Publications by authors named "Masayuki Nakao"

93 Publications

A Reasonable Definition of Oligo-Recurrence in Non-Small-Cell Lung Cancer.

Clin Lung Cancer 2021 Oct 25. Epub 2021 Oct 25.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: The concept of oligo-recurrence in non-small-cell lung cancer (NSCLC) has been suggested to describe the possibility of achieving long-term survival or even cure with local therapy for recurrence despite having recurrent disease. Oligo-recurrence involves a limited number of metachronous recurrences that can be treated with local therapy. However, the number of recurrences that constitutes an oligo-recurrence has varied among studies and remains to be defined. The aim of this study was to elucidate the number of recurrences that constitutes an oligo-recurrence in NSCLC.

Patients And Methods: We retrospectively reviewed 577 patients with NSCLC who had underwent complete resection and developed recurrence between 1990 and 2009, and these patients were evaluated. Patients were categorized according to the number of recurrences, and postrecurrence survival (PRS) was compared between groups.

Results: Altogether, 270 patients underwent local therapy for all recurrent lesions. In these patients, sex (female), histological type (adenocarcinoma), gene mutation status, recurrence-free interval <1 year, and presence of 1 or 2 recurrences were factors associated with prolonged PRS. Additionally, all patients who maintained a cancer-free status for at least 5 years after treatment for recurrence and were considered possibly cured, had 1 or 2 recurrences.

Conclusion: Among patients receiving radical local therapy, the PRS was particularly longer among those with 1 or 2 recurrences, and these patients were able to aim for postrecurrence cure. Thus, a reasonable threshold to define oligo-recurrence in NSCLC is 1 or 2 recurrences that can be treated with local therapy.
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http://dx.doi.org/10.1016/j.cllc.2021.10.013DOI Listing
October 2021

Three-dimensional image simulation for lung segmentectomy from unenhanced computed tomography data.

Gen Thorac Cardiovasc Surg 2021 Nov 23. Epub 2021 Nov 23.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital, The Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

We developed a novel three-dimensional (3D) image simulation system, focused on pulmonary segmentectomy. The novel algorithms run by the software, which are independent of the differences in computed tomography (CT) values of vascular structures, enabled the creation of 3D images from unenhanced CT data with accuracy comparable to that from contrast-enhanced CT data. To evaluate the anatomical accuracy, we compared it between images created from unenhanced and contrast-enhanced CT in seven patients who underwent thoracoscopic segmentectomy. With regard to the automatic recognition of pulmonary vessels, the 3D image from unenhanced CT falsely recognized one or two points in two cases, whereas that from contrast-enhanced CT false recognitions in one case. Both 3D images had similar creation time and capability for identifying the intersegmental plain. The novel 3D image simulation for segmentectomy from unenhanced CT had sufficient anatomical accuracy for practical use but required attention due to inevitable minor false recognition.
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http://dx.doi.org/10.1007/s11748-021-01750-xDOI Listing
November 2021

Positive bag lavage cytology during thoracoscopic surgery for lung cancer is a significant predictor of locoregional recurrence.

Gen Thorac Cardiovasc Surg 2021 Nov 20. Epub 2021 Nov 20.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Objectives: Advances in thoracoscopic surgery have made skin incisions smaller, but there are concerns about cancer cell contamination during sample extraction. We performed retrieval bag lavage cytology (BLC) during thoracoscopic surgery to evaluate the risk of cancer dissemination and the prognostic influence of BLC status.

Methods: BLC was investigated in 893 patients who underwent thoracoscopic lobectomy or segmentectomy for lung cancer between 2013 and 2018. The clinicopathological features and prognosis were compared between the BLC-positive and BLC-negative groups.

Results: Forty-nine patients (5.5%) were positive for BLC. BLC correlated with pleural invasion (49.0% vs. 12.9%, P < 0.001); however, BLC was positive in 3.3% of cases without pleural invasion. Multivariate analysis revealed that tumor size, lymph node metastasis, lymphatic and pleural invasion were predictive factors for positive BLC. Prognosis was poorer in the BLC-positive group than in the BLC-negative group (5-year overall survival, 73.6% vs. 90.2%, P < 0.001); nevertheless, positive BLC was not an independent prognostic factor. The locoregional recurrence rate was higher among BLC-positive patients than among BLC-negative patients, whereas there was no significant difference in the distant recurrence rate. Positive BLC was associated with locoregional recurrence (hazard ratio 1.87, P = 0.044) and the correlation was stronger in stage I lung cancer. There were no cases of extraction bag breakage or port-site recurrence.

Conclusions: BLC positivity was correlated with the risk of locoregional recurrence in patients with surgically resected lung cancer, although it was not an independent prognostic factor. Careful manipulation is essential for extracting specimens from the thoracic cavity.
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http://dx.doi.org/10.1007/s11748-021-01745-8DOI Listing
November 2021

Prognostic Impact of Mediastinal Lymph Node Dissection in Octogenarians With Lung Cancer: JACS1303.

Clin Lung Cancer 2021 Sep 24. Epub 2021 Sep 24.

Department of General Thoracic Surgery, Dokkyo Medical University, Shimotsuga, Japan; The Japanese Association for Chest Surgery, Kyoto, Japan.

Introduction: The prognostic significance of mediastinal lymph node dissection (MLND) in elderly patients with non-small cell lung cancer (NSCLC) remains unclear. This post hoc analysis of a nationwide multicenter cohort study (JACS1303) evaluated the prognostic significance of MLND in octogenarians with NSCLC.

