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Only a small fraction of tumor-infiltrating lymphocytes can specifically recognize and attack cancer cells in PD-1/PD-L1 blockade therapy. Here, we investigate approaches to expand the neoantigen-specific CD8

Virtual-assisted lung mapping is a preoperative bronchoscopic multi-spot dye-marking technique used in sublobar lung resection for hardly palpable lung nodules. However, the number of marks required per nodule remains unknown. Therefore, we examined the correlation between the number of intraoperative visible marks and the successful resection rate.We retrospectively examined 210 consecutive patients with 256 lesions who underwent virtual-assisted lung mapping during January 2014-December 2020 at our hospital. When a nodule was not resected at the initial attempt, or when a nodule was very close to the cut margin in the resected specimen and required additional resection, we categorized it as unsuccessful resection. We divided 256 lesions into successful and unsuccessful groups and compared the numbers of intraoperative visible marks between the two groups.Of 797 attempted marks, 738 (92.4%) were visible during the surgery. Fourteen (5.4%) of 256 lesions were determined to be unsuccessful according to the study criteria. There was a remarkable difference in the average numbers of intraoperative visible marks between both groups (3 [interquartile range: 2-4] vs. 2 [interquartile range: 1-2.8]; p 0.01). Multivariable logistic analysis revealed a significant difference in the number of intraoperative visible marks (odds ratio: 0.28, 95% confidence interval: 0.14-0.57; p 0.001) between both groups.Successful sublobar lung resection requires three or more intraoperative visible marks established using virtual-assisted lung mapping per lung nodule.

Purpose To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. Methods Patients’ data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. Results Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient’s age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. Conclusion The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

BackgroundLung transplantation is the final option for end-stage respiratory diseases. Postoperative monitoring of patients’ physical condition and performance of appropriate interventions for any abnormalities are important to improve the long-term success of lung transplantation. In Japan, patients’ handwritten self-management charts are widely used to record data for home spirometry, vital signs, and medication dosages. However, handwritten data are not suitable for assessment. We developed an internet-based real-time monitoring system (LT-FollowUp) that can easily assess patient data and detect any abnormalities that arise without delay. The aim of this pilot study was to examine the acceptability of LT-FollowUp to patients.MethodsThis was a prospective single-arm pilot cohort study. Lung transplant patients were recruited consecutively at regular outpatient visits from October 2020. Patients were instructed to enter their self-measurements (pulmonary functions and vital signs) and immunosuppressant dosages twice a day.Acceptability was assessed by the data filling rate. The changes in filling rate over time were evaluated using a linear mixed-effects model for repeated measurements.ResultsA total of 19 patients were included in the study. There were no significant differences in the filling rates between the handwritten charts and LT-FollowUp.ConclusionLT-FollowUp is an acceptable system for patients. Further development of the LT-FollowUp system may lead to better long-term clinical outcomes of lung transplantation.

Few studies have assessed the comprehensive skeletal muscle depletion associated with loss of muscle quantity (sarcopenia) and reduced muscle quality in cancer patients. This study aimed to clarify the impact of skeletal muscle depletion on outcomes after non-small cell lung cancer surgery.Data for 341 patients with pathologic stages 1 to 3A non-small cell lung cancer who underwent lobectomy and mediastinal lymph node dissection from 2009 to 2013 were retrospectively reviewed. The integrative pectoralis muscle index (IPMI) was assessed by multiplying the normalized pectoralis muscle area (area/body mass index) and mean radiodensity on chest images. Postoperative outcomes were compared among sex-specific quartiles of IPMI. The trend of continuous and categorical variables was analyzed using the Jonckheere-Terpstra test and the Cochrane-Armitage test, respectively.Respiratory strength declined with decreasing quartiles of IPMI (P0.001). The risk of major complications escalated with the decrease of IPMI among four quartiles (7.1 %, 16.7 %, 18.4 %, and 22.4 %; P = 0.008). The hospital stay was prolonged for patients with reduced IPMI (P = 0.001). Patients in the lowest and highest quartiles had the worst and best 5-year overall survival, respectively, compared with those in the two intermediate quartiles of IPMI (67.0 %, 87.9 %, and 81.2 %, respectively; P=0.001). Multivariate analysis identified the lowest quartile of IPMI as an independent poor prognostic factor (hazard ratio, 1.88; 95 % confidence interval, 1.11-3.19; P = 0.020).Comprehensive skeletal muscle profiling, including morphometric mass and componential density on chest imaging, has the potential to refine risk stratification and prognostication in non-small cell lung cancer.

