A randomized phase III trial of postoperative adjuvant therapy for completely resected stage IA-IIIA lung cancer using an anti­angiogenetic agent: irsogladine maleate.

AIM: Although angiogenesis plays an important role in the invasion and metastasis of solid tumors, very few anti-angiogenetic drugs have been developed. Reexamining the anti-angiogenetic effects of existing drugs such as Thalidomide is another possible strategy for drug discovery. Irsogladine maleate (IM) is a drug invented to treat gastric ulcers; however, several reports have shown that IM also exerts anti-angiogenetic effects in vitro, in vivo and in humans. In order to elucidate whether treatment with IM would improve the prognoses of patients with resected lung cancer, we conducted a randomized trial. METHODS: In the control group, uracil-tegafur (250 mg/m2/day) was administered for two years to patients with resected stage IB - IIIA lung cancer, and no adjuvant therapy was administered to those with stage IA disease. In the study group, IM (4 mg/body/day) was additionally administered for two years. RESULTS: No significant differences were observed in the major prognostic factors among 305 eligible patients between the study and control groups. Adverse effects were minimal. The overall survival of the patients in the study and control groups were not statistically different. When the analysis was stratified by regimen, among the patients with resected stage IA disease, disease-specific survival in the study group was slightly higher than that in the control group; however, the difference was not significant (p=0.07). CONCLUSION: Although it could not be proven that IM improves the prognoses of resected lung cancer patients, IM might have some effect on resected stage IA disease, and another trial should be conducted.

[Sarcomatoid carcinoma of the thymus which caused acute epicarditis].

Thymic carcinoma is rare. Particularly sarcomatoid carcinoma of the thymus is a very rare disease it has been reported in only 15 patients to date. The prognosis is very poor and diagnosis and treatment have not yet been established. We report a case of 63-year-old man who was initially diagnosed with acute pericarditis and was finally found to be sarcomatoid carcinoma of the thymus. He underwent surgery and the tumor was completely resected. However, 6 months after surgery, local recurrence was noted. The patient was treated by radiotherapy followed by paclitaxel monotherapy. Partial remission was achieved transiently with paclitaxel, but the tumor again recurred. He died 33 months after surgery. The possibility of diseases like this tumor must be kept in mind for a patient with chest symptoms. Paclitaxel monotherapy is likely to be effective in treating sarcomatoid carcinoma of the thymus.

[Obvious enlargement of the pulmonary hamartoma: report of a case].

A 72-year-old man was admitted to our hospital due to abnormal shadow in the right hilum by a routine chest X-ray. When we had another look at a chest X-ray that had been taken 6 years before, we had found a pulmonary nodule of 18 mm in size. The chest X-ray and computed tomography (CT) taken at admission showed a round nodule with calcification in the same site, with increasing in size to 30 mm. The tumor could not be clinically diagnosed and the surgery was scheduled because the nodule had grown and the possibility of a malignant tumor was suggested. At surgery, the tumor was easily enucleated and the pathological diagnosis was chondromatous hamartoma. Although pulmonary hamartoma is a benign tumor, operation should be performed when the tumor had grown.

[Pulmonary schwannoma with hypervascularity; report of a case].

A 54-year-old female was admitted to our hospital with a mass shadow in the right pulmonary hilum. The chest computed tomography (CT) scan revealed a well-circumscribed mass in the lower lobe of the right lung. Bronchoscopic examination showed a submucosal tumor in the right basal bronchus which bled easily, and the angiogram showed a tumor with hypervascularity. The tumor was suspected to be a sclerosing hemangioma or malignant tumor. A right basal segmentectomy was performed, and the pathological diagnosis was that of schwannoma. During the 8 year follow-up period, she exhibited no evidence of recurrence.

Removal of cartilage rings of the graft and omentopexy for extended tracheal autotransplantation.

