Mitsutaka Kadokura

Expression of Eotaxin by Normal Airway Epithelial Cells after Influenza Virus A Infection

Background: Viral infection is known to cause lung inflammatory disease, including bronchial asthma. The mechanisms of inflammatory cell accumulation into the airways after viral infection are not well understood. Eotaxin is a CC chemokine which is a potent and specific agonist for CC chemokine receptor 3 (CCR3). CCR3 is expressed on eosinophils, basophils and T lymphocytes. These cells are known to be key cells in the pathogenesis of asthma. Although it has recently been demonstrated that airway epithelial cells express eotaxin in vivo and in vitro, there are few data about its epxression in viral infection. We hypothesized that eotaxin may play an important role in attracting inflammatory cells to the airways after viral infection, and analyzed whether viral infection attracts eotaxin in bronchial epithelial cells in vitro. Methods: Human airway epithelial cells obtained from bronchial tissue at lobectomy for lung cancer were infected with influenza virus A (subtype H3N2). The cells and cultured media were collected 8, 24, and 48 h after infection. Eotaxin mRNA was analyzed with reverse transcriptase-polymerase chain reaction. Eotaxin protein levels in the culture media were analyzed by enzyme-linked immunosorbent assay. We also studied a blocking assay to analyze the intervention of proinflammatory cytokines in its production induced by influenza virus. Results: Eotaxin mRNA appeared to be expressed constitutively in uninfected cells but was expressed more clearly in infected cells. Eotaxin protein release into culture media significantly increased after infection. Anti-TNF-α and anti-IL-1β antibodies did not alter the eotaxin protein levels after viral infection. Conclusions: These results suggest that influenza virus A infection in airway epithelial cells activates the expression of eotaxin and that eotaxin may participate in the pathogenesis of airway inflammatory disease caused by viral infection, such as infectious type asthma.

Tumor dimension and prognosis in surgically treated lung cancer: for intentional limited resection.

Tumors with a maximum dimension of 3 cm are categorized as T1, whereas those greater than 3 cm are T2 by TNM classification. Some physicians suggest that early-stage peripheral lung cancer should have a maximum tumor diameter of 2 cm and that limited surgery (segmentectomy without lymph node dissection) is acceptable for the patients. In this study, the relationship between the tumor dimension and prognosis was analyzed in 207 patients with surgically treated primary non–small-cell lung cancer (SCLC). The 5-year survival rate of those with tumors 3 cm or less and without lymph node (LN) metastases was 86%, which was significantly higher than that of those with tumors more than 3 cm and without hilar and mediastinal LN metastases (65%) (p < 0.05). However, 33% of the patients with tumors 3 cm or less had LN metastases, and the 5-year survival rate did not differ between those with tumors 3 cm or less (60%) and those with tumors more than 3 cm (54%). Twenty-eight percent of patients with tumors 2 cm or less had LN metastases, and the 5-year survival rate of the patients with tumors 2 cm or less was 62%. The 5-year survival rate of those with tumors 2 cm or less and without LN metastases was 88%. Forty-six patients with tumors 2 cm or less included 5 cases with an intrapulmonary metastasis in the same lobe (11%). In conclusion, a size of 3 cm is an appropriate boundary as the T factor. Because those with tumors 2 cm or less have a relatively high percentage of LN metastases, intraoperative frozen sections of LN should be considered for those undergoing limited surgery for primary non-SCLCs 2 cm or less. Intrapulmonary metastases also should be considered for those undergoing limited surgery even if the maximum dimension of the primary tumor is less than 2 cm.

Analysis of the anatomic changes in the thoracic cage after a lung resection using magnetic resonance imaging.

The thoracic cage after a lung resection is filled by the remaining lobes, the elevated diaphragm, the diminished thoracic cage, and by mediastinal shifting. The changes in the thorax after a lung resection were quantified using magnetic resonance imaging. The study group consisted of 39 patients who had undergone a lobectomy, four who had undergone a pneumonectomy, and 14 controls. The left ventricular angle, ascending aortic angle, mediastinal shift, longitudinal length of the thoracic cage, the distance between the thoracic apex and the level of the aortic valve, and diaphragmatic elevation were all measured. After a right lower lobectomy, the mediastinum shifted more rightward than after a right upper lobectomy. The diaphragm became more greatly elevated after a right upper lobectomy than after a right lower lobectomy. When a chest wall resection was added to a right upper lobectomy, the mediastinal anatomical changes decreased. After a left upper lobectomy, the degree of mediastinal shifting was greater than after a left lower lobectomy. A left upper lobectomy shifted the mediastinum at the level of the right atrium. This method is easily reproducible and was found to be effective for quantifying the changes in the thorax after a lung resection.

