Publications by authors named "Masanori Tsuchida"

106 Publications

Maximum Standardized Uptake Value on Positron Emission Tomography is Associated With More Advanced Disease and High-risk Features in Lung Adenocarcinoma.

Semin Thorac Cardiovasc Surg 2021 Jul 25. Epub 2021 Jul 25.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been widely used for preoperative staging of lung adenocarcinomas. The aim of this study was to determine whether a high maximum standardized uptake value (SUVmax) could correlate with pathological characteristics in those patients. We retrospectively reviewed patients with clinical stage 0-IA lung adenocarcinoma who underwent preoperative F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography followed by curative anatomical resection. To identify more advanced disease and high-risk features, representing visceral pleural involvement, pulmonary metastasis, lymph node involvement, and lymphovascular involvement in resected surgical specimens, univariate and multivariate logistic regression analyses were performed. The optimal cutoff point for the SUVmax was determined by receiver operating characteristic analysis. In 2 groups divided according to the cutoff point, the disease-free survivals were calculated and compared using the Kaplan-Meier method and the log-rank test. More advanced disease and high-risk features were identified in 55 (18.9%) of the 291 patients. SUVmax was significantly correlated with more advanced disease and high-risk features, as did the consolidation/tumor ratio on computed tomography. Only 2 (1.2%) of the 169 patients with a SUVmax <3.20 showed more advanced disease and high-risk features, compared with 43.4% of patients with a SUVmax ≥3.20. The disease-free survival was significantly higher in patients with a SUVmax <3.20 than in those with a SUVmax ≥3.20 (P = 0.002). A high SUVmax correlates with more advanced disease and high-risk features in patients with clinical stage 0-IA lung adenocarcinoma. The SUVmax should be considered when deciding treatment strategy in early-stage lung adenocarcinoma.
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http://dx.doi.org/10.1053/j.semtcvs.2021.07.019DOI Listing
July 2021

Oncological issues in staging mediastinal lymph node metastases in left lung cancer.

Asian J Surg 2021 Apr 30. Epub 2021 Apr 30.

Department of General Thoracic Surgery, Southern Tohoku General Hospital, Research Institute for Neuroscience & Respirology, Koriyama, Japan.

Objective: We aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL).

Methods: This multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy.

Results: Mediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis.

Conclusions: The prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.
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http://dx.doi.org/10.1016/j.asjsur.2021.04.003DOI Listing
April 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 Apr 26. 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
April 2021

Mutational signatures in squamous cell carcinoma of the lung.

J Thorac Dis 2021 Feb;13(2):1075-1082

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Tumor mutational burden (TMB) has been identified as one of the predictors for the response to anti-programmed cell death-1 (anti-PD-1) antibody therapy and reported to correlate with smoking history in lung adenocarcinoma. However, in squamous cell carcinoma of the lung, the association between TMB and clinicopathological background factors, such as smoking history, has not been reported, including in our previous study. The mutational signature is a tool to identify the mutagens that are contributing to the mutational spectrum of a tumor by investigating the pattern of DNA changes. Here, we analyzed the mutational signature in lung squamous cell carcinoma to identify mutagens affecting the TMB.

Methods: Seven representative mutational signatures including signature 7 (SI7) [ultraviolet (UV)-related], SI4 (smoking), SI6/15 [mismatch repair (MMR)], SI2/13 [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)], and SI5 (clock-like) were analyzed in Japanese patients with lung squamous cell carcinoma (n=67) using data generated by next-generation sequencing consisting of a 415-gene panel. The relationships between signatures and clinico-pathological data including TMB and programmed death-ligand 1 (PD-L1) expression were analyzed.

Results: Although the reconstructed mutational counts were small with targeted sequencing (median: 30.1, range: 13.3-98.7), the distributions of signatures were comparable among samples, with 56 cases containing more than four signatures. The smoking-related SI4 was found in 45 cases and was significantly related with pack-year index (PYI) (P=0.026). The reconstructed mutation counts were highly correlated with SI4 (r=0.51, P<0.0001), whereas the correlation was weak with SI6/15 (MMR-related) and SI2/13 (APOBEC-related). There was no mutational signature related with PD-L1 expression. Some patients exhibited unique signatures; the patient with the highest mutational counts had a MMR signature, and another patient with a prominent UV signature had occupational exposure to UV, as he was employed as a neon sign engineer.

Conclusions: Mutational signatures can predict the cause of lung squamous cell carcinoma. Tobacco smoking is the mutagen most related with TMB.
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http://dx.doi.org/10.21037/jtd-20-2602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947495PMC
February 2021

Surgical outcomes of ipsilateral metachronous second primary lung cancer.

