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Prognostic Relevance (prognostic + relevance)
Selected AbstractsPrognostic relevance of cytogenetic abnormalities in primary myelofibrosis: comparison of recent reports from Japan, the Mayo Clinic and MD Anderson Cancer CenterEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2009Ayalew Tefferi No abstract is available for this article. [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] Prognostic relevance of TGF-,1 and PAI-1 in cervical cancerINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Suzanne Hazelbag Abstract Cervical carcinoma is a human papilloma virus (HPV)-related immunogenic type of malignancy, in which escape of the tumor from the hosts' immune response is thought to play an important role in carcinogenesis. The multifunctional cytokine transforming growth factor-,1 (TGF-,1) is involved in immunosuppression, stroma and extracellular matrix formation and controlling (epithelial) cell growth. The plasminogen activating (PA) system plays a key role in the cascade of tumor-associated proteolysis leading to extracellular matrix degradation and stromal invasion. Changes in expression of components of this system, including plasminogen activator inhibitor-1 (PAI-1), have been associated with poor prognosis in a variety of solid tumors. The present study was undertaken to assess the role of both components on relapse, survival and other clinicopathologic parameters in cervical cancer. The expression of TGF-,1 mRNA in 108 paraffin-embedded cervical carcinomas was detected by mRNA in situ hybridization. Immunohistochemistry was used to investigate the expression of PAI-1 protein. The presence of cytoplasmatic TGF-,1 mRNA in tumor cells was not significantly correlated with the other clinicopathologic parameters investigated or with a worse (disease-free) survival. Expression of the PAI-1 protein in tumor cells was strongly correlated with worse overall and disease-free survival, in addition to well-known prognostic parameters such as lymph node metastasis, depth of tumor infiltration, tumor size and vasoinvasion. In the multivariate analysis, PAI-1 turned out to be a strong independent prognostic factor. In a subgroup of patients without lymph node metastases, PAI-1 was predictive for worse survival and relapse of disease, too. Our results show that the (enhanced) expression of PAI-1 by carcinoma cells is correlated with worse (overall and disease-free) survival of patients with cancer of the uterine cervix. The expression of TGF-,1 in itself is not associated with worse survival in these patients. Although simultaneous presence of the 2 factors was observed in all tumors, induction of PAI-1 by TGF-,1 could not be demonstrated in our group of cervical carcinomas. © 2004 Wiley-Liss, Inc. [source] Prognostic relevance of in vitro response to cell stimulation via surface IgD in binet stage a CLLBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010Fortunato Morabito First page of article [source] Reduction rate of lymph node metastasis as a significant prognostic factor in esophageal cancer patients treated with neoadjuvant chemoradiation therapyDISEASES OF THE ESOPHAGUS, Issue 2 2007S. Aiko SUMMARY., Tumor regression is used widely as a measure of tumor response following radiation therapy or chemoradiation therapy (CRT). In cases of esophageal cancer, a different pattern of tumor shrinkage is often observed between primary tumors and metastatic lymph nodes (MLNs). Regression of MLNs surrounded by normal tissue may be a more direct measure of the response to CRT than regression of a primary tumor as exfoliative mechanical clearance does not participate in shrinkage of MLNs. In this study we evaluated the significance of the reduction rate (RR) of MLNs as a prognostic factor in esophageal cancer patients treated with neoadjuvant CRT. Forty-two patients with marked MLNs were selected from 93 patients with esophageal carcinoma who had received neoadjuvant CRT. The RRs of the primary tumor and the MLNs were calculated from computed tomography scans. In 20 patients, surgical resection was carried out following CRT. Univariate analysis was used to determine which of the following variables were related to survival: size of the primary tumor and MLNs; RRs of both lesions; degree of lymph node (LN) metastasis; clinical stage; and surgical resection. Multivariate analysis was then performed to assess the prognostic relevance of each variable. The primary tumor was larger than the MLNs in 69% of patients before CRT and in 40% of patients after CRT. In 79% of the patients, the RR of the primary tumor was greater than the RR of the MLNs. The results of the univariate analyses showed that a high RR of the MLNs and surgical resection after CRT were associated with significantly improved survival. The multivariate analysis demonstrated that the RR of MLNs had the strongest influence on survival. The RR of LN metastasis should be evaluated as an important prognostic predictor in patients with marked LN metastasis of esophageal cancer treated with CRT. [source] Cytogenetic abnormalities in essential thrombocythemia: prevalence and prognostic significanceEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Naseema Gangat Abstract Objectives:, In the current study we describe cytogenetic findings as well as clinical correlates and long-term prognostic relevance of abnormal cytogenetics at the time of diagnosis of essential thrombocythemia (ET). Patients and methods:, The study cohort