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Value of p53 expression, cellular proliferation, and DNA content as prognostic indicators in renal cell carcinoma.

OBJECTIVE: In renal cell carcinoma (RCC) little is known about the basic mechanisms of cell proliferation and differentiation leading to growth, invasion, and eventual metastasis. In the present study, the prognostic significance of proliferative activity, p53 activity, and ploidy is analyzed. METHODS: In 90 patients with RCC overexpression of the p53 protein. DNA ploidy and proliferation status as determined by the monoclonal antibodies Ki-67 and Ki-S5 were analyzed in addition to tumor malignancy grade and stage and correlated with the clinical course. RESULTS: During the follow-up period (average 38 months) 23% of the patients had a progressive course. Only the Ki-S5 index correlated with stage, grade, and clinical course. Ploidy, p53, and Ki-67 correlated neither with tumor stage and grade nor with the clinical course. CONCLUSION: The proliferation activity determined with the monoclonal antibody Ki-S5 represents the most promising prognostic factor of the pathological indicators considered for the clinical course of RCC.

Adult↗

Thrombocytosis as a useful prognostic indicator in patients with lung cancer.

BACKGROUND: Thrombocytosis can accompany various cancers including lung cancer. This finding has recently been suggested to indicate poor prognosis. OBJECTIVES AND METHODS: We retrospectively examined the clinical records of 611 patients with lung cancer to investigate whether there is a correlation between thrombocytosis, other clinicopathologic factors, and survival. RESULTS: Ninety-eight of the patients (16%) manifested thrombocytosis at the time of their first evaluation at our hospital. Thrombocytosis and age (p = 0.0006) and thrombocytosis and performance status (p = 0.0002) are significantly correlated, but thrombocytosis is not related to gender, tumor histology, clinical stage, or serum lactate dehydrogenase concentrations. Survival is significantly shorter in patients with thrombocytosis: [median survival time (MST) 7.5 months; n = 98] than without thrombocytosis (MST 10.1 months; n = 513; p = 0.0029). Multivariate analysis of prognostic factors using the Cox proportional hazards model indicated that thrombocytosis had independent prognostic significance. CONCLUSION: Thrombocytosis at the first patient evaluation is an independent prognostic factor in lung cancer.

Adult↗

Prognostic indicators in fungemia of the surgical patient.

OBJECTIVE: The objective of this study is to identify prognostic factors affecting mortality in surgical patients with culture-proved fungemia and to examine how amphotericin B affects mortality after controlling for these factors. DESIGN: The study is based on a retrospective logistic regression analysis of general surgical patients with blood cultures positive for fungi. We analyzed the patients' ages; whether they received triple antibiotics, had diabetes, had malignant neoplasia, received steroids, had concomitant bacteremia, or took antibiotics for greater than 7 days; and total dose of amphotericin B. SETTING: The study was carried out at a university-based county hospital. PATIENTS: Analysis of microbiology records for blood cultures that were positive for fungi from November 1987 to January 1992 revealed 63 general surgical patients. Patients with burns and those undergoing organ transplantation were excluded. Forty charts were complete and available for review. MAIN OUTCOME: Death was the outcome variable studied. RESULTS: Stepwise logistic regression analysis of death revealed age to be a risk factor for mortality. Treatment with at least 210 mg of amphotericin B was associated with relative risk of death of 0.055. CONCLUSION: Amphotericin B is effective even at low doses at decreasing the mortality in surgical patients with fungemia. On the other hand, increasing age is associated with an increased risk of mortality. Found not to be associated were concomitant bacteremia, concurrent triple antibiotic therapy, malignant neoplasia, and steroid use.

Age Factors↗

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the oral cavity and tongue base.

