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Neurological paraneoplastic syndrome is a relatively rare condition in patients with malignant tumors. Recently, it has been reported that anti-Aquaporin 4 (AQP4) antibody is highly specific for neuromyelitis optica. The patient was a 76-year-old man. He underwent right upper lobectomy for squamous cell carcinoma of the lung. Although the immediate postoperative course was uneventful, neurological symptoms became apparent from postoperative day (POD) 4. Magnetic resonance imaging showed longitudinally extended edematous lesions in the spinal cord, and a cerebrospinal fluid examination was positive for anti-AQP4 antibody, leading to the diagnosis of paraneoplastic neuromyelitis optica. Despite multiple rounds of steroid pulse therapy and plasma exchange, the neurological symptoms worsened and the patient died on POD 46. The development of neuromyelitis optica in the early postoperative period could be related to the influence of surgical stress or epidural anesthesia.

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.

Background Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that occurs in premature infants and the prognosis is variable depending on the comorbidities including fibrosis, emphysema, or pulmonary hypertension (PH). We present a case of a 9-year-old girl who developed PH associated with severe BPD (BPD-PH) and underwent bilateral lung transplantation (BLTx). Case description A 9-year-old girl was admitted to our department to undergo BLTx. She was born at 23 weeks and 4 days gestation with a weight of 507 g. She received ventilation for the first 2 months and required further respiratory care due to repetitive, severe respiratory infections. She was diagnosed with BPD-PH at 6 months of age and oral administration of pulmonary vasodilators were initiated. She was registered as a lung transplant candidate at 4 years of age after the life-threatening exacerbation. Chest computed tomography (CT) revealed severe lung conditions with ground-glass opacities and emphysematous low-density areas in the upper and lower lobes. BLTx from a brain-dead male donor was performed. The pathological findings of her resected lung revealed saccular, hypoplastic lung with alveolar repair/regeneration, and medial hypertrophy and muscularization of peripheral arteries. The postoperative course was mostly uneventful. She was free from oxygen administration and showed no signs of PH after 6 months of the surgery. Conclusion This is the first case report of BLTx in a pediatric, irreversible BPD-PH patient with detailed pathohistological findings and clinical examination. Lung transplantation is one of the treatment options for severe BPD-PH.

Infections caused by the Scedosporium genus have become recognized as a fatal complication after lung transplantation in Europe and Australia, but the reports have been rare from Asian countries including Japan. We present a case of pneumonia caused by a mixed infection of Scedosporium apiospermum (SA) and Lomentospora prolificans (LP) that developed after augmentation of immunosuppression for chronic lung allograft dysfunction (CLAD) after lung transplantation. A 13-year-old man underwent bilateral lung transplantation for pulmonary hypertension. One year after surgery, he was treated with a series of augmented immunosuppressive therapy for severe acute rejection and subsequent CLAD. Three months following the first steroid pulse therapy, his serum β-D-glucan elevated without any sign of fungal infection by other tests. The serum β-D-glucan once returned to a normal level by empirical administration of micafungin; however, the patient's condition worsened again by discontinuation of it. He did not recover by restarting micafungin, and computed tomography (CT) scans eventually demonstrated new infiltrates in his lung field 6 weeks after the elevation of serum β-D-glucan. Microscopic findings of transbronchial lung biopsy specimens showed filamentous fungi, and the culture of bronchoalveolar lavage fluid revealed the growth of SA and LP. Despite subsequent voriconazole administration, he died 14 days after the start of voriconazole. Early and aggressive inspection including bronchoscopy should be performed for the diagnosis of Scedosporium infection in immunocompromised patients, even if CT scans and sputum culture show no evidence of infection.

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

The purpose of this study was to assess whether the anesthetic type is associated with the prognosis of pathological stage I non-small cell lung cancer (NSCLC). Clinicopathological data from 431 consecutive patients who underwent lobectomy for NSCLC between 2010 and 2016 were collected. Patients were classified into groups according to the type of anesthesia: propofol-based total intravenous anesthesia (TIVA) or inhalation anesthesia (INHA). We investigated the prognostic differences between these two groups. A total of 72 patients in the TIVA group and 158 patients in the INHA group were eligible for the analysis. Recurrence was observed in 4 (5.6%) patients in the TIVA group and 19 (12.0%) patients in the INHA group (P = 0.159), and all-cause death occurred in 4 (5.6%) patients in the TIVA group and 24 (15.2%) patients in the INHA group (P = 0.049). The 5-year recurrence-free survival (RFS) and overall survival rates of the TIVA/INHA groups were 91.7%/77.4% and 94.4%/83.5%, respectively. TIVA was associated with a significantly better prognosis. A multivariable analysis of factors associated with RFS revealed that the type of anesthesia as a significant prognostic factor (P = 0.047). Propofol-based TIVA was associated with a better prognosis in comparison to INHA in patients with surgically resected pathological stage I NSCLC.

