Masao Edagawa

Beneficial effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy

BACKGROUND A prospective study on the vasodilatory effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy is reported. METHODS Twelve patients with thoracic esophageal cancer who underwent esophagectomy were enrolled in this study. In all patients, the esophagogastrostomy was performed in the cervical region, and the stomach was used for reconstruction. Immediately after the creation of the gastric tube, baseline blood flow was measured at the oral end, in the center, and at the pyloric ring of the gastric tube using a laser Doppler flowmeter. The prostaglandin E1 group (n = 6) was then infused with prostaglandin E1 until postoperative day 2; the control group (n = 6) received saline. At +5 minutes and +40 minutes after administration, blood flow was again measured at the same three sites. RESULTS The control group did not show a significant increase of blood flow to any site over time. For the prostaglandin E1 group, blood flow at +40 minutes increased from the baseline measurements significantly at a rate of 63%, 39%, and 36%, respectively. CONCLUSIONS Prostaglandin E1 has a characteristic vasodilating effect on the area of impaired microcirculation of the gastric tube, thereby increasing blood flow to the affected area.

Clinical and immunohistochemical study of eight cases with thymic carcinoma.

BackgroundThymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate the biological characteristics of thymic carcinoma, we reviewed 8 patients.MethodsThere were 2 men and 6 women: ages ranged from 19 to 67 years old (mean 54.8 years). None of these patients had concomitant myasthenia gravis and pure red cell aplasia. No patient had stage I disease, 1 stage II, 5 stage III, and 2 stage IV. The pathologic subtypes of thymic carcinoma included 5 squamous cell carcinomas, 1 adenosquamous cell carcinomas, 1 clear cell carcinoma, and 1 small cell carcinoma. Immunohistochemical study was performed using antibodies against p53, bcl-2, Ki-67, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), nm23-H1, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and factor VIII.ResultsCurative resection could be done in 4 patients (50%). Our data indicates a trend toward an association between complete resection and patient survival. Expression of p53, bcl-2, CEA, EMA, nm23-H1, VEGF and FGF-2 was detected in 5/8, 3/8, 4/8, 5/8, 6/8, 5/8 and 3/8, respectively. Mean Ki-67 labeling index and microvessel density was 7.01 and 34.36 (per 200× field), respectively. When compared with our previous studies, immunohistochemical staining of these proteins in thymomas, the expression rates of these proteins in thymic carcinomas were higher than those in thymomas.ConclusionsIn this small series, it is suggested that a complete resection suggests a favorable result. Immunohistochemical results reveal that the expression of these proteins might indicate the aggressiveness of thymic carcinoma.

Distribution of Mast Cells in Mediastinal Lymph Nodes from Lung Cancer Patients

BackgroundMast cells have been documented to have several key functions with regards to malignant neoplasms. However, the functional significance of their accumulation is largely unknown. An analysis of the mast cell profile in mediastinal lymph nodes from lung cancer patients is reported here.MethodsOne hundred thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. All cancer negative nodes were obtained from stage I patients. Mast cells were stained with Alcian blue and safranin O. Metastatic cancer cells were stained using anti-cytokeratin antibody.ResultsImmunohistochemical studies with cytokeratin revealed micro metastasis in 9/71 (12.68%) nodes previously diagnosed as histological negative. In tumor-free mediastinal lymph nodes, the mast cell count was significantly higher than in metastatic nodes. In all cases, mast cells were observed primarily in the T-cell area.ConclusionsAn inverse relationship was observed between the number of mast cells and the amount of tumor tissue. The presence of mast cells primarily in the T-cell area implies a relationship between mast cells and the T-cell system. From the present study it is not possible to conclude whether mast cells in lymph nodes are for or against tumor spread.

Reduction of post-ischemic lung reperfusion injury by fibrinolytic activity suppression.

BACKGROUND Although extensive studies on the detailed mechanisms of ischemia-reperfusion injury have been conducted, the implication of the fibrinolytic system has not been known. To determine the role of the fibrinolytic system in ischemia-reperfusion injury, we used tranexamic acid, a synthetic specific plasmin and tissue-type plasminogen activator inhibitor, to suppress fibrinolytic activity in a rabbit lung ischemia-reperfusion model. METHODS New Zealand White rabbits were randomly divided into two groups: a simple ischemia group and a group injected with tranexamic acid before left hilar occlusion. After 2 hours of warm ischemia, plasma was collected from pulmonary vessels. Fibrin zymography was used to ascertain fibrinolytic activity, and enzyme-linked immunosorbent assay was used to determine soluble thrombomodulin levels as a marker for endothelial cells damage. Changes in left pulmonary function including arterial oxygen tension, peak airway pressure, and pulmonary vascular resistance were recorded during reperfusion after the 2 hours of warm ischemia. RESULTS Fibrinolytic activity and soluble thrombomodulin levels increased in the vessels of the ischemic lung, indicating endothelial cell injury. The increased fibrinolytic activity and the rise in soluble thrombomodulin were suppressed by the preadministration of tranexamic acid, resulting in remarkably improved pulmonary function during reperfusion. After 2 hours of reperfusion, the wet-to-dry weight ratios and histological studies showed reduced pulmonary edema in the group that had received tranexamic acid. CONCLUSION These findings suggest that the fibrinolytic system is involved in the onset mechanism of ischemia-reperfusion injury through induced endothelial cell damage and increased vascular permeability.

Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

BackgroundWe assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma.MethodsFormalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody.ResultsExpression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87).ConclusionsIn patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion.

