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Venturino A, Colloca GA. Prognostic Effect of CEA Cut-Off in Patients with Resectable Colorectal Liver Metastases: A Meta-Analysis and Meta-Regression. J Gastrointest Cancer 2025; 56:117. [PMID: 40358861 DOI: 10.1007/s12029-025-01244-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/04/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND Although preoperative carcinoembryonic antigen (CEA) is a variable used in most prognostic scores assessing the outcome of patients with colorectal liver metastases (CRLM) undergoing resection, it is unclear what the optimal cut-off is or in which patient subgroups CEA is most relevant. The purpose of this study is to evaluate the prognostic effect of CEA in resected CRLM patients and to explore in which subgroups CEA is most closely associated with overall survival (OS). METHODS A systematic literature search was performed, selecting studies that evaluated a relationship between preoperative CEA and OS in patients undergoing CRLM radical surgery. A meta-analysis assessed the overall effect size of the relationship on the selected study cohorts, based on CEA cut-off. An evaluation of 21 baseline variables was performed to explore their possible effect on the relationship between CEA and OS. RESULTS The study confirms a significant negative prognostic effect of increased CEA on OS (HR 1.46, CI 1.30-1.65), but heterogeneity among studies is significant. The effect is consistent for all CEA cut-offs, although the relationship tends to weaken in more recent studies for cut-offs < 10 ng/mL. Meta-regressions also suggest that the prognostic effect may be more pronounced in the elderly. In addition, the effect of CEA ≥ 20 ng/mL on OS appears significantly reduced in the subgroup with mutated RAS carcinoma. CONCLUSIONS For patients with resectable CRLM, the CEA cut-off should be increased to 20 ng/mL, and evaluation in prospective studies of the more pronounced negative prognostic effect of preoperative CEA in the elderly and wild-type RAS CRLM patients is recommended.
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Affiliation(s)
| | - Giuseppe A Colloca
- Oncologia Medica & Innovation, Via Aicardi n. 37, I-18100, Imperia, Italy
- U. O. Oncologia Territoriale, AUSL Bologna, Bologna, Italy
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Mei P, Huang L, Lin L, Chen Y, Guo X. The prognostic utility of the ratio of lymphocyte to monocyte in patients with metastatic colorectal cancer: a systematic review and meta-analysis. Front Oncol 2025; 15:1394154. [PMID: 39963108 PMCID: PMC11830611 DOI: 10.3389/fonc.2025.1394154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 01/07/2025] [Indexed: 02/20/2025] Open
Abstract
Background Although advancements in treatment have resulted in improved overall outcomes for patients diagnosed with colorectal cancer, the prognosis remains unfavorable for individuals with metastatic colorectal cancer (mCRC). The association between lymphocyte/monocyte ratio (LMR) and clinical outcomes in mCRC patients is a subject of controversy. To systematically evaluate the correlation between LMR and prognostic factors in individuals with mCRC, we conducted this meta-analysis. Methods The databases PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for all relevant studies from their inception until October 26, 2024. Study selection was conducted based on predetermined inclusion and exclusion criteria. The primary outcomes of interest included prognosis measures such as overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and cancer-specific survival (CSS) in patients with metastatic colorectal cancer. Random-effects models or fixed-effects models were used to determine the pooled risk ratio (HR) and corresponding 95% confidence interval (CI) for each outcome indicator. Additionally, the pooled odds ratio (OR) and its corresponding 95% CI were calculated for LMR and clinicopathological characteristics. Results Fourteen studies involving 3,089 patients were included in the analysis. The pooled analysis found that high LMR was correlated with better OS (HR: 0.55, 95% CI: 0.49-0.62, p<0.00001), PFS (HR: 0.68, 95% CI: 0.57-0.81, p<0.0001) and CSS(HR: 0.55, 95% CI: 0.32-0.95, p=0.03),The prognostic value of high LMR values for DFS(HR: 0.93, 95% CI: 0.78-1.12, p=0.46) in patients with metastatic rectal cancer was not found to be significant. We performed subgroup analyses based on study characteristics to confirm the robustness of our findings. Further clinicopathological analysis showed no significant difference between patients with elevated LMR and those without elevated LMR. Conclusions In conclusion, the results demonstrate a robust correlation between elevated LMR levels and a favorable prognosis in terms of overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) among patients diagnosed with metastatic colorectal cancer. However, further high-quality prospective studies are warranted to validate our findings since the majority of current investigations have relied on retrospective study designs. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024496467, identifier CRD42024496467.
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Affiliation(s)
- Pingping Mei
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Li Huang
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lu Lin
- Anorectal Department, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Yan Chen
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiutian Guo
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Yuan C, Zeng L, Duan H, Suksatit B. Meta-analysis of the prognostic value of serum carcinoembryonic antigen in patients with colorectal cancer liver metastases after hepatectomy. Eur J Cancer Prev 2024; 33:334-346. [PMID: 37997904 DOI: 10.1097/cej.0000000000000859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023]
Abstract
OBJECTIVES Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. This meta-analysis was aimed at evaluating whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cutoff date of 27 February 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS This meta-analysis included 36 studies involving a total of 11 143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS: HR = 1.61, 95% CI = 1.49-1.75, P < 0.001) and recurrence-free survival (RFS: HR = 1.27, 95% CI = 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor overall survival (OS: HR = 2.66, 95% CI = 2.10-3.38, P < 0.001). CONCLUSION High preoperative and postoperative serum CEA levels in patients with CRCLM were significantly associated with poor prognosis, independent of treatment modality, mode of analysis, case origin, and cutoff value classification.
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Affiliation(s)
- Chenzhao Yuan
- Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand
| | - Lumin Zeng
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Hongxiang Duan
- Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand
- School of Nursing, Chengdu University, Chengdu, China
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Tang F, Huang CW, Tang ZH, Lu SL, Bai T, Huang Q, Li XZ, Zhang B, Wu FX. Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis. World J Gastrointest Surg 2023; 15:2890-2906. [PMID: 38222018 PMCID: PMC10784827 DOI: 10.4240/wjgs.v15.i12.2890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/03/2023] [Accepted: 11/28/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.
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Affiliation(s)
- Fan Tang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Cheng-Wen Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Hong Tang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shao-Long Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qing Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xing-Zhi Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bin Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of High-Incidence-Tumor Prevention & Treatment, Ministry of Education, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Plahuta I, Mencinger M, Peruš I, Magdalenić T, Turk Š, Brumec A, Potrč S, Ivanecz A. Ranking as a Procedure for Selecting a Replacement Variable in the Score Predicting the Survival of Patients Treated with Curative Intent for Colorectal Liver Metastases. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2003. [PMID: 38004052 PMCID: PMC10673064 DOI: 10.3390/medicina59112003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/04/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023]
Abstract
Background and Objectives: The issue of a missing variable precludes the external validation of many prognostic models. For example, the Liverpool score predicts the survival of patients undergoing surgical therapy for colorectal liver metastases, but it includes the neutrophil-lymphocyte ratio, which cannot be measured retrospectively. Materials and Methods: We aimed to find the most appropriate replacement for the neutrophil-lymphocyte ratio. Survival analysis was performed on data representing 632 liver resections for colorectal liver metastases from 2000 to 2020. Variables associated with the Liverpool score, C-reactive protein, albumins, and fibrinogen were ranked. The rankings were performed in four ways: The first two were based on the Kaplan-Meier method (log-rank statistics and the definite integral IS between two survival curves). The next method of ranking was based on univariate and multivariate Cox regression analyses. Results: The ranks were as follows: the radicality of liver resection (rank 1), lymph node infiltration of primary colorectal cancer (rank 2), elevated C-reactive protein (rank 3), the American Society of Anesthesiologists Classification grade (rank 4), the right-sidedness of primary colorectal cancer (rank 5), the multiplicity of colorectal liver metastases (rank 6), the size of colorectal liver metastases (rank 7), albumins (rank 8), and fibrinogen (rank 9). Conclusions: The ranking methodologies resulted in almost the same ranking order of the variables. Elevated C-reactive protein was ranked highly and can be considered a relevant replacement for the neutrophil-lymphocyte ratio in the Liverpool score. These methods are suitable for ranking variables in similar models for medical research.
