Publications by authors named "Jinlin Cao"

24 Publications

  • Page 1 of 1

CircRNA_100395 Carried by Exosomes From Adipose-Derived Mesenchymal Stem Cells Inhibits the Malignant Transformation of Non-Small Cell Lung Carcinoma Through the miR-141-3p-LATS2 Axis.

Front Cell Dev Biol 2021 25;9:663147. Epub 2021 Mar 25.

Department of Medical Oncology, Shulan (Hangzhou) Hospital, Affiliated to Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.

Objective: The specific purpose of this study is to investigate the impact exosomes from adipose-derived mesenchymal stem cell (AMSC) has on non-small cell lung carcinoma (NSCLC) and the relative applications.

Methods: circ_100395, miR-141-3p, and LATS2 were expressed and detected in NSCLC and paracancerous tissues as well as NSCLC cell lines. Pearson correlation analysis, Dual-Luciferase Reporter Assay and RNA pull-down assay were used to validate their expression and interaction, respectively. After isolation and culture of AMSCs, exosomes were extracted and identified. EdU, epithelial-mesenchymal transition (EMT), and cell colony formation assay were used to distinguish the biological activity of the cells. Expression Hippo/YAP signalling pathway-related proteins were measured by western blotting. Subsequently, tumour volume and weight were confirmed based on xenograft nude mice models, Ki-67 and LATS2 expression was observed by immunohistochemistry.

Results: circ_100395 was lowly expressed in NSCLC tissues or cells. The negative correlations and interactions were confirmed between circ_100395 and miR-141-3p, miR-141-3p, and LATS2. AMSC-derived exosomes with overexpression of circ_100395 (exo-circ_100395) significantly inhibited the biological activity as well as EMT of H1650 cells and Hippo/YAP signalling pathway activity. In addition, exo-circ_100395 markedly reduced tumour volume and weight as well as Ki-67 and LASP1 expression . However, overexpressed miR-141-3p or knocked down LATS2 alleviated the above effects.

Conclusion: Exo-circ_100395 can increase LATS2 expression by sponging miR-141-3p to regulate Hippo/YAP signalling pathway, thereby inhibiting NSCLC malignant transformation.
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http://dx.doi.org/10.3389/fcell.2021.663147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027360PMC
March 2021

Herbicide Resistance: Another Hot Agronomic Trait for Plant Genome Editing.

Plants (Basel) 2021 Mar 24;10(4). Epub 2021 Mar 24.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.

Weeds have continually interrupted crop plants since their domestication, leading to a greater yield loss compared to diseases and pests that necessitated the practice of weed control measures. The control of weeds is crucial to ensuring the availability of sufficient food for a rapidly increasing human population. Chemical weed control (herbicides) along with integrated weed management (IWM) practices can be the most effective and reliable method of weed management programs. The application of herbicides for weed control practices calls for the urgency to develop herbicide-resistant (HR) crops. Recently, genome editing tools, especially CRISPR-Cas9, have brought innovation in genome editing technology that opens up new possibilities to provide sustainable farming in modern agricultural industry. To date, several non-genetically modified (GM) HR crops have been developed through genome editing that can present a leading role to combat weed problems along with increasing crop productivity to meet increasing food demand around the world. Here, we present the chemical method of weed control, approaches for herbicide resistance development, and possible advantages and limitations of genome editing in herbicide resistance. We also discuss how genome editing would be effective in combating intensive weed problems and what would be the impact of genome-edited HR crops in agriculture.
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http://dx.doi.org/10.3390/plants10040621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064318PMC
March 2021

A nomogram for predicting the risk of lymph node metastasis in T1-2 non-small-cell lung cancer based on PET/CT and clinical characteristics.

Transl Lung Cancer Res 2021 Jan;10(1):430-438

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Accurately predicting the risk level for a lymph node metastasis is critical in the treatment of non-small cell lung cancer (NSCLC). This study aimed to construct a novel nomogram to identify patients with a risk of lymph node metastasis in T1-2 NSCLC based on positron emission tomography/computed tomography (PET/CT) and clinical characteristics.

Methods: From January 2011 to November 2017, the records of 318 consecutive patients who had undergone PET/CT examination within 30 days before surgical resection for clinical T1-2 NSCLC were retrospectively reviewed. A nomogram to predict the risk of lymph node metastasis was constructed. The model was confirmed using bootstrap resampling, and an independent validation cohort contained 156 patients from June 2017 to February 2020 at another institution.

Results: Six factors [age, tumor location, histology, the lymph node maximum standardized uptake value (SUVmax), the tumor SUVmax and the carcinoembryonic antigen (CEA) value] were identified and entered into the nomogram. The nomogram developed based on the analysis showed robust discrimination, with an area under the receiver operating characteristic curve of 0.858 in the primary cohort and 0.749 in the validation cohort. The calibration curve for the probability of lymph node metastasis showed excellent concordance between the predicted and actual results. Decision curve analysis suggested that the nomogram was clinically useful.