Interact Cardiovasc Thorac Surg 2021 05;32(6):896-903

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Objectives: The optimal surgical approach for metachronous second primary lung cancer (MSPLC), especially ipsilateral MSPLC, remains unclear. This study aimed to review postoperative complications and examine surgical outcomes based on the extent of resection after surgery for ipsilateral MSPLC.

Methods: Clinical data from 61 consecutive patients who underwent pulmonary resection for ipsilateral MSPLC according to the Martini-Melamed criteria between January 2005 and December 2017 in 3 institutes were retrospectively reviewed.

Results: Postoperative complications were identified in 12 patients (19.7%). Regarding the combination of initial and second surgery, intraoperative bleeding was significantly greater in patients with anatomic-anatomic resection than in others (P < 0.001). Operation time was significantly longer in patients with anatomic-anatomic resection than in others (P < 0.001). However, postoperative complications showed no significant differences based on the combination of surgeries. Five-year overall survival rates in patients with anatomic resection and wedge resection after second surgery were 75.8% and 75.8%, respectively (P = 0.738), and 5-year recurrence-free survival rates were 54.2% and 67.6%, respectively (P = 0.368). Cox multivariate analysis identified ever-smoker status (P = 0.029), poor performance status (P = 0.011) and tumour size >20 mm (P = 0.001) as independent predictors of poor overall survival, while ever-smoker status (P = 0.040) and tumour size >20 mm (P = 0.007) were considered independent predictors of poor recurrence-free survival.

Conclusions: Regarding postoperative and long-term outcomes for patients with ipsilateral MSPLC, surgical intervention is safe and offers good long-term survival. Wedge resection is an acceptable provided tumours ≤2 cm and ground-glass opacity-predominant as a second surgery for early-stage ipsilateral MSPLC.
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http://dx.doi.org/10.1093/icvts/ivab025DOI Listing
May 2021

Radical segmentectomy as a potential alternative surgical treatment with curative intent in early-stage non-small cell lung cancer.

J Thorac Dis 2020 Oct;12(10):6115-6119

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

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http://dx.doi.org/10.21037/jtd-20-1582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656425PMC
October 2020

Salvage surgery to treat tumor regrowth after stereotactic body radiotherapy in primary non-small cell lung cancer.

J Thorac Dis 2020 Oct;12(10):5289-5298

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Stereotactic body radiotherapy (SBRT) is considered to be an effective and safe treatment in patients with primary lung cancer. If local recurrence is confirmed following SBRT, surgical treatment is a possibility. The present study aimed to clarify the safety and survival outcomes of salvage surgery in primary lung cancer patients with local recurrence following SBRT.

Methods: All subjects were patients with primary lung cancer who underwent surgical treatment for local recurrence following SBRT during the period from July 2005 to July 2015. We evaluated the reason for SBRT selection, the surgical procedure, postoperative complications, and prognosis.

Results: Of 932 patients underwent SBRT as treatment for primary lung cancer, 48 patients (5.2%) had local recurrence alone and 19 patients (2.0%) underwent salvage surgery. SBRT was selected in eight medically operable patients who refused surgery, and in 11 patients considered medically inoperable by their pulmonologist. Lobectomy was performed in 15 patients. Postoperative complications were documented in 4 patients (21.1%). Incomplete resection was performed in 2 patients. Stage progression was confirmed in 7 patients (36.8%). The 5-year overall survival (OS) was 72.5% and the 5-year disease-free survival (DFS) was 65.2%.

Conclusions: We evaluated patients who underwent salvage surgery due to local recurrence of lung cancer following SBRT. We found that salvage surgery could be performed safely without affecting SBRT outcomes. We further infer that cases of complete resection are likely to be associated with good prognosis, and that SBRT should be selected only after careful consideration because complete resection is not possible in all cases.
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http://dx.doi.org/10.21037/jtd-20-2253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656326PMC
October 2020

Frequent Germline and Somatic Single Nucleotide Variants in the Promoter Region of the Ribosomal RNA Gene in Japanese Lung Adenocarcinoma Patients.

Cells 2020 11 3;9(11). Epub 2020 Nov 3.

Histopathology Core Facility, Niigata University Faculty of Medicine, Niigata 951-8510, Japan.

Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called "ribosomopathies," including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions -248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 ( = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis ( < 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.
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http://dx.doi.org/10.3390/cells9112409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692307PMC
November 2020

Left upper lobectomy is a risk factor for cerebral infarction after pulmonary resection: a multicentre, retrospective, case-control study in Japan.

