Publications by authors named "Calvin S H Ng"

181 Publications

A new method for accurately localizing and resecting pulmonary nodules.

J Thorac Dis 2020 Sep;12(9):4973-4984

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

With the use of low-dose CT for early screening of lung cancer, more and more early lung cancers are found. At the same time, patients with small lung nodules have also increased, it is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. Many studies have reported preoperative and intraoperative methods for localizing lung nodules before minimally invasive resection. Methods for preoperative localization include CT-guided hook-wire positioning, coil positioning, or dye injection and radionuclide location Methods for intraoperative localization include intraoperative ultrasound localization and tactile pressure-sensing localization. After the localization of pulmonary nodules under the guidance of CT patients need to restrict their activities; otherwise, it is easy for the nodules to move, causing the operation to fail, and may also cause complications such as pneumothorax, puncture site pain, and pulmonary parenchymal bleeding. In the past, we injected melamine dye under the guidance of electromagnetic navigation bronchoscope to locate lung nodules. The purpose of this case is introducing a new method for accurately localizing and resecting pulmonary nodules by injecting indocyanine green (ICG) under the guidance of electromagnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope.
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http://dx.doi.org/10.21037/jtd-20-2089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578447PMC
September 2020

ARTIS Pheno-the future of thoracic hybrid theatre for lung nodule resection?

J Thorac Dis 2020 Sep;12(9):4602-4605

Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

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http://dx.doi.org/10.21037/jtd-2020-50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578484PMC
September 2020

Surgery beyond coronavirus disease 2019.

ANZ J Surg 2020 10 28;90(10):1865-1866. Epub 2020 Aug 28.

Department of Cardiac, Thoracic and Vascular Surgery, National University Heart Centre Singapore, Singapore.

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http://dx.doi.org/10.1111/ans.16245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436604PMC
October 2020

Hybrid Theater Facilitates Lung-Preserving Multimodal Treatment for Multiple Pulmonary Metastases.

Ann Thorac Surg 2021 02 17;111(2):e89-e92. Epub 2020 Jul 17.

Division of Cardiothoracic Surgery, Department of Surgery, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. Electronic address:

A patient with a history of hepatocellular carcinoma was found to have multiple pulmonary metastases. Staged treatments were combined into a single operation session in the hybrid theater, encompassing bronchoscopic microwave ablation of central right upper lobe lesions and uniportal surgical wedge resections of peripheral right middle lobe lesions. All lung metastases were successfully treated with adequate margin clearance. Microwave ablation under the guidance of electromagnetic navigation bronchoscopy in the hybrid theater is a novel contribution to the multimodal operative management of multiple pulmonary neoplasms. It is a unique choice for patients with multilobar, subcentimeter metastases, and with concerns about lung function preservation.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.098DOI Listing
February 2021

Screening-detected pure ground-glass opacities: malignant potential beyond conventional belief?

Transl Lung Cancer Res 2020 Jun;9(3):816-818

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

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http://dx.doi.org/10.21037/tlcr.2020.03.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354109PMC
June 2020

Use of custom made 3-dimensional printed surgical guide for manubrio-sternal resection of solitary breast cancer metastasis: case report.

AME Case Rep 2020 30;4:12. Epub 2020 Apr 30.

Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

A 44-year-old lady with solitary 4.4-cm metastasis to the manubrium from a previously resected invasive ductal carcinoma of the left breast underwent manubrio-sternal resection. We describe our unique approach of using 3-dimensional (3D)-computed tomography (CT) image segmentation planning for reconstructing desirable resection boundaries, design of ideal superficial and deep surgical resection guides, and followed by 3D printing of guides using autoclavable thermoplastic for use during surgery. The surgical guides over the ribs and sternum rapidly and accurately define resection lines intraoperatively, achieve good surgical margins, and could reduce resection and reconstruction related morbidity for performing complex surgical resection of the chest wall. The patient was discharged 2 weeks postoperatively and remained free from local recurrence on CT scan 1-year after resection.
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http://dx.doi.org/10.21037/acr.2020.03.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221324PMC
April 2020

The comparison of electromagnetic with virtual bronchoscopic navigation accuracy at hybrid operating room in patient with sternal wires.

AME Case Rep 2020 20;4. Epub 2020 Jan 20.

