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PubMed1994

Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis.

Levels of plasma cytokines and circulating endotoxin were assessed in 41 patients with severe intra-abdominal sepsis. Comparison was made with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system. Blood samples were taken within 24 h of onset of the sepsis syndrome and at serial times thereafter. Increased levels of interleukin (IL) 6 (range 50-25,500 pg/ml) were detectable in all patients with sepsis. Eighteen of the 19 deaths were attributable to sepsis and higher levels of IL-6 at the onset of the sepsis syndrome correlated with a poor outcome. The sensitivity of IL-6 concentration in predicting mortality was 86.4 per cent with a specificity of 78.9 per cent and an overall correct classification rate of 82.9 per cent. IL-6 level was a better predictor than APACHE II score (sensitivity 72.7 per cent, specificity 57.9 per cent, correct classification rate 65.9 per cent). Levels of tumour necrosis factor alpha, IL-1 beta and endotoxin did not correlate with mortality rate. Plasma IL-6 concentrations may help in planning future strategies to decrease the mortality rate associated with sepsis.

Abdomen↗
PubMed1989

Preoperative left ventricular wall stress, ejection fraction, and aortic valve gradient as prognostic indicators in aortic valve stenosis.

Patients with aortic valve stenosis (AS) and left ventricular (LV) dysfunction may dramatically improve after aortic valve replacement, but operative risk is high. In an earlier study, all patients with low preoperative wall stress and low ejection fraction, or with low aortic valve gradient, died or had persistent heart failure after operation. Because wall stress is difficult to calculate, we reassessed its effect and the effect of other preoperative characteristics on outcome in 66 consecutive catheterization patients with predominant aortic stenosis referred for valve replacement. Despite ejection fraction that was inordinately low compared with afterloading wall stress in nine patients, seven patients improved with surgery. All three patients with ejection fraction less than 20% improved after surgery. Two of three patients with mean aortic valve gradients of less than 30 mm Hg improved. Mortality was 33% in patients with mean gradient less than 30 mm Hg and 19% with mean gradient less than 50 mm Hg. In the 54 patients with calculated aortic valve areas of less than or equal to 0.8 cm2, 1 (2%) had continuing heart failure, while 6 of 12 (50%, P less than .01) patients with aortic valve areas of 0.9-1.2 cm2 had continued symptoms of or died of heart failure. Patients who died or failed to improve after operation were older (71 +/- 9 years) than those who improved (65 +/- 9 years, P = .02). We conclude that wall stress calculations do not predict which patients with aortic stenosis will benefit from aortic valve replacement and that poor left ventricular function and low mean aortic valve gradient do not absolutely preclude operation. On the other hand, low gradient, non-critical valve area, and advanced age are all relative contraindications to aortic valve replacement in aortic stenosis.

Aged↗
PubMed2002

Low natural killer activity and central nervous system disease as a high-risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis HLH (FHL) is fatal, unless patients are rescued with hematopoietic stem cell transplantation (SCT). Although the molecular identification of FHL now is possible at least in part from perforin gene study, many cases escape detection or never are tested due to the lack of specific hallmarks, making diagnosis difficult. To the authors' knowledge, it remains to be determined whether persistently low natural killer cell (NK) activity and a high incidence of central nervous system (CNS) disease increase the probability of FHL. METHODS: The authors analyzed 42 HLH patients age < 2 years, 13 of whom developed overt CNS disease and 5 of whom demonstrated persistently deficient NK activity (Group 1). The remaining 24 patients had no CNS disease and had NK activity of moderate decrease to within the normal range (Group 2). RESULTS: In Group 1, CNS symptoms were detected in 6 cases within 1 month and between 4.5-9 months in 6 other patients. In these cases, spotty lesions demonstrating a high T2 signal in the white matter were noted on brain magnetic resonance imaging. The survival was significantly poor for patients in Group 1 unless they were rescued with SCT, which was performed in 5 of the 13 patients with CNS disease and in all 5 patients with persistent NK activity deficiency. SCT was successful in 9 patients, with no CNS sequelae reported after the transplantation. Conversely, the prognosis of the 24 patients in Group 2 was better and only 1 patient required SCT. CONCLUSIONS: Very young HLH patients (age < 2 years) who are at high risk of fatal FHL with persistently deficient NK activity and/or overt CNS disease require appropriate SCT to reverse CNS disease and achieve a complete cure.

