Video-assisted thoracoscopic surgery as the gold standard for lung cancer surgery.

Surgical resection remains the only effective means of cure in the vast majority of patients with early-stage lung cancer. It can be performed via a traditional open approach (particularly thoracotomy) or a minimally invasive approach. VATS is 'keyhole' surgery in the chest, and was first used for lung cancer resection in the early 1990s. Since then, a large volume of evolving clinical evidence has confirmed that VATS lung cancer resection offered proven safety and feasibility, better patient-reported post-operative outcomes, less surgical trauma as quantified by objective outcome measures and equivalent or better survival than open surgery. This has firmly established VATS as the surgical approach of choice for early-stage lung cancer today. Although impressive new non-surgical lung cancer therapies have emerged in recent years, VATS is also being constantly rejuvenated by the development of 'next generation' VATS techniques, the refinement of VATS sublobar resection for selected patients, the utilization of bespoke post-operative recovery programmes for VATS and the synthesis of VATS into multi-modality lung cancer therapy. There is little doubt that VATS will remain as the gold standard for lung cancer surgery for the foreseeable future.

The Advent of Ultra-high Volume Thoracic Surgical Centers in Shanghai.

BACKGROUND: A core principle in surgery is that high surgical volumes are conducive toward better outcomes. Ultra-high volume centers (UHVCs) have now emerged in thoracic surgery in China that now perform a volume of thoracic operations far greater than even traditional international centers of excellence. METHODS: In 2016, two hospitals in Shanghai performed over 10,000 major pulmonary, esophageal and mediastinal resections each. A qualitative analysis of the lessons learned in achieving such large operation volumes was undertaken. RESULTS: The advent of these UHVCs gives important insights for not only thoracic surgeons, but for surgical oncologists and surgeons globally. First, these ultra-high volumes were achieved to a large degree by cancer screening-but the success of the screening programs relies on reaching wider patient groups and allowing for affordable 'self-screening.' Second, the ultra-high clinical volumes at UHVCs offer unique opportunities for surgical training and research, potentially changing paradigms for academic surgery. Third, these ultra-high volumes may place new stresses on existing healthcare resources and prompt novel management strategies in response. CONCLUSIONS: The UHVCs represent a revolutionary development in modern surgery, and it behooves surgeons to both accept the challenges and harness the advantages they may bring.

Plasma miR-940 may serve as a novel biomarker for gastric cancer.

It was reported that circulating microRNAs could be applied as non-invasive biomarkers for cancer monitoring. The purpose of this study was to identify plasma miRNA that may serve as a novel biomarker for gastric cancer and to evaluate its clinical application. MicroRNA profiles were generated from plasma samples of 5 patients with gastric cancer (GC) versus 5 healthy controls (HC). MicroRNA-940 (miR-940) was one of the most downregulated miRNAs with fold change of 0.164. It was revealed that the expression of miR-940 was downregulated in both the initial set (N = 30, P < 0.0001) and the validation set (N = 80, P < 0.0001) of plasma samples of patients with gastric cancer. The sensitivity was obviously higher than the current biomarkers CEA and CA19-9 (81.25 % vs. 22.54 % and 15.71 %). MiR-940 was also significantly downregulated in gastric cancer tissue samples (N = 34, P = 0.0015), as well as in cancer cell lines (N = 7). Importantly, miR-940 was significantly highly expressed in stomach tissue samples than in other types of tissue samples including the liver, breast, thyroid, and lung. Moreover, there was a trend of lower expression of miR-940 from early to advanced stage of gastric cancer. Target prediction suggested that miR-940 regulated cell signaling including NF-κB and Wnt/ß-catenin, as well as pathways of cell communication and adhesion. These pathways play critical roles in gastric cancer initiation and progression. It is the first report that miR-940 may mainly express in the stomach. Downregulation of plasma miR-940 may serve as a novel biomarker for detection of gastric cancer.

Thoracoscopic segmentectomy for trans-fissure ground-glass opacity.

