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Prognostic indicators of colon tumors. The Gastrointestinal Tumor Study Group experience.

This study sought to replicate and expand findings reported by the National Surgical Adjuvant Breast and Bowel Project (NSABP) on prognostic factors in resectable colon cancer. Mantel-Haenszel tests and the Cox model were used to analyze prognostic significance and effect of primary disease symptoms and tumor location in 572 patients from the Gastrointestinal Tumor Study Group (GITSG), with resected Dukes' B2 and C colon cancer. Tumor location (left, right, and rectosigmoid/sigmoid) was of low prognostic importance (P greater than 0.10), and did not effect survival or disease-free survival (P greater than 0.10). Obstruction was an important indicator of prognosis, independent of Dukes' stage (P = 0.03). Bowel perforation is associated with poor prognosis in disease-free survival (P = 0.001). Rectal bleeding had a positive impact on survival (P = 0.08). Thus, obstruction, perforation, and rectal bleeding (but not location) are found to be prognostic factors in patients with Dukes' B2 or C colon cancer.

Colonic Neoplasms↗

Prognostic indices in breast cancer are related to race.

African-American (AA) women have a higher mortality from breast cancer than Caucasians (C). This may be attributed to stage of disease at presentation, but specific prognostic factors are not well identified. We sought to identify prognostic factors in our database of early-stage (stage I and II) breast cancer from 1990 to 1999. There were 153 tumors in 150 AA women and 773 tumors in 760 C women. Prognostic factors are listed according to race with relative risk (RR) and 95 per cent confidence intervals. AA women presented significantly more often than C women under the age of 50 years (RR = 1.8) with palpable disease (RR = 1.3), higher-grade tumors (RR = 1.5), more estrogen receptor-negative disease (RR = 1.7), more progesterone receptor-negative disease (RR = 1.4), higher proliferation indices (RR = 1.9), and more lymph node-positive disease (RR = 1.6). Many of these adverse prognostic features persisted in "good" prognostic groups, i.e., those women over the age of 50 years with tumors <20 mm and having node-negative disease. We conclude that prognostic factors are related to race with AA women presenting at an earlier age and more often with palpable disease. More importantly AA women presented significantly more often with higher-grade tumors, hormone receptor-negative tumors, higher proliferation indices, and node-positive disease. These findings may explain a higher breast cancer mortality in AA women.

Adult↗

2',5' oligoadenylate synthetase activity in bovine peripheral blood mononuclear cells following bovine herpesvirus type-1-induced respiratory disease: a prognostic indicator?

Following aerosol-challenge of nonimmune calves with bovine herpesvirus type-1 (BHV-1) the levels of 2',5' oligoadenylate (2-5A) synthetase in peripheral blood mononuclear cells (PBML) increased significantly to peak 4-5 days after BHV-1 infection. This corresponded temporally to the period of highest susceptibility to secondary bacterial infection. Ten days post virus infection, the enzyme levels had returned to baseline values. Aerosol challenge with bacteria (Pasteurella haemolytica) did not induce 2-5A synthetase activity in PBML, neither did it influence the kinetics of 2-5A synthetase induction by virus infection during a dual viral-bacterial infection. Pretreatment of animals with bovine recombinant interferons (IFNs) 0-96 h prior to virus challenge curtailed the viral infection and thus reduced the levels of 2-5A synthetase induced by endogenously produced IFN. A relationship between 2-5A synthetase levels on day 5 post virus infection and clinical outcome of the dual infection was noted. Moreover, the high 2-5A synthetase levels could be correlated with low plasma Zn levels, another indicator of clinical respiratory disease. These results indicate that these two parameters, 2-5A synthetase and plasma Zn, in combination have potential prognostic value in viral-bacterial infections of the respiratory tract.

2',5'-Oligoadenylate Synthetase↗

Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: a case-control study.

