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Prediction of persistent carbohydrate intolerance in patients with gestational diabetes.

A 12-month prospective study was carried out in 120 Chinese patients with gestational diabetes who were found to have persistent carbohydrate intolerance at 6 weeks postpartum. The 75 g OGTT and WHO diagnostic criteria were employed for both antepartum and postpartum assessment. By 12 months, persistent carbohydrate intolerance was found in 13.3% of the patients only, 6 patients were diabetic while 10 had impaired glucose tolerance. Of those whose carbohydrate tolerance reverted to normal, 85% did so within the first 6 months. The clinical variables were analysed by multiple discriminant analysis using the logistic model. Five prognostic variables which were predictive of persistent carbohydrate intolerance at 12 months were identified. In order of decreasing predictive value, these included a high fasting glucose during pregnancy and at the first postnatal visit, a high antepartum 2 h blood glucose, the requirement of insulin during pregnancy, and a high postpartum 2 h blood glucose. Macrosomia, gestational age at diagnosis and a family history of diabetes were not predictive of persistent carbohydrate intolerance. Multiparity, maternal age and body mass index were of marginal significance only. The fitted logistic model provides a mechanism to estimate the probability of persistent carbohydrate intolerance. Such information will be helpful in patient counselling and in the efficient planning of postpartum medical follow-up.

Adult↗

Prognostic significance of N-terminal pro-atrial natriuretic factor (1-98) in acute myocardial infarction: comparison with atrial natriuretic factor (99-126) and clinical evaluation.

OBJECTIVE: To evaluate the prognostic significance of plasma N-terminal pro-atrial natriuretic factor (1-98) concentrations measured in the subacute phase after acute myocardial infarction, and to compare the predictive value of measurement of N-terminal pro-atrial natriuretic factor (1-98) with the measurement of atrial natriuretic factor (99-126) and with clinical assessment of the degree of heart failure. DESIGN: Prospective observational. SETTING: Norwegian central hospital. PATIENTS: 139 patients (mean (SD) age 66.9 (11.1) years, 71.2% males) with acute myocardial infarction. Patients in cardiogenic shock or with severe heart failure (New York Heart Association class IV) were excluded. MAIN OUTCOME MEASURE: Cardiovascular death within 12 months. RESULTS: During the follow up period 15 patients died. In a univariate Cox proportional hazards model N-terminal pro-atrial natriuretic factor (1-98) was significantly related to mortality (p = 0.0003). In a multivariate model the prognostic value of N-terminal pro-atrial natriuretic factor (1-98) was better than that of atrial natriuretic factor (99-126) and clinical assessment of heart failure (N-terminal pro-atrial natriuretic factor (1-98), p = 0.0003; atrial natriuretic factor (99-126), p = 0.4513; heart failure, p = 0.0719). The odds ratio estimate of patients in whom plasma concentrations of N-terminal pro-atrial natriuretic factor (1-98) were greater than 2000 pmol/l was 25 (95% confidence interval 2.8-225.0) compared with patients with plasma concentrations less than 1000 pmol/l. CONCLUSIONS: These results suggest that determination of plasma N-terminal pro-atrial natriuretic factor (1-98) in the subacute phase of myocardial infarction may provide clinically relevant prognostic information that is superior to that obtained from atrial natriuretic factor (99-126) measurements and clinical evaluation.

Aged↗

The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases.

The grade of a tumour is gauged on the subjective assessment of a number of histopathological parameters. The problems associated with this exercise were viewed from a historical perspective and survival analysis of 447 patients receiving surgery for rectal adenocarcinoma was undertaken. Only deaths from rectal adenocarcinoma were included as events in the survival analysis. Seven grade-related parameters were scored by one observer. A grading system was constructed using the Cox regression model. The variables in the best-fitting parsimonious model comprised lymphocytic infiltration, tubule configuration and pattern of growth. Scores were derived from the model and a four grade system was created in which the groups were of similar size. Good reproducibility of the selected histopathological parameters was demonstrated. Grade-related parameters were then allowed to compete with stage-related parameters in an overall model of pathological prognostic categories. The parameters selected in the best model were number of affected lymph nodes, the presence of lymphocytic infiltration and extent of spread through bowel wall. A set of five prognostic categories was developed from this model.