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

We describe a case of a 63-year-old lady with an incidental small right upper lobe ground glass opacity (GGO) lesion, who had history of open-heart surgery with bypass grafts for coronary artery disease. Video-assisted thoracic surgery (VATS) excisional biopsy with pre-operative localization was planned. Localization by percutaneous approach is challenging due to position of GGO shielded by both the scapular and ribs. Electromagnetic navigation accuracy may be affected by steel sternal wires but its effect has not been reported on literature. Both virtual and electromagnetic navigation bronchoscopy platforms were used with real-time cone-beam CT confirmation in the hybrid operating room to perform dye marking. Both navigation methods successfully marked the GGO for lung resection. Our case demonstrated that the accuracy of electromagnetic navigation in the presence of steel sternal wire is satisfactory for dye marking and the use of intra-operative cone-beam CT in hybrid operating room is invaluable for the success of navigational bronchoscopy.
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http://dx.doi.org/10.21037/acr.2019.12.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082328PMC
January 2020

Hybrid operating room-one stop for diagnosis, staging and treatment of early stage NSCLC.

J Thorac Dis 2020 Feb;12(2):123-131

Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, China.

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http://dx.doi.org/10.21037/jtd.2019.08.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061185PMC
February 2020

Surgical access trauma following minimally invasive thoracic surgery.

Eur J Cardiothorac Surg 2020 08;58(Suppl_1):i6-i13

Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Surgical access trauma has important detrimental implications for immunological status, organ function and clinical recovery. Thoracic surgery has rapidly evolved through the decades, with the advantages of minimally invasive surgery becoming more and more apparent. The clinical benefits of enhanced recovery after video-assisted thoracoscopic surgery (VATS) may be, at least in part, the result of better-preserved cellular immunity and cytokine profile, attenuated stress hormone release and improved preservation of pulmonary and shoulder function. Parameters of postoperative pain, chest drain duration, hospital stay and even long-term survival are also indirect reflections of the advantages of reduced access trauma. With innovations of surgical instruments, optical devices and operative platform, uniportal VATS, robotic thoracic surgery and non-intubated anaesthesia represent the latest frontiers in minimizing trauma from surgical access.
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http://dx.doi.org/10.1093/ejcts/ezaa025DOI Listing
August 2020

Postlobectomy major haemorrhage: known knowns, known unknowns and unknown unknowns.

Eur J Cardiothorac Surg 2020 03;57(3):470-471

Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

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http://dx.doi.org/10.1093/ejcts/ezz302DOI Listing
March 2020

Devising the guidelines: the techniques of pulmonary nodule localization in uniportal video-assisted thoracic surgery-hybrid operating room in the future.

J Thorac Dis 2019 Sep;11(Suppl 16):S2073-S2078

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.

Pulmonary nodules beneath the pleura can be hard to visualize or palpate, especially during the uniportal thoracoscopic surgery. Conventionally, thoracic surgeons would use adjuvant modalities to localize the lesion preoperatively, of which computed tomography-guided hookwire implantation has been adopted most widely due to its feasibility and high success rate. However, procedure-associated complications such as pneumothorax and wire dislodgement can cause patient discomfort or localization failure. Occasionally more healthy tissue is resected than needed to guarantee the lesion is removed and with an adequate margin. A thoracotomy is necessary for specific scenario. With the development of imaging technology, it is now possible to replace the traditional workflow carried out in the radiology suite by centralizing the hookwire placement and uniportal minimally-invasive pulmonary resection inside the hybrid theater which equipped with advanced imaging devices. Theoretically, the advanced intra-operative imaging-guided techniques help to precisely locate and resection pulmonary lesion in a potentially tissue-sparing and quick paradigm.
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http://dx.doi.org/10.21037/jtd.2019.01.82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783707PMC
September 2019

Ambient fine particulate matter inhibits 15-lipoxygenases to promote lung carcinogenesis.

J Exp Clin Cancer Res 2019 Aug 16;38(1):359. Epub 2019 Aug 16.

Department of Surgery, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T, Hong Kong.

Background: Epidemiological observations have demonstrated that ambient fine particulate matter with d < 2.5 μm (PM) as the major factor responsible for the increasing incidence of lung cancer in never-smokers. However, there are very limited experimental data to support the association of PM with lung carcinogenesis and to compare PM with smoking carcinogens.

