Application Of Selective Lymph Node Dissection In Clinical Stage T1 Non-small Cell Lung Cancer

Background and SignificanceLung cancer is the malignant tumor with the highest morbidity and mortality in China and the world.According to the latest estimates from the United States,the number of new cases of lung cancer in the United States will amount to 228,820 in 2020,accounting for 12.67%of all malignant tumors.The World Health Organization estimates that the morbidity and mortality of lung cancer will continue to rise worldwide,among which non-small cell lung cancer(NSCLC)accounts for about 80%～85%of total lung cancer,and ground glass opacitys(GGO)and solitary pulmonary nodules(SPN)are the most common types of clinical stage T1(tumor diameter<3.0 cm)NSCLC.In the 1990s,Ginsberg’s research at Memorial Sloan-Kettering Cancer Center established lobectomy+lymph node dissection as the standard surgical treatment for lung cancer.Today,radical lobectomy+systematic lymph node dissection recommended by The National Comprehensive Cancer Network(NCCN)remains the standard surgical treatment.Changes in the high-risk factors of lung cancer lead to changes in the disease spectrum of lung cancer:non-smoking,air pollution and other potential factors lead to an increasing number of GGO,with the substantial increase in economic level and physical examination awareness,the detection rate of SPN increases significantly,the proportion of lung adenocarcinoma increases,and the tumor patients become younger.The epidemiological migration of lung cancer has prompted people to rethink lobectomy+systematic lymph node dissection:①based on effectiveness--complete removal of tumors and metastatic lymph nodes to achieve the effect of oncology resection;②based on safety--reduce surgical trauma and perioperative complications,promote enhanced recovery after surgery(ERAS).The main purpose is to completely remove the tumor tissue while preserving the normal structure and function of the body to the greatest extent,and reducing the dissection of non-metastatic lymph nodes is an important part of the reducing surgical trauma.Clinically,we found that for patients with clinical stage T1 NSCLC,the vast majority of lymph nodes dissected during surgery did not have cancer metastasis,and the lymph nodes with cancer metastasis were mostly characterized by sequential and regional lymph node metastasis.Based on the above,some scholars proposed selective lymph node dissection(SLND).SLND known as lobe-specific lymphnode dissection(L-SLD),refers to the selective removal of lymph nodes and their surrounding tissue in the hilum and specific mediastinal regions based on the location of the primary tumor.Compared with systematic lymph node dissection,selective lymph node dissection has a smaller operation range,fewer lymph nodes resected,and reduced surgical trauma,whether this reduction in trauma is statistically significant,we will use the perioperative clinical indicators(operation time,postoperative complications,etc.)and immune indicators(non-specific immunity,cellular immunity,humoral immunity)for double evaluation.Based on the above analysis,we designed this subject and divided it into two parts to study selective lymph node dissection:The part Ⅰ,through retrospective analysis of the clinical data of patients with clinical stage T1 NSCLC undergoing systematic lymph node dissection,to explore the rule of lymph node metastasis in NSCLC,and analyze the factors affecting lymph node metastasis;The part II,through a comparative study of perioperative parameters and immune indexes of cTl stage NSCLC patients undergoing systematic lymph node dissection and selective lymph node dissection,to explore the safety and therapeutic advantages of selective lymph node dissection.Part I Analysis of the rule of lymph node metastasis in stage cTl non-small cell lung cancer and factors affecting lymph node metastasisObjective:To analyze the characteristics of lymph node metastasis in clinical state T1 non-small cell lung cancer(NSCLC),to summarize the rules of lymph node metastasis and factors affecting lymph node metastasisMethods:To analyze the types and rules of lymph node metastases,and the relationship between lymph node metastasis and pulmonary pleural invasion,thrombosis of vascular carcinoma,tumor size and pathological types,We retrospectively selected 841 patients with clinical stage T1 NSCLC performing lobectomy and systematic lymphadenectomy in our hospital.Results:Among 841 patients with clinical stage T1 NSCLC,92 patients had lymph node metastasis(10.9%),hilar lymph nodes metastasis rate was the highest(7.8%),in 257 cases of tumors in the right upper lobe and 186 cases in the left upper lobe,the metastasis rate of superior mediastinal lymph nodes were all 7.0%,and the metastasis rate of subcarinal lymph nodes were 1.6%and 0%,and no metastasis was found in inferior mediastinal lymph nodes,subcarinal lymph nodes metastases in the upper lung tumors were all accompanied by hilar and/or superior mediastinal lymph node metastases;The metastasis rates of superior mediastinal,subcarinal and inferior mediastinal lymph nodes were 3.5%,6.4%and 0.58%,respectively,in 171 patients with tumors in the right lower lobe,and 4.0%,2.6%and 2.0%,respectively,in 151 patients with tumors in the left