Masahiro Miyajima

Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial–mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause. IPF has a distinct histopathological pattern of usual interstitial pneumonia in which fibroblastic foci (FF) represent the leading edge of fibrotic destruction of the lung. Currently there are three major hypotheses for how FF are generated: (1) from resident fibroblasts, (2) from bone marrow-derived progenitors of fibroblasts, and (3) from alveolar epithelial cells that have undergone epithelial–mesenchymal transition (EMT). We found that FF dissociated capillary vessels from the alveolar epithelia, the basement membranes of which are fused in normal physiological conditions, and pushed the capillaries and elastic fibers down ~100 μm below the alveolar epithelia. Furthermore, the alveolar epithelial cells covering the FF exhibited a partial EMT phenotype. In addition, normal human alveolar epithelial cells in vitro underwent dynamic EMT in response to transforming growth factor-β signaling within 72 h. Because it seems that resident fibroblasts or bone marrow-derived cells cannot easily infiltrate and form FF between the alveolar epithelia and capillaries in tight contact with each other, FF are more likely to be derived from the epithelial-to-mesenchymal transitioned alveolar epithelia located over them. Moreover, histology and immunohistochemistry suggested that the FF formed in the lung parenchyma disrupt blood flow to the alveolar septa, thus destroying them. Consequently, collapse of the alveolar septa is likely to be the first step toward honeycombing in the lung during late stage IPF. On the basis of these findings, inhibition of transforming growth factor-β signaling, which can suppress EMT of the alveolar epithelial cells in vitro, is a potential strategy for treating IPF.

Thoracoscopic Mediastinal Lymph Node Dissection for Lung Cancer

In lung cancer, mediastinum lymphatic spread occurs. We review our technique and experience of thoracoscopic mediastinal lymphnode dissection (MLND). Between 1997 and 2011, 992 patients with primary lung cancer underwent thoracoscopic major pulmonary resection with MLND. Initially we used a combination of electrocautery and clips to divide blood vessels and lymphatic channels; our current technique relies on a vessel sealing system (VSS) which is expeditious and leads to less lymphorrhea. Furthermore, dissection of station 7 nodes is performed after each main bronchus or right intermediate bronchus is taped with a 0 silk suture, which is then brought out of the thorax through the access incision for antero-lateral retraction of the tracheal carina. We dissect between 3 and 4 N2 lymph node stations and a total of approximately 20 N2 lymph nodes. Postoperative complications related to MLND occurred in 35 of 992 patients (3.5%), 15 (1.5%) for recurrent laryngeal nerve injury, 3 (0.3%) for bilateral vagal injury, 14 (1.4%) for chylothorax and 3 (0.3%) for airway injury. However, none were lethal. Thoracoscopic mediastinal dissection is safe and feasible in treating lung cancer. We believe our technique and VSS are very useful for thoracoscopic MLND.

Suppression of alloreactivity and allograft rejection by SP600125, a small molecule inhibitor of c-jun N-terminal kinase

Background. c-Jun N-terminal kinase (JNK) is reported to play crucial roles in T-cell activation and differentiation, and SP600125 is a small molecule that inhibits JNK. The aim of this study was to examine immunosuppressive action of this compound. Methods. Rat heterotopic heart transplantation, popliteal lymph node (PLN) hyperplasia bioassay and lymphocyte proliferation assay. Results. SP600125 treatment reduced histological rejection, and dose-dependently extended median survival time of cardiac allografts from 7 days (vehicle) up to 20 days (40 mg/kg/day). Alloantigen-induced PLN hyperplasia was also inhibited by SP600125 in a similar fashion. SP600125 suppressed mixed lymphocyte reaction and OX52-positive lymphocyte proliferation (IC50: 1.5–5.7 &mgr;M). Thus, SP600125 inhibits both T-lymphocyte expansion in vitro and T-cell–mediated alloimmune responses in vivo. In addition, SP600125 interacted with cyclosporine additively to prolong cardiac allograft survival. Conclusion. Our data provide the first evidence indicating the potential for JNK as a therapeutic target to inhibit the alloimmune response.