BACKGROUND: Nuclear deoxyribonucleic acid (DNA) content is a prognostic factor in several tumors, and decisions regarding treatment have been made using this parameter. Nevertheless, there is no agreement in head and neck cancer. The purpose of the present study was to ascertain whether tumor DNA content correlated with prognosis in cases of primary squamous cell carcinoma (SCC) of the oral cavity and tongue base. METHODS: A retrospective study of formalin-fixed, paraffin-embedded tissue from patients with histologically confirmed SCC of the oral cavity and tongue base was performed using flow cytometry. Tumor DNA content was studied in 109 sets of specimens from previously untreated patients. All of them underwent surgical resection at the University "Hospital de La Princesa" between 1982 and 1992. Clinical parameters (age, sex, site of primary tumor, clinical stage, adjuvant therapy received, and disease-free and overall survival) and histologic parameters (histopathologic stage, tumor differentiation, type of inflammatory infiltration, presence of perineural invasion) were recorded in all cases. An exhaustive statistical analysis was applied. RESULTS: Only the histograms of 93 patients were adequate for consideration. In flow cytometric analysis, DNA aneuploidy was observed in 51 tumors (55%). The proportion of aneuploid tumors was significantly higher in advanced-stage carcinomas (p < .05), tumors with perineural invasion (p < .05) and in men (p < .05). In the 24 patients with lymph node metastasis, the incidence of aneuploidy was 82% (19 of 24) (p < .05). The rate of metastasis and aneuploidy increased as the degree of differentiation decreased (p < .05 for both). Patients with aneuploid carcinomas in both early and advanced stages had shorter relapse-free and overall survival periods than did the patients with diploid tumors (p < .001 for both). A Cox regression analysis demonstrated that ploidy was the single most important prognostic factor in determining relapse and death (p < .001 for both). CONCLUSIONS: The results indicate that tumor DNA analysis by flow cytometry appears to be useful as a supplement to clinical and histologic evaluation in predicting the tendency of SCC of the oral cavity and tongue base to metastasize to regional lymph nodes and to predict the outcome of the disease.

Adult↗

Early prognostic indicators of outcome in ischemic childhood stroke.

The aim of this study was to identify early prognostic factors in children with ischemic arterial stroke. Presenting symptoms, patterns of infarction on magnetic resonance imaging and computed tomography scans, and etiologic findings were compared with clinical outcome in a consecutive series of 31 children with ischemic arterial stroke. Presentation with an altered level of consciousness, seizures, or both and a completed or cortical completed stroke of the middle cerebral artery were found to be significant risk factors for poor outcome. No significant correlation was found between prognosis of childhood stroke and etiology, age at presentation, or gender.

Adolescent↗

Significance of immunohistochemical nodal micrometastasis as a prognostic indicator in potentially curable oesophageal carcinoma.

BACKGROUND: The number of positive lymph nodes is an important prognostic predictor in patients with oesophageal cancer. However, the significance of nodal micrometastasis in patients with overt nodal metastasis is unknown. The aim of this study was to clarify the clinical implications of nodal micrometastasis in patients undergoing curative oesophagectomy for oesophageal cancer. METHODS: Cervical, mediastinal and abdominal lymph nodes systematically removed from 104 patients with oesophageal cancer were examined immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes (none, between one and four, five or more). RESULTS: Univariate analysis showed T stage, nodal micrometastasis and number of overt nodal metastases to be significant prognostic factors after oesophagectomy. Multivariate analysis revealed nodal micrometastasis and number of overt nodal metastases to be independent prognostic factors. The presence of micrometastases had a significant adverse effect on postoperative survival in patients with no overt metastasis and in patients with one to four overt metastatic nodes, but no such impact in patients with five or more overt metastatic nodes. CONCLUSION: Assessment of nodal status by both histological examination for overt metastases and immunohistochemical examination for micrometastases is useful in stratifying patients undergoing curative oesophagectomy.

Adult↗

p53, mitosis, apoptosis and necrosis as prognostic indicators of long-term survival in breast cancer.

