ABSTRACT

Conclusion:

Hematological inflammatory markers are useful in predicting the pathology outcome of kidney masses before surgery.

Results:

The mean age of 116 patients included in the study was 55.36±13.93 years. While pathology results of 26 (22.4%) patients were benign, results of 90 (77.6%) patients were malignant. The neutrophil and neutrophil lymphocyte ratio were significantly lower in the benign group. According to the Fuhrman grade of renal cell carcinoma, platelet and platelet lymphocyte ratio were higher in aggressive groups, whereas lymphocyte count was lower.

Method:

One hundred sixteen patients who were operated for kidney mass between January 2010 and October 2020 were included in the study. Retrospectively, preoperative platelets, neutrophils, lymphocytes and their rates were compared with pathology results.

Objective:

Despite the recent advances in imaging methods, the rate of 10-20% is still insufficient in predicting the pathology of renal masses. Therefore, we aimed to examine whether hematological inflammatory markers were useful in predicting pathology outcome.

Introduction

Among urogenital tumors, renal tumors are seen in third place in order of incidence and in first place in order of mortality (1). Patients present to the clinic with the complaints of flank pain, palpable mass, and hematuria. However, this triad is present in 5-10% of cases and is associated with advanced disease (2).

Today, renal masses are incidentally detected earlier, thanks to the increasing use and the quality of imaging methods (3). Accordingly, surgical treatments give more positive results (4). Despite these improvements in radiological imaging, it is still insufficient to predict pathology of kidney tumors. In 10-20% of patients, especially in benign masses such as angiomyolipoma which has poor adipose tissue and oncocytoma, the distinction between benign and malignant cannot be made (5). For this reason, additional data are needed to predict the outcome of pathology before surgery.

Many studies have shown that systemic inflammation is effective in the formation and progression of cancer. Systemic inflammation increases in the number of platelets and neutrophils, and decreases in the number of lymphocytes. It has been shown in some studies that these hematological values can be used to predict prognosis in kidney tumors (6). However, we did not find any study in the literature regarding the use of these parameters to predict malignancy.

In this study, it was evaluated whether platelet, neutrophil, lymphocyte and their ratios could be used to predict pathology results in kidney masses.

Materials and Methods

After getting approval from the Local Ethics Committee (Van Yüzüncü Yıl University, KAEK, decision number: 2020/09-21, date: 04.12.2020) and obtaining consent form from patients, in accordance with the latest Helsinki Declaration, the files of patients who underwent radical and partial nephrectomy in our clinic between January 2010 and October 2020 were retrospectively reviewed. Age, gender, tumor side, diameter, operation, pathology results of the patients, platelet, neutrophil, lymphocyte values and ratios, platelet/lymphocyte (PLR), platelet/neutrophil (PNR), and neutrophil/lymphocyte rate (NLR) were evaluated together with pathology results. Fuhrman system was used for tumor grades. Patients with chronic diseases that could alter inflammatory parameters, such as diabetes mellitus, chronic kidney disease, chronic liver disease, sarcoidosis, amyloidosis, and inflammatory bowel diseases, were excluded from the study. And those using drugs such as steroid and anti-inflammatories, which could alter inflammatory parameters, were excluded from the study.

Statistical Analysis

Age, tumor size, neutrophil, lymphocyte, platelet, PLR, NLR, and PNR were expressed as mean and standard deviation, and gender, direction, and pathology results were expressed as numbers and percentages. One-Way analysis of variance was used to compare the groups in terms of inflammatory parameters. Statistical significance level was taken as 5% in calculations and SPSS (ver.21) statistical package program was used for analyses.

Results

The mean age of 116 patients included in the study at the time of diagnosis was 55.36±13.93 years. Seventy (60.3%) of the patients were male and 46 (39.7%) were female. Tumor size was 6.62±4.20 cm on average. Radical nephrectomy was applied to 77 of the patients (66.4%), and partial nephrectomy to 39 (33.6%) of the patients. While 90 (77.6%) of the pathology results were malignant, 26 (22.4%) of them were benign. Of the malignant pathologies, 86 were renal cell carcinoma (RCC), and 4 were transitional cell carcinomas. According to the Fuhrman grading of RCCs, 26 were grade 1, 38 were grade 2, 17 were grade 3, and 5 were grade 4. Of the benign pathologies, 12 were oncocytomas, 6 were angiomyolipoma, 4 were xanthogranulomatous pyelonephritis, and 4 were multicystic lesions. The preoperative platelet was 268,700±82,560, neutrophil was 5,430±2,220, lymphocyte was 2,140±750, PNR ratio was 55.21±21.55, PLR ratio was 140.99±70.88, NLR ratio was 2.82±1.53. The comparison of inflammatory parameters with pathology results are shown in Table 1, 2.