Surg Today 2020 Nov 17;50(11):1383-1392. Epub 2020 Jun 17.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Purpose: The anatomical site of resected lobes may influence postoperative cerebral infarction. The objective of the current study was to determine if left upper pulmonary lobectomy is a risk factor for postoperative cerebral infarction.

Methods: This was a retrospective case-control study in patients undergoing pulmonary lobectomy from 2004 to 2013 in Japan. We retrospectively identified 610 patients from 153 institutions who had developed postoperative cerebral infarction following pulmonary lobectomy. The control group consisted of 773 patients who underwent lobectomy without cerebral infarction during a randomly selected single month in 2009 at the same institutions.

Results: Factors associated with cerebral infarction were age [10-year intervals, odds ratio (OR): 1.46; 95% confidence interval (CI): 1.23-1.73; p < 0.001], male sex (OR 1.92; 95% CI 1.29-2.86; p = 0.001), presence of comorbidities (OR 1.82; 95% CI 1.35-2.44; p < 0.001), perioperative anti-platelet or anti-coagulant drug use (OR 1.71; 95% CI 1.20-2.45; p = 0.003), and lobectomy. Subgroup analyses revealed that cerebral infarction was strongly associated with left upper lobectomy.

Conclusions: Our findings suggest that left upper lobectomy is associated with a higher risk of cerebral infarction than other types of lobectomy, particularly in the early postoperative period.
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http://dx.doi.org/10.1007/s00595-020-02032-4DOI Listing
November 2020

Impact of postoperative complications on outcomes of second surgery for second primary lung cancer.

Surg Today 2020 Nov 1;50(11):1452-1460. Epub 2020 Jun 1.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan.

Purpose: The best surgical approach for second primary lung cancer remains a subject of debate. The purpose of this study was to review the postoperative complications after second surgery for second primary lung cancer and to investigate the outcomes based on these complications.

Methods: The clinical data of 105 consecutive patients who underwent pulmonary resection for multiple primary lung cancers between January, 1996 and December, 2017, were reviewed according to the Martini-Melamed criteria.

Results: After the second surgery, low body mass index (BMI) (< 18.5 kg/m) (P = 0.004) and high Charlson comorbidity index (CCI) (P = 0.002) were independent predictors of postoperative complications. Survival analysis revealed the 5-year overall survival rates of 74.5% and 61.4% for patients without postoperative complications and those with postoperative complications (P = 0.044), respectively, but the 5-year cancer-specific survival rates of 82.5% and 80.0% (P = 0.926), respectively. During this period, there were significantly more respiratory-related deaths of patients with complications than of those without complications (P = 0.011).

Conclusion: Surgical intervention is feasible and potentially effective for second primary lung cancer but may not achieve positive perioperative and long-term outcomes for patients with a low BMI or a high CCI. Treatment options should be considered carefully for these patients.
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http://dx.doi.org/10.1007/s00595-020-02038-yDOI Listing
November 2020

Adverse impact of univentricular pacing for the patient with functional single ventricle: successful conversion to cardiac resynchronization therapy.

Surg Case Rep 2020 May 13;6(1):101. Epub 2020 May 13.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata City, 951-8510, Japan.

Background: In a Fontan candidate, univentricular pacing may cause delay in interventricular conduction, which induces asynchronous contraction. Cardiac resynchronization therapy is expected to be an effective mode of therapy in such a case.

Case Presentation: A 7-month-old girl, diagnosed with dextrocardia, congenitally corrected transposition of the great artery [situs solitus, L-loop, and L-transposition], ventricular septal defect, infundibular and pulmonary valvular stenosis, and straddling of the tricuspid valve, was considered as a candidate for the Fontan procedure. She had undergone Blalock-Taussig shunt, and epicardial univentricular pacemaker implantation for persistent complete atrioventricular block. She underwent a bidirectional cavopulmonary shunt concomitant with ventricular lead translocation from the morphological left ventricle to the morphological right ventricle. After discharge, ventricular dyssynchrony was noted and cardiac failure persisted. She was converted to cardiac resynchronization therapy (CRT) at 13 months of age. Two-dimensional speckle tracking imaging was used by cardiologists to determine the most suitable pacing site. CRT rapidly corrected the heart failure; thus, she underwent the Fontan procedure after 1.5 years. Five years have passed since the cardiac resynchronization therapy; her interventricular synchrony is maintained well and the level of brain natriuretic peptide remains within normal range.