Conclusions: We set up and validated a novel and effective nomogram that can predict the risk of lymph node metastasis for individual patients with T1-2 NSCLC. This model may help clinicians to make treatment recommendations for individuals.
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http://dx.doi.org/10.21037/tlcr-20-1026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867781PMC
January 2021

Perioperative comparison of video-assisted thoracic surgery and open lobectomy for pT1-stage non-small cell lung cancer patients in China: a multi-center propensity score-matched analysis.

Transl Lung Cancer Res 2021 Jan;10(1):402-414

Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Compared with open surgery, video-assisted thoracic surgery (VATS) has innovated the concept of the minimally invasive approach for non-small cell lung cancer (NSCLC) patients in past decades. This present study aimed to compare the perioperative and lymph node dissection outcomes between VATS lobectomy and open lobectomy for pathological stage T1 (pT1) NSCLC patients from both surgical and oncologic perspectives.

Methods: This was a retrospective multicenter study. Patients who underwent surgical resection for pT1 NSCLC between January 2014 and September 2017 were retrospectively reviewed from 10 thoracic surgery centers in China. Perioperative and lymph node dissection outcomes of pT1 NSCLC patients who accepted VATS or open lobectomies were compared by propensity score matching (PSM) analysis.

Results: Of the 11,360 patients who underwent surgery for pT1 NSCLC, 7,726 were enrolled based on the selection criteria, including 1,222 cases of open lobectomies and 6,504 cases of VATS lobectomies. PSM resulted in 1,184 cases of open lobectomies and 1,184 cases of VATS lobectomies being well matched by common prognostic variables, including age, sex, and surgical side. VATS lobectomy led to better perioperative outcomes, including less blood loss (133.5±200.1 233.3±318.4, P<0.001), lower blood transfusion rate (2.4% 6.4%, P<0.001), shorter postoperative hospital stay (8.6±5.7 10.1±5.1, P<0.001), less chest drainage volume (1,109.5±854.0 1,324.1±948.8, P<0.001), and less postoperative complications (4.9% 8.2%, P<0.001). However, open lobectomy had better lymph node dissection outcomes than VATS, with increased lymph node dissection numbers (16.1±9.4 13.7±7.7, P<0.001) and more positive lymph nodes being dissected (1.5±3.9 1.1±2.5, P=0.002). Compared with VATS, open lobectomy harvested more lymph node stations (5.5±1.9 5.2±1.8, P=0.001), including more pathological N2 (pN2) lymph node stations (3.4±1.4 3.1±1.3, P<0.001).

Conclusions: VATS lobectomy was associated with better perioperative outcomes, such as less blood loss, lower blood transfusion rate, shorter postoperative hospital stay, less chest drainage volume and less postoperative complications. Open lobectomy has improved lymph node dissection outcomes, as more lymph nodes and positive lymph nodes were dissected for pT1 NSCLC patients during surgery.
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http://dx.doi.org/10.21037/tlcr-20-1132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867771PMC
January 2021

Surgical Outcomes of Lobectomy Versus Limited Resection for Clinical Stage I Ground-Glass Opacity Lung Adenocarcinoma 2 Centimeters or Smaller.

Clin Lung Cancer 2021 Mar 16;22(2):e160-e168. Epub 2020 Oct 16.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: To compare the surgical outcomes of patients with clinical stage I ground-glass opacity (GGO) lung adenocarcinomas with maximum diameters of ≤ 2 cm who underwent lobectomy versus limited resection.

Patients And Methods: We retrospectively reviewed cases of clinical stage I GGO lung adenocarcinoma with a diameter ≤ 2 cm that were treated via lobectomy or limited resection in our department between January 2011 and September 2018. The clinical characteristics and surgical outcomes were analyzed using a propensity score-matched comparison and a Cox regression model.

Results: A total of 552 patients were identified; 128 patients with pure GGO were excluded. Four hundred twenty-four patients met our criteria, including 242 (57.1%) who underwent lobectomy and 182 (42.9%) who underwent limited resection. No perioperative mortality occurred in either group. The overall 5-year survival rate of the entire cohort was 88%. Patients who underwent limited resection tended to have a shorter operation time, smaller blood loss volume, fewer removed nodes, and a shorter postoperative stay. However, the groups did not differ in terms of postoperative complications. Lobectomy and limited resection could lead to equivalent overall survival in patients with GGO-dominant tumor, while lobectomy showed better overall survival than limited resection in patients with solid-dominant tumor.

