|Year : 2019 | Volume
| Issue : 5 | Page : 701-706
Are calculated ratios and red blood cell and platelet distribution width really important for the laryngeal cancer and precancerous larynx lesions
A Kara, M Guven, D Demir, MS Yilmaz, ME Gundogan, S Genc
Department of Otorhinolaryngology, Sakarya University Training and Research Hospital, Korucuk, Sakarya, Turkey
|Date of Acceptance||25-Mar-2019|
|Date of Web Publication||15-May-2019|
Asst Prof. A Kara
Sakarya University Training and Research Hospital, 54000, Korucuk, Sakarya
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: In this research, it is planned to investigate the differences in neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, reticulocyte distribution width, and platelet distribution width values of groups of benign laryngeal lesion, precancerous laryngeal lesion, and laryngeal squamous cell carcinoma and among patients with different stages of tumors in laryngeal carcinoma and precancerous laryngeal lesion groups, and whether these values carry a prognostic features. Materials and Methods: The investigated parameters determined from preoperative blood samples of patients have been compared among the groups and in the subgroups according to severity of illness in laryngeal carcinoma and precancerous laryngeal lesion groups. Also, the laryngeal carcinoma and precancerous laryngeal lesion groups were divided into two subgroups as good and poor prognosis and were compared with patients having good prognosis requiring no additional treatment during the follow-up, and the statistical significance of the differences was examined. Results: On comparison, statistically significant differences were only observed between the gross larynx carcinoma group and other lesions. Apart from that, when the values were evaluated in terms of prognosis, no significant statistical results were found in any of the values. Conclusion: Despite the significant statistical results seen in the gross tumors, it is known that there are more objective methods for identifying those lesions in clinical use. We conclude that caution should be exercised when using these new hematological parameters, which can be affected by many factors.
Keywords: Inflammation, larynx, lymphocyte, neutrophil, red blood cell distribution width, thrombocyte
|How to cite this article:|
Kara A, Guven M, Demir D, Yilmaz M S, Gundogan M E, Genc S. Are calculated ratios and red blood cell and platelet distribution width really important for the laryngeal cancer and precancerous larynx lesions. Niger J Clin Pract 2019;22:701-6
|How to cite this URL:|
Kara A, Guven M, Demir D, Yilmaz M S, Gundogan M E, Genc S. Are calculated ratios and red blood cell and platelet distribution width really important for the laryngeal cancer and precancerous larynx lesions. Niger J Clin Pract [serial online] 2019 [cited 2019 May 26];22:701-6. Available from: http://www.njcponline.com/text.asp?2019/22/5/701/258276
| Introduction|| |
Laryngeal squamous cell carcinomas (LSCCs) are the most common of the head and neck cancers. When all cancer types are taken into consideration, laryngeal carcinoma has a frequency of 1%–2%. The 2017 American data showed a frequency of 13,360 new cases and 3600 mortality rate. Even though there are many disturbing symptoms of laryngeal carcinoma, such as hoarseness of voice, swallowing difficulties, and otalgia, the availability of basic laryngoscopic methods that can be performed clinically in precancerous lesions and early-stage laryngeal carcinomas for clinicians for early diagnosis, advanced stage referrals are still seen. Therefore, finding of biomarkers or reagents, which may contribute to early diagnosis, may contribute to treatment of this disease, which has a high risk of morbidity and mortality.
The treatment of LSCC can be performed in a wide variety of forms. While methods such as total laryngectomy or concomitant chemoradiotherapy are used for advanced local tumors, hot and cold partial laryngeal surgeries can now be performed for many tumors localized in the larynx., Vocal cord tumors can also be treated by preserving phonological functions with an effective radiotherapy. Prognostic evaluations are also very important for this disease which has so many different treatment methods. For tumors with poor prognostic characteristics independent of the histopathological type, choosing aggressive surgical approach would absolutely be beneficial. Therefore, investigating prognostic biomarkers or reagents in this context is important.