PURPOSE: The purpose of this study is to determine the prognostic significance of overexpression of the HER-2 neu oncoprotein with respect to local relapse following conservative surgery and radiation therapy (CS + RT). METHODS AND MATERIALS: Twenty consecutive patients who sustained a local recurrence as the first and only site of failure following CS + RT comprised the case population base for this study. Only patients who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive local-relapse patients, the patient database was searched for 20 matching control patients who did not sustain a local relapse. Each control patient was matched to the index case with respect to age, menopausal status, follow-up, primary histology, axillary nodal status, and primary tumor size. Both index cases and the matched control group received full course radiation therapy, to a total dose of 64 Gy to the tumor bed. The paraffin-embedded blocks of the original primary tumor of the local-relapse cases and the primary tumor of 20 matched controls were processed for immunohistochemical staining of the HER-2 neu oncoprotein. Each slide was rated on the 3-point scale, 0 representing no stain, 1+ indicating light staining, and 2+ denoted heavy staining (overexpression). RESULTS: Of the 20 index cases, with each of the matched controls, 16 were evaluable for analysis. The 4 cases that were eliminated had inadequate paraffin-embedded material in either the case or the match control for adequate staining. By design of the study, the index case group and control group had similar ages (52 years index vs. 51.4 control), follow-up (10.8 years index vs. 10.5 years control), and histologies. For the immunostaining, a value of 2+ was considered to denote high activity and overexpression, and 0 and 1+ were considered negative values. Using these criteria, a total of 9 of the 16 index cases (56%) exhibited overexpression of HER-2 neu oncoprotein, and only 3 of the 16 control cases (18%) demonstrated high immunoreactivity. The difference in immunostaining between the index and control cases was statistically significant by a Pierson chi-square analysis at the p = 0.03 level. CONCLUSIONS: In this matched case-control study, overexpression of the HER-2 neu oncoprotein appears to have prognostic significance with respect to local relapse in the conservatively treated breast. The correlation of overexpression of HER-2 neu by multivariable analysis with other prognostic factors for local recurrence warrants further investigation. The clinical implications of the study are discussed.

Adult↗

In vivo propionate oxidation as a prognostic indicator in disorders of propionate metabolism.

Biochemical markers such as plasma and urinary metabolite concentrations and in vitro enzyme activity are of limited prognostic value in the most common disorders of propionate metabolism, methylmalonic acidaemia (MMA) and propionic acidaemia (PA). In vivo propionate oxidation was compared with conventional prognostic measures as predictors of clinical severity in seven children with MMA and six with PA. Propionate oxidation was measured using a continuous infusion of [1-13C]propionate and was expressed as the rate of appearance of 13CO2 as a percentage of the propionate infusion rate. Children with MMA (mean oxidation 51.2%, range 17.5-91.6, P less than 0.05) and with PA (mean oxidation 36.3%, range 3.0-91.1, P = NS) oxidised substantially less propionate than controls (mean oxidation 81.9%, range 69.4-101.0, n = 5). Percentage oxidation was a better predictor of the clinical severity score (r = 0.75, P less than 0.01) than was in vitro enzyme activity, plasma propionate or methylmalonate concentration or urinary metabolite excretion. Studies were repeated after an interval of 1-3 weeks in six of the subjects; the percentage oxidation in each subject was virtually unchanged between studies (coefficient of variation 8.6%). These results suggest that in vivo oxidation measurements using [13C]propionate are both reproducible and prognostically useful in disorders of propionate metabolism.

Adolescent↗

Analysis of imaging modalities, staging systems, and prognostic indicators for renal cell carcinoma.

A retrospective analysis of 314 patients with renal cell carcinoma was done focusing mainly on imaging modalities and prognostic significance of tumor stage using both the Robson and TNM systems. Computerized tomography (CT) scan proved to be the most effective modality for staging. Overall staging accuracy was 62 and 68 percent for TNM and Robson staging, respectively, and understaging was more frequent than overstaging. The actuarial five-year survival using the Robson system was 73 percent for Stage A, 68 percent Stage B, 51 percent Stage C, and 20 percent Stage D. The main limitation of the Robson system is the heterogeneity of the Stage C group which includes patients with renal vein and those with nodal involvement with a significant difference in survival. The survival by the TNM system showed no difference in those with T1, T2, T3a and T3b disease but a significant difference in those with T3c or T4a. One hundred sixteen patients (37%) presented with metastatic disease with a median survival of seventeen months (range 2-204) for those with solitary metastasis and six months (range 1-132) for those with multiple metastases (the difference was not statistically significant). Except for anecdotal cases, nephrectomy with or without treatment of the metastases did not seem to affect survival significantly. The presence of spindle cell, alone or in association with clear or granular cell, affected the prognosis adversely. Thirty-one patients had their tumors identified incidentally. Their stage at diagnosis was earlier than the symptomatic group (Stage T1-T2: 77% vs 34%), and there was a significant difference in the disease-free survival at fifty-four months between the two groups (79% vs 57%, respectively).

Adult↗

Expression profiling identifies chemokine (C-C motif) ligand 18 as an independent prognostic indicator in gastric cancer.

