Publications by authors named "Hecheng Li"

106 Publications

REPLY: THE CONTINUED DEBATE ON ROBOTIC SEGMENTECTOMY-AGREE TO DISAGREE.

J Thorac Cardiovasc Surg 2021 Jan 15. Epub 2021 Jan 15.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1016/j.jtcvs.2020.12.006DOI Listing
January 2021

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1).

Eur J Cancer 2021 Feb 26;144:232-241. Epub 2020 Dec 26.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

Background: To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable oesophageal squamous cell carcinoma (ESCC) (ClinicalTrials.gov number, NCT03792347).

Methods: Twenty resectable ESCC patients, regardless of programmed death ligand-1 status, received preoperative pembrolizumab with concurrent chemoradiotherapy (PPCT). Preoperative therapy includes carboplatin (area under the curve of 2 mg per milliliter per minute, once a week for 5 weeks), paclitaxel (50 mg/m, once a week for 5 weeks), radiotherapy (23 fractions of 1.8 Gy, 5 fraction a week) and pembrolizumab (2 mg/kg) on days 1 and 22. Within 4-6 weeks after preoperative therapy, patients underwent surgery. The primary end-point was safety and secondary outcome measures were feasibility, pathologic complete response (pCR) rate and radiographic response. Immune signature of CD8 T cells was evaluated in surgical specimens using immunohistochemistry and immunofluorescence.

Results: All patients have received PPCT successfully, except one patient who missed the last dose of chemotherapy due to leukopenia. Grade III and higher adverse events (AEs) were observed in 13 patients (13/20, 65%), and one patient had a grade V AE. The most frequent grade III AE was lymphopenia (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR rate was 55.6% (10/18). The percentage of transcription factor 1 positive cells was significantly higher in specimens of pCR group than those of non-pCR group (p value = 0.010).

Conclusions: PPCT was safe, did not delay surgery, and induced a pCR in 55.6% of resected tumours. A phase II multicentre study is undergoing for further confirmation of efficacy (NCT04435197).
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http://dx.doi.org/10.1016/j.ejca.2020.11.039DOI Listing
February 2021

Long-term and short-term outcomes of robot- versus video-assisted anatomic lung resection in lung cancer: a systematic review and meta-analysis.

Eur J Cardiothorac Surg 2020 Dec 23. Epub 2020 Dec 23.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objectives: Minimally invasive thoracic surgery has evolved with the introduction of robotic platforms. This study aimed to compare the long-term and short-term outcomes of the robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) for anatomic lung resection.

Methods: We searched published studies that investigated RATS and VATS in anatomic lung resection. Long-term outcomes (disease-free survival and overall survival) and short-term outcomes (30-day mortality, postoperative complications, conversion rate to open surgery and lymph node upstaging) were extracted. The features were compared and tested as hazard ratios (HRs) and odds ratios (ORs) at a 95% confidence interval (CI).

Results: Twenty-five studies with 50 404 patients (7135 for RATS and 43 269 for VATS) were included. The RATS group had a longer disease-free survival than the VATS group (HR: 0.76; 95% CI: 0.59-0.97; P = 0.03), and the overall survival showed a similar trend but was not statistically significant (HR: 0.77; 95% CI: 0.57-1.05; P = 0.10). The RATS group showed a significantly lower 30-day mortality (OR: 0.55; 95% CI: 0.38-0.81; P = 0.002). No significant difference was found in postoperative complications (OR: 1.01; 95% CI: 0.87-1.16; P = 0.94), the conversion rate to open surgery (OR: 0.92; 95% CI: 0.56-1.52; P = 0.75) and lymph node upstaging (OR: 0.89; 95% CI: 0.52-1.54; P = 0.68).

Conclusions: RATS has comparable short-term outcomes and potential long-term survival benefits for anatomic lung resection compared with VATS.
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http://dx.doi.org/10.1093/ejcts/ezaa426DOI Listing
December 2020

Evolutionary algorithm using surrogate models for solving bilevel multiobjective programming problems.

PLoS One 2020 17;15(12):e0243926. Epub 2020 Dec 17.

School of Mathematics and Statistics, Xidian University, Xi'an, China.

