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PubMedDate not supplied

Prognostic value of cathepsin-D expression in female breast cancer.

Expression of an acidic lysosomal protease, cathepsin-D (CD), was analysed immunohistochemically in a series of 151 breast carcinomas with special reference to its prognostic significance, Strong expression of CD was detected in 22% of cases. This intense expression was significantly associated with a number of established prognostic factors, including the non-ductal type of carcinoma (p = 0.0243) and metastases at the time of diagnosis (p = 0.0068). On the other hand, high expression of CD was not related to the lymph-node status, tumour size, ER/PR content or histological grade. Patients with CD overexpression has a significantly lower survival probability (p = 0.0478) than did the patients with low expression of this protease. The relationship between the high expression of CD and short disease-free survival was almost significant (p = 0.0519). Intense immunostaining of CD was associated with a significantly impaired disease outlook in patients with confirmed lymph node metastasis (N+) (p = 0.0137) but not in those with negative lymph nodes (N-) (p = 0.0620). In Cox's multivariate analysis, expression of CD had no independent prognostic value over the conventional prognostic factors. The results suggest that expression of CD is of borderline significance in evaluating the intrinsic malignancy of female breast cancer in general. The potential of CD as a prognostic factor in specific subgroups of breast cancers will be the subject of further studies.

Breast Neoplasms↗

PubMedDate not supplied

c-erbB-2 overexpression may be used as an independent prognostic factor for breast cancer patients.

Insight into correlations between specific gene amplification and the clinical behavior of tumors may provide new prognostic tools High c-erbB-2 expression is an early feature in some breast tumors, whereas c-myc may be involved in the development of neoplasia. After an initial flurry of excitement about their prognostic significance, controversy has arisen about their independent importance. In an attempt to solve this problem, we decided to study c-erbB-2 and c-myc amplification and overexpression in 62 unselected breast carcinomas. This was done in order to correlate them statistically with one another, as well as with other prognostic parameters. A positive correlation was discovered between c-erbB-2 amplification and overexpression (P = 0.02); however, the correlations between c-erbB-2 amplification and c-myc amplification and overexpression (P = 0.06 and P = 0.095 respectively) were found to be negative. In addition, no correlation was found to exist between c-erbB-2 amplification and Cathepsin-D, steroid receptors, node status and menopausal status, as well as between c-erbB-2 overexpression and Cathepsin-D, node invasiveness, tumor status, grade or menopausal status. In conclusion, the c-erbB-2 overexpression has positive correlation with only a few other prognostic parameters, and therefore can be used as an independent prognostic factor.

Breast Neoplasms↗

PubMed1995

[Prognostic factors in uterine cervical and corpus cancer].

We have studied the prognostic factors for cancer of uterine cervix and corpus. Prognostic factors for cervical cancer include clinical stage, histological type, pelvic and paraaortic lymph node metastasis and CPL classification of carcinoma. Prognostic factors for cancer of uterine corpus are concerned with clinical stage, histological type and histological differentiation, muscle invasion, lymph node metastasis, perineal washing cytology and so forth. The clinical stage of course, reflects the prognosis. Although one of the important prognostic factors is lymph no metastasis, there may be recurrence in patients with a poor prognosis in cases in which lymph node metastasis has not been observed. In order to distinguish such cases and to improve their prognosis, it is important to provide treatment individually but combined chemotherapy or radiation therapy, for example, with efforts to detect various prognostic factors.

Female↗

PubMed1993

Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study.