BACKGROUND & AIMS: Gastric cancer is one of the major cancers worldwide. Expression profiling has proven useful in delineating novel prognostic markers in various cancer types. We previously analyzed gene-expression patterns in 90 gastric adenocarcinomas by using complementary DNA microarrays and prioritized a list of genes whose expression levels predict patient outcome. METHODS: We identified a specific gene of interest, chemokine (C-C motif) ligand 18 (CCL18), on the basis of a high absolute standardized log Cox hazard ratio, a high variance in expression among all tumor samples, and putative biologic function. Detailed analysis of CCL18 expression with clinicopathologic and survival data was performed (n = 89). Quantitative reverse-transcription polymerase chain reaction was used to verify the microarray expression data and was further applied to analyze an independent cohort of tumor samples (n = 59). The cellular source of CCL18 was determined with immunohistochemistry and in situ hybridization. RESULTS: High CCL18 expression levels were associated with prolonged overall (P = 0.001; hazard ratio, 0.586) and disease-free (P = 0.002; hazard ratio, 0.416) patient survival in the array-based data set by univariate analysis. The observations were confirmed in an independent set of 59 patients by using quantitative reverse-transcription polymerase chain reaction. In multivariate analysis, tumor stage and CCL18 levels were independent prognostic factors for predicting both overall and disease-free survival. We found that CCL18 was expressed by a subpopulation of tumor-associated macrophages that were preferentially located at the tumor invasion front. CONCLUSIONS: Macrophage-derived CCL18 may function as a local antitumor immunomodulator that affects patient outcome. Our study suggests CCL18 as a novel candidate for antitumor therapeutics and risk stratification in gastric cancer patients.

Adenocarcinoma↗

Natural killer cell activity in patients with hepatocellular carcinoma: a new prognostic indicator after hepatectomy.

BACKGROUND: Natural cytotoxicity mediated by natural killer (NK) cells is believed to play an important role in host anticancer defense mechanisms. The aim of this study was to examine the prognostic significance of NK cell activity after hepatectomy in patients with hepatocellular carcinoma. METHODS: The NK cell activity in 210 patients with hepatocellular carcinoma was measured and evaluated in relation to clinicopathologic variables using univariate and multivariate analyses. RESULTS: The NK cell activity was decreased significantly in hepatocellular carcinoma patients compared with the control groups (P < 0.001). No correlation was observed between NK cell activity and the clinicopathologic variables. Multivariate analyses indicated that NK cell activity as well as intrahepatic metastases, platelet count, and serum albumin level were independent prognostic factors. CONCLUSIONS: This study suggests that the preoperative NK cell activity will help predict recurrence and prognosis after hepatectomy in patients with hepatocellular carcinoma.

Adult↗

Thoracotomy for pulmonary metastatic osteosarcoma. An analysis of prognostic indicators of survival.

Removal of pulmonary metastases of osteosarcoma by thoracotomy is an accepted treatment; however, few investigators have analyzed the value of various prognostic factors in estimating survival. A review of all patients undergoing thoracotomy for recurrent osteosarcoma with pulmonary metastases treated at St. Jude Children's Research Hospital is reported. Since 1968, two thirds (39/59) of all patients who developed pulmonary metastases have had a total of 66 thoracotomies. Nine patients are alive with no evidence of disease, and six additional patients are alive with disease. Analyzed in 39 evaluable patients, the prognostic factors that correlate with survival by univariate analysis are: sex, number of nodules detected radiographically and resected, completeness of resection, and tumor location (bilateral versus unilateral). By Cox regression analysis, only sex and the number of nodules detected either radiographically or during surgery, and resected, had statistically significant correlation with survival. Thoracotomy is curative for some patients with pulmonary metastatic osteosarcoma and Prognostic factors predictive for survival are defined.

Child↗

Haematological prognostic indices after myocardial infarction: evidence from the diet and reinfarction trial (DART).

Data from the Diet and Reinfarction Trial were examined to check the prognostic effects of plasma fibrinogen, plasma viscosity, white blood cell count, haemoglobin and mean platelet volume in 92 deaths among 1755 men who had recently recovered from acute myocardial infarction. All these variables were significantly associated with all-cause mortality over the following 18 months (haemoglobin negatively, the others positively). Those who gave up smoking following their infarct had a lower mortality than those who continued to smoke (4.1% and 7.9% respectively), and this effect appeared to be mediated by fibrinogen levels. Smoking habit accounted for only part of the prognostic effect of fibrinogen and white blood cell count. Haematological variables have an important prognostic significance after myocardial infarction. Cessation of smoking after myocardial infarction is worthwhile and has a favourable effect on plasma fibrinogen.

