370 resultados para multivariate analysis
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BACKGROUND: In obstetrics, post-dural puncture headache is a well-recognised complication. Typical symptoms include fronto-temporal or occipital headache, worsening with ambulation and improving in the decubitus position. Occasionally, patients present with non-postural headache, although relatively little is known about this atypical presentation. The purpose of this study was to determine the incidence, associated signs and risk factors for this atypical manifestation of post-dural puncture headache. METHODS: We analysed a series of 27 064 parturients having a neuraxial procedure between January 2001 and December 2010. Using data from electronic anaesthesia patient records, medical charts and a postpartum quality audit, we identified all parturients with atypical post-dural puncture headache. We assessed the incidence and used uni- and multivariate analysis to identify associated risk factors. RESULTS: Amongst 142 parturients with post-dural puncture headache, eight (5.6%, 95% CI 1.7-9.4%) had atypical non-postural headache. Associated symptoms were stiffness and pain in the cervical, thoracic or lumbar vertebral area, visual disturbances and vertigo. Significant risk factors for developing atypical signs were previous migraine, odds ratio 6.1 (95% CI 1.2-28.7), a more cephalad level of needle insertion, odds ratio 17.2 (95% CI 1.4-210.1) and identification of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter, odds ratio 5.5 (95% CI 1.2-24.4). Following multivariate analysis, recognition of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter was the most significant predictor of non-orthostatic postdural puncture headache. CONCLUSION: Anaesthetists should be aware of this atypical clinical presentation, particularly if there is a past history of migraine, a more cephalad level of needle insertion or identification of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter.
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BACKGROUND: Many factors affect survival in haemodialysis (HD) patients. Our aim was to study whether quality of clinical care may affect survival in this population, when adjusted for demographic characteristics and co-morbidities. METHODS: We studied survival in 553 patients treated by chronic HD during March 2001 in 21 dialysis facilities in western Switzerland. Indicators of quality of care were established for anaemia control, calcium and phosphate product, serum albumin, pre-dialysis blood pressure (BP), type of vascular access and dialysis adequacy (spKt/V) and their baseline values were related to 3-year survival. The modified Charlson co-morbidity index (including age) and transplantation status were also considered as a predictor of survival. RESULTS: Three-year survival was obtained for 96% of the patients; 39% (211/541) of these patients had died. The 3-year survival was 50, 62 and 69%, respectively, in patients who had 0-2, 3 and >or=4 fulfilled indicators of quality of care (test for linear trend, P < 0.001). In a Cox multivariate analysis model, the absence of transplantation, a higher modified Charlson's score, decreased fulfilment of indicators of good clinical care and low pre-dialysis systolic BP were independent predictors of death. CONCLUSION: Good clinical care improves survival in HD patients, even after adjustment for availability of transplantation and co-morbidities.
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PURPOSE: Chemotherapy (CT) combined with radiation therapy (RT) is the standard treatment for limited disease small-cell lung cancer (LDSCLC). Many questions including RT dose, fractionation, and sequence of RT/CT administration remain controversial. In this paper, we retrospectively assessed the outcome of patients with LDSCLC treated with radiation of at least 50 Gy.METHODS AND MATERIALS: From December 1997 to January 2006, 69 consecutive patients with LDSCLC were treated at our institutions. Treatment consisted of at least 4 cycles of CT, and 3D conformal thoracic RT. The median age was 61 years (range, 37-78 years). Sequential or concomitant CT/RT was given in 47 (68%) and 22 (32%) of the patients, respectively. The median RT dose was 60 Gy. Prophylactic cranial irradiation (PCI) was administered in 47 (68%) patients.RESULTS: With a median follow-up of 36 months (range, 6-107), 16 patients were alive without disease. The median overall survival time was 24 months, with a 3-year survival rate of 29%. The 3-year disease-free survival (DFS) and loco-regional control (LRC) rates were 23% and 60%, respectively. A better DFS was significantly associated with performance status (PS) 0 (p = 0.004), complete response to treatment (p = 0.03), and PCI group (p = 0.03). A trend towards improved overall survival (OS) was observed for patients who underwent PCI (p = 0.07). Patients treated with sequential CT/RT had a better outcome than those treated with concomitant treatment (3-year DFS rate 27% vs. 13%; p = 0.04). However, PCI was delivered more frequently for the sequential group. No significant dose-response relationship was found in terms of LRC. The multivariate analysis showed that complete response to treatment was the only significant factor for OS.CONCLUSION: Complete response to treatment was the most important factor for OS. A better DFS was significantly associated with the PCI group. We did not find a significant difference in outcome between patients receiving doses of 60 Gy or more and patients receiving 60 Gy or less.
