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Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis.

OBJECTIVE: We tested the hypothesis that there is prognostic significance to the level of expression of the protooncogene HER-2/neu in advanced ovarian cancer, as prior studies have suggested. STUDY DESIGN: We determined expression of HER-2/neu by immunohistochemistry, with monoclonal antibody 9G6 and the indirect immunoperoxidase technique, on frozen tumor specimens from 105 patients with stage III or IV epithelial ovarian cancer. All patients were treated at Memorial Sloan-Kettering Cancer Center, and no patient was lost to follow-up. Median follow-up among surviving patients is 34 months. HER-2/neu expression was scored as negative, weak, 1+, 2+, or 3+. The staining pattern of normal ovarian epithelium was scored negative to 1+. Multivariate analysis was performed to evaluate the prognostic significance of HER-2/neu expression. RESULTS: Twenty-five of the 105 patients (24%) showed strong membrane staining (3+); the other tumor specimens showed weaker membrane staining or no immunoreactivity. There was no correlation of HER-2/neu expression with any of a variety of clinical factors, including stage, grade, cell type, and residual tumor. No significant survival difference was found between patients with levels of staining intensity similar to those of normal ovarian epithelium and those with increased expression (3+). Median survival times were 36 and 27 months, respectively, for the two groups (95% confidence intervals 29 to 45 and 18 to 39 months). Multivariate analysis of possible prognostic factors showed that HER-2/neu overexpression conferred a marginal worsening of survival (p = 0.09) for the subgroup of patients in whom a negative surgical reassessment was not achieved after chemotherapy. CONCLUSION: HER-2/neu expression does not appear to be an important prognostic factor in patients with advanced epithelial ovarian cancer.

Adult↗

Identification of Schistosoma haematobium, S. bovis and S. curassoni by multivariate analysis of cercarial papillae indices.

The disposition of cercarial papillae of 68 pre-identified Schistosoma species was established. All the cercariae originated from Africa and Madagascar and were either obtained from natural or experimental infections, and belonged to three species Schistosoma haematobium, S. bovis and S. curassoni. Discriminant analysis was based on nine characters: average values, skewness and kurtosis of three cercarial indices (AD, AL and U) for each sample or isolate. AD, AL correspond respectively to the relative distance between dorsal and lateral papillae. U corresponds to the total number of tail stem papillae. With the exception of two cases of the 68 (one of them corresponding to cercariae shed by a non-African experimentally infected snail), the method enabled discrimination of S. haematobium, S. bovis and S. curassoni.

Animals↗

Spatial and spectral correlations in MALDI mass spectrometry images by clustering and multivariate analysis.

Matrix-assisted laser desorption/ionization mass spectrometry imaging is a technique for direct analysis of tissue sections without the use of molecular tags or contrast agents. The combination of spatial and mass resolution results in large and complex data sets that require powerful and efficient analysis and interpretation tools. Conventional images, derived from a specific analyte mass, do not identify the spatially localized correlations between analytes that are latent in the data. A new approach to find and visualize these correlations is presented. Clustering methods are used to classify pixels by spectral similarity, facilitating definition of distinct spatial regions. Principal component and discriminant analyses are combined to comprehensively identify changes in the mass spectra between regions. Images are generated by projecting the spectra of each pixel on the discriminant spectra; contrast is then a function of multiple correlated peaks.

Algorithms↗

Factors predisposing to dislocation after primary total hip arthroplasty: a multivariate analysis.

We conducted this study to determine the relative influence of various mechanical and patient-related factors on the incidence of dislocation after primary total hip asthroplasty (THA). Of 2,023 THAs, 21 patients who had at least 1 dislocation were compared with a control group of 21 patients without dislocation, matched for age, gender, pathology, and year of surgery. Implant positioning, seniority of the surgeon, American Society of Anesthesiologists (ASA) score, and diminished motor coordination were recorded. Data analysis included univariate and multivariate methods. The dislocation risk was 6.9 times higher if total anteversion was not between 40 degrees and 60 degrees and 10 times higher in patients with high ASA scores. Surgeons should pay attention to total anteversion (cup and stem) of THA. The ASA score should be part of the preoperative assessment of the dislocation risk.

Adult↗

The efficacy of percutaneous tetracycline instillation for sclerosis of recurrent thyroid cysts: a multivariate analysis.

