Background:Postoperative acute exacerbation of interstitial pneumonia (IP-AE) is highly lethal after lung resection. Whether a symptom-free, routine computed tomography (rCT) can detect IP-AE early enough to justify pre-emptive steroids is unknown. We therefore aimed to assess the diagnostic accuracy of early postoperative rCT for detecting clinical IP-AE (cIP-AE) and to identify a high-specificity rCT score threshold that could support pre-emptive steroid treatment. Methods:This single-center, retrospective diagnostic-accuracy study analyzed 120 consecutive lung-cancer patients with underlying interstitial pneumonia (IP) who underwent high-resolution rCT within 7 days after surgery. Eligibility was based on preoperative high-resolution computed tomography (HRCT) demonstrating IP, irrespective of postoperative pathological confirmation. Two thoracic radiologists independently graded each scan on a five-point likelihood scale; a summed 10-point score (range, 2-10) was defined as the sum of the two readers' five-point ratings, assigned retrospectively. Diagnostic accuracy was expressed as sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC). The ROC analysis assessed the ability of the rCT score to detect cIP-AE. For analysis, the proposed treatment threshold was the lowest score, giving 100% specificity. Results:IP-AE developed in 14 patients (11.6%). The ROC for cIP-AE detection yielded an AUC of 0.956. A summed score ≥9 achieved 100% specificity and detected 36% of presymptomatic events, whereas ≥6 increased sensitivity (86%) but lowered specificity (89%). Five patients received steroid pulse therapy solely on the basis of rCT; four of the five scans scored ≥9 and one scored 8. Thirty- and 90-day mortality were 0.8% and 3.3%, respectively, and no grade ≥3 steroid-related toxicity occurred. Conclusions:A single rCT obtained within 1 week of lung resection can reveal radiological IP-AE (rIP-AE) before clinical decline. Using a score ≥9 confines early steroid treatment to patients with near-certain disease, avoiding unnecessary exposure. Prospective studies should confirm whether this high-specificity strategy improves survival and resource utilization.

OBJECTIVES:Sleep-disordered breathing significantly affects perioperative outcomes; however, it remains frequently undiagnosed. We aimed to evaluate the utility of a novel carbon nanotube sensor system for detecting postoperative breathing abnormalities and investigated its association with postoperative complications following thoracic surgery. METHODS:In this prospective study, 86 patients who underwent anatomical lung resection without previously diagnosed obstructive sleep apnoea were monitored using carbon nanotube sensors from the immediate postoperative period through the first postoperative day. Abnormal breathing was defined as an ≥30% reduction in the peak sensor signal from baseline lasting more than 10 s, in accordance with standard hypopnea criteria used in polysomnography. Patient characteristics and complications were compared using Fisher's exact and Mann-Whitney U test. Multivariate logistic regression identified predictors of major complications. RESULTS:Twenty-three patients (26.7%) exhibited abnormal breathing events (sleep-disordered breathing). This group had a higher proportion of males (87% vs 61.9%, P = .035), had more difficult intubation (42.1% vs 13.5%, P = .018), and more frequently received epidural anaesthesia in addition to general anaesthesia (65.2% vs 36.5%, P = .027). Multivariate analysis identified sleep-disordered breathing as an independent predictor of major complications (Clavien-Dindo grade ≥3; odds ratio 4.41, 95% CI 1.14-13.8, P = .011) and prolonged air leakage (odds ratio 15.6, 95% CI 2.39-102, P = .004). CONCLUSIONS:The carbon nanotube sensor showed potential for detecting undiagnosed sleep-disordered breathing after thoracic surgery, independently associated with increased risk of major complications, particularly prolonged air leakage. CLINICAL TRIAL REGISTRATION:UMIN-CTR (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035066). Trial number: UMIN000031533.

