Skip to main content
Erschienen in: Journal of Gastrointestinal Surgery 5/2020

10.12.2019

Peri-tumoural CD3+ Inflammation and Neutrophil-to-Lymphocyte Ratio Predict Overall Survival in Patients Affected by Colorectal Liver Metastases Treated with Surgery

verfasst von: Matteo Maria Cimino, Matteo Donadon, Simone Giudici, Carlotta Sacerdote, Luca Di Tommaso, Massimo Roncalli, Domenico Mavilio, Kelly Hudspeth, Guido Torzilli

Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Systemic and local inflammation plays an important role in many cancers and colorectal liver metastases (CRLM). While the role of local immune response mediated by CD3+ tumour-infiltrating lymphocytes is well-established, new evidence on systemic inflammation and cancer, such as neutrophil-lymphocyte ratio (NLR), is emerging. The aim of this study is to seek an association between the CD3+ lymphocytes and NLR with patients’ prognosis and possibly stratifying it accordingly.

Methods

From January 2005 to January 2013, 128 consecutive patients affected by CRLM and treated with chemotherapy and surgery were included in the study. Different cutoff levels were calculated with ROC curves for each of the biomarkers, and their relative outcome in terms of overall survival (OS) and recurrence-free survival (RFS) was determined. Associating the two biomarkers, three risk groups were determined: low risk (two protective biomarkers), intermediate risk (one protective biomarker) and high risk (no protective biomarker).

Results

After a median follow-up of 45 months, median OS and RFS were 44 and 9 months, respectively. For OS, 29 (22.66%), 59 (46.09%) and 40 (31.25%) patients were in the low, intermediate and high-risk groups, respectively. Adjusted Cox regression analysis showed an increased risk of death in the intermediate group (HR 2.67 p = 0.007 95% CI 1.31–5.42) and high-risk group (HR 2.86 p = 0.005 95% CI 1.37–5.99) compared to the low-risk group (reference).

