BACKGROUND: Inflammation may play an important role in cancer progression, and a high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in solid tumors. METHODS: A systematic review of electronic databases was conducted to identify publications exploring the association of blood NLR and clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled hazard ratios were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. RESULTS: One hundred studies comprising 40559 patients were included in the analysis, 57 of them published in 2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages. Hazard ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and 2.27, respectively (all P < .001). CONCLUSIONS: A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis

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Pathology and genetics of tumours of the lung , pleura, thymus and heart

There is increasing and consistent evidence that cancer-associated inflammation is a key determinant of outcome in patients with cancer. Various markers of inflammation have been examined over the past decade in an attempt to refine stratification of patients to treatment and predict survival. One routinely available marker of the systemic inflammatory response is the neutrophil-lymphocyte ratio (NLR), which is derived from the absolute neutrophil and absolute lymphocyte counts of a full blood count. To date, over 60 studies (>37,000 patients) have examined the clinical utility of the NLR to predict patient outcomes in a variety of cancers. The present systematic review examines and comments on the clinical utility of the NLR. The NLR had independent prognostic value in (a) unselected cohorts (1 study of >12,000 patients), (b) operable disease (20 studies, >4000 patients), (c) patients receiving neoadjuvant treatment and resection (5 studies, >1000 patients), (d) patients receiving chemo/radiotherapy (12 studies, >2000 patients) and (e) patients with inoperable disease (6 studies, >1200 patients). These studies originated from ten different countries, in particular UK, Japan, and China. Further, correlative studies (15 studies, >8500 patients) have shown that NLR is elevated in patients with more advanced or aggressive disease evidenced by increased tumour stage, nodal stage, number of metastatic lesions and as such these patients may represent a particularly high-risk patient population. Further studies investigating the tumour and host-derived factors regulating the systemic inflammatory response, in particular the NLR, may identify novel treatment strategies for patients with cancer.

The systemic inflammation-based neutrophil–lymphocyte ratio: Experience in patients with cancer

In the past 25 years, a majority of cancer studies have focused on examining functional consequences of activating and/or inactivating mutations in critical genes implicated in cell cycle control. These studies have taught us a great deal about the functions of oncogenes and tumor suppressor genes and the signaling pathways regulating cell proliferation and/or cell death. However, such studies have largely ignored the fact that cancers are heterogeneous cellular entities whose growth is dependent upon reciprocal interactions between genetically altered “initiated” cells and the dynamic microenvironment in which they live. This review highlights the aspects of cancer development that, like organogenesis during embryonic development and tissue repair in adult mammals, are regulated by interactions between epithelial cells, activated stromal cells, and soluble and insoluble components of the extracellular matrix.

Tumor stroma and regulation of cancer development.

Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. There is substantial evidence in advanced cancer that host factors, such as weight loss, poor performance status and the host systemic inflammatory response, are linked, and the latter is an important tumor-stage-independent predictor of outcome. Indeed, the systemic inflammatory response, as evidenced by an elevated level of C-reactive protein, is now included in the definition of cancer cachexia. This review examines the role of the systemic inflammatory response in predicting survival in patients with primary operable cancer. Approximately 80 studies have evaluated the role of the systemic inflammatory response using biochemical or hematological markers, such as elevated C-reactive protein levels, hypoalbuminemia or increased white cell, neutrophil and platelet counts. Combinations of such factors have been used to derive simple inflammation-based prognostic scores, such as the Gl...

Role of systemic inflammatory response in predicting survival in patients with primary operable cancer

Minute pulmonary meningothelial-like nodules (MPMNs), previously known as minute pulmonary chemodectomas, are relatively rare lesions. They are small (1-3 mm) and often multiple. Pathologically, they represent an interstitial nodular proliferation of small oval or spindle-shape cells arranged in a "zellenballen" nesting pattern. The function and origin of the cells are unknown. These nodules are associated with specific conditions, including thromboembolism, cardiac disease, and malignancy. We describe a patient with MPMNs and adenocarcinoma of the lung in whom HRCT showed tiny (1-3 mm in diameter) nodules of ground-glass attenuation.

Minute pulmonary meningothelial-like nodules: high-resolution computed tomography and pathologic correlations.