Materials And Methods: We included 622 octogenarians with NSCLC who underwent lobectomy. The median follow-up duration was 41.1 months. We compared survival and perioperative outcomes between patients who did and did not undergo MLND.

Results: In total, 414 (67%) patients underwent MLND (ND2 group), whereas 208 (33%) did not undergo MLND (ND0-1 group). The disease stage was more advanced in the ND2 group than in the ND0-1 group. Disease-free survival was slightly greater in the ND0-1 group with marginal significance (P= .079). In the matched cohort (N = 228), which mainly consisted of patients with clinical stage I disease (96%), there was no significant difference between the 2 groups regarding overall and disease-free survival (P= .908 and P = .916, respectively). Operative time and blood loss were significantly lower in the ND0-1 group than in the ND2 group in the entire cohort (P< .001 and P = .050, respectively) and in the matched cohort (P = .003 and P= .046, respectively).

Conclusion: Based on a nationwide prospective database, we found limited prognostic impact of MLND, suggesting that MLND can be omitted for octogenarians with early-stage NSCLC.
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http://dx.doi.org/10.1016/j.cllc.2021.09.007DOI Listing
September 2021

Relationship between the three-dimensionally measured tumor doubling time of lung cancer and underlying interstitial lung disease: A retrospective case-control study.

Cancer Treat Res Commun 2021 Aug 18;29:100446. Epub 2021 Aug 18.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Objective: The coexistence of interstitial lung disease (ILD) is associated with poor prognosis in patients with lung cancer. The tumor doubling time (TDT) of lung cancer reflects cancer aggressiveness and is related to its prognosis. However, the relationship between the TDT of lung cancer and underlying ILD has not been fully evaluated. This study aimed to identify this crucial relationship.

Materials And Methods: Patients with lung cancer who underwent surgery between 2007 and 2020 were reviewed retrospectively. The propensity score matching method was used to balance the characteristics of patients with ILD (n = 100) and those without ILD (n = 100). TDT was calculated based on the difference of three-dimensional volumes defined from the two-time CT scans before surgery. We compared the TDT of lung cancer and other characteristics between the two groups.

Results: The median TDT of all patients was 149 days. The TDT was significantly shorter in patients with ILD (134 days) than in those without (204 days). The rate of short-term tumor enlargement (TDT < 90 days) was significantly higher in patients with ILD than in those without ILD, and ILD was an independent factor related to short-term tumor enlargement (odds ratio, 2.30; p = 0.015). We focused on 25 patients with usual interstitial pneumonitis (UIP) findings of patients with ILD. However, the presence of the UIP pattern was not related to the TDT among patients with ILD.

Conclusion: ILD was an independent predictor of short-term tumor enlargement in lung cancer patients, regardless of the presence of the UIP pattern.
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http://dx.doi.org/10.1016/j.ctarc.2021.100446DOI Listing
August 2021

Thoracoscopic right upper lobectomy in a patient with bronchial and pulmonary vein anomalies.

JTCVS Tech 2020 Dec 13;4:316-318. Epub 2020 Aug 13.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.xjtc.2020.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304485PMC
December 2020

The predictive power of artificial intelligence on mediastinal lymphnode metastasis.

Gen Thorac Cardiovasc Surg 2021 Dec 16;69(12):1545-1552. Epub 2021 Jun 16.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Objective: The aim of this study was to create the preoperative predictive model on mediastinal lymph-node metastasis based on artificial intelligence in surgically resected lung adenocarcinoma.

Methods: We enrolled 301 surgical resections of patients with clinical stage N0-1 lung adenocarcinoma, who received positron emission tomography preoperatively between 2015 and 2019. We randomly assigned the patients into two groups: the training (n = 201) and validation groups (n = 100). The training group was used to obtain basic data for learning by artificial intelligence, whereas the validation group was used to verify the constructed algorithm. We used an automatic machine learning platform, to create artificial intelligence model. For comparison, multivariate analysis was performed in the training group, whereas for calculating and verifying the prediction accuracy rate, significant predicting factors were applied to the validation group.

Results: Of the 301 patients, 41 patients were diagnosed as mediastinal lymph node metastasis. In multivariate analysis, the maximum standardized uptake value was an individual predictive factor. The accuracy rate of artificial intelligence model was 84%, and the specificity was 98% which were higher than those of the maximum standardized uptake value (61% and 57%). However, in terms of sensitivity, artificial intelligence model remarked low at 12%.

Conclusions: An artificial intelligence-based diagnostic algorithm showed remarkable specificity compared with the maximum standardized uptake value. Although this model is not ready to practical use and the result was preliminary because of poor sensitivity, artificial intelligence could be able to complement the shortcomings of existing diagnostic modalities.
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http://dx.doi.org/10.1007/s11748-021-01671-9DOI Listing
December 2021

Novel three-dimensional image simulation for lung segmentectomy developed with surgeons' perspective.