Review of related literature on the subject showed that many of the ratios detected easily by whole blood count can be used for early diagnosis of LSCCs and as prognostic markers. However, we believe that relevant studies should continue due to the low sensitivity and specificity ratios in the reviewed publications and the negative results in similar studies conducted for different diseases.
In this study, we planned to compare neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), reticulocyte distribution width (RDW), and platelet distribution width (PDW) values of the groups of patients with benign laryngeal lesion (BLL), precancerous laryngeal lesion (PLL), and LSCC and to compare the effects of severity of the disease with the values for groups of patients with LSCC and PLL. In addition, the prognostic values of the mentioned values for LSCC and PLL groups have been examined in this study. The effect of PLR values on patients with PLL and the correlation of NLR, PLR, LMR, RDW, and PDW with prognosis of PLL have been studied in the literature for the first time.
| Materials and Methods|| |
The research protocol was conducted in accordance with the ethical regulations of the Declaration of Helsinki and in adherence to Turkish law and regulations. Patients diagnosed with BLL, PLL, and LSCC and treated between January 2008 and January 2018 in Otorhinolaryngology Clinic of the University of Sakarya Training and Research Hospital were included in this research. Patients with systemic diseases such as acute coronary artery disease, active stage of connective tissue disease, vasculitis, inflammatory intestinal disease, chronic renal failure, and chronic liver failure were excluded from the study.
Two milliliters of peripheral venous blood samples taken from the patients before the surgical operations was examined with Cell- Dyn 3700 (Abbott, USA) SL device, and neutrophil, lymphocyte, platelet, and monocyte counts and RDW and PDW values were recorded. From the data, NLR and PLR values were obtained by dividing neutrophil and platelet counts by lymphocyte counts; by proportioning lymphocyte counts with monocyte counts, LMR values were calculated. Data acquired were compared among groups and among subgroups of PLL and LSCC formed according to the severity of the disease. Also, patients requiring additional therapies after initial treatments due to recurrence in LSCC and PLL groups were considered as patients with poor prognosis and they were also compared with patients requiring no additional treatment with good prognosis during the follow-up and significant statistical differences were examined.
Using the 8th Edition of Cancer Staging Manuel of the American Joint Committee on Cancer, the laryngeal carcinoma group was divided into four subgroups as stages T1, T2, T3, and T4. Patients with stages T2, T3, and T4 tumors were also examined under the gross tumor title. Likewise, patients in the PLL group were classified as mild, moderate, and severe carcinoma in situ(CIS)/dysplasia according to the World Health Organization classification criteria and were analyzed statistically.,
Statistical analysis was performed using IBM SPSS 20.0 version statistical software program (IBM Corporation, Armonk, NY, USA) for Windows. The mean ± standard deviation was used for continuous variables, and the percentage values were used for categorical variables. Kolmogorov–Smirnov analysis was performed for normality distribution analysis, and as a result of this analysis nonparametric tests were preferred. Mann–Whitney U-test was used for pairwise comparisons and Kruskal–Wallis test was used for multiple comparisons among the groups. In the case of statistical significance as a result of multiple comparisons, Friedman test and pairwise comparisons as post hoc tests were performed. P values less than 0.05 were considered as statistically significant.
| Results|| |
A total of 116 patients treated for PLL, 186 for LSCC, and 151 for BLL were included in the research. The average age of the group of patients with PLL was 57.57 ± 10.15 years, and 7% of the group were females and 93% were males. The average age of LSCC group was 62.9 ± 9.89 years, and 7% and 93% consisted of females and males, respectively, while the mean age of BLL group was 50.63 ± 11.9 years, with 28% females and 72% males. Data are summarized in [Table 1].
