Clinical outcomes of left upper segmentectomy vs. lobectomy for early non-small-cell lung cancer: a nationwide database study in Japan.

PURPOSE: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe. METHODS: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis. RESULTS: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38). CONCLUSION: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe.

Effect of revised organ transplant law in Japan on lung transplantation.

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

[Management of Tracheobronchial Injuries due to Brunt Trauma].

BACKGROUND: Tracheobronchial injuries resulting from blunt trauma are relatively rare among chest injuries. However, if these injuries are not managed properly, they can be fatal. The prognosis is intricately linked to the precise diagnosis and treatment. We herein report three cases of tracheobronchial trauma that required surgical intervention. Case 1:A 17-year-old male sustained injuries when his torso became entangled in heavy machinery. The diagnosis revealed a tear in the right main bronchus, which required transportation with left single- lung ventilation. The patient was treated by tracheobronchial reconstruction. Case 2:A 71-year-old male experienced trauma when his car collided with a utility pole. He was transported to the hospital after tracheal intubation due to a laceration of the tracheal membranous area. The site of the injury was closed with sutures. Case 3:A 17-year-old female who had been struck by a train suffered acute respiratory failure and was transported to the hospital after intubation. Veno-venous extracorporeal membrane oxgenation (VV-ECMO) was initiated in response to poor oxygenation. Complete rupture of the right middle bronchial trunk and laceration of the right main bronchial membrane were observed, and bronchoplasty was performed. CONCLUSION: A swift and accurate diagnosis, coupled with timely and judicious therapeutic interventions, play a pivotal role in managing tracheal and bronchial injuries.

What are the risk factors for postoperative home oxygen therapy in patients with lung cancer?

Background: Home oxygen therapy (HOT) is used to treat chronic respiratory diseases and is sometimes required in patients with lung cancer after radical surgery. We aimed to identify the risk factors for postoperative home-based oxygen therapy in patients with lung cancer. Methods: Patients who underwent surgery for primary lung cancer at Chiba University Hospital between January 2019 and March 2021 were included. Patients who did not undergo complete resection, died in hospital after surgery, or used oxygen therapy preoperatively were excluded. Eligible patients were divided into HOT and non-HOT groups. They were retrospectively analyzed for risk factors for postoperative HOT using medical records in a multivariate analysis. Results: A total of 410 patients were included in this study, 24 (5.9%) of whom required HOT after surgery. The HOT group comprised significantly more men, heavy smokers, and patients with pulmonary comorbidities, low percent forced expiratory volume, percent forced vital capacity, predicted postoperative forced expiratory volume in 1 s, and postoperative pulmonary complications on univariate analysis. In a multivariate analysis, independent risk factors for postoperative HOT were pulmonary comorbidities [odds ratio (OR): 5.94; 95% confidence interval (CI): 1.64-21.5; P=0.002) and postoperative pulmonary complications (OR: 5.39; 95% CI: 2.14-13.5; P<0.001). The postoperative HOT application rate was calculated according to a formula developed for this purpose. Conclusions: Comorbid pulmonary diseases and postoperative pulmonary complications were significantly associated with postoperative HOT in patients with lung cancer.

Effects of case volume on short- and long-term outcomes following cadaveric lung transplantation in Japan.

Background: Despite the low number of lung transplantations (LTs) in Japan, 10 LT facilities are accredited and good outcomes have been reported. A database review was conducted to clarify the impact of case volume at LT facilities in Japan on short- and long-term outcomes. Methods: All cadaveric LT cases treated between 2000 and 2021 in Japan were analyzed using the database of the Japanese Society of Lung and Heart-Lung Transplantation (JSLHT). The nine institutions represented were categorized into the low-volume (LV; <80 cumulative LT cases, <8 LTs/year, n=5) and high-volume (HV; ≥80 cumulative LT cases, ≥8 LTs/year, n=4) centers. Ninety-day and 1-year mortality, as well as 5- and 10-year survival data were evaluated. Results: A total of 658 cadaveric LTs were performed at the nine institutions. The 90-day rates of mortality at the HV and LV centers were 3.5% and 3.9%, respectively (P=0.801), while the 1-year mortality rates were 9.2% and 11.5%, respectively (P=0.199). Additionally, log-rank analysis of Kaplan-Meier curves showing case volume did not reveal a significant difference in long-term survival between the HV and LV centers (P=0.272), though the LV centers had wide differences for long-term outcomes (P=0.030). Conclusions: Case volume did not have effects on short- or long-term outcomes following LT in Japan, while there were large variations in long-term outcomes among the LV centers compared to those of the HV centers.