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Affiliation(s)
- Irena Plahuta
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Matej Mencinger
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Institute of Mathematics, Physics and Mechanics, Jadranska 19, 1000 Ljubljana, Slovenia
| | - Iztok Peruš
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Faculty of Natural Science and Engineering, University of Ljubljana, Aškerčeva cesta 12, 1000 Ljubljana, Slovenia
| | - Tomislav Magdalenić
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Špela Turk
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Aleks Brumec
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Stojan Potrč
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Arpad Ivanecz
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
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Li Y, Xu T, Wang X, Jia X, Ren M, Wang X. The prognostic utility of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with colorectal liver metastasis: a systematic review and meta-analysis. Cancer Cell Int 2023; 23:39. [PMID: 36855112 PMCID: PMC9976405 DOI: 10.1186/s12935-023-02876-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 02/17/2023] [Indexed: 03/02/2023] Open
Abstract
The neutrophil-to-lymphocyte ratio is used to reflect body's inflammatory status with prognostic value in different cancers. We aimed to investigate the influence of preoperative NLR in the prognosis of CRLM patients receiving surgery using meta-analysis. Data in Cochrane Library, PubMed, Embase, and Web of Science databases created before October 2022 were recruited. Meta-analysis was carried out with RevMan 5.3 and Stata16 software, and the primary outcome indicators included overall survival (OS), and secondary outcome indicators included disease-free survival (DFS) and relapse-free survival (RFS). The pooled risk ratio (HR) and 95% confidence interval (CI) for each outcome indicator were determined using random-effects models or fixed-effects models. The pooled odds ratio (OR) and corresponding 95% confidence intervals (CI) for NLR and clinicopathological characteristics were determined with a fixed-effects model. 18 papers published between 2008 and 2022 (3184 patients in total) were included. The pooled analysis found that high preoperative NLR was correlated with poor OS (multivariate HR = 1.83, 95% CI = 1.61-2.08, p < 0.01), DFS (multivariate HR = 1.78, 95% CI = 1.16-2.71, p < 0.01) and RFS (multivariate HR = 1.46, 95% CI = 1.15-1.85, p < 0.01), but NLR was not related to clinicopathological features of CRLM patients correlation. In conclusion, NLR is an independent risk factor for poor prognosis in patients with CRLM. More large-scale clinical researches are required in the future to demonstrate the inclusion of preoperative NLR as a prognostic indicator for CRLM patients to guide postoperative adjuvant chemotherapy.
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Affiliation(s)
- Yanqing Li
- grid.462400.40000 0001 0144 9297Graduate School of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, 014000 China
| | - Tianxiang Xu
- grid.440229.90000 0004 1757 7789Abdominal Tumor Surgery, Center of Tumor, Inner Mongolia People’s Hospital, Hohhot, 010017 China
| | - Xin Wang
- grid.462400.40000 0001 0144 9297Graduate School of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, 014000 China
| | - Xiangdong Jia
- grid.440229.90000 0004 1757 7789Abdominal Tumor Surgery, Center of Tumor, Inner Mongolia People’s Hospital, Hohhot, 010017 China
| | - Meng Ren
- grid.440229.90000 0004 1757 7789Abdominal Tumor Surgery, Center of Tumor, Inner Mongolia People’s Hospital, Hohhot, 010017 China
| | - Xiaoxia Wang
- Intensive Care Unit, Inner Mongolia People's Hospital, Hohhot, 010017, China.
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Lin N, Li J, Yao X, Zhang X, Liu G, Zhang Z, Weng S. Prognostic value of neutrophil-to-lymphocyte ratio in colorectal cancer liver metastasis: A meta-analysis of results from multivariate analysis. Int J Surg 2022; 107:106959. [PMID: 36265780 DOI: 10.1016/j.ijsu.2022.106959] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/27/2022] [Accepted: 10/11/2022] [Indexed: 11/22/2022]
Abstract
We aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer liver metastasis (CRLM). A comprehensive search was conducted across PubMed, MedLine, and the Cochrane Library databases for articles published from January 1, 2000 to April 30, 2022 that investigated the long-term prognostic value of NLR in CRLM; only studies with multivariate analyses were enrolled. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. A total of 2,522 patients in 12 studies were selected; the meta-analysis demonstrated that elevated NLR correlated with poor overall survival (OS) and disease-free survival (DFS) (HR, 1.95, 95%CI, 1.698-2.223, P < 0.01; HR, 1.80, 95%CI, 1.363-2.363, P < 0.01; respectively). The 5-year OS and disease-free survival rates were higher in the patients with normal NLR than in patients with high NLR (47% vs. 27%, P < 0.01; 37% vs. 6%, P < 0.01, respectively). Further analysis of clinicopathological parameters indicated no significant difference between the patients with and without elevated NLR. Begg's and Egger's tests for publication bias revealed no significant publication bias (P = 0.891 and P = 0.926, respectively). Multivariate analysis revealed that NLR had an excellent prognostic ability in CRLM, which can be used in deciding the treatment and predicting the clinical outcomes. Further multicenter randomized controlled trials are required to verify this conclusion.
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Affiliation(s)
- Nanping Lin
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, China Department of Laboratory, Fujian Medical University Union Hospital, China
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Papakonstantinou M, Fiflis S, Christodoulidis G, Giglio MC, Louri E, Mavromatidis S, Giakoustidis D, Papadopoulos VN, Giakoustidis A. Neutrophil-to-lymphocyte ratio as a prognostic factor for survival in patients with colorectal liver metastases: A systematic review. World J Clin Oncol 2022; 13:822-834. [PMID: 36337307 PMCID: PMC9630990 DOI: 10.5306/wjco.v13.i10.822] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 07/08/2022] [Accepted: 10/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The inflammatory response to tumor has been proven to be closely related to the prognosis of colorectal cancer. Neutrophil to lymphocyte ratio (NLR) is a widely available inflammatory biomarker that may have prognostic value for patients with colorectal liver metastasis (CRLM). AIM To assess the role of NLR as a prognostic factor of survival and tumor recurrence in patients with CRLM. METHODS A systematic literature search of PubMed, Cochrane Library and clinicaltrials.gov was conducted by two independent researchers in order to minimize potential errors and bias. Conflicts were discussed and settled between three researchers. Studies including patients undergoing different types of medical interventions for the treatment of CRLM and evaluating the correlation between pretreatment NLR and disease-free survival (DFS) and overall survival (OS) were included in the review. Nineteen studies, involving 3283 patients matched our inclusion criteria. RESULTS In the studies included, NLR was measured before the intervention and the NLR thresholds ranged between 1.9 and 7.26. Most studies used 5 as the cut-off value. Liver metastases were treated with hepatectomy with or without chemotherapy regimens in 13 studies and with radiofrequency ablation, radioembolization, chemoembolization or solely with chemotherapy in 6 studies. High NLR was associated with decreased OS and DFS after liver resection or other medical intervention. Moreover, high NLR was associated with poor chemosensitivity. On the contrary, CRLM patients with low pretreatment NLR demonstrated improved OS and DFS. NLR could potentially be used as a predictive factor of survival and tumor recurrence in patients with CRLM treated with interventions of any modality, including surgery, chemotherapy and ablative techniques. CONCLUSION NLR is an inflammatory biomarker that demonstrates considerable prognostic value. Elevated pretreatment NLR is associated with poor OS and DFS in patients with CRLM who are submitted to different treatments.
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Affiliation(s)
- Menelaos Papakonstantinou
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Stylianos Fiflis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | | | - Mariano Cesare Giglio
- Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples 80138, Italy
| | - Eleni Louri
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Savvas Mavromatidis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Dimitrios Giakoustidis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Vasileios N Papadopoulos
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Alexandros Giakoustidis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
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9
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Supanimitjaroenporn P, Kirtsreesakul V, Tangthongkum M, Leelasawatsuk P, Prapaisit U. Prognostic value of pretreatment lymphocyte-to-monocyte ratio in patients with advanced oral cavity cancer. Laryngoscope Investig Otolaryngol 2022; 7:740-745. [PMID: 35734053 PMCID: PMC9194982 DOI: 10.1002/lio2.790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 03/09/2022] [Accepted: 03/21/2022] [Indexed: 11/07/2022] Open
Abstract
Introduction Lymphocyte-to-monocyte ratio (LMR) has been reported as a prognostic factor in many cancers but the data are to date limited for its use in oral cavity cancer. The purpose of this study was to evaluate the prognostic value of LMR in advanced-stage oral cavity cancer. Methods Data from 211 advanced-stage oral cancer patients treated with curative intent between January 2009 and December 2015 were obtained from the hospital information system. Pretreatment LMR and other hematologic parameters were recorded and an LMR cutoff value was calculated. Overall survival between the groups above (high LMR) and below (low LMR) the cutoff was compared and hazard ratios from univariate and multivariate analyses using a Cox proportional hazards model calculated. Results Overall survival and disease-specific survival were better in the high LMR group. The 5-year overall survival rates were 31.6% and 15% in the high LMR and low LMR groups, respectively. Multivariate analysis using a Cox proportional hazards model showed that treatment modality and LMR were the only factors associated with overall survival. Conclusion Low LMR was associated with poor survival outcome in patients with advanced-stage oral cavity cancer. Level of Evidence 2b.
