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PubMed1998

Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival.

We have determined the expression of transforming growth factor alpha (TGF alpha), amphiregulin (AR), CRIPTO, the epidermal growth factor receptor (EGFR), erbB-2, erbB-3, and tumor angiogenesis in a series of 195 patients with stage I-IIIA non-small cell lung cancer (NSCLC) treated with radical surgery to define their usefulness as prognostic indicators of survival. A variable degree of specific staining in cancer cells was observed for the three growth factors and for the three growth factor receptors in the majority of NSCLC patients. A statistically significant association between overexpression of TGF alpha, AR, and CRIPTO was observed. Enhanced expression of AR was significantly correlated with enhanced expression of erbB-2 and advanced T-stage. A direct association was also detected for overexpression of TGF alpha and of erbB-2 or erbB-3, respectively. Sex, tumor size, nodal status, stage, microvessel count, as a measure of neovascularization, and AR overexpression significantly correlated with overall survival at univariate analysis. In a Cox multivariate analysis, the only characteristics with an independent prognostic effect on OAS were microvessel count [relative hazard (RH), 6.61; P < 0.00001), nodal status (RH, 1.59; P = 0.0013), and AR overexpression (RH, 1.72; P = 0.02). These results suggest that evaluation of neoangiogenesis and of certain growth factors, such as AR, can be useful in addition to conventional pathological staging to select high-risk NSCLC patients who may benefit from post-surgical systemic therapies.

Adult↗
PubMed1992

Tissue polypeptide antigen in breast cancer cytosol: a new effective prognostic indicator.

Since 1982 we have been evaluating oestrogen and progesterone receptors (PgR), cathepsin D and the cytosolic levels of the tumour marker, tissue polypeptide antigen (TPA), in 257 patients radically resected for breast cancer (follow-up 24-81 months). TPA was measured by an immunoradiometric assay previously validated for cytosol. No significant associations were found between cytosolic TPA and age, tumour size, lymph-node status, receptor status and cathepsin D. TPA+ cases showed a significantly longer disease-free survival (DFS) and overall survival (OS) than TPA-patients (log-rank P < 0.0001). The prognostic value of cytosolic TPA was also demonstrated after stratification by nodal status, PgR and cathepsin D. The prognostic value of TPA was independent of the other prognostic indicators, being the most powerful among the evaluated indices (Cox multivariate analysis: chi 2 15.5 for DFS, 11.4 for OS). We conclude that cytosolic TPA is a powerful additional prognostic factor in primary breast cancer. Its prognostic role should therefore be extensively evaluated.

Antigens, Neoplasm↗
PubMed1983

Evaluation of serum beta 2-microglobulin as a prognostic indicator in myelomatosis.

Serum beta 2-microglobulin (beta 2-m) is frequently increased in patients with myelomatosis. The possibility that it could provide a biochemical indicator of prognosis was tested in a group of 129 patients from 3 centres, all serum analyses being carried out in one laboratory by radioimmunoassay. A strong association between the pretreatment serum beta 2-m level and survival was demonstrated, the data for the 2 main subgroups being very similar. In further detailed analyses of 64 patients, serum beta 2-m proved to be a stronger indicator of prognosis than current "standard" clinical and laboratory data, including stage determined by the method of Durie and Salmon and the combination of haemoglobin level and blood urea. The association between serum beta 2-m and survival remained close after treatment as indicated by the findings at one year. The serum beta 2-m in myeloma reflects the tumour mass and also reduced glomerular filtration when renal failure supervenes. It is concluded that the serum beta 2-m is a powerful prognostic indicator in myelomatosis and of considerable value in the investigation of patients with the disease.

Beta-Globulins↗
PubMed1994

Quantitative analysis of mutant p53 protein in breast tumor cytosols and study of its association with other biochemical prognostic indicators in breast cancer.

Breast tumors are thought to originate, grow, and metastasize in an environment which includes steroid hormone receptors, their cognate steroid ligands, and many gene products which are regulated by steroid hormone receptor-ligand complexes. In this paper we describe highly sensitive and quantitative immunofluorometric procedures for measuring three proteins that are candidate prognostic indicators in breast cancer, namely, the p53 tumor suppressor gene product, carcinoembryonic antigen (CEA), and prostate specific antigen (PSA). These proteins were quantified in over 950 cytosolic tumor extracts along with estrogen and progesterone receptors (ER, PR). Association analysis between all five biochemical parameters revealed strong negative associations between p53 and receptors and strong positive associations between CEA and receptors. Negative associations between p53 and CEA and between CEA and PSA were also found. These associations, not quantitatively studied in previous reports, are related to each other using a hypothetical model. The observed associations may further contribute to the understanding of the biology of breast tumors.

