研究者詳細 - 加勢田　馨

論文 - 加勢田　馨

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Initial single-institutional experience with salvage surgery for stage IV non-small cell lung cancer.

Hishida T, Oka N, Yano K, Omura S, Okubo Y, Masai K, Kaseda K, Ohgino K, Terai H, Yasuda H, Asakura K

Interdisciplinary cardiovascular and thoracic surgery 2025年02月

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Thoracic posture-related morphological changes in patients with pectus excavatum versus healthy controls

Suzuki T., Asakura K., Yamada Y., Masai K., Yamada M., Yokoyama Y., Okubo Y., Kaseda K., Hishida T., Jinzaki M.

European Journal of Cardio-thoracic Surgery 66 （ 5 ） 2024年11月

ISSN 10107940

OBJECTIVES. Cases of severe pectus excavatum presenting with worsening cardiopulmonary symptoms in the upright position have been reported. However, the underlying mechanism remains unclear. We evaluated posture-related morphological changes of the thorax in patients with pectus excavatum. METHODS. Chest morphology was evaluated preoperatively using upright and supine computed tomography in 21 patients with pectus excavatum and 35 healthy volunteers. The minimum anterior–posterior thoracic diameter, depression depth, and Haller index on horizontal sections, as well as the T6-12 plumb line distance on sagittal sections, were compared between the 2 positions. RESULTS. In patients with pectus excavatum (median age, 22 years; 18 males and 3 females), the minimum anterior–posterior diameter was smaller (4.5 vs 5.1 cm, P < 0.001) and the Haller index was greater (10.1 vs 6.4, P < 0.001) in the upright position than in the supine position. The T6-T12 plumb line distance was longer in the upright position (2.4 vs 0.8 cm, P < 0.001), while the depression depth showed no significant difference. Healthy volunteers exhibited similar changes. The degree of spinal curvature increased in the upright position due to the anterior shift of the lower thoracic vertebrae, resulting in a shorter anterior–posterior diameter, irrespective of chest wall deformity. One patient with dyspnoea only in the upright position exhibited compression of the right inferior pulmonary vein only on upright computed tomography. CONCLUSIONS. The minimum anterior–posterior diameter is shorter in the upright position. This may explain the worsening of cardiopulmonary symptoms in patients with severe pectus excavatum when in an upright position.

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Clinical impact of multiple pectus bars on surgical outcomes following pectus excavatum repair

Oka N., Masai K., Okubo Y., Kaseda K., Hishida T., Asakura K.

Interdisciplinary Cardiovascular and Thoracic Surgery 39 （ 4 ） 2024年10月

OBJECTIVES: The Nuss procedure, a minimally invasive surgery for pectus excavatum, has undergone various improvements. However, the impact of using multiple bars on thoracic shape changes and surgical outcomes remains unclear. METHODS: We retrospectively evaluated patients who underwent the Nuss procedure for pectus excavatum between August 2014 and September 2021. We divided the patients into 2 groups based on the number of bars placed and identified differences in surgical outcomes and morphological characteristics. RESULTS: A total of 225 patients were evaluated, of whom 132 were classified into the ≤2 bar group (using 1 or 2 bars) and 93 into the ≥3 bar group (using 3 or more bars). There was no difference in the preoperative Haller index [median (interquartile range), 4.59 (3.67–6.16) vs 4.67 (4.12–6.14), P ¼ 0.227], and asymmetric excavatum was more frequently observed in the ≥3 bar group (81% vs 51%, P < 0.001). The preoperative sternal torsion angle was larger in the ≥3 bar group, but no difference was found between the 2 groups postoperatively. The incidence of postoperative complications (≥grade 3) was comparable between groups (10% vs 17%, P ¼ 0.105); however, postoperative pleurisy was more frequently observed in the ≥3 bar group (12% vs 4%, P ¼ 0.021). In univariable and multivariable analyses, ≥3 bar placement was the only risk factor for postoperative pleurisy. CONCLUSIONS: The placement of multiple bars (≥3 bars) is useful for the correction of asymmetric pectus excavatum, but attention should be paid to the potential risk of postoperative pleurisy.

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Validity of Simple Thymomectomy for Clinical Stage I Thymoma without Myasthenia Gravis: A Propensity Score-Matched Analysis

Hishida, T; Suzuki, T; Omura, S; Okubo, Y; Masai, K; Kaseda, K; Asakura, K

JOURNAL OF THORACIC ONCOLOGY 19 （ 10 ） S274 - S274 2024年10月

ISSN 1556-0864

Multiple Lung Resections for Metastases from Pheochromocytoma to Reduce Catecholamine Production.

Yano K, Okubo Y, Ishiguro Y, Masai K, Kaseda K, Emoto K, Miyashita K, Hisihida T, Asakura K

Annals of thoracic surgery short reports 2 （ 3 ） 488 - 491 2024年09月

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Surgically resected sarcomatoid carcinoma of the lung: a nationwide retrospective study in 2010

Kaseda K., Asakura K., Shintani Y., Okami J., Toyooka S., Sato Y., Watanabe S.I., Chida M., Suzuki H., Miyaoka E., Yoshino I., Date H.

BMC Cancer 24 （ 1 ） 938 2024年08月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 1471-2407

Background: Sarcomatoid carcinoma of the lung is a rare histological type of non-small cell lung cancer with a poor prognosis. We aimed to investigate the clinicopathological characteristics and prognostic factors of surgically resected sarcomatoid carcinoma of the lung. Methods: We retrospectively reviewed 14999 patients who underwent surgical resection for non-small cell lung cancer accumulated by the Japanese Joint Committee of Lung Cancer Registry in 2010. Clinicopathological characteristics and survival were compared between the sarcomatoid carcinoma and other non-small cell cancer groups. The prognostic factors in the sarcomatoid carcinoma group were identified using a multivariate Cox proportional hazard model. Results: Patients with sarcomatoid carcinoma comprised 1.4% of all patients. The sarcomatoid carcinoma group demonstrated a more aggressive pathology with presentation at more advanced stages, requiring more frequent extensive surgical resections. The sarcomatoid carcinoma group had remarkably poorer overall and recurrence-free survival than the other non-small cell lung cancer group. Adjuvant chemotherapy was associated with improved survival for pathological stage II–III sarcomatoid carcinoma cases rather than for pathological stage I disease. In the multivariate analysis, larger tumor size, lymphatic permeation, and no adjuvant chemotherapy were associated with the sarcomatoid carcinoma group’s overall and recurrence-free survival. Conclusions: Surgically resected sarcomatoid carcinoma of the lung has a higher aggressive and metastatic potential and a worse prognosis than other non-small cell lung cancers. Adjuvant chemotherapy, which was associated with enhanced survival in patients with pathological stage II–III of the disease, could be considered for treating patients with pathological stage II–III sarcomatoid carcinoma of the lung.

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高度漏斗胸に対してCombined Ravitch and Nuss Procedureを施行後に側弯の進行を認めたLoeys-Dietz症候群の一例

杉野功祐, 政井恭兵, 大久保祐, 加勢田馨, 菱田智之, 朝倉啓介

日本呼吸器外科学会雑誌（一般社団法人日本呼吸器外科学会） 38 （ 5 ） 470 - 475 2024年07月

ISSN 09190945

Loeys-Diez症候群（LDS）はMarfan症候群類縁の先天性結合織疾患で，骨格系の異常として漏斗胸を併存することが知られている．我々は漏斗胸手術後に側弯の進行を認めたLDSの一例を経験した．患者は9歳，男児．5歳時に遺伝子検査でLDSと診断された．Haller index 9.81の高度漏斗胸とCobb角8.5度の軽度側弯があり，漏斗胸に対してRavitch法とNuss法を組み合わせた術式（Combined Ravitch and Nuss Procedure：CRN法）を施行した．左右の肋軟骨を一部分節切除した後に2本のチタンバーを挿入し胸骨挙上術を施行した．術後のHaller indexは3.57となり，漏斗胸の改善が得られたが，側弯はCobb角34.2度に増悪した．術後早期に側弯の進行を認めたため，側弯症に対して装具治療を行った．術後4ヵ月で側弯の改善がみられ，現在経過観察中である．側弯症を合併する漏斗胸の場合，漏斗胸治療により側弯の進行を認める可能性がある．本症例では結合組織の脆弱性が背景にあり，漏斗胸の矯正が過度の側弯変形を招いた可能性が示唆された．

Clinicopathological predictors of postoperative long-term myasthenic status in resected thymoma with myasthenia gravis

Suzuki T., Hishida T., Suzuki S., Okubo Y., Masai K., Kaseda K., Asakura K., Emoto K., Asamura H.

