Publications by authors named "Noriaki Sakakura"

69 Publications

Novel strategy to treat lung metastases: Hybrid therapy involving surgery and radiofrequency ablation.

Thorac Cancer 2021 Jun 9. Epub 2021 Jun 9.

Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: This study was performed to evaluate the clinical outcomes of hybrid treatment involving surgical resection and percutaneous radiofrequency ablation for patients with multiple lung metastases.

Methods: Seventeen patients (6 men, 11 women; median age, 52 years; range, 16-78 years) underwent hybrid treatment involving surgery and radiofrequency ablation to treat multiple lung metastases (median number, 4; range, 2-26) between May 2014 and February 2020. The primary lesions were colorectal carcinoma (n = 9), uterine endometrial carcinoma (n = 3), osteosarcoma (n = 2), renal cell carcinoma (n = 1), glottic carcinoma (n = 1), and fibrolamellar hepatocellular carcinoma (n = 1). Twenty-four sessions each of surgery and radiofrequency ablation were performed. Safety, disease-free survival, and overall survival were evaluated. Safety was assessed according to the Clavien-Dindo Classification.

Results: A grade IVa adverse event of empyema developed in one patient (4%, 1/24) after surgery. A grade IIIa adverse event of pneumothorax and a grade II adverse event of lung abscess occurred in four (17%, 4/24) and one session (4%, 1/24) after radiofrequency ablation, respectively. During the median follow up of 34 months (range, 8-67 months), 10 patients (59%, 10/17) developed new metastases. The 5-year disease-free survival rate was 32%. Four or fewer lung metastases (p = 0.008) and metastases from colorectal carcinoma (p = 0.02) were factors significantly associated with longer disease-free survival. One patient (6%, 1/17) died of tumor progression 29 months after initial treatment. The 5-year overall survival rate was 88%.

Conclusions: The strategy of hybrid treatment involving surgery and radiofrequency ablation may offer good outcomes for patients with multiple lung metastases.
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http://dx.doi.org/10.1111/1759-7714.14041DOI Listing
June 2021

Clinical Guideline-Guided Outcome Consistency for Surgically Resected Stage III Non-Small Cell Lung Cancer: A Retrospective Study.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Thoracic Oncology, Aichi Cancer Center, Nagoya 464-8681, Japan.

Clinical guidelines can help reduce the use of inappropriate therapeutics due to localism and individual clinician perspectives. Nevertheless, despite the intention of clinical guidelines to achieve survival benefit or desirable outcomes, they cannot ensure a robust outcome. This retrospective study aimed to investigate whether guideline-consistency, including adjuvant treatments after surgical resection (ATSR) and guideline-matched first-line treatment for recurrence (GMT-R), according to the genomic profiles and immune status, could influence overall survival (OS). From 2006 to 2017, the clinical data of 308 patients with stage III non-small cell lung cancer (NSCLC) after surgical resection were evaluated. ATSR and GMT-R were allowed in 164 (53.2%) and 129 (62.3%) patients cases after surgical pulmonary resection, among which 207 (67.2%) recurrences were identified. The 5-year OS in guideline-consistent cases was significantly better than that in guideline-inconsistent cases ( < 0.01). Subgroup analyses further showed that the 5-year OS after propensity adjustment was significantly better in guideline-consistent than in guideline-inconsistent cases ( < 0.01), but not in either ATSR or GMT-R ( = 0.24). These data suggest that the guideline-consistent alternatives, which comprise ATSR or GMT-R, can contribute to survival benefits in pathological stage III NSCLC. However, only either ATSR or GMT-R has a potential survival benefit in these patients.
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http://dx.doi.org/10.3390/cancers13112531DOI Listing
May 2021

Robotic open-thoracotomy-view approach using vertical port placement and confronting monitor setting.

Interact Cardiovasc Thorac Surg 2021 May 11. Epub 2021 May 11.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Objectives: Robotic lung resections (RLRs) are conventionally performed using look-up views of the thorax from the caudal side. To conduct RLR with views similar to those in open thoracotomy, we adopted a vertical port placement and confronting upside-down monitor setting, which we called robotic 'open-thoracotomy-view approach'. We herein present our experience of this procedure.

Methods: We retrospectively reviewed 58 patients who underwent RLR (43 with lobectomy; 15 with segmentectomy) with 3-arm open-thoracotomy-view approach using the da Vinci Surgical System between February 2019 and October 2020. The patient cart was rolled in from the left cranial side of the patient regardless of the side to be operated on. Robotic ports were vertically placed along the axillary line, and 2 confronting monitors and 2 assistants were positioned on each side of the patient. The right-side monitor, which was set up for the left-side assistant to view, projected the upside-down image of the console surgeon's view.

Results: All procedures were safely performed. The median duration of surgery and console operation was 215 and 164 min, respectively. Emergency conversion into thoracotomy and severe morbidities did not occur, and the median postoperative hospitalization duration was 3 days. In all procedures, the console surgeon and 2 assistants had direct 'bird-eye' views of the cranially located intrathoracic structures and instrument tips, which are sometimes undetectable with the conventional look-up view.

Conclusions: The open-thoracotomy-view approach setting is a possible option for RLR. It offers natural thoracotomy views and can circumvent some of the known limitations of the conventional procedure.
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http://dx.doi.org/10.1093/icvts/ivab033DOI Listing
May 2021

Sarcopenia is poor risk for unfavorable short- and long-term outcomes in stage I non-small cell lung cancer.

