Hirofumi Uehara

Predictors of long-term compensatory response of pulmonary function following major lung resection for non-small cell lung cancer.

Long‐term pulmonary function which might include compensatory response (CR) significantly influences quality of life of long‐term survivor after major lung resection. We investigated long‐term pulmonary function after major lung resection.

Therapeutic potential of recombinant thrombomodulin for lung injury after pneumonectomy via inhibition of high-mobility group box 1 in mice.

BACKGROUND Surgical acute respiratory distress syndrome (ARDS) is an extremely critical condition which may occur after major lung resection. Despite advances in minimally invasive surgical procedures and progress in the therapeutic management of this disease, prognosis remains poor. In this study, we investigated the contribution of high-mobility group box 1 (HMGB1) in a surgical ARDS model and evaluated the possible therapeutic effect of recombinant thrombomodulin (rTM) for the treatment of surgical ARDS. METHODS C57BL/6J mice underwent left pneumonectomy. rTM was injected at 12 hours before surgery, followed by 12 hours for 3 days after surgery. Lipopolysaccharide (LPS) was administered at 2 hours after surgery. We conducted a histologic analysis and measured HMGB1, IL-6, IL-1&bgr;, and TNF-&agr; in bronchoalveolar lavage fluid on day 3 after pneumonectomy. Data were compared between the treatment groups. RESULTS On histologic analysis, left pneumonectomy followed by LPS administration induced both severe inflammatory cellular infiltration and alveolar wall congestion with hemorrhage. rTM administration rescued these histologic changes. The level of HMGB1, IL-6, IL-1&bgr;, and TNF-&agr; in bronchoalveolar lavage fluid was significantly increased by LPS administration after pneumonectomy and significantly decreased by rTM administration with LPS and pneumonectomy (p < 0.001). Also, LPS alone showed no statistical differences in HMGB1 or proinflammatory cytokine level compared with pneumonectomy (PNX) group. In addition, the survival outcome was also improved by rTM administration. CONCLUSIONS LPS administration after left pneumonectomy could induce the severe lung injury. PNX and LPS have similar contribution to this model and may play a synergistic role in this process. rTM may have the potential therapeutic effect for surgical ARDS via suppression of HMGB1 and the secretion of proinflammatory cytokines induced by the administration of LPS after left pneumonectomy.

Immunological effect of local ablation combined with immunotherapy on solid malignancies

Recent comprehensive investigations clarified that immune microenvironment surrounding tumor cells are deeply involved in tumor progression, metastasis, and response to treatment. Furthermore, several immunotherapeutic trials have achieved successful results, and the immunotherapeutic agents are available in clinical practice. To enhance their demonstrated efficacy, combination of immunotherapy and ablation has begun to emerge. Local ablations have considerable advantages as an alternative therapeutic option, especially its minimal invasiveness. In addition, local ablations have shown immune-regulatory effect in preclinical and clinical studies. Although the corresponding mechanisms are still unclear, the local ablations combined with immunotherapy have been suggested in the treatment of several solid malignancies. This article aims to review the published data on the immune-regulatory effects of local ablations including stereotactic body radiotherapy, cryoablation, radiofrequency ablation, and high-intensity-focused ultrasound. We also discuss the value of local ablations combined with immunotherapy. Local ablations have the potential to improve future patient outcomes; however, the effectiveness and safety of local ablations combined with immunotherapy should be further investigated.

Usefulness of Plasma Exosomal MicroRNA-451a as a Noninvasive Biomarker for Early Prediction of Recurrence and Prognosis of Non-Small Cell Lung Cancer

Objectives: The aim of this study was to clarify the usefulness of plasma exosomal microRNA-451a (miR-451a) as a novel biomarker for the early prediction of recurrence and prognosis in non-small cell lung cancer (NSCLC) patients after curative resection. Methods: Before surgery, plasma samples were collected and exosomal microRNA (miRNA) levels were evaluated. We first profiled specific exosomal miRNAs related to recurrence in 6 NSCLC patients with stage IA cancer by miRNA microarray. We then validated the usefulness of selected miRNAs as biomarkers using the other 285 NSCLC patients. Results: Plasma exosomal miR-451a showed the highest upregulation in the NSCLC patients with recurrence in the miRNA microarray analysis. A significant positive correlation was demonstrated between exosomal miR-451a levels and NSCLC tissue miR-451a levels. Exosomal miR-451a showed a significant association with lymph node metastasis, vascular invasion, and stage. In stage I, II, or III patients, the overall survival (OS) and disease-free survival (DFS) rates among the high-exosomal-miR-451a patients were significantly worse than those among the low-exosomal-miR-451a patients. In Cox multivariate analysis, exosomal miR-451a showed significance for OS and DFS. Conclusion: Plasma exosomal miR-451a might serve as a reliable biomarker for the prediction of recurrence and prognosis in NSCLC patients with stage I, II, or III cancer.