A bilevel programming problem with multiple objectives at the leader's and/or follower's levels, known as a bilevel multiobjective programming problem (BMPP), is extraordinarily hard as this problem accumulates the computational complexity of both hierarchical structures and multiobjective optimisation. As a strongly NP-hard problem, the BMPP incurs a significant computational cost in obtaining non-dominated solutions at both levels, and few studies have addressed this issue. In this study, an evolutionary algorithm is developed using surrogate optimisation models to solve such problems. First, a dynamic weighted sum method is adopted to address the follower's multiple objective cases, in which the follower's problem is categorised into several single-objective ones. Next, for each the leader's variable values, the optimal solutions to the transformed follower's programs can be approximated by adaptively improved surrogate models instead of solving the follower's problems. Finally, these techniques are embedded in MOEA/D, by which the leader's non-dominated solutions can be obtained. In addition, a heuristic crossover operator is designed using gradient information in the evolutionary procedure. The proposed algorithm is executed on some computational examples including linear and nonlinear cases, and the simulation results demonstrate the efficiency of the approach.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243926PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746194PMC
February 2021

Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial.

J Thorac Oncol 2021 Feb 8;16(2):310-317. Epub 2020 Dec 8.

Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Institute of Thoracic Oncology, Fudan University, Shanghai, People's Republic of China. Electronic address:

Introduction: The optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer.

Methods: Between March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio. Analyses were done according to the intention-to-treat principle. The primary end point was overall survival (OS), calculated from the date of randomization to the date of death from any cause.

Results: Demographic characteristics were similar in the two arms. The median follow-up time was 55 months (95% confidence interval [CI]: 52-58). OS (hazard ratio [HR] = 1.019, 95% CI: 0.727-1.428, p = 0.912) and the disease-free survival (DFS) (HR = 0.868, 95% CI: 0.636-1.184, p = 0.371) were comparable between the two arms. The cumulative 5-year OS was 63% in the three-field arm, as compared with 63% in the two-field arm; 5-year DFS was 59% and 53%, respectively. On the basis of whether the patients had mediastinal or abdominal lymph node metastasis or not, OS was also comparable between the two arms. In this cohort, only advanced tumor stage (pathologic TNM stages III-IV) was identified as the risk factor associated with reduced OS (HR = 3.330, 95% CI: 2.140-5.183, p < 0.001).

Conclusions: For patients with middle and lower thoracic esophageal cancer, there was no improvement in OS or DFS after esophagectomy with three-field lymphadenectomy over two-field lymphadenectomy.
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http://dx.doi.org/10.1016/j.jtho.2020.10.157DOI Listing
February 2021

Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.

Nat Commun 2020 12 8;11(1):6268. Epub 2020 Dec 8.

Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.
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http://dx.doi.org/10.1038/s41467-020-20019-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722722PMC
December 2020

Technical details of the abdominal part during full robotic-assisted minimally invasive esophagectomy.

Dis Esophagus 2020 Nov;33(Supplement_2)

Department of General-, Visceral- and Transplant Surgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

The full robotic-assisted minimally invasive esophagectomy (RAMIE) is an upcoming approach in the treatment of esophageal and junctional cancer. Potential benefits are seen in angulated precise maneuvers in the abdominal part as well as in the thoracic part, but due to the novelty of this approach the optimal setting of the trocars, the instruments and the operating setting is still under debate. Hereafter, we present a technical description of the 'Mainz technique' of the abdominal part of RAMIE carried out as Ivor Lewis procedure. Postoperative complication rate and duration of the abdominal part of 100 consecutive patients from University Medical Center in Mainz are illustrated. In addition, the abdominal phase of the full RAMIE is discussed in general.
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http://dx.doi.org/10.1093/dote/doaa084DOI Listing
November 2020

Interactions between the enhanced recovery after surgery pathway and risk factors for lung infections after pulmonary malignancy operation.

Transl Lung Cancer Res 2020 Oct;9(5):1831-1842

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Lung infection is a common complication after thoracic surgery and can lead to severe consequences. Our study was designed to explore the risk factors for postoperative lung infections (POLI) following pulmonary malignancy operation and assess the protective effect of enhanced recovery after surgery (ERAS) and their potential interactive relationships.

Methods: A retrospective study included 1,768 patients who underwent surgery between 2013 and 2017 in Ruijin Hospital, Shanghai Jiaotong University School of Medicine was performed. Uni- and multivariate analyses were performed to identify risk factors. Andersson's model was applied to evaluate the additive interaction between these factors.

Results: Smoking [95% confidence interval (CI): 1.178-2.198], preoperative heart disease (95% CI: 1.448-4.091), and massive intraoperative blood loss (95% CI: 1.568-3.674) were independent risk factors for postoperative lung infections (POLI), whereas ERAS implementation was protective (95% CI: 0.249-0.441). Interaction analyses indicated that non-ERAS was reciprocally independent with smoking and surgical procedure. It had a synergistic interaction with heart disease [attributable proportion due to interaction (AP) =0.540 (95% CI: 0.179-0.901), synergy index (S) =2.580 (95% CI: 1.016-6.551)], and poor lung function [AP =0.395 (95% CI: 0.016-0.775)], as well as a tendency of antagonistic interaction with blood loss.

