渡邊 俊和

BACKGROUND: Patients with thoracic malignancy and interstitial pneumonia (IP) are often excluded from clinical trials, consequently lacking quantitative evidence of poorer prognosis and lower programmed death-ligand 1 (PD-L1) testing rates. METHODS: We evaluated the real-world impact of comorbid IP on biomarker adoption and survival in thoracic malignancy patients receiving first-line systemic therapy at a tertiary teaching hospital between 2016 and 2023. RESULTS: Among 1247 patients, 98 (7.5%) had comorbid IP. Multigene testing rates in IP patients were similar to those in non-IP patients. Only three actionable genomic alterations were found in the IP group, highlighting PD-L1 testing as the key element. PD-L1 testing was underutilized in the IP group (63.3%) compared with the non-IP group (75.1%). Immune checkpoint inhibitor (ICI) therapy was utilized in 12.2% of IP versus 29.3% in non-IP, despite comparable clinical situations. Comorbid IP predicted worse survival (hazard ratio: 1.789; 95% confidence interval: 1.373-2.331; p < 0.001). Although survival significantly improved in non-IP after 2020, no benefit was observed in IP. A multivariable model incorporating an IP × Period interaction confirmed comorbid IP remained a negative prognostic factor, highlighting recent advances have not bridged the survival disparity for this high-risk group. CONCLUSIONS: Despite recent progress, patients with comorbid IP experience limited clinical benefit, characterized by lower rates of PD-L1 testing, restricted use of immune checkpoint inhibitors, and absence of post-2020 survival gains. This large-scale and quantitative evidence demonstrates persistent disparities and their prognostic significance, reflecting the limited applicability of current immunotherapy-based strategies in this high-risk population.

Abstract Background Lung transplantation is a vital option for patients with end-stage lung disease. However, it faces a significant challenge due to the shortage of compatible donors, which particularly affects individuals with small chest cavities and pediatric patients. The novel approach of cadaveric lobar lung transplantation is a promising solution to alleviate the donor shortage crisis. Both the mid-term and long-term outcomes of lobar lung transplantation are comparable to those of standard lung transplantation. However, patients undergoing lobar lung transplantation reported a significantly higher rate of primary graft dysfunction compared to patients undergoing standard lung transplantation. Therefore, careful donor selection is critical to improve outcomes after lobar transplantation. However, no established method exists to evaluate each lung lobar graft of deceased donors. This case report describes a case of cadaveric lobar lung transplantation to overcome size mismatch and donor shortage, with particular emphasis on lobar graft evaluation. Case presentation A 39-year-old woman with scleroderma-related respiratory failure was listed for deceased donor lung transplantation due to a rapidly progressing disease. Faced with a long waiting list and impending mortality, she underwent bilateral living-donor lobar lung transplantation donated by her relatives. Post-transplant complications included progressive pulmonary vein obstruction and pleural effusion, which ultimately required retransplantation. An oversized donor with pneumonia in the bilateral lower lobes was allocated. Lung ultrasound was used to evaluate each lung lobar graft during procurement. The right upper and middle lobes and left upper lobe were confirmed to be transplantable, and lobar lung redo transplantation was performed. The patient’s post-transplant course was uneventful, and she was discharged home and returned to her daily activities. Conclusions This case highlights the clinical impact of cadaveric lobar lung transplantation as a feasible and effective strategy to overcome the shortage of donor lungs, especially in patients with small thoracic cavities. By establishing donor lung evaluation techniques and overcoming anatomical and logistical challenges, cadaveric lobar lung transplantation can significantly expand the donor pool and offer hope to those previously considered ineligible for transplantation.

