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Multivariate Survival Analysis (multivariate + survival_analysis)
Selected AbstractsClass II restorations in primary teeth: 7-year study on three resin-modified glass ionomer cements and a compomerEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2004V. Qvist The aim of this randomized study was to compare the longevity and cariostatic effects of 1565 class II restorations in primary teeth placed by 15 clinicians in the Danish Public Dental Health Service in 971 children, aged 3.6,14.9 yr. The restorations were performed using three resin-modified glass ionomer cements and one compomer (polyacid-modified composite resin) with and without their respective cavity conditioners. The restorations were in contact with 1023 unrestored proximal surfaces in 853 primary and 170 permanent teeth. The study was terminated after 7 yr with 1% of the restorations in function, 7% patient dropouts, 18% failed restorations, and operative treatment on 24% of the adjacent surfaces. Multivariate survival analyses showed that the restorative material and cavity conditioning influenced the survival of restorations but not the progression of caries on adjacent surfaces. The 50% survival times were estimated to exceed 5 yr for the restorations and 4.5 yr for the adjacent unfilled surfaces in all treatment groups. It was concluded that resin-modified glass ionomer cement and compomer are both appropriate materials for class II restorations in primary teeth. The differences in longevity and cariostatic effects among the four materials used with and without conditioner were less than the intra-individual differences between clinicians. [source] Prognostic value of p27kip1 expression in adenocarcinoma of the pancreatic head regionHPB, Issue 3 2006Jerzy Mielko Abstract Background. p27kip1 is a tumour suppressor gene, functioning as a cyclin-dependent kinase inhibitor, and an independent prognostic factor in breast, colon, and prostate adenocarcinomas. Conflicting data are reported for adenocarcinoma of the pancreas. The aim of this study was to establish the prognostic value of p27kip1 expression in adenocarcinoma of the pancreatic head region. Patients and methods. The study included 45 patients (male/female ratio 2:1; mean age 59, range 38,82 years) with adenocarcinomas of the pancreatic head region: 24 , pancreatic head, 18 , periampullary and 3 , uncinate process. The patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus-preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1). Eight patients received adjuvant chemotherapy postoperatively. Follow-up time ranged from 3 to 60 months. Tumours were staged according to the pTNM classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded blocks from tumour sections. Quantitative determination of p27kip1 expression was based on the proportion of p27kip1 -positive cells (< 5%= negative). Survival analysis was carried out using the Kaplan-Meier method and Cox regression model. Results. Positive p27kip1 expression was detected in 22 tumours (49%), whereas 23 tumours (51%) were p27kip1 -negative. There were no significant correlations between p27kip1 index and stage or lymph node involvement. Median survival time in patients with p27kip1 -positive tumours was 19 months, whereas in patients with p27kip1 -negative tumours it was 18 months (p=0.53). A significant relationship was found between p27kip1 -negative tumours and radical resection (p=0.04). Multivariate survival analysis revealed that the localization of the tumour (pancreatic head/uncinate process vs periampullary) was the only significant and independent prognosticator (p=0.01, Cox regression model). Resection margins involvement and grade remained nearly significant prognostic factors (p=0.07 and p=0.09, respectively). Conclusion. We conclude that p27kip1 has limited overall prognostic utility in resected carcinoma of the pancreatic head region, but its potential role as a marker of residual disease needs to be further assessed. [source] Invasive front grading: reliability and usefulness in the management of oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2003Faleh A. Sawair Abstract Background:, The value of histological grading was examined with emphasis on reliability of assessment in 102 cases of intraoral squamous cell carcinoma from Northern Ireland with known outcome. Methods:, Two pathologists independently graded the invasive tumour front blinded to the stage and outcome. Results:, Intraobserver agreement was acceptable but interobserver agreement was not satisfactory. The degree of keratinisation was assessed most consistently while nuclear polymorphism was the least reliable feature. Multivariate survival analysis showed that the total grading score was associated with overall survival while the pattern of tumour invasion was the most valuable feature in estimating regional lymph node involvement. The number of positive lymph nodes was strongly associated with regional relapse, while the treatment