lower lobe,superior mediastinal lymph nodes metastases were all accompanied by hilar and/or subcarinal lymph nodes metastases;The metastasis rates of superior mediastinal lymph nodes and subcarinal lymph nodes were 2.6%and 3.9%,respectively,in 76 patients with tumors in the middle lobe of the right lung,no metastasis with inferior mediastinal lymph nodes was observed.Lymph node metastasis is easier in patients with pulmonary pleural invasion or thrombosis of vascular cancer.The larger the tumor diameter is,the greater the possibility of lymph node metastasis is,and there was no significant correlation with the pathological type of adenocarcinoma or squamous cell carcinoma.Conclusions:1.In patients with clinical stage T1 NSCLC,lymph node metastasis has certain lung lobe specificity,upper lobe tumors are prone to superior mediastinal lymph nodes metastases,right middle lobe tumors rarely have inferior mediastinal lymph nodes metastases,and all patients with non-regional lymph node metastasis are accompanied by hilar and/or regional lymph node metastasis.2.NSCLC patients with lesions larger than 2.0 cm in diameter and whose texture is purely solid or with visceral pleura invasion are prone to non-regional lymph node metastasis.3.Tumor size,pleural invasion,and thrombosis of vascular carcinoma are all independent risk factors for NSCLC lymph node metastasis.Part Ⅱ Comparison of perioperative parameters and immune indexes in patients with stage cTl non-small cell lung cancer with selective lymph node dissection and systematic lymph node dissectionObjective:To investigate whether selective lymph node dissection(SLND)can reduce the acute inflammatory response and non-specific immune function caused by surgical trauma compared with systematic lymph node dissection,whether it can better protect the body’s cellular immunity and humoral immunity,reduce clinical indicators such as operation time,intraoperative blood loss,pleural effusion drainage volume,thoracic drainage tube retention time,postoperative hospital stay or postopetative complications.Methods:According to the selection criteria,patients with clinical stage T1 non-small cell lung cancer(NSCLC)suitable for surgery were selected,and informed consents were signed with the patients or their family members before surgery.During the operation,lung tumors and lobe-specific lymph nodes were excised and sent for fast frozen pathology.NSCLC patients with no metastasis in lobe-specific lymph nodes were selected as the research subjects.The itinerate nurses used a random lottery to divide the selected subjects into the selective lymph node dissection group(SD group)and the systematic lymph node dissection group(CD group).At 24 hours before surgery and at the 1st and 3rd postoperative days(POD),all patients were sampled for fasting venous blood to detect cytokine indicators(IL-6,CRP),cellular immune indicators(lymphocytes,NK cells,CD4+,CD8+,CD4+/CD8+)and humoral immune indicators(IgG,IgA,IgM).During hospitalization,clinically indicators of patients were recorded,such as operation time,intraoperative blood loss,pleural effusion drainage volume,thoracic drainage tube retention time,postoperative hospital stay,and postoperative complications.The differences between the two groups in non-specific immunity,cellular immunity,humoral immunity and clinical indicators were compared.Results:Compared with CD group,the operation time,intraoperative blood loss,pleural effusion drainage volume and postoperative hospital stay were significantly reduced in SD group(P<0.05);Although there were no statistically differences in thoracic drainage tube retention time and postoperative complications between the two groups(P>0.05),the values in SD group were lower than those in CD group.At POD1 and POD3,CRP and IL-6 in the two groups were significantly higher than those before surgery(P<0.05),and the values in CD group were significantly higher than those in SD group at the same time point(P<0.05).Lymphocytes and NK cells of the two groups at POD1 and POD3 were significantly lower than those before surgery(P<0.05),but there were no statistical differences between the two groups at the same time point(P>0.05).CD4+and CD4+/CD8+in SD group were significantly higher than those in CD group at POD1(P<0.05);CD8+in SD group was significantly lower than that in CD group at POD3(/P<0.05).At POD1 and POD3,IgG in the two groups was significantly lower than that before surgery(P<0.05),while IgA and IgM were not significantly decreased(P>0.05);There were no significant differences in IgG,IgA and IgM between the two groups at the same time point(P>0.05).Conclusions:Compared with systematic lymph node dissection,SLND has the following advantages1.It can reduce the operation time,intraoperative blood loss,pleural effusion drainage volume and postoperative hospital stay,which is beneficial to patients’ rapid recovery after surgery.2.It can reduce the acute increase of cytokines(CRP,IL-6)caused by surgery,reduce the body’s acute inflammatory response and non-specific immune damage.3.It can reduce the damage of cellular immune function caused by surgery,which is beneficial to the early recovery of cellular immune function.4.There is no significant difference between the two lymph node dissection methods on humoral immunity.