Adjuvant treatment for patients with incidentally resected limited disease small cell lung cancer-a retrospective study.

Background: With the exception of very early-stage small cell lung cancer (SCLC), surgery is not typically recommended for this disease; however, incidental resection still occurs. After incidental resection, adjuvant salvage therapy is widely offered, but the evidence supporting its use is limited. This study aimed to explore proper adjuvant therapy for these incidentally resected SCLC cases. Methods: Patients incidentally diagnosed with SCLC after surgery at the Shanghai Pulmonary Hospital in China from January 2005 to December 2014 were included in this study. The primary outcome was overall survival. Patients were classified into different group according to the type of adjuvant therapy they received and stratified by their pathological lymph node status. Patients' survival was analyzed using a Kaplan-Meier analysis and Cox regression analysis. Results: A total of 161 patients were included in this study. Overall 5-year survival rate was 36.5%. For pathological N0 (pN0) cases (n=70), multivariable analysis revealed that adjuvant chemotherapy (ad-chemo) was associated with reduced risk of death [hazard ratio (HR): 0.373; 95% confidence interval (CI): 0.141-0.985, P=0.047] compared to omission of adjuvant therapy. For pathological N1 or N2 (pN1/2) cases (n=91), taking no adjuvant therapy cases as a reference, the multivariable analysis showed that ad-chemo was not associated with a lower risk of death (HR: 0.869; 95% CI: 0.459-1.645, P=0.666), while adjuvant chemo-radiotherapy (ad-CRT) was associated with a lower risk of death (HR: 0.279; 95% CI: 0.102-0.761, P=0.013). Conclusions: Patients who incidentally receive surgical resection and are diagnosed with limited disease SCLC after resection should be offered adjuvant therapy as a salvage treatment. For incidentally resected pN0 cases, ad-chemo should be considered and for pN1/2 cases, ad-CRT should be received.

Retraction Notice to: Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma.

[This retracts the article DOI: 10.1016/j.omtn.2021.01.019.].

Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma.

Hypoxia is a common feature of solid tumors and has been associated with tumor aggressiveness and poor prognosis. Exosomes are involved in mediating cellular-environment interactions. Circular RNAs (circRNAs) are a class of non-coding RNA broadly found in cells and exosomes. However, the functions and regulatory mechanisms of exosomal circRNAs induced by hypoxia remain poorly understood in lung adenocarcinoma (LUAD) development. Differentially expressed circRNAs were identified between exosomes extracted from hypoxic and normoxic conditions through microarray analysis. We focused on hsa-circ-0003439 found on chromosome 1 and derived from SET domain bifurcated histone lysine methyltransferase 1 (SETDB1), and thus we named it circSETDB1. We discovered that exosomes obtained from hypoxic LUAD cells improved the migration, invasion, and proliferation capacity of normoxic LUAD cells. circSETDB1 was found to be significantly upregulated in hypoxia-induced exosomes from LUAD cell lines compared with exosomes in the normal condition. Moreover, knockdown of circSETDB1 significantly inhibited cell malignant growth in vitro. Importantly, we showed that circSETDB1 was upregulated in serum exosomes in LUAD patients, and exosomal circSETDB1 levels were closely associated with disease stage. Finally, using RNA immunoprecipitation (RIP), bioinformatics, and luciferase reporter assays, we elucidated the implication of a circSETDB1/miR-7/specificity protein 1 (Sp1) axis in the development and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma.

Expert consensus on resection of chest wall tumors and chest wall reconstruction.

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T3-4N0-1M0. As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years.

ES-MDA: Enhanced Similarity-based MiRNA-Disease Association.

Accumulating evidence demonstrate that miRNAs can be treated as critical biomarkers in various complex human diseases. Thus, the identifications on potential miRNA-disease associations have become a hotpot for providing better understanding of disease pathology in this field. Recently, with various biological datasets, increasingly computational prediction approaches have been designed to uncover disease-related miRNAs for further experimental validation. To improve the prediction accuracy, several algorithms integrated miRNA similarities of known miRNA-disease associations to enhance the miRNA functional similarity network and disease similarities of known miRNA-disease associations to enhance the disease semantic similarity network. It is anticipated that machine learning methods would become an effective biological resource for clinical experimental guidance.

HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma.

In this study, we identified a circular form of ASPH RNA (circASPH), expression of which was upregulated in lung adenocarcinoma and the human lung adenocarcinoma cell lines. We also found a positive correlation between circASPH level and the T and N stages of lung adenocarcinoma patients. Patients with higher levels of circASPH had a shorter overall survival. Moreover, we demonstrated that circASPH was directly regulated by HMGA2 and Twist1. The direct positive regulation of circASPH by Twist1 was dependent on the presence of HMGA2. Functional assays indicated that circASPH promoted the proliferation, migration, and invasion of lung adenocarcinoma cell lines in vitro. The promoting effect of tumor growth by circASPH was also observed in vivo. Mechanistically, circASPH was identified to act as a molecular sponge for miR-370 and abrogate miR-370-mediated inhibition of HMGA2. Finally, we demonstrated that the oncogenic function of circASPH was HMGA2-dependent. These findings reveal the oncogenic functions of the HMGA2-circASPH-HMGA2 axis and may be useful in developing circRNA-based therapeutic strategies for lung adenocarcinoma.

Application of preoperative embolization during surgery for the destroyed lung.

BACKGROUND: The destroyed lung has been a challenge in the clinical practice of thoracic surgery, and severe adhesions and massive bleeding during surgery are the main obstacles faced by surgeons. This study aimed to investigate the efficacy of the preoperative embolization of blood vessels in adhesions during surgery for the destroyed lung. METHODS: A total of 7 patients underwent preoperative embolization for lung resection of destroyed lungs between June 2016 and February 2019. Preoperative embolization was performed for 45 min to 2 h within 48 h before surgery. The embolized arteries included the intercostal artery, radial artery, subclavian artery and their branches, and the number of embolized arteries ranged from 5 to 13. RESULTS: A posterolateral incision was made in these patients, and endoscope-assisted separation of the adhesions at the top of the chest wall and on the lateral chest wall was performed. The operation time ranged from 3.5 to 8 h, and the blood loss was 1,200-5,000 mL. The postoperative drainage was in the normal range. One patient developed multiple organ failure and bronchopleural fistulas (BPF) one month after surgery, which was resolved after active drainage and argon cauterization; another patient developed BPF 7 months after surgery, which was resolved after placement of a nonreturn valve in the subsegmental bronchi via bronchoscopy. CONCLUSIONS: Surgery of the destroyed lung is a great challenge in clinical practice, mainly due to the risk of the blood supply in the adhesions. Preoperative embolization may reduce intraoperative blood loss and surgical difficulty.

Specific gut microbiome signature predicts the early-stage lung cancer.

Alterations of gut microbiota have been implicated in multiple diseases including cancer. However, the gut microbiota spectrum in lung cancer remains largely unknown. Here we profiled the gut microbiota composition in a discovery cohort containing 42 early-stage lung cancer patients and 65 healthy individuals through the 16S ribosomal RNA (rRNA) gene sequencing analysis. We found that lung cancer patients displayed a significant shift of microbiota composition in contrast to the healthy populations. To identify the optimal microbiota signature for noninvasive diagnosis purpose, we took advantage of Support-Vector Machine (SVM) and found that the predictive model with 13 operational taxonomic unit (OTU)-based biomarkers achieved a high accuracy in lung cancer prediction (area under curve, AUC = 97.6%). This signature performed reasonably well in the validation cohort (AUC = 76.4%), which contained 34 lung cancer patients and 40 healthy individuals. To facilitate potential clinical practice, we further constructed a 'patient discrimination index' (PDI), which largely retained the prediction efficiency in both the discovery cohort (AUC = 92.4%) and the validation cohort (AUC = 67.7%). Together, our study uncovered the microbiota spectrum of lung cancer patients and established the specific gut microbial signature for the potential prediction of the early-stage lung cancer.

Lung transplantation in China between 2015 and 2018.