Blood Viscosity↗

Long-term follow up of progesterone receptor status in benign meningioma: a prognostic indicator of recurrence?

OBJECT: A long-term prospective analysis of patients with benign meningioma was undertaken to determine whether progesterone receptor (PR) status of the excised tumor has any influence on recurrence. METHODS: Between 1983 and 1985, a total of 62 meningiomas in 53 patients (age range 19-79 years, mean age 55.6 years) were studied for clinical, histological, and pathological characteristics, including hormone receptor status and DNA features. Progesterone receptor status was quantified by cryostat section assay, and then factors affecting recurrence were analyzed. During 1997 all case records were reviewed to determine whether tumor had recurred in any patient, and PR status was correlated with tumor recurrence. Of the 62 tumors, 60 were benign, and of the benign tumors 29 (48%) were PR positive. Patients harboring 14 of the 60 benign tumors were lost to follow up. Of the 46 tumors included in the final analysis, 13 were recurrent (all within 5 years) and 33 were nonrecurrent. Of the 33 nonrecurrent tumors, 14 had not recurred 5 to 10 years postresection and 19 had not recurred after more than 10 years. Chi-square analysis of the results did not show an association between recurrence and patient's sex, extent of resection, histological subtype, or tumor site but did show an association between recurrence and PR negativity (p = 0.013). CONCLUSIONS: The results indicate that benign meningiomas that are PR positive are less likely to recur, a finding that has prognostic and therapeutic implications.

Adult↗

Feline mammary adenocarcinoma: tumor size as a prognostic indicator.

Mammary carcinomas and adenocarcinomas (MACs) are relatively common tumors in cats. The postexcisional survival period of affected cats is inversely proportional to tumor size, but the reported median survival periods for different tumor size categories is quite variable. This variability diminishes the prognostic value of reported data. In our study, cats with MACs greater than 3 cm in diameter had a 12-month median survival period, whereas those with MACs less than 3 cm in diameter had a 21-month survival period. Survival periods for cats with MACs smaller than 3 cm ranged from 3 to 54 months; therefore, tumor size alone is of limited prognostic value in cats with MACs smaller than 3 cm in diameter. In cats with MACs larger than 3 cm in diameter, tumor size appears to have much higher prognostic relevance, because this study, as well as others, have indicated that cats with MACs greater than 3 cm in diameter have a poor prognosis, with median survival periods ranging from 4 to 12 months.

Adenocarcinoma↗

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region.

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

Aged↗

Serum C-reactive protein correlates with survival in colorectal cancer patients but is not an independent prognostic indicator.

BACKGROUND: C-reactive protein (CRP) is an acute-phase protein synthesized in liver and up-regulated by pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor (TNF). Elevated CRP has been reported to be associated with reduced crude survival rates in patients with colorectal cancer. OBJECTIVE: To investigate the prognostic significance of preoperative serum CRP in relation to the disease-specific survival rate and expression of different cytokines. METHODS: One hundred and seventy-two consecutive patients with colorectal cancer, whose primary lesions were resected, were selected from April 1995 to December 1999. Preoperative serum CRP levels were measured, and the relationship between the elevation of CRP and clinicopathological factors was investigated. Prognostic significance was analysed by univariate and multivariate tests. RESULTS: One-third of patients had increased CRP levels, and this was associated with larger tumour size, lymph node or liver metastasis, and advanced Dukes' stage. Higher CRP levels were also related to the elevation of IL-6 and IL-8. The most important prognostic factor predicting survival was Dukes' stage (P < 0.001). Multivariate analysis indicated that CRP level is not an independent factor predicting survival. CONCLUSIONS: A preoperative elevation of serum CRP does not have the independent prognostic significance reported by earlier studies. Whether the elevated CRP can predict the development of cachexia or whether this association characterizes a pattern in tumour behaviour remains to be determined.

Adult↗

Prognostic indices for mortality of hospitalized children in central Africa.

A hospital-based follow-up study was conducted between 1986 and 1988 at Lwiro (South Kivu Province, Zaire). Of 1,129 children in the study, three of four were severely malnourished, and 17.4% died. This study analyzes the mortality in hospital; its objectives are to evaluate the prognostic power of edema and anthropometric and biologic indicators and to seek indices that perform better. Receiver operating characteristic curves were established for each parameter under study and for each index constructed. Areas under receiver operating characteristic curves were highest for biologic indicators, and simple indices, obtained by counting the number of risk factors present, performed best. In the absence of biologic parameters, the authors suggest classifying children as at risk of dying when they present with edema and/or with arm circumference of less than 115 mm. When biologic measurements are possible, in addition to edema and arm circumference, the authors suggest taking serum albumin and transthyretin into account. For serum albumin and transthyretin, mortality risk is defined in terms of values of less than 16 g/liter and 6.5 mg/dl, respectively. Children will be classified as at risk of dying when they present with at least two of the four risk factors. The resulting diagnostic test has a high sensitivity (91.2%) and positive and negative predictive values of 40.8% and 97.9%, respectively.

