研究者詳細 - 加勢田　馨

論文 - 加勢田　馨

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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

[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

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。

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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