Conclusions: Intraoperative blood loss, heart disease, and smoking are independent risk factors of POLI. ERAS implementation is a protective factor and is firstly verified to be more effective on reducing POLI in patients with heart diseases, poor lung function, and less intraoperative blood loss. We provide evidences to implement ERAS and a clue of the most optimal indications for ERAS.
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http://dx.doi.org/10.21037/tlcr-20-401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653160PMC
October 2020

Long Noncoding RNA LINC01133 Promotes the Malignant Behaviors of Renal Cell Carcinoma by Regulating the miR-30b-5p/Rab3D Axis.

Cell Transplant 2020 Jan-Dec;29:963689720964413

Department of Urology, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Renal cell carcinoma (RCC) is the most common type of kidney cancer with rising incidence. Long noncoding RNA (lncRNA) LINC01133 is a novel lncRNA that is involved in the development of several types of cancers. However, the role of LINC01133 in RCC has not been reported. Thus, in this study, we investigated the functions of LINC01133 in RCC. The qualitative real-time polymerase chain reaction analysis was performed to examine the levels of LINC01133 in RCC tissues and adjacent tissues, as well as RCC cell lines. The results showed that LINC01133 was highly expressed in RCC tissue specimens and cell lines. Downregulation of LINC01133 significantly inhibited the proliferation, migration, and invasion of RCC cells. Further mechanistic investigations proved that LINC01133 directly interacted with microRNA (miR)-30b-5p and regulated the miR-30b-5p expression in RCC cell lines. Moreover, miR-30b-5p exhibited tumor-suppressive activity in RCC cell lines, which was mediated by targeting Ras-related protein Rab-3D (Rab3D). study showed that LINC01133 knockdown suppressed tumor growth in the nude mice. Taken together, these findings indicated that LINC01133 might be an oncogene in RCC through regulation of the miR-30b-5p/Rab3D axis. Thus, LINC01133 might serve as a potential therapeutic target for the treatment of RCC.
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http://dx.doi.org/10.1177/0963689720964413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784578PMC
October 2020

Uniportal video-assisted thoracic surgery for the treatment of lung cancer: a consensus report from Chinese Society for Thoracic and Cardiovascular Surgery (CSTCVS) and Chinese Association of Thoracic Surgeons (CATS).

Transl Lung Cancer Res 2020 Aug;9(4):971-987

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Uniportal video-assisted thoracoscopic surgery (UniVATS) has been widely adopted in China, where several ultra-high volume thoracic surgical and training centers are located. The objective of this consensus from Chinese experts was to summarize the current application and give reference for the future development of UniVATS in the treatment of lung cancer. A panel of 41 experts from 21 Chinese hospitals was invited to join this project. The Delphi method was used in this consensus consisting of two rounds of voting. The questionnaire was based on the current clinical evidence. Forty (97.6%) experts completed the 2 rounds of questionnaires. The experts' experience was relatively similar. We defined the UniVATS as monitor-dependent surgery, no use of rib-spreading and single incision less than 4 cm. Tumor with stage of T1-T3 and N0-N2 is considered amenable to UniVATS. Other consensus was reached on several points outlining the safety and feasibility, surgical skills, learning curve, short-term and long-term outcomes for lung cancer, and current application of subxiphoid and nonintubated UniVATS approach. This consensus statement represents a collective agreement among Chinese experts to suggest that UniVATS is an effective alternative to multi-portal approach, although high-level evidence is expected in the future. Some agreements can be referred in the training of young surgeons.
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http://dx.doi.org/10.21037/tlcr-20-576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481589PMC
August 2020

Molecular heterogeneity of anti-PD-1/PD-L1 immunotherapy efficacy is correlated with tumor immune microenvironment in East Asian patients with non-small cell lung cancer.

