METTL14 enhances the m6A modification level of lncRNA MSTRG.292666.16 to promote the progression of non-small cell lung cancer.

BACKGROUND: m6A modification has close connection with the occurrence, development, and prognosis of tumors. This study aimed to explore the roles of m6A modification and its related mechanisms in non-small cell lung cancer (NSCLC). METHODS: NSCLC tissues and their corresponding para-cancerous tissues were collected to determine the m6A levels of total RNA/lncRNAs and the expression of m6A modification-related genes/lncRNAs. Then, A549 cells were transfected with si-METTL14 or oe-METTL14, and the cell transfection efficiency was assessed. Subsequently, the viability, apoptosis, cell colony formation, migration and invasion of the different cells were determined. Finally, the nude mouse tumorigenicity experiments were performed to observe the effects of METTL14 in vivo. RESULTS: Compared to the para-NSCLC tissues, the m6A level and METTL14 expression were both significantly increased in the NSCLC tissues (P < 0.05). Based on the expression of METTL14 in the different cell lines, A549 cells were chosen for further experiments. Then, the A549 cells with METTL14 knockdown and overexpression were successfully established, as well as it was found that METTL14 knockdown could inhibit the viability, colony formation, migration, and invasion of A549 cells, while facilitate their apoptosis. In vivo experiments also showed that METTL14 knockdown could inhibit tumor formation and growth. Additionally, the m6A level of MSTRG.292666.16 was higher in the NSCLC tissues; and after METTL14 knockdown, the expression and m6A level of MSTRG.292666.16 were both significantly reduced in A549 cells, and vice versa. CONCLUSION: METTL14 may promote the progression of NSCLC through up-regulating MSTRG.292666.16 and enhance its m6A modification level.

DNMT3A governs tyrosine kinase inhibitors responses through IAPs and in a cell senescence-dependent manner in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis. Using NSCLC organoid models, we observed that high DNMT3A levels reduced TKI susceptibility of NSCLC cells via upregulating inhibitor of apoptosis proteins (IAPs). Simultaneously, the DNMT3Ahigh subset, which escaped apoptosis, underwent an early senescent-like state in a CDKN1A-dependent manner. Furthermore, the cellular senescence induced by TKIs was observed to be reversible, whereas DNMT3Ahigh cells reacquired their proliferative characteristics in the absence of TKIs, resulting in subsequent tumour recurrence and growth. Notably, the blockade of DNMT3A/IAPs signals enhanced the efficacy of TKIs in DNMT3Ahigh tumour-bearing mice, which represented a promising strategy for the effective treatment of NSCLC.

Temporal genomic heterogeneity guiding individualized therapy in recurrent non-small cell lung cancer.

Introduction: Despite the benefit of adjuvant systemic therapy for patients with resected non-small cell lung cancer (NSCLC), the risk of postoperative recurrence remains high. Our objective was to characterize temporal genetic heterogeneity between primary resected and recurrent tumors, and its impact on treatment outcomes. Methods: In this study, next-generation sequencing (NGS) testing was performed on tissue specimens and circulating tumor DNA (ctDNA) collected at postoperative recurrence, and results were compared to the genotypes of initial surgical specimens. Results: Of forty-five patients with matched primary and post-operative recurrent tumors, EGFR status switched in 17 patients (37.8%) at post-operative recurrence and 28 patients (62.2%) had no genotype change (17 mutant, 11 wild-type). Based on the changes of EGFR status, patients were divided into 4 groups. Following subsequent treatment with EGFR TKI o chemotherapy: In group A, with sustained sensitive mutation, the percentage achieving partial response (PR) was the highest, at 72.2%, the median progression-free survival (PFS) was 17 months, and the median overall survival (OS) was 44.0 months respectively; In group B, with genotype changed from wild-type to mutant, 50% achieved PR, PFS was 10 months, and OS was 35 months; In group C, in which mutant status shifted to wild-type or new co-mutation emerged, the percentage achieving PR was 30%, PFS was 9 months, and OS was 35 months. In group D, with sustained wild type, the percentage achieving PR was 27.3%, PFS was 8 months, and OS was 22 months. Discussion: Genotypic shift between paired primary and post-operative recurrent tumors was not infrequent, and this temporal genomic heterogeneity substantially impacted subsequent treatment outcomes.

Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II-III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial.

BACKGROUND: This trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II-III non-small-cell lung cancer (NSCLC). METHODS: Patient eligibility mainly involved treatment-naive, clinical stage II-III and wild-type EGFR/ALK NSCLC. The patients received 2-4 cycles of toripalimab (240 mg q3w) plus carboplatin-based chemotherapy. After the second treatment cycle, all patients were re-evaluated by a multidisciplinary team. Candidates eligible for surgery underwent surgery; otherwise, patients received the remaining treatment cycles. The primary endpoints were safety and major pathological response (MPR). Secondary endpoints were R0 resection rate, progression-free survival (PFS) and overall survival (OS). RNA sequencing of baseline and post-treatment samples was conducted to explore the transcriptomic characteristics of the therapeutic response. RESULTS: In total, 50 eligible patients were enrolled, including 12 (24.0%) with resectable disease (RD) and 38 (76.0%) with potentially resectable disease (PRD). Treatment-related adverse events (TRAEs) were recorded in 48 cases (96.0%). Severe TRAEs occurred in 3 (6.0%) cases, including myelosuppression, drug-induced liver injury and death related to haemoptysis. The objective response rate (ORR) was 76.0%, with 8 (16.0%) patients having a complete response (CR), 30 (60.0%) partial response (PR), 10 (20.0%) stable disease (SD) and 2 (4.0%) progressive disease (PD). Surgery could be achieved in 12 (100%) patients with RD and 25 (65.8%) with PRD; 1 (2.0%) with PRD refused surgery. Therefore, R0 resection was performed for all 36 (100%) patients who underwent surgery; 20 (55.6%) achieved MPR, including 10 (27.8%) with a complete pathological response (pCR). The CHI3L1 (chitinase-3-like protein 1) immunohistochemistry (IHC) expression of baseline tumour samples could predict the therapeutic response (AUC=0.732), OS (P=0.017) and PFS (P=0.001). Increased PD-1 expression, T cell abundance and immune-related pathway enrichment were observed in post-treatment samples compared to baseline in the response group (CR+PR) but not in the non-response group (SD+PD). CONCLUSIONS: Neoadjuvant toripalimab plus chemotherapy was safe and effective, with a high MPR and manageable TRAEs for II-III NSCLC, even converting initially PRD to RD. Disparate transcriptomic characteristics of therapeutic efficiency were observed, and CHI3L1 expression predicted therapeutic response and survival. TRIAL REGISTRATION: ChiCTR1900024014, June 22, 2019.

Exosomes derived from M2 type tumor-associated macrophages promote osimertinib resistance in non-small cell lung cancer through MSTRG.292666.16-miR-6836-5p-MAPK8IP3 axis.

BACKGROUND: Osimertinib resistance limits the treatment of epidermal growth factor receptor-(EGFR)-mutated non-small-cell lung carcinoma (NSCLC). The mechanisms of osimertinib resistance need to be elucidated to determine alternative treatment strategies. This study explores the role of M2 type tumor-associated macrophage (TAM)-derived exosomal MSTRG.292666.16 in osimertinib resistance, and its related competing endogenous RNA (ceRNA) mechanism. METHODS: M2 type TAMs were induced with 200 ng/mL phorbol 12-myristate 13-acetate, 20 ng/mL IL-4 and IL-13, and M2 type macrophage markers were measured by RT-qPCR. Next, the exosomes were isolated and characterized. Tumor formation in nude mice was conducted using H1975 cells under different treatment conditions. Small RNA sequencing was performed on exosomes derived from sensitive and resistant plasma, and ceRNA networks were constructed. Fluorescence in situ hybridization was used to observe the localization of MSTRG.292666.16, and a ceRNA network (MSTRG.292666.16-miR-6836-5p-MAPK8IP3) was selected for further validation. RESULTS: M2 type TAMs, and M2 type TAM-derived exosomes were successfully induced and isolated. Nude mice results showed that M2 type TAM-derived exosomes and MSTRG.292666.16 overexpression significantly increased tumor volume after administration of osimertinib for 4 weeks. M2 type TAMs were found in the resistant plasma, and MSTRG.292666.16 localized in the cytoplasm of H1975 cells. In addition, the genes in the ceRNA networks were significantly enriched in eight GO terms and seven KEGG pathways, including the MAPK signaling pathway. Subsequently, the levels of MSTRG.292666.16 and MAPK8IP3 significantly increased in both resistant plasma-derived exosomes and M2 type TAM-derived exosomes, while miR-6836-5p levels were significantly reduced. Finally, MSTRG.292666.16, miR-6836-5p, and MAPK8IP3 were part of the same network. CONCLUSIONS: M2 type TAM-derived exosomes promoted osimertinib resistance in NSCLC by regulating the MSTRG.292666.16/miR-6386-5p/MAPK8IP3 axis.

