Distal splenorenal shunt with splenopancreatic disconnection for portal hypertension in biliary atresia

This study evaluated the long-term effects of distal splenorenal shunt with splenopancreatic disconnection (DSRS-SPD) on portal hypertension (PH) in biliary atresia (BA) patients. Five patients with BA underwent DSRS-SPD at the age of 3.3 to 8.5 years. They had been free from jaundice after hepatic portoenterostomy (HPE); however, they gradually developed gastroesophageal varices and hypersplenism. Portal venous pressure after anastomosis was 37.2 ± 6.1 cmH₂O, as high as that before anastomosis (37.8 ± 3.3 cmH₂O). Postoperatively, liver function tests became worse within 2 weeks; however, they returned to preoperative levels within 1 month without any further treatment. No patient developed a significant encephalopathy throughout the observed period. During follow-up of 4 to 12 years, the shunt was patent in all patients. Spleen size decreased after operation. Abdominal-wall venous dilatation completely disappeared in two of four patients. The platelet counts gradually increased and were significantly higher 3 years (126.6 ± 59.3 × 10³/mm³) after DSRS-SPD than preoperative values (66.0 ± 24.2 × 10³/mm³). White blood cell counts showed no significant changes. No patient developed a gastrointestinal hemorrhage postoperatively, although three had had repeated hemorrhages before the operation. Two patients showed disappearance of varices endoscopically at 2 years and 7 months after DSRS-SPD, respectively, but had recurrent varices at 7 and 11 years, respectively. The endoscopic findings regarding varices 3 to 7 years after DSRS-SPD were as follows: decreased number (80%); decreased length (40%); improvement of form (20%); improvement of fundamental color (60%); disappearance of red-color sign (100%); disappearance of gastric varices (75%); and disappearance of acute gastric mucosal lesions (100%). Although one patient later underwent liver transplantation because of progression of liver cirrhosis, all five are doing well. From these results, DSRS-SPD may prove to be a safe and feasible procedure for intrahepatic PH after HPE for BA and may improve gastroesophageal varices and hypersplenism on long-term follow-up. Accepted: 13 July 1998     

Uterine pleomorphic rhabdomyosarcoma in a patient receiving tamoxifen therapy

INTRODUCTION: Tamoxifen has been used as adjuvant therapy for the treatment of breast cancer. Its use has been associated with the development of proliferative endometrial lesions such as polyps, hyperplasia, and carcinoma. Mesenchymal tumors including malignant mixed mullerian tumors, endometrial stromal sarcomas, adenosarcomas, and leiomyosarcomas have been more recently described with tamoxifen use. CASE REPORT: This report describes the first case of a pure uterine rhabdomyosarcoma in a patient receiving tamoxifen therapy. DISCUSSION: Although uterine rhabdomyosarcomas are rare tumors and may arise de novo, we discuss the possible role of tamoxifen in the development of these mesenchymal tumors.     

Clinical application of argatroban as an alternative anticoagulant for extracorporeal circulation

The authors attempted experimental and clinical use of argatroban as an alternative anticoagulant in left heart bypass with the centrifugal pump, percutaneous cardiopulmonary support (PCPS), and extracorporeal membrane oxygenation (ECMO) to determine if it has complementary effects in preventing thrombus formation without aggravating bleeding tendency. Its reversible binding to thrombin and its short half-life contributed to reduce the risk of excessive blood loss without clot formation within the extracorporeal circulation circuit during thoracic aortic surgery using left heart bypass. PCPS and ECMO were safely performed at doses ranging from 0.5 to 10 micrograms/kg/min to maintain activated clotting time at approximately 200 seconds. Although experimental studies showed argatroban to be advantageous in preserving platelet and fibrinogen, further clinical investigations are necessary.     

Alteration of tumor phenotypes of B16 melanoma after genetic remodeling of the ganglioside profile

Gangliosides have been thought to be tumor markers of various neuroectoderm-derived cancers. However, their roles in malignant phenotypes of cancer cells are not well understood. We have performed the remodeling of ganglioside profiles of mouse melanoma B16 (B78 subline) by introducing GM2/GD2 synthase cDNA, and analyzed the phenotypic changes such as cell morphology, growth, adhesion and c-fos gene expression. Although newly expressed GM2 was clearly detected, GM2-positive transfectant cells showed rather reduced growth rates in vivo and in vitro, lower expression levels of c-fos gene and increased levels of cell adhesion to extracellular matrices compared to control cells. These results suggested that GM2 is involved in the regulation of cell-cell or cell-extracellular matrix interaction, and negatively control cell proliferation.     

Therapeutic Effect of Ansamitocin Targeted to Tumor by a Bispecific Monoclonal Antibody

We have constructed a murine hybrid hybridoma that secretes a bispecific monoclonal antibody (mAb) by fusing a hybridoma secreting an anti-ansamitocins mAb with a hybridoma secreting an anti-human transferrin receptor (TfR) mAb that binds to human A431 epidermoid carcinoma cells. The bispecific mAb, reactive to both ansamitocins and TfR, was purified by a combination of hydrophobic column chromatography and hydroxyapatite high-performance liquid chromatography, and evaluated in in vivo experiments using human tumor cell-implanted nude mice. Ansamitocin P-3 targeted through one of the antigen combining sites of the bispecific mAb was potentially more effective in suppressing the growth of established A431 tumor xenografts implanted on nude mice than unconjugated ansamitocin P-3 or the immunoconjugate of ansamitocin P-3 and monospecific anti-ansamitocins antibody, and the targeted ansamitocin P-3 finally eradicated the tumor mass. The bispecific mAb also played an important role in reducing such undesirable side-effects of ansamitocin P-3 as the loss of body weight, the damage to liver functions and the decrease in the number of white blood cells.     

New Hepatocellular Carcinoma Cell Line SUHC-1 Established from a Patient with Hepatitis C Virus RNA in Serum

A new human hepatocellular carcinoma cell (HCC) line, designated SUHC-1, was derived from a Japanese patient with hepatocellular carcinoma having antibody to hepatitis C virus (HCV) and HCV-RNA in his serum, and established in tissue culture. This cell line exhibited typical epithelial cell morphology in culture as observed by phase-contrast and electron microscopy. The SUHC-1 cells produced albumin and α₂-macroglobulin. Chromosomal analysis showed several rearrangements at short and long arms of chromosome 1, 17 and 20 (1p–, 1q–, i(1q), i(17q) and 20q +) with a modal number of 91. HCV-RNA was not detected in the supernatant of SUHC-1 cells by nested polymerase chain reaction assay or in the SUHC-1 cells by the in situ hybridization method. We concluded that complete HCV does not exist in the SUHC-1 cell line. The SUHC-1 cell line is the first line of HCC to have been derived from a patient with persistent HCV infection, and may provide a suitable model for studies of hepatocarcinogenesis related to HCV.