New ET-Kyoto solution containing N-acetylcysteine, nitroglycerin, and dibutyryl cyclic AMP provides reliable 30-hour canine lung preservation.
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Biomedical subjects
Publications and source records attributed to H Yokomise.
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To investigate the chance of discovery of metastatic lung tumors and the five-year survival rates of patients undergoing surgical resection, we followed 99 patients who underwent initial surgical treatment at our hospital between 1979 and 1996. With regard to primary organs or sites, 32 patients had rectal cancer, 27 patients had breast cancer, 19 patients had colon cancer and 21 patients had osteosarcoma. For 22 of 99 patients (22%), discovery was due to subjective symptoms such as cough and sputum (n = 12), chest (or back) pain (n = 7) or hemosputum (n = 5). Ten of 19 patients (53%) with colon cancer experienced subjective symptoms which led to the discovery of metastases. In 76 of 99 patients (78%), metastatic lung lesions were not discovered through subjective symptoms. In 63 of those 76 patients, such lesions were initially found by plain chest roentgenography or CT. In 20 of 21 patients (95%) who had osteosarcoma, metastatic lung tumors were discovered by chest roentgenography or CT. In 14 of 76 patients, all of whom had metastatic lung carcinomas, the lesions were discovered through elevated levels of tumor markers. Therefore the importance of periodic chest roentgenography and tumor marker testing was demonstrated. Disease-free interval (DFI) was over six years in five of 32 patients (16%) with rectal cancer and 13 of 27 (48%) with breast cancer. DFI was less than five years for 15 of 19 patients (79%) with colon cancer, and less than two years for 16 of 21 (75%) with osteosarcoma. Thus, DFI differed according to the sites of the tumors. The five-year survival rates of 97 patients were examined. Patients were divided according to the sites of their primary tumors, and then subdivided according to the type of surgery they received. Patients were thus divided into five categories: I) those who underwent incomplete resection of metastatic lung lesions, II) those who underwent complete resection of both pulmonary lesions and involved mediastinal lymph nodes, III) those who had undergone previous treatment for tumors in organs other than the lung, IV) those who underwent complete resection of multiple lung lesions, and V) those who underwent complete resection of solitary lung lesions. For all primary sites, none of the patients in group I) survived for more than two years. Therefore complete resection seems very important for the treatment of metastatic lung tumors. With regard to the other groups, several facts were noted. For rectal cancer, the five-year survival rate of groups V) and III) was 55.6% in either case. Therefore complete resection of rectal cancer metastatic to the lung may improve the five-year survival rate even for patients who have previously been treated for cancers in organs other than the lung. For colon cancer, the five-year survival rate of group V) was 51.4%. Complete resection of only a solitary lung lesion may improve the five-year survival rate for colon cancer. For breast cancer, the five-year survival rate of group V) was 37.5% and that of group II) was 60.0%. This may indicate that for patients who have both pulmonary lesions and mediastinal lymph node involvement, complete resection of both is important. For osteosarcoma the five-year survival rate of group IV) was 26.0%. Thus, osteosarcoma patients have a chance of survival if they undergo complete resection of lung metastases.
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The relationship between the expression of adult T-cell leukemia-derived factor, human thioredoxin (ADF/TRX), and rejection in transplanted canine lungs was investigated in this study. Of a total 27 adult mongrel dogs, 24 underwent allotransplantation of the left lung with no immunosuppressant and the other three underwent autotransplantation of the left lung. Of the allotransplanted dogs, five were killed on postoperative day (POD) 1, five on POD 2, seven on POD 3, and seven on POD 5, while all three autotransplanted dogs were killed on POD 5. Histological examination was performed on the 24 allotransplanted left lungs (group A), 12 autologous right lungs (group B), and bilateral lungs of the three autotransplanted dogs (group C). The lung tissue was stained with anti-ADF antibody, and the high-ADF-producing cells (ADFh cells) in a randomly chosen field were counted as an index of ADF expression. As the signs of rejection in the group A lungs became more severe with time, the ADFh cells increased in number: 1.68 +/- 1.15, 6.08 +/- 3.44, 14.03 +/- 6.09, and 47.74 +/- 18.89, on PODs 1, 2, 3, and 5, respectively. However, the number of ADFh cells in the group B and group C lungs did not become significantly different from that on POD 1 in group A. These results suggested that ADF/TRX expression may be useful for the early diagnosis of rejection of transplanted lungs.