Conclusion: Patients with small GGO lung adenocarcinoma had a favorable prognosis after surgery. The oncologic surgical procedures of lobectomy and limited resection yielded comparable outcomes in patients with clinical stage I GGO-dominant lung adenocarcinomas ≤ 2 cm, while lobectomy showed better survival than limited resection in patients with solid-dominant tumor.
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http://dx.doi.org/10.1016/j.cllc.2020.09.022DOI Listing
March 2021

[Clinical Evaluation of Absorbable Regenerated Oxidized Cellulose in Lung Cancer Surgery].

Zhongguo Fei Ai Za Zhi 2020 Jun;23(6):492-495

Department of Thoracic Surgery, the First Affiliated Hospital of Zhejiang University, Zhejiang University School of Medicine, Hangzhou 310003, China.

Background: Thoracoscopic safe and effective hemostasis is an important condition for rapid rehabilitation of thoracic surgery. Placing hemostatic materials during surgery is a commonly used method in lung cancer laparoscopic surgery. Among them, resorbable oxidized cellulose is a commonly used hemostatic material. This research aims to observe the hemostatic effect of resorbable oxidized cellulose in lung cancer surgery.

Methods: A retrospective analysis of 42 patients with thoracoscopic lung cancer undergoing radical surgery in the Department of Thoracic Surgery, First Affiliated Hospital of Zhejiang University School of Medicine from July 1, 2018 to December 1, 2018, and intraoperative use of regenerative oxidized cellulose to stop bleeding The clinical and pathological data were selected and the perioperative indicators were selected as the outcome events for statistical analysis.

Results: The mean operative time was (120.5±57.3) min. The mean intraoperative blood loss was (26.8±21.6) mL. The average postoperative drainage volume was (513.6±359.5) mL. The average postoperative chest tube indwelling time was (2.6±1.2) d.

Conclusions: The use of absorbable regenerated oxidized cellulose in the radical operation of thoracoscopic lung cancer has a good hemostasis effect, and is suitable for hemostasis of wounds after lymph node dissection.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.101.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309556PMC
June 2020

[Minimally Invasive Therapies for Early Stage Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2020 Jun 28;23(6):479-486. Epub 2020 Feb 28.

Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China.

Lung cancer is the most common cancer and the leading cause of cancer death in the world, among which non-small cell lung cancer (NSCLC) accounts for about 85% of the total lung cancer. With the widespread of computed tomography (CT) and other imaging screening methods, the pathological types of lung cancer have changed from central squamous cell carcinoma to the early-stage lung adenocarcinoma, which is manifested as isolated pulmonary nodules and ground glass nodules on CT. Early diagnosis and treatment of lung cancer is of crucial clinical significance, and the continuous development and improvement of minimally invasive interventional techniques provide more options for lung cancer treatment, such as stereotactic radiation, percutaneous ablation, and bronchial intervention. This paper will make a review on the principle, advantages, disadvantages and prospects of minimally invasive interventional therapy commonly used in clinical practice.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.101.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309551PMC
June 2020

Novel preoperative nutritional assessment tool and prognostic model for ESCC patients.

J Cancer 2019 10;10(17):3883-3892. Epub 2019 Jun 10.

Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive tumor types worldwide, and malnutrition prevails in these patients. However, there is no preoperative nutritional assessment tool specifically designed for patients with ESCC. : Patients who received esophagectomy from 2004 to 2016 were consecutively included. The preoperative nutritional risk factors for ESCC were screened by univariate and multivariate Cox regression analysis to construct a new nutritional scoring tool. A prognostic model of ESCC based on the new scoring tool was further proposed. : A total of 510 ESCC patients were enrolled. A novel BLUT (BMI-lymphocyte-uric acid-triglyceride) scoring tool based on BMI, lymphocyte count, uric acid level, and triglyceride level was proposed, which could effectively predict the prognosis of ESCC patients (log rank P<0.001), and it was better than the traditional nutritional assessment tools. The C-index and 95% confidence interval (CI) of the nomogram based on the BLUT scoring tool was 0.735(0.698-0.772). It had good prognostic efficacy and was significantly better than the model based on T stage and N stage (P=0.038). The calibration curve of internal and external validation suggested a good fitting effect with the real situation in judging the 1-year, 3-year, and 5-year survival status. : The BULT scoring tool could distinguish the heterogeneity of preoperative nutritional status and the BLUT-based nomogram had good prognostic performance for ESCC patients.
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http://dx.doi.org/10.7150/jca.31286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692628PMC
June 2019

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways.

Cell Death Dis 2018 07 26;9(8):817. Epub 2018 Jul 26.

Department of Thoracic surgery, The first Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China.