Breast Neoplasms↗
PubMedDate not supplied

Transforming growth factor alpha (TGF-alpha) expression in biopsies of colorectal carcinoma is a significant prognostic indicator.

BACKGROUND: Predicting the outcome of patients with colorectal adenocarcinoma (CRCA) prior to surgery would be valuable in selecting high-risk individuals who may benefit from pre-operative adjuvant therapy. The aim of this study is to determine whether the expression of TGF-alpha in preoperative biopsies of patients with CRCA constitutes a significant prognostic indicator. METHODS: We studied the expression of TGF-alpha in preoperative biopsies of 106 patients with CRCA, who had at least 5 years follow-up, using an anti-TGF-alpha monoclonal antibody and utilizing the ABC immunoperoxidase technique. For survival analysis, we used the actuarial survival method, and the Log Rank test for statistical significance. RESULTS: CRCAs with low TGF-alpha expression (less than 25% of the tumor cells immunoreactive for TGF-alpha) had a significantly poorer survival than those with high TGF-alpha expression (more than 25%). After excluding from analysis biopsies showing mucinous or poorly differentiated CRCA, known predictors of poor prognosis, the results remained significant (p = 0.0289). CONCLUSION: It is concluded, therefore, that low or absent expression of TGF-alpha in pre-operative biopsies of patients with CRCA, as detected by immunohistochemistry, is a significant predictor of an unfavorable outcome.

Actuarial Analysis↗
PubMed1997

Telomerase activity in neuroblastoma: is it a prognostic indicator of clinical behaviour?

Neuroblastomas show remarkable biological heterogeneity, resulting in favourable prognosis or unfavourable prognosis due to aggressive growth despite multimodal therapy. Recently, we proposed that aggressive tumours express telomerase at a high level while the favourable tumours lack or have low telomerase expression. To evaluate the correlation between telomerase activity and other biological characteristics reported as prognostic markers (MYCN gene amplification, loss of heterogeneity (LOH) in the short arm of chromosome 1, trk-A expression, Ha-ras p21 expression, and DNA ploidy), we investigated these biological features in 105 untreated neuroblastomas. In these cases, 23 showed high telomerase activity, 78 showed low activity, and telomerase activity was undetectable in 4 cases. Most tumours with genetic alterations (MYCN amplification or 1p32 LOH) showed high telomerase activity. Most tumours with low or undetectable activity were aneuploid, and showed trk-A and Ha-ras expression. Three of the four tumours with undetectable telomerase activity regressed. In 2 of the tumours with low telomerase activity, the residual tumours maturated and showed repression of telomerase activity. Thus, the level of telomerase activity correlated with other genetic alterations and/or gene expression and may be a useful prognostic indicator in neuroblastoma.

Age Factors↗
PubMed1991

Prognostic indicators for the development of AIDS in HIV antibody positive haemophiliac patients: results of a three-year longitudinal study.

In February 1986, 40 out of 75 adult patients with haemophilia A attending St. James's University Hospital were human immunodeficiency virus (HIV) antibody positive. Over a three-year period these patients were prospectively studied with regard to possible prognostic indicators for the development of the acquired immune deficiency syndrome (AIDS). Using the Centres for Disease Control (CDC) classification of HIV infection, 17 patients (42.5%) developed group 4 disease during this time, giving an actuarial three-year progression rate of 44%, and 5 patients (12.5%) died. The following parameters measured at recruitment were found independently to predict progression to AIDS: a serum beta 2-m level of greater than 3.5 mg/l, (chi 2 = 15.95, P less than 0.001), a serum IgA level of greater than 4.5 milligram(s) (chi 2 = 6.08, P less than 0.02) and p24 antigenaemia (chi 2 = 5.7, P less than 0.05). The actuarial three-year progression rate in those patients abnormal by two or more of these parameters was 100% (n = 7), compared to only 7% in patients who were normal by all three values (n = 15). CD4+ lymphocyte counts and CD4+:CD8+ ratios were significantly lower in HIV positive compared with HIV negative patients (P less than 0.01), but did not predict the development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Which prognostic indicator should we use for clinical practice in the initial evaluation and follow-up of IIP: should we depend on PFT, HRCT or...what?

Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and fibrotic disorders of the lung parenchyma that cause restrictive physiology and impair gas exchange. Usual interstitial pneumonia and non-specific interstitial pneumonia comprise the majority of idiopathic interstitial pneumonia cases. Previous studies have identified the histopathologic pattern as the most important baseline factor in determining prognosis. The non-invasive diagnosis of these diseases is sometimes uncertain but histological evaluation is an imperfect gold-standard. In some cases, the biopsy specimen may not be representative of the entire lung. In other cases, there may be differences in interpretation of the histological findings. HRCT has also assumed a greater role in the diagnosis and management of patients with idiopathic interstitial pneumonia. Factors affecting prognosis are discussed controversially. Histological criteria, clinical features, or lung function parameters are not clear prognostic indicators. Increased interstitial abnormalities in the HRCT, parameters indicating restrictive lung function, desaturation at 6MWT and abnormal gas exchange are possible determinants of survival. The prognostic value of pulmonary function trends over time may prove more useful. Longitudinal behavior is a more accurate determinant of outcome than evaluation at a single point in time. It is important to remember that no predictor of survival can ever reliably predict an individual patient's prognosis. Physicians should realize this limitation, and use predictor tools as general prognostic guides, not crystal balls. However, due to the great variability in the natural history of the disease, close monitoring of the patients may be necessary to evaluate the individual course of each patient.

Biopsy, Needle↗
PubMed1991

IgM-associated primary diffuse mesangial proliferative glomerulonephritis: natural history and prognostic indicators.

Fifty-four adults with primary mesangial proliferative glomerulonephritis and IgM deposition were observed for a minimum of three years or until end-stage renal failure. The actuarial renal survival was 80 per cent at 5 years and 64 per cent at 10 years; multivariate analysis identified microscopic haematuria, extent of mesangial proliferation and global glomerular sclerosis as independent prognostic indicators.

Adolescent↗
PubMed1976

Natural history of bell's palsy: the salivary flow test and other prognostic indicators.

Fifty-one patients with Bell's palsy were evaluated within two days of onset and followed for six months without surgical intervention or effective medical treatment in order to observe the natural history of the disease. Sixty-three percent had a complete return while 37 percent had incomplete return. Age, the presence of pain, and taste alterations had no prognostic value. The progression of the palsy, response to maximal stimulation and salivary flow testing were approximately 80 percent accurate in predicting outcome. The salivary flow test was the most useful prognostic indicator since salivary flow became reduced within two days of onset in the patients likely to develop denervation while the other tests did not become altered until 3 to 14 days after onset. In patients with Bell's palsy, the salivation test seems to be the only method capable of predicting denervation before it begins; therefore, it should be ideal for selecting patients for appropriate treatment.

Adult↗
PubMed1977

Prognostic indices for survival during postcardiotomy intra-aortic balloon pumping. Methods of scoring and classification, with implications for left ventricular assist device utilization.

To define more clearly a salvageable patient for possible utilization of a left ventricular assist device prior to multiple organ failure and irretrievability during postcardiotomy intra-aortic balloon pumping (IABP), we made prospective and retrospective analyses to determine prognostic indices for survival. Serial left ventricular function curves (IABP on-off), scoring methods, hemodynamic and renal function tracking trajectories, survival versus nonsurvival data envelopes, and classification methods were developed and used. All patients requiring postcardiotomy IABP support who were in Class A survived; 80 percent of the patients in Class B survived. All patients who remained in Class C for 12 hours or more following operation with IABP support died. These preliminary analyses suggest that the postcardiotomy IABP-supported patient with a score of less than 6 who remains in Class C for 12 hours or more is at the highest possible risk and is a probably candidate for more effective support with a left ventricular assist device.

Assisted Circulation↗
PubMed1986

The N-terminal propeptide of collagen type III in serum as a prognostic indicator in primary biliary cirrhosis.