Concomitant mitral and tricuspid valve infective endocarditis: report of a case.

A rare case of native valve endocarditis affecting both the normal mitral and tricuspid valves is presented. A 25-year-old woman with an acute ischemic stroke was found to have vegetation secondary to infective endocarditis as the embolic source. One month after the onset of embolic cerebrovascular intervention, a valve repair with the implantation of artificial chordae, sliding commissuroplasty, and ring annuloplasty resulted in a complete recovery.

Descending or Thoracoabdominal Aortic Aneurysm Repair Without Intercostal Vessel Reconstruction Using Contrast Magnetic Resonance Angiography: Report of Two Cases

Abstract Two high-risk patients underwent a graft replacement for descending thoracic or thoracoabdominal aortic aneurysms without the reconstruction of any intercostal and lumbar arteries. The first patient was an 81-year-old woman with asthma and renal dysfunction who was diagnosed to have a descending thoracic aortic aneurysm extending from the Th8 to Th12 level. Contrast magnetic resonance angiography (MRA) demonstrated the Adamkiewicz artery to originate from the left second lumbar artery. The second patient was a 59-year-old man with left ventricular dysfunction due to aortic and mitral stenoses who was diagnosed to have a Crawford type IV thoracoabdominal aortic aneurysm. Contrast MRA showed the Adamkiewicz artery to originate from the left ninth intercostal artery. In general, the reestablishment of the spinal cords blood supply, whenever possible, is generally considered to be necessary in such patients to prevent spinal cord injury. However, the reimplantation of intercostal vessels is the most complex aspect of this surgical modality, and therefore, it may cause a substantial increase in the cardiopulmonary bypass time. However, at least in some cases, such as the two cases presented herein, the use of contrast MRA was found to reduce the risk in surgery for descending thoracic or thoracoabdominal aortic aneurysms by eliminating the need for any intraoperative management of the intercostal and lumbar arteries.

Two separate thoroscopic segmentectomies with vessel sealing system

Total thoracoscopic segmentectomy is an appealing concept in terms of providing a parenchyma-sparing treatment. We describe our technique of two seperate total thoracoscopic segmentectomies by using a vessel sealing system (VSS). A 76-year old female with four gradually enlarging ground glass lesions on the right segment 2 (10 and 3 mm) and segment 6 (8 and 3 mm) was admitted to our institute for surgical diagnosis and treatment. Preoperative three-dimensional computed tomography showed that the A2 is composed of descending A2 and ascending A2, branch of V6 coursed to V2 and B1a originated from B2 and B1b from B3. Two separate segmentectomies were subsequently scheduled. Pulmonary vessel division was performed with VSS after proximal ligation. Intersegmental division by VSS and electrocautery was performed with the use of inflation-deflation demarcation line and the pulmonary veins along the intersegmental plane (V2a and V2c for segment 2 and V6b and V6c for segment 6) as guides to confirm the intersegmental plane after pulmonary artery and bronchial divisions. The intraoperative frozen-section examinations revealed adenocarcinoma in situ. Two separate segmentectomies were successfully completed, with a total operative time of 240 min and blood loss of 30 ml. VSS is a very useful and safe device for intersegmental division and pulmonary vessel division.

Video-assisted thoracoscopic surgery node dissection for lung cancer treatment

PurposeMediastinal node dissection (MND) is an integral component of the surgical treatment for non-small cell lung cancer (NSCLC). Although video-assisted thoracoscopic surgery (VATS) has been used increasingly for lung cancer treatment, the accuracy of by VATS MND still remains controversial. We reviewed the surgical results of VATS MND for NSCLC.MethodsA systematic review of literature was performed, and articles that fully described the surgical procedure, devices, and results of VATS MND were selected to compare the efficacy of MND by VATS and thoracotomy.ResultsVarious techniques and equipments have been shown to perform adequate MND, but there is an argument as to the method of estimation of the accuracy of MND. Most of the recent studies showed that the nodal upstaging and number of dissected nodes are significantly lower by VATS than after thoracotomy. Oppositely, some studies showed VATS noninferiority in these issues. Complications such as chylothorax, pleural effusion, bleeding, and nerve damage were similar in both groups.ConclusionsAlthough ND by VATS remains controversial, VATS MND is becoming easier and more feasible owing to the development of more advanced endoscopic cameras and equipments. We should learn further to become more adept at performing adequate ND by VATS.

