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Our recent work has challenged 4°C as an optimal lung preservation temperature by showing storage at 10°C to allow for the extension of preservation periods. Despite these findings, the impact of 10°C storage has not been evaluated in the setting of injured donor lungs.Aspiration injury was created through bronchoscopic delivery of gastric juice (pH: 1.8). Injured donor lungs (n = 5/group) were then procured and blindly randomized to storage at 4°C (on ice) or at 10°C (in a thermoelectric cooler) for 12 hours. A third group included immediate transplantation. A left lung transplant was performed thereafter followed by 4 hours of graft evaluation.After transplantation, lungs stored at 10°C showed significantly better oxygenation when compared to 4°C group (343 ± 43 mm Hg vs 128 ± 76 mm Hg, p = 0.03). Active metabolism occurred during the 12 hours storage period at 10°C, producing cytoprotective metabolites within the graft. When compared to lungs undergoing immediate transplant, lungs preserved at 10°C tended to have lower peak airway pressures (p = 0.15) and higher dynamic lung compliances (p = 0.09). Circulating cell-free mitochondrial DNA within the recipient plasma was significantly lower for lungs stored at 10°C in comparison to those underwent immediate transplant (p = 0.048), alongside a tendency of lower levels of tissue apoptotic cell death (p = 0.075).We demonstrate 10°C as a potentially superior storage temperature for injured donor lungs in a pig model when compared to the current clinical standard (4°C) and immediate transplantation. Continuing protective metabolism at 10°C for donor lungs may result in better transplant outcomes.

Over 2.5% of deaths in Canada occur as a result from medical assisting in dying (MAID), and a subset of these deaths result in organ donation. However, detailed outcomes of lung transplant recipients using these donors is lacking. This is a retrospective single center cohort study comparing lung transplantation outcomes after donation using MAID donors compared to neurologically determined death and controlled donation after circulatory death (NDD/cDCD) donors from February 2018 to July 2021. Thirty-three patients received lungs from MAID donors, and 560 patients received lungs from NDD/cDCD donors. The donor diagnoses leading to MAID provision were degenerative neurological diseases (n = 33) and end stage organ failure (n = 5). MAID donors were significantly older than NDD/cDCD donors (56 [IQR 49-64] years vs. 48 [32-59]; p = .0009). Median ventilation period and 30 day mortality were not significantly different between MAID and NDD/cDCD lungs recipients (ventilation: 1 day [1-3] vs 2 days [1-3]; p = .37, deaths 0% [0/33] vs. 2% [11/560], p = .99 respectively). Intermediate-term outcomes were also similar. In summary, for lung transplantation using donors after MAID, recipient outcomes were excellent. Therefore, where this practice is permitted, donation after MAID should be strongly considered for lung transplantation as a way to respect donor wishes while substantially improving outcomes for recipients with end-stage lung disease.

Background Fibrin glue effectively controls air leakage in lung surgery; however, allogenic fibrin glue cannot eliminate the risks of infection and allergy despite current sterilization methods. Autologous fibrin glue (AFG) could be a good alternative, but is not commonly used worldwide because of its limited availability and lack of evidence. Herein, we report clinical outcomes of AFG in thoracic surgery. Methods We retrospectively analyzed patients who underwent lobectomies or segmentectomies between November 2016 and September 2017 in our institution. We used two types of AFGs. One was a partially-autologous fibrin glue (PAFG), the components of which are largely autologous but which contains allogenic thrombin. The other was a completely-autologous fibrin glue (CAFG) which has no allogenic components. PAFG was used in the first half of the study period, after which CAFG was used from March 2017 onward. Patients who did not undergo AFG generation were categorized as the non-AFG group. The perioperative outcomes of the three groups were evaluated. Results A total of 207 patients underwent lung surgery, including 118 lobectomies and 89 segmentectomies. Among them, 83 patients received PAFG, 94 received CAFG, and 30 received non-AFG. The mean postoperative drainage period was within a few days in each group (PAFG vs. CAFG vs. non-AFG: 3.23±3.91 vs. 3.16±4.04 vs. 3.17±4.16 days, respectively; P=0.405), and the incidence of postoperative prolonged air leakage was within an acceptable range (PAFG vs. CAFG vs. non-AFG: 13.3% vs. 12.8% vs. 16.7%, respectively; P=0.821). Conclusions The use of AFG is clinically feasible for patients who undergo lobectomies or segmentectomies. AFGs could be a viable alternative to conventional allogenic fibrin glues.