Objectives One of the serious problems after lung transplantation is chronic lung allograft dysfunction (CLAD). Most CLAD patients pathologically characterized by obliterative bronchiolitis (OB). Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)-Ig is a combination protein of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA4. The aim of the study was to examine the effect of CTLA4-Ig therapy on OB using a mouse intrapulmonary tracheal transplantation (IPTT) model. Methods IPTT was performed between BALB/c (donor) and C57BL/6 (recipient) mice. Abatacept, which is a commercially available form of CTLA4-Ig, was intraperitoneally injected in recipient mice immediately after surgery, on days 7, 14, and 21. The mice in the control group received human IgG. Results We performed semi-quantitative analysis of graft luminal obliteration at post-transplant day 28. We calculated the obliteration ratio of the lumen of the transplanted trachea in each case. The obliteration ratio was significantly lower in the CTLA4-Ig group than that in the control group (91.2 ± 2.1% vs. 47.8 ± 7.9%, p = 0.0008). Immunofluorescent staining revealed significantly decreased lymphoid neogenesis in the lung. Conclusions CTLA4-Ig therapy attenuated tracheal obliteration with fibrous tissue in the mouse IPTT model. The attenuation of fibrous obliteration was correlated with the inhibition of lymphoid neogenesis.

OBJECTIVES The objective of the present study was to examine the effect of venovenous (VV) extracorporeal membrane oxygenation (ECMO) use on the haemodynamics during single lung transplantation (SLT) and postoperative course. METHODS Forty-seven patients who underwent SLT for end-stage lung diseases in our lung transplant centre between January 2010 and December 2019 were included in this study. The recipients were divided into 3 groups according to the type of intraoperative ECMO. No type of ECMO was intra-operatively used in the patients of the no use of ECMO (NO ECMO) group. The patients in the venoarterial (VA) and VV ECMO groups were put on VA and VV ECMO during the surgery, respectively. The data were compared among the 3 groups. RESULTS There were 13 SLT cases in the NO ECMO group, 23 SLT cases in the VA ECMO group and 11 SLT cases in the VV ECMO group. Re-exploration for bleeding was performed in 3 (13.0%) recipients in the VA ECMO group. No recipients required re-exploration in the other groups. In the NO ECMO group, systolic pulmonary arterial pressure (PAP) was significantly elevated during the main pulmonary artery clamp on the SLT side and it was decreased in the VA ECMO group because of the bypass flow. Interestingly, systolic PAP was significantly decreased in the VV ECMO group as well. CONCLUSIONS VV ECMO decreases the PAP during SLT, which could be a choice for extracorporeal life support during lung transplant surgery for patients, even those with pulmonary hypertension.

BackgroundIntraoperative contralateral pneumothorax during one-lung ventilation is a rare but life-threatening complication. Although the exact incidence is unknown, only 14 cases with this complication have been reported until now.Case presentationA 67-year-old Japanese man with a weight of 80 kg, height of 162.2 cm, and body mass index of 30.4 kg/m2underwent three-port video-assisted thoracic surgery for lung cancer with one-lung ventilation. He had suffered from traumatic right rib fractures 6 weeks before the referral. Fifteen minutes before the end of the surgery, the systolic blood pressure suddenly dropped to about 50 mmHg, which was immediately recovered by intravenous injection of phenylephrine. This episode occurred during chest closure after the completion of the left upper lobectomy, and one-lung ventilation was soon switched to two-lung ventilation. Contralateral tension pneumothorax was noted by the postoperative chest x-ray. As the patient was complicated with obesity and a past history of rib fractures, increased airway pressure during one-lung ventilation related to obesity together with the persistent compression of the visceral pleura by the fractured ends of the ribs was considered to be the factors responsible for this critical complication.ConclusionsPatient backgrounds such as obesity and past history of rib fractures should be noted carefully as risk factors for intraoperative contralateral pneumothorax during one-lung ventilation. We present the clinical course and discuss the mechanism of development of this potentially life-threatening complication in the present case with a review of the literature.