Adenocarcinoma↗

Prognostic implications of different cell cycle analysis models of flow cytometric DNA histograms of 1,301 breast cancer patients: results from the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).

Conflicting prognostic results with regard to DNA flow cytometric cell cycle variables have been reported for breast cancer patients. An important reason for this may be related to differences in the interpretation of DNA histograms. Several computer programs based on different cell cycle fitting models are available resulting in significant variations in percent S-phase and other cell cycle variables. Our present study evaluated the prognostic value of percent S-phase cells obtained using 5 different cell cycle analysis models. Flow cytometric DNA histograms obtained from 1,301 fresh frozen breast cancer samples were interpreted with 5 different cell cycle analysis models using a commercially available computer program. Model 1 used the zero order S-phase calculation and "sliced nuclei" debris correction, model 2 added fixed G2/M- to G0/G1-phase ratio, and model 3 added correction for aggregates. Model 4 applied the first-order S-phase calculation and sliced debris correction. Model 5 fixed the coefficients of variation CVs of the G0/G1- and G2/M-phases in addition to applying the sliced nuclei debris correction and zero order S-phase calculation. The different models yielded clearly different prognostic results. The average percent S-phase cells of the aggregate correction model (model 3) provided the best prognostic value in all cases for overall survival (OS) as well as disease-free survival (DFS) (OS: p < 0.0001; DFS: p < 0.0001), in lymph node-positive cases (OS: p < 0.0001; DFS: p = 0.004) and in DNA-diploid subgroups (OS: p = 0.004; DFS: p = 0.001). For the lymph node negative and DNA-non-diploid subgroups, the percent S-phase of the second cell cycle reached slightly better prognostic significance than the average percent S-phase cells. In multivariate analysis, the average percent S-phase of the aggregate correction model had the best additional prognostic value to tumor size and lymph node status. In conclusion, different cell cycle analysis models yield clearly different prognostic results for invasive breast cancer patients. The most important prognostic percent S-phase variable was the average percent S-phase cells when aggregate correction was included in cell cycle analysis.

Adult↗

Additive or sequential nucleoside analogue therapy compared with continued zidovudine monotherapy in human immunodeficiency virus-infected patients with advanced disease does not prolong survival: an observational study.

To study the effect of sequential or additive use of zalcitabine or didanosine on survival in 308 human immunodeficiency virus-infected patients with advanced disease treated with zidovudine, an observational study using time-dependent Cox proportional hazards models was done. Changing to sequential or additive therapy was based on deterioration of a patient's health status, a significant drop in CD4 cell count, or intolerance for zidovudine. The median CD4 cell count at baseline was 110 x 10(6)/L; 42% of patients had AIDS. The median count before a change in therapy was 50 x 10(6)/L. Additive or sequential treatment was associated with an increased risk for death (relative hazard, 1.59; 95% confidence interval [CI], 1.01-2.49; and 1.58; 95% CI, 1.10-2.37, respectively). Adjustment of the models for prognostic factors failed to substantially affect this observation. Possibly the lack of benefit in this study is because patients switched therapy at advanced stages, whereas the switch may be more effective in early disease.

Adult↗

Differences between echocardiographic measurements of left ventricular dimensions and function by local investigators and a core laboratory in a 2-year follow-up study of patients with an acute myocardial infarction.

AIMS: To examine differences in measurements of left ventricular dimensions and function, and prognostic value between local investigators and a core laboratory in a multicentre serial echocardiographic study. METHODS AND RESULTS: Seven hundred and fifty-six patients with acute myocardial infarction and preserved left ventricular function were examined at baseline and after 3 months with measurements by the biplane Simpson's method, and followed prospectively from 3 to 24 months. At baseline and 3 months local investigators relative to the core laboratory measured lesser end-diastolic volume by 8 and 6 ml (P<0.001), end-systolic volume by 3 and 2 ml (P<0.01), and ejection fraction by 0.0 and 0.6% (P<0.01), respectively. Local investigators and the core laboratory measured an increase in left ventricular end-diastolic volume of 8.6 and 6.9 ml, and in left ventricular end-systolic volume of 5.2 and 4.3 ml, and a decrease in left ventricular ejection fraction of 0.6 and 0.0%. Using the Cox proportionate hazards model, the prognostic value for subsequent clinical endpoints was significant both for the 3-month values (P<0.05) and changes (P<0.005) measured by the core laboratory, but not by local investigators. CONCLUSION: Only measurements in the core laboratory had significant prognostic value for subsequent clinical endpoints. These results strongly support the use of a core laboratory in studies employing echocardiographic measurements.