Exosomal long non-coding RNA MSTRG.292666.16 is associated with osimertinib (AZD9291) resistance in non-small cell lung cancer.

Acquired resistance of osimertinib is encountered in clinic treatment of non-small cell lung cancer (NSCLC). However, the molecular mechanisms of osimertinib resistance are not fully revealed. This study aimed to investigate the roles of exosomes in delivering osimertinib resistance in NSCLC. Exosomes were successfully isolated. LncRNA sequencing identified a total of 123 differentially expressed lncRNAs, including 45 upregulated lncRNAs and 78 downregulated lncRNAs. The relative expression level of lncRNA MSTRG.292666.16 was significantly upregulated in osimertinib-resistant plasma, osimertinib-resistant H1975R cells and their derived exosomes, compared with those in osimertinib- sensitive plasma, H1975 cells and exosomes (P < 0.05). Besides, osimertinib-resistant exosomes could regulate gene expressions induced by osimertinib, including miRNA-21, miRNA-125b, TGFß, ARF6 and c-Kit. Osimertinib-resistant exosomes could be taken up by osimertinib-sensitive H1975 cells and resulting in osimertinib-resistance in vivo. Knockdown of lncRNA MSTRG.292666.16 decreased osimertinib resistance of H1975R cells. Our results suggest that exosomal lncRNA MSTRG.292666.16 might be associated with osimertinib resistance in NSCLC.

[Shanghai Pulmonary Hospital Experts Consensus on the Management of Ground-Glass Nodules Suspected as Lung Adenocarcinoma (Version 1)].

Background and objective As computed tomography (CT) screening for lung cancer becomes more common in China, so too does detection of pulmonary ground-glass nodules (GGNs). Although anumber of national or international guidelines about pulmonary GGNs have been published,most of these guidelines are produced by respiratory, oncology or radiology physicians, who might not fully understand the progress of modern minimal invasive thoracic surgery, and these current guidelines may overlook or underestimate the value of thoracic surgery in the management of pulmonary GGNs. In addition, the management for pre-invasive adenocarcinoma is still controversial. Based onthe available literature and experience from Shanghai Pulmonary Hospital, we composed this consensus about diagnosis and treatment of pulmonary GGNs. For lesions which are considered as adenocarcinoma in situ, chest thin layer CT scan follow-up is recommended and resection can only be adopt in some specific cases and excision should not exceed single segment resection. For lesions which are considered as minimal invasive adenocarcinoma, limited pulmonary resection or lobectomy is recommended. For lesions which are considered as early stage invasive adenocarcinoma, pulmonary resection is recommend and optimal surgical methods depend on whether ground glass component exist, location, volume and number of the lesions and physical status of patients. Principle of management of multiple pulmonary nodules is that primary lesions should be handled with priority, with secondary lesions taking into account.
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Competitive evolution of NSCLC tumor clones and the drug resistance mechanism of first-generation EGFR-TKIs in Chinese NSCLC patients.