Fluorescent probes that can selectively detect tumour lesions have great potential for fluorescence imaging-guided surgery. Here, we established a library-based approach for efficient screening of probes for tumour-selective imaging based on discovery of biomarker enzymes. We constructed a combinatorial fluorescent probe library for aminopeptidases and proteases, which is composed of 380 probes with various substrate moieties. Using this probe library, we performed lysate-based

OBJECTIVE: There is little evidence of the outcome of pulmonary metastasectomy for uterine tumors when comparing different histologies. This study aimed to delineate the primary histology that leads to more favorable outcomes after pulmonary metastasectomy. METHODS: The database of the Metastatic Lung Tumor Study Group of Japan for 1984 to 2016 was used to analyze the outcomes of patients with gynecologic malignancies who underwent pulmonary metastasectomy. Prognostic factors and long-term outcomes were compared according to the histology of the primary uterine tumors, specifically adenocarcinoma, squamous cell carcinoma, and sarcoma. The adjusted hazard risks according to disease-free intervals (DFIs) and the number and maximum size of resected tumors were also analyzed to delineate the pattern of risk trends. RESULTS: A total of 319 patients were included in the analysis (122 with adenocarcinomas, 113 with squamous cell carcinomas, 46 with sarcomas, and 38 with other types). The 5-year survival rate was 66.5% for the entire cohort, 71.6% for the patients with adenocarcinoma, 61.3% for those with squamous cell carcinoma, and 55.4% for those with sarcoma. Multivariate analyses identified the positive prognostic factors as DFI ≥12 months in adenocarcinoma and sarcoma and the primary site (corpus) of uterine tumors in adenocarcinoma. The nonlinear adjusted hazard risks indicated that a shorter DFI was associated with an elevated risk of death in patients with adenocarcinoma and sarcoma. CONCLUSIONS: The survival outcome after pulmonary metastasectomy varies according to primary tumor histology, and the prognostic factors differ among histologic subtypes. Surgical indications should be determined based on the prognostic factors for each histology.

OBJECTIVES The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS Of the 663 patients enrolled in the 2 studies, 559 patients’ follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. Subj collection 152, 1542

A 54-year-old man with hereditary hemorrhagic telangiectasia and severe hypoxemia was referred for lung transplantation. Embolization had not been performed because of numerous bilateral small pulmonary arteriovenous malformations. Although he appeared to be qualified for lung transplantation, we instead performed bilateral thoracoscopic multiple wide wedge resections because of his age, lifestyle as a farmer, and relatively clustered distribution of arteriovenous malformations. Intermittent bilateral ventilation was needed because of poor oxygenation in the early stages of the operation, but his oxygenation improved as the resection progressed. His postoperative oxygenation improved significantly, and lung transplantation was avoided.

The Kanehira bitterling, Acheilognathus rhombeus, is a freshwater fish, discontinuously distributed in western Japan and the Korean Peninsula. Unusually among bitterling it is an autumn-spawning species and shows developmental diapause. Consequently, the characterization of its evolutionary history is significant not only in the context of the fish assemblage of East Asia, but also for understanding life-history evolution. This study aimed to investigate the phylogeography of A. rhombeus and its sister species Acheilognathus barbatulus, distributed in China, using a mitochondrial analysis of the ND1 gene from 311 samples collected from 50 localities in Japan and continental Asia. Phylogenetic analysis revealed that A. barbatulus is included in A. rhombeus and genetically closer to Japanese A. rhombeus than to Korean A. rhombeus. Divergence of Korean A. rhombeus and A. barbatulus from Japanese A. rhombeus was estimated to be from the late Pliocene (3.44 Mya) and the early Pleistocene (1.98 Mya), respectively. Each event closely coincided with the time of the Japan Sea opening. Japanese A. rhombeus comprised seven lineages: three in Honshu and four in Kyushu. One lineage in central Kyushu was genetically closer to the Honshu lineages than to other lineages in northern Kyushu. Divergence of Japanese lineages was estimated to be from the early to middle Pleistocene (0.55-0.93 Mya), during a period of geological and paleoclimatic change, including volcanic activity. Population expansion in the late Pleistocene (