Chi-Square Distribution↗

Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee.

BACKGROUND: As part of the international cooperative effort to develop a complete set of International Neuroblastoma Risk Groups, the International Neuroblastoma Pathology Committee (INPC) initiated activities in 1994 to devise a morphologic classification of neuroblastic tumors (NTs; neuroblastoma, ganglioneuroblastoma, and ganglioneuroma). METHODS: Six member pathologists (H.S., I.M.A., L.P.D., J.H., V.V.J., and B.R.) discussed and defined morphologically based classifications (Shimada classification; risk group and modified risk group proposed by Joshi et al.) on the basis of a review of 227 cases, using various pathologic characteristics of the NTs. The classification-grading system was evaluated for prognostic significance and biologic relevance. RESULTS: The INPC has adopted a prognostic system modeled on one proposed by Shimada et al. It is an age-linked classification dependent on the differentiation grade of the neuroblasts, their cellular turnover index, and the presence or absence of Schwannian stromal development. Based on morphologic criteria defined in this article, NTs were classified into four categories and their subtypes: 1) neuroblastoma (Schwannian stroma-poor), undifferentiated, poorly differentiated, and differentiating; 2) ganglioneuroblastoma, intermixed (Schwannian stroma-rich); 3) ganglioneuroma (Schwannian stroma-dominant), maturing and mature; and 4) ganglioneuroblastoma, nodular (composite Schwannian stroma-richlstroma-dominant and stroma-poor). Specific features, such as the mitosis-karyorrhexis index, the mitotic rate, and calcification, were also included to allow the prognostic significance of the classification to be tested. Recommendations are made regarding the surgical materials to use for an optimal pathobiologic assessment and the practical handling of samples. CONCLUSIONS: The current article covers the essentials and important points regarding the histopathologic evaluation of NTs. Using the morphologic criteria described herein, the INPC is proposing the International Neuroblastoma Pathology Classification. It is reported in a companion article in this issue (Cancer 1999;86:363-71).

Biometry↗

Biostatistical modeling using traditional preoperative and pathological prognostic variables in the selection of men at high risk for disease recurrence after radical prostatectomy for prostate cancer.

PURPOSE: Biostatistical models predicting the risk of recurrence after radical prostatectomy for clinically localized prostate cancer are necessary. Identifying these high risk patients shortly after surgery, while tumor burden is minimal, makes them candidates for possible adjuvant therapy and/or investigational phase II clinical trials. This study builds on previously proposed models that predict the likelihood of early recurrence after radical prostatectomy. MATERIALS AND METHODS: In our analysis we evaluate age, race, prostatic acid phosphatase and nuclear grade with the established prognostic variables of pretreatment prostate specific antigen, postoperative Gleason sum and pathological stage. RESULTS: After multivariable Cox regression analysis using only statistically significant variables that predicted recurrence we developed an equation that calculates the relative risk of recurrence (Rr) as: Rr = exp[(0.51 x Race) + (0.12 x PSAST) + (0.25 x Postop Gleason sum) + (0.89 x Organ Conf.). These cases are then categorized into 3 distinct risk groups of relative risk of recurrence of low (< 10.0), intermediate (10.0 to 30.0) and high (> 30.0). Kaplan-Meier survival analysis of these 3 risk groups reveals that each category has significantly different risks of recurrence (p < 0.05). This model is validated with an independent cohort of radical prostatectomy patients treated at a different medical center by multiple primary surgeons. CONCLUSIONS: This model suggests that race, preoperative prostate specific antigen, postoperative Gleason sum and pathological stage are important independent prognosticators of recurrence after radical prostatectomy for clinically localized prostate cancer. Race should be considered in future models that attempt to predict the likelihood of recurrence after surgery.