Gen Thorac Cardiovasc Surg 2021 Sep 14;69(9):1360-1365. Epub 2021 Jun 14.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital, The Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

We developed a novel three-dimensional (3D) image simulation system that is especially focused on pulmonary segmentectomy using new 3D computed tomography (CT) software. Based on contrast-enhanced high-resolution computed tomography (HRCT) images, the new software can quickly construct 3D pulmonary and bronchovascular images and generate a proposal for the appropriate segments to be resected. We performed the 3D image simulation and evaluated its accuracy in 20 patients for whom thoracoscopic segmentectomy was planned. We evaluated the anatomical validity comparing with HRCT findings and anatomical consistency with the operative findings on a three-point scale, respectively. The 3D image was evaluated as "good" for anatomical validity in 19 cases (95%) and for anatomical consistency with operative findings in 18 cases (90%). The novel 3D image simulation appeared to be easy to prepare, was anatomically reliable, and, therefore, was determined to be potentially useful.
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http://dx.doi.org/10.1007/s11748-021-01666-6DOI Listing
September 2021

Survival of Octogenarians with Early-Stage Non-small Cell Lung Cancer is Comparable Between Wedge Resection and Lobectomy/Segmentectomy: JACS1303.

Ann Surg Oncol 2021 Nov 26;28(12):7219-7227. Epub 2021 Apr 26.

Department of General Thoracic Surgery, Dokkyo Medical University, Shimotsuga, Japan.

Background: Anatomic resection with lymph node dissection or sampling is the standard treatment for early non-small cell lung cancer (NSCLC), and wedge resection is an option for compromised patients. This study aimed to determine whether wedge resection can provide comparable prognoses for elderly patients with NSCLC.

Methods: The study analyzed the clinicopathologic findings and surgical outcomes during a median follow-up period of 39.6 months for 156 patients with solid dominant (consolidation-to-tumor ratio > 0.5) small (whole tumor size ≤ 2 cm) NSCLC among 892 patients 80 years of age or older with medically operable lung cancer between April 2015 and December 2016.

Results: The 3-year overall survival (OS) rates after wedge resection and after segmentectomy plus lobectomy did not differ significantly (86.5 %; 95 % confidence interval [CI], 74.6-93.0 % vs 83.7 % 95 % CI, 74.0-90.0 %; P = 0.92). Multivariable Cox regression analysis of OS with propensity scores showed that the surgical procedure was not an independent prognostic predictor (hazard ratio [HR], 0.84; 95 % CI, 0.39-1.8; P = 0.64). The 3-year OS rates were slightly better after wedge resection for 97 patients who could tolerate lobectomy than after segmentectomy plus lobectomy (89.4 %; 95 % CI, 73.8-95.9 % vs 75.8 %; 95 % CI, 62.0-85.2 %; P = 0.14). The cumulative incidence of other causes for death was marginally higher after segmentectomy plus lobectomy than after wedge resection (P = 0.079).

Conclusions: Wedge resection might be equivalent to lobectomy or segmentectomy for selected patients 80 years of age or older with early-stage NSCLC who can tolerate lobectomy.
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http://dx.doi.org/10.1245/s10434-021-09835-wDOI Listing
November 2021

Two Cases of Lower Lobe Pneumatoceles Following Upper Lobectomy.

Ann Thorac Surg 2021 12 16;112(6):e403-e406. Epub 2021 Mar 16.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Postoperative pneumatocele is a rare complication of lung surgery. Here we describe 2 cases of pneumatoceles arising from the unaltered bottom part of the lower lobe a month or more after upper lobectomy. Based on histopathologic findings, we speculated that (1) negative pressure created by the volumetric gap between the thoracic cavity and the remnant lung and (2) increased positive pressure by the check valve mechanism from kinking or flexion of the airway after an upward movement of the remnant lung play crucial roles in the pathogenesis of postoperative pneumatoceles.
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http://dx.doi.org/10.1016/j.athoracsur.2021.02.081DOI Listing
December 2021

Comparison of local therapy in patients with lung oligo-recurrence of non-small-cell lung cancer.

J Surg Oncol 2021 May 8;123(8):1828-1835. Epub 2021 Mar 8.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Background And Objectives: The effectiveness of local therapy has been reported in non-small-cell lung cancer (NSCLC) patients with oligo-recurrence. However, there is still no clear consensus on the choice of local therapy. We aimed to examine the choice of local therapy in NSCLC patients with lung oligo-recurrence.

Methods: Among 1760 consecutive NSCLC patients who underwent complete resection between 1990 and 2008, 535 patients developed recurrence. Lung oligo-recurrence was defined as 1-5 metachronous recurrences limited to the lungs only; such recurrence was found in 97 patients. We examined the differences in the prognosis of each therapy for these patients.

Results: The 5-year postrecurrence survival (PRS) rates in patients who underwent local therapy (n = 54) and those who did not (n = 43) were 55.6% and 31.1%, respectively; it was significantly higher in patients who underwent local therapy (p = 0.004). Among 47 patients who underwent resection or radiation therapy, the 5-year PRS rates were 61.5% and 47.6% (p = 0.258), and the 5-year postrecurrence progression-free survival rates were 30.3% and 24.7% (p = 0.665), respectively, without any significant difference.

Conclusions: Patients with lung oligo-recurrence should consider local therapy individually, depending on their general condition.
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http://dx.doi.org/10.1002/jso.26453DOI Listing
May 2021

Validation of the Japanese National Clinical Database Risk calculator for lung cancer surgery focused on postoperative morbidity.

Gen Thorac Cardiovasc Surg 2021 Aug 8;69(8):1222-1229. Epub 2021 Mar 8.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Objectives: To validate the efficacy of the Japanese National Clinical Database risk calculator, which predicts major morbidity in lung cancer surgery based on preoperative clinical characteristics.

