[Factors Influencing the Progression Trend of Early Lung Cancer and CT Findings].

BACKGROUND: It has been known that the volume doubling time (VDT) of different lung nodule types is different. At present, there is still a lack of studies about the volume doubling time of lung cancer with different pathological types. The purpose of the study is to explore the factors influencing the progression of the early-stage adenocarcinoma, and provide some reference for the follow-up strategy of lung nodules by retrospective analysis of the image data of 143 early-stage adenocarcinoma. METHODS: 143 cases of the early adenocarcinoma were classified according to the 2015 World Health Organization Classification of Lung Tumors and the Eighth edition of the tumor-node-metastasis (TNM) classification of lung cancer. The volume doubling time was calculated with reference to the revised Schwartz formula. RESULTS: Among the 143 cases of the early adenocarcinoma, 50 cases (34.97%) were in progression. By multivarIate analysis, there were several factors associated with the progression of the early adenocarcinoma: the follow-up time, the dimension of nodule, the pathological type, the nodule type and the pathological stage. The VDT of lepidic predominant adenocarcinoma (LPA) is (594±272) d. The VDT of the invasive adenocarcinoma with lepidic part, but not predominant, is (520±285) d. The VDT of the invasive adenocarcinoma without lepidic part is (371±183) d. CONCLUSIONS: About 35% of the early adenocarcinoma is in progress. Whether with the lepidic component is a positive factor to the speed of tumor progression.

Lymph node dissection and survival in patients with early stage nonsmall cell lung cancer: A 10-year cohort study.

It is still debatable whether complete mediastinal lymph node dissection (MLND) is associated with better survival than mediastinal lymph node sampling (MLNS) in surgical treatment of nonsmall cell lung cancer (NSCLC). We aimed to assess the impact of lymph node dissection on long-term survival among stage I NSCLC patients.In this cohort study, 317 stage I NSCLC Chinese patients in Shanghai Chest Hospital were followed up for at least 10 years to evaluate the impact of different lymph node dissection modes on their survival. Among them, 161 patients were in the MLND group and 156 in the MLNS group. Overall survival and median survival times were calculated for the 2 groups. The association between lymph node dissection and the survival of NSCLC patients was assessed using Cox proportional-hazard models.Patients in the MLND group presented better survival (median survival time = 154.67 months) than those in the MLNS group (median survival time = 124.67 months). The MLNS had higher mortality than the MLND group, with the crude hazard ratio of the MLNS group relative to the MLND group as 1.32 (95% confidence interval [CI] 0.97, 1.78). After adjusting for age and sex, the association between lymph node dissection and mortality (hazard ratio 1.36, 95% CI 1.00, 1.84) was statistically significant (P = .047). Further adjusting for baseline clinical characteristics, the association (hazard ratio 1.40, 95% CI 1.02, 1.92) remained statistically significant (P = .036). The association between lymph node dissection mode and mortality was strong among patients with tumor size between 2.0 and 3.0 cm (hazard ratio 2.79, 95% CI 1.45, 5.37).We found that the MLND was associated with better survival for patients with early-stage NSCLC, compared with the MLNS. The effects of MLND on survival may depend on tumor size. Our findings have important implications in the treatment of early-stage NSCLC. Further prospective studies with a large sample size are needed to confirm our findings.

[Advance in Diagnose and Treatment Strategies of Adenocarcinoma in Situ].

Adenocarcinoma in situ (AIS) is a new concept which was introduced to the 2011 The International Association for the Study of Cancer (IASLC)/ American Thoracic Society (ATS)/ European Respiratory Society (ERS) International Multidisciplinary Classification of Lung Adenocarcinoma firstly and an important supplement of The 2015 World Health Organization Classification of Lung Tumors. Because AIS is at an early stage of development of lung adenocarcinoma, the deepening understanding of its pathology, differential diagnosis, treatment strategies, has an important significance for the improvement of the prognosis of lung adenocarcinoma. This review will provide a systematic review of the main progress of occurrence and development, pathological characteristics, differential diagnosis and treatment strategy of AIS, in order to provide theoretical basis for the further research of AIS.