Conclusion

Systemic and local immune response index allows stratification of patients in different OS and RFS risk groups.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011; 61:69–90.CrossRef Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011; 61:69–90.CrossRef
2.
Zurück zum Zitat Manfredi S, Lepage C, Hatem C, et al. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 2006; 244:254–9.CrossRef Manfredi S, Lepage C, Hatem C, et al. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 2006; 244:254–9.CrossRef
3.
Zurück zum Zitat Cummings LC, Payes JD, Cooper GS. Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer. 2007; 109:718–26.CrossRef Cummings LC, Payes JD, Cooper GS. Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer. 2007; 109:718–26.CrossRef
4.
Zurück zum Zitat Leporrier J, Maurel J, Chiche L, et al. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg 2006; 93:465–74.CrossRef Leporrier J, Maurel J, Chiche L, et al. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg 2006; 93:465–74.CrossRef
5.
Zurück zum Zitat Dexiang Z, Li R, Ye W, et al. Outcome of patients with colorectal liver metastasis: analysis of 1,613 consecutive cases. Ann Surg Oncol 2012; 19:2860–8.CrossRef Dexiang Z, Li R, Ye W, et al. Outcome of patients with colorectal liver metastasis: analysis of 1,613 consecutive cases. Ann Surg Oncol 2012; 19:2860–8.CrossRef
6.
Zurück zum Zitat Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long term survival following liver resection for hepatic colorectal metastases. Annals of surgery. 2002; 235:759–66.CrossRef Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long term survival following liver resection for hepatic colorectal metastases. Annals of surgery. 2002; 235:759–66.CrossRef
7.
Zurück zum Zitat Fong Y, Salo J. Surgical therapy of hepatic colorectal metastasis. Semin Oncol. 1999; 26:514–23.PubMed Fong Y, Salo J. Surgical therapy of hepatic colorectal metastasis. Semin Oncol. 1999; 26:514–23.PubMed
8.
Zurück zum Zitat Karanjia ND, Lordan JT, Fawcett WJ, et al. Survival and recurrence after neo-adjuvant chemotherapy and liver resection for colorectal metastases: a ten year study. Eur J Surg Oncol. 2009 ;35:838-43.CrossRef Karanjia ND, Lordan JT, Fawcett WJ, et al. Survival and recurrence after neo-adjuvant chemotherapy and liver resection for colorectal metastases: a ten year study. Eur J Surg Oncol. 2009 ;35:838-43.CrossRef
9.
Zurück zum Zitat De Jong MC, Pulitano C, Ribero D, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009; 250:440–8.PubMed De Jong MC, Pulitano C, Ribero D, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009; 250:440–8.PubMed
10.
Zurück zum Zitat McMillan DC. An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer. Proc Nutr Soc. 2008; 67:257–62.CrossRef McMillan DC. An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer. Proc Nutr Soc. 2008; 67:257–62.CrossRef
11.
Zurück zum Zitat McMillan DC, Crozier JE, Canna K, Angerson WJ, McArdle CS. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007; 22:881–6.CrossRef McMillan DC, Crozier JE, Canna K, Angerson WJ, McArdle CS. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007; 22:881–6.CrossRef
12.
Zurück zum Zitat Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420:860–7.CrossRef Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420:860–7.CrossRef
13.
Zurück zum Zitat Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008; 454:436–44.CrossRef Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008; 454:436–44.CrossRef
14.
Zurück zum Zitat Halama N, Michel S, Kloor P, et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 2011 71:5670-7.CrossRef Halama N, Michel S, Kloor P, et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 2011 71:5670-7.CrossRef
15.
Zurück zum Zitat Katz SC, Bamboat ZM, Maker AV, et al. Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases. Ann Surg Oncol. 2013 ; 20:946–55.CrossRef Katz SC, Bamboat ZM, Maker AV, et al. Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases. Ann Surg Oncol. 2013 ; 20:946–55.CrossRef
16.
Zurück zum Zitat Neofytou K, Smyth EC, Giakoustidis A, et al. The preoperative lymphocyte-to-monocyte ratio is prognostic of clinical outcomes for patients with liver-only colorectal metastases in the neoadjuvant setting. Ann Surg Oncol. 2015 ; 22:4353–62.CrossRef Neofytou K, Smyth EC, Giakoustidis A, et al. The preoperative lymphocyte-to-monocyte ratio is prognostic of clinical outcomes for patients with liver-only colorectal metastases in the neoadjuvant setting. Ann Surg Oncol. 2015 ; 22:4353–62.CrossRef
17.
Zurück zum Zitat Neofytou K, Smyth EC, Giakoustidis A, et al. Elevated platelet-to-lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor. Med oncol. 2014 ; 31:239–48.CrossRef Neofytou K, Smyth EC, Giakoustidis A, et al. Elevated platelet-to-lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor. Med oncol. 2014 ; 31:239–48.CrossRef
18.
Zurück zum Zitat Neal CP, Cairns V, Jones MJ, et al. Prognostic performance of inflammation as prognostic indices in patients with resectable colorectal liver metastases. Med Oncol. 2015; 32:144–55.CrossRef Neal CP, Cairns V, Jones MJ, et al. Prognostic performance of inflammation as prognostic indices in patients with resectable colorectal liver metastases. Med Oncol. 2015; 32:144–55.CrossRef
19.
Zurück zum Zitat Chang Z, Zheng J, Ma Y, et al . The neutrophil-to-lymphocyte ratio as a predictor for recurrence of colorectal liver metastases following radiofrequency ablation. Med Oncol. 2014 ;31:855.CrossRef Chang Z, Zheng J, Ma Y, et al . The neutrophil-to-lymphocyte ratio as a predictor for recurrence of colorectal liver metastases following radiofrequency ablation. Med Oncol. 2014 ;31:855.CrossRef
20.
Zurück zum Zitat Zeman M, Maciejewski A, Poltorak S, et al. Evaluation of outcomes and treatment safety of patients with metastatic colorectal cancer to the liver with estimation of prognostic factors. Pol Przegl Chir. 2013; 85:333–9.CrossRef Zeman M, Maciejewski A, Poltorak S, et al. Evaluation of outcomes and treatment safety of patients with metastatic colorectal cancer to the liver with estimation of prognostic factors. Pol Przegl Chir. 2013; 85:333–9.CrossRef
21.
Zurück zum Zitat Kishi Y, Kopetz S, Chun YS, et al. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol. 2009; 16:614–22.CrossRef Kishi Y, Kopetz S, Chun YS, et al. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol. 2009; 16:614–22.CrossRef
22.