Surgery Today （Surgery Today） 54 （ 7 ） 787 - 794 2024年07月

ISSN 09411291

Purpose: Surgical patients with thymoma and myasthenia gravis (MG) must have their MG status and oncological outcomes critically monitored. We aimed to identify clinicopathological predictors of the postoperative MG status. Methods: We conducted a retrospective review of 40 consecutive surgical patients with MG-related thymomas between 2002 and 2020. The quantitative myasthenia gravis score (QMGS) and Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS) were used to evaluate postoperative MG status. Results: All patients underwent extended total thymectomy. The most common WHO type was type B2 (32%), while 65% of patients had type B1–B3 and 35% had type A–AB thymomas. Eleven patients (28%) achieved controlled MG status in MGFA-PIS 6 months after surgery. This controlled status was observed more frequently in type A–AB than in B1–B3 (57% vs. 12%, p = 0.007). In a multivariate analysis, WHO type (A–AB or B1–B3) was an independent predictor of worsening episodes of MG based on the QMGS (Type B1–B3, hazard ratio: 3.23, 95% confidence interval: 1.12–9.25). At the last follow-up, 23 patients (58%) achieved controlled MG status. The 5-year overall survival rate of all patients was 93.7%. Conclusion: The WHO type of thymoma is an informative predictor of postoperative MG status in patients with MG-related thymoma.

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Glomus Tumor of Intrathoracic Chest Wall: a Case Report

Ishiguro Y., Masai K., Sugino K., Yano K., Nomura R., Okubo Y., Kaseda K., Hishida T., Asakura K., Kurebayashi Y., Minami Y.

Japanese Journal of Lung Cancer （Japanese Journal of Lung Cancer） 64 （ 3 ） 208 - 209 2024年06月

ISSN 03869628

40歳女性．左肺尖部に5.9 cm大の腫瘤影を認め，経皮的生検を行った所，カルチノイド腫瘍が疑われ，画像上は肺尖部胸壁浸潤癌を考え，手術の方針とした．胸腔内を観察すると腫瘍は胸壁から発生しており，胸壁腫瘍を切除した．病理では類円形核と好酸性の胞体を有する異型の弱い腫瘍細胞が増生し，形態像と免疫染色所見から胸壁発生のグロムス腫瘍と診断した．胸壁発生のグロムス腫瘍の報告は極めて少なく，文献的考察を加えて報告する．

Quality of life, psychological states, and personality traits in patients with pectus excavatum

Matsuda K., Fujisawa D., Masai K., Miyazaki N., Suzuki S., Okubo Y., Kaseda K., Asakura K., Hishida T., Asamura H.

JTCVS Open （JTCVS Open） 19 355 - 369 2024年06月

Objective: The quality of life (QOL) and psychological states of patients with pectus excavatum (PE) have yet to be well understood. This study aimed to evaluate the health-related QOL (HRQOL), psychological states, and personality traits of patients with PE, alongside the associations of these factors with the severity of PE. Methods: A cross-sectional evaluation was prospectively performed in patients scheduled to undergo PE repair surgery between July 2019 and April 2021. The primary outcome was the patients’ HRQOL, and the secondary outcomes were depression, social anxiety, self-efficacy, and personality traits. Results: In total, 129 patients were subjected to analyses. Patients' HRQOL had a lower role component summary score (mean ± standard deviation: 41.8 ± 12.8, P < .001) than the general population controls. Patients' HRQOL had a significantly better physical component summary (54.0 ± 10.4, P < .001) and mental component summary (53.3 ± 8.8, P < .001) than that of the general population. Fourteen patients' (10.9%) and 56 patients' (43.4%) scores indicated the presence of depression and social anxiety disorder, respectively. Patients’ self-efficacy (46.1 ± 11.4, P, .001) and level of extraversion (46.5 ± 11.8, P < .001) were lower than those of the general population. No significant correlation was found between the severity of PE and these scores. Conclusions: Our study revealed that patients with PE had decreased social-role QOL, depressive tendencies, increased social anxiety, lower self-efficacy, and introversion. No correlation between the severity of PE and the patients’ psychological outcomes leads us to conclude that surgical implications of PE should not be decided solely by a physical index.

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胸壁に発生したグロムス腫瘍の1切除例

石黒勇輝, 政井恭兵, 杉野功祐, 矢野海斗, 野村塁, 大久保祐, 加勢田馨, 菱田智之, 朝倉啓介, 紅林泰, 南優子

肺癌（(NPO)日本肺癌学会） 64 （ 3 ） 208 - 209 2024年06月

ISSN 0386-9628

Nuss procedure for the treatment of pectus excavatum with dyspnea following oropharyngeal cancer surgery: a case report

Masai K., Nakai T., Okubo Y., Kaseda K., Hishida T., Asakura K.

Journal of Surgical Case Reports （Journal of Surgical Case Reports） 2024 （ 1 ） rjad714 2024年01月

ISSN 2042-8812

Pectus excavatum (PE) causes cardiopulmonary dysfunction depending on the degree and form of the depression. The patient was a 74-year-old woman with a history of PE. Fourteen years ago, a total glossolaryngectomy was performed for oropharyngeal cancer. Two years later, the patient gradually experienced difficulty in breathing. Computed tomography (CT) revealed severe PE and right main bronchial stenosis. We performed a Nuss procedure for PE repair to surgically release the stenosis of the right main bronchus. Postoperative chest CT showed improvement in the sternal depression and right main bronchial stenosis. Furthermore, shortness of breath was relieved postoperatively. Oropharyngeal cancer surgery may cause tracheal support disruption, leading to leftward shift and severe stenosis of the right main bronchus due to sternum depression. This is an important report regarding respiratory distress caused by a combination of PE and post-oropharyngeal cancer surgery.

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Survival impact of pathologic features after salvage lung resection following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer

Oka N., Hishida T., Kaseda K., Suzuki Y., Okubo Y., Masai K., Asakura K., Emoto K., Asamura H.

General Thoracic and Cardiovascular Surgery 2024年

ISSN 18636705

Purpose: Salvage surgery for primary lung cancer is expected to become increasingly common. This study aimed to clarify the survival impact of pathologic characteristics after salvage surgery. Methods: Consecutive patients who underwent salvage surgery following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer from 2010 to 2020 were enrolled in this study. The tumor slides were reviewed to determine the size of the tumor bed and the proportions of viable tumor, necrosis, and stroma. Results: A total of 23 patients were evaluated, and 18 had clinical stage IIIB–IV disease. Six received chemoradiotherapy and 17 received systemic therapy alone. A major pathologic response (MPR, ≤ 10% of viable tumor) was observed in 6 patients, and 4 patients achieved a pathological complete response. The 3-year overall and recurrence-free survival rates (OS and RFS) were 78.6% and 59.2%, respectively. There was no significant difference in OS between patients with and without MPR, and even non-MPR patients achieved a favorable 3-year OS of 70.2%. Meanwhile, patients with high (≥ 30%) stroma showed significantly better OS than those with low (< 30%) stroma (3-year OS: 100% vs. 23.3%, p < 0.001). Conclusions: This study showed that the proportion of stroma can be useful for predicting long-term survival after salvage surgery. Further large-scale studies are warranted to confirm the current findings.

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Prognostic factors affecting survival in patients with non-small cell lung cancer treated with salvage surgery after drug therapy: a multi-institutional retrospective study

Suzuki S., Asakura K., Okui M., Izawa N., Sawafuji M., Sakamaki H., Shigenobu T., Tajima A., Oka N., Masai K., Kaseda K., Hishida T., Yasuda H., Fukunaga K., Asamura H.

World Journal of Surgical Oncology （World Journal of Surgical Oncology） 21 （ 1 ） 290 2023年12月

Background: The prevalence of salvage surgeries after drug therapy for non-small cell lung cancer (NSCLC) has risen, mainly due to recent progress in molecular-targeted drugs and immune checkpoint inhibitors for NSCLC. While the safety and effectiveness of salvage surgery after drug therapy for NSCLC have been studied, its indications remain unclear. We aimed to identify the prognostic factors affecting survival in patients with advanced-stage (stages III–IV) NSCLC treated with salvage surgery after drug therapy. Methods: A retrospective investigation was conducted on patients who received salvage surgery after drug therapy at four hospitals between 2007 and 2020. Salvage surgery was defined as surgery after drug therapy for local progression, tumor conversion to resectable status, and discontinuation of prior drug therapy owing to serious complications. Results: Thirty-two patients received cytotoxic agents alone (n = 12 [38%]), tyrosine kinase inhibitors (TKIs; n = 16 [50%]), or immune checkpoint inhibitors (n = 4 [13%]) as prior drug therapy. In 11 (34%) and 21 (66%) patients, the clinical stage before treatment was III or IV, respectively. The median initial and preoperative serum carcinoembryonic antigen (CEA) levels were 10.2 (range, 0.5–1024) ng/mL and 4.2 (range, 0.6–92.5) ng/mL, respectively. Among the patients, 28 (88%) underwent lobectomy, 2 (6%) underwent segmentectomy, and 2 (6%) underwent wedge resection. Complete resection of the primary lesion was accomplished in 28 (88%) patients. Postoperative complications were documented in six (19%) patients. Mortality rates were 0% at 30 days and 3% at 90 days post-operation. The 5-year overall survival rate stood at 66%, while the 5-year progression-free survival rate was 21%. Multivariate analyses showed that prior TKI therapy and preoperative serum CEA level < 5 ng/mL were prognostic factors influencing overall survival (hazard ratio [95% confidence interval]: 0.06 [0.006–0.68] and 0.03 [0.002–0.41], respectively). The 5-year overall survival in the 11 patients with both favorable prognosticators was 100%. Conclusions: In this study, prior TKI therapy and preoperative serum CEA level < 5 ng/mL were favorable prognostic factors for overall survival in patients with NSCLC treated with salvage surgery. Patients with these prognostic factors are considered good candidates for salvage surgery after drug therapy.