Anthropometry↗

MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators.

BACKGROUND: Although mucin expressions appear to be correlated with prognoses in patients with various cancers, several studies have reported conflicting and inconclusive results on the prognostic significance of mucin expression in gastric carcinomas. METHODS: To clarify the correlations between clinicopathologic profiles and the patients' survival, the expression of MUC1, MUC2, MUC5AC, MUC6 mucins and the p53 protein were evaluated immunohistochemically in 300 consecutive gastric carcinomas using the tissue-array method. In addition, 59 gastric adenomas and 57 adenoma-associated carcinomas were investigated. RESULTS: MUC1 was expressed in 2 (3.4%) cases of gastric adenoma, and MUC2 in 19 (32.2%) cases of gastric adenoma, out of a total of 59 lesions. In consecutive gastric carcinomas, 24.3% of gastric carcinomas expressed MUC1, 27.3% expressed MUC2, 38.0% expressed MUC5AC and 12.7% expressed MUC6. The rate of MUC1 expression in gastric carcinomas was significantly higher than in associated gastric adenomas (P < 0.01). The patients with MUC1-positive carcinomas showed significantly poorer survival than those with MUC1-negative carcinomas. On the other hand, MUC2, MUC5AC and MUC6 expressions were not significantly associated with patient survival. Interestingly, combined evaluation revealed that the group with the MUC1-negative plus p53-negative expression pattern showed a better prognosis than the remaining cases. In contrast, the group with the MUC2-negative plus p53-positive pattern showed a worse prognosis. CONCLUSIONS: Mucin expression is altered in gastric adenoma and carcinoma, and MUC1 mucin expression is significantly associated with poorer outcome in gastric carcinomas. A MUC1-negative plus p53-negative pattern or a MUC2-negative plus p53-positive pattern may predict outcome in patients with gastric carcinomas.

Adenoma↗

Fibronectin as a prognostic indicator in portal hypertension.

Plasma fibronectin levels were measured in 33 patients with portal hypertension and compared with modified Child's grading and a previously described prognostic index. Outcome at one year from blood sampling was recorded. Mean plasma fibronectin level was 304.1 mg/ml (sem 24.3) and significantly lower levels were found in patients who had had a variceal bleed within the previous seven days. Plasma fibronectin levels tended to be lower in patients with poor liver function as assessed by modified Child's grading but this did not achieve statistical significance. Plasma fibronectin alone was not an accurate predictor of one year survival in these patients but only one of seven patients who had a plasma fibronectin level below 300 mg/l in association with a poor prognostic index survived for one year.

Esophageal and Gastric Varices↗

Early prognostic indicators of outcome in infants with neonatal cerebral infarction: a clinical, electroencephalogram, and magnetic resonance imaging study.

OBJECTIVE: The aim of this study was to identify prognostic factors in newborns with cerebral infarction. DESIGN: Antenatal and perinatal factors and early clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) findings were compared with neurodevelopmental outcome in 24 children with evidence of cerebral infarction on neonatal MRI. RESULTS: Out of 24 infants, 19 had an infarction in the territory of a major cerebral vessel and 5 in the borderzone between cerebral arteries. Neuromotor outcome was normal in 17 and abnormal in 7 infants. Of these 7 infants, 5 infants showed a definite hemiplegia, whereas the other 2 showed some asymmetry of tone or function but no definite hemiplegia. None of the adverse antenatal or perinatal factors was significantly associated with abnormal outcome. Neonatal clinical examination was also not always predictive of the outcome. The extent of the lesion on MRI was a better predictor. In particular, it was the concomitant involvement of hemisphere, internal capsule and basal ganglia that was always associated with an abnormal outcome whereas the involvement of only one or two of the three tended to be associated with a normal outcome. EEG was also very helpful. Abnormal background activity either unilateral or bilateral was found in 6 infants and 5 out of 6 developed hemiplegia. In contrast, the presence of seizure activity in presence of a normal background was not related to abnormal outcome. CONCLUSIONS: Early MRI and EEG can help to identify the infants with cerebral infarction who are likely to develop hemiplegia.

Cerebral Infarction↗