This study was designed to evaluate the prognostic importance of p53, mitosis, apoptosis and necrosis with long-term follow-up in Japanese patients with breast cancer. Four hundred and twenty-two patients with breast cancer were studied. We investigated 7 factors, including p53, mitotic index (MI), apoptotic index (AI), necrosis, lymph-node status (n), clinical tumor size (T) and lymphatic vessel invasion, followed for a median of 10 years. p53 accumulation was found in 30.1%, MI in 35.2%, AI in 36.3% and necrosis in 38.5%. p53 accumulation was correlated with MI (p = 0.0324), AI (p = 0.0010), necrosis (p = 0.0003), T (p = 0.0320), n (p < 0.0001), estrogen receptor (p = 0.0005) and progesterone receptor (p = 0.0287). Univariate analysis showed that p53, MI and necrosis were significantly predictive of 20-year overall survival (OS) or of 20-year relapse-free survival (RFS) (p < 0.0001 or p = 0.0003, p< 0.0001 or p < 0.0001 and p = 0.0131 or p = 0.0068, respectively), but AI was not. Multivariate analysis showed that p53 was an independent prognostic factor with RFS in all the patients, especially, with relapse-free survival (RFS) in the patients with T1 and with RFS and overall survival (OS) in the patients with a node-negative tumor. MI was an independent prognostic factor with OS in all the patients and with RFS and OS in the patients with a node-negative tumor. However, AI and necrosis were not independent predictors.

Adolescent↗

Preoperative computerized dynamic posturography as a prognostic indicator of balance function in patients with acoustic neuroma.

We conducted a study to determine the prognostic reliability of preoperative computerized dynamic posturography (CDP) in patients undergoing surgical excision of an acoustic neuroma. Our goal was to determine the correlation between objective preoperative assessments of balance function and subjective postoperative patient self-assessments. To that end, we retrospectively reviewed the records of 21 adults who had undergone preoperative CDP, and we subsequently obtained their subjective assessments of balance function by follow-up telephone surveys at least 1 year postoperatively. We conclude that although CDP has proven to be useful in many aspects of balance evaluation, it did not appear to be a valuable predictor of subjective postoperative balance function in these patients.

Adult↗

Early undifferentiated connective tissue disease: III. Outcome and prognostic indicators in early scleroderma (systemic sclerosis).

OBJECTIVE: To characterize the course of early scleroderma and to delineate prognostic factors present within 1 year of disease onset that might identify patients at high risk. DESIGN: Inception cohort study. SETTING: Ten university-based rheumatology clinics participating in the Cooperative Systematic Studies of Rheumatic Diseases Program. PATIENTS: Forty-eight patients who had had scleroderma for less than 1 year. MEASUREMENTS: Fifteen patients with early scleroderma who died were compared with those still living during the initial study period (1982 to 1992). Kaplan-Meier survival estimation and Cox proportional hazards analysis were used to analyze baseline variables for their ability to predict survival duration. RESULTS: Eight of 15 deaths were due to cardiac or pulmonary system failure. The estimated 5-year survival rate was 68%. Baseline factors that were the most predictive of a poor outcome included the presence of abnormal cardiopulmonary signs and abnormal urine sediment (pyuria, hematuria). CONCLUSION: Evidence of early cardiopulmonary disease, renal disease, inflammation, or immune activation may identify a subset of patients with scleroderma who will experience rapidly progressive disease and early death.

Adult↗

Nutritional status--a prognostic indicator in head and neck cancer.