Methods: In total, 660 patients who underwent complete surgical resection of primary lung cancer were enrolled. The predicted rate of major morbidity determined using the risk calculator was compared between the patients with and without major morbidity. We performed receiver operating characteristic curve analysis to determine their cut-off values to predict major morbidity and assessed the associated factors with major morbidity. Major morbidity was defined as the Clavien-Dindo classification grade IIIa or greater.

Results: The predicted rate of major morbidity was significantly higher in patients with major morbidity than in those without (P < 0.001). The cut-off value of the predicted rate of major morbidity to predict major morbidity was 3.0% (area under curve 0.741; sensitivity and specificity, 85.3% and 54.3%, respectively). The predicted rate of major morbidity ≥ 3.0% was significantly associated with occurrence of major morbidities (odds ratio 6.9; 95% confidence interval 2.63-18.04; P < 0.001) and the predicted rate of major morbidity had the highest odds ratio over other risk factors. This condition, namely the predicted rate of major morbidity ≥ 3.0%, was met in 315 (47%) of the total cases. However, only 29 (9%) of these cases had major morbidity in practice.

Conclusions: The risk calculator was fairly useful for estimating high-risk patients; however, it was not possible to identify a specific cut-off value to predict major morbidity in this cohort.
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http://dx.doi.org/10.1007/s11748-021-01617-1DOI Listing
August 2021

Correlation Between Smoking Status and Short-term Outcome of Thoracoscopic Surgery for Lung Cancer.

Ann Thorac Surg 2021 Mar 2. Epub 2021 Mar 2.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: Smoking has a major role in the risk of postoperative pulmonary complications. This study aimed to elucidate the correlation between smoking status and pulmonary complications after thoracoscopic surgery for lung cancer.

Methods: A total of 1751 patients who underwent thoracoscopic lobectomy or segmentectomy for lung cancer between April 2011 and March 2020 were assessed. The rate of pulmonary complications was evaluated according to smoking status and preoperative duration of smoking cessation. Univariate and multivariate logistic regression analyses were performed.

Results: Pulmonary complications were observed in 50 patients (2.9%), whereas 3 (0.2%) died within 90 days of surgery. The rate of pulmonary complications was higher in smokers than in nonsmokers (4.6% vs 0.9%; P < .001), and smoking history was an independent risk factor for pulmonary complications (odds ratio, 3.31; P = .007). The complication rate in patients with a cessation period of more than 2 months was significantly lower than that in patients who ceased smoking within 2 months (4.0% vs 8.5%; P = .043), but it was still higher than that in nonsmokers (4.0% vs 0.9%; P < .001). In the multivariable analysis for smokers, preoperative short-term smoking cessation within 2 months, male sex, histologic type, tumor size, and cardiopulmonary comorbidities were associated with pulmonary complications instead of pack-year smoking history.

Conclusions: Smoking habits and preoperative smoking cessation were independently associated with pulmonary complications after thoracoscopic surgery for lung cancer. A preoperative smoking cessation period of 2 months or more is preferable for reducing the risk of such complications.
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http://dx.doi.org/10.1016/j.athoracsur.2021.01.063DOI Listing
March 2021

The utility of three-dimensional computed tomography for prediction of tumor invasiveness in clinical stage IA lung adenocarcinoma.

J Thorac Dis 2020 Dec;12(12):7218-7226

Department of Thoracic Surgical Oncology, Cancer Institute Hospital, The Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: It is critical to have an accurate measurement of solid tumor size in order to predict the invasiveness of small lung adenocarcinomas. Some lesions cannot be measured accurately via High-resolution computed tomography (HRCT) due to their irregular shape and unclear borders. For this reason, we evaluated the relative efficacy of three-dimensional (3D) CT for predicting invasive adenocarcinoma.

Methods: We evaluated 195 patients with clinical stage IA adenocarcinomas, including 109 with lesions documented as invasive that were surgically resected at our institute during 2017. All lesions were categorized as either (I) lesions that were difficult to evaluate (i.e., hazy lesions; HL) or (II) more typical lesions (TL). The relationships between solid tumor size as determined by HRCT, solid tumor volume as determined by 3D CT and pathologic diagnosis were evaluated.

Results: Fifty-seven patients (29%) were diagnosed with HL. We set the cut-off value for the solid volume at 225 mm as predictive for invasive adenocarcinoma. When evaluating all 195 patients as a group, the accuracy, sensitivity, and specificity based on the solid tumor volume were similar to those based on the solid tumor size. When we limit our analysis to the HL group, the specificity based on solid tumor volume (65.5%) was higher than that based on solid tumor size (44.8%) with a difference that approached statistical significance (P=0.070).

Conclusions: 3D CT was equivalent to HRCT for predicting invasive adenocarcinoma and may be particularly useful for diagnosing lesions that are difficult to evaluate on HRCT.
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http://dx.doi.org/10.21037/jtd-20-2131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797862PMC
December 2020

Outcomes of nodal upstaging comparing video-assisted thoracoscopic surgery versus open thoracotomy for lung cancer.

Lung Cancer 2021 02 20;152:78-85. Epub 2020 Dec 20.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Objectives: In early stage non-small cell lung cancer, the optimal surgical approach for lymph node dissection remains controversial. Without a uniform standard for the quality of lymph node dissection, outcomes of nodal upstaging comparing video-assisted thoracoscopic surgery (VATS) versus open thoracotomy (OPEN) also remain controversial. Thus, we compared the clinical outcomes of nodal upstaging between each approach.