Ricolinostat (ACY-1215), a first-in-class selective HDAC6 inhibitor, exhibits antitumor effects alone or in combination with other drugs in various cancers. However, its efficacy in esophageal cancer remains unclear. In this study, we found that the high expression of HDAC6 was associated with poor prognosis in esophageal squamous cell carcinoma (ESCC) tissues. Then, we identified that ACY-1215 significantly inhibited cellular proliferation in ESCC, and caused G2/M phase arrest and apoptosis. We further demonstrated that ACY-1215 treatment reduced the expression of PI3K, P-AKT, P-mTOR, and P-ERK1/2 and increased that of Ac-H3K9 and Ac-H4K8. In addition, using miRNA microarray and bioinformatics analysis, we detected that ACY-1215 promoted miR-30d expression, and PI3K regulatory subunit 2 (PIK3R2) was a direct target of miR-30d. Anti-miR-30d partially rescued the G2/M phase arrest and apoptosis caused by ACY-1215 treatment. The reductions in PI3K, P-AKT, and P-mTOR expression were also partially reversed by miR-30d inhibitor. Furthermore, the effects of ACY-1215 inhibited ESCC proliferation were validated in a mouse xenograft model in vivo. In conclusion, our study showed that ACY-1215 suppressed proliferation and promoted apoptosis in ESCC via miR-30d/PI3K/AKT/mTOR and ERK pathways and that ACY-1215 may be a promising antitumor agent in ESCC.
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http://dx.doi.org/10.1038/s41419-018-0788-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062526PMC
July 2018

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Authors:
Jinlin Cao Jian Hu

Ann Thorac Surg 2018 11 30;106(5):1592-1593. Epub 2018 Jun 30.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou 310003, China. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2018.05.078DOI Listing
November 2018

Survival rates after lobectomy versus sublobar resection for early-stage right middle lobe non-small cell lung cancer.

Thorac Cancer 2018 08 21;9(8):1026-1031. Epub 2018 Jun 21.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Lung cancer in the right middle lobe has a poorer prognosis than tumors located in other lobes. The optimal surgical procedure for early-stage non-small cell lung cancer (NSCLC) in the right middle lobe has not yet been elucidated. The aim of this study was to compare survival rates after lobectomy and sublobar resection for early-stage right middle lobe NSCLC.

Methods: Patients who underwent lobectomy or sublobar resection for stage IA right middle lobe NSCLC tumors ≤ 2 cm between 2004 and 2014 were identified from the Surveillance, Epidemiology and End Results database of 18 registries. Cox regression model analysis was used to evaluate the prognostic factors. The lung cancer-specific survival (LCSS) and overall survival (OS) rates between the two groups were compared.

Results: A total of 861 patients met our criteria, including 662 (76.9%) patients who underwent lobectomy and 199 (23.1%) patients who underwent sublobar resection. No statistical differences in LCSS and OS rates were identified between the groups of patients with stage IA right middle lobe NSCLC ≤ 1 cm. For tumors > 1-2 cm, lobectomy was associated with more favorable LCSS and OS rates compared to sublobar resection.

Conclusion: Lobectomy and sublobar resection deliver a comparable prognosis for patients with stage IA right middle lobe NSCLC ≤ 1 cm. For tumors > 1-2 cm, lobectomy showed better survival rates than sublobar resection.
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http://dx.doi.org/10.1111/1759-7714.12782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068437PMC
August 2018

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Authors:
Jinlin Cao Jian Hu

Ann Thorac Surg 2018 10 5;106(4):1261. Epub 2018 Jun 5.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2018.05.019DOI Listing
October 2018

Prognostic impact of lymphadenectomy on outcomes of sublobar resection for stage IA non-small cell lung cancer ≤2 cm.

J Thorac Cardiovasc Surg 2018 08 6;156(2):796-805.e4. Epub 2018 Apr 6.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Objective: To investigate the prognostic impact of lymph node (LN) dissection on sublobar resection for stage IA non-small cell lung cancer (NSCLC) tumors ≤2 cm.

Methods: All patients who underwent sublobar resection for stage IA NSCLC tumors ≤2 cm were identified from the Surveillance, Epidemiology and End Results database. Patients were classified into no-LN dissection and LN dissection groups, and the latter was subclassified by the extent of LN dissection (1-3 regional LNs or ≥4 regional LNs). These groups were compared in terms of lung cancer-specific survival (LCSS) and overall survival (OS) rates. Propensity score-matched comparative analysis and a Cox regression model were used.

Results: A total of 3269 patients met our criteria, including 1459 (44.6%) who underwent no LN dissection, 891 (27.3%) who underwent dissection of 1 to 3 regional LNs, 919 (28.1%) who underwent dissection of ≥4 regional LNs. Compared with no LN dissection, LN dissection was associated with more favorable LCSS and OS rates in patients who underwent sublobar resection for stage IA tumors ≤2 cm. More extensive regional LN dissection (≥4 regional LNs) was associated with better LCSS and OS rates compared with less extensive regional LN dissection (1 to 3 regional LNs). A multivariable analysis of our patient population revealed independent associations of no LN dissection and less extensive regional LN dissection with poorer LCSS and OS rates compared with overall LN dissection and more extensive regional LN dissection, respectively.

