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Patient Prognosis (patient + prognosis)
Selected AbstractsAdvanced Heart Failure: Prognosis, Uncertainty, and Decision MakingCONGESTIVE HEART FAILURE, Issue 5 2007Jane G. Zapka ScD Heart failure is a serious clinical management challenge for both patients and primary care physicians. The authors studied the perceptions and practices of internal medicine residents and faculty at an academic medical center in the Southeast to guide design of strategies to improve heart failure care. Data were collected via a self-administered survey. Eighty-nine faculty and resident physicians in general internal medicine and geriatrics participated (74% response rate). Items measured perceived skills and barriers, adherence to guidelines, and physician understanding of patient prognosis. Case studies explored practice approaches. Clinical knowledge and related scales were generally good and comparable between physician groups. Palliative care and prognostic skills were self-rated with wide variance. Physicians rated patient noncompliance and low lifestyle change motivation as major barriers. Given the complexities of caring for elderly persons with heart failure and comorbid conditions, there are significant opportunities for improving physician skills in decision making, patient-centered counseling, and palliative care. [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] Prognostic indicators of gastric carcinoma confined to the muscularis propriaHISTOPATHOLOGY, Issue 1 2007H Son Aims:, Gastric carcinoma confined to the muscularis propria (MPGC) is considered an intermediate-stage carcinoma. A method of discriminating between more favourable and less favourable prognostic groups of this entity is critically needed in dealing with this heterogeneous disease. The aim of this study was to examine the correlation between survival of patients with MPGC and its various clinicopathological parameters. Methods and results:, Various clinicopathological parameters were studied in 171 tissue samples including: macroscopic appearance, size, age, sex, stage, invasion depth, Lauren and Ming classifications, extent, lymphatic emboli and nodal metastasis. Tumours macroscopically resembling early gastric cancers, younger patient age, absence of lymphatic tumour emboli and lower stage were significantly associated with better prognosis of MPGC by univariate analysis. Tumours macroscopically resembling early gastric cancers, younger patient age and Lauren's diffuse type were significantly associated with a better prognosis of MPGC by multivariate analysis. Conclusions:, These indicators are practical parameters for predicting patient prognosis in clinical practice. The description of these parameters should be carefully noted in the final report and pathologists should evaluate the macroscopic appearance of MPGC. [source] Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Dipok Kumar Dhar Abstract KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1 -expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention. © 2004 Wiley-Liss, Inc. [source] Neutrophils: key mediators of tumour angiogenesisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2009Simon Tazzyman Summary It is now well known that most malignant tumours contain a significant amount of leucocytic infiltrates the presence of which has, on many occasions, been linked to poor patient prognosis. These leucocyte populations are recruited to tumours by chemotactic factors released by either viable or necrotic tumour cells, or by cells within the tumour stroma. In recent times, most studies have analysed the role that tumour-associated macrophages (TAM) have on tumour progression. However, there is now increasing evidence to show that neutrophils also actively participate in this process. Whilst there are some data to suggest that neutrophil-derived factors can promote genetic mutations leading to tumourigenesis, or secrete factors that promote tumour cell proliferation; there is now substantial evidence to show that neutrophils, like TAM, significantly affect tumour angiogenesis. In this review, we discuss the likely mechanisms by which neutrophils are recruited into the tumour and then elaborate on how these cells may induce tumour vascularization by the secretion of powerful pro-angiogenic factors. We also discuss possible future chemotherapeutic strategies that are aimed at limiting tumour angiogenesis by inhibiting neutrophil recruitment. [source] Pre-emptive renal transplantation in childrenINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2001Hiroshi Harada Abstract Background: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). Methods: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. Results: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. Conclusion: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy. [source] Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2006Takashi Hase Background:, The aim of this study was to evaluate the relationship between the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in cancer cells and fibroblasts at the invasive front of oral squamous cell carcinoma (OSCC), and the pathologic and clinical characteristics. Methods:, Sections of 61 biopsy specimens of primary OSCC were immunostained to assess the expression of bFGF and FGFR-1 in cancer cells and fibroblasts at the invasive front. Results:, The bFGF and FGFR-1 expressions in the cancer cells were evident in all specimens, whilst, in fibroblasts, they were detected in 41 (67%) of 61 specimens. These expressions in the fibroblasts occurred notably more often in high-invasive OSCC specimens than low-invasive OSCC specimens. The prevalence of bFGF and FGFR-1 expressions in cases with lymph node metastasis was significantly higher (P < 0.05) than in cases without metastasis. Moreover, these expressions were well correlated with patient prognosis. Conclusion:, This study concludes that bFGF and FGFR-1 expressions in fibroblasts at the invasive front are linked to the mode of invasion and the prognosis in OSCC. [source] Debulking surgery for incompletely operated advanced epithelial ovarian carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2009Murat Gultekin MD Abstract Background and Objectives There is still no any data about the role of re-operation and re-debulking in previously incompletely operated advanced staged patients with epithelial ovarian carcinoma (EOC). In this study, the authors aimed to analyze the effect of an incomplete primary surgery on patient prognosis. Methods Clinicopathological variables of 317 advanced staged EOC patients were retrospectively collected. Results Twenty-nine patients had an initial incomplete surgery and referred to our center for debulking while remaining 288 had undergone primary debulking surgery at our institution. Comparison of the two groups with respect to clinicopathological variables could not reveal significant difference. Median survival was 3.24 years for re-operated patients while it was 2.07 years for patients who had undergone primary debulking surgery. Upon multivariate analysis, final optimal debulking, tumor grade and a history of an incomplete surgery before the final debulking were the significant prognosticators. A subgroup analysis of re-staged patients could not reveal a significant role for either the type or the time interval between the operations. Conclusion A history of an incomplete primary surgery does not seem to adversely affect patient prognosis and the optimal cytoreductive success achieved in final debulking surgery is still the most important prognostic factor. J. Surg. Oncol. 2009;100:258,260. © 2009 Wiley-Liss, Inc. [source] Nutritional status and prognosis in cirrhotic patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2006F. GUNSAR SUMMARY Background and Aim, The potential prognostic value for survival of nutritional status in cirrhotics after adjusting Child,Pugh classification and Model for End-Stage Liver Disease has not been evaluated. Methods, We used Kaplan,Meier and Cox proportional hazards regression models to identify factors associated with mortality in a cohort of 222 cirrhotics [M/F:145/77 median age 52 (18,68) years] with prospectively collected nutritional parameters as well as modified subjective global nutritional assessment, Royal Free Hospital-Subjective Global Assessment index. Follow-up was censored at the time of transplantation. Other variables were ones in Child,Pugh and Model for End-Stage Liver Disease scores, age, aetiology of cirrhosis and renal function, Results, Pretransplant mortality (Kaplan,Meier) was 21% by 2 years (135 patients were transplanted). Among the nutritional parameters, only Royal Free Hospital-Subjective Global Assessment remained significantly associated with mortality in multivariable models (P = 0.0006). The final model included the following variables: urea (P = 0.0001), Royal Free Hospital-Subjective Global Assessment (P = 0.003), age (P = 0.0001), Child,Pugh grade (P = 0.009) and prothrombin time (P = 0.003). The results were similar when the Child,Pugh grade was replaced by the Model for End-Stage Liver Disease score in the model, and whether a competing risks model was used. Conclusions, Nutritional indices add significantly to both Child,Pugh grade and Model for End-Stage Liver Disease scores when assessing the patient prognosis. [source] Evidence-based medicine: the time has come to set standards for staging,THE JOURNAL OF PATHOLOGY, Issue 4 2010Phil Quirke Abstract For international communication in cancer, staging systems such as TNM are essential; however, the principles and processes used to decide about changes in every new edition of TNM need to be subject to debate. Changes with major impact for patient treatment are introduced without evidence. We think that TNM should be a continual reactive process, rather than a proactive process. Changes should only occur after extensive discussion within the community, and before the introduction of any changes these should be tested for reproducibility and compared to the currently used gold standard. TNM should not be used to test hypotheses. It should introduce established facts that are beneficial to predicting patient prognosis. TNM should thus be restructured on a basis equivalent to evidence-based guidelines. The strength of the evidence should be explicitly stated and the evidence base given. It is time for the principles of staging to be widely debated and new principles and processes to be introduced to ensure that we are not in the same situation in the future. The disparity between therapeutic decision making and TNM staging is marked and we would appeal for the radical overhaul of TNM staging to make it fit for the twenty-first century. TNM is central to the management of cancer patients and we must protect and enhance its reputation. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to prognosis and completion lymph node dissectionBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2007S. Debarbieux Summary Background, Sentinel lymph node (SLN) positivity has been found to be strongly associated with a poor prognosis in melanoma. Objectives, This large referral centre study was conducted: (i) to confirm the powerful prognostic value of SLN biopsy (SLNB); (ii) to correlate patient prognosis to the micromorphometric features of SLN metastasis in SLN-positive patients; and (iii) to correlate these micromorphometric features to the likelihood of positive completion lymph node dissection (CLND). Patients and methods, SLNB was performed in 455 cases of primary melanoma between January 1999 and December 2004; for patients with positive SLN, the following micromorphometric features were registered: size of the largest metastasis (two diameters), depth of metastasis, number of millimetric slices involved, maximum number of metastases on a single section, presence of intracapsular lymphatic invasion and extracapsular spread. Kaplan,Meier survival curves were compared with the log-rank test; multivariate analysis was performed using a Cox regression model. Dependence of CLND status on micromorphometric features of SLN was assessed by the ,2 test and predictive values of the different features were evaluated by multivariate analysis using a logistic regression model. Results, A positive SLN was identified in 98 of our 455 cases. Survival was significantly shorter in SLN-positive patients than in SLN-negative patients. Extracapsular invasion was found to be an independent prognostic factor of disease-free survival; ulceration of the primary and the maximum diameter of the largest metastasis were identified as independent predictive factors of disease-specific survival. Age and the lowest diameter of the largest metastasis were identified as independent predictive criteria of positive CLND, whereas depth of metastasis was not. Positivity of CLND was not significantly associated with a worse prognosis. Conclusions, Our study confirms the previously demonstrated strong prognostic value of SLNB. It also confirms the relationship between tumour burden in the SLN (evaluated by the maximum diameter of the largest metastasis) and clinical outcome. We point out a new micromorphometric feature of SLN, which seems to be predictive of CLND status: the lowest diameter of the largest metastasis. [source] Correlative analysis of gene expression profile and prognosis in patients with gliomatosis cerebriCANCER, Issue 16 2009Oscar Fernando D'Urso PhD Abstract BACKGROUND: In modern clinical neuro-oncology, the pathologic diagnoses are very challenging, creating significant clinical confusion and affecting therapeutic decisions and prognosis. METHODS: TP53 and PTEN gene sequences were analyzed, and microarray expression profiling was also performed. The authors investigated whether gene expression profiling, coupled with class prediction methodology, could be used to determine the prognosis of gliomatosis cerebri in a more consistent manner than standard pathology. RESULTS: The authors reported the results of a molecular study in 59 cases of gliomatosis cerebri, correlating these results with prognosis. The well-known prognostic factors of gliomas (ie, age, Karnofsky performance status, histology [grade 2 vs 3], and contrast enhancement) were found to be predictive of response or outcome in only a percentage of patients but not in all patients. The authors identified a 23-gene signature that was able to predict patient prognosis with microarray gene expression profiling. With the aim of producing a prognosis tool that is useful in clinical investigation, the authors studied the expression of this 23-gene signature by real-time quantitative polymerase chain reaction. Real-time expression values relative to these 23 gene features were used to build a prediction method able to distinguish patients with a good prognosis (those more likely to be responsive to therapy) from patients with a poor prognosis (those less likely to be responsive to therapy). CONCLUSIONS: The results of the current study demonstrated not only a strong association between gene expression patterns and patient survival, but also a robust replicability of these gene expression,based predictors. Cancer 2009. © 2009 American Cancer Society. [source] Tissue biomarkers in renal cell carcinoma: Issues and solutions,CANCER, Issue S10 2009Arianna Di Napoli MD Abstract Renal cell carcinoma (RCC) is an aggressive malignancy that is associated with a high rate of metastasis. Although several promising therapeutic strategies are now available for the treatment of patients with metastatic kidney cancer, the prognosis of these patients remains poor. Research is ongoing to identify RCC-specific biomarkers that can improve early diagnosis, surveillance of tumor progression, and prediction of patient prognosis. The identification of biomarkers that may predict response to specific therapies also will be useful in stratifying patients with RCC for treatment selection. Unfortunately, biomarker detection and measurement in kidney tumor tissues can be biased significantly by the lack of standardization in tissue sample acquisition, storage, and analysis. Consequently, the establishment of standardized operating procedures is necessary to maximize the accuracy of tissue-based biomarker assays. Herein, the authors discuss current issues in tissue-based translational research aimed at identifying clinically useful biomarkers for kidney cancer. Cancer 2009;115(10 suppl):2290-7. © 2009 American Cancer Society. [source] Hypermethylation of E-cadherin is an independent predictor of improved survival in