Conclusion: We describe the successful conversion from single ventricular pacing to CRT, in a case of congenitally corrected transposition of the great artery indicated for the Fontan procedure. The long-term prognosis of cardiac resynchronization therapy is undetermined in the pediatric population; therefore, further follow-up is required.
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http://dx.doi.org/10.1186/s40792-020-00863-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221050PMC
May 2020

Generation of Lungs by Blastocyst Complementation in Apneumic Fgf10-Deficient Mice.

Cell Rep 2020 05;31(6):107626

Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori Chuo-ku, Niigata 951-8510, Japan. Electronic address:

The shortage of donor lungs hinders lung transplantation, the only definitive option for patients with end-stage lung disease. Blastocyst complementation enables the generation of transplantable organs from pluripotent stem cells (PSCs) in animal models. Pancreases and kidneys have been generated from PSCs by blastocyst complementation in rodent models. Here, we report the generation of lungs using mouse embryonic stem cells (ESCs) in apneumic Fgf10 Ex1/Ex3mice by blastocyst complementation. Complementation with ESCs enables Fgf10-deficient mice to survive to adulthood without abnormalities. Both the generated lung alveolar parenchyma and the interstitial portions, including vascular endothelial cells, vascular and parabronchial smooth muscle cells, and connective tissue, largely originate from the injected ESCs. These data suggest that Fgf10 Ex1/Ex3blastocysts provide an organ niche for lung generation and that blastocyst complementation could be a viable approach for generating whole lungs.
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http://dx.doi.org/10.1016/j.celrep.2020.107626DOI Listing
May 2020

A novel suture technique in closing the single drainage tube hole in uni-portal video-assisted thoracoscopic surgery.

Ann Transl Med 2020 Apr;8(7):424

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

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http://dx.doi.org/10.21037/atm.2020.03.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210167PMC
April 2020

Primary lung squamous cell carcinoma and its association with gastric metastasis: A case report and literature review.

Thorac Cancer 2020 06 25;11(6):1708-1711. Epub 2020 Mar 25.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Nearly 50% of primary lung carcinoma patients present with distant metastasis at their first visit. However, gastrointestinal tract (GIT) metastasis is an infrequent impediment. Herein, we report a case of progressive dysphagia and epigastralgia as an initial manifestation of recurrence as gastric metastasis of primary lung squamous cell carcinoma (SCC) after curative surgery. A 64-year-old man was diagnosed with primary lung SCC of the right lower lobe, and underwent thoracoscopic lower lobectomy. One year after lobectomy, computed tomography (CT) scan showed a gastric fundal mass located in the gastric cardia which measured 5 cm. Endoscopic biopsies and histopathology subsequently confirmed that tumor was SCC. The patient then underwent proximal gastrectomy with resection of the diaphragmatic crus. Following surgery, histopathological examination revealed gastric metastasis from primary lung SCC. KEY POINTS: Gastric metastasis of primary lung carcinoma is one of the rarest phenomena. Gastrointestinal symptoms should raise suspicion of the presence of advanced metastatic disease with poor prognosis.
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http://dx.doi.org/10.1111/1759-7714.13410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262906PMC
June 2020

Characteristics and risk factors of recurrence in clinical stage I non-small cell lung cancer patients undergoing anatomic segmentectomy.

Gen Thorac Cardiovasc Surg 2020 Sep 20;68(9):1011-1017. Epub 2020 Mar 20.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

Objective: Although lobectomy is the standard surgical procedure for small-sized non-small cell lung cancer (NSCLC), segmentectomy has been performed for various reasons. The aim of this study was to investigate the characteristics of and risk factors for recurrence in early-stage NSCLC patients undergoing segmentectomy.

Methods: We retrospectively reviewed 179 patients with clinical stage I NSCLC who underwent segmentectomy. Preoperative factors were analyzed using the log-rank test for univariate analyses. Multivariate analyses were performed using a Cox proportional hazards regression model to identify independent risk factors for recurrence. For the significant factors, optimal cutoff points were determined by receiver operating characteristic (ROC) analysis.

Results: During the follow-up period of 51 months, 18 patients developed recurrence; 5 had locoregional (including 2 with margin recurrences only), 9 had distant, and 4 had both locoregional and distant recurrence. Multivariate and ROC analysis identified radiologic solid tumor size with a cutoff point of 1.5 cm as an independent risk factor for recurrence. Three patients in the solid size < 1.5 cm group (n = 119) developed recurrence, 2 of whom had surgical margin recurrence, compared to 15 patients in the solid size ≥ 1.5 cm group (n = 60).