To assess the effect of chemotherapy on postoperative survival of patients with small cell lung carcinoma (SCLC), 46 patients who underwent surgery at Kyoto University between 1976 and 1991 were retrospectively reviewed. Seventeen patients (37.0%) received chemotherapy prior to as well as after surgery (neoadjuvant therapy group), 23 (50.5%) received chemotherapy only after surgery (adjuvant therapy group), and the other six received no chemotherapy (non-chemotherapy group). The 5-year survival rate of patients with c-Stage I or II disease in the neoadjuvant therapy group was as high as 80.0%, which seemed to be higher, although with no statistical significance, than that in the adjuvant therapy group (37.7%, P = 0.10). The 5-year survival rate of patients with c-Stage III (IIIa or IIIb) disease in the neoadjuvant therapy group, although not satisfactory (10.0%), was significantly higher than that in the adjuvant therapy group (0.0%, P = 0.04). No patients in the non-chemotherapy group had survived 5 years. Moreover, multivariate analysis showed that failure to employ preoperative chemotherapy was the strongest prognostic factor causing a poor prognosis (P = 0.01). On the other hand, eight (30.8%) out of 26 patients with c-Stage I or II disease postoperatively proved to have mediastinal lymph node involvement (pN2-3), and two (7.7%) proved to have intrapulmonary metastasis (PM). Considering the advantage of preoperative chemotherapy and the discrepancy between c- and p-stage, sufficient chemotherapy prior to surgery should be employed, and may realize a good prognosis in patients with c-Stage I or II disease. In contrast, patients with c-Stage III disease are not appropriate as candidates for surgery even if preoperative chemotherapy is performed.
Lung transplantation is now an accepted therapeutic option for patients with end-stage lung disease, and an early diagnosis of rejection is essential in the management of these patients. Adult T-cell leukemia-derived factor (ADF), known as a human homolog of thioredoxin, has been shown to be induced by a variety of stresses. In this study we examined ADF expression in lung tissues and bronchoalveolar lavage cells after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Allotransplantations were performed in adult mongrel dogs, and immunosuppression was performed from the day of operation to the fifth postoperative day. No immunosuppressant was given from the sixth to the tenth postoperative days. Animals were put to death on the tenth postoperative day. Bronchoalveolar lavage was performed on the fifth and tenth postoperative days, and the lavage cells and lung tissues were examined immunohistochemically with anti-ADF antibody. The grades of rejection were as follows: grade 1 in two animals, grade 2 in three animals, and grade 3 in two animals. The percentages of ADF high-producer cells in bronchoalveolar lavage cells on the fifth and tenth postoperative days were 4.29% +/- 2.65% and 26.6% +/- 3.99%, respectively (p < 0.01). The percentages of ADF high-producer cells in normal healthy dogs and in those with grade 1, grade 2, and grade 3 rejection were 3.00% +/- 1.64%, 20.5% +/- 9.00%, 25.5% +/- 6.06%, and 34.5% +/- 6.50%, respectively. The percentage in each rejection group was significantly higher than that in normal healthy dogs (p < 0.05). These results suggest that examination of bronchoalveolar lavage cells with ADF staining may be useful in the early diagnosis of rejection.
We previously reported that trehalose, a reduced disaccharide, was effective in the preservation of lungs. In this study, we investigated the possibility of prolonged cryopreservation of tracheas in a preservative solution containing trehalose. Five rings of cervical trachea were removed and immersed in the preservative solution. The harvested tracheas were then cryopreserved and stored in a deep freezer at -85 degrees C. One month later, five rings of mediastinal trachea were removed. The cryopreserved cervical tracheas were thawed and autotransplanted in place of the excised mediastinal trachea (n = 6). The anastomotic site and graft were then covered with an omental pedicle. All six animals survived for more than 6 months. All grafts survived without any evidence of atrophy or stenosis. Microscopic examination of the grafts showed that the integrity of the tracheal tissues was maintained. Our findings show that consistent cryopreservation of the trachea for 1 month is possible in a preservative solution containing trehalose.