Cancer Biol Med 2020 Aug;17(3):768-781

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

The aim of this study was to investigate how the tumor immune microenvironment differs regarding tumor genomics, as well as its impact on prognoses and responses to immunotherapy in East Asian patients with non-small cell lung cancer (NSCLC). We performed an integrated analysis using publicly available data to identify associations between anti-programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1) immunotherapy efficacy and classic driver oncogene mutations in East Asian NSCLC patients. Four pooled and clinical cohort analyses were used to correlate driver oncogene mutation status and tumor microenvironment based on PD-L1 and CD8 tumor-infiltrating lymphocytes (TILs). Immune infiltrating patterns were also established for genomic NSCLC subgroups using the CIBERSORT algorithm. Based on East Asian NSCLC patients, TIDE analyses revealed that for anti-PD-1/PD-L1 immunotherapy, epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-rearranged tumors yielded inferior responses; however, although Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors responded better, the difference was not statistically significant (EGFR: = 0.037; ALK: < 0.001; KRAS: = 0.701). Pooled and clinical cohort analyses demonstrated tumor immune microenvironment heterogeneities correlated with oncogenic patterns. The results showed remarkably higher PD-L1- and TIL-positive KRAS-mutant tumors, suggesting KRAS mutations may drive an inflammatory phenotype with adaptive immune resistance. However, the EGFR-mutant or ALK-rearranged groups showed a remarkably higher proportion of PD-L1-/TIL-tumors, suggesting an uninflamed phenotype with immunological ignorance. Notably, similar to triple wild-type NSCLC tumors, EGFR L858R-mutant tumors positively correlated with an inflammatory phenotype, suggesting responsiveness to anti-PD-1/PD-L1 immunotherapy ( < 0.05). Furthermore, the CIBERSORT algorithm results revealed that EGFR-mutant and ALK-rearranged tumors were characterized by an enriched resting memory CD4 T cell population ( < 0.001), as well as a lack of CD8 T cells ( < 0.01), and activated memory CD4 T cells ( = 0.001). Our study highlighted the complex relationships between immune heterogeneity and immunotherapeutic responses in East Asian NSCLC patients regarding oncogenic dependence.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476088PMC
August 2020

Dual inhibition of HDAC and tyrosine kinase signaling pathways with CUDC-907 attenuates TGFβ1 induced lung and tumor fibrosis.

Cell Death Dis 2020 09 17;11(9):765. Epub 2020 Sep 17.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Rd, Shanghai, 200025, China.

TGFβ1 signaling is a critical driver of collagen accumulation in pulmonary fibrotic diseases and a well-characterized regulator of cancer associated fibroblasts (CAF) activation in lung cancer. Myofibroblasts induced by TGFβ1 and other factors are key players in the pathogenesis of lung fibrosis and tumor. Tremendous attention has been gained to targeting myofibroblasts in order to inhibit the progression of fibrosis and myofibroblast-induced tumor progression and metastasis. Here we determined the therapeutic efficacy of simultaneously targeting PI3K and HDAC pathways in lung myofibroblasts and CAF with a single agent and to evaluate biomarkers of treatment response. CUDC-907 is a first-in-class compound, functioning as a dual inhibitor of HDACs and PI3K/AKT pathway. We investigated its effects in counteracting the activity of TGFβ1-induced myofibroblasts/CAF in regard to cell proliferation, migration, invasion, apoptosis in vitro antifibrosis efficiency in vivo. We found that CUDC-907 inhibited myofibroblasts/CAF cell proliferation, migration and apoptosis in a dose-dependent manner and caused cell cycle arrest at G1-S phase. CUDC-907 not only inhibited myofibroblasts markers expression, but also significantly inhibited the phosphorylation level of AKT, mTOR, Smad2/3, and promoted acetylation of histones. Furthermore, the observed inhibitory effect was also confirmed in bleomycin-induced mice lung fibrosis and nude mouse transplanted tumor model. Overall, these data suggest that dual inhibition of HDAC and the tyrosine kinase signaling pathways with CUDC-907 is a promising treatment strategy for TGFβ1-induced lung and tumor fibrosis.
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http://dx.doi.org/10.1038/s41419-020-02916-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499263PMC
September 2020

The classification and treatment strategies of post-esophagectomy airway-gastric fistula.

J Thorac Dis 2020 Jul;12(7):3602-3610

Department of Thoracic Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

Background: Airway-gastric fistulas (AGFs) are rare but life-threatening complications after esophagectomy for esophageal cancer. Their effective and reasonable management is challenging and still controversial. This study reports the classification and management strategies of post-esophagectomy AGF based on a retrospective analysis of 26 cases in two large volume centers in China.

Methods: Between January 2000 and December 2017, 6,316 consecutive patients with esophageal carcinoma underwent esophagectomy. AGF was verified in 26 patients. The patients with AGF were divided into two types based on the anatomic characteristics of the fistula. Type I was characterized by the presence of fistula orifices in digestive tract that were higher than those in the airway and were treated with conservative management. Type II had both fistula orifices located on the same horizontal plane and were treated with surgical management. Pearson Chi-Square (R software) was used to compare mortality rates.