A cohort of 98 HIV-infected initially AIDS-free homosexual men from the Multicenter AIDS Cohort Study (MACS) was followed for 6 years to investigate whether CD8+ cell subsets have prognostic value for progression to AIDS. In the present study, four subsets of CD8+ T cells that previously have been shown to be selectively elevated in HIV-infected asymptomatic persons, specifically the CD8+ T cell subsets that were CD38+, HLA-DR+, CD57+ and L-selectin negative (Leu8-), were measured. Forty-nine of the 98 developed AIDS. Prognostic value of these CD8+ cell subsets was evaluated using the proportional hazards model. Levels of both CD38+ CD8+ and Leu8- CD8+ cells individually had prognostic value for progression to AIDS. In contrast, CD57+ CD8+ and HLA-DR+ CD8+ cell subsets levels did not have prognostic value. After adjustment for level of CD4+ T cells, however, only the elevation in the CD38+ CD8+ cell subset had additional prognostic value. These results suggest that the level of CD38+ CD8+ cells could be used together with the CD4+ T cell level to more accurately predict progression to AIDS among HIV-infected men. These results provide further support for the observation that dramatic and progressive activation of CD8+ T cells in HIV infection occurs. The power of elevated levels of the CD38+ CD8+ subset to predict poor prognosis in this cohort suggests these CD8+ T cells reflect an immune stimulation that is ultimately unable to control disease progression.

ADP-ribosyl Cyclase↗

PubMed1995

Plasma calprotectin: a new prognostic marker of survival in alcohol-induced cirrhosis.

Plasma levels of calprotectin were determined in 84 patients with alcohol-induced cirrhosis. Calprotectin is released from disintegrating neutrophils, and plasma levels seem to reflect activation and turnover of such cells. The purpose of the study was to investigate the degree of activation of neutrophils, which has been indicated to be increased and a cause of neutrophil exhaustion in these patients. Additionally, on follow-up after a median observation period of 559 days, we investigated the prognostic value of calprotectin for survival. No difference was found in calprotectin levels when comparing healthy controls with patients with compensated cirrhosis and those with decompensated cirrhosis. However, high calprotectin concentrations (> median) were a significant prognostic marker of poor survival (P = .001, log-rank test). Using a multivariate Cox proportional hazard model, the prognostic value of calprotectin seemed independent of severity of liver disease evaluated on eight clinical and biochemical variables of liver disease. Divided into groups by the median calprotectin concentration, analysis of survival was performed in the whole series of patients (n = 84) as well as in patients who were completely without signs of recent or actual infection (n = 54). In both groups, calprotectin levels (> median) showed a much higher prognostic value than albumin, prothrombin complex, bilirubin, and ascites. During follow-up, calprotectin levels (> median) were also a predictor of recurrent infection (P = .009). Thus, in patients with alcoholic cirrhosis, plasma calprotectin seems to be a new prognostic marker of survival, which seems independent of the severity of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Invasive node-negative breast carcinoma: multivariate analysis of the prognostic value of peritumoral vessel invasion compared with that of conventional clinico-pathologic features.

The prognostic value of the determination of peritumoral vessel invasion (PVI) in node-negative breast cancer (NNBC) patients is still controversial. This is mainly related to the subjective criteria of evaluation of this histologic finding using morphological methods only. In this study, to assess PVI by stricter criteria, we used both conventional morphological and immunocytochemical techniques, using antibodies specific to endothelial cells (i.e. factor VIII-related antigen and the CD-31 antibody). In a series of 233 evaluable NNBC, with a median follow-up of 5 years, we found that 11% of the tumors (25 out of 233) were PVI-positive. A weak association was observed only between PVI and tumor size (p = 0.076). In univariate analysis PVI significantly predicted relapse-free survival (p = 0.0009), but not overall survival (p = 0.1208). The odds of relapse and death for patients with PVI-positive carcinomas were 4.36 and 2.24 times higher than for those with PVI-negative tumors. As far as relapse-free survival is concerned, tumor size (p = 0.0012), histologic grading (p = 0.022), estrogen receptor (p = 0.016) and progesterone receptor expression (p = 0.017) also had a significant prognostic value. Only tumor size significantly predicted overall survival (p = 0.0038) in this series. For 5-year relapse-free survival both PVI (p = 0.014) and tumor size (p = 0.017) were significant and independent prognostic variables by multivariate analysis. Our results demonstrate that PVI and tumor size are important histological features to identify high-risk NNBC patients. Further studies are needed to compare the prognostic significance of PVI and tumor size with that of novel biological prognostic indicators of emerging importance in this neoplasia.

Adult↗

PubMed1994

[The incremental prognostic value of the scintigraphic indices of myocardial hypoperfusion in patients with a maximal stress test].

