Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Objective:To establish tumor specific protein (SP70) targeted tumor cell enrichment technology and to assess applicational value of next-generation sequencing (NGS) analysis for enriched circulating tumor cell (CTC) in precision medicines of non-small cell lung cancer (NSCLC).Methods:The monoclonal antibody NJ001 was covalently coupled to the surface of magnetic beads to build targeted magnetic bead enrichment technology based on SP70. The limit of detection, coincidence rate, interference experiment, recovery test and clinical performance were evaluated. From March 2016 to August 2017, NGS analysis with or without pre-treatment of targeted enrichment for serous fluids of 43 NSCLC in the First Affiliated Hospital with Nanjing Medical University were compared (Kappa or Fisher exact test).Results:The CTC enrichment technology based on SP70 targeted immunomagnetic beads can specifically enrich tumor cells. The limit of detection was 10 4 SPC-A1 cells/L, and the coincidence rate, sensitivity and specificity were 100% (3/3). The endogenous interfering substances such as red blood cells, hemoglobin, white blood cells, epithelial cells and triglycerides had no interfering effects, as well as the exogenous interfering substances such as EDTA-K2, cefoxitin, carboplatin and paclitaxel. The recovery rate was 56.0% (56 000/100 000). A total of 30 gene mutations including 65 loci were found in 43 NSCLC under SP70 targeted enrichment, with a higher detection rate compared with unenrichment method [95.0% (19/20) vs 65.0% (13/20), χ 2=5.625, P=0.044]. Conclusion:In this study, SP70-targeted enriched CTC liquid biopsy method was established, with higher sensitivity and specificity of NGS detection than unenrichment method.

Surgical operation is one of the significant parts of the comprehensive therapeutic methods of lung cancer. In the history of the development of lung cancer operation, scholars and predecessors at home and abroad have gradually established the current status of lung cancer operation and the framework of comprehensive treatment after continuous understanding of local anatomy of lung, continuous innovation of surgical equipment and continuous reform of surgical methods. In the continuous development and improvement of lung cancer surgical diagnosis and treatment procedures, a set of standardized diagnosis and treatment process of lung cancer screening, early diagnosis and treatment, standardized surgery process, rapid perioperative recovery, postoperative adjuvant treatment and follow-up has been formed. The achievements of lung cancer operation are achieved by scholars standing on the shoulders of giants. In the process of pioneering and innovating, we should go back and review the road that our predecessors have taken, and draw energy from it to continue to create new brilliance in lung cancer operation. In this paper, the evolution history of lung cancer surgery is summarized in order to improve the clinician's understanding of the history of lung cancer surgery.
Humans ; Lung Neoplasms/surgery* ; Early Detection of Cancer ; Lung

Colchicine/therapeutic use* ; Coronary Artery Disease ; Coronary Disease/prevention & control* ; Humans ; Plaque, Atherosclerotic

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.

OBJECTIVETo explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B-cell lymphoma/leukemia-2 (BCL-2) in acute myeloid leukemia (AML) and its significance.

METHODSThe expression levels of PTEN and BCL-2 mRNA and protein in bone marrow samples from 80 AML patients including 56 de novo patients, 16 patients in remission, 8 relapsed patients and 30 cases of non-hematologic diseases (as control) were detected by real-time PCR and Western blot, respectively, and the relationship between PTEN and BCL-2 expression and clinical pathological parameter was analyzed.

RESULTSThe expression levels of both mRNA and protein of PTEN in newly diagnosed AML group and relapse group were significantly lower than those in the control and remission group (P<0.01). The expression levels of both mRNA and protein of BCL-2 in newly diagnosed group and relapse group were significantly higher than those in the control and remission group (P<0.01). The mRNA expression of PTEN and BCL-2 was did not related with the age, sex and white blood count in AML patients. The expression levels of PTEN negatively correlated with expression BCL-2 with AML(r=-0.432, r=-0.569).

CONCLUSIONPTEN and BCL-2 participate in the occurrence and development of AML, and may be used as indicators for the evaluation of chemotheraeutic efficacy.

Background: Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection. Methods: We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses. Results: During follow-up (median, 86 months; range, 24–160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resec-tion had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017). Conclusions: Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

BACKGROUNDBoth uniportal and triportal thoracoscopic lobectomy and sublobectomy are feasible for early-stage non-small cell lung cancer (NSCLC). The aim of this study was to compare the perioperative outcomes of uniportal and triportal thoracoscopic lobectomy and sublobectomy for early-stage NSCLC.