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BACKGROUND: Mantle cell lymphoma is a clinically heterogeneous disease characterized by overexpression of cyclin D1 protein. Blastoid morphology, high proliferation, and secondary genetic aberrations are markers of aggressive behavior. Expression profiling of mantle cell lymphoma revealed that predominance of the 3'UTR-deficient, short cyclin D1 mRNA isoform was associated with high cyclin D1 levels, a high "proliferation signature" and poor prognosis. DESIGN AND METHODS: Sixty-two cases of mantle cell lymphoma were analyzed for cyclin D1 mRNA isoforms and total cyclin D1 levels by real-time reverse transcriptase polymerase chain reaction, and TP53 alterations were assessed by immunohistochemistry and molecular analysis. Results were correlated with proliferation index and clinical outcome. RESULTS: Predominance of the short cyclin D1 mRNA was found in 14 (23%) samples, including four with complete loss of the standard transcript. TP53 alterations were found in 15 (24%) cases. Predominance of 3'UTR-deficient mRNA was significantly associated with high cyclin D1 mRNA levels (P=0.009) and more commonly found in blastoid mantle cell lymphoma (5/11, P=0.060) and cases with a proliferation index of >20% (P=0.026). Both blastoid morphology (11/11, P<0.001) and TP53 alterations (15/15, P<0.001) were significantly correlated with a high proliferation index. A proliferation index of 10% was determined to be a significant threshold for survival in multivariate analysis (P=0.01). CONCLUSIONS: TP53 alterations are strongly associated with a high proliferation index and aggressive behavior in mantle cell lymphoma. Predominance of the 3'UTR-deficient transcript correlates with higher cyclin D1 levels and may be a secondary contributing factor to high proliferation, but failed to reach prognostic significance in this study.
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BACKGROUND: Obesity and African American ethnicity are established independent risk factors for the development of chronic kidney disease. No data exist about the association between obesity and renal hemodynamics in the African region. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 301 nondiabetic participants (97 lean, 108 overweight, and 96 obese) of African descent with a positive family history of hypertension from the Seychelles islands. PREDICTOR: Body mass index (BMI). OUTCOMES: Glomerular hyperfiltration, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction. MEASUREMENTS: GFR and ERPF were measured using inulin and para-aminohippurate clearances, respectively. Participants' baseline demographics, laboratory data, and blood pressure were measured using standard techniques. RESULTS: The prevalence of glomerular hyperfiltration (defined as GFR >or=140 mL/min) increased across BMI categories (7.2%, 14.8%, and 27.1% for lean, overweight, and obese participants, respectively; P < 0.001). Higher BMI was associated with higher median GFR (99, 110, and 117 mL/min for lean, overweight, and obese participants, respectively; P < 0.001), ERPF (424, 462, and 477 mL/min, respectively; P = 0.01), and filtration fraction (0.23, 0.24, and 0.25; P < 0.001). Multivariate analyses adjusting for age, sex, blood pressure, fasting glucose level, and urinary sodium excretion and accounting for familial correlations confirmed the associations between high BMI (>25 kg/m(2)) and increased GFR, ERPF, and filtration fraction. No association between BMI categories and GFR was found with adjustment for body surface area. LIMITATIONS: Participants had a positive family history of hypertension. CONCLUSION: Overweight and obesity are associated with increased GFR, ERPF, and filtration fraction and a high prevalence of glomerular hyperfiltration in nondiabetic individuals of African descent. The absence of associations between BMI categories and GFR indexed for body surface area raises questions regarding the appropriateness of indexing GFR for body surface area in overweight populations.