The additional prognostic value of thallium imaging in patients who are capable of performing a maximal, symptom-limited electrocardiographic stress test is still uncertain. Thus, we evaluated the incremental prognostic value of exercise thallium-201 indexes of myocardial hypoperfusion in 296 patients with suspected or known coronary artery disease who performed a maximal ECG stress test. At 2 year follow-up 20 hard events (16 cardiac deaths and 4 non fatal myocardial infarctions) and 44 soft events (myocardial revascularization procedures) occurred. Considering total events, thallium imaging provided significant additional prognostic information to clinical and exercise stress test data in all patients (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, whichever the end-point considered, thallium imaging did not add incremental prognostic value. When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give incremental prognostic information in patients with previous myocardial infarction but not in the subset of patients without previous infarction.

Adult↗

PubMedDate not supplied

Cathepsin-D and c-erb-B 2 have an additive prognostic value for breast cancer patients.

In breast cancer, axillary lymph node invasiveness is the major prognostic factor in predicting relapse and metastasis. Nevertheless, since 30% of node-negative tumours also relapse, it is necessary to develop other independent prognostic factors. Oncogene amplification and overexpression as well as the level of cathepsin-D have been proposed as additional prognostic factors. Recent studies suggest that the acidic lysosomal proteinase cath-D, present in all cells and known to be secreted in breast cancer cells, may be implicated in the process of tumour invasion and metastasis. We have compared the cytosolic cath-D level with the amplification and the overexpression of the oncogenes c-myc and c-erb-b-2 in 62 breast carcinomas (52 primary and 10 metastatic). Using a cut-off level of 60 pmol/mg protein, the status of cath-D showed a positive correlation with c-myc amplification (P = 0.01) or overexpression (P = 0.02). In contrast, no correlation was found between cath-D and c-erb-B-2 amplification or overexpression. Also, no correlation was found between cath-D and established prognostic factors such as node invasiveness, steroid receptors, grade and menopausal status. Nevertheless, a weak correlation was found between cath-D levels and tumour status (P = 0.05). In conclusion, in breast cancer, a high cytosolic cath-D concentration is more frequent in tumours with c-myc amplification and overexpression but is dissociated from c-erb-B-2 amplification or overexpression, suggesting that the determination of cath-D, as well as the latter two markers, will have an additional prognostic value.

Breast Neoplasms↗

PubMed1994

Prognostic factors and survival in malignant pleural mesothelioma.

Malignant pleural mesothelioma is a lethal disease and little is known about prognostic factors. The prognostic significance of age, stage of disease, gender and histological subtype was studied in 167 new cases of cytologically (15%) or histologically (85%) proven malignant pleural mesothelioma in the Rotterdam area, during the period 1987-1989. Median survival of all patients was 242 days. Univariate analysis identified age, stage and histopathological subtype as significant prognostic factors, which was confirmed in multivariate analysis. Median survival rates for patients < 65, 65-74 and > or = 75 yrs were 359, 242 and 131 days, respectively. Patients with Stage I disease had a median survival of 359 days compared to 147 and 112 days, respectively, for patients with Stage II and the combination of Stages III and IV. Mixed histopathological subtype (190 days) was less favourable than sarcomatous (207 days) and epithelial (252 days) subtypes. Using a Cox proportional hazard model in patients with malignant pleural mesothelioma, age, histological subtype and stage were identified as independent prognostic factors. These prognostic factors should be taken into account when starting or evaluating treatment studies.

Age Factors↗

PubMed1994

Prognostic factors in the management of ureteric injuries.

The outcome of 137 ureteric injuries was analysed with respect to previous radiotherapy, site, type and length of the injury and time of treatment, to evaluate the prognostic significance of each of these factors. The length of the injury was the most important prognosticator of treatment outcome (P = < 0.0005). Previous radiotherapy and timing of treatment had prognostic significance (P = < 0.05) but the predictive value seemed to be linked to the frequent association with injury length. The site and the type of injury had no prognostic significance. The unfavourable prognostic significance of extensive injury length appeared to be related to the treatment procedures (urinary diversions) which in themselves carry a high failure rate. Knowledge of the impact of these factors on the outcome of ureteric injuries is valuable in choosing the best treatment option for each patient.