modality and status of the surgical margins correlated with local relapse. Conclusions:, Grading of selected features in OSCC is reliable and can facilitate treatment planning. [source] Limited prognostic value of tissue protein expression levels of BCl-2 in Danish ovarian cancer patients: from the Danish ,MALOVA' ovarian cancer studyAPMIS, Issue 8 2010ESTRID V.S. Høgdall Høgdall EVS, Christensen L, Kjaer SK, Blaakaer J, Christensen IJ, Høgdall CK. Limited prognostic value of tissue protein expression levels of BCl-2 in Danish ovarian cancer patients. APMIS 2010; 118: 557,64. The purpose of the study was to determine the expression of BCl-2 in epithelial ovarian tumors and to correlate expression levels with selected clinicopathologic parameters, time to progression and prognosis of the disease. Using tissue arrays (TA), we analyzed BCl-2 expression in tissues from 191 women diagnosed with low malignant potential ovarian tumors (LMP) and from 582 patients diagnosed with ovarian cancer (OC). Using 30% as cutoff level for BCl-2 overexpression, 5% of LMPs were positive with a higher proportion of serous ovarian tumor of LMP, compared to mucinous ovarian tumor of LMP (p = 0.02). Women with a BCl-2-positive LMP tumor were older than women with a BCl-2 negative tumor (p = 0.02). Ten percent of OCs were positive for BCl-2 expression (,30%). No significant association was found between BCl-2 expression levels and histologic type of tumors (serous vs mucinous, p = 0.19). A 30% cutoff value or a percentage scale showed that BCl-2 expression had no prognostic value, both in univariate and in multivariate survival analyses. No difference in time to progression was observed between patients with BCl-2-positive and negative tumors. These data suggest that BCl-2 expression may not be of important clinical value in the treatment of Danish OC patients. [source] An intraductal papillary component is associated with prolonged survival after hepatic resection for intrahepatic cholangiocarcinoma,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2004Y. Tajima Background: The outcome after surgery for intrahepatic cholangiocarcinoma (ICC) is dismal and data on long-term survival are not available. This study evaluated prognostic indicators and characteristic features of long-term survivors after hepatic resection for ICC. Methods: Thirty-one patients who had undergone hepatic resection for ICC were studied. Univariate and multivariate survival analyses of clinicopathological data included an intraductal papillary carcinoma component (IDPCC) in the tumour, which was defined as the histological demonstration of cancer cells growing in a papillary fashion into the lumen of the large bile duct. Results: The overall cumulative survival rate after hepatic resection for ICC was 51·2 per cent at 1 year and 24·5 per cent at 5 years, with a mean(s.d.) survival time of 11(4) months. The presence of IDPCC (P = 0·003), curative resection (P = 0·009) and the absence of perineural invasion (P = 0·040) were identified as favourable independent prognostic factors in multivariate analysis. Eight patients with IDPCC had a 5-year survival rate of 87·5 per cent and a mean(s.d.) survival time of 69(13) months. All seven patients who survived for more than 5 years after surgery had IDPCC, regardless of the gross appearance of the tumour. Conclusion: An IDPCC in the tumour resulted in long-term survival after hepatic resection for ICC. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node,negative breast carcinomaCANCER, Issue 3 2004Peggy Manders M.Sc. Abstract BACKGROUND The ability of a solid tumor to grow and metastasize has a significant dependence on protease systems, such as the plasminogen activation system. The plasminogen activation system includes the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1), among other molecules. Both uPA and PAI-1 are established prognostic factors for patients with breast carcinoma. In the current study, the authors investigated whether the complex of uPA with PAI-1 is also associated with the natural course of this malignancy. METHODS Cytosolic levels of uPA, PAI-1, and the uPA:PAI-1 complex were measured in tumor tissue from 576 patients with lymph node,negative invasive breast carcinoma using quantitative enzyme-linked immunosorbent assays. Patients did not receive adjuvant systemic therapy, and the median follow-up duration was 61 months (range, 2,187 months) after primary diagnosis. Correlations with well known clinicopathologic factors were assessed, and univariate and multivariate survival analyses were performed. RESULTS uPA:PAI-1 complex levels were positively associated with adverse histologic grade and inversely correlated with estrogen and progesterone receptor status. On univariate analysis, increased levels of the uPA:PAI-1 complex were found to be associated with reduced recurrence-free survival (RFS) and overall survival (OS) rates. On multivariate analysis, uPA:PAI-1 complex levels were found to be an independent predictor of OS (P = 