Therapeutic effect of a CDDP-epirubicin-Lipiodol emulsion on advanced hepatocellular carcinoma

Prior injection of an anticancer agent and Lipiodol mixture is a key point for the treatment of hepatocellular carcinoma (HCC). We therefore prepared a new, improved emulsion of Lipiodol containing a high dose ofcis-diamminedichloroplatinum (CDDP) and epirubicin by replacing the ionic contrast medium (Urografin 67) with a nonionic contrast medium (Iopamidol; Iopamiron 300) and adding phosphatidyl choline. This CDDP-epirubicin-Lipiodol emulsion (CELE) was examined pharmacologically and chemically with the following results. The size of these particles is less than 10 m (diameter) for up to 24 h; the release of 28%–34% of the CDDP and 80%–90% of the epirubicin was estimated in the dissolution test, and 85% of the CDDP and 35% of the epirubicin was retained in the organs in the moment calculation. CELE was injected into 58 HCC patients via a celiac angiographic catheter. In 36 of these patients, the CELE injection was followed by transcatheter arterial embolization (TAE) therapy. Following the administration of CELE as one-shot injection therapy for stage IV HCC, the 1-year survival rate was 59% and the 2-year survival rate was 27%. Moreover, in patients (stage II, 12; stage III, 8; stage IV, 16) who received CELE and subsequently underwent TAE therapy, the 1-year survival rate was 90% and the 2-year survival rate was 67%. The nonionic contrast medium with Lipiodol forms finer emulsified particles, and these particles are more capable of penetrating into the tumor. In addition, the greater pharmacological stability of these particles provides a slow-release effect and prolonged stability of their shape. Finally, theoretically, the use of two major anticancer agents such as CDDP and epirubicin showed a greater clinical effect in the treatment of HCC than either our earlier suspension or a single anticancer agent.Work presented at the Third International Symposium on Treatment of Liver Cancer, Seoul, Korea, 12–13 February 1993     

Remaining solvents in dry cleaned over clothes]

We examined remaining solvents in dry cleaned trousers to estimate the magnitude of environmental pollution. A cleaning solvent of petroleum hydrocarbon was analyzed by means of capillary column mass spectrum gas chromatography. Principal ingredients were identified to be nonane, decane and undecane. The same main components were detected in dry cleaned trousers. Total amounts of evaporated vapor from a pair of trousers (480 g) in 5 days after dry cleaning were nonane (0.73 mg), decane (1.53 mg) and undecane (1.09 mg). The levels on the fifth day were 5%(nonane), 18%(decane) and 32%(undecane) of the first day's concentration, respectively. The half times of the remaining solvents were 1.0 day (nonane), 1.7 days (decane) and 2.7 days (undecane), respectively.     

A method for detection of a cytokine and its mRNA in the central nervous system of the developing rat

We report here an effective and concise method to determine the localization of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, and its mRNA in the central nervous system of pre- and postnatal rats. This method allows for double staining to demonstrate localization of different molecules on the same tissue specimen at the levels of mRNA and proteins by in situ hybridization and immunohistochemistry, respectively. Additionally, the present method gives results more quickly than the conventional isotopic techniques. By use of this method, we carried out immunohistochemistry with an anti-rat MIF polyclonal antibody and demonstrated positive staining using the avidin-biotin complex method (ABC method). To detect its mRNA, we performed nonradioactive in situ hybridization using a digoxigenin (DIG)-labeled RNA probe prepared from a full length fragment of rat MIF cDNA. MIF was strongly expressed in the telencephalon on embryonic day 16. Non-radioactive in situ hybridization with a DIG-labeled RNA probe as well as the immunohistochemistry described here could be applicable to characterize localization of mRNA and proteins of different molecules on the same tissue specimen.     

Inverted T graft: novel technique using composite radial and internal thoracic arteries

BACKGROUND: Multiple arterial revascularization is feasible because of the excellent long-term patency of the arterial grafts compared with venous grafts. We present a new operative technique for multiple arterial revascularization using composite radial and internal thoracic arterial grafts. METHODS: Between January and September 1997, 12 patients had coronary artery bypass grafting with inverted T graft. The indications for inverted T graft were aortic calcification in 4 patients, repeat coronary artery bypass grafting in 1 patient, and total arterial revascularization in 7 young patients. The inverted T graft was constructed by interconnecting the coronary arteries and radial artery with end-to-side and side-to-side anastomoses, and by anastomosing the internal thoracic artery to the side of radial artery. RESULTS: Overall, 38 distal anastomoses (average number per patient, 3.2) were made with an inverted T graft. There were no deaths or perioperative myocardial infarctions. Postoperative angiography disclosed that all of the anastomoses were patent. CONCLUSION: This technique allows multiple arterial revascularizations without technical difficulty. It is useful in patients with aortic calcification, repeat coronary artery bypass grafting patients, and young patients who are candidates for total arterial revascularization.     