Methods: To study whether PM can contribute to lung tumorigenesis in a way similar to smoking carcinogen 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) via 15-lipoxygenases (15-LOXs) reduction, normal lung epithelial cells and cancer cells were treated with NNK or PM and then epigenetically and post-translationally examined the cellular and molecular profiles of the cells. The data were verified in lung cancer samples and a mouse lung tumor model.

Results: We found that similar to smoking carcinogen NNK, PM2.5 significantly enhanced cell proliferation, migration and invasion, but reduced the levels of 15-lipoxygenases-1 (15-LOX1) and 15-lipoxygenases-2 (15-LOX2), both of which were also obviously decreased in lung cancer tissues. 15-LOX1/15-LOX2 overexpression inhibited the oncogenic cell functions induced by PM2.5/NNK. The tumor formation and growth were significantly higher/faster in mice implanted with PM2.5- or NNK-treated NCI-H23 cells, accompanied with a reduction of 15-LOX1/15-LOX2. Moreover, 15-LOX1 expression was epigenetically regulated at methylation level by PM2.5/NNK, while both 15-LOX1 and 15-LOX2 could be significantly inhibited by a set of PM2.5/NNK-mediated microRNAs.

Conclusion: Collectively, PM2.5 can function as the smoking carcinogen NNK to induce lung tumorigenesis by inhibiting 15-LOX1/15-LOX2.
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http://dx.doi.org/10.1186/s13046-019-1380-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697918PMC
August 2019

EGFR-AS1/HIF2A regulates the expression of FOXP3 to impact the cancer stemness of smoking-related non-small cell lung cancer.

Ther Adv Med Oncol 2019 13;11:1758835919855228. Epub 2019 Jun 13.

Department of Surgery, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.

Background: Early data showed that FOXP3 could induce epithelial-mesenchymal transition by stimulating the Wnt/β-catenin signaling pathway in non-small cell lung cancer (NSCLC). However, how the expression of FOXP3 is regulated in NSCLC remains unknown. We thus explored the impacts of the long noncoding RNA EGFR antisense RNA 1 (EGFR-AS1) and hypoxia-inducible factor-2A (HIF2A) on FOXP3 expression and the cancer stemness of NSCLC.

Methods: Lung tissues samples from 87 patients with NSCLC and two NSCLC cell lines were used in this study. The regulation of FOXP3 and lung cancer cell stemness by EGFR-AS1 and HIF2A was determined at molecular levels in NSCLC tissue samples and cultured cells in the presence/absence of the smoking carcinogen, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (also known as nicotine-derived nitrosamine ketone). The results were confirmed in tumor xenograft models.

Results: We found that NNK decreased the expression of EGFR-AS1 in the long term, but increased the expression of HIF2A and FOXP3 to stimulate lung cancer cell stemness. EGFR-AS1 significantly inhibited FOXP3 expression and NSCLC cell stemness, whereas HIF2A obviously promoted both. The enhancement of lung cancer stemness by FOXP3 was, at least partially, stimulating Notch1, as the inhibition of Notch1 could markedly diminish the effect of FOXP3.

Conclusions: FOXP3, the expression of which is under the fine control of EGFR-AS1, is a critical molecule that promotes NSCLC cancer cell stemness through stimulating the Notch1 pathway.
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http://dx.doi.org/10.1177/1758835919855228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598324PMC
June 2019

Evidence for surgical resections in oligometastatic lung cancer.

J Thorac Dis 2019 Apr;11(Suppl 7):S969-S975

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

With the advent of advanced technology in performing diagnostics for lung cancer, an incremental increase in the number of patients with oligometastatic disease is currently being managed with intent to cure. As treatment of selected types of patients with oligometastasis show favourable outcomes, the past notion of managing these patients palliatively is fast becoming extinct. Selection of patients based on established criterion together with surgical metastasectomy combined with multiple ablative techniques with or without systemic chemotherapy offers a reasonable rate of treatment success which provides basis for treating such patient population. As more evidence becomes available to suggest that the oligometastatic state of lung cancer does exist, and are potentially curable, a better understanding of the condition is necessary for clinicians, and surgeons to provide optimal care. In this review we present some of the clinical basis which may cause a paradigm shift in management of patients with oligometastatic lung disease.
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http://dx.doi.org/10.21037/jtd.2019.04.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535472PMC
April 2019

Uniportal video-assisted thoracic surgery lobectomy: a consensus report from the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS).

