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[Relation between progression of atherosclerosis and the phenomenon of restenosis after coronary angioplasty].

The authors undertook a retrospective study of medium-term coronary angiographic controls of a group (Gr) of patients (pts) who had undergone coronary angioplasty for rapidly progressive lesions, to determine whether the rate of progression of a coronary stenosis before angioplasty affected the risk of restenosis. 89 pts underwent primary angioplasty with absence of restenosis at 6 months, but required another angioplasty for another lesion. Angiographic follow-up after the 2nd procedure was performed in 86 pts (96%). The coronary lesion dilated at the 2nd angioplasty procedure was analysed quantitatively with four measurements: one immediately before angioplasty, one after, one at the 6 months control, and finally, one measurement 6 months before the angioplasty during the procedure on the 1st site. Multivariate statistical analysis showed that the only predictive factor of post-angioplasty loss in the general population was the immediate gain (F = 11.82; p < 0.005). On the other hand, no correlation was found between progression of the lesion before angioplasty and loss. The rapidly progressive nature of the lesion was defined with a threshold of 0.4 mm, corresponding to the variability of the quantitative angiographic system. Analysis of the procedure parameters showed a lower inflation pressure in the Gr with rapidly progressive lesions (6.58 +/- 21 atm vs 7.63 +/- 1.96 atm; p < 0.05). The immediate gain was significantly greater in the rapidly progressive lesion Gr (0.82 +/- 0.34 vs 0.67 +/- 0.29 mm; p = 0.05). The loss at the 6 months control was identical in the two Gr (0.31 +/- 0.50 vs 0.31 +/- 0.42 mm; p < 0.05). The loss/gain ratio was also comparable (0.37 +/- 0.76 vs 0.45 +/- 0.52; p > 0.05). These results show that rapidly progressive atherosclerosis does not increase the risk of post-angioplasty restenosis.

Aged↗

Socio-economic and dietary influences on leg length and trunk length in childhood: a reanalysis of the Carnegie (Boyd Orr) survey of diet and health in prewar Britain (1937-39).

Social class differences in height have been recognised for many centuries. However, few studies have examined the extent to which these differences are made up of differences in leg length or trunk length. This paper reanalyses cross-sectional information on children examined in Britain in the 1930s. We assess associations between socio-economic status and diet and the components of childhood stature. The analyses were based on the records of 2990 children aged 2 years to 14 years 9 months who were examined in the Carnegie (Boyd Orr) survey of diet and health (1937-39). z-Scores for the measures of childhood stature were calculated using polynomial regression techniques with the study population as the standard. Univariable and multivariable statistical techniques were used to assess the relationships between childhood height, leg length and trunk length, and dietary and socio-economic factors measured at the level of the household. Leg length was the component of stature most strongly associated with measures of childhood diet and socio-economic status. A greater part of the difference in stature between socio-economic groups was caused by differences in leg length rather than trunk length. In multiple regression analyses, district of residence and family food expenditure were generally the two factors most strongly related to stature. In a subsample of the surveyed children, for whom birthweight information was available, trunk length and leg length were equally strongly related to birthweight. Leg length appears to be a particularly sensitive indicator of childhood socio-economic circumstances. Although contemporary studies highlight the importance of biological factors in determining childhood height, the data analysed in this study suggest that socio-economic circumstances were also important in explaining height differentials in prewar Britain.

Adolescent↗

Multivariate relationships between groundwater chemistry and toxicity in an urban aquifer.

Multivariate statistical methods were used to investigate the causes of toxicity and controls on groundwater chemistry from 274 boreholes in an urban area (London) of the United Kingdom. The groundwater was alkaline to neutral, and chemistry was dominated by calcium, sodium, and sulfate. Contaminants included fuels, solvents, and organic compounds derived from landfill material. The presence of organic material in the aquifer caused decreases in dissolved oxygen, sulfate and nitrate concentrations, and increases in ferrous iron and ammoniacal nitrogen concentrations. Pearson correlations between toxicity results and the concentration of individual analytes indicated that concentrations of ammoniacal nitrogen, dissolved oxygen, ferrous iron, and hydrocarbons were important where present. However, principal component and regression analysis suggested no significant correlation between toxicity and chemistry over the whole area. Multidimensional scaling was used to investigate differences in sites caused by historical use, landfill gas status, or position within the sample area. Significant differences were observed between sites with different historical land use and those with different gas status. Examination of the principal component matrix revealed that these differences are related to changes in the importance of reduced chemical species.