CHANGES IN LUNG LOBAR VOLUME AND BRONCHIAL DEFORMITY AFTER RIGHT UPPER LOBECTOMY

To explore the anatomical repositioning of the middle lobe following right upper (RU) lobectomy, we measured the lobar volumes of the lung and the branching angles of the airway, and defined their changes after RU lobectomy in a rabbit model. Groups A1 (n=10) and A2 (n=10) were control groups and groups B1 (n=10) and B2 (n=10) underwent RU lobectomy. Casting material was introduced into the airway and a heart-lung bloc was removed form the thoracic cavity in all groups. In groups A1 and B1, the volume of each lobe of the bilateral lungs was measured, while in groups A2 and B2, bronchial casts were made and the branching angles of the airway were measured. The volume ratio of the right upper lobe (RUL) to the total lung was 12.0 ± 0.4% in group A1; however, after RU lobectomy, the volume ratio of the right middle lobe (RML) to the total lung increased from 8.7 ± 0.6% in group A1 to 13.5 ± 0.8% in group B1. The volume of the left lung also increased from 43.0 ± 0.5% in group A1 to 48.8 ± 1.1% in group B1. The angle between the truncus intermedius and the RML bronchus was significantly smaller in group B2, at 109.0 ± 3.5°, than in group A2, in which it was 138.5 ± 1.7°. The angle between the RML bronchus and the coronal plane was 57.5 ± 2.5° in group A2 and 33.5 ± 3.3° in group B2. Our method of measuring the bronchial branching angle subsequent to RU lobectomy proved useful to illustrate postoperative positional changes and expansion of the remaining lobes.

Benign solitary fibrous tumor of the parietal pleura which invaded the intercostal muscle

A 29-year-old woman who underwent evaluation for a 3-month history of left-sided back pain proved to have a left pleural tumor accompanied by a bloody pleural effusion (cytological class II). Three years previously, a chest roentgenogram had been normal. The tumor originated from the parietal pleura at the level of the first three intercostal muscles and was excised completely in continuity with these muscles, including a margin of normal muscle. The tumor measured 15x12 cm and the pathologic diagnosis was benign solitary fibrous tumor; while the tumor invaded the intercostal muscles, no histologically malignant features were present. Long-term follow-up is planned because a possibility of local recurrence exists.

Video-assisted thoracic surgery for primary myelolipoma of the posterior mediastinum

BackgroundMyelolipoma is an uncommon tumor comprising adipose tissue and normal hematopoietic cells and mainly occurs in the adrenal cortex. Mediastinal myelolipoma is very rare; we report a case of posterior mediastinal myelolipoma that required surgical resection.Case PresentationA 56-year-old male was diagnosed with a posterior mediastinal tumor by computed tomography. The tumor was originally noted in 2005, and during follow-up in March 2014, it was found to have increased in size. During consultation at our hospital, on magnetic resonance imaging (MRI), we considered the possibility that the tumor was malignant. Consequently, we resected the tumor by video-assisted thoracic surgery (VATS). The histopathological findings revealed that the tumor had undergone intrathoracic extramedullary hematopoiesis. However, after considering the patient’s background and histopathological findings, we diagnosed the tumor as a thoracic extra-adrenal myelolipoma.ConclusionsPathological analysis was instrumental in clarifying the diagnosis. We recommend surgery as a treatment option for posterior mediastinal tumors.

Effects of Initial Low Flow Reperfusion and Surfactant Administration on the Viability of Perfused Cadaveric Rat Lungs