A consensus on liquid biopsy from the 2016 Chinese Lung Cancer Summit expert panel.

The diagnosis and treatment of lung cancer have evolved into the era of precision medicine. Liquid biopsy, a minimally invasive approach, has emerged as a promising practice in genetic profiling and monitoring of lung cancer. Translating liquid biopsy from bench to bedside has encountered various challenges, including technique selection, protocol standardisation, data analysis and cost management. Regarding these challenges, the 2016 Chinese Lung Cancer Summit expert panel organised a trilateral forum involving oncologists, clinicians, clinical researchers, and industrial expertise on the 13th Chinese Lung Cancer Summit to formally discuss these controversies. Six consensuses were reached to guide the use of liquid biopsy and perform precision medicine in both clinic and research.

[Analysis on the Prognostic and Survival Factors of Synchronous Multiple Primary Lung Cancer].

BACKGROUND: Synchronous multiple primary lung cancer (sMPLC) is a sparse disease in the past, but there has been a gradual increase in the morbidity of sMPLC recently. However, studies on large sample have never been undertaken. The purpose of this study is to investigate the diagnosis, treatment and prognosis of sMPLC through analyzing the clinical data, and provide supports for the management of sMPLC. METHODS: According to Martini-Melamed criteria, 357 patients were diagnosed sMPLC. The pathological staging is on the basis of the 8th edition tumor-node-metastasis (TNM) staging from International Association for the Study of Lung Cancer (IASLC). RESULTS: There were 269 patients with double primary lung cancer, 65 patients with triple primary lung cancer and 23 patients with four or more primary lung cancer. Lesions (68.55%, 571/833) were frequently in upper lobe, especially the right upper lobe. Adenocarcinoma (95.56%, 796/833) was the mainly pathological type, followed by squamous cell carcinoma (2.40%, 20/833). The acinar predominant subtype was the main part (70.81%, 313/442) of the all adenocarcinoma specimens. Most of the lesions (68.35%, 244/357) were stage Ib or low. Among the initial lesion and the following lesions ,patients who had the same pathological type (92.72%, 331/357) were more than the different (7.28%, 26/357), of which adenocarcinoma-adenocarcinoma occupied the major proportion (99.40%, 329/331). The 3-year overall survival (OS) and 5-year overall survival were respective 91.93% and 84.37%. Multivariate analysis found that smoking history (P=0.012), the diameter of the maximum lesion (P=0.027), lymph node metastasis (P=0.015) and pleural invasion (P<0.001) were the independent risk factors for prognosis. CONCLUSIONS: Tumours in patients with sMPLC are more frequently in the right upper lobe. Adenocarcinoma was the mainly pathological type. Smoking history, the diameter of the maximum lesion, lymph node metastasis and pleural invasion were the independent risk factors for prognosis. Early diagnosis and active operation can obtain better prognosis.

[Localizating and Extracting Small Peripheral Nodules of Lung with Simulating 
Radiaotherapy Combining Methylene Blue Staining].

BACKGROUND: With the extensively application of HRCT (high resolution CT) and the popularization of early lung cancer screening, the proportion of small nodullar lung cancer to be operated increases rapidly. Identifying the focus lesions quickly and accurately in operation has shown to be a challenge. We carried out this research trying to make use of and evaluate a new method that localizaes and extracts small peripheral pulmonary nodules by way of simulating radiaotherapy combining methylene blue staining. METHODS: From February 2012 to January 2015, 97 patients with 100 peripheral pulmonary nodules ≤10 mm in size were simulated puncturing using a radiotherapy planning. When the anaesthesia came into use, methylene blue dye was injected to the virtually identified point corresponding to the surface point, according to the angle and depth previously computed by the radiotherapy planning. The video-assisted thoracoscopic surgery (VATS) wedge resections of the marked lesions were undertaken and the specimens were sent for frozen pathologic examination. The interval time from anesthesia-completing to puncture and injection, The interval time from methylene blue injection to identifying the stained area and the distances between the centre point of the stains and edge of coloured lesion were recorded. RESULTS: Our preoperative localization procedure was successful in 96 of 100 (96%) nodules. The interval time from anesthesia-completing to puncture and injection of methylene blue were (4.85±1.25) min. The interval time from methylene blue injection to identifying the stained area was (16.36±2.36) min. The distances between the centre point of the stains and edge of coloured lesion were (4.78±2.51) mm. No complication was observed in all participants. CONCLUSIONS: The new method of locating peripheral pulmonary nodules by simulating simulating radiaotherapy combining methylene blue staining has a high success rate and no complication for localizing small peripheral pulmonary lesions, avoiding the fear and pain of the patients untaken puncture without anaesthesia reducing radial damage.