A left ventricular assist device (LVAD) is an effective method to rescue severe heart failure. Although some require a biventricular assist, the control method for the biventricular assist device (BVAD) with a rotary pump is rarely shown. The objective of this study was to investigate the strategy for controlling BVAD with rotary pumps by in vivo studies. Using 5 piglets, we set a BVAD through a left thoracotomy and made global ischemia for 30 min by clamping the base of the ascending aorta. After unclamping, the analysis of pumping performance acted for 6 h reperfusion. We set the target flow of the LVAD and set the right ventricular assist device (RVAD) speed limit as less than when the atrial collapse occurs. To detect the ventricular collapse without any specific sensor, we calculated the index of current amplitude from motor current waveform and simultaneous mean current value. In all cases, over 6 h of observation was performed, and the RVAD was weaned almost automatically.

Control strategy for biventricular assistance with mixed-flow pumps.

Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast

The index of motor current amplitude (ICA) has feasibility in continuous-flow ventricular assist device control. It can demonstrate the safe range of pump speed, which exists between the starting point of total assistance (t-point) and the starting point of sucking (s-point). The objective of this study was to investigate how the ICA characteristic curve changes with each condition of contractility, preload, and afterload changes. We changed preload, afterload, and contractility of closed-mock circulation and plotted the change of the ICA value against pump speed. Then the shift of ICA characteristic curve against the change of each condition was considered. When preload increased, ICA characteristic curves showed the expansion of a safe range. When afterload increased, ICA characteristic curves were shifted to the high rotation side, slightly narrowing a safe range. When contractility increased, ICA characteristic curves showed the shift of a convex above to narrowing of a safe range. As these shift patterns were observed even when the driving conditions of a circuit changed, reproducibility was checked. Understanding the feature of a shift pattern of ICA characteristic curves correctly, a possibility that change of the heart function could be predicted by change of ICA value and a possibility for a flexible control method based on ICA, according to hemodynamic state, were suggested.

The index of motor current amplitude has feasibility in control for continuous flow pumps and evaluation of left ventricular function.

Background:Onlyafewstudieshavereportedany prognosticimpactofthepreoperativehemoglobinlevelitself in resectable non-small cell lung cancer (NSCLC). The survival impact of preoperative hemoglobin level and the relationshipbetweenhemoglobinandserumCEAlevelwere investigated. Patients and Methods: Two hundred and forty consecutive NSCLC patients were reviewed retrospectively. Results:The 5-year survival of patients with low and those with a normal hemoglobin level was 42.99% and 73.47%, respectively. Both univariate and multivariate analyses indicated the independent prognostic impact of the hemoglobinlevel.TheresultforstageIpatientswasidentical. Patientswithnormalhemoglobincouldbesubdividedinto2 groups based on their serum CEA level; the 5-year survival of patients with normal and those with elevated CEA was 81.72% and 57.24%, respectively. Conclusion: The preoperative hemoglobin level was a prognostic factor for NSCLCpatients.ThecombineduseofhemoglobinandCEA levelsmightbeusefultopredicttheprognosisofpatients. Multiple prognostic factors have been reported in the literature for patients with NSCLC. However, the majority of these factors cannot be obtained preoperatively. Moreover some of these factors are available only as research tools. Currently, serum carcinoembryonic antigen (CEA) level is the most inexpensive and routinely available preoperative factor measurable. Several reports have indicated that elevated preoperative serum CEA levels are associated with very poor survival after surgical resection (1-5). We believe that the measurement of such factors are important and should be valued. Among such preoperative factors, the hemoglobin level was reported as a prognostic factor (6-12). Although a low hemoglobin level was reported to impact outcome in patients with NSCLC receiving chemotherapy or radiation therapy (7-12), only a few studies have reported its impact on the outcome of patients with resectable NSCLC (13, 14). Moreover, its relationship with the CEA level is also unknown. In the present study, therefore, the prognostic impact of preoperative hemoglobin level and the relationship between hemoglobin and serum CEA in NSCLC were retrospectively investigated Patients and Methods The present study was conducted from 2000 through 2004, including all patients with lung cancer who had a thoracotomy for intended surgical resection. Two hundred and forty consecutive lung cancer patients who underwent surgical resection were included in this study. There were 157 men and 83 women, with ages ranging from 26 to 85 years, with an average of 66.4 years. Overall follow- up periods ranged from 29 to 90 months. The preoperative hemoglobin levels were obtained before

Toshio Onitsuka

Papers

Minute pulmonary meningothelial-like nodules: high-resolution computed tomography and pathologic correlations.

Control strategy for biventricular assistance with mixed-flow pumps.

Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast

The index of motor current amplitude has feasibility in control for continuous flow pumps and evaluation of left ventricular function.

Impact of Preoperative Hemoglobin Level on Survival of Non-small Cell Lung Cancer Patients