Published papers

Case Presentation: A 70-year-old woman who had received a diagnosis of pneumonia in the right lower lobe was treated with antibiotics at a general practitioner's clinic 9 months earlier. Her pneumonia had improved, but the cough and lung infiltrates persisted for > 6 months, so the patient was referred to our hospital. She had undergone surgery for breast cancer 30 years earlier but had no other medical history. She was not taking any medications and had no history of smoking, including passive smoking.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The purpose of this study was to assess surgical outcomes of salvage surgery for clinical stage IV non-small-cell lung cancer. A total of 14 patients who underwent lung resection following systemic therapy between 2010 and 2022 were included in this study. Systemic therapy prior to surgery included agents including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in eight patients and non-TKI agents in six (chemotherapy alone: four, chemotherapy plus immune checkpoint inhibitors: two). During a median follow-up of 5.2 years, the EGFR-TKI group showed a favourable 5-year overall survival of 83%; however, it was due to treatment after relapse, and there were no 4-year relapse-free survivors. The non-EGFR-TKI group showed a 5-year relapse-free survival of 33%, and 2 patients have survived more than 3 years without any relapse and further treatment. When considering the role of surgery in multimodal treatment for initial c-stage IV non-small-cell lung cancer, salvage surgery following non-TKI therapy (chemotherapy with or without immune checkpoint inhibitor) can be regarded as genuine salvage surgery.

Introduction: Thymic neuroendocrine tumors (TNETs) are rare malignancies characterized by aggressive clinical behavior and limited therapeutic options. In small cell lung cancer (SCLC), molecular subtypes based on the expression of lineage-defining transcription factors (TFs)—ASCL1, NEUROD1, POU2F3, and YAP1—have been proposed. However, the TF landscape of TNETs remains poorly defined. Given the pathological similarities among neuroendocrine tumors across organs, we aimed to investigate whether the TF-based classification system used in SCLC is applicable to TNETs. Methods: Sixteen pathologically confirmed TNETs—including large cell neuroendocrine carcinoma (LCNEC), thymic small cell carcinoma (TSCC), atypical carcinoid (AC), and typical carcinoid (TC)—were retrospectively analyzed. Immunohistochemistry was performed to evaluate classical neuroendocrine (NE) markers (synaptophysin, chromogranin A, CD56) and TFs (ASCL1, NEUROD1, POU2F3, YAP1). H-scores were calculated, and tumors were categorized according to TFs expression profiles. Results: Synaptophysin was strongly expressed in all cases, while chromogranin A and CD56 showed variable expression, with reduced levels in LCNEC and TSCC. The combined NE score was significantly higher in carcinoid tumors compared to LCNEC and TSCC. For TFs, ASCL1 expression was observed in 93.8 % of cases, whereas NEUROD1 and POU2F3 were rarely or not expressed. YAP1 expression was confined to LCNEC cases, all of which co-expressed ASCL1 and YAP1. Based on H-scores, TNETs were classified into three subgroups: (1) ASCL1-positive/YAP1-negative (n = 12, 75 %), (2) ASCL1/YAP1 double-positive (n = 3, 19 %), and (3) double-negative (n = 1, 6 %). Conclusion: This study reveals molecular heterogeneity among TNETs. Notably, ASCL1 and YAP1 co-expression characterizes all LCNEC cases, making a distinct TF landscape in high-grade TNETs.

A pheochromocytoma is a malignant tumor with metastatic potential. Moreover, the cardiovascular effects of abnormal amounts of catecholamines resulting from pheochromocytoma impact prognosis. Resection of the primary tumor is useful for reducing catecholamine production; however, the significance of resection of metastases remains unclear. Herein, we report a case in which multiple lung resections for metastases from pheochromocytoma were performed 5 years after primary tumor resection. Complete resection of 6 pulmonary lesions was achieved, maintaining reduced catecholamine levels and blood pressure without any sign of recurrence for a year.

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.

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.

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.

Sublobar resection is an established surgical option for early-stage non-small cell lung cancer. However, evidence remains limited regarding its use for tumours >20 mm in real-world settings. We evaluated characteristics and outcomes of limited resection in this context and identified predictors of local recurrence. We retrospectively analysed 165 patients with clinical stage I non-small cell lung cancer with tumours >20 mm who underwent limited resection between 2007 and 2017. Clinical, pathological, and radiological data were reviewed. The primary end-point was local recurrence, assessed using competing risk analysis. Overall survival and disease-free survival were estimated using Kaplan-Meier and Cox models. We analysed 165 patients with 13 local recurrence events. Among them, 146 (88.5%) had identifiable reasons for not undergoing lobectomy. Segmentectomy and wedge resection were performed in 59% and 41% of cases, respectively. Lymph node dissection was performed in all segmentectomies and in 20% of wedge resections. The 5-year overall and disease-free survival rates were 64.0% and 62.1%. Local recurrence occurred in 8%, more frequently after wedge resection than segmentectomy (13% vs 4%, P = .04). Solidpredominant tumours with a consolidation-to-tumour ratio greater than 0.5 accounted for 76% and were independently associated with lower disease-free survival (hazard ratio, 2.65; P = .05) and higher local recurrence (hazard ratio: infinite; P < .001). No local recurrence was observed in tumours with a ground-glass opacity-predominant pattern. Limited resection showed acceptable outcomes in lung cancers >20 mm, especially with ground-glass opacity; solidpredominant CT patterns were strongly linked to recurrence.

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.