consisted of a consecutive group of patients with ET who fulfilled the World Health Organization diagnostic criteria, and in whom cytogenetic analysis was performed at diagnosis. Results:, A total of 402 patients were studied (median age, 56 yrs; median follow-up 70 months). The prevalence of abnormal cytogenetics at diagnosis was 7% (28 of 402). The most common cytogenetic anomalies were trisomy 9 (four patients), abnormal chromosome 1 (three patients) and trisomy 8 (two patients). Parameters at diagnosis that were significantly associated with abnormal cytogenetics included palpable splenomegaly (P = 0.03), current tobacco use (P = 0.04); venous thrombosis (P = 0.02), and anemia with a hemoglobin of <10 g/dL (P = 0.02); but did not include JAK2V617F mutation status, or advanced age. During follow up, patients with abnormal cytogenetics did not have shorter survival, or increased transformation to acute leukemia or myelofibrosis. Conclusion:, Cytogenetic anomalies at diagnosis are relatively uncommon in ET, and do not predict evolution into more aggressive myeloid disorders, or inferior survival. [source] Frequency and prognostic relevance of cyclin D1 dysregulation in multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2001Thomas Rasmussen Abstract:Objective: Cyclin D1 dysregulation has been found with varying frequencies in multiple myeloma (MM) and has been suggested to be associated with a poor prognosis. The aim of this study was to investigate the frequency of cyclin D1 dysregulation in patients being treated for MM and to test whether cyclin D1 dysregulation is a prognostic factor for MM patients. Methods: To achieve the above aims we designed a highly sensitive and reproducible real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for quantitation of cyclin D1 mRNA. Using this assay, 110 diagnostic bone marrow (BM) samples from patients with MM were screened for cyclin D1 dysfuntion. Results: The real-time assay was able to detect the presence of 0.01% cyclin D1 positive cells allowing a safe detection in MM BM samples. In 42% (46/110) of MM BM samples a ,,3-fold increase in cyclin D1 mRNA was observed compared to the cyclin D1 level in normal BM. In the remaining group of MM patients the cyclin D1 mRNA levels were comparable to normal donors. Follow-up of 76 MM patients showed no significant (P = 0.35) difference in survival between cyclin D1 positive and negative MM patients. In addition, cyclin D1 dysregulation did not correlate with known prognostic factors. Conclusion: The developed real-time RT-PCR assay for detection of cyclin D1 mRNA levels offers a fast and safe screening for cyclin D1 dysfunction. When a large cohort of MM patients was screened, the cyclin D1 gene was found to be frequently dysregulated, but there was no significant correlation to survival or known prognostic parameters. [source] Increased levels of inflammatory chemokines in amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2009J. Kuhle Background and purpose:, Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS. Methods:, We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1, (MIP-1,), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients. Results:, MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = ,0.407; P = 0.075). Conclusions:, We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease. [source] Transcriptional regulation of ASK/Dbf4 in cutaneous melanoma is dependent on E2F1EXPERIMENTAL DERMATOLOGY, Issue 12 2008Sandeep Nambiar Background:, Melanoma is a complex genetic disease, the management of which will require an in-depth understanding of the biology underlying its initiation and progression. Recently, we have reported the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggested upregulation of ASK/Dbf4 as a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma. As trans -acting factor binding is fundamental to understand the regulation of gene expression, this study focuses on characterization of the specific transcriptional regulation of ASK/Dbf4 in melanoma. Objective:, We investigated whether ASK/Dbf4 is a transcriptional target of the important cell cycle regulator E2F1 in melanoma. Results:, As evidenced by gel supershift assays on nuclear extracts from various melanoma cell lines (SK-MEL-28, MV3, M13, A375 and BLM), E2F1 bound to the ASK/Dbf4 minimal promoter (MP). In addition, cisplatin-mediated abrogation of E2F1 binding to the ASK/Dbf4 MP resulted in a transcriptional decrease in ASK/Dbf4. Further, the current study also demonstrated that ASK/Dbf4 regulation was refractory to UVB, a well-known risk factor for melanoma. Conclusions:, In summary, our study not only elucidated that ASK/Dbf4, a novel cell survival gene in melanoma was transcriptionally regulated by E2F1, but also that the induction of ASK/Dbf4 was refractory to UVB exposure suggesting that its upregulation was not an early event in melanomagenesis. [source] ,-Adrenoceptor gene variation and intermediate physiological traits: prediction of distant phenotypeEXPERIMENTAL PHYSIOLOGY, Issue 7 2010John H. Eisenach Intermediate physiological phenotype is the genetic and environmental influence on functional physiological characteristics with direct prognostic relevance to distant, more complex phenotypes, such as cardiovascular and metabolic disease. Increasingly available and affordable genotyping techniques have created an explosion of information on candidate gene variation and its relationship to intermediate physiological traits. Variation