Results: From January 2000 and December 2017, 26 cases occurred AGF in 6,316 consecutive patients with esophageal carcinoma underwent esophagectomy and the incidence of AGF was 0.4%. Ten of 12 patients with type I AGF survived. Nine of 14 patients with type II AGF died. There was a significantly difference in the mortality rates between patients with AGF type I and II, which was 16.7% (2/12) and 64.3% (9/14) (χ=6.003, P=0.014), respectively.

Conclusions: AGF may be classified into two types according to the anatomic characteristics. Type I patients may be cured by conservative management and type II patients, require surgical intervention with pedicled tissues flap wrapping of the airway.
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http://dx.doi.org/10.21037/jtd-20-284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399427PMC
July 2020

Double lung transplantation for Sjögren's syndrome-related interstitial lung disease: a case report and review of literature.

Ann Transl Med 2020 Jul;8(14):888

Department of Thoracic Surgery, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.

In this study, we present a case of 65-year-old male patient with suspected Sjögren's syndrome-related interstitial lung disease (SS-ILD) with initial symptoms of limb edema and acute respiratory failure. He was treated with immunosuppressor, respiratory support, dialysis, immunomodulatory, and anti-inflammatory medications. However, no significant response was shown to anti-fibrotic treatments and his respiratory function deteriorated. Double lung transplantation was thus indicated considering the irreversible interstitial changes in both lungs. The surgical procedure was complicated, and the role of enhanced recovery after surgery (ERAS) for this critical patient was discussed. The patient experienced hemorrhage, pulmonary infection, and peripheral neuropathy after surgery, but he was cured by the multidisciplinary team. He had a satisfactory quality of life at 1-year follow-up. This case report describes the details of double lung transplantation in a patient with advanced SS-ILD. Important considerations include the indications for and timing of transplantation, the effects of long-term immunosuppression on wound healing, and extrapulmonary organ dysfunction. Based on a review of the published literature and a consideration of the short-term outcomes, lung transplantation for this individual with an autoimmune disease appears to be safe and feasible. SS-ILD should not be a contraindication to transplantation; however, patients with advanced pulmonary involvement should be carefully selected after a multidisciplinary evaluation. More long-term follow-up and further comparative studies are needed in the future.
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http://dx.doi.org/10.21037/atm-20-3516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396791PMC
July 2020

Robotic segmentectomy: We are still on the way.

J Thorac Cardiovasc Surg 2020 08;160(2):e87-e88

Department of Thoracic Surgery, Ruijin Hospital, Shanghai, China; Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1016/j.jtcvs.2020.04.072DOI Listing
August 2020

Mouse Double Minute 2 Homolog-Mediated Ubiquitination Facilitates Forkhead Box P3 Stability and Positively Modulates Human Regulatory T Cell Function.

Front Immunol 2020 19;11:1087. Epub 2020 Jun 19.

Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Regulatory T cells (Treg cells) are essential for maintaining immune tolerance, and the dysfunction of Treg cells may cause autoimmune diseases and tumors. Forkhead box P3 (FOXP3) is the key transcription factor controlling Treg cell development and suppressive function. Mouse double minute 2 homolog (MDM2), an E3 ubiquitin ligase, has been identified as an oncoprotein that mediates the ubiquitination and degradation of tumor suppressor p53; however, whether it has functions in Treg cells remains unknown. Here, we demonstrate that MDM2 positively regulates human Treg cell suppressive function via its mediated ubiquitination and stabilization of FOXP3. Knockdown of MDM2 with shRNA in human primary Treg cells leads to the impaired ability of FOXP3 to regulate the expression levels of downstream genes and the attenuated suppressive capacity of Treg cells, due to FOXP3 instability. Consistently, MDM2 overexpression in human Treg cells enhances FOXP3 stability and Treg cell suppressive capacity. Mechanistically, MDM2 interacts with FOXP3, and mainly mediates monoubiquitination and polyubiquitination of FOXP3, thus stabilizing the protein level of FOXP3. We have also found lysine residues in FOXP3 required for MDM2-mediated ubiquitination. In addition, TCR/CD28 signaling upregulates the expression level of MDM2 and its mediated FOXP3 ubiquitination in human Treg cells. Therefore, our findings reveal that MDM2 in Treg cells could be a potential therapeutic target for treating autoimmune diseases and tumors.
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http://dx.doi.org/10.3389/fimmu.2020.01087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318079PMC
June 2020

Robotic or thoracoscopic segmentectomy: Each complements the other.