Ann Transl Med 2021 Feb;9(4):325

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Background: Sarcopenia characterized by skeletal muscle loss may influence postoperative outcomes through physical decline and weakened immunity. We aimed to investigate clinical significance of sarcopenia in resected early-stage non-small cell lung cancer (NSCLC).

Methods: We retrospectively reviewed 315 consecutive patients with pathologic stage I NSCLC who had undergone lobectomy with systematic nodal dissection. Sarcopenia was defined as the lowest quartile of psoas muscle area on the 3rd vertebra on the high-resolution computed tomography (HRCT) image. Clinicopathological variables were used to investigate the correlation to postoperative complications as well as overall and recurrence-free survival.

Results: Upon multivariable analysis, male sex [odds ratio (OR) =5.780, 95% confidence interval (CI): 2.681-12.500, P<0.001], and sarcopenia (OR =21.00, 95% CI: 10.30-42.80, P<0.001) were independently associated with postoperative complications. The sarcopenia group showed significantly lower 5-over all survival (84.4% 69.1%, P<0.001) and recurrence-free survival (77.2% 62.0%, P<0.001) comparing with the non-sarcopenia group. In a multivariable analysis, sarcopenia was an independent prognostic factor [hazard ratio (HR) =1.978, 95% CI: 1.177-3.326, P=0.010] together with age ≥70 years (HR =1.956, 95% CI: 1.141-3.351, P=0.015) and non-adenocarcinoma histology (HR =1.958, 95% CI: 1.159-3.301, P=0.016).

Conclusions: This is the first study which demonstrates that preoperative sarcopenia is significantly associated with unfavorable postoperative complications as well as long-term survival in pathologic stage I NSCLC. This readily available factor on HRCT may provide valuable information to consider possible choice of surgical procedure and perioperative management.
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http://dx.doi.org/10.21037/atm-20-4380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944314PMC
February 2021

Subsegmental resection preserves regional pulmonary function: A focus on thoracoscopy.

Thorac Cancer 2021 04 14;12(7):1033-1040. Epub 2021 Feb 14.

Department of Surgery, Division of Thoracic Surgery, The Teikyo University, Tokyo, Japan.

Background: The aim of this study was to evaluate regional postoperative preserved pulmonary function (PPPF) and three-dimensional (3D) volumetric changes according to the number of resected subsegments and investigate the factors that most affected pre-/post PPPF.

Methods: Patients who underwent thoracoscopic lobectomy (n = 73), and segmentectomy (n = 87) were eligible for inclusion in the study. They were classified according to the number of resected subsegments which ranged from 1 to 10. The percentage of pre-/postoperative forced expiratory volume in 1 s (FEV1) was used for comparison. Furthermore, lung volumetric changes were calculated using 3D computed tomography (CT) volumetry.

Results: The percentage of pre-/postoperative EFV1 between 4 and 5-7 and between 5-7 and 10 were significant (p = 0.03 and p < 0.01, respectively), but not between 1-2 to 4 (p = 0.99). The difference between volumetric changes in the left lower lobe of patients with a number of resected subsegments was significant (p < 0.01). On univariate and multivariate analyses, chronic inflammation was significant for decrease in recovery percentages. When the PPPF was compared among resected subsegments, it gradually decreased with an increase in the number of patients without a postoperative procrastination of inflammation (p < 0.01).

Conclusions: Segmentectomy is feasible and useful for PPPF. Even a relatively large-volume resection procedure where 5-7 subsegments are resected can preserve pulmonary function. Chronic inflammation was statistically identified as a risk factor for postoperative preserved pulmonary function.

Key Points: .
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http://dx.doi.org/10.1111/1759-7714.13841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017248PMC
April 2021

Comparison of surgical outcomes between thoracoscopic anatomical sublobar resection including and excluding subsegmentectomy.

Gen Thorac Cardiovasc Surg 2021 May 2;69(5):850-858. Epub 2021 Jan 2.

Department of Thoracic Surgery, Aichi Cancer Center, 1-1 Kanokoden Chikusa-ku, Nagoya, 464-8681, Japan.

Objectives: Despite the ubiquitous utilization of anatomical sublobar resection for malignant lung tumors, the effectiveness and feasibility of subsegmentectomy remains unclear. This study therefore compared the perioperative outcomes between anatomical sublobar resection including (IS) and excluding (ES) subsegmentectomy.

Methods: Patients who had undergone anatomical sublobar resection at our institution from January 2013 to March 2019 were retrospectively reviewed. Clinicopathologic characteristics and perioperative outcomes of the IS group (n = 58) were then analyzed the compared to those of the ES group (n = 203).

Results: No statistically significant differences in age, sex, comorbidities, tumor location, preoperative pulmonary function, or tumor size on imaging were found between both groups. The IS group had significantly higher preoperative computed tomography-guided marking rates (40% vs. 18%; p < 0.01) and used significantly more staplers for intersegmental dissection than the ES group [4, interquartile range (IQR): 3-4 vs. 3, IQR: 3-4; p = 0.03]. Both groups had comparable 30-day mortality (0% vs. 0%; p > 0.99), intraoperative complications (7% vs. 10%; p = 0.61), and postoperative complications (5% vs. 8%; p = 0.58). After propensity score matching, the IS group experienced significantly lesser blood loss than the ES group (5 mL, IQR: 1-10 vs. 5 mL, IQR: 5-20; p = 0.03). Both groups experienced no local recurrence and demonstrated similar postoperative pulmonary functions after surgery.

