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Terms modified by Poor Survival Selected AbstractsGlut3 Expression in Biopsy Specimens of Laryngeal Carcinoma Is Associated With Poor Survival,THE LARYNGOSCOPE, Issue 2 2002Susan Baer MD Abstract Objectives/Hypothesis The aim of the study was to determine the clinical significance of the expression of Glut1 and Glut3 proteins in biopsy specimens of squamous cell carcinoma (SCC) of the larynx. Study Design A retrospective study. Methods Using immunohistochemistry, we immunostained sections of formalin-fixed, paraffin-embedded tissues from 48 biopsies of invasive SCC of the larynx for Glut1 and Glut3. The percentages of positive cells were recorded, then correlated with overall patient survival using the Kaplan-Meier method and the Breslow-Gehan-Wilcoxon test for statistical significance. Results All cases were positive for Glut1, and Glut1 expression was not associated with survival difference at any cut-off value. Eighteen (38%) of the cases were Glut3-negative and 30 (62%) were Glut3-positive. Glut3-positive cases were associated with poorer survival than Glut3-negative cases (P = .0336). No significant difference was found between Glut3-negative and Glut3-positive groups in respect to sex, tumor site (glottic vs. supraglottic), nodal or distant metastasis, or treatment modality. However, there were significantly more poorly differentiated tumors in the Glut3-positive group than in the Glut3-negative group (27% vs. 0%, respectively;P = .0182, Fisher's Exact Test). After poorly differentiated tumors were excluded from the survival analysis, Glut3 immunoreactivity remained a significant marker of poor prognosis (P = .0385). Conclusion Immunohistochemical detection of Glut3 in biopsy specimens of SCC of the larynx is a marker of poorer prognosis. [source] Diameter of Involved Nerves Predicts Outcomes in Cutaneous Squamous Cell Carcinoma with Perineural Invasion: An Investigator-Blinded Retrospective Cohort StudyDERMATOLOGIC SURGERY, Issue 12 2009AMY S. ROSS MD BACKGROUND Perineural invasion (PNI) has been associated with poor prognosis in cutaneous squamous cell carcinoma (CSCC), but it is unclear how different degrees of nerve involvement affect prognosis. OBJECTIVE To determine whether the diameter of nerves invaded by CSCC affects outcomes of recurrence, metastasis, and disease-specific and overall survival. METHODS A retrospective cohort study was conducted of patients with CSCC with PNI. Dermatopathologists blinded to subject outcomes determined the diameter of the largest involved nerve. RESULTS Data were obtainable for 48 patients. Small-caliber nerve invasion (SCNI) of nerves less than 0.1 mm in diameter was associated with significantly lower risks of all outcomes of interest. Disease-specific death was 0% in subjects with SCNI, versus 32% in those with large-caliber nerve invasion (LCNI) (p=.003). Other factors associated with significantly worse survival were recurrent or poorly differentiated tumors or tumor diameter of 2 cm or greater or depth of 1 cm or greater. On multivariate analysis, only tumor diameter and age predicted survival. CONCLUSIONS The individual prognostic significance of factors associated with poor survival remains uncertain. Small-caliber nerve invasion may not adversely affect outcomes. Defining PNI as tumor cells within the nerve sheath and routine recording of diameter of involved nerves, tumor depth, and histologic differentiation on pathology reports will facilitate further study. [source] Prediction of poor survival by cyclooxygenase-2 in patients with T4 nasopharyngeal cancer treated by radiation therapy: Clinical and in vitro studiesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2005Wen-Cheng Chen MD Abstract Background. This study was undertaken to determine the status of cyclooxygenase-2 (COX-2) in nasopharyngeal cancer (NPC) in Taiwanese patients and its relationship to survival after radiotherapy (RT). In addition, the effect of NS-398, a potent selective COX-2 inhibitor, was tested in vitro alone and in combination with radiation on NPC-BM1 human NPC cells as a prelude to using this drug along with RT in the treatment of patients with NPC. Methods. Thirty-seven patients diagnosed with T4N0,3M0 NPC were enrolled into this study. COX-2 expression was determined by immunohistochemical staining of formalin-fixed, paraffin-embedded tumor tissue. Patient survival was the clinical end point. The effects of COX-2 expression on cell survival and radioresistance was tested in vitro using the selective COX-2 inhibitor NS-398 in conjunction with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) and clonogenic assays. Results. COX-2 immunoreactivity was detected in 62% of NPC tumors, and expression levels were high in 43%. Survival analysis showed the 5-year overall survival rates for patients who had high COX-2 expression was 27% compared with 60% for those with low/absent expression (p = .047). Pattern of failure analysis showed no significant difference between high and low COX-2 expression in locoregional failure (27% vs 25%, p = .91). However, patients with N0 to N1 disease and high COX-2 expression had a significantly higher incidence of distant metastasis compared with patients with stage N0 to N1 disease and low COX-2 expression (83% vs 15%, p = .004). This difference was not observed in patients with N2 to N3 disease. This difference contributed to worse survival of patients whose tumors had high COX-2 expression levels. The selective COX-2 inhibitor NS-398 was directly cytotoxic to NPC-BM1 cells in vitro, as judged in an MTT assay (viable cells decreased from 92% to 76%, 52%, and 22%, with increases of NS-398 from 20 to 40, 60, and 80 ,M, respectively). Radiation-induced cell death was also increased by treatment with NS-398. At a 10% survival level, 40 ,M NS-398 increased radiation cytotoxicity by a factor of 1.37, whereas 60 ,M increased it by a factor of 4.9. Conclusions. COX-2 overexpression is a predictor for poor survival for advanced stage NPC. In vitro, NS-398 radiosensitizes the NPC-BM1 cell line, providing a basis for testing the combination of COX-2 inhibitors with radiation in the treatment of patients with NPC. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Outcome of treatment for advanced cervical metastatic squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2005Jonathan Clark FRACS Abstract Background. Patients with advanced cervical metastases from mucosal squamous cell carcinoma have a poor prognosis because of their high risk of regional and distal failure. This study aims to evaluate the outcomes of patients with clinical N2 or N3 disease managed with surgery and postoperative radiotherapy. Methods. From a comprehensive computerized database, 181 entered patients who had neck dissection for N2 or N3 disease between 1988 and 1999 were evaluated. The mean age was 62 years, and minimum follow-up was 3 years. Results. A total of 233 neck dissections were performed in 181 patients, including 163 comprehensive and 70 selective dissections. Postoperative radiotherapy was given in 82% of cases. The local control rate was 75% at 5 years, and control of disease in the treated neck was achieved in 86%. Macroscopic extracapsular spread (ECS) significantly increased regional recurrence (p = .001). Adjuvant radiotherapy significantly improved neck control (p = .004) but did not alter survival. Patients with ECS (both microscopic and macroscopic) who received radiotherapy had a significantly better survival than did patients with ECS who did not receive radiotherapy. Disease-specific survival for the entire group was 39% at 5 years. By use of multivariate analysis, macroscopic ECS and N2c neck disease were independent adverse prognostic factors for survival (p = .001). Conclusions. Despite a high rate of control in the treated neck, the poor survival (39%) in this patient group indicates that adjuvant therapeutic strategies need to be considered. © 2004 Wiley Periodicals, Inc. Head Neck27: 87,94, 2005 [source] Rim versus sagittal mandibulectomy for the treatment of squamous cell carcinoma: Two types of mandibular preservationHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2003Mario Fernando Muñoz Guerra MD Abstract Background. The role of conservative mandibulectomy for patients with bone invasion from squamous cell carcinoma remains poorly defined. However, marginal mandibular resection is biomechanically secure in its design while maintaining the mandibular continuity. This procedure has proven to be a successful method of treating squamous cell carcinoma with limited mandibular involvement. Purpose. The purpose of this study was to analyze our results after the use of a marginal technique for the treatment of oral and oropharyngeal cancer and to compare two types of mandibular conservative procedures: rim resection versus sagittal inner mandibulectomy. Methods. A retrospective review of a cohort of 50 patients (global group) who underwent mandibular conservative resection for previously untreated squamous cell carcinoma was performed. Two subgroups were considered: rim group (n = 37) and sagittal group (n = 13). Clinical evaluation and preoperative radiologic studies were the means used to evaluate bony invasion and to decide on the extent of mandibulectomy. The treatment outcome after these two types of mandibular resection was calculated and compared using analysis by the Pearson ,2 test, logistic regression model for multivariate analysis, and the Kaplan-Meier method to determine survival. Results. In the sagittal group, specimens from 2 patients (11.7%) demonstrated tumor invasion on decalcified histologic examination, whereas the rim group showed 11 cases (29.7%) with bone invasion. Local recurrence was observed in the follow-up of 10 patients. No statistical relationship was found between the presence of histologic bone invasion and the risk of local recurrence. The size of bone resection >4 cm (p = .002) and tumor invasion of surgical margins (p = .039) were found to be associated with increased local recurrence rates. In multivariate analysis, lymph node affectation significantly correlated with histologic mandibular involvement (p = .02). In the global group, the 5-year observed survival rate was 56.97%. Overall survival and rate of recurrence were comparable in both groups. In the global group, tumor infiltration beyond the surgical margin was statistically related with poor survival (p = .01). Conclusions. Analysis of this series disclosed that marginal mandibulectomy is effective in the control of squamous cell carcinomas that are close to or involving the mandible. In carefully selected patients, sagittal bone resection seems to be as appropriate as rim resection in the local control of these tumors. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000,000, 2003 [source] Postradiotherapy surveillance practice for head and neck squamous cell carcinoma,too much for too little?,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2003David L. Schwartz MD Abstract Introduction. Limited information is available regarding surveillance patterns after head and neck cancer radiotherapy. We cataloged follow-up for a specified patient cohort treated at three neighboring university, community, and Veterans Administration institutions. Methods. One hundred fifteen patients were treated with curative intent between 1994,1998 with definitive or postoperative radiotherapy for newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. One hundred patients had continuous follow-up at their treating institution and were included for analysis. Median follow-up until disease recurrence or censorship was 28.5 months. Results. Median follow-up frequency was 5.7 visits/year and was highly variable. Although visit frequency correlated with disease stage and the presence of high-risk disease features, this association was lost when patients with early recurrences were removed from analysis. Procedure and test utilization closely mirrored visit frequency, resulting in a wide range of estimated yearly charges ($0,15,668/year; median, $1,772/year). Actuarial 3-year overall survival for the study group was 71%. Eighty-six percent (19 of 22) of potentially salvageable locoregional failures were discovered secondary to symptomatic complaint rather than by test results. Disease failure, whether detected by symptom or testing, predicted for poor survival (22% at 24 months after recurrence). Conclusions. Postradiotherapy surveillance for head and neck cancer is inconsistently pursued. A proven correlation between intensive follow-up and improved patient survival is lacking. Surveillance directed by patient symptoms should be investigated as an alternative approach. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000,000, 2003 [source] External auditory canal eccrine spiradenocarcinoma: A case report and review of literatureHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2003Tanya K. Meyer MD Abstract Background. Eccrine spiradenocarcinoma is a rare dermal appendage carcinoma believed to arise from transformation of a long-standing benign spiradenoma. This tumor demonstrates highly malignant biologic behavior with a high recurrence rate, frequent lymph node metastases, and overall poor survival. Methods. We report the first case of eccrine spiradenocarcinoma arising in the external auditory canal. The management of this tumor, its histopathologic characteristics, and a review of literature are presented. Results. A literature review identified 17 cases of eccrine spiradenocarcinoma in the head and neck region. Local recurrence occurred in 58.8% of patients, with an average of 23 months from diagnosis. Lymph node metastasis occurred in 35.3%, with an average of 31 months from diagnosis. Other metastatic sites included skin, bone, and lung. Disease-specific mortality was 22.2%. Conclusions. Eccrine spiradenocarcinoma is an aggressive tumor with a poor prognosis. Primary treatment should include wide local excision with or without regional lymphadenectomy. Isolated successful treatments have been documented with adjuvant hormonal manipulation, chemotherapy, and radiation therapy. © 2003 Wiley Periodicals, Inc. Head Neck 25: 505,510, 2003 [source] Squamous cell carcinoma of the buccal mucosa: One institution's experience with 119 previously untreated patients,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2003Eduardo M. Diaz Jr. MD, FACS Abstract Background. Squamous cell carcinoma (SCC) of the buccal mucosa is a rare, but especially aggressive, form of oral cavity cancer, associated with a high rate of locoregional recurrence and poor survival. We reviewed our institution's experience with 119 consecutive, previously untreated patients with buccal SCC. Methods. We reviewed the charts of 250 patients who were seen at The University of Texas M. D. Anderson Cancer Center between January, 1974, and December, 1993. Of these, 119 were untreated and were subsequently treated exclusively at our institution. Patients who were previously treated elsewhere or whose lesions arose in other sites and only secondarily involved the buccal mucosa were excluded. Results. Patients with T1- or T2-sized tumors had only a 78% and 66% 5-year survival, respectively. Muscle invasion, Stensen's duct involvement, and extracapsular spread of involved lymph nodes were all associated with decreased survival (p < .05). Surgical salvage for patients with locoregional recurrence after radiation therapy was rarely successful. Conclusions. SCC of the buccal mucosa is a highly aggressive form of oral cavity cancer, with a tendency to recur locoregionally. Patients with buccal mucosa SCC have a worse stage-for-stage survival rate than do patients with other oral cavity sites. © 2003 Wiley Periodicals, Inc. Head Neck 25: 267,273, 2003 [source] Metastatic squamous cell carcinoma of the neck from an unknown primary: Management options and patterns of relapse,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2002Shahrokh Iganej MD Abstract Purpose Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients. Methods and Materials From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients. Results Except for two patients, all patients have had a minimum follow-up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p = .006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5-year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension. Conclusions Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated. © 2002 Wiley Periodicals, Inc. Head Neck 24: 236,246, 2002; DOI 10.1002/hed.10017 [source] Prognostic relevance of circulating matrix metalloproteinase-2 in acute myeloid leukaemia patientsHEMATOLOGICAL ONCOLOGY, Issue 3 2007Salah Aref Abstract Matrix metalloproteinases (MMPs) were postulated to have important implication in progression and invasiveness of many malignant disorders. On the other hand the biological role of MMP-2 in acute myeloid leukaemia (AML) is not fully clear. Serum samples from 37 adult patients with AML had been taken before chemotherapy was administered. In addition 20 out of the 37 patients were analysed again after achieving complete remission (CR). Ten samples from healthy volunteers were evaluated as the control. Total MMP-2 levels were measured using ELISA Kit obtained from R&D system. MMP-2 serum levels were significantly lower in pretreatment AML patients than that in the normal controls (p,=,0.000) and in CR (p,=,0.007). No significant correlations were detected between pretreatment sMMP-2 levels and FAB subtypes, peripheral blood blast cell counts, peripheral blood WBCs, bone marrow blast cell counts or blast cell distribution ratio. The prognostic value of MMP-2 was evaluated by dividing AML patients into high and low MMP-2 groups using the pretreatment median MMP-2 level of the AML group as the cut-off. The authors found that patients in the high group survived for a significantly shorter time than those patients in the lower MMP-2 group. High pretreatment levels of sMMP-2 among AML patients were associated with poor survival. Prospective studies are recommended to establish the clinical value of longitudinal sMMP-2 measurement. Copyright © 2007 John Wiley & Sons, Ltd. [source] The kidney disease wasting: Inflammation, oxidative stress, and diet-gene interactionHEMODIALYSIS INTERNATIONAL, Issue 4 2006Kamyar KALANTAR-ZADEH Abstract The 350,000 maintenance hemodialysis (MHD) patients in the United States have an unacceptably high mortality rate of >20%/year. Almost half of all deaths are assumed to be cardiovascular. Markers of kidney disease wasting (KDW) such as hypoalbuminemia, anorexia, body weight and fat loss, rather than traditional cardiovascular risk factors, appear to be the strongest predictors of early death in these patients. The KDW is closely related to oxidative