Current topics in surgery for multiple ventricular septal defects.

In this review article, we describe several topics, including the sandwich technique, the transatrial re-endocardialization technique, the limited apical left ventriculotomy approach and device closure. The sandwich technique was introduced for the closure of muscular ventricular septal defects (VSD) by sandwiching the septum between two felt patches placed in the left and right ventricle. This technique requires neither the transection of muscular trabeculae nor ventriculotomy. Although the sandwich technique has resulted in the improvement of surgical outcomes, cases of postoperative cardiac dysfunction have been reported. Multiple smaller VSDs have been closed with transatrial re-endocardialization. Septal dysfunction may be avoided through this technique, in which the septal trabeculae are approximated in two layers of superficial, endocardial running sutures. Recently, a number of reports have recommended a limited apical left ventriculotomy approach. With this technique, a much shorter incision of around 1 cm at the apex of the left ventricle may be sufficient for achieving the complete closure of apical muscular VSDs. The transcatheter or perventricular device closure of muscular VSDs has increasingly been performed with good results. Although favorable early and mid-term results of device closure have been reported, this method is not always safer or less invasive than surgical closure. Long-term evaluations should be performed to determine whether the right and left ventricular functions are affected by treatment with relatively large devices in the heart.

Complete thoracoscopic diaphragm plication using carbon dioxide insufflation: report of a case.

Diaphragm plication has become the accepted treatment for major respiratory impairment caused by diaphragmatic eventration and paralysis. Various open and minimally invasive plication techniques have been described and while video-assisted thoracoscopic diaphragm plication appears to be a safe and effective alternative to open surgery, the workspace is limited. We describe how we performed complete thoracoscopic diaphragm plication using carbon dioxide (CO2) insufflation for a patient with unilateral diaphragmatic eventration. Using CO2 insufflation seems to dramatically improve the workspace.

Current topics in surgery for isolated total anomalous pulmonary venous connection.

Surgical correction of total anomalous pulmonary venous connection (TAPVC) remains a challenge, with reported early mortality rates of up to 20%. In this review article, we describe several topics, including surgery for neonates, diagnoses with multidetector computed tomography (MDCT), and primary sutureless repair. Several studies have reported mortality rates of around 10%, and demonstrated unchanged hospital mortality in neonates, despite improvement of the overall mortality of cohorts including older patients. Previous reports identified a low body weight at the time of the operation, preoperative pulmonary venous obstruction (PVO), and a prolonged cardiopulmonary bypass time as risk factors for hospital mortality. With the development of new technologies, MDCT has become a good diagnostic modality for use in the pre- and post-operative evaluation. MDCT delineates the drainage site of the vertical vein and the atypical vessel into the systemic vein, and it can also evaluate the existence of obstruction in the vertical vein. Following favorable experiences with post-repair PVO, the indications for sutureless repair as a primary operation have been expanded for infants, including those at risk of developing PVO after the repair of TAPVC. Primary sutureless repair has proven especially useful for difficult patient groups, such as those with congenital PVO, infracardiac TAPVC with small pulmonary veins, or mixed-type TAPVC.

Differential distribution of lymphatic clearance between upper and lower regions of the lung.

BACKGROUND AND OBJECTIVE: Many lung diseases arise as the consequence of inhalational injury. When pathogenic materials are inhaled, it is possible that their clearance routes become the main focus of injury in the lung. Lymphatic clearance is important in the removal from the lung of small inhaled particles. The leak of toxic agents from the lymphatic flow potentially explains the topographic distribution of diffuse lung diseases triggered by inhaled materials, for example asbestosis. The aim of this study was to evaluate the differences in lymphatic distribution across various craniocaudal levels of the lung by using carbon dust deposition (CDD) as a tracing marker. METHODS: We evaluated 61 HE-stained slides of the normal lung area from 61 lobectomy specimens. The intensity of CDD was scored into five degrees (0-4) in bronchiolovascular (BV) areas and subpleural/septal (SP) areas per slide. The distribution was highlighted by subtraction scores of SP areas from those of bronchiolovascular areas. RESULTS: The subtraction scores of the upper lung area were significantly greater than those in the lower area, whereas there was no significant difference in scores by pulmonary lobes. CONCLUSIONS: Our results indicated that the main lymphatic clearance routes vary according to the craniocaudal levels, and are predominant in BV areas of the upper areas and in SP areas of the lower areas of the lung. This may explain the histological variations in anatomical distribution observed in the biopsy specimens of some diffuse lung diseases.