Age of Onset↗
PubMed2005

ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications.

This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse.

Adolescent↗
PubMedDate not supplied

Prognostic indicators of hepatic injury following jejunoileal bypass performed for refractory obesity: a prospective study.

To evaluate factors predisposing to liver injury following jejunoileal bypass, 27 patients underwent clinical evaluation and liver biopsy prior to bypass and at 3, 6, 12, 18, and 24 months and yearly thereafter. Nineteen patients developed increased fatty infiltration of the liver, 1 developed cryptogenic cirrhosis, and 7 developed steatonecrosis, central hyaline sclerosis, or cirrhosis indistinguishable from alcoholic liver disease during the period of rapid weight loss. Two of these 7 patients developed clinical liver failure; inactive cirrhosis evolved after parenteral alimentation and reanastomosis in one, and after oral nutritional supplementation in the other. Four of 5 asymptomatic patients resolved to inactive cirrhosis as weight loss diminished. Each of the 7 patients had pericentral fibrosis on pre-bypass liver biopsies, suggesting a previous hepatic injury. These patients were older (p less than 0.02) and, 3 months following bypass, had greater cumulative per cent weight loss (p less than 0.05), higher levels of serum aspartate aminotransferase (p less than 0.005), and greater 45-min bromosulfophthalein retention (p less than 0.02). Histologic evidence of pericentral fibrosis identified patients at risk to develop steatonecrosis and cirrhosis; these lesions occurred in older patients who had greater weight loss following jejunoileal bypass.

Adolescent↗
PubMed1996

Presence of autonomic neuropathy is a poor prognostic indicator in patients with advanced liver disease.

Autonomic neuropathy (AN) is seen in both alcohol-induced and non-alcohol-induced liver disease, and when present is an independent predictor of mortality. We postulated that patients who were awaiting liver transplantation are likely to have a high prevalence of autonomic neuropathy with an associated increase in mortality. To test our hypothesis, we evaluated the presence of autonomic neuropathy using a battery of tests in 33 patients awaiting liver transplantation and prospectively followed them to determine their prognosis. Twenty-two of 33 (67%) patients with liver disease had evidence of autonomic neuropathy; of these, 12 (36%) had evidence of definite and 10 (31%) had early autonomic neuropathy. The prevalence of AN was similar in alcohol-induced and non-alcohol-induced liver disease. Using Child-Pugh classification, 14.3% Child A, 31.3% Child B, and 60% Child C had definite autonomic neuropathy. Six patients died during a median observation period of 10 months, and all had AN. Kaplan-Meier survival analysis showed a significantly higher mortality (P=.05) in patients with AN. On the basis of this observation, we suggest that consideration should be given for early liver transplantation in patients with advanced liver disease and autonomic neuropathy.

Adult↗
PubMed2003

New prognostic indicator for non-small-cell lung cancer, quantitation of thymidylate synthase by real-time reverse transcription polymerase chain reaction.

