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

Distinction between non-invasive and invasive thymomas is almost impossible by histologic examination alone, because the morphology of invasive thymoma does not significantly differ from that of non-invasive thymoma [1,2]. However, tumor invasiveness is regarded as the most important factor affecting survival in thymoma [3]. In the present study, we examined the expression of some cancer-related proteins in thymoma by immunohistochemistry to determine whether the expression of these proteins is different between non-invasive and invasive thymomas.

Relationship between expression of cancer-related proteins and tumor invasiveness in thymoma.

Mechanical cardiac assistance can be critical in saving the lives of patients with acute cardiac failure. However, currently used methods of ventricular assistance require advanced technical knowledge and equipment, and only small numbers of patients can be provided with them. Our aim was to develop new cannulas to construct a less invasive biventricular assist system that would permit easy application without thoracotomy. We prepared 2 centrifugal pumps and 4 uniquely shaped cannulas and conducted experiments to investigate the potential and problems of the system. In the first experiment, the system was attached to 6 dogs with ventricular fibrillation to confirm whether our system could maintain cardiac output. In the second experiment, the system was installed for 3 days in 3 goats, and changes in aminotransferases, BUN, creatinine, and plasma free hemoglobin levels were examined. In Experiment 1, it was demonstrated that the system was able to maintain circulation in dogs. In Experiment 2, although the flow rate of the pumps was maintained over 3 days, increased hemolysis and deteriorating renal function were observed. Although these problems need to be solved, the system was still helpful in the management of acute biventricular failure for short periods and may be clinically useful in the near future.

Potentialities and problems of a novel bilateral ventricular assist system without thoracotomy.

OBJECTIVES Despite extensive studies of tumor angiogenesis in non-small cell lung cancer, only a few studies had concentrated on pN2 disease. METHODS Sixty patients with pN2 non-small cell lung cancer who had undergone a complete resection with a systematic mediastinal lymph node dissection were reviewed retrospectively. Immunohistochemical study, using antibodies against factor VIII, was conducted. We compared between 5-year survivors and the others rather than the cumulative survival rate. RESULTS There were 13 patients (21.7%) survived longer than 5 years after a surgical resection. The microvessel density in survivor and non-survivor group was 22.9+/-14.8 and 24.3+/-21.9, respectively. This data indicated that microvessel density might not be related to the ratio of 5-year survivors (P=0.723). Multivariate analysis also showed that microvessel density was not independent prognostic factor. CONCLUSIONS We failed to find a prognostic significance of tumor angiogenesis in pN2 disease. Although tumor angiogenesis might be important for the development and maintenance, it was not identified as a prognostic factor of pN2 non-small cell lung cancer.

Lack of prognostic significance of tumor angiogenesis in resected pN2 non-small cell lung cancer

Although not uncommon in adults, thymomas are the least common mediastinal tumors in children. The behavior of these tumors in children is partially distinct with a much more rapid course and a poor prognosis. A symptom-free 6-year-old boy was treated for malignant thymoma detected incidentally on a chest X-ray in a school mass examination. At operation, the tumor was found to have already invaded the surrounding tissue. Complete removal at the base of the invasive tumor is the treatment of choice.

Primary malignant thymoma in a-6-year-old boy

A 70-year-old male with tricuspid regurgitation due to a blunt chest trauma inflicted 16 years previously underwent prosthetic valve replacement. At surgery, a tear, which produced tricuspid regurgitation, was found around the annulus of the anterior leaflet of the tricuspid valve. Since this area has not been reported as a location for heart trauma-producing tricuspid regurgitation, a possible mechanism of tricuspid regurgitation is discussed in this patient.

Toshio Onitsuka

Papers

Relationship between expression of cancer-related proteins and tumor invasiveness in thymoma.

Potentialities and problems of a novel bilateral ventricular assist system without thoracotomy.

Lack of prognostic significance of tumor angiogenesis in resected pN2 non-small cell lung cancer

Primary malignant thymoma in a-6-year-old boy

Tricuspid regurgitation due to chest trauma: an unusual laceration around the annulus of the anterior leaflet.