in ,-adrenoceptor genes is an intense focus of investigation because ,-adrenoceptors are: (1) ubiquitous in organ system distribution; (2) integral to a multitude of physiological processes; (3) well described in cardiovascular and metabolic disease; and (4) major pharmacological treatment targets. Furthermore, knowledge of functional gene variants in these receptors predates the description of the human genome. This review highlights the influence of common gene variation in the three ,-adrenoceptor subtypes on intermediate physiological phenotype predictive of cardiovascular disease and obesity. Although further information is needed to replicate this information across populations, this review condenses and summarizes growing trends in specific pleiotropic effects of ,-adrenoceptor polymorphisms and suggests which variants may be predictive of distant phenotype. [source] PPFIA1 and CCND1 are frequently coamplified in breast cancerGENES, CHROMOSOMES AND CANCER, Issue 1 2010Ana-Maria Dancau Recently, amplification of PPFIA1, encoding a member of the liprin family located about 600 kb telomeric to CCND1 on chromosome band 11q13, was described in squamous cell carcinoma of head and neck. Because 11q13 amplification is frequent in breast cancer, and PPFIA1 has been suggested to contribute to mammary gland development, we hypothesized that PPFIA1 might also be involved in the 11q13 amplicon in breast cancer and contribute to breast cancer development. A tissue microarray containing more than 2000 human breast cancers was analyzed for gene copy numbers of PPFIA1 and CCND1 by means of fluorescence in situ hybridization. PPFIA1 amplification was found in 248/1583 (15.4%) of breast cancers. Coamplification with CCND1 was found in all (248/248, 100%) PPFIA1 -amplified cancers. CCND1 amplification without PPFIA1 coamplification was found in additional 117 (4.7%) tumors. Amplification of both PPFIA1 and CCND1 were significantly associated with high-grade phenotype (P = 0.0002) but were unrelated to tumor stage (P = 0.7066) or nodal stage (P = 0.5807). No difference in patient prognosis was found between 248 CCND1/PPFIA1 coamplified tumors and 117 tumors with CCND1 amplification alone (P = 0.6419). These data show that PPFIA1 amplification occurs frequently in breast cancer. The higher incidence of CCND1 amplification when compared with PPFIA1, the lack of prognostic relevance of coamplifications, and the fact that PPFIA1 amplification was found exclusively in CCND1 -amplified cancers suggest that PPFIA1 gene copy number changes represent concurrent events of CCND1 amplification rather than specific biological incidents. © 2009 Wiley-Liss, Inc. [source] Imbalances of chromosome arm 1p in pediatric and adult germ cell tumors are caused by true allelic loss: A combined comparative genomic hybridization and microsatellite analysisGENES, CHROMOSOMES AND CANCER, Issue 11 2006Susanne Zahn Previous studies on childhood germ cell tumors (GCTs) report highly variable frequencies of losses at chromosome arm 1p. Since deletions at 1p portend a poor prognosis in other embryonal tumors, this study aims to clarify the question of the frequency of true allelic loss at 1p and whether it constitutes a prognostic parameter. We analyzed 13 GCTs from different gonadal and extragonadal sites of children (4 teratomas, 9 malignant GCTs) and 18 GCTs of adolescents and adults (3 teratomas; 15 malignant GCTs) using automated microsatellite analysis with 23 polymorphic markers and chromosomal "high resolution" comparative genomic hybridization (HR-CGH). With this combined approach, we detected loss of heterozygosity (LOH) at 1p in 8/9 childhood malignant GCTs with concordant data from HR-CGH and microsatellite analyses. In contrast, LOH at 1p was not detected in childhood teratomas (0/4) and constituted a rare event in GCTs of adolescence and adulthood (3/18). The commonly deleted region was located at distal 1p36-pter, with a proximal boundary between the markers D1S450 and D1S2870. These data unequivocally demonstrate that deletion at 1p is common in childhood GCTs and results in allelic loss. This observation argues for the presence of a classical tumor suppressor at distal 1p. Considering the high frequency of LOH at 1p and the overall favorable prognosis of childhood GCTs, a prognostic impact of LOH at 1p in childhood GCTs appears unlikely. However, since two postpubertal tumors with LOH at 1p progressed, a prognostic relevance in this age group seems possible, warranting a prospective evaluation. © 2006 Wiley-Liss, Inc. [source] Importance of molecular analysis in detecting cervical lymph node metastasis in head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2006Mohamed N. Elsheikh MD Abstract Background. Because of the impact of nodal status on treatment and survival in squamous cell carcinoma of the head and neck, accurate staging of cervical lymph nodes is critical. This article explores the value of molecular analyses in the detection of cervical lymph node metastasis. Methods. A review of the literature was carried out and combined with our own experience regarding the role of molecular analyses in detecting cervical lymph node metastasis. Results. Few studies have demonstrated the diagnostic and prognostic relevance of molecular analysis in detecting tumor cells in lymph nodes. Nodal staging was improved by the use of molecular techniques; when compared with histopathologic examination, however, the small sample size of these studies did not allow definitive conclusions. Conclusions. Molecular analysis is exquisitely sensitive in detecting very small cancer deposits within lymph nodes. It provides an oncologic basis that may be used to guide therapy and influence outcomes. It should be recommended for diagnostic use in controlled studies of patients without evidence of lymph node metastasis on routine hematoxylin,eosin,stained sections. The clinical significance of these types of metastases, however, must be determined with carefully designed and controlled prospective clinical trials. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Response to intraarterial induction chemotherapy: A prognostic parameter in oral and oropharyngeal cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2006Adorján F. Kovács MD Abstract Background. Patients with head and neck cancer and good pathologic response to neoadjuvant systemic induction chemotherapy have a better prognosis for survival than do those with stable or progressive disease. Thus, induction chemotherapy could theoretically help in stratifying further treatment, but toxicity is much too high. The prognostic implication of superselective intraarterial high-dose cisplatin administered by a femoral approach, which has much less toxicity, is not yet known. Methods. One hundred eighty-seven unselected consecutive patients with previously untreated oral and oropharyngeal squamous cell carcinoma received intraarterial high-dose cisplatin for induction and were assessed for response by visual examination and palpation. This treatment was followed by surgery and adjuvant radiation with concomitant systemic chemotherapy. Omission of a modality depended on individual contraindications and not on preselection. The consequence of omissions has been the constitution of several treatment arms. The overall and disease-free survival in relation to clinical local response after intraarterial induction chemotherapy was calculated using the Kaplan,Meier method. Additional analysis excluded bias caused by stages and treatment arms. Results. Explorative statistics using the log-rank and chi-square tests demonstrated a strong prognostic relevance of response to intraarterial chemotherapy irrespective of stage and treatment. Conclusions. Our results are encouraging for prospective randomized studies and molecular genetic investigations with intraarterial chemotherapy. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevanceHISTOPATHOLOGY, Issue 5 2007S Langbein Aims:, Lectins, and especially galectins, appear to be important in malignancy-associated processes. The aim was to analyse comprehensively the presence of galectins in urothelial tumours. Methods and results:, Non-cross-reactive antibodies against seven family members from the three subgroups (prototype: galectin-1, -2 and -7; chimera type: galectin-3; tandem-repeat type: galectin-4, -8 and -9) were used. Gene expression was monitored in specimens of normal urothelium, fresh tumour tissue and cell lines by real-time polymerase chain reaction (PCR). The presence and evidence of tumour-associated up-regulation were shown for galectin-1 and -3. This was less clear-cut for galectin-4 and -8. Galectin-7 was expressed in all cell lines; galectin-2 and -9 were detected at comparatively low levels. Galectin-2, -3 and -8 up-regulation was observed in superficial tumours, but not in muscle-invasive tumours (P < 0.05). Immunoreactivity correlated with tumour grading for galectin-1, -2 and -8, and disease-dependent mortality correlated with galectin-2 and -8 expression. Binding sites were visualized using labelled galectins. Conclusions:, The results demonstrate a complex expression pattern of the galectin network in urothelial carcinomas. Galectin-1, -2, -3 and -8 are both potential disease markers and also possible targets for bladder cancer therapy. [source] Survivin in esophageal cancer: An accurate prognostic marker for squamous cell carcinoma but not adenocarcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Antonio Rosato Abstract We quantified the expression of survivin, both as mRNA in real-time PCR and protein in immunohistochemistry, in tumor samples of 112 patients with esophageal cancer (56 squamous cell carcinomas and 56 adenocarcinomas). Overall survival of squamous cell carcinoma patients with high survivin mRNA levels was significantly less than that of patients with low survivin mRNA levels (p = 0.0033). Distribution pattern of survivin (nuclear vs. cytoplasmic or mixed) was not correlated to survival, while the extent of immunostaining was significantly correlated to survivin mRNA values (p = 0.016) and had prognostic relevance in univariate analysis (p = 0.0012). Cox's proportional-hazard regression model showed that tumor survivin expression in esophageal squamous cell carcinoma was the most important prognostic factor, independent of tumor stage and other histopathological factors, both as mRNA relative value (p = 0.0259) and protein immunostaining (p = 0.0147). In esophageal adenocarcinoma, survivin expression and pattern of distribution had no prognostic relevance. Thus, quantifying survivin expression provides a prognostic marker only for esophageal squamous tumors. © 2006 Wiley-Liss, Inc. [source] Prognostic impact of hematogenous tumor cell dissemination in patients with stage II colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Moritz Koch Abstract Adjuvant chemotherapy is not routinely recommended in patients with colorectal cancer stage UICC II. Some of these