Animals↗

Locomotor ecology of wild orangutans (Pongo pygmaeus abelii) in the Gunung Leuser Ecosystem, Sumatra, Indonesia: a multivariate analysis using log-linear modelling.

The large body mass and exclusively arboreal lifestyle of Sumatran orangutans identify them as a key species in understanding the dynamic between primates and their environment. Increased knowledge of primate locomotor ecology, coupled with recent developments in the standardization of positional mode classifications (Hunt et al. [1996] Primates 37:363-387), opened the way for sophisticated multivariate statistical approaches, clarifying complex associations between multiple influences on locomotion. In this study we present a log-linear modelling approach used to identify key associations between orangutan locomotion, canopy level, support use, and contextual behavior. Log-linear modelling is particularly appropriate because it is designed for categorical data, provides a systematic method for testing alternative hypotheses regarding interactions between variables, and allows interactions to be ranked numerically in terms of relative importance. Support diameter and type were found to have the strongest associations with locomotor repertoire, suggesting that orangutans have evolved distinct locomotor modes to solve a variety of complex habitat problems. However, height in the canopy and contextual behavior do not directly influence locomotion: instead, their effect is modified by support type and support diameter, respectively. Contrary to classic predictions, age-sex category has only limited influence on orangutan support use and locomotion, perhaps reflecting the presence of arboreal pathways which individuals of all age-sex categories follow. Effects are primarily related to a tendency for adult, parous females to adopt a more cautious approach to locomotion than adult males and immature subjects.

Age Factors↗

Sequence signature analysis of chromosome identity in three Drosophila species.

BACKGROUND: All eukaryotic organisms need to distinguish each of their chromosomes. A few protein complexes have been described that recognise entire, specific chromosomes, for instance dosage compensation complexes and the recently discovered autosome-specific Painting of Fourth (POF) protein in Drosophila. However, no sequences have been found that are chromosome-specific and distributed over the entire length of the respective chromosome. Here, we present a new, unbiased, exhaustive computational method that was used to probe three Drosophila genomes for chromosome-specific sequences. RESULTS: By combining genome annotations and cytological data with multivariate statistics related to three Drosophila genomes we found sequence signatures that distinguish Muller's F-elements (chromosome 4 in D. melanogaster) from all other chromosomes in Drosophila that are not attributable to differences in nucleotide composition, simple sequence repeats or repeated elements. Based on these signatures we identified complex motifs that are strongly overrepresented in the F-elements and found indications that the D. melanogaster motif may be involved in POF-binding to the F-element. In addition, the X-chromosomes of D. melanogaster and D. yakuba can be distinguished from the other chromosomes, albeit to a lesser extent. Surprisingly, the conservation of the F-element sequence signatures extends not only between species separated by approximately 55 Myr, but also linearly along the sequenced part of the F-elements. CONCLUSION: Our results suggest that chromosome-distinguishing features are not exclusive to the sex chromosomes, but are also present on at least one autosome (the F-element) in Drosophila.

Animals↗

Timing of conception and the risk of spontaneous abortion among pregnancies occurring during the use of natural family planning.