BACKGROUND: One of the serious problems in longer-size tracheal transplantation is infection or severe stenosis of the graft, probably caused by an inadequate blood supply even with omentopexy. For obtaining an appropriate blood supply, we experimentally developed a new technique that included removal of some cartilage rings of the graft and omentopexy. METHODS: Twenty-one adult mongrel dogs were used. In group A (n = 11), a nine-cartilage ring length of the trachea in which six of nine rings were removed, leaving one cartilage ring at each end of the graft and another in the center, was autotransplanted with omentopexy. Two artificial tracheal rings outside the graft were used for maintaining the lumen. In group B (n = 10), a nine-cartilage ring length of the trachea was autotransplanted with omentopexy. RESULTS: In group A, all dogs survived until being sacrificed, whereas 5 group B dogs died of graft infection and mediastinitis (p<0.05 versus group A). Mucosal blood flow of the graft in group A was normal and higher than in group B (p<0.05). Grade of the graft stenosis at death or sacrifice was 14%+/-1% in group A and 58%+/-25% in group B (p<0.05). CONCLUSIONS: Removal of some cartilage rings improved blood supply to the graft and resulted in satisfactory survival and nonsignificant tracheal stenosis in extended tracheal autotransplantation.

Potentiation of tumoricidal properties of murine macrophages by Nocardia rubra cell wall skeleton (N-CWS).

Intraperitoneal injection of squalene-treated cell wall skeleton of Nocardia rubra (N-CWS) caused increase in number of peritoneal exudate cells (PEC). Adherent macrophages obtained from N-CWS-treated PEC suppressed growth of methylcholanthrene-induced fibrosarcoma (Meth-A), when injected intradermally with the tumor cells into BALB/c mice. The macrophages showed strong cytotoxicity against Meth-A cells in vitro. When treated with 10 micrograms/ml of N-CWS in vitro, proteose peptone-induced macrophages acquired tumoricidal property but resident macrophages showed no cytotoxicity after the treatment. In the supernatant of spleen cells cultured for 72 hours in the presence of N-CWS (10 micrograms/ml), the presence of (a) factor(s) with macrophage activating effect was observed. This factor, shown to be identical to macrophage activating factor (MAF) in molecular weight, showed synergy with N-CWS in potentiating macrophage cytotoxicity against tumor cells.

Alterations of angiotensin II Receptor levels in sutured wounds in rat skin.

Angiotensin II receptor levels have been shown to vary with postoperative time in tissue harvested from full-thickness dermal excisional wounds on adult rats. This study examined the expression of AII receptors in a sutured wound model. Two full-thickness incisional wounds were made in the dorsal skin of adult Sprague-Dawley rats and sutured immediately under general anesthesia. The wound tissues were harvested at 0, 0.5, 1, 2, 4, 24 h and on days 2, 3, 4, 5, 7, and 10 after the wounding. The levels of 125I-Sar1.Ile8-AII bound to membrane preparations of the wound tissues decreased at early time points (from 0.5 to 4 h), increased from day 1 to day 7, and returned to nonsurgical levels by day 10. Competitive binding studies showed that the receptors were predominantly of the AT1 receptor subtype. These results suggest that an immediate and transient reduction in AII receptor expression occurred after wounding, followed by an increase in the number of AII receptors that was maintained for 5 to 7 days postoperatively. Because these data are consistent with those observed after excisional wounding, temporal changes in AII receptor expression may be integral to the process of wound healing.

Expression of cyclin protein after thermal skin injury in a guinea pig model.

In this study, an immunohistochemical stain for cyclin was used to quantitate proliferating elements in hair follicles at the edge of and within thermal burn areas. Biopsy specimens from thermal injury in the guinea pig (day 1 through day 28) were sectioned and stained with MIB-1 antibody, which recognizes cyclin, a protein expressed during epithelial cell proliferation. At the edge of the burn, 89 +/- 6.1 (SD) cells per medium power field (x 10, mpf) were MIB-1-positive on days 1 through 16. On day 17, the number of positive cells increased, reaching peak values on days 20 to 28 (271 +/- 12.7 cells/mpf). Within the burn, minimal staining was observed from day 1 to day 15 (12.7 +/- 1.6 cells/mpf). Thereafter the number of MIB-1-positive cells increased and plateaued with an average of 96.4 +/- 9.0 cells/mpf on days 20 through 28. In conclusion, immunohistochemical staining of dermal biopsy specimens with MIB-1 antibody may provide a quantitative method for the evaluation of tissue damage and healing after thermal injury.

[Mediastinal mature teratoma with elevated serum SCC levels--a report of 2 cases].

This is a report of two cases of mature mediastinal teratoma associated with elevated serum SCC levels. The first patient was a 17-year-old female admitted to our hospital for severe left chest pain. Chest x-ray film and CT scan showed a mediastinal tumor. The preoperative serum SCC level was elevated. Resection was performed and the pathological diagnosis was mature teratoma. The second patient was a 32-year-old male admitted to our hospital for severe anterior chest pain. A chest CT scan showed a mediastinal tumor. The preoperative serum SCC level was high. Surgery was performed and the pathological diagnosis was mature teratoma. The cause of the high serum SCC levels was unclear, but we suspect that the pulmonary atelectasis may have caused it.

