Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure. However, ischemia–reperfusion injury (IRI) inevitably occurs after lung transplantation. ...The most severe form of IRI leads to primary graft failure, which is an important cause of morbidity and mortality after lung transplantation. IRI may also induce rejection, which is the main cause of mortality in recipients. Despite advances in donor management and graft preservation, most donor grafts are still unsuitable for transplantation. Although the pulmonary endothelium is the primary target site of IRI, the pathophysiology of lung IRI remains incompletely understood. It is essential to understand the mechanism of pulmonary IRI to improve the outcomes of lung transplantation. Therefore, we reviewed the state-of-the-art in the management of pulmonary IRI after lung transplantation. Recently, the ex vivo lung perfusion (EVLP) system has been clinically introduced worldwide. Various promising therapeutic strategies for the protection of the endothelium against IRI, including EVLP, inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, and mesenchymal stromal cell therapy, are awaiting clinical application. We herein review the latest advances in the field of pulmonary IRI in lung transplantation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum‐based chemotherapy in patients with resected stage IB–IIIA non‐small cell lung ...cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin‐based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator‐assessed disease‐free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death‐ligand 1 (PD‐L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention‐to‐treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all‐randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD‐L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease‐free survival improvement with atezolizumab vs BSC was observed in the PD‐L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio HR, 0.52; 95% confidence interval CI, 0.25–1.08), all‐randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab‐related grade 3/4 adverse events occurred in 16% of patients; no treatment‐related grade 5 events occurred. Adjuvant atezolizumab showed disease‐free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
This manuscript reports a subgroup analysis of Japanese patients in the global phase 3 IMpower010 study evaluating adjuvant atezolizumab vs best supportive care (BSC) following platinum‐based chemotherapy in resected stage IB‐IIIA non‐small cell lung cancer. Disease‐free survival (DFS) improvement with atezolizumab versus BSC was observed in the Japanese stage II‐IIIA population with PD‐L1 expression on ≥1% of tumor cells; in the Japanese all‐randomized stage II‐IIIA and ITT (stage IB‐IIIA) populations, unstratified DFS hazard ratios favored atezolizumab vs BSC. Adjuvant atezolizumab had a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lung cancer is the leading cause of death and the second most prevalent cancer worldwide. Recent improvements in radiological technologies enable the early detection of lung cancer. A minimally ...invasive approach has become a standard therapy for early-stage lung cancer, and therefore, the need for preoperative and intraoperative simulations has increased. Software evolution has broadened the possibilities of three-dimensional (3D) reformatting of computed tomography (CT), resulting in the wide use of 3D CT images in thoracic surgery. However, several issues need to be resolved for future improvement in current 3D CT imaging, such as the necessity of contrast-enhanced CT, the limitation of describing small branches of pulmonary vessels, and the static images not coping with surgical or deflated deformation. This narrative review summarizes the current situation and concerns of 3D CT imaging and its history and explores novel strategies to solve these issues. Radiologic reconstruction technology allows the wide use of three-dimensional (3D) computed tomography (CT) images in thoracic surgery. A minimally invasive surgery has become one of the standard therapies in thoracic surgery, and therefore, the need for preoperative and intraoperative simulations has increased. Three-dimensional CT images have been extensively used, and various types of software have been developed to reconstruct 3D-CT images for surgical simulation worldwide. Several software types have been commercialized and widely used by not only radiologists and technicians, but also thoracic surgeons. Three-dimensional CT images are helpful surgical guides; however, in almost all cases, they provide only static images, different from the intraoperative views. Lungs are soft and variable organs that can easily change shape by intraoperative inflation/deflation and surgical procedures. To address this issue, we have developed a novel software called the Resection Process Map (RPM), which creates variable virtual 3D images. Herein, we introduce the RPM and its development by tracking the history of 3D CT imaging in thoracic surgery. The RPM could help develop a real-time and accurate surgical navigation system for thoracic surgery.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer ...surgery, which were identified by our previous prospective observational study.
Methods
Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed.
Results
Between 2014 and 2017, 564 patients (
n
= 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27–2.92, 2.01–5.58, 3.64–23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively.
Conclusions
Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region ...and identified the Y‐box as a cis‐acting element. As a parallel analysis of database records for 149 non–small‐cell lung cancer (NSCLC) cancer patients, we screened for trans‐acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer‐binding protein γ (CEBPγ) or Y‐box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide‐dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y‐box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.
Schematic illustration showing CEBPγ functions for cancer cell migration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and objective
Bronchoscopy is an airborne particle‐generating procedure. However, few methods for safe bronchoscopy have been developed. To reduce airborne particles during bronchoscopy, ...we created an ‘e‐mask’, which is a simple, disposable mask for patients. Our objective was to evaluate the e‐mask's protective ability against airborne particles and to assess respiratory adverse events and complications.
Methods
Patients with stage 2–4 chronic obstructive pulmonary disease were excluded. We performed visualization and quantifying experiments on airborne particles with and without the e‐mask. We prospectively evaluated whether wearing the e‐mask during bronchoscopy was associated with the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, and patients with >45 mm Hg end‐tidal carbon dioxide (EtCO2) elevation, in addition to complications, compared to historical controls.