This study aimed to analyze cause-specific mortality in lung cancer patients over 80 years old undergoing surgery. This retrospective, multi-institutional analysis included patients aged ≥ 80 years who underwent radical surgery for primary lung cancer from January 1998 to December 2015. Preoperative clinical data, surgical results, survival, and cause of death were evaluated. Competing risk analysis for cause-specific mortality was performed. Of the 337 patients (median age 82 years) enrolled and analyzed, 68.1% were male. There were 52 and 44 cancer-specific and non-cancer-specific deaths, respectively. On competing risk regression analysis, non-cancer-specific deaths were significantly associated with male sex (hazard ratio [HR]: 3.06, 95% confidence interval [CI]: 1.02–9.12, p = 0.046), coronary artery disease (HR: 2.49, 95% CI: 2.49 [1.14–5.47], p = 0.02), interstitial pneumonia (HR: 3.58, 95% CI: 1.73–7.40, p

Micronodular thymoma with lymphoid stroma (MNT) is a rare subtype of thymic neoplasms. Therefore, clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established.A 69-year-old woman was admitted to our hospital because of an abnormal shadow detected by chest radiography. Further imaging revealed an anterior mediastinal tumor measuring 65×28×15 mm. We performed thymectomy for diagnosis and treatment. Histopathological examination revealed spindle cells comprised multiple micronodules separated by abundant interstitial lymphocytes and lymphoid follicles. Immunohistochemical staining showed that the tumor was positive for cell adhesion molecule (CAM), cytokeratin (CK) 5/6, and terminal deoxynucleotidyl transferase. The histopathological diagnosis was MNT and the stage was I by the World Health Organization classification. The patient remained free of recurrence for seven years after surgery.When the lesion is completely resected, MNT has a good prognosis. Therefore, MNT is considered to be a borderline tumor with good prognosis and no reports of recurrences, distant metastasis, or tumor-related deaths exist thus far. However, preoperative diagnosis is difficult in most cases. Hence, complete surgical resection is recommended for suspicious mediastinal masses, if feasible, for both accurate diagnosis and to ensure long-term survival.

Development of chronic lung allograft dysfunction involves various alloimmune-independent insults including those mediated by Toll-like receptor (TLR) signaling, which is known to activate alloimmune responses. We hypothesized that TLR signaling may also contribute to the activation of fibroblasts and promoting allograft airway fibrosis. Mouse orthotopic tracheal transplants were conducted between major histocompatibility complex (MHC)-mismatched Balb/c donor and wild-type C3H or C3H-derived TLR4 mutant recipients (nonfunctional TLR4). Immunohistochemistry on day 21 showed significantly smaller alpha-smooth muscle actin (α-SMA)-positive areas in TLR4 mutant recipients than wild-type recipients (P = .01). No difference was found for CD3+ T-cell infiltration. Proliferation of alloreactive T cells derived from the recipient spleen showed no difference between TLR4 mutant and wild-type recipients in a mixed lymphocyte reaction. The effect of TLR4 signaling was examined in primary pulmonary fibroblast cultures both with lipopolysaccharide (LPS) and transforming growth factor (TGF)-β1. Stimulation with LPS significantly increased expression of α-SMA mRNA in wild-type fibroblasts cultured with TGF-β1 compared with the control without LPS (P = .001). Taken together, these findings suggest disruption of TLR signaling leads to reduced activation of fibroblasts without affecting T-cell infiltration and proliferation in this model. TLR4-mediated activation of fibroblasts may be a potentially important mechanism of allograft remodeling.