[Endovascular stent-graft insertion followed by resection of a locally-advanced lung tumor that invaded the thoracic aorta].

A 52-year-old man with fever and dyspnea was admitted to our hospital. Chest computed tomography showed a mass measuring 3.5×3.0 cm in the S(1+2) segment of the left lung with involvement of the aorta. Although cytological examination using broncho fiberscopy did not show any malignancy, we suspected the mass to be T4N0M0 lung cancer. The tumor was diagnosed as having invaded the aorta using intravascular ultrasound. First, an endovascular graft was inserted, and then, a left upper lobectomy with resection of the infiltrated aortic wall was performed without cardiopulmonary bypass. The patient had an uneventful recovery without any complications. Pathological examination revealed the tumor to be a large-cell carcinoma. We think that an aortic endograft can be useful for resection of an infiltrated aortic wall, although further studies are necessary.

[Lung biopsy by video-assisted thoracic surgery in patient with untreated Evans syndrome].

A 78-year-old man referred to our hospital with the chief complaints of anorexia, general malaise, rash, and weight loss. Laboratory examination revealed pancytopenia, hyperglobulinemia, generalized adenopathy, and multiple pulmonary nodules. Video-assisted thoracic surgery (VATS) was performed to diagnose pulmonary nodules. After operation, it was difficult to achieve hemostasis for a while. Finally, the patient was diagnosed as pulmonary cryptococcosis and Evans syndrome.

Inducible capillary formation in lymphatic endothelial cells by blocking lipid phosphate phosphatase-3 activity.

Lymphangiogenesis plays critical roles under normal and/or pathological conditions; however, the molecular contributors to this event were unknown until recently. In the present study, we first employed gene chip analysis and confirmed that lipid phosphate phosphatase-3 (LPP3) expression was increased until capillary formation in the conditionally immortalized rat lymphatic endothelial cell line. Signaling responses occur when several lipids induce acute biological functions; further, lipid phosphate phosphatases (LPPs) control their functions via dephosphorylation; however, there is no report on the association between LPP3 and lymphangiogenesis. siRNA-targeted LPP3 significantly increased capillary formation of human lymphatic endothelial cells; in contrast, it decreased cell adhesion to the basement membrane matrix. Furthermore, the inducible effect of the LPP inhibitor on capillary formation was observed. For the first time, we report that LPP3 abolishes accelerated abnormal lymphangiogenesis. Blocking LPP3 activities may aid in the development of novel therapy for lymph vessel defects.

Spontaneous Hemothorax Caused by Pulmonary Micro-Venous Hemangioma.

Various etiologies of spontaneous hemothorax have been reported, though the cause remains unidentified in some patients despite an exploratory thoracotomy. We report on an 89-year-old man with spontaneous hemothorax resolved by partial resection of the lung using complete video-assisted thoracoscopic surgery. The histopathologic findings revealed a ruptured micro-venous hemangioma located just below the bleeding visceral pleura. To the best of our knowledge, this is the first report of spontaneous hemothorax caused by a pulmonary micro-venous hemangioma.

Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-ß-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.

Rare lipomatous tumor of the posterior mediastinum in children.

The mediastinum is a unique anatomic area containing various structures and pluripotent cells, which allow for the development of a range of tumors. We report two pediatric cases of a lipomatous tumor of the posterior mediastinum. Complete surgical excision of the mass in each was achieved through a lateral thoracotomy. Histopathologic findings showed a lipoma in one case and a lipoblastoma in the other. A lipomatous tumor in the posterior mediastinum is extremely rare and preoperative diagnosis is difficult. When an operative plan is being considered, the presence of a potentially malignant tumor should be kept in mind.

Calpain 1 and -2 play opposite roles in cord formation of lymphatic endothelial cells via eNOS regulation.