patients, however, develop recurrent disease. Therefore, valid prognostic criteria are needed to identify high-risk patients who might benefit from adjuvant therapy. Disseminated tumor cells, detected in blood and bone marrow, may prove to be a valid marker, however, the prognostic relevance of these cells remains debated. In our study, we examined the prognostic significance of disseminated tumor cells in blood and bone marrow of patients with stage II colorectal cancer. Ninety patients with potentially curative (R0) resection of colorectal cancer stage II were prospectively enrolled into the study. Bone marrow and blood samples were examined for disseminated tumor cells by CK 20 RT-PCR. Patient, tumor and treatment factors were analyzed as prognostic factors. Multivariate analysis confirmed tumor cell detection in blood (hazard ratio 2.1, p = 0.03) and T-category (hazard ratio 2.2, p = 0.02) to be independent prognostic factors for relapse-free survival. Tumor cell detection in postoperative blood samples (hazard ratio 7.7, p < 0.001) and number of removed lymph nodes (hazard ratio 6.4, p < 0.001) were independent prognostic factors for disease-specific survival. Detection of circulating tumor cells in blood samples of patients with stage II colorectal cancer identifies patients with poor outcome. This finding should be confirmed by further studies and could then be used as a basis for conducting a randomized trial evaluating the effect of adjuvant chemotherapy in stage II patients. © 2006 Wiley-Liss, Inc. [source] Anaemia in heart failure: a common interaction with renal insufficiency called the cardio-renal anaemia syndromeINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2008A. Palazzuoli Summary Background:, Although many studies have found a high prevalence of anaemia in patients with congestive heart failure (CHF), few have carefully examined the relationship between the CHF and the prevalence of anaemia and chronic renal insufficiency (CRI). Patients with advanced renal failure, significant anaemia, diffuse atherosclerosis, respiratory disease and more elderly patients have been systematically excluded from the great majority of the randomised clinical trials. Discussion:, Both anaemia and renal insufficiency are very common associated diseases associated with increased mortality, morbidity and rate of hospitalisation in CHF patients. Impaired renal function is associated with adverse outcomes because it represents a marker of coexistent disease and more diffuse atherosclerosis. In patients with CHF, progressive renal dysfunction leads to a decrease in erythropoietin (EPO) levels with reduced erythrocyte production from bone marrow. This may explain the common association between CHF, anaemia and CRI in clinical practice. The normalisation of haemoglobin concentration by EPO in patients with CHF and CRI results in improved exercise capacity by increasing oxygen delivery and improving cardiac function. Conclusion:, In this review, we describe the mechanisms linking anaemic status, CRI and CHF, the prognostic relevance of each disease, treatment implications, and potential benefit of EPO administration. [source] Transforming growth factor ,1 (TGF,1) expression in head and neck squamous cell carcinoma patients as related to prognosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2003Angela F. Logullo Abstract Background:, Transforming growth factor ,1 (TGF,1) is a negative growth regulator in keratinocytes, and in vitro studies lead to the concept that loss of TGF,1 responsiveness is a critical step in epithelial carcinogenesis. Objective:, To investigate the prognostic relevance of TGF,1 expression in head and neck squamous cell carcinoma (HNSCC). Materials and methods:, TGF,1 distribution was determined by immunohistochemistry in oral cavity/oropharynx (n = 79), larynx (n = 36) and hypopharynx (n = 25) tumors and in matched normal adjacent mucosa. TGF,-type I and II receptors were determined in 20 cases of differentiated oral cavity/hypopharynx tumors. Cases were considered positive if displaying reactivity in >10% of the cells. Results:, TGF,1-positive expression was found in 47.2% of larynx, 36.7% of oral cavity/oropharynx and in 24% of the hypopharynx tumors. Reactivity in >60% of the cells was displayed only by 11.4% of HNSCC. All normal controls were positive. TGF,1-positive expression did not correlate with clinico pathological parameters. An association with differentiation was verified only in oral cavity/oropharynx tumors (P , 0.001). TGF,1 was also not related to 5 years survival (Kaplan,Meier). Strong and diffuse expression of TGF,-RII was identified in 19/20 cases regardless of TGF,1 immunoreactivity. Out of 17 TGF,1-positive oral cavity/oropharynx tumors, only nine expressed TGF,-RI suggesting a disruption of the TGF,1 pathway. We conclude that TGF,1 protein immunostaining is not a useful biomarker in assessment of prognosis in HNSCC. [source] Staging of esophageal carcinoma: Length of tumor and number of involved regional lymph nodes.JOURNAL OF SURGICAL ONCOLOGY, Issue 5 2006Are these independent prognostic factors? Abstract Background and Objectives New potential prognostic indicators aside from the TNM classification have been proposed. The aim of this study was to analyze the prognostic relevance of tumor length as well as number of involved regional lymph nodes (LNM) in patients with esophageal carcinoma. Methods Two hundred thirteen patients with esophageal carcinoma (116 squamous cell- and 97 