Aging exacerbates murine lung ischemia-reperfusion injury by excessive inflammation and impaired tissue repair response.

Donor shortage is a major problem in lung transplantation (LTx), and the use of lungs from elderly donors is one of the possible solutions in a rapidly aging population. However, the utilization of organs from donors aged >65 years has remained infrequent and may be related to a poor outcome. To investigate the molecular events in grafts from elderly donors early after LTx, the left lungs of young and old mice were subjected to 1 hour of ischemia and subsequent reperfusion. The left lungs were collected at 1 hour, 1 day, and 3 days after reperfusion and subjected to wet-to-dry weight ratio measurement, histological analysis, and molecular biological analysis, including RNA sequencing. The lungs in old mice exhibited more severe and prolonged pulmonary edema than those in young mice after ischemia reperfusion, which was accompanied by upregulation of the genes associated with inflammation and impaired expression of cell cycle-related genes. Apoptotic cells increased and proliferating type 2 alveolar epithelial cells decreased in the lungs of old mice compared with young mice. These factors could become conceptual targets for developing interventions to ameliorate lung ischemia-reperfusion injury after LTx from elderly donors, which may serve to expand the old donor pool.

Prognostic value of perioperative changes in the prognostic nutritional index in patients with surgically resected non-small cell lung cancer.

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

Recovery of physical function in lung transplant recipients with sarcopenia.

BACKGROUND: Lung transplant (LTX) can provide a survival benefit and improve physical function for selected patients with advanced pulmonary disease. Sarcopenia is a systemic muscle-failure that can be found in a variety of life stages and disabilities. In this study, we follow the evolution of each variable defined in sarcopenia and the outcomes in LTX recipients with post-transplant sarcopenia. METHODS: Patients who underwent LTX at Tohoku University Hospital between 2013 and 2018 were consecutively included in the retrospective cohort study, with follow-up to 2019. Sarcopenia was defined by low muscle mass (the cross-sectional area (CSA) of erector spinae muscle (ESM) in thoracic CT with a threshold < 17.24 cm2/m2) and either low muscle strength (hand-grip with a threshold of < 26 kg in males and of < 18 kg in females) or physical performance (6-min walk distance with a threshold < 46.5% of predicted distance). RESULTS: Fifty-five recipients were included into the study, of whom 19 patients were defined as sarcopenic and 36 as non-sarcopenic. The muscle mass improved after transplant in both sarcopenic and non-sarcopenic individuals: the median ESM-CSA enlarged from 17.25 cm2/m2 in 2 months post-LTX to 18.55 cm2/m2 in 12 months (p < 0.001) and 17.63 cm2/m2 in 36 months (p < 0.001) in non-sarcopenic individuals, while in sarcopenic patients it improved from 13.36 cm2/m2 in 2 months to 16.31 cm2/m2 in 12 months (p < 0.005) and 18.01 cm2/m2 in 36 months (p < 0.001). The muscle mass in sarcopenia substantially recovered to close to non-sarcopenic conditions within 36-months (p < 0.001 in 2 months and p = 0.951 in 36 months). Accordingly, muscle strength and physical performance in both groups improved over time. No difference in survival was seen in both groups (Log-rank p = 0.096), and sarcopenia was not associated with an overall hazard of death (p = 0.147). There was no difference in the cumulative incidence of chronic lung allograft dysfunction between patients with or without sarcopenia (Log-rank p = 0.529). CONCLUSIONS: Even patients with post-transplant sarcopenia have a chance to recover physical function to levels close to those without sarcopenia several years post LTX.

Prognostic significance of propofol-based intravenous anesthesia in early-stage lung cancer surgery.

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: Propofol-based TIVA was associated with a better prognosis in comparison to INHA in patients with surgically resected pathological stage I NSCLC.

[Aspergillus Empyema with Bronchopleural Fistula due to Destroyed Lung after Postoperative Radiotherapy for Thymoma].

A 35-year-old man underwent adjuvant chemoradiation therapy to the surgical margin of the thymoma. Five years after the therapy, an area of the right upper lung lobe, which was included in the irradiation field, developed destroyed lung, resulting in Aspergillus empyema with bronchopleural fistula. To control the infection, an open window thoracostomy was performed. As the bronchopleural fistula resulted in pneumonia, bronchial embolization was performed with an Endobronchial Watanabe Spigot. After the empyema cavity was cleaned, the empyema space was closed with omental and muscular flap, thoracoplasty. Negative pressure wound therapy was carried out because of poor wound healing. The patient is doing well without relapse 15 months after the thoracoplasty.

[Long-term Outcome of Pulmonary Segmentectomy for Lung Cancer].