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Combined Ravitch and Nuss procedure for pectus excavatum with dyspnea following scoliosis repair

Oka N., Masai K., Okubo Y., Kaseda K., Hishida T., Asakura K.

Journal of Surgical Case Reports （Journal of Surgical Case Reports） 2023 （ 11 ） rjad618 2023年11月

ISSN 2042-8812

Pectus excavatum (PE) is often associated with scoliosis and can elicit cardiovascular disturbances under rare conditions. Here we report a patient who was treated with a combined Ravitch and Nuss procedure for PE with dyspnea following scoliosis repair to improve her symptoms. The patient was a 49-year-old woman with a history of PE and scoliosis. Right inferior pulmonary vein stenosis was caused by posterior spinal fusion for scoliosis prior to the PE repair. We could safely correct the chest wall deformity and treat dyspnea by performing a modified Ravitch repair in combination with the Nuss procedure.

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Feasibility and Survival Outcomes of "Salvage Surgery" for Initially Clinical Stage IV Non-small Cell Lung Cancer

Hishida, T; Oka, N; Okubo, Y; Masai, K; Kaseda, K; Asamura, H; Asakura, K

JOURNAL OF THORACIC ONCOLOGY 18 （ 11 ） S592 - S593 2023年11月

ISSN 1556-0864

Clinicopathological Analyses for Predicting Survival After Salvage Surgery for Initially Unresectable Lung Cancer

Oka, N; Hishida, T; Kaseda, K; Oshiro, Y; Sakurada, A; Sugino, K; Aoki, H; Ishiguro, Y; Imoto, T; Okubo, Y; Masai, K; Asakura, K; Emoto, K; Asamura, H

JOURNAL OF THORACIC ONCOLOGY 18 （ 11 ） S572 - S572 2023年11月

ISSN 1556-0864

Combined Ravitch and Nuss procedure for patients with severe pectus excavatum: technique and initial results

Masai K., Okubo Y., Kaseda K., Hishida T., Asakura K.

Journal of Surgical Case Reports （Journal of Surgical Case Reports） 2023 （ 10 ） rjad576 2023年10月

ISSN 2042-8812

The Nuss procedure for pectus excavatum (PE) is both less invasive and very simple compared to the Ravitch procedure. However, it may be difficult to perform the Nuss procedure in cases of severe PE. Therefore, we developed a Combined Ravitch and Nuss (CRN) procedure and examined its effectiveness in patients with severe PE. Nine patients with severe PE underwent the CRN procedure. Data on patient characteristics and perioperative results were collected retrospectively. The median Haller index (HI) was 15.4 (range, 6.3-29.3). No significant intraoperative adverse events were noted. Postoperatively, marked improvements in HI were seen in all cases (3.29, range, 2.72-4.96). Two surgical site infections on the shallow layer and one wound seroma occurred. No recurrences were observed during the observation period. Our novel CRN procedure is useful for achieving adequate and sustainable sternal elevation with less invasiveness for patients with severe PE.

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臨床経験肺原発MALTリンパ腫切除例の臨床病理学的特徴

岡直幸, 政井恭兵, 大久保祐, 加勢田馨, 菱田智之, 江本桂, 朝倉啓介

胸部外科（南江堂） 76 （ 8 ） 623 - 628 2023年08月

ISSN 00215252

肺原発MALTリンパ腫切除例の臨床病理学的特徴

岡直幸, 政井恭兵, 大久保祐, 加勢田馨, 菱田智之, 江本桂, 朝倉啓介

胸部外科（(株)南江堂） 76 （ 8 ） 623 - 628 2023年08月

ISSN 0021-5252

2012年1月～2022年12月に手術を施行した肺原発MALTリンパ腫7例(男性2例、女性5例、年齢中央値70歳)の臨床病理学的特徴および画像的特徴について検討した。術前胸部CT所見はすりガラス結節影4例、単発腫瘤影1例、充実性結節影1例、両肺に多発するすりガラス結節影1例であり、腫瘍辺縁の境界は不明瞭で、5例で腫瘍内部に気管支透亮像を確認した。FDG-PETでは1例を除き有意な集積を認めなかった。術前にMALTリンパ腫と診断されていた単発腫瘤影例は左肺上区域切除を施行し、多発結節影を認めた1例では診断目的に肺部分切除を施行し、原発性肺癌疑いの5例は開胸生検目的に肺部分切除を施行した。多発肺結節に対する生検例1例を除く6例で完全切除が施行され、7例全例で病理組織学的にMALTリンパ腫と診断した。術後在院日数の中央値は5日であり、2例に術後補助治療としてrituximabを投与した。術後生存期間の中央値は52ヵ月で、6例が生存中である。

[Clinicopathological Features and Imaging Characteristics of Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma].

Oka N, Masai K, Okubo Y, Kaseda K, Hishida T, Emoto K, Asakura K

Kyobu geka. The Japanese journal of thoracic surgery 76 （ 8 ） 623 - 628 2023年08月

ISSN 0021-5252

Feasibility and safety of percutaneous cryoablation under local anesthesia for the treatment of malignant lung tumors: a retrospective cohort study

Kaseda K., Asakura K., Nishida R., Okubo Y., Masai K., Hishida T., Inoue M., Yashiro H., Nakatsuka S., Jinzaki M., Asamura H.

Journal of Thoracic Disease （Journal of Thoracic Disease） 14 （ 11 ） 4297 - 4308 2022年11月

ISSN 20721439

Background: In our institution, computed tomography (CT)-guided percutaneous cryoablation has been performed in patients with malignant lung tumors under local anesthesia. This study aimed to examine the feasibility and safety of percutaneous cryoablation for the treatment of malignant lung tumors. Methods: From July 2002 to December 2016, 227 patients (56 with primary lung cancer and 171 with metastatic lung tumor) underwent percutaneous cryoablation for the treatment of malignant lung tumors using a cryosurgical unit at our institution. Demographic factors, duration of post-treatment hospitalization, and adverse event and mortality rates were retrospectively investigated in 366 treatment sessions targeting 609 lesions. Results: The median diameter of the targeted tumor was 1.3 cm. All the cryoablation procedures were completed under local anesthesia, and the median duration of post-treatment hospitalization was two days. Adverse events (grade 2 or higher) were observed in 79 sessions (21.6%), with pneumothorax being the most common. In five sessions (1.4%), patients had grade 3 adverse events. There was no 30-day mortality; however, there were two 60-day mortality (0.5%) due to acute exacerbation of interstitial pneumonia. In multivariate analysis, independent predictors of adverse events were comorbid interstitial pneumonia [odds ratio (OR) =2.20; 95% confidence interval (CI): 1.04–4.64] and no history of pulmonary resection on the treated side (OR =3.04; 95% CI: 1.65–5.62). Conclusions: Cryoablation is a feasible and safe treatment for malignant lung tumors with acceptable adverse event rates. However, the mortality risk in patients with comorbid interstitial pneumonia should be fully recognized.

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Safety and efficacy of salvage surgery for non-small cell lung cancer: a retrospective study of 46 patients from four Keio-affiliated hospitals

Suzuki S., Asakura K., Okui M., Sawafuji M., Shigenobu T., Tajima A., Kaseda K., Masai K., Hishida T., Asamura H.

General Thoracic and Cardiovascular Surgery （General Thoracic and Cardiovascular Surgery） 70 （ 10 ） 891 - 899 2022年10月

ISSN 18636705

Objectives: Advances in drug therapy and radiotherapy for non-small cell lung cancer resulted in an increased number of salvage surgeries for initially unresectable tumors. This study aimed to evaluate the safety and efficacy of salvage surgery for non-small cell lung cancer. Methods: We defined salvage surgery as (1) surgery for local recurrence/residual tumor after definitive chemoradiotherapy/radiotherapy (salvage surgery in a narrow sense) or (2) conversion surgery after non-surgical treatment. We retrospectively analyzed patients who underwent salvage surgery at four Keio University-affiliated hospitals. Results: Forty-six patients were included. The initial clinical stage was I in 4 patients (9%), III in 19 (41%), and IV in 23 (48%). Initial treatment before salvage surgery was chemoradiotherapy in 10 patients (24%), radiotherapy in 4 (9%), and drug therapy in 32 (67%). Pneumonectomy, lobectomy, segmentectomy, and wedge resection were performed in 2 (4%), 37 (80%), 3 (7%), and 4 (9%) patients, respectively. Complete resection was achieved in 41 patients (89%). Postoperative complications occurred in 11 patients (24%). Initial chemoradiotherapy/radiotherapy was an independent predictor of postoperative complications (odds ratio 10, p = 0.03). The 30- and 90-day mortality rates were 0 and 2%, respectively. The 5-year overall and progression-free survival rates were 66 and 30%, respectively. Conclusion: The safety and efficacy of salvage surgery for non-small cell lung cancer were acceptable. Salvage surgery was a viable treatment option for selected patients with recurrent/residual tumors after non-surgical treatments.