Purpose. The dynamic state of epinephrine (Ep) in the plasma of patients with out-of-hospital cardiac arrest (OHCA) remains unclear. The purpose of this study was to evaluate the relationship between the plasma levels of catecholamines (such as epinephrine (Ep), norepinephrine (Nep), and dopamine) and vasopressin (antidiuretic hormone (ADH)) and the acquisition of return of spontaneous circulation (ROSC) in OHCA patients. Methods. This was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were enrolled. The levels of catecholamines and ADH in the plasma were measured using blood samples immediately obtained on arrival at our hospital and before the administration of Ep. Patients in whom Ep was already administered prior to obtaining blood samples were excluded. Patients were divided into two groups: with and without ROSC, that is, ROSC (+) and ROSC (−) groups, respectively. The plasma levels of these agents and the conditions of resuscitation were compared between the two groups. Results. A total of 96 patients with OHCA were analyzed. The ROSC (+) and ROSC (−) groups included 34 and 62 patients, respectively. There were no significant differences observed between the two groups in age, cause of cardiopulmonary arrest, and prehospital resuscitation time. The plasma levels of Ep and Nep were significantly lower in the ROSC (+) group than in the ROSC (−) group. However, there were no significant differences in the plasma levels of dopamine and ADH between the two groups. Conclusion. Increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with OHCA.

Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.

Hiroaki Kuroda,1 Shin Koyama,1 Mingyon Mun,2 Jun Nakajima,3 Kazuhito Funai,4 Ichiro Yoshino,5 Yoshikane Yamauchi,6 Masafumi Kawamura6 On behalf of the Metastatic Lung Tumor Study Group of Japan1Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; 2Department of Thoracic Surgical Oncology, Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan; 3Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan; 4First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan; 5Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan; 6Department of Surgery, Teikyo University School of Medicine, Tokyo, JapanCorrespondence: Hiroaki Kuroda, Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan, Tel +81-52-762-6111, Fax +81-52-763-5233, Email h-kuroda@aichi-cc.jpPurpose: Metastatic head and neck squamous cell carcinoma (HNSCC) is relatively poor; however, depending on the selected cases, pulmonary metastasectomy can be a practical therapeutic option. This study aimed to identify the outcomes of complete metastasectomy based on each primary site and to investigate unfavorable prognostic factors.Patients and Methods: We used the database from the Metastatic Lung Tumour Study Group of Japan. Between November 1980 and April 2017, 231 patients were deemed eligible. According to anatomy and the current epidemiology of HNSCC, the patients were divided into three groups: nasopharynx, oropharynx, and salivary gland (n = 40, Group 1), oral cavity, tongue, and paranasal sinuses (n = 69, Group 2), and larynx and hypopharynx (n = 122, Group 3).Results: The 5-year overall survival after complete pulmonary metastasectomy was 58.5%, 25.0%, and 46.9% in G1, 2, and 3, respectively (p < 0.01). Multivariate analyses revealed unfavourable prognostic factors to be G2, and pathological maximum diameter was > 20 mm. Therefore, on dividing group 1 and 3 with or without diameter, the 5-year overall survival was significantly worse in HNSCC with a diameter > 20 mm (n = 74) than that in the remnant (n = 88; 61.9% vs 35.5%; p < 0.01).Conclusion: According to the multi-institutional Japanese data, pulmonary metastasectomy from HNSCC indicates a potential survival benefit. Oral cavity, tongue, and paranasal sinuses cancer, and tumour size (> 20 mm) were poor prognostic factors for pulmonary metastasectomy from head and neck cancer.Keywords: pulmonary metastasectomy, head and neck squamous cell carcinoma, pulmonary metastasis, survival outcomes

