Lymph Node Metastasis In Non-small Cell Lung Cancer And The Status Of Interlobar Fissures | Posted on:2020-06-10 | Degree:Doctor | Type:Dissertation | Country:China | Candidate:H Li | Full Text:PDF | GTID:1364330572988724 | Subject:Oncology | Abstract/Summary: | PDF Full Text Request | PART-1 LYMPH NODE METASTASIS OUTSIDE OF A TUMOR-BEARING LOBE IN PRIMARY LUNG CANCER FOR LESIONS LIMITED TO THE VICINITY OF THE FISSURE AND THE STATUS OF FISSURES Background:Lung cancer is the most commonly diagnosed cancer clinically and is also one of the leading causes of death.Lobectomy with systematic nodal dissection has been a standard surgery for non-small cell lung cancer(NSCLC).In the 8th Tumor Node Metastasis(TNM)classification,currently,tumors invading the surface of the interlobar pleura are still classified as T2,unless other T factors are identified that induce a higher category.This classification is made regardless of fissure status at the site of tumor invasion(interlobar pleura only or trans-fissural and into the parenchyma of the adjacent lobe).Although the new TNM staging system does not consider fissure status in the diagnosis of adjacent lobe invasion,previous results have indicated that interlobar fissure status affects survival in patients with adjacent lobe invasion.Furthermore,no specific surgical strategies have been recommended when this condition occurs.The feasibility of anatomical or non-anatomical resections(lobectomy plus segmentectomy for tumor-bearing tissue,or limited wedge resection of the adjacent lobe)is currently controversial.Moreover,the optimal resection method for lymph node dissection is unclear.Incomplete fissures indicating partial fusion between lobes may also alter the spread of disease within the lung.Because of anatomical variations,the extent and frequency of lymph node metastases into an adjacent lobe(non-tumor-bearing lobe)are unclear and can ultimately affect the success of the surgical procedure.After completing the anatomical lobectomy of a tumor-bearing lobe,removal of highly suspicious N1 nodes around the artery and bronchus of the adjacent(non-tumor-bearing)lobe and segment should be considered.However,this could cause excess bleeding,air leakage,and incidental injury to the bronchovascular structures,even though it would provide a more definitive staging and further guidance for prognosis and target adjuvant treatments.Objectives:The new Tumor Node Metastasis(TNM)staging system does not recognize fissure status with respect to adjacent lobe invasion in lung cancer.Furthermore,no specific surgical strategies have been recommended for lymph node dissections around adjacent non-tumor bearing lobes according to fissure status.Therefore,this study was undertaken to investigate the necessity of removing additional adjacent lobe lymph nodes in patients with non-small cell lung cancer(NSCLC)for lesions limited to in the vicinity of the interlobar fissure.Materials and methods:From August 2013 to March 2015,332 patients who underwent systematic mediastinal lymph node dissection were retrospectively reviewed.The bronchial lymph nodes including the hilar nodes,intersegmental nodes and segmental nodes were identified and separated.These tissues were subjected to pathologic examination and the status of the fissures was also recorded.The statistical analysis was performed to identify the significant predictors of lymph node metastasis.Results:The patients were divided into an NALI(non-adjacent lobe invasion)group(n=295)and an ALI(adjacent lobe invasion)group(n=37).There was a significant difference in tumors with pN2 disease between the ALI and NALI groups(37.8%vs.8.8%,P=0.001).ALI tumors had significantly more frequent pleural involvement than NALI tumors(62.2%vs.43.1%,P=0.035).The frequency of N2 involvement among tumors invading across the complete fissure was higher than that of the tumors invading across the incomplete fissure(44.4%vs.14.3%,P=0.015).However,the frequency of N1 involvement among tumors invading across the incomplete fissure was not statistically different than that of tumors not invading across incomplete fissure(32.1%vs.24.2%,P=0.357).No correlation was seen between skip metastasis and tumor size(P=0.567),pathological type(P=0.421),fissures status(P=0.697)and invading through fissure or not(P=0.454).Regarding lymph node metastasis in NTBL(non-tumor-bearing lobe),1 5(12.7%)patients had lymph node metastases in NTBLs.Pleural involvement was an independent predictor of lymph node metastasis in an NTBL.Conclusions:A greater frequency of N2 lymph nodes existed in NSCLC with invading adjacent lobe across complete fissure,extensive lymphatic resection within the hilum and non-tumor-bearing lobe in tumors with pleural involvement are justifiable and necessary.PART-2 DETECTION OF MICROMETASTASIS AND LYMPHATIC PATHWAYS ASSOCIATED SENTINEL LYMPH NODES IN PRIMARY LUNG CANCER FOR LESIONS LIMITED TO IN THE VICINITY OF THE INTERLOBAR FISSUREBackground Lobectomy with systematic nodal dissection has been a standard surgery for non-small cell lung cancer(NSCLC).It is also widely accepted the extent of lymph dissection is limited in the lobe-specific nodal area for clinical stage I-II patients.Because of anatomical variations,the extent and frequency of lymph node metastases in the tumors invading across the fissure into an adjacent lobe are unclear.By considering assessment of adjacent regional lymph node metastasis and performing lymphadenectomy of specific lymph node involvement,the surgeons can relatively reduce the extent of lymph node dissection,decrease operative trauma and determine the staging and guide adjuvant treatment,but localizing metastatic disease within locoregional lymphatics to accurately stage and guide therapy represents a clinical challenge.Perhaps the lymphatic drainage in lesions limited to in the vicinity of the interlobar fissure is different from that in lobe-specific nodal spread.The route of lymphatic metastasis and patterns of lymph node metastasis in a tumor-bearing lobe and adjacent lobes,which can ultimately affect the success of the surgical procedure and the determination of the extent of lymph dissection,intraoperative SLN mapping may help thoracic