Table 1

Table 2

Discussion

Inflammation plays a key role in cancer (7). Cytokines and growth factors produced together with systemic inflammation trigger carcinogenesis and cause tumor development and proliferation. The inflammatory role of chronic inflammation in hepatocellular carcinoma caused by viral infection, in bladder cancer by chronic stones and infection, and in colon cancer by inflammatory bowel disease has been demonstrated (8-10).

After learning the role of inflammation in cancer, it has become important to show systemic inflammation in a correct, easy and cheap way. Complete blood count (CBC) shows systemic inflammation very easily, quickly, accurately and at a low cost for the patient and physician with many parameters it includes (11,12). The most important inflammatory markers of CBC are neutrophils, lymphocytes and thrombocytes. While neutrophilia is associated with chronic inflammation in cancer, studies have shown that lymphopenia and thrombocytosis are associated with poor prognosis in many types of cancer (11). Also, studies show that CBC inflammation parameters can help in diagnosis. One study indicated that NLR and PLR could be used in some cases to differentiate benign prostatic hyperplasia from prostate cancer (13).

Platelet, one of the systemic inflammation parameters in CBC, is effective in tumor development. Thrombocytes produce these effects through vascular endothelial growth factor, platelet-derived growth factor (PDGF), fibroblast growth factor and transforming growth factor-beta (14). Both absolute neutrophil count and NLR are used as the markers of inflammation. Although neutrophils are the main defenders of the immune system, their increasing numbers both trigger the activation of tumor cells and cause suppression of anti-tumoral mechanisms (15). Neutrophils act through cytokines and growth factors (16). Lymphocytes, another element of the systemic response, inhibit tumor cell proliferation and migration, and kill tumor cells with a cytotoxic effect (17). Lymphocytes can suppress tumor cells through CD3, CD4, CD8, and p46 and improve survival in patients with cancer (2). Many studies have shown that neutrophil and neutrophil-lymphocyte ratios can be used to predict cancer prognosis (18). However, we could not see enough studies in the literature regarding the use of neutrophils to predict preoperative malignancy. In one of these studies, Tangal et al. (19) stated that neutrophil-lymphocyte ratios were not useful in predicting malignancy and the Fuhrman’s degree in kidney masses. However, in our study, both the neutrophil value and the neutrophil-lymphocyte ratio were found to be significantly higher in the malignant group. It is observed that Tangal et al. (19) did not exclude patients with additional systemic diseases from the study. However, systemic diseases and malignancies change neutrophil and lymphocyte counts (11).

The other hematological parameter of systemic inflammation is lymphocytes. In none of the studies we encountered in the literature, the number of lymphocytes was evaluated alone, and in all studies, it was studied in the form of NLR or PLR. Increased NLR has been reported to be associated with poor prognosis in breast, colorectal, esophagus and prostate cancer (20-23). On the other hand, Karaoğullarından et al. (14) showed in their study that PLR increased in direct proportion to the diameter of the tumor (14). In addition, lymphocytopenia has been associated with poor prognosis in many studies (24). In our study, lymphocyte level was higher in benign tumors. However, it was not statistically significant. It is possible to obtain statistically significant results in studies with higher case series.

The Fuhrman histopathological rating system is the most commonly used method in RCCs today. The importance of Fuhrman core rating in predicting survival was demonstrated in the study of Gudbjartson et al. (25) on 629 patients. Although Viers et al. (26) showed an important relationship between NLR and Fuhrman’s degree, no significant results were obtained in the study of Arda et al. (27). In our study, no relationship was found between neutrophil count, NLR and Fuhrman grade. However, in RCC patients, it was observed that platelets increased significantly as the degree of prostitution increased. We observed that the lymphocyte count decreased significantly inversely with the Fuhrman grade and the PLR significantly according to the Fuhrman grade.

The retrospective design and relatively small number of patients are the limitations of our study.

Conclusion

Systemic inflammation parameters such as neutrophil, lymphocyte and platelet levels can be used to predict postoperative pathology outcomes before surgery.

Ethics

Ethics Committee Approval: After getting approval from the Local Ethics Committee (Van Yüzüncü Yıl University, KAEK, decision number: 2020/09-21, date: 04.12.2020).

Informed Consent: Informed consent was obtained.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Concept: M.D., R.E., R.A., K.E., Design: M.D., R.E., K.T., K.E., Data Collection or Processing: M.D., R.E., R.A., Analysis or Interpretation: M.D., K.E., R.A., Literature Search: M.D., K.T., Writing: M.D., K.E., R.E., R.A.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The author declared that this study has received no financial support.

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Differentiation of Benign and Malignant Kidney Masses via Inflammation Parameters