Highlights • We successfully performed thoracoscopic simultaneous resection of bilateral lung cancers with a PAPVC. • A single-stage procedure can achieve hemodynamic improvement for some patients with a PAPVC. • A single-stage procedure can reduce the duration of treatment. • A single-stage procedure of bilateral lung cancers is a feasible option for some patients with a PAPVC. • This is the first report regarding concomitant thoracoscopic resection of bilateral lung cancers and a PAPVC., Introduction Simultaneous resection of bilateral lung cancers is technically challenging but may be preferable to a staged procedure in patients with a partial anomalous pulmonary venous connection (PAPVC) in an affected lobe. We performed single-stage resection of bilateral lung cancers in a patient with a PAPVC. Presentation of case A 73-year-old man was diagnosed as having bilateral lung cancers (right, cT3N1M0, stage IIIA and left, cT2aN0M0, stage IB). Left upper trisegmentectomy was performed, followed by right upper lobectomy with deep wedge bronchoplasty. A PAPVC was found incidentally in the affected right upper lobe and successfully divided. The postoperative course was uneventful and he commenced chemoradiotherapy. Discussion Resection of the PAPVC, which was located in the same lobe as the lung cancer, would have mitigated load increase in the right heart and may have alleviated the adverse effects of bilateral lung resection. Moreover, the single-stage procedure likely shortened the overall duration of treatment. Conclusion Single-stage bilateral thoracoscopic resection may have advantages over staged procedures in some patients with PAPVCs.

A red rash developed on both hands of a 54-year-old man. At age 56, he was admitted to our hospital because of an abnormal shadow detected by chest roentgenogram. A detailed examination revealed an anterior mediastinal tumor and dermatomyositis. Thymectomy was performed, and pathologic examination revealed thymic carcinoma. After the surgery, the dermatomyositis symptoms improved. Although dermatomyositis associated with thymic carcinoma is extremely rare, we should account for the possibility of thymic carcinoma–associated dermatomyositis. This will allow for early identification and treatment of malignant tumors, and symptom severity may reflect the degree disease control.

The impact of red cell distribution width (RDW) on outcomes in elderly patients after surgery for non-small cell lung cancer (NSCLC) is not fully understood.We retrospectively analyzed 992 NSCLC patients who underwent curative resection between 1998 and 2012. The following variables were included in the analyses to evaluate the role of RDW: age, gender, smoking index, leukocyte count, neutrophil to lymphocyte ratio (NLR), hemoglobin, platelet count, albumin, C-reactive protein, carcinoembryonic antigen, respiratory function, histology, T factor, N factor, surgical approach, surgical procedures, complications and prognosis.High RDW (13.8) was an independent risk factor for morbidity [hazard ratio (HR) 2.1; P0.01], recurrence (HR 2.0; P=0.01), overall survival (OS) (HR 2.1; P0.01) and disease-free survival (DFS) (HR 2.0; P0.01) in elderly patients (age ≥75 years, n=275), whereas it was not in younger patients (age75 years, n=717). The surgical outcome was extremely poor in those older than 80 years with a RDW greater than 15% (morbidity, 56%; postoperative stay, 23 days; OS, 24%; DFS, 0%). RDW was unaffected by age (R =0.01; P=0.86) and elevated RDW without anemia was more prognostic than high RDW due to anemia in elderly patients.High RDW was significantly associated with high morbidity and reduced survival in elderly patients who underwent resection for NSCLC. Therefore, this parameter should be taken into account when surgery is considered in the elderly.