Eur J Cardiothorac Surg 2019 Aug;56(2):224-229

Department of Surgery, Thoracic Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Objectives: Our goal was to report the results of the first consensus paper among international experts in uniportal video-assisted thoracoscopic surgery (UniVATS) lobectomy obtained through a Delphi process, the objective of which was to define and standardize the main procedural steps, optimize its indications and perioperative management and identify elements to assist in future training.

Methods: The 40 members of the working group were convened and organized on a voluntary basis by the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS). An e-consensus finding exercise using the Delphi method was applied to require 75% agreement for reaching consensus on each question. Repeated iterations of anonymous voting continued for 3 rounds.

Results: Overall, 31 international experts from 18 countries completed all 3 rounds of questionnaires. Although a technical quorum was not achieved, most of the responders agreed that the maximum size of a UniVATS incision should be ≤4 cm. Agreement was reached on many points outlining the currently accepted definition of a UniVATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions.

Conclusions: The UVIG Consensus Report stated that UniVATS offers a valid alternative to standard VATS techniques. Only longer follow-up and randomized controlled studies will predict whether UniVATS represents a valid alternative approach to multiport VATS for major lung resections or whether it should be performed only in selected cases and by selected centres. The next step for the ESTS UVIG is the establishment of a UniVATS section inside the ESTS databases.
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http://dx.doi.org/10.1093/ejcts/ezz133DOI Listing
August 2019

Optimal Approach to Lobectomy for Non-Small Cell Lung Cancer: Systemic Review and Meta-Analysis.

Innovations (Phila) 2019 Apr;14(2):90-116

11 Inova Fairfax Medical Campus, Virginia Commonwealth University, Falls Church, Richmond, VA, USA.

Objective: Video-assisted thoracic surgery (VATS) lobectomy was introduced over 25 years ago. More recently, the technique has been modified from a multiport video-assisted thoracic surgery (mVATS) to uniportal (uVATS) and robotic (rVATS), with proponents for each approach. Additionally most lobectomies are still performed using an open approach. We sought to provide evidence-based recommendations to help define the optimal surgical approach to lobectomy for early stage non-small cell lung cancer.

Methods: Systematic review and meta-analysis of articles searched without limits from January 2000 to January 2018 comparing open, mVATS, uVATS, and rVATS using sources Medline, Embase, and Cochrane Library were considered for inclusion. Articles were individually scrutinized by ISMICS consensus conference members, and evidence-based statements were created and consensus processes were used to determine the ensuing recommendations. The ACC/AHA Clinical Practice Guideline Recommendation Classification system was used to assess the overall quality of evidence and the strength of recommendations.

Results And Recommendations: One hundred and forty-five studies met the predefined inclusion criteria and were included in the meta-analysis. Comparisons were analyzed between VATS and open, and between different VATS approaches looking at oncological outcomes (survival, recurrence, lymph node evaluation), safety (adverse events), function (pain, quality of life, pulmonary function), and cost-effectiveness. Fifteen statements addressing these areas achieved consensus. The highest level of evidence suggested that mVATS is preferable to open lobectomy with lower adverse events (36% versus 42%; 88,460 patients) and less pain (IIa recommendation). Our meta-analysis suggested that overall survival was better (IIb) with mVATS compared with open (71.5% versus 66.7% 5-years; 16,200 patients). Different VATS approaches were similar for most outcomes, although uVATS may be associated with less pain and analgesic requirements (IIb).

Conclusions: This meta-analysis supports the role of VATS lobectomy for non-small cell lung cancer. Apart from potentially less pain and analgesic requirement with uVATS, different minimally invasive surgical approaches appear to have similar outcomes.
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http://dx.doi.org/10.1177/1556984519837027DOI Listing
April 2019

The Landscape of Actionable Molecular Alterations in Immunomarker-Defined Large-Cell Carcinoma of the Lung.

J Thorac Oncol 2019 07 9;14(7):1213-1222. Epub 2019 Apr 9.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, China; Li Ka-Shing Institute of Health Sciences, Sir Y.K. Pao Cancer Center, the Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Introduction: Patients with pulmonary large-cell carcinoma (LCC) have poor prognosis and limited treatment options. The identification of clinically actionable molecular alterations helps to guide personalized cancer treatment decisions.