adenocarcinoma) were included in this study. Treatment of choice was subtotal en bloc esophagectomy including "2-field" lymphadenectomy. The median number of examined lymph nodes (LNs) was 28. Eighty patients (38%) received preoperative radio-chemotherapy according to a standardized protocol. Histopathology consisted of tumor stage, residual tumor, grading, and number of examined and involved LN. Univariate and multivariate prognostic values were calculated. Results Length of tumor correlated with pT/ypT-category (P,<,0.01). Univariate but not multivariate analysis showed better survival for tumors ,3 cm (P,<,0.05). Patients with 1,5 LNM had significantly better prognoses than those with more than 5 LNM (Hazard ratio 2.7, 95% CI,=,1.7,4.2) (P,<,0.01). Patients without LNM and more than 15 examined LN showed significantly better prognosis than those with fewer examined LN (Hazard ratio,=,0.3, 95% CI,=,0.1,0.6) (P,<,0.01). Conclusions A revision of the TNM classification for esophageal carcinoma should subdivide the pN1-category according to the number of LNM. J. Surg. Oncol. 2006;94:355,363. © 2006 Wiley-Liss, Inc. [source] Prognostic factors for patients with cirrhosis and kidney dysfunction in the era of MELD: results of a prospective studyLIVER INTERNATIONAL, Issue 7 2006Michael Schepke Abstract: Background/Aim: Hepatorenal syndrome (HRS) is associated with a poor prognosis. The incidence and prognostic impact of kidney dysfunction due to other causes in cirrhotic patients are less well known. The current study prospectively evaluated the incidence and the prognostic relevance of different etiologies of kidney failure in cirrhotic patients. Methods: Eighty-eight consecutive patients with cirrhosis and serum creatinine ,1.5 mg/dl were enrolled. The etiologies of kidney dysfunction were analyzed, and prognostic factors including Model for End-Stage Liver Disease (MELD) score were evaluated in a multivariate Cox model. Results: HRS was present in 35 (40%) patients (15 HRS 1, 20 HRS 2), followed by renal parenchymal disease (23%), drug-induced kidney dysfunction (19%) and prerenal failure due to bleeding or infections (15%). HRS patients had a significantly higher MELD score and shorter survival. In addition to the MELD score, only HRS 1 was independently predictive for survival. HRS 2 patients had a similar outcome as patients with non-HRS kidney dysfunction. Conclusions: In patients with cirrhosis and renal failure, hepatorenal syndrome is associated with a worse prognosis than kidney dysfunction due to other conditions but only HRS type 1 has independent prognostic relevance in addition to the MELD score in these patients. [source] ZAP-70 expression is associated with increased risk of autoimmune cytopenias in CLL patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Roberta Zanotti Autoimmune cytopenias (AIC) are frequent in chronic lymphocytic leukemia (CLL) patients, but risk factors and prognostic relevance of these events are controversial. Data about the influence on AIC of biological prognostic markers, as ZAP-70, are scanty. We retrospectively evaluated AIC in 290 CLL patients tested for ZAP-70 expression by immunohistochemistry on bone marrow biopsy at presentation. They were 185 men, median age 63 years, 77.9% Binet stage A, 17.6% B and 4.5% C. AIC occurred in 46 patients (16%): 31 autoimmune hemolytic anemias, 10 autoimmune thrombocytopenias, four Evans syndromes, and one pure red cell aplasia. Of the 46 cases of AIC, 37 (80%) occurred in ZAP-70 positive patients and nine (20%) in ZAP-70 negatives. ZAP-70 expression [Hazard Ratio (HR) = 7.42; 95% confidence interval (CI): 2.49,22.05] and age >65 years (HR = 5.41; 95% CI: 1.67,17.49) resulted independent risk factors for AIC. Among the 136 patients evaluated both for ZAP-70 expression and IGHV status, the occurrence of AIC was higher in ZAP-70 positive/IGHV unmutated cases (35%) than in patients ZAP-70 negative/IGHV mutated (6%) or discordant for the two parameters (4%; P < 0.0001). In ZAP-70 positive patients, occurrence of AIC negatively influenced survival (HR = 1.75; 95% CI: 1.06,2.86). The high risk of developing AIC in ZAP-70 positive CLL, particularly when IGHV unmutated, should be considered in the clinical management. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis,prognostic relevance is independent of IPSS or karyotype,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Ayalew Tefferi The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty-two patients (,24%) required transfusions at diagnosis whereas 22 (,9%) became transfusion-dependent and 170 remained transfusion-independent during the first year postdiagnosis; after a median follow-up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS- and karyotype-independent prognostic weight of transfusion status. Among IPSS intermediate-1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate-2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancerAPMIS, Issue 2 2010KYRIAKOS ZAFIRELLIS Zafirellis K, Zachaki A, Agrogiannis G, Gravani K. Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancer. APMIS 2010; 118: 115,24. Nitric oxide synthases (NOS) are expressed in colorectal cancer. The aim of this study was to examine the inducible NOS (iNOS) expression in colorectal cancer and to investigate its prognostic relevance. Tissue sections of primary tumors from 132 patients undergoing curative resection for colorectal cancer were immunohistochemically examined for iNOS expression. The expression pattern of iNOS was correlated with various clinicopathological characteristics and survival. iNOS immunoreactivity was observed in the cytoplasm of tumor epithelial cells in 60 patients (45.5%) and positively correlated with lymph node involvement (p = 0.019). No significant correlation was found between iNOS expression and various clinicopathological characteristics, including age, gender, tumor location, tumor size, tumor grade, T stage, and Union International Contra la Cancrum (UICC) stage. Survival analysis showed a significant correlation between iNOS-positive tumors and poor disease-specific survival (p < 0.0001), with independent prognostic significance in multivariate analysis (HR = 4.42; p < 0.0001). Patients with stage II disease and iNOS-positive tumors had significantly worse disease-specific survival than those with iNOS-negative tumors (p < 0.0001). In addition, patients with stage III disease and iNOS-positive tumors had significantly worse disease-specific survival than those with iNOS-negative tumors (p = 0.001). The ability of iNOS to predict outcome in colorectal cancer patients may be independent of other known prognostic factors, providing a new molecular marker with significant potential for clinical utility. [source] Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovariesAPMIS, Issue 4 2003Correlation with clinicopathologic factors, survival Recently, considerable attention has been focused on the role of the small heat-shock protein group hsp27, hsp70 and hsp90 in the clinical outcome of several malignancies. However, conflicting data exist regarding the prognostic role of hsp27 expression in ovarian carcinoma, and the prognostic significance of hsp70 and hsp90 expression still remains unknown in these tumours. The purpose of this study was to investigate immunohistochemically whether hsp27, hsp70 and hsp90 expression was associated with clinicopathological parameters and survival in 52 epithelial ovarian carcinomas. Chi-square test, Kaplan-Meier and Cox regression analysis were used for statistical analysis. Among clinicopathological parameters, hsp27, hsp70 and hsp90 expression was only correlated with FIGO stage; hsp70 and hsp90 positivity failed to detect survival. However, the overall survival rate of patients with hsp27 expression was 13%, which was significantly worse than that of patients without hsp27 expression (47%) (p<0.01). The prognosis was also adversely affected by FIGO stage (p<0.01) and presence of ascites (p<0.01). In multivariate analysis, hsp27 expression and FIGO stage were independent prognostic variables. Our results indicate that hsp70 and hsp90 expression had no prognostic relevance in epithelial ovarian carcinomas. However, hsp27 expression and FIGO stage in these tumours could be reliable indicators of prognosis. [source] Functional and prognostic relevance of the ,173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 5 2003Fabrizio De Benedetti Objective To address the functional and prognostic relevance of the ,173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. Methods A total of 136 patients with systemic-onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Results Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Conclusion Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA. [source] Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2006Hong Chang Summary The prevalence and prognostic relevance of recurrent gains of CKS1B (cyclin kinase subunit 1B) gene at chromosome 1q21 region was investigated by interphase fluorescence in situ hybridisation in a cohort of 99 multiple myeloma (MM) patients treated with intensive chemotherapy followed by autologous stem cell transplantation. CKS1B amplification (3,8 CKS1B signals) was detected in 31of 99 (31%) patients and was associated with deletions of p53 (P = 0·003) and 13q (P = 0·039) but not with translocation t(11;14) or t(4;14). CKS1B amplification was associated with bone marrow plasmacytosis (P = 0·02), but there was no correlation with patient age, gender, disease stage, lytic bone lesions, albumin, creatinine, C-reactive protein or beta-2 microglobulin levels. Patients with CKS1B amplification had a significantly shorter progression-free survival than those without such amplification (18·5 vs. 25·7 months, P = 0·035). Likewise, a shorter overall survival (44·8 months vs. not reached) was observed; however, the difference did not reach statistical significance (P = 0·20). Seven patients had paired bone marrows obtained at diagnosis and at relapse, the percentage of cells with CKS1B amplification and the level of amplification were significantly increased in the relapse marrows. In this cohort of patients, CKS1B was frequently amplified in MM and may represent genetic instability associated with disease progression. [source] The prognostic role of comorbidity in salivary gland carcinomaCANCER, Issue 7 2008Chris H. J. Terhaard MD Abstract BACKGROUND. Patients with head and neck cancer are prone to develop significant comorbidity mainly because of the high incidence of tobacco and alcohol abuse, both of which are etiologic and prognostic factors. However, to the authors' knowledge little is known regarding the prognostic relevance of comorbidity in patients with salivary gland cancer. METHODS. A retrospective cohort of 666 patients with salivary gland cancer was identified within the Dutch Head and Neck Oncology Cooperative Group database. For multivariate analysis, a Cox proportional hazards model was used to study the effect of