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Clinicopathological Analyses for Predicting Recurrence After Complete Resection of Thymoma

Suzuki, T; Hishida, T; Yano, K; Imoto, T; Oka, N; Maeda, C; Okubo, Y; Masai, K; Kaseda, K; Asakura, K; Emoto, K; Asamura, H

JOURNAL OF THORACIC ONCOLOGY 17 （ 9 ） S333 - S333 2022年09月

ISSN 1556-0864

Separate evaluation of unilateral lung function using upright/supine CT in a patient with diaphragmatic paralysis

Suzuki T., Asakura K., Yamada Y., Yamada M., Yokoyama Y., Okubo Y., Masai K., Kaseda K., Hishida T., Asamura H., Jinzaki M.

Radiology Case Reports （Radiology Case Reports） 17 （ 8 ） 2826 - 2830 2022年08月

ISSN 1930-0433

Background: Unilateral diaphragmatic paralysis is a condition in which the unilateral diaphragm is paralyzed and elevated. Orthopnea due to lung compression by an elevated diaphragm in the supine position is common in patients with unilateral diaphragmatic paralysis. Although its symptom is posture-dependent, the effect of posture on lung function in unilateral diaphragmatic paralysis has not been studied. Computed tomography (CT) can be used to assess lung volume. However, conventional CT cannot be performed in the upright position. A pulmonary function test can be performed in both upright and supine positions. However, it cannot evaluate the function of each lung separately. Case presentation: We report a case of a 79-year-old man with unilateral diaphragmatic paralysis. He presented with difficulty in inspiration, specifically in the supine position, and underwent both conventional supine CT and newly developed upright CT to assess the effect of posture on the function of each lung. The difference between expiratory and inspiratory lung volumes on CT in the supine position was less than that in the upright position by 46% and 4% on affected and healthy sides, respectively. We previously reported that the difference between expiratory and inspiratory lung volumes on CT correlated with inspiratory capacity on the pulmonary function test. A 46% decline in inspiratory capacity on the affected side in the supine position likely caused orthopnea in this patient. Conclusions: Supine/upright CT is helpful to assess the influence of posture on unilateral lung function in patients with unilateral diaphragmatic paralysis.

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Ehlers-Danlos症候群を背景に発症した気胸に対する2手術例

西田梨紗, 菱田智之, 政井恭兵, 加勢田馨, 江本桂, 淺村尚生

日本呼吸器外科学会雑誌（特定非営利活動法人日本呼吸器外科学会） 36 （ 5 ） 554 - 561 2022年07月

ISSN 09190945

Ehlers-Danlos症候群（EDS）はコラーゲンやその修飾酵素の遺伝子異常により結合組織脆弱性を来す遺伝性疾患群である．我々はEDS合併の気胸手術を2例経験した．症例1は43歳女性，網膜剥離の既往と両肺多発空洞を有していた．左初発気胸に対し左肺下葉の空洞性病変を切除したが，staple lineおよび把持した肺実質から気漏を生じ修復を要した．既往，術前画像，術中所見からEDSを疑い，術後の遺伝子検査にて古典型EDSの診断に至った．症例2は38歳女性，下行結腸穿孔の既往があり血管型EDSと診断されていた．右気胸再発に対し右肺上葉の囊胞縫縮術を施行したが，把持した肺実質から気漏を認め，肺部分切除と壁側胸膜擦過を追加した．2例とも切除標本では組織中の弾性線維は維持されていたが肺実質は極めて脆弱であり，EDS合併が疑われる気胸手術では組織脆弱性に注意した愛護的な操作が肝要である．

Double stapling method for closure of intraoperative alveolar air leakage adjacent to the staple line: a randomized experimental study on ex vivo porcine lungs

Suzuki T., Asakura K., Egawa T., Kawauchi M., Okubo Y., Masai K., Kaseda K., Hishida T., Asamura H.

Journal of Thoracic Disease （Journal of Thoracic Disease） 14 （ 6 ） 2045 - 2052 2022年06月

ISSN 20721439

Background: Alveolar air leakage from a pleural defect around the staple line is one of the complications after wedge resection of the lung. An intraoperative closure of the pleural defect by suturing can cause additional pleural rupture due to tension of the pleura adjacent to staple lines. Therefore, we have introduced a novel closure method for pleural defect adjacent to the staple line, named the double stapling method. This study compared the efficacy of two closure methods; the double stapling method and conventional suturing method with pledgets using ex vivo porcine lungs. Methods: The double stapling method involves closing the pleural defect by suturing the two parallel staple lines at both sides of the pleural defect. This method was developed to distribute the pleural tension around the needle holes of suturing. As a model of pleural defect adjacent to the staple line after wedge resection, wedge resection of the caudal lobe of left porcine lungs was performed, and a superficial square pleural defect (10 mm × 10 mm) adjacent to the staple line was made by scalpel. The defect was closed using the following two methods: (I) suturing with pledgets (n=10); and (II) double stapling method (n=10). The lobe was inflated in water at an airway pressure of 20, 25, and 30 cmH2O; closure success or failure was judged by the absence or presence of air leakage. Results: The closure success was confirmed in 2 (20%) out of 10 cases in the suturing with pledgets group and 9 (90%) out of 10 in the double stapling method group (P=0.007). In 4 out of 10 cases in the suturing with pledgets group, new pleural clefts longer than 3 mm were created around the needle holes of suturing. Conclusions: Ex vivo experiments have suggested the superiority of the double stapling method for the intraoperative closure of alveolar air leakage adjacent to the staple line after wedge resection, compared to conventional suturing with the pledget method.

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Hemoptysis after coil embolization for pulmonary arteriovenous malformation: Histopathological confirmation of bronchial epithelium extension

Yanagihara T., Shimohira M., Inoue M., Nakayama K., Tamura M., Nakatsuka S., Hattori H., Emoto K., Yokota K., Okuda K., Nakanishi R., Kaseda K., Maeda C., Asakura K., Hiwatashi A.

Radiology Case Reports （Radiology Case Reports） 17 （ 6 ） 2101 - 2105 2022年06月

ISSN 1930-0433

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画像上肺癌との鑑別が困難であった潰瘍性大腸炎に合併した肺肉芽腫の切除例

岡直幸, 政井恭兵, 加勢田馨, 朝倉啓介, 菱田智之, 淺村尚生

日本呼吸器外科学会雑誌（特定非営利活動法人日本呼吸器外科学会） 36 （ 4 ） 382 - 388 2022年05月

ISSN 09190945

症例は51歳，女性．潰瘍性大腸炎に対して19年前より薬物療法が開始され，寛解が維持されていた．胸部CT検査で左肺下葉に内部に低吸収域を伴う腫瘤影を認めた．増大傾向を認め，原発性肺癌が疑われたため左肺下葉切除術を施行した．病理組織所見では悪性所見は認めず，高度な炎症性細胞浸潤，膿瘍形成，杯細胞減少など潰瘍性大腸炎活動期の腸管病変に類似した所見であったため，臨床経過と併せて潰瘍性大腸炎合併肺肉芽腫と診断した．潰瘍性大腸炎を含めた炎症性腸疾患はさまざまな臓器に腸管外合併症を認めることがあり，炎症性腸疾患に合併する肉芽腫は肺癌との画像診断は困難である．病理組織学的にも多彩な所見を示すため，少量の検体量では確定診断は困難な場合が多く，手術検体を用いた病理組織学的診断が必要となることがある．

Four cases of completion lobectomy for locally relapsed lung cancer after segmentectomy

Suzuki S., Asakura K., Masai K., Kaseda K., Hishida T., Asamura H.

World Journal of Surgical Oncology （World Journal of Surgical Oncology） 19 （ 1 ） 47 2021年12月

Background: Although completion lobectomy is the treatment of choice for local recurrence of non-small cell lung cancer after segmentectomy, few cases have been reported. We report four patients who underwent completion lobectomies for staple line recurrence after segmentectomy for stage I non-small cell lung cancer. Case presentation: Three women aged 65, 82, and 81 years underwent completion lower lobectomy after superior segmentectomy of the same lobe for local recurrence of stage I non-small cell lung cancer. A 67-year-old man, who had a tumor recurrence on the staple line after apical segmentectomy with superior mediastinal nodal dissection for stage I non-small cell lung cancer, underwent completion right upper lobectomy. These four patients underwent segmentectomy because of comorbidities or advanced age. Local recurrence was confirmed by computed tomography-guided needle biopsy. The interval between the two operations was 37, 39, 41, and 16 months, respectively. Although minimal hilar adhesion was seen for the three completion lower lobectomies, tight adhesions after apical segmentectomy made completion right upper lobectomy quite difficult to dissect, which led to injury of the superior pulmonary vein. No recurrence was recorded after completion lobectomies for 62, 70, 67, and 72 months, respectively. Conclusions: Although completion lobectomy is one of the most difficult modes of resection, among several completion lobectomies, completion lower lobectomy after superior segmentectomy without superior mediastinal nodal dissection was relatively easy to perform because of fewer hilar adhesions.

