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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.

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.

Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we find that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological conditions. Elevated accumulation of CEBPB in NRF2-activated NSCLCs is found to be one of the prerequisites for establishment of the unique NRF2-dependent enhancers, among which the NOTCH3 enhancer is shown to be critical for promotion of tumor-initiating activity. Enhancer remodeling mediated by NRF2-CEBPB cooperativity promotes tumor-initiating activity and drives malignancy of NRF2-activated NSCLCs via establishment of the NRF2-NOTCH3 regulatory axis., Aberrant activation of NRF2 in cancer cells contributes to tumorigenicity and therapeutic resistance. Here, the authors show that NRF2 cooperates with CEBPB and remodels enhancers to confer tumor-initiating activity on NRF2- activated non-small cell lung cancers.

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

An enhanced recovery after surgery (ERAS) program might be effective for postoperative recovery in elderly patients undergoing thoracic surgery. This study aimed to clarify the impact of ERAS on the post-operative recovery of elderly patients, with regard to shortening hospital stay and reducing complications after open thoracic surgery. We used a prospectively collected database and retrospectively accessed the data of patients who underwent lobectomies or segmentectomies for pulmonary malignancies from April 2013 to March 2018 and evaluated outcomes after implementation of ERAS. ERAS patients were those who completed an ERAS program. The control patients were those who underwent surgery before June 2015 and later operated patients who did not receive ERAS. Propensity score matching was performed to balance the characteristics of patients in both groups. Patients were also divided into the following three groups for evaluating the efficacy of ERAS: patients aged

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 2/m2) and either low muscle strength (hand-grip with a threshold of 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 2/m2 in 36 months (p 2/m2 in 2 months to 16.31 cm2/m2 in 12 months (p 2/m2 in 36 months (p p 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.

Background Spread through air spaces (STAS) identified in lung cancer is considered to be a risk factor for recurrence after surgery. The purpose of this study is to clarify the prognostic impact of STAS in sublobar resections. Methods We studied 514 patients with clinical stage IA cancers: 329 underwent lobectomies and 185 underwent sublobar resections. We assessed the prognostic impact of STAS in the cases with a sublobar resection for stage IA lung cancer versus the cases with a lobectomy. Results STAS was found in 73 of 329 (22.2%) lobectomy cases and 31 of 185 (16.8%) sublobar resection cases. For overall survival, univariate analysis revealed that STAS was not a prognostic factor in the lobectomy group, but it was a significantly worse prognostic factor for the sublobar resection group in both univariate and multivariate analyses. For the recurrence-free rate, multivariate analysis showed STAS was not a risk factor in the lobectomy group, but it was a significant risk factor for the sublobar resection group in both univariate and multivariate analyses. Patients with STAS and sublobar resection had a significantly higher rate of pulmonary metastases than did patients with STAS and lobectomy (8 of 31 [25.8%] vs 6 of 73 [8.2%]). Conclusions STAS is a prognostic factor of poor outcomes for sublobar resection in patients with lung cancer. The worse prognosis for sublobar resection would be associated with STAS.

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.

A 65-year-old man presented with obstructive pneumonia due to squamous cell carcinoma of the lung, which invaded the right main bronchus. Argon plasma coagulation was performed, which reduced his symptoms. Right pneumonectomy was performed after preoperative chemotherapy; the pathological diagnosis was T3N1M0 Stage IIIA. Fifteen months after surgery, he presented with bloody sputum. Bronchoscopy showed multiple endotracheal tumors, and a pathological examination revealed squamous cell carcinoma; the same histology as the primary lung cancer. We hypothesized that direct implantation during bronchoscopic therapy or hematogenous or lymphatic spread might have led to metastasis. A careful follow-up is required after bronchoscopic therapy.

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.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.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.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.

Only a few studies have examined the effects of regular acetaminophen drip infusion as postoperative analgesia in lung cancer surgery.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).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.Postoperative analgesia with acetaminophen was conducted safely, but its effect on postoperative pain did not differ from the conventional analgesia.