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BACKGROUND: Increasingly, patients receiving methadone treatment are found in low threshold facilities (LTF), which provide needle exchange programmes in Switzerland. This paper identifies the characteristics of LTF attendees receiving methadone treatment (MT) compared with other LTF attendees (non-MT). METHODS: A national cross-sectional survey was conducted in 2006 over five consecutive days in all LTF (n=25). Attendees were given an anonymous questionnaire, collecting information on socio-demographic indicators, drug consumption, injection, methadone treatment, and self-reported HIV and HCV status. Univariate analysis and logistic regression were performed to compare MT to non-MT. The response rate was 66% (n=1128). RESULTS: MT comprised 57.6% of the sample. In multivariate analysis, factors associated with being on MT were older age (OR: 1.38), being female (OR: 1.60), having one's own accommodation (OR: 1.56), receiving public assistance (OR: 2.29), lifetime injecting (OR: 2.26), HIV-positive status (OR: 2.00), and having consumed cocaine during the past month (OR: 1.37); MT were less likely to have consumed heroin in the past month (OR: 0.76, not significant) and visited LTF less often on a daily basis (OR: 0.59). The number of injections during the past week was not associated with MT. CONCLUSIONS: More LTF attendees were in the MT group, bringing to light an underappreciated LTF clientele with specific needs. The MT group consumption profile may reflect therapeutic failure or deficits in treatment quality and it is necessary to acknowledge this and to strengthen the awareness of LTF personnel about potential needs of MT attendees to meet their therapeutic goals.
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BACKGROUND/OBJECTIVES: To assess the distribution of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO). SUBJECTS/METHODS: A total of 881 obese (body mass index (BMI) > or =30 kg/m2) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1β, IL-6 and TNF-α were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay. RESULTS: On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-α and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight+obese individuals (BMI > or =25 kg/m2, n=2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1β. Significantly lower IL-6 and TNF-α levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat. CONCLUSIONS: MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-α. Conversely, no association with IL-1β levels was found.
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INTRODUCTION: The cell surface endopeptidase CD10 (neutral endopeptidase) and nuclear factor-κB (NF-κB) have been independently associated with prostate cancer (PC) progression. We investigated the correlations between these two factors and their prognostic relevance in terms of biochemical (prostate-specific antigen, PSA) relapse after radical prostatectomy (RP) for localized PC. PATIENTS AND METHODS: The immunohistochemical expression of CD10 and NF-κB in samples from 70 patients who underwent RP for localized PC was correlated with the preoperative PSA level, Gleason score, pathological stage and time to PSA failure. RESULTS: CD10 expression was inversely associated with NF-κB expression (p < 0.001), stage (p = 0.03) and grade (p = 0.003), whereas NF-κB was directly related with stage (p = 0.006) and grade (p = 0.002). The median time to PSA failure was 56 months. CD10 and NF-κB were directly (p < 0.001) and inversely (p < 0.001) correlated with biochemical recurrence-free survival, respectively. CD10 expression (p = 0.022) and stage (p = 0.018) were independently associated with time to biochemical recurrence. CONCLUSION: Low CD10 expression is an adverse prognostic factor for biochemical relapse after RP in localized PC, which is also associated with high NF-κB expression. Decreased CD10 expression which would lead to increased neuropeptide signaling and NF-κB activity may be present in a subset of early PCs.
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BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/μL (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/μL (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/μL. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons.
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AIMS: We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS: Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION: Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.