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Micronodular thymoma with lymphoid stromaの二切除例

大村征司, 政井恭兵, 加勢田馨, 朝倉啓介, 菱田智之, 淺村尚生

日本呼吸器外科学会雑誌（特定非営利活動法人日本呼吸器外科学会） 35 （ 6 ） 705 - 711 2021年09月

ISSN 09190945

Micronodular thymoma with lymphoid stroma（リンパ性間質を伴う小結節性胸腺腫，以下MNTLS）は胸腺腫の1.4%を占める比較的稀な胸腺腫の一型である．今回我々は二例のMNTLSを経験した．症例1．60歳女性．胸部CTで前縦隔に17 mm大の結節を指摘され，胸腔鏡下前縦隔腫瘍切除術を施行した．症例2．70歳女性．胸部CTで前縦隔に18 mm大の結節を指摘され，胸腔鏡下前縦隔腫瘍切除術を施行した．いずれの腫瘍もBリンパ球が豊富な間質を背景に，腫瘍細胞が敷石状に広がっており，MNTLSと診断した．MNTLSは，針生検や迅速診断ではAB型胸腺腫や胸腺リンパ濾胞過形成と誤診される可能性もあるが，過去の報告では予後は良い疾患であり症例1においては術後4年，症例2においては術後1年6ヵ月経過した現在も無再発生存中である．文献的考察を加えて報告する．

Debulking surgery for malignant tumors: The current status, evidence and future perspectives

Hishida T., Masai K., Kaseda K., Asakura K., Asamura H.

Japanese Journal of Clinical Oncology （Japanese Journal of Clinical Oncology） 51 （ 9 ） 1349 - 1362 2021年09月

ISSN 03682811

Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.

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内視鏡治療が奏効せず気管管状切除・再建術を要した挿管後気管狭窄の1例

田中浩登, 大塚崇, 菱田智之, 大村征司, 鈴木幹人, 政井恭兵, 加勢田馨, 朝倉啓介, 淺村尚生

気管支学（特定非営利活動法人日本呼吸器内視鏡学会） 43 （ 3 ） 231 - 236 2021年05月

ISSN 02872137

背景．挿管後気管狭窄に対する治療は，外科的な気管切除・再建術が長期開存性に優れるとされ推奨されてきた．一方，近年内視鏡機器・技術の進歩に伴い，内視鏡下拡張術の報告も増加しているが，その適応や長期成績は十分検討されていない．症例．患者は23歳，女性．1年前に交通外傷で他院に搬送され，意識障害に対して5日間の経口気管内挿管，人工呼吸管理が施行された．抜管40日後より，咳嗽と呼吸困難を自覚し，喘息として治療されたが軽快しないため，精査・加療目的に当院へ紹介受診となった．胸部CT画像および気管支鏡検査所見上，狭窄長2.1 cmの瘢痕性気管狭窄を認め，挿管後気管狭窄の診断の元，緊急で硬性気管支鏡による拡張術を施行した．しかし，その後に再狭窄が生じ，硬性鏡下に拡張術を再度行ったが再々狭窄を認めたため，気管管状切除・端々吻合術を施行した．術後2年6カ月経過した現在，再狭窄の徴候は認めていない．結論．瘢痕性の挿管後気管狭窄に対し，硬性鏡下での拡張術を複数回施行したものの再狭窄を繰り返したため，外科的気道再建術を行い良好な経過を得た1例を経験した．

Video-Assisted Thoracoscopic Surgery for Stage I Thymoma: Short-Term Outcomes and Appropriate Indications

Suzuki, T; Hishida, T; Maeda, C; Matsuda, K; Nakagomi, T; Omura, S; Tanaka, H; Masai, K; Kaseda, K; Asakura, K; Asamura, H

JOURNAL OF THORACIC ONCOLOGY 16 （ 3 ） S389 - S390 2021年03月

ISSN 1556-0864

A case of solitary pulmonary metastasis from thymoma resected 19 years after surgery

Suzuki M., Kaseda K., Masai K., Asakura K., Hishida T., Hayashi Y., Asamura H.

Japanese Journal of Lung Cancer （Japanese Journal of Lung Cancer） 60 （ 5 ） 401 - 406 2020年10月

ISSN 03869628

© 2020 The Japan Lung Cancer Society. Background. Thymoma is a low-grade malignant epithelial tumor arising in the thymus and rarely metastasizes to distant sites after complete resection. We herein report a rare case of solitary pulmonary metastasis of type Bl thymoma. Case. A woman in her 70s underwent thymectomy with partial resection of the pericardium and right upper lobe for type Bl thymoma 19 years ago. The pathological stage was T3N0M0 Stage III with invasion to the right lung. She received postoperative radiotherapy of 50 Gy with 25 Fr and had no evidence of recurrence until the detection of a 0.8-cm solitary pulmonary nodule in the right lower lobe on follow-up computed tomography (CT) performed 13 years after surgery. The pulmonary nodule gradually grew over the next seven-year follow-up, so we performed wedge resection of the right lower lobe for the diagnosis and treatment. Pathologically, the nodule consisted of epithelial cells with slightly large nuclei and inconspicuous atypia surrounded by a lot of lymphocytes. Immunohistochemically, the epithelial cells were positive for AE1/AE3 and CK19, while the lymphocytes were positive for CD3 and TdT. These findings were similar to those shown in the initial thymoma specimen, and the diagnosis of pulmonary metastasis of type Bl thymoma was made. The patient is doing well 23 months after pulmonary metastasectomy with no evidence of re-recurrence of thymoma. Conclusion. We herein report a resected case of slow-growing pulmonary metastasis from type Bl thymoma with a review of the literature. In cases of type A-Bl thymoma, we should consider the possibility of late recurrence and perform long-term follow-up.

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Recent and current advances in FDG-PET imaging within the field of clinical oncology in NSCLC: A review of the literature

Kaseda K.

Diagnostics （Diagnostics） 10 （ 8 ） 2020年08月

© 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Lung cancer is the leading cause of cancer-related deaths around the world, the most common type of which is non-small-cell lung cancer (NSCLC). Computed tomography (CT) is required for patients with NSCLC, but often involves diagnostic issues and large intra- and interobserver variability. The anatomic data obtained using CT can be supplemented by the metabolic data obtained using fluorodeoxyglucose F 18 (FDG) positron emission tomography (PET); therefore, the use of FDG-PET/CT for staging NSCLC is recommended, as it provides more accuracy than either modality alone. Furthermore, FDG-PET/magnetic resonance imaging (MRI) provides useful information on metabolic activity and tumor cellularity, and has become increasingly popular. A number of studies have described FDG-PET/MRI as having a high diagnostic performance in NSCLC staging. Therefore, multidimensional functional imaging using FDG-PET/MRI is promising for evaluating the activity of the intratumoral environment. Radiomics is the quantitative extraction of imaging features from medical scans. The chief advantages of FDG-PET/CT radiomics are the ability to capture information beyond the capabilities of the human eye, non-invasiveness, the (virtually) real-time response, and full-field analysis of the lesion. This review summarizes the recent advances in FDG-PET imaging within the field of clinical oncology in NSCLC, with a focus on surgery and prognostication, and investigates the site-specific strengths and limitations of FDG-PET/CT. Overall, the goal of treatment for NSCLC is to provide the best opportunity for long-term survival; therefore, FDG-PET/CT is expected to play an increasingly important role in deciding the appropriate treatment for such patients.

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Clinicopathological and prognostic features of operable non-small cell lung cancer patients with diabetes mellitus

Kaseda K., Hishida T., Masai K., Asakura K., Hayashi Y., Asamura H.

Journal of Surgical Oncology （Journal of Surgical Oncology） 123 （ 1 ） 332 - 341 2020年

ISSN 00224790

© 2020 Wiley Periodicals LLC Background: The aim of this study was to investigate the clinicopathological and prognostic features of operable non-small cell lung cancer (NSCLC) patients with diabetes mellitus (DM). Methods: A total of 1231 surgically resected NSCLC patients were retrospectively reviewed. Clinicopathological characteristics were compared between patients with DM (DM group, n = 139) and those without DM (non-DM group, n = 1092). The clinical factors associated with postoperative complications and prognostic factors were identified. Results: The DM group had distinct clinicopathological features. No significant differences in histological invasiveness or stage were found. The presence and control status of DM were independent predictors of postoperative complications. No significant differences in recurrence-free survival or cancer-specific survival were observed; however, the DM group had worse overall survival (OS). The DM group had a higher number of deaths from other diseases than the non-DM group, and these patients had significantly higher postoperative hemoglobin A1c levels than patients with cancer-related death. Conclusion: The presence and control status of preoperative DM are useful predictors of both postoperative complications and OS in operable NSCLC patients. Concomitant diabetes-related complications have a negative effect on long-term survival in diabetic NSCLC patients, and long-term glycemic control is important to prolong OS.