J Thorac Cardiovasc Surg 2020 09 3;160(3):e175. Epub 2020 Jun 3.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1016/j.jtcvs.2020.04.110DOI Listing
September 2020

Primary small cell carcinoma of the esophagus: progression in the last decade.

Ann Transl Med 2020 Apr;8(7):502

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Primary small cell carcinoma of the esophagus (PSCCE) is a highly malignant tumor that is diagnosed by endoscopic biopsy and immunohistochemistry. Because of its low incidence, a high degree of malignancy, and rapid progress, it is difficult to conduct large, randomized controlled trials and to establish a standard treatment plan for this disease. In recent years, several retrospective studies have been reported, and with the rise of emerging therapies, PSCCE has gradually become a focus of thoracic surgery. This paper reviews progress in the diagnosis and treatment of PSCCE in recent years.
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http://dx.doi.org/10.21037/atm.2020.03.214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210214PMC
April 2020

Retrievable covered metallic segmented Y airway stent for gastrorespiratory fistula of carina or main bronchi.

J Thorac Cardiovasc Surg 2020 Mar 19. Epub 2020 Mar 19.

Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objective: To evaluate the feasibility of new retrievable covered metallic segmented Y airway stents modified with 3-dimensional (3D) printing for gastrorespiratory fistula involving carina or main bronchi.

Methods: We designed a new retrievable covered metallic segmented Y airway stent to fit the anatomical characteristics of the carina region in individual patients. All stents were individually customized based on a 3D-printed mold. Six patients with gastrorespiratory fistula and aspiration pneumonia after esophagectomy underwent the stent implantation. The stents were retrieved when the fistula was cured or stent-related complications occurred.

Results: Seven Y stents were successfully implanted and removed in 6 patients. All stents expanded well, and the fistulas were completely sealed. Aspiration pneumonia was controlled in 6 patients. The median Karnofsky Performance Status scores significantly improved after stenting compared with those before stent implantation (P = .024). Sputum retention was the most common complication after stenting and was treated with aspiration under bronchoscopy (33.33%). Excessive granulation tissue proliferation was found in 1 patient (16.7%) and was treated with cryotherapy. The indwelling time of the stent was 64 days (interquartile range, 52-69 days). After stent removal, bronchoscopy, gastroscopy, and computed tomography of the chest showed cured fistulas in all patients, and no stents showed fractures.

Conclusions: Retrievable covered metallic segmented Y airway stents modified with 3D printing appear to be feasible for the treatment of gastrorespiratory fistula involving carina or main bronchi.
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http://dx.doi.org/10.1016/j.jtcvs.2020.03.019DOI Listing
March 2020

Management of non-small cell lung cancer with resistance to epidermal growth factor receptor tyrosine kinase inhibitor: case discussion.

J Thorac Dis 2020 Mar;12(3):159-164

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

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http://dx.doi.org/10.21037/jtd.2020.01.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138979PMC
March 2020

Desmoglein-2 modulates tumor progression and osimertinib drug resistance through the EGFR/Src/PAK1 pathway in lung adenocarcinoma.

Cancer Lett 2020 07 7;483:46-58. Epub 2020 Apr 7.

Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, PR China. Electronic address:

Desmoglein-2 (DSG2), a member of the cadherin superfamily, has been implicated in cell-cell adhesion and tumorigenesis. Here, we demonstrate that high DSG2 expression in both lung adenocarcinoma (LUAD) cell lines and tissues is associated with poor prognosis in LUAD patients. Notably, DSG2 overexpression promoted cell proliferation and migration, and increased resistance to the EGFR tyrosine kinase inhibitor osimertinib, whereas DSG2 silencing could reverse these results. Moreover, direct interaction between DSG2 and EGFR in the cell membrane stimulated EGFR signaling to promote tumorigenesis, and loss of DSG2 resulted in EGFR translocation into the cytoplasm. In addition, DSG2 was required for EGFR binding to Src; consequently, DSG2 silencing inhibited tumor cell malignancy via suppression of the EGFR-Src-Rac1-PAK1 signaling pathway. Consistent with these findings, a nude mouse xenograft model using H1975 cells demonstrated that DSG2 promoted LUAD cell growth in vivo and increased osimertinib resistance. Collectively, these observations are the first to elucidate a unique role for DSG2 in the development and progression of lung adenocarcinoma via EGFR signaling.
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http://dx.doi.org/10.1016/j.canlet.2020.04.001DOI Listing
July 2020

Robot-assisted thoracoscopic surgery for mediastinal masses: a single-institution experience.