Introduction: TP53 is a strong tumor suppressor gene; its deactivation contributes to carcinogenesis and influences clinical outcomes. However, the prognostic influence of p53 deactivation on early relapse in patients with surgically resected non- small cell lung cancer remains unclear. Materials and methods: A cohort of 170 patients with primary stage I through III lung adenocarcinoma (LADC) and lung squamous cell carcinoma who underwent complete resection at Tokyo Medical and Dental University was screened for TP53 mutations using panel testing, and association studies between TP53 mutations and clinical data, including histology and postoperative recurrence, were performed. The association between TP53 mutations and postoperative recurrence was validated using data from 604 patients with MSK-IMPACT from The Cancer Genome Atlas. Additional immunohistochemistry for p53 was performed on some subsets of the Tokyo Medical and Dental University population. Results: Mutations in TP53 were recurrently observed (35.9%; 61 out of 170) in the Tokyo Medical and Dental University cohort. In the histology-stratified analysis, patients with LADC histology showed TP53 mutations that were associated with poor relapse-free survival (log-rank test; P = .020), whereas patients with lung squamous cell carcinoma histology showed TP53 mutations that were not (P =.99). The poor prognosis of TP53 mutation-positive LADCs was validated in The Cancer Genome Atlas-LADC cohort (log-rank test; P = .0065). Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between TP53 mutations and abnormal IHC Conclusions: TP53 mutation is a potential marker for worse prognosis in surgically resected LADC; immunohistochemistry for p53 could be a surrogate method to identify patients with LADC with a worse prognosis. (JTCVS Open 2024;20:183-93)

Background and aims: The Global Leadership Initiative on Malnutrition (GLIM) developed a new method for evaluating malnutrition; however, no consensus has been reached regarding the use of these criteria. Therefore, this study aimed to investigate the association between nutritional status assessed using the GLIM criteria and outcomes of lung cancer after surgery.Methods: Patients with non-small cell lung cancer who underwent lung resection and bioelectrical impedance analysis to estimate muscle mass before surgery were included. Their background, pathological stage, recurrence, and prognosis were investigated. Patients were divided into two groups according to the GLIM criteria: normal nutrition and malnutrition groups.Results: The normal and malnutrition groups comprised 110 and 88 patients, respectively. Malnutrition was significantly associated with poor overall survival after surgery (P = 0.025) but not with disease-free survival. Multivariate analysis showed that malnutrition (hazard ratio [HR]:2.374, P = 0.020), advanced pathological stage of lung cancer (HR: 1.919, P = 0.002), and the presence of postoperative complications (HR: 2.035, P = 0.047) were significantly associated with poor overall survival.Conclusion: Malnutrition assessed using the GLIM criteria was associated with the prognosis of patients with postoperative non-small cell lung cancer. Preoperative assessment using the GLIM criteria would allow for effective nutritional and rehabilitative interventions to improve prognosis.(c) 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

症例は80歳男性．5 cm大の腰背部腫瘤を自覚し，以後5ヵ月で18 cm大までの急速な増大を認め，当院に紹介となった．MRIでは左腰背部皮下に170×140×80 mmの腫瘤を認めた．生検で脂肪肉腫疑いの診断となり，形成外科と合同で腰背部腫瘤を含む広範胸壁切除再建を計画した．壁側胸膜を温存し，皮膚，筋層，第8-12肋骨切除を伴う腫瘍切除を行った．胸壁再建にはチタンプレート2本とポリプロピレンメッシュ，遊離広背筋皮弁を使用し良好な術後経過であった．術後病理診断では多形性肉腫の診断が得られた．今回我々は広範囲な胸壁切除を伴う巨大胸壁原発悪性軟部腫瘍に対して，プレートを要する骨性胸郭再建と遊離広背筋皮弁を用いる軟部組織の再建を行い，切除し得たので報告する．