head and neck squamous cell carcinoma,CANCER, Issue 7 2008Carmen J. Marsit PhD Abstract BACKGROUND. The loss of E-cadherin (ECAD) protein expression has been linked to aggressive head and neck squamous cell carcinoma (HNSCC). Promoter hypermethylation of the cadherin 1, type 1 (CDH1) gene (encoding ECAD) is 1 mechanism by which this protein can be inactivated, although this epigenetic alteration of the gene has not been linked conclusively to poorer patient outcome and, in fact, may be associated with better patient prognosis. METHODS. The authors investigated the prevalence of CDH1 promoter hypermethylation in a population-based case series of 340 primary HNSCC tumors using methylation-specific polymerase chain reaction. They also studied the association between CDH1 hypermethylation and patient demographic characteristics using multivariate analysis and examined the impact of CDH1 hypermethylation on patient survival using both univariate and multivariate methods. RESULTS. Hypermethylation of CDH1 was significantly more prevalent (P < .03) among individuals with a low smoking history independent of whether they were seropositive for human papillomavirus type 16 (HPV-16). Patients who had tumors with CDH1 hypermethylation had significantly better overall survival compared with patients who had tumors without hypermethylation (P < .02; log-rank test). This effect was independent of HPV-16 status and demonstrated a significant hazard ratio of 0.5 (95% confidence interval, 0.3-0.9) in a model that controlled for HPV-16 serology, age, sex, and tumor stage. CONCLUSIONS. The current results suggested that hypermethylation of CDH1 occurs more commonly in patients with HNSCC who are low smokers, suggesting that an additional factor may be driving this epigenetic alteration. Clinically, CDH1 hypermethylation may hold powerful prognostic potential in addition to that observed with HPV serology, and the authors concluded that it should be pursued in additional studies. Cancer 2008. © 2008 American Cancer Society. [source] Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancerCANCER, Issue 8 2008Aurelia Noske MD Abstract BACKGROUND The human nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) mediates the nuclear export of proteins and messenger RNAs and, thus, is an important regulator of subcellular distribution of key molecules. Whereas cell-biologic studies have suggested a fundamental role for CRM1 in the regulation of mitosis, the expression of this protein in human tumor tissue has not been investigated to date. METHODS In this study, the expression of CRM1 was analyzed in a cohort of 88 ovarian tumors and 12 ovarian cell lines for the first time to the authors' knowledge. RESULTS Immunohistochemistry revealed increased nuclear (52.7%) and cytoplasmic (56.8%) expression of CRM1 in 74 carcinomas compared with the expression revealed in borderline tumors and benign lesions. Similarly, CRM1 expression was increased in ovarian cancer cell lines compared with human ovarian surface epithelial cells. Cytoplasmic CRM1 expression was related significantly to advanced tumor stage (P = .043), poorly differentiated carcinomas (P = .011), and higher mitotic rate (P = .008). Nuclear CRM1 was associated significantly with cyclooxygenase-2 (COX-2) expression (P = .002) and poor overall survival (P = .01). Because it was demonstrated previously that blocking of CRM1 by leptomycin B (LMB) contributes to the inhibition of nuclear export, the authors used a set of mechanistic assays to study the effects of CRM1 inhibition in cancer cells. Treatment of OVCAR-3 cells with LMB revealed a significant reduction of cell proliferation and increased apoptosis as well as suppressed interleukin-1,-induced COX-2 expression. CONCLUSIONS The current results indicated that CRM1 is expressed in a subpopulation of ovarian carcinomas with aggressive behavior and is related to poor patient outcome. A correlation also was demonstrated between CRM1 and COX-2 expression in ovarian cancer tissue. Furthermore, the treatment of ovarian cancer cells with LMB revealed a reduction in COX-2 expression. Therefore, the authors suggest that CRM1 may be an interesting biomarker for the assessment of patient prognosis and a molecular target for anticancer treatment. Cancer 2008. © 2008 American Cancer Society. [source] Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancerCANCER, Issue 5 2006Hojoong Kim MD Abstract BACKGROUND. Despite many reports about the involvement of DNA methyltransferases (DNMTs) in human cancers, including nonsmall cell lung cancer (NSCLC), the clinicopathologic significance of DNMTs in primary NSCLC remains to be elucidated. METHODS. The relation between the mRNA levels of DNMTs (1 and 3b) and the promoter methylation of the p16, RAR,2, H-cadherin, GSTP1, RIZ, and FHIT genes and the clinicopathologic features in 102 fresh-frozen tissues and paraffin blocks were retrospectively studied. The mRNA levels of the DNMTs were assessed via semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), and the methylation status of the CpG islands were determined by methylation-specific PCR. RESULTS. The mRNA levels of DNMT1 and DNMT3b were elevated in 53% and 58% of 102 NSCLCs, respectively. Hypermethylation of p16, RAR,2, H-cadherin, GSTP1, RIZ, and FHIT occurred in 37%, 38%, 34%, 18%, 9%, and 31% of patients, respectively. Univariate analysis showed that elevated DNMT mRNA levels were not significantly associated with the hypermethylation of 6 genes. However, the elevated mRNA levels of DNMT1 were determined