The prognostic nutritional index (PNI) is an immunonutrition index. Although preoperative PNI (pre-PNI) has been reported as a prognostic factor for patients with surgically resected non-small cell lung cancer (NSCLC), it is unclear whether postoperative PNI (post-PNI) and perioperative PNI change is a prognostic factor. Clinicopathological data from 262 consecutive patients who underwent lobectomy for NSCLC were collected. Pre-PNI and post-PNI were calculated within 1 month before surgery and at 1 month after surgery, respectively. We investigated which clinicopathological factors contributed to the post-PNI, the differences in prognosis according to the post-PNI status, and the impact of perioperative PNI change on prognosis. We set 50 and 45 as an optimal cutoff value of pre-PNI and post-PNI for OS using a receiver operating characteristic curve. Patients who were older and male and who had lower pre-PNI, larger thoracotomy size, longer operative duration, larger blood loss during surgery, and postoperative pulmonary complications showed significantly lower post-PNI. The 5-year overall survival (OS), lung cancer-specific survival, and recurrence-free survival rates for the high/low post-PNI groups were 87.4%/58.4% (P

The gastrointestinal tract is one of the locations that lung cancers cause metastasis. A 70-year-old male underwent right lower lobectomy while presenting fecal occult blood with a preoperative colonoscopy showing colon polyps as the cause. The pathological diagnosis was pleomorphic carcinoma of the lung, with stage pT3N0M0. Seven months after the lung surgery, the patient presented with sudden-onset abdominal pain and severe anemia. Computed tomography scanning revealed a large mass in the abdominal cavity, and subsequent intestinal endoscopy demonstrated jejunum tumors. Partial jejunum resection was successfully performed. The patient developed multiple peritoneal nodules suggesting metastatic tumors but well responded to an immune checkpoint inhibitor. It can be challenging to diagnose gastrointestinal metastasis in routine radiography; therefore, endoscopic examination, including the small intestine, might be an important option when a lung cancer patient with advanced clinical stage presents with abdominal symptoms, including fecal occult blood.

With de novo cancer, esophagectomy after lung transplantation (LTx) can be challenging because of intrathoracic adhesions, delayed wound healing, and postoperative pulmonary complications, which might be lethal.A 52-year-old woman with esophageal cancer had undergone bilateral LTx for end-stage diffuse panbronchiolitis at 50 years of age. Thoracoscopic esophagectomy was performed. Bilateral bronchial arteries and subcarinal and bilateral bronchial lymph nodes were preserved to maintain blood supply to the transplanted bronchi. No ischemic changes were observed in either bronchi. The patient's postoperative course was uneventful. Although she underwent chemoradiation therapy for recurrence at the left cervical paraesophageal lymph node, she remains alive with good disease control and well-maintained respiratory function.Minimally invasive surgery with careful attention to blood supply to the transplanted bronchi was useful for treating esophageal cancer after LTx.

The significance of clinicopathological features of pre- and post-resection pleural lavage cytology (PLC) for non-small cell lung carcinoma (NSCLC) currently remains unknown. Between January 2010 and December 2012, pre- and post-resection PLC were performed for NSCLC in 565 patients at Tohoku University, Miyagi Cancer Center, or Sendai Medical Center. The relationship between the clinicopathological features and patient outcomes was analyzed. Twenty-two patients (3.9%) had positive findings from pre- or post-resection PLC. Both PLC were correlated with pT and pl factors, while only post-resection PLC was correlated with pN factor (p

Appropriate selection for surgery is particularly important in T4 non-small cell lung cancer patients. In clinical settings, patients those who are positive for T4 criteria occasionally are also positive for T3 factors which are independently defined from original T4 or even have multiple T4 factors. Significance of these factors on prognosis is still unknown. We retrospectively reviewed clinicopathorogical data of 113 patients with T4 non-small cell lung cancer those who underwent surgery between 1990 and 2015 in Tohoku University Hospital. Significance on prognosis of single or multiple T4 factors and with or without independent T3 factors were statistically analyzed. No significant difference was seen in the 5-year survival rate between patients with single (35.6%) and multiple (31.4%) T4 factors (P = 0.94), but the rate was significantly lower when patients also had independent T3 factors (19.6%) compared with when they did not (42.5%) (P = 0.011). The 5-year survival rate was particularly lower among patients with invasion of the chest wall or parietal pleura (8.1%) than in those without (40.6%) (P = 0.0052). Invasion of the chest wall or parietal pleura is poor prognostic factors in T4 non-small cell lung cancer patients.

Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation. Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan. During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged

Background Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that occurs in premature infants and the prognosis is variable depending on the comorbidities including fibrosis, emphysema, or pulmonary hypertension (PH). We present a case of a 9-year-old girl who developed PH associated with severe BPD (BPD-PH) and underwent bilateral lung transplantation (BLTx). Case description A 9-year-old girl admitted to our department to undergo BLTx. She was born at 23 weeks and 4 days gestation with a weight of 507 grams. She received ventilation for the first 2 months and required further respiratory care due to repetitive, severe respiratory infections. She was diagnosed with BPD-PH at 6 months of age and oral administration of pulmonary vasodilators were initiated. She was registered as a lung transplant candidate at 4 years of age after the life-threatening exacerbation. Chest computed tomography (CT) revealed severe lung conditions with ground-glass opacities and emphysematous low-density areas in the upper and lower lobes. BLTx from a brain-dead male donor was performed. The pathological findings of her resected lung revealed saccular, hypoplastic lung with alveolar repair/regeneration and medial hypertrophy and muscularization of peripheral arteries. The postoperative course was mostly uneventful. She was free from oxygen administration and showed no signs of PH after 6 months of the surgery. Conclusion This is the first case report of BLTx in a pediatric, irreversible BPD-PH patient with detailed pathohistological findings and clinical examination. Lung transplantation is one of the treatment options for severe BPD-PH.