BackgroundDiabetes mellitus (DM) is a major disease that may influence survival outcomes and the incidence of postoperative complications in patients with non-small cell lung cancer (NSCLC). However, the effects of DM on survival and postoperative complications have not yet been investigated. We aimed to elucidate the surgical outcomes and impact of perioperative intensive glucose control (IC) in patients with DM.MethodsThis study included NSCLC patients who underwent curative resection at a single institution between 2013 and 2017. DM was confirmed in patients treated by referral doctors or in those with HbA1c<6.5% without medication. At our institution, IC is performed in many patients with DM.ResultsA total of 854 patients were recruited: 163 in the DM and 691 in the non-DM groups. Multivariate analysis revealed DM was associated with poor recurrence-free survival (HR, 1.37; P =.046, respectively) and tended to be associated with overall survival (HR, 1.43; P =.077). The incidence of postoperative complications did not differ between the DM and non-DM groups (P =.73). However, 90-day mortality was significantly higher in the DM group (3/163 vs. 0/691, P =.007). In patients with DM, IC was independently associated with the incidence of postoperative complications (P =.042).ConclusionsOur results suggest that DM is a prognostic predictor of poor overall survival and relapse-free survival. IC may reduce postoperative complications in patients with DM. Preoperative assessment and perioperative glycemia control for DM patients may be important for those with surgically treated NSCLC.

OBJECTIVES:While segmentectomy is considered a viable option for small peripheral non-small-cell lung cancer, its efficacy for central lesions remains uncertain. This study aimed to assess the oncological outcomes of segmentectomy for central lesions compared to peripheral ones. METHODS:We retrospectively examined 338 clinical stage IA non-small-cell lung cancer patients who underwent thoracoscopic anatomical segmentectomy at our institution from January 2013 to December 2021. Patients were divided into 2 groups based on intrapulmonary tumour location: inner two-thirds (central group, n = 82) and outer one-third (peripheral group, n = 256). RESULTS:The gender, body mass index, performance score, smoking, comorbidities and preoperative pulmonary function were similar in both groups. On computed tomography images, tumour diameter and consolidation-to-tumour ratio were comparable between the groups. The central group had significantly greater tumour-to-pleura distances [mm, 23 (18-27) vs 11 (8-14); P < 0.001], shorter margin distances [mm, 20 (15-20) vs 20 (20-20); P < 0.001] and larger resected lung volumes based on subsegment count [4 (3-6) vs 3 (3-5); P = 0.004] than the peripheral group. Surgery duration, bleeding, hospitalization or drainage period, mortality, readmission and pathological stage were equivalent between the groups. The central group showed significantly more postoperative pleural effusions (5% vs 1%; P = 0.03) than the peripheral group, with no adverse impact on postoperative pulmonary functions. During the follow-up period, local-only recurrence rates were 0% and 8% in the respective groups (Gray test P = 0.07), and total recurrence rates were 6% and 11% (Gray test P = 0.70), with no significant differences. Moreover, no significant inter-group difference in overall survival rates was observed (82% vs 93%; P = 0.15). CONCLUSIONS:Segmentectomy may be a promising therapeutic option for early-stage non-small-cell lung cancer located in the inner two-thirds of the parenchyma.

背景．細気管支腺腫/線毛性粘液結節性乳頭状腫瘍（bronchiolar adenoma/ciliated muconodular papillary tumor：BA/CMPT）は稀な良性腫瘍であるが，Computed tomograpy（CT）経過などについては不明な点が多く，悪性との鑑別が重要である．今回，CTで1.5年間の経過観察を行い，増大傾向を認めた1例を経験したので報告する．症例．症例は67歳男性，1年6ヵ月前にCTで右下葉小結節を指摘され経過観察されていたが，1年6ヵ月後のCTで増大傾向を認め，手術の方針となった．インジゴカルミン・リピオドールによるCTガイド下マーキングを実施したのちに，右下葉部分切除術を行った．詳細な病理組織学的検討の結果，BA/CMPTと診断された．自験例の10例についての臨床背景，CTの経過，遺伝子変異の特徴についてまとめ，報告を行った．結論．増大傾向を認めたBA/CMPTの1例を経験した．BA/CMPTは稀な組織型であり，CTで増大傾向を示し，ドライバー遺伝子変異を認める悪性のポテンシャルを有する症例もあり，悪性との鑑別が極めて重要である．

AbstractBackgroundThe recurrence rate of non‐small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high‐risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis.Materials and MethodsA cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer‐associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA).ResultsMutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse‐free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log‐rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log‐rank test, p = 0.10).ConclusionMutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.