[Research Progress in Diagnosis and Management Strategies 
of Multiple Primary Lung Cancer].

Although the morbidity of multiple primary lung cancer (MPLC) has been increasing year by year, it is still controversial about pathogenesis, differential diagnosis and management strategies of MPLC. This review provides a snapshot of the main progress of pathogenesis, differential diagnosis and management strategies of MPLC.

[Analysis of the Choice of Operation Mode and Prognosis Factors of Patients with Tumors of the Lung Metastasis].

BACKGROUND: Concept of treatment for pulmonary metastatic tumor has been changed. The aim of this study is to analysis of the choice of operation mode and prognosis factors of patients with tumors of the lung metastasis. METHODS: The clinical data of 57 patients with pulmonary metastases who underwent operations from January 2006 to December 2009 were retrospectively analyzed. Difference of conventional open thoracic surgery and thoracoscope surgery was compared. The relationship between gender, age, type of surgery, disease-free interval (DFI), the number of metastatic tumor, the size of tumor, chemotherapy and prognosis was explored. RESULTS: Among the patients, there was no perioperative mortality. Postoperative 1-, 3-, 5-year survival rates were 81.3%, 46.5% and 29.2%, the median survival time was 33.8 months. Multivariate analysis showed that DFI, the number and diameter of metastasis tumor were independent prognostic factors. CONCLUSIONS: Reasonable choice of surgical treatment can improve the survival of pulmonary metastatic tumor patient. Thoracoscopic surgery method is preferred. Operation effect of patients with tumor diameter less than 4 cm in solitary pulmonary metastasis has better effect.

[Effect of EGFR-TKI on lymphangiogenesis of lung cancer with EGFR mutation].

BACKGROUND AND OBJECTIVE: This study aims to explore the effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) on the lymphangiogenesis of lung cancer with EGFR mutation, as well as to determine the function of EGFR targeted therapy in relation to the inhibition of lymphangiogenesis during lung cancer treatment. METHODS: The EGFR double mutant lung cancer cell line NCI-H1975 is used to construct lung cancer xenograft models. The models are divided into two groups: the solvent control group and the EGFR-TKI treatment group. Each group includes five mice. The inhibitory effect of EGFR-TKI on the growth of transplanted tumors was observed. Immunohistochemical method and lymphatic endothelium specific antibody D2-40 were used in the experiment to observe the influence of EGFR-TKI on lymphangiogenesis in lung cancer. RESULTS: The weight and relative volume of tumors in the EGFR-TKI treated group were less than those in the solvent control group. The average lymphatic vessel density of EGFR-TKI-treated mice was 6.44 per case. This value was 10.70 per case in the solvent control group. Lower density of lymphangiogenesis was found in the EGFR-TKI treated group (P=0.023). The area and longest diameter of neonatal lymphatic vessel of the EGFR-TKI treated group were less than those of the solvent control group. Moreover, EGFR-TKI exhibited no significant effect on the invasion of tumor cells into the lymphatic vessel (P=0.519). CONCLUSIONS: EGFR-TKI can inhibit lymphangiogenesis in EGFR mutant lung cancer while suppressing vessel diameter and expansion area.