OBJECTIVE: Our purpose was to ascertain the effects of timing of conception on the risk of spontaneous abortion. STUDY DESIGN: To assess these effects, women who conceived while using natural family planning were identified in five centers worldwide between 1987 and 1993. Timing of conception was determined from 868 natural family planning charts that recorded day of intercourse and indices of ovulation (cervical mucus peak obtained according to the ovulation method and/or basal body temperature). Conceptions on days - 1 or 0 with respect to the natural family planning estimated day of ovulation were considered to be "optimally timed," and all other conceptions were considered as "non-optimally timed." The rate of spontaneous abortions per 100 pregnancies was examined in relation to timing of conception, ages, reproductive history, and other covariates with bivariate and multivariate statistical methods. RESULTS: There were 88 spontaneous abortions among 868 pregnancies (10.1%). The spontaneous abortion rate was similar for 361 optimally timed conceptions (9.1%) and 507 non-optimally timed conceptions (10.9%). However, among 171 women who had experienced a spontaneous abortion in a prior pregnancy, the rate of spontaneous abortion in the index pregnancy was significantly higher with non-optimally timed conceptions (22.6%) as compared with optimally timed conceptions (7.3%). This association was not observed among 697 women with no history of pregnancy loss. The adjusted relative risk of spontaneous abortion among women with non-optimally timed conceptions and a history of pregnancy loss was 2.35 (95% confidence intervals 1.42 to 3.89). The excess risk of spontaneous abortion was observed with both preovulatory and postovulatory conceptions. CONCLUSIONS: Overall, there is no excess risk of spontaneous abortion among the pregnancies conceived during natural family planning use. However, among women with a history of pregnancy loss, there is an increased risk of spontaneous abortion associated with preovulatory or postovulatory delayed conceptions.

Abortion, Spontaneous↗

Early and late determinants of survival after surgery of left ventricular aneurysm.

The fate of 103 patients consecutively operated upon for chronic left ventricular aneurysm between 1978 and 1986 was examined with a multivariate statistical approach to verify the operative indications and results. In the early risk phase, up to 39 days after operation, 15 patients (15%) died. Mortality was mostly due to a low output syndrome and was significantly related to older age and to functional (NYHA) and anginal (CCS) class. In the late risk phase, starting 1.9 years after surgery, 9 patients died (10%) and the significant risk factors were anterior aneurysm and older age at operation. Actuarial survival curves showed 82% survival at 5 years and 61% at 9.5 years. In 25 patients older than 50 years and with an anterior aneurysm, these rates were 51% and 34%, respectively. Improved functional class was observed in 87% of the patients interviewed, but 30% complained of angina or new infarctions. Survival free of ischemia was 64% at 5 years and 13% at 9.5 years. This development of ischemic recurrences was significantly related to older age and to incomplete revascularization despite multiple grafts. These results suggest modification of the grafting policy and of the techniques of repair in identified high-risk subsets.

Actuarial Analysis↗

Multivariate neurocognitive and emotional profile of a mannosidosis murine model for therapy assessment.

alpha-Mannosidosis is a lysosomal storage disorder caused by lysosomal alpha-mannosidase (LAMAN) deficiency that leads to neurocognitive dysfunctions, psychotic symptoms and emotional changes in human patients. A murine mannosidosis model, LAMAN-deficient mice, was examined on a behavioral task battery that included test for neuromotor, exploratory and neurocognitive (spatial learning and memory) abilities, and multivariate statistical analyses were used to identify behavioral and neurocognitive domains that are most heavily affected by LAMAN deficiency. In addition, we further investigated synaptic plasticity recordings on hippocampal slices that may relate to these behavioral alterations. Correlation analysis revealed significant intra- and intertask correlations and factor analysis that included all 21 behavioral variables identified three main factors (exploration/emotionality, locomotion and learning/memory abilities). Significant correlations were observed between genotype, and factor 1 (exploration/emotionality) and factor 3 (learning/memory abilities). Discriminant function analysis showed that "path length in the open field test" and "time spent in the target quadrant during the water maze probe trial" were the most decisive variables to distinguish between the genotypes. We therefore suggest that these variables would be especially important in forthcoming therapy assessment experiments using this murine mannosidosis model. LAMAN-deficient mice displayed severe changes in synaptic plasticity, which may have contributed to the neurocognitive impairments observed. The present report further shows that targeted deletion of the LAMAN gene in mice mimics many aspects of human alpha-mannosidosis, and these data provide a basis for future therapeutic experiments.

Animals↗

Preoperative radiochemotherapy and radical resection for stages II to IV oral and oropharyngeal cancer: grade of regression as crucial prognostic factor.