to be significantly associated with the hypermethylation of the p16 promoter (odds ratio [OR] = 2.70, 95% confidence interval [95% CI], 1.02,7.15; P = .02), after controlling for age, gender, pack-years smoked, histology, and pathologic stage. The hazard of failure in cases with elevated mRNA levels of DNMT1 was 3.51 (95% CI, 1.18,12.76; P = .02) times higher than that in those without. The elevated mRNA levels of DNMT3b were not ultimately associated with patient prognosis. CONCLUSIONS. Elevated mRNA expression of DNMT1 may be an independent prognostic factor in NSCLC and CpG island hypermethylation in NSCLC may be maintained by a complex interaction of several factors rather than by a simple transcriptional up-regulation of DNMT1. Cancer 2006. © 2006 American Cancer Society. [source] Bronchopulmonary carcinoid in multiple endocrine neoplasia type 1,CANCER, Issue 3 2005Nirupa Sachithanandan M.B.B.S. Abstract BACKGROUND Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal-dominant syndrome associated with neoplasia of pituitary, pancreas, parathyroid, and foregut lineage neuroendocrine tissue. Although enteropancreatic carcinoid has been well described in patients with MEN 1, it was believed that bronchopulmonary carcinoid was relatively uncommon, occurring in approximately 5% of patients. It is unclear whether the increased screening of asymptomatic patients with MEN 1 will facilitate early diagnosis of this tumor and improve patient prognosis. METHODS The authors reviewed the patient records and, when available, thoracic computed tomographic (CT) images of 129 MEN 1-affected adult members of a single family to determine the prevalence and prognosis of bronchopulmonary nodules and carcinoid. RESULTS Among 129 patients, a diagnosis of bronchopulmonary carcinoid was noted in the records for 6 individuals (1 male and 5 females; 5%). Thoracic CT scans also were available for review from 32 of those patients. Twelve patients (38%) had pulmonary nodules evident on CT scans. Only hypergastrinemia was significantly more common in patients with pulmonary nodules; otherwise, the spectrum of neoplasia was similar between individuals with and without pulmonary lesions. Histologic diagnoses were available in four patients (three female) with abnormal CT images, and carcinoid was confirmed in each patient. No deaths or distant metastases occurred among the patients despite long-term follow-up (mean, 127 months). CONCLUSIONS The findings suggested that bronchopulmonary carcinoid is more prevalent in patients with MEN 1 than was recognized previously. Furthermore, the diagnosis did not appear to portend a poor prognosis in the majority of affected patients. Cancer 2005. © 2004 American Cancer Society. [source] Hyperthermic intraperitoneal intraoperative chemotherapy after cytoreductive surgery for the treatment of abdominal sarcomatosisCANCER, Issue 9 2004Clinical outcome, prognostic factors in 60 consecutive patients Abstract BACKGROUND Abdominal sarcomatosis is a rare nosologic entity with a poor prognosis. After a Phase I study on cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative chemotherapy (HIIC), the authors reported the results of the treatment of 60 patients using this novel multimodal approach. METHODS Twenty-nine patients had multifocal primary disease and 31 patients had recurrent abdominal sarcoma. Tumor histology was represented by visceral (n = 26 [43%]) and retroperitoneal (n = 34 [57%]) sarcoma. All patients underwent cytoreductive surgery (with no or minimal residual disease) and 90-minute HIIC with doxorubicin (15.25 mg/L of perfusate) and cisplatin (43 mg/L). The clinical outcome and the prognostic value of 11 clinicopathologic variables were analyzed. RESULTS No postoperative deaths occurred. The morbidity rate was 33% and the moderate to severe locoregional toxicity rate was 15%. The median time to local disease progression and the median overall survival were 22 months and 34 months, respectively. Using multivariate analysis, histologic grading and completeness of surgical cytoreduction predicted patient prognosis, indicating that both local progression-free and overall survival were affected significantly by tumor aggressiveness and local disease control. CONCLUSIONS Although these results were encouraging, there was no definitive conclusion reached regarding the therapeutic activity of this locoregional treatment. In addition, the toxicity rate was substantial. In the absence of effective systemic agents, the therapeutic potential of cytoreductive surgery plus HIIC should be explored further in comparative trials. Cancer 2004. © 2004 American Cancer Society. [source] Matrix metalloproteinase-7 expression and biologic aggressiveness of cholangiocellular carcinomaCANCER, Issue 2 2002Shiro Miwa M.D. Abstract BACKGROUND Matrix metalloproteinase-7 (MMP-7) recently has been reported to play a role in tumor cell invasion. The objective of the current study was to examine the expression of MMP-7 in patients with cholangiocellular carcinoma. METHODS Twenty-six patients underwent resection of cholangiocellular carcinoma, leaving no macroscopic evidence of residual tumor. Immunostaining was performed to evaluate the relation between MMP-7 expression and clinicopathologic features and patient prognosis. The immunostaining pattern of the tumor cells for MMP-7 was classified as negative (,) (n = 9), positive (+) (n = 11), or strongly positive (++) (n = 6). Western blot analysis was performed to investigate the expression of active or latent forms in cancerous and