Experimental study of a novel thermotherapy for hepatocellular carcinoma using a magnesium ferrite complex powder that produces heat under a magnetic field

BACKGROUND/AIMS: The anti-cancerous effect on hepatocellular carcinoma of a newly established form of thermotherapy, which uses an implant heating system, was evaluated. As a new material for application in hyperthermia, the authors developed a powder type Mg-ferrite complex that produces heat under a relatively low-power magnetic field. METHODOLOGY: This material suspended in Lipiodol was injected into tumors on the backs of mice that consisted of human hepatocellular carcinoma cells. Hyperthermia was performed by directing a magnetic charge on tumor-bearing mice that contained the Mg-ferrite complex. The temperature of the tumor was kept at 42-43 degrees C, while the magnetic field power ranged from 50 to 80G. RESULTS: A 10-min hyperthermia treatment was insufficiently effective against tumor growth. Systemic injection of doxorubicin (ADM) before hyperthermia appeared to enhance the anti-cancerous effect, but the difference was little and did not reach a statistically significant level (repeated measure analysis of variance). The anticancerous effect of hyperthermia for 15 minutes, in contrast, was marked. The nodules had almost completely disappeared by the end of the experiment. CONCLUSIONS: In conclusion, it is suggested that hyperthermotherapy using this newly developed Mg-ferrite complex might become an option for low-invasive therapy for advanced hepatocellular carcinoma in humans.     

Compressive stenosis of the inferior vena cava due to localized ascites after living-donor liver transplantation

A 54-year-old woman was admitted to our hospital following the diagnosis of decompensated liver cirrhosis with hepatitis C. She underwent living-donor liver transplantation, performed using the left hepatic lobe with the middle hepatic vein donated by her husband. After the transplantation, the patient suffered from massive ascites with liver dysfunction. Computed tomography demonstrated stenosis of the suprahepatic inferior vena cava (IVC) with focal collection of fluid. A second laparotomy was performed 19 days after the transplantation. When the encapsulated localized ascites on both sides of the IVC was opened, the ascites was flushed away. Subsequently, the grafted liver was easily mobilized and it was placed in the natural position without any tension, and the pressure gradient of the IVC was improved. Herein, we report a very rare case of compression stenosis of the IVC resulting in Budd-Chiari syndrome caused by localized encapsulated ascites.     

Measurement of Intrahepatic Pressure as an Index of Hepatic Sinusoidal Pressure

Intrahepatic pressure was measured in 148 patients with liver disease (32 outpatients, 116 inpatients) and 13 controls with almost normal liver histology (inpatients), with a 23-gauge needle (inner diameter 0.38 mm). Intrahepatic pressure was significantly elevated in the group order of chronic active hepatitis without bridging necrosis (n = 17, 9.2 +/- 3.0 mm Hg), chronic active hepatitis with bridging necrosis (n = 24, 12.3 +/- 5.7), and posthepatitic liver cirrhosis (n = 65, 18.8 +/- 4.2), compared with controls (n = 13, 6.8 +/- 2.7), whereas it was not elevated in the group of idiopathic portal hypertension (n = 9, 7.8 +/- 2.5 mm Hg), acute hepatitis (n = 10, 8.4 +/- 2.6 mm Hg), and chronic persistent hepatitis (n = 23, 7.9 +/- 2.7 mm Hg), compared with controls. As complications, four patients had abdominal discomfort continuing for more than a day; however, patients were allowed to walk after they had rested on their beds for 30 min. In 37 patients (27 with cirrhosis, seven idiopathic portal hypertension, and three others), portal vein and/or hepatic vein catheterization was performed during the same procedure of intrahepatic pressure measurement. Intrahepatic pressure showed significant correlations with corrected wedged hepatic vein pressure (r = 0.91), portohepatic gradient (r = 0.69), wedged hepatic vein pressure (r = 0.79), and portal vein pressure (r = 0.68). Slopes were 0.97, 0.83, 0.66, and 0.65, respectively. In conclusion, intrahepatic pressure reflects hepatic sinusoidal pressure (corrected wedged hepatic vein pressure), and intrahepatic pressure starts to elevate at the stage of chronic active hepatitis.     

A case of hepatocellular carcinoma with tuberculoma within tumor tissue

We made a diagnosis of hepatocellular carcinoma and performed partial resection of the liver in a 72 year-old woman. Granulomas were observed within hepatocellular carcinoma in the surgical specimen. Microscopic findings demonstrated the granulomas particularly within the tumor, and showed that they were composed of epithelioid cells with caseous necrosis. These tuberculomas compressed the tumor cells, and many lymphocytes had infiltrated the tumor around the tuberculomas. The cancer stage of the patient was early and her prognosis is good.     

Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.     

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.     

Protein-losing gastropathy associated with autoimmune disease: successful treatment with prednisolone

99m Tc-labeled human serum albumin scintigram showing abnormal radioactivity in the stomach. Endoscopic gastric biopsies revealed nonspecific inflammation, but marked intramural edema. Based on a slight elevation of antinuclear antibody level, autoimmune disease was suspected to be involved in this patient. Administration of prednisolone, as a diagnostic therapy, alleviated the hypoproteinemia, hypoalbuminemia, and hypercholesteremia. These findings suggest that an autoimmune mechanism could have been involved in this case of protein-losing gastropathy. Received: September 4, 2000 / Accepted: February 23, 2001     

Systemic capillary leak syndrome

A 40-year-old woman was referred to our hospital with severe hypovolemic shock and anasarca. The laboratory findings showed marked hemoconcentration and a decrease in total serum protein with the presence of monoclonal IgG-lambda. She had had a similar episode of generalized edema 2 years previously. We diagnosed the patient as having typical systemic capillary leak syndrome (SCLS) and she improved gradually after infusion of albumin-containing fluid. SCLS is a very rare condition caused by unexplained episodic capillary hyperpermeability. Its treatment has remained largely supportive and the prognosis is generally poor. Awareness of SCLS is necessary for improvement of the outcome.