A dichotomy exists in the literature concerning the efficacy of sclerosing agent tetracycline hydrochloride for treatment of thyroid cysts. However, the studies vary in patient selection and none employed a statistical method for simultaneous analysis of multiple factors that might affect the outcome of therapy. We, therefore, studied the efficacy of percutaneous instillation of tetracycline for eradication of recurrent thyroid cysts, using a multivariate analysis. Thirty-seven patients with recurrent, cytologically benign thyroid cysts (not cured after 3 aspirations) were studied. Twenty-three patients were given tetracycline instillations [100 mg/ml, range (R): 1-4 ml]. The remainder underwent only repeated needle aspiration. They were followed for 33 +/- 12 (SD) months, R: 12-58 months. Cure was achieved in 21 out of 23 cases after tetracycline instillation within 2 +/- 1.7 months (R: 1-6 months) and in 12 out of 14 cases after aspiration alone within 9.9 +/- 11.3 months (R: 1-43 months, 4-10 aspirations). Multivariate survival analysis using the Cox proportional-hazards regression model demonstrated significantly shorter time interval before cure in the group with tetracycline instillation (p = 0.001). The volume, color or duration of cysts and levothyroxine (L-T4) treatment did not appear to influence the outcome of therapy. After initial cure by tetracycline instillation, 5 cases had relapse. Three were later cured by reinstillation of tetracycline or by repeated aspirations (R: 1-3 times). Complications of tetracycline instillation included brief episode of neck pain and development of a foreign body granuloma in a single patient. In conclusion, tetracycline instillation is a quick and effective procedure for treating recurrent thyroid cysts.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Radiation therapy in early glottic carcinoma: uni- and multivariate analysis of prognostic factors affecting local control.

PURPOSE: The purpose of this report is to clarify prognostic factors affecting local control of T1 and T2 glottic tumors and to define an optimal regimen for radiation therapy. METHODS AND MATERIALS: Two hundred and ten patients (199 males, 11 females, age range 30 to 86 years with an average of 62 years) with previously untreated invasive squamous cell carcinoma of the glottis were treated with radiation therapy at the University of Tokyo between January 1972 and December 1989. Endoscopic microsurgery was introduced as an integral part of treatment in 1974. From 1974 to 1979 the radiation dose was gradually reduced, reaching a mean of 20 Gy in 2 weeks in 1979. From 1980 to 1983, the total dose increased to 50.4 Gy, with a fraction size of 1.8 Gy, over a mean of 5.6 weeks. From 1984 onward, the mean total radiation dose increased to 60 Gy with a fraction of 2 Gy. RESULTS: Recurrence-free 5 year survival rates for T1a, T1b, and T2 were 79%, 73%, and 67%, respectively. When the relationship between radiation dose and local control rates was analyzed for each year from 1974 to 1989, total doses were strongly associated with local control for patients with T1a disease. Age, sex, daily dose, total dose, radiation machine (Co-60 or 10 MV Lineac), treatment technique (anterior wedged pair or parallel opposed fields), treatment volume, use of endoscopic microsurgery, and involvement of the anterior commissure were examined for effects upon relapse-free survival in T1a disease by uni- and multivariate analysis. Total dose was the only significant factor for T1a disease (p < 0.02). The effect of these variables upon relapse-free survival in T2 disease as well as the effect of cord mobility, and number of involved sites was examined by multivariate analysis. Total dose (p < 0.03), cord mobility (p < 0.05), and number of involved sites (p < 0.04) significantly affected relapse-free survival in T2 disease. CONCLUSION: At least 50 Gy is required for treatment of T1 disease when 2 Gy is used as a daily dose, even if endoscopic microsurgery is performed. Better local control of T2 disease in patients with impaired cord mobility or more than three involved sites leads to an improved prognosis; we recommend doses of at least 70 Gy or use of hyperfractionation in such patients with these factors. Although the daily dose did not significantly affect prognosis in multivariate analyses, 1.8 Gy is not recommended for treatment of T2 tumors instead of 2 Gy.

Adult↗

Resection of lung metastases from soft-tissue sarcomas. A multivariate analysis.

From 1970 through 1986, 78 patients underwent 162 thoracotomies for removal of lung metastases from soft-tissue sarcomas. A multivariate analysis showed that the presence of a local recurrence, an incomplete pulmonary resection, and a shorter disease-free interval were poor prognostic factors. Patients who underwent multiple thoracotomies survived longer from the time of initial thoracotomy. The histologic type of sarcoma and the number of metastases resected showed no statistical significance. The median survival of the 61 patients who had a complete resection was 21 months. Patients with five or fewer metastases resected had an overall 5-year survival of 22% compared with 21% for patients who had six or more metastases resected. However, patients with five or fewer metastases showed a trend toward a higher 10-year disease-free survival. A complete resection of pulmonary metastases from soft-tissue sarcoma can prolong survival even if multiple metastases are present, although patients with fewer metastases may have a longer disease-free survival.