Conclusions: IS may be a feasible and acceptable therapeutic option for malignant lung tumors. Nonetheless, future investigations are required to further validate the current findings.
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http://dx.doi.org/10.1007/s11748-020-01556-3DOI Listing
May 2021

Selection of Pathological N0 (pN0) in Clinical IA (cIA) Lung Adenocarcinoma by Imaging Findings of the Main Tumor.

Ann Thorac Cardiovasc Surg 2020 Dec 18. Epub 2020 Dec 18.

Department of Surgery, Teikyo University Hospital, Tokyo, Japan.

Objectives: We would like to clarify the imaging findings of the main tumor that may omit the requirement for lymph node dissection in clinical IA (cIA) lung adenocarcinoma.

Methods: A total of 336 patients with cIA lung adenocarcinomas with normal preoperative carcinoembryonic antigen (CEA) who underwent surgical resection were analyzed. We investigated the association between various computed tomography (CT) imaging findings or the maximum standardized uptake value (SUVmax) of fluorodeoxyglucose-position emission tomography (FDG-PET) and lymph node metastasis. The maximum tumor diameter was calculated from the CT images using both the lung window setting (LD) and mediastinal window setting (MD). The diameter of the solid component (CD) was defined as consolidation diameter in lung window setting. The solid component ratio (C/T) was defined as CD/LD.

Results: SUVmax, MD, and C/T were independent factors related to lymph node metastasis, but CD was not (p = 0.38). The conditions required for the positive predictive value (PPV) to reach 100% were 10.6 mm for MD, 12.5 mm for CD, and 0.55 for C/T. SUVmax did not reach 100%.

Conclusions: In cIA lung adenocarcinoma with CEA in the normal range, we found that it may be possible for lymph node dissection to be omitted by MD, CD, and C/T.
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http://dx.doi.org/10.5761/atcs.oa.20-00240DOI Listing
December 2020

Clinical adjustability of radiological tools in patients with surgically resected cT1N0-staged non-small-cell lung cancer from the long-term survival evaluation.

J Thorac Dis 2020 Nov;12(11):6655-6662

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Various radiological tools have been introduced to determine the malignancy or prognosis of lung carcinomas. We retrospectively summarized the clinical outcomes to evaluate whether radiological tools such as consolidation-to-tumor ratio (CTR), tumor disappearance ratio (TDR), and mediastinal diameter (MD) are suitable for surgically resected non-small-cell lung cancer (NSCLC).

Methods: This retrospective study included 260 patients (128 men and 132 women; median age, 64 years) with cT1N0-staged NSCLC who underwent thoracotomy. Disease-free survival (DFS) and overall survival (OS) outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards model.

Results: When the adjusted hazard ratios (HRs) with reference to cT1a/1 mi were calculated, significant differences were observed in cT1b and cT1c for DFS (P=0.04 and P<0.01, respectively) and in cT1c for OS (P=0.01). For HRs with reference to CTR (≤0.5), a significant difference was only observed in CTR (>0.5) for DFS (P=0.01). For HRs with reference to TDR (≤25%), significant differences were observed in TDR (>75%) for DFS (P=0.02) and OS (P=0.02). For HRs with reference to MD (≤5 mm), significant differences were observed in 6-20 mm (P=0.04) and >20 mm (P=0.02) for DFS and in >20 mm (P=0.02) for OS.

Conclusions: All radiological tools revealed significant correlations with prognosis in the patients with cT1N0-staged NSCLCs. We recommend the use of MD in a clinical context. However, further investigation of this issue is needed.
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http://dx.doi.org/10.21037/jtd-20-1610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711385PMC
November 2020

Efficacy of Xenon Light With Indocyanine Green for Intersegmental Visibility in Thoracoscopic Segmentectomy.

J Surg Res 2021 03 3;259:39-46. Epub 2020 Dec 3.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address:

Background: We previously reported useful methods that can be implemented to identify intersegmental boundary lines (IBLs) by using an intravenous indocyanine green (ICG) fluorescence imaging system (ICG-FS) during a thoracoscopic anatomical segmentectomy (TAS). The aim of this study was to evaluate the recently released third-generation ICG-FS that features an emphasizing xenon-light source for IBL identification.

Methods: We prospectively studied cases involving 106 consecutive patients who underwent TAS. Intraoperatively, we used the third-generation ICG-FS, the conventional ICG methods (CIM) emphasizing xenon-light (CIM-X), and the spectra-A method (SAM) emphasizing xenon-light (SAM-X), for IBL identification. Furthermore, 16 of the 106 patients (15%) could be simultaneously evaluated using old-generation ICG-FSs, CIM, and SAM. All images were completely quantified for illuminance and for three colors, red, green, and blue.

Results: IBLs were successfully identified in all the patients (100%) with no adverse events. The SAM-X significantly increased the illuminance, especially in the resecting segments, compared to the CIM (39.0 versus 22.2, P < 0.01) and SAM (39.0 versus 29.3, P < 0.01), with enhanced red color compared to the CIM (33.1 versus 21.9, P < 0.01) and SAM (33.1 versus 14.0, P < 0.01). Furthermore, the SAM-X significantly increased the illuminance contrast compared to the CIM-X (34.1 versus 15.3, P < 0.01).

Conclusions: The present study suggests that the SAM-X potentially provided images with the highest visibility and colorfulness compared to the older generation ICG-FSs or CIM-X. Secure IBL identification can be more easily and safely performed using the SAM-X.
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http://dx.doi.org/10.1016/j.jss.2020.11.028DOI Listing
March 2021

Comparison of Surgical Outcomes Between Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma.