OBJECTIVES The availability of new techniques may affect surgeons’ procedure selection and thereby affect clinical outcomes. This study aimed to evaluate the effect of the availability of virtual-assisted lung mapping (VAL-MAP) on the selection of lung resection methods. METHODS Members of the Japanese Association for Chest Surgeons were invited to participate in a web-based survey. Participants were divided into those who had never used VAL-MAP (group 0), those who had used only VAL-MAP 1.0 (multiple dye marks on the pleural surface; group 1) and those who had used VAL-MAP 2.0 (multiple dye marks and intrabronchial microcoils for three-dimensional mapping; group 2). Participants were shown chest computed tomography images of 6 ground-glass opacity nodules and asked to choose surgical procedures to resect the nodules with sufficient resection margins greater than the lesion diameter or 2 cm. RESULTS There were 197 surgeons in group 0, 49 in group 1 and 26 in group 2. All groups showed a similar trend of avoiding wedge resection for deeply located nodules. However, group 1 showed a trend of disagreeing with the selection of wedge resection compared with group 0 as measured by a Likert scale (1–5) by −0.21 points (95% confidence interval, −0.41 to −0.008 points, P = 0.042). This tendency disappeared in group 2. CONCLUSIONS The availability of VAL-MAP 1.0 led to the selection of segmentectomy, while the availability of VAL-MAP 2.0 led to aggressive deep wedge resection.

Objectives This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan. Background Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy. Methods This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected. Results Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia. Conclusions This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA.

Background A bronchial fistula is a relatively rare and potentially fatal complication after lung transplantation. Thoracic surgeons and pulmonologists often face challenges when selecting treatment options. We herein report an exceptional case of intrabronchial migration of a nonabsorbable hemostatic agent, which had been placed around the pulmonary artery at the time of lung transplantation, through a bronchial fistula. Case presentation A 61-year-old man developed respiratory distress 1 year after left single-lung transplantation for idiopathic interstitial pneumonia. Bronchoscopic examination revealed an apparent foreign body protruding from the mediastinum into the distal site of the bronchial anastomosis. The foreign body was easily removed bronchoscopically and appeared to be a hemostatic agent that had been placed during the previous lung transplantation. The patient developed a similar clinical episode and finally developed hemoptysis. Computed tomography revealed a foreign body located between the bronchus and pulmonary artery, partially protruding into the bronchial lumen. Given the possibility of a bronchopulmonary arterial fistula, surgical treatment was performed. The foreign body was located between the bronchus and left pulmonary artery and was easily removed. Multiple bronchial fistulas were found, and all were closed with direct sutures. Bypass grafting of the left pulmonary artery was then performed, initially with a homograft but eventually with an extended polytetrafluoroethylene graft. The patient was finally discharged 5 months after the surgery. Conclusion We experienced an extremely rare case of intrabronchial migration of hemostatic agents used during the previous lung transplantation through a bronchial fistula, which were successfully managed by direct bronchial closure and bypass grafting of the left pulmonary artery.