Conclusions: This propensity score-matched analysis reveals an association of LN dissection, particularly more extensive regional LN dissection (≥4 regional LNs), with better survival rates in patients who undergo sublobar resection for stage IA NSCLC tumors ≤2 cm.
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http://dx.doi.org/10.1016/j.jtcvs.2018.03.122DOI Listing
August 2018

Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

Thorac Cancer 2018 05 24;9(5):656-661. Epub 2018 Mar 24.

Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy.
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http://dx.doi.org/10.1111/1759-7714.12624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928351PMC
May 2018

Semi-quantitative Analysis of EBUS Elastography as a Feasible Approach in Diagnosing Mediastinal and Hilar Lymph Nodes of Lung Cancer Patients.

Sci Rep 2018 02 23;8(1):3571. Epub 2018 Feb 23.

Department of Thoracic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.

This study aimed to semi-quantitatively evaluate the elastographic imaging color distribution of mediastinal and hilar lymph nodes (LNs), and explored its utility in helping define malignant and benign LNs for lung cancer patients. We prospectively collected patients who underwent preoperative mediastinal staging of suspected lung cancer by EBUS-TBNA. We analyzed the elastography color distribution of each LN and calculated the blue color proportion (BCP). The LN elastographic patterns were compared with the final EBUS-TBNA pathological results. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of BCP. We sampled and analyzed 79 LNs from 60 patients. The average BCP in malignant LNs was remarkably higher than that in benign LNs (57.1% versus 30.8%, P < 0.001). The area under the ROC curve (AUC) for the BCP was 0.86 (95% CI: 0.78-0.94). The best cutoff BCP for differentiating between benign and malignant LNs was determined as 36.7%. All the 16 LNs (20.3%) with a BCP lower than 27.9% were diagnosed as benign tissues. Our study suggests that elastography is a feasible technique that may safely help to predict LN metastasis during EBUS-TBNA. We found a clear BCP cutoff value to help define positive and negative LNs.
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http://dx.doi.org/10.1038/s41598-018-22006-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824841PMC
February 2018

Survival Rates After Lobectomy, Segmentectomy, and Wedge Resection for Non-Small Cell Lung Cancer.

Ann Thorac Surg 2018 05 17;105(5):1483-1491. Epub 2018 Feb 17.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: This study aimed to compare the survival rates after lobectomy, segmentectomy, and wedge resection for the eighth edition of the tumor, node, metastasis classification for stage IA non-small cell lung cancer (NSCLC).

Methods: Patients who underwent lobectomy, segmentectomy, or wedge resection for stage IA NSCLC were identified from the Surveillance, Epidemiology, and End Results database. A Cox regression model and propensity-matched analysis were used. The overall survival (OS) rates and lung cancer-specific survival (LCSS) rates among the three groups were compared by tumor size.

Results: A total of 16,819 patients met our criteria. Although the OS rate was better for lobectomy than for wedge resection, no statistical differences in the LCSS rate were identified among the three treatment groups of patients with tumors that were 1.0 cm or smaller. For tumors from 1.1 to 2.0 cm, lobectomy and segmentectomy showed no statistical differences in the LCSS rate, but both conferred better OS and LCSS rates than wedge resection. For tumors from 2.1 to 3.0 cm, the OS and LCSS rates were better for lobectomy than for segmentectomy or wedge resection, but similar for segmentectomy and wedge resection.

Conclusions: Lobectomy, segmentectomy, and wedge resection are comparable oncologic procedures for patients with stage IA NSCLC that is 1.0 cm or smaller. For tumors from 1.1 to 2.0 cm, lobectomy and segmentectomy could lead to equivalent survival rates but showed better survival rates than that observed with wedge resection. For tumors from 2.1 to 3.0 cm, lobectomy is still the standard surgical procedure; for patients who are unsuitable candidates for lobectomy, segmentectomy and wedge resection show similar survival rates.
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http://dx.doi.org/10.1016/j.athoracsur.2018.01.032DOI Listing
May 2018

The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans.

J Cardiothorac Surg 2017 Dec 20;12(1):119. Epub 2017 Dec 20.

Department of Thoracic Surgery, First Affiliated Hospital of Zhejiang University, No. 79 Qingchun Road, Zhejiang, Hangzhou, 310003, China.

Background: Many patients who receive lung transplantation (LT) operations develop varying degrees of bronchiolitis obliterans (BO) after the surgeries. Epithelial-mesenchymal transition (EMT) is considered to be related to the process of bronchiolitis obliterans. In this study we simulated the pathological process of post-lung transplantation bronchiolitis obliterans, and explored the correlation between BO and EMT of small airway epithelial cells.