Ann Thorac Surg 2020 Nov 23. Epub 2020 Nov 23.

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.

Background: Invasive mucinous adenocarcinoma (IMA) is a rare subtype of invasive lung adenocarcinoma. However, the clinical course and prognostic outcomes following IMA resection, particularly postoperative recurrence, remain unclear.

Methods: We pathologically reevaluated 1362 lung adenocarcinoma resections performed at our institution, categorizing cases into the IMA group (72 cases) and non-IMA group (1290 cases). The IMA group was further classified into pneumonia and nodular types based on preoperative computed tomography.

Results: Overall, the IMA group had lower carcinoembryonic antigen levels (3 vs. 8 ng/mL; p < .01), fewer lymph node metastasis (4% vs. 24%; p < .01), and more KRAS mutations (56% vs. 7%; p < .01) than the non-IMA group. Although postoperative recurrence rates did not differ between both groups (32% vs. 27%; p = 0.35), lung recurrence occurred more frequently in the IMA group (83% vs. 17%; p < .01). Propensity score-matched pair analysis showed that the IMA group had fewer lymph node metastasis (3% vs. 35%; p < .01), more KRAS mutations (56% vs. 9%; p < .01), and higher intrapulmonary recurrence rate (84% vs. 31%; p < .01) than the non-IMA group. The 5-year overall survival rates did not differ between both groups (74% vs. 81%; p = 0.26). However, among patients with intrapulmonary recurrence, those in the IMA group had significantly worse prognosis than those in the non-IMA group (35% vs. 77%; p < .01).

Conclusions: Intrapulmonary recurrence, which induced significantly worse prognosis, was more likely to occur in the IMA than non-IMA group.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.042DOI Listing
November 2020

The cranial-side parietal pleura pick-up method and the edge closure technique as a closure method for open thoracotomy.

J Thorac Dis 2020 Sep;12(9):5053-5055

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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http://dx.doi.org/10.21037/jtd-20-1212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578462PMC
September 2020

The impact of same-day chest drain removal on pulmonary function after thoracoscopic lobectomy.

Gen Thorac Cardiovasc Surg 2021 Apr 29;69(4):690-696. Epub 2020 Oct 29.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

Objectives: This study aims to assess the feasibility and impact on long-term pulmonary function of chest drain removal on the operation day following thoracoscopic right upper lobectomy for clinical stage I non-small cell lung cancer.

Methods: We retrospectively evaluated the data of 116 patients between May 2013 and March 2019. We evaluated the correlations of clinical parameters of chest drain removal and medium- and long-term pulmonary function by comparing removal on operation day (R group) and retainment (D group).

Results: The R group comprised 64 patients, and the D group had 52 patients. Fifty patients (96.2%) in the D group had chest drain removed within 3 postoperative days. Since February 2016, chest drain removal on operation day was performed in 64 of 74 patients (86.5%) according to our chest drain removal protocol. Removal of chest drains on operation day was associated with shorter postoperative hospitalization (p < 0.01) and lower postoperative complications ≧ grade II of the Clavien-Dindo classification (p = 0.026). Only one patient in the R group needed reinsertion. The R group had greater spirometry results at 3- and 12-postoperative months (POM). R group patients had statistically improved pulmonary functions from 3 to 12POM, while those in the D Group were stagnated at 6POM.

Conclusions: Removal of chest drains on operation day using our protocol is safe and feasible for thoracoscopic right upper lobectomy. This protocol was statistically associated with slightly better long-term pulmonary function, which could not bring clinically meaningful medium- and long-term benefit.
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http://dx.doi.org/10.1007/s11748-020-01516-xDOI Listing
April 2021

Four Hours Postoperative Mobilization is Feasible After Thoracoscopic Anatomical Pulmonary Resection.

World J Surg 2021 Feb 23;45(2):631-637. Epub 2020 Oct 23.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

Background: We aimed to analyze the feasibility and risk factors associated with early mobilization (EM) within 4 h after thoracoscopic lobectomy and segmentectomy.

Methods: This study retrospectively evaluated 214 consecutive patients who underwent thoracoscopic anatomical pulmonary resection using our EM protocol between October 2017 and February 2019. We compared the correlations of the patients' characteristics including the total number of drugs and perioperative parameters such as air leak, and orthostatic hypotension (OH) between the EM (E group) and failed EM (F group) groups. Second, we evaluated risk factors for OH, which often causes critical complications.

Results: A total of 198 patients (92.5%: E group) completed the EM protocol, whereas 16 patients did not (7.5%: F group). The primary causes of failure were severe pain, air leak, postoperative nausea and vomiting, and OH (n = 1, 3, 8, and 4). Upon univariate analysis, air leakage, OH, and non-hypertension were identified as risk factors for failed EM (all p <0.05). EM was associated with a shortened chest tube drainage period (p <0.01). Thirty patients (14%) experienced OH, and 20% of them failed EM. A total number of drugs ≥5 (p = 0.015) was an independent risk factor for OH. Operative and anesthetic variables were not associated with EM or OH.

Conclusions: The EM protocol was safe and useful for tubeless management. Surgeons should be advised to actively prevent air leak. Our EM protocol achieved a low frequency of OH in mobilization. Due to its versatility, our mobilization protocol may be promising, especially in patients without severe comorbidities. Clinical registration number: The study protocol was approved by the Review Board of Aichi Cancer Center (approval number: 2020-1-067).
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http://dx.doi.org/10.1007/s00268-020-05836-0DOI Listing
February 2021

Primary pneumonectomy, pneumonectomy after induction therapy, and salvage pneumonectomy: a comparison of surgical and prognostic outcomes.