Results
In the visualization experiment, more than ten thousand times of airborne particles were generated without the e‐mask than with the e‐mask. The volume of airborne particles was significantly reduced with the e‐mask, compared to that without the e‐mask (p = 0.011). Multivariate logistic regression analysis revealed that wearing the e‐mask had no significant effect on the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, (p = 0.959); however, wearing the e‐mask was a significant factor in >45 mm Hg EtCO2 elevation (p = 0.026). No significant differences in complications were observed between the e‐mask and control groups (5.8% vs. 2.5%, p = 0.395).
Conclusion
Wearing the e‐mask during bronchoscopy significantly reduced the generation of airborne particles during bronchoscopy without increasing complications.
A new type of endoscopic mask (e‐mask) reduced the number and volume of dispersed airborne particles during bronchoscopy. No significant differences in adverse events or complications during bronchoscopy were observed between the use of the e‐mask and a patient wearing no mask, supporting its enhanced protection and safety during bronchoscopy.
See related Editorial
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The coverage technique using absorbable mesh was first described in a European guideline published in 2015 as a preventive method for the recurrence of spontaneous pneumothorax. We performed a ...meta-analysis based on a literature search of primary studies that compared the postoperative recurrence rate of primary spontaneous pneumothorax between the use and nonuse of polyglycolic acid sheet coverage. Two reviewers independently selected and evaluated the quality of the relevant studies. The risk ratio in each study was calculated in a random-effect meta-analysis. Statistical heterogeneity among the included studies was quantitatively evaluated using the I
index, and publication bias was assessed using a funnel plot. A total of 19 retrospective cohort studies were analyzed: 1524 patients who underwent wedge resection alone (the control group) and 1579 who received additional sheet coverage. Polyglycolic acid sheet coverage was associated with a lower recurrence rate than that in the control group (risk ratio: 0.27, 95% confidence interval 0.20-0.37, P < 0.001; I
0%). The funnel plot suggested possible publication bias. The covering technique reduced the recurrence rate of pneumothorax after thoracoscopic surgery to one-fourth.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Postoperative loss of exercise capacity and pulmonary function is a major concern among lung cancer patients. In this study, the time for a stair‐climbing to 12‐m height was used to ...investigate whether preoperative chest 3D‐computed tomography (CT) could be a useful tool for predicting postoperative variations in exercise capacity and pulmonary function.
Methods
Seventy‐eight patients undergoing lobectomy for suspected stage I lung cancer were prospectively enroled. Preoperatively, lobe volume and low attenuation volume (LAV) were evaluated using the SYNAPSE VINCENT system. Preoperative data on stair‐climbing time, spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) at baseline and 6‐month postoperative data were used to evaluate variations in exercise capacity and pulmonary function. Maximal oxygen uptake (VO2t) was evaluated based on the stair‐climbing time.
Results
Significant differences in the variation of exercise capacity at 6 months postoperatively were found between the groups categorized by target lobe volume and LAV status: The large volume/LAV (+) group had a greater decline in VO2t. Mean loss of VO2t was −6.2%, −1.4%, −1.6% and −0.1% in the large volume/LAV (+), large volume/LAV (−), small volume/LAV (+) and small volume/LAV (−) groups, respectively. The large volume/LAV (−) group had a greater decline in forced expiratory volume in 1 s. The small volume/LAV (+) group showed a reduced decline in the DLCO.
Conclusions
Analysis of chest 3D‐CT scans is a potential tool for predicting the loss of exercise capacity and pulmonary function after lung lobectomy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Psoas muscle mass is a surrogate marker for sarcopenia: a depletion of skeletal muscle mass. This study was conducted to elucidate the prognostic significance of the psoas muscle index ...(PMI: cross-sectional area of the bilateral psoas muscle at the umbilical level on computed tomography/height
2
cm
2
/m
2
) in patients undergoing surgery for lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC).
Methods
One hundred and sixty-five patients with SCC and 556 patients with ADC who underwent R0 resection between 2007 and 2014 were reviewed for analysis. In SCC patients, the mean value (standard deviation) of the PMI was 6.15 (1.49) in men and 4.65 (1.36) in women. Among ADC patients, the PMI was 7.12 (1.60) in men and 5.29 (1.22) in women. Clinicopathological characteristics as well as the survival were evaluated.
Results
The PMI was associated with the age, body mass index (BMI), and serum albumin. In the multivariable Cox regression analysis, after adjusting for age, BMI, serum albumin, sex, pathological stage, and diffusing capacity for carbon monoxide, the PMI showed a significant association with the overall survival (OS) and disease-free survival (DFS) in SCC patients (hazard ratios 0.50 and 0.56, 95% confidence intervals 0.39–0.65 and 0.45–0.71, respectively). On the other hand, in ADC patients, the PMI had no impact on the OS or DFS.
Conclusions
The PMI was significantly associated with the survival of lung SCC patients, but not of lung ADC patients, suggesting the presence of a previously unidentified relationship between skeletal muscle and lung SCC progression.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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