As shown in [Table 2], NLR, PLR, LMR, RDW, and PDW values were calculated separately for each group and were compared using Kruskal–Wallis analysis. According to these analyses, even though the difference between RDW and PDW was not statistically significant, significant statistical differences were observed among the groups for NLR, PLR, and LMR values. Thus, the values showing significant statistical differences were evaluated among themselves. As a result, it was noted that the differences between BLL, PLL, and T1 stage tumors and gross tumors were statistically significant. However, when BLL, PLL, and T1 stage tumors were compared among themselves, statistically significant results were not observed. In the post hoc analysis examined for PLR and LMR values, the differences between groups of patients with BLL and PLL and gross tumors were statistically significant. The results are summarized in [Table 2].
|Table 2: Comparison of the groups for NLR, PLR, LMR, RDW, and PDW measurements|
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The PLL group was examined in three subgroups as mild, moderate, and severe dysplasia/CIS. In each group, there were 65 (56%), 25 (21.6%), and 26 (22.4%) patients, respectively. As shown in [Table 3], NLR, PLR, LMR, RDW, and PDW values were calculated and compared separately for each group. While NLR value was the highest in severe dysplasia group, PLR and LMR were the highest in moderate dysplasia group. RDW and PDW values were observed to be the highest in mild dysplasia group. When data were compared using Kruskal–Wallis analysis, there was no statistically significant difference between any of the comparisons. The results are listed in [Table 3].
|Table 3: Comparison of the subgroups in PLL group for NLR, PLR, LMR, RDW, and PDW measurements|
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Patients in the laryngeal carcinoma group were examined by separating them into four groups according to T stages, as T1, T2, T3, and T4 stage tumors. There were 76 (40.9%), 28 (15.1%), 26 (14%), and 56 (30.1%) patients in each group, respectively. NLR, PLR, LMR, RDW, and PDW values were calculated and compared separately for each group as shown in [Table 4]. While NLR, PLR, and RDW values were the highest in T3 tumor group, LMR values were the highest in T4 tumor group. PDW values were observed to be the lowest in T4 tumor group. No increase in proportion to T stage was observed at any given value. When data were compared using Kruskal–Wallis analysis, only the differences between T1 and T2 tumor groups and T1 and T4 tumor groups at NLR value were statistically significant. The results are given in [Table 4].
|Table 4: Comparison of the subgroups in LSCC group for NLR, PLR, LMR, RDW, and PDW measurements|
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In all, 43 patients (23.1%) diagnosed with LSCC required additional treatment during follow-up due to recurrence. These patients were considered to have poor prognosis and were compared with patients having good prognosis in NLR, PLR, LMR, RDW, and PDW values using Mann–Whitney U-test. As a result, it was seen that no values constituted statistical significance. The results are summarized in [Table 5].
|Table 5: Comparison of NLR, PLR, LMR, RDW, and PDW measurements for prognostic value in LSCC group|
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Fifteen patients (12.9%) diagnosed with PLL required additional treatment during their follow-up due to recurrence and progression. Patients considered to have poor prognosis were compared with patients having good prognosis in NLR, PLR, LMR, RDW, and PDW values using Mann–Whitney U-test. As a result, it was seen that no values constituted statistical significance. The results are listed in [Table 6].
|Table 6: Comparison of NLR, PLR, LMR, RDW, and PDW measurements for prognostic value in PLL group|
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| Discussion|| |
In recent years, studies with various types of cancers have found significant correlation between inflammatory response and initiation, promotion, progression, and metastasis of tumors.,,, There are scientific articles in which lymphocyte infiltration around the tumor was associated with good prognosis and neutrophil domination in tumor stroma was associated with poor prognosis., High neutrophil and platelet values were correlated with angiogenesis and thus with risk of metastasis., Diagnostic and prognostic correlations between hepatocellular carcinoma, pancreatic carcinoma, renal cell carcinoma, oral cavity carcinoma, and laryngeal carcinoma with elevation of NLR, PLR, LMR, RDW, and PDW values can be detected easily by whole blood count using hypothesis based on this scientific basis.,,, In addition, there are studies showing that NLR and PLR values increase even in precancerous carcinoma.,
In the literature, there is only one study examining the difference in NLR values among BLL, PLL, and LSCC, and in this study laryngeal cancers were included in the comparison regardless of T stages and as a result of the study, statistically significant differences were observed in all groups in terms of NLR. In another study by Fu et al., it was reported that PDW value can also be used to differentiate malignant lesions from benign lesions. In this study, it was observed that the difference between BLL, PLL, and T1 stage laryngeal cancer was not statistically significant except for the difference between others and gross tumors. To have a clinical significance of a diagnostic laboratory test, it is important to identify the disease before causing clinical complaints and even at the stage where a clinician could not realize the disease during the examination or to carry stimulant characteristics. When this situation was evaluated for laryngeal tumors, even though patients with BLL, PLL, and LSCC came to the clinic with similar clinical complaints, the main challenge for the clinicians was the distinction between BLL, PLL, and T1 stage laryngeal cancers. T2 and larger tumors do not pose a major diagnostic challenge. We conclude that the clinical benefit of statistical differences stated in the literature can be discussed.