0.039), but not RFS (P = 0.240). When uPA and PAI-1 levels were not included in the multivariate analysis, uPA:PAI-1 complex levels became a significant predictor of both RFS and OS (P = 0.029 and P = 0.007, respectively). CONCLUSIONS The results of the current study demonstrate that uPA:PAI-1 complex levels have prognostic value on univariate analysis. In addition, increased uPA:PAI-1 complex levels were significantly associated with poor OS on multivariate analysis. Increased uPA:PAI-1 complex levels were also significantly associated with reduced RFS rates after the exclusion of uPA and PAI-1 levels from the multivariate analysis model. Cancer 2004. © 2004 American Cancer Society. [source] Low expression of p27Kip1 is associated with tumor size and poor prognosis in patients with renal cell carcinoma,CANCER, Issue 4 2002Toshiro Migita M.D. Abstract BACKGROUND Proliferative activity in tumors depends on regulation of the cell cycle. p27Kip1 (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC). METHODS Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed. RESULTS In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC. CONCLUSIONS The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma. Cancer 2002;94:973,9. © 2002 American Cancer Society. DOI 10.1002/cncr.10338 [source] The prognostic value of serum S100B in patients with cutaneous melanoma: A meta-analysisINTERNATIONAL JOURNAL OF CANCER, Issue 10 2008Simone Mocellin Abstract S100B protein detected in the serum of patients with cutaneous melanoma has been long reported as a prognostic biomarker. However, no consensus exists on its implementation in the routine clinical setting. This study aimed to comprehensively and quantitatively summarize the evidence on the suitability of serum S100B to predict patients' survival. Twenty-two series enrolling 3393 patients with TNM stage I to IV cutaneous melanoma were reviewed. Standard meta-analysis methods were applied to evaluate the overall relationship between S100B serum levels and patients' survival (meta-risk). Serum S100B positivity was associated with significantly poorer survival (hazard ratio [HR] = 2.23, 95% CI: 1.92,2.58, p < 0.0001). Between-study heterogeneity was significant, which appeared to be related mainly to dissemination bias and the inclusion of patients with stage IV disease. Considering stage I to III melanoma (n = 1594), the meta-risk remained highly significant (HR = 2.28, 95% CI: 1.8,2.89; p < 0.0001) and studies' estimates were homogeneous. Subgroup analysis of series reporting multivariate survival analysis supported S100B as a prognostic factor independent of the TNM staging system. Our findings suggest that serum S100B detection has a clinically valuable independent prognostic value in patients with melanoma, with particular regard to stage I-III disease. Further investigation focusing on this subset of patients is justified and warranted before S100B can be implemented in the routine clinical management of melanoma. © 2008 Wiley-Liss, Inc. [source] Angiopoietin-2 expression in breast cancer correlates with lymph node invasion and short survivalINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Christian Sfiligoi Abstract Angiogenic factors produced by tumor cells are essential for tumor growth and metastasis. In our study, the expression of Angiopoietin-1 (ANG1) and Angiopoietin-2 (ANG2) mRNA in archival human breast cancer tumor samples and in 6 breast cancer cell lines was investigated. Total RNA from biopsies of 38 breast cancer patients was extracted and ANG1 and ANG2 mRNA expression was measured by means of quantitative real-time RT-PCR (Taqman®). Matching data with available clinicopathologic and biochemical data revealed a significant association between ANG2 expression and axillary lymph node invasion. Univariate and multivariate survival analysis, by means of Kaplan-Meier method and Cox's proportional hazards model, showed significant and independent association between ANG2 mRNA level and both disease-free (p < 0.0001) and overall survival (p < 0.0003). An important fact is that, notwithstanding the small number of cases examined, this association was confirmed also in the group of lymph node-negative patients (DFS, p < 0.003; OS, p < 0.020). Immunohistochemical analysis demonstrated that Ang2 is expressed by both tumor cells and endothelial elements. Expression in tumor cells was confirmed by studying a panel of human breast carcinoma cell lines in culture by RT-PCR. In ZR75.1 and T47D cells, expression of ANG2 mRNA was increased up to 10-fold by treatment with estrogen within 24 hr. Although preliminary, these data suggest a possible role of ANG2 as a prognostic factor for primary breast cancer. © 2002 Wiley-Liss, Inc. [source] Errors in completion of referrals among older urban adults in ambulatory careJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 1 2010Michael Weiner MD MPH Abstract Rationale, aims and objectives, Clinical care often requires referrals, but many referrals never result in completed