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Mutations of the TP53 and Ki-ras genes have been reported to be of prognostic importance in colorectal carcinomas. An increased intracellular concentration of the p53 protein, although not identical to, is sometimes seen in tumours with TP53 mutation and has been correlated with poor prognosis in some tumour types. Previous colorectal cancer studies, addressing the prognostic importance of Ki-ras mutation and TP53 aberrations, yielded contradictory results. The aim of this study was to determine in a clinically and therapeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months (3-144 months) whether or not p53 protein expression, TP53 mutation and K-ras mutation correlated with prognosis. p53 staining was performed by immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded tissue. Mutations in exons 5-8 of the TP53 gene and in codons 12 and 13 of the K-ras gene were assayed in paraffin-embedded tissue by the single-strand conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of the Ki-ras codons 12 or 13. In a univariate analysis, patients with wild-type TP53 status showed a trend towards better survival, compared with those with mutated TP53 (log-rank test, P = 0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours (P = 0.010). The presence or absence of mutations in Ki-ras did not correlate with prognosis (P = 0.703). In multivariate analysis, only p53 immunoreactivity emerged as an independent marker for prognosis hazard ratio (HR) = 2.16, 95% confidence interval (CI) 1.12-4.11, P = 0.02). Assessment of p53 protein expression is more discriminative than TP53 mutation to predict the outcome of Dukes' stage B tumours and could be a useful tool to identify patients who might benefit from adjuvant therapy.
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To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.
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The respiratory behavior during affective states is not completely understood. We studied breathing pattern responses to picture series in 37 participants. We also measured end-tidal pCO2 (EtCO2) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. Minute ventilation (MV) and inspiratory drive increased with self-rated arousal. These relationships reflected increases in inspiratory volume rather than shortening of the time parameters. EtCO2 covaried with pleasantness but not arousal. Eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of valence and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal
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OBJECTIVE: This article analyses the influence of treatment duration on survival in patients with invasive carcinoma of the cervix treated by radical radiation therapy. METHOD: Three hundred and sixty patients with FIGO stage IB-IIIB carcinoma of the cervix were treated in Lausanne (Switzerland) with external radiation and brachytherapy as first line therapy. Median therapy duration was 45 days. Patients were classified according to the duration of the therapies, taking 60 days (the 75th percentile) as an arbitrary cut-off. RESULTS: The 5-year survival was 61% (S.E. = 3%) for the therapy duration group of less than 60 days and 53% (S.E. = 7%) for the group of more than 60 days. In terms of univariate hazard ratio (HR), the relative difference between the two groups corresponds to a 50% increase of deaths (HR = 1.53, 95% CI = 1.03-2.28) for the longer therapy duration group (P = 0.044). In a multivariate analysis, the magnitude of estimated relative hazards for the longer therapies are confirmed though significance was reduced (HR = 1.52, 95% CI = 0.94-2.45, P = 0.084). CONCLUSION: These findings suggest that short treatment duration is a factor associated with longer survival in carcinoma of the cervix.
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The clinical relevance of accurately diagnosing pleomorphic sarcomas has been shown, especially in cases of undifferentiated pleomorphic sarcomas with myogenic differentiation, which appear significantly more aggressive. To establish a new smooth muscle differentiation classification and to test its prognostic value, 412 sarcomas with complex genetics were examined by immunohistochemistry using four smooth muscle markers (calponin, h-caldesmon, transgelin and smooth muscle actin). Two tumor categories were first defined: tumors with positivity for all four markers and tumors with no or incomplete phenotypes. Multivariate analysis demonstrated that this classification method exhibited the strongest prognostic value compared with other prognostic factors, including histological classification. Secondly, incomplete or absent smooth muscle phenotype tumor group was then divided into subgroups by summing for each tumor the labeling intensities of all four markers for each tumors. A subgroup of tumors with an incomplete but strong smooth muscle differentiation phenotype presenting an intermediate metastatic risk was thus identified. Collectively, our results show that the smooth muscle differentiation classification method may be a useful diagnostic tool as well as a relevant prognostic tool for undifferentiated pleomorphic sarcomas.