A prospective study into the nutritional status of 114 patients with untreated primary squamous cell carcinoma of the head and neck was undertaken to assess its possible prognostic value for survival. Nutritional status was evaluated by anthropometry, creatinine height index estimation, serum albumin and transferrin assays, and nitrogen balance studies. Weight change and other anthropometric indices found to be the most reliable nutritional parameters were averaged to derive a clinically useful, general nutritional status score. A nutritional deficit was found in 43 of the 114 patients (37.7%) and was associated with neoplasms of the upper gastrointestinal tract in more than 80% of the patients. Life table analysis showed a statistically very highly significant difference between the survival of the adequately nourished patients (57.5% at 2 years) and the survival of the undernourished patients (7.5% at 2 years) (chi 2 = 36.08; P = .0). These results indicate that nutritional deficiency is an important adverse prognostic factor in head and neck cancer. Undernutrition probably exerts its effect, at least in part, by causing secondary immunologic dysfunction.

Adult↗

Prostate specific antigen and prostatic acid phosphatase immunoreactivity as prognostic indicators of advanced prostatic carcinoma.

To determine whether the prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) immunoreactivities in prostatic carcinoma are reliable prognostic factors, the PSA and PAP immunohistochemical distribution was examined in needle biopsy specimens of 80 patients with advanced prostatic carcinoma. Our results indicated a higher cancer-specific survival rate in patients with a greater PSA or PAP immunostaining. Furthermore, a multivariate analysis of possible prognostic factors, that is patient age, clinical stage, Gleason score, serum PAP, PSA and PAP immunostaining scores, and the initial treatment, has confirmed that the difference in PAP immunoreactivity is the most important prognostic factor (p < 0.01) for advanced prostatic carcinoma, with the Gleason score (p = 0.06), clinical stage (p = 0.09) and PSA immunoreactivity (p = 0.48) being the second, third and fifth prognostic factors, respectively.

Acid Phosphatase↗

Prognostic indicators following enucleation for posterior uveal melanoma. A multivariate analysis of long-term survival with minimized loss to follow-up.

Most previous reports on survival following enucleation for uveal malignant melanoma do not contain cumulative survival rates, do not use a multivariate approach and are liable to a considerable loss to follow-up. In this study, the long-term survival and tumour-related mortality were studied in 340 patients. Archival specimens containing posterior uveal melanomas were initially examined and sectioned by one pathologist. There was no loss to follow-up 6 to 22 years after enucleation. At the end of study, 233 (68.5%) individuals were dead; 137 (40.3%) of melanoma-related causes and 96 (28.2%) of other causes. Melanoma-related deaths appeared from 24 to 6848 days (18 years 8 months) after enucleation. The cumulative 5-year survival proportion based on melanoma-related deaths was 70% and the corresponding 10-year proportion was 56%. Multivariate Cox regression indicated that the largest tumour dimension, cell type, and tumour location all had independent prognostic value, the associated hazard ratios ranged from 1.2 to 1.4, suggesting a moderate increase of the relative risk. Pair-wise comparisons of the parameters indicated that large tumours were more common in the anterior choroid or ciliary body than in the posterior choroid. Similarly, large tumours were more often necrotic, composed of epitheloid cells, or featured extrascleral extension. Tumours with significant scleral invasion or extrascleral extension were more common in elderly patients.

Adult↗

Prognostic indicators in patients with seminal vesicle involvement following radical prostatectomy for clinically localized prostate cancer.

PURPOSE: We identify prognostic factors in patients with seminal vesicle involvement and negative lymph nodes following radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 93 patients who underwent radical prostatectomy and had seminal vesicle invasion without lymph node metastasis were evaluated. Patients who underwent neoadjuvant/adjuvant hormonal or radiation therapy were excluded from study. Preoperative serum prostate specific antigen (PSA), biopsy and radical prostatectomy specimen Gleason score, surgical margin status, presence of extraprostatic extension and evidence of biochemical disease progression were determined prospectively. Biochemical failure was defined as a single serum PSA elevation greater than 0.4 ng./ml. RESULTS: The presence of positive surgical margins (p = 0.001), and Gleason score 7 or higher from preoperative biopsies (p = 0.03) and from the radical prostatectomy specimen (p = 0.01) were significant predictors of disease progression at a median followup of 43.3 months. Patients with preoperative PSA less than 10 ng./ml. had a better disease-free survival (p = 0.07). On multivariate analysis, after adjusting for biopsy Gleason score, prostatectomy Gleason score and serum PSA, positive surgical margins remained a statistically significant predictor of disease progression (p = 0.002). CONCLUSIONS: Surgical margin status is an independent predictor of disease recurrence in patients with seminal vesicle involvement and negative lymph nodes following radical prostatectomy. Serum PSA 10 ng./ml. or greater and specimen Gleason score 7 or greater also were adverse prognostic factors in these patients. Conversely, patients with negative surgical margins and lymph nodes have a better prognosis than previously expected, despite seminal vesicle invasion.