Solitary fibrous tumors are typically benign and usually develop in the pleura. We herein report the first case of a solitary fibrous tumor that was pathologically malignant and developed in the left atrial endocardium. A 24-year-old woman underwent resection of a malignant solitary fibrous tumor in her right forearm at another hospital. Computed tomography demonstrated a mass in her right pleura 2 months after the surgery. She was referred to our hospital, and a tumor in her left atrium was subsequently found. She underwent resection of these tumors, and pathological examination showed that they were both malignant solitary fibrous tumors.

Background The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation in selected cases, which may reduce the difficulty in achieving anastomosis under intubation of the left main bronchus. However, with median sternotomy, the ascending aorta requires repeated mobilization to expose the operative field for anastomosis, which can cause an aortogenic embolic stroke. Case presentation A 70-year-old Asian man presenting 6 months after developing hemoptysis was diagnosed with right upper lobe lung cancer (stage T4N0M0), invading the lower trachea and basal bronchus. Preoperative computed tomography revealed ascending aorta calcification. Right sleeve pneumonectomy was performed using median sternotomy with diseased lung ventilation. The ascending aorta was repeatedly mobilized to adequately expose the tracheobronchial bifurcation. Surgery was uneventful, but he did not recover complete consciousness even after termination of anesthesia. Mild paralysis of both upper extremities was observed. Head magnetic resonance imaging on postoperative day 1 revealed multiple small acute infarctions in the brain, possibly caused by mobilization of the aorta. He received anticoagulation therapy and rehabilitation and was discharged on postoperative day 30. Conclusion The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation. However, the possibility of aortogenic embolic stroke should be considered when calcification of the ascending aorta is observed on preoperative computed tomography.

The treatment of patients with brain metastases associated with non-small-cell lung cancer (NSCLC) is frequently challenging. Starting in 2003, we conducted a phase II study of surgery for patients with clinical T1-2N0-1 NSCLC with oligometastasis. The aim of this subset study was to assess the clinical significance of bifocal treatment for synchronous brain metastases in T1-2N0-1 NSCLC using prospectively collected data. In this phase II study of clinical T1-2N0-1 NSCLC patients with oligometastasis, 47 patients were enrolled from December 2003 to December 2016. Among them, 18 NSCLC patients with synchronous brain metastases were investigated in this subset analysis. Fourteen patients underwent complete resection, and 4 underwent incomplete resection of the primary lung cancer. The number of synchronous brain metastases was one in 14 and multiple in 4 patients. After surgery for the primary lung cancer, 12 of 18 patients underwent treatment for their brain lesions, including stereotactic radiosurgery (SRS) in 10, surgical resection in 1, and SRS followed by surgical resection in 1. In 5 of the 18 patients (28%), the brain lesion was diagnosed as benign on follow-up radiological imaging. The 5-year overall survival rate after enrollment was 31.8% for all 18 patients and 35.2% for the 13 patients with brain metastases. Univariate analysis showed that having multiple brain lesions was a significant factor related to a worse prognosis. For patients with suspected brain metastases associated with NSCLC, bifocal local treatment could be an acceptable therapeutic strategy, especially for solitary brain metastasis.

Introduction Surgery for N2 stage IIIA NSCLC is not recommended in major guidelines. Nevertheless, it has been noted that single-station N2 may have a better prognosis than multistation N2 and that surgery can be performed as the main therapeutic option. Methods We conducted a prospective phase II study for single-station clinical N2 (cN2) NSCLC to evaluate the efficacy and safety of surgical resection without induction therapy. Complete resection with lobectomy, bilobectomy, or pneumonectomy followed by ipsilateral mediastinal lymphadenectomy was performed in 32 of 34 enrolled patients, whereas the remaining two patients underwent incomplete resection. Three-quarters of the patients underwent subsequent adjuvant chemotherapy. Results The 5-year overall survival rate was 58.5% (95% confidence interval: 41.9–75.4) for all 34 patients, and eight patients (23.5%) with pN0 or pN1 seemed to have been enrolled. The 5-year overall survival rates for single-station cN2 without and with hilar node enlargement were 81.3% and 37.5%, respectively (p = 0.025). Surgical mortality was 0% for all, and no considerable perioperative complications were noted; however, two patients died of interstitial pneumonia and unknown cause within 3 months after surgical resection. Conclusions This is the very first prospective study on the surgical approach for cN2 NSCLC, and our result partially validated the proposed classification of the N descriptor in the new staging system. The treatment for single-station cN2 without hilar node enlargement would better if it were similar to that for cN1 disease. Induction chemotherapy or chemoradiotherapy may not be needed for such an entity.