Introduction Two strategies for selecting neoantigens as targets for non–small cell lung cancer vaccines were compared: (1) an “off-the-shelf” approach starting with shared mutations extracted from global databases and (2) a personalized pipeline using whole-exome sequencing data on each patient’s tumor. Methods The Catalogue of Somatic Mutations in Cancer database was used to create a list of shared missense mutations occurring in more than 1% of patients. These mutations were then assessed for predicted binding affinity to HLA alleles of 15 lung cancer patients, and potential neoantigens (pNeoAgs) for each patient were selected on this basis. In the personalized approach, pNeoAgs were selected from missense mutations detected by whole-exome sequencing of the patient’s own samples. Results The list of shared mutations included 22 missense mutations for adenocarcinoma and 18 for squamous cell carcinoma (SCC), resulting in a median of 10 off-the-shelf pNeoAgs for each adenocarcinoma (range 5–13) and 9 (range 5–12) for each SCC. In contrast, a median of 59 missense mutations were identified by whole-exome sequencing (range 33–899) in adenocarcinoma and 164.5 (range 26–232) in SCC. This resulted in a median of 46 pNeoAgs (range 13–659) for adenocarcinoma and 95.5 (range 10–145) for SCC in the personalized set. We found that only one or two off-the-shelf pNeoAgs were included in the set of personalized pNeoAgs—and then in only three patients, with no overlap seen in the remaining 12 patients. Conclusions Use of an off-the-shelf pipeline is feasible but may not be satisfactory for most patients with non–small cell lung cancer. We recommend identifying personal mutations by comprehensive genome sequencing for developing neoantigen-targeted cancer immunotherapies.

An 18-year-old male patient who had undergone single-incision thoracoscopic surgery for left spontaneous pneumothorax was diagnosed with bilateral recurrent pneumothorax. We performed thoracoscopic reoperation and observed adhesions between the previous incision and the left lung. A bulla that was thought to be the cause of the recurrent left pneumothorax was found on the mediastinal side of previously ligated lesions. Longer incisions during single-incision thoracoscopic surgery may be more likely to cause adhesions. Despite the restricted view during surgery, care must be taken to identify all bullae. Use of reinforcement techniques is also important to prevent recurrence.

The azygoesophageal recess (AER) is known as a possible cause of bulla formation in patients with spontaneous pneumothorax. However, there has been little focus on the depth of the AER. We evaluated the relationship between the depth of the AER and pneumothorax development. We conducted a retrospective study of 80 spontaneous pneumothorax patients who underwent surgery at our institution. We evaluated the depth of the AER on preoperative computed tomography scans. Ruptured bullae at the AER were found in 12 patients (52.2%) with secondary spontaneous pneumothorax (SSP) and 8 patients (14.0%) with primary spontaneous pneumothorax (PSP) (p

A 59-year-old man was referred to our department for evaluation of an asymptomatic abnormal mediastinal shadow detected on chest roentgenogram. Computed tomography (CT) of the chest showed an anterior mediastinal tumor with ring calcification. Thymectomy through a median sternotomy was performed. Pathologic examination showed an encapsulated type B2 thymoma with ring calcification. Microscopically, the calcified layer was within the fibrous capsule layer. A part of the fibrous capsule was thought to become calcified like a ring. Although focal calcification is sometimes found in thymomas, ring calcification is rare.

After median sternotomy, the sternum is commonly closed using metal wires, which sometimes cause complications because they are permanent foreign bodies. As an alternative, we used a combination of absorbable sutures and pins for full median sternotomy in 24 adult general thoracic surgery patients. There were three cases of sternal dehiscence detectable by computed tomography, none of which required re-operation. Two of these patients had diabetes mellitus (DM) and the third patient was on corticosteroid therapy. In an appropriately selected patient population that excludes patients with DM or who are undergoing corticosteroid therapy, we have not observed any sternal complications. We concluded that our technique is clinically feasible with appropriate patient selection.