Aged↗

Molecular staging in stage II and III melanoma patients and its effect on long-term survival.

PURPOSE: To assess the prognostic value of serial reverse transcriptase polymerase chain reaction (RT-PCR) -based measurements of tyrosinase mRNA in peripheral blood of stage II and III melanoma patients. PATIENTS AND METHODS: During routine follow-up of American Joint Committee on Cancer stage II and III melanoma patients, serial testing for tyrosinase transcripts in peripheral blood was performed by RT-PCR. The PCR results were compared with the clinical data collected during the follow-up. RESULTS: Over a period of 3 years, 111 patients (78 stage II and 33 stage III patients) were enrolled, and tyrosinase determinations were carried out. The 6-year disease-specific survival probability was 97% for patients always showing negative RT-PCR results and 67% for patients who tested positive at least once. In a Cox proportional hazards model, the prognostic value of sex, age, site of primary tumor, histologic subtype, stage, Breslow's tumor thickness, Clark level, and the time-dependent variable PCR result was assessed. Patients with a positive RT-PCR test had a distinctly higher risk of dying from melanoma, with a hazard ratio of 12.6 (95% CI, 3.4 to 46.3; P < .001). CONCLUSION: Our study shows a strong association between PCR and disease-specific survival time. Detection of tyrosinase mRNA in peripheral blood may be of similar importance for the clinical course of melanoma as the detection of micrometastatic disease in the sentinel lymph node. Whether a combination of these two factors leads to a better definition of the prognosis of melanoma patients is under investigation in current studies.

Adult↗

[Effects and prognostic factors of HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia].

OBJECTIVE: To retrospectively analyze the curative effects and prognostic factors of HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia patients (CML). METHODS: Of the 35 CML patients, 26 were males and 9 were females, with a median age of 32 (12 - 50) years. 30 patients were in chronic phase of CML, 5 patients were in accelerated phase. Allo-HSCT from HLA identical siblings was performed for 35 patients, of whom 11 received bone marrow transplantation (BMT) and 24 peripheral blood stem cell transplantation (PBSCT). Conditioning regimens was TBI (total-body irradiation) + CY (CTX) protocol in 8 patients and BU/CY protocol in 27 patients. The average follow-up was 48 months (range 7 - 108 months). RESULTS: 34 (97.1%) patients were successfully engrafted. Among them, 21 patients (60.0%) had three years disease-free (DFS) survival. The overall 5-year survival (OS) was 57.1%. Two patients (5.7%) relapsed. Transplant-related mortality occurred in 12 patients. Hemorrhagic cystitis (HC) occurred in 5 patients and HVOD was observed in 1 patient. Acute graft-versus-host disease (aGVHD) occurred in 18 patients (51.4%), among them 7 patients (20.0%) were of grade III-IV. Chronic GVHD was in 17 patients (48.5%). There was no significant difference in 3-years DFS between BMT group and PBSCT group (54.5% vs. 62.5%, P > 0.05). The 3-year disease-free survival (DFS) was 42.9% in TBI/CY group and 55.6% in BU/CY group (P > 0.05). In univariate prognostic analysis model, the DFS at 3 years is 75% and 47.4% for < or =30 years patients and >30 years patients, respectively, P < 0.05. The 3-year DFS of patients with first chronic phase is higher than patients with advanced diseases (61.3% vs. 40%, P < 0. 05). The 3-year DFS in patients of grade I - II GVHD was higher than that in patients of grade III-IV GVHD (81.8% vs. 14.3%, P < 0.05). CONCLUSION: The patients who had transplantation done within 1 year after diagnosis during their first chronic phase of disease and who had low-grade GVHD have better prognosis. Those patients who had III-IV acute GVHD are prone to incorporate severe infection, which was a worse prognostic factor of allo-HSCT for chronic myelogenous leukemia.

Adolescent↗

Survival and prognostic factors in BRCA1-associated breast cancer.