Background and Objectives To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients. Methods To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000. Results Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung. Conclusions We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.

Background Broncho-pleural fistula (BPF) and respiratory failure (RF) are life-threatening complications after lung cancer surgery and can result in long-term hospitalization and decreased quality of life. Risk assessments for BPF and RF in addition to mortality and major morbidities are indispensable in surgical decision-making and perioperative care. Methods The characteristics and operative data of 80,095 patients who had undergone lung cancer surgery were derived from the 2014 and 2015 National Clinical Database (NCD) of Japan datasets. After excluding 1501 patients, risk models were developed from these data and validated by another dataset for 42,352 patients derived from the 2016 NCD dataset. Receiver operating characteristic curves were generated for postoperative BPF and RF development. The concordance-index was used to assess the discriminatory ability and validity of the model. Results BPF and RF occurred in 259 (0.3%) and 420 patients (0.5%), respectively, in the model development dataset and in 129 (0.3%) and 198 patients (0.5%), respectively, in the model validation dataset. Characteristic variables including types of surgery and comorbidities were identified as risk factors for BPF and RF, respectively. The concordance indexes of assessments for BPF and RF were 0.847 (p

The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17–84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution. Anterior mediastinal masses and nodules were classified into two disease categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma) and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell lymphoblastic lymphoma, Hodgkin’s lymphoma, and malignant germ cell tumors) groups. The sensitivity and specificity of maximum standardized uptake value (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The SUVmax distributions of the WHO histological thymoma types and Masaoka stage thymomas extensively overlapped. Masaoka stage III thymomas had significantly higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification, the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.

The presence of epidermal growth factor receptor (EGFR) mutations is an established prognostic factor for patients with advanced lung adenocarcinoma. Here, we examined whether EGFR mutation status is a prognostic factor for patients who had undergone surgery.Clinicopathologic data from 1,463 patients who underwent complete surgical resection for lung adenocarcinoma between 2005 and 2012 were collected. Differences in postoperative recurrence-free survival and overall survival according to EGFR mutation status were evaluated.Of 835 eligible patients, the numbers of patients with wild-type EGFR (WT), exon 19 deletion (Ex19), and exon 21 L858R (Ex21) were 426, 175, and 234, respectively. Patients with Ex19 had a significantly higher incidence of extrathoracic recurrence than patients with Ex21 (p = 0.004). The 5-year recurrence-free survival rates for patients with WT, Ex19, and Ex21 were 63.0%, 67.5%, and 78.2%, respectively. The Ex21 group had a significantly longer recurrence-free survival than the WT group (p0.001) and the Ex19 group (p = 0.016). The 5-year overall survival for patients with WT, Ex19, and Ex21 were 76.9%, 86.5%, and 87.5%, respectively. Patients with Ex19 and Ex21 had a significantly longer overall survival than patients with WT (Ex19, p = 0.009; Ex21, p0.001). Multivariate analysis for recurrence-free survival showed that Ex19 was significantly associated with a worse prognosis than Ex21 (p = 0.019).Patients with Ex19 had significantly shorter recurrence-free survival and had extrathoracic recurrence more frequently than patients with Ex21 among patients with resected lung adenocarcinoma, implying that Ex19 could be a worse prognostic factor.

Lung transplantation is accepted as an effective modality for patients with end-stage pulmonary lymphangioleiomyomatosis (LAM). Generally, bilateral lung transplantation is preferred to single lung transplantation (SLT) for LAM because of native lung-related complications, such as pneumothorax and chylothorax. It remains controversial whether SLT is a suitable surgical option for LAM. The objective of this study was to evaluate the morbidity, mortality and outcome after SLT for LAM in a lung transplant center in Japan. We reviewed the records of 29 patients who underwent SLT for LAM in our hospital between March, 2000 and November, 2017. The data collected included the pre-transplant demographics of recipients, surgical characteristics, complications, morbidity, mortality and survival after SLT for LAM. The most common complication after SLT for LAM was contralateral pneumothorax (n = 7; 24.1%). Six of these recipients were treated successfully with chest-tube placement and none required surgery for the pneumothorax. The second-most common complication was chylous pleural effusion (n = 6; 20.7%) and these recipients were all successfully treated by pleurodesis. The 5-year survival rate after SLT for LAM was 79.5%. LAM-related complications after SLT for this disease can be managed. SLT is a treatment option and may improve access to lung transplantation for patients with end-stage LAM.