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Affiliation(s)
- Pasawat Supanimitjaroenporn
- Department of Otolaryngology, Head and Neck Surgery, Faculty of MedicinePrince of Songkla UniversityHat YaiThailand
| | - Virat Kirtsreesakul
- Department of Otolaryngology, Head and Neck Surgery, Faculty of MedicinePrince of Songkla UniversityHat YaiThailand
| | - Manupol Tangthongkum
- Department of Otolaryngology, Head and Neck Surgery, Faculty of MedicinePrince of Songkla UniversityHat YaiThailand
| | - Peesit Leelasawatsuk
- Department of Otolaryngology, Head and Neck Surgery, Faculty of MedicinePrince of Songkla UniversityHat YaiThailand
| | - Usaporn Prapaisit
- Department of Otolaryngology, Head and Neck Surgery, Faculty of MedicinePrince of Songkla UniversityHat YaiThailand
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Polk N, Budai B, Hitre E, Patócs A, Mersich T. High Neutrophil-To-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammation Index (SII) Are Markers of Longer Survival After Metastasectomy of Patients With Liver-Only Metastasis of Rectal Cancer. Pathol Oncol Res 2022; 28:1610315. [PMID: 35570841 PMCID: PMC9091167 DOI: 10.3389/pore.2022.1610315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 03/23/2022] [Indexed: 11/13/2022]
Abstract
Background: The literature data regarding colon cancer patients with liver-only metastases (CLM) show that NLR determined before metastasectomy is a prognostic marker of shorter relapse-free survival (RFS), but no results has been reported to date for rectal cancer patients with liver-only metastases (RLM). This study aimed to investigate the NLR and SII in CLM and RLM. Methods: Relapse-free (RFS) and overall survival (OS) were evaluated in 67 CLM and 103 RLM patients with a median follow-up of 46.5 and 59.8 months, respectively. Pre- and/or postoperative chemotherapy ± targeted treatment was applied in 96% and 87% of CLM and RLM patients, respectively. The cut-off level for hematologic parameters were determined by receiver operating characteristic (ROC) analysis. Univariate analysis was performed by Kaplan-Meier method and log rank test. For multivariate analysis Cox regression was applied. Results: In univariate analysis low NLR (cut-off 2) and SII (535) were predictors of longer RFS in case of CLM (p < 0.01). In contrast, for RLM high NLR (2.42) and SII (792) were predictors of longer RFS (p < 0.001). For RLM both NLR and SII proved to be independent markers of RFS (HR 0.66 (95% CI 0.52–0.84) and 0.73 (0.57–0.91), respectively) and OS (0.76 (0.58–0.99) and 0.66 (0.5–0.87), respectively). Only NLR (1.44 (1.04–1.99)) was independent marker of RFS for CLM. The preoperative treatment has not influenced the role of NLR or SII. Conclusion: In contrast to CLM, in RLM the high NLR or SII determined before metastasectomy proved to be independent prognostic factors of longer RFS and OS.
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Affiliation(s)
- Nándor Polk
- Departmet of Visceral Surgery, National Institute of Oncology, Budapest, Hungary
| | - Barna Budai
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
| | - Erika Hitre
- Medical Oncology and Clinical Pharmacology "B" Department, National Institute of Oncology, Budapest, Hungary
| | - Attila Patócs
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.,Clinical Central Laboratory, National Institute of Oncology, Budapest, Hungary.,Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary
| | - Tamás Mersich
- Departmet of Visceral Surgery, National Institute of Oncology, Budapest, Hungary
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11
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Alay H, Laloglu E. Can Endocan Be a Novel Marker in the Diagnosis of Brucellosis? Vector Borne Zoonotic Dis 2022; 22:232-237. [PMID: 35404144 DOI: 10.1089/vbz.2021.0103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Handan Alay
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Esra Laloglu
- Department of Medical Biochemistry, Faculty of Medicine, Ataturk University, Erzurum, Turkey
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12
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Huang L, Hu Z, Luo R, Li H, Yang Z, Qin X, Mo Z. Predictive Values of the Selected Inflammatory Indexes in Colon Cancer. Cancer Control 2022; 29:10732748221091333. [PMID: 35403443 PMCID: PMC9006378 DOI: 10.1177/10732748221091333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Purpose Ample evidence has revealed that the lymphocyte-to-monocyte ratio (LMR), albumin-to-globulin ratio (AGR), and mean platelet volume (MPV) are cancer-related inflammatory markers. The present study aimed to combine these indicators to better assess the progression of colon cancer. Methods This retrospective study enrolled 251 patients with colon cancer, 171 patients with benign colon diseases, and 187 healthy control subjects. The receiver operating characteristic curve and area under the curve (AUC) were used to determine the diagnostic values of the selected inflammatory index. Results The levels of LMR, AGR, and MPV were decreased in the colon cancer group compared with the healthy control and benign colon disease groups. The LMR, AGR, and MPV were all correlated with tumor size. Moreover, LMR and AGR was associated with lymph node metastasis and clinical stage, AGR was related to distant metastasis. Both the LMR (P = .030) and AGR (P = .005) were negatively correlated with the concentration of carcinoembryonic antigen (CEA). The AUC value of MPV combined with CEA had a good diagnostic ability for distinguishing colon cancer cases (AUC = .950) and patients with benign colon diseases (AUC = .886) from controls. Meanwhile, the combination of LMR or AGR with CEA could enhance larger AUC (.746 for LMR + CEA, .737 for AGR + CEA) than CEA, LMR, or AGR alone in detecting colon cancer from benign colon diseases. Conclusions CEA combined with the LMR, AGR, or MPV may be used as better blood-based biomarkers in the progression of colon cancer patients.
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Affiliation(s)
- Li Huang
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zuojian Hu
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Ruixian Luo
- Department of Blood Transfusion, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Hailan Li
- Department of Blood Transfusion, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Ziji Yang
- Department of Blood Transfusion, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Xue Qin
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhuning Mo
- Department of Blood Transfusion, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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13
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Cantero-Cid R, Montalbán-Hernández KM, Guevara J, Pascual-Iglesias A, Pulido E, Casalvilla JC, Marcano C, Serrano CB, Valentín J, Bonel-Pérez GC, Avendaño-Ortiz J, Terrón V, Lozano-Rodríguez R, Martín-Quirós A, Marín E, Pena E, Guerra-Pastrián L, López-Collazo E, Aguirre LA. Intertwined leukocyte balances in tumours and peripheral blood as robust predictors of right and left colorectal cancer survival. World J Gastrointest Oncol 2022; 14:295-318. [PMID: 35116118 PMCID: PMC8790415 DOI: 10.4251/wjgo.v14.i1.295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 08/07/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) accounts for 9.4% of overall cancer deaths, ranking second after lung cancer. Despite the large number of factors tested to predict their outcome, most patients with similar variables show big differences in survival. Moreover, right-sided CRC (RCRC) and left-sided CRC (LCRC) patients exhibit large differences in outcome after surgical intervention as assessed by preoperative blood leukocyte status. We hypothesised that stronger indexes than circulating (blood) leukocyte ratios to predict RCRC and LCRC patient outcomes will result from combining both circulating and infiltrated (tumour/peritumour fixed tissues) concentrations of leukocytes. AIM To seek variables involving leukocyte balances in peripheral blood and tumour tissues and to predict the outcome of CRC patients. METHODS Sixty-five patients diagnosed with colon adenocarcinoma by the Digestive Surgery Service of the La Paz University Hospital (Madrid, Spain) were enrolled in this study: 43 with RCRC and 22 with LCRC. Patients were followed-up from January 2017 to March 2021 to record overall survival (OS) and recurrence-free survival (RFS) after surgical interventions. Leukocyte concentrations in peripheral blood were determined by routine laboratory protocols. Paraffin-fixed samples of tumour and peritumoural tissues were assessed for leukocyte concentrations by immunohistochemical detection of CD4, CD8, and CD14 marker expression. Ratios of leukocyte concentration in blood and tissues were calculated and evaluated for their predictor values for OS and RFS with Spearman correlations and Cox univariate and multivariate proportional hazards regression, followed by the calculation of the receiver-operating characteristic and area under the curve (AUC) and the determination of Youden's optimal cutoff values for those variables that significantly correlated with either RCRC or LCRC patient outcomes. RCRC patients from the cohort were randomly assigned to modelling and validation sets, and clinician-friendly nomograms were developed to predict OS and RFS from the respective significant indexes. The accuracy of the model was evaluated using calibration and validation plots. RESULTS The relationship of leukocyte ratios in blood and peritumour resulted in six robust predictors of worse OS in RCRC: CD8+ lymphocyte content in peritumour (CD8pt, AUC = 0.585, cutoff < 8.250, P = 0.0077); total lymphocyte content in peritumour (CD4CD8pt, AUC = 0.550, cutoff < 10.160, P = 0.0188); lymphocyte-to-monocyte ratio in peritumour (LMRpt, AUC = 0.807, cutoff < 3.185, P = 0.0028); CD8+ LMR in peritumour (CD8MRpt, AUC = 0.757, cutoff < 1.650, P = 0.0007); the ratio of blood LMR to LMR in peritumour (LMRb/LMRpt, AUC = 0.672, cutoff > 0.985, P = 0.0244); and the ratio of blood LMR to CD8+ LMR in peritumour (LMRb/CD8MRpt, AUC = 0.601, cutoff > 1.485, P = 0.0101). In addition, three robust predictors of worse RFS in RCRC were found: LMRpt (AUC = 0.737, cutoff < 3.185, P = 0.0046); LMRb/LMRpt (AUC = 0.678, cutoff > 0.985, P = 0.0155) and LMRb/CD8MRpt (AUC = 0.615, cutoff > 1.485, P = 0.0141). Furthermore, the ratio of blood LMR to CD4+ LMR in peritumour (LMRb/CD4MRpt, AUC = 0.786, cutoff > 10.570, P = 0.0416) was found to robustly predict poorer OS in LCRC patients. The nomograms showed moderate accuracy in predicting OS and RFS in RCRC patients, with concordance index of 0.600 and 0.605, respectively. CONCLUSION Easily obtainable variables at preoperative consultation, defining the status of leukocyte balances between peripheral blood and peritumoural tissues, are robust predictors for OS and RFS of both RCRC and LCRC patients.