stress (SOX). Such SOX markers as serum myeloperoxidase are associated with pro-inflammatory cytokines and poor survival in MHD patients. Identifying the conditions that modulate the KDW/SOX-axis may be the key to improving outcomes in MHD patients. Dysfunctional lipoproteins such as a higher ratio of the high-density lipoprotein inflammatory index (HII) may engender or aggravate the KDW, whereas functionally intact or larger lipoprotein pools, as in hypercholesterolemia and obesity, may mitigate the KDW in MHD patients. Hence, a reverse epidemiology or "bad-gone-good" phenomenon may be observed. Diet and gene and their complex interaction may lead to higher proportions of pro-inflammatory or oxidative lipoproteins such as HII, resulting in the aggravation of the SOX and inflammatory processes, endothelial dysfunction, and subsequent atherosclerotic cardiovascular disease and death in MHD patients. Understanding the factors that modulate the KDW/SOX complex and their associations with genetic polymorphism, nutrition, and outcomes in MHD patients may lead to developing more effective strategies to improve outcomes in this and the 20 to 30 million Americans with chronic disease states such as individuals with chronic heart failure, advanced age, malignancies, AIDS, or cachexia. [source] Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survivalHISTOPATHOLOGY, Issue 4 2008A Fleischmann Aims:, To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node-positive, hormone treatment-naive patients undergoing radical prostatectomy and extended lymphadenectomy. Methods and results:, The median number of nodes examined per patient was 21 (range 9,68), and the median follow-up time was 92 months (range 12,191). ENE was observed in 71 patients (70%). They had significantly more, larger and less differentiated nodal metastases, paralleled by significantly larger primary tumours at more advanced stages and with higher Gleason scores than patients without ENE. ENE defined a subgroup with significantly decreased biochemical recurrence-free (P = 0.038) and overall survival (P = 0.037). In multivariate analyses the diameter of the largest metastasis and Gleason score of the primary tumour were independent predictors of survival. Conclusions:, ENE in prostatic cancer is an indicator lesion for advanced/aggressive tumours with poor outcome. However, the strong correlation with larger metastases suggests that ENE may result from their size, which was the only independent risk factor in the metastasizing component. Consequently, histopathological reports should specify the true indicator of poor survival in the lymphadenectomy specimens, which is the size of the largest metastasis in each patient. [source] Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanomaHISTOPATHOLOGY, Issue 7 2007F Piras Aims:, Survivin is expressed in neoplastic cells and appears to be associated with resistance to therapy and shorter survival in various types of tumours. The aim of the present study was to determine whether nuclear or cytoplasmic expression of survivin is related to disease recurrence and overall survival of patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. Methods and results:, Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections of primary cutaneous melanoma from 50 patients. Survival rates were estimated using the Kaplan,Meier method and compared using the log rank test. Association of clinical variables (gender, age, tumour location, thickness, Clark level and AJCC stage) with survivin expression was analysed by Fisher's exact test. Patients with nuclear immunoreactivity for survivin had an increased risk of disease recurrence during the first three postoperative years (P < 0.05) and of death (P < 0.05). Cytoplasmic immunoreactivity was not correlated with either survival or clinical variables. Conclusions:, Nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with Stage I and II melanoma. [source] Clinical features and predictors of survival of AIDS-related non-Hodgkin's lymphoma in a population-based case series in Sydney, AustraliaHIV MEDICINE, Issue 5 2004MC Robotin Objectives To analyse clinical features and predictors of survival for AIDS-related non-Hodgkin's lymphoma (NHL) in the era of highly active antiretroviral therapy (HAART), compared to earlier in the HIV epidemic. Methods All AIDS-NHL cases diagnosed at three inner Sydney hospitals caring for people with AIDS during 1985,2001 were identified through medical record searches. Demographic, clinical, immunological and histopathological information was recorded. Year of NHL diagnosis was grouped into three periods, corresponding to whether monotherapy (1985,1991), dual therapy (1992,1995) or HAART (1996,2001) was the main treatment for HIV infection. Statistical comparisons were made between the pre-HAART and post-HAART eras. Results Three hundred cases of AIDS-NHL were identified. Divergent trends were identified for systemic and primary central nervous system (CNS) NHL. For systemic NHL, the CD4 count at NHL diagnosis increased markedly to 208 cells/,L in the post-HAART era (P=0.014) and there was a trend towards presentation as the first AIDS-defining illness (69%, P=0.053), and as earlier stage NHL disease (42%, P=0.048). Median survival time increased from 4.2 months in 1985,1991 to 19 months in the post-HAART era (P<0.001). In a multivariate model, predictors of poor survival from systemic NHL included: NHL diagnosis after another AIDS-defining illness (P<0.001), stage 4 NHL (P<0.001), presentation at extra lymphatic sites (P=0.001), and nonreceipt of chemotherapy (P=0.002). After adjusting for the factors, those diagnosed in the era of HAART had a significant 56% reduction in rate of death (P<0.001). In contrast, for CNS NHL, clinical features were little changed and survival did not improve in the era of HAART. Conclusions Systemic NHL is presenting earlier in the course of HIV disease, and at a less advanced NHL stage. There has been a marked improvement in survival in the era of HAART even after adjustment for other prognostic variables. In contrast, primary CNS NHL remains a disease which presents late in the course of HIV infection and is associated with a very poor prognosis. [source] Prognostic evaluation of epidermal fatty