A simple nomogram for predicting occult lymph node metastasis of non-small cell lung cancer from preoperative computed tomography findings, including the volume-doubling time.

PURPOSE: Latent lymph node metastasis is a clinical concern in the surgical treatment of non-small cell lung cancer (NSCLC). The present study identified a simple tool, including the volume-doubling time (VDT), for evaluating the risk of nodal metastasis. METHODS: We reviewed, retrospectively, 560 patients who underwent radical resection for cN0M0 NSCLC. The whole tumor VDT and solid component VDT (SVDT) for differentiating the histological type and adenocarcinoma subtype were analyzed and a nomogram was constructed using variables selected through a stepwise selection method. The model was assessed through a calibration curve and decision curve analysis (DCA). RESULTS: Lymph node metastases were detected in 89 patients (15.9%). The SVDT tended to be longer in patients with adenocarcinoma (294.5 days, p < 0.0001) than in those with other histological types of NSCLC, but was shorter when the solid/micropapillary component was predominant (127.0 days, p < 0.0001). The selected variables (tumor location, solid component diameter, consolidation tumor ratio, SVDT, and carcinoembryonic antigen) demonstrated significant differences and were used for the nomogram. The calibration curve indicated consistency, and the DCA showed validity across most threshold ranges from 0 to 68%. CONCLUSIONS: The established nomogram is a useful tool for the preoperative prediction of lymph node metastasis, and the SVDT was the most influential factor in the nomogram.

Surgery for Secondary Spontaneous Pneumothorax with Chronic Lung Diseases.

PURPOSES: Secondary spontaneous pneumothorax (SSP) is occasionally observed in elderly patients suffering from diffuse lung diseases. The purpose of this study was to analyze the outcomes of surgical treatment of SSP patients with chronic lung diseases. METHODS: In total, 242 patients who underwent surgery for spontaneous pneumothorax at Chiba University Hospital from January 2006 to October 2016 were included in this study. The patients' records were reviewed retrospectively for data on their background, surgical treatment, morbidity, mortality, and recurrence. RESULTS: Of the spontaneous pneumothorax cohort, primary spontaneous pneumothorax (PSP) accounted for 144 patients. Among the 98 patients with SSP, 57 cases were caused by chronic obstructive pulmonary disease (COPD) and 21 were caused by interstitial pneumonia (IP). The postoperative complication rate was 19.3% in the COPD group, 42.9% in the IP group, and 11.1% in the PSP group. The recurrence rate was 5.3% in the COPD group, 28.6% in the IP group, and 21.5% in the PSP group. CONCLUSIONS: The morbidity and recurrence were comparable between PSP and SSP cases with COPD, whereas these values were unfavorable in SSP cases with IP compared with PSP ones. Surgical intervention should be carefully considered in SSP patients with IP.

Lobulated tumor contour as a predictor of preoperative tumor invasion of the lung or pericardium in thymoma patients.

PURPOSE: Preoperative investigations to detect invasion to neighboring organs are important for deciding on the most appropriate surgical approach for thymoma. We evaluated preoperative computed tomography (CT) findings in thymoma patients to identify the CT features associated with tumor invasion. METHODS: Clinicopathologic information on 193 patients who underwent surgical resection for thymoma at Chiba University Hospital between 2002 and 2016 was collected retrospectively. The surgical pathology identified invasion of thymoma in 35 patients: in the lung (n = 18), pericardium (n = 11), or both (n = 6). Contact lengths between the tumor contour and lung (CLTL) or pericardium (CLTP) were measured at the maximum section of the tumor on axial CT. Univariate and multivariate analyses were performed to analyze the relationship between pathological invasion of the lung or pericardium and the clinicopathologic features. RESULTS: The mean CLTL and CLTP were significantly longer in patients with invasion of the neighboring organs than in those without invasion. A lobulated tumor contour was identified in 95.6% of the patients with invasion of the neighboring organs. A multivariate analysis revealed that a lobulated tumor contour was significantly associated with both lung and pericardial invasion. CONCLUSIONS: A lobulated tumor contour was significantly associated with lung and/or pericardial invasion in thymoma patients.