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A case of lipofibroadenoma of the thymus

Hamada K., Kaseda K., Omura S., Suzuki M., Tanaka H., Suzuki Y., Kuriyama S., Sakamaki H., Shima T., Yotsukura M., Masai K., Hashimoto K., Takahashi Y., Hishida T., Ohtsuka T., Hayashi Y., Nakatani Y., Asamura H.

Japanese Journal of Lung Cancer （Japanese Journal of Lung Cancer） 58 （ 3 ） 237 - 238 2018年06月

ISSN 03869628

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Role of Surgery in Multimodality Treatment for Non-small Cell Lung Cancer;Current Status and Future Perspectives

Shima T., Masai K., Hishida T., Kaseda K., Hashimoto K., Takahashi Y., Otsuka T., Asamura H.

Kyobu geka. The Japanese journal of thoracic surgery （Kyobu geka. The Japanese journal of thoracic surgery） 71 （ 4 ） 244 - 248 2018年04月

ISSN 00215252

Recent improvement of outcomes for resected non-small cell lung cancer (NSCLC) has been contributed not only by increased detection of early-stage disease and improvement of preoperative diagnosis/perioperative management but also by improvement of multimodality treatment. The introduction of newly developed systemic therapies including molecular targeted agents and immune checkpoint inhibitors dramatically changed clinical outcomes of advanced NSCLC. Accordingly, the role of surgery during the multimodality treatment will be changed more than ever. In this article, we overviewed the current status of the multimodality treatment for clinical stageⅢ (N2)disease and postoperative adjuvant therapy and discussed the role of surgery during these situations. We also discussed the future perspectives of the role of surgery during the multimodality treatment for advanced NSCLC.

Prognostic significance of preoperative plasma D-dimer level in patients with surgically resected clinical stage I non-small cell lung cancer: a retrospective cohort study.

Kaseda K, Asakura K, Kazama A, Ozawa Y.

J Cardiothorac Surg （Springer） 28 （ 12 ） 102 2017年11月

研究論文（学術雑誌）, 査読有り, ISSN 1749-8090

BACKGROUND: Plasma D-dimer level, a marker of hypercoagulation, has been reported to be associated with survival in several types of cancers. The present study aimed to evaluate the prognostic significance of preoperative D-dimer levels in patients with surgically resected clinical stage I non-small cell lung cancer (NSCLC). METHODS: Participants comprised 237 patients with surgically resected clinical stage I NSCLC. In addition to factors such as age, sex, and smoking status, the association between preoperative D-dimer level and survival was explored. RESULTS: Patients were divided into two groups according to D-dimer level: Group A, </= 1.0 mug/ml (n = 170); and Group B, > 1.0 mug/ml (n = 67). The 5-year recurrence-free survival rate was 81.6% for Group A and 66.6% for Group B (p < 0.001). The 5-year overall survival rate was 93.6% for Group A and 84.7% for Group B (p = 0.002). Multivariate survival analysis identified D-dimer level as an independent prognostic factor, along with age, maximum standardized uptake value of the primary tumor, and pathological stage. CONCLUSIONS: Preoperative D-dimer level is an independent prognostic factor in patients with surgically resected clinical stage I NSCLC.

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Determination of poor prognostic immune features of tumour microenvironment in non-smoking patients with lung adenocarcinoma

Kinoshita, T., Kudo-Saito, C., Muramatsu, R., Fujita, T., Saito, M., Nagumo, H., Sakurai, T., Noji, S., Takahata, E., Yaguchi, T., Tsukamoto, N., Hayashi, Y., Kaseda, K., Kamiyama, I., Ohtsuka, T., Tomizawa, K., Shimoji, M., Mitsudomi, T., Asamura, H. and Kawakami, Y.

Eur J Cancer 86 15 - 27 2017年11月

ISSN 1879-0852

We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8(+) T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8(+) T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58). We found that high infiltration of activated CD8(+) T cells expressing interferon gamma (IFN-gamma) and granzyme was correlated with postoperative survival in patients with non-adenocarcinoma. On the contrary, CD8(+) T-cell accumulation was identified as a worse prognostic factor in patients with adenocarcinoma, particularly in non-smokers. Infiltrating CD8(+) T cells were significantly less activated in this microenvironment with high expression of various immunoregulation genes. Potentially immunoregulatory CD8(+) FOXP3(+) T cells and immunodysfunctional CD8(+) GATA3(+) T cells were increased in adenocarcinoma of non-smokers. CD4(+) FOXP3(+) regulatory T cells expressing chemokine receptor-4 (CCR4)- and chemokine ligand (CCL17)-expressing CD163(+) M2-like macrophages also accumulated correlatively and significantly in adenocarcinoma of non-smokers. These characteristic immune cells may promote tumour progression possibly by creating an immunosuppressive microenvironment in non-smoking patients with lung adenocarcinoma. Our findings may be helpful for refining the current strategy of personalised immunotherapy including immune-checkpoint blockade therapy for NSCLC.

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Clinical and pathological characteristics of EGFR mutation in operable early-stage lung adenocarcinoma

Yotsukura, M., Yasuda, H., Shigenobu, T., Kaseda, K., Masai, K., Hayashi, Y., Hishida, T., Ohtsuka, T., Naoki, K., Soejima, K., Betsuyaku, T. and Asamura, H.

Lung Cancer 109 45 - 51 2017年07月

ISSN 1872-8332

OBJECTIVES: Over the past decade, the biological and clinical characteristics of lung cancer with epidermal growth factor receptor (EGFR) mutation have been well studied. However, most studies have focused on advanced inoperable cancer, and not on resected early-stage lung adenocarcinoma. We aimed to elucidate the differences in the clinicopathological characteristics and postoperative prognosis according to the EGFR mutation status in early-stage lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively collected clinical and pathological data from 369 patients with pathological stage I or II lung adenocarcinoma who underwent complete resection. Clinicopathological characteristics and postoperative prognosis were compared depending on the EGFR mutation status, using the Chi-squared test and the log-rank test, respectively. RESULTS AND CONCLUSION: Of the 369 patients, 160 (43.3%) had EGFR mutation, of which 64 (40.0%) were exon 19 deletion (Del-19) and 90 (56.3%) were exon 21 point mutation L858R. Although there was no difference in overall survival (OS) between patients with and without EGFR mutation (p=0.086), tumors with EGFR mutation were associated with a lower consolidation to tumor ratio (CTR) (p <0.001) and a higher incidence of a lepidic growth pattern by pathological evaluation (p <0.001) compared to those without EGFR mutation. Among tumors with EGFR mutation, there was no difference in OS (p=0.140) between Del-19 and L858R. Tumors with L858R were associated with a lower CTR (p=0.046), and tended to have a higher incidence of a lepidic growth pattern by pathological evaluation (p=0.073) compared to those with Del-19. In conclusion, although EGFR mutation status was not a prognostic indicator after surgery in early-stage lung adenocarcinoma, L858R and Del-19 had different radiological and pathological features.

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Clinicopathological and prognostic features of surgically resected pathological stage I lung adenocarcinoma harboring epidermal growth factor receptor and K-ras mutation.

Kaseda K, Asakura K, Kazama A, Ozawa Y

Thoracic Cancer 8 （ 3 ） 229 - 237 2017年05月

査読有り, ISSN 1759-7714

BACKGROUND: This study aimed to evaluate mutations of the epidermal growth factor receptor (EGFR) and K-ras genes and their clinicopathological and prognostic features in patients with resected pathological stage I adenocarcinoma. METHODS: We examined 224 patients with surgically resected lung adenocarcinoma and analyzed the prognostic and predictive value of these mutations in 162 patients with pathological stage I adenocarcinoma. RESULTS: Mutations of the EGFR and K-ras genes were detected in 100 (44.6%) and 19 (8.5%) of all tumors, and in 81 (50.0%) and 17 (10.5%) of the pathological stage I tumors, respectively. EGFR mutations were significantly associated with female gender, smoking habit (never smoker), and low grade. By contrast, K-ras mutations were significantly associated with male gender, smoking habit (ever smoker), and the presence of mucinous components. No significant differences were observed in recurrence-free or overall survival between the EGFR-mutant, K-ras-mutant, and wild-type groups (five-year recurrence-free survival 77.8% vs. 87.8% vs. 79.5%; five-year overall survival 82.8% vs. 82.4% vs. 79.2%, respectively). Multivariate analysis showed that neither EGFR nor K-ras mutation was an independent prognostic factor. CONCLUSIONS: The present study demonstrated that pathological stage I adenocarcinoma harboring EGFR and K-ras gene mutations have distinct clinicopathological features. The presence of these mutations alone were not prognostic factors in patients with resected pathological stage I adenocarcinoma.

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Risk Factors for Predicting Occult Lymph Node Metastasis in Patients with Clinical Stage I Non-small Cell Lung Cancer Staged by Integrated Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Kaseda K, Asakura K, Kazama A, Ozawa Y.