OBJECTIVES: The trans-fissure ground-glass opacity (GGO) is a special category of lesions, with a diameter always exceeding 2 cm. It is located on a fused fissure, 'seizing' 2 neighbouring lobes simultaneously. The segmentectomy for the trans-fissure GGO is never reported. METHODS: Between August 2016 and December 2022, patients operated with a trans-fissure GGO were included. The patients' backgrounds and surgical data were summarized. All procedures were performed with the help of preoperative three-dimensional computed tomography bronchography and angiography. RESULTS: A total of 84 patients were included. The selection criteria included a consolidation tumour ratio <50% and a lesion size >2 and ≤3 cm. Thirty-six patients were operated with lobectomy + wedge (the traditional method group) and 48 patients were operated with anatomical segmentectomy + function-preserving sublobectomy (the new method group). The median operative time was 87 min in the traditional group and 98 min in the new method group, and the median blood loss was 60 ml in the traditional group and 70 ml in the new method group. The median duration of hospital stays was 4 days in the traditional group and 2 days in the new method group. In the traditional method group, there was 1 case of postoperative air leakage and 5 cases of haemoptysis. In the new method group, 2 cases of postoperative air leakage were identified. The median size of the tumour in the resected segment was 2.6 cm in the traditional group and 2.5 cm in the new method group. The median margin was 2.5 cm in the traditional group and 3.3 cm in the new method group. CONCLUSIONS: The trans-fissure GGO could be safely resected en bloc by segmentectomy with a well-designed surgical procedure and appropriate preoperative planning.

Real-world first round results from a charity lung cancer screening program in East Asia.

Background: Screening with low-dose computed tomography (LDCT) has been proven to potentially reduce the rate of mortality of lung cancer. Lack of real-world data outside of protocolized trials has been cited as an impediment to its more widespread implementation, especially in Asia. This report aims to provide such real-world data. Methods: A single round of LDCT was provided through a community-based charity program in Hong Kong, China to asymptomatic adults with a family history of lung cancer and/or smoking history. Anonymized data from this program were analyzed. Results: LDCT was performed for 99 participants, including 98 (99%) who had one or more family members with history of lung cancer, and 70 (71%) who were never-smokers. After a single round of screening, a positive LDCT was noted in 47 participants (47%). A sister with a history of lung cancer (28% vs. 8%, P=0.01) and a multiplex family (MF) (47% vs. 23%, P=0.02) were factors associated with a positive LDCT. After a median period of 10 months (range, 5-16 months) following LDCT, lung cancer (all adenocarcinoma) was diagnosed as a direct consequence of positive LDCT findings in six participants (6%), of whom four had stage I disease and five received surgery with curative intent. In the 47 participants with a positive LDCT, having a sister with a history of lung cancer was associated with an increased risk of lung cancer (relative risk =5.23; 95% confidence interval: 1.09-25.21). Detected lesions categorized as Lung Imaging Reporting and Data System (Lung-RADS) 3 or above (odds ratio =12.08; 95% confidence interval: 1.27-114.64) or deemed by an experienced specialist to be suspicious (odds ratio =63.33; 95% confidence interval: 5.48-732.29) were significantly more likely to turn out to be a lung cancer. Conclusions: This real-world data demonstrates that a single round of LDCT screening at a community level in East Asia can detect potentially curable lung cancer at a rate comparable to those reported by protocolized trials. When considering future LDCT screening programs in East Asia, a family history of lung cancer may be a key factor indicating a person for screening, and how features of a LDCT-detected lesion should trigger further intervention warrant further definition.

Resectable non-stage IV nonsmall cell lung cancer: the surgical perspective.

Surgery remains an essential element of the multimodality radical treatment of patients with early-stage nonsmall cell lung cancer. In addition, thoracic surgery is one of the key specialties involved in the lung cancer tumour board. The importance of the surgeon in the setting of a multidisciplinary panel is ever-increasing in light of the crucial concept of resectability, which is at the base of patient selection for neoadjuvant/adjuvant treatments within trials and in real-world practice. This review covers some of the topics which are relevant in the daily practice of a thoracic oncological surgeon and should also be known by the nonsurgical members of the tumour board. It covers the following topics: the pre-operative selection of the surgical candidate in terms of fitness in light of the ever-improving nonsurgical treatment alternatives unfit patients may benefit from; the definition of resectability, which is so important to include patients into trials and to select the most appropriate radical treatment; the impact of surgical access and surgical extension with the evolving role of minimally invasive surgery, sublobar resections and parenchymal-sparing sleeve resections to avoid pneumonectomy.

Pathologic classification of adenocarcinoma of lung.