Introduction: Comprehensive cancer genomic profiling tests have been implemented in the clinic to guide patients and physicians to decide optimal treatments. Most tests analyze genomic DNA to detect genomic alterations in a few hundred genes. RNA panels have advantages over DNA panels when detecting fusion and exon skipping events. Methods: Between April 2017 and March 2022, non-small cell lung cancer samples were analyzed by Todai OncoPanel (TOP), a dual targeted DNA/RNA panel with matched tumor/normal pair analysis. Informed consent was obtained from all patients. Publicly available genomic data from approved panels in Japan, all of which are DNA-only panels, was downloaded from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database on 2022/11/3. Results: Sixty-one samples were analyzed. The median age of the patients was 62, and 35 were men. The histology of the samples included 52 adenocarcinoma and 9 squamous cell carcinoma. Of the 52 adenocarcinoma samples, pathogenic or likely pathogenic mutations were detected in 46 (88%), and 40 samples (77%) harbored potentially druggable targets. With the DNA panel, 23 (44%) TP53 loss-of-function mutations, 17 (33%) EGFR activating mutations, 6 (12%) ERBB2 activating mutations, 5 (10%) KRAS activating mutations, 5 (10%) RB1 loss-of-function mutations, 3 (6%) BRAF activating mutations, and 3 (6%) MET exon 14 splice site mutation were detected. Meanwhile, with the RNA panel, three MET exon 14 skipping and 15 fusion genes in 16 patients (16/61 = 26%) were detected, all in adenocarcinoma. Specifically, EML4-ALK, KIF5B-RET, and CD47-MET were detected from one sample each, and 12 others were all novel fusions with unknown pathogenicity. Overall, 5 out of 61 (8.1%) non-small cell lung cancer samples harbored MET exon 14 skipping or fusion. Using the C-CAT database, 37 MET exon 14 splice site mutations and 2 rearrangements were found in 1,514 non-small cell lung cancer samples (2.6%) from the C-CAT database (p = 0.009). One BRCA1 and one BRCA2 pathogenic germline variants were detected from the TOP germline panel. Conclusion: Analysis of non-small cell lung cancer using TOP led to detection of a high percentage of druggable targets. TOP RNA panel may detect MET exon 14 skipping and fusions at higher sensitivity. Citation Format: Hidenori Kage, Shinji Kohsaka, Kenji Tatsuno, Aya Shinozaki-Ushiku, Hideaki Isago, Kousuke Watanabe, Motohiro Kato, Tetsuo Ushiku, Kiyoshi Miyagawa, Takahide Nagase, Jun Nakajima, Hiroyuki Aburatani, Hiroyuki Mano, Katsutoshi Oda. Detection of METexon 14 skipping and fusions in non-small cell lung cancer by comprehensive genomic profiling using a dual targeted DNA/RNA panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 256.

This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P

Pulmonary metastasectomy is a common treatment for selected patients with pulmonary metastases. Among pulmonary resections, wedge resection is considered sufficient for pulmonary metastases. However, a major problem with wedge resection is the risk of local recurrence, especially at the surgical margin. The aim of this prospective study was to explore the frequency of and the risk factors for recurrence at the surgical margin in patients who underwent wedge resection for pulmonary metastases. Between September 2013 and March 2018, 177 patients (220 lesions) with pulmonary metastases from 15 institutions were enrolled. We studied 130 cases (169 lesions) to determine the frequency of and risk factors associated with recurrence at the surgical margin in patients who underwent wedge resection. Moreover, we evaluated the recurrence-free rate and disease-free survival after wedge resection. A total of 81 (62.3%) patients developed recurrence. Recurrence at the surgical margin was observed in 11 of 130 (8.5%) cases. The 5-year recurrence-free rate was 89.1%. Per patient, multivariable analysis revealed that the presence of multiple pulmonary metastases was a significant risk factor for recurrence. Per tumor, distance from the surgical margin and tumor/margin ratio were risk factors for local recurrence. The 5-year disease-free survival rate was 34.7%, and the presence of multiple pulmonary metastases and small surgical margin were risk factors for disease-free survival by univariable analysis. Among patients who undergo wedge resection for pulmonary metastasis, patients with multiple pulmonary metastases tend to develop recurrence at the surgical margin.

Background/aim A mixture of anticancer agents and iodized poppy seed oil (IPSO) has been widely used for intra-arterial chemotherapy of hepatocellular carcinoma. However, the anticancer agents can easily separate from IPSO, so the therapeutic potential is limited. We developed epirubicin-entrapped water-in-oil-in-water emulsion (WOW-Epi) using a double-membrane emulsification technique. Materials and methods We delivered WOW-Epi through a hepatic arterial injection to VX2 hepatic tumor rabbit model (1.2 mg/kg). Results VX2 tumor growth was selectively suppressed in the WOW-Epi-treated group compared with the control treated groups. The accumulation of WOW in nearby cancer cells was confirmed via electron-microscopy. Endocytosis seemed to be the mechanism underlying the uptake of WOW. Conclusion WOW-Epi led to tumour growth suppression in vivo. WOW does not cause toxicity to arterial vessels. WOW-Epi will be hopefully used for repeated intra-arterial chemotherapy to HCC patients in the near future.