acid-binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approachINTERNATIONAL JOURNAL OF CANCER, Issue 10 2008Zhengyu Li Abstract With the aim to translate the discovery from proteomic research into clinical applications, we identified epidermal fatty acid-binding protein (E-FABP) and calcyphosine (CAPS) by MALDI-Q-TOF MS and validated their overexpressions by immunoblotting. Their expression statuses were examined by immunohistochemistry in 39 normal endometrium, 29 endometrial intraepithelial neoplasia (EIN) and 84 endometrial cancer (EC) cases. We evaluated the correlations to the clinicopathologic characteristics and determined whether these proteins had prognostic significance. Expressions of E-FABP and CAPS were increased 2.64- and 2.18-fold in EC by immunoblotting. Immunoreactivity of both E-FABP and CAPS were stronger in EC than in EIN or normal tissues (p < 0.001 and < 0.001). Stronger immunoreactivity of E-FABP and CAPS were shown to present with poor differentiation (p = 0.032 and 0.001), but no relevance was observed with staging (p = 1.368 and 4.306). Survival analysis indicated that immunoreactivity of CAPS was correlated to poor survival (p = 0.018), but E-FABP status appeared to be no correlation to the clinical outcome of patients (p = 0.865). Multivariate analysis indicated that CAPS might be an independent prognostic factor for survival in patients with EC (p = 0.008). Results demonstrated the ubiquitous overexpressions of E-FABP and CAPS in EC and the correlations to the clinicopathologic parameters. CAPS might be a potential prognostic factor for survival in patients with EC. The research pattern from proteomics to clinical specimens would have widespread applications. © 2008 Wiley-Liss, Inc. [source] Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Tanya R. Newton Abstract The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed late-stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9,29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. © 2006 Wiley-Liss, Inc. [source] Testing alternate ecological approaches to seagrass rehabilitation: links to life-history traitsJOURNAL OF APPLIED ECOLOGY, Issue 5 2010Andrew D. Irving Summary 1.,Natural resources and ecosystem services provided by the world's major biomes are increasingly threatened by anthropogenic impacts. Rehabilitation is a common approach to recreating and maintaining habitats, but limitations to the success of traditional techniques necessitate new approaches. 2.,Almost one-third of the world's productive seagrass meadows have been lost in the past 130 years. Using a combined total of three seagrass species at seven sites over 8 years, we experimentally assessed the performance of multiple rehabilitation methods that utilize fundamentally different ecological approaches. 3.,First, traditional methods of transplantation were tested and produced varied survival (0,80%) that was site dependent. Secondly, seedling culture and outplanting produced poor survival (2,9%) but reasonable growth. Finally, a novel method that used sand-filled bags of hessian to overcome limitations of traditional techniques by facilitating recruitment and establishment of seedlings in situ produced recruit densities of 150,350 seedlings m,2, with long-term survival (up to 38 months) ranging from 0 to 72 individuals m,2. 4.,Results indicate that facilitating seagrass recruitment in situ using hessian bags can provide a new tool to alleviate current limitations to successful rehabilitation (e.g. mobile sediments, investment of time and resources), leading to more successful management and mitigation of contemporary losses. Hessian bags have distinct environmental and economic advantages over other methods tested in that they do not damage existing meadows, are biodegradable, quick to deploy, and cost less per hectare (US$16 737) than the estimated ecosystem value of seagrass meadows (US$27 039 year,1). 5.,Synthesis and applications. This research demonstrates how exploring alternate ecological approaches to habitat rehabilitation can expand our collective toolbox for successfully re-creating complex and productive ecosystems, and alleviate the destructive side-effects and low success rates of more traditional techniques. Moreover, new methods can offer economic and environmental solutions to the restrictions placed upon managers of natural resources. [source] Effect of Donor Age on Long-Term Survival Following Cardiac TransplantationJOURNAL OF CARDIAC SURGERY, Issue 2 2006Veli K. Topkara M.D. Our objective was to analyze the effect of donor age on outcomes after cardiac transplantation. Methods: We retrospectively studied 864 patients who underwent cardiac transplantation at New York Presbyterian Hospital , Columbia University between 1992 and 2002. Patients were divided into two groups; donor age <40 years (Group A, n = 600) and donor age ,40 years (Group B, n = 264). Results: Characteristics including gender, body mass index, and cytomegalovirus (CMV) status were significantly different between the two donor age groups. Race, CMV status, toxoplasmosis status, left ventricular assist device prior to transplant, diabetes mellitus, and retransplantation were similar in both the recipient groups, while age, gender, and BMI were different. Early mortality was lower in Group A, 5%, versus 9.5% in Group B. Multivariate analysis revealed recipient female gender (odd ratio (OR) = 1.71), retransplantation (OR = 1.63), and increased donor age (OR = 1.02) as significant predictors of poor survival in the recipient population. Actuarial survival at 1 year (86.7% vs 81%), 5 years (75% vs 65%), and 10 years (56% vs 42%) was significantly different as well with a log rank p = 0.002. Conclusions: These findings suggest that increased donor age is an independent predictor of long-term survival. However, the shortage of organs makes it difficult to follow strict guidelines when placing hearts; therefore, decisions need to be made on a relative basis. [source] Hepatitis C virus risk: a hepatitis C virus related syndromeJOURNAL OF INTERNAL MEDICINE, Issue 5 2000C. Mazzaro Abstract. Mazzaro C, Panarello G, Tesio F, Santini G, Crovatto M, Mazzi G, Zorat F, Tulissi P, Pussini E, Baracetti S, Campanacci L, Pozzato G (Pordenone General Hospital, Pordenone; University