J Thorac Dis 2020 May;12(5):2672-2682

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Surgical outcomes of pneumonectomy for lung cancer differ based on various therapeutic strategies.

Methods: One hundred and fifty-one patients who underwent pneumonectomy were divided into three groups based on patients' therapeutic conditions: a primary pneumonectomy group (no preoperative treatment, n=137), an induction group (planned surgery after induction chemotherapy or chemoradiotherapy, n=10), and a salvage group (surgery for residual or enlarged lesions after radical non-operative therapies, n=4).

Results: Multivariate analysis showed that completeness of resection (P=0.003), subcategorization of whether there was no invasion, infiltration only to the main bronchus or pleura, or invasion of other deeper structures (P=0.008), and the presence or absence of mediastinal lymph node metastasis (P=0.033) were significant prognostic factors. Severe postoperative complications occurred in 5.1% (7/137), 20% (2/10), and 0% (0/4) in the primary pneumonectomy, induction, and salvage groups, respectively. Among patients with pN0-1 disease, the 3-year overall survival rate was 58.7% in the primary pneumonectomy group, 100% and 40% in cases with high and low pathological effects in the induction group, respectively, and 50% in the salvage group. Among patients with pN2 disease, this rate was 41.4% in the primary pneumonectomy group, and no patients survived for postoperative 2 years in the other groups.

Conclusions: For patients undergoing pneumonectomy, subcategorization based on the invasion status (none/bronchus/pleura or other deeper structures) is a crucial prognostic factor. To consider pneumonectomy in the induction or salvage setting, selecting patients with pN0-1 disease may be mandatory.
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http://dx.doi.org/10.21037/jtd.2020.03.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330390PMC
May 2020

Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non-Small-Cell Lung Cancer with Rearrangement.

Int J Mol Sci 2020 Apr 9;21(7). Epub 2020 Apr 9.

Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.

Programmed death-ligand 1 (PD-L1) expression is a predictor of immune checkpoint inhibitor (ICI) treatment efficacy. The clinical efficacy of ICIs for non-small-cell lung cancer (NSCLC) patients harboring major mutations, such as or mutations, is limited. We genotyped 190 patients with advanced lung adenocarcinomas who received nivolumab or pembrolizumab monotherapy, and examined the efficacy in NSCLC patients with or without major mutations. Among the patients enrolled in the genotyping study, 47 patients harbored mutations, 25 patients had mutations, 5 patients had a mutation, 6 patients had a mutation, and 7 patients had rearrangement. The status of PD-L1 expression was evaluated in 151 patients, and the rate of high PD-L1 expression (≥50%) was significantly higher in patients with mutations. The progression-free survival was 0.6 (95% CI: 0.2-2.1) months for -positive patients and 1.8 (95% CI: 1.2-2.1) months for -positive patients. All patients with rearrangement showed disease progression within three months from the initiation of anti-PD-1 treatment. Our data suggested that ICI treatment was significantly less efficacious in patients with rearrangement than in patients with mutations, and PD-L1 expression was not a critical biomarker for ICI treatment for patients with one of these mutations.
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http://dx.doi.org/10.3390/ijms21072623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178012PMC
April 2020

Is skeletal muscle mass an optimal marker for postoperative outcomes in lung cancer patients?

J Thorac Dis 2019 Dec;11(12):5643-5645

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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http://dx.doi.org/10.21037/jtd.2019.11.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988079PMC
December 2019

Clinicopathological Features, Surgical Outcomes, Oncogenic Status and PD-L1 Expression of Pulmonary Pleomorphic Carcinoma.

Anticancer Res 2019 Oct;39(10):5789-5795

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background/aim: Pulmonary pleomorphic carcinoma (PPC) is rare, and few studies have reported its features. We assessed the clinicopathological features, surgical outcomes, oncogenic status and programmed death-ligand 1 (PD-L1) expression of PPC.

Patients And Methods: We retrospectively reviewed data from 22 consecutive patients who underwent resection of PPC between 2007 and 2017.

Results: The predominant tissue type of the epithelial component was adenocarcinoma in 15 patients (68%) and the others in 7 patients (32%), and the 3-year disease-free survival rate tended to be better in patients with an adenocarcinoma component compared to patients with another component (40.0% vs. 17.1%, p=0.059). PD-L1 expression was observed in all eight tumors whose PD-L1 status could be examined and high PD-L1 expression (≥50%) was frequent (5/8, 63%).

Conclusion: A predominant adenocarcinoma epithelial component in PPC might be associated with better survival outcomes and high PD-L1 expression might be frequent in PPC.
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http://dx.doi.org/10.21873/anticanres.13782DOI Listing
October 2019

Favorable clinical application for segmental bronchial closure based on experiment results.

J Thorac Dis 2019 Jun;11(6):2267-2273

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan.

Background: We previously reported the clinical application of powered vascular staple (PVS) for closure of subsegmental or segmental bronchus (SSB). This study aimed to measure breakdown pressure in experiment and to investigate bronchopleural fistula (BPF) after thoracoscopic segmentectomy (TS).