Methods: We transplanted the left lungs of F344 rats to Lewis rats by the Tri-cuff anastomosis and established the allogeneic rat left lung orthotopic transplantation model. Cyclosporine and lipopolysaccharide were administrated appropriately after the surgery. The histological structure and the expression levels of the EMT markers was observed with the methods of HE staining, Masson staining and immunohistochemistry. The analysis of enumeration data was performed using Fisher's Exact test and Spearman's rank correlation was used for the correlation analysis.

Results: Inflammatory cell infiltration, fibroplasia of bronchiole walls and significant lumen stenosis were found in the pulmonary mesenchyme of the transplanted lungs. The positive expression rate of E-cadherin in the transplanted lungs was 38.50% (5/13), significantly lower than that in the normal lung tissues [87.50% (7/8)] (P < 0.05), while the positive expression rate of Vimentin was 76.92% (10/13) which is significantly higher than that in the normal lung tissues [25.00% (2/8)] (P < 0.05). And a negative correlation existed between the expression levels of E-cadherin and Vimentin (r = -0.750, P < 0.01).

Conclusions: In the disease model we established in this study, we found pathological changes that met BO characteristics happened in the transplanted lungs. Meanwhile, the small airway epithelial cells of transplanted lungs underwent an epithelial-mesenchymal transition, which indicated a role of EMT in the BO airway remodeling.
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http://dx.doi.org/10.1186/s13019-017-0673-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738918PMC
December 2017

An "alternative finger" in robotic-assisted thoracic surgery: intraoperative ultrasound localization of pulmonary nodules.

Med Ultrason 2017 Nov;19(4):374-379

Department of Thoracic Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Aim: Robotic-assisted thoracic surgery (RATS) has become a promising treatment for pulmonary neoplasms. During RATS, intraoperative ultrasonography can act as an "alternative finger" to "touch" and locate lesions, especially pulmonary nodules. This study was aimed to investigate the efficacy of intraoperative ultrasonographic localization during da Vinci RATS procedures.

Material And Methods: Patients with pulmonary nodules were randomly divided into an Experimental Group and Control Group in which nodules were respectively located using intraoperative ultrasonography or by the surgeon's anatomic knowledge. The success rates and relevant localization factors were compared between the groups and analyzed to conclude the efficacy of intraoperative ultrasonography. Additionally, the intraoperative ultrasonography learning curve was analyzed to evaluate each surgeon's ability to independently perform intraoperative ultrasonography.

Results: Thirty-four patients were included in the study (n = 17/group). Respectively, the Experimental Group and Control Group comprised 41.2% and 58.9% women (p= 0.937), and had average ages of 55.5 and 55.8 years. In the Experimental group, ultrasonographic localization for mixed ground-glass nodules with CT values of -500 to -100 Hounsfield units had an efficacy of 87.5%. By contrast, the localization efficacy in Control Group was 20.0% (p=0.032).A single surgeon without prior experience performed intraoperative ultrasonography in 20 cases, and the latter 10 procedures required significantly less time relative to the former 10 procedures (p=0.000).

Conclusions: During RATS, the use of intraoperative ultrasonography as an "alternative finger" to "touch" and findthe accurate location of pulmonary nodules, especially mixed ground-glass nodules, is warranted.
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http://dx.doi.org/10.11152/mu-1053DOI Listing
November 2017

Wnt3a Expression Is Associated with Epithelial-Mesenchymal Transition and Impacts Prognosis of Lung Adenocarcinoma Patients.

J Cancer 2017 2;8(13):2523-2531. Epub 2017 Aug 2.

Department of Thoracic Surgery, The first Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and migration during cancer metastasis. Wnt3a is one of the ligands in canonical Wnt/β-catenin signaling pathway, which contributes to the carcinogenesis and progression of lung cancer cell lines. The aim of this study was to evaluate the association between Wnt3a and EMT-related proteins (E-cadherin and N-cadherin), and to further investigate its impact on prognosis of lung adenocarcinoma patients. A total of 147 lung adenocarcinoma patients were included and their clinicopathological characteristics were collected in this retrospective study. The expression levels of Wnt3a, E-cadherin and N-cadherin in post-surgery cancerous and adjacent normal tissues were assessed by immunohistochemistry. The association between Wnt3a and EMT-related proteins and their prognostic values were systematically evaluated. HCC827 and PC9 cell lines were treated with Wnt3a to detect the expression of EMT-related and Wnt/β-catenin signaling-associated proteins, as well as the migration and invasion abilities. High Wnt3a expression level was significantly associated with low E-cadherin (<0.001) and high N-cadherin (<0.001) expression levels in lung adenocarcinoma tissues. Besides, high Wnt3a level predicted poorer lung adenocarcinoma survival by univariate Cox analysis (=0.001), while the multivariate result was not significant (=0.355). Subgroup analysis suggested that the prognostic value of Wnt3a expression level was significant in stage T1-T2 (log rank =0.003) and stage N0 (log rank =0.031) patients. The multivariate Cox analysis suggested N-cadherin was an independent prognostic factor for lung adenocarcinoma patients (=0.012). After including these markers into a nomogram, the Harrell's C-index of the nomogram was 0.755. The decision-curve analysis of our nomogram performed net benefit at the threshold probability from 21.6% to 82.0%, and the current model had a better prognostic value than TNM-classification with a lower Akaike information criterion (AIC) value of 166.54. experiments suggested that Wnt3a could regulate EMT-related proteins and promotes invasion and migration abilities. Wnt3a could regulate EMT-related proteins and promote the migration and invasion process of lung adenocarcinoma. Although its value as an independent prognostic factor was limited, the combined model suggested good prognostic performance for lung adenocarcinoma patients.
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http://dx.doi.org/10.7150/jca.18560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595082PMC
August 2017