Materials And Methods: We retrospectively evaluated 1319 surgically resected lung cancer cases between 2008 and 2017 at our institute. Moreover, 348 VATS and 348 OPEN cases were extracted using propensity score matching. We investigated the frequency, prognosis, and post-recurrence course of nodal upstaging between each approach.

Results: A total of 193 nodal upstaging cases were identified. Nodal upstaging was more frequent in the OPEN group (24 %) than the VATS group (9%) (p < 0.001). However, multivariable analysis revealed the surgical approach was not significantly associated with nodal upstaging (OPEN: odds ratio, 1.3; 95 % confidence interval, 0.93-2.02; p = 0.108) and, after matching, nodal upstaging with each approach were of equivalent frequency (p = 0.752). The median follow-up period was 5.0 years. Nodal upstaging was an independent prognostic factor for worse overall survival, cancer-specific survival, and recurrence-free survival in multivariable analyses (all p < 0.001). Of all cases, 222 recurred after surgery. There were no significant differences in recurrence patterns and initial recurrence sites depending on surgical approach. The 5-year post-recurrence survival rate was 52 % after VATS and 30 % after OPEN; however, this difference was not statistically significant (p = 0.052). Moreover, post-recurrence survival rate was not significantly different between the VATS and OPEN groups (pN0: p = 0.268, pN1: p = 0.437, and pN2: p = 0.144).

Conclusion: Outcomes of nodal upstaging between VATS and OPEN were found to be equivalent. The difference in the frequency of nodal upstaging was not due to inferior quality of lymph node dissection with VATS; rather, that difference resulted from selection bias.
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http://dx.doi.org/10.1016/j.lungcan.2020.12.017DOI Listing
February 2021

Different perspectives and viewpoints on the postoperative management of EGFR-mutant lung cancer.

Ann Transl Med 2020 Sep;8(18):1201

Department of Thoracic Surgical Oncology, Cancer Institute Hospital, The Japanese Foundation for Cancer Research, Tokyo, Japan.

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http://dx.doi.org/10.21037/atm.2020.04.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576077PMC
September 2020

Effects of Transcranial Direct Current Stimulation on Brain Networks Related to Creative Thinking.

Front Hum Neurosci 2020 16;14:541052. Epub 2020 Oct 16.

Creative Design Laboratory, Department of Mechanical Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

Human creative thinking is unique and capable of generating novel and valuable ideas. Recent research has clarified the contribution of different brain networks (default mode network, DN; executive control network; salience network) to creative thinking. However, the effects of brain stimulation on brain networks during creative thinking and on creative performance have not been clarified. The present study was designed to examine the changes in functional connectivity (FC) and effective connectivity (EC) of the large-scale brain network, and the ensuing changes in creative performance, induced by transcranial direct current stimulation (tDCS). Fourteen healthy male students underwent two tDCS sessions, one with actual stimulation and one with sham stimulation, on two separate days. Participants underwent tDCS (anode over the left dorsolateral prefrontal cortex, DLPFC; cathode over the right inferior parietal lobule, IPL) for 20 min. Before and after the tDCS session, electroencephalography signals were acquired from 32 electrodes over the whole head during the creative thinking task. On FC analysis, the delta band FC between the posterior cingulate cortex and IPL significantly increased only after real stimulation. We also found that the change of flexibility score was significantly correlated with the change in: (i) delta band FC between mPFC and left lateral temporal cortex (LTC) and (ii) alpha band FC between IPL and right LTC. On EC analysis, decreased flow within the DN (from left LTC to right IPL) was observed. Our results reveal that tDCS could affect brain networks, particularly the DN, during creative thinking and modulate key FC in the generation of flexible creative ideas.
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http://dx.doi.org/10.3389/fnhum.2020.541052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596331PMC
October 2020

Bilateral lung cancer resection with preservation of an accessory cardiac lobe.

BMJ Case Rep 2020 Nov 2;13(11). Epub 2020 Nov 2.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

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http://dx.doi.org/10.1136/bcr-2020-239604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607584PMC
November 2020

Prognostic impact and distinctive characteristics of surgically resected anaplastic lymphoma kinase-rearranged lung adenocarcinoma.

J Thorac Cardiovasc Surg 2020 Oct 8. Epub 2020 Oct 8.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Objective: Anaplastic lymphoma kinase (ALK) rearrangement is a representative lung cancer with driver mutation because of the efficacy of ALK-tyrosine kinase inhibitors. ALK-tyrosine kinase inhibitors are extensively used for ALK-rearranged lung cancer, whereas the therapeutic benefit of surgery remains unclear. Thus, we aimed to assess the clinical benefit of surgery in ALK-rearranged lung cancer and to elucidate the oncologic characteristics of ALK-rearranged lung cancer through surgically resected cases.

Methods: We retrospectively evaluated 1925 lung adenocarcinoma cases surgically resected between 1996 and 2017 at our institute. Moreover, 75 ALK-rearranged and 75 non-ALK-rearranged cases were extracted using propensity score matching. The survival rates, prognostic factors, and post-recurrence state were assessed.