Abstract Background Lung transplantation (LTx) is a crucial therapeutic strategy for patients suffering from end-stage respiratory diseases, necessitating precise donor-recipient size matching to ensure optimal graft function. While standard allocation protocols rely on predicted lung capacity based on factors such as sex, age, and height, a subset of patients with respiratory diseases presents an additional challenge – thoracic or vertebral deformities. These deformities can complicate accurate volume predictions and may impact the success of lung transplantation. Methods In this retrospective cohort study of patients who underwent LTx at Tohoku University Hospital between January 2007 and April 2022, with follow-up until October 2022, the primary objective was to assess the influence of thoracic and vertebral deformities on perioperative complications, emphasizing interventions, such as volume reduction surgery. The secondary objective aimed to identify any noticeable impact on long-term prognoses in recipients with these deformities. Results Of 129 LTx recipients analyzed, 17.8% exhibited thoracic deformities, characterized by pectus excavatum, while 16.3% had vertebral deformities. Perioperative complications, requiring delayed chest closure, tracheostomy, and volume reduction surgery, were more prevalent in the deformity group. Thoracic deformities were notably associated with the need for volume reduction surgery. However, long-term prognoses did not differ significantly between patients with deformities and those without. Vertebral deformities did not appear to significantly impact perioperative or long-term outcomes. Conclusions This study highlights the prevalence of thoracic deformities in LTx recipients, correlating with increased perioperative complications, particularly the potential need for volume reduction surgery. Importantly, these deformities do not exert a significant impact on long-term prognoses. Additionally, patients with vertebral deformities, such as scoliosis and kyphosis, appear to be manageable in the context of LTx.

Lung transplant (LTx) recipients face a significant risk from coronavirus disease 2019 (COVID-19), with elevated hospitalization mortality rates even post-vaccination. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) typically induces pneumonia in even healthy individuals, it can also infect the transplanted lungs of LTx recipients, potentially leading to graft dysfunction. Despite the prevalence of COVID-19 pneumonia in LTx recipients, data on its characteristics and associated risk factors remain limited. This retrospective study analyzed data from LTx recipients at Tohoku University Hospital between January 2001 and November 2023. COVID-19 cases were identified, and patient records, including thoracic computed tomography (CT) evaluations, were reviewed. Patient characteristics, vaccination history, immunosuppressant use, and comorbidities were assessed. Descriptive analysis was utilized for data presentation. Among 172 LTx recipients, 39 (22.7%) contracted COVID-19, with 9 (23%) developing COVID-19 pneumonia. COVID-19 incidence in LTx recipients aligned with national rates, but pneumonia risk was elevated. Delayed antiviral therapy initiation was noted in pneumonia cases. Remdesivir was uniformly administered and remained the primary treatment choice. LTx recipients are susceptible to COVID-19 pneumonia, warranting vigilance and tailored management strategies. Pre-transplant vaccination and prompt COVID-19 diagnosis and treatment are imperative for optimizing outcomes in this population.

BACKGROUND: Interstitial lung disease (ILD) represents a heterogeneous group of lung disorders characterized by fibrotic lung tissue changes. In regions with severe donor shortages, single-lung transplantation (SLTx) is often preferred over bilateral lung transplantation for advanced ILD. However, temporal changes and complications in the retained native lung remain poorly understood. METHODS: A retrospective analysis of 149 recipients who had undergone SLTx was conducted, including 34 ILD SLTx recipients. Native-lung volume, radiological alterations, and perfusion were assessed at distinct post-SLTx time points. Statistical analyses compared ILD and non-ILD SLTx groups. RESULTS: Our study revealed a progressive reduction in native-lung volume over time, accompanied by radiographic deterioration and declining perfusion. Complications in the retained native lung were observed, such as pneumothorax (29.4%), pulmonary aspergillosis (11.8%), and acute exacerbation (8.9%). Long-term survival rates were similar between ILD and non-ILD SLTx recipients. CONCLUSIONS: This study illuminates the unique challenges and complications with respect to the native lung following SLTx for ILD. Ongoing monitoring and tailored management are essential. Despite limitations, this research contributes to our understanding of the temporal progression of native-lung complications post-SLTx for ILD, underscoring the need for further investigation.

Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in lung-transplant (LTx) recipients. Given the high susceptibility of LTx recipients to CMV infection, this study explores the effectiveness and safety of letermovir prophylaxis. A retrospective analysis of using letermovir for LTx recipients at Tohoku University Hospital (January 2000 to November 2023) was conducted. Case summaries from other Japanese transplant centers and a literature review were included. Six cases at Tohoku University Hospital and one at Kyoto University Hospital were identified. Prophylactic letermovir use showed positive outcomes in managing myelosuppression and preventing CMV replication. The literature review supported the safety of letermovir in high-risk LTx recipients. Despite limited reports, our findings suggest letermovir's potential as prophylaxis for LTx recipients intolerant to valganciclovir. Safety, especially in managing myelosuppression, positions letermovir as a promising option. However, careful consideration is important in judiciously integrating letermovir into the treatment protocol.