METHODSA total of 405 patients with lung lesions underwent thoracoscopic lobectomy or sublobectomy through a uniportal or triportal procedure in approximately 7-month period (From November 2014 to May 2015). A propensity-matched analysis, incorporating preoperative variables, was used to compare the short-term outcomes of patients who received uniportal or triportal thoracoscopic lobectomy and sublobectomy.

RESULTSFifty-eight patients underwent uniportal and 347 patients underwent triportal pulmonary resection. The conversion rate for uniportal and triportal procedure was 3.4% (2/58) and 2.3% (8/347), respectively. The complication rate for uniportal and triportal procedure was 10.3% and 9.5%, respectively. There was no perioperative death in either group. Most patients had early-stage NSCLC in both groups (uniportal: 45/47, 96%; triportal: 313/343, 91%). Propensity score-matching analysis demonstrated no significant differences in operation time, intraoperative blood loss, numbers of dissected lymph nodes, number of stations of lymph node dissected, duration of chest tube, and complication rate between uniportal and triportal group for early-stage NSCLC. However, the duration of postoperative hospitalization was longer in the uniportal group (6.83 ± 4.17 vs. 5.42 ± 1.86 d, P = 0.036) compared with the triportal group.

CONCLUSIONSUniportal thoracoscopic lobectomy and sublobectomy is safe and feasible, with comparable short-term outcomes with triportal thoracoscopic pulmonary resection. Uniportal lobectomy and sublobectomy lead to similar cure rate as triportal lobectomy and sublobectomy for early NSCLC.

Adult ; Aged ; Blood Loss, Surgical ; Carcinoma, Non-Small-Cell Lung ; pathology ; surgery ; Female ; Humans ; Length of Stay ; Lung ; pathology ; surgery ; Lung Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Operative Time ; Pneumonectomy ; adverse effects ; methods ; Prospective Studies ; Thoracic Surgery, Video-Assisted ; adverse effects ; methods ; Treatment Outcome

OBJECTIVETo compare the instructive value of the 6th and 7th editions of the UICC-AJCC staging system in prognosis of esophageal cancer (EC) patients.

METHODSThe staging and prognosis of 1397 esophageal carcinoma patients undergoing curative resection from Jan. 2003 to Dec. 2006 in our hospital were retrospectively reviewed and analyzed according to the 6th AJCC staging system and the 7th UICC-AJCC staging system.

RESULTSThe 5-year overall survival (OS) of EC patients with curative resection was 38.5% (481/1250 cases), with a follow-up rate of 89.5% (1250/1397 case). In overall terms, both the editions were statistically significant discriminators of OS (P < 0.05). The 5-year OS of stages I, II and III patients were 64.9%, 43.5%, 25.2% according to the 6th edition, and 63.5%, 44.5%, 23.5% according to the 7th edition, respectively. Distinct differences in survival were present among patients categorized as stage Ia and Ib according to the 7th edition (P < 0.05), with a 5-year OS of 80.0% and 58.3%, respectively. Similarly, according to the 7th edition, the 5-year overall survivals (OS) of the stages IIIa, IIIb and IIIc patients were 28.2%, 18.4% and 16.7%, respectively, showing that the prognoses were significantly different (P < 0.05). In addition, according to the 7th edition, the prognoses of patients in stages N0, N1, N2 and N3 were also significantly different (P < 0.01), and the 5-year OS were 50.0%, 31.5%, 18.7% and 16.7%, respectively.

CONCLUSIONSBoth the 6th and 7th editions of UICC-AJCC staging system are significant discriminators for survival of esophageal cancer patients. The 7th edition is proved to be more accurate in prognosis. The number of lymph node metastases is an important predictor of prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; classification ; pathology ; surgery ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; methods ; Retrospective Studies ; Survival Rate

OBJECTIVETo compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT).

METHODSData of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed.

RESULTSIn the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications.

CONCLUSIONSTo compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

Age Factors ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Length of Stay ; Lung Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Operative Time ; Pneumonectomy ; adverse effects ; classification ; methods ; Postoperative Complications ; etiology ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies ; Smoking ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy ; adverse effects ; methods