Thymidylate synthase (TS) is an enzyme that catalyzes an important DNA biosynthesis process. The gene expression of TS has not been reported in non-small-cell lung cancer (NSCLC) patients. To clarify the correlation between TS mRNA levels and clinicopathological features of NSCLC, we examined 70 Stage I and II NSCLC patients for intra-tumoral expression of TS using TaqMan reverse transcription polymerase chain reaction (RT-PCR) assay and immunohistochemistry methods. We also investigated the TS promoter 28 bp polymorphism in 48 cancer tissues using PCR amplification of genomic DNA. Lung cancer tissue showed higher TS mRNA levels than normal lung tissue (Mann-Whitney U-tests; p = 0.0020). Further, TS mRNA expression was correlated with immunohistochemical TS expression (p = 0.029). We obtained 2 different DNA fragments, which indicated triple-repeat (3R) and double-repeat (2R) type alleles. Cancer tissues with the 3R/3R genotype showed significantly higher TS mRNA levels as compared to those with other genotypes (p = 0.0019). The TS genotype was also correlated with immunohistochemical TS expression (chi(2) test; p = 0.0079). The disease-free survival of the low TS mRNA level group was significantly better than those with high TS mRNA levels (log-rank test; p = 0.010), however, there were no significant differences found by immunohistochemical evaluation (p = 0.34) or TS genotype analysis (p = 0.11). A multivariate analysis revealed that high TS mRNA levels independently contributed to disease-free survival. The quantitation of TS mRNA levels is clinically more sensitive and useful for determining the prognosis of Stage I and II NSCLC patients than an immunohistochemical evaluation.

Aged↗
PubMed2006

Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma.

Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 +/- 16.6 vs. 52.2 +/- 6.2 ng/mL [p < 0.001]; VEGF, 55.1 +/- 7.6 vs. 32.1 +/- 2.4 ng/mL [p < 0.001]; mean +/- SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p = 0.017]; median time to progression, 5 vs. 10 months [log-rank, p = 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.

Adult↗
PubMed1981

Lymphoproliferative responses to autologous tumor extracts as prognostic indicators in patients with resected breast cancer.

Patients with operable breast cancer were tested postoperatively to assess lymphoproliferative responses. Patients with lymphocytes capable of recognizing and proliferating in response to autologous tumor extracts had a significantly longer disease-free interval than those with a low response to their autologous extract. In this group of patients, immunological responses to autologous tumors predicted subsequent clinical course better than pathological evaluation based on tumor presence in axillary lymph nodes. Low or negative reactivity to autologous tumor often was not accompanied by a general, impaired ability to respond in LP assays. In fact, patients with low autologous tumor response and normal MLC were at particularly high risk for recurrence.

Axilla↗
PubMed1981

Estrogen receptor quantitation and staging as complementary prognostic indicators in breast cancer: a study of 583 patients.

Estrogen receptor (ER) quantity was measured at the time of primary diagnosis on 583 patients with breast cancer seen at the major treatment centre in British Columbia between 1975 and 1979. Survival rates (overall, recurrence-free and post-recurrence) were assessed relative to ER concentration, staging, menopausal status, age, differentiation, and therapy. A linear trend in increased survival was demonstrable through variations in ER concentration from less than 1 to greater than 260 fmoles/mg cytosol protein. This trend was highly significant and remained after adjustment for stage, menopausal status, and age, and was seen for all groups of patients except those with metastatic disease. The association of high ER concentration with increased recurrence-free survival was not due to differing responses to adjuvant therapy, but the trend in post-recurrence survival was only significant in patients who had received hormonal therapy. Survival was as strongly associated with receptor concentration as with staging, and these two factors were almost completely independent. A proportional hazards model was fitted to produce predictions of survival, and showed that TNM stage III patients with high ER concentrations have a better survival than stage I or II patients with lower ER concentrations. This suggests that quantitative assessment of ER status is essential to definition of risk in breast cancer patients and that stratification in clinical trials and consideration for adjuvant therapy ought to be guided, in part, by a standardized ER-quantitative determination performed on the primary tumor.

Adult↗
PubMed1994

Flow-cytometric and quantitative histologic parameters as prognostic indicators for occult retroperitoneal disease in clinical-stage-I non-seminomatous testicular germ-cell tumors.