Background/Aim: Tumor cell destruction by boron neutron capture therapy (BNCT) is attributed to the nuclear reaction between (10)B and thermal neutrons. The accumulation of (10)B atoms in tumor cells without affecting adjacent healthy cells is crucial for effective BNCT. We previously reported that several types of liposomal boron delivery systems (BDS) delivered effective numbers of boron atoms to cancer tissues, and showed tumor-growth suppression after thermal neutron irradiation. In the present study, we examined the effects of BNCT after intra-arterial infusion of (10)B-borono-dodecaborate ((10)BSH) by liposomal BDS in rabbit hepatic cancer models. Materials and Methods: We prepared (10)BSH-entrapped transferrin-conjugated polyethylene glycol liposomes constructed with distearoyl-boron lipid (TF-PEG-DSBL), and performed thermal neutron irradiation at the Kyoto University Institute for Integrated Radiation and Nuclear Science after intra-arterial infusion into rabbit VX-2 hepatic tumors. Results: Concentrations of (10)B in VX-2 tumors on delivery with TF-PEG-DSBL liposomes reached 25 ppm on day 3 after the injection. Tumor growth was suppressed by thermal neutron irradiation after intra-arterial injection of this (10)BSH-containing liposomal BDS, without damage to normal cells. Conclusion: The present results demonstrate the applicability of (10)B-containing TF-PEG-DSBL liposomes as a novel intra-arterial boron carrier in BNCT for cancer.

Proton solid electrolytes, which exhibit high proton conductivity and thermal stability in a wide range of intermediate temperatures, are desirable for operating fuel cells at a temperature suitable for applications such as automobiles and cogeneration systems. A new proton conductor NaMg1−xLixHx(PO3)3·yH2O was synthesised by a coprecipitation method. Powder X-ray structure refinement reveals that the three-dimensional tunnel framework is formed by the sharing of corner oxygens of zigzag PO4 tetrahedral chains and face-shared (NaO6)(MgO6) chains. In the three-dimensional tunnel, the oxygen sites of water for crystallisation were observed. In Fourier transform infrared spectroscopy (FTIR) measurement, an increase in absorption peaks corresponding to the modes of O–H and P–O–H bonds for x in NaMg1−xLixHx(PO3)3·yH2O was observed, which reflects the introduction of protons to the crystal structure. Although a multi-step weight loss due to desorption of water of crystallisation was observed for thermogravimetry (TG) curves, NaMg1−xLixHx(PO3)3·yH2O retained the framework up to 800 °C. The proton conductivity shows a positive tendency for x. NaMg0.8Li0.2H0.2(PO3)3·yH2O exhibited a high proton conductivity of over 10−2 S cm−1 in the temperature range of 150–500 °C, and the value reached 2.4 × 10−2 S cm−1 at 225 °C under a non-humidified atmosphere. The proton conductivity of NaMg0.8Li0.2H0.2(PO3)3·yH2O changed with the amount of crystalline water. In a humidified atmosphere (pH2O = 4 kPa), NaMg0.8Li0.2H0.2(PO3)3·yH2O exhibited a conductivity of over 10−3 S cm−1 from room temperature to 500 °C and reached 2.6 × 10−2 S cm−1 at 225 °C. After keeping the dehydrated sample in the humidified atmosphere at room temperature for 2 h, NaMg0.8Li0.2H0.2(PO3)3·yH2O showed a proton conductivity of over 10−2 S cm−1 again in the intermediate temperature range.