Conclusions: The indication for segmentectomy should be decided upon with caution, and the segments to be resected should be carefully considered to secure an appropriate surgical margin in this low-risk subgroup of patients because they may have a relatively higher risk of surgical margin recurrence, despite being at decreased risk.
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http://dx.doi.org/10.1007/s11748-020-01338-xDOI Listing
September 2020

[Resection of Multiple Thymic Carcinomas of the Thymus].

Kyobu Geka 2019 Nov;72(12):993-996

Department of Thoracic Surgery, Shibata Hospital, Shibata, Japan.

The patient was a 70-year-old woman who was found to have 2 mediastinal tumors on chest computed tomography(CT). One was located in the anterior mediastinum, and the other was in the upper mediastinum. Based on previous imaging studies, it was revealed that the 2 tumors had been increasing in size for 5 years. Thymectomy via median sternotomy was performed. Histopathologically, 3 tumors revealed to be in the thymus without direct invasion of the adjacent organs. All were thymic squamous cell carcinomas of 3.0×1.8×1.6 cm, 2.5×1.6×1.2 cm and 0.7 cm in size. No lymphatic invasion was observed and all tumors were pathologically stage I. Thus, we considered the 3 tumors were multi-centric primary tumors.
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November 2019

[Dedifferentiated Liposarcoma of the Anterior Mediastinum;Report of a Case].

Kyobu Geka 2019 Oct;72(11):958-961

Department of Thoracic Surgery, Niigata Prefectural Shibata Hospital, Shibata, Japan.

A 69-year-old man was pointed out the anterior mediastinal mass on chest computed tomography (CT). Since the thymoma was suspected, thymectomy was performed through median sternotomy. The tumor was encapsulated and did not directly invade adjacent organs. The tumor was 8.3×5.3×8.2 cm in size. Histological examination of the resected specimen showed a large mucinous component and a small fibrous component, both containing many atypical spindle cells and multinuclear giant cells, and fat cells and atypical lipoblasts observed in a small part of the specimen. The postoperative pathological diagnosis was dedifferentiated liposarcoma. No relapse is observed without adjuvant therapy at 1 year after surgery.
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October 2019

Superior Vena Cava Flap to Reroute Partial Anomalous Pulmonary Venous Connection.

World J Pediatr Congenit Heart Surg 2019 09;10(5):645-647

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata Prefecture, Japan.

A 46-year-old man who had undergone atrial septal defect closure during childhood was referred for surgery for residual partial anomalous pulmonary venous connection. The anomalous pulmonary veins were connected to the higher (cephalad) segment of the superior vena cava. As the usual caval division technique was not applicable, we chose to utilize the anterior wall of the superior vena cava as a flap for anomalous pulmonary vein rerouting. Bovine pericardium was used to reconstruct the systemic venous pathway. Systemic or pulmonary venous stenosis was not detected. The patient was discharged with a sinus rhythm.
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http://dx.doi.org/10.1177/2150135119862596DOI Listing
September 2019

Swing-back and trap-door technique repair for interrupted aortic arch with right-sided descending aorta.

Interact Cardiovasc Thorac Surg 2019 11;29(5):818-819

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

A right-sided descending aorta with a left aortic arch is a rare congenital anomaly in which the aortic arch crosses the midline from the left side of the trachea coursing to the descending aorta in the right thoracic cavity. The surgical repair of an interrupted aortic arch with a right-sided descending aorta carries great risks of bronchial and oesophageal obstruction. Herein, we describe a case of successful surgical repair of an interrupted aortic arch with a right-sided descending aorta using the swing-back and trap-door techniques.
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http://dx.doi.org/10.1093/icvts/ivz175DOI Listing
November 2019

[Thoracoscopic Left Upper Division Segmentectomy for Multiple Ground-glass Nodules Using Preoperative Virtual-assisted Lung Mapping].

Kyobu Geka 2019 Jul;72(7):528-533

Division of Thoracic and Cardiovascular Surgery, Niigata University, Niigata, Japan.