of Trieste, School of Medicine, Trieste, Italy). Hepatitis C virus risk: a hepatitis C virus-related syndrome. J Intern Med 2000 247: 535,545. Background. The association between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been recently described in many reports. Objective. The aim of this study was to evaluate the long-term prognosis of hepatitis C virus-positive patients affected by mixed cryoglobulinemia with or without kidney involvement. Patients. At total of 119 hepatitis C virus-positive patients affected by mixed cryoglobulinemia were divided in two groups. Group A: mixed cryoglobulinemia without kidney involvement (103 cases); group B: mixed cryoglobulinemia with glomerulonephritis (GN) (16 cases). A further 37 patients affected by mesangio-proliferative glomerulonephritis (MPGN) were evaluated as controls (group C). Methods. Anti-hepatitis C virus antibodies were determined by commercial kits and hepatitis C virus-RNA was detected by polymerase chain reaction (PCR) amplification of the 5, untranslated region (5,UTR) of the virus. The hepatitis C virus genotype was determined according to Okamoto. Liver biopsy was performed in 62 patients, bone marrow biopsy in 65 patients, and kidney biopsy in all patients with proteinuria. Results. In group A, 46 patients (45%) were affected by chronic liver disease (CLD), 21 (20%) by low-grade non-Hodgkin's lymphoma (NHL) and 16 (15%) by both diseases. All patients of group B were affected by type I membrano-proliferative glomerulonephritis, 3 (19%) by chronic liver disease, 6 (37%) by low-grade non-Hodgkin's lymphoma, and 7 (44%) by both diseases. Several genotypes of hepatitis C virus were found, but Type 1b was prevalent. In group C, no patient showed chronic liver disease or non-Hodgkin's lymphoma. Younger age, higher mean blood pressure, lower C4 serum level, and poorer survival significantly distinguished group B from group A. Survival rates at 5 years were: 87.4% for group A, 89.5% for group C, and 50.0% for group B. None of the patients of group B developed kidney failure requiring dialysis, whilst infections were the leading cause of death. Conclusions. In hepatitis C virus-positive patients, the presence of mixed cryoglobulinemia associated with kidney involvement seems to indicate a new syndrome characterized by immune system impairment, lack of progression to kidney failure, and poor survival (hepatitis C virus-Risk syndrome). [source] Morphometric analysis of CD34-positive vessels in salivary gland adenoid cystic and mucoepidermoid carcinomasJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2009H. Luukkaa Background:, Carcinomas of the salivary glands are uncommon and morphologically a diverse group of malignancies. To evaluate the prognostic value of CD34 immunostaining of the vessels in adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC), an automated image analysis method was used. Method:, In a nationwide study, covering salivary gland cancer (SGC) patients in Finland 1991,1996, 37 AdCC and 18 MEC patients (M 25, F 30, age 25,90, mean 63) were included. In addition to clinical characteristics the size, shape, staining intensity and vessel density in CD34 immunostained histologic samples were measured. Results:, Altogether 4433 vessels were measured from AdCC and 2615 from MEC tumor. Of the total tumor vessels measured, 2651 were from patients who deceased with disease (Group I) and 4397 were from specimens derived from those who did not die of disease (Group II) during the 10-year follow-up. The staining intensity was significantly higher in MEC than in AdCC tumor (P = 0.0005). In MEC, the Group I patients had a higher staining intensity among high-grade patients compared with patients with low grade disease, whereas the tumors in Group II had a lower staining intensity among the high-grade compared with the low grade tumors (P = 0.018). A higher vessel density was found in patients with MEC in group II compared with group I (P = 0.017). Conclusions:, The staining intensity of CD34 positive vessels in MEC was higher than in AdCC. In MEC, higher staining intensity of vessels in high-grade tumors and lower vessel density in all MEC patients, predicted poor survival. [source] Neoadjuvant strategies for the treatment of locally advanced esophageal cancer,JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010John R. Hyngstrom MD Abstract Patients with locally advanced esophageal carcinoma have consistently poor survival following surgery with associated high systemic and local-regional failure rates. Neoadjuvant therapeutic strategies have been employed in an attempt to improve outcome with variable success. Randomized trials of either neoadjuvant chemotherapy or chemoradiotherapy have shown conflicting results regarding survival and local-regional control. Future efforts should focus on identifying novel agents and targets to improve therapeutic efficacy. J. Surg. Oncol. 2010; 101:299,304. © 2010 Wiley-Liss, Inc. [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] Elevated activities of MMP-2 in the non-tumorous lung tissues of curatively resected stage I NSCLC patients are associated with tumor recurrence and a poor survival,JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2007Sang-Hui Kim Abstract Background and Objectives We wanted to assess whether the level of enzyme activity for a particular matrix metalloproteinase (MMP), and not the amount of expressed protein, in lung tissue could be used as a reliable prognostic biomarker for tumor recurrence leading to poorer survival in a certain subgroup of patients who have undergone curative resection for stage I human NSCLC. Methods We determined what type of MMP was significant for tumor recurrence by using a mouse model of pulmonary metastasis with inoculating the footpad with H460 human cancer cells. We then looked for any association between tumor recurrence and the level of enzyme activities for the selected MMP in the tumor and also in the pathologically non-tumorous tissues from 34 stage I lung cancer patients. Results We obtained H460/PM6 cells having a highly metastatic potential after six repeated cycles of pulmonary metastasis by using the mouse footpad inoculated with the metastasized cancer cells in the previous cycle. We started with human lung cancer