OBJECTIVES:Double-lumen endobronchial tubes (DLTs) are essential for differential lung ventilation during pulmonary lobectomy, but they are more rigid, longer, larger in diameter and irritable. Coughing at extubation sometimes causes airway and lung injury, which causes severe air leaks, prolonged cough and sore throat. We examined the prevalence of cough-associated air leaks at extubation and postoperative cough or sore throat after lobectomy and evaluated the efficacy of supraglottic airway (SGA) in preventing these complications.METHODS:Patient characteristics and operative and postoperative factors data were collected from patients who underwent pulmonary lobectomy between January 2013 and March 2022. After propensity score matching, these data were compared between the SGA and DLT groups.RESULTS:A total of 1069 patients with lung cancer (SGA, 641; DLTs, 428) were enrolled and coughing at extubation occurred in 100 (23.4%) patients in the DLT group, 65 (65.0%) showed increased cough-associated air leaks at extubation and 20 (30.8%) showed prolonged air leaks. Coughing at extubation occurred in 6 (0.9%) in the SGA group. In 193 patients from each group after propensity score matching, coughing at extubation and the associated air leak increase were significantly lower in the SGA group. Visual analogue scale of postoperative cough and sore throat on postoperative days 2, 7 and 30 were significantly lower in the SGA group.CONCLUSIONS:SGA is effective and safe for preventing cough-associated air leaks and prolonged postoperative cough or sore throat at extubation following pulmonary lobectomy.

PURPOSE:The present study clarified the sensitivity of the BRAF tyrosine kinase inhibitor mechanism in patients with BRAF compound mutation and predicted the sensitivity using molecular dynamics simulation. METHODS:We examined 16 BRAF tumors with p.V600E-positive non-small-cell lung cancer. RESULTS:One patient (6.2%) had a BRAF p.V600E and p.K601_W604 compound mutation with a good clinical response to dabrafenib and trametinib. Molecular dynamics simulation also complemented the effect. CONCLUSIONS:The combination of a genetic analysis and computational simulation model may help predict the sensitivity for dabrafenib in cases with a rare BRAF compound mutation. The construction of a genomic and simulation fused database is important for the development of personalized medicine in this field.

Background The incidence of postoperative delirium after anatomical lung resection ranges from 5 to 16%. This study aimed to analyze the risk factors and prognosis of postoperative delirium in anatomical lung resection for lung cancer. Methods This study included 1351 patients undergoing anatomical lung resection between April 2010 and October 2020. We analyzed the perioperative risk factors of postoperative delirium. We also compared postoperative complications and survival between the delirium and non-delirium groups. Results Postoperative delirium was identified in 44 (3.3%) of 1351 patients who underwent anatomical lung resection for lung cancer. Age, peripheral vascular disease, depression, and current smoking status were independent risk factors for postoperative delirium in the multivariate analysis. The percentage of postoperative delirium was 0.6% in never smokers and 6.0% in current smokers. The delirium and non-delirium groups showed significant differences in overall survival (p = 0.0144) and non-disease-specific survival (p = 0.0080). After propensity score matching, the two groups did not significantly differ in overall survival (p = 0.9136), non-disease-specific survival (p = 0.8146), or disease-specific survival (p = 0.6804). Conclusions Age, peripheral vascular disease, depression, and current smoking status were considered independent risk factors for postoperative delirium in anatomical lung resection for lung cancer. Smoking cessation for at least four weeks before surgery is recommended for reducing incidence of post-operative delirium.

