Expression of Stem Cell Factor in Feline Mast Cell Tumour.

Stem cell factor (SCF) is a ligand of the molecule Kit, which is expressed in mast cells and is important for mast cell proliferation, migration and survival. Mast cell tumours (MCTs) are associated with mutations of c-kit, a proto-oncogene encoding the Kit protein. In this study, we examined SCF expression in 23 samples of feline MCTs. SCF expression was detected in 10 cutaneous MCTs and a case of splenic mastocytosis. In the cutaneous MCTs, SCF-positive tumour cells were located at the margins. Kit was expressed in eight of the 10 cutaneous cases of SCF-expressing MCTs. In these cases, Kit-positive cells were located near to SCF-positive cells, and SCF/Kit double-positive tumour cells were found. Ki67-positive tumour cells were not found near to SCF-positive cells. These results suggest that SCF autocrine/paracrine mechanisms are involved in the expansion of cutaneous MCTs, but not in tumour proliferation.

In vivo metabolism of a new anticancer agent, 6-N-formylamino-12, 13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3,4-c]carbazole-5,7(6H)-dione (NB-506) in rats and dogs: pharmacokinetics, isolation, identification, and quantification of metabolites.

6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3, 4-c]carbazole-5,7(6H)-dione (NB-506), a potent inhibitor of DNA topoisomerase I, is currently under development for the treatment of cancer. We investigated the pharmacokinetics of NB-506 after i.v. administration in rats and dogs. The plasma concentration of NB-506 decreased biexponentially in rats and dogs with terminal half-lives of approximately 2 h. The area under the curve increased nonlinearly with increasing dose in rats. In contrast, there was a linear relationship between the area under the curve and the dose in dogs. In rats, the plasma clearance decreased with increasing dose up to 187.5 mg/m2 but remained virtually unchanged at the highest dose. The Vdss of NB-506 in rats and dogs was much greater than the plasma volume, indicating that NB-506 is highly distributed to tissue from plasma in these animals. There were marked species differences in the plasma concentrations of ED-501 after i.v. administration of NB-506 to rats and dogs. To better understand the mechanisms of nonlinear pharmacokinetics in rats, in vivo metabolites were determined. After i.v. administration of [14C]NB-506 to rats, two unknown metabolites (RBM-1 and RBM-2), deformyl metabolite (ED-501), and unchanged drug (NB-506) were identified. Mass and NMR spectra analysis revealed that RBM-1 is an 11-O-glucuronide of NB-506 (ED-594) and that RBM-2 is an 11-O-glucuronide of ED-501 (ED-595). In this study, the pharmacokinetics of NB-506 was demonstrated to be nonlinear in rats, probably because of saturation of the enzyme systems catalyzing the deformylation and glucuronidation of NB-506 in rats.

[Direct approach to the site of injury of the thoracic duct in treatment of chylothorax after pulmonary resection].

Chylothorax, a rare complication after pulmonary resection, has no single established treatment. Generally, conservative therapy is tried first, but surgery should be done without delay if chyle leakage is severe. A 73-year-old woman underwent upper left lobectomy for lung cancer. Two days later, chylothorax was diagnosed, and because chyle leakage was great, emergency re-thoracotomy was done on day 4 after the first operation. With the preoperative ingestion of 200 ml of milk and 20 g of margarine, chyle leakage from the injured thoracic duct was readily located in the upper mediastinum. Closure of the trunk of the thoracic duct may be undertaken, but a direct approach to the site of injury is more preferable, because the trunk may have collateral.

[Differential diagnosis between peripheral lung cancer invading the chest wall and chest-wall tumors].

Preoperative histological diagnosis of lung cancer is usually based on findings from a transbronchial biopsy specimen of the tumor obtained through a fiberoptic bronchoscope. However, peripheral pulmonary tumors can be difficult to diagnose in this way. We report two patients with lung cancer invading the chest wall for whom histological diagnoses were not possible by transbronchial biopsy. Treatment for lung cancer is different from that for chest-wall tumors, so preoperative differential diagnosis of these conditions is important. Other organs should be searched to exclude metastatic chest-wall tumors. Percutaneous needle biopsy done under ultrasonic guidance made the histological diagnosis of lung cancer possible in both cases.

[Flap of the musculus latissimus dorsi to prevent alveolar air leakage from sectional plane of the lung after resection of metastatic pulmonary and chest wall tumor].

Alveolar air leakage after pulmonary resection usually heals with adequate pleural drainage, but must be more actively treated if leakage may be severe. If left untreated, the postresection space can lead to empyema. We used a muscle flap to prevent alveolar air leakage from a large sectional plane of the lung resected because of metastases in the lung and chest wall. A 48-year-old man complained of pain and a mass on the right side of his back. He had undergone resection and chemotherapy for clear cell sarcoma that originated on the back of the left hand when 43 years of age, wedge resection of the right lower lobe of the lung for a metastatic pulmonary tumor at 46 years, and lobectomy of the same lobe for a recurrence of the metastatic pulmonary tumor at 47 years. The diagnosis was of a metastatic tumor to the right chest wall with peripheral pulmonary tumors of the right upper and middle lobes. Resection of the chest wall and the lung including the tumors was done. Much air leakage from the extensive sectional plane of the right upper and middle lobes was seen intraoperatively, and this plane was therefore covered with a flap of the musculus latissimus dorsi. Chest tubes were removed on day 7 postoperatively when air leakage was no longer seen. Subcutaneous emphysema, which appeared on day 14 postoperatively, required redrainage of the pleural air space, but pleurodesis was effective. Use of a muscle flap was simple and effective for covering of a sectional plane of the lung, and should be considered when alveolar air leakage may be extensive.