Aged↗

Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer.

AIMS: Recent studies have drawn attention to intratumoral microvessel density (MVD) as a prognostic factor in invasive breast cancer. Various methods have been applied to assess MVD and the prognostic value of MVD in different studies varies considerably. Counting of microvessels in the most highly vascularized area (hot spot) of a tumour is the method most widely used. In this study we compared three counting methods. METHODS AND RESULTS: To assess MVD in 112 cases of invasive breast cancer with long-term follow-up we performed microvessel counting in the hot spot of the tumour in four and 10 fields of vision (HS-MVD4 and HS-MVD10) and microvessel counting in 10 fields of vision distributed systematically over the whole tumour area (global MVD). The HS-MVD4, HS-MVD10 and global MVD showed good correlations with each other. HS-MVD4 provided the highest number of microvessels (median value 71) followed by HS-MVD10 and global MVD, with median values of 58 and 39, respectively. HS-MVD4 showed the best prognostic value for overall survival (P = 0.0001) whereas HS-MVD10 showed less (P = 0.01) and the global MVD showed no (P = 0.75) prognostic value. In univariate analysis, the HS-MVD4 was the second strongest prognostic factor after tumour size. In multivariate survival analysis, the HS-MVD4, mitotic activity index (MAI), lymph node status and tumour size were found to be independent prognostic factors. When combining MVD4 and MAI in lymph node negative patients, none of the patients with low MVD (< 71/mm2) and a low MAI (< 10 per 10 HPF) died, in contrast to patients with a high MVD or high MAI who have a 10-year survival of 57%. CONCLUSIONS: These data suggest that the hot spot MVD in four fields of vision is a major independent prognostic factor for overall survival in invasive breast cancer. For the first time, it is shown that hot spot MVD provides additional prognostic information to well established factors like lymph node status and the MAI, and may therefore be useful for designing treatment strategies in invasive breast cancer.

Breast Neoplasms↗

Diagnostic and prognostic indices in primary open angle glaucoma: a color Doppler study.

The authors compute a diagnostic (Di) and a prognostic (Pi) index in primary open angle glaucoma. Four groups of patients were studied. Group A consisted of subjects under 50 years of age, group B of subjects over 50 years of age, group C of patients with normal tension glaucoma and group D with high tension glaucoma. All patients underwent color doppler imaging of the ophthalmic, posterior ciliary and choroid arteries. The Di of the choroid vessels were 0.967 +/- 0.011 (gp. A), 1.112 +/- 0.010 (gp. B), 1.506 +/- 0.008 (gp. C) and 2.891 +/- 0.083 (gp. D). The Pi of the posterior ciliary arteries were 22.700 +/- 1.160 (gp. A), 20.000 +/- 0.943 (gp. B), 15.100 +/- 0.568 (gp. C) and 12.100 +/- 0.083 (gp. D). Confirmation of these data might validate them as a tool for preventing the evolution of glaucomatous optic neuropathy.

Adult↗

[Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the larynx].

Celluar DNA content has been found to be an important prognostic factor in many head and neck tumours, yet within the larynx few studies have examined its effect on survival. 31 patients with squamous carcinoma of the larynx treated in years 1983-85 by total laryngectomy were studied. The tumours were classified according to the TNM classification 1987 and graded histopathologically according to Jaccobson's classification. Quantitative DNA content was determined with the use of image cytometry performed by an image analyzer (CAS-200). Quantitative DNA analysis correlated with tumor grade and patient outcome within 6 years of follow-up.