Associated with an increase of small-sized lung cancer or metachronous second primary lung cancer, we have more opportunities to perform sublobar resection. Difficulties of identifying tumor location and appropriate surgical margin for small-sized ground-glass opacity (GGO) dominant lesions in thoracoscopic surgery is the big issue of sublobar resection. Virtual-assisted lung mapping (VAL-MAP) that makes markings on the lung surface through some peripheral bronchi by bronchoscopically projects intrapulmonary anatomy on the lung surface and literally draw a map. We report a case of thoracoscopic left upper division segmentectomy for multiple ground-glass nodules (GGNs) using preoperative VAL-MAP. A 65-year-old women who had undergone right upper lobectomy for primary lung cancer, and had multiple GGNs in the bilateral lungs was followed up as an outpatient. Eleven years after initial pulmonary resection, 2 lesions in the left upper division became bigger, and we decided to perform surgery for 4 GGNs in the left upper division including these 2 lesions. We preoperatively made bronchoscopic dye markings through B1+2c, B3a and B4a for in the left upper lobe. The 3 markings were intraoperatively identified. We decided the resection line based on the markings and performed thoracoscopic left upper division segmentectomy. The pathological diagnosis was minimally invasive adenocarcinoma, adenocarcinoma in situ and pneumonitis. Surgical margins were negative. VAL-MAP will assume an important role as an intraoperative navigation system for sublobar resection.
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July 2019

The impact of emphysema on surgical outcomes of early-stage lung cancer: a retrospective study.

BMC Pulm Med 2019 Apr 4;19(1):73. Epub 2019 Apr 4.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata-shi, Niigata, 951-8510, Japan.

Background: The presence of emphysema on computed tomography (CT) is associated with an increased frequency of lung cancer, but the postoperative outcomes of patients with pulmonary emphysema are not well known. The objective of this study was to investigate the association between the extent of emphysema and long-term outcomes, as well as mortality and postoperative complications, in early-stage lung cancer patients after pulmonary resection.

Methods: The clinical records of 566 consecutive lung cancer patients who underwent pulmonary resection in our department were retrospectively reviewed. Among these, the data sets of 364 pathological stage I patients were available. The associations between the extent of lung emphysema and long-term outcomes and postoperative complications were investigated. Emphysema was assessed on the basis of semiquantitative CT. Surgery-related complications of Grade ≥ II according to the Clavien-Dindo classification were included in this study.

Results: Emphysema was present in 63 patients. The overall survival and relapse-free survival of the non-emphysema and emphysema groups at 5 years were 89.0 and 61.3% (P < 0.001), respectively, and 81.0 and 51.7%, respectively (P < 0.001). On multivariate analysis, significant prognostic factors were emphysema, higher smoking index, and higher histologic grade (p < 0.05). Significant risk factors for poor recurrence-free survival were emphysema, higher smoking index, higher histologic grade, and presence of pleural invasion (P < 0.05). Regarding Grade ≥ II postoperative complications, pneumonia and supraventricular tachycardia were more frequent in the emphysema group than in the non-emphysema group (P = 0.003 and P = 0.021, respectively).

Conclusion: The presence of emphysema affects the long-term outcomes and the development of postoperative complications in early-stage lung cancer patients.
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http://dx.doi.org/10.1186/s12890-019-0839-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449985PMC
April 2019

p53 plays a crucial role in endothelial dysfunction associated with hyperglycemia and ischemia.

J Mol Cell Cardiol 2019 04 18;129:105-117. Epub 2019 Feb 18.

Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan. Electronic address:

p53 is a guardian of the genome that protects against carcinogenesis. There is accumulating evidence that p53 is activated with aging. Such activation has been reported to contribute to various age-associated pathologies, but its role in vascular dysfunction is largely unknown. The aim of this study was to investigate whether activation of endothelial p53 has a pathological effect in relation to endothelial function. We established endothelial p53 loss-of-function and gain-of-function models by breeding endothelial-cell specific Cre mice with floxed Trp53 or floxed Mdm2/Mdm4 mice, respectively. Then we induced diabetes by injection of streptozotocin. In the diabetic state, endothelial p53 expression was markedly up-regulated and endothelium-dependent vasodilatation was significantly impaired. Impairment of vasodilatation was significantly ameliorated in endothelial p53 knockout (EC-p53 KO) mice, and deletion of endothelial p53 also significantly enhanced the induction of angiogenesis by ischemia. Conversely, activation of endothelial p53 by deleting Mdm2/Mdm4 reduced both endothelium-dependent vasodilatation and ischemia-induced angiogenesis. Introduction of p53 into human endothelial cells up-regulated the expression of phosphatase and tensin homolog (PTEN), thereby reducing phospho-eNOS levels. Consistent with these results, the beneficial impact of endothelial p53 deletion on endothelial function was attenuated in EC-p53 KO mice with an eNOS-deficient background. These results show that endothelial p53 negatively regulates endothelium-dependent vasodilatation and ischemia-induced angiogenesis, suggesting that inhibition of endothelial p53 could be a novel therapeutic target in patients with metabolic disorders.
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http://dx.doi.org/10.1016/j.yjmcc.2019.02.010DOI Listing
April 2019

Left colic artery aneurysm rupture after stent placement for abdominal aortic aneurysm associated with neurofibromatosis type 1.