Results: Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved cancer-specific survival (hazard ratio, 0.2; 95% confidence interval, 0.05-0.88; P = .033). In the matched cohort, the 5-year cancer-specific survival rates after surgery in the ALK-rearranged and non-ALK-rearranged groups were 97% and 77%, respectively. The ALK-rearranged group had a significantly better cancer-specific survival than did the non-ALK-rearranged group (log-rank test; P = .003). With respect to post-recurrence state, oligo-recurrence was highly frequent in the ALK-rearranged group, and post-recurrence survival was significantly improved by administration of either ALK-tyrosine kinase inhibitors (log-rank test; P = .011) or local ablative therapies (log-rank test; P = .035).

Conclusions: Surgically resected ALK-rearranged lung adenocarcinoma has excellent long-term outcome. Not only ALK-tyrosine kinase inhibitors but also a combination of local and systemic therapies may be important treatment strategies for ALK-rearranged lung adenocarcinoma even in the post-recurrence state.
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http://dx.doi.org/10.1016/j.jtcvs.2020.09.120DOI Listing
October 2020

Characteristics of surgically resected non-small cell lung cancer patients with post-recurrence cure.

Thorac Cancer 2020 11 22;11(11):3280-3288. Epub 2020 Sep 22.

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: The prognosis of postoperative recurrence in patients with non-small cell lung cancer (NSCLC) is poor. However, depending on the recurrence patterns and treatment options, some patients can achieve long-term survival following recurrence. In this study, we investigated the clinicopathological characteristics of NSCLC patients with curable disease who developed postoperative recurrence.

Methods: This retrospective study enrolled 535 patients who had developed recurrence from among 1760 consecutive patients with NSCLC who underwent curative resection from 1990 to 2008. Post-recurrence cure was defined as being cancer-free for at least five years after treatment for recurrence in patients who had undergone radical local treatment or chemotherapy. The clinicopathological characteristics associated with post-recurrence cure were analyzed.

Results: Among 535 patients who developed recurrence, 24 (4.5%) achieved post-recurrence cure. The median post-recurrence follow-up duration was 151 (85-275) months for those who achieved post-recurrence cure. The solitary recurrent lesions and local treatment for the initial recurrence site were significantly more for patients who could be cured after they developed recurrence. All patients with post-recurrence cure received only radical local treatment for the recurrent lesions.

Conclusions: Some patients with solitary recurrent NSCLC lesions can be cured with only radical local treatment.

Key Points: Significant findings of the study The post-recurrence cure patients maintained a cancer-free status for five years after treatment for recurrence without a second recurrence. All patients with post-recurrence cure received only radical local treatment for recurrence and had significantly higher number of solitary recurrent lesions. What this study adds Some patients with solitary recurrent NSCLC lesions after resection can be cured with only radical local treatment.
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http://dx.doi.org/10.1111/1759-7714.13669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605994PMC
November 2020

Biocompatible and flexible paper-based metal electrode for potentiometric wearable wireless biosensing.

Sci Technol Adv Mater 2020 Jun 24;21(1):379-387. Epub 2020 Jun 24.

Department of Mechanical Engineering, School of Engineering, the University of Tokyo, Tokyo, Japan.

A paper-based electrode is a very attractive component for a disposable, nontoxic, and flexible biosensor. In particular, wearable biosensors, which have recently been attracting interest, not only require these characteristics of paper-based electrodes but must also be able to detect various ions and biomolecules in biological fluids. In this paper, we demonstrate the detection ability of paper-based metal electrodes for wearable biosensors as part of a wireless potentiometric measurement system, focusing on the detection of pH and sodium ions. The paper-based metal electrodes were obtained by simply coating a silicone-rubber-coated paper sheet with a Au (/Cr) thin film by sputtering then modifying it with different functional membranes such as an oxide membrane (TaO) and a fluoropolysilicone (FPS)-based Na-sensitive membrane, corresponding to the targeted ions. Satisfactory and stable detection sensitivities of the modified paper-based Au electrodes were obtained over several weeks even when they were bent to a radius of curvature in the range of 6.5 to 25 mm, assuming use in a flexible body patch biosensor. Moreover, the Na concentration in a sweat sample was evaluated using the paper-based Au electrode with the FPS-based Na-sensitive membrane in a wireless and real-time manner while the electrode was bent. Thus, owing to their complex mesh structure, flexible paper sheets should be suitable for use as potentiometric electrodes for wearable wireless biosensors.
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http://dx.doi.org/10.1080/14686996.2020.1777463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476484PMC
June 2020

Testicular seminoma with a progressing pulmonary nodule and mediastinal lymphadenopathy without retroperitoneal metastasis.

IJU Case Rep 2020 Sep 7;3(5):211-214. Epub 2020 Jul 7.

Department of Urology Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan.

Introduction: Testicular germ cell cancer has a relatively good prognosis even if visceral and/or lymph node metastases are present thanks to chemotherapy. Yet chemotherapy can lead to various adverse events. Therefore, it is crucial to distinguish whether a suspected metastatic disease is metastasis or not.

Case Presentation: A 33-year-old male visited our hospital to receive subsequent therapy for suspected recurrent seminoma with a progressing pulmonary nodule and mediastinal lymphadenopathy after orchiectomy. The pathological diagnosis of needle aspiration and resected specimen of the several lesions was consistent with epithelioid cell granuloma without caseous necrosis. Based on these findings, the lung and mediastinal lymph node lesions were diagnosed as sarcoidosis.

Conclusion: In cases where the simultaneous occurrence of other benign or malignant diseases is suspected, pathological confirmation is necessary for appropriate decision-making.
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http://dx.doi.org/10.1002/iju5.12191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469829PMC
September 2020

Focally Ossified Minimally Invasive Adenocarcinoma of the Lung Coexisting With Occult Pulmonary Metastases From Thyroid Cancer.