Abstract. To expand the cadaveric lung donor pool, protecting the endothelium and alveoli from warm ischemia and reperfusion injury is important. The effects of initial low flow reperfusion and surfactant administration were studied in non–heart-beating donor lungs. The rat heart-lung bloc was excised immediately (group 1) or 30 min (groups 2–4) after euthanasia (n= 6 in each group). The graft was ventilated and reperfused (50 ml/min) immediately after excision for 1 h in groups 1 and 2. In groups 3 and 4, the reperfusion flow rate was increased gradually to 50 ml/min, while ensuring that the pulmonary arterial pressure did not exceed 40 mmHg. Then the graft was reperfused for 1 h. Surfactant was introduced into the airway in group 4 before reperfusion. Airway pressure (AWP) and pulmonary arterial pressure were monitored during reperfusion. After reperfusion, the wet/dry weight ratio (W/D) of the right lung was calculated, and histologic examination using trypan blue staining of the left lung was performed. In group 2, lung failure appeared in all animals during reperfusion. In group 3, although all lungs were reperfused for 1 h, AWP and W/D were higher than in group 1. In group 4, AWP and W/D were lower than in group 3. Histologic examination showed that surfactant administration had attenuated the alveolar cell death. To avoid damage caused by high pulmonary arterial pressure associated with graft reperfusion, iniital low flow reperfusion was beneficial in cadaveric lungs. Surfactant administration before reperfusion was effective in preventing pulmonary edema.

The Usefulness of Positron-Emission Tomography Findings in the Management of Anterior Mediastinal Tumors

PURPOSE We performed a retrospective analysis to evaluate the usefulness of positron-emission tomography/computed tomography (PET/CT) findings in the classification and management of anterior mediastinal tumors. METHODS Between 2006 and 2015, 105 patients with anterior mediastinal tumor received PET/CT. 18F-fluorodeoxyglucose (18F-FDG)-PET images were obtained 60 minutes after the injection of 18F-FDG. RESULTS The histological classifications were as follows: thymoma (n = 49), thymic carcinoma (TC) (n = 19), malignant lymphoma (ML) (n = 8), teratoma (n = 7), thymic cyst (n = 14), and others (n = 8). Upon visual inspection (SUV max: >2.0), all of the malignant tumors showed 18F-FDG accumulation (with the exception of one type A thymoma). Two of the 14 thymic cysts and three of the seven teratomas showed slight 18F-FDG accumulation. The SUV max values of the low-grade thymomas, high-grade thymomas, TCs and MLs were 3.14 ± 0.73, 4.34 ± 1.49, 8.59 ± 3.05, and 10.08 ± 2.53, respectively, with significant differences between the low- and high-grade thymomas, and between TCs and MLs. The sensitivity, specificity and accuracy of 18F-FDG in the detection of low-grade thymomas and thymomas with a maximum diameter of ≤50 mm and an SUV max of ≤3.4 were 85%, 48%, and 60%, respectively. CONCLUSION FDG-PET/CT is an objective and useful modality in the differential diagnosis and management of anterior mediastinal tumors.

Platelets as participants in hyperacute guinea pig-to-rat lung xenorejection

It is well known that xenotransplantation leads to immediate graft dysfunction. This study was designed to specifically examine the role of platelets in mediating lung hyperacute xenorejection (HXR) in a guinea pig-to-rat model. A total of 18 lungs were perfused with blood using an ex vivo apparatus. The animals were divided into the following four groups: a CE group comprising circuit only with rat blood; a SYN group comprising rat lungs and blood; a XE group comprising guinea pig lungs and rat blood; and an SH group comprising guinea pig lungs and rat blood with sarpogrelate hydrochloride, a suppresser of platelet aggregation. The platelet and serotonin in the blood were lower and the wet/dry weight ratio of the lung (W/D) in the XE group were higher than those in the SYN group after perfusion. The platelet count was higher, but the serotonin and W/D were lower in the SH group than in the XE group. These results suggest that platelets strongly affect HXR. Thus, the administration of drugs to suppress platelet aggregation would reduce xenotransplanted lung edema.

Pulmonary adenocarcinoma metastatic to the gingiva

Abstract Gingival metastasis from lung cancer is very uncommon. We report a case of distant metastasis of pulmonary adenocarcinoma in the mandibular gingiva. A 54-year-old man was admitted to our hospital on September 1, 1997 with hemoptysis. Right upper lobectomy with mediastinal lymph node dissection was performed on September 16. On the 14th postoperative day, the patient complained of a gingival swelling. In the lower right premolar area, a wide pedunculated mass was seen on the mandibular gingiva. Excisional biopsy of the tumor was performed, and histopathological examination revealed that the tumor was a metastatic lesion from the pulmonary adenocarcinoma. The patient received 46.8 Gy of linac irradiation to the tumor area and the entire oral condition improved markedly. However, bilateral adrenal gland metastases were recognized, and left inguinal lymph node metastasis was detected 2 months after lung resection. He developed tumor metastases to multiple organs and died of respiratory failure on December 12, 1997.