Toshiki Hirata

Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded

BACKGROUND We analyzed the operative outcome of extensive surgery for invasive thymoma, especially in those with thymomas invading the superior vena cava, the left innominate vein, or both. METHODS We treated 41 patients with invasive thymoma, including 34 stage III, 5 stage IVa, and 2 stage IVb thymomas. Thirty-eight patients received radiotherapy preoperatively or postoperatively. In 12 patients with invasion of the superior vena cava or innominate vein, we performed angioplasty, reconstruction, or both. RESULTS The overall 5-year survival rate was 77% and the 10-year survival rate was 59%. In the stage III group, there was a significant difference between those with complete and those with incomplete resection. Ten of 12 patients who had angioplasty with or without reconstruction of the superior vena cava or innominate vein survived without recurrence of the tumors. CONCLUSION Angioplasty and vascular reconstruction are recommended because successful treatment for invasive thymomas depends on complete resection of the tumors.

Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung

Human thioredoxin is a polypeptide with thiol groups, possessing reducing activity, which is proved to have the ability to reduce active oxygens. This study evaluated the effect of human thioredoxin on the ischemia-reperfusion lung injury and the roles of human thioredoxin on active oxygens by chemiluminescence examination. The left hilum of the lung of Japanese white rabbits was occluded for 110 minutes and then reperfused for 90 minutes. Ten, 30, 60, and 90 minutes after reperfusion the right hilum was occluded for 5 minutes and the pulmonary functions of the left lung were examined. The animals were divided into four groups, three ischemia groups and a sham group (without occlusion; n = 6). The ischemia groups received human thioredoxin, 60 mg/kg (n = 10), N-acetylcysteine, 150 mg/kg (n = 7), or saline solution (control, n = 10) during reperfusion. Three rabbits in the human thioredoxin group and the control group were used to measure active oxygens with a cypridina luciferin analog. An additional group of reperfused lungs (n = 3) that were given superoxide dismutase after 110 minutes of ischemia was established to identify chemiluminescence examination. Compared with the sham group, reperfusion after 110 minutes of ischemia produced a significant lung injury in the control group. Among the ischemia groups, the human thioredoxin group showed significantly higher arterial oxygen tension at 30, 60, and 90 minutes after reperfusion than the control group, although there was no significant difference between the N-acetylcysteine and control groups. Histologically, intraalveolar exudation, interstitial thickening, and cellular infiltration were seen in the control group, whereas in the thioredoxin group alveolar structure was well preserved. In the measurement of active oxygens the chemiluminescence in the human thioredoxin group was less than that in the control group and as little as that in the group administered superoxide dismutase. We concluded human thioredoxin attenuated ischemia-reperfusion injury by involving active oxygens in rabbit lungs.

Attenuation of ischaemia reperfusion injury by human thioredoxin.

BACKGROUND--Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury. METHODS--Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 micrograms/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 degrees C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. RESULTS--In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls. CONCLUSIONS--These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals.

Mutations in Keap1 are a potential prognostic factor in resected non-small cell lung cancer.

Mutations in Kelch‐like ECH‐associated protein 1 (Keap1) have been reported to protect tumor cells from chemotherapeutic agents. However, their prognostic significance in nonsmall cell lung cancer (NSCLC) is still unclear. In this study, we examined the effect of Keap1 gene mutations on survival and disease‐free interval using resected primary NSCLC tissue.

Clinical features of surgical resection for pulmonary metastasis from breast cancer

BACKGROUND AND OBJECTIVES Metastatic breast cancer has been defined as a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. To confirm the role of resection of pulmonary metastases from breast cancer and to identify possible prognostic factors, we reviewed our institutional experience. METHODS Between 1991 and 2007, 41 patients with pulmonary metastases from breast cancers underwent complete pulmonary resection. All patients had obtained or had obtainable locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of metastasectomy and to analyze prognostic factors for overall survival after metastasectomy. RESULTS All patients were female with a median age of 55 years (range, 35-81 years). The overall survival rate after metastasectomy was 51% at 5 and 10 years. On multivariate analysis, fewer than four pulmonary metastases and a disease-free interval of more than 3 years were significantly favorable prognostic factors for overall survival (p=0.023 and 0.024, respectively). CONCLUSIONS The current practice of pulmonary metastasectomy for breast cancers in our institution was well justified. Pulmonary metastasectomy in patients with previous breast cancer might be justified when fewer than four pulmonary metastases or a disease-free interval of more than 3 years.

Effects of Euro-Collins, University of Wisconsin, and new extracellular-type trehalase-containing Kyoto solutions in an ex vivo rat lung preservation model.

BACKGROUND We have previously reported the effects of trehalose-based extracellular-type Kyoto (ET-K) solution in lung preservation. Now, we have developed a new ET-K solution by adding three substances--N-acetyl cysteine, dibutyryl cyclic AMP, and nitroglycerin, to ET-K solution. We studied the effects of new ET-K solution in lung preservation, and compare it with Euro-Collins (EC) and University of Wisconsin (UW) solutions using an ex vivo rat reperfusion model. METHODS The perfusion circuit was initiated by 30 ml of fresh mixed venous blood obtained from three haparinized rats. By means of a double-head roller pump, the blood passed from the venous blood reservoir through the pulmonary artery to be perfused in the examined lung. The lung effluent was returned at the same flow rate to the deoxygenator fresh lung. Four experimental groups were allocated. In group 1 (fresh group, n=6), lung was flushed with saline and reperfused immediately. In the other groups (group 2: new ET-K group, n=6; group 3: UW group, n=6; and group 4: EC group, n=6), lung was flushed with the new ET-K and prostanglandin E1 (PGE1), UW and PGE1, and EC and PGE1, respectively. After 17-hr preservation, the preserved lung was reperfused. RESULTS In all six animals of the EC group, ventilation of the experimental lung was discontinued at 20 min after reperfusion because of the exudate in the endotracheal tube that resulted from pulmonary edema. The shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure in the new ET-K and UW groups were significantly better than those in the EC group, but were almost equal to those in the fresh group. CONCLUSION The postpreservation pulmonary functions with the new ET-K solution were better than those with the EC solution, and were equal to those with the UW solution. This new solution is expected to contribute to the increase in donor lungs for clinical lung transplantation. In addition, this ex vivo rat reperfusion model is simple and highly reliable, and can be widely used in the studies of pulmonary preservation.