Recently, the 1999/2004 World Health Organization (WHO) classification of adenocarcinoma became less useful from a clinical standpoint as most adenocarcinomas belonged to the mixed subtype and the term bronchioloalveolar carcinoma (BAC) gave rise to much confusion among clinicians. For these reasons a new adenocarcinoma classification was introduced in 2011 by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS). This represents an international, multidisciplinary effort joining pathologists, molecular biologists, pulmonary physicians, thoracic oncologists, radiologists, and thoracic surgeons. Currently, a distinction is made between pre-invasive lesions, minimally invasive and invasive lesions. The confusing term BAC is not used anymore and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Several aspects of this classification are discussed with main emphasis on its correlation with imaging techniques and its impact on diagnosis, treatment and prognosis. On chest computed tomography (CT) a distinction is made between solid and subsolid nodules, the latter comprising ground glass opacities (GGO), and partly solid lesions. Several studies incorporating CT and positron emission tomographic (PET) data show a good imaging-pathologic correlation. With the implementation of screening programs early lung cancer has become a hotly debated topic and sublobar resection is currently reconsidered for early lesions without lymph node involvement. This new classification will also have an impact on the TNM classification. Thoracic surgeons will continue to play a major role in the application, evaluation and further refinement of this new adenocarcinoma classification.

Transition from multiportal video-assisted thoracic surgery to uniportal video-assisted thoracic surgery and evolution to uniportal robotic-assisted thoracic surgery?

The greatest disruptive innovation in lung cancer surgery in modern times has been the switch from open thoracotomy to video-assisted thoracic surgery (VATS). More recently, the transition from multiportal VATS (MVATS) to uniportal VATS (UVATS) has represented another mini-advance in reducing surgical access trauma. In the search for the next breakthrough in lung cancer surgery, a number of promising candidates have emerged, including screening, sublobar resections, 3D technology, enhanced peri-operative care pathways, ablative therapy and multi-modality management. However, could the way forwards be simply a further minimization of surgical access trauma, and could this be achieved by uniportal robotic surgery? Emergence of a 'winning' candidate will depend on a systematic evaluation of the evidence for the benefits and costs of each.

Synergistic markers based on inter-covariate association estimate treatment option with lower propensity to covariates.

Background: Propensity constitutes a common problem in identifying clinical outcome prediction model whose covariates include the treatment option, which is assumed to be randomly assigned but indeed dependent of other covariates in the training data. The genuine effect of treatment option cannot be elucidated under the influence of propensity. Existing approaches, such as matched-pairs study design, still cannot solve the problem for imbalanced or small datasets. Methods: This work proposed an anti-propensity estimate of treatment option, which is generated by support vector classifier based on two synergistic markers that represent the lower and upper limits of inter-covariate association level. The algorithm for generating the synergistic markers was illustrated and the performance was evaluated on a public dataset of gene expression levels, which were obtained from surgically excised tumor samples in non-small cell lung cancer (NSCLC) patients where treatment option, i.e., adjuvant therapy or not, was known. Results: Six covariates represented by the expression levels of ZNF217, ERCC3, PMS1, PIK3CB, BARD1, and MAPK1, were selected to generate two synergistic markers and classifier for estimating the adjuvant therapy option with substantially attenuated propensity. The estimation accuracy attained an area under the receiver-operating characteristics curve, 0.78, in the test set. Conclusions: The proposed synergistic markers demonstrated a parsimonious and anti-propensity estimation of treatment option, which is ready for the further evaluation and application in the clinical outcome prediction model.

The SUPER reporting guideline suggested for reporting of surgical technique: explanation and elaboration.

Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.

Reporting guidelines for surgical technique could be improved: a scoping review and a call for action.

OBJECTIVES: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement. STUDY DESIGN AND SETTING: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021. RESULTS: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description. CONCLUSION: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change.

The SUPER reporting guideline suggested for reporting of surgical technique.

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

Tissue tropism of swine influenza viruses and reassortants in ex vivo cultures of the human respiratory tract and conjunctiva.