World Journal of Surgery 40 （ 12 ） 2976 - 2983 2016年12月

研究論文（学術雑誌）, 査読有り, ISSN 1432-2323

BACKGROUND: Lymph nodes in patients with non-small cell lung cancer (NSCLC) are often staged using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). However, this modality has limited ability to detect micrometastases. We aimed to define risk factors for occult lymph node metastasis in patients with clinical stage I NSCLC diagnosed by preoperative integrated FDG-PET/CT. METHODS: We retrospectively reviewed the records of 246 patients diagnosed with clinical stage I NSCLC based on integrated FDG-PET/CT between April 2007 and May 2015. All patients were treated by complete surgical resection. The prevalence of occult lymph node metastasis in patients with clinical stage I NSCLC was analysed according to clinicopathological factors. Risk factors for occult lymph node metastasis were defined using univariate and multivariate analyses. RESULTS: Occult lymph node metastasis was detected in 31 patients (12.6 %). Univariate analysis revealed CEA (P = 0.04), SUV(max) of the primary tumour (P = 0.031), adenocarcinoma (P = 0.023), tumour size (P = 0.002) and pleural invasion (P = 0.046) as significant predictors of occult lymph node metastasis. Multivariate analysis selected SUV(max) of the primary tumour (P = 0.049), adenocarcinoma (P = 0.003) and tumour size (P = 0.019) as independent predictors of occult lymph node metastasis. CONCLUSIONS: The SUV(max) of the primary tumour, adenocarcinoma and tumour size were risk factors for occult lymph node metastasis in patients with NSCLC diagnosed as clinical stage I by preoperative integrated FDG-PET/CT. These findings would be helpful in selecting candidates for mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration.

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Value of the Glasgow Prognostic Score as a Prognostic Factor in Resectable Non-Small Cell Lung Cancer

Yotsukura, M., Ohtsuka, T., Kaseda, K., Kamiyama, I., Hayashi, Y. and Asamura, H.

J Thorac Oncol 11 （ 8 ） 1311 - 1318 2016年08月

ISSN 1556-1380

BACKGROUND: Over the past decade, the Glasgow prognostic score (GPS), which is based on serum C-reactive protein and albumin levels, has been reported to be associated with the prognosis of patients with several types of inoperable and operable cancers. However, its applicability to operable non-small cell lung cancer (NSCLC) has not yet been established. METHODS: We retrospectively collected data from patients with pathological stage I or II NSCLC who underwent complete resection. A total of 1048 patients were categorized as either GPS-0 (n = 817 [78.0%]), GPS-1 (184 [17.6%]), or GPS-2 (47 [4.5%]). Survival curves were estimated using the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the relationship between prognosis and GPS status. RESULTS: The 5-year overall survival (OS) rates were 91.2%, 78.3%, and 75.8% for GPS-0, GPS-1, and GPS-2, respectively. There were significant differences in OS between GPS-0 and GPS-1 (p < 0.001) and between GPS-0 and GPS-2 (p < 0.001). Ten variables demonstrated to be associated with OS in a univariate analysis were subjected to a multivariate analysis. The results showed that male sex (p = 0.031), vascular invasion (p < 0.001), lymph node metastasis (p < 0.001), and GPS (p = 0.025) were significantly associated with OS. CONCLUSIONS: A high GPS is significantly associated with poor OS. Although the biological mechanism that underlies this association is not clear, this inflammation-based score may be a useful indicator of the prognosis in patients with resectable NSCLC.

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Identification of false-negative and false-positive diagnoses of lymph node metastases in non-small cell lung cancer patients staged by integrated (18F-)fluorodeoxyglucose-positron emission tomography/computed tomography: A retrospective cohort study

Kaseda, K., Watanabe, K., Asakura, K., Kazama, A. and Ozawa, Y.

Thorac Cancer 7 （ 4 ） 473 - 80 2016年07月

ISSN 1759-7706

BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of integrated (18) F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of non-small cell lung cancer (NSCLC), and to investigate potential risk factors for false-negative and false-positive HMLN metastases. METHODS: We examined the data of 388 surgically resected NSCLC patients preoperatively staged by integrated FDG-PET/CT. Risk factors for false-negative and false-positive HMLN metastases were analyzed using univariate and multivariate analyses of clinicopathological factors. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of integrated FDG-PET/CT in detecting HMLN metastases were 47.4%, 91.0%, 56.3%, 87.7%, and 82.5%, respectively. On multivariate analysis, the maximum standardized uptake value (SUVmax) of the tumor (P = 0.042), adenocarcinoma (P = 0.003), and tumor size (P = 0.017) were risk factors for false-negative HMLN metastases, and history of lung disease (P = 0.006) and tumor location (central; P = 0.025) were risk factors for false-positive HMLN metastases. CONCLUSIONS: The present study identified risk factors for false-negative and false-positive HMLN metastases in NSCLC patients staged by preoperative integrated FDG-PET/CT. These findings would be helpful in selecting appropriate candidates for mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration.

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Solitary pulmonary metastasis from occult papillary thyroid carcinoma

Kaseda K, Watanabe K, Sakamaki H, Kazama A.

Thoracic Cancer 7 （ 2 ） 261 - 3 2016年03月

ISSN 1759-7706

Pulmonary metastases from thyroid carcinoma typically cause a micronodular or miliary pattern throughout both lungs. Metastasis consisting of a solitary pulmonary nodule measuring 20 mm in diameter is rare. Here we report a case of a 66-year-old woman without a history of papillary thyroid carcinoma who presented with a pulmonary nodule measuring 20 mm in diameter, found on chest computed tomography during a health checkup. The patient underwent a right lobectomy. Microscopic examination showed well-differentiated papillary adenocarcinoma. Immunohistochemical findings were consistent with a diagnosis of pulmonary metastasis from papillary thyroid carcinoma. Solitary metastasis to the lung from occult thyroid carcinoma is quite rare, but if a pulmonary nodule is encountered in a patient without a history of thyroid carcinoma, the possibility must be considered.

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Pulmonary arterial enlargement predicts cardiopulmonary complications after pulmonary resection for lung cancer: a retrospective cohort study

Asakura, K., Mitsuboshi, S., Tsuji, M., Sakamaki, H., Otake, S., Matsuda, S., Kaseda, K. and Watanabe, K.

J Cardiothorac Surg 10 113 2015年09月

ISSN 1749-8090

BACKGROUND: The finding of pulmonary arterial enlargement on computed tomography has been reported to be associated with pulmonary hypertension. On the other hand, pulmonary hypertension is a known risk factor for thoracic surgery. We investigated whether pulmonary arterial enlargement predicts cardiopulmonary complications following pulmonary resection for lung cancer. METHODS: We reviewed 237 consecutive patients who underwent pulmonary resection for lung cancer. Preoperative patient characteristics (sex, age, Brinkman index, cardiopulmonary comorbidities, cardiothoracic ratio, pulmonary function, and pulmonary arterial enlargement) and surgical data (surgical procedure, pathological stage, postoperative complications, mortality, and length of postoperative hospital stay) were analyzed. In order to evaluate preoperative pulmonary arterial enlargement, we measured the diameter of the main pulmonary artery at its bifurcation and that of the ascending aorta at its widest point using chest computed tomography and calculated the ratio of the former diameter to the latter. RESULTS: In all, 16 patients developed postoperative cardiopulmonary complications and 221 did not. One patient died from postoperative pneumonia. The mean age of patients who developed postoperative cardiopulmonary complications was significantly higher than that of those who did not (78 +/- 5 years vs 69 +/- 9 years, P=0.0001). The pulmonary artery-to-ascending-aorta ratio was significantly higher in patients who developed postoperative complications than in those who did not (0.94 +/- 0.15 vs. 0.81 +/- 0.11, P=0.03). Other preoperative patient characteristics and surgical data did not differ significantly between the groups. On multivariate analysis, pulmonary artery-to-ascending-aorta ratio (0.1-point increase; odds ratio 2.3, 95 % confidence interval 1.5-3.5; P=0.0002) and age (1-year increase; odds ratio 1.2, 95 % confidence interval 1.1-1.3; P=0.03) were found to be independent predictors of postoperative cardiopulmonary complications. CONCLUSIONS: A finding of pulmonary arterial enlargement on computed tomography is a potential predictor of postoperative cardiopulmonary complications after lung cancer surgery.

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Surgical resection of lung adenocarcinoma after crizotinib treatment: report of a case

Kaseda K, Watanabe K, Asakura K, Kazama A.

World Journal of Surgical Oncology 13 74 2015年02月

ISSN 1477-7819

A 45-year-old female was diagnosed as having lung adenocarcinoma harboring an anaplastic lymphoma kinase (ALK) rearrangement, stage IV (T2bN3M1b). She was treated with crizotinib as second-line chemotherapy. The clinical stage after crizotinib treatment was ycT2aN0M0, stage IB. We performed a left lower lobectomy and lymph node dissection aimed at local control and pathological confirmation of the remaining tumor. The final pathological stage was ypT2aN2M0, stage IIIA with Ef 1b. To the best of our knowledge, this is the first case report of surgical resection in ALK rearrangement-positive lung adenocarcinoma after crizotinib treatment.