The purpose of this study was to assess the prognostic value of histological response to preoperative radiochemotherapy in an established multimodal therapy concept for advanced oral and oropharyngeal cancer. Two hundred and twenty-two patients who underwent preoperative radiochemotherapy (RCT: 50 Gy, mitomycin C and fluorouracil) and radical surgery were retrospectively evaluated. Resected tumours of all patients were histologically analysed and response to RCT was classified in histopathological grades of regression (RG). In a multivariate statistical analysis, RG was compared with established factors regarding their predictive value for overall and disease-specific survival. The 5-year overall survival probability in the different groups of histopathological regression grades were: RG1 (no vital tumour): 73.4%, RG2 (minimal tumour remnants encompassing less than 5%): 72.1%, RG3 (5-50% vital tumour cells): 41.9%, RG4 (more than 50% vital tumour): 37.9%. For disease-specific survival probability no significant differences were found between both groups of "responders" (RG1 and RG2) nor between "non-responders" (RG3 and RG4), whereas responders and non-responders differed significantly from each other (log-rank test; p < 0.001). T-classification, N-classification and disease stage, histological grading, tumour site, age, and sex had less prognostic value than RG in a Cox regression model. In the neoadjuvant multimodal therapy concept, histological response to preoperative RCT is a crucial prognostic factor even when surgical R0-resection is accomplished. Thus, non-responders have to be regarded as high-risk patients for recurrence and may benefit from further therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Rigor and relaxed outer dynein arms in replicas of cryofixed motile flagella.

A method of image classification based on multivariate statistics has been developed and applied to freeze-etch images of outer dynein arms (ODAs) from cockerel sperm flagella. Demembranated flagella were cryofixed in three different nucleotide states: rigor (i.e. no added ATP); relaxed (i.e. 1 mM ATP plus vanadate); and active (i.e. 1 mM ATP). Freeze-etch replica fragments from them were coded to conceal their identities and sampled for flagella. From these a total of 6048 individual ODA images were successfully windowed and aligned, covering an angular range of 66 degrees. Each nucleotide condition produced a statistically significant ODA morphology. The relaxed and active morphologies differed only in the angulation of their heads, with the relaxed ODA favouring a more tilted position. The rigor morphology was more distinct and showed a conformational change involving a 12 nm distal shift relative to the A-tubule and highly variable heads and B-links, suggesting an ability to develop tension. Outer arms were classified by discriminant analysis as being either rigor-like, relaxed-like or active-like, and 80% of all ODAs were correctly classified. The misclassification of the remaining 20% indicated morphological heterogeneity in some of the groups. From the rigor group, 8.8% of the ODAs were misclassified as relaxed-like or active-like (i.e. non-rigor-like). It is speculated that this is a consequence of mechanochemical interactions between the B-tubules and the rigor ODAs and/or contaminating ATP remaining after demembranation. Active flagella were found to show all three morphologies, with 5.4% in the rigor conformation and 18.6% in the relaxed conformation. The finding of rigor-like and relaxed-like ODAs in flagella exposed to ATP is discussed in relation to the cross-bridge cycle.

Adenosine Triphosphate↗

Attachment style, childhood adversity, and behavioral risk among young men who have sex with men.

PURPOSE: To examine relationships among childhood adversity, attachment style (one's core beliefs regarding the self and others), and the following risk behaviors and contexts among young men who have sex with men (YMSM): homelessness, daily substance use, participation in sex work, involvement in the criminal justice system, and being out of school or work. METHODS: Using a targeted sampling approach, we recruited 569 YMSM aged 17-28 years from natural venues in New York City including bars, clubs, parks, and bus stations. Youth completed a structured interview assessing lifetime and current risk and protective contexts and behavior. Data were analyzed using univariate and multivariate statistical methods, including hierarchical logistic regression. RESULTS: After controlling for demographic characteristics and childhood adversity, YMSM with a fearful attachment style were more likely to have been homeless (OR 2.93, 95% CI 1.65-5.18), to have participated in sex work (OR 2.35, 95% CI 1.44-3.85), to use substances daily (OR 2.79, 95% CI 1.29-6.03), to have been involved in the criminal justice system (OR 2.04, 95% CI 1.38-3.01), and to be out of school/work (OR 2.47, 95% CI 1.47-4.15). Three subgroups were particularly vulnerable: YMSM who identified as heterosexual, or bisexual, and/or transgender. CONCLUSIONS: A fearful attachment style contributes to some YMSM remaining outside of the protective systems of family, school, and work, and is associated with risky contexts where they are less likely to encounter prosocial peers and adults. Further, it is associated with risk behavior. Although gay-identified youth are generally found to have poor outcomes when compared with the general population of adolescents, in the present report, YMSM who identified as heterosexual were at particular risk. Attachment theory can guide interventions by informing how individuals experience relationships and manage developmental transitions.