Methods: Part 1: a total of 30 cadaveric pigs were used, and bronchi were categorized into the following four groups: small [S, bronchial outer diameter (BOD) of 4-8 mm, n=8], medium (M, 9-10 mm, n=9), and large (L, >10 mm, n=13). We additionally added a single additional suture to compensate for weak sites with large BOD (group R, n=6). The pressure was slowly increased, and stump breakdown was observed. Part 2: we investigated the morbidity of BPF formation at follow-up of at least 6 months in a total of 217 patients.

Results: Part 1: the mean leak pressure was the highest in M, followed by groups S, R and L'. However, the significant difference was not found between S and R. Part 2: no BPF was observed, clinically.

Conclusions: Based on experimental results and clinical experience, the proper selection of PVS should contribute to the safety, feasibility, and success as SSB closure.
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http://dx.doi.org/10.21037/jtd.2019.06.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626799PMC
June 2019

Thoracoscopic lobectomy using indocyanine green fluorescence to detect the interlobar fissure in a patient with displaced B3 and absence of fissure: A case report.

Thorac Cancer 2019 07 19;10(7):1654-1656. Epub 2019 Jun 19.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

A 90-year-old woman was admitted to our hospital with suspected lung adenocarcinoma. Preoperative three-dimensional reconstructed computed tomography revealed displacement of the anterior segmental bronchus (B3) arising from the right middle lobe bronchus with absence of the fissure between the right upper and middle lobes. A complete thoracoscopic right upper lobectomy was successfully performed. It is crucial to identify such anomalies prior to lung resection to avoid intraoperative complications during thoracoscopic lobectomy or segmentectomy. Additionally, intravenous indocyanine green with a fluorescence system was useful to identify the proper interlobar fissure boundary intraoperatively. To the best of our knowledge, this is the first reported case of thoracoscopic lobectomy for lung cancer with displaced B3 and absence of the interlobar fissure to be performed by applying the intravenous indocyanine green method.
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http://dx.doi.org/10.1111/1759-7714.13104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610257PMC
July 2019

Successful postoperative recovery management after thoracoscopic lobectomy and segmentectomy using an ERAS-based protocol of immediate ice cream intake and early ambulation: a 3-year study.

Cancer Manag Res 2019 7;11:4201-4207. Epub 2019 May 7.

Department of Thoracic Surgery.

Enhanced recovery after surgery (ERAS) protocols are well known for reducing post-operative complications, facilitating early recovery and reducing hospitalization. In this study, we developed ERAS protocols involving immediate ice cream intake for checking postoperative chylothorax and subsequent early ambulation in order to investigate whether these methods have postoperative benefits. We retrospectively evaluated 500 patients who underwent thoracoscopic segmentectomy and/or lobectomy (TSL) between January 2014 and September 2017. The patients were divided into two groups: 271 patients for Phase I and 229 for Phase II. Ice cream intake commenced during Phase I. Phase I patients were made to walk on the following day, whereas Phase II ambulate within 4 hrs after immediate ice-cream intake. The mean ice cream intake was significantly higher in Phase II than in Phase I (81.6% vs 56.1%). In Phase II, 91.2% and 94.0% were able to ambulate within 4 and 6 hrs, respectively. Minor postoperative complications (Clavien-Dindo I-II classification) were lower in Phase II (3.1%) than in Phase I (10.4%); however, we found no statistical significance (=0.08). Multivariate analysis showed that ice cream intake and removal of chest drainage tube within 4-6 hrs significantly contributed to the reduction of hospitalization to ≤3 postoperative days (=0.03 and <0.01). The results of this study suggested that our ERAS protocol represented by immediate ice cream intake, and early ambulation is feasible and can help in reducing postoperative complications, chest drainage duration, and hospitalization after TSL.
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http://dx.doi.org/10.2147/CMAR.S195219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511617PMC
May 2019

Surgical complication and postoperative pulmonary function in patients undergoing tumor surgery with thoracic wall resection.

Oncol Lett 2019 Mar 31;17(3):3446-3456. Epub 2019 Jan 31.

Department of Orthopedic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, Japan.

Postoperative complications of thoracic wall resection include respiratory complications, skin necrosis and infection. The aim of the present study was to examine postoperative complications in patients who required combined thoracic wall resection during the surgical removal of a tumor. The present study included 68 patients; there were 50 patients with lung tumors and 18 patients with musculoskeletal tumors. The clinical factors associated with complications were compared between the two groups. Preoperative and postoperative pulmonary function tests were performed to examine the residual pulmonary function in 16 patients. Thoracic cage reconstruction was performed in 46 patients. Postoperative complications occurred in 30 (44.1%) patients, and one patient died from postoperative pneumonitis. Compared with the pulmonary function preoperative test results, the postoperative results revealed a decrease in the mean vital capacity percentage and an increase in the mean forced expiratory volume within 1 sec as a percent of the forced vital capacity. In patients with lung tumors, pneumonectomy can result in an increased rate of complications following thoracic wall resection. Residual pulmonary function is affected by impaired thoracic cage expansion and removal of the lung. However, the results of the present study demonstrated that these complications can be somewhat stabilized by thoracic wall reconstruction.
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http://dx.doi.org/10.3892/ol.2019.9997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396184PMC
March 2019

The Utility of Indigo Carmine and Lipiodol Mixture for Preoperative Pulmonary Nodule Localization before Video-Assisted Thoracic Surgery.

J Vasc Interv Radiol 2019 03;30(3):446-452

Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya Aichi, Japan.

Purpose: To evaluate the safety and efficacy of a mixture of indigo carmine and lipiodol (MIL) as a marker of pulmonary nodule before video-assisted thoracic surgery (VATS).