noncancerous lesions in four patients. RESULTS The survival rates in patients with MMP-7 expression judged to be (,), (+), and (++) were 75%, 80%, and 0%, respectively, at 1 year, and 47%, 24%, and 0%, respectively, at 3 years. The survival rate of MMP-7 (++) patients was significantly lower than that of MMP-7 (+) patients (P = 0.003) and MMP (,) patients (P = 0.008). At last follow-up, 3 patients in the MMP-7 (,) group had survived for > 5 years. Western blot analysis demonstrated that there were two types of cholangiocellular carcinoma: those producing both latent and active MMP-7 and those producing only the latent form. CONCLUSIONS Although the results of the current study are based on a small number of patients, they suggest that MMP-7 expression is a significant prognostic factor in patients with cholangiocellular carcinoma and that cholangiocellular carcinoma demonstrating strongly positive expression of MMP-7 on immunostaining may have a higher malignant potential compared with that showing negative or positive expression of MMP-7. Cancer 2002;94:428,34. © 2002 American Cancer Society. [source] Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the futureCANCER SCIENCE, Issue 2 2009Yoshinao Oda In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation-associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18,SSX, EWS,FLI1, and PAX3,FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor-suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed-type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1tumor-suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E-cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200,208) [source] Allelotype Analysis of Common Epithelial Ovarian Cancers with Special Reference to Comparison between Clear Cell Adenocarcinoma with Other Histological TypesCANCER SCIENCE, Issue 7 2002Satoshi Okada Determination of the histological type of epithelial ovarian cancer is clinically important to predict patient prognosis. To estimate accurately the chromosomal regions that frequently show loss of heterozygosity (LOH) in each histological type, LOH at 55 loci on 38 chromosomal arms was examined by means of laser capture microdissection and PCR-LOH analysis in 45 epithelial ovarian cancers composed of clear cell adenocarcinoma (CCA), serous adenocarcinoma (SEA), endometrioid adenocarcinoma (EMA) and mucinous adenocarcinoma (MUA). In addition, p53 (exons 5,8) gene mutations and the nuclear immunoreactivity of p53 proteins in these tumors were examined by PCR-SSCP and immunohistochemistry. In CCA, LOH was detected primarily on 1p (69%) followed by 19p (45%) and 11q (43%). On the other hand, in SEA, LOH was detected in at least 50% of cases on 1p, 4p, 5q, 6p, 8p, 9q, 12q, 13q, 15q, 16p, 17p, 17q, 18p, 18q, 19p, 20p and Xp. The incidences of LOH on 5q, 12q, 13q and 17p were significantly lower in CCA than in SEA (P=0.019, 0.031, 0.0035 and 0.012). EMA showed a tendency for frequent LOH on 7p, whereas MUA showed significantly high occurrence of LOH at 17p13.1. The incidences of p53 mutation and p53 nuclear immunoreactivity also differed between CCA and SEA: 0% and 7% in the former and 64% and 45% in the latter (P=0.0006 and 0.039). These findings clarify that there are differences in LOH distribution patterns among different histological subtypes of epithelial ovarian cancer. In CCA, p53 tumor-suppressor gene (TSG) is not involved in carcinogenesis and tumor-suppressor genes located on 1p are considered to play an important role in tumor development. [source] Prognostic Significance of Matrix Metalloproteinase-7 (MMP-7) Expression at the Invasive Front in Gastric CarcinomaCANCER SCIENCE, Issue 3 2002Xiu Ping Liu To evaluate the clinicopathological significance of matrix metalloproteinase-7 (MMP-7) expression in gastric carcinoma, we investigated immunohistochemically MMP-7 expression in 214 gastric carcinomas, and examined its relations with the clinicopathologic parameters including patient prognosis. MMP-7 expressed predominantly in cancer cells, and MMP-7-positive tumor cells were preferentially found in deeply invading nests, especially at the invasive front. The mean MMP-7 labeling index (LI) at the invasive front was significantly higher in tumors invading or penetrating the muscularis propria and in stages II-IV than within the submucosal layer and in stage I, respectively (P<0.001). Statistical analysis revealed that MMP-7 LI at the invasive front was related to lymph node metastasis, vascular invasion, and lymphatic permeation, when all 214 cases were examined as one group (P<0.05 for all), and the cases with high MMP-7 expression at the invasive front showed significantly more unfavorable prognosis as compared with that of low MMP-7 expression tumors (P<0.01). Multivariate analysis revealed that TNM stage and MMP-7 expression status at the invasive front were independent prognostic factors (P=0.0017, relative risk (RR)=3.12; P=0.0019, RR=2.67, respectively). Our findings indicated that expression of MMP-7 at the invasive front is closely associated with local invasiveness, and might be a reliable prognostic marker for patients with gastric carcinoma. [source] 4368: Hypermethylation of tumour suppressor genes in ocular adnexal lymphomaACTA OPHTHALMOLOGICA, Issue 2010H MA Purpose Promoter hypermethylation occurs in various tumours, including ocular adnexal lymphomas (OAL), and is a mechanism by which tumour suppressor genes can be inactivated during tumourigenesis. This study aimed to investigate the levels of hypermethylation and specific