evaluations. We determined the extent to which referral-based consultations were completed in a US medical institution. Factors associated with completion were identified. Method, In a cross-sectional analysis, we analysed billing records and electronic and paper-based medical records for patients aged 65 years or older receiving health care between July 2000 and June 2002 in an integrated, urban, tax-supported medical institution on an academic campus. All referrals in ambulatory care, scheduling of consultation within 180 days, and completion were assessed. We conducted a multivariate survival analysis to identify factors associated with completion. Results, We identified 6785 patients with encounters. Mean age was 72 years, and, of the participants, 66% were women, 55% were African-American and 32% were Medicaid eligible. Of the 81% with at least one primary-care visit in ambulatory care, 63% had at least one referral. About 8% of referrals required multiple orders before an appointment was scheduled. Among 7819 orders for specialty consultation in ambulatory care, 71% led to appointments, and 70% of appointments were kept (completed = 0.71*0.70 or 50%). Scheduling of consultations varied (12% to 90%) by specialty. Medicare, singular orders, location of referral and lack of hospitalization were independently significantly associated with scheduling of appointments. Conclusions, Among older adults studied, half of medical specialty referrals were not completed. Multiple process errors, including missing information, misguided referrals and faulty communications, likely contribute to these results. Information systems offer important opportunities to improve the referrals process. [source] Abnormal Expression of p16INK4a, Cyclin D1, Cyclin-Dependent Kinase 4 and Retinoblastoma Protein in Gastric Carcinomas,JOURNAL OF SURGICAL ONCOLOGY, Issue 1 2008Ichiro Kishimoto MD Abstract Background and Objectives The p16INK4a (p16), cyclin D1, cyclin-dependent kinase (CDK) 4 and retinoblastoma (Rb) genes are components of the Rb pathway that controls the G1-S checkpoint of the cell cycle. The aim of this study was to assess the relationship between their abnormalities and clinicopathological features in gastric carcinomas. Mehtods Immunohistochemical analysis of the encoded proteins was performed on a series of 158 cases. Results Loss of p16/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively. At least 1 of these abnormalities was found in 86% of the cases and a positive correlation was noted between p16 and pRb (P,=,0.009). Cyclin D1 (P,=,0.042) and CDK4 (P,=,0.008) overexpession was inversely associated with lymph node metastasis and depth of invasion, respectively. Loss of pRb expression was more frequently in diffuse type lesions than in the intestinal type (P,=,0.022). The patients with p16+/pRb,/cyclin D1,/CDK4, or p16,/pRb+/cyclin D1,/CDK4, tumors demonstrated particularly poor survival. With multivariate survival analysis, only depth of invasion and TNM stage could be proven as independent predictors. Conclusions The Rb pathway is disrupted in the vast majority of gastric carcinomas. This study also identified specific immunohistochemical marker profiles for prognosis. J. Surg. Oncol. 2008;98:60,66. © 2008 Wiley-Liss, Inc. [source] Concise semiquantitative histological scoring system for immunoglobulin A nephropathyNEPHROLOGY, Issue 6 2009LEI JIANG SUMMARY: Aim: Immunoglobulin A nephropathy (IgAN) is a common and progressive glomerulonephritis. Histological lesions of IgAN are variable and considered as a risk factor for renal outcome. Establishing a relatively concise histological semiquantitative scoring system would be valuable in clinical practice. Methods: Renal biopsy sections of 293 patients with primary IgAN from two centres in China were reviewed. A histological scoring system was established based on multivariate survival analysis of semiquantitative histological indices, using end-stage renal disease (ESRD) as the end-point event. Results: Four indices , extracapillary glomerular activity index (exGAI), mesangial proliferation index (MsI), glomerular chronicity index (GCI) and tubulointerstitial chronicity index (TCI) , independently correlated with ESRD (relative risk (RR) = 1.16, 2.27, 1.29 and 1.80, respectively). The four indices and the sum of their scores (Total I) constituted the scoring system. Patients with exGAI of 4 or more, GCI of 4 or more, MsI of 2 or more and TCI of 2 or more were considered as having a higher risk for progression (P < 0.05). A score of 4 or more on the exGAI index could identify the patients who should be treated with immunosuppressive drugs, which showed a lower incidence of ESRD than that without (24.3% vs 52.4%, P = 0.031). Conclusion: It suggested that the present concise scoring system could serve as prognostic and therapeutic indications. [source] Prognostic significance of ,-catenin and topoisomerase II, in de novo acute myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2009Chih-Cheng Chen The