Patients And Methods: A consecutive cohort of 789 resected NSCLC cases were reviewed. Fifty-nine NSCLC cases lacking morphologic differentiation, accounting for 7.5% of all resected NSCLCs, were identified and further characterized by immunohistochemistry according to the 2015 WHO lung tumor classification. Molecular alterations were investigated by multiple technologies including target capture sequencing, immunohistochemistry, and fluorescence in situ hybridizations.

Results: Of 59 NSCLC cases lacking morphologic differentiation, 20 (33.9%) were reclassified as adenocarcinoma (LCC-AD), 14 (23.7%) as squamous cell carcinoma (LCC-SqCC), and 25 (42.4%) as LCC-Null. Approximately 92% of LCC-Null, 95% of LCC-AD, and 86% of LCC-SqCC harbored clinically relevant alterations. Alterations characteristic of adenocarcinoma (EGFR, KRAS, ALK receptor tyrosine kinase [ALK], ROS1, and serine/threonine kinase 11 [STK11]) were detected in the LCC-AD subgroup but not in LCC-SqCC, whereas squamous-lineage alterations (phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha [PIK3CA], SRY-box 2 [SOX2], fibroblast growth factor receptor 1 [FGFR1], and AKT1) were detected in the LCC-SqCC subgroup but not in the LCC-AD group. Although some LCC-Null tumors displayed a genetic profile similar to either adenocarcinoma or squamous-cell carcinoma, more than half of the LCC-Null group were completely devoid of recognizable lineage-specific genetic profiles. High programmed death ligand 1 expression and high frequency of cell cycle regulatory gene alterations were found in the LCC-Null group offering alternative options of targeted therapy.

Conclusions: This comprehensive molecular study provided further insight into the genetic architecture of LCC. The presence of clinically actionable alterations in a majority of the tumors allowed personalized treatment to emerge.
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http://dx.doi.org/10.1016/j.jtho.2019.03.021DOI Listing
July 2019

Electromagnetic Navigation Bronchoscopy in Hybrid Theater.

Front Surg 2019 19;6:10. Epub 2019 Mar 19.

Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, China.

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http://dx.doi.org/10.3389/fsurg.2019.00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433845PMC
March 2019

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

Ann Surg Oncol 2019 Jul 21;26(7):2053-2062. Epub 2019 Mar 21.

Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China.

Background: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS.

Methods: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB).

Results: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003).

Conclusions: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.
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http://dx.doi.org/10.1245/s10434-019-07318-7DOI Listing
July 2019

Mutation Profile of Resected -Mutated Lung Adenocarcinoma by Next-Generation Sequencing.

Oncologist 2019 10 14;24(10):1368-1374. Epub 2019 Mar 14.

State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China

Background: The efficacy of adjuvant targeted therapy for operable lung cancer is still under debate. Comprehensive genetic profiling is needed for detecting co-mutations in resected epidermal growth factor receptor ()-mutated lung adenocarcinoma (ADC), which may interfere the efficacy of adjuvant tyrosine kinase inhibitor (TKI) treatment.

Materials And Methods: Mutation profiling of 416 cancer-relevant genes was conducted for 139 resected stage I-IIIa lung ADCs with mutations using targeted next-generation sequencing. Co-mutation profiles were systematically analyzed.

Results: Rare alterations other than exon 19 deletion and L858R, such as L861Q (∼3%) and G719A (∼2%), were identified at low frequencies. Approximately 10% of patients had mutations in exon 20 that could confer resistance to first-generation TKIs. Ninety-one percent of patients harbored at least one co-mutation in addition to the major mutation. was the top mutated gene and was found more frequently mutated at later stage. Markedly, mutations were found only in stage II-III ADCs. Conversely, mutations were more frequent in stage I ADCs, whereas mutations were observed exclusively in this group. Thirty-four percent of patients with TKI-sensitizing mutations had genetic alterations involving EGFR downstream effectors or bypass pathways that could affect the response to EGFR TKIs, such as , , and .

Conclusion: Operable lung ADCs with TKI-sensitizing mutations are associated with a high proportion of co-mutations. Mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy.