As it is known, the risk of malignant transformation increases when the lesion depth increases in laryngeal dysplasia. For this reason, patients with laryngeal precancerous lesions are classified and compared as mild, moderate, and severe CIS/dysplasia. However, in addition to the statistical insignificance of the difference, the parameters examined showed no increase in correlation with dysplasia severity, suggesting that these parameters were not effective in determining the severity of dysplasia. In a similar study in which this comparison was performed, the results, which were statistically insignificant and independent of dysplasia severity, were observed to be similar to this study.
In a study conducted by Duzlu et al., laryngeal carcinoma was divided into T1, T2, T3, and T4 stages, and when these groups were compared there was no significant difference in terms of NLR. In addition, it was also noted in the same article that the NLR values of T3 stage tumors were found to be smaller than T2 stage tumors. In another study conducted by Du et al., PLR values were examined in addition to NLR values and similar comparisons like the study by Duzlu et al. were observed. They stated that the differences among the groups were statistically significant. However, no information has been presented on which groups have the difference. In another study conducted by Kara et al., when the NLR and PLR values were compared between T stages in a similar way, the difference between the NLR values was not significant and the difference between the PLR values was found to be significant. However, despite the significant difference when the data of the study were examined, PLR value was the highest in T4 tumor group, and PLR average of T1 tumors was higher than T2 and T3 tumors. In the study presented, groups were compared in terms of different parameters similarly, and statistical significance was only determined in the NLR value. Because of this significance, Friedman test and pairwise comparisons as post hoc tests were performed to understand in which groups the differences are formed. In consequence of this test, only the differences between T1 and T2 and T1 and T4 tumors were found to be statistically significant. However, as the data for T3 stage tumors for NLR are the highest in all groups, the clinical meaning of statistical significance is questioned as PLR value was found to be lower in T1 tumors compared with T2 and T3 in the study conducted by Kara et al.; the parameters evaluated were not statistically significant in terms of prognosis.
It was also thought that the mentioned hematological tests might also be helpful as prognostic markers for laryngeal cancer. It was concluded in the study conducted by Du et al. that NLR ratio higher than 3.18 was an indicator of poor prognosis and was associated with recurrence. Zeng et al. came to the same conclusion by accepting the cut-off value as 3.0. There are some other studies showing that the PLR and LMR values are beneficial in demonstrating laryngeal cancer prognosis., In two other studies conducted in this respect, receiver operating characteristic curve was used to identify the cut-off value and it was stated that NLR value had prognostic value., However, when the statistics of the study by Fu et al. were examined, it was observed that the sensitivity and specificity rates of the test were lower than 70% in addition to the low area under curve values of both studies. The parameters evaluated in this study and the study by Duzlu et al. were not statistically significant in terms of prognosis.
The association of mentioned hematological parameters with disease recurrence or progression in patients with dysplasia has not been previously examined in literature. As stated in our study results, the parameters evaluated were not statistically significant in terms of prognosis.
| Conclusion|| |
Because the data obtained in this study are difficult to control and could be affected by cases such as tinnitus, some psychiatric disorders, some types of headaches, smoking, and so on cannot be used clinically to distinguishing LSCC from other laryngeal lesions.,,, Besides, the data we obtained about the use of mentioned markers as prognosis reagents conflict with the literature. We believe that more comprehensive, detailed, and objective studies should be conducted since the cut-off values used in literature studies are rather low in terms of sensitivity and specificity rates and these values were not shared in some studies.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]