Our study was performed to clarify whether the combination of DNA flow-cytometric and quantitative histopathological parameters improves the prediction of occult metastatic disease in clinical stage-I non-seminomatous testicular germ-cell tumors (NSGCT). We used archival paraffin primary-tumor tissue of 67 clinical stage-I NSGCT patients who had undergone retroperitoneal lymph-node dissection (RPLND). According to the RPLND specimens, 24 patients were at pathological stage I and 43 at pathological stage II. Archival blocks were redissected for histological re-evaluation. In addition, 50 microns sections were prepared according to the Hedley technique in order to obtain nuclear suspensions which were processed for flow cytometry (FC). In univariate analysis, the percentage of embryonal carcinoma, the percentage of immature teratoma and vascular invasion were the most accurate predictive histopathological parameters. The percentage of aneuploid cells in S-phase was the best predictive FC parameter. In multivariate analysis, the percentage of embryonal carcinoma and the S-phase fraction of aneuploid cells were the only independent markers for occult metastatic disease. According to this statistical approach, 91.0% of pathological stage-I and stage-II cases were correctly classified. Sensitivity was 95.3% and specificity was 83.3%. Using histopathological criteria alone, only 56.7% NSGCT patients were correctly classified.

Aneuploidy↗
PubMed2003

p53 alteration is not an independent prognostic indicator, but affects the efficacy of adjuvant chemotherapy in human pancreatic cancer.

BACKGROUND AND OBJECTIVES: Mutations in the p53 gene are found in more than 50% of human cancers and are observed in 60-80% of pancreatic cancers. The clinicopathologic implications of p53 abnormalities and their effects on the efficacy of the adjuvant chemotherapy for pancreatic cancer remain controversial. METHODS: We investigated the p53 status in core exon-4 to -9 (codon 33-331) by direct DNA sequencing in a series of 72 pancreatic cancers and analyzed the effects of p53 abnormalities on the patients' survival and the efficacy of adjuvant chemotherapy. RESULTS: p53 mutations were found in 62.5% (45/72) of cases, including 38 point mutations and 7 frameshift mutations. The subtypes of p53 mutations included 68.9% (31/45) transitions and 15.6% (7/45) transversions. 39.5% (15/38) of point mutations were CGT (Arg) to CAT (His) mutation at codon-273 of exon-8. 34.2% (13/38) of point mutations were CGG (Arg) to TGG (Trp) mutation at codon-248 of exon-7. Of seven frameshift mutations, four were seen at exon-4, two at exon-5, and one at exon-6. Of overall cases, p53 abnormalities were not associated with a poorly differentiated grade and an advanced stage. The relationship of adjuvant chemotherapy to survival is approaching statistical significance. Univariate analysis showed that in the p53 mutation group, the patients who received adjuvant chemotherapy had a better survival ratio than that of patients who did not do. Multivariate analysis indicated that in the group with p53 mutations, the significant factors for survival were adjuvant chemotherapy, histologic grade, and clinical stage. However, in the group with a wild-type p53 gene, only histologic grade was a significant factor. In addition, 34.7% (25/72) of the cases harbor p53 polymorphism mutation only at codon-72 of exon-4, which did not show any significant effect on the pathology, prognosis, and efficacy of adjuvant chemotherapy of the pancreatic cancers. CONCLUSIONS: A p53 abnormality was not an independent factor for evaluating the prognosis of patients with pancreatic cancer, but was a beneficial indicator for selecting a reasonable strategy of adjuvant chemotherapy against pancreatic cancer.

Adult↗
PubMed2003

Role of MUC1 and MUC5AC expressions as prognostic indicators in gastric carcinomas.

BACKGROUND AND OBJECTIVES: The aim of this study is to clarify the relationship between the expression of MUC1 and MUC5AC mucins and the clinicopathological features in human gastric carcinomas using the mouse monoclonal antibodies VU-4H5 and Clone 45M1, respectively. Furthermore, the possibility of using phenotypes (MUC1+/MUC5AC+, MUC1+/MUC5AC-, MUC1-/MUC5AC-, MUC1-/MUC5AC+) to predict prognosis of the patients is evaluated. METHODS: Formalin-fixed, paraffin wax-embedded tissues from 76 cases of gastric cancer were examined for the expression of MUC1 and MUC5AC mucin antigens immunohistochemically using the avidin-biotin-peroxidase method. RESULTS: Of the 76 cases, MUC1 and MUC5AC immunoreactivities were observed in 49 (64.5%) and in 32 (42.1%) of gastric carcinoma tissues, respectively. MUC1 expression was significantly correlated to the depth of invasion, lymph node metastasis, peritoneal dissemination, and tumor stage. On the other hand, MUC5AC was inversely associated with depth of invasion, lymph node metastasis, liver metastasis, and tumor stage. Multivariate analyses indicated that tumor stage and MUC1 mucin expression were independently correlated with overall survival. The patients with MUC1+/MUC5AC- antigen staining in carcinoma tissues showed the lowest survival rate among four phenotypes. In contrast, the patients with MUC1-/MUC5AC+ antigen staining in carcinoma tissues showed the highest survival rate. CONCLUSIONS: Altogether these data suggest that combined evaluation of MUC1 and MUC5AC mucin staining may be clinically helpful to predict outcome in patients with gastric cancer.