Relationship between onset of spontaneous pneumothorax and weather conditions

OBJECTIVES Spontaneous pneumothorax (SP) results from the rupture of blebs or bullae. It has been suggested that changes in weather conditions may trigger the onset of SP. Our aim was to examine the association between the onset of primary SP with weather changes in the general population in Sapporo, Japan. METHODS From January 2008 through September 2013, 345 consecutive cases with a diagnosis of primary SP were reviewed. All cases of primary SP developed in the area within 40 km from the Sapporo District Meteorological Observatory. Climatic measurements were obtained from the Observatory, which included 1‐h readings of weather conditions. Logistic regression model was used to obtain predicted risks for the onset of SP with respect to weather conditions. RESULTS SP occurred significantly when the atmospheric pressure decreased by − 18 hPa or less during 96 h before the survey date (odds ratio = 1.379, P = 0.026), when the pressure increased by 15 hPa or more during 72 h before the survey date (odds ratio = 1.095, P = 0.007) and when maximum fluctuation in atmospheric pressure over 22 hPa was observed during 96 h before the survey date (odds ratio = 1.519, P = 0.001). Other weather conditions, including the presence of thunderstorms, were not significantly correlated with the onset of pneumothorax. CONCLUSIONS Changes in atmospheric pressure influence the onset of SP. Future studies on the relationship between the onset of SP and weather conditions on days other than before the onset and with large number of patients may enable us to predict the onset of SP in various regions and weather conditions.

Elevated expression of JAM-A promotes neoplastic properties of lung adenocarcinoma

A cell–cell adhesion protein, junctional adhesion molecule‐A (JAM‐A), has been shown to be involved in neoplasia of various organs. However, the fundamental role of JAM‐A in tumorigenesis is still under debate because dysregulated expression of this protein has distinct effects, playing opposite roles in carcinogenesis depending on the target tissues. In the present study, we found elevated levels of JAM‐A expression in lung adenocarcinoma and its preinvasive lesions, including atypical adenomatous hyperplasia and adenocarcinoma in situ by immunohistochemistry. We also showed that suppression of constitutive JAM‐A expression conferred target cells with increased susceptibility to apoptosis in lung adenocarcinoma cells. Consequently, inhibition of JAM‐A activity decreased colony‐forming capability in vitro and tumorigenicity in vivo. The transformed phenotype following suppression of JAM‐A expression was sufficient to reduce motile and invasive capacities. Importantly, knockout of JAM‐A had striking effects on cells. Our observations suggest that increased expression of JAM‐A promotes neoplasia of lung adenocarcinoma. In addition, an anti‐JAM‐A antibody efficiently reduced cell proliferation and provoked apoptosis, indicating the potential feasibility of JAM‐A‐inhibitory cancer therapy.

Total thoracoscopic lung segmentectomy of anterior basal segment of the right lower lobe (RS8) for NSCLC stage IA (case report)

A 69-year-old woman with a pulmonary nodule in anterior basal segment of the right lower lobe (RS8) was referred to our department. The diameter of the tumor was 12 mm, and it had increased over a few months. First, video-assisted thoracoscopic lung surgery (VATS) biopsy of the pulmonary nodule was carried out. Frozen section examination of this nodule confirmed the diagnosis of bronchioloalveolar carcinoma (BAC). Segmentectomy of RS8 with lower mediastinal node dissection (ND2a-1) was performed. The intersegmental plane was identified using the intersegmental veins as landmarks and the demarcation between the resected (inflated) and preserved (collapsed) lungs. Electrocautery at 70 watts was used to divide the intersegmental plane. A vessel sealing system was used to seal and cut the pulmonary arteries. Postoperative histopathological examination revealed that the tumor was T1aN0M0 BAC, and the minimal distance between the surgical margin and the tumor edge was 15 mm. The patient was discharged from hospital on postoperative day 5 without any complications.