BACKGROUND: Lung transplantation (LT) has been demonstrated as the only effective therapy for patients with end-stage lung diseases. Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require well-organized programs and registry data collection based on the large population. This study aimed to summarize and analyze the data of LT development in China. METHODS: We retrospectively collected and analyzed data from the China Lung Transplantation Registry (CLuTR). Key data were reported from the registry with transplant types, indications, donor and recipient characteristics, outcomes and survival. The survival <30 days, 1-year and 3-year survival rates were estimated with risk factors identified. RESULTS: CLuTR contained data from 1053 lung transplants performed through January 1st, 2015 to December 31st, 2018 reported by 18 registered transplant centers. The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis. The total <30 days, 1-year and 3-year survival rates in CLuTR were 81.45%, 70.11%, and 61.16% with discrepancy by indications. Large proportion of recipients who were more than 60 years old required higher standard of care. Infection-related complications resulted in more death events in the early post-surgery periods. New York Heart Association grading at listing, extra-corporeal membrane oxygenation usage peri-transplantation, allograft dysfunction (primary graft dysfunction >Grade 0), renal insufficiency (estimated glomerular filtration rate <60 mL·min·1.73 m), were independently associated with a higher risk for 3-year mortality in the entire cohort. CONCLUSIONS: Facing more end-stage of lung diseases and comorbidities, this study analyzed the outcomes and survival of LT recipients in China. Further prospectively stratified analyses with longer follow-up will be needed.

Traditional Chinese Medicine Treatment as Adjuvant Therapy in Completely Resected Stage IB-IIIA Non-Small-Cell Lung Cancer: Study Protocol for a Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

Adjuvant chemotherapy (AC) has been proven to yield an approximately 5% improvement in 5-year survival for patients with early-stage non-small-cell lung cancer. With such small gains in survival, the optimal treatment regimen remains to be established. Traditional Chinese medicine (TCM) treatment in combination with AC is frequently used in China. The efficacy and safety of this integrated approach should be scientifically evaluated. We present the rationale and study design of the Combined Adjuvant Chemotherapy and Traditional Chinese Medicine (ACTCM) trial (ChiCTR-IPR-16009062). The ACTCM trial, a prospective multicenter double-blind randomized placebo-controlled study, will recruit 312 patients overall from 5 clinical research centers in China. Within 6 weeks of the thoracic surgery, eligible participants with stages IB-IIIA non-small-cell lung cancer will be randomly assigned in a 1:1 ratio to either the treatment or control group. Patients in the treatment group will receive AC combined with TCM herbal treatment for 4 cycles, then TCM herbal plus injection treatment for 4 cycles. Patients in the control group will receive AC combined with TCM placebo for 4 cycles and then TCM placebo for 4 cycles. Treatment will be discontinued if disease progression or unacceptable toxicity occurs. The primary end point is 2-year disease-free survival. Secondary end points include disease-free survival and quality of life. Other end points are TCM symptoms, performance status, and safety of the regimens. Recruitment started in October 2016 and is ongoing.

Prevalence and Risk Factors of Acute Pulmonary Embolism in Patients with Lung Cancer Surgery.

Acute pulmonary embolism (PE) is one of the serious complications with high mortality after thoracic surgery. The authors aimed to determine the prevalence of PE events and evaluate additional risk factors for PE in patients with lung cancer surgery. Patients underwent lung cancer resections during January 2012 to July 2015 and had 30-day postoperative follow-up were included. Those with incomplete or miscoded data were excluded. The number of postoperative PE events was recorded retrospectively. Analyses were used to evaluate risk factors of PE during the hospitalization. The authors reviewed 11,474 patients who underwent surgery for lung cancer. The overall 30-day incidence of PE after thoracic surgery at their institution was 0.53%. The 30-day PE incidence without chemical prophylaxis was 0.57% (55/9,726) and the mortality rate was 10%. Multivariate analyses revealed that age over 66 (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.05-1.12, p < 0.001), more extensive surgery than lobectomy (OR: 2.34, 95% CI: 1.28-4.25, p = 0.006) and stage IV of lung cancer (OR: 4.22, 95% CI: 1.50-11.9, p = 0.007) were associated with an increased risk of PE. Using these additional risk factors, based on readily available clinical characteristics, can help to risk-stratify patients and warrant extended chemical prophylaxis for patients to reduce the incidence of acute PE.