BACKGROUND: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the classical tumour and treatment factors is unclear in BRCA1-associated BC. PATIENTS AND METHODS: We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic. To correct for ascertainment bias, the group of index patients undergoing DNA testing more than 2 years after BC diagnosis (n = 53) was separated from the other BRCA1-patients (n = 170). All BRCA1-associated patients were matched in a 1:2 ratio for age and year of diagnosis to sporadic BC patients. We compared the occurrence of ipsi- and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS). By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in BRCA1-associated and sporadic breast cancers. RESULTS: For the total group of 669 cases, the median follow-up was 5.1 years, the median age at diagnosis 39 years. We confirmed the existence of the typical BRCA1-associated tumour type and the high CBC incidence. No significant differences between BRCA1-associated and sporadic tumours were found with respect to ipsilateral BC recurrence (HR(mult) 0.7; P = 0.24), DDFS (HR(mult) 1.2; P = 0.37) or BC-specific survival (HR(mult) 1.3; P = 0.23). A trend towards a worse survival was found for BRCA1-associated ductal BC (HR(mult) 1.5, P = 0.07). Prognostic factors for BRCA1-associated BC were age at diagnosis, tumour size and morphology, and nodal status. Further, survival was non-significantly improved by systemic treatment and a bilateral salpingo-oophorectomy. No effect on survival of a contralateral prophylactic mastectomy was seen. CONCLUSIONS: BRCA1-associated BC is characterised by specific tumour characteristics, a high incidence of CBC and a trend towards a worse survival for the ductal tumour type. Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients.

Breast Neoplasms↗

CD31/PECAM automated and quantitative immunocytochemical assays in breast carcinomas: correlation with patient follow-up.

The purpose of this study was to determine the prognostic significance of quantitative CD31 immunohistochemical assays. CD31 assays were performed on a series of 167 breast carcinoma specimens under optimal technical conditions that involved frozen sections, an automated immunoperoxidase technique, and computer-assisted analysis of digitized colored microscopic images. Results of automated quantitative immunohistochemical assays were correlated with patient follow-up (9.6 years). Patients were divided into two subgroups: those who had axillary lymph node-positive (N+) disease and those who had lymph node-negative (N-) disease. The marked immunocytochemical expression of CD31 in tumors (cutoff point, 20%) was significantly (P = .033) associated with a poor overall survival rate (Kaplan-Meier, log rank test); however, a significant association was not observed in the N+ and N- subgroups. CD31-immunostained tumor cell surfaces larger than 20% correlated with the metastasis-free survival rate (P = .004) in all patients and in the N+ subgroup (P = .005) but not in the N- subgroup. In addition, marked immunocytochemical expression of CD31 correlated with the short-term disease-free survival rate (P = .04) in the N+ subgroup but not in the N- subgroup. In multivariate analysis (proportional hazards regression, Cox model) the prognostic significance of CD31 was independent of tumor size and histologic type but not of grade. The results suggest that, under optimal technical conditions (automated and quantitative immunohistochemical assays on frozen sections), immunohistochemical expression of CD31 is a significant prognostic indicator of overall and metastasis-free survival rates. CD31 has limited prognostic value, however, and is not a completely independent prognostic indicator because it is related to nodal status.

Adult↗

Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: identification of responders incorporating the age factor.

