Poorer Disease-free Survival (poorer + disease-free_survival)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer

GENES, CHROMOSOMES AND CANCER, Issue 7 2006
Ling-Ming Tseng
Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various tumors, including breast cancer. However, it still remains unclear whether the alterations in mtDNA are related to the clinicopathological features and/or the prognosis in the breast cancer. We analyzed somatic mutations in the D-loop region, the common 4,977-bp deletion, and the copy number of mtDNA in breast cancer and paired nontumorous breast tissues from 60 Taiwanese patients. We found that 18 of the 60 (30%) breast cancers displayed somatic mutations in mtDNA D-loop region. The incidence of the 4,977-bp deletion in nontumorous breast tissues (47%) was much higher than that in breast cancers (5%). The copy number of mtDNA was significantly decreased in 38 of the 60 (63%) breast cancers as compared to their corresponding nontumorous breast tissues (P = 0.0008). The occurrence of D-loop mutations was associated with an older onset age (,50 years old, P = 0.042), and tumors that lacked expressions of estrogen receptor and progesterone receptor (P = 0.024). Patients with mtDNA D-loop mutation and breast cancer had significantly poorer disease-free survival than those without mutation, when assessed by Kaplan,Meier curves and log-rank test (P = 0.005). Multivariate Cox regression analysis indicated that a D-loop mutation is a significant marker that is independent of other clinical variables and that it can be used to assess the prognosis of patients. Our findings suggest that somatic mutations in mtDNA D-loop can be used as a new molecular prognostic indicator in breast cancer. © 2006 Wiley-Liss, Inc. [source]


Interaction of tumour biology and tumour burden in determining outcome after hepatic resection for colorectal metastases

HPB, Issue 2 2010
Dhanny Gomez
Abstract Aims:, To determine the outcome of colorectal liver metastasis (CRLM) patients based on tumour burden, represented by tumour number and size, and tumour biology as assessed by an inflammatory response to tumour (IRT) and margin positivity. Methods:, Data were collated from CRLM patients undergoing resection from January 1993 to March 2007. Patients were divided into: low (,3 metastases and/or ,3 cm); moderate (4,7 metastases and/or >3,,5 cm); and high (,8 metastases and/or >5 cm) tumour burden. Results:, Seven hundred and five patients underwent resection, of which 154 (21.8%), 262 (37.2%) and 289 (41.0%) patients were in the low, moderate and high tumour burden groups, respectively. The 5-year disease-free (P < 0.001) and overall (P < 0.001) survival were significantly different between the groups. IRT (P < 0.001), extent of resection (P < 0.001) and margin (P < 0.001) also differed between the groups. Sub-group analysis revealed that IRT was the only adverse predictor for disease-free and overall survival in the low group. In the moderate group, IRT predicted poorer disease-free survival on multi-variate analysis. In the high group, R1 resection and transfusion were predictors of poorer disease-free survival and age ,65 years, R1 resection and IRT were adverse predictors of overall survival. Conclusion:, Resection margin influenced the outcome of patients with high tumour burden, hence the importance of achieving clear margins. IRT influenced the outcome of patients with less aggressive disease. [source]


Effect of type of resection on outcome of hepatic resection for colorectal metastases,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2007
R. J. B. Finch
Background: Non-anatomical liver resections have become more common in the management of colorectal liver metastases. This study examined survival and patterns of recurrence following surgery for colorectal liver metastases. Methods: Data were collected prospectively on all patients who had hepatic surgery for colorectal liver metastases at St James' University Hospital, Leeds between 1993 and May 2003, and analysed with respect to type of resection. Results: A total of 96 patients underwent non-anatomical liver resection, 280 patients had an anatomical resection, and 108 patients had a combined procedure. There was no significant difference in overall survival between the anatomical and non-anatomical groups (hazard ratio 1·14 (95 per cent confidence interval 0·60 to 2·17); P = 0·691). Intrahepatic recurrence was significantly less common in the anatomical group, whereas morbidity and mortality rates were lower in the non-anatomical group. On multivariable analysis, multiple metastases and poorer primary T stage predicted poorer overall survival and a positive resection margin predicted poorer disease-free survival. Conclusion: Non-anatomical resection can be performed with lower rates of surgical morbidity and mortality than anatomical resection, and does not disadvantage the patient in terms of overall survival. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]


Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer

CANCER SCIENCE, Issue 3 2007
Sun Lee
Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low-oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease-free survival (relative risk, 6.1; 95% confidence interval, 1.3,28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9 expression (P = 0.001), suggesting that CA9-expressing tumor cells had a higher metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with positive tumor cells observed predominantly in the area away from the blood vessels. In contrast, CA12 expression was observed in only 29 of 74 primary tumors (39%), without a specific pattern. These findings indicate that expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. Selective application of new treatment modalities based on CA9 expression to prevent LN metastases may improve overall treatment outcome in patients with uterine cervical cancer. (Cancer Sci 2007; 98: 329,333) [source]


Microsatellite and chromosomal stable colorectal cancers demonstrate poor immunogenicity and early disease recurrence

COLORECTAL DISEASE, Issue 6 2009
A. Banerjea
Abstract Objective, Colorectal cancers may demonstrate chromosomal instability (CSI) or microsatellite instability (MSI-H). A third group of microsatellite and chromosome stable (MACS) colorectal cancer has been described more recently. Patients with MSI-H colorectal cancers demonstrate improved outcome and a pronounced inflammatory infiltrate. Enhanced host immune response and increased immunogenicity might explain these observations. This study aims to further characterize colorectal cancer immunogenicity. Method, Microsatellite stability status was determined in resected tumour samples. Microsatellite stable (MSS) tumour samples were stratified by DNA ploidy status, as determined by flow cytometry into aneuploid MSS (CSI) and diploid MSS (MACS) cancers. Lymphocyte proliferation, quantified by bromodeoxyuridine incorporation assays assessed tumour protein immunogenicity and ELISA assays quantified inflammatory cytokine release. Kaplan,Meier survival curves and multivariate analyses were used to determine prognostic value. Results, Patients with MSI-H colorectal cancer had improved outcome but those with MACS cancers undergoing curative surgery had significantly poorer disease-free survival (P = 0.002). The MACS phenotype was an independent predictor of poor outcome (HR = 2.44, 1.33,4.47, P = 0.004). Lymphocyte proliferation assays confirmed enhanced immunogenicity of MSI-H proteins and reduced immunogenicity of MACS proteins (P < 0.0001). In vitro levels of IFN-, (P = 0.004) and IL-18 (P < 0.0001) mirrored these differences in lymphocyte activity. Conclusions, Stratification of colorectal cancer by MSI and ploidy status may have prognostic value in patients undergoing curative surgery. MSI-H cancers display enhanced immunogenic properties but the immune response to MACS cancers appears to be absent and this may contribute to their poor prognosis. [source]