Female↗

PubMed1994

Development and validation of a prognostic index predicting death after upper gastrointestinal bleeding in patients with liver cirrhosis: a multicenter study.

Prognostic factors of the outcome of upper gastrointestinal bleeding in patients with cirrhosis are insufficiently defined. Pertinent clinical, biochemical, and endoscopic data of 332 upper gastrointestinal bleedings in 268 patients with cirrhosis observed in the participating centers during 31 months were recorded. Clinical data were analyzed until 40 days after bleeding. A further set of 82 bleedings was used as a validation group. Ninety-two of the 268 patients died within the time of the study, and 28 of the 82 patients of the validation group died. According to a stepwise logistic regression analysis, s-creatinine, ascites on admission, previous diagnosis of hepatocellular carcinoma, s-bilirubin, prothrombin index, varices as definite or probable source of bleeding, gender, and presentation with hemathemesis were the best set of covariates for predicting outcome. From them a prognostic index was developed and validated in the 82 further bleedings. Sensitivity and specificity in the cumulated training and test sets were 75 and 80%, respectively. In the present material, the prognostic index was significantly more efficient than Child-Pugh score or the prognostic index proposed by Garden et al. These data show that it is possible to predict the outcome of upper gastrointestinal bleeding in cirrhosis on the basis of few easily available data. The prognostic index we proposed and validated may become useful to predict the outcome of a bleeding and to select or stratify patients in clinical trials.

Esophageal and Gastric Varices↗

PubMed1994

A practical view of prognostic factors for staging, adjuvant treatment planning, and as baseline studies for possible future therapy.

At this time the initial prognostic assessment of breast cancer patients is still most powerfully driven by basic histopathologic information, axillary nodal involvement, and tumor size. Estrogen and progesterone receptor status are important initial pieces of information for many patients, but this information is more important in deciding the most appropriate type of treatment, rather than the prognosis of the patient. Histologic and nuclear grading can provide important prognostic information, but broader application of this information awaits better methods to ensure accuracy and decrease intraobserver variability. Whether flow cytometry-derived information can be used to select patient subsets at very low risk of relapse awaits prospective validation in cooperative group trials. A number of new prognostic tests such as cathepsin D that have shown promise in some studies await definitive prospective validation. Further development of techniques to integrate prognostic factor information and the use of this information in individualized prognostic factor decisions is needed.

Algorithms↗

PubMed1993

Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989.

BACKGROUND: Multivariate analyses in papillary thyroid carcinoma (PTC) have shown that age, tumor size, local invasion and distant metastasis are independent predictive variables. This study attempted to define a reliable prognostic scoring system for predicting PTC mortality rates with 15 candidate variables that included completeness of primary tumor resection but excluded histologic grade and DNA ploidy. METHODS: The study group comprised 1779 patients with PTC (followed up for > 26,000 patient-years), divided by treatment dates into 1940 to 1964 (n = 764) and 1965 to 1989 (n = 1015). Cox model analysis and stepwise variable selection led to a prognostic model initially derived from the training set (n = 764). The initial prognostic score was thereafter validated externally with the later (1965 to 1989) "test" data set. RESULTS: The final model included five variables abbreviated by metastasis, age, completeness of resection, invasion, and size (MACIS). The final prognostic score was defined as MACIS = 3.1 (if aged < or = 39 years) or 0.08 x age (if aged > or = 40 years), + 0.3 x tumor size (in centimeters), +1 (if incompletely resected), +1 (if locally invasive), +3 (if distant metastases present). Twenty-year cause-specific survival rates for patients with MACIS less than 6, 6 to 6.99, 7 to 7.99, and 8+ were 99%, 89%, 56%, and 24%, respectively (p < 0.0001). CONCLUSIONS: Because the five variables needed for MACIS scoring are readily available after primary operation, such a prognostic system could have widespread applicability in assessment of PTC.

Aged↗

PubMed1993

Mortality in pneumococcal meningitis: a multivariate analysis of prognostic factors.