PURPOSE: Although many studies have reported on the resistance mechanism of first-generation EGFR TKIs (1st EGFR TKIs) treatment, large-scale dynamic ctDNA mutation analysis based on liquid biopsy for non-small cell lung cancer (NSCLC) in the Chinese population is rare. Using in-depth integration and analysis of ctDNA genomic mutation data and clinical data at multiple time points during the treatment of 53 NSCLC patients, we described the resistance mechanisms of 1st EGFR TKIs treatment more comprehensively and dynamically. The resulting profile of the polyclonal competitive evolution of the tumor provides some new insights into the precise treatment of NSCLC. EXPERIMENTAL DESIGN: A prospective study was conducted in patients with advanced NSCLC with acquired resistance to erlotinib, gefitinib or icotinib. By liquid biopsy, we detected mutations in 124 tumor-associated genes in the context of drug resistance. These 124 genes covered all tumor therapeutic targets and related biological pathways. During the entire course of treatment, the interval between two liquid biopsies was two months. RESULTS: Unlike the common mutations tested in tissue samples, our data showed a higher coverage of tumor heterogeneity (32.65%), more complex patterns of resistance and some new resistance mutation sites, such as EGFR p.V769M and KRAS p.A11V. The major resistance-associated mutations detected were still EGFR p.T790M (45.28%), other point mutations in EGFR (33.9%), and KRAS and NRAS mutations (15.09%). These mutation ratios might be considered as a preliminary summary of the characteristics of Chinese patients. In addition, starting from the two baseline mutations of the EGFR gene (19del vs. L858R), we first described the detailed mutation profile of the EGFR gene. Although there was no significant difference in the number of patients with EGFR p.19del and EGFR p.L858R baseline mutations (24% vs. 16%, P = 0.15), patients from the EGFR p.19del baseline group were much more likely to develop EGFR p.T790M resistance mutations (62.1% vs. 19.3%, P = 0.007). Through careful integration of gene mutation information and clinical phenotype information, an interesting phenomenon was found. Although the variant allele fraction (VAF) of the EGFR p.T790M mutation was significantly linearly correlated with that of the EGFR drug-sensitive mutation (r = 0.68, P = 0.00025), neither VAF was associated with the tumor volume at the advanced stage. It was shown that other tumor clones might contribute more to the resistance to 1st EGFR TKIs treatment than tumor clones carrying the EGFR p.T790M mutation when resistance developed. By further analysis, we found that, in some patients, when the primary tumor clones detected were those carrying EGFR-/- mutations (both types the EGFR p.19del/p.L858R and EGFR p.T790M mutation types were missing), most of them showed a poor prognosis and ineffective late treatment, indicating that EGFR-/- played a more important role than EGFR p.T790M in the process of NSCLC drug resistance in these patients. From the perspective of the clonal evolution of NSCLC tumor cells, these phenomena could be explained by the competitive evolution between different tumor clones. In addition, two new mutations, KRAS p.A11V and EGFR p.V769M, emerged significantly during drug resistance in NSCLC patients and had shown obvious competitive clonal evolution characteristics. Combined with clear clinical drug resistance phenotypic information, we believed that these two new mutations might be related to new drug resistance mechanisms and deserve further study. We have also seen an interesting phenomenon. In some patients undergoing 1st EGFR TKIs treatment, the EGFR p.T790M mutation appeared, disappeared, and reappeared, and this spatial and temporal diversity of the EGFR p.T790M mutation was regulated by targeted drug and chemotherapy and was correlated with the individual tumor mutation profile. CONCLUSIONS: The constitution and competitive evolution of the tumor clones have a decisive influence on treatment and can be regulated by targeted drugs and chemotherapy. Additionally, EGFR p.T790M spatial and temporal diversity during treatment warrants more attention, and this spatial and temporal diversity may be useful for the choice of treatment strategies for certain NSCLC patients. Through longitudinal cfDNA sample analysis, the resistance mechanism and dynamic clinical features of Chinese NSCLC patients are systematically established as reliable and meaningful to understand acquired resistance and make further personalized treatment decisions dynamically. Two new potential drug resistance-associated mutations in EGFR and KRAS have been found and are worthy of further study. Finally, our research shows that the evolutionary process of tumor cloning can be artificially regulated and intervened, possibly providing a new way to treat tumors.

Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients.

Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped. Dose-adjusted trough blood concentrations (C/D ratio, mg/kg body weight) in lung transplant patients during the first 4 postoperative weeks were calculated. Results. IL-18 rs5744247 allele C and rs1946518 allele A were associated with fast tacrolimus metabolism. Combined analysis showed that the numbers of low IL-18 mRNA expression alleles had positive correlation with tacrolimus C/D ratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimus C/D ratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimus C/D ratios difference of IL-10 polymorphisms was found in our data. Conclusions. IL-18 polymorphisms may influence tacrolimus elimination in lung transplantation patients.

[Relationship between ID1 and EGFR-TKI Resistance 
in Non-small Cell Lung Cancer].

BACKGROUND: Non-small cell lung cancer (NSCLC) presents the highest morbidity and mortality among malignant tumors worldwide. The overall effective rate of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is 30% to 40%, and PFS (progression-free sruvival) is 12 months. However, EGFR-TKI resistance is typical in clinical observations, and this phenomenon significantly affects tumor suppression. To overcome this resistance, a new prognostic factor associated with lung cancer drug resistance should be discovered. This study investigated the relationship between the inhibitor of differentiation 1 (ID1) and non-small cell lung cancer EGFR-TKI resistance in vivo and in vitro to determine any statistical significance and discuss the underlying mechanism. METHODS: Western blot and qRT-PCR were used to quantify the expression of ID1 in lung cancer. IHC was used to detect the expression of ID1 in pathological tissues (lung cancer tissues and adjacent tissues). MTT was used to detect cell proliferation, in which the cells were treated with gefitinib after being transfected by ID1 slow virus vector. Lung cancer cells were inoculated in nude mice until the tumor diameter grew to certain measurement. Gefitinib treatment was started, and the tumor volume was estimated. RESULTS: ID1 was highly expressed in NSCLC (P<0.05). Both ID1 expression and drug resistance of EGFR-TKI in NSCLC were positively correlated (P<0.05). The treatment group with gefitinib showed obviously less expression than the control group. CONCLUSIONS: ID1 is highly expressed in NSCLC. ID1 expression was positively related to drug resistance of EGFR-TKI in NSCLC. Gefitinib can be used to effectively treat NSCLC, and the mechanism may be associated with an increased level of STAT3 phosphorylation.

Single-port video-assisted thoracic surgery in 1063 cases: a single-institution experience†.

OBJECTIVES: Single-port video-assisted thoracic surgery (VATS) technique has been used for thoracic diseases. There was no report about single-port VATS in large series. Outcomes following single-port VATS were analysed to determine its efficacy and safety. METHODS: From June 2012 to June 2014, 1063 single-port VATSs were performed by four surgeons. Patient demographics, perioperative parameters, histopathology and outcomes were analysed. RESULTS: There were 1063 patients (524 men and 539 women). The median age was 56.1 ± 8.7 years (range, 15-86 years). Lobectomy was performed in 569 patients, segmentectomy in 162, wedge resection in 264, pleural biopsy in 7, drainage of effusion in 20, pleural tumour resection in 5, mediastinal tumour resection in 54, mediastinal tumour biopsy in 2, bilobectomy in 7, sleeve lobectomy in 3 and pneumonectomy in 2. Synchronous bilateral single-port VATS was performed in 27 cases, whereas metachronous bilateral single-port VATS was performed in 5 cases. Pathological diagnoses included primary lung cancer in 635 cases, metastatic lung cancer in 19, mediastinal tumour in 56, pleural disease in 32 and benign pulmonary conditions in 353. Fifteen intraoperative vascular injuries were identified in 15 patients. The total conversion rate was 4.6%. The average operation time was 135 ± 31 min (range, 30-230 min), and the average blood loss was 117 ± 47 ml (range, 50-2000 ml). The median intensive care unit stay was 1 day (0-4 days). The postoperative hospital stay was 6.2 ± 2.6 days on average. There was no operative death, and operative complications occurred in 59 patients (5.6%). The 1-year overall survival and 1-year disease-free survival for the primary lung cancer group were 98 and 96%, respectively. CONCLUSIONS: Our findings indicate that single-port VATS for thoracic diseases is safe and feasible.

[Analysis of misdiagnosis of 38 cases of solitary fibrous tumor of the pleura].