OBJECTIVE: Pulmonary segmentectomy has been performed for patients with radiographic early-stage lung cancer. This retrospective study investigated the validity of choice of procedures at our institute by examining the survival outcomes of lung cancer patients who underwent surgery. METHOD: Data from 354 consecutive patients with pT1a~c N0 M0 stages I A1~3 non-small cell lung cancer who underwent surgery between 2004 and 2014 were extracted (segmentectomy group:84 patients, lobectomy group:270 patients). Overall, recurrence-free and cancer-specific survival of patients operated by segmentectomy and lobectomy was compared using the Cox proportional hazard model. RESULT: The segmentectomy group had a higher average age and frequency of history of another cancer and smaller lung cancers and its diameter and solid components than the lobectomy group. By univariate and multivariate analyses, surgical procedures were not identified as independent risk factors for overall, recurrence-free and cancer-specific survival. CONCLUSION: In this study cohort, the mode of surgical procedure between segmentectomy and lobectomy did not affect relapse and prognosis in pathological stages I A1~3 lung cancer. The choice of procedures at our institute seemed to be appropriate in this study period.

[Long-term Results of Sublobar Resection for Lung Cancer;a 10-year Follow-up Study].

As a treatment for lung cancer, sublobar resection has been performed not only for high-risk patients but also for patients with radiographic early stage lung cancer. Although many studies revealed the short-term results of sublobar resection, long-term outcomes are still unclear. Here, we examined the 10-year follow-up results of sublobar resection for lung cancer, especially in overall survival(OS), cause-specific survival(CSS)and recurrence or death dynamics. Data from 48 consecutive patients who underwent sublobar resection for lung cancer between 2004 to 2008 were collected(21 patients:segmentectomy, 27:wedge resection). The median length of follow-up was 10 years. During follow-up, recurrences developed in 12 patients(25%)and 19 patients(40%)died, including 9(19%)patient deaths due to lung cancer. The 3-/5-/10-year OS and CSS rates for all patients were 81/77/61% and 87/85/80%, respectively. In terms of recurrence or death, 11 out of 12 patients with recurrences were diagnosed within the 3rd year. The peak of death due to lung cancer was shown to be years after surgery to which wedge resection contributed. On contrast, small peaks of non-cancer death were shown to be 8-10 years after surgery without relation to surgical procedure.

[Postoperative Analgesia with Regular Acetaminophen Drip Infusion after Surgery for Lung Cancer].

BACKGROUND: Only a few studies have examined the effects of regular acetaminophen drip infusion as postoperative analgesia in lung cancer surgery. METHODS: We consecutively collected the medical data of 282 patients who underwent complete resection for lung cancer and divided them into 2 groups according to their postoperative analgesia;248 patients with conventional analgesia( group C) and 34 who received acetaminophen( group A). RESULTS: There was no significant difference in the surgical approach, length of surgical incision, or postoperative pain scale between the 2 groups. Postoperative vital signs and laboratory data were also not significantly different. CONCLUSION: Postoperative analgesia with acetaminophen was conducted safely, but its effect on postoperative pain did not differ from the conventional analgesia.

[Giant Intrathoracic Goiter Requiring Emergency Airway Management;Report of a Case].

An 81-year-old woman with acute respiratory distress was referred to our hospital. Computed tomography showed a large mass in the upper mediastinum with severe tracheal stenosis. Endotracheal intubation was performed under the preparation of extracorporeal membrane oxygenation and high-frequency jet ventilation, and the tumor was completely removed. The pathologic diagnosis was a goiter. Post-operatively, respiratory distress disappeared. No tumor recurrences have been noted for more than 2 years after surgery.

[Surgical Resection for Locally Advanced Lung Cancer].

Lung cancer invading neighboring anatomical structures is categorized as T3 or T4 and is regarded as locally advanced lung cancer. The 8th Edition Lung Cancer Stage Classification reclassified tumors 5~7 cm in size as T3 and tumors >7 cm or invading the diaphragm as T4. The purpose of this study was to evaluate the treatment results for resectable cT3-4N0-1M0 non-small cell lung cancer. From 1985 to 2016, 138 patients were surgically treated in our hospital, and their median follow-up was 78 months. Overall, the 5-year survival was 50%. According to the cT factor, the 5-year survival was 60% in patients with 5~7 cm tumors, 35% in patients with >7 cm tumors, and 58% in the group with chest wall invasion;however, no patients with tumors invading the diaphragm, pericardium or great vessels survived 5 years postoperatively. Preoperative chemotherapy was given to 16 patients( 12%), and 6 of those patients received chemoradiotherapy;40 patients (29%) received postoperative chemotherapy. All patients who received preoperative chemoradiotherapy followed by surgery had a complete resection and good pathological effects. While surgery alone is associated with an insufficient prognosis in patients with T3-T4 lung cancer, the addition of preoperative treatment is promising for improving survival.