genes that are hypermethylated in different subtypes of OAL using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and pryrosequencing. Methods DNA was extracted from formalin-fixed, paraffin-embedded tissues from 33 extra-marginal zone B-cell lymphomas (EMZL) and 37 non-EMZL. Using two MS-MLPA assays (MRC-Holland) the methylation status and copy number of 36 genes was detected. MS-MLPA results were validated using pyrosequencing. Results MLPA and pyrosequencing results were comparable with 75-100% concordancy. Ten common genes were hypermethylated in the EMZL and non-EMZL, diffuse large B-cell lymphomas (DLBCL) and mantle cell lymphomas (CDH13, DAPK1, ESR1, GATA5, IGSF4, PAX6, RAR,, THBS1, TIMP3, and WT1). In non-EMZLs, a greater number of genes showed hypermethylation when diagnosed in the orbit and patients had a poorer prognosis. Deletion of the 9p21 region was seen in 7/13 DLBCLs including the p14ARF, p15 and p16 genes. Conclusion Hypermethylation is a feature of OALs suggesting a role for epigenetic deregulation in OAL development. In non-EMZLs greater epigenetic deregulation may be indicative of poorer patient prognosis. We hypothesise that EMZL, DLBCL and mantle cell lymphomas share a similar epigenetic aetiology and that genes in the 9p21 region may be important to DLBCL development. Correlation of hypermethylation and copy number data with clinical presentation and follow-up could reveal biomarkers of diagnostic and prognostic value in OALs. [source] Bacillus Calmette-Guérin-pulsed dendritic cells stimulate natural killer T cells and ,,T cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007Michio Naoe Background: Immunotherapy with bacillus Calmette-Guérin (BCG) for bladder cancer is successful, although the precise mechanism is unclear. Natural killer (NK) cells are a candidate for BCG-activated killer cells, but the roles of other T lymphocytes, such as NKT cells and ,,T cells, are not fully understood. Mycobacterium tuberculosis is a potent activator of both NKT cells and ,,T cells. However, it is known that the patient's prognosis is good if there are increased numbers of dendritic cells (DCs) in the urine after BCG therapy. Therefore, we investigated whether DCs are matured by BCG and whether BCG-pulsed DCs stimulate NKT cells and ,,T cells. Methods: Naïve Pan T cells were isolated form peripheral blood mononuclear cells (PBMCs) and DCs were obtained by culturing CD14+ monocytes with granulocyte,macrophage colony-stimulating factor and interleukin-4. The DCs were pulsed with BCG and their maturation was measured by fluorescence-activated cell sorter analysis using the CD86 antibody. Naïve T lymphocytes were stimulated by coculture with BCG-pulsed DCs in vitro, followed by FACS analysis to estimate the ratio and activation of NKT cells and the ratio of ,,T cells. The 51Cr (chromium) release assay was used to estimate the cytotoxic activity of the stimulated T cells. Cytolytic proteins in the patient's PBMCs were measured during BCG therapy using semiquantitative reverse transcriptase-polymerase chain reaction. Results: The DCs were matured by BCG stimulation and the number of NKT cells and ,,T cells increased after culturing with BCG-pulsed DCs. The BCG-pulsed DCs also activated the NKT cells and ,,T cells. Also, the lymphocytes that were cocultured with the BCG-pulsed DCs showed unspecific cytotoxic activity against a bladder cancer cell line. Conclusion: Sensitization of NKT cells and ,,T cells by BCG-pulsed DCs might be one of the mechanisms of BCG immunotherapy. [source] Integrating the Principles of Evidence-Based Practice: Prognosis and the Metabolic SyndromeJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 5 2004APRN-C, Mary Jo Goolsby EdD Current health care trends and pressures have based decision making and practice of practitioners. Evidence-based practice has evolved in response to these trends. Evidence-based practice requires providers to be proficient in statistical analysis and critique of the evidence. This article user a hypothetical patient's prognostic concerns to depict a practitioner's integration of the principles of evidence-based practice as she considers clinical practice guidelines, expert opinion, and a prognostic study relative to her patient's prognosis. Statistical measures evident in a prognostic study, such as a absolute risk, baseline risk, relative risk, survival curves, and hazard ratios are defined. [source] The role of p53 in pigmentation, tanning and melanomaPIGMENT CELL & MELANOMA RESEARCH, Issue 5 2008Neil F. Box Summary p53 has a central role in skin pigmentation and may impact on melanoma at all stages, however, as it's mutation frequency in melanoma is low, it's role has been somewhat under-appreciated. During normal skin function, p53 in the keratinocyte is a transducer of the skin tanning signal and an essential component of what is effectively a keratinocyte-melanocyte signaling cycle that regulates skin pigmentation. It is clear that this cycle functions optimally in skin of dark pigmentation. When melanin biosynthesis is genetically disrupted in skin of white complexion, we propose that this cycle operates as a promoter of melanocyte proliferation. The cell autonomous function of p53 in melanocytes is not well described, however, the balance of the evidence suggests that p53 is an effective tumor suppressor and the myriad of mechanisms by which the p53 pathway may be dysregulated in tumors attests to it importance as a tumor suppressor. In this review, we outline the known mechanisms that impair p53 