BACKGROUND: Spread through air spaces (STAS) is regarded as a significant risk factor for lung cancer recurrence. STAS consists of micropapillary clusters, solid nests, or single cells beyond the edge of the tumor into air spaces in the surrounding lung parenchyma. However, the patterns of lung cancer recurrence have not been clarified in patients with STAS. The aim of this study was to explore STAS and recurrence patterns in patients who underwent lung cancer surgery. METHODS: Between January 2000 and December 2017, a total of 1,426 patients underwent complete resection of lung cancer. We studied 848 patients with pathological stage I disease who underwent surgery. Recurrence patterns and recurrence-free rates were determined from pathological findings, particularly the presence of STAS. Locoregional recurrences included surgical margin recurrences, hilar and mediastinal lymph node metastases, ipsilateral lobe metastases, and pleural dissemination, whereas distant recurrences included extrathoracic organ and contralateral lobe metastases. RESULTS: STAS was observed in 139 of 848 (16.4%) cases. Recurrences developed in 108 (12.7%) cases: locoregional recurrences in 76 (9.0%), distant metastases in 27 (3.2%), and both in 5 (0.6%) cases. Among recurrences, pleural dissemination developed in 12 (1.4%) and pulmonary metastases in 46 (5.4%) cases. Five-year recurrence-free rates were 65.4% among patients with STAS and 89.0% among patients without STAS. Univariate and multivariate analyses revealed that STAS was a significant risk factor for recurrence (P

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.

Background Mediastinal hematoma rarely occurs after a minor traffic injury. Case presentation A woman in her forties was transferred to the emergency room by ambulance due to a traffic accident. Computed tomography (CT) revealed no abnormal findings, and she went home. Two days after the accident, the contrast-enhanced CT was repeated, which revealed cervical and mediastinal hematomas. Because it was possible that there was active bleeding from the right inferior thyroid artery, embolization of the right inferior thyroid artery was performed; however, her condition further deteriorated, so we performed emergency surgery to achieve hemostasis and remove the hematoma. Because of oozing from the right thyroid lobe, we performed right hemithyroidectomy and drainage of mediastinal space and right thoracic cavity. Since there was no bleeding site in the mediastinum, we thought that the mediastinal hematoma was due to bleeding from the thyroid gland. Her postoperative course was uneventful, and she is doing well at 9 months of follow-up after surgery. Conclusions It is possible that mediastinal hematoma might be caused by a minor traffic injury.

Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It is used as anti-cancer therapy in patients with EGFR-TKI sensitizing mutations and EGFR T790M mutations and is recommended for treatment of patients with EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) after progression on first-line EGFR-TKIs or frontline treatment in EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC (1,2). Common adverse effects of osimertinib are similar to other EGFR-TKIs and are generally mild in severity and reversible (1). Previous reports have suggested an association between gefitinib or erlotinib treatment and organ bleeding or tumor hemorrhage (3-8). But to date there have been no reports of a similar association between osimertinib and tumor hemorrhage. Herein, we report an unusual case of hemorrhage of a pancreatic metastasis from lung adenocarcinoma after osimertinib therapy.

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.

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.

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.

In 1978, the first case of hepatitis E was identified as non-A, non-B hepatitis. Hepatitis E virus (HEV) infection is believed to be one of the common causes of enterically transmitted acute hepatitis in developing countries and is rare in developed countries, except in patients with a history of travel. However, an increasing number of chronic HEV infection cases have recently been reported in developed countries. In these countries, immunosuppressed patients with HEV infection, such as organ transplant recipients, human immunodeficiency virus (HIV)-infected patients or patients with haematological malignancies, could develop chronic hepatitis E (CHE) infection. Approximately 60% of HEV infections in immunocompromised patients after solid organ transplantation evolve to CHE without antiviral treatment. Clinical manifestations of CHE are often nonspecific symptoms. Many patients with CHE infection are asymptomatic, but some have jaundice, fatigue, abdominal pain, fever and asthenia. Several extrahepatic manifestations have also been reported. Although chronic HEV infection can result in progressive severe liver failure and cirrhosis, diagnosis is often controversial because of the lack of specific diagnostic criteria. Many CHE cases are diagnosed by HEV RNA-positive serum or stool for >6 months. Immunosuppressive drugs, interferon-alpha and ribavirin have been used for treatment. Diagnostic reverse-transcription polymerase chain reaction is useful for estimating treatment efficacy. Preventive measures for HEV infection have been discussed, while systematic guidelines have not yet been reported.

Objectives: To assess whether oral care (tooth brushing, regular dental visits, and use of dentures) affects mortality in elderly individuals with tooth loss. Design: A 4-year prospective cohort study. Setting: Ohsaki City, Japan. Participants: Twenty-one thousand seven hundred thirty community-dwelling individuals aged 65 and older. Measurements: In a baseline survey in 2006, data were collected on number of remaining teeth and oral care status as measures of dental health. Data were also collected on age, sex, education level, smoking, alcohol drinking, time spent walking daily, medical history, psychological distress, and energy and protein intake as covariates. During the 4-year follow-up between 2006 and 2010, information on mortality was obtained from Ohsaki City government. Results: The multivariate-adjusted Cox proportional hazards model showed an inverse dose-response relationship between number of remaining teeth and mortality (P for trend