J Thorac Dis 2020 Feb;12(2):105-113

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: The objectives of this study were to evaluate the feasibility and safety of robot-assisted thoracic surgery (RATS) using the da Vinci robotic system for mediastinal mass resection and to describe the surgical approach for masses in different mediastinal regions.

Methods: We retrospectively reviewed data from 84 patients who underwent RATS for resection of a mediastinal mass from June 2015 to April 2019. The results were analyzed with descriptive statistics.

Results: The mediastinal mass was resected successfully in all patients, with one patient requiring conversion to conventional open surgery. There were no intraoperative complications. The most common diagnoses were thymoma (n=17), bronchogenic cyst (n=16), and schwannoma (n=12). The surgical approach was determined by the location of the lesion and the planned extent of surgical resection. Resection was performed in the lateral decubitus position in 29 patients with posterior mediastinal tumor, semi-lateral decubitus position in 42 patients who only need resection of anterior mediastinal mass, and reverse Trendelenburg position in 13 patients undergoing thymectomy. The mean (± standard deviation) operation time was 91.86±56.42 min, duration of chest tube use was 1.83±0.93 days, and postoperative hospital stay was 3.62±7.52 days. Three patients (3.5%) developed postoperative complications: one chylous fistula, which required reoperation, and one case each of atrial fibrillation and pulmonary infection, which were treated conservatively.

Conclusions: Our experience demonstrated that different surgical approaches of RATS are safe and feasible for mediastinal mass resection. An appropriate approach can be selected based on the mediastinal region in which the tumor is located.
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http://dx.doi.org/10.21037/jtd.2019.08.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061195PMC
February 2020

Robotic lung cancer surgery: from simple to complex, from surgery to clinical study.

J Thorac Dis 2020 Feb;12(2):51-53

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

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http://dx.doi.org/10.21037/jtd.2019.09.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061191PMC
February 2020

Editorial to the 4 Ruijin International Thoracic Symposium (RITS 2019)-Special Issue.

J Thorac Dis 2020 Feb;12(2):50

Department of Thoracic Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai200025, China.

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http://dx.doi.org/10.21037/jtd.2019.08.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061189PMC
February 2020

Methods for Dissecting Intersegmental Planes in Segmentectomy: A Randomized Controlled Trial.

Ann Thorac Surg 2020 07 12;110(1):258-264. Epub 2020 Mar 12.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai. Electronic address:

Background: The perioperative outcomes of the use of stapling devices versus electrocautery to dissect intersegmental planes in patients undergoing segmentectomy for small pulmonary lesions is still unclear. The aim of this randomized controlled trial was to compare the perioperative outcomes of these two methods.

Methods: A single-center, prospective, participant-blinded, randomized controlled trial (NCT03192904) was conducted with a preplanned sample size of 136. The primary outcome was the incidence of postoperative complications. Secondary outcomes included duration of operation, blood loss during operation, first-day drainage volume, duration of drainage, postoperative hospital stay, loss of lung function, and medical costs.

Results: The trial was stopped early as a result of a marked difference in the primary outcome between groups at a scheduled interim check of the data after recruiting 70 patients. The incidence of postoperative complications (eg, air leakage) was higher in the electrocautery group than in the stapler device group (11/32, 34.4% vs 2/33, 6.1%, P = .004). There were no differences in duration of operation, blood loss during operation, first-day drainage volume, duration of drainage, postoperative hospital stays, loss of lung function, or total medical cost, although the per-patient cost of medical materials was higher in the stapler device group (US$4214.6 ± 1185.4 vs $3260.1 ± 852.6, P < .001).

Conclusions: Among patients undergoing segmentectomy, the use of stapler devices to divide intersegmental planes decreased postoperative complications without further compromising lung function or increasing economic burden.
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http://dx.doi.org/10.1016/j.athoracsur.2020.02.013DOI Listing
July 2020

Early outcomes of robotic versus thoracoscopic segmentectomy for early-stage lung cancer: A multi-institutional propensity score-matched analysis.

J Thorac Cardiovasc Surg 2020 Nov 25;160(5):1363-1372. Epub 2020 Jan 25.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objectives: Anatomical segmentectomy via robotic thoracic surgery and video-assisted thoracic surgery (VATS) are minimally invasive surgical approaches for treatment of early-stage non-small cell lung cancer (NSCLC). However, few research studies have compared early outcomes.

