Relationship between the Type of Non-Small Cell Lung Cancer and Infiltration of Lymphatic Drainage

Introduction: Malignant cells invasion of lymphatic drainage represents the basic precondition of metastasis and the disease progress. The invasion of tumor depends on its pathomorphologic characteristics, out of which one of the most significant role is the type. Aim of the Study: Descriptive analysis of operated patients, estimation of frequency and representativeness of the stated types of NSCLC in the monitored group, analysis of malignant cells of lung cancer in lymphatic drainage on the basis of the type of primary tumor. Patients and Methods: The study included 331 patients, who underwent the surgery during which the malignant infiltration was removed, in addition to the dissection of lymph nodes drainage. Results: Out of the total number of operated patients, 257 of them were male gender, while 74 were female gender, with the average age of 63.52 years (21-80). The relation of gender structure of the patients in relation to gender was statistically significant (p=0.00). The ratio between squamous cell carcinoma to adenocarcinoma was 182:140, while the other types of tumor were insignificant. Statistically, there was no significant difference in the frequency of two most common types of lung cancer (χ2test= 3.02; p=0.09). There was no statistically significant connection between the type of tumor and N1 metastasis (χ2=1.55; p=0.46), as well as in the ratio between the type of tumor and malignant infiltration of lymph nodes, level N2 (χ2=2.33; p=0.32). Conclusion: There is no connection between the type of lung cancer and invasion of levels N1 and N2 of lymph nodes.


Introduction
According to all statistical data and relevant data basis, non-small cell lung cancer (NSCLC) is a disease with a permanent increase of frequency of morbidity and mortality, and it represents a big health issue of our time. It is the second most frequent detected cancer in male gender and also the first cause of death, while it is the third most frequent malignant tumor in female gender and the third most frequent malignant cause of death. [1][2][3] In the past, the most common cancer was the one of discus respirationary epithelium, while according to the latest reports, a part of malignancy of lymphatic origin has reached 40% from the total number of new cases. 4 The third, significantly smaller types are the remaining macrocellular tumors and transitive forms.
As it is a systematic disease, the first modern pathohistological classification of lung cancer was published by the World Health Organization (WHO) in 1952 and until now, it has been revised for several times. Multidisciplinary classification proposed by the International Agency for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS) and the European Respiratory Society (ATS) from 2011 is presently valid. The latter was approved by WHO, it has been valid since January 2015 and according to it, the tumors of this group have been classified into three sorts. 5,6 According to the above mentioned classification, the most redefined is adenocarcinoma which is divided in three subgroups (preinvasive lesions, invasive adenocarcinoma with constructive predominations and rare forms of adenocarcinoma). Planocellular and other types of carcinoma also had small redefining. Each of the mentioned type of NSCLC has additional pathomorphological characteristics and invasion, which is demonstrated in its tendency to penetrate the basal stroma, lymph vascular infiltration, and lymphogenic and hematogenic metastasis. [5][6][7] According to the presently valid, The Eight Edition of the TNM Classification of Malignant Tumors, approved by WHO and which has been valid since January 2017, "N" parameter represents the presence/absence of malignant cells lymphatic drainage, and is therefore, in a phase of disease, significant in both therapy and prognosis. In relation to the previous classiffication from 2010, it has remained unchanged, apart from a descriptive grouping of nodes in already valid numeral positions, and it actually represents the Naruke map, which was reviewed by Mointana and Dresler in 1996. Infiltration of drainage nodes by tumor (N1-2) represents a precondition for dissemination, while level N3 represents a progressed level of the disease and contraindication for surgical treatment. [7][8][9][10][11] Aim of the Study The aim of this study is a descriptive analysis of operated patients, estimation of frequency and representativeness of the stated types of NSCLC in the monitored group, analysis of malignant cells of lung cancer in lymphatic drainage on the basis of the type of primary tumor, and a display of statistical dependence of the noted variables.

Patients and Methods
This analysis included 331 patients who were operationally treated at the Clinic for Thoracic Surgery UKC in Sarajevo, with the application of some of the thoracosurgical operational procedures, during which, apart from the tumor removal, a disection of lymphatic drainage was also performed. All the patients were preoperationally diagnosed and they belonged to a clinical level cTNM Ia, Ib, IIa, Iib. Cases of level IIIa were also selected. The analysis excluded the patients who were pre-operationally treated by neoadjuvant therapy.
The data needed for this research were obtained from the history of disease, operational protocols and on the basis of defined pathohistological post-resectional analysis, which were done at the Department for Cytology and pathology at UKC in Sarajevo, and they minimally contained concretely defined type of tumor and patohistological status of drainage lymph nodes.
The results are demonstrated descriptively, numerically, in charts and in graphics with legends and textual description of certain obtained values and variables. The data were analyzed by demonstration of absolute values and values expressed in percentage, and by calculation of the arithmetic means and standard deviation. Nonparameter data were analyzed by chi-square test. The given level of statistical significance was ( alfa) p < 0.05.  The value of χ2 test was 2.33, while p=0.32, and therefore it was bigger than given 0,05, which means that there was a statistically significant connection between the type of tumor and N2 metastasis.

Discussion
Long-term cumulative effect of a great number of potent cancers, long developing flow of the disease and a hidden clinical picture represent the reason for detection of the disease in an advanced phase. Analysis of the age of our examined group has showed that that the one in the total number of the operated patients was 62.69 years (male 63.52; female 59.81). A patient at the age of 82, who has undergone the operation, is the proof of the above mentioned. The occurrence of the disease in a female patient at the age of 21 is explained by a genetic tendency of inheriting, and it has earlier been proved in a great number of studies. 2,3,12 Out of the total number of the operated patients (331), the participation of people of male gender (257) was significantly higher in relation to female gender (74), and the reason for this may be found in more frequent smoking habits of males as well as the professional orientations and the fact that the male gender is more exposed to cancer. 3

Conclusion
There is no significant difference in the frequency of appearance between the two most common types of nonsmall cell lung cancer, nor there is a statistical connection between the types of cancer and malignant invasion of N1 level of lymph nodes, while this relation is statistically significant when we talk about N1 infiltration.