Materials And Methods: One hundred sixty-eight sessions of pulmonary marking were performed using MIL before VATS for 184 nodules (mean size, 1.2 ± 0.6 cm; range, 0.3-3.6 cm) on 157 patients (83 men and 74 women; median age, 66 years). The mean distance between the lung surface and the nodule was 0.8 ± 0.7 cm (range, 0-3.9 cm). MIL was injected near the nodule using a 23-gauge needle. Mean number of 1.2 ± 0.4 (range, 1-3) punctures were performed in a session for the target nodules, with mean number of 1.1 ± 0.3 (range, 1-3). Successful targeting, localization, and VATS were defined as achievement of lipiodol accumulation at the target site on computed tomography, detection of the nodule in the operative field by fluoroscopy or visualization of dye pigmentation, and complete resection of the target nodule with sufficient margin, respectively.

Results: The successful targeting rate was 100%, and the successful localization rate was 99.5%, with dye pigmentation for 160 nodules (87.0%) and intraoperative fluoroscopy for 23 nodules (12.5%). Successful VATS was achieved for 181 nodules (98.4%). Two nodules (1.1%) were not resectable, and surgical margin was positive in 1 nodule (0.5%). Complications requiring interventions occurred in 5 sessions (3.0%) and included pneumothorax with chest tube placement (n = 3) and aspiration (n = 2). No complication related to the injected MIL occurred.

Conclusions: MIL was safe and useful for preoperative pulmonary nodule marking.
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http://dx.doi.org/10.1016/j.jvir.2018.08.024DOI Listing
March 2019

Salvage surgery for small cell lung cancer after chemoradiotherapy.

Jpn J Clin Oncol 2019 Apr;49(4):389-392

Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.

There are few reports on the use of salvage surgery for small cell lung cancer (SCLC). Five patients who underwent resection of post-chemoradiotherapy residual lesion/local reprogression of SCLC between 2005 and 2017 were included in the study. We retrospectively reviewed their surgical outcomes and prognosis to assess the feasibility and potential efficacy of salvage surgery. Indications for salvage surgery were local reprogression (four patients) and residual lesion (one patient) with ycN0 disease. Complete pathological resection was achieved in four patients; however, malignant pleural effusion was diagnosed in one patient after the surgery. Morbidity and mortality rates were 0%. Estimated 5-year survival rate was 67%. Recurrence and death after surgery occurred only in the patient with malignant pleural effusion. We demonstrate the feasibility of salvage surgery in SCLC. In carefully-selected patients, especially those without lymph node involvement, salvage surgery may provide effective local control and favorable survival outcomes.
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http://dx.doi.org/10.1093/jjco/hyz010DOI Listing
April 2019

Evaluation of lobar lymph node metastasis in non-small cell lung carcinoma using modified total lesion glycolysis.

J Thorac Dis 2018 Dec;10(12):6932-6941

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Volumetric parameters based on 3-dimensional reconstruction have recently been introduced for cancer staging. We aimed to improve the ability to diagnose hilar lymph node metastasis in patients with non-small cell lung cancer.

Methods: We evaluated 142 patients with non-small cell lung cancer who underwent right upper lobectomy and radical lymph node dissection. Metastatic involvement of right upper lobar lymph nodes was assessed using high-resolution computed tomography (HRCT) and 18F-2-floro-2-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT).

Results: On receiver operating characteristic (ROC) curve analysis, the area under the curves (AUC) for short axis, maximum of standardized uptake value (SUV), total lesion glycolysis (TLG) and modified TLG (mTLG) were 0.79, 0.77, 0.76, and 0.87, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mTLG, using the optimal cut off value (2.45), for diagnosis of lobar lymph node metastasis were 71%, 88%, 44%, and 96%, respectively. Hilar asymmetric uptake (HAU) of FDG was larger in true-positive cases than in false-negative cases (P<0.01). Furthermore, the size of metastatic foci in the lymph node was smaller in false-negative cases (P=0.012).

Conclusions: Modified TLG is a good parameter to diagnose metastatic right upper lobar lymph nodes. Micrometastasis in the lymph node is difficult to predict using the current diagnostic method. However, more careful evaluation is required in patients with symmetric FDG accumulation at hilar region because hilar lymph nodes respond to various causes such as benign pulmonary diseases.
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http://dx.doi.org/10.21037/jtd.2018.11.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344716PMC
December 2018

Importance of avoiding surgery delays after initial discovery of suspected non-small-cell lung cancer in clinical stage IA patients.

Cancer Manag Res 2019 20;11:107-115. Epub 2018 Dec 20.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan,

Introduction: The natural history of consolidation on computed tomography (CT) rarely includes invasive cancers, and evidence of the ideal timing for surgical intervention via long-term follow-up studies remains unknown.

Methods: Between January 2012 and June 2017, pulmonary resection was undertaken in 293 clinical IA patients who were followed-up for > 6 months after the first detection of potential non-small-cell lung cancer (NSCLC) opacities. We evaluated the corresponding HRs and compared the recurrence risk with the CT follow-up duration.

Results: HRs calculated for the longest intervals were compared between two patient subsets: a shorter-interval surgery group (SISG: 41.3%; mean follow-up interval, 13.5±5.3 months) and a longer-interval surgery group (58.7%; mean follow-up interval, 54.9±25.6 months). On Cox multivariate regression analyses, CT consolidation (ratio >0.5), an abnormal carcinoembryonic antigen and a triple-negative mutation showed an independent association with an unfavorable prognosis, as measured by disease-free survival after the first detection of potential NSCLC opacities. The longer-interval surgery group fared significantly better than the SISG in terms of 5-year overall survival after the first detection (99.3% vs 93.1%, <0.01); the 3-year overall survival after the first detection was significantly shorter in the high-risk SISG (presence of two factors from the three) than that in the low-risk SISG (presence of 0 or one factor; 100% vs 73.3%, <0.01).