[Malignant lymphoma of the chest wall in a patient with chronic empyema].

A 76-year-old man presented with the chief complaints of appetite loss and general fatigue. He was admitted with the initial diagnosis of empyema necessitatis, and right thoracic drainage was performed. Nevertheless, the subcutaneous mass in the right side of the chest wall did not shrink, and examination of a specimen obtained by percutaneous needle biopsy resulted in the diagnosis of non-Hodgkin's lymphoma, intermediate lymphocytic type. The patient was treated with Adriamycin, vincristine, prednisolone, and cyclophosphamide, but died of pneumonia and cachexia five months after symptoms first appeared. The diagnosis of intermediate lymphocytic lymphoma, B cell type was made at autopsy. Only 53 cases of malignant lymphoma associated with chronic empyema have been reported in Japan. Surgery was often not done because of the patient's advanced age or poor pulmonary function; diagnosis was often difficult. However, review of the 53 reported cases suggested that resection of the tumor, if possible, would improve the prognosis. Malignant lymphoma should be considered when there is chronic empyema, because such cases are now being reported more frequently.

Extension of surgical indications for hepatocellular carcinoma by portal vein embolization.

We studied, clinically and experimentally, hypertrophy of the part of the liver not embolized after portal vein embolization (PVE). The subjects of the clinical study were 29 patients with hepatocellular carcinoma (HCC) who underwent embolization of the right first portal branch; 19 patients had cirrhosis, and 10 did not. The volume of the liver was calculated from computed tomograms obtained before PVE and 2 weeks after. In all patients, the volume of the nonembolized (left) lobe increased significantly. For the experimental study, we used male Wistar rats. Normal rats were untreated, and in the other rats cirrhosis was induced with carbon tetrachloride. The portal branch that supplies 70% of the total volume of the liver was embolized. The rats underwent one of four procedures: 70% PVE, 70% portal vein ligation, 70% hepatectomy, or laparotomy only. Rats wre killed at different times after surgery, and the livers were removed and weighed. The mitotic index and DNA synthesis were measured in the nonembolized lobe (PVE group), in the lobe not supplied by the ligated branch (ligation group), or in the remaining liver (hepatectomy group). The liver weight, mitotic index, and DNA synthesis were high in the PVE, ligation, and hepatectomy groups for both normal rats and rats with cirrhosis. PVE caused cell proliferation and hypertrophy in the nonembolized part of the liver in the normal rats and even in those with cirrhosis. We concluded that PVE can extend the surgical indications for patients with HCC and underlying cirrhosis.

[Preoperative percutaneous transhepatic portal vein embolization to extend the indications for hepatectomy and to increase the safety of extended hepatectomy for hepatocellular carcinoma].

The usefulness of preoperative percutaneous transhepatic portal vein embolization (PTPE) in extending the indications for hepatectomy and increasing the safety of extended hepatectomy for hepatocellular carcinoma was studied in 21 patients who underwent right hepatic lobectomy with PTPE of the right first portal branch (group E), in 15 such patients but without PTPE (group N), and in seven such patients who underwent PTPE at this location but could not undergo surgery (group U). The mean volume of the left lobe increased but the results of a 15-minute indocyanine green retention test were worsened 2 weeks after PTPE and again 4 weeks after hepatectomy, but these changes after hepatectomy were almost the same in groups E and N. The worsening of liver function and coagulation test results was less in group E than in group N. The mean prognosis score was better in group E two weeks after PTPE than before, but not in group U. The four patients in group E with high portal vein pressure (> or = 30 cmH2O) or a high prognosis score (> or = 50 points) after PTPE developed hepatic failure after surgery. Preoperative PTPE was useful in extending the indications for hepatectomy and increasing the safety of extended hepatectomy. Evaluation of the clinical course after PTPE was also useful when decisions about the operative method to be used were being made.

[Preoperative portal vein embolization for hepatocellular carcinoma].

We performed preoperative portal vein embolization (PVE) for 71 patients with hepatocellular carcinoma (HCC), 59 of whom underwent hepatectomy about two weeks after PVE. The purpose of the PVE was usually to embolize the portal vein supplying the area to be resected. After PVE, the non-embolized part of the liver became hypertrophic and the embolized part of the liver became atrophic. Of the 22 patients who underwent right lobectomy after PVE of the right first branch of the portal vein, the mean results of a test of 15-minute indocyanine green retention after PVE increased significantly less than the mean for six patients who could not undergo right lobectomy after PVE of their right first branch. The extent of this increase and the liver volume of the left lobe 4 weeks after right lobectomy were higher in another 15 patients who did not undergo PVE than 22 patients who underwent PVE. PVE is useful as one preparation for hepatectomy of patients with HCC, because the embolized part of the liver was damaged by PVE, but mean liver function was compensated by the part of the liver that was not embolized and regenerated.