itself and its immediate regulators or target genes during melanomagenesis. Due to the importance of this pathway, it is clear that p53 disruptions may relate directly to a patient's prognosis. This pathway will continue to be a focus of investigation, particularly with respect to targeted experimental chemotherapeutics. [source] Prognostic factors of tracheobronchial mucoepidermoid carcinoma,15 years experienceRESPIROLOGY, Issue 2 2008Chien-Hung CHIN Background and objectives: Mucoepidermoid carcinoma of the tracheobronchial tree is a rare tumour which displays a variable degree of clinical aggressiveness and malignancy. The relationship between the patient's prognosis and the tumour's histological features and clinical behaviour is uncertain. The aim of this study was to identify the clinicopathological features and analyse the outcomes of patients with this type of cancer. Methods: A retrospective analysis of the medical records of patients diagnosed with mucoepidermoid carcinoma of the lung between 1991 and 2006 was conducted. Results: The study comprised 15 patients. Higher histological grade tumours had a higher proportion of squamoid cells (P = 0.019); the tumours of patients with lymph node metastases also had a higher proportion of squamoid cells than did the tumours of patients without lymph node metastases (P = 0.015). Patients with early stage tumours (stage IA, IB, IIB) had better outcomes (10-year survival rate = 87.5%), than did patients with late-stage tumours (stage IIIB, IV) (1-year survival rate = 28.6%; 2-year survival rate = 0%, P = 0.001). Patients with lower-grade tumours (grade 1 and grade 2) had better outcomes (1-year survival rate = 80%; 5-year survival rate = 57.1%) than did patients with higher-grade tumours (grade 3) (1-year survival rate = 20%, P = 0.035). Tumour staging was a significant independent predictor of survival on Cox proportional hazards analysis. Conclusions: The proportion of squamoid cells on tumour histology may be an indicator of the level of tumour malignancy. Tumour, node, metastasis staging is a significant determinant of prognosis in patients with tracheobronchial mucoepidermoid carcinoma. [source] Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopyNMR IN BIOMEDICINE, Issue 4 2010Beathe Sitter Abstract Absolute quantitative measures of breast cancer tissue metabolites can increase our understanding of biological processes. Electronic REference To access In vivo Concentrations (ERETIC) was applied to high resolution magic angle spinning MR spectroscopy (HR MAS MRS) to quantify metabolites in intact breast cancer samples. The ERETIC signal was calibrated using solutions of creatine and TSP. The largest relative errors of the ERETIC method were 8.4%, compared to 4.4% for the HR MAS MRS method using TSP as a standard. The same MR experimental procedure was applied to intact tissue samples from breast cancer patients with clinically defined good (n,=,13) and poor (n,=,16) prognosis. All samples were examined by histopathology for relative content of different tissue types and proliferation index (MIB-1) after MR analysis. The resulting spectra were analyzed by quantification of tissue metabolites (,-glucose, lactate, glycine, myo-inositol, taurine, glycerophosphocholine, phosphocholine, choline and creatine), by peak area ratios and by principal component analysis. We found a trend toward lower concentrations of glycine in patients with good prognosis (1.1,µmol/g) compared to patients with poor prognosis (1.9,µmol/g, p,=,0.067). Tissue metabolite concentrations (except for ,-glucose) were also found to correlate to the fraction of tumor, connective, fat or glandular tissue by Pearson correlation analysis. Tissue concentrations of ,-glucose correlated to proliferation index (MIB-1) with a negative correlation factor (,0.45, p,=,0.015), consistent with increased energy demand in proliferating tumor cells. By analyzing several metabolites simultaneously, either in ratios or by metabolic profiles analyzed by PCA, we found that tissue metabolites correlate to patients' prognoses and health status five years after surgery. This study shows that the diagnostic and prognostic potential in MR metabolite analysis of breast cancer tissue is greater when combining multiple metabolites (MR Metabolomics). Copyright © 2010 John Wiley & Sons, Ltd. [source] Erythropoietin for the treatment of anemia associated with hematological malignancyHEMATOLOGICAL ONCOLOGY, Issue 1 2001T. J. Littlewood Abstract Anemia is common in patients with hematological malignancy. Most patients will have their anemia attributed to the anemia of chronic disease. The anemia of chronic disease is caused by cytokine mediated suppression of erythropoiesis and low serum erythropoietin levels are found in the majority of patients with cancer. Many of these anemic patients will be symptomatic with fatigue. Data from many studies indicates that treatment of anemic patients with erythropoietin will increase their hemoglobin concentration, decrease transfusion need and also improve their quality of life. A recent study also suggests that improving the hemoglobin level may improve the patients' prognosis but this finding needs to be confirmed. Copyright © 2001 John Wiley & Sons, Ltd. [source] Nm23-H1 expression of metastatic tumors in the lymph nodes is a prognostic indicator of oral squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Yi-Fen Wang Abstract We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens. © 2007 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||