J Thorac Imaging 2020 Nov;35(6):W119-W122

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

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http://dx.doi.org/10.1097/RTI.0000000000000551DOI Listing
November 2020

An extremely rare case of rapidly growing mediastinal well-differentiated liposarcoma with a sclerosing variant: a case report.

Surg Case Rep 2020 Jul 3;6(1):158. Epub 2020 Jul 3.

Department of Thoracic Surgical Oncology, the Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.

Background: Liposarcoma arising from the mediastinum is rare, accounting for less than 1% of mediastinal tumors. Furthermore, a rapidly growing well-differentiated liposarcoma is extremely rare. A well-differentiated liposarcoma is usually considered a low-grade malignancy. However, we present an extremely rare case of a sclerosing variant of well-differentiated liposarcoma that grew rapidly within a year.

Case Presentation: A 77-year-old man with a giant mass in the left thoracic cavity was referred to our hospital. This mass measured about 10 cm and occupied the left-sided mediastinum on a chest radiography; however, there was no abnormal finding on the previous year's chest radiography. Chest-enhanced computed tomography revealed a well-circumscribed 11-cm mass in the left-sided anterior mediastinum. Positron emission tomography showed accumulation of fluorodeoxyglucose uptake in this tumor (maximum standard uptake value = 3.3). The radiological findings of computed tomography and positron emission tomography indicated that this tumor was a benign or low-grade malignancy; therefore, the chest radiographic findings were difficult to explain. To explain this discrepancy and establish the diagnosis, tumor resection was performed via left posterolateral thoracotomy. Intraoperatively, the left phrenic nerve and pericardium were adhered tightly to the tumor, so we resected them. The tumor was well-circumscribed and fibrous; therefore, the initial diagnosis was solitary fibrous tumor. However, based on its histopathological and immunohistochemical patterns, the tumor was diagnosed as a sclerosing variant of well-differentiated liposarcoma. Five years postoperatively, the patient remains alive with no evidence of disease recurrence.

Conclusions: A well-differentiated liposarcoma is usually considered a low-grade malignancy. Nevertheless, the giant tumor in the present case appeared within 1 year. Thus, this was an extremely rare case of a sclerosing variant of well-differentiated liposarcoma with rapid growth.
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http://dx.doi.org/10.1186/s40792-020-00928-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334334PMC
July 2020

Oncological outcomes after lobe-specific mediastinal lymph node dissection via multiport video-assisted thoracoscopic surgery.

Eur J Cardiothorac Surg 2020 08;58(Suppl_1):i92-i99

Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Koto-ku, Tokyo, Japan.

Objectives: We retrospectively investigated oncological outcomes after video-assisted thoracoscopic surgery (VATS) lobectomy with lobe-specific mediastinal lymph node dissection (MLND).

Methods: Between April 2008 and December 2016, a total of 660 patients underwent VATS lobectomy with lobe-specific MLND for clinical T1-3N0M0 non-small-cell lung cancer, of which 54 (8.2%) patients had pathological node-positive disease (18 N1 and 36 N2). We evaluated their oncological outcomes.

Results: The predominant histological type was adenocarcinoma (87%). Six (33%) patients in the pN1 and 11 (31%) patients in the pN2 received adjuvant chemotherapy. The median follow-up period was 51.6 months. Postoperative recurrence was observed in 5 (28%) pN1 and 22 (61%) pN2 patients. One (6%) pN1 and 12 (33%) pN2 patients experienced locoregional recurrence. None of the pN1 patient experienced local recurrence at the dissected zone, whereas 11 (31%) pN2 patients had lymph node recurrence, including four at the dissected area and three in the area omitted from dissection in the lobe-specific MLND. The 5-year overall survival rates were 88.1% in the pN1 patients and 80.0% in the pN2 patients; the 5-year recurrence-free survival rates were 63.9% in the pN1 patients and 34.8% in the pN2 patients. In pN2 patients, pathological T classification was a prognostic factor for overall survival (P < 0.001) and recurrence-free survival (P = 0.034), and single-station N2 disease was also prognostic factor for overall survival (P = 0.023).

Conclusions: Recurrence at the omitted zone is an issue for this type of MLND. For pN1 patients, adequate MLND is an important factor for curative treatment. However, for pN2 patients, systemic treatment after recurrence may also contribute to survival.
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http://dx.doi.org/10.1093/ejcts/ezaa166DOI Listing
August 2020

Outcomes after thoracoscopic surgery in octogenarian patients with clinical N0 non-small-cell lung cancer.

Jpn J Clin Oncol 2020 Aug;50(8):926-932

Department of Thoracic Surgical Oncology, Cancer Institute Hospital, The Japanese Foundation for Cancer Research, Tokyo, Japan.

Objective: The number of surgeries for elderly patients with lung cancer is increasing. In our institute, thoracoscopic lobectomy and hilar lymph node dissection are the standard procedure for octogenarian patients with clinical N0 non-small-cell lung cancer. The aim of this study was to determine the outcome of our strategy for octogenarian patients.

Methods: Seventy octogenarian patients with clinical N0 non-small-cell lung cancer who underwent surgery were enrolled (O group). As a control group, 205 septuagenarian patients were also enrolled (S group). We compared several clinicopathological factors and outcomes.