Intraarterial chemotherapy for uterine cervical adenocarcinoma: evaluation of its efficacy as neoadjuvant therapy

We performed preoperative intraarterial chemotherapy in twenty cases of uterine cervical adenocarcinoma (stage Ib: 2, II: 15, III: 3) and evaluated the efficacy of this therapy. The dosages used were 75-120 mg of CDDP, 10-20 mg of MMC and 30-60 mg of EPIR. These drugs were administered by intraarterial one-shot infusion twice every three weeks. In five cases, complete response (CR) of the primary lesion was confirmed by histologic examination. There were no cases of CR inpatients with well differentiated adenocarcinoma. Stage reduction was achieved in all cases except three. In all but one case, more than 50% volume reduction was recognized on MR images. These results were not significantly different from those in cases of uterine cervical squamous cell carcinoma in which we performed this therapy. Therefore, we concluded that intraarterial chemotherapy is highly effective and should be carried out as neoadjuvant therapy for advanced uterine cervical adenocarcinoma.     

Resection and reconstruction of the great vessels for lung cancer and mediastinal tumor

Between January 1994 and December 1997, 17 patients with lung cancer and 5 patients with mediastinal tumor underwent extensive resection and reconstruction of the great vessels. In patients with lung cancer, the aorta was resected under cardiopulmonary bypass in 4 patients, the superior vena cava in 12, and the left main pulmonary artery with combined resection of the left atrium in 1 and the aorta in 1. In five patients who underwent resection of the superior vena cava, subcarinal resection and reconstruction were also performed. Three patients died within 30 days after surgery. Six patients died of cancer between 3 months and 2 years after surgery. Two patients who underwent aortic resection for node negative lung cancer have survived more than 3 years after surgery. Six patients have survived between 6 months and 2 years after surgery. The histologic type of mediastinal tumor was thymic cancer in 3 patients, invasive thymoma in 1 and malignant lymphoma in 1. In patients who underwent resection of the superior vena cava for mediastinal tumor, bilateral brachiocephalic vein reconstruction was performed in 4 patients and the left brachiocephalic vein reconstruction in 1. One patient underwent resection of the right atrium. The patient with invasive thymoma has survived for more than 3 years. Two of 3 patients with thymic cancer died within 2 years. When complete resection is achieved with combined resection of the great vessels, survival may be anticipated in patients with N0 lung cancer or in those with invasive thymoma.     

Role of reactive oxygen in phospholipase A2 activation by ischemia/reperfusion of the rat kidney

Purpose. To investigate the role of phospholipase A₂ (PLA₂) in reperfusion injury of the kidney in an in vivo animal model, renal mitochondrial PLA₂ activity was measured under three different conditions. Methods. Male Wistar rats (n = 72) anesthetized with pentobarbital underwent renal ischemia surgically for 45 min and were reperfused for the indicated time (renal ischemia/reperfusion). Treatments included reperfusion for various predetermined periods (phase 1), exposure to hyperbaric oxygen (phase 2), and administration of reactive oxygen species (ROS) scavenger (phase 3). Thereafter, each kidney was harvested, and mitochondrial PLA₂ activity was measured by a radioisotope technique. Results. Ischemia/reperfusion resulted in time-related PLA₂ activation in the renal mitochondria up to 48 h of reperfusion after renal ischemia. Renal mitochondrial PLA₂ activity was further augmented by hyperbaric oxygen exposure prior to reperfusion, whereas administration of the ROS scavengers suppressed mitochondrial PLA₂ activity. Conclusion. These data suggest that ROS may play an important role in the in vivo activation of PLA₂ associated with renal ischemia/reperfusion. Received for publication on July 6, 1998; accepted on November 30, 1998     

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: Report of a case

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutaneous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile, duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.     

Protective effects of the TNF-ceramide pathway against glutamate neurotoxicity on cultured mesencephalic neurons

Pretreatments with TNF-alpha and lower concentrations of C2-ceramide protected cultured mesencephalic neurons from excitotoxicity in a dose-dependent manner. These protective effects are reduced by cotreatment with N,N-dimethylsphingosine (DMS), an inhibitor of sphingosine kinase. Since the pretreatment with sphingosine-1-phosphate (SPP) showed a neuroprotective effect, our data suggest that protective effects of TNF and C2-ceramide could be attributable to their further metabolism to SPP.