[High risk indication of postoperative chemotherapy 
in early stage non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: More than 35% Ib stage lung cancers have metastasised or recurrenced after operation, whose prognosis still remain poor. There're much controversy over the necessity of adjuvant chemotherapy to them. This aim of this study is investigated the clinical and pathological characters influencing prognosis of the stage Ib non-small cell lung cancer (NSCLC) and to explore the indication of postoperative chemotherapy. METHODS: NSCLC patients (281 cases) who underwent lobectomy were examined. Cox proportional-hazards ratios were used to identify independent prognostic factors for survival. Kaplan-Meier survival curves were calculated to estimate survival rates. RESULTS: Kaplan-Meier analysis show that, cancerous embolus in the blood vessel or lymphatic vessel, histologic grade and tumor location were remarkerbly associated with mortality risk (P<0.05). The poor histologic grade and cancerous embolus in the blood vessel were closely associated with increased mortality risk on multivariate analysis in stage Ib NSCLC. CONCLUSIONS: The low histologic grade and cancerous embolus in the blood vessel or lymphatic vessel are closely correlated with survival in the stage Ib NSCLC and can be an index for the postoperative chemotherapy.

[The application of mediastinoscopy in the differential diagnosis and preoperative staging on lung cancer].

BACKGROUND AND OBJECTIVE: To discuss the clinical application of mediastinoscopy in the differential diagnosis and preoperative staging on lung cancer. METHODS: A total of 361 cases of patients were included in the study, of which 162 cases were undiagnosed mediastinal tumor patients before operation, and 199 patients were suspected or diagnosed with lung cancer or mediastinal lymph nodes enlargment(short diameter ≥1.0 cm). All patients underwent surgery, including 308 cases standard cervical mediastinoscopy (SCM) , 53 cases parasternal mediastinoscopy (PM). RESULTS: Taking pathology diagnosis as the gold standard, the mediastinoscopy diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value are 98.11%, 97.62%, 100%, 100%, 91.67% and 98.28%, 98.03%, a 100%, 100%, 100% to mediastinal masses and mediastinal lymph node metastasis of lung cancer. Total seven cases suffered from complications of surgery-related, the complication rate was 1.93 percent (P<0.05). CONCLUSIONS: The trauma of the mediastinoscopy is slight, which is safe, reliable, able to take in sufficient tissue quantities. Mediastinoscopy is highly helpful not only in diagnostic of mediastinal mass, but also in the differential diagnosis of lung cancer, and it's an important method and the gold standard of preoperative staging on lung cancer.

[Research for mediastinal lymph node desection style of stage Ib upper lobe non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Lymphatic metastasis is the most important way for the spread of lung cancer and is one of the important factors affecting the prognosis. Existing studies showed that compared to middle or lower lobe NSCLC, upper lobe non-small cell lung cancer (NSCLC) has a higher probability of occurring regional mediastinal lymph node metastasis. The purpose of this study is to research the prognostic factors and lymphadenectomy of stage Ib upper lobe NSCLC. METHODS: A retrospective study of 147 consecutive subjects (76 and 71 for right and left upper lobe NSCLC respectively) who had undergone curative resection for stage Ib upper lobe NSCLC was performed. A total of 925 lymph nodes were removed during the surgery in all enrolled patients and a total of 491 mediastinal lymph nodes (266 and 225 for superior and inferior mediastinal lymph nodes respectively) were removed. Kaplan-Meier product method and Log-rank test were used for univariate survival analysis and Cox regression model was used for multivariate survival analysis. RESULTS: ①Both univariate and multivariate analysis showed that age, tumor size and number of removed superior mediastinal lymph node stations were the important prognostic factors of stage Ib upper lobe NSCLC; ②For stage Ib right upper lobe NSCLC, station 4 lymph node was of statistical significance to the prognosis (P=0.021); while for stage Ib left upper lobe NSCLC, station 5 lymph node was of statistical significance to the prognosis (P=0.024). CONCLUSIONS: In surgically treated stage Ib upper lobe NSCLC patients, age, tumor size and number of removed superior mediastinal lymph node stations are the important prognostic factors. And in this kind of patients, lobe-specific systematic lymph node dissection may be a more efficient procedure during the surgery.