[Extralobar Sequestration Difficult to Establish Preoperative Diagnosis;Report of a Case].

Pulmonary sequestration is a rare congenital pulmonary anomaly. Here we report a case of extralobar sequestration with calcification. A 34-year-old man was admitted to our department because of a tumor shadow on the chest radiological examination. Computed tomography examination revealed a mass measuring 5 cm above the left diaphragm. The mass contained cysts and calcification. Aberrant vessels were not detected. Teratoma, hamartoma or solitary fibrous tumor were suspected and the surgical treatment was performed. The postoperative pathological diagnosis was extralobar pulmonary sequestration.

[A Case of Gastric Cancer with Splenic Artery Aneurysm, Intraoperative ICG Fluorography Is Useful in Evaluating the Blood Flow of Stomach and Spleen].

An 81-year-oldwoman with advancedgastric cancer was referredto our hospital. Preoperative contrast-enhancedCT revealeda roundcalcification of the splenic hilum with 15mm in diameter as a splenic artery aneurysm. She underwent transcatheter arterial embolization(TAE)for the splenic artery aneurysm. Celiac artery angiography showedcollateral arterial network of the spleen from left gastric artery. Surgery for the gastric cancer was performed1 4 days after TAE. We cut the right gastric andbilateral epigastric arteries. After the left gastric artery clamping, we performedintraoperative indocyanine green(ICG)fluorography. ICG fluorography confirmedthat the bloodflow of the upper thirdof the stomach andspleen were maintained. We safely performed distal gastrectomy, and the postoperative course was uneventful.

[Hemorrhagic Cerebral Infarction after Right Segmental Lung Resection；Report of a Case].

Postoperative hemorrhagic cerebral infarction is rare but fatal complication. We report a case of hemorrhagic cerebral infarction after lung cancer surgery without a history of atrial fibrillation and cerebrovascular disease. A 58-year-old man who have a history of diabetes mellitus, hypertension and dyslipidemia underwent right segmental lung resection. During surgery, he had no atrial fibrillation episode. On postoperative day 1, he presented a slight consciousness disturbance. On the day 2, he suffered from a headache and nausea. Brain computed tomography demonstrated a hemorrhagic infarction at the right posterior cerebral artery territory. Transesophageal echocardiography and magnetic resonance angiography did not show the thrombus. The symptoms were gradually improved with intensive medical therapy, and he was discharged with a left homonymous hemianopsia. Although a diagnosis of the consciousness disturbance in the early-phase postoperative period is difficult, perioperative cerebral infarction should be recognized as a postoperative complication.

Successful complete thoracoscopic resection of costal osteochondroma: A case report.

Osteochondroma rarely occurs in the ribs; therefore, the treatment is not standardized. There are few studies of resection via complete thoracoscopic surgery (CTS), although video-assisted thoracoscopic surgery with mini-thoracotomy has been reported. Herein, we report a case of costal osteochondroma managed with CTS. A 23-year-old woman presented to our hospital due to left chest pain. Chest computed tomography revealed a bone-like structure protruding into the thoracic cavity from the left fourth rib. Thus, surgery was performed to obtain a definitive diagnosis and provide appropriate treatment. The tumor was resected from the base at the border of the normal bone via CTS using three 5.5-mm ports. A pathological diagnosis of costal osteochondroma was made. The patient had an uneventful clinical course and did not present with a recurrence 1 year after surgery. Therefore, CTS can be a good approach for cases with slim and stalked costal osteochondroma.

Clinical, Genomic, and Transcriptomic Featurses of Lung Adenocarcinoma With Uncommon EGFR Mutation.