Adolescent↗

Multivariate analysis of single unit cells in electron crystallography.

High-resolution electron cryomicroscopy of two-dimensional protein crystals is associated with extremely noisy raw data in which even the crystal lattice often cannot be discerned. Correlation averaging procedures, aimed at calculating the total average of all unit cells of crystals in order to reduce noise, are now used routinely in electron crystallography. Multivariate statistical analysis (MSA) may be used for finding not only the average structure but also for quantifying the systematic departures from that average within the population of individual unit cells. We show that the MSA approach is applicable to single unit-cell images in the low-dose (< 10 electrons/A2), high-resolution (< 5 A) realm using 400 keV electron spot-scan images of ice-embedded gp32*I protein crystals. Our feasibility study opens a pathway toward exploiting these naturally occurring variations on the unit-cell theme in order to achieve higher-resolution three-dimensional reconstruction results, or to better understand the dynamic behaviour of molecules within two-dimensional crystals. We explain how single unit-cell images can be processed and classified into homogeneous groups, and we review how the results of such discriminate averaging may subsequently be exploited within the context of conventional "h, k"-space electron crystallographic approaches. Variations among the individual unit cells may thus be one of the most significant resolution-limiting factors currently experienced in electron crystallography. The quantitative assessment and exploitation of such variations may lead to an increased performance of electron crystallographic procedures.

Bacteriophage T4↗

Clinicopathological factors in early squamous cell carcinoma of the tongue and floor of the mouth, in Biscay (the Basque Country, Spain).

OBJECTIVES: A study is made of the main clinicopathological factors in squamous cell carcinoma (SCC) of the tongue and floor of the mouth in the province of Vizcaya (Biscay) (The Basque Country, Spain), and their relation to patient prognosis. DESIGN: A retrospective study was made of 40 patients with early (clinical stage I/II) SCC of the tongue and floor of the mouth. A previously designed protocol was used to record the clinical and histopathological data, which were subjected to descriptive and comparative bi- and multivariate statistical and survival analyses. RESULTS: There were 34 males and 6 females, with a mean age of 55.7 years (range 33-81). In 23 cases the SCC was located in the tongue, and in 17 cases in the floor of the mouth. The average tumor diameter was 2.6 cm; 65% of the neoplasms were ulcerated. The mean clinical course was 3.4 months, with an average tumor growth rate or velocity of 268 (Evans formula). Thirty-four patients were smokers and 33 consumed alcohol. All SCC of the floor of the mouth, and all regional recurrences, were diagnosed in smokers and drinkers. Survival at 5 years was 65%. Well differentiated SCC were diagnosed in 52.5% of cases. The average histological malignancy grade was 1.96, and was higher in males, tongue malignancies, T2 lesions, tumors with growth velocities above 200, and in recurrent neoplasms. CONCLUSIONS: Early SCC of the tongue and floor of the mouth in Vizcaya affects mainly male smokers and drinkers of alcohol under the age of 60 years. A relationship is observed between the histopathological findings (particularly invasion mode and stage) and patient prognosis.

Adult↗

-Dual nucleoside therapy for HIV infection: analysis of results and factors influencing viral response and long term efficacy.

We performed a retrospective analysis of our experience with dual nucleoside regimens to look for predictors of long term benefit. The study evaluated a cohort of 68 HIV-infected patients treated at 3 Italian hospital-based facilities. The results were evaluated using univariate and multivariate statistical analysis. Fourty-three males and 25 females were treated for 22 +/- 14 months. Sixty three patients (92.6%) suffered no or low-grade side-effects. Thirty-four patients (50%) reached a viral load <400 copies/ml (undetectable). Viremia remained persistently undetectable in 9 cases (13.2%). Variable relapses of viremia were seen in 13 patients (19.1%) even though their therapys were not modified. Eight patients (11.8%) showed relapsing viremias persistently around or below 10,000 copies/ml. All patients reaching undetectable viremia but one showed increasing or stable CD4+ cell counts. Factors predicting favourable response were: pre-treatment CD4+ T-cells >150/microl, pre-treatment viremia <50,000 copies/ml, pre-treatment lymphocytes >1,500/microl, and no previous exposure to NRTI. Total lymphocyte counts and CD4+ T-cells showed a significant correlation. Dual NRTI regimens may be still considered for patients unable to tolerate HAART regimens and presenting with favourable predictors of response.