Implications For Practice: The efficacy of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer harboring mutation after surgical resection is still under debate. Next-generation sequencing of 416 cancer-relevant genes in 139 resected lung cancers revealed the co-mutational landscape with background mutation. Notably, the study identified potential EGFR TKI-resistant mutations in 34.71% of patients with a drug-sensitizing mutation and who were naive in terms of targeted therapy. A comprehensive mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy for these patients.
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http://dx.doi.org/10.1634/theoncologist.2018-0567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795151PMC
October 2019

Latest technology in minimally invasive thoracic surgery.

Ann Transl Med 2019 Jan;7(2):35

Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

From the introduction of video-assisted thoracoscopic surgery (VATS) in the 1990s, to performing major lung resections using a uniportal VATS approach, technology has paved the way for the development of minimally invasive thoracic surgery. Natural orifice access to achieve a 'no port' approach, is also on the rise, with advancements in bronchoscopic techniques for diagnosis and therapy, as well as development of soft robotics to achieve desired flexibility, dexterity and stability in future platforms, which may involve deployment to bring the surgeon totally inside the body. Development of haptic feedback in robotic platforms to enhance the surgical experience is also a major goal, with vibrotactile and mechanical feedback generation, to replicate the traditional touch. In addition, the aid of technology in the form of procedural guidance mechanisms, like augmented reality, will further improve the safety and accuracy of future operations.
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http://dx.doi.org/10.21037/atm.2018.12.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381267PMC
January 2019

Electromagnetic Navigation Bronchoscopy Triple Contrast Dye Marking for Lung Nodule Localization.

Thorac Cardiovasc Surg 2020 04 11;68(3):253-255. Epub 2019 Jan 11.

Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong.

Small pulmonary lesions can be difficult to localize during video-assisted thoracoscopic surgery. Electromagnetic navigation bronchoscopy (ENB) dye marking of the lesion, particularly when guided by cone beam computed tomography in the hybrid operating room (HOR), is an emerging approach. However, issues with confirmation of dye injection and intraoperative visualization of the colored dye can be unpredictable and challenging. To address these uncertainties, we present our technique of ENB dye marking localization of lung nodule using the triple-contrast dye method in the HOR.
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http://dx.doi.org/10.1055/s-0038-1676964DOI Listing
April 2020

The Optimal Treatment for Stage IIIA-N2 Non-Small Cell Lung Cancer: A Network Meta-Analysis.

Ann Thorac Surg 2019 06 14;107(6):1866-1875. Epub 2018 Dec 14.

Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Respiratory Disease, Guangzhou, China; State Key Laboratory of Respiratory Disease, Guangzhou, China; National Clinical Research Center for Respiratory Disease, Guangzhou, China.

Background: The optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to address this important issue through a Bayesian network meta-analysis.

Methods: We performed a search of electronic databases for randomized controlled trials comparing the following treatments: surgery, radiotherapy, chemotherapy, and their multiple combinations before March 25, 2018. Pooled data on overall survival and treatment-related deaths were analyzed within the Bayesian framework.

Results: Eighteen eligible trials reporting 13 treatments were included. In terms of overall survival, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy, which tended to be consistent (hazard ratio [HR] 1.14, 95% credible interval [CrI] 0.21 to 5.93), ranked superior to other treatments. Notably, neoadjuvant chemotherapy followed by surgery and adjuvant radiotherapy was significantly more effective in prolonging survival than surgery alone (HR 0.38, 95% CrI 0.18 to 0.81), surgery plus adjuvant radiotherapy (HR 0.51, 95% CrI 0.29 to 0.92) and potentially surgery plus adjuvant chemotherapy (HR 0.49, 95% CrI 0.23 to 1.05). Overall, with 29% as the highest possibility of causing the fewest treatment-related deaths, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy was the safest treatment option.

Conclusions: Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy has the greatest possibility to be the optimal treatment with the best overall survival and fewest treatment-related deaths for stage IIIA-N2 NSCLC.
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http://dx.doi.org/10.1016/j.athoracsur.2018.11.024DOI Listing
June 2019

Novel method for rapid identification of micropapillary or solid components in early-stage lung adenocarcinoma.

J Thorac Cardiovasc Surg 2018 12 2;156(6):2310-2318.e2. Epub 2018 Aug 2.