[A comparative study on the diagnosis and staging of lung cancer between mediastinoscopy and EBUS-TBNA].

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been gradually universal application, but its value in the preoperative staging of lung cancer and mediastinal mass biopsy remains to be explored. The aim of this study is to evaluate the value of clinical application between mediastinoscopy and EBUS-TBNA, desiring to provide an objective basis for the rational choice applications. METHODS: Between July 2009 and December 2012, mediastinoscopy patients with 361 cases accepted biopsy, including 199 cases of lung cancer and 162 cases of mediastinal mass of unknown origin, EBUS-TBNA patients with 348 cases accepted biopsy, including 216 cases of lung cancer and 132 cases of mediastinal mass. Comparing the diagnostic results and related indicators of two methods, this article analyzed the clinical value both the preoperative staging of lung cancer and the diagnosis of mediastinal mass. RESULTS: Taking pathology diagnosis as the gold standard, the accuracy, sensitivity and specificity of mediastinoscopy and EBUS-TBNA are 98.33%, 98.17%, 100% and 90.80%, 90.00%, 100%. Two techniques in the diagnosis and staging of lung cancer have not statistically significant (P>0.05), but in the diagnosis of mediastinal mass have statistical significance (P<0.05). CONCLUSIONS: Mediastinoscopy and EBUS-TBNA have a similar role in the diagnosis and staging of lung cancer; but mediastinoscopy for mediastinal mass is superior to EBUS-TBNA.

[Pathological characteristic and clinical management of pulmonary carcinoid].

BACKGROUND AND OBJECTIVE: Treatment of pulmonary carcinoid is a comprehensive modality focusing on surgery. Thus, accurate and timely preoperative and intraoperative pathological diagnoses are very crucial. The aim of this study is to retrospectively analyze the pathological characteristics of pulmonary carcinoid, its natural history, and patterns of disease progression to obtain evidence for clinical decision making. METHODS: Clinical and pathological data of 32 patients with pulmonary carcinoid were retrieved and retrospectively analyzed. The pathological characteristics and their relationship with clinical diagnosis and treatment effect were systematically studied. RESULTS: Among the 32 patients, 18 had typical carcinoid and 14 had atypical carcinoid. The male-to-female ratio was 2.2:1, and the average age was (44±15) years. Almost half of the patients were discovered by accident. The average maximum diameter was (3.1±1.3) cm. About 27 of all 32 cases (84.4%) were stage I, 2 were stage IIa, 2 were stage IIIa, and 1 was stage IV. The follow-up time was 5.2-9.7 years. The 5-year progression free survival of 15 typical carcinoid patients and 12 atypical carcinoid patients were 100% and 92.9%, respectively. The characteristic neuroendocrine morphology and variable expression levels of cytokeratin, chromogranin A, synaptophysin, CD56, and index of Ki-67 were important factors that differentiated pulmonary carcinoid from other tumors. CONCLUSIONS: Pathological diagnosis of pulmonary carcinoid must combine morphology with immunohistochemistry. Early-stage patients can also achieve good effect after surgery.

[Prognostic value of lymphangiogenesis and lymphatic vessel invasion in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Studies have shown that tumor metastasis in a variety of tumors is associated with lymphangiogenesis and lymphatic vessel invasion (LVI). Tumor metastasis is an important factor that affects the prognosis of patients. The aim of this study is to determine the prognostic value of lymphangiogenesis and LVI in non-small cell lung cancer (NSCLC). METHODS: We marked the endothelial cells of lymph vessels in lymphangiogenesis with specific monoclonal antibody D2-40. Immunohistochemistry was used to detect the expression of lymphangiogenesis and LVI in 79 cases of stage I-III NSCLC. RESULTS: The intratumoral lymphatic vessel density (ITLVD) was significantly higher in patients with N2 disease than those with N0 disease (P=0.015). The ITLVD was significantly higher in patients with LVI+ than that in those with LVI- (P = 0.009). The ITLVD was also remarkably higher in poorly differentiated tumors than that in highly differentiated ones (P = 0.007). The ITLVD was remarkably higher in adenocarcinoma than that in squamous cell carcinomas (P = 0.025). Kaplan-Meier revealed that the survival rates of patients with higher ITLVD were remarkably poorer than those with lower ITLVD (P = 0.007). Thus, the ITLVD is an important prognostic factor of NSCLC. The peritumoral lymphatic vessel density is not correlated with the prognosis. CONCLUSIONS: The ITLVD level is an important prognostic factor of NSCLC.

