elderly, stage (p=.0001) and external dose (p=.0006). CONCLUSION: Although this was a preliminary study, age was not a significant prognostic factor for esophageal cancer patients in the non-surgery group, and making the external dose more than 60 Gy appears to be effective for improving survival of elderly as well as younger patients.

Adenocarcinoma↗

PubMed2006

Recent advances in the detection of bone marrow micrometastases: A promising area for research or just another false hope? A review of the literature.

The presence of early disseminated tumor cells (DTC), otherwise termed micrometastases or minimal residual disease, in the bone marrow (BM), or other secondary compartments, such as the blood and the lymph nodes, is the main reason for recurrence of patients with early stage epithelial cancers after "curative" resection of the primary tumor. There is increasing evidence, that the detection of DTC in BM aspirates may provide additional and independent prognostic information and aid in the stratification of these patients for adjuvant clinical treatment. However, the clinical relevance of micrometastases has not yet been firmly established. In addition, the molecular events and interactions that prevail in early metastatic disease and determine the formation or not of overt metastases remain poorly understood. The methods currently used for the detection of micrometastatic cells include extremely sensitive immunocytochemical and molecular assays, often in conjunction with enrichment techniques for the purification of tumor cells and additional increase of their sensitivity. Nevertheless, the specificity of these methods is mostly inadequate. After the impressive advances of molecular cytogenetics, a highly accurate and global assessment of the genetic status of tumors is now possible. Therefore, the greatest challenge of our time is the application of these novel technologies for the clarification of the key molecular events that initiate metastatic spread. This will further enable us to identify the highly specific and sensitive diagnostic and prognostic markers as well as the therapeutic targets which are so urgently needed.

Animals↗

PubMed1999

Outcome of biphenotypic acute leukemia.

BACKGROUND AND OBJECTIVE: Although biphenotypic leukemia is now a defined entity, outcome of this rare form of acute leukemia has not been well documented. We present the first comprehensive study analyzing induction and consolidation therapy of biphenotypic leukemia and correlate outcome to prognostic factors. DESIGN AND METHODS: In this retrospective study, the incidence of biphenotypic leukemia was found to be 3.6% from 693 adult and pediatric acute leukemias referred to our center for treatment over the last 8 years. Of these, 15 were B-lymphoid/myeloid, 8 were T-lymphoid/myeloid, one was T/B lymphoid and one had trilineage differentiation. RESULTS: Induction of remission in de novo cases was achieved in 70% of patients and relapse of disease occurred in 15%. The use of combined lymphoid and myeloid drugs for induction resulted in a high incidence of early deaths (25%). The overall probability of survival at 2 years was 39.4%. Patients with secondary disease had a uniformly poor outcome with low remission rates and high relapse rates. INTERPRETATION AND CONCLUSIONS: Prognosis was most strongly related to the presence of the Philadelphia chromosome (p=0.03) and age under 15 years (p=0.01). We conclude that patients with biphenotypic leukemia should have risk stratification with treatment tailored to their prognostic factors.

Acute Disease↗

PubMed2005

Correlation of gamma-catenin expression with good prognosis in medulloblastomas.

OBJECT: Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined. METHODS: Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade M0) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the M0 group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease. CONCLUSIONS: Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator.

Adolescent↗

PubMedDate not supplied

Dipyridamole technetium 99m sestamibi myocardial tomography as an independent predictor of cardiac event-free survival after acute ischemic events.

BACKGROUND: A total of 137 consecutive patients with recent uncomplicated myocardial infarction (n = 31) or unstable angina (n = 106) were studied to determine the relative prognostic value of predischarge clinical risk stratification and intravenous dipyridamole stress sestamibi (MIBI) myocardial tomography in patients unable to exercise maximally after an acute ischemic coronary event. METHODS AND RESULTS: Patients were followed up after the index study for 10 +/- 5 months (range 1 to 23 months) to ascertain cardiac events that occurred in 20 patients (15%): nonfatal myocardial infarction (n = 5) or cardiac death (n = 15). Cardiac event rates were 35% in patients with a recent myocardial infarction and 8% in the group with unstable angina (p < 0.001). Patients with these cardiac events had more frequent abnormal MIBI study results, fixed defects, and reversible plus fixed (combined) defects (all p < 0.05). The univariate relative risk of death or myocardial infarction associated with an abnormal MIBI study was 6.0 (95% confidence limits 0.8 to 44.7). Multivariate stepwise logistic regression models identified an abnormal MIBI study and either fixed or reversible MIBI defects as being predictive of death or myocardial infarction (all p < 0.05). The Mantel-Haentzel 1-year cardiac event-free survival rate was excellent in 27 patients with a normal MIBI single-photon computed emission tomographic scan (100%) but significantly reduced in the 110 patients with an abnormal MIBI study (80%; p < 0.05 vs normal subjects). The presence of combined MIBI defects was associated with the poorest event-free survival rate (66%; difference not significant vs fixed or reversible defects only). CONCLUSION: We conclude that predischarge dipyridamole MIBI tomography provided independent prognostic information in this population of patients who were unable to exercise after a recent acute ischemic coronary event.

Aged↗

PubMed2006

Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome.

Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome. Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome. Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients.

Adolescent↗

PubMed2004

[Preliminary results of the use of MRD test among children with acute lymphoblastic leukaemia].