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Affiliation(s)
- Ramón Cantero-Cid
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Karla Marina Montalbán-Hernández
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Jenny Guevara
- Digestive Surgery Service, La Paz University Hospital, Madrid 28046, Spain
| | - Alejandro Pascual-Iglesias
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Elisa Pulido
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - José Carlos Casalvilla
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Cristóbal Marcano
- Digestive Surgery Service, La Paz University Hospital, Madrid 28046, Spain
| | | | - Jaime Valentín
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Gloria Cristina Bonel-Pérez
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - José Avendaño-Ortiz
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Verónica Terrón
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Roberto Lozano-Rodríguez
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Alejandro Martín-Quirós
- Emergency Department and Emergent Pathology Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Elvira Marín
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Eva Pena
- Pathologic Anatomy Service, Hospital La Paz, Madrid 28046, Spain
| | | | - Eduardo López-Collazo
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
| | - Luis Augusto Aguirre
- Tumor Immunology Laboratory, The Innate Immune Response Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid 28046, Spain
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14
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Wang J, Li J, Wei S, Xu J, Jiang X, Yang L. The Ratio of Platelets to Lymphocytes Predicts the Prognosis of Metastatic Colorectal Cancer: A Review and Meta-Analysis. Gastroenterol Res Pract 2021; 2021:9699499. [PMID: 34764993 PMCID: PMC8577954 DOI: 10.1155/2021/9699499] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 10/15/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND In recent years, the incidence of colorectal cancer (CRC) has continued to increase. Although the overall prognosis of CRC has improved with the continuous improvement of the level of treatment, the prognosis of metastatic colorectal cancer (mCRC) is still poor. The purpose of our study is to explore the prognostic value of platelet to lymphocyte ratio (PLR) in mCRC. METHODS The PubMed, Web of Science, and Embase (via OVID) were systematically searched to obtain all relevant research. We used hazard ratio (HR) with 95% confidence interval (CI) to assess the associations of PLR and overall survival (OS) and progression free survival (PFS). RESULTS A total of twelve studies containing 1452 patients were included in this meta-analysis. Pooled analysis showed that high levels of PLR were associated with poor OS (HR: 1.72, 95% CI: 1.27-2.33, and P < 0.01) and PFS (HR: 1.64, 95% CI: 1.16-2.31, and P = 0.033). CONCLUSION Our analysis suggested that high levels of PLR pretreatment may be an effective predictive biomarker for the prognosis of mCRC patients.
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Affiliation(s)
- Jinming Wang
- Cancer Research Center Nantong, Nantong Tumor Hospital & Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Jing Li
- Cancer Research Center Nantong, Nantong Tumor Hospital & Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Sheng Wei
- Cancer Research Center Nantong, Nantong Tumor Hospital & Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Jie Xu
- Cancer Research Center Nantong, Nantong Tumor Hospital & Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Xiaohui Jiang
- Department of General Surgery, Nantong Tumor Hospital & Affiliated Tumor Hospital of Nantong University, Nantong, China
| | - Lei Yang
- Department of Oncology, Nantong Tumor Hospital & Affiliated Tumor Hospital of Nantong University, Nantong, China
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15
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Pletcher E, Gleeson E, Shaltiel T, Leigh N, Sullivan B, Labow D, Magge D, Golas B, Cohen N, Sarpel U. Lymphocyte-to-monocyte ratio predicts survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Biomark Med 2021; 15:965-975. [PMID: 34289740 DOI: 10.2217/bmm-2020-0720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: Lymphocyte-to-monocyte ratio (LMR) predicts overall survival (OS) in patients with colorectal cancer. We explored LMR in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Materials & methods: We identified all patients undergoing CRS/HIPEC for colorectal or appendiceal adenocarcinoma at our institution. We analyzed LMR's relationship with clinicopathologic variables with Kaplan-Meier log-rank survival analyses and multivariable Cox regression models with 5-year OS. Results: Two hundred and sixteen patients underwent CRS/HIPEC. Five-year OS for low LMR (≤3.71) was 35.2 versus 60.4% for elevated LMR (hazard ratio [HR]: 2.0; 95% CI: 1.1-3.5; p = 0.02). On multivariable Cox-regression, elevated LMR was significantly associated with OS (p ≤ 0.05). Conclusion: LMR is an independent predictor of OS in patients undergoing CRS/HIPEC for colorectal and appendiceal adenocarcinoma.
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Affiliation(s)
- Eric Pletcher
- Division of Surgical Oncology, Department of Surgery, Mount Sinai West, NY 10019, USA
| | - Elizabeth Gleeson
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, NY 10029, USA
| | - Tali Shaltiel
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, NY 10029, USA
| | - Natasha Leigh
- Division of Surgical Oncology, Department of Surgery, Mount Sinai West, NY 10019, USA
| | - Brianne Sullivan
- Division of Surgical Oncology, Department of Surgery, Mount Sinai West, NY 10019, USA
| | - Daniel Labow
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, NY 10029, USA
| | - Deepa Magge
- Division of Surgical Oncology, Department of Surgery, Mount Sinai West, NY 10019, USA
| | - Benjamin Golas
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, NY 10029, USA
| | - Noah Cohen
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, NY 10029, USA
| | - Umut Sarpel
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, NY 10029, USA
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16
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Okuno K, Tokunaga M, Yamashita Y, Umebayashi Y, Saito T, Fukuyo R, Sato Y, Saito K, Fujiwara N, Hoshino A, Kawada K, Matsuyama T, Kinugasa Y. Preoperative lymphocyte-to-monocyte ratio is the most predictive inflammatory response marker of survival in gastric cancer. Langenbecks Arch Surg 2021; 406:2287-2294. [PMID: 34165594 DOI: 10.1007/s00423-021-02230-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 06/02/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE Systemic inflammatory responses play a key role in cancer progression, and detecting the predictive inflammatory response markers is needed. The present study explored inflammatory response markers capable of predicting survival in patients with gastric cancer. METHODS We enrolled 264 patients, who underwent curative gastrectomy for clinical stage (cStage) I-III gastric cancer between 2012 and 2015. The cut-off point of eight preoperative inflammatory response markers was determined by receiver operating characteristic (ROC) curve analysis. The marker with the highest Harrell's concordance index (C-index) was adopted for subsequent univariate and multivariate analyses using the Cox proportional-hazards model. RESULTS Among eight representative inflammatory response markers, lymphocyte-to-monocyte ratio (LMR; cut-off point, 4.60) achieved the highest C-index (0.633). The 5-year survival rate was significantly worse in patients with LMR < 4.60 than in those with LMR ≥ 4.60 (67.5% versus 89.0%, P < 0.001). In multivariate analysis, LMR < 4.60 was identified as an independent prognostic factor (hazard ratio: 2.372; 95% confidence interval: 1.266-4.442; P = 0.007). CONCLUSION In this study, LMR had the strongest ability to predict the survival of patients with gastric cancer among other inflammatory response markers, with lower LMRs being associated with poor survival following curative gastrectomy.
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Affiliation(s)
- Keisuke Okuno
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Masanori Tokunaga
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
| | - Yamato Yamashita
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Yuya Umebayashi
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Toshifumi Saito
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Ryosuke Fukuyo
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Yuya Sato
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Katsumasa Saito
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Naoto Fujiwara
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Akihiro Hoshino
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Kenro Kawada
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Takatoshi Matsuyama
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
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Fishbein A, Hammock BD, Serhan CN, Panigrahy D. Carcinogenesis: Failure of resolution of inflammation? Pharmacol Ther 2021; 218:107670. [PMID: 32891711 PMCID: PMC7470770 DOI: 10.1016/j.pharmthera.2020.107670] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2020] [Indexed: 02/06/2023]
Abstract
Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.