[Retrospective study on lobe-specific lymph node dissection for patients with early-stage non-small cell lung cancer].

BACKGROUND: The aim of this study is to explore the effects of different modes of lymph node dissection in early-stage non-small cell lung cancer (NSCLC) on the survival rate, to study the prognostic factors, and to discuss the clinical application of lobe-specific lymph node dissection. METHODS: A total of 379 patients with completely resected pathological stage I NSCLC between the years 1998 and 2005 at Shanghai Chest Hospital were retrospectively analyzed. Among the patients, 148 were placed in the systematic lymph node dissection group and 150 in the lobe-specific lymph node dissection group. All of them were in pathological stage I (T1a-2aN0M0). The differences between the two groups were compared. RESULTS: No statistical difference was found between the two sets of data in terms of the clinical and pathological features of distribution (P > 0.05). The overall survival distribution between the two groups had no statistical difference (P > 0.05). The pathological stage, pathological type, and tumor size significantly differed between the two groups. The duration of surgery, blood loss, blood transfusion, drain secretion, duration of drainage, and duration of hospital stay also significantly differed between the two groups (P < 0.01). The complications significantly differed between the two groups as well (P < 0.05). CONCLUSIONS: Systematic lymph node dissection does not improve the five-year survival rates in pathological stage I NSCLC. The pathological stage, pathological type, and tumor size critically affect the prognosis. Lobe-specific lymph node dissection can significantly reduce complications and perioperative risks.

[The advance and new methods explore of pulmonary tiny lesions preoperative localization].

Pulmonary peripheral tiny lesions are difficult to be localized during operation. The current each preoperative localization methods still exist defects and limited to application which can not adapt to urgent need for increasing numbers of the clinical pulmonary tiny lesions. This paper intends to summarize the present relevant progress, and introduce our recent attempt to explore a new method.

[Expression and prognostic value of VEGF-C and lymphangeogenesis in lung adenocarcinoma and squamous cell carcinoma].

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor-C (VEGF-C), a member of the VEGF family, has been proven to be a relatively special VEGF. When binding to its receptor VEGFR-3, it activates lymphangiogenesis, which likely induces lymph node metastasis in tumors. The aim of this study is to characterize the expression and prognostic value of VEGF-C and lymphangiogenesis in lung adenocarcinoma and squamous cell carcinoma. METHODS: Through immunohistochemistry, the lymph vessel endothelial cells undergoing lymphangiogenesis were stained with podoplanin to detect the expression of VEGF-C and lymphangiogenesis in 98 cases with stage IIIa (N2) lung adenocarcinoma and squamous cell carcinoma. RESULTS: The expression rate of the VEGF-C was positively correlated with the lymphatic microvessel density (LMVD; r=0.783, P<0.01). The LMVD was remarkably higher in VEGF-C positive expression group than that in the VEGF-C negative expression group. The expression rate of VEGF-C and lymphangiogenesis in lung adenocarcinoma was significantly higher than that in lung squamous cell carcinoma (P<0.01). Kaplan-Meier analysis showed that the survival rates in patients with positive VEGF-C expression were significantly lower than those in patients with negative VEGF-C expression (P<0.05). CONCLUSIONS: Lymphangiogenesis rates are significantly higher in lung adenocarcinoma than that in squamous cell carcinoma. VEGF-C expression is an independent prognostic factor of stage IIIa (N2) lung adenocarcinoma and squamous cell carcinoma.