OBJECTIVE: To improve the preoperative diagnostic rate of solitary fibrous tumor(SFTP) of the pleura through the analysis on clinical characteristics and misdiagnosis reasons of SFTP. METHODS: A retrospective review of the clinical records of 38 cases of SFTP in our hospital from January 2004 to June 2014 was conducted. The follow-up data were also reviewed. RESULTS: There were 18 males and 20 females, aging from 20 to 78 years (median, 53.8 years). Twenty-one cases were asymptomatic while other 17 had cough, chest pain, chest tightness and other symptoms. The levels of serum tumor markers were normal in 28 cases. The preoperative diagnosis was lung cancer in 9 cases, pleural mesothelioma in 5, neurofibroma in 5, pulmonary benign tumors in 4, pulmonary infection in 3, inflammatory granuloma in 5, pyothorax in 2, tuberculous pleuritis in 3, and pulmonary sequestration in 2 cases. The misdiagnosis rate was 84.4%, with misdiagnosis time ranging from 7 days to 10 years (median, 5.4 months). All the patients received thoracic surgical treatment. Among them, 33 cases were diagnosed as benign SFTP while 5 were diagnosed as malignant SFTP. Follow-up periods ranged from 1 to 118 months (median, 45 months). Three cases were lost, 2 died 11 months and 18 months after operation, and 3 reported recurrence. CONCLUSION: SFTP is a rare tumor which can be misdiagnosed easily. Awareness of its presentation and clinical course may help the clinician to consider referral to the thoracic surgeon for resection.

Uniportal video-assisted thoracoscopic lobectomy with en bloc chest wall resection.

BACKGROUND: Lobectomy with chest wall resection was traditionally performed by thoracotomy or by conventional video-assisted thoracoscopic surgery (VATS) during the last decade. However, this procedure can be performed by using only a single incision thoracoscopic approach. METHODS: The publications of uniportal VATS lobectomy requiring chest wall resection describes the use of one incision for the lobectomy (uniportal approach) and a posterior or lateral incision for the chest wall resection. This additional incision ensures a better control from outside and inside to achieve a costal resection with good oncologic margins. RESULTS: This video shows a total uniportal VATS lobectomy with en bloc chest wall resection through a single 5-cm incision with no rib spreading. The total surgical time was 150 minutes. The postoperative course of the patient was uneventful. CONCLUSIONS: Uniportal VATS lobectomy with en-bloc chest wall resection is a feasible and safe technique. The full procedure can be performed by using only a single incision in selected cases.

Progressive chest wall bleeding caused by bronchial stump nails after lobectomy.

BACKGROUND: Postoperative intrathoracic active bleeding is a serious complication after general thoracic surgery. Yet, progressive chest wall bleeding caused by a bronchial stump nail after lobectomy has rarely been reported. The purpose of this report was to review the causes, surgical treatment, and prevention of progressive chest wall bleeding caused by a bronchial stump nail in patients after lobectomy. METHODS: Between January 2011 and February 2013, approximately 5,000 patients underwent lobectomies for various thoracic diseases in the Department of Thoracic Surgery of Shanghai Pulmonary Disease Hospital in China. Among the 5,000 patients, four required reexploration for progressive postoperative chest wall bleeding caused by bronchial stump nails. RESULTS: Staples were used without covers for the bronchial stumps in these patients. At the time of reoperation, we noted that the main site of bleeding was the pleura corresponding to the bronchial stump. The bleeding pleura sites were coagulated and sutured, and complete hemostasis of the pleura was achieved. The nails on the staple that may have caused the bleeding were removed. Then, muscle or hemostatic material was applied to separate the bronchial stump and corresponding pleura. CONCLUSIONS: Performing surgery carefully and understanding the risk from bronchial stump nails are keys to preventing progressive postoperative bleeding.

A novel technique to increase the length of tracheal resection by adding an autologous pedicled pectoralis major myocutaneous flap transposition.

Resection of the trachea is usually limited by the length of involvement. We present a case of long segment tracheal resection performed by adding an autologous pedicled pectoralis major myocutaneous flap transposition. By applying of this technique, a segment of trachea as long as 7.5 cm was safely resected without complications.