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Affiliation(s)
- Anna Fishbein
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
| | - Bruce D. Hammock
- Department of Entomology and Nematology, and UCD Comprehensive Cancer Center, University of California, Davis, CA 95616, USA
| | - Charles N. Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Dipak Panigrahy
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA,Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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18
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Lin CH, Chou WC, Wu YY, Lin CY, Chang KP, Liao CT, Ho TY, Yeh CM, Liu CJ, Hung SP, Lee CH, Chen PJ, Chou YC, Fan KH, Huang BS, Tung-Chieh Chang J, Wang CC, Tsang NM. Prognostic significance of dynamic changes in lymphocyte-to-monocyte ratio in patients with head and neck cancer treated with radiotherapy: results from a large cohort study. Radiother Oncol 2021; 154:76-86. [PMID: 32941957 DOI: 10.1016/j.radonc.2020.09.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 08/23/2020] [Accepted: 09/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND PURPOSE We sought to investigate whether dynamic changes in lymphocyte-to-monocyte ratio (LMR) occurring during the course of radiotherapy (RT) may have prognostic value in patients with head and neck cancer (HNC). MATERIALS AND METHODS We retrospectively reviewed the clinical records of patients with HNC who underwent RT at our center between 2005 and 2013. Generalized estimating equations were used to longitudinally assess changes in LMR through the course of RT. Delta-LMR was calculated as the difference between LMR measured during treatment and baseline LMR values. Freedom from metastasis (FFM) and overall survival (OS) served as the main outcome measures. RESULTS A total of 1431 patients with HNC were enrolled. After a median follow-up of 9 years, 636 (44.4%) patients died and 240 (16.8%) had distant metastases. Compared with patients with low delta-LMR at two weeks, those with high delta-LMR experienced less favorable outcomes (five-year OS: 73% versus 59%, respectively, p < 0.001; five-year FFM: 87% versus 80%, respectively, p = 0.015). Similar findings were observed for delta-LMR measured at four weeks (five-year OS: 72% versus 60%, p < 0.001; five-year FFM: 86% versus 79%, respectively, p = 0.002) and six weeks (five-year OS: 72% versus 57%, p < 0.001; five-year FFM: 87% versus 79%, respectively, p = 0.002). Multivariate analysis identified delta-LMR as an independent prognostic factor for both FFM and OS. CONCLUSION Delta-LMR is a simple and inexpensive biomarker that may be clinically useful for predicting FFM and OS in patients with HNC treated with RT.
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Affiliation(s)
- Chia-Hsin Lin
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Wen-Chi Chou
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyaun, Taiwan.
| | - Yao-Yu Wu
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Chien-Yu Lin
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Kai-Ping Chang
- Department of Otolaryngology-Head Neck Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University at Lin-Kou, Taoyuan, Taiwan.
| | - Chun-Ta Liao
- Department of Otolaryngology-Head Neck Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University at Lin-Kou, Taoyuan, Taiwan.
| | - Tsung-Ying Ho
- Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
| | - Chiu-Mei Yeh
- Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
| | - Chia-Jen Liu
- Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
| | - Sheng-Ping Hung
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Ching-Hsin Lee
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Po-Jui Chen
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Yung-Chih Chou
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Kang-Hsing Fan
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Bing-Shen Huang
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan; Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan.
| | - Joseph Tung-Chieh Chang
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan; Department of Radiation Oncology, Xiamen Chang Gung Memorial Hospital, Fujian, China.
| | - Chun-Chieh Wang
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan.
| | - Ngan-Ming Tsang
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan City, Taiwan; Department of Radiation Oncology, Fangliao General Hospital, PingTung Hsien, Taiwan.
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The Change of Systemic Immune-Inflammation Index Independently Predicts Survival of Colorectal Cancer Patients after Curative Resection. Mediators Inflamm 2020; 2020:4105809. [PMID: 33293896 PMCID: PMC7718069 DOI: 10.1155/2020/4105809] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 09/12/2020] [Accepted: 09/27/2020] [Indexed: 12/17/2022] Open
Abstract
Background The systemic immune-inflammation index (SII) has an important role in predicting survival in some solid tumors. However, little information is available concerning the change of the SII (∆SII) in colorectal cancer (CRC) after curative resection. This study was designed to evaluate the role of ∆SII in CRC patients who received surgery. Methods A total 206 patients were enrolled in this study. Clinicopathologic characteristics and survival were assessed. The relationships between overall survival (OS), disease-free survival (DFS), and ∆SII were analyzed with both univariate Kaplan-Meier and multivariate Cox regression methods. Results Based on the patient data, the receiver operating characteristic (ROC) optimal cutoff value of ∆SII was 127.7 for OS prediction. The 3-year and 5-year OS rates, respectively, were 60.4% and 36.7% in the high-∆SII group (>127.7) and 87.6% and 79.8% in the low-∆SII group (≤127.7). The 3-year and 5-year DFS rates, respectively, were 54.1% and 34.1% in the high-∆SII group and 80.3% and 78.5% in the low-∆SII group. In the univariate analysis, smoking, pathological stages III-IV, high-middle degree of differentiation, lymphatic invasion, vascular invasion, and the high-ΔSII group were associated with poor OS. Adjuvant therapy, pathological stages III-IV, vascular invasion, and ΔSII were able to predict DFS. Multivariate analysis revealed that pathological stages III-IV (HR = 0.442, 95% CI = 0.236-0.827, p = 0.011), vascular invasion (HR = 2.182, 95% CI = 1.243-3.829, p = 0.007), and the high-ΔSII group (HR = 4.301, 95% CI = 2.517-7.350, p < 0.001) were independent predictors for OS. Adjuvant therapy (HR = 0.415, 95% CI = 0.250-0.687, p = 0.001), vascular invasion (HR = 3.305, 95% CI = 1.944-5.620, p < 0.001), and the high-ΔSII group (HR = 4.924, 95% CI = 2.992-8.102, p < 0.001) were significant prognostic factors for DFS. Conclusions The present study demonstrated that ∆SII was associated with the clinical outcome in CRC patients undergoing curative resection, supporting the role of ∆SII as a prognostic biomarker.
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Ciocan A, Hajjar NA, Graur F, Oprea VC, Ciocan RA, Bolboacă SD. Receiver Operating Characteristic Prediction for Classification: Performances in Cross-Validation by Example. MATHEMATICS 2020; 8:1741. [DOI: 10.3390/math8101741] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
The stability of receiver operating characteristic in context of random split used in development and validation sets, as compared to the full models for three inflammatory ratios (neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR) and platelet-to-lymphocyte (PLR) ratio) evaluated as predictors for metastasis in patients with colorectal cancer, was investigated. Data belonging to patients admitted with the diagnosis of colorectal cancer from January 2014 until September 2019 in a single hospital were used. There were 1688 patients eligible for the study, 418 in the metastatic stage. All investigated inflammatory ratios proved to be significant classification models on both the full models and on cross-validations (AUCs > 0.05). High variability of the cut-off values was observed in the unrestricted and restricted split (full models: 4.255 for NLR, 2.745 for dNLR and 255.56 for PLR; random splits: cut-off from 3.215 to 5.905 for NLR, from 2.625 to 3.575 for dNLR and from 134.67 to 335.9 for PLR), but with no effect on the models characteristics or performances. The investigated biomarkes proved limited value as predictors for metastasis (AUCs < 0.8), with largely sensitivity and specificity (from 33.3% to 79.2% for the full model and 29.1% to 82.7% in the restricted splits). Our results showed that a simple random split of observations, weighting or not the patients with and whithout metastasis, in a ROC analysis assures the performances similar to the full model, if at least 70% of the available population is included in the study.
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Preoperative lymphocyte-to-monocyte ratio versus platelet-to-lymphocyte ratio as a prognostic predictor for non-small cell lung cancer patients. J Med Biochem 2020; 39:160-164. [PMID: 33033447 DOI: 10.2478/jomb-2019-0031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 05/12/2019] [Indexed: 11/21/2022] Open
Abstract
Background We investigated the prognostic value of the preoperative lymphocyte-to-mononuclear ratio (LMR) and platelet-to-lymphocyte ratio (PLR) in a large cohort of patients with non-small cell lung cancer (NSCLC). Methods Clinical-pathological data from 507 NSCLC patients at Taizhou Hospital of Zhejiang Province between 2010 and 2016 were retrospectively evaluated. X-tile software was used to assess the optimal cutoff levels for LMR and PLR. Univariate and multivariate Cox regression models were used to assess the prognostic factors. Results The median follow-up duration after surgical resection was 34.5 months. Patients were stratified into 2 groups by LMR (2.6 and > 2.6) and PLR (179.6 and > 179.6). Our results revealed that lower LMR (HR = 3.163 (1.821-5.493), P = 0.000), age (HR = 2.252 (1.412-3.592), P = 0.001), T stage (HR = 3.749 (2.275-6.179), P = 0.000), N stage (HR = 3.106 (1.967-4.902), P = 0.000), and cut edge (HR = 3.830 (1.077-13.618), P = 0.038) were considered to be independent indicators for overall survival (OS) of NSCLC patients. For disease-free survival (DFS), age, sex, T stage, N stage, LMR and cut edge were verified to be independent prognostic factors in patients with NSCLC. Conclusions In the study cohort, reduced LMR was a robust independent predictor for both OS and DFS in patients with NSCLC who underwent surgical resection.