Adolescent↗

Characterization of poly(L-lysine)-graft-poly(ethylene glycol) assembled monolayers on niobium pentoxide substrates using time-of-flight secondary ion mass spectrometry and multivariate analysis.

Control of protein adsorption onto solid surfaces is a critical area of biomaterials and biosensors research. Application of high performance surface analysis techniques to these problems can improve the rational design and understanding of coatings that control protein adsorption. We have used static time-of-flight secondary ion mass spectrometry (TOF-SIMS) to investigate several poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) adlayers adsorbed electrostatically onto negatively charged niobium pentoxide (Nb(2)O(5)) substrates. By varying the PEG graft ratio (i.e., the number of lysine monomers per grafted PEG chain) and the molecular weights of the PLL and PEG polymers, the amount of protein adsorption can be tailored between 1 and 300 ng/cm(2). Detailed multivariate analysis using principal component analysis (PCA) of the positive and negative ion TOF-SIMS spectra showed changes in the outermost surface of the polymer films that were related to the density and molecular weight of the PEG chains on the surface. However, no significant differences were noted due to PLL molecular weight, despite observed differences in the serum adsorption characteristics for adlayers of PLL-g-PEG polymers with different PLL molecular weights. From the PCA results, multivariate peak intensity ratios were developed that correlated with the thickness of the adlayer and the enrichment of the PEG chains and the methoxy terminus of the PEG chains at the outermost surface of the adlayer. Furthermore, partial least squares regression was used to correlate the TOF-SIMS spectra with the amount of protein adsorption, resulting in a predictive model for determining the amount of protein adsorption on the basis of the TOF-SIMS spectra. The accuracy of the prediction of the amount of serum adsorption depended on the molecular weight of the PLL and PEG polymers and the PEG graft ratio. The combination of multivariate analysis and static TOF-SIMS provides detailed information on the surface chemistry and insight into the mechanism for protein resistance of the coatings.

Adsorption↗

Prognostic factors in high-grade malignant glioma. A multivariate analysis of 76 cases with postoperative radiotherapy.

PURPOSE: Patients with malignant gliomas have a limited survival prognosis. We retrospectively analyzed data of malignant glioma patients with the aim of defining prognostic factors on which individualized treatment strategies might be built on. PATIENTS AND METHODS: Seventy-six patients with primary malignant glioma (51 glioblastoma multiforme, 20 anaplastic astrocytoma, 4 anaplastic oligo-astrocytoma, 1 anaplastic glioma) were postoperatively irradiated with 5 and 8 Me V photons, 2 Gy per fraction to a median total dose of 60 Gy (range 50 to 70 Gy). RESULTS: The youngest quartile of patients (up to 45 years) had the highest 3-year survival rates (mean +/- SE: 15 +/- 8%) and median survival time (17.9 months, 95% confidence interval: 9.2, 24.2 months) as compared to the oldest quartile (> 61 years) with no 3-year survivor and a median survival time of 9.7 months (7.2, 12.3 months). The middle quartiles (46 to 61 years) showed intermediate results. The difference between the youngest and oldest quartile (p = 0.01) and the middle quartile versus the oldest quartile (p = 0.04) was significant. In univariate analysis, tumor size (p = 0.04 for -30 mm vs > 50 mm) was of importance. In multivariate analysis only age of the patient reached statistical significance (p = 0.03). As compared to the youngest quartile of patients, the oldest quartile had a relative risk of 2.1 (95% confidence interval: 0.9, 5.1) of dying from the disease; the age group of 46 to 61 years had a relative risk of 2.0 (0.9, 4.3). CONCLUSIONS: Age of the patient is the most important factor for survival prognosis favouring younger age (< or = 45 years). The possible implications for radiation therapy are discussed.

Adolescent↗

Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors.