BACKGROUND: Analyzing HLA polymorphism in lung transplantation (LTx) is important, given its impact on LTx recipient survival and graft function. Accordingly, we conducted a retrospective study to examine the influence of HLA mismatch and donor-specific antibodies (DSA) on short-term outcomes and early-phase post-LTx complications. METHOD: HLA antigen or eplet mismatch in LTx patients at Tohoku University Hospital from 2018 to 2023 was determined, and DSA was measured on admission for surgery to identify preformed DSA and at weeks 4 to 12 post-LTx for de novo DSA, respectively. RESULTS: The participants were 45 LTx recipients, HLA-A/B/DR antigen mismatch (5-6 of 6) being identified in 57%, HLA-A/B/Cw/DR/DQ mismatch (8-10 of 10) in 57%, and HLA eplet mismatch (>61) in 46%. The prevalence of preformed DSA was 24%, and persistence (uncleared) was 16%. The incidence of de novo DSA was 16% after LTx. During the study,16 recipients experienced grade 3 primary graft dysfunction (PGD), 8 developed acute rejection, and 5 died. No HLA-related variables were significantly associated with post-LTx mortality and were not risk factors for high-grade PGD or acute rejection. CONCLUSION: Despite limitations in sample size, resulting in tentative findings, the study serves as a crucial pilot study for an ongoing multicenter prospective trial in Japan.

INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.

OBJECTIVE: The prevalence of obstructive sleep apnea (OSA) in Japan is 9% among males and 3% among females. Up to 2.5 million patients are estimated to suffer from the disease, but limited number of facilities are capable of carrying out polysomnography (PSG), leaving more than 80% of these individuals are undiagnosed. In recent years, the development of new portable sleep monitoring (PMs) devices has been remarkable. We evaluate the correlation between the results of the LS-140 PMs device (Fukuda Denshi Tech Co. Ltd.), released in 2017, and those of PSG. METHODS: We obtained contemporaneous data from the same patients by equipping 58 patients with PMs (LS-140) devices while they underwent PSG. Our primary outcome was Case 2 of the intraclass correlation coefficient (ICC), i.e., the ICC (2.1). And we used a Bland-Altman analysis to compare the apnea-hypopnea index (AHI) given by PSG and the respiratory event index (REI) given by LS-140 and examined the sensitivity and specificity of the REI relative to the AHI in the diagnosis of OSA. We also carried out the same comparison but in terms of the presence or absence of periodic limb movements (PLMs). RESULTS: The ICC (2.1) between The REI and the AHI was 0.944, a rather high value (p<0.0001). The mean difference between AHI and REI values was -3.6 (p<0.0001), indicating a negative fixed bias. Sensitivity may decrease in groups with PLMs. CONCLUSION: The REI and the AHI are highly correlated, giving LS-140 sufficient diagnostic sensitivity and specificity to screen for OSA.

BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data. RESULTS: The numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups. CONCLUSIONS: MPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.

Although endobronchial ultrasound guided transbronchial biopsy (TBB) with a guide sheath (EBUS-GS) is widely used for diagnosis of peripheral pulmonary lesions, the diagnostic contribution of cytology (bronchial brushing, bronchial washing and biopsy forceps rinse) has not been established. To determine the diagnostic contribution of cytological examination to EBUS-GS-TBB, we reviewed medical records of patients with lung malignancies who had undergone TBB with EBUS-GS (EBUS-GS group, n=187) or TBB without EBUS-GS (conventional TBB [CTBB] group, n=197) at Nagoya University Hospital. Although the mean size of target lesions was significantly larger in the CTBB group than the EBUS-GS group, the total diagnostic rate was equivalent between two groups (EBUS-GS: 73.3%, CTBB: 66.0%). In the EBUS-GS group, cytological procedures increased the diagnostic rate by 9.1% (17/137), compared with only 4.1% (8/130) in the CTBB group. Sensitivity of cytology among biopsy-negative patients was significantly higher in EBUS-GS group than CTBB group (P=0.022). Furthermore, in the EBUS-GS group, among 17 patients whose malignant diagnoses could only be established cytologically, bronchial brushing contributed to the malignant diagnosis in 64.7% (11/17). These data may suggest that cytological examination, especially bronchial brushing, may be an important diagnostic contributor in EBUS-GS-TBB.