Conclusion: Our study indicates that the patients with potential NSCLC opacities who are able to wait for more than 2 years prior to pulmonary resection may be likely to have a favorable prognosis, whereas early judgment for surgical resection should be required for avoiding surgical delays.
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http://dx.doi.org/10.2147/CMAR.S180757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305139PMC
December 2018

Detection of abundant megakaryocytes in pulmonary artery blood in lung cancer patients using a microfluidic platform.

Lung Cancer 2018 11 16;125:128-135. Epub 2018 Sep 16.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. Electronic address:

Objectives: The lung was recently re-discovered as a hematopoietic organ for platelet production in mice. However, evidence for the role of the lung in thrombopoiesis in humans is still limited. In this study, we examined megakaryocytes in the pulmonary and systemic circulation, specifically in pulmonary arterial blood (PAB), venous blood (PVB) and peripheral blood using a newly developed microfluidic platform for rare cell isolation.

Materials And Methods: We analyzed 23 lung cancer patients who underwent surgery in our institute. PAB and PVB were obtained from the resected lung immediately after surgery. Blood samples were size-selected using a filtration-based microfluidic device and enriched rare cells on glass slide specimens were stained with Papanicolaou (Pap), immunocytochemistry (ICC), and immunofluorescence (IF). Lung tissues were also analyzed by immunohistochemistry.

Results: Pap/ICC/IF showed the presence of abundant CD61+/cytokeratin- giant cells with a megakaryocyte lineage in PAB, but only a few in PVB. These megakaryocytes were found to consist of CD61+/CD41+ immature megakaryocytes and CD61+/CD41- mature megakaryocytes with the potential to produce platelets. These findings were confirmed by the conventional hematological analysis of blood smears stained with Giemsa. In analysis of lung cancer, CD61+ megakaryocytes were observed exclusively in the capillaries of non-cancerous tissue, whereas platelets were selectively observed in the tumor blood vessels of cancerous tissue.

Conclusions: These results indicate that numerous megakaryocytes migrate from systemic bone marrows to accumulate in PAs and arrest of mature megakaryocytes in the capillaries of normal lung, suggesting the possibility that the lung plays a physiological role in the systemic thrombopoiesis in lung cancer patients.
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http://dx.doi.org/10.1016/j.lungcan.2018.09.011DOI Listing
November 2018

Spontaneous regression of lung squamous cell carcinoma with synchronous mediastinal progression: A case report.

Thorac Cancer 2018 12 11;9(12):1778-1781. Epub 2018 Oct 11.

Division of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Spontaneous regression (SR) of cancer implies the partial or complete disappearance of malignant disease without or with adequate medical treatment. Typically, SR of cancer is a sporadic event, especially in non-small cell lung cancer (NSCLC). Although the underlying mechanism of SR remains unknown, stimulation of an immunological response has been proposed. Herein, we report the case of a 56-year-old woman exhibiting SR of NSCLC with a mediastinal disease. Despite regression of the primary site after a lung biopsy, simultaneous progression of mediastinal lymph node metastasis occurred. Specimens obtained by surgical resection pathologically confirmed both primary and metastatic sites. Reportedly, primary and metastatic tumors shrink synchronously in SR of metastatic NSCLCs. Thus, the fact that the SR of NSCLC can present inconsistent development in primary and metastatic sites should be considered, and direct intervention is recommended if physicians diagnose this phenomenon.
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http://dx.doi.org/10.1111/1759-7714.12892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275820PMC
December 2018

Design variations in vertical muscle-sparing thoracotomy.

J Thorac Dis 2018 Aug;10(8):5115-5119

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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http://dx.doi.org/10.21037/jtd.2018.07.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129928PMC
August 2018

Contribution of smoking habit to the prognosis of stage I KRAS-mutated non-small cell lung cancer.

Cancer Biomark 2018 ;23(3):419-426

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: One of the known risk factors for non-small cell lung cancer (NSCLC) is somatic mutation in the Kirsten rat sarcoma (KRAS) gene. The relationship with smoking is well known.

Methods: We retrospectively studied the data of 92 patients who underwent pulmonary resection January 2003 and June 2012 and were diagnosed as KRAS-mutated pathological stage I adenocarcinoma.

Results: Among them, 33 patients who were non to light smoker (NLS) (smoking index, 0 to 400) were compared with 59 middle to heavy smoker (MHS) (> 400). The 5-year overall survival (OS) was significantly better in NLS (96.9%) than in MHS (80.0%); however, no significant difference was observed compared with wild-type KRAS (92.8%) (p= 0.66). The presence of p53 was significantly associated with smoking history (p< 0.01). The 5-year OS for NLS with p53-negative KRAS codon 12-mutated NSCLC (n= 28) was significantly better (96.3%) than that for MHS with both p53-positive and -negative KRAS mutation (p= 0.03 and p< 0.03, respectively).

Conclusions: A non to light smoking habit might contribute to an improvement in prognosis that is equivalent to that of wild-type KRAS, and p53 mutation did not affect survival in smokers harboring KRAS codon 12.
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http://dx.doi.org/10.3233/CBM-181483DOI Listing
March 2019