The 2009 pandemic influenza H1N1 (H1N1pdm) virus was generated by reassortment of swine influenza viruses of different lineages. This was the first influenza pandemic to emerge in over 4 decades and the first to occur after the realization that influenza pandemics arise from influenza viruses of animals. In order to understand the biological determinants of pandemic emergence, it is relevant to compare the tropism of different lineages of swine influenza viruses and reassortants derived from them with that of 2009 pandemic H1N1 (H1N1pdm) and seasonal influenza H1N1 viruses in ex vivo cultures of the human nasopharynx, bronchus, alveoli, and conjunctiva. We hypothesized that virus which can transmit efficiently between humans replicated well in the human upper airways. As previously reported, H1N1pdm and seasonal H1N1 viruses replicated efficiently in the nasopharyngeal, bronchial, and alveolar epithelium. In contrast, representative viruses from the classical swine (CS) (H1N1) lineage could not infect human respiratory epithelium; Eurasian avian-like swine (EA) (H1N1) viruses only infected alveolar epithelium and North American triple-reassortant (TRIG) viruses only infected the bronchial epithelium albeit inefficiently. Interestingly, a naturally occurring triple-reassortant swine virus, A/SW/HK/915/04 (H1N2), with a matrix gene segment of EA swine derivation (i.e., differing from H1N1pdm only in lacking a neuraminidase [NA] gene of EA derivation) readily infected and replicated in human nasopharyngeal and bronchial epithelia but not in the lung. A recombinant sw915 with the NA from H1N1pdm retained its tropism for the bronchus and acquired additional replication competence for alveolar epithelium. In contrast to H1N1pdm, none of the swine viruses tested nor seasonal H1N1 had tropism in human conjunctiva. Recombinant viruses generated by swapping the surface proteins (hemagglutinin and NA) of H1N1pdm and seasonal H1N1 virus demonstrated that these two gene segments together are key determinants of conjunctival tropism. Overall, these findings suggest that ex vivo cultures of the human respiratory tract provide a useful biological model for assessing the human health risk of swine influenza viruses.

The future of Asian Cardiovascular Annals: Goals and quality.

The positional statement of the Asian Cardiovascular and Thoracic Annals is presented.

Expert consensus on indocyanine green fluorescence imaging for thoracoscopic lung resection (The Version 2022).

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the Chinese Guidelines on Video-assisted Thoracoscopy, and the National Comprehensive Cancer Network (NCCN) guidelines on the management of pulmonary lesions. Each of the statements was discussed and agreed upon with a unanimous consensus amongst the panel. A total of 6 consensus statements were developed. Fluorescence-guided thoracoscopy has unique advantages in the visualization of pulmonary nodules, and recognition and resection of the anterior plane of the pulmonary segment. The expert panel agrees that fluorescence-guided thoracoscopic surgery has the potential to become a routine operation for the treatment of pulmonary lesions.

A novel KIF5B-ALK variant in nonsmall cell lung cancer.

BACKGROUND: The anaplastic lymphoma kinase (ALK) gene is involved frequently in chromosomal translocations, resulting in fusion genes with different partners found in various lymphoproliferative conditions. It was recently reported in nonsmall cell lung cancer (NSCLC) that the fusion protein encoded by echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene conferred oncogenic properties. The objective of the current study was to identify other possible ALK fusion genes in NSCLC. METHODS: Immunohistochemical analysis was used to screen for aberrant ALK expression in primary NSCLC. The authors used 5' rapid amplification of complementary DNA ends to screen for potential, novel 5' fusion partners of ALK other than EML4-ALK. Reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization analyses were used to confirm the identity of 5' fusion partners. The genomic breakpoint was verified using genomic sequencing. Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4-ALK was performed to assess downstream signaling and functional effects. RESULTS: The authors identified a novel gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 15 to ALK exon 20 in a primary lung adenocarcinoma. Western blot analysis of clinical tumor tissues revealed the expression of a protein whose size correlated with that of the predicted KIF5B-ALK. Overexpression of KIF5B-ALK in mammalian cells led to the activation of signal transducer and activator of transcription 3 and protein kinase B and to enhanced cell proliferation, migration, and invasion. CONCLUSIONS: The discovery of the novel KIF5B-ALK variant further consolidated the role of aberrant ALK signaling in lung carcinogenesis.

Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract.

The novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited by pandemic H1N1pdm and seasonal H1N1 influenza viruses in ex vivo cultures of human conjunctiva, nasopharynx, bronchus, and lung, as well as in vitro cultures of human nasopharyngeal, bronchial, and alveolar epithelial cells. We found comparable replication and host-responses in seasonal and pandemic H1N1 viruses. However, pandemic H1N1pdm virus differs from seasonal H1N1 influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in its receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection with H1N1pdm. A greater viral replication competence in bronchial epithelium at 33 degrees C may also contribute to the slight increase in virulence of the pandemic influenza virus. In contrast with highly pathogenic influenza H5N1 virus, pandemic H1N1pdm does not differ from seasonal influenza virus in its intrinsic capacity for cytokine dysregulation. Collectively, these results suggest that pandemic H1N1pdm virus differs in modest but subtle ways from seasonal H1N1 virus in its intrinsic virulence for humans, which is in accord with the epidemiology of the pandemic to date. These findings are therefore relevant for understanding transmission and therapy.