[Effect of preoperative concurrent chemo-radiotherapy for thymic carcinoma].

Ten cases of thymic carcinoma were operated in our hospital from 1975 to 2000. Preoperative concurrent chemo-radiotherapy was performed in 3 cases among them according to same protocol. The 3 patients had same poorly differentiated carcinomas. They underwent 2 courses of systemic chemotherapy [cisplatin (CDDP) + etoposide (VP-16)] with concurrent radiotherapy (40 Gy). We had one complete-response, one partial-response and one no-response by the induction therapy. Only the no-responder underwent one more course of chemotherapy [CDDP + gemcitabine (GEM)]. Operations were performed four weeks after the end of the induction therapy. All patients underwent complete resections, but the no-responder needed cardiopulmonary bypass for combined resection of right atrium. Two cases are living without recurrence more than 2 years and half, but the no-responder died from infection (empyema) at 34th postoperative day. Therefore, it was revealed that the induction concurrent chemo-radiotherapy for thymic carcinomas is extremely effective for some patients but invalid for other cases.

[Surgical osteoplasty of the left main coronary artery using the right internal thoracic artery].

A 39-year-old female with a history of progressive refractory angina required medical treatment. A coronary angiography showed 75% left coronary ostial stenosis without any other atherosclerotic lesions. The isolated ostial stenosis of the left main coronary artery was reconstructed by patch angioplasty, using a proximal segment of the right internal thoracic artery. The transaortic patch angioplasty was performed using a superior approach, which allowed a good exposure of the left coronary artery to the aorta without difficulty. A postoperative coronary angiography showed satisfactory patency, and a small biopsy of the ostial tissue demonstrated findings compatible with fibromuscular dysplasia. Based on this outcome, a proximal segment of the internal thoracic artery appears to provide a suitable patch material for enlarging the left coronary ostium.

[Surgically treated cases of pulmonary arteriovenous fistula].

We report three cases of pulmonary arteriovenous fistula (PAVF) in which we performed limited resection. Case 1: female, 75 of age. CT and pulmonary angiography revealed PAVF of 2 cm in diameter in the right S8, and partial resection was performed. Case 2: female, 45 of age. CT and pulmonary angiography revealed PAVF of 7 cm in diameter in the right S10, and occlusion of fistula was performed. Case 3: male, 43 of age. CT pulmonary angiography and 3 D-CT revealed PAVF of 3 cm in diameter in the right S6, and occlusion of fistula was performed. The last case was accompanied by Rendu-Osler-Weber disease. Three patients showed a good postoperative course, without developing new fistula. Occlusion of fistula allows to close feeding artery and draining vein safely and securely. Considering invasion and preservation of pulmonary function after surgery, occlusion of fistula may be a primary option for treating PAVF.

[A case of primary malignant fibrous histiocytoma of the lung].

A 68-year-old woman presented with a complaint of coughing and chestroentgenography and computed tomography revealed a very large, irregular mass in the left inferior lobe of the lung. The suspected preoperative diagnosis was sarcoma. Therefore, a complete resection of that mass was considered to be difficult. The patient received preoperative chemotherapy including cisplatin with vindesine as employed for non-small cell lung cancer. She demonstrated a clinical response after three cycles of the chemotherapy and underwent surgery successfully. A postoperative diagnosis of MFH was made based on the histology of the tumor, which was pleomorphic with a storiform pattern. The tumor cells showed positive immunostaining for alpha 1-antitrypsin and alpha 1-antichymotrypsin but were negative for SMA and S-100 protein. The patient underwent a further three cycles of postoperative chemotherapy and has remained disease-free for 12 months after tumor resection.

[A case report of mitral valve aneurysm].

A case of aneurysm of the mitral valve associated with aortic valve regurgitation is presented. The patient was 45-years-old female who complained of palpitation and underwent both aortic and mitral valve replacement. We could not detect the aneurysm by the transthoracic echocardiography because of it's small size (14 mm in diameter). The transesophageal echocardiography showed the aneurysm of the anterior mitral valve leaflet toward the left atrium clearly. This report describes that transesophageal echocardiography appears to be available for accurate diagnosis of the mitral valve disease, especially for the mitral valve aneurysm.

