Publications by authors named "Junbiao Hang"

13 Publications

  • Page 1 of 1

Development and validation of an autophagy-related prognostic signature in esophageal cancer.

Ann Transl Med 2021 Feb;9(4):317

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

Background: Autophagy has a dual function in cancer, and its role in carcinogenesis of the esophagus remains poorly understood. In the present study, we explored the prognostic value of autophagy in esophageal cancer (ESCA), one of the leading causes of cancer-related deaths worldwide.

Methods: Using ESCA RNA-sequencing (RNA-Seq) data from 158 primary patients with ESCA, including esophageal adenocarcinoma and esophageal squamous cell carcinoma, were downloaded from The Cancer Genome Atlas (TCGA) for this study. We obtained differentially expressed autophagy-related genes (ARGs) by the "limma" package of R. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses unveiled several fundamental signaling pathways associated with the differentially expressed ARGs in ESCA. Univariate Cox regression analyses were used to estimate associations between ARGs and overall survival (OS) in the TCGA ESCA cohort. A Cox proportional hazards model (iteration =1,000) with a lasso penalty was used to create the optimal multiple-gene prognostic signature utilizing an R package called "glmnet".

Results: A prognostic signature was constructed with four ARGs (, , and ) in the training set, which significantly divided ESCA patients into high- and low-risk groups in terms of OS [hazard ratio (HR) =1.508, 95% confidence interval (CI): 1.201-1.894, P<0.001]. In the testing set, the risk score remained an independent prognostic factor in the multivariate analyses (HR =1.572, 95% CI: 1.096-2.257, P=0.014). The area under the curve (AUC) of the receiver operating characteristic (ROC) predicting 1-year survival showed a better predictive power for the prediction model. The AUC in training and testing cohorts were 0.746 and 0.691, respectively. Therefore, the prognostic signature of the four ARGs was successfully validated in the independent cohort.

Conclusions: The prognostic signature may be an independent predictor of survival for ESCA patients. The prognostic nomogram may improve the prediction of individualized outcome. This study also highlights the importance of autophagy in the outcomes of patients with ESCA.
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http://dx.doi.org/10.21037/atm-20-4541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944288PMC
February 2021

The Prognostic Value of Tumor Mutation Burden and Immune Cell Infiltration in Thymic Epithelial Tumors.

Ann Clin Lab Sci 2021 Jan;51(1):44-54

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

Objective: The question of whether the tumor mutation burden (TMB) is associated with either improved survival outcomes or improvement of immunotherapies remains controversial in various malignancies. The aim of this study is to investigate the genomic landscape of the relationship between TMB and immune cell infiltration in thymic epithelial tumors (TETs).

Methods: We downloaded somatic mutation data, transcriptome sequencing data, and clinical information of TETs from the Cancer Genome Atlas (TCGA) database. We assessed the abundance of 22 immune fractions between low-TMB (TMB-L) and high-TMB (TMB-H) groups using the "CIBERSORT" package.

Results: Missense mutation had the highest frequency of mutation among the nine variant classifications in TETs. Higher TMB levels were associated with poor survival outcomes (<0.05), and higher Masaoka stages (<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (<0.01). The infiltration levers of naive CD4(+) T cells and regulatory T cells were significantly higher in the TMB-L group than in the TMB-H group, and this was further associated with better overall survival (OS) in patients with TETs.

Conclusion: The present study indicates that the prognosis of TMB-H patients with TETs is significantly poorer than is that of TMB-L patients, which might result from the different levels of infiltration of naive CD4(+) T cells and regulatory T cells.
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January 2021

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

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

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

Early Outcomes of Robot-Assisted Versus Thoracoscopic-Assisted Ivor Lewis Esophagectomy for Esophageal Cancer: A Propensity Score-Matched Study.

Ann Surg Oncol 2019 May 6;26(5):1284-1291. Epub 2019 Mar 6.

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

Background: Both robot-assisted Ivor Lewis esophagectomy (RAILE) and conventional thoracoscopic-assisted Ivor Lewis esophagectomy (TAILE) are minimally invasive surgical techniques for the treatment of middle and distal esophageal cancer. However, no research studies comparing early outcomes between RAILE and TAILE have been reported.