Adult↗

Lateral facial soft-tissue prediction model: analysis using Fourier shape descriptors and traditional cephalometric methods.

This study was designed to investigate the relationship between traditional skeletal cephalometric measurement and Fourier analysis of the lateral soft-tissue profile. A random sample of 121 untreated subjects of European descent, with wide ranges of malocclusions and underlying facial patterns, was selected in the Orthodontic Unit at the University of Melbourne. Lateral cephalograms were available for all subjects. Both traditional lateral cephalometric analysis and Fourier soft-tissue profile analysis were carried out. Multivariate statistical analysis among 11 hard-tissue cephalometric measurements and the first 50 Fourier harmonics was then performed. This analysis formed the basis for a subsequently proposed soft-tissue prediction model. From this model, 50 predicted x- and y-harmonics were generated for each subject in the total sample. Calculation of Pearson's correlation coefficients between the actual and predicted harmonics revealed strong relationships for many of the lower-order harmonics. To further test the model, the prediction-coefficients derived from all 121 subjects were then used to make predictions for the first 50 x- and y-harmonics for a subgroup of 10 independent test subjects. Once again, Pearson's correlations between the actual and predicted harmonics of the test model in the lower-order harmonics revealed strong associations. Superimposition of the actual and predicted soft-tissue outlines, however, revealed that much actual detail in the region between the nose and the chin was still lost using the predicted Fourier harmonics. This suggests that soft-tissue prediction based on this Fourier test model, while already useful in Forensic facial reconstruction, may not yet be appropriate for useful diagnosis and planning in clinical disciplines.

Adolescent↗

Application of multivariate, fuzzy set and neural network analysis in quantitative cytological examinations.

Multivariate statistical methods have been used in several studies to increase the diagnostic reliability of TV image analyser systems. In recent years some algorithms for decision support (fuzzy logic) and for pattern recognition (neural nets), both non-linear, were developed. This paper reports on preliminary results obtained with these methods in quantitative cytology and compares them to the traditional classifiers. A total of 21 normal, 15 dysplastic and 23 malignant, gastric imprint smears were Feulgen stained and analysed on a Leitz Miamed DNA cytophotometer system. Mean DNA content, the 2c deviation index (2cDI), 5c exceeding rate (5cER), G1, S, G2 phase fraction ratios, cell nucleus area and form factor were determined. Diagnostic accuracy of the discriminant analysis was 96% for the malignant cases, 87% for dysplasias and 81% for normal cases. Cluster analysis gave no significant result. Our diagnostic system utilizing fuzzy logic has made the diagnostic borders adjustable and reliable. The back-propagation neural net correctly classified the normal and malignant cases (100%) and all but one of the dysplasias (98%). The non-linear mathematical methods improved the reliability of the diagnostic system. These new algorithms gave results comparable to traditional classifiers. The application of these methods to clinical samples is encouraging.

Algorithms↗

Free flap reconstruction of the head and neck: analysis of 241 cases.