cells, H460, and we found that among the tested MMPs we tested for, the level of MMP-2 mRNA was elevated. No significant difference was seen in the level of enzyme activity of the MMP-2 cells from the curatively resected tumor tissues of the stage I NSCLC patients who were later found with or without recurrence. However, the level of MMP-2 enzyme activity was found to be significantly different between the non-tumorous lung tissues from patients later found with and without recurrence, and it was associated with the 5-year survival rate. Conclusions This observation suggests that the higher level of MMP-2 enzyme activity in the non-tumorous tissues from the patients could be used as a prognostic biomarker to predict post-operative tumor recurrence and survival for patients with stage I NSCLC. The elevated enzyme activity of MMP-2 in the non-tumorous tissue resected from stage I NSCLC could be used as a prognostic indicator for post-operative tumor recurrence and the patients' poor survival. Further, this could be an important aid for physicians' making decision on whether to subject particular patients to post-operative adjunct chemotherapy. J. Surg. Oncol. 2007;95:337,346. © 2007 Wiley-Liss, Inc. [source] Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007B. Y. HA Summary Background Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5,16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects. Aim To examine the clinical outcomes of TACI. Methods We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates. Results Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I,III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014). Conclusions TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I,III; randomized controlled trials are needed to compare TACI to TACE. [source] Prophylaxsis against recurrance of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 yearsLIVER INTERNATIONAL, Issue 1 2008Nevin Yilmaz Abstract Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection is associated with a high rate of graft loss and poor survival, unless re-infection can be prevented. Human hepatitis B immune globulin (HBIG) has long been utilized to prevent re-infection. More recently, an anti-viral agent has been utilized along with HBIG. However, the regimens utilized have varied considerably among LT programmes and the optimal regimen has never been defined. We conducted a retrospective analysis of 41 patients who underwent LT for HBV at our centre since 1985 and received either HBIG with or without an anti-viral agent. The mean age of these patients was 46 years; 81% were male and 88% white. The mean and maximal follow-up were 5.9 and 15 years respectively. Eight out of 15 E-antigen-positive patients who received HBIG alone developed recurrence after a mean of 17 months. In contrast, none of 10 E-Ag-negative patients who received HBIG alone and none of the 10 E-antigen-positive patients who received both HBIG and either lamivudine or adefovir developed recurrence. As long as the anti-HB surface remained detectable, no absolute minimum serum level appeared to lead to recurrent HBV. We concluded that recurrence of HBV following LT can be prevented in E-antigen-positive patients with a combination of HBIG and an anti-viral agent. In contrast, recurrence can be prevented in E-antigen-negative patients with HBIG alone. Maintaining a serum anti-HB surface level above a minimum arbitrary titre of 200 pg/mL did not appear to be necessary for effective HBIG prophylaxis. [source] Clinical characteristics and outcome of patients with cirrhosis and refractory ascitesLIVER INTERNATIONAL, Issue 5 2004Richard Moreau Abstract: Background: In patients with cirrhosis, refractory ascites is associated with a poor prognosis and is an indication for liver transplantation. However, factors that determine prognosis remain unclear. Aims: To investigate the predictive factors of prognosis in patients with refractory ascites. Methods: Seventy-five patients with refractory ascites were followed-up for 18±13 months (mean±SD) and survival was analyzed. Results: The 1-year probability of survival was 52%. Univariate analyses showed that older patients, hepatocellular carcinoma and diabetes, all assessed at entry, were associated with significantly increased risk ratios of death. The risk ratio of death was significantly lower in abstinent alcoholics than in patients with nonalcoholic cirrhosis. The risk ratio of death did not significantly differ between patients with nonalcoholic cirrhosis and nonabstinent alcoholics. Child,Pugh score at entry had no prognostic value. Multivariate analysis showed that older age, hepatocellular carcinoma, diabetes and abstinence were independent prognostic factors. Conclusions: In patients with cirrhosis and refractory ascites, older age, hepatocellular carcinoma and diabetes, but not Child,Pugh score at entry, were independent predictive factors of poor survival while abstinence was an independent predictive factor of good survival. These findings should be taken into account when deciding on liver transplantation in patients with refractory ascites. [source] The natural history of hepatitis C cirrhosis after liver transplantationLIVER TRANSPLANTATION, Issue 9 2009Roberto J. Firpi Hepatitis C after liver transplantation leads to graft cirrhosis in up to 30% of patients within 5 years, but limited data exist regarding the clinical course of cirrhosis after transplantation. The aims of this study were to report the natural history of hepatitis C cirrhosis after liver transplantation and to identify risk factors for decompensation and survival. Hepatitis C patients underwent protocol liver biopsies yearly after liver transplantation. After cirrhosis was identified by biopsy, the outcomes of interest were the development of decompensation, death, or retransplantation for hepatitis C. Kaplan-Meier and Cox regression analysis was used to determine survival and risk factors for decompensation and mortality. Out of 502 liver transplants performed for hepatitis C, 88 patients (18%) had cirrhosis within 3.7 years. Seventy-one patients were compensated at diagnosis. The cumulative probability of decompensation 1 year after cirrhosis was 30%. A Model for End-Stage Liver disease score , 16 was predictive of