Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas

Jamieson, Nigel B.; Glen, Paul; McMillan, Donald C.; McKay, Colin; Carter, R; Imrie, C. W.

doi:10.1038/sj.bjc.6602305

Cited by 134 publications

(105 citation statements)

References 17 publications

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“…The basis of the discrepancies between the present and previous studies is not clear. Nevertheless, the results of the present study are consistent with previous pre-/postoperative C-reactive protein findings in colorectal, pancreatic and bladder cancer Jamieson et al, 2005;Hilmy et al, 2005). Furthermore, if there were to be a significant conversion rate from a systemic inflammatory state (C-reactive protein 410 mg l À1 ) to a noninflammatory state (C-reactive protein p10 mg l À1 ) following resection then the prognostic value of markers of the systemic inflammatory response would be significantly degraded.…”

Section: Discussionsupporting

confidence: 90%

“…It has recently become clear that the systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is an important prognostic factor independent of tumour stage in patients undergoing potentially curative surgery for a number of solid tumours including colorectal (Nielsen et al, 2000;McMillan et al, 2003); gastro-oesophageal (Ikeda et al, 2003;Crumley et al, 2006), pancreatic (Jamieson et al, 2005) and urinary bladder (Hilmy et al, 2005) cancers.…”

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confidence: 99%

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The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer

et al. 2006

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The systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is a stageindependent prognostic factor in patients undergoing curative nephrectomy for localised renal cancer. However, it is not clear whether the systemic inflammatory response arises from the tumour per se or as a result of an impaired immune cytokine response. The aim of the present study was to examine C-reactive protein, interleukin-6 and interleukin-10 concentrations before and following curative resection of renal cancer. Sixty-four patients with malignant renal disease and 12 with benign disease, undergoing resection were studied. Preoperatively, a blood sample was collected for routine laboratory analysis with a further sample stored before analysis of interleukin-6 and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique. The blood sampling procedure and analyses were repeated at approximately 3 months following resection. Circulating concentrations of both interleukin-6 and interleukin (Pp0.01) were higher and a greater proportion were elevated (Po0.05) in malignant compared with benign disease. The renal cancer patients were grouped according to whether they had evidence of a systemic inflammatory response. In the inflammatory group T stage was higher (Po0.01), both interleukin-6 and interleukin-10 concentrations were higher (Po0.001) and elevated (Po0.10) compared with the non-inflammatory group. Tumour volume was weakly correlated with C-reactive protein (r 2 ¼ 0.20, P ¼ 0.002), interleukin-6 (r 2 ¼ 0.20, P ¼ 0.002) and interleukin-10 (r 2 ¼ 0.24, P ¼ 0.001). Following nephrectomy the proportion of patients with elevated C-reactive protein, interleukin-6 and interleukin-10 concentrations did not alter significantly. An elevated preoperative C-reactive protein was associated with increased tumour stage, interleukin-6 and interleukin-10 concentrations. However, resection of the primary tumour did not appear to be associated with significant normalisation of circulating concentrations of C-reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of systemic inflammatory response is unlikely to be solely be determined by the tumour itself, but may be as a result of an impaired immune cytokine response in patients with renal cancer.

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Section: Discussionsupporting

confidence: 90%

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The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer

et al. 2006

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“…Indeed, the systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, has been shown to be a disease-independent prognostic factor in a variety of tumours, when resections are carried out with curative intent (McMillan et al, 2003;Hilmy et al, 2005;Jamieson et al, 2005).…”

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An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer

et al. 2006

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There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of tumours. The aim of the present study was to examine the relationship between clinicopathological status, preoperative C-reactive protein concentration and cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. One hundred and twenty patients attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow, who were selected for potentially curative surgery, were included in the study. Laboratory measurements of haemoglobin, white cell, lymphocyte and platelet counts, albumin and C-reactive protein were carried out at the time of diagnosis. All patients underwent en-bloc resection with lymphadenectomy and survived at least 30 days following surgery. On multivariate analysis, only the positive to total lymph node ratio (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.44 -2.84, Po0.001) and preoperative C-reactive protein concentration (HR 3.53, 95% CI 1.88 -6.64, Po0.001) were independent predictors of cancer-specific survival. The patient group with no evidence of a preoperative systemic inflammatory response (C-reactive protein p10 mg l À1 ) had a median survival of 79 months compared with 19 months in the elevated systemic inflammatory response group (Po0.001). The results of the present study indicate that in patients selected to undergo potentially curative resection for gastro-oesophageal cancer, the presence of an elevated preoperative C-reactive protein concentration is an independent predictor of poor cancer-specific survival.

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“…Furthermore, the presence of systemic inflammation is recognised as a predictor of worse outcome in patients with malignancy. Raised levels of CRP, an acute phase protein (APP), and proinflammatory cytokines, especially IL-6, are strong, independent prognostic factors for survival in a number of tumour types including breast, renal cell, prostate and colorectal cancers (Jamieson et al, 2005;Al Murri et al, 2006;Crozier et al, 2006;Lamb et al, 2006;McArdle et al, 2006). IL-6 has further been implicated in promotion of tumour growth, invasion and metastasis, and the development of drug resistance (Kato et al, 1998;Esper and Harb, 2005).…”

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Downregulation of drug transport and metabolism in mice bearing extra-hepatic malignancies

et al. 2007

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There is increasing evidence of a systemic inflammatory response associated with malignancy, which may have an impact on both drug disposition and resistance to cytotoxic therapy. The impact of inflammation on drug disposition was studied in mice bearing a number of common tumour xenografts. C57BL/6 mice were inoculated with tumour xenografts. Hepatic expressions of Cyp3a and drug transporters were analysed at the mRNA, protein and functional levels (Cyp3a only). Circulating serum cytokines and the hepatic expression of acute phase proteins (APPs) were measured. Intratumoral levels of multidrug resistance genes were determined. Tumour xenografts elicited an inflammatory response that coincided with repression in hepatic Cyp3a11 activity and the expression of a number of hepatic drug transporters. With tumour growth, a progressive reduction in hepatic Cyp3a11 mRNA expression was seen. Conversely, an increase in the hepatic APP expression and circulating interleukin (IL)-6 levels was observed. Furthermore, a correlation was seen between increased intratumoral expression of the multidrug resistance gene, Mdr1a, and levels of circulating IL-6. Malignancy results in reduced hepatic drug disposition that correlates with an associated inflammatory response. Reduction of inflammation may improve the clinical outcome for patients receiving chemotherapeutic agents that undergo hepatic metabolism.

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Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas

Cited by 134 publications

References 17 publications

The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer

The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer

An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer

Downregulation of drug transport and metabolism in mice bearing extra-hepatic malignancies

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