Zurück zum Zitat Belgihiti J, Clavien PA, Gadzijev, et al. The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000;2:333–9CrossRef Belgihiti J, Clavien PA, Gadzijev, et al. The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000;2:333–9CrossRef
23.
Zurück zum Zitat Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004; 240:205–13.CrossRef Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004; 240:205–13.CrossRef
24.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumours. European Organisation for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 2; 92:205–16.CrossRef Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumours. European Organisation for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 2; 92:205–16.CrossRef
25.
Zurück zum Zitat Donadon M, Hudspeth K, Cimino M. Increased infiltration of natural killer cells and T cells in colorectal liver metastases improves patient overall survival. J Gastrointest Surg. 2017 ;21:1226-1236CrossRef Donadon M, Hudspeth K, Cimino M. Increased infiltration of natural killer cells and T cells in colorectal liver metastases improves patient overall survival. J Gastrointest Surg. 2017 ;21:1226-1236CrossRef
26.
Zurück zum Zitat Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140:883–99.CrossRef Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140:883–99.CrossRef
27.
Zurück zum Zitat Gomez D, Morris-Stiff G, Wyatt J, et al. Surgical technique and systemic inflammation influences long-term disease-free survival following hepatic resection for colorectal metastasis. J Surg Oncol. 2008; 98:371–6.CrossRef Gomez D, Morris-Stiff G, Wyatt J, et al. Surgical technique and systemic inflammation influences long-term disease-free survival following hepatic resection for colorectal metastasis. J Surg Oncol. 2008; 98:371–6.CrossRef
28.
Zurück zum Zitat Kusumanto YH, Dam WA, Hospers GA, et al. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003; 6:283–7.CrossRef Kusumanto YH, Dam WA, Hospers GA, et al. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003; 6:283–7.CrossRef
29.
Zurück zum Zitat Fridlender ZG, Sun J, Kim S, et al. Polarisation of tumour-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009; 16:183–94.CrossRef Fridlender ZG, Sun J, Kim S, et al. Polarisation of tumour-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009; 16:183–94.CrossRef
30.
Zurück zum Zitat Turner N, Wong HL, Templeton A, et al. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria. Int J Cancer. 2016 ; 138:671–8.CrossRef Turner N, Wong HL, Templeton A, et al. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria. Int J Cancer. 2016 ; 138:671–8.CrossRef
31.
Zurück zum Zitat Moles A, Murphy L, Wilson CL, et al. A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse. J Hepatol. 2014 ;60:782-91.CrossRef Moles A, Murphy L, Wilson CL, et al. A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse. J Hepatol. 2014 ;60:782-91.CrossRef
32.
Zurück zum Zitat Woodfin A, Voisin MB, Beyrau M, et al. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol. 2011 ;12:761-9.CrossRef Woodfin A, Voisin MB, Beyrau M, et al. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol. 2011 ;12:761-9.CrossRef
33.
Zurück zum Zitat Yaghoubi N, Soltani A, Ghazvini K, et al. PD-1/PD-L1 blockade as a novel treatment for colorectal cancer. Biomed Pharmacother. 2019 110:312–18.CrossRef Yaghoubi N, Soltani A, Ghazvini K, et al. PD-1/PD-L1 blockade as a novel treatment for colorectal cancer. Biomed Pharmacother. 2019 110:312–18.CrossRef
34.
Zurück zum Zitat Lipson EJ, Sharfman WH, Drake CG et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 2013; 19:462–8.CrossRef Lipson EJ, Sharfman WH, Drake CG et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 2013; 19:462–8.CrossRef
35.
Zurück zum Zitat Mlecnik B, Van den Eynde M, Bindea G et al. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival. J Natl Cancer Inst. 2018 ;110:97-108CrossRef Mlecnik B, Van den Eynde M, Bindea G et al. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival. J Natl Cancer Inst. 2018 ;110:97-108CrossRef
36.
Zurück zum Zitat Mao R, Zhao JJ, Bi XY, et al. A low neutrophil-to-lymphocyte ratio before preoperative chemotherapy predicts good outcomes after the resection of colorectal liver metastases. J Gastrointest Surg 2019 23:563–70.CrossRef Mao R, Zhao JJ, Bi XY, et al. A low neutrophil-to-lymphocyte ratio before preoperative chemotherapy predicts good outcomes after the resection of colorectal liver metastases. J Gastrointest Surg 2019 23:563–70.CrossRef
37.
Zurück zum Zitat Dupré A, Berhane S, Chan AWH, et al. Multicentre validation of a clinical prognostic score integrating the systemic inflammatory response to the host for patients treated with curative-intent for colorectal liver metastases: The Liverpool score. Eur J Surg Oncol. 2019 ;45:999-1004.CrossRef Dupré A, Berhane S, Chan AWH, et al. Multicentre validation of a clinical prognostic score integrating the systemic inflammatory response to the host for patients treated with curative-intent for colorectal liver metastases: The Liverpool score. Eur J Surg Oncol. 2019 ;45:999-1004.CrossRef
38.
Zurück zum Zitat Wu Y, Li C, Zhao J et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict chemotherapy outcomes and prognosis in patients with colorectal cancer and synchronous liver metastasis. World J Surg Oncol. 2016 ;14: 1044-9. Wu Y, Li C, Zhao J et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict chemotherapy outcomes and prognosis in patients with colorectal cancer and synchronous liver metastasis. World J Surg Oncol. 2016 ;14: 1044-9.
39.
Zurück zum Zitat Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 14:1208–15.CrossRef Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 14:1208–15.CrossRef
Metadaten
Titel
Peri-tumoural CD3+ Inflammation and Neutrophil-to-Lymphocyte Ratio Predict Overall Survival in Patients Affected by Colorectal Liver Metastases Treated with Surgery
verfasst von
Matteo Maria Cimino
Matteo Donadon
Simone Giudici
Carlotta Sacerdote
Luca Di Tommaso
Massimo Roncalli
Domenico Mavilio
Kelly Hudspeth
Guido Torzilli
Publikationsdatum
10.12.2019
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Surgery / Ausgabe 5/2020
Print ISSN: 1091-255X
Elektronische ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-019-04458-9

Weitere Artikel der Ausgabe 5/2020

Journal of Gastrointestinal Surgery 5/2020 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.