To identify responders when protein-bound polysaccharide (PSK) is used in adjuvant immunochemotherapy after curative resection of colorectal cancers, we examined the host and tumor factors that affect the prognosis incorporating the age factor. A total of 101 patients who had undergone macroscopic curative resection of colorectal cancer were treated with mitomycin C + fluoropyrimidine oral antineoplastics + PSK (MFP therapy) for two years in principle. These cases were divided into two age groups of <65 years [n=55; 54.8 +/- 8.3 years (mean +/- SD)] and > or =65 years (n=46; 69.1 +/- 3.3 years). Host factors including humoral factors (complement C3 and C4), immunosuppressive acidic protein (IAP), lymphocyte transformation (cellular factors) induced by various mitogens [phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK], and tumor markers (CEA, CA19-9) were measured. The cases were divided by the cut-off value of each parameter into > or = cut-off value and < cut-off value groups, and the 5-year survival rates were compared. The cut-off values obtained for these parameters and the tumor factor (Dukes class) were subjected to multivariate analysis to identify the markers that affect prognosis. The 5-year mortality rate was 74.5% in the <65 age group and 56.8% in the > or =65 age group, with a tendency of better prognosis in the <65 age group (p=0.1109). Compared to the <65 age group, the > or =65 age group showed higher levels of C3 (2-way ANOVA: p=0.0582), C4 (p=0.0009) and IAP (p=0.0110) over time, but lower PSK-induced stimulation index (SI) as an indicator of cellular immunity) (p=0.0001) and PHA-induced SI (p=0.2650) over time. These results indicated that compared to patients aged <65 years, patients aged > or =65 years were characterized by lowered cellular immunity in addition to augmented complement production and an aggravated immunosuppressive state, suggesting the presence of some differences in host immune function with aging. Using the Cox proportional hazard model, the prognostic determinant was found to be Dukes C in the <65 age group, and CEA level in the > or =65 age group. The present results suggested that analysis of prognostic determinants of this therapy should take into account the age factor. Especially in elderly subjects, responders to PSK may be identified using the preoperative CEA value.

Adult↗

Prognostic factors of hepatic encephalopathy after portacaval anastomosis: a multivariate analysis in 50 patients.

Portacaval anastomosis has proved to be effective in avoiding active and recurrent hemorrhage from gastroesophageal varices in liver cirrhosis. However, hepatic encephalopathy is the most common and serious complication of this procedure. The aim of this study was to investigate by multivariate analysis the predictive factors of development of hepatic encephalopathy in 50 Child's A and B cirrhotic patients whose variceal bleeding was treated with emergency (n = 17) or elective (n = 33) portacaval anastomosis. The etiology of the cirrhosis was alcoholic in 74% of cases. The mean follow-up was 22.7 +/- 16.6 months (range 1-60 months). The 2-yr probability of suffering from at least one episode of hepatic encephalopathy in the overall group was 43%. The multivariate analyses (Cox's regression method) of 37 variables based upon clinical history, physical examination, and laboratory data disclosed that only five of these variables had independent predictive value: need for diuretic treatment in the days prior to surgery, absence of hepatomegaly, and serum levels of total bilirubin, gamma-globulin, and hemoglobin. According to the contribution of each one of these factors to the final model, a prognostic index was obtained which allowed the division of patients in two different groups of risk for developing hepatic encephalopathy (20% and 74%, respectively, after 2 yr of surgery; p = 0.0002). This index may help to better choose those candidates for portacaval anastomosis.

Adult↗

Incidence and survival trends of esophageal carcinoma in the United States: racial and gender differences by histological type.

BACKGROUND: The incidence of esophageal adenocarcinoma in White males has been reported to be increasing. The aims of this study were to determine: 1) the incidence trends of esophageal carcinoma in the United States with an emphasis on histologic type, sex, and ethnicity, 2) whether the reported increase in stage IV tumors can be confirmed, and 3) survival trends and factors affecting survival. METHODS: Data from the SEER program of the National Cancer Institute with submission dates 1973-98 were used. Data on Hispanics were available for analysis only for the years 1992-98. Statistical analysis was performed utilizing SEER*Stat and SAS statistical software packages. RESULTS: The incidence of adenocarcinoma in White males is still rising (7.8%/year, P < 0.0001); however, the same trend was observed for White females (6.48%/year; P < 0.0001). Hispanic males (3.91 %/year; P < 0.02), and Hispanic females (9.4%/ year; P < 0.04). The incidence of squamous cell carcinoma has been steadily declining in White males and females and in Black females since 1973, with the incidence showing a dramatic and significant decline in Black males beginning in 1992 (8.53%/year; P = 0.0009). Stage 4 carcinoma is declining in incidence. Survival of patients with esophageal carcinomas has been improving. In a Cox multivariate model, independent prognostic factors in esophageal carcinoma included tumor stage, tumor type, gender, race, age at diagnosis, and year of diagnosis. CONCLUSIONS: 1) The incidence of adenocarcinoma continues to rise in White males and females, but also in Hispanics, while squamous cell carcinoma is declining; 2) the incidence of stage 4 carcinomas has been declining, and 3) survival has been steadily improving, independently of all other risk factors.