OBJECTIVES: The mortality due to pneumococcal meningitis remains high, ranging from 15 to 60%. The purpose of this study was to analyze the prognosis of pneumococcal meningitis using a multivariate approach. The objectives were to select the most accurate initial mortality risk factors in pneumococcal meningitis and to determine an individual probability of death according to these prognostic factors. METHODS: The records of 105 consecutive cases of proven pneumococcal meningitis were retrospectively reviewed. The following parameters, recorded at presentation were considered for prognostic analysis: age, sex, duration of symptoms and antimicrobial chemotherapy before admission, underlying debilitating conditions, occurrence of seizures, pneumococcal bacteraemia or pneumonia, Glasgow coma scale score, Simplified Acute Physiological Score (SAPS), Cerebral Spinal Fluid (CSF) leucocyte count, CSF protein level, CSF glucose level and CSF/blood glucose ratio. Those parameters having a prognostic value after univariate logistic regression analysis were then entered into a multivariate stepwise logistic regression model. RESULTS: In multivariate analysis, a fatal outcome was best predicted by 4 variables. In descending order, these were the Glasgow coma scale score, age, CSF glucose level and concomitant pneumonia. The risk of dying was ten times higher in patients with Glasgow coma scale score < 7, seven times higher in patients older than 45 or having a CSF glucose level lower than 0.6 mmol/L and 4 times higher in patients with pneumonia. The logistic model provided an equation for the probability of dying that proved to have predictive values greater than 80% in determining the individual prognostic of pneumococcal meningitis. CONCLUSIONS: Our results are in agreement with most of previously published findings. We further demonstrated that the individual prognosis of pneumococcal meningitis could be accurately predicted with only 4 variables and highlighted the preeminent prognostic value of Glasgow coma scale score.

Adolescent↗

PubMed1993

Routine tests of renal function, alcoholism, and nutrition improve the prognostic accuracy of Child-Pugh score in nonbleeding advanced cirrhotics.

In an attempt to improve the prognostic capacity of Child-Pugh score in nonbleeding cirrhotics, 110 consecutive in-patients without gastrointestinal hemorrhage at admission were studied and followed up for 24 months or until death. Fifty-five of the 110 patients (50%) died during this period. Mean survival time was 18.8 +/- 1.4 months (mean +/- SEM). In addition to Child-Pugh score, eight variables, including anthropometric nutritional parameters, routine renal function tests, and alcoholism markers, were recorded at admission. The ability of these variables to improve the prognostic capacity of the Child-Pugh score was assessed with the proportional hazard Cox's regression procedure, using a stepwise method for covariate selection, after including the Child-Pugh score at the first step. Thus, in addition to Child-Pugh score (beta = 0.302), three variables were included in the final model: serum urea (beta = 0.113), MCV (beta = 0.027), and mid-arm muscle circumference (beta = -0.025). According to the contribution of each of these factors to the model, a prognostic index was obtained to estimate survival in the individual patient. An assessment of the predictive power of the model was made by means of a split-sample technique. The prognostic index described in this study may contribute to improve the selection of nonbleeding patients with advanced cirrhosis to receive specific therapies such as transplantation. However, its true clinical relevance will be established only by prospectively comparing its prognostic value with that of the Child-Pugh score in a new sample of patients.

Alcohol Drinking↗

PubMed1993

[Prognostic significance of the histological classification and staging for patients with a malignant non-Hodgkin lymphoma].

OBJECTIVE: To assess the prognostic significance of histological classification, grade and stage with regard to overall survival in patients with non-Hodgkin's lymphoma (NHL). DESIGN: Retrospective analysis. SETTING: University Hospital St Radboud, Nijmegen. METHOD: All consecutive 346 patients with NHL diagnosed in the period January 1978-December 1990 were included in this one-centre study. Recorded data included histological type according to the Kiel classification, histological grading according to the International Working Formulation (IWF), Ann Arbor stage, age, sex, tumour mass, number of extranodal sites, serum LDH and ESR. Grading according to the IWF was assessed retrospectively for those patients whose primary disease had been diagnosed before 1982. The observation period ended September 1st, 1991. Overall survival was calculated according to Kaplan-Meier. The significance of the prognostic parameters was studied using both univariate and multivariate stepwise regression analysis. RESULTS: There were 209 men and 137 women with a median age of 56 years (range 15-85). No initial treatment was given to 8% of the patients. After a median follow-up of 52 months, 179 patients (52%) had died; the calculated median survival time was 49 months. Patients with low-grade NHL had a significantly better short-term prognosis than the remaining patients. Related to clinical stage, only patients with stage I disease had distinctly longer survival times than those with more advanced disease. Multivariate analysis revealed serum LDH, age, stage and histological classification to be the most important independent prognostic variables. CONCLUSION: Even in multivariate analysis, histological classification and Ann Arbor stage have prognostic significance with regard to overall survival in patients with NHL. However, serum LDH levels proved to be the most important prognostic parameter.