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

Objectives The incidence of small-sized pulmonary adenocarcinomas with ground-glass opacity (GGO) has recently increased, with excellent postoperative prognosis. The limited resection of such cancers has been deemed to be acceptable based on retrospective studies. We conducted a prospective multi-institutional study evaluating the validity of limited resection for small-sized pulmonary adenocarcinoma with GGO. Methods The inclusion criteria were 25-80 years of age, no prior treatment, a maximum tumour diameter of 8-20 mm, a GGO ratio of ≥ 80%, clinical T1N0M0, lower 18F-fluorodeoxyglucose accumulation than the mediastinum, resectable by sublobar resection, pulmonary lobectomy tolerable and an intraoperative pathological diagnosis of bronchiloalveolar carcinoma. Wedge resection was preferred, but segmentectomy was permitted. Disease-specific survival and overall survival were analysed. Results From November 2006 to April 2012, 73 patients were enrolled from 13 institutions. One patient was ineligible, and the remaining 72 patients were preregistered. The tumours of 3 and 14 patients were intraoperatively diagnosed as benign lesions and adenocarcinomas with mixed subtype, respectively. Intraoperative cytological/histological examination of surgical margin was not performed in 2 patients, and the remaining 53 patients were ultimately eligible for this study. The mean tumour size was 14.0 mm and the mean GGO ratio was 95.9%. Thirty-nine and 14 patients underwent wedge resection and segmentectomy, respectively. Although all tumours were intraoperatively diagnosed as bronchioloalveolar carcinomas, 6 were ultimately diagnosed as adenocarcinoma with a mixed subtype. No completion lobectomy was performed. As of 1 May 2017, no recurrence of the original lung cancer was observed during 60.0-126.3 months after surgery. Two patients died from other diseases. The 5-year disease-specific and overall survival rates were 100% and 98.1%, respectively. The reduction in the pulmonary function after limited resection was minimal. Conclusions With these criteria, limited resection was performed safely without any recurrence, and the postoperative pulmonary function was well preserved. The outcomes of limited resection for small-sized lung cancer with GGOs that met the criteria of this study were satisfactory.

OBJECTIVES Using data obtained from a Japanese nationwide annual database with web-based data entry, we developed a risk model of mortality and morbidity after lung cancer surgery. METHODS The characteristics and operative and postoperative data from 80 095 patients who underwent lung cancer surgery were entered into the annual National Clinical Database of Japan data sets for 2014 and 2015. After excluding 1501 patients, the development data set for risk models included 38 277 patients entering in 2014 and the validation data set included 40 317 patients entering in 2015. Receiver–operating characteristic curves were generated for the outcomes of mortality and composite mortality/major morbidity. The concordance index was used to assess the discriminatory ability and validity of the model. RESULTS The 30-day mortality and overall mortality rates, including in-hospital deaths, were 0.4% and 0.8%, respectively, in 2014, and 0.4% and 0.8%, respectively, in 2015. The rate of major morbidity was 5.6% in 2014 and 5.6% in 2015. Several risk factors were significantly associated with mortality, namely, male sex, performance status, comorbidities of interstitial pneumonia and liver cirrhosis, haemodialysis and the surgical procedure pneumonectomy. The concordance index for mortality and composite mortality/major morbidity was 0.854 (P

Purpose Idiopathic pleurparenchymal fibroelastosis (IPPFE) is a relatively new disease entity of interstitial pneumonia characterized by upper lobe dominant fibrosis and flat chest. The purpose of this study is to evaluate the outcome of lung transplantation for IPPFE in comparison with idiopathic pulmonary fibrosis (IPF). Methods We retrospectively reviewed patients with IPPFE and those with IPF aged 20 or over who underwent lung transplantation between 1998 and 2018. Data were collected from all nine lung transplant centers in Japan, under the support of Japanese Society of Lung and Heart-Lung Transplantation. Results One hundred patients were eligible, including 31 IPPFE and 69 IPF patients. Patients with IPPFE were more likely to be women (58% vs 28%; P Conclusion The survival of patients with IPPFE after lung transplantation was comparable with those with IPF. However, patients with IPPFE showed longer ICU stay, limited improvement in pulmonary function, and no improvement in low BMI, suggesting systemic or extrapulmonary problems such as stiff chest wall in patients with IPPFE.