Adult↗
PubMed2005

Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract.

Factors that determine the clinical course and outcome of patients with gastrointestinal (GI) carcinoid tumors are complex and multifaceted. These include the site of origin within the GI tract, the size of the primary tumor, and the anatomical extent of disease, whether localized, regional, or metastatic to distant sites. The new World Health Organization (WHO) histological classification of endocrine tumors, including carcinoids, represents a significant advance in terms of providing a consistent framework for histopathological interpretation that should facilitate multicenter research on treatment outcomes. Histochemical indicators of a poorer prognosis are the degree of expression of the proliferation protein Ki-67 and the p53 tumor suppressor protein. Adverse clinical indicators are the malignant carcinoid syndrome, carcinoid heart disease, and high concentrations of the tumor markers, urinary 5-HIAA and plasma chromogranin A.

Biomarkers, Tumor↗
PubMed1977

The histomorphologic spectrum of endocervical (Müllerian) adenocarcinoma--a potential prognostic indicator.

A review of all patients with endocervical adenocarcinoma seen at the Universtiy of Kentucky Medical Center from 1962 through 1972 yielded 15 patients with tissue-verifiable primary endocervical adenocarcinoma that had no associated sarcomatous or squamoid features. These patients varied from 17 to 73 years old with a mean age of 47 years. A malignant clear cell pattern was present in 8 patients and in 3 of these individuals that prominent morphologic feature was associated with hobnail cells. Five patients with clear cell carcinomatous changes in the endocervix were born prior to the use of diethylstilbestrol (DES) and 2 of the remaining 3 patients were exposed to DES during the first trimester of pregnancy. Other morphologic types of endocervical adenocarcinoma included mucinous adenocarcinoma in 9 patients (60%) and basaloid adenocarcinoma in one patient (7%). Cellular atypia of endocervical glands, which in some areas was consistent with adenocarcinoma in situ was found in 9 of the 15 patients with invasive endocervical cancers. Both vessel invasion by tumor cells and tumor necrosis were associated with a poor prognosis.

Adenocarcinoma↗
PubMed1986

Testicular seminomas in Saudi Arabia: clinical characteristics, prognostic indicators, and recommendations for management.

Thirty Saudi patients with pure testicular seminoma were treated at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, between January 1977 and June 1983. Disease characteristics in Saudi Arabia including clinical findings, response to therapy, and prognosis are described and compared to those in other populations reported in the literature. Symptom durations were 3 to 42 months. Many of the patients presented with an extensive tumor burden and a poor performance status. There was a higher incidence of anaplastic seminoma and of cryptorchidism than in other series and a relatively high incidence of elevated betahuman chorionic gonadotropin (B-HCG). Patients initially underwent funiculo-orchiectomy. Twenty-two patients received radiation therapy and four received chemotherapy. Patients with limited disease responded well to orchiectomy and radiation therapy. However, those with extensive tumor burden had an unsatisfactory response to radiation therapy. Preradiation chemotherapy is recommended for patients with massive retroperitoneal metastases, nodal disease above the diaphragm, or extranodal disease and patients with minimal or moderate sized retroperitoneal nodal disease associated with an elevated B-HCG.

Chorionic Gonadotropin↗