Methods: A retrospective analysis was made of 184 patients, 76 in the RAILE group and 108 in the TAILE group, who underwent minimally invasive Ivor Lewis esophagectomy between December 2014 and June 2018. Propensity score-matched analysis was performed between the two groups based on demographics, comorbidities, American Society of Anesthesiologists score, tumor location, tumor size, and pathological stage. Perioperative outcomes were compared.

Results: Two conversions to thoracotomy occurred in the RAILE group. There was no 30-day in either group. Sixty-six matched pairs were identified for each group. Within the propensity score-matched cohorts, the operative time in the RAILE group was significantly longer than that in the TAILE group (302.0 ± 62.9 vs. 274.7 ± 38.0 min, P = 0.004). There was no significant difference in the blood loss [200.0 ml (interquartile range [IQR], 100.0-262.5 ml) vs. 200.0 ml (150.0-245.0 ml), P = 0.100], rates of overall complications (28.8 vs. 24.2%, P = 0.554), length of stay [9.0 days (IQR 8.0-12.3 days) vs. 9.0 days (IQR 8.0-11.3 days), P = 0.517], the number of total dissected lymph nodes (19.2 ± 9.2 vs. 19.3 ± 9.5, P = 0.955), and detailed categories of lymph nodes.

Conclusions: RAILE demonstrated comparable early outcomes compared with TAILE and should be considered as an alternative minimally invasive option for treating esophageal cancer.
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http://dx.doi.org/10.1245/s10434-019-07273-3DOI Listing
May 2019

The Role of Operation in the Treatment of Boerhaave's Syndrome.

Biomed Res Int 2018 28;2018:8483401. Epub 2018 Jun 28.

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

Purpose: This study aims to discuss the appropriate treatment strategy for spontaneous esophageal rupture.

Methods: Clinical data from twenty-one cases were retrospectively analyzed. The parameters included etiology, time interval between onset and treatment, therapy methods, prognosis, and length of stay.

Results: The ratio of males/females was 17/4, age range was 32-82 years (mean = 43.1), and the time interval between onset and treatment was as follows: <24 h: nine cases (42.8%); 24-48 h: six cases (28.6%); and >72 h: six cases (28.6%). All patients underwent operative treatment, and the following primary healing rates were achieved: <24 h: 88.9%, 24-48 h: 66.7%, and >72 h: 0. No patients died in this study. All patients were discharged with recovery, and the average hospitalization times were 18.1 days (<24 h), 27.8 days (24-48 h), and 51.2 days (>72 h).

Conclusions: Surgical treatment remains an effective method for treating spontaneous esophageal rupture, and the shorter the time interval between onset and treatment, possibly the better the prognosis.
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http://dx.doi.org/10.1155/2018/8483401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046182PMC
January 2019

Detection of Epithelial-Mesenchymal Transition Status of Circulating Tumor Cells in Patients with Esophageal Squamous Carcinoma.

Biomed Res Int 2018 26;2018:7610154. Epub 2018 Jun 26.

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

Purpose: To investigate the correlation between the status of epithelial-mesenchymal transition (EMT) of circulating tumor cells (CTCs) and esophageal squamous cell carcinoma (ESCC).

Methods: The demographic data and blood samples of 21 patients with ESCC were collected retrospectively. CTCs were enriched by using optimized CanPatrolTM CTC enrichment technique. CTCs were identified and characterized according to the EMT markers (e-CTCs: epithelial CTCs; mix-CTCs: epithelial-mesenchymal-mixed CTCs; m-CTCs: mesenchymal CTCs). The correlation between CTCs and demographic data was analyzed.

Results: Total 129 CTCs were detected in all the patients: 11(8.5%) CTCs of them were e-CTCs, 76(58.9%) were mix-CTCs, and 42(32.6%) were m-CTCs. The average number of CTCs from each patient was 6.1 ± 7.1 which included 0.5 ± 0.9 of e-CTCs, 3.6 ± 5.2 of mix-CTCs, and 2.0 ± 2.7 of m-CTCs; the difference between the three groups was significant ( = 0.017): the number of total CTCs was correlated with the number of mix-CTCs (2 = 0.883, < 0.01) and m-CTCs (2 = 0.639, < 0.01) but not e-CTCs (2 = 0.012, = 0.641) and the number of CTCs was correlated with the N stage and TNM stage in this study (2 = 0.698 and 2 = 0.359).