comorbidity on overall survival and disease-specific survival. RESULTS. According to the Adult Comorbidity Evaluation-27 (ACE-27) index, 394 patients (64%) had grade 0 comorbidity, 119 patients (19%) had grade 1 comorbidity, 71 patients (12%) had grade 2 comorbidity, and 29 patients (5%) had grade 3 comorbidity. In multivariate analysis for overall survival, the ACE-27 comorbidity grade was a strong independent prognostic variable. The hazards ratio (HR) of death, including all causes, was 1.5 (95% confidence interval [CI], 1.1-2.1) for patients with ACE-27 grade 1 comorbidity versus grade 0 comorbidity (P < .007). The HR was 1.7 (95% CI, 1.2-2.5) for grade 2 comorbidity (P = .003) and 2.7 (95% CI, 1.5-4.7) for grade 3 comorbidity versus grade 0 comorbidity (P = .001). In the current analysis, ACE-27 comorbidity grade was not an independent prognostic factor for disease-free survival. CONCLUSIONS. To the authors' knowledge, this is the first study concerning the prevalence and relevance of the prognostic comorbidity variable ACE-27 grade in patients with salivary gland cancer. Overall survival, but not disease-free survival, was correlated strongly with ACE-27 grade. Compared with other studies that investigated the effect of comorbidity on patients with head and neck cancer, patients with salivary gland cancer had less comorbidity. Their comorbid status appeared to be reasonably comparable to that of patients with other nonsmoking- and nonalcohol-related cancers. Cancer 2008. © 2008 American Cancer Society. [source] Frequency and prognostic relevance of disseminated tumor cells in bone marrow of patients with metastatic renal cell carcinomaCANCER, Issue 7 2006Alexander Buchner M.D. Abstract BACKGROUND The prognostic relevance of disseminated cytokeratin-positive (CK+) tumor cells in the bone marrow of patients with different types of carcinoma has been demonstrated in several studies. In this prospective study, the frequency and prognostic value of CK+ tumor cells was investigated in the bone marrow of 55 consecutive patients with metastatic renal cell carcinoma (M1 RCC) in comparison with 256 M0 RCC patients from a previous study. METHODS Aspiration of bone marrow from the anterior iliac crest was performed immediately before tumor resection in RCC patients. Cytospins were made and stained by immunocytochemistry using the APAAP (alkaline phosphatase-antialkaline phosphatase) protocol and monoclonal antibodies CK2 and A45-B/B3. Twenty-seven patients with no evidence of any malignant disease served as a control group. RESULTS CK+ tumor cells were detected in 42% (23 of 55 patients) of the M1 patients and 25% (63 of 256 patients) of the M0 patients (P <.01). No CK+ cells (0 of 27 patients) were detected in the control group. In the M1 group, CK, patients demonstrated a trend toward a better outcome compared with CK+ patients (log-rank test, P = .19). This difference was significant when applying a higher threshold (0,2 CK+ cells vs. , 3 CK+ cells; P <.05). On multivariate analysis, the detection of , 3 CK+ cells in the bone marrow was found to be an independent prognostic factor (P <.001). CONCLUSIONS The results of the current study indicate that disseminated CK+ cells play a role in the biology of tumor spread of RCC, and that their immunocytochemical detection can be useful in assessing the prognosis of patients with M1 disease. Cancer 2006. © 2006 American Cancer Society. [source] The diagnostic and prognostic relevance of human telomerase reverse transcriptase mRNA expression detected in situ in patients with nonsmall cell lung carcinomaCANCER, Issue 5 2003Yuka Fujita M.D. Abstract BACKGROUND The objectives of this study were to evaluate the diagnostic and prognostic relevance of human telomerase reverse transcriptase (hTERT) detected in situ in patients with nonsmall cell lung carcinoma (NSCLC) and to investigate the possible correlations between hTERT mRNA in NSCLC and the patients' clinicopathologic features, including survival. METHODS hTERT mRNA was detected by in situ hybridization in 146 samples from patients with NSCLC. The signal intensity of hTERT mRNA expression was evaluated by two independent observers. The expression level was defined subjectively as strong, moderate, or weak. RESULTS hTERT mRNA was detected mainly in the cytoplasm of tumor cells. It was detected in the cytoplasm of 100% of samples from patients with NSCLC but was not detected in normal lung tissue, except in activated lymphocytes. There was a significant correlation between hTERT mRNA expression and pathologic tumor status, pathologic disease stage (pStage), and Ki-67 labeling index. There was no significant correlation between hTERT mRNA expression and age, gender, pathologic lymph node status (pN), histology, or tumor differentiation. The 5-year survival rates for patients with strong and moderate hTERT mRNA expression levels were 46.9% and 77.9%, respectively; the difference was statistically significant (P = 0.0001). A multivariate analysis of survival using a stepwise procedure revealed that hTERT mRNA expression, pN status, pStage, and age were statistically significant prognostic factors (P = 0.0029, P = 0.0012, P = 0.0237, and P = 0.0496, respectively). CONCLUSIONS The findings suggested that hTERT mRNA expression may be useful for the diagnosis of NSCLC and also may be an independent prognostic factor for patients with NSCLC. Cancer 2003;98:1008,13. © 2003 American Cancer Society. DOI 10.1002/cncr.11611 [source] | ||||||||||||||||||||||||||||