surgeons optimize resections and enhance patient selection for adjuvant therapy.Objective:To investigate detection of micrometastasis and lymphatic pathways associated sentinel lymph nodes in primary lung cancer for lesions limited to the vicinity of the fissure.Materials and methods:From August 2015 to April 2016,35 patients who underwent lobectomy and systemic mediastinal lymph node dissection were examined,the primary tumor was injected with the staining(methylene blue solution)and radioisotope assay(technetium sulfide colloid detection).Intraoperative scintigraphic readings of both the primary tumor and SLN were obtained with a hand-held gamma counter.The location of SLN was observed and recorded.The expression of CK19 in lymph nodes was detected by IHC and RT-PCR technique.The related factors of regional lymph node metastasis were analyzed.Results:Thirty-two patients had abnormal radioactivity and blue-stained lymph nodes(SLN)(91.4%),the sensitivity of SLN was 88.9%,the accuracy was 93.7%,and the false negative rate was 12.5%.The detection rate of SLN metastatic lymph nodes was not related to the location,pathological type,tumor sized andtrans-lobeinvasion,but was related to the pathological stage(P=0.001).The positive rate of CK19 was 39.1%(43/110)in IHC examination of SLN metastatic lymph nodes.Compared with H&E staining,the difference was significant(P=0.031).The positive rate of CK19 expression in lymph nodes detected by RT-PCR technique was 45.5%(50/110),and the detection rate of micrometastasis was higher than that by H&E and IHC.Conclusion:Detection of CK19 expression in SLN can improve the detection rate of micrometastasis,and can effectively access the extent of lymph node dissection in primary lung cancer for lesions limited to the vicinity of the fissure.SLN might serve as a marker to tailor the extension of lymph node dissection.PART-3 EXPRESSION OF FLOTILLIN-1 CORRELATES WITH TUMOR PROGRESSION AND PROGNOSIS IN PATIENTS WITH NON-SMALL CELL LUNG CANCERBackground:The proportion of non-small cell lung cancer(NSCLC)in lung cancer is still high,accounting for about 80%.Numerous research advances,viewpoint updates,and clinical trial results in the therapeutic field have also changed the concept of treatment.Research on the etiology and genetics of lung cancer has prompted people to have an in-depth analysis of the pathogenesis and raise more questions.The transformation of lung tissue from normal structure to malignant lesions such as precancerous lesions-in situ carcinoma-microinvasive-invasive carcinoma is a multi-step and multi-factor cascading reaction process,in which many molecules participate and take on different roles.Just like imaging screening to detect more early cases,the development of treatment and frequent updates of guidelines,has not reduced the sustained growth of its incidence,and a large number of detection of GGO,GGN lesions will bring more clinical questions,The study of mechanisms remains to be deepened,and the selection of more sensitive and specific indicators is of great value for the early diagnosis and evaluation of NSCLC.A variety of cell transduction molecules are closely related to tumorigenesis.It is found that Flotillin-1 participates in a variety of signaling pathways,such as AKT/FOXO3a,TGF-β/Smad3 regulation,its expression and clinical stage of tumor,metastasis,infiltration and prognosis,etc.are related and have the effect of regulating tumorigenesis and development.The regulation mechanism is still unclear.In other tumors such as breast,urinary and digestive tract tumors,abnormal expression of Flotillin-1 and tumorigenesis have beenfound.However,there are few reports on the relationship between Flotillin-1 expression and NSCLC.The study of molecular expression on the tumorigenesis and the relationship between tumor progression and prognosis remains to be deepened,elucidating the mechanism of molecular and the signal in cells.The role and status of the transduction process can provide useful exploration for finding therapeutic targets and studying the pathogenesis of tumors.In the process of transforming from normal tissue to malignant lesion,many factors are involved in the process of precancerous lesion-carcinoma in situ-invasive cancer,many molecules play different roles in participating in the process.Recent studies have revealed that flotillin-1 plays important roles in cancer progression.However,the role of flotillin-1 in development and progression of non-small cell lung cancer(NSCLC)remains largely unknown.Objectives:To investigate the expression pattern and clinicopathological significance of flotillin-1 in patients with NSCLC.Materials and methods:From Feb.2013 to Sept.2015,106 patients who underwent lobectomy plus systematic mediastinal lymph node dissection were retrospectively reviewed.Real-time quantitative polymerase chain reaction was applied to examine flotillin-1 mRNA expression in 52 pairs of NSCLC tissues and adjacent noncancerous tissues.Immunohistochemistry was performed to examine flotillin-1 protein expression in paraffin-embedded tissues from 106 NSCLC patients.Statistical analyses were peformed to evaluate relationship between flotillin-1 expressions with clinicopathological characteristics.Results:Flotillin-1 mRNA expression was evidently upregulated in NSCLC tissues compared with that in the adjacent noncancerous tissues(78.8%vs 21.6%,P=0.023).In the 106 cases of tested NSCLC samples,flotillin-1 protein level was positively correlated with tumor size,tumor stage,and lymph node metastasis.Patients with higher flotillin-1 expression had shorter overall survival time,whereas those with lower flotillin-1 expression had longer survival time.Flotillin-1 expression was an independent predictor of survival time in NSCLC.Conclusions:Flotillin-1 may play an important role in NSCLC tumorigenesis,Flotillin-1 expression was probably an independent predictor of survival. | Keywords/Search Tags: | Non-small cell lung cancer, lymph node, Surgery, Adjacent lobe invasion, Interlobar fissure, Sentinel lymph node, Micrometastasis, CK19, IHC, RT-PCR, Flotillin-1, Prognosis | PDF Full Text Request | Related items |
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