Calcineurin inhibitors are a commonly used immunosuppressive drug and over 80% of lung transplant (LTx) recipients use tacrolimus. Sustained-release tacrolimus (SRT) was developed as a once-daily formulation, resulting in slower release and reduction in peak concentration compared with twice-daily immediate-release tacrolimus (IRT). Previous reports indicate that SRT may carry fewer side effects than IRT; however, the impact of SRT in bronchiolitis obliterans syndrome (BOS) after LTx is unclear.Our study objective was to evaluate the effect of SRT in BOS after LTx.We investigated the effect of SRT for BOS among 75 LTx recipients who were alive in 2017 in our LTx program. All analyses were carried out using student t test or F test.Thirty-five recipients took IRT, 32 recipients used SRT, 7 recipients used cyclosporine, and 1 patient who received bone marrow and a lung graft from the same donor did not use a calcineurin inhibitor. The most frequent reason for conversion of IRT to SRT was kidney dysfunction, followed by other IRT complications. Five recipients underwent conversion of IRT to SRT because of decline of forced expiratory volume in 1 second (FEV1) with fluctuation of the tacrolimus trough level. After induction of SRT, the fluctuation of the tacrolimus trough level was significantly reduced in 4 of 5 patients (P .05). Before drug form conversion, the FEV1 in these 5 patients was significantly decreased; however, this exacerbation of FEV1 was attenuated after SRT induction (P .05).SRT appeared to stabilize decline of FEV1 in patients with BOS possibly due to reducing the fluctuation of tacrolimus trough blood concentration.

Purpose Lung transplantation (LTx) is an effective treatment for patients with end-stage pulmonary lymphangioleiomyomatosis (LAM). However, native lung-related complications, such as chylothorax, chylous sputum, and native lung hyperinflation, can develop after a single LTx. LAM lesion recurrence in transplanted lungs and abdominal LAM lesions may also occur post-LTx. Further, while sirolimus therapy can be used to treat these complications, its efficacy and tolerability in patients with LAM after LTx remain unclear. This study aimed to evaluate the effect of sirolimus on post-LTx LAM complications. Methods We retrospectively reviewed the records of LTx recipients who received sirolimus for treating post-LTx LAM complications from March 2000 to December 2019. Results Of the 40 patients who underwent LTx for LAM treatment, eight underwent sirolimus treatment for post-LTx LAM complications. Two patients exhibited chylous sputum; two, chylous ascites; one, chylothorax; one, native lung hyperinflation; one, LAM recurrence in the transplanted lung; and one, angiomyolipoma. Patients’ immunosuppressive regimen consisting of tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids was not changed, but the target trough level of TAC was reduced with the baseline levels of TAC and sirolimus being 5 ng/mL each. Sirolimus was discontinued for one patient because nausea occurred soon after the first dose. LAM lesions improved or were suppressed in six patients (Figure 1). The forced expiratory volume at 1 s post-sirolimus administration was stable (Figure 2). Acute rejection and infection were not observed, but one patient underwent a second LTx on the contralateral side due to chronic lung allograft dysfunction. Conclusion Providing sirolimus immunosuppressive therapy after LTx for LAM treatment can be effective in managing post-LTx LAM complications and may be acceptable when combined with TAC, MMF, and steroids.

Background General theory of anesthetic managements for nontransplant procedures in lung transplant patients was proposed. However, there are few literatures reporting the perioperative management of thoracoabdominal major surgery following lung transplantation in detail. Herein, we scrupulously report a perioperative management of esophagectomy in a patient who previously underwent bilateral lung transplantation (BLTx), focusing on protection of the transplanted lungs and the respiratory function of the patient. Case presentation A 50-year-old woman was listed for cadaveric BLTx for severe respiratory failure due to end-stage diffuse panbronchiolitis. She underwent BLTx under veno-arterial extracorporeal membranous oxygenation support. Blood loss during the BLTx was 13,675 mL, and mild lung edema developed. She was weaned from the ventilator on the sixth postoperative day (POD) and discharged on the 65th POD. Two years after the BLTx, respiratory function improved markedly, but she was diagnosed with esophageal cancer and was scheduled for thoracoscopic esophagectomy with radical lymph node dissection, hand-assisted laparoscopic gastric mobilization, and anastomosis of the gastric conduit to the cervical esophagus via posterior mediastinum. We were concerned that impaired lymphatic drainage could cause pulmonary edema or lymphangiogenesis could cause a severe immunologic response against the lung grafts. To avoid graft injury and rejection, we addressed lung protective ventilation, reduced transfusion volume, continued immunosuppressive agents, administered volatile anesthetics, and prevented dynamic pain by epidural analgesia. These factors and the improved respiratory function may have contributed to successful management of esophagectomy. During the perioperative period, the major respiratory problems were a slight right lung edema and a persistent pulmonary air leak due to the division of thoracic adhesions, which resolved on 13th POD. Conclusions Cancer surgeries in lung transplant recipients become more common. When such patients undergo thoracoabdominal major surgery, we should pay special attention to respiratory function, operative stress, immunosuppressive therapy, transfusion volume for the prevention of lung edema, and thoracic adhesions.

Purpose We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT). Methods We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group). Results The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group. Conclusion EVL-CT may predict the outcome of the early phase after lung transplantation.