Successful Treatment of a Bronchial Inflammatory Pseudotumor by Bronchoplasty in an 8-Year-Old Boy : Report of a Case

We report herein the rare case of an 8-year-old boy in whom an inflammatory pseudotumor of the upper lobe bronchus of the right lung was successfully treated by bronchoplasty. A bronchoscopy was initially performed to investigate the cause of pulmonary atelectasis in the right upper lobe, which revealed a tumor in the right main bronchus. Thus, a thoracotomy followed by bronchotomy of the right main bronchus was carried out. The tumor was seen to have polypoid protrusion into the right main bronchus at the orifice of the upper lobe. A bronchoplasty with a wedge resection of the right main bronchus and right upper lobectomy was carried out, effectively preserving right pulmonary function. Histological examination confirmed the diagnosis of an inflammatory pseudotumor. The patient had an uneventful postoperative course and has been free of recurrence for 3 years since his operation.

A case of pulmonary metastasis from breast cancer following an 18-year disease-free interval that responded to tamoxifen treatment.

A 61-year-old woman was admitted to our hospital with an abnormal shadow on chest roentgenogram. She had undergone a radical mastectomy for right breast cancer 18 years previously. Since pleural dissemination was noted at the time of thoracotomy, only tumor biopsy was performed. Although a decisive diagnosis could not be obtained histologically, the tumor resembled breast cancer and the estrogen receptor status was positive. She underwent post-operative chemotherapy and tamoxifen treatment. After tamoxifen treatment, complete response was observed. The patient is now doing well without recurrence about 10 years after thoracotomy. Based on the clinical course, we obtained both a definitive diagnosis and complete remission.

Protection of isolated lung from reperfusion injuries by rinsing with high colloidal osmotic solution with deferoaxmine.

We examined the efficacy of rinsing isolated lungs subjected to prolonged hypothermic storage with a high colloidal osmotic pressure solution prior to ex vivo blood reperfusion in order to preserve physiologic functions, suppress peroxidation of mitochondrial membranes, and inhibit infiltration of neutrophils. Isolated rabbit lungs were flushed with a Rinse-1 solution (289 mOsm/kg H2O) to remove remaining blood and immersed in physiologic saline at 8 degrees C for 24 hr. The control group received blood reperfusion immediately after storage; the Rinse-1 group was rinsed with Rinse-1 solution before blood reperfusion and the Rinse-2 group with Rinse-2 solution (312 mOsm/kg H20) including deferoxamine. Reperfused blood was passed through an artificial membranous lung to reduce oxygen tension (PO2) to the venous level, and time-dependent changes in airway pressure (AWP), pulmonary artery pressure (PAP), and PO2, as a measure of gas-exchange capability were examined. We estimated the lipid peroxide level in mitochondrial membranes as thiobarbituric acid-reactive substances (TBARS), i.e., malonedialdehyde, and neutrophil infiltration into lung tissue by measuring myeloperoxidase activity after 60 min of blood reperfusion. The PO2 was significantly higher in both rinsed groups compared with the control, while neither AWP nor PAP was significantly different in the three treatment groups. Both mitochondrial TBARS and myeloperoxidase activity were significantly higher in the control group compared with either rinsed group. These results indicate that rinsing stored lungs with a solution of high colloidal osmotic pressure prior to blood reperfusion was effective in preserving physiologic function and inhibiting neutrophil infiltration. Addition of deferoxamine was markedly effective in reducing TBARS formation and lessening reperfusion injury of stored lungs.

Lack of prognostic significance of tumor angiogenesis in resected pN2 non-small cell lung cancer.

OBJECTIVES Despite extensive studies of tumor angiogenesis in non-small cell lung cancer, only a few studies had concentrated on pN2 disease. METHODS Sixty patients with pN2 non-small cell lung cancer who had undergone a complete resection with a systematic mediastinal lymph node dissection were reviewed retrospectively. Immunohistochemical study, using antibodies against factor VIII, was conducted. We compared between 5-year survivors and the others rather than the cumulative survival rate. RESULTS There were 13 patients (21.7%) survived longer than 5 years after a surgical resection. The microvessel density in survivor and non-survivor group was 22.9+/-14.8 and 24.3+/-21.9, respectively. This data indicated that microvessel density might not be related to the ratio of 5-year survivors (P=0.723). Multivariate analysis also showed that microvessel density was not independent prognostic factor. CONCLUSIONS We failed to find a prognostic significance of tumor angiogenesis in pN2 disease. Although tumor angiogenesis might be important for the development and maintenance, it was not identified as a prognostic factor of pN2 non-small cell lung cancer.

A rapidly growing benign intrathoracic neurofibroma after lung lobectomy.

A 67-year-old male underwent a right upper lung lobectomy for lung cancer in January 1993. Follow-up chest X-rays revealed a progressive and rapidly growing intrathoracic mass in the right thorax. The mass, however, did not resemble a tumor recurrence, and the patient complained only of shortness of breath. Computerized tomography and magnetic resonance imaging confirmed the presence of the intrathoracic mass and its associated compression of the residual lung. A right thoracotomy was performed in January 1998, and a mass found arising from the sympathetic nerve trunk was resected. Microscopic examination revealed stellate or spindle-shaped cells in myxoid stroma with sparsely distributed collagen fibers. Immunohistochemically, the cells were positive for neuron-specific enolase, and the tumor was identified as neurofibroma. The patient did not suffer from von Recklinghausens disease, and there was no family history of the disease. After resection of the neurofibroma, the compressed lung was able to re-expand, and the patients shortness of breath disappeared. At one year postoperative, the patient remains well, and there is no evidence of recurrence.