Calpains are a family of calcium-dependent proteases. Two isoforms, calpain 1 and 2, have been implicated in angiogenesis and endothelial cell adhesion and migration. Calpains regulate the function of eNOS;however, the relation of calpains and eNOS to lymphangiogenesisis still unclear. In the present study, we evaluated the role of calpain and eNOS in the formation of cords by lymphatic endothelial cells on Matrigel. Human lymphatic microvascular dermal-derived endothelial cells were transfected with siRNA against calpain 1 or 2. Calpain 2 knockdown, but not calpain 1 knockdown, significantly reduced cord formation, adhesion, and migration on Matrigel. These decreases correlated with a reduction in eNOS, and phosphorylated eNOS and Hsp90 levels, as assayed by immunoprecipitation and western blotting. In contrast, the knockdown of calpain 1, but not calpain 2,increased cell adhesion, enhanced migration, and stabilized late-stage cord formation by increasing cord length compared to the control. These differences correlated with an increase in the level of phosphorylated eNOS. The results indicated that the functions of calpains and eNOS are important for cord formation by lymphatic endothelial cells. For the first time, we have found different functions of calpain 1 and 2. Calpain 1 is involved in the degradation of eNOS and Hsp90 and the phosphorylation of eNOS,while calpain 2 regulates eNOS phosphorylation during cord formation by lymphatic endothelial cells on Matrigel.

Management of pulmonary venous obstruction.

Although improved surgical techniques have led to significantly better outcomes of surgery for total anomalous pulmonary venous connection, the risk of progressive pulmonary venous obstruction continues to be a clinical problem. Both obstructed total anomalous pulmonary venous connection and post-repair pulmonary venous obstruction are associated with a significant risk of recurrent obstruction or death, requiring reoperation for stenosis. In general, side to side anastomosis of the pulmonary venous confluence to the functional left atrium has been performed for supracardiac and infracardiac total anomalous pulmonary venous connection. Repair of total anomalous pulmonary venous connection to the coronary sinus invariably involved unroofing the coronary sinus, followed by pericardial patch closure of the atrial septal defect. Recently, sutureless technique has been adopted as the primary operation for the subgroups of patients that are thought to be at high risk for post-repair pulmonary venous obstruction, such as those with total anomalous pulmonary venous connection associated with right isomerism, infracardiac total anomalous pulmonary venous connection with small individual pulmonary veins, or mixed-type total anomalous pulmonary venous connection. Because the sutureless technique does not require direct anastomosis to the confluence, aggressive resection of the obstructed pulmonary venous tissue can be achieved, and surgically induced distortion of the suture line can be avoided, which may help to prevent subsequent pulmonary venous obstruction. Conventional management strategies for recurrent pulmonary venous obstruction have typically been associated with poor outcomes. Recent reports have supported the use of the sutureless technique to treat post-repair pulmonary venous obstruction.

eNOS and Hsp90 interaction directly correlates with cord formation in human lymphatic endothelial cells.

Endothelial nitric oxide synthase (eNOS) and heat shock protein 90 (Hsp90) have been reported to contribute to angiogenesis and lymphangiogenesis. However, the functions of these proteins during lymphangiogenesis are unclear. In the present study, we first observed the cord formation pattern of human dermal microvascular lymphatic endothelial cells (HMVEC-dLy) on Matrigel over 2 to 8 h. The length of cord formation increased, peaked at 4 h, and then started to decline after 6 to 8 h of incubation. siRNA-targeted NOS3 significantly reduced the cord formation ability of HMVEC-dLy cells by 27% relative to control. This result confirmed the importance of eNOS in cord formation by human lymphatic endothelial cells. In addition, immunoprecipitation and Western blotting indicated that the interaction between eNOS and Hsp90 was maximal at 4 h, and then the proteins dissociated. This interaction correlated with the observation of cord formation of human lymphatic endothelial cells on Matrigel. Moreover, we found that the eNOS level decreased as the eNOS and Hsp90 complex disassociated during the late stage of cord formation. An Hsp90 inhibitor, 17-DMAG, was able to inhibit the eNOS and Hsp90 interaction, decrease the level of eNOS, and significantly inhibit cord formation to 38% of the level observed in the control. For the first time, we report that the interaction between eNOS and Hsp90 plays an important role in determining eNOS levels and in regulating cord formation of human lymphatic endothelial cells in vitro.

A case of acute psittacosis with severe abdominal pain.

We report the case of a psittacosis patient with severe abdominal pain who subsequently developed acute respiratory failure. The main symptoms of psittacosis are considered to be upper respiratory inflammation and influenza-like symptoms. However, it should be emphasized that digestive symptoms can be prominent in psittacosis patients. Early diagnosis of this condition is difficult and there is a need for an effective method for rapid diagnosis.