The serum level of N-terminal propeptide of collagen III (Col 1-3) has received increasing attention as a possible marker of liver fibrosis. Elevated levels have been reported in patients with primary biliary cirrhosis (PBC). We measured Col 1-3 levels in 24 patients with PBC (mean age 56 +/- 8 years) and compared their value as a prognostic marker with serum bilirubin and IgM levels, the aminopyrine demethylating capacity (ABT) and presence of clinical symptoms. Mean observation time was 5.1 +/- 2.7 years. When these parameters and age were evaluated as predictive factors for survival, only bilirubin, Col 1-3 levels and symptom status variables were found to be significant. When tested as explanatory variables for survival in a stepwise linear logistic regression model Col 1-3 was identified as the strongest significant (P less than 0.001) explanatory variable followed by bilirubin (P less than 0.01) whereas the symptom status emerged as a non-significant variable. The results suggest that the serum level of Col 1-3 may be a useful prognostic indicator in PBC, which is independent of the bilirubin level.

Adult↗
PubMed2001

Transiently evoked otoacoustic emissions as a prognostic indicator in idiopathic sudden hearing loss.

Idiopathic sudden sensorineural hearing loss (ISHL) remains a controversial topic. So far, there are no proven objective auditory factors to establish prognosis. Otoacoustic emissions reflect the functional integrity of the outer hair cells. The aim of this study was to assess the presence of transiently evoked otoacoustic emissions (TEOAEs) in the early stages of ISHL cases as a prognostic indicator. Thirty patients hospitalized for ISHL were included in the study. All patients underwent pure-tone audiometry (PTA) and TEOAE recordings on the admission day and at least three measures on the subsequent eight days. The audiometric threshold improvement at each frequency was correlated with the TEOAE parameters on each measure. Finally, the presence of TEOAEs on early examination was correlated with PTA threshold improvement. Twenty-three out of 30 patients experienced hearing recovery. Fourteen of the recovered patients had recordable TEOAEs or acceptable TEOAE peak amplitudes in some frequency bands on the first two measures, despite having audiometric thresholds greater than 40 dB HL. It thus seems that TEOAEs might serve as a clinical tool for prediction of recovery in ISHL cases.

Hearing Loss, Sudden↗
PubMed2005

Two pragmatic trials of treatment for shoulder disorders in primary care: generalisability, course, and prognostic indicators.

OBJECTIVE: To investigate predictors of long term prognosis in patients treated for shoulder pain in primary care. METHODS: Data were taken from two pragmatic randomised clinical trials investigating the effectiveness of conservative treatments for shoulder pain presenting to primary care. Shoulder pain severity, disability, and perceived recovery measured in the long term (UK, 18 months; Netherlands, 12 months) were considered as outcome measures. Prognostic indicators measured before randomisation were determined by linear regression (pain severity and disability) and logistic regression (perceived recovery). RESULTS: 316 adults with a new episode of shoulder pain were recruited (UK, n = 207; Netherlands, n = 109). In multivariate analysis, greater shoulder disability at follow up was associated with higher baseline disability score, concomitant neck pain, and a gradual onset and longer duration of shoulder symptoms. Pain scores at follow up were higher in women and in those with longer baseline duration of symptoms and higher baseline pain or disability scores. Being female, reporting gradual onset of symptoms, and a higher baseline disability score each independently reduced the likelihood of perceived recovery. CONCLUSIONS: The results suggest that there is no long term difference in outcome between patients with shoulder pain treated with different clinical interventions in different clinical settings, or having different clinical diagnoses. Baseline clinical characteristics of this consulting population, rather than the randomised treatments which they received, were the most powerful predictors of outcome. Whether this highlights the need for earlier intervention or reflects different natural histories of shoulder pain is a topic for further research.

Anti-Inflammatory Agents↗
PubMed2006

Dupuytren's diathesis revisited: Evaluation of prognostic indicators for risk of disease recurrence.

PURPOSE: The term diathesis relates to certain features of Dupuytren's disease (DD) and dictates an aggressive course of disease. The initial description of DD diathesis included 4 factors: (1) ethnicity, (2) family history, (3) bilateral DD, and (4) ectopic lesions (DD outside the palm). The degree of diathesis is considered important in predicting recurrence and extension of DD after surgical management. Prognostic indicators of risks associated with surgery are important. We aimed to evaluate these 4 factors and known associated risk factors to formulate a statistical predictive value for DD diathesis. METHODS: Caucasian patients diagnosed with DD between the ages of 25 and 90 years (n = 322) from Northwest England were assessed for DD diathesis with a clinical history and examination. DD diathesis assessment was analyzed by calculating the odds ratios of developing recurrent DD using logistic regression. RESULTS: The observed recurrence rates in the presence of notable risk factors and corresponding odds ratios of recurrent DD were calculated. Of note, recurrent disease was observed in 121 (46%) males, 105 (47%) with bilateral DD, 68 (48%) with a family history of DD, 75 (47%) with age at onset younger than 50 years, 35 (52%) in those with ectopic lesions, and in 26 (63%) with Garrod's pads. CONCLUSIONS: The original DD diathesis factors have been evaluated and modified. The original factors of family history, bilateral DD, and ectopic lesions now include 2 additional factors: male gender and age at onset of younger than 50 years. Family history and ectopic disease have now been modified to specify family history with one or more affected siblings/parents and ectopic lesions in the knuckles (Garrod's pads) alone. The presence of all new DD diathesis factors in a patient increases the risk of recurrent DD by 71% compared with a baseline risk of 23% in those DD patients with none of the earlier-described factors. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Adult↗
PubMed2001

Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have recently been reported, but it was unclear whether deletions arose during disease progression or at the time of the Ph translocation. Fluorescence in situ hybridization (FISH) analysis was used to assess the deletion status of 253 patients with CML. The strength of deletion status as a prognostic indicator was then compared to the Sokal and Hasford scoring systems. The frequency of deletions was similar at diagnosis and after disease progression but was significantly increased in patients with variant Ph translocations. In patients with a deletion, all Ph(+) metaphases carried the deletion. The median survival of patients with and without deletions was 38 months and 88 months, respectively (P =.0001). By contrast the survival difference between Sokal or Hasford high-risk and non-high-risk patients was of only borderline significance (P =.057 and P =.034). The results indicate that deletions occur at the time of the Ph translocation. An apparently simple reciprocal translocation may therefore result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations. Deletion status is also a powerful and independent prognostic factor for patients with CML. The prognostic significance of deletion status should now be studied prospectively and, if confirmed, should be incorporated into management decisions and the analysis of clinical trials.

Adult↗
PubMed1999

Maximum Density of Tumor Staining Obtained by Preoperative IV-DSA as a Prognostic Indicator for Node-Negative Breast Cancer.

BACKGROUND: We previously demonstrated that the density of tumor enhancement by intravenous digital subtraction angiography (IV-DSA) is correlated with the number of tumor microvessels and that the incidence of distant metastasis is highin patients with breast cancer who show a high maximum density of tumor enhancement (MAX) on IV-DSA. In the present study, we evaluated the prognostic value ofMAX for node-negative breast cancer patients. Patients and METHODS: A total of 128 node-negative breast cancer patients underwent preoperative IV-DSA, and the region of interest (ROI) was set in the areas enhanced by IV-DSA of the breast. MAX was calculated by the time-density curve. Patients were divided into two subgroups: those with MAX >/= 9 (n=35) and those with MAX < 9 (n=93). RESULTS: Patients with recurrence had a significantly higher MAX value than those without recurrence (11.8 +/- 3.8 vs 7.1 +/- 3.0, p<0.01). The disease-free survival rate was significantly worse in patients with higher MAX values than in those with lower MAX values (p <0.001). Multivariate analysis showed that MAX was the strongest predictor of disease-free survival (p =0.026). CONCLUSIONS: These results suggest that the maximum density obtained by IV-DSA is a strong, independent prognostic indicator for node-negative breast cancer patients.

Journal Article↗
PubMed1998

Postcastration eventration in 18 horses: the prognostic indicators for long-term survival (1985-1995).

Castration of horses is considered a common and routine surgical procedure, but the potential for complications is high. By far the most serious of these is eventration. The objectives of this study were to determine the long-term survival of horses undergoing surgical treatment of indirect (1) inguinal eventration of the small intestine following castration, and to identify prognostic indicators for survival. The case records of 18 horses undergoing surgical treatment of postcastration eventration (PCE) between 1985 and 1995 were reviewed. Follow-up information was obtained by telephone interviews 2 to 13 y postoperatively. A Cox proportional hazard regression model was fitted to determine which clinical features were of significant influence to survival. Clinical features with a significant negative influence on survival were an inguinal surgical approach for correction, an increased length of prolapsed bowel, and performance of bowel resection and anastomosis. Significant postoperative complications developed in 89% of cases; 44% of cases in the "inguinal" surgical approach group developed peritonitis, compared with 10% in the "midline" approach group. Of all horses in this study, 72% were discharged from the hospital; however, only 40% of horses in the inguinal approach group were discharged. The long term survival rate (> 1 y) for all horses in this study was 44%, with a median survival time of 3-1/2 mo.

Animals↗