A prominent cause of death in patients with advanced gastric cancer is peritoneal metastasis or recurrence. There is no definite preventive surgery or treatment in such cases. Cancer tissue is more heat labile than normal tissue, and the administration of anticancer drugs interacts synergically with hyperthermia. The ability of anticancer drugs to eradicate the malignant cells is dependent not only on the dose of the antineoplastic drug but also on the number of tumor cells. Therefore, for success, the combination therapy of cytoreductive surgery and IPHC may be necessary in advanced gastric cancer. We performed this study to evaluate the toxicity and the clinical efficacy of IPHC in far-advanced gastric cancer and to assess the concentration of CDDP. Twenty one patients (11 females and 10 males) with gross serosal invasion (with or without peritoneal metastasis) underwent cytoreductive surgery and were treated with IPHC via hyperex-GHT-cpl (Green Cross Med. Corp. Korea) before closure of the abdominal wound. The IPHC was done using CDDP (200~400 mg/m2) and MMC (30~50 mg/m2) with 10 liters of normal saline as the perfusate. The peritoneal temperature during the IPHC was maintained at 42oC for 60 minutes. We used a modified peritoneal cavity expander to achieve free flow of the perfusate. The concentrations of the plasma and the perfusate were measured by atomic absorption spectrometry (Varian 300 A). Sixteen patients were stage IV, 3 were IIIb, and 2 were IIIa. The plasma concentraton of CDDP was 1.8 ug/ml at 10 minutes after perfusion and reached a maximal concentration (MXC) of 3.6 ug/ml. The area under the time-concentration curve (AUC) of the plasma at the 48th hour after perfusion was 3031.1 ug.min/ml. At the 24th hour, the maximum concentration of CDDP in the perfusate was 16.2 ug/ml. The AUC of the perfusate was 1703.3 ug min/ml at the 24th hour and 1817.7 ug min/ml at the 48th hour. The ratio of AUC of perfusate and the AUC of the plasma were 0.92 at the 24th hour and 0.59 at the 48th hour. The postoperative compllications were lymphatic leakage (2), pneumonia (1), and paralytic ileus (1). The most common drug-related complications of IPHC were anemia (WHO grade I), hematuria, leukopenia, jaundice, and thrombocytopenia in such order. These side effects were eliminated by conservative treatment within 4 weeks postoperatively. We could not determine the long term survival rate because of the short follow up period. However, the mean survival of the cases was about 12.0 months. The three deaths among the resected cases were due to extraperitoneal recurrences. The combination therapy of IPHC and cytoreductive is available for clinical use with a high AUC, high intraperitoneal CDDP concentration with a reasonable plasma concentration and has no threatening complications or mortality.
Absorption ; Anemia ; Area Under Curve ; Cause of Death ; Female ; Fever ; Follow-Up Studies ; Hematuria ; Hot Temperature ; Humans ; Intestinal Pseudo-Obstruction ; Jaundice ; Leukopenia ; Mortality ; Neoplasm Metastasis ; Perfusion ; Peritoneal Cavity ; Plasma ; Pneumonia ; Recurrence ; Spectrum Analysis ; Stomach Neoplasms* ; Survival Rate ; Thrombocytopenia ; Wounds and Injuries

No abstract available.
Neoplasm Metastasis*

The superior orbital fissure syndrome is a rare condition characterized by opthalmoplegia, ptosis, and proptosis of the eye, fixation and dilation of the pupil, and anesthesia of the upper eyelid and forehead. Tumor metastasis to the orbit is uncommon and there were only 11 histologically proven cases of metastatic hepatocellular carcinoma to the orbit. There was only one case of metastatic hepatocellular carcinoma to the orbit with superior orbital fissure syndrome. The prognosis were poor for all reported cases, but palliative radiotherapy could be some help. We report a rare case of metastatic hepatocellular carcinoma to the orbit with superior orbital fissure syndrome.
Anesthesia ; Carcinoma, Hepatocellular* ; Exophthalmos ; Eyelids ; Forehead ; Neoplasm Metastasis ; Orbit* ; Prognosis ; Pupil ; Radiotherapy