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Prognostic value of nomogram based on pre-treatment inflammatory markers in patients with pulmonary-only synchronous metastases from colorectal cancer. Int Immunopharmacol 2019; 77:106001. [PMID: 31734191 DOI: 10.1016/j.intimp.2019.106001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 10/22/2019] [Accepted: 10/23/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The inflammatory markers were important factors affecting proliferation, invasiveness and metastasis of tumors. However, the prognostic value of inflammatory markers and related nomogram in patients with pulmonary-only synchronous metastases (POSM) from colorectal cancer has not been reported. MATERIALS AND METHODS A total of 98 POSM patients undergoing resection of colorectal cancer were included. The Kaplan-Meier survival analysis and Cox regression analysis were used to estimate the overall survival (OS) and progression-free survival (PFS). The nomogram was built based on multivariate Cox analysis model and evaluated by calibration curve, concordance index (C-index) and receiver operating characteristics (ROC). RESULTS The multivariate analysis showed that neutrophil-to-lymphocyte ratio (NLR) was prognostic factor of OS (HR = 2.73, 95%CI: 1.54-4.84) and PFS (HR = 1.78, 95%CI: 1.13-2.82). Elevated alkaline phosphatase (ALP) also was predictor of poor OS (HR = 1.99, 95%CI: 1.12-3.51) and PFS (HR = 2.23, 95%CI: 1.40-3.55). The early N stage and solitary pulmonary metastases had significant survival benefit for OS, while advanced T stage was independently related with worse PFS. Nomograms were consist of above significant risk factors, with C-index of 0.742 for OS and 0.656 for PFS. The calibration curves showed non-significant deviations between predicted and actual probability of OS and PFS. CONCLUSIONS Pre-treatment NLR and ALP were independently associated with OS and PFS in POSM patients. The nomograms involving inflammatory markers and clinicopathological factors were practical in predicting survival, which may help to guide use of therapeutic strategy and cancer surveillance.
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Basile D, Gerratana L, Buonadonna A, Garattini SK, Perin T, Grassilli E, Miolo G, Cerrito MG, Belluco C, Bertola G, De Paoli A, Cannizzaro R, Lavitrano M, Puglisi F, Canzonieri V. Role of Bruton's Tyrosine Kinase in Stage III Colorectal Cancer. Cancers (Basel) 2019; 11:E880. [PMID: 31238520 PMCID: PMC6627163 DOI: 10.3390/cancers11060880] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 06/16/2019] [Accepted: 06/19/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Bruton's tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. MATERIALS AND METHODS This retrospective study evaluated 87 consecutive stage III CRC patients treated at the National Cancer Institute of Aviano (1999-2017). Multiple specimens were collected and analyzed for staining intensity and percentage of tumor cells positive for p65BTK. Prognostic impact was tested by univariate Cox regression analysis. RESULTS After a median follow-up of 82.59 months, median disease-free survival (DFS) and overall survival (OS) were 11.67 months and 31.33 months, respectively. Interestingly, 10% of patients did not express p65BTK. For the immunohistochemistry IHC intensity 1, the best cutoff point was 1% of p65BTK positivity; for IHC intensity 2, it was 50%; and for IHC intensity 3, it was 80%. Through univariate analysis, patients with highly expressed p65BTK (IHC intensity 3 and ≥80%) were shown to have the worst prognosis in terms of DFS (HR: 6.23; p = 0.005; 95% C.I. 1.75-22.79) and OS (HR: 2.54; p = 0.025; 95% C.I. 1.12-5.76). CONCLUSIONS p65BTK is frequently expressed in CRC and, if highly expressed, is an unfavourable prognostic factor. However, further confirmation is needed and its potential targeting needs to be studied.
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Affiliation(s)
- Debora Basile
- Department of Medicine (DAME), University of Udine, 33100 Udine (UD), Italy.
- Department of Medical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Lorenzo Gerratana
- Department of Medicine (DAME), University of Udine, 33100 Udine (UD), Italy.
- Department of Medical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Angela Buonadonna
- Department of Medical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Silvio Ken Garattini
- Department of Medicine (DAME), University of Udine, 33100 Udine (UD), Italy.
- Department of Medical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Tiziana Perin
- Pathology Unit, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
- CRO Biobank IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Emanuela Grassilli
- Department of Medicine and Surgery, University of Milano-Bicocca, 33081 Milan, Italy.
| | - Gianmaria Miolo
- Department of Medical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Maria Grazia Cerrito
- Department of Medicine and Surgery, University of Milano-Bicocca, 33081 Milan, Italy.
| | - Claudio Belluco
- Surgical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Giulio Bertola
- Surgical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Antonino De Paoli
- Radiation Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Renato Cannizzaro
- Division of Oncological Gastroenterology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Marialuisa Lavitrano
- Department of Medicine and Surgery, University of Milano-Bicocca, 33081 Milan, Italy.
| | - Fabio Puglisi
- Department of Medicine (DAME), University of Udine, 33100 Udine (UD), Italy.
- Department of Medical Oncology, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
| | - Vincenzo Canzonieri
- Pathology Unit, IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
- CRO Biobank IRCCS CRO National Cancer Institute, 33081 Aviano (PN), Italy.
- Department of Medical, Surgical and Health Science, University of Trieste School of Medicine, 34100 Trieste (TS), Italy.
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Peng J, Zhao Y, Luo Q, Chen H, Fan W, Pan Z, Wang X, Zhang L. High WNT6 expression indicates unfavorable survival outcome for patients with colorectal liver metastasis after liver resection. J Cancer 2019; 10:2619-2627. [PMID: 31258769 PMCID: PMC6584936 DOI: 10.7150/jca.32817] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 05/07/2019] [Indexed: 02/06/2023] Open
Abstract
Objective: As a member of the Wnt family, WNT6 contributes to tumorigenesis and the development of various types of cancer. However, the expression status of WNT6 in colorectal liver metastasis (CRLM) and its prognostic value remain to be elucidated. In this study, we evaluated the association of WNT6 expression with survival outcomes in CRLM patients undergoing liver resection. Methods: The medical records of 106 consecutive CRLM patients undergoing curative tumor resection between October 1996 and December 2011 were retrospectively selected. WNT6 expression was detected using immunohistochemistry (IHC) analyses on paraffin-embedded specimens. The IHC score was determined according to the percentage and intensity of positively stained cells. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test, and independent prognostic factors were determined by Cox regression modeling. Results: We found that WNT6 was commonly expressed in 93.4% (99/106) of colorectal cancer tissues. The median IHC score of WNT6 expression was significantly lower in patients receiving preoperative chemotherapy than those without preoperative chemotherapy (1.33 vs. 2.33, P = 0.033). Survival analysis indicated that patients with high WNT6 expression had poorer 5-year OS than those with low WNT6 expression (31.0% vs. 62.2%, P = 0.012). The 5-year OS rate was significantly lower in the high WNT6 group than in the low WNT6 group (36.8% vs. 79.9%, P = 0.013) in low-risk patients but was comparable among the high-risk patients (22.7% vs. 34.7%, P = 0.433). Multivariate analysis indicated that high WNT6 expression was independently associated with poor OS (hazard ratio [HR]: 2.089; 95% confidence interval [CI]: 1.231-3.545; P = 0.006). Conclusions: High expression of WNT6 was associated with unfavorable oncologic prognosis in patients with CRLM undergoing liver resection. Detection of WNT6 expression may be valuable for guiding postoperative treatment.
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Affiliation(s)
- Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
| | - Yixin Zhao
- Department of Anesthesiology & Operating Theatre, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
| | - Qiuyun Luo
- Department of Clinical Laboratory, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
| | - Hao Chen
- Department of Clinical Laboratory, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
| | - Wenhua Fan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
| | - Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
| | - Xueping Wang
- Department of Clinical Laboratory, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
| | - Lin Zhang
- Department of Clinical Laboratory, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China
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Yalon M, Toren A, Jabarin D, Fadida E, Constantini S, Mehrian-Shai R. Elevated NLR May Be a Feature of Pediatric Brain Cancer Patients. Front Oncol 2019; 9:327. [PMID: 31114757 PMCID: PMC6502986 DOI: 10.3389/fonc.2019.00327] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 04/11/2019] [Indexed: 12/17/2022] Open
Abstract
Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important role in cancer pathogenesis and in the response to immunotherapy treatments. T lymphocytes are key elements for the response of the immune system to cancer cells and have been associated with prognosis of different cancers. Neutrophils on the other hand, which secrete pro-angiogenic and anti-apoptotic factors, enhance the ability of tumor cells to grow and develop into metastases. We conducted a retrospective study of 120 pediatric brain cancer patients and 171 elective pediatric patients hospitalized in Dana Children's Hospital and Sheba Medical Center. Data on age, sex, treatment, lymphocyte, neutrophil, and monocyte count were collected from routinely performed preoperative blood tests. Neutrophil-to-lymphocyte ratio (NLR), and the lymphocyte-to-monocyte ratio (LMR) were calculated and significance was determined by paired T test. p < 0.05 was considered as statistically significant. NLR was significantly higher in the pediatric brain cancer patients. The high NLR in pediatric brain cancer patients is the result of a combination of low lymphocytes and high neutrophils. Both of these factors can have a role in cancer development and propagation and also in response to therapy.