Pulmonary mucormycosis is an extremely rare disease. It often occurs in immunocompromised patients, such as patients with diabetes and those on long-term steroid use. The prognosis of the disease is poor despite the administration of antifungal agents and removal of the necrotic tissue. Herein, we present a successfully treated case of pulmonary mucormycosis in a patient with type 2 diabetes who underwent left pneumonectomy because of the involvement of the left main pulmonary artery and the left main bronchus. Irrespective of the infected organ, complete debridement of the infected tissue and treatment with antifungal agents are essential for treating mucormycosis.

Background: Postoperative cerebral embolic stroke is a serious complication of pulmonary lobectomy, occurring in 1.1% of patients undergoing lobectomy through video-assisted thoracoscopic surgery (VATS). The mechanism of this complication is thought to be embolic stroke caused by thrombus formed due to stagnation in the pulmonary vein stump after VATS lobectomy. There have been few reports demonstrating the utility of endovascular treatment (EVT) for cerebral embolic stroke after VATS lobectomy. Case description: In our case series, cerebral embolic stroke occurred after VATS pulmonary lobectomy for lung cancer, including the left upper lobe in three cases and the right lobe in one. The median duration of ischemic stroke after VATS was 4.5 days (interquartile range, 2-9 days). The median time from stroke onset to puncture was 130 min. Successful recanalization was achieved in all cases, and two patients achieved favorable clinical outcomes (modified Rankin scale, 0-2). Conclusion: We report a case series of four patients who underwent EVT for acute embolic stroke after VATS lobectomy for lung cancer. EVT is considered a reasonable and feasible therapeutic option for this condition.

Mediastinal bronchogenic cysts, regarded as congenital foregut abnormalities, are uncommon. These cysts can compress adjacent structures, causing obstructive symptoms and complications. A 57-year-old man was admitted to our hospital with complaints of tachycardia, dyspnea, and chest pain. Enhanced computed tomography revealed a 90 × 90 mm, well-defined subcarinal cystic mass causing significant compression and stenosis of the right main bronchus, right pulmonary artery, and right inferior pulmonary vein. The mass was successfully excised using one window and two-port video-assisted thoracoscopic surgery with partial resection and repair of pulmonary artery, and the postoperative course was good with no recurrence.

Introduction: The aim of this study is to evaluate the clinical backgrounds, including driver mutations, of those patients with early stage NSCLC who experienced recurrence beyond 5 years after complete resection. Methods: We used a cohort of 512 consecutive cases of surgically resected NSCLC without other malignances from 2006 to 2011 in Aichi Cancer Center Hospital. The inclusion criteria for this cohort were patients with primary NSCLC who underwent a surgically curable operation. Results: A total of 172 patients (32.8%) had recurrence after the surgery. Among the recurrent cases, 17 patients (3.3%) had a relapse more than 5 years after the surgery, and all except one (16 of 17, 94.1%) had driver mutations, including gene rearrangements. Conclusions: Even in early stage NSCLC after complete resection, it was found that some cases had a relapse more than 5 years after the surgery. Most of these cases had some kind of driver mutations; so more than 5 years of postoperative surveillance may be beneficial, especially in those with driver gene mutants.

OBJECTIVES:The purposes of this study are to clarify the details of the ALK tyrosine kinase inhibitor (TKI) resistance mechanism in rebiopsy cases and to predict novel resistance gene alterations using molecular dynamics simulation.METHODS:A total of 21 patients with ALK-positive NSCLC who underwent a rebiopsy after ALK TKI failure were included in this analysis. ALK fluorescence in situ hybridization and reverse transcription polymerase chain reaction were performed with paired initial and rebiopsy tumor specimens.RESULTS:Nine patients had no known ALK resistance mechanisms. Four had ALK amplification. L1196M, I1171N, and G1269A, mutations that are known to indicate resistance to ALK TKIs, were detected in one patient each. Small cell carcinoma and sarcomatoid transition were found in one case each. L1196Q, P1094H, and exon 24 76-base pair insertion were detected after the second-generation ALK TKIs.CONCLUSIONS:The combination of a genetic analysis and a computational simulation model may make a prediction of resistance mechanisms for overcoming ALK TKI resistance, and the construction of a genomic and simulation fused database is important for the development of personalized medicine in this field.