We developed a new solution, ET-Kyoto (ET-K) solution, and compared its efficacy in 20 h lung preservation with that of Euro-Collins (EC) solution in a canine left lung transplantation model. The lungs were flushed with ET-K solution (ET-K group, n = 5), with EC solution plus prostaglandin E1 (PGE1) pretreatment (EC + PGE1 group, n = 6) or with EC solution (EC group, n = 6), and were stored at 4 degrees C for 20 h. The function of left lung grafts was assessed 40, 70, and 130 min after transplantation. The arterial pressure of oxygen (PaO2) in the ET-K group was significantly greater than in the EC + PGE1 group (p < 0.05 or p < 0.01) and in the EC group (p < 0.01). The peak inspiratory pressure and wet to dry weight ratio in the ET-K group were significantly lower than in the EC + PGE1 group and in the EC group (p < 0.05 or p < 0.01). Pulmonary vascular resistance in the ET-K group 130 min after reperfusion was significantly lower than in the EC group (p < 0.05). All the transplanted lungs in the EC + PGE1 group and the EC group showed histological evidence of pulmonary edema, whereas all in the ET-K group showed no signs of edema. We concluded that ET-K solution is superior to EC solution with or without PGE1 pretreatment in 20 h canine lung preservation.
Eighteen patients underwent combined preoperative irradiation and radical resection for a Pancoast tumor at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1977 and 1993. Four patients were applied a full radiation dose of 50-70 Gy and fourteen patients were applied a reduced dose of 33-40 Gy preoperatively. Eleven of these fourteen were applied a supplemental dose postoperatively up to a total dose of at least 50 Gy. Fourteen lobectomies, three partial resections, and one pneumonectomy were performed with combined resection of chest wall or adjacent structures: rib in 14, vertebra in 4, brachiocephalic vein in 3, subclavian artery in 2, spinal nerve in 3, sympathetic truncus in 2, phrenic nerve in 2 cases. Chest walls were reconstructed with marlex mesh in 5 patients, and two subclavian arteries and one brachiocephalic vein were repaired with artificial grafts. In 13 patients complete resections were achieved, but in the other 5 only incomplete resections leaving residual tumor were achieved. Incomplete resections consisted of 4 positive stumps at the brachial plexus of the apex and one aortic involvement by a metastatic lymph node. There was one operative death. Median survival was 21.6 months and the 5-year-survival rate was 38.5% for all 18 patients. In the complete resection group 5-year-survival was 56.4%, but in the incomplete-resection group 0%, showing a significantly more favorable result for the complete resection group. It is considered that evidence of incomplete resection influences the prognosis and that particularly tumor invasion to the brachial plexus may serve as a limiting factor for surgery.
A surgical case of pulmonary metastases of polymorphous low-grade adenocarcinoma (PLGA) originating from the minor salivary gland in the soft palate in a 62-year-old woman is reported. PLGA has been to be a locally invasive carcinoma without distant metastases; thus our case is the first reported case with histologically-proven distant metastases to the lung. We emphasise that attention should be paid to distant metastases especially to the lung even in case of PLGA.
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.
Operative technique and long-term results of seventeen patients with apical invading lung cancers were evaluated. External radiation therapy was administered preoperatively in all but one. Thirteen lobectomies, three wedge resections and one pneumonectomy were performed with combined resections of chest wall (and adjacent structures) 12, vertebra 3, brachicephalic vein 2, subclavian artery 1, lower part of brachial plexsus 3, sympathetic trunk 2 and phrenic nerve 1. Chest walls were reconstructed with marlex meshes in 5, the subclavian artery and one brachiocephalic vein were with artificial grafts. Operations were considered relative curative in 10, relative non-curative in 2 and absolutely non-curative in 5. Absolutely non-curative operations were due to cancer-positive stump of brachial plexus in the apex in four and metastatic lymph node invading aorta in one. Over all five-year survival rate was 35.3% and median survival was 20 months. Five-year survivals in patients with curative operations and non-curative operations were 60% and 0%, respectively, and the former was significantly higher. Surgical margin is a large factor for long-term result and invasion to the brachial plexus is thought to be a limiting factor for surgery.
Postpneumonectomy fistula is one of the most serious complications in general thoracic surgery and remains difficult to manage. From 1984 to 1991, we successfully used pedicled omentum for the treatment of postpneumonectomy bronchopleural fistulas (omentoplasty) in five patients, four of whom had thoracic empyema. For bronchopleural fistulas without early postoperative infection, single-stage closure was performed which was then covered with pedicled omentum. Omentoplasty was performed successfully in patients with thoracic empyema, after open or closed drainage. Open thoracotomy was useful when closed drainage was ineffective. Even after open thoracotomy, closure of the wound was achieved. All five patients could be discharged. Omentoplasty was useful in the therapy of postpneumonectomy bronchopleural fistula even in the presence of thoracic empyema.