Impact of pregabalin on early phase post-thoracotomy pain compared with epidural analgesia

Background The purpose of this randomized study was to compare the effects of pregabalin with epidural analgesia on early phase post-thoracotomy pain. Methods This study was conducted on 90 adult patients who underwent thoracotomy. Patients were randomly divided into two groups, an epidural analgesia group, where 45 patients received 0.2% ropivacaine hydrochloride and fentanyl through a thoracic epidural catheter, and a pregabalin group, where 45 patients received 75 mg pregabalin orally twice daily. Both groups were also administered orally with celecoxib along with each treatment. Numerical rating scale (NRS) and sleep interference rate (SIR) were evaluated on the first day, third day, and fifth day after surgery. Anesthetic induction time, operation time, recovery time, the use of additional analgesic drugs and adverse effects were also examined. Results NRS and SIR were significantly lower in the pregabalin group at all time points (P<0.05). The number of patients requiring additional analgesic drugs within 24 hours after surgery showed no difference between the two groups; however, the number was significantly decreased in the pregabalin group after post-operative day 1 (P<0.001). Adverse effects including pneumonia, dysuria, constipation and nausea were identified among many patients in the epidural analgesia group (P<0.05). Operation time and recovery time were the same for both groups, while the epidural analgesia group showed a significantly longer anesthetic induction time (P<0.001). Conclusions Pregabalin is considered to be a safe and effective treatment method which is an alternative to epidural analgesia for acute post-thoracotomy pain.

Surgical removal of a foreign body in the pulmonary artery

Foreign bodies, such as a fragmented catheter or metallic objects from industrial accidents, that have accidentally entered a major cardiac vessel or pulmonary artery have been successfully removed non-surgically via intravenous catheterization. We report the rare case of a cracked iron hammer fragment that had entered the femoral vein and migrated to the pulmonary artery through major blood vessels without causing hemorrhage, which eventually required surgical removal. A 19-year-old man accidentally smashed an iron hammer that broke into small pieces, one of which entered his femoral vein and eventually lodged in the pulmonary artery. After non-surgical intravenous catheterization to remove this foreign body was unsuccessful, it was removed surgically under video-assisted thoracoscopy. Foreign body residue over the long term can cause hemorrhage, pulmonary infarction, infection, and/or abscess. Transvenous recovery is the primary non-surgical means of removing a foreign body from the pulmonary artery. It is less harmful than surgical removal and causes fewer complications. Nevertheless, it is essential to be ready to execute a surgical approach for foreign body removal when other interventions have failed.

Atraumatic tension hemothorax associated with ruptured aneurysm of intercostal artery–azygous fistula: a case report

Atraumatic tension hemothorax is extremely rare. We report a case of 62-year-old woman presented with obstructive and hypovolemic shock status by tension hemothorax due to ruptured aneurysm of congenital intercostal artery–azygous fistula. Contrast-enhanced computed tomography and aortography revealed an aberrant 12th intercostal artery flowing into the aneurysm with a fistula draining into the azygous vein and the rupture of aneurysm. Our experience indicates that the rupture of congenital arteriovenous fistulas (AVFs) of systemic circulation in the thoracic cavity might cause not only hypovolemic shock but also atraumatic tension hemothorax. Surgery following preoperative endovascular embolization offers a feasible treatment strategy for ruptured aneurysms associated with AVFs.

Thoracic aortic endografts used to resect the left subclavian artery infiltrated by malignant tumours

Endograft placement is a minimally invasive procedure used to repair thoracic aortic aneurysms. This technique is used for treating aneurysms and aortic dissections or ruptures, but it can also be applied for the resection of malignant tumours with vascular invasion. We describe the successful use of the thoracic endovascular aortic repair technique to remove a malignant tumour infiltrating the left subclavian artery in a 50-year-old man. The resection of the left subclavian artery infiltrated by thoracic malignant tumours may require temporary cardiopulmonary bypass, direct clamping of the aorta or extracorporeal circulation techniques. However, the off-label use of thoracic endovascular aortic repair avoids the need for these high-risk surgical techniques. After the surgical removal of the mass and combined aortic resection without complications, the patient was eligible to undergo chemotherapy/radiotherapy, thus improving his prognosis.

Pericardial Conduit for Pulmonary Artery Reconstruction by Surgical Stapling

Pulmonary artery reconstruction in lung cancer surgery is an effective surgical method to avoid pneumonectomy that leads to longer survival times with few adverse effects. The pericardium is often used for the interposition of a prosthetic conduit. A pericardial conduit can be easily and precisely constructed by surgical stapling, which facilitates pulmonary artery reconstruction. In this report, the process and pitfalls of surgical stapling are described.

Carbon dioxide insufflation and thoracoscopic ultrasonography image of pure ground-glass nodule

Thoracic surgeons frequently encounter early lung cancer showing a pure ground-glass nodule. Although thoracoscopic wedge resection is used extensively, it cannot be easily located for surgical procedures. Thoracoscopic ultrasonography is a real-time and less invasive technique for small lung lesion localization during thoracoscopic surgery. However, this technique has not been widely adopted because residual air in the lung results in poor ultrasound images. A 64-year-old woman was found to have pure ground-glass nodule. For intraoperative localization, we performed thoracoscopic ultrasonography. To deflate the lung, we insufflated carbon dioxide into the thoracic cavity and maintained an intrathoracic pressure of 10 mmHg for 5 min. We easily achieved complete lung collapse without any complications; pure ground-glass nodule clearly showed as a hyperechoic lesion. We performed thoracoscopic wedge resection with a pathological diagnosis of adenocarcinoma in situ. Carbon dioxide insufflation into the thoracic cavity may be effective for complete lung deflation, which is useful to detect small lung nodules.