Surg Case Rep 2019 Jan 23;5(1):12. Epub 2019 Jan 23.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease of the skin and soft tissue. Aneurysms associated with NF1 can occur, but a secondary aneurysm rupture is very rare, with very few cases reported in literature.

Case Presentation: We describe the case of a 67-year-old female with NF1 who underwent endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm (AAA) rupture. She developed a type Ib endoleak requiring a redo-EVAR. Eighteen days after her primary operation, she was found to have two new left colic artery aneurysms. She required emergency surgery consisting of a left hemicolectomy and transverse colon colostomy. Pathology showed neurofibromatous changes to the peri-vasculature tissue, consistent with her underlying disease.

Conclusions: Although rare, secondary aneurysms can occur following AAA repair. Patients with soft tissue connective tissue disorders, like NF1, may be at an increased risk for development of these secondary aneurysms. Endovascular repair appears to be a safe approach for NF1 patients with AAA, but endovascular management can be challenging in the setting of NF1. Surgeons should be ready to convert to open surgery if the patient displays persistent signs of bleeding or structural changes related to connective tissue disorders like NF1.
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http://dx.doi.org/10.1186/s40792-019-0570-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346692PMC
January 2019

A novel parameter for pulmonary blood flow during palliative procedures: velocity time integral of the pulmonary vein†.

Eur J Cardiothorac Surg 2019 May;55(5):823-828

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Objectives: The main goal of palliative procedures for congenital heart defects is adequate pulmonary blood flow (PBF), but precise intraoperative PBF evaluation is sometimes difficult. The purpose of this preliminary study was to investigate the usefulness of velocity time integral of the pulmonary vein (PV-VTI) measured by transoesophageal echocardiography (TOE) at the time of palliative procedure as a parameter for PBF.

Methods: Case histories of 63 patients who underwent palliative procedures (bilateral pulmonary artery banding in 18 patients, main pulmonary artery banding in 22 patients and systemic-to-pulmonary artery shunt in 23 patients) and whose intraoperative PV-VTI was measured by TOE from 2011 to 2017 at our centre were retrospectively reviewed. Low-body-weight infants, cases in which cardiopulmonary bypass was used and cases that were anatomically difficult to measure were excluded.

Results: PV-VTIs measured at 4 orifices of the pulmonary veins were all significantly decreased in both the bilateral pulmonary artery banding and main pulmonary artery banding groups and increased in the systemic-to-pulmonary artery shunt group immediately after the procedure. There were significant correlations between the velocity time integrals of both right and left pulmonary veins and arterial oxygen saturation (r = 0.564 and 0.703). Nine patients (6 bilateral pulmonary artery banding and 3 systemic-to-pulmonary artery shunt) required unplanned early reoperation due to inadequate PBF; their PV-VTIs were significantly different from those of patients not requiring reoperation. No major complications related to TOE occurred postoperatively.

Conclusions: The PV-VTI measured by TOE during palliative procedures reflected the change of PBF and could help identify patients at higher risk of early reoperation due to inadequate PBF. This parameter may be a useful additional tool for evaluating intraoperative PBF.
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http://dx.doi.org/10.1093/ejcts/ezy465DOI Listing
May 2019

Early and mid-term outcomes of simultaneous thoracic endovascular stent grafting and combined resection of thoracic malignancies and the aortic wall.

Gen Thorac Cardiovasc Surg 2019 Feb 1;67(2):227-233. Epub 2018 Sep 1.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

Objectives: To aim of this study was to clarify the safety of simultaneous thoracic aortic endografting and combined resection of the aortic wall and thoracic malignancy in a one-stage procedure over the early and mid-term periods.

Methods: From March 2013 to December 2017, 6 patients underwent aortic endografting followed by one-stage en bloc resection of the tumor and aortic wall. Thoracic surgeons and cardiovascular surgeons discussed predicted tumor invasion range and resection site, stent placement position, stent length and size, and the surgical procedure, taking into account the safe margin.