Comparison of the perioperative outcomes in antero-superior mediastinal tumor resection performed by transcervical resection and video-assisted thoracoscopic surgery.

BACKGROUND: It remains controversial that whether transcervical resection (TC) was associated with better outcomes than video-assisted thoracoscopic surgery (VATS) in the treatment of antero-superior mediastinal tumors. We aimed to compare the safety and reliability between TC and VATS. METHODS: Between 2010 and 2012, 80 consecutive patients underwent antero-superior mediastinal tumor resection via TC (n=31) or VATS (n=49). Perioperative outcomes were compared. A propensity score-matched analysis was performed to control the potential confounders. RESULTS: A total of 41 men and 39 women with median age of 52.5 years were enrolled. No patient died during the perioperative course. After propensity matching, TC group was associated with less intraoperative blood loss (35.1±18.7 vs. 93.7±136.1 mL, P=0.034), less postoperative drainage (65.6±76.8 vs. 335.0±154.9 mL, P<0.001), shorter length of postoperative hospital stay (3.2±1.2 vs. 4.1±1.3 days, P=0.003) and less hospitalization expense (22,252.3±4,761.7 vs. 26,514.2±4,052.8 CNY, P=0.002) compared to VATS group. One patient with VATS was converted to open surgery due to intraoperative vessels damage. The postoperative complication was null in TC group while it was 6.1% (n=3) in VATS group (P=0.279), including 1 case of prolonged chest tube drainage and 2 cases of recurrent laryngeal nerve injury. CONCLUSIONS: TC for antero-superior mediastinal tumors is a safe procedure with better perioperative outcomes compared to VATS.

Nonintubated-Awake Anesthesia for Uniportal Video-Assisted Thoracic Surgery Procedures.

Nonintubated video-assisted thoracic surgery (VATS) strategies are gaining popularity. This review focuses on noninutbated VATS, and discusses advantages, indications, anesthetic techniques, and approaches to intraoperative crisis management. Advances in endoscopic, endovascular, and robotic techniques have expanded the range of surgical procedures that can be performed in a minimally invasive fashion. The nonintubated thoracoscopic approach has been adapted for use with major lung resections. The need for general anesthesia and endotracheal intubation has been reexamined, such that regional or epidural analgesia may be sufficient for cases where lung collapse can be accomplished with spontaneous ventilation and an open hemithorax.

A rare case of left innominate vein aneurysm mimicking thymoma.

Thoracic venous aneurysms are very rare conditions, even more unusual from left innominate vein. We report a case of a 57-year-old male who presented an anterior mediastinal mass suspicious of thymoma by chest computed tomography. Median sternotomy was performed aiming for total thymectomy, but intraoperative findings and final pathology confirmed the diagnosis of left innominate vein aneurysm. The patient underwent aneurysmectomy and reconstruction of the left innominate vein. The patient remains well 2 years after surgery. The new thoughts provoked by this case are that video-assisted thoracic surgery for this condition is dangerous and mediastinal mass should be evaluated further by magnetic resonance imaging, venography or venous phase computed tomography.

Resection of giant mediastinal liposarcoma via '⊣ shape' incision.

Primary mediastinal liposarcomas are extremely rare conditions often resected through standard median sternotomy or lateral thoracotomy. However, the management of a very huge mediastinal tumor involving hemithorax through these two common surgical approaches is always challenging. Herein, we report a case of applying median sternotomy with a sternum transection plus a right fourth intercostal thoracotomy ('⊣ shape' incision) to resect a giant primary anterior mediastinal liposarcoma extending into the whole right thorax. The final pathological diagnosis was a well-differentiated liposarcoma. The patient experienced an uneventful recovery. The '⊣ shape' incision is a good backup for the extension of standard median sternotomy and provides a better exposure for both mediastinum and hemithorax.