Surgical treatment for chronic pulmonary coccidioidomycosis: a retrospective study from a single institution.

PURPOSE: Coccidioidomycosis, caused by the Coccidioides species, is a well-known disease in the Southwestern United States and North Mexico, with scattered reports in Latin America countries. While this disease is still rare in Japan and other Asian countries, its incidence has been increasing over the last two decades. Coccidioides species are highly infectious and require caution when encountered. This study presents a case series of chronic pulmonary coccidioidomycosis surgically treated at a single institution. METHODS: We conducted a retrospective chart review of six patients who underwent lung resection for pulmonary coccidioidomycosis at Chiba University Hospital between January 2007 and December 2021. RESULTS: All six patients had travelled to the Southwestern United States. Preoperative serology was negative for the anti-Coccidioides antibody in four patients and positive in two. Chest computed tomography revealed a single, well-defined round nodule in all patients. Preoperative biopsy taken from three patients failed to obtain a definitive diagnosis. Histopathological examination of the resected pulmonary nodules revealed granulomas that contained numerous spherules with many endospores, thereby confirming the diagnosis of pulmonary coccidioidomycosis. CONCLUSIONS: Pulmonary coccidioidomycosis should be suspected based on travel history and radiological findings. Meticulous care should be taken during specimen processing to prevent cross infection.

Can modified frailty index predict postoperative complication after lung cancer surgery?

PURPOSE: The impact of the modified frailty index (mFI) on postoperative complications after lung cancer surgery was investigated. METHODS: Patients who underwent lung cancer surgery in 2017 were included. 30-day postoperative mortality and morbidity were evaluated according to their Clavien-Dindo classification. mFI values are presented as the sum of values of 11 included items. Logistic regression was used to assess the effect of mFI on postoperative severe complication incidence. RESULTS: Among 190 patients considered, severe postoperative complications (Grade 3 or more) were observed in 30 (16%). No patients died within 30 days of surgery. The incidence of severe complications was 3.6% in patients with mFI of 0, 16.2% in patients with mFI of 1, 23.4% in patients with mFI of 2, and 31.6% in patients with mFI of 3 or more, and was correlated with the grade of mFI. Univariate and multivariate analyses showed that the high mFI was significantly predictive of postoperative complications. Frail patients of mFI ≥ 2 were at 3.0-fold greater risk of severe complications than non-frail patients of mFI 0 or 1. CONCLUSION: mFI was associated with morbidity after lung cancer surgery. Preoperative frailty assessment and appropriate intervention to frail patients would be required to improve postoperative outcomes.

Benefit of Adjuvant Chemotherapy for Patients Older Than 75 Years With Completely Resected p-Stage II-IIIA Non-Small-Cell Lung Cancer: A Retrospective Cohort Study Using Japanese Nationwide Real-World Data.

BACKGROUND: The efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non-small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC. PATIENTS: We extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016. METHODS: We classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS). RESULTS: Overall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N. CONCLUSION: ACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age.

Nationwide prospective registry database of patients with newly diagnosed untreated pleural mesothelioma in Japan.

Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma.

Reduction of mycophenolate mofetil dosage to limit prolonged viral shedding in solid organ transplant recipients with COVID-19: Two case reports.

Solid organ transplant (SOT) recipients with coronavirus disease-2019 (COVID-19) experience prolonged viral shedding, and they are forced to stay in the hospital because of the requirement for COVID-19 isolation. Here, we present two cases (lung and renal transplant recipients), wherein the isolation period was shortened by reducing the dosage of mycophenolate mofetil (MMF). Both patients recovered well from COVID-19 pneumonia. This case study suggests that a reduction in MMF dosage may lead to a shorter hospitalization period in SOT recipients with COVID-19.