UNLABELLED: The purpose of the study was to monitor minimal residue disease (MRD) among children with ALL and to evaluate the possibility of using this test to detect and monitor the minimal residual disease (MRD test) in the stratification of risk groups on a parallel basis with other recognised prognostic factors. MATERIALS AND METHODS: 56 children, with de novo diagnosed ALL, comprised test group. Control group consisted of 10 healthy persons. DNA was isolated from peripheral blood and bone marrow. During research applied was the PCR method with the use of starters specific for conservative IgH and TCR delta gene fragments. ALL therapy was monitored by evaluation of MRD in the 15th and 33rd day of treatment and prior to supportive treatment. Stratification into risk groups, based on the MRD test results was compared with the stratification conducted in accordance with the recognised prognostic factors, such as: primary leucocytosis, steroid therapy response, drug resistance and karyotype. RESULTS: Among 52 children (92.8%) of the 56, which were tested prior to the start of treatment, obtained the sought for rearrangement, 90-120bp size stripe being an amplified regrouping of the VDJ fragment. Among all the tested healthy persons, the test result was negative. Testing the IgH and TCR delta gene regrouping allowed to demonstrate clonality of the neoplastic process during the diagnosis in 92.8% of the cases. In some of them the regrouping had a bi- or oligoclonal character. The number of patients with a positive MRD test result was dependent on the phase of treatment. Positive results were recorded among 10% of the patients (4/39) during clinical remission, among 86% (6/7) deceased and among 80% (4/5) suffering from relapse. Among 16.7% (2/13) of the patients with determined relapse or who died due to the course of illness process were also observed negative MRD test results. Steroid resistance was stated among 18/56 children, out of which 8/56 obtained a positive MRD test result in the 33rd day of treatment. Among 3 of them the result was maintained prior to supportive treatment. Leucocytosis during diagnosis above 50 thousand was recorded among 10/56 patients. Among 5 of them determined was rearrangement on the 33rd day of treatment, and for 1 prior to supportive treatment. Cytogenetic tests showed a correct karyotype for 19 out of 56 tested children. In this group steroid resistance was determined among 8 children, high preliminary leucocytosis among 5 and in 17 cases of the tested rearrangement. Stratification into therapeutic groups based on classical prognostic factors in most cases was the same with the stratification based on the MRD test results. The accuracy of the latter method was greater. CONCLUSIONS: The use of MRD test has its application in risk group qualification. MRD test is helpful in determining relapses prior to the appearance of clinical symptoms. Among the tested group of children with ALL a positive MRD test result was a bad prognostic factor. It seams that the use of a combined analysis of the risk factors and the MRD test results in a significant manner contribute to a more complex evaluation of the patient's condition.

Adolescent↗

PubMed2006

Molecular prognostic markers in resectable colorectal liver metastases: a systematic review.

BACKGROUND: Determination of prognosis in patients with resectable colorectal liver metastases (CLM) is desirable in order to improve case selection for surgery and tailor adjuvant treatment according to individual recurrence risk. Conventional clinicopathological factors lack the sensitivity to accurately achieve this goal. Consideration of tumour biology and the identification of molecular prognostic markers may allow more accurate risk stratification. METHOD: This systematic review examines evidence from published manuscripts looking at molecular markers in resectable colorectal liver metastases and their correlation with disease recurrence and survival following hepatectomy. RESULTS: Studies have yielded promising results in the search for prognostic molecular markers of CLM. Molecular biomarkers from varied aspects of tumour biology have been examined and a number of these, including proliferation indices, telomerase, thymidylate synthase, microvessel density and thrombospondin-1 appear to have prognostic utility in this context. Validation of other markers, notably p53, has been limited by a failure of methodologies to account for their biological complexity. CONCLUSIONS: A biomarker-based approach may yield significant benefits through informed treatment of resectable metastatic colorectal malignancy. Standardised retrospective analyses are necessary to confirm preliminary findings and identify existing and novel markers for inclusion into prospective studies. Assessment and verification of multiple molecular markers in this manner may allow molecular profiling of metastases and tailoring of therapy according to the biological aggressiveness of individual tumours. The advent of genomic- and proteomic-based technologies will allow the simultaneous analysis of multiple molecular markers and the derivation of disease profiles associated with disease recurrence and poor survival.

Apoptosis↗

PubMed2003

Medium- to long-term prognostic impact of dipyridamole thallum-201 myocardial single-photon emission computed tomography in elderly patients.

Dipyridamole thallium-201 single-photon emission computed tomography (SPECT) has not been extensively evaluated for risk stratification and the medium- to long-term prognostic value in elderly cardiac patients who are unable to exercise. The present study group comprised 210 consecutive patients aged at least 70 years with known or suspected coronary artery disease (CAD). The SPECT findings were classified as a reversible, fixed, or combined (reversible and fixed) defect. Of the 210 patients, 201 (77+/-5 years, 85 male) were successfully followed for 49+/-26 months. Thirteen (7%) patients had cardiac events: cardiac death (n=10), non-fatal myocardial infarction (n=1), or coronary artery bypass grafting (n=2). Cardiac events occurred in 3 of 112 patients with normal SPECT and in 10 of 89 patients with an abnormal scan (0.7% /year vs 2.8% /year, p=0.01). Stepwise Cox regression analysis revealed that the significant predictors of cardiac events were combined defects (relative risk 7.3) and the number of defect areas (relative risk 4.4). The predictive value of dipyridamole thallium-201 SPECT is maintained over 4 years in mixed populations of elderly CAD patients who are unable to exercise.

Aged↗