Pulmonary resection in the treatment of 43 patients with well-localized, cavitary pulmonary multidrug-resistant tuberculosis in Shanghai.

OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis resistant to at least isoniazid and rifampicin in vitro, poses a significant challenge to the control of TB worldwide. Despite global efforts to control tuberculosis, it remains the leading cause of death from an infectious agent. Although modern tuberculosis treatment relies on chemotherapy, surgery is accepted as adjuvant treatment for multidrug-resistant tuberculosis. METHODS: In a retrospective cohort study, 43 MDR-TB patients (28 males and 15 females: mean age 45.3 years) who underwent pulmonary resection between January 1993 and December 2011 were reviewed. Every patient with well-localized, cavitary lesions showed sputum-positive preoperatively. Individually tailored treatment regimens were selected at a once-weekly staff conference following review of the patient's case history and drug susceptibility results. The variables that affected treatment outcomes were identified through multivariate regression analysis. RESULTS: There was no surgical mortality. Forty (93.0%) patients demonstrated sputum conversion and/or remained negative after surgery. Each patient had completed treatment, and during a mean of 81 follow-up months (range 18-214 months), 1 patient relapsed. This patient was cured after another course of treatment. Operative procedures included 30 (69.8%) lobectomies, 2 (4.7%) bilobectomies, 8 (18.6%) pneumonectomies and 3 (6.98%) lobectomies plus segmentectomy. There were no operation-related deaths, and there were five major postoperative complications (11.6%). Overall, 40 of 43 (93.0%) MDR-TB patients remained free of TB following surgery. The duration of chemotherapy before surgery had correlation with postoperative outcome (P = 0.001). CONCLUSIONS: The proper selection of the patients and early decision for surgical intervention can achieve a high success rate of pulmonary MDR-TB with well-localized pulmonary cavities.

[Cytokine responses after lobectomy for early non-small cell lung cancer: a prospective randomized comparison of video-assisted thoracic surgery and open thoracotomy].

OBJECTIVE: To compare video-assisted thoracic surgery (VATS) and open thoracotomy (OT) on acute inflammatory responses and immunosuppression after lobectomy for early non-small cell lung cancer (NSCLC). METHODS: Present prospective randomized study. OT or VATS lobectomy was performed in patients who met enter criteria and clinical data was collected. Plasma concentration of IL-6, IL-8 and IL-10 were measured before surgery and at postoperative day (POD) 1 and POD 3. There were 271 patients underwent lobectomy for early NSCLC, including of 133 patients in group VATS and 138 patients in group OT from January 2007 to June 2008. There were 132 males and 139 females, aging from 19 ∼ 70 years with a mean of (56 ± 8) years. RESULTS: Compared with OT group, shorter postoperative hospital stay [(8.2 ± 2.5) d vs. (9.8 ± 6.2) d, P = 0.03], lower morbidity rate (11.3% vs. 21.7%, P = 0.02) and lower increase of plasma concentration of IL-6 at POD 1 [(35 ± 25)% vs. (65 ± 43)%, P = 0.00], IL-6 at POD 3 [(14 ± 22)% vs. (55 ± 44)%, P = 0.00] and IL-10 at POD 1 [(25 ± 20)% vs. (43 ± 35)%, P = 0.00] were observed in patients of VATS group. CONCLUSION: VATS lobectomy for early NSCLC is associated with less acute inflammatory responses and less immunosuppression when compared with OT.

Bronchial angiolipoma.

Angiolipoma occurs preferentially in the extremities and trunk. We present a patient with involvement of the bronchus and describe successful localized resection of the lesion.

Radical resection of a pulmonary blastoma involving the pulmonary artery.

Pulmonary blastoma is a rare malignant lesion with a poor prognosis. We described a case of a 47-year-old woman with a large biphasic pulmonary blastoma, involving the left pulmonary artery. Under cardiopulmonary bypass, it was treated with radical left intrapericardial pneumonectomy and pulmonary thromboendarterectomy. Subsequent chemotherapy and radiotherapy was used. Three years postoperatively, the patient was clinically and radiologically free of tumor.