Methods: A retrospective analysis was made of 774 patients, 298 who received robotic and 476 who received VATS, who underwent minimally invasive segmentectomy for early-stage NSCLC at 3 academic institutions between June 2015 and August 2019. Perioperative outcomes were compared after propensity score-matching on the basis of age, gender, body mass index, percent forced expiratory volume in 1 second, smoking status, American Society of Anesthesiologists score, type of segmentectomy, tumor size, and institution.

Results: There were 257 patients in each group after propensity score-matching. The baseline characteristics and type of segmentectomy were comparable. Three conversions to thoracotomy occurred in the VATS group, and 1 in the robotic group (P = .624). There was no significant difference in operative time (147.91 ± 52.42 vs 149.23 ± 49.66 minutes; P = .773), blood loss (50 mL [interquartile range (IQR), 50-100 mL] vs 100 mL [IQR, 30-100 mL]; P = .177), rates of overall complications (17.9 vs 14.8%; P = .340), and length of stay (4 days [IQR, 3-5 days] vs 4 days [IQR, 3-5 days]; P = .417) between the robotic and VATS groups, respectively. Robotic segmentectomy was more costly ($12,019.30 ± 1678.30 vs $7834.80 ± 1291.20; P < .001) because of the amortization and consumables of the robotic system. There were a greater number of N1 lymph nodes and N1 stations in the robotic group.

Conclusions: Segmentectomy with robotic and VATS are safe and feasible for early-stage NSCLC treatment. A robotic approach might lead to a better N1 lymph node dissection.
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http://dx.doi.org/10.1016/j.jtcvs.2019.12.112DOI Listing
November 2020

Next-generation sequencing in thymic epithelial tumors uncovered novel genomic aberration sites and strong correlation between TMB and MSH6 single nucleotide variations.

Cancer Lett 2020 04 19;476:75-86. Epub 2020 Feb 19.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. Electronic address:

Thymic epithelial tumors (TET) including thymomas and thymic carcinomas are rare, but they are common primary tumors in the anterior mediastinum. The etiology and tumorigenesis of TET remain unclear. To better understand the novel aberrations of this rare tumor and provide more significant mutation sites for targeted therapy, we performed next-generation sequencing detection on 55 patients with TET. Our results showed that most genes in 12 core pathways harbored aberrations of indeterminate potential. In 4 genes (ARID1A, KMT2C, TGFBR2 and MAP3K1), the indel frequency was above 90%. Dozens of genes, including TGFBR2, KMT2C, PRKDC, ATR, CHD2, SDHA, KDM5A, CHEK1, MSH6 and POLE, possessed frameshift indel with different frequencies in different hotspot sites, which could be the new targets of therapy for TET. For the first time, we revealed a strong correlation between the tumor mutational burden and single nucleotide variations, but not frameshift, on DNA mismatch repair gene MSH6 in TET.
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http://dx.doi.org/10.1016/j.canlet.2020.02.001DOI Listing
April 2020

Endoscope-assisted mediastinal drainage therapy for anastomosis leakage after esophagectomy: a retrospective cohort study.

Ann Transl Med 2019 Dec;7(23):747

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: Anastomosis leakage after esophagectomy is a major threat which leads to many subsequent complications even mortality. But current diagnosis and treatment methods are inefficient. This retrospective study aims to evaluate the utilization of endoscope-assisted mediastinal drainage therapy in treatment for anastomosis leakage after esophagectomy.

Methods: Between January 2014 and June 2018, 51 patients were confirmed anastomosis leakage using gastroscopy. Of them, 23 patients were treated with endoscope-assisted mediastinal drainage therapy (drainage group); and the other 28 patients received endoscope-assisted biomedical fibrin glue occlusion (occlusion group). Short-term clinical outcomes were examined. Factors related to length of postoperative hospitalization (LPH) was analyzed.

Results: Endoscope provided highly accurate information on the condition of anastomosis leakage. And there was no evidence that early endoscopy could cause damage to the anastomosis or gastric conduit. One patient from drainage group and two from occlusion group discharged against medical advice. Other 48 patients were completely cured without reoperation or mortality. The median LPH was 32 days in drainage group (range from 17 to 80 days) and 81 days in occlusion group (range from 32 to 190 days), respectively (P<0.05). Linear regression indicated statistically significant correlation between LPH and length from diagnosis to drainage or occlusion (R=0.688, P<0.001).

Conclusions: Endoscope-assisted mediastinal drainage therapy is a satisfactory treatment for anastomosis leakage. Early diagnosis and treatment may facilitate the recovery of anastomosis leakage and reduce LPH.
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http://dx.doi.org/10.21037/atm.2019.11.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989978PMC
December 2019