Adenocarcinoma↗

[Hazard ratio estimated from a proportional hazard model including two strongly correlated prognostic factors].

Estimates of hazard ratio from hypothetical survival data were examined, under the condition that the survival is affected by two prognostic factors X1 and X2 with two discrete values (0, 1) which are strongly correlated. Survival curves from the data were assumed to fit an exponential function. As an example, following numbers of subjects were used; 100 cases with X1 = 0 and X2 = 0, 10 cases with X1 = 1 and X2 = 0, 10 cases with X1 = 0 and X2 = 1, and 100 cases with X1 = 1 and X2 = 1. When the hazard ratio of X1 = 1 or X2 = 1 to X1 = 0 and X2 = 0 was 3, univariate analysis gave reasonable estimates around 3. Under the same condition, estimates of hazard ratio from multivariate analysis including the two variables X1 and X2 varied widely, depending on the survivals of 20 cases with X1 = 1 X2 = 0 or X1 = 0 X2 = 1. Probability of having extremely deviated estimates was demonstrated. The result illustrated successfully some points we should take into account when proportional hazard models including strongly correlated variables are applied.

Actuarial Analysis↗

Prognostic significance of Nm23/NDPK expression in breast carcinoma, assessed on 10-year follow-up by automated and quantitative immunocytochemical assays.

The Nm23 gene has been described as an antimetastatic gene; in some studies, disease progression in patients with solid tumours is related to Nm23 protein expression, which can be detected by immunohistochemical procedures. Detection of Nm23-H1 protein in breast cancer may be relevant for the monitoring of patient therapy, provided that the technical procedures are reliable and cost-effective. The aim of the present study was to determine the prognostic significance of Nm23, assessed by quantitative immunocytochemical assays (Nm23 ICAs), under optimal technical conditions. Nm23-H1 ICAs were performed on frozen sections, using an automated immunoperoxidase technique (Ventana) and computer-assisted analysis of digitized colour microscopic images (SAMBA), in a series of 168 breast carcinomas. The results of automated quantitative ICAs were correlated with patients' follow-up (129 months). Nm23-H1 immunocytochemical expression in histological sections of tumours in which more than 3 per cent of the surface area was positively stained was significantly (0.012) correlated with longer metastasis-free survival in both node-positive and node-negative groups of patients (P = 0.032 and P = 0.036, respectively) (Kaplan-Meier log-rank test, NCSS 6.0.1 software). Nm23 expression (cut-point 3 per cent) did not, however, correlate with overall survival, or with the recurrence-free survival. In multivariate analysis (proportional hazards regression, Cox model), the prognostic significance of Nm23 in terms of metastasis-free survival was independent of tumour size and grade, and of histological grade, in the entire cohort of patients. It is concluded that Nm23 immunodetection is only of limited practical clinical relevance in breast carcinoma, even when assessed under optimal technical conditions.

Adult↗

Beta-2 microglobulin and lactate dehydrogenase levels are useful prognostic markers in early stage primary gastric lymphoma.

The optimal management of primary gastric lymphoma (PGL) remains undecided because a definitive classification for therapeutic decision is not available. The International Index Project has proved to be useful in patients with nodal disease, but in extranodal presentation it has not been tested. We reviewed 297 patients with early stage PGL. They were initially classified according to the prognostic features of the International Index Project. No influence on duration of time to treatment failure (TTF) or overall survival was observed. For this reason we developed a logistical model to identify prognostic factors in patients with early stage PGL. Levels of beta-2 microglobulin and lactic dehydrogenase were observed to have prognostic significance in both univariate and multivariate analysis. With these parameters we constructed a logistical model to identify patients at low risk (TTF = 76%; at 7 years overall survival was 96%), statistically different to patients at high risk (TTF = 34% and overall survival = 22%). The number of patients at intermediate risk were too small to compare with the other groups. Because pathological or other clinical or laboratory prognostic features cannot help in the identification of a prognostic model, we propose that the use beta-2 microglobulin and lactic dehydrogenase can define different groups at risk and develop a prognostic system to define the best therapeutic approach in this patients.

Adult↗