OBJECTIVES The Glasgow Prognostic Score (GPS), which is calculated with C-reactive protein (CRP) and albumin (Alb) values, is a prognostic indicator for various types of cancers. However, its role in lung cancer still remains unclear, and its optimal cut-off values are controversial. Here, we evaluated the significance of the GPS and adjusted GPS (a-GPS) using our institution's cut-off values in patients undergoing resection for primary lung cancer. METHODS We analysed 1043 lung cancer patients who underwent resection between 1998 and 2012. The overall survival (OS) probabilities of the GPS subgroups were estimated using the Kaplan-Meier method and were compared using the log-rank test. The prognostic significance of the GPS and the a-GPS was assessed by the Cox proportional hazards model with clinicopathological variables and inflammation markers, such as the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR). The GPS was calculated based on cut-off values of 1.0 mg/dl for CRP and 3.5 g/dl for Alb, as previously reported. The a-GPS was calculated based on cut-off values 0.3 mg/dl for CRP and 3.9 g/dl for Alb, which are the standard thresholds used by our institution. RESULTS The GPS and the a-GPS were correlated with preoperative factors, such as age, sex, smoking status, the NLR and the PLR, and oncological factors, including the pathological stage, histological type and level of lymphovascular invasion. The 5-year OS rates were 82, 55 and 55% with GPS 0, 1 and 2 (1 vs 0: P < 0.01; 2 vs 1: P = 0.66), respectively, and 88, 67 and 59% with a-GPS 0, 1 and 2 (1 vs 0: P < 0.01; 2 vs 1: P = 0.04), respectively. Multivariable analysis revealed that the GPS [1 vs 0, hazard ratio (HR): 1.63, 2 vs 0, HR: 1.44] and the a-GPS (1 vs 0, HR: 2.00, 2 vs 0, HR: 2.10) were independent prognostic factors. The a-GPS classification showed a clearer prognostic distribution than the GPS classification. CONCLUSIONS The GPS is a useful prognostic indicator of the OS in lung cancer surgery. The optimal cut-off values for GPS estimation may need to be re-evaluated.

A 64-year-old woman with a mediastinal tumor incidentally found on computed tomography( CT) was referred to our hospital. CT and magnetic resonance imaging( MRI) showed the tumor had a clear border and was located on the right side of the 12th thoracic vertebra, spanning the thoracic and abdominal cavities. She was suspected of having a benign neurogenic tumor of the mediastinum. She underwent tumor resection through the tenth intercostal space via a posterolateral thoracotomy. We easily resected the tumor using this approach. Pathological examination revealed a benign schwannoma of the mediastinum. Although this approach is rarely chosen by thoracic surgery, it is sometimes useful for the resection of mediastinal tumors near the diaphragm.

A 51-year-old man was referred to our hospital with an abnormal nodule in the right lung field. Computed tomography revealed a homogeneous nodule adjacent to the diaphragm, which appeared to be an extrapulmonary lesion. No hilar or mediastinal lymph node swelling was detected, and positron-emission tomography showed no significant uptake. At surgery, 2 red papillary tumors were found, originating from the right diaphragm, and tumor extirpation was performed. The pathological diagnosis was cavernous hemangioma.

Significant frequency of ruptured bullae at the azygoesophageal recess (AER) in secondary pneumothorax patients was reported recently. In normal anatomy, the AER usually exists only in the right thorax. We herein report a case of secondary spontaneous pneumothorax due to a ruptured bulla at a leftsided AER-like structure in a patient with right aortic arch. The case was a 70-year-old man who developed left spontaneous pneumothorax secondary to pulmonary emphysema. He was initially treated by thoracic drainage, but in vain, and finally referred to our department because of prolonged air leakage. Preoperative computed tomography demonstrated a bulla formation at a recess between the rightsided descending aorta and thoracic vertebrae. In thoracoscopic surgery, we confirmed air leakage from the bulla at the recess and the bulla was subsequently ligated. To the best of our knowledge bulla formation at a left-sided AER-like structure has never been reported. Local overinflation of the lung parenchyma may have been a cause of bulla formation in this case.