Prognostic performance of three lymph node staging schemes for patients with Siewert type II adenocarcinoma of esophagogastric junction.

Sci Rep 2017 08 31;7(1):10123. Epub 2017 Aug 31.

Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

The prognostic performance of different lymph node staging schemes for adenocarcinoma of esophagogastric junction (AEG) remains controversial. The objective of the present study was to compare the prognostic efficacy of the number of lymph node metastases (LNMs), the positive lymph node ratio (LNR) and the log odds of positive lymph nodes (LODDS). Patients diagnosed with Siewert type II AEG were included from the Surveillance, Epidemiology, and End Results database. Harrell's C-index statistic, Schemper's proportion of explained variation (PEV), the Akaike information criterion (AIC) and restricted cubic spine analyses were adopted to assess the predictive accuracy of LNM, LNR and LODDS. A total of 1302 patients with post-surgery Siewert type II AEG were included. LNM, LNR and LODDS all showed significant prognostic value in the multivariate Cox regression analyses. LODDS performed higher predictive accuracy than LNM and LNR, with relatively higher C-index, higher Schemper's PEV value and lower AIC value. For patients with no nodes involved, LODDS still performed significantly discriminatory utility. LODDS showed more accurate prognostic performance than LNM and LNR for post-surgery Siewert type II AEG, and it could help to detect survival heterogeneity for patients with no positive lymph nodes involved.
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http://dx.doi.org/10.1038/s41598-017-09625-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579029PMC
August 2017

A nomogram for predicting the risk of invasive pulmonary adenocarcinoma for patients with solitary peripheral subsolid nodules.

J Thorac Cardiovasc Surg 2017 02 24;153(2):462-469.e1. Epub 2016 Oct 24.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Objective: The subsolid nodule is a common clinical concern. The aim of this study was to construct a nomogram to predict the risk of invasive pulmonary adenocarcinoma in patients with a solitary peripheral subsolid nodule.

Methods: We reviewed the records of 293 patients who had undergone resection of a solitary peripheral subsolid nodule, including the results of pathologic examinations after surgical resection. Clinical parameters and imaging features were analyzed by the use of univariable and multivariable logistic regression analysis. A nomogram to predict the risk of invasive pulmonary adenocarcinoma was constructed and validated with bootstrap resampling.

Results: Two hundred seventy-three patients were included for analysis; 35 were diagnosed as benign, 3 as atypical adenomatous hyperplasia, 18 as adenocarcinoma in situ, 58 as minimally invasive adenocarcinoma, and 159 as invasive pulmonary adenocarcinoma. After final regression analysis, the computed tomography attenuation, nodule size, spiculation, signs of vascular convergence, pleural tags, and solid proportion were identified and were entered into the nomogram. The nomogram showed a robust discrimination, with an area under the receiver operating characteristic curve of 0.894. The calibration curves for the probability of invasive pulmonary adenocarcinoma showed optimal agreement between the probability as predicted by the nomogram and the actual probability.

Conclusions: We developed a nomogram that can predict the risk of invasive pulmonary adenocarcinoma for patients with a solitary peripheral subsolid nodule. Validation by the use of bootstrap resampling revealed optimal discrimination and calibration, indicating that the nomogram may have clinical utility. This model has the potential to assist clinicians in making treatment recommendations.
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http://dx.doi.org/10.1016/j.jtcvs.2016.10.019DOI Listing
February 2017

Clinical Nomogram for Predicting Survival of Esophageal Cancer Patients after Esophagectomy.

Sci Rep 2016 05 24;6:26684. Epub 2016 May 24.