BACKGROUND AND PURPOSE: To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer. MATERIALS AND METHODS: From July 1987 through July 1994, 109 women with stage II and III breast cancer receiving modified radical mastectomies were managed by postoperative electron beam irradiation. Doses of 46 to 50.4 Gy were delivered to the chest wall covered with bolus, internal mammary nodes, supraclavicular nodes and axillary lymph nodes via 12 or 15 MeV single portal electron beam. Seventeen patients received additional 10-16 Gy surgical scar boost via 9 MeV electron beam. Comparison of pre-treatment and post-treatment chest X-ray films were used to monitor the development of pulmonary fibrosis. RESULTS: Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P<0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P<0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis. CONCLUSIONS: In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis.

Adult↗

c-erbB2 gene amplification and protein expression in ovarian epithelial tumors: evaluation of their respective prognostic significance by multivariate analysis.

c-erbB2 gene amplification or over-expression has been reported in ovarian cancer, but their prognostic value remains conflicting. To investigate the respective prognostic significance of c-erbB2 gene amplification and protein over-expression, tumor samples were obtained from 65 patients with ovarian adenocarcinoma (9 FIGO stage I, 7 stage II, 38 stage III and II stage IV) followed up for a median period of 71 months. c-erbB2 gene amplification (> or = 2.5 a.u.) was detected in 9/65 (14%) adenocarcinomas and in none of 5 benign and 8 borderline ovarian epithelial tumors also analyzed. Specimens from 52 of the 65 adenocarcinomas were available for immunohistochemical analysis. c-erbB2 protein expression was observed in 23/52 (44%) adenocarcinomas. No correlation was found between c-erbB2 gene copy number and protein expression. There was no correlation of c-erbB2 gene copy number or protein expression with any of the clinico-pathological factors analyzed (i.e., FIGO stage, histological type, histological grade and residual tumor). On univariate analysis, c-erbB2 gene amplification was associated with poorer survival (p = 0.04). However, in the multivariate analysis of clinico-pathological factors and c-erbB2 gene copy number, c-erbB2 gene amplification did not retain any independent prognostic significance (p = 0.19). No significant survival difference was found between patients with and without c-erbB2 protein over-expression in univariate or multivariate analyses. Therefore, neither c-erbB2 gene amplification nor c-erbB2 protein over-expression appears to be a significant prognostic marker in patients with ovarian carcinoma.

Adenocarcinoma↗

Prediction of progression following radical prostatectomy. A multivariate analysis of 721 men with long-term follow-up.

We studied 721 men with clinically confined disease who underwent radical prostatectomy. No patient received preoperative or postoperative radiotherapy or hormone therapy until progression occurred. For those men without progression, the mean follow-up was 6.5 years with a median of 6 years (range 1 to 12 years). Because patients with lymph node metastases or seminal vesicle invasion had such a high risk of progression, enhanced prognostication was not needed in men with these findings. Thus we focused this analysis on the 617 men without lymph node metastases or seminal vesicle invasion. In the multivariate analysis, Gleason score (P < 0.0001), surgical margins (P = 0.004), and capsular penetration (P = 0.007) were all independent predictors of progression. Tumors with a Gleason score of 2 through 4 were almost invariably cured, with a 10-year progression-free risk of 96%. At the opposite end of the spectrum, the 10-year actuarial progression-free risk for men with a Gleason score of 8 through 9 was 35%. Men with Gleason score 2 through 4 or 8 through 9 tumors could not be stratified into different risks of progression based on the presence or extent of capsular penetration or margin status. For the men with Gleason score 5 through 7 tumors (88.2% of cases), predicting their risk of progression was enhanced by knowledge of their tumor's capsular penetration and margin status. Tumors with a Gleason score of 5 through 6 and 7 were each stratified into three groups with different risks of progression. Using the actuarial curves within this study, physicians will be able to more accurately determine a patient's risk of progression following radical prostatectomy based on a combination of the radical prostatectomy Gleason score, extent of capsular penetration, and status of surgical margins of resection.

Disease Progression↗

Prognostic value of lymphovascular space invasion determined with hematoxylin-eosin staining in early stage cervical carcinoma: results of a multivariate analysis.

BACKGROUND: Our aim was to study the prognostic value of the presence of lymphovascular space invasion (LVSI) in patients with stage IB and II cervical carcinoma treated by initial surgery. PATIENTS AND METHODS: A retrospective analysis was performed on 193 patients who underwent, between 1985 and 1998, an initial radical hysterectomy with pelvic (+/- para-aortic) lymphadenectomy using midline laparotomy for stage IB (180 patients) or II (13 patients) cervical carcinoma. Postoperative therapy was delivered according to prognostic factors. RESULTS: The rate of LVSI correlated significantly with tumor stage, nodal status and the location of positive nodes. Using univariate analysis, tumor size (<4 or >/= 4 cm), LVS status and nodal status were prognostic factors. At multivariate analysis, two prognostic factors were identified: LVS status and nodal status. In a subgroup of 89 patients with a small tumor (</=2 cm) and absence of nodal or isthmic involvement, the overall survival was significantly correlated with the presence of LVSI. CONCLUSIONS: LVSI is a frequent occurrence in patients with early stage cervical cancer. It represents an unfavorable prognostic factor in univariate and multivariate analyses. Such results suggest that improvement is needed in the treatment of patients with a small tumor and LVS invasion.