PURPOSE: The purpose of this study is to identify the clinical, genomic, and transcriptomic features of patients with lung adenocarcinoma (LUAD) harboring uncommon epidermal growth factor receptor (EGFR) mutations (UCM) compared with common EGFR mutations (CM). MATERIALS AND METHODS: In this multicenter retrospective cohort study, clinicopathological data were collected from 1047 consecutive patients who underwent complete surgical resection for LUAD, as well as EGFR mutation analysis, between 2005 and 2012 at 4 institutions. Differences in postoperative overall survival (OS) and recurrence-free survival (RFS) according to EGFR mutation status were evaluated. For the genomic and transcriptomic analyses, 5 cohorts from public databases were evaluated. RESULTS: Of 466 eligible patients, 415 (89.1%) and 51 (10.9%) had CM and UCM, respectively. The 5-year OS and RFS rates in the CM/UCM groups were 86.8%/77.0% and 74.8%/59.0%, respectively. OS and RFS were significantly shorter in the UCM than CM group (both P < .01). Multivariable analysis of OS showed that UCM was an independent prognostic factor (hazard ratio 1.72, 95% confidential interval 1.01-2.93). According to the genomic analysis, tumors with UCM had a significantly higher tumor mutation burden and TP53 mutation frequency. Transcriptomic analysis showed that the T-cell-inflamed gene signature, a biomarker of the treatment for immunotherapy, was significantly associated with tumors with UCM. CONCLUSION: UCM were associated with a poor prognosis in patients with surgically resected EGFR-mutated LUAD. Tumors with UCM had unique genomic and transcriptomic features suggestive of a tumor microenvironment responsive to immunotherapy.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Long-term follow-up of a consecutive cohort validating an epidermal growth factor receptor mutation as an independent risk factor for postoperative recurrence in lung adenocarcinoma.

OBJECTIVES: Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were recently reported to be effective as adjuvant therapy for resected lung adenocarcinoma (ADC) harbouring common EGFR mutations. However, whether the EGFR mutation is a direct risk factor for postoperative recurrence remains unknown. Therefore, we conducted a multi-institutional observational study to compare postoperative survival according to EGFR mutation status. METHODS: We collected the medical records of consecutive patients who underwent surgical resection for ADC between 2005 and 2012 at 4 participating institutions. Recurrence-free survival (RFS) and overall survival (OS) associated with EGFR mutation status were evaluated. We further analysed survival after pair-matching patients' clinicopathological characteristics. RESULTS: EGFR mutations were harboured by 401 of 840 (48%) enrolled patients. The number of patients with an EGFR mutation (M group) differed from that with the EGFR wild-type sequence (W group) in terms of sex, smoking history and pathological stage. The median follow-up period was 85 months. The five-year RFS/OS rates of the M and W groups were 70%/85% and 61%/75%, respectively (P < 0.001 for both groups). However, multivariable analysis revealed that EGFR mutation status was not independently related with both RFS and OS. In pair-matched analysis, the RFS and OS curves of the patients with an EGFR mutation and wild-type sequence were not statistically different, either. CONCLUSIONS: Long-term follow-up of consecutive patients did not show that a common EGFR mutation was an independent risk factor of recurrence or prognostic factor for completely resected lung ADC.

Efficacy of platinum-based adjuvant chemotherapy for epidermal growth factor receptor-mutant lung adenocarcinoma.

Background: The ADAURA trial reported that osimertinib improved overall survival (OS) as an adjuvant chemotherapy for pathological stage IB-IIIA epidermal growth factor receptor (EGFR) mutant lung cancer compared with a placebo. Currently, platinum-based adjuvant chemotherapy is the standard treatment for patients with or without EGFR mutations. This study aimed to evaluate the efficacy of platinum-based adjuvant chemotherapy in patient with stage II-IIIA EGFR mutant lung adenocarcinoma. Methods: We collected the medical records of consecutive patients who underwent surgical resection for lung adenocarcinoma between 2005 and 2012 at the four participating institutions. The data of 173 patients with different EGFR mutation status were retrospectively evaluated to determine the efficacy of platinum-based adjuvant chemotherapy for OS and recurrence-free survival (RFS). We further analyzed OS using the inverse probability of treatment weighting method with propensity scores. Results: The median age was 69 years (range, 45-85 years); 95 (54.9%) were male and 74 (42.8%) had EGFR mutations. A total of 43 patients with EGFR mutants (58.1%) and 43 patients with wild-type EGFR tumors (43.4%) received platinum-based adjuvant chemotherapy. No differences in RFS and OS were observed between EGFR mutant and wild-type EGFR in lung adenocarcinoma without adjuvant therapy. However, wild-type EGFR showed an improvement in OS with platinum-based adjuvant chemotherapy in inverse probability of treatment weighting analysis, whereas those with EGFR mutations showed no significant difference in OS between the surgery-only group and the adjuvant group. The deletion of exon 19 and exon 21 L858R point mutation showed no significant differences in OS between the surgery-only group and the adjuvant group, respectively. The hazard ratio (HR) exceeded 1 for uncommon EGFR mutations. Conclusions: Platinum-based adjuvant chemotherapy may be less effective for EGFR-mutant lung adenocarcinoma, regardless of the mutation type.

Pneumonia With Scedosporium apiospermum and Lomentospora prolificans in a Patient After Bilateral Lung Transplantation for Pulmonary Hypertension: A Case Report.

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 ß-D-glucan elevated without any sign of fungal infection by other tests. The serum ß-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 ß-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.