Proton solid electrolytes, which exhibit high proton conductivity at a wide range of low-intermediate temperatures (150-300 °C), are key materials for the development of fuel cells for automobiles and cogeneration systems. In this study, a benitoite-type polyphosphate, KMg1-xH2x(PO3)·yH2O, which has a non-combustible and layered structure, was investigated as a new proton conductor. The benitoite-type KMg1-xH2x(PO3)·yH2O was synthesised by a coprecipitation method. The solid solution formed in the range of x = 0-0.100 in KMg1-xH2x(PO3)3·yH2O. Multi-step weight loss due to dehydration was observed for TG/DTA measurement at 30 °C and 150 °C. We observed enhanced peaks of the vibration bands at around 1117 cm-1 and 1229 cm-1, which were attributed to the symmetric and asymmetric PO2 vibration modes, and at 743 cm-1 and 970 cm-1 due to the ns(P-O-P) and nas(P-O-P) modes as well as broad absorbance peaks at 2300 cm-1 and 2700 cm-1 corresponding to the vibration modes of ns(P-O-H) with increasing x for FTIR spectra, which suggest the introduction of protons to the crystal structure. Proton conductivity increased from x = 0 to 0.10 and then decreased at x = 0.125, where the impurity phase was observed. The sample with x = 0.10 in benitoite-type KMg1-xH2x(PO3)3·yH2O exhibited high proton conductivity of 1.4 × 10-3 S cm-1 at 150 °C and 6.5 × 10-3 S cm-1 at 250 °C under a non-humidified N2 gas flow.

1. For effective biodiversity conservation, verifying the correspondence of conservation sites among taxa and identifying the environmental characteristics of these sites are essential; however, only a few such studies have been performed in estuaries. The aim of the present study was to verify the surrogacy of estuarine gobies and crabs, to identify tidal rivers of high conservation priority, and to describe their environmental characteristics. / 2. Distribution data for gobies and crabs were collected from 158 tidal rivers in the Kyushu region, Japan. Three conservation scenarios were analysed based on the distribution data of gobies alone, of crabs alone, and of both taxa, in order to assess the correspondence of the conservation candidates (i.e. tidal rivers) between taxa. / 3. The degree of correspondence was poor for the candidates selected on the basis of the distribution data of gobies or crabs separately. More efficient candidates were selected based on the data for both taxa. The environmental characteristics of tidal rivers with high irreplaceability for conservation differed between the taxa. Tidal rivers forming and maintaining large tidal flats covered with fine sediment might have high irreplaceability for goby conservation, whereas rivers with saltmarshes connected to supratidal and intertidal zones might have high irreplaceability for crab conservation. / 4. Tidal rivers with a high priority for conservation were identified by overlapping the candidates for three scenarios. These tidal rivers are not necessarily large, but have steep basins with river mouths that are less exposed to ocean waves. Moreover, the percentage of artificial areas in these rivers was low, suggesting that these rivers have not been exposed to excessive anthropogenic disturbance that leads to loss of estuarine habitat. / 5. These results show that gobies and crabs are not surrogates for one another.

In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial thymectomy, the prognosis is greatly improved by ensuring a sufficient margin from the tumor, and therefore intraoperative fluorescent imaging of the tumor is especially valuable in thoracoscopic and robotic surgery, where tactile information is not available. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been applied for fluorescence imaging of some types of tumors in the resected tissues, and here we aimed to examine its validity for the imaging of thymoma and thymic carcinoma. 22 patients with thymoma or thymic carcinoma who underwent surgery between February 2013 and January 2021 were included in the study. Ex vivo imaging of specimens was performed, and the sensitivity and specificity of gGlu-HMRG were 77.3% and 100%, respectively. Immunohistochemistry (IHC) staining was performed to confirm expression of gGlu-HMRG's target enzyme, γ-glutamyltranspeptidase (GGT). IHC revealed high GGT expression in thymoma and thymic carcinoma in contrast to absent or low expression in normal thymic parenchyma and fat tissue. These results suggest that gGlu-HMRG is a promising candidate as an intraoperative navigation tool for thymoma and thymic carcinoma.

Multiple situations necessitate extracorporeal membrane oxygenation( ECMO) during lung transplantation. ECMO can also be used as a bridge to lung transplantation. We describe five cases in which bridging ECMO was successfully utilized, including three cases of living donor lung transplantation. ECMO can also be used as an alternative to cardiopulmonary bypass for intraoperative support during lung transplantation, and postoperatively, primary graft dysfunction, rejection, and infection can cause reversible respiratory failure which warrants ECMO. It can also be used for patients with pulmonary arterial hypertension in the early postoperative period to help their hearts adjust to new circulation. Eight patients with pulmonary arterial hypertension who underwent lung transplantation at our institu-tion received intraoperative and early postoperative ECMO support and their postoperative courses were uneventful. In this report, we review the indications for ECMO and the type of ECMO required for each of the various issues that can arise during lung transplantation, based on the literature and our experiences.