Conclusions: Mix-CTCs and m-CTCs might play an important role in progression of ESCC; the number of CTCs in ESCC might have the potential to be a predictor of prognosis.
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http://dx.doi.org/10.1155/2018/7610154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038679PMC
January 2019

Comparison of video-assisted thoracic surgery with open surgery in the treatment of ectopic mediastinal parathyroid tumors.

J Thorac Dis 2017 Dec;9(12):5171-5175

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

Background: To investigate the therapeutic effect of different surgical treatment for ectopic mediastinal parathyroid tumors and pathological features.

Methods: A total of 21 patients who were diagnosed with ectopic mediastinal parathyroid tumors and underwent surgeries in our department from May 1995 to May 2015 were collected and retrospectively analyzed.

Results: Twenty-one patients including 8 female (36.4%) and 13 male (63.6%) were collected. Among these patients, 9 cases were treated with video-assisted thoracic surgery (VATS), while 13 cases were treated with open surgery (including one secondary open operation after thoracoscopic operation). The average size of mediastinal tumors was 2.17±1.22 cm. For the post-operational pathology, 16 cases (76.2%) were diagnosed as ectopic parathyroid adenoma; 4 cases (19.0%) were diagnosed as parathyroid hyperplasia, while only 1 case (4.8%) was diagnosed as parathyroid adenocarcinoma.

Conclusions: Parathyroid adenoma accounts for the major pathological type of ectopic mediastinal parathyroid tumors. In addition, the correct diagnosis with precise preoperative location was the key for the treatment of ectopic mediastinal parathyroid tumors accompanied with hyperparathyroidism. Surgical intervention was demonstrated to be an effective way for the treatment of ectopic mediastinal parathyroid tumors with satisfied therapeutic outcome, especially for the VATS due to its unique clinical advantages. However, there may some difficulties when locating ectopic mediastinal parathyroid tumor less than 1 cm and the operators should be very cautious when performing thoracoscopic operations.
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http://dx.doi.org/10.21037/jtd.2017.11.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757062PMC
December 2017

Surgical treatment of ectopic adrenocorticotropic hormone syndrome with intra-thoracic tumor.

J Thorac Dis 2016 May;8(5):888-93

Department of Thoracic Surgery, Shanghai Jiaotong University Medical School affiliated Ruijin Hospital, Shanghai 200025, China.

Background: The study was to review the clinical manifestations and laboratory examinations of ectopic adrenocorticotropic hormone (ACTH) syndrome, and to analyze the efficacy of surgical treatment.

Methods: The clinical data, surgical therapy, and outcome of 23 cases of ectopic ACTH syndrome accompanied by intra-thoracic tumors were reviewed. The tumors were removed from all the patients according to the principles of radical resection.

Results: The tumors were confirmed as associated with ectopic ACTH secretion in 19 cases. Hyperglycemia and hypokalemia were recovered, while plasma cortisol, plasma ACTH and 24-hour urinary free cortisol (UFC) levels were significantly reduced after surgery in these 19 cases. Recurrences of the disease were found in six cases during following-up, and five of them died.

Conclusions: The thoracic cavity should be a focus in routine examinations of patients with symptoms of Cushing's syndrome (CS), because ectopic ACTH-producing tumors are commonly found in bronchus/lung and mediastinum. Despite the incidence of the pulmonary nodule secondary to opportunistic infection in some cases, surgery is still the first choice if the tumor is localized. The surgical procedure should be performed according to the principles in resection of lung cancer and mediastinal tumor. The surgical efficacy is significant for short-term periods; however, the recurrence of the disease in long-term periods is in great part related to distal metastasis or relapse of the tumor.
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http://dx.doi.org/10.21037/jtd.2016.03.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842786PMC
May 2016

Gefitinib, an EGFR tyrosine kinase inhibitor, activates autophagy through AMPK in human lung cancer cells.

J BUON 2014 Apr-Jun;19(2):466-73

Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China.

Purpose: To investigate the effects of autophagy on growth inhibition by gefitinib in non-small cell lung cancer (NSCLC) cell lines and its probable mechanism.