BRAF mutations are rare driver mutations in non-small cell lung cancer (NSCLC), accounting for 1%-2% of the driver mutations, and the mutation spectrum has a wide range in contrast to other tumors. While V600E is a dominant mutation in melanoma, more than half of the mutations in NSCLCs are non-V600E. However, treatment with dabrafenib plus trametinib targets the BRAF V600E mutation exclusively. Therefore, distinguishing between V600E and non-V600E mutations is crucial for biomarker testing in NSCLC in order to determine treatment of choice. Immunohistochemistry (IHC) using the BRAF V600E mutation-specific antibody is clinically used in melanoma patients, but little is known about its application in NSCLC, particularly with regard to the assay performance for non-V600E mutations. In the present study, we examined 117 tumors with BRAF mutations, including 30 with non-V600E mutations, using BRAF mutation-specific IHC. None of the tumors with non-V600E mutations, including two compound mutations, showed a positive reaction. Furthermore, all V600E mutations were positive except for one case with combined BRAF V600E and K601_W604 deletion. Our findings confirmed that the BRAF V600E mutation-specific IHC is specific without any cross-reactions to non-V600E mutations, suggesting that this assay can be a useful screening tool in clinical practice.

Comprehensive genetic panel testing generally requires that the analyzed tissues have a percent tumor nuclei (%TN) content of 20% or more to achieve assay performance comparable to the validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intraobserver variability, and examines whether focused training and feedback can improve pathologist performance. Nine referring institution pathologists (all board-certified and working at the core institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors that had been subjected to comprehensive genetic panel testing with the FoundationOne CDx assay. The %TN estimates provided by referring institution pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's pathologist (a board-certified pathologist at Foundation Medicine, Inc.) and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pretraining round of the evaluation, and the differences in the averaged %TN from the tumor sequencing institution and computational standards were statistically significant. However, the posttraining second-round results became significantly concordant with the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program.

BACKGROUND:RNA-based sequencing is considered ideal for detecting pathogenic fusion-genes compared to DNA-based assays and provides valuable information about the relative expression of driver genes. However, RNA from formalin-fixed paraffin-embedded tissue has issues with both quantity and quality, making RNA-based sequencing difficult in clinical practice. Analyzing stamp-derived RNA with next-generation sequencing (NGS) can address the above-mentioned obstacles. In this study, we validated the analytical specifications and clinical performance of our custom panel for RNA-based assays on the Ion Torrent platform. METHODS:To evaluate our custom RNA lung panel, we first examined the gene sequences of RNA derived from 35 NSCLC tissues with diverse backgrounds by conventional methods and NGS. Next, we moved to the clinical phase, where clinical samples (all stamp-derived RNA) were used to examine variants. In the clinical phase we conducted an NGS analysis while simultaneously applying conventional approaches to assess the feasibility and validity of the panel in clinical practice. RESULTS:In the prerun phase, all of the variants confirmed with conventional methods were detected by NGS. In the clinical phase, a total of 80 patients were enrolled and 80 tumor specimens were sequenced from February 2018 to December 2018. There were 66 cases in which the RNA concentration was too low to be measured, but sequencing was successful in the vast majority of cases. The concordance between NGS and conventional methods was 95.0%. CONCLUSIONS:RNA extraction using stamp specimens and panel sequencing by NGS were considered applicable in clinical settings. KEY POINTS:Significant findings of the study Next-generation sequencing using RNA from stamp specimens was able to detect driver gene changes in non-small cell lung cancer including fusion genes with the same accuracy as conventional methods. What this study adds Using RNA from stamp specimens obtained from biopsy increases the number of candidate cases for RNA sequencing in clinical settings.