Ken Onodera’s research while affiliated with Tohoku University and other places

Purpose The expression of PD-L1 is linked to lung cancer severity; however, its prognostic value after resection is unclear. In this study, we investigated its role in resected lung cancers. Methods We analyzed 658 patients with stage pIA–IIIA NSCLC who underwent complete resection. We assessed the PD-L1 expression by stage and its link to cancer severity, focusing further on its prognostic impact in resected stage I cell lung cancer. Results The high expression of PD-L1 increased with disease progression (13.0% in IA to 36.2% in III). In stage I non-small cell lung cancer, elevated PD-L1 expression levels were more common in patients with serum CEA levels ≥ 5 (26.0%), SUVmax ≥ 5 (26.7%), and squamous cell carcinoma (41.5%). PD-L1-negative patients showed a better prognosis than PD-L1-positive patients, even with the use of immune checkpoint inhibitors following relapse (5-year OS: 94.3% vs. 83.2%, p < 0.01). Conclusion The expression of PD-L1 in lung cancer appears to be associated with oncological severity and may influence the prognosis of early-stage disease. Additionally, in early-stage lung cancer, immune checkpoint inhibitors may not fully compensate for the negative prognostic impact of the high expression of PD-L1.

Background OK-432 (Picibanil), derived from Streptococcus pyogenes type A3, is widely used for both cancer immunotherapy and pleurodesis to manage pleural effusions and air leaks. While its efficacy and safety in pleurodesis are well-established, its potential immunomodulatory effects on long-term survival outcomes in lung cancer patients remain unclear. This study aims to evaluate whether OK-432 pleurodesis influences postoperative survival and recurrence outcomes following pulmonary lobectomy for non-small cell lung cancer. Methods This retrospective study analyzed data from 413 patients who underwent pulmonary lobectomy for non-small cell lung cancer between January 2010 and December 2016. Patients were categorized into two groups: those who underwent OK-432 pleurodesis for prolonged air leaks or chylothorax (n=23) and a control group receiving other treatments or none (n=390). We examined demographics, surgical outcomes, and postoperative complications, assessing survival and recurrence using the Kaplan-Meier method and Cox proportional hazards models. Results The administration of OK-432 effectively managed air leaks and chylothorax without significant complications. There were no statistically significant differences in overall survival (OS), lung cancer-specific survival (LCSS), or recurrence-free survival (RFS) between the groups. Advanced pathological stages were significant predictors of mortality and recurrence. Conclusions While OK-432 pleurodesis is effective for the management of air leaks and chylothorax following pulmonary lobectomy, this study did not demonstrate any impact on OS, LCSS, or RFS. These findings confirm the utility of OK-432 in addressing immediate postoperative challenges but do not support its use as a prognostic factor in the long-term management of lung cancer. Further investigation is necessary to explore the full spectrum of OK-432’s biological effects and potential benefits in a broader oncological context.

A 70-year-old man underwent chest computed tomography (CT), which revealed a rapidly growing tumor in the left upper lobe. The tumor was diagnosed as pulmonary pleomorphic carcinoma by CT-guided biopsy (cT3N0M0; PD-L1 100%). Since a superior sulcus tumor was suspected, multimodal therapy was considered. However, an implantable cardioverter-defibrillator on the ventral side of the tumor was also considered when determining treatment options. The tumor was progressing rapidly, making it necessary to expedite the initiation of treatment. Thus, combination chemotherapy including pembrolizumab was initiated. The patient developed interstitial pneumonia, which was suspected to be drug-related, making it difficult to continue chemotherapy. However, the tumor had regressed and we decided to perform surgery. Ultimately, the tumor was diagnosed as pulmonary pleomorphic carcinoma (ypT1miN0M0) with Ef2. Four years after surgery, the patient was alive, had not experienced recurrence, and required no additional treatment. In this study, we present a patient with locally advanced pulmonary pleomorphic carcinoma characterized by high PD-L1 expression who underwent surgery after pembrolizumab combination chemotherapy, resulting in long-term recurrence-free survival. Preoperative PD-1/PD-L1 inhibitor therapy may be effective for perioperative treatment of locally advanced pleomorphic pulmonary carcinoma with high PD-L1 expression.

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.

Purpose Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC). Methods The present study included 422 patients with stage I–IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively. Results One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching. Conclusion Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis.

Purpose This single-institution retrospective cohort study was conducted to assess the prognostic significance of perioperative changes in the prognostic nutritional index (PNI) in patients who underwent surgery for non-small cell lung cancer (NSCLC). Methods Clinicopathological data were collected from 441 patients who underwent lobectomy for NSCLC between 2010 and 2016.The PNI ratio (postoperative PNI/preoperative PNI) was used as an indicator of perioperative PNI changes. Prognostic differences were investigated based on PNI ratios. Results The optimal cut-off value of the PNI ratio for overall survival (OS) was set at 0.88 using a receiver operating characteristic curve. The PNI ratio was inversely related to a high smoking index, interstitial lung disease, and postoperative pulmonary complications. The 5-year OS rates for the high vs. low PNI ratio groups were 88.2% vs. 68.5%, respectively (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.90–4.86). Multivariable analysis revealed that a low PNI ratio was significantly associated with poor prognosis (HR: 2.94, 95% CI: 1.77–4.87). The PNI ratio was a more sensitive indicator than postoperative PNI status alone for identifying patients at high risk of mortality, particularly those with non-lung cancer causes. Conclusion The perioperative PNI change is a significant prognostic factor for patients with NSCLC.

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.

Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using box-counting analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering.

Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs. Fullsize Image