Results: The median age of the O group was 82. There was no significant difference in the comorbidity ratio between the two groups. The 5-year overall survival ratio for the O group (72.8%) was significantly worse than that for the S group (88.3%). However, multivariate analysis proved age was not an independent predictor of outcome. The rates of recurrences involving ipsilateral mediastinal lymph nodes were equal in the two groups. After propensity score matching, clinical T1 patients were dominant (85%) in two matched group and no statistically significant differences were observed in the 5-year overall survival between the two groups.

Conclusions: Our strategy for octogenarian patients with non-small-cell lung cancer, including omission of mediastinal lymph node dissection, was determined to be feasible, in particularly with cT1N0 disease.
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http://dx.doi.org/10.1093/jjco/hyaa061DOI Listing
August 2020

A rapidly growing mature mediastinal teratoma with a testicular epidermoid cyst and familial Mediterranean fever.

Respir Med Case Rep 2020 17;29:100988. Epub 2019 Dec 17.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Anterior mediastinal teratomas are common and are generally characterized as slow growing tumors. Very few reports documenting rapidly growing tumors exist. Here, we describe a case of a mature teratoma showing rapid growth in 1 year treated with complete surgical resection.
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http://dx.doi.org/10.1016/j.rmcr.2019.100988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118410PMC
December 2019

Co-occurrence of bilateral pneumothorax and pneumoperitoneum.

BMJ Case Rep 2020 Mar 17;13(3). Epub 2020 Mar 17.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

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http://dx.doi.org/10.1136/bcr-2020-234628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078692PMC
March 2020

Insulinoma-associated Protein 1 (INSM1) Is a Better Marker for the Diagnosis and Prognosis Estimation of Small Cell Lung Carcinoma Than Neuroendocrine Phenotype Markers Such as Chromogranin A, Synaptophysin, and CD56.

Am J Surg Pathol 2020 06;44(6):757-764

Division of Pathology, The Cancer Institute.

To diagnose small cell lung carcinoma (SCLC), neuroendocrine (NE) phenotype markers such as chromogranin A, synaptophysin, and CD56 are helpful. However, because they are dispensable, SCLCs occur without apparent NE phenotypes. Insulinoma-associated protein 1 (INSM1) is a transcription factor for NE differentiation and has emerged as a single practical marker for SCLC. Using the surgical samples of 141 pulmonary NE tumors (78 SCLCs, 44 large cell NE carcinomas, and 19 carcinoids), and 246 non-NE carcinomas, we examined the immunohistochemical expression and prognostic relevance of INSM1 in association with NE phenotype markers. We evaluated its sensitivity and specificity for SCLC diagnosis, as well as its usefulness to diagnose SCLC without NE marker expression and to estimate the prognosis. INSM1 was expressed in SCLCs (92%, 72/78), large cell NE carcinomas (68%, 30/44), and carcinoids (95%, 18/19). In addition, among SCLCs with no expression of NE phenotype markers (n=12), 9 (75%) were positive for INSM1. These data suggest the superiority of INSM1 to the phenotype markers. Only 7% of adenocarcinomas (9/134) and 4% of squamous cell carcinomas (4/112) were positive for INSM1. SCLC with low-INSM1 expression (n=28) had a significantly better prognosis (P=0.040) than the high-INSM1 group (n=50). Our study revealed that INSM1 is highly sensitive and specific to detect SCLC and can estimate prognosis. INSM1 will be a promising marker for SCLC.
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http://dx.doi.org/10.1097/PAS.0000000000001444DOI Listing
June 2020

Utility of Maximum CT Value in Predicting the Invasiveness of Pure Ground-Glass Nodules.

Clin Lung Cancer 2020 05 30;21(3):281-287. Epub 2020 Jan 30.

Department of Thoracic Surgical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan.

Purpose: To predict the histologic invasiveness of pure GGNs using the maximum CT value.

Patients And Methods: One hundred eighty patients underwent a resection of pure GGNs. On preoperative CT imaging studies, we selected the axial section that showed the densest component of each GGN. The CT value was measured using a DICOM (Digital Imaging and Communication in Medicine) viewer, excluding portions of vessels and bronchi. The correlation between the CT value and GGN histologic diagnosis was analyzed.

Results: The numbers of patients with atypical adenomatous hyperplasia, adenocarcinoma-in-situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) were 9, 108, 56, and 7, respectively. One of the IAC tumors exhibited lymphatic invasion, and there were no cases of vascular invasion. In comparison to preinvasive lesions (atypical adenomatous hyperplasia and AIS), invasive lesions (MIA and IAC) were correlated with a higher maximum CT value (-404 ± 113 Hounsfield units [HU] vs. -216 ± 125 HU, P < .01). The cutoff point of maximum CT value was determined at -300 HU using receiver operating characteristic curve analysis, and exhibited sensitivity and specificity of 83% and 88%, respectively. Multivariate analysis revealed that maximum CT value was an independent predictor of histologic invasiveness (odds ratio 39, P < .01). The interobserver reliability was satisfactory (intraclass correlation coefficient, 0.738; unweighted kappa-values, 0.722).

Conclusion: IAC and MIA accounted for 4% and 31% of the pure GGN lesions, respectively. Higher maximum CT value (≥ -300 HU) was a useful predictor of histologic invasiveness.
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http://dx.doi.org/10.1016/j.cllc.2020.01.015DOI Listing
May 2020
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