Background. Acute kidney injury (AKI) is a common complication after lung transplant (LTx), and continuous renal replacement therapy (CRRT) is increasingly of use to critically ill patients who have developed AKI. However, the optimal timing or threshold of kidney impairment for which to commence CRRT after LTx has been uncertain. There has also been limited information on the impact of CRRT among LTx recipients (LTRs) introduced in the early posttransplant period on survival, graft function, and renal function. We aimed to review LTRs who developed AKI requiring CRRT postoperatively and followed their long-term outcomes at Tohoku University Hospital (TUH). Methods. Medical records of consecutive patients who underwent LTx at TUH between 2000 and 2018 were reviewed, with follow-up to 2019 inclusive. Results. Although mortality in those who required CRRT (n = 21) was increased versus those who did not require CRRT (n = 85)(P = 0.024), conditional survival beyond 3-month posttransplant was not affected (P = 0.131). Additionally, the cumulative incidence of chronic lung allograft rejection (P = 0.160) and the development of chronic kidney disease (P = 0.757) were not significant between groups. Conclusions. The initiation of CRRT posttransplant may be a useful strategy to preserve cardiac and optimize volume management among critically ill patients.

Purpose We previously reported that sleep quality is impaired in waitlisted patients for lung transplantation in Japan, and that respiratory symptoms and psychological status were main contributive factors to sleep quality. However, it is unknown whether sleep quality would improve after lung transplantation or not. Then we aim to assess changes in sleep quality and other patient reported measures including health related quality of life (HRQL) after lung transplantation. Methods In this multicentric study, we prospectively collected patient-reported data of 56 lung transplant recipients. We assessed sleep quality using the Pittsburgh Sleep Quality Index (PSQI), HRQL using the St. George's Respiratory Questionnaire (SGRQ), psychological status using Hospital Anxiety and Depression Scale (HADS) and dyspnea using modified Medical Research Council Dyspnea Scale (mMRC). We then examined the changes in sleep quality, HRQL, psychological status and dyspnea within about one year after lung transplantation. We also assessed PSQI subscale scores to examine the details of changes in sleep quality. Results Interstitial pneumonia (n=24), pulmonary complication after post hematopoietic stem cell transplantation (n=8), chronic obstructive pulmonary disease (n=7) and lymphangioleiomyomatosis (n=7) were the four most frequent indications. HRQL, psychological status and dyspnea significantly improved after lung transplantation (p 5) changed significantly from 51.7% (at baseline) to 62.5% (after lung transplantation) (p = 0.25). In PSQI subscales, sleep medication worsened significantly (p= 0.04) after lung transplantation. Conclusion While lung transplantation had positive impacts on HRQL, psychological status and dyspnea, sleep quality remained unchanged. Sleep quality should be followed separately from those patient-reported measures not to miss its worsening.

In the original publication, Fig. 3 has been incorrectly published. The correct version of Fig. 3 is given in this Correction.

Clamshell incision is a standard approach for bilateral lung transplantation, providing a good operative field; however, once wide dehiscence occurs, its management is sometimes difficult because of intense immunosuppression and malnutrition of the recipient. A 22-year-old man with idiopathic pulmonary arterial hypertension underwent cadaveric bilateral lung transplantation through a clamshell incision using standard cardiopulmonary bypass. He developed wound dehiscence on postoperative day (POD) 20 that resulted in exposure of the bilateral fifth ribs and open pneumothorax. Considering the extreme malnutrition and emaciation of the recipient, we avoided initial closure of the dehiscence. After the debridement of necrotic tissue, negative pressure wound therapy was initiated on POD 25 and was continued for approximately 6 months with trafermin spray application. Eventually, the wound, including the fifth ribs, was completely covered with granulation tissue except for the wire tying the sternum. On POD 217, the patient underwent removal of the sternal wire followed by split-thickness skin grafting. His wound was successfully closed and he was discharged without activity limitation on POD 265.

We report a case of bilateral lung transplantation (BLT) after preservation of the donor graft for 16 h 5 min with EP-TU, an extracellular phosphate-buffered lung preservation solution. The recipient was a 26-year-old woman with idiopathic pulmonary arterial hypertension and the graft ischemic time was prolonged significantly because of the time required to induce peripheral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) under local anesthesia, and address the severe intrathoracic and pericardial adhesions from past surgery for partial anomalous pulmonary venous return, with concurrent annular plication of the tricuspid valve. After the operation, ECMO and continuous hemodiafiltration were started preemptively to protect the grafts against excessive edema. Postoperative chest X-ray showed diffuse bilateral infiltrates, which improved within a few days and she was weaned off ECMO on day 9. Successful BLT after a graft ischemic time of over 16 h has rarely been described in clinical lung transplantation.