Wnt/,-catenin signaling is important for controlling self-renewal of hematopoietic stem cells and its constitutive activation has recently been documented in a significant proportion of acute myeloid leukemia (AML) cases. Topoisomerase II, (Topo II,) is a marker of cell proliferation and a crucial target for anthracycline cytotoxicity, the mainstay of management employed in AML. We retrospectively investigated the prognostic roles of ,-catenin and topo II, in a cohort of 59 patients with newly diagnosed AML by immunohistochemistry. Aberrant ,-catenin expression was demonstrated in 13 patients (22%), and it was more likely to occur in those with unfavorable karyotypes. Advanced age and poor performance status adversely influenced the achievement of complete remission, while neither aberrant ,-catenin expression nor enhanced topo II, activity did. On multivariate survival analysis, four factors independently predicted a shortened overall survival: aberrant ,-catenin expression, high topo II, activity, poor-risk cytogenetics, and presence of at least one comorbidity factor. Our results suggest that both ,-catenin and topo II, independently predicted an adverse prognosis and might serve as new markers for risk stratification in AML patients. Am. J. Hematol., 2009. © 2008 Wiley-Liss, Inc. [source] Methylthioadenosine phosphorylase and activated insulin-like growth factor-1 receptor/insulin receptor: potential therapeutic targets in chordoma,THE JOURNAL OF PATHOLOGY, Issue 5 2010Josh Sommer Abstract Currently there is no effective chemotherapy for chordoma. Recent studies report co-expression of insulin-like growth factor-1 receptor (IGF1R) and its cognate ligand in chordoma, but it is unknown whether this receptor tyrosine kinase is activated in these tumours. Additionally, genetic studies have confirmed frequent deletions of chromosome 9p in chordomas, which encompasses the cyclin-dependent kinase inhibitor 2A (CDKN2A) locus. Another gene in this region, methylthioadenosine phosphorylase (MTAP), is an essential enzyme of the purine salvage pathway and has therapeutic relevance because MTAP-deficient cells are particularly sensitive to inhibitors of de novo purine synthesis. We investigated whether these pathways might be potential therapeutic targets for chordoma. Paraffin-embedded tissue samples from 30 chordomas were analysed by immunohistochemistry for expression of the phosphorylated isoforms of IGF1R or the insulin receptor (pIGF1R/pIR) and selected downstream signalling molecules, including BCL2-associated agonist of cell death protein (BAD). Expression of CDKN2A and MTAP proteins was also assessed. Skeletal chondrosarcomas, benign notochordal cell tumours, and fetal notochord were studied for comparison. Phosphorylated IGF1R/IR was detected in 41% of chordomas, together with activated downstream signalling molecules, and pIGF1R/pIR was absent in benign notochordal cell tumours and fetal notochord. Thirty-nine per cent of chordomas were negative for MTAP immunoreactivity. Patients with pIGF1R/pIR-positive tumours showed significantly decreased median disease-free survival in multivariate survival analysis (p = 0.036), whereas phosphorylation of BAD at serine-99 was found to be associated with a favourable prognosis (p = 0.002). Approximately 40% of chordomas demonstrate evidence of activation of the IGF1R/IR signalling pathway or loss of a key enzyme in the purine salvage pathway. Aberrant signalling cascades and disrupted metabolic pathways such as these may represent opportunities for novel targeted therapeutic approaches for the treatment of chordoma. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Intraocular pressure and progression in exfoliative eyes with ocular hypertension or glaucomaACTA OPHTHALMOLOGICA, Issue 6 2000Mika Harju ABSTRACT. Purpose: This retrospective study was conducted in exfoliative eyes in order to study the influence of IOP and other possible factors on the conversion from ocular hypertension (OHT) to glaucoma and progression of glaucoma. Methods: 139 patients with exfoliation OHT or glaucoma with exfoliation syndrome were included (mean follow-up 5.2±3.6 years). The effects of age, gender, weighted mean IOP, maximum IOP, stage of glaucoma at the first visit, refraction, glaucoma medication, and interventions on the hazard of progression were studied by multivariate survival analysis. Results: Conversion from OHT to glaucoma or progression of glaucoma was detected in 63 eyes (45.3%). A significant association with progression was found for age (relative risk 1.042; p-value 0.043), weighted mean IOP (1.076; <0.001), and stage of glaucoma (1.436; <0.001). History of trabeculectomy (0.360; 0.002) related to a decreased risk. Conclusion: The risk of conversion from OHT to glaucoma and progression of glaucoma increased in exfoliative eyes with severity of stage of glaucoma, weighted mean IOP, and the age of the patient. A history of trabeculectomy was related to decreased risk of progression. [source] | ||||||||||||||||||||||