A disintegrin and metalloprotease 12 (ADAM12) is a prognostic factor in resected pathological stage I lung adenocarcinoma

A disintegrin and metalloprotease 12 (ADAM12) has multiple domains and functions, and it plays important roles in the development of cancer. We conducted a retrospective study to determine whether the expression of the membrane type of ADAM12 (ADAM12‐L) could be a prognostic factor in resected pathological (p‐) stage I lung adenocarcinoma.

Clinical Experience with Lung-Imaging Fluorescence Endoscope (LIFE) in Patients with Lung Cancer

Abstract: British Columbia Cancer Research Center developed a new technique for detection of lung cancer with a device called the lung-imaging fluorescence endoscope (LIFE). Our aim was to confirm whether LIFE system would be useful in diagnosis of dysplasia of bronchial mucosa and lung cancer. Thirty patients with suspected lung cancer were included in this study. All patients underwent bronchoscopic examination by LIFE following examination by the conventional white-light bronchoscope. Pathological examination was performed for the abnormal areas detected by white-light or fluorescence bronchoscopic examination. Malignant tumors were diagnosed in 12 patients by both conventional bronchoscopy and LIFE; one dysplasia was also diagnosed by conventional bronchoscopy. The LIFE system diagnosed malignancy in four regions and one dysplasia that conventional bronchoscopy could not. Malignant lesions diagnosed by conventional bronchoscopy at three locations were proved later by the LIFE system to be benign. The sensitivity and specificity of the conventional bronchoscope for detection of dysplasia and cancer were 65% and 71%, respectively. The LIFE systems sensitivity was 90% and its specificity was 77.4%. No complications related to the LIFE system were detected throughout the course of this study. We conclude that the LIFE system can detect minute malignant lesions which are commonly non-detectable by conventional bronchoscopy without any complications. This method may be applicable in the screening of high risk groups for lung cancer.

Effect of Recombinant Human Adult T Cell Leukemia-Derived Factor on Rat Lung Reperfusion Injury

The formation of reactive oxygen species (ROS) is a major factor responsible for reperfusion injury in lungs. Adult T cell leukemia derived factor (ADF), a polypeptide made of 104 amino acids, is induced by a variety of stresses including X-ray, ultraviolet, H2O2, and mitogen. ADF has a reducing activity, which catalyzes the proton transfer between thiol-radical of cystein-containing proteins. Furthermore, ADF has a protective activity of ROS which are formed by xanthine oxidase and other alternative pathways in vitro. Using a rat in vivo model of lung ischemia, we examined the protective effect of recombinant human ADF (rhADF) against ischemia reperfusion injury of the lung. Ischemia, lasting for 75 min, was induced in the left lung of rats at 23 degrees C. The lung was then reperfused. These animals were divided into two groups: group 1 (n = 6, treatment with normal saline) and group 2 (n = 6, treatment with 28 micrograms/g of rhADF). One minute after the beginning of reperfusion, arterial oxygen tension (PaO2) decreased significantly in both groups (p < 0.01), without any significant intergroup difference (55.5 +/- 9.8, 49.8 +/- 8.6 mm Hg, respectively). Twenty minutes after reperfusion, PaO2 was significantly higher (p < 0.05) in group 2 (113.0 +/- 8.1 mm Hg) than in group 1 (72.3 +/- 13.6 mm Hg). The wet/dry weight ratio was significantly higher in group 1 (7.31 +/- 0.54) than in group 2 (5.82 +/- 0.36). Histologically, lung injury tended to be milder in group 2 than in group 1. These results suggest that rhADF has a protective effect against ischemia reperfusion injury of the rat lung.

Significance of tumor recurrence before pulmonary metastasis in pulmonary metastasectomy for soft tissue sarcoma.

BACKGROUND Resection for pulmonary metastasis from soft tissue sarcomas is an accepted method for treatment, but it is still debatable which patients will benefit from surgical intervention. To find an entity of patients benefiting from pulmonary metastasectomy, we reviewed our institutional experience. METHODS Between 1990 and 2007, 23 patients with pulmonary metastases from soft tissue sarcomas underwent complete pulmonary resection. All patients had obtained locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of pulmonary metastasectomy and to identify possible prognostic factors for survival after metastasectomy. RESULTS Overall survival rate after metastasectomy was 43% and 29% at 5 and 10 years, respectively. Disease-free survival rate was 9% at 1 year after pulmonary resection. On multivariate analysis, no tumor recurrence (neither locoregional recurrence nor extrapulmonary metastasis) before pulmonary metastasis provided a significantly favorable overall survival (P=0.038). In addition, repeat metastasectomy for recurrent pulmonary metastasis also provided a favorable overall survival (P=0.041). CONCLUSIONS Our data suggested that patients most likely to benefit from pulmonary metastasectomy for soft tissue sarcoma have no tumor recurrence before pulmonary metastasis. Furthermore, patients with repeat metastasectomy for recurrent pulmonary metastasis also presented a significantly longer survival.