Department of Thoracic Surgery, The first Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The aim of this study was to construct an effective clinical nomogram for predicting the survival of esophageal cancer patients after esophagectomy. We identified esophageal cancer patients (n = 4,281) who underwent esophagectomy between 1988 and 2007 from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Clinically significant parameters for survival were used to construct a nomogram based on Cox regression analyses. The model was validated using bootstrap resampling and a Chinese cohort (n = 145). A total of 4,109 patients from the SEER database were included for analysis. The multivariate analyses showed that the factors of age, race, histology, tumor site, tumor size, grade and depth of invasion, and the numbers of metastases and retrieved nodes were independent prognostic factors. All of these factors were selected into the nomogram. The nomogram showed a clear prognostic superiority over the seventh AJCC-TNM classification (C-index: SEER cohort, 0.716 vs 0.693, respectively; P < 0.01; Chinese cohort, 0.699 vs 0.680, respectively; P < 0.01). Calibration of the nomogram predicted the probabilities of 3- and 5-year survival, which corresponded closely with the actual survival rates. This novel prognostic model may improve clinicians' abilities to predict individualized survival and to make treatment recommendations.
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http://dx.doi.org/10.1038/srep26684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877645PMC
May 2016

Log Odds of Positive Lymph Nodes Predicts Survival in Patients After Resection for Esophageal Cancer.

Ann Thorac Surg 2016 Aug 13;102(2):424-32. Epub 2016 May 13.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: The number of lymph node metastases (LNMs) and the positive lymph node ratio (LNR) have been shown to be significant independent prognostic factors in predicting overall survival in patients with esophageal cancer. Our aim was to evaluate whether a novel prognostic indicator-the log odds of positive lymph nodes (LODDS)-predicts survival in esophageal cancer.

Methods: Patients who underwent esophagectomy for esophageal cancer between 1988 and 2007 were identified from the Surveillance, Epidemiology, and End Results (SEER) database of 18 registries, and a Chinese patient cohort was subjected to validation. The prognostic efficacy of LNM, LNR, and LODDS was compared. Prognostic performance was measured using Harrell's C-index statistic, Schemper's proportion of explained variation, and the Akaike information criterion (AIC).

Results: A total of 4,123 patients in the SEER database and 134 patients in the Chinese cohort met our criteria in this study. LODDS gave a better prognostic performance than either LNM or LNR in both the SEER database and the Chinese cohort. Multivariate analyses showed significant values for LNM, LNR, and LODDS as prognostic factors (p < 0.001). However, only LODDS was a significant prognostic factor regardless of the number of lymph nodes retrieved (p = 0.677). Furthermore, after stratification of patients with no nodes involved or all nodes involved, the values of LODDS still distinguished the heterogeneity efficiently.

Conclusions: LODDS predicts survival more accurately than either LNM or LNR in patients undergoing resection for esophageal cancer, especially for patients with an insufficient number of lymph nodes retrieved.
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http://dx.doi.org/10.1016/j.athoracsur.2016.03.030DOI Listing
August 2016

Hypokalemic periodic paralysis induced by thymic hyperplasia and relieved by thymectomy.

JAMA Neurol 2013 Nov;70(11):1436-9

Department of Thoracic Surgery, 117 PLA Hospital, Hangzhou, China.

Importance: Hypokalemic periodic paralysis is a muscle channelopathy based on mutations or predisposing variants or secondary to potassium wasting. In contrast to myasthenia gravis, an association with thymic hyperplasia has not yet been reported, to our knowledge.

Observations: We report a male patient in his mid-20s with progressive episodes of flaccid muscle weakness, associated low serum potassium levels, and a pathologic decrement in the long exercise test. Because the familial inheritance in the family was initially unknown, thorough diagnostic tests were performed including contrast-enhanced computed tomography scan, which displayed a mass in the anterior mediastinum. The test results for autoantibodies against myasthenia gravis (acetylcholine receptor, muscle-specific tyrosine kinase, and low-density lipoprotein receptor-related protein 4) and other end plate channelopathies were negative, and test results for hypokalemia-inducing hormones (thyroid, corticotropin, and cortisol) were negative. Surgery identified a thymus of 13 × 8 × 3 cm(3). Histologic analysis was consistent with thymic hyperplasia of the follicular subtype and immunohistologic analysis showed cytokeratin 5/6 in hyperplastic epithelial cells. A 2-year follow-up revealed the postoperative absence of weakness episodes. As in 30% of familial cases, molecular genetics testing failed to identify a mutation in periodic paralysis genes.

Conclusions And Relevance: Thymic hyperplasia can clinically manifest susceptibility to hypokalemic periodic paralysis. For patients with late onset or increasing weakness episodes, we recommend imaging to assess for thymic enlargement and thymectomy at thymic hyperplasia.
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http://dx.doi.org/10.1001/jamaneurol.2013.3918DOI Listing
November 2013