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Affiliation(s)
- Michal Yalon
- Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel
| | - Amos Toren
- Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.,The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Dina Jabarin
- The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Edna Fadida
- Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel
| | - Shlomi Constantini
- Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel
| | - Ruty Mehrian-Shai
- Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel
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Li Z, Xu Z, Huang Y, Zhao R, Cui Y, Zhou Y, Wu X. Prognostic values of preoperative platelet-to-lymphocyte ratio, albumin and hemoglobin in patients with non-metastatic colon cancer. Cancer Manag Res 2019; 11:3265-3274. [PMID: 31114364 PMCID: PMC6489677 DOI: 10.2147/cmar.s191432] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 03/12/2019] [Indexed: 02/05/2023] Open
Abstract
Purpose: Preoperative platelet-to-monocyte ratio (PLR), albumin and hemoglobin are suggested prognostic indicators in various malignancies. However, the prognostic values of PLR, albumin and hemoglobin remain elusive. The objective of the present study was to evaluate the prognostic values of PLR, albumin and hemoglobin in stage I-III colon cancer. Patients and methods: A total of 312 patients with non-metastatic colon cancer undergoing curative resection were enrolled in this study. The prognostic values of PLR, albumin and hemoglobin were identified by receiver operating characteristics, and univariate and multivariate analyses. Results: Univariate analysis revealed that preoperative PLR, albumin and hemoglobin were significantly associated with overall survival (OS) and that preoperative PLR and albumin were significantly associated with progression-free survival (PFS). Multivariate analysis revealed that preoperative PLR was significantly associated with OS. Conclusion: Reduced preoperative PLR was significantly associated with better OS in patients with stage I-III colon cancer. Preoperative PLR was an independent prognostic indictor for OS in patients with colon cancer undergoing curative resection.
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Affiliation(s)
- Zhigui Li
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
| | - Zhaofen Xu
- Department of Pathology, The Second People's Hospital, Neijiang, Sichuan 641000, People's Republic of China
| | - Yuqian Huang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
| | - Rui Zhao
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
| | - Yaping Cui
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
| | - Yong Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
| | - Xiaoting Wu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China
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Choi YH, Lee JW, Lee SH, Choi JH, Kang J, Lee BS, Paik WH, Ryu JK, Kim YT. A High Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Advanced Gallbladder Cancer Receiving Chemotherapy. Cancer Epidemiol Biomarkers Prev 2019; 28:1045-1051. [PMID: 30842131 DOI: 10.1158/1055-9965.epi-18-1066] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 11/26/2018] [Accepted: 02/25/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to be prognostic markers in various cancers. However, the prognostic value of these inflammatory biomarkers, particularly MLR, in gallbladder cancer remains to be determined. METHODS From 2005 to 2016, 178 patients with histologically confirmed gallbladder adenocarcinoma who underwent palliative chemotherapy were queried in this study. The association between survival and various clinical and laboratory variables, including MLR, NLR, and PLR, was investigated. The optimal cutoff values for MLR, NLR, and PLR were determined using the maxstat package of R. RESULTS Patients with high MLR (>0.24) were expected to have shorter progression-free survival [PFS; hazard ratio (HR), 2.100; 95% confidence interval (CI), 1.397-3.157; P < 0.001] and overall survival (OS; HR, 2.533; 95% CI, 1.664-3.856; P < 0.001) compared with patients with low MLR (≤0.24). In multivariate Cox model, CA 19-9, stage, and MLR were independent factors for PFS. MLR was also an independent predictor of OS along with PLR, age, and CA 19-9, whereas NLR was not significantly associated with OS. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve of MLR for predicting OS was greater than that of NLR and PLR at most time points. CONCLUSIONS MLR independently predicts survival in gallbladder cancer patients undergoing chemotherapy. Future prospective studies are needed to validate its value as a prognostic biomarker. IMPACT MLR is an inexpensive and easily available biomarker for predicting prognosis in patients with gallbladder cancer undergoing chemotherapy.
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Affiliation(s)
- Young Hoon Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.,Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Woo Lee
- Department of Gastroenterology, Mediplex Sejong Hospital, Incheon, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
| | - Jin Ho Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jinwoo Kang
- Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ban Seok Lee
- Department of Internal Medicine, Kang-Il Hospital, Gimhae, Korea
| | - Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Kon Ryu
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yong-Tae Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Mao Y, Chen D, Duan S, Zhao Y, Wu C, Zhu F, Chen C, Chen Y. Prognostic impact of pretreatment lymphocyte-to-monocyte ratio in advanced epithelial cancers: a meta-analysis. Cancer Cell Int 2018; 18:201. [PMID: 30534002 PMCID: PMC6282251 DOI: 10.1186/s12935-018-0698-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 12/02/2018] [Indexed: 02/06/2023] Open
Abstract
Background There is increasing evidence that inflammation-based biomarkers are associated with tumor microenvironment which plays important roles in cancer progression. A high lymphocyte-to-monocyte ratio (LMR), has been suggested to indicate favorable prognoses in various epithelial cancers. We performed a meta-analysis to quantify the prognostic value of LMR in advanced-stage epithelial cancers undergoing various treatment. Methods We searched PubMed, EMBASE, Web of science and Cochrane Library up to July 2018 for relevant studies. We included studies assessing the prognostic impact of pretreatment LMR on clinical outcomes in patients with advanced-stage epithelial cancers. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results A total of 8984 patients from 35 studies were included. A high pretreatment LMR was associated with favorable OS (HR = 0.578, 95% CI 0.522–0.641, P < 0.001) and PFS (HR = 0.598, 95% CI 0.465–0.768, P < 0.001). The effect of LMR on OS was observed among various tumor types. A higher pretreatment LMR was associated with improved OS in chemotherapy (n = 10, HR = 0.592, 95% CI 0.518–0.676, P < 0.001), surgery (n = 10, HR = 0.683, 95% CI 0.579–0.807, P < 0.001) and combined therapy (n = 11, HR = 0.507, 95% CI 0.442–0.582, P < 0.001) in the subgroup analysis by different therapeutic strategies. The cut-off value for LMR was 3.0 (range = 2.35–5.46). Subgroup analysis according to the cut-off value showed a significant prognostic value of LMR on OS and PFS in both subgroups. Conclusions A high pretreatment LMR is associated with favorable clinical outcomes in advanced-stage epithelial cancers undergoing different therapeutic strategies. LMR could be used to improve clinical decision-making regarding treatment in advanced epithelial cancers. Electronic supplementary material The online version of this article (10.1186/s12935-018-0698-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yiming Mao
- 1Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Gusu District, Suzhou, 215004 China.,3Department of Thoracic Surgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, China
| | - Donglai Chen
- 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zhengming Road, Yangpu District, Shanghai, 200433 China
| | - Shanzhou Duan
- 1Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Gusu District, Suzhou, 215004 China
| | - Yuhuan Zhao
- 1Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Gusu District, Suzhou, 215004 China
| | - Changjiang Wu
- 4Department of Intensive Care Unit, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, China
| | - Feng Zhu
- 3Department of Thoracic Surgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, China
| | - Chang Chen
- 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, 507 Zhengming Road, Yangpu District, Shanghai, 200433 China
| | - Yongbing Chen
- 1Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Gusu District, Suzhou, 215004 China
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29
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McCluney SJ, Giakoustidis AA, Segler A, Bissel J, Miller RL, Valente R, Hutchins RR, Abraham A, Bhattacharya S, Kocher HM. Predicting complications in hepatic resection for colorectal liver metastasis: the lymphocyte-to-monocyte ratio. ANZ J Surg 2018; 88:E782-E786. [PMID: 30014560 DOI: 10.1111/ans.14725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 05/01/2018] [Accepted: 05/05/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Colorectal cancer is one of the most common malignancies worldwide; whilst approximately 20% of patients have hepatic disease at presentation. Hepatic resection remains the gold standard of care; however, it is associated with significant morbidity. We sought to establish whether the lymphocyte-to-monocyte ratio (LMR) could help predict post-operative complications, thus improving patient outcomes. METHODS We performed a retrospective cohort study of patients undergoing hepatic resection at a single centre. Baseline demographics and complications within 30 days following surgery were recorded. White blood cell counts and C-reactive protein (CRP) were recorded pre-operatively, and until post-operative day 7. RESULTS A total of 188 operations were included. About 47.3% of resections had a complicated recovery, of which 31.46% were major. The median LMR was 1.29 across the cohort, 1.60 for uncomplicated procedures, 1.14 for those with complications and 0.85 in major complications. For detecting major complications versus an uncomplicated recovery, median LMR was the best parameter (area under the curve 0.78), whilst it was the only parameter to accurately predict such complications within 48 hours of surgery (area under the curve 0.72 on day 1). It was consistently the most accurate parameter at detecting uncomplicated versus complicated recovery, minor versus major complications, and major complications versus an uncomplicated recovery, at numerous timepoints over the post-operative period. CONCLUSION The LMR appears better at predicting complications following hepatic resection for colorectal liver metastases, as opposed to conventionally measured parameters.