Carcinoma, Squamous Cell↗

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC.

OBJECTIVES: Non-small cell lung cancer (NSCLC) tissue produces numerous growth factors, which are multifunctional and considered predictive of patient survival. This study sought to evaluate the relationship between concentrations of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) in NSCLC tissue and clinicopathological factors, and determine whether these factors correlate with long-term survival. METHODS: We retrospectively investigated 71 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, for whom the primary curative approach was surgery, and who received no chemotherapy or radiotherapy prior to surgery. bFGF, VEGF, HGF were measured in extracts prepared from these 71 frozen tissue samples by ELISA. Five- and 10-year survival was obtained to determine the most important predictors of long-term survival. RESULTS: Among clinicopathological parameters, the mean concentration of bFGF was significantly higher in tissue extracts from cases involving metastatic nodal involvement (87.5+/-69.3 ng/100 mg protein) than in those without nodal involvement (57.6+/-42.5 ng; P<0.05). Levels of VEGF in adenocarcinoma (26.8+/-34.0 ng) were higher than for squamous cell carcinoma (12.2+/-13.8 ng; P<0.05). HGF levels also demonstrated histological differences (14.7+/-7.7 vs. 10.6+/-9.7 ng, P<0.05). bFGF protein levels were basically the same, but showed no statistically significant differences with respect to histological type (72.5+/-55.2 vs. 63.6+/-51.5 ng). Patients with high levels of bFGF or VEGF showed significantly worse survival rates than patients with low levels (P=0.0059; P=0.0134). In particular, high concentrations of both bFGF and VEGF correlated with markedly poor prognosis (P<0.0001). Multivariate analysis indicated that lymph node involvement and levels of bFGF and VEGF were independent prognostic factors in cases of NSCLC (adenocarcinoma or squamous cell carcinoma) involving patients who had undergone curative resection. CONCLUSIONS: Adenocarcinoma associated with lung cancer is regarded to have biological characteristics that distinguish it from squamous cell carcinoma. Node invasion may be associated with bFGF. bFGF and VEGF augment each other and are associated with leading to poor prognosis. The results of this study suggests that effective therapy to block angiogenesis may need to address at least both of these factors in cases of NSCLC.

Aged↗

Prognostic indices in ovarian cancer. Their significance in treatment planning.

Ovarian cancer exhibits a wide spectrum of behavior, the effectiveness of therapies varies and the circumstances of patients differ. Better outcomes will require more selective treatment strategies considerate of these variables. 1. The need for treatment As long as outcome is affected more by disease than by treatment, survival will be determined by the bulk and growth-rate of residual tumor-prognostic factors reflect these. They indicate the need for treatment, but not whether benefit is likely. FIGO stage is the international standard, but this alone is inadequately predictive. Grade reflects virulence, but subjectivity has limited its usefulness. Newer quantitative pathology techniques (such as DNA ploidy) more reproducibly reflect behavior. Prognostic factors can be used to define subsets of patients at differing degrees of disease risk. 2. Efficacy of treatment No response predictors are yet of practical use in selecting primary chemotherapy on an individual basis. Generally, response is more likely if the tumor is less extensive and if dose and treatment frequency are higher. Monitoring biomarkers can more quickly identify those with a suboptimal response who may require a change or discontinuation of treatment. Re-laparotomy has limited usefulness. Response predictors for second-line treatment (e.g. the failure-free interval) are available and also have implications for new drug testing. 3. Suitability of treatment Advanced age or serious additional illness may render intensive treatment inappropriate. The informed patient's wishes are of prime importance. An evolving strategy of selective management is described.

Antineoplastic Combined Chemotherapy Protocols↗