Effect of membrane solubilization on the inhibition of rat and hamster liver microsomal type I 11ß-hydroxysteroid dehydrogenase by bile acids.

The aim of this study was to investigate the differences between rats and hamsters, Two of the most widely used experimental animals, with respect to the effects of microsomal membrane solubilization on the inhibition of liver 11ß-hydroxysteroid dehydrogenase (11ß-HSDI) enzyme by bile acids. Liver microsome fractions were prepared, and the 11ß-HSDI enzymatic activity was measured using cortisone as a substrate. The substrate and various concentrations of bile acids were added to the assay mixtures. After incubation, the products were extracted and analyzed using high-performance liquid chromatography. To investigate the effect of detergent on the inhibitory effects of bile acids, we conducted inhibition tests using Triton X-100-solubilized animal liver microsomes. When solubilized microsomes were used, all bile acids inhibited 11ß-HSDI from rats and hamsters to various degrees. 7α-Hydroxycholanoic acids (cholic acid and chenodeoxycholic acid) in particular had strong inhibitory activities. In hamsters, 7ß-hydroxycholanoic acid (ursodeoxycholic acid) was the strongest inhibitor among the bile acids tested, although its effect was not very strong. When nonsolubilized microsomes were used, deoxycholic acid did not inhibit but rather enhanced the enzymatic activity in both animals. Microsomal content of cholesterol and phospholipids are significantly different between rats and hamsters. Species differences in bile acid inhibition of nonsolubilized microsomes might be reflected not only by structural difference of bile acids, which affect membrane solubilization and enzyme activity directly, but also species difference in microsomal membrane lipid content.

Recurrence of thymoma: clinicopathological features, re-operation, and outcome.

BACKGROUND: Even after complete resection, recurrence of thymoma is not infrequently observed, and treatment of recurrent thymoma remains controversial. STUDY DESIGN: One hundred and twenty-six patients underwent surgically complete resection for thymoma, and 24 of them had a recurrence. Surgical treatment of recurrent thymoma was attempted in 15 patients for a total of 18 times. In the present study, the relevance of clinicopathological features and the re-operation on the survival rate after the recurrence were determined. RESULTS: The most frequent recurrent type was pleural dissemination (92%), with local recurrence observed in 5%. Overall 5- and 10-year survivals after recurrence were 37 and 16%, respectively. Disease-free interval after initial operation and complication of myasthenia gravis had no significant effect on postrecurrent survival. The use of postoperative mediastinal irradiation had no effect on reducing the recurrence rate or improving survival after recurrence. Two of 15 patients who underwent re-operation died of major complications after It. pleuropneumonectomy for severe pleural dissemination. In the present study, the re-operation was not significantly effective for prolongation of postrecurrence survival. CONCLUSION: Our study showed that re-operation should not be attempted for all patients with recurrent thymoma. Because effect of subtotal resection for severe pleural recurrence is disappointing, total resection for minimal pleural dissemination or small local recurrence will be undertaken to improve postrecurrent survival. Careful follow-up for > 10 years will increase the chance of the total resection of the recurrent thymoma.

Pulmonary epithelioid hemangioendothelioma coexistent with pulmonary metastasis of thyroid cancer.

We report a 45-year-old man with epithelioid hemangioendothelioma (EH) and simultaneous pulmonary metastasis of thyroid cancer in his lung. Thyroid cancer, and multiple small nodules in both lungs were noted. He underwent total thyroidectomy followed by radiotherapy with 131I. However, 131I scintigraphy showed poor uptake of radionuclide in the nodules, and the size of the nodules remained unchanged. The diagnostic thoracoscopic biopsy showed two types of nodules, some were positive for thyroglobulin and cytokeratin, and others were reactive for factor VIII. The former nodules were diagnosed as pulmonary metastases of thyroid cancer, and the latter EH.

Clinicopathological significance of core 2 beta1,6-N-acetylglucosaminyltransferase messenger RNA expressed in the pulmonary adenocarcinoma determined by in situ hybridization.

Cell surface carbohydrates of epithelial cells play important roles in tumor progression. Previously, we have shown that expression of core 2 branched O-glycans in colorectal cancer is closely correlated with the vessel invasion and depth of invasion (K. Shimodaira et al., Cancer Res., 57: 5201-5206, 1997). To test whether this is also the case in human lung cancer, we have examined the expression pattern of core 2 beta1,6-N-acetylglucosaminyltransferase (C2GnT) mRNA responsible for the biosynthesis of core 2 branched O-glycans in 41 cases of lung cancer. Using in situ hybridization, C2GnT mRNA was detected in 73.2% of the lung cancer cells, irrespective of the histopathological type; whereas in normal lung tissues, its expression was restricted to the basal cells of bronchial mucosa. These results indicate that the expression level of C2GnT mRNA was significantly enhanced in association with malignant transformation. Statistical analysis between the C2GnT mRNA expressed in pulmonary adenocarcinoma and clinicopathological variables revealed that the expression of C2GnT was correlated with vessel invasion and lymph node metastasis with significant difference (P < 0.05), but expression of sialyl Le(x), which is frequently expressed in the adenocarcinoma, was not significantly correlated with lymph node metastasis. These results indicate that C2GnT mRNA detected by in situ hybridization reflects the malignant potentials of pulmonary adenocarcinoma, because lymph node metastasis is the most affecting factor to the patients' prognosis.