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. Electronic address:

Objective: Sublobar resection may be insufficient for early-stage lung adenocarcinoma with micropapillary or solid components because of the associated higher incidence of locoregional recurrence. This study sought to establish a novel method for rapidly identifying their presence to facilitate decision making for sublobar resection.

Methods: Antibody arrays of adhesion and apoptosis molecules were applied for adenocarcinomas with or without micropapillary/solid components to identify differentially expressed proteins. A semi-dry dot-blot system that visualizes the presence of target proteins was used to determine the presence of micropapillary or solid components in a prospective cohort of patients with clinical stage I who underwent operation. Sensitivity and specificity were calculated by comparing semi-dry dot-blot results with pathologic examinations.

Results: Insulin-like growth factor-binding protein 2 and P-cadherin were found more frequently in the micropapillary or solid positive group, and these were used as the target proteins in the semi-dry dot-blot system for detection of micropapillary or solid components. A total of 68 nodules with a mean size of 2.3 ± 0.7 cm, including 13 (19.1%) with a micropapillary and 20 (29.4%) with a solid pattern, were recruited. Micropapillary or solid (+) lesions were more likely to have lymph node upstaging, greater diameter, and higher maximum standardized uptake value. The specificity and sensitivity for detecting the minor presence of micropapillary or solid component using the semi-dry dot-blot method were 94.4% (95% confidence interval, 81.3-99.3) and 65.6% (95% confidence interval, 46.8-81.4), respectively. The average test duration was 26.9 ± 2.5 minutes.

Conclusions: Detecting insulin-like growth factor-binding protein 2 and P-cadherin via the semi-dry dot-blot method could identify micropapillary or solid components in early-stage lung adenocarcinoma in a short processing time.
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http://dx.doi.org/10.1016/j.jtcvs.2018.07.054DOI Listing
December 2018

Catheter-based alternative treatment for early-stage lung cancer with a high-risk for morbidity.

J Thorac Dis 2018 Jun;10(Suppl 16):S1864-S1870

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

The mainstream treatment modality for early stage non-small cell lung cancer (NSCLC) is surgery; however, many patients are deemed inoperable and warrant alternative therapeutic options. Several minimally invasive catheter-based therapies are emerging as viable alternatives. In this review, we evaluate the outcomes from radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (CRA) and photodynamic therapy (PDT) for early-stage lung cancer. Novel technical developments have allowed for endobronchial thermal ablation to be conducted in a hybrid theatre setting, which may optimize treatment outcomes and minimise treatment-related complications.
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http://dx.doi.org/10.21037/jtd.2018.03.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035930PMC
June 2018

Video-assisted thoracic surgery for tiny pulmonary nodules with real-time image guidance in the hybrid theatre: the initial experience.

J Thorac Dis 2018 May;10(5):2933-2939

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Background: Localization of tiny lung nodules during video-assisted thoracic surgery (VATS) resection can be challenging. Real-time image-guided hookwire localization of the target lesions immediately followed by VATS lung resection in the hybrid operating theatre setting is an emerging approach.

Methods: We retrospectively reviewed our experience with this form of hybrid operating theatre image-guided VATS (iVATS) for lung nodules 1.5 cm or less, or soft in consistency. These patients were compared with matched cohort who received standard hookwire localization in the radiology department.

Results: From February 2014 to September 2017, lung nodules of indeterminate nature in 32 consecutive patients with mean size 9.1±4.6 mm underwent iVATS. All were accurately localized by hookwire and successfully resected. There was no postoperative mortality. There were 21 (66%) malignant lesions, all with adequate resection margins. Major outcomes were compared with a comparable cohort of 8 patients who received standard hookwire localization and VATS (sVATS) performed at separate departments operation suites. sVATS groups has significantly longer 'at-risk' period for pneumothorax progression and hookwire dislodgement (109.5±57.1 minutes for sVATS 41.1±15.0 minutes for iVATS, P=0.011), and a higher risk of hookwire dislodgement (25% for sVATS 0 for iVATS, P=0.036).

Conclusions: Real-time image-guided hookwire localization in the hybrid theatre setting is an effective facilitator of VATS resection of tiny lung nodules in selected patients, and may have added advantages in terms of safety and localization accuracy over the conventional sVATS method.
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http://dx.doi.org/10.21037/jtd.2018.05.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006094PMC
May 2018