Adult↗

[Changes in lymphocyte subsets in chronic inflammatory diseases and neoplasms in the elderly. I. Multivariate analysis of variance and factoral analysis].

The variations of lymphocyte subsets have been studied both in neoplastic and chronic inflammatory elderly patients compared to a control group. The interpretation of the Multivariate Analysis of Variance (MANOVA) and of the Factorial Analysis has demonstrated the opposite role of TCD4 subset, mainly involved in the inflammatory process, and of TCD8 subset in regard of the neoplastic ones. We report the slight and yet significant increase of NK related to age. Independently from the disease pattern, factorial analysis permitted a comparison between the variations of lymphocyte subsets and the different grades of immunoresponse.

Aged↗

[Morphometrical study of physical growth in infant cynomolgus monkeys using multivariate analysis].

We describe the relative growth in infant cynomolgus monkeys (Macaca fascicularis). The multivariate analyses using the principal component analysis and multivariate allometric analysis were applied to biometrical data of laboratory-bred cynomolgus monkeys aged from birth to 12 weeks. All the animals had been bred and reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N. I. H., Japan. As the result of the principal component analysis, the cumulative contribution ratio of the 1st and 2nd principal components (PC1 and PC2) accounted for 88.2% and 85.7% in males and females, respectively. This indicates that the morphologic traits (15 traits) grow normally in size, but the analysis did not detect any differences in growth rate among the traits. So, the multivariate allometric analysis was applied to the same data. The traits concerning the face and truck showed relatively high growth rates compared to head breadth, whereas the limbs and arms grew slowly.

Analysis of Variance↗

Multivariate analysis of recurrence after anterior resection for colorectal carcinoma.

We performed a multivariate analysis of survival data from 278 patients who underwent potentially curative anterior resection with hand-sewn anastomosis for nonobstructing colorectal carcinoma to evaluate the interaction of the resection margin with distance from the anal verge and their contributions to local and distant recurrence. Cumulative 5-year disease-free survival was 66 percent for the 258 patients with complete follow-up. Forty-nine patients (19 percent) had local recurrence and 42 (16 percent) developed initial distant metastases. Local recurrence rates increased with increasing age and with more advanced Dukes' stage. It developed in twice as many patients with colostomies as without colostomies. Distant metastases developed significantly more often in patients with nodal involvement and in patients with resection margins exceeding 3.5 cm. Forty-four percent of patients with lesions within 14 cm of the anal verge resected with margins of at least 3.5 cm developed distant recurrence. This study suggests that aggressive pelvic dissection to achieve resection margins greater than 3.5 cm may contribute to tumor dissemination and subsequent distant metastases.

Adenocarcinoma↗

A multivariate analysis of pathologic factors influencing prognosis of colorectal cancer in 1067 cases.

Multivariate analysis (risk state analysis) was performed to evaluate the single and joint effects of pathologic variables on the survivals of 1067 cases of colorectal carcinoma. Nineteen of the twenty-eight variables analyzed were found to have statistically significant prognostic value, with over half having a strong influence on prognosis. The first seven, ranked in order of their effects on survival, are metastasis in lymph nodes, depth of invasion, histologic grading, lymphocyte infiltration of the cancer, GH (immune response in regional lymph nodes), growth pattern and fibrous proliferation around the cancer. The joint effects of combinations of these major variables are even more striking than those of single ones.

Colorectal Neoplasms↗

[A method of multivariate analysis of data in the study of the effects of space flight factors on the rat brain neuron structure].

The usage of some methods of multivariate analysis for neuro-morphological studies is discussed. The alterations of dendritic trees of pyramidal neurons of layer III of visual cortex of the rat exposed to the influence of space flight aboard biosputnik "Cosmos-1887" were studied and the results are described to illustrate the methods power. o-technique of factor analysis was shown to be suitable for processing of the data obtained from an experiment with complex environmental conditions.

Animals↗