decompensation and poor survival, whereas successful interferon treatment was found to reduce this risk (relative risk = 0.05). Once decompensation occurred, 1-year survival was 46%. In conclusion, the results confirm an accelerated natural history of hepatitis C cirrhosis after liver transplantation and demonstrate poor survival after decompensation. The Model for End-Stage Liver Disease can stratify risk for decompensation and survival, whereas successful antiviral therapy may be protective. Liver Transpl 15:1063,1071, 2009. © 2009 AASLD. [source] Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinomaLIVER TRANSPLANTATION, Issue 10 2008Mauricio Silva Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden , 10 cm). Patients with cirrhosis and HCC included on the waiting list (WL) from 1991 to 2006 were retrospectively analyzed. Outcomes in patients who had tumors within and beyond the MC were compared. The survival analysis was done (1) with the intention-to-treat principle and (2) among transplanted patients. A total of 281 patients were included in WL. Twenty-four cases did not undergo OLT (a dropout rate of 8.5%); all but 1 case had tumors within the MC. Of the 257 transplanted patients, 26 had tumors beyond the MC in the pre-OLT evaluation. Based on the intention-to-treat analysis, the 5-year survival was 56% versus 66% in patients who had tumors within and beyond the MC, respectively (P = 0.487). Among transplanted patients, the 5-year survival was 62% versus 69%, respectively (P = 0.734). Through multivariate analysis, microvascular invasion was an independent prognostic factor of poor survival (P = 0.004). The recurrence probabilities at 1 and 5 years were 7% versus 12% and 14% versus 28% in patients with tumors within and beyond the MC, respectively (P = 0.063). The multivariate analysis demonstrated that both poorly differentiated tumors (P < 0.001) and microvascular invasion (P < 0.001) increased the risk of recurrence. The expansion to up to 3 nodules, each up to 5 cm, and a cumulative tumor burden , 10 cm did not result in a reduction of survival in comparison with patients who had tumors within the MC. Liver Transpl 14:1449,1460, 2008. © 2008 AASLD. [source] Biliary inorganic phosphate as a tool for assessing cold preservation-reperfusion injury: A study in the isolated perfused rat liver modelLIVER TRANSPLANTATION, Issue 2 2003Luciana L. Almada Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. The bile flow has been suggested as an index of ischemic damage, and severely impaired bile flow seems to be predictive of poor survival in experimental studies. Looking for injury markers, biliary inorganic phosphate has the potential of being a useful endogenous marker of diminished hepatobiliary function because this anion is excreted in the bile by a paracellular pathway and it can detect changes in permeability. The goal of this study was to evaluate the effects of cold preservation-reperfusion of the liver on bile flow and bile inorganic phosphate and their relationship with storage-related graft failure. The isolated and perfused rat liver was used to evaluate the injury for ischemia-reperfusion. The intrahepatic resistance, lactate dehydrogenase release, and potassium and biliary inorganic phosphate concentration were used to estimate viability and function of freshly isolated or cold-preserved livers. The intrahepatic resistance and the bile flow were consistent and significantly decreased throughout the perfusion time in relation to the increment in storage. Inorganic phosphate is more concentrated in bile from preserved livers, showing an alteration in paracellular pathway, confirmed by the biliary excretion of horseradish peroxidase. After preservation, concentration and excretion of the paracellular marker were increased during the first peak. The second peak appears earlier in preserved livers (10 minutes) with a different shape but without changes in concentration. In conclusion, inorganic phosphate in bile shows changes in paracellular permeability as occurs in livers after 48 hours of cold preservation. [source] Response to Cardiac Resynchronization Therapy in Patients with Heart Failure and Renal InsufficiencyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7 2010EVAN C. ADELSTEIN M.D. Background: Renal insufficiency (RI) adversely impacts prognosis in heart failure (HF) patients, partly because renal and cardiac dysfunction are intertwined, yet few cardiac resynchronization therapy (CRT) studies have examined patients with moderate-to-severe RI. Methods: We analyzed 787 CRT-defibrillator (CRT-D) recipients with a glomerular filtration rate (GFR) measured prior to implant. Patients were grouped by GFR (in mL/min/1.73 m2): ,60 (n = 376), 30,59 (n = 347), and <30 (n = 64). Overall survival, changes in left ventricular (LV) ejection fraction and LV end-systolic diameter, and GFR change at 3,6 months were compared among CRT-D groups and with a control cohort (n = 88), also stratified by GFR, in whom LV lead implant was unsuccessful and a standard defibrillator (SD) was placed. All patients met clinical criteria for CRT-D. Results: Among CRT-D recipients, overall survival improved incrementally with higher baseline GFR (for each 10 mL/min/1.73 m2 increase, corrected hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.13,1.30, P < 0.0001). Survival among SD and CRT-D patients within GFR < 30 and GFR , 60 groups was similar, whereas CRT-D recipients with GFR 30,59 had significantly better survival compared to SD counterparts (HR 2.23, 95% CI 1.34,3.70; P = 0.002). This survival benefit was associated with improved renal and cardiac function. CRT recipients with GFR , 60 derived significant echocardiographic benefit but experienced a GFR decline, whereas those with GFR < 30 had no echocardiographic benefit but did improve GFR. Conclusions: CRT may provide the largest survival benefit in HF patients with moderate RI, perhaps by improving GFR and LV function. Severe baseline RI predicts poor survival and limited echocardiographic improvement despite a modest GFR increase, such that CRT may not benefit those with GFR < 30 mL/min/1.73 m2. CRT recipients with normal renal function derive echocardiographic benefit but no overall survival advantage. (PACE 2010; 850,859) [source] |