Distally located small common bile duct stones are often difficult to treat or grasp endoscopically. Therefore, multiple devices, such as baskets or balloon catheters, are frequently used in such cases. However, it is desirable to use a single device for stone extraction from the perspective of cost-effectiveness. In this multicenter study, we evaluated the efficacy of a new eight-wire basket catheter for extracting small (≤10 mm) common bile duct stones.We retrospectively analyzed the records of 144 patients who underwent stone extraction using the eight-wire basket catheter for common bile duct stones ≤10 mm. The success rate of complete stone extraction and the risk factors for the difficulty in stone extraction with the eight-wire catheter alone were mainly evaluated.The success rate of stone extraction with the eight-wire catheter alone was 86.1%. The final rate of complete stone extraction was 98.0%. The mean of the maximum diameter of the common bile duct and the largest stone dimension were 10.5 ± 3.5, and 5.1 ± 2.1 mm, respectively. Common bile duct diameter ≥12 mm and stone diameter ≥6 mm were identified as independent risk factors for the difficulty in stone extraction with the eight-wire catheter alone.The success rate of the new eight-wire basket for small common bile duct stone extraction was acceptable. The device is beneficial and could be used from the start for the extraction of small stones 6 mm.

OBJECTIVES Even after transplantation of favourable donor lungs, some recipients require prolonged weaning from mechanical ventilation, indicating a poor prognosis. We investigated the effects of prolonged mechanical ventilation (PMV) for >14 days on the recovery and survival of patients who underwent cadaveric lung transplantation in relation to their physical traits. METHODS We retrospectively reviewed patients who underwent cadaveric lung transplantation (age ≥15 years) at a single centre between April 2015 and December 2020 and classified them into PMV and non-PMV groups (>14 and ≤14 days of mechanical ventilation postoperatively, respectively). The factors predicting PMV comprised clinical factors (e.g. marginal donor) and physical features, namely flat chest, narrow fourth intercostal space (length, 40% and sarcopenia, according to the logistic regression analysis. The log-rank test was used to examine the association between TMOR >40% and 3-year prognosis. RESULTS The PMV group comprised 17 (33%) of 51 recipients. Multivariable logistic analysis showed that the TMOR >40% (odds ratio, 7.3; 95% confidence interval, 1.3–40.1; P = 0.023) was an independent preoperative predictive factor for PMV postoperatively. Stepwise analysis revealed intraoperative extracorporeal membrane oxygenation and reoperation as postoperative predictive factors in addition to TMOR >40%. Recipients with TMOR >40% had significantly worse 3-year survival than other recipients (71.2% vs 100.0%, respectively; P = 0.008). CONCLUSIONS Recipients with a TMOR >40% may be long-term ventilator dependent and have a poor prognosis.

This report describes the case of a patient who underwent bilateral lung transplantation for idiopathic pulmonary arterial hypertension with coexisting partial anomalous pulmonary venous return and tracheal bronchus. The hypoplastic and low-positioned left atrial orifice caused by abnormal reflux of the right upper pulmonary vein and high-positioned right upper lobe bronchus made right anastomosis challenging. To prevent excessive tension on left atrial anastomosis, the donor's right main bronchus was anastomosed to the recipient's bronchus intermedius, a maneuver that resulted in successful anastomosis and an uneventful postoperative course.

BACKGROUND: Pulmonary metastasectomy (PM) for breast cancer-derived pulmonary metastasis is controversial. This study aimed to assess the prognostic factors and implication of PM for metastatic breast cancer using a multi-institutional database. METHODS: Clinical data of 253 females with pulmonary metastasis of breast cancer who underwent PM between 1982 and 2017 were analyzed retrospectively. RESULTS: The median patient age was 56 years. The median follow-up period was 5.4 years, and the median disease-free interval (DFI) was 4.8 years. The 5- and 10-year survival rates after PM were 64.9% and 50.4%, respectively, and the median overall survival was 10.1 years. Univariate analysis revealed that the period of PM before 2000, a DFI