Methods: The mRNA and protein levels of Beclin 1, authophagy related 5 (Atg5) and Atg7 were assessed. H460 and Calu6 NSCLC cell lines were transfected with plasmids expressing green fluorescent protein (GFP)-LC3 and the formation of autophagosome was monitored under fluorescent microscope. In addition, H460 cells were treated with agonists of autophagy (everolimus and 3-methyladenine/ 3MA), AMP-activated protein kinase (AMPK) inhibitor (Compound C) and gefitinib, respectively. Cells were stained and studied under microscope. Cell colonies were counted and growth inhibition was calculated. Phosphorylated acetyl-Coenzyme A carboxylase (ACC) and AMPK were detected. Moreover, H460 cells were transfected with small interfering RNA (siRNA) against AMPK2 subunit and AMPK 2 was knocked down.

Results: LCII was accumulated to a higher level after treatment with gefitinib than that without addition of gefitinib, and gefitinib increased GFP punctuated cells. Besides, everolimus enhanced the autophagic process induced by gefitinib. Consistent with this, everolimus enhanced the growth inhibition of gefitinib on H460 cells. Also, incubation with gefitinib could significantly increase AMPK phosphorylation and phosphorylated ACC. Compound C AMPK inhibitor could reverse the activation of gefitinib on autophagy, as determined by Beclin 1, Atg5 and Atg7 mRNA levels. Knockdown of AMPK2 also significantly inhibited the activation of autophagy by gefitinib.

Conclusion: Inhibition of AMPK by its antagonist (Compound C) or siRNA predominantly blocked the induction of autophagy by gefitinib.
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September 2014

ATG7 deficiency promote apoptotic death induced by Cisplatin in human esophageal squamous cell carcinoma cells.

Bull Cancer 2013 Jul-Aug;100(7-8):15-21

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, 200025 Shanghai, China.

Cisplatin-(DDP)-based adjuvant chemotherapy is widely used for the treatment of esophageal cancer. However, DDP-based combinatorial treatments can eventually result in tumor resistance response. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored. In this study, we aimed to understand the role of autophagy in ESCC cells resistance to Cisplatin and discuss its potential therapeutic implication. We found that exposure to Cisplatin induced a significant increase in LC3 formation. While the proliferation of ESCC cells was inhibited upon Cisplatin exposure, inhibition of autophagy by ATG7 interference further increased the sensitivity to chemotherapy. Meanwhile, the Cisplatin-induced apoptotic cell death was significantly enhanced. These results suggest that autophagy may function importantly in ESCC cells resistance to Cisplatin. Intriguingly, the resistance could be recovered by autophagy inhibition. This also points to potential therapy for ESCC by perturbing autophagy.
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http://dx.doi.org/10.1684/bdc.2013.1749DOI Listing
September 2013

The experimental study of hemodynamic changes and pathological morphology after artery anastomosis.

Int J Low Extrem Wounds 2012 Sep;11(3):231-4

Shanghai Jiaotong University, Shanghai, China.

The purpose of this article is to dynamically observe hemodynamic and medium-term pathomorphological changes and to investigate the pathophysiological variation at the vascular anastomotic stoma. Eighteen New Zealand white rabbits underwent right common carotid artery in situ anastomosis, and the hemodynamic changes of anastomotic stoma were recorded by color Doppler ultrasonography before surgery and 5 minutes, 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, 12 weeks, and 16 weeks after surgery. Pathological sections of stoma were made and the pathomorphological changes viewed. Artery anastomoses were preformed successfully in 15 rabbits; 4 rabbits suffered postoperative death. It took 1.22 ± 0.77 hours to complete every operation. All the data involved, mean velocity, peak systolic velocity, and resistant index, had no significant differences between preoperative and postoperative follow-up. The obvious differences were found in the diameters of stoma 5 minutes, 1 week, 2 weeks, and 3 weeks after operation (P values were .002, .001, .003, and .008, respectively). The variance of stoma diameters 2 weeks later was also different from those after 1 week, but no other differences were observed during other weeks. The decrease in stoma diameters after anastomosis was clear, with the maximum decrease occurring 2 weeks after the operation, after which the diameters of stoma became stable 16 weeks after the operation. Some collagens around anastomoses could be found by the pathological sections of stoma, which indicated that the deposition of collagen might be related to the decrease in stoma diameter.
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http://dx.doi.org/10.1177/1534734612457029DOI Listing
September 2012