[Case of primary aorto-jejunal fistula caused by gram-positive cocci].

A 46 year-old man was transferred to our department with a pulsating abdominal mass and back pain. On arrival he suddenly developed hematemesis. CT suggested the presence of an infrarenal aortic aneurysm and the jejunum was filled with contrast medium. An emergency operation was done. We found an aorto-jejunal fistula at the branching point of the renal artery. We directly sutured the aortic wall laceration and the jejunum wall in two layers. Then we resected infrarenal pseudoaneurysm as completely as possible, with replacement by a Dacron Y-shaped prosthesis. Culture of the aortic wall showed gram-positive cocci, but the species could not be identified. Gram stain of the aortic wall also showed infection by gram-positive cocci. The patient is alive and well 3 months after surgery.

[Measurement of portal blood flow in man by a continuous local thermodilution method. III. Effects of dopamine on systemic and portal hemodynamics after hepatectomy].

We gave dopamine (3 micrograms/kg/min, 30 min) intravenously on the third day after hepatectomy to 19 patients, and studied the effects of the drug on systemic and portal hemodynamics. In another 42 patients, administration of dopamine at the same rate was started soon after hepatectomy and continued for about 2 weeks; the clinical results were evaluated. After hepatectomy, the systemic hemodynamics were hyperdynamic and the portal hemodynamics were hypodynamic. After 30 min of dopamine administration, the oxygen pressure in portal blood increased, and because portal blood flow also increased, the oxygen delivery to the liver increased. The mechanism involved an increased proportion of portal venous flow to cardiac output, and a decrease in the splanchnic resistance, not portal venous resistance. Probably, specific dopamine receptors played important role in the increase in the superior mesenteric arterial blood flow. Among 42 patients given small dosage of dopamine, the clinical symptoms of five of seven who had developed liver failure improved. None of the other 35 patients given dopamine preventively developed liver failure. Dopamine in small doses is useful for the management of liver failure after liver resection.

Results of treatment of patients with hepatocellular carcinoma with severe cirrhosis of the liver.

We retrospectively classified patients with hepatocellular carcinoma by the results of tests of 15-minute indocyanine green retention (ICGR15). Of the 201 patients with hepatocellular carcinoma admitted to our department in the past 6 years, 36 patients were assigned to group 1 (ICGR15 less than 10.0%), 81 patients to group 2 (ICGR15 = 10.1-20.0%), and 84 patients to group 3 (ICGR15 greater than or equal to 20.1%). Of the total 201 patients, 72% underwent liver resection (78% of group 1 patients, 80% of group 2 patients, and 62% of group 3 patients). We regarded the cirrhosis of the patients in group 3 as severe and studied their survival rate classified by the treatment used. Of these 84 patients, 52 patients were treated by liver resection, about half of whom were treated preoperatively by transcatheter arterial embolization (TAE). Another 9 patients were treated preoperatively by both TAE and portal vein embolization (PVE). At 2 years, and again at 3 years, the survival rate was significantly higher when TAE was used preoperatively than with resection alone. We think that the possibility of performing needed liver resection will be enlarged by preoperative PVE and that liver resection can be done more safely after use of PVE in some patients.

Resection of hepatocellular carcinoma with obstructive jaundice caused by compression of the common hepatic duct.

We treated a patient with hepatocellular carcinoma in whom jaundice was caused by obstruction of the common hepatic duct because of compression by the tumor. Percutaneous transhepatic cholangiodrainage was performed preoperatively. The tumor was entirely in the medial segment of the liver, without invasion of the hepatic ducts, and medial segmentectomy was performed. As of the end of 1985, 58 cases of hepatocellular carcinoma complicated by extrahepatic obstructive jaundice have been reported in Japan. In only four was obstructive jaundice caused by extraluminal biliary compression. We review ten patients treated by liver resection.

[Chemotherapy of balloon-occluded arterial infusion in a patient with unresectable hepatocellular carcinoma and autoimmune hemolytic anemia].

The patient, a 76-year-old woman, was found to have a tumor in the epigastrium in April 1983 and was admitted to our hospital. She was diagnosed as having hepatocellular carcinoma in the left lobe of the liver with intrahepatic metastases in the right lobe. The patient also had autoimmune hemolytic anemia. Because of this condition and the metastases, we decided that the tumor was not resectable. Transcatheter arterial embolization was unsuccessful, and therefore, beginning on June 28, 1983, the patient was treated three times using balloon-occluded arterial infusion of 10 mg of mitomycin C and 30 mg of adriamycin into the proper hepatic artery. After these treatments, the serum alpha-fetoprotein level returned to normal levels. CT scans and hepatic angiography showed that the main tumor and the metastases had become smaller. The patient presently shows no evidence of disease, three years after treatment.