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.
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Thoracoscopy was performed in a total of 424 patients at our institute from January 1970 to December 1993. The indications for thoracoscopy were pneumothorax (121 cases), primary lung cancer (98 cases), mediastinal tumor (45 cases), metastatic lung tumor (23 cases), pleuritis (35 cases), diffuse lung disease (38 cases), tuberculosis (20 cases), benign lung tumor (10 cases), and other (34 cases). By 1990, diagnostic thoracoscopy had been performed in 383 patients. Since 1991, thoracoscopy has been used therapeutically for spontaneous pneumothorax (24 cases), mediastinal and chest wall tumors (9 cases), pulmonary nodules (2 cases), and others (8 cases). Findings useful for diagnosis were obtained in 326 cases and biopsy was performed in 173 cases. Thoracoscopy was especially useful in the diagnosis of diffuse lung disease, pleuritis, and small pulmonary nodules. Recent advances in endoscopic equipment and refinement of thoracoscopic techniques have expanded the application of this procedure. Our experience indicates a markedly expanded role for thoracoscopy in the diagnosis and treatment of thoracic diseases, with less postoperative morbidity.
Human thioredoxin, which was previously recognized as adult T-cell leukemia-derived factor, has many physiologic activities, one of which is a radical scavenger effect. Its ability to reduce reperfusion injury was assessed in vivo in a canine lung transplantation model. In 19 dogs, left lung allotransplantation was performed after 100 minutes of warm ischemia. The function of the transplanted lung was assessed after clamping of the contralateral pulmonary artery. In the human thioredoxin group (n = 6), human thioredoxin 30 mg/kg was given to the recipients during reperfusion. In the N-acetylcysteine group (n = 5), N-acetylcysteine 150 mg/kg, known as a radical scavenger, was given in the same manner. In both groups, arterial oxygen tension was significantly higher than in the control group (n = 8). In the human thioredoxin group, peak inspiratory pressure was significantly lower than in the control group. Macroscopic and microscopic examinations showed an almost normal appearance of the lung tissues in the human thioredoxin and N-acetylcysteine groups, in contrast to the abnormal findings in the control group. Thus it would appear that human thioredoxin has a protective effect on transplanted lungs, as does N-acetylcysteine, and that its action may be a radical scavenger effect.
Trehalose is a nonreducing disaccharide that stabilizes the cell membrane under various stressful conditions. A previous study demonstrated that trehalose was effective in 12-hour canine lung preservation. We have developed new preservation solutions containing trehalose: an extracellular type ET-Kyoto solution (Na 100 mmol/L, K 44 mmol/L) and an intracellular type IT-Kyoto solution (Na 20 mmol/L, K 130 mmol/L). The composition of these solutions is identical except for the electrolyte content. We examined their efficacy in 20-hour lung preservation. Canine lungs were flushed with ET-Kyoto (group A, n = 6), with IT-Kyoto and prostaglandin E1 (25 micrograms/kg) (group B, n = 6), or with Euro-Collins solution and prostaglandin E1 (25 micrograms/kg) (group C, n = 7), and stored for 20 hours at 4 degrees C. Left lung transplantation was performed and evaluated for up to 130 minutes. The flush time was similar in the three groups. Arterial oxygen tensions (inspired oxygen fraction = 0.5) in group A were uniformly excellent (303.3 +/- 7.0 mm Hg 70 minutes after reperfusion and 303.0 +/- 19.6 mm Hg 130 minutes after reperfusion) and significantly higher than in group B (202.6 +/- 32.0 mm Hg, p < 0.05, and 197.8 +/- 44.0 mm Hg, p = 0.054, respectively) or group C (185.9 +/- 23.0 mm Hg, p < 0.01, and 155.7 +/- 36.3 mm Hg, p < 0.05, respectively). Peak inspiratory pressure in group A was significantly lower than in groups B and C (p < 0.05). Wet/dry weight ratio in group A was significantly lower than in groups B (p < 0.05) and C (p < 0.01). Histologic and scanning electron microscopic examinations showed better preservation in group A than in groups B and C. We conclude that ET-Kyoto is superior to IT-Kyoto and to Euro-Collins solution for 20-hour lung preservation.