OBJECTIVE: We undertook this study of free flap reconstruction of the head and neck to stratify patients and procedures, to determine how donor site preference changed over time, to assess medical and surgical outcomes, and to identify variables associated with complications. METHODS: We analyzed computerized medical records from 236 patients who underwent a total of 241 reconstructions at a tertiary academic medical center in St. Louis between 1989 and 1998. We created a more detailed retrospective database of 141 of those patients by using 48 perioperative variables and 7 adverse outcome measures. Multivariate statistical models were used to analyze associations between variables and outcomes. RESULTS: The fibula became the preferred donor site for mandibular reconstruction, and the radial forearm became the preferred donor site for pharyngoesophageal reconstruction. For the 241 procedures, the mortality rate was 2.1%, the median length of stay was 11 days, and the flap survival rate was 95%. Administration of more than 7 L of crystalloid during surgery and age over 55 were associated with major medical complications. Blood transfusion, prognostic comorbidity, and number of surgeons correlated with length of stay. Cigarette smoking and receipt of more than 7 L of crystalloid during surgery were associated with overall flap complications, and weight loss of more than 10% before surgery, more than one operating surgeon, and cigarette smoking were associated with major flap complications. CONCLUSIONS: Risk to patients and transferred tissue is low in free flap head and neck reconstruction. Age, smoking history, and weight loss should be considered during patient selection. Fluid balance should be considered during and after surgery. Division of labor for patient care should be carefully delineated among surgeons in a teaching setting.

Adolescent↗

Malignant fibrous histiocytoma: outcome and prognostic factors following conservation surgery and radiotherapy.

PURPOSE: Malignant fibrous histiocytoma is the most common type of soft tissue sarcoma. This communication presents an analysis of outcome and prognostic factors based on a retrospective review of patients with this disease treated by conservation surgery and radiotherapy. METHODS AND MATERIALS: From 1966 to 1991, 271 consecutive patients with malignant fibrous histiocytoma were treated with conservation surgery and radiotherapy. The outcome with local control, metastatic relapse, and survival as end points was evaluated by univariate and multivariate statistics to delineate independently significant prognostic factors. RESULTS: Postoperative radiation at a mean dose of 62.8 Gy was used in 195 patients and preoperative radiation at a mean dose of 50 Gy was used in 76 patients. At a median follow-up of 7.3 years, 123 patients (45%) developed disease relapse at some site. Fifty-seven (21%) developed local recurrence leading to an actuarial local relapse rate of 26% at 10 years, 83 (31%) developed metastatic relapse for a 10-year actuarial metastatic rate of 33%, and the 5-, 10-, and 15-year survival rates were 68, 60, and 46%, respectively. For local control, prior local recurrence (in 53 patients) was identified as an adverse factor, yielding a 10-year recurrence rate of 42% compared to 22% for 218 patients without prior disease (p < 0.01). Also, a positive surgical margin (in 46 patients) was adverse with a 10-year local recurrence rate of 39% compared to a recurrence rate of 17% with negative margins (167) (p=0.01). Patients with pathologically undocumented resection margins (58) had a local recurrence rate similar to those with positive margins (41% at 10 years). Tumor site (extremity vs. nonextremity), location (proximal vs. distal), size (< or = 5 cm vs. > 5 cm), and histology (myxoid vs. nonmyxoid) were not significant determinants of local outcome. For metastatic relapse, the major determinants of outcome were histology (myxoid vs. nonmyxoid) and tumor size. Myxoid tumors (59 patients) had a low metastatic propensity (13% 10-year metastatic rate) compared to nonmyxoid tumors (212 patients) (40% 10-year metastatic rate) (p < 0.01). Size was an important covariate for metastases for both myxoid and nonmyxoid tumors. For nonmyxoid tumors the 10-year metastatic rates were 23 and 51% for lesions less than or greater than 5 cm. For myxoid tumors a significant metastatic rate appeared only for tumors exceeding 10 cm (10-year metastatic rates of 8% vs. 44% for tumors less than vs. greater than 10 cm). In this retrospective review we found no evidence that adjuvant chemotherapy decreased the metastatic rate. In multivariate analysis for metastatic relapse and survival, tumor histology (nonmyxoid vs. myxoid) and size (< 5 cm vs. > 5 cm) were the only independent determinants of outcome. CONCLUSION: Malignant fibrous histiocytoma is a heterogeneous disease and its myxoid variant must be recognized as a distinct entity. Both variants are locally aggressive and require equally aggressive local therapy. Conservation surgery striving for negative margins with radiation therapy provides acceptable local control and is the treatment of choice for this disease. Patients with myxoid tumors do not require systemic therapy; patients with nonmyxoid disease exceeding 5 cm are at significant risk for metastases and the development of effective adjuvant treatment is an important research tool.

Adolescent↗