[Clinical study of operated nine thymic carcinomas].

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.

[Assessment of the new TNM classification for resected lung cancer].

To evaluate the revised TNM classification, we investigated the prognoses of 552 consecutive patients who had resection of non-small-cell lung cancer between April 1982 and March 1996. According to the new classification, the 5-year survival rate was 76.9% for stage I A, 57.2% for stage I B (I A versus I B, p < 0.0005), 47.7% for stage IIA, 49.8% for stage IIB, 18.6% for stage IIIA (IIB versus IIIA, p = 0.005), 16.7% for stage IIIB, and 7.9% for stage IV (IIIB versus IV, p = 0.02). Especially for patients in stage I A, there was significant difference in survival between patients with the tumor size within 1.5 cm and those with larger than 1.5 cm. The survival rate for T3N0M0 patients was significantly better than that for T3N1-2M0, but there was no significant difference between patients with T3N0M0 disease and those with T2N1M0 disease. Concerning the pm1 patients, the survival rate was significantly better than other stage IIIB patients. Our results supported the revision for dividing stage I and putting T3N0M0 into stage IIB. However, the classification is controversial about dividing stage II and putting pm1 as T4 disease. Furthermore, subgrouping of T1N0M0 disease by tumor size, T3 by tumor invaded organ will be necessary in the next revisions.

[Two cases of the bronchial cyst located in the anterior mediastinum].

Bronchial cysts are common cystic tumors around the tracheobronchial tree in the middle and posterior mediastinum and rarely locate in the anterior mediastinum. We reported two cases of the bronchial cyst located in the anterior mediastinum. One case was a 57 year-old-female. A thymic cyst was suspected and the extended total thymectomy was performed through the mediansternotomy. The microscopic examination showed bronchial epithelium and cartilage in the cystic wall. The another case was 71 year-old-male operated by thoracoscopic surgery for the cystic tumor in the anterior mediastinum. Microscopic examination showed bronchial epithelium and gland in the cystic wall.

[A case of thymic carcinoid with multiple endocrine neoplasm (MEN)-type I].

We presented a case of thymic carcinoid with MEN type I. A 43-year-old woman who followed at MEN type I for 4 years was pointed out an abnormal shadow by chest X-ray. Chest CT levealed the presence of two anterior mediastinal tumors. Extended total thymectomy was performed through the median sternotomy. There were 3 tumors in thymus. Histological examination revealed three tumors in the thymus and all of the tumor were diagnosed carcinoid. Our experience suggests that CT or MRI of the chest should be considered as part of clinical screening in patients with MEN type I.

[Catamenial pneumothorax under video-assisted thoracoscopic surgery: a case report].

A 46-year-old woman complained four times of chest pains due to repeated right pneumothorax. This was improved by the right thoracic drainage each time. She was diagnosed as having catamenial pneumothorax from the fact that each episode of pneumothorax began with the first day of her menstrual cycle. She was admitted to our hospital in Jan. 1996 and operated on by the obliteration of pleuro-peritoneal fistulas on right diaphragm under video-assisted thoracoscopic surgery (VATS). No other abnormal lesions were found in the right pleural cavity and right lung. In this case, the pathophysiological mechanisms of pneumothorax might have been caused by the air influx from the peritoneal cavity to the right pleural cavity through the fistulas on the right diaphragm. VATS is minimally invasive surgery and very useful for the treatment of pleuro-peritoneal fistulas on the diaphragm. It should be emphasized that hormonal therapy is necessary after VATS of catamenial pneumothorax.

[An evaluation of pathologic T3 lung cancer].

A total of 35 pT3 patients of lung cancer underwent pulmonary resection from 1983 to 1997 in our department. The overall five-year survival rate of the 35 cases was 35.8%. There was no significant difference between the five-year survival rate of squamous cell carcinoma and that of adenocarcinoma. A superior outcome was observed for cases of curative resection compared with that of non-curative resection. Five-year survival rates of 19 patients with N0 disease, 16 patients with N1 or N2 disease were 46.6% and 22.2% respectively (p < 0.05). There was no significant differences among the survival rates according to the site of tumor invasion. We concluded that the long-term survival of patients with pathologic T3 disease critically depended on the lymph node state and completeness of resection.

Chronic cholecystitis following hemobilia due to traumatic intrahepatic injury.

We report a patient who presented with colicky abdominal pain, hematemesis, and melena following a blunt abdominal injury sustained in an automobile accident. Serologic tests suggested liver dysfunction and computed tomography (CT) revealed dilatation of the intrahepatic bile duct. Duodenoscopy demonstrated hemobilia originating from the duodenal papilla of Vater. Angiography revealed a pseudoaneurysm of the hepatic artery and angiographic embolization sucessfully stopped the hemorrhaging. However, even following the angiographic embolization, the patient remained symptomatic and repeat CT demonstrated thickening of the gallbladder wall and a lesion resembling a blood clot. We strongly suspected cholecystitis and performed a laparoscopic cholecystectomy. Grossly, the resected specimen revealed wall thickening with a congested mucosa and three blood clots; histologically, these changes were consistent with a diagnosis of chronic cholecystitis. The clinical message of this paper is that patients should be observed for this usual complication of hemobilia after liver injury.