The patient was a 17-year-old girl. She underwent treatment for osteosarcoma when she was around 10 ~ 11 years old. A follow-up chest computed tomography(CT) revealed one small pulmonary nodule 6 years later. The orthopedist thought it was metastasis. The patient was referred to our division and treated with thoracoscopic partial resection. The final pathological diagnosis was a primary lung adenocarcinoma.This case is unique because the patient is juvenile and had a history of another cancer, i.e., osteosarcoma. Her primary lung cancer is a 2nd malignancy. The incidence of 2nd malignant neoplasm is one of the significant late effects of pediatric cancer treatment. When pulmonary lesions are detected in young patient with histories of neoplasms, primary lung cancer as a 2nd malignant neoplasm as well as pulmonary metastasis from 1st neoplasm, should be considered as differential diagnosis.

Introduction Lung cancer is the leading cause of cancer death in Japan, however, it has been difficult to detect and diagnose precisely lung cancer with a diameter less than 1cm to date. The purpose of this study is to investigate clinical application of novel GGT-targeted fluorescence probe for detecting the primary lung cancer in an intraoperative manner. Methods As a fluorescence probe for γ-glutamyltranspeptidase (GGT), γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) was used. gGlu-HMRG is non-fluorescent, but is converted to a highly fluorescent hydroxymethyl rhodamine green (HMRG) upon reaction with the enzyme, which tends to accumulate in GGT-overexpressing cancer cells. First, we examined GGT activity of lung cancer cell lines, A549, H460, H441, H82 and H226, by applying gGlu-HMRG and evaluating fluorescence intensities by confocal fluorescence microscopy. We also compared mRNA expression level of GGT1 (one of the subtypes of GGT) by qRT-PCR. Further, by transfecting siRNA targeted to GGT1, we investigated the target of gGlu-HMRG. Next we performed in vivo imaging of orthotopic A549 lung cancer xenograft model in nude mouse to confirm the validity of fluorescence imaging. Finally, we carried out ex vivo fluorescence imaging of 73 human lung cancers and normal lung tissues which were surgically resected, and the fluorescence intensities were analyzed by Receiver Operating Characteristics curve. Results A549, H460 and H441 cells with high GGT1 expression could be visualized with high fluorescence intensity after application of gGlu-HMRG within several minutes, whereas H82 and H226 cells with relatively low GGT1 expression could not. We ascertained that the target of gGlu-HMRG was GGT1 by fluorescence imaging and qRT-PCR with lung cancer cell lines transfected with siRNA for GGT1. In lung cancer xenograft model, pleural dissemination, hilar and mediastinal lymph node metastasis and the surface of lung cancer were clearly detected within 15 minutes after topical drip of gGlu-HMRG. We confirm that every fluorescent lesion was adenocarcinoma pathologically. In ex vivo human lung cancer fluorescence imaging, the sensitivity, specificity and accuracy were calculated to be 43.8% (32/73cases), 84.9% (62/73cases) and 64.4% (94/146), respectively. The adenocarcinomas, cancer of female or never smoker were more significantly detected by fluorescence imaging (p Conclusions We suggest that intraoperative application of gGlu-HMRG to detect pleural dissemination, small mediastinal lymph nodal metastasis, or other small foci of the lung cancer cells on surgical margin might be feasible when the cancer cells overexpress GGT. Intraoperative application of fluorescence probe is highly expected in near future. Citation Format: Haruaki Hino, Mitsuaki Kawashima, Tomonori Murayama, Junji Ichinose, Kentaro Kitano, Kazuhiro Nagayama, Jun-ichi Nitadori, Masaki Anraku, Tomohiro Murakawa, Kasue Mizuno, Sayaka Tanaka, Mako Kamiya, Nobuhiro Nishiyama, Kazunori Kataoka, Kohei Miyazono, Yasuteru Urano, Jun Nakajima. Rapid Cancer Imaging By GGT-targeted Fluorescence Probe For Primary Lung Cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5113. doi:10.1158/1538-7445.AM2015-5113