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胸腺原発MALTリンパ腫の1切除例

加勢田馨

日本呼吸器外科学会雑誌 2014年12月

Surgery for secondary pneumothorax caused by Hermansky-Pudlak syndrome

Kaseda K, Goto T, Emoto K, Hayashi Y.

Eur Respir J 44 （ 6 ） 1714 - 5 2014年12月

ISSN 1399-3003

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Carbon monoxide-releasing molecule attenuates allograft airway rejection

Ohtsuka, T., Kaseda, K., Shigenobu, T., Hato, T., Kamiyama, I., Goto, T., Kohno, M. and Shimoda, M.

Transpl Int 27 （ 7 ） 741 - 7 2014年07月

ISSN 1432-2277

Acute rejection after lung transplantation is the main risk factor for the development of bronchiolitis obliterans (BO). Carbon monoxide (CO) can provide anti-inflammatory effects and may serve to limit tissue injury in airway transplant. Here, we tested the ability of carbon monoxide releasing molecule-2 (CORM-2) to prevent airway rejection. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Experimental groups were treated with multiple doses of CORM-2. Histopathological evaluation of luminal obliteration was blindly reviewed. Immunohistochemistry and real-time RT-PCR analyses were performed. Allografts treated with CORM-2 revealed a striking reduction of thickening in epithelial and subepithelial airway layers (P < 0.01) at day 7 in orthotopic trachea transplantation model compared with allografts treated with vehicle. In heterotopic trachea transplantation model, CORM-2 treated allografts showed a reduction of luminal obliteration (P < 0.01) at days 14 and 21. There was also a concordant decrease in CD3(+) lymphocytes and macrophages in CORM-2 treated allografts. IFN-gamma, IL-2 and IL17A mRNA expressions were reduced dramatically by systemic administration of CORM-2. These data implicate CORM-2-derived CO has an important protective function in experimental BO, and may represent a target for the therapeutic intervention of chronic lung allograft rejection.

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Solitary glandular papilloma of the peripheral lung: a report of two cases

Kaseda K, Horio H, Harada M, Hishima T.

World Journal of Surgical Oncology 19 2014年05月

Surgical treatment of a solitary pulmonary metastasis from eyelid sebaceous carcinoma: report of a case

Kaseda K, Ohtsuka T, Hayashi Y, Emoto K, Asakura K, Kamiyama I, Goto T, Kohno M.

World Journal of Surgical Oncology 23 2014年04月

Carcinoids among multiple lung tumorlets: carcinoids or aggregates of tumorlets?

Kaseda K, Izumi Y, Hayashi Y, Goto T, Ohtsuka T, Kohno M.

Pathology International 64 （ 2 ） 91 - 3 2014年02月

ISSN 1440-1827

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Aldehyde dehydrogenase 1 expression in cancer cells could have prognostic value for patients with non-small cell lung cancer who are treated with neoadjuvant therapy: identification of prognostic microenvironmental factors after chemoradiation

Zenke, Y., Ishii, G., Ohe, Y., Kaseda, K., Yoshida, T., Matsumoto, S., Umemura, S., Yoh, K., Niho, S., Goto, K., Ohmatsu, H., Kuwata, T., Nagai, K. and Ochiai, A.

Pathol Int 63 （ 12 ） 599 - 606 2013年12月

ISSN 1440-1827

Prognostic factors for patients with non-small cell lung cancer (NSCLC) who have been treated with neoadjuvant therapy have not been fully assessed. The purpose of this study was to analyze prognostic biomarkers in NSCLC after treatment with neoadjuvant therapy, with special reference to the immunophenotypes of both the cancer cells and stromal cells. A total of 52 patients with NSCLC who were treated with neoadjuvant therapy followed by complete resection were included. We examined the expressions of nine markers in the cancer cells and stromal cells. The 5-year disease-free survival rate of patients with high aldehyde dehydrogenase 1 (ALDH1) expression levels in their cancer cells was significantly lower than those with a low ALDH1 level (47.3% vs. 21.5%, respectively; P = 0.023). The other molecules expressed in cancer cells did not exhibit any prognostic value. In NSCLC without neoadjuvant therapy (case control, n = 104), expression of ALDH1 in cancer cells was not correlated with prognosis (P = 0.507). A multivariate analysis identified ALDH1 expression in cancer cells as significantly independent prognostic factors for disease-free survival (P = 0.045). The current study indicated that the immunophenotypes of ALDH1 in cancer cells could have prognostic value for patients with NSCLC who are treated with neoadjuvant therapy.

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Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma

Kaseda, K., Ishii, G., Aokage, K., Takahashi, A., Kuwata, T., Hishida, T., Yoshida, J., Kohno, M., Nagai, K. and Ochiai, A.

Cancer Sci 104 （ 9 ） 1262 - 9 2013年09月

ISSN 1349-7006

Histological vascular invasion (VI) by tumors is reportedly a risk factor influencing recurrence or survival after surgical treatment; however, few studies have evaluated which VI features affect recurrence or survival. The objective of this study was to evaluate how VI features affect recurrence in lung adenocarcinoma patients. We selected 106 patients with pathological stage I lung adenocarcinoma who showed VI and examined the properties of intravascular tumors associated with recurrence. First we investigated the relationship between the frequency of VI in a histological cross-section and the incidence of recurrence; however, a significant impact was not observed. Microscopic examination revealed the intravascular tumors were composed of not only cancer cells but also non-cancerous cells. To examine whether the characteristics of intravascular cancer cells and/or non-cancerous cells have prognostic value, we examined the expression levels of epithelial-mesenchymal transition-related markers in cancer cells and the numbers of infiltrating non-cancerous cells, including macrophages, endothelial cells, and fibroblasts. High levels of E-cadherin expression in the intravascular cancer cells were significant predictors of recurrence (P = 0.004), whereas the expressions of CD44, CD44 variant 6, and vimentin were not. Large numbers of intravascular CD204(+) macrophages (P = 0.016), CD34(+) microvessels (P = 0.007), and alpha-smooth muscle actin (+) fibroblasts (P = 0.033) were also significant predictors of recurrence. Our results indicated VI with abundant stromal cell infiltrates might be a predictor of recurrence and suggested the tumor microenvironment created by cancer cells and stromal cells within the blood vessel may play an important role during the metastatic process.

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Successful surgical resection of leiomyoma obstructing the trachea

Kaseda K, Anraku M, Goto T, Ohtsuka T, Kohno M, Izumi Y, Hayashi Y, Nomori H.

General Thoracic and Cardiovascular Surgery 61 （ 8 ） 476 - 8 2013年08月

ISSN 1863-6713

We report a case of 51-year-old woman with a severely airway-obstructing leiomyoma who underwent successful tracheal resection. A preoperative tumor biopsy was avoided not to cause any risk of suffocation. At surgery, an endotracheal intubation distal to the tumor was achieved with a bronchoscopic guidance. A segmental resection of the trachea with a primary end-to-end anastomosis was performed via a half-splitting median sternotomy. Negative surgical margins for tumor were confirmed intraoperatively. Final pathological diagnosis was a primary tracheal leiomyoma. Definitive surgical resection is a treatment of choice for such airway-obstructing, wide-based leiomyoma. Although a bronchoscopic removal of the tumor is an alternative choice, the risks of suffocation, positive surgical margins, and perforation of the trachea need to be carefully discussed if it is considered.

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Aorticopulmonary paraganglioma

Hato, T., Kaseda, K., Harada, M. and Horio, H.

Gen Thorac Cardiovasc Surg 59 （ 12 ） 812 - 4 2011年12月

ISSN 1863-6713

We describe a 61-year-old woman with an anterior mediastinal paraganglioma. The patient complained of a chronic cough that had lasted about 6 months. Her chest computed tomography (CT) showed a highly enhanced mediastinal tumor in the aorticopulmonary window. We surgically resected this tumor thorough a left anterior thoracotomy. Although numerous feeding vessels and firm adhesions with the pericardium hindered the procedure, macroscopically complete resection was achieved. Postoperatively, the tumor was diagnosed as an aorticopulmonary paraganglioma. As these highly enhanced tumors in the anterior mediastinum on CT images are unusual, a differential diagnosis including mediastinal hemangioma, epithelioid hemangioendothelioma, Castleman's disease, choriocarcinoma, metastatic tumor (especially from renal cell carcinoma), and paraganglioma should be considered.

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Rosai-Dorfman disease mimicking mediastinal lymphoma

Kaseda K, Horio H, Hishima T, Hato T, Harada M.

General Thoracic and Cardiovascular Surgery 59 （ 5 ） 385 - 7 2011年05月

ISSN 1863-6713

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Somatic-type malignancyを伴った縦隔原発胚細胞性腫瘍の1例

加勢田馨

胸部外科 2009年12月

右肺全摘を要した若年者定型カルチノイド

加勢田馨

胸部外科 2009年08月

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