Adolescent↗

PubMedDate not supplied

Prognostic significance of serum CA 242 in pancreatic cancer. A comparison with CA 19-9.

The prognostic value of the novel tumour marker CA 242 was studied in 175 patients with pancreatic cancer and the results were compared with those of CA 19-9. Preoperative serum levels of CA 242 and CA 19-9 were determined by commercially available assays. Patients were classified according to UICC TNM-stage, and divided into three groups of resectable, non-resectable and advanced disease. The lowest cut-off levels that divided patients into groups with significant difference in survival were calculated. Patients with resectable disease and preoperative CA 242 below 25 U/ml had a significantly better prognosis than those with a higher level (p < 0.05). The corresponding cut-off values were 100 U/ml in non-resectable (p < 0.05) and 3500 U/ml in advanced disease (p < 0.05). It is noteworthy that the overall survival rate of patients who underwent resection for cure, but had a high preoperative CA 242 level, approached that of patients with non-resectable disease. In multivariate analysis, only resectability (p < 0.0001) and preoperative serum CA 242 level (p = 0.01) were independent prognostic factors. If TNM-stage was used instead of resectability, the results were similar (stage p < 0.0001, CA 242 p = 0.006). When CA 242 was excluded from the model, preoperative serum CA 19-9 level approached the borderline of significance as an independent prognostic factor (p = 0.07). In conclusion, the preoperative serum level of the novel tumour marker CA 242 is an independent prognostic factor in pancreatic cancer. CA 242 yielded more prognostic information than CA 19-9.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1996

Needle biopsy of hepatocellular carcinoma: assessment of prognostic contribution of histologic parameters including proliferating cell nuclear antigen labeling and correlations with clinical outcomes. Group d'Etude et de Traitement du Carcinoma Hépatocellulaire.

BACKGROUND: Although many studies concerning the prognostic factors of resected hepatocellular carcinoma have been performed, the prognostic information provided by needle biopsy of these tumors has not yet been extensively studied. METHODS: One hundred twenty-four white patients with histologically-confirmed hepatocellular carcinoma were entered into a prospective study from 1990 to 1992 with followed-up through October 1994. Most of the patients had cirrhosis (79%). Patients were classified according to Okuda's staging: Stage I (50%), Stage II (47%), and Stage III (3%). The one-year survival rate was estimated at 58% in Okuda's Stage I, and 15% in Stages II and III. Edmondson's grading, mitotic index, and proliferating cell nuclear antigen labeling index were studied on each biopsy. Univariate and multivariate analyses were performed to determine the prognostic significance of the different parameters. RESULTS: According to Edmondson's critera, 13 of the hepatocellular carcinomas were Grade I, 63 Grade II, 42 Grade III, and 6 Grade IV. There was a significant correlation between Edmondson's grade, mitotic index, and proliferating cell nuclear antigen labeling index (P < 0.01). Univariate analysis showed both the histologic grade (P < 0.001) and mitotic index (P < 0.05) correlated with survival. Cox's model indicated that Edmondson's grading yields additional prognostic information for Okuda's staging (P < 0.001). The one-year survival rate for Okuda's Stage I was 76% for Edmondson's Grades I + II versus 23% for Grades III + IV. CONCLUSIONS: Edmondson's grading appears to be an important prognostic parameter for patients with hepatocellular carcinoma, and could help stratify patients for clinical trials.

Adult↗