No abstract available.
Cisplatin*

No abstract available.
Drug Therapy* ; Granulocytes* ; Humans*

No abstract available.
Craniopharyngioma*

The transforming growth factor-beta 1 was known as having the most important influence on chondrocytes among various growth factors, being abundant in articular chondrocytes and osteocytes. We performed in vitro monolayer cultures of human articular chondrocytes from normal and osteoarthritic patients and studied the transforming growth factor-beta 1 responsiveness of those chondrocytes. The cell-growth curve indicated that the primary osteoarthritic chondrocyte culture with transforming growth factor-beta 1 showed a more rapid growth pattern than normal chondrocytes with or without TGF-beta 1 and osteoarthritic chondrocytes without TGF-beta 1. The osteoarthritic group showed a sharp decline in growth pattern with subsequent culture. The shape of osteoarthritic chondrocytes was bigger and more bizarre compared to those of normal chondrocytes. With subsequent culture, this change became prominent. The transforming growth factor-beta 1 increased the [3H]-TdR uptake in each group. The phenotypes of chondrocytes were more clearly expressed in the normal group. The chondrocytes lost their phenotype (production of collagen type II) following subculture in each group. The transforming growth factor-beta 1 could not inhibit or delay the dedifferentiation process (loss of phenotype).
Cartilage, Articular/drug effects* ; Cartilage, Articular/cytology ; Cell Division/drug effects ; Cells, Cultured ; Human ; Osteoarthritis/pathology ; Reference Values ; Transforming Growth Factor beta/pharmacology*

OBJECTIVES: To quantitate apoptosis and Fas antigen expression of T lymphocytes by activation in aplastic anemia (AA) and compare with that of normal controls and completely-recovered AA, and to investigate the apoptotic sensitivity to anti-fas antibody of activated T lymphocytes in AA. METHODS: We studied the expression of Fas antigen on fresh T lymphocytes of twenty patients with AA [13 newly diagnosed, 7 recorvered AA after immunosuppressive therapy (IST)], and investigated the activation-induced cell death (AICD) and Fas expression by activation [interleukin-2 (200 U/ml) and phytohemagglutinin (50 micrograms/ml)] in 5 newly-diagnosed AA, 5 normal controls and 5 AA in complete response (CR). Apoptotic sensitivity to anti-Fas antibody was assessed by the time-course kinetics of induction of cell death by anti-Fas antibody (500 ng/ml). RESULTS: There was no significant difference of Fas antigen expression on freshly-isolated T lymphocytes among newly-diagnosed severe AA, normal control s and patients with AA in CR after IST. In normal controls, T lymphocytes death was greatly increased at 3 days of activation, and Fas antigen expression on T lymphocytes was increased above baseline at day 1 of activation. In contrast, in newly-diagnosed AA, T lymphocytes showed delayed cell death, which correlated with a slowed increase of Fas antigen expression by activation. Also, anti-Fa s antibody sensitivity of activated T lymphocytes was decreased in newly-diagnosed AA. In completely recovered AA, these abnormal AICD and Fas antigen expressions by activation were recovered to normal range. CONCLUSIONS: Abnormal AICD plays a role in the immune pathophysiology of AA, and defective Fas system is involved in this process.
Anemia, Aplastic/pathology ; Anemia, Aplastic/immunology* ; Antigens, CD95/blood ; Apoptosis ; Case-Control Studies ; Human ; In Vitro ; Lymphocyte Transformation ; T-Lymphocytes/pathology* ; T-Lymphocytes/immunology* ; Time Factors