Results: The proximal site of aortic endografting was the: aortic arch in 2 cases (subclavian artery (SCA) occlusion in one, and SCA fenestration in one); distal arch just beneath the SCA in 2; descending aorta in 2. Pulmonary resection involved lobectomy in 2 patients, pneumonectomy in 2, and completion pneumonectomy in 1. Aortic resection was limited to the adventitia in 2 cases, extended to the media in 3, and extended to the intima in 1. An endograft-related complication, external iliac artery intimal damage requiring vessel repair, was observed in one case. No complications associated with aortic resection were observed. Two postoperative complications of atrial fibrillation and chylothorax developed. There were no surgery-related deaths. During follow-up, no late endograft-related complications such as migration or endoleaks occurred.

Conclusions: Early and mid-term outcomes of stent graft-related complications are acceptable. Simultaneous thoracic aortic endografting and combined resection of the aortic wall and thoracic malignancies are feasible in one stage on the same day.
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http://dx.doi.org/10.1007/s11748-018-1003-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342828PMC
February 2019

Survival after repeated surgery for lung cancer with idiopathic pulmonary fibrosis: a retrospective study.

BMC Pulm Med 2018 Aug 10;18(1):134. Epub 2018 Aug 10.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata-shi, Niigata, 951-8510, Japan.

Background: Patients with idiopathic pulmonary fibrosis (IPF) have a high risk of developing lung cancer, but few studies have investigated the long-term outcomes of repeated surgery in such patients. The purpose of this study was to evaluate the surgical outcomes of repeated lung cancer surgery in patients with IPF.

Methods: From January 2001 to December 2015, 108 lung cancer patients with IPF underwent pulmonary resection at two institutions; 13 of these patients underwent repeated surgery for lung cancer, and their data were reviewed.

Results: The initial procedures of the 13 patients were lobectomy in 8, segmentectomy in 2, and wedge resection in 3. The subsequent procedures were wedge resection in 10 and segmentectomy in 3. The clinical stage of the second tumor was stage IA in 12 and stage IB in 1. Postoperatively, 3 patients (23.1%) developed acute exacerbation (AE) of IPF and died. The rate of decrease in percent vital capacity was significantly higher in patients with AE than in those without AE (p = 0.011). The 3-year overall survival rate was 34.6%. The causes of death were cancer-related in 7, AE of IPF in 3, and metachronous lung cancer in 1.

Conclusions: Despite limited resection, a high incidence of AE was identified. The early and long-term outcomes of repeated surgery in lung cancer patients with IPF were poor because of the high risk of AE of IPF and lung cancer recurrence. Long-term intensive surveillance will be required to determine whether surgical intervention is justified in patients with multiple primary lung cancers and IPF.
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http://dx.doi.org/10.1186/s12890-018-0703-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086038PMC
August 2018

Common driver mutations and smoking history affect tumor mutation burden in lung adenocarcinoma.

J Surg Res 2018 10 30;230:181-185. Epub 2018 Jul 30.

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Recent progress in genomic analysis using next-generation sequencing technology has enabled the comprehensive detection of mutations and tumor mutation burden (TMB) in patients. A high TMB (TMB-H) tumor is defined as one with high somatic mutational rates, which correlates with clinical responses to certain treatments such as immunotherapies. We determined TMB in lung adenocarcinoma and clarified the characteristics of patients with TMB-H in relation to common driver mutations and smoking history.

Materials And Methods: Genomic aberrations and TMB were determined in Japanese patients with lung adenocarcinoma (n = 100) using next-generation sequencing of 415 known cancer genes. TMB-H was defined as > 20 mutations per megabase (Mb) of sequenced DNA.

Results: The median TMB was 13.5 (5-33) mutations/Mb. Ten of 100 (10%) patients showed TMB-H, and the others showed low TMB (TMB-L). Only two of 10 (20%) patients with TMB-H had one of the common driver mutations (ALK and ERBB2 mutation), whereas 57 of 90 (63%) patients with TMB-L had one of the driver mutations, including ALK, EGFR, ERBB2, ROS, RET, and MET (P < 0.05). Notably, no EGFR mutation was observed in patients with TMB-H. Eight of 10 (80%) patients with TMB-H had recent smoking history, whereas only 17 of 90 (19%) patients with TMB-L had recent smoking history (P < 0.001).

Conclusions: We found that TMB-H is associated with smoking history, whereas TMB-L is associated with the common driver mutations in lung adenocarcinoma, which may impact treatment strategies for these patients.
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http://dx.doi.org/10.1016/j.jss.2018.07.007DOI Listing
October 2018

Surgical resection of a giant polycystic seminoma of the mediastinum.

J Thorac Dis 2018 Jun;10(6):E438-E441

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

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http://dx.doi.org/10.21037/jtd.2018.05.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051824PMC
June 2018
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