[Ruptured bronchial artery aneurysm; report of a case].

A 74-year-old man who went into shock following an acute hemomediastinum and left hemothorax was operated on. Postoperative angiographies revealed a saccular aneurysm of the left bronchial artery of 2.0 cm in diameter. Sixty days after the initial operation, the aneurysm was resected under F-F bypass. A saccular aneurysm was found at the root of the left bronchial artery, which had a very short segment between the aneurysm and the aorta. Pathological study of aneurysm revealed thinning of the wall and lack of tunica media.

[A case of lung cancer (small cell carcinoma) occurring esophago-pericardial fistula and purulent pericarditis].

A 72-year-old woman who had had an endoscopic sclerotherapy for esophageal varices presented with high fever and severe cough. Chest X-ray and CT demonstrated a pneumopericardium and pericardial effusion. Esophagoscopy and esophagography revealed an esophageal perforation into the pericardial cavity and into the lung. Consequently, drainage and irrigation of the pericardial cavity and mediastinum were done for MRSA infection. However, these procedures failed to reduce the inflammation, and she expired because of liver failure soon after placing a covered stent in the esophagus. Postmortem examination revealed small cell carcinoma in the left lung invading into the esophagus and pericardium.

[Postoperative chylothorax treated with fibrin glue and absorbent mesh: a case report].

A 66-year-old man was treated by graft replacement for a thoracic aortic aneurysm. Chylothorax occurred on postoperative day 2. In spite of cessation of oral intake and IVH management, chest tube drainage did not decrease, the patient became malnourished. A chest X-ray and CT scan revealed the massive pleural effusion. Reoperation assisted with a thoracoscopy was carried out for chylothorax on postoperative day 27. Because we were unable to find the thoracic duct and the leakage point, the fibrin glue and absorbent mesh was applied to parietal and mediastinal pleura. Four days after reoperation, the chest tube was removed. This method is useful for this type of a chylothorax and lymphorrhea.

[A Rastelli operation with a reconstruction of the central pulmonary artery for a pulmonary atresia with an absent left pulmonary artery].

A Rastelli procedure was successfully performed on a 6-year-old girl with an absence of the intrapericardial pulmonary artery and the left pulmonary artery (PA), following a right B-T shunt. The central PA was reconstructed with an 18 mm diameter xenopericardial roll behind the ascending aorta and the superior vena cava. After intracardial repair, the Rastelli operation was performed using an 18 mm diameter composite graft which consisted of a valved xenopericardial roll and a knitted Dacron graft. Since the size of the right PA was large enough to undergo this surgical procedure (the preoperative right PA index was 300 mm2/m2), the postoperative peak systolic pressure ratio of the right ventricle to the left ventricle declined from 1.0 to 0.64. Although the patient showed slight signs of right ventricular failure on the operative day, the postoperative course was uneventful.

[A case of intrapleural rupture of pulmonary arteriovenous fistula].

The hemothorax due to rupture of arteriovenous fistula is very rare and only 6 cases of this complication have been reported in Japanese literature. 44-year-old male complained of chest pain and dyspnea. A chest roentgenogram revealed right pleural effusion and an abnormal pulmonary shadow. By further examination including pulmonary angiography, the rupture of pulmonary arteriovenous fistula into right pleural cavity was diagnosed. Partial resection of the right lung containing arteriovenous fistula was successfully performed and postoperative course was uneventful.

Endovascular treatment for dural arteriovenous fistula of the anterior condylar confluence involving the anterior condylar vein. A report of two cases.

SUMMARY: Anterior condylar confluence (ACC) dural arteriovenous fistula (AVF) is a rare anomaly. We describe two cases of ACC dural AVF involving the anterior condylar vein that were successfully treated with selective transvenous coil embolization. The first patient presented with headache and right pulse-synchronous tinnitus, and demonstrated abnormal flow medial to the jugular bulb within the right hypoglossal canal on source image of magnetic resonance angiography (MRA). Arterioangiography disclosed a dural AVF in this area, supplied mainly by the meningeal branches of the bilateral ascending pharyngeal artery. We diagnosed ACC dural AVF involving the anterior condylar vein and transvenous embolization was successfully performed. The second patient presented with right pulse-synchronous tinnitus. Views of source image of MRA and arterioangiography were similar to the first case and, again, transvenous embolization was successfully performed. ACC dural AVF is a rare condition and knowledge of the anatomy of the venous system around the craniocervical junction is required for successful treatment.