PURPOSE: The purposes of this study were to evaluate the biodistribution and effect of Ho-166 radionuclide by intra-arterial injection of the Ho-166 chitosan complex in dogs and to assess the clinical efficacy and side effects of this complex in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In an experimental study, 20 mCi of Ho-166 chitosan complex was injected into the left hepatic artery of six adult dogs. The distribution of radioactivity in each organ was calculated using a gamma camera scan at regular intervals. A beta ray radioactivity count (cpm) of blood and urine was performed periodically, and hematologic and hepatic function were regularly assessed. At 4, 8 and 12 weeks after intra-arterial injection, bone marrow and liver were pathologically evaluated. Twenty-five patients with a single, nodular HCC mass 3 -9 cm in diameter were treated by intra-arterial injection of Ho-166 chitosan complex, and immediately after the procedure a gamma camera scan was obtained. A beta ray radioactivity count(cpm) of blood was performed periodically, hematologic and hepatic function were regularly evaluated, and CT scans and angiograms were obtained 3 months after the procedure. On the basis of the CT and angiographic findings, the treatment effects were classified as complete (CR), partial (PR) or non-response(NR). RESULTS: In the animal study, blood radioactivity peaked immediately after injection and then declined rapidly. Urinary excretion was 0.17%. The proportion of radioactivity in each organ per whole body was 25% in the left lobe of the liver, 7% in the right lobe, 3% in the lung, 1.4 -3% in the bladder, and 2% in bone. WBC and platelet counts declined maximally at 3 -4 weeks and recovered at 12 weeks. The cellularity of bone marrow was 25% at 4 weeks and 55% at 12 weeks, findings which correlated well with the observed hematologic changes. In the clinical study of 25 HCC patients, CR was achieved in 17 (68%) cases, PR in 5 (20%) and NR in 3 (12%). At gamma camera imaging immediately after treatment, tumor radioactivity was localized in 76% of cases. In six cases (24%) WBC and platelet counts decreased 50% or more compared with their pretreatment level. In 67 -75% of cases, SGOT and SGPT were, within 1 -3 days, 2 -3 times higher than their pre-treatment level, and recovered at post 4 weeks. CONCLUSION: Ho-166 chitosan complex administrated intra-arterially localized the target organ with minimal side effects, and we therefore suggest that it may be used in the treatment of nodular and hypervascular HCC. Further study of its dosimetry and possible hematologic side reactions is needed, however.
Adult ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Beta Particles ; Bone Marrow ; Carcinoma, Hepatocellular* ; Chitosan* ; Dogs ; Gamma Cameras ; Hepatic Artery ; Humans ; Injections, Intra-Arterial* ; Liver ; Lung ; Platelet Count ; Radioactivity ; Radionuclide Imaging ; Tomography, X-Ray Computed ; Urinary Bladder

The expression of the WT-1 gene which is found exclusively in human leukemic blasts frequently disappears from bone marrow of leukemia patients in complete remission (CR). Using semiquantitative RT-PCR, we investigated the expression of the WT-1 gene in peripheral bloods (PBs) of 33 patients with acute leukemia (AML 26; ALL 7) and monitored its expression after achievement of CR. None of the 6 normal controls expressed detectable levels of WT-1 transcripts (< 10(-4), background level), whereas 31 (93.9%) of 33 patients expressed variable levels of WT-1 transcripts (range, 10(-4) to 10(1)) at diagnosis. The level of WT-1 expression was not different between AML and ALL. By monitoring WT-1 gene expression in PB of 31 patients during CR, 5 patients relapsed (two from the 18 patients with undetectable levels of WT-1 gene expression and three from the 13 with WT-1 gene expression in low levels). Three of the 5 relapsed patients showed preceding reappearance or rise of WT-1 gene expression. From these results, we reconfirmed that the WT-1 gene is a pan-acute leukemic marker, which can be used to monitor minimal residual leukemia (MRL) after chemotherapy or in patients with CR.
Gene Expression/physiology* ; Human ; Leukemia, Lymphocytic, Acute/genetics* ; Leukemia, Lymphocytic, Acute/blood* ; Leukemia, Myelocytic, Acute/genetics* ; Leukemia, Myelocytic, Acute/blood* ; Neoplasm, Residual ; Nephroblastoma/genetics* ; Polymerase Chain Reaction ; Transcription, Genetic ; Tumor Markers, Biological