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Affiliation(s)
- Simon J McCluney
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK.,Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Alexandros A Giakoustidis
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Angela Segler
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Juliane Bissel
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Robert L Miller
- The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Roberto Valente
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Robert R Hutchins
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Ajit Abraham
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Satyajit Bhattacharya
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Hemant M Kocher
- Barts and The London HPB Centre, Department of Surgery, The Royal London Hospital, Barts Health NHS Trust, London, UK.,Barts Cancer Institute, Queen Mary University of London, London, UK
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30
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Pan Z, Peng J, Lin J, Chen G, Wu X, Lu Z, Deng Y, Zhao Y, Sui Q, Wan D. Is there a survival benefit from adjuvant chemotherapy for patients with liver oligometastases from colorectal cancer after curative resection? Cancer Commun (Lond) 2018; 38:29. [PMID: 29843800 PMCID: PMC5993126 DOI: 10.1186/s40880-018-0298-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 03/08/2018] [Indexed: 12/20/2022] Open
Abstract
Background Although colorectal oligometastases to the liver can potentially be cured with aggressive local ablation, the efficacy of adjuvant chemotherapy (ACT) for such metastasis remains unclear. The present study explored the effects of ACT on patients with colorectal liver oligometastases (CLO) after curative resections and aimed to identify patients who could benefit from ACT. Methods We retrospectively analyzed 264 eligible patients with CLO who underwent curative resection between September 1999 and June 2015. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test; prognostic factors were a by Cox regression modeling. Results Among 264 patients, 200 (75.8%) patients received ACT and 64 (24.2%) did not receive ACT. These two groups did not significantly differ in clinicopathologic characteristics, and had comparable 3-year OS and RFS rates (RFS: 42.1% vs. 45.7%, P = 0.588; OS: 69.7% vs. 62.7%, P = 0.446) over a median follow-up duration of 35.5 months, irrespective of preoperative chemotherapy. ACT markedly improved 3-year OS in high-risk patients with Memorial Sloan-Kettering Cancer Center clinical risk scores (MSKCC-CRS) of 3–5 (68.2% vs. 33.8%, P = 0.015), but presented no additional benefit in patients with MSKCC-CRS of 0–2 (72.2% vs. 78.6%, P = 0.834). In multivariate analysis, ACT was independently associated with improved OS in patients with MSKCC-CRS of 3–5. Conclusions ACT might offer a prognostic benefit in high-risk patients with CLOs after curative liver resection, but not in low-risk patients. Therefore, patients’ risk status should be determined before ACT administration to optimize postoperative therapeutic strategies.
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Affiliation(s)
- Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Junzhong Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Xiaojun Wu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Zhenhai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Yuxiang Deng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Yujie Zhao
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Qiaoqi Sui
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Desen Wan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
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Yang Y, Xu H, Zhou L, Deng T, Ning T, Liu R, Zhang L, Wang X, Ge S, Li H, Ba Y. Platelet to lymphocyte ratio is a predictive marker of prognosis and therapeutic effect of postoperative chemotherapy in non-metastatic esophageal squamous cell carcinoma. Clin Chim Acta 2018; 479:160-165. [PMID: 29325800 DOI: 10.1016/j.cca.2018.01.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 01/06/2018] [Accepted: 01/08/2018] [Indexed: 01/01/2023]
Abstract
Increasing evidence has indicated that inflammatory biomarkers, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), can be used as prognostic indicators in esophageal squamous cell carcinoma (ESCC). However, the best predictor for prognosis in ESCC remains controversial. Few studies have focused on the association between inflammatory biomarkers and postoperative chemotherapy. A cohort of 515 non-metastatic ESCC patients was retrospectively reviewed. Harrell's concordance index (c-index) was used to identify the optimal cut-off values of the inflammatory markers, and their prognostic value was compared. Cox multivariate analysis indicated that, among these inflammatory biomarkers, PLR (≥133 vs. <133) was the only independent prognostic factor for poor OS [hazard ratio = 1.370, 95% confidence intervals = 1.076-1.745, p = .011]. The c-index values of PLR were higher compared with NLR and PNI. For patients with PLR < 133, the surgery plus chemotherapy group had significantly longer OS than the surgery group alone (p = .004), but the significant difference of OS between these two groups was not observed in patients with PLR ≥ 133 (p = .624). PLR is a predictive marker of prognosis and therapeutic effect of postoperative chemotherapy in non-metastatic ESCC.
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Affiliation(s)
- Yuchong Yang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Hao Xu
- Department of General Surgery, Peking University First Hospital, Beijing 100030, PR China
| | - Likun Zhou
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Ting Deng
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Tao Ning
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Rui Liu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Le Zhang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Xia Wang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Shaohua Ge
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Hongli Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China
| | - Yi Ba
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, PR China.
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32
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Melichar B, Hrůzová K, Krčmová LK, Javorská L, Pešková E, Solichová D, Hyšpler R, Malířová E, Vošmik M, Bartoušková M, Klos D, Študentová H. Association of peripheral blood cell count-derived ratios, biomarkers of inflammatory response and tumor growth with outcome in previously treated metastatic colorectal carcinoma patients receiving cetuximab. Pteridines 2017; 28:221-232. [DOI: 10.1515/pterid-2017-0016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/07/2023] Open
Abstract
Abstract
The aim of the present study was to investigate the association of peripheral-blood cell count (PBC)-derived ratios, other biomarkers of inflammation and biomarkers of tumor growth with outcome in a cohort of patients presenting for the next line of therapy after the failure of prior systemic treatment. The data of 51 patients with advanced/metastatic colorectal carcinoma treated with cetuximab in the second or higher line of therapy were retrospectively analyzed. The median duration of cetuximab therapy and the median survival were 5.1 and 12.1 months, respectively. C-reactive protein (CRP), but not urinary neopterin correlated significantly with PBC-derived ratios. Both CRP and urinary neopterin correlated positively with carcinoembryonic antigen (CEA) concentrations and biomarkers of liver dysfunction. Although a number of parameters predicted overall survival in univariate analysis, only hemoglobin, CEA change and serum bilirubin were independent predictors of survival. In conclusion, in patients with metastatic colorectal carcinoma and predominantly liver metastases, the outcome of therapy in the advanced line setting was associated with initial hemoglobin level, a decrease of CEA concentration and initial presence of liver dysfunction. Urinary neopterin did not correlate with PBC-derived ratios, in contrast to CRP, but both urinary neopterin and serum CRP concentrations correlated with laboratory parameters of liver dysfunction.
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Affiliation(s)
- Bohuslav Melichar
- Department of Oncology , Palacký University Medical School and Teaching Hospital , I.P. Pavlova 6 , 779 00 Olomouc , Czech Republic
- Institute of Molecular and Translational Medicine , Palacký University Medical School and Teaching Hospital , I.P. Pavlova 6 , 779 00 Olomouc , Czech Republic
- Department of Oncology and Radiotherapy , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
- Fourth Department of Medicine , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Klára Hrůzová
- Department of Oncology , Palacký University Medical School and Teaching Hospital , I.P. Pavlova 6 , 779 00 Olomouc , Czech Republic
| | - Lenka Kujovská Krčmová
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Teaching Hospital , Hradec Králové , Czech Republic
- Department of Analytical Chemistry , Charles University School of Pharmacy , Hradec Králové , Czech Republic
| | - Lenka Javorská
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Teaching Hospital , Hradec Králové , Czech Republic
- Department of Analytical Chemistry , Charles University School of Pharmacy , Hradec Králové , Czech Republic
| | - Eliška Pešková
- Fourth Department of Medicine , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Dagmar Solichová
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Radomír Hyšpler
- Third Department of Medicine (Gerontology and Metabolic Care) , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
- Department of Clinical Biochemistry , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Eva Malířová
- Department of Clinical Biochemistry , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Milan Vošmik
- Department of Oncology and Radiotherapy , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
| | - Marie Bartoušková
- Department of Oncology , Palacký University Medical School and Teaching Hospital , I.P. Pavlova 6 , 779 00 Olomouc , Czech Republic
| | - Dušan Klos
- First Department of Surgery , Palacký University Medical School and Teaching Hospital , I.P. Pavlova 6 , 779 00 Olomouc , Czech Republic
| | - Hana Študentová
- Department of Oncology , Palacký University Medical School and Teaching Hospital , I.P. Pavlova 6 , 779 00 Olomouc , Czech Republic
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