Long-term nintedanib treatment for progressive pulmonary fibrosis associated with Hermansky-Pudlak syndrome type 1 followed by lung transplantation.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease that often causes progressive pulmonary fibrosis (HPS-PPF) in some genetic types with high mortality rates. No effective treatment for HPS-PPF other than lung transplantation has been established. Herein, we report a case of HPS type 1 with progressive pulmonary fibrosis treated with long-term nintedanib administration followed by lung transplantation. The resected lungs revealed diffuse interstitial lung lesions, including fibroblastic foci, suggesting the potential beneficial effects of anti-fibrotic drugs in HPS-PPF. Together with previous reports, the present case suggests that nintedanib might be a safe and effective drug for HPS-PPF.

Outcomes of carbon ion radiotherapy compared with segmentectomy for ground glass opacity-dominant early-stage lung cancer.

PURPOSE: This study aimed to compare the outcomes of patients with ground-grass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) who were treated with carbon ion radiotherapy (CIRT) versus segmentectomy. METHODS: A retrospective review of medical records was conducted. The study included 123 cases of clinical stage 0/IA peripheral NSCLC treated with single-fraction CIRT from 2003 to 2012, 14 of which were determined to be GGO-dominant and were assigned to CIRT group. As a control, 48 consecutive patients who underwent segmentectomy for peripheral GGO-dominant clinical stage IA NSCLC were assigned to segmentectomy group. RESULTS: The patients in CIRT group, compared with segmentectomy group, were significantly older (75 ± 7.2 vs. 65 ± 8.2 years, P = 0.000660), more likely to be male (13/14 vs. 22/48, P = 0.00179), and had a lower forced vital capacity (91 ± 19% vs. 110 ± 13%, P = 0.0173). There was a significant difference in the 5-years overall survival rate (86% vs. 96%, P = 0.000860), but not in the 5-years disease-specific survival rate (93% vs. 98%, P = 0.368). DISCUSSION: Compared with segmentectomy, CIRT may be an alternative option for patients with early GGO-dominant NSCLC who are poor candidates for, or who refuse, surgery.

Targeting PD-1/PD-L1 inhibits rejection in a heterotopic tracheal allograft model of lung transplantation.

Immune checkpoint molecules such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have revolutionized the field of lung cancer treatment. As part of our study, we examined the role of these proteins in acute rejection in a mouse model of heterotopic tracheal transplantation. Recipient mice were untreated (Allo group) or treated with anti-PD-L1 (aPDL1 group) or PD-L1 Fc recombinant protein (PD-L1 Fc group). A further group of C57BL/6 mice received isografts (Iso group). The occlusion rate was significantly higher in the Allo group than in the Iso group (p = 0.0075), and also higher in the aPD-L1 group (p = 0.0066) and lower in the PD-L1 Fc group (p = 0.030) than in the Allo group. PD-L1 Fc recombinant protein treatment significantly decreased interleukin-6 and interferon-γ levels and reduced the CD4+/CD8+ T cell ratio, without increasing PD-1 and T-cell immunoglobulin mucin 3 expression in CD4+ T cells. These data suggest that PD-L1 Fc recombinant protein decreases the levels of inflammatory cytokines and the proportion of CD4+ T cells without exhaustion. The PD-L1-mediated immune checkpoint mechanism was associated with rejection in the murine tracheal transplant model, suggesting a potential novel target for immunotherapy in lung transplantation.

A narrative review on the management of patients awaiting lung transplantation in Japan.

Background and Objective: The number of lung transplantations performed in Japan is increasing, and post-transplant outcomes are relatively favorable. A major concern is the extremely long waiting time and the high mortality rate on the waitlist. The management of patients before transplantation is very important and essential for further improvement of outcomes. In this review, we summarize the management of patients awaiting lung transplantation in Japan. Methods: A literature search was conducted via PubMed in November 2022 using the following keywords: lung transplantation, waiting, management, recipient, and Japan. Peer-reviewed academic journal articles published in English were also included. Key Content and Findings: A growing number of studies have evaluated the management of pre-transplant patients. This includes infection control, vaccination, respiratory disease-specific treatment, malignancy, nutrition, rehabilitation, psychosocial assessment, and health-related quality of life (HRQOL) for patients on the waitlist. Each is important, and various evaluation methods and strategies to improve outcomes have been reported. Conclusions: Proper and multifaceted management of pretransplant patients is extremely important to reduce the mortality of candidates for lung transplantation. Integrated management is crucial to the success and survival of lung transplant recipients.