Kenji Katakai

Hepatocellular carcinoma with portal vein tumor thrombosis: clinical characteristics, prognosis, and patient survival analysis.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a poor prognosis. New therapeutic modalities, such as continuous hepatic arterial infusion chemotherapy (CHAIC), have recently been reported to be promising strategies. The aim of this study was to evaluate the clinical characteristics, prognosis, and survival of patients with PVTT according to treatment regimen. One hundred ninety-three patients with HCC complicated with PVTT at the time of diagnosis were included in this study. All patients were newly diagnosed to have HCC and were observed from January 1992 to December 2003. CHAIC was performed using an implanted drug delivery system with low-dose cisplatin and 5-fluorouracil. Clinical characteristics, prognosis, and patient survival were analyzed by the Kaplan-Meier method and Coxs proportional hazards model. The mean age of the patients complicated with PVTT was 64.3±10.3 years (range, 20–88 years). The survival of the 193 patients with PVTT was 37.5%, 24.0%, 18.9%, and 8.3% at 1, 2, 3, and 5 years, respectively. According to treatment, the survival of patients who underwent surgical treatment was the best, followed by CHAIC, transcatheter arterial infusion/embolization, and supportive care. The 3-year survivals for each treatment regimen were 53.0%, 19.3%, 15.0%, and 4.0%, respectively. Although the survival of patients who received surgical treatment was best, such patients were restricted. There was no difference in survival between treated and untreated patients demonstrating Child-Pugh grade C. In Child B patients, treatment for HCC significantly increased survival (P<0.01). Coxs proportional hazards model revealed the Child-Pugh classification to be an independent prognostic factor for patients with HCC and PVTT (P<0.01). We conclude that the prognosis of HCC with PVTT was quite poor. The treatment did not improve the survival of Child C patients. As a result, the prevention, early diagnosis, and development of new treatment strategies are required.

Hepatocellular Carcinoma in Young Adults: The Clinical Characteristics, Prognosis, and Findings of a Patient Survival Analysis

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, HCC is rare in young Japanese patients and the clinical features of young patients with HCC have not yet been fully studied. This study was designed to determine the clinical characteristics and prognosis of patients with HCC who are younger than aged 40 years. A retrospective analysis was performed for patients newly diagnosed with HCC and observed from January 1990 to December 2003 at our hospitals. Patients younger than aged 40 years at the diagnosis of HCC were defined as the young group and were reviewed. There were 20 patients (16 males) with HCC who were younger than aged 40 years. The mean age at diagnosis was 33.6 (range, 20–39) years. Fifteen of 20 patients were positive for hepatitis B surface antigen (HBsAg) and 2 patients were positive for hepatitis C virus antibody. According to the Child-Pugh grading, the liver function was relatively good in all patients. Because most of the patients did not receive periodic follow-up, this disease often was discovered at an advanced stage, usually after the appearance of some symptoms. Although intensive treatment was performed for such young patients, the survival was nevertheless poor. Most patients died from this cancer within 1 year. However, one patient who received periodic follow-up and also was in relatively good physical condition had a better prognosis, and he survived for 88 months. Young patients with HCC tended to have a poor prognosis because of advanced stage of HCC, despite a well-preserved liver function and aggressive treatment. Screening for HCC and an early diagnosis is needed for such patients to demonstrate an improved prognosis, especially for HBsAg-positive patients.

Changes in Distribution of Cystatin C, Apolipoprotein E and Ferritin in Rat Hypothalamus after Hypophysectomy

To clarify the mechanism underlying the process of degeneration of injured CNS neurons, we have immunohistochemically examined the distribution of cystatin C, apolipoprotein E, IgG, transferrin and ferritin in the hypophysectomized rat hypothalamus. Stainings for ferritin revealed that reactive microglial cells massed in the paraventricular and supraoptic nuclei 14 days after hypophysectomy, when the degeneration of vasopressin neuronal cell bodies was apparent. Cystatin C‐positive magnocellular neurons first appeared at 4 days and the number of intensely‐stained cells increased rapidly up to the 7th day of hypophysectomy, followed by a decrease thereafter. Most of such cystatin C‐positive neurons were simultaneously stained with anti‐vasopressin serum. Accumulation of apolipoprotein E in extra‐cellular spaces was obvious in the both hypothalamic magnocellular nuclei at 7 days. Several apolipoprotein E‐positive cells were localized in the supraoptic nucleus, although the number of apolipoprotein E‐positive cells was much smaller than that of cystatin C‐positive cells. The experiments performed with the transferrin and IgG antibodies showed undetectable levels of such molecules in and around the degenerating magnocellular neurons during whole experimental periods. These findings suggest the importance of cystatin C and apolipoprotein E in the process of degeneration and/or regeneration of magnocellular neurons after hypophysectomy.

Meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy

Following hypophysectomy the regenerating fibers of magnocellular neurons are known to establish new neurohemal connections with reorganized vasculatures in the median eminence, which lead to establishment of a posterior pituitary-like structure. In order to examine the role of the meninges (the pia mater and the arachnoid) in this regeneration process, we implanted the meningeal tissues obtained from neonatal rat pups into the third ventricle of the adult rats, and then hypophysectomized the host animals. Ten days after hypophysectomy, the meningeal tissue grafts were found to be densely innervated by regenerating vasopressin-immunoreactive fibers. Such fibers had dots and frequently formed large punctuations. On the contrary, few vasopressin fibers were found within the cortical tissue grafts. Further, the exposure of primary hypothalamic cell cultures to the medium conditioned by meningeal cell cultures promoted not only the survival of vasopressin-immunoreactive neurons but also the outgrowth and aborization of the neurites. The survivals of cortical and cerebellum neurons in culture were also promoted by the conditioned medium. These findings raise the possibility that the meninges play an important role in the axonal regeneration process after hypophysectomy.

Elevated plasma resistin concentrations in patients with liver cirrhosis

Background:  Resistin, an adipose‐derived polypeptide hormone, has been proposed to be a candidate in insulin resistance, although its role in humans remains controversial. Liver cirrhosis (LC) is characterized by an elevated number of circulating proinflammatory cytokines, hyperinsulinemia and insulin resistance. The aim of this study was to determine the plasma resistin levels in patients with LC.

Pro-Opiomelanocortin-Containing Neurons in Rat Median Eminence

A significant number of pro-opiomelanocortin (POMC)-containing cells were detected in the rat median eminence (ME) by immunocytochemistry using an antibody raised against a synthetic peptide corresponding to the cleavage site between adrenocorticotropin and beta-lipotropin moieties. Distribution of POMC-positive cells was restricted to the internal zone of the anterior parts of the ME. Such cells were observed as early as the 14th day of gestation in the area of the primitive ME, long before glial fibrillary acidic protein-positive cells appeared postnatally in this structure. Dissociated cell cultures obtained from the ME of 1-day-old rats produced cells immunoreactive for neurofilaments and the POMC moiety. Such cells displayed a neuronal morphology: the cell body was oval (13-18 microns) with long and fine beaded fibers. These findings clearly demonstrate the early appearance of POMC neurons in the developmental ME, a target organ of the hypothalamic infundibular neurons.

Prostaglandin-D-synthase (β-trace protein) levels in rat cerebrospinal fluid

The precise role of prostaglandin-D-synthase (beta-trace protein), the major constituent of cerebrospinal fluid, is unclear. In the present study, a sensitive and highly specific fluoroimmunoassay was developed. The measurement of the enzyme levels in rat CSF revealed a developmental change in the CSF levels with the highest value of 66 +/- 8 microg/ml at 7 days after birth. No significant difference in the levels was seen between different times of day. Subcutaneous injections of all-trans retinoic acid caused a dramatic decrease in the protein levels in a dose- and time-dependent manner. These findings may raise the possibility that prostaglandin-D-synthase in CSF is involved in retinoic acid action on the brain.

Glutamine is involved in the dependency of brain neuron survival on cell plating density in culture

THE mechanism by which neuronal cell viability in culture is dependent on cell plating density is unclear. To address this question, dissociated cells from the neonatal rat cortex were cultured in a chemically defined medium. Medium conditioned with cortical cells plated at high density (2000 cells/mm2) promoted the survival of neurons grown at low cell density (100 cells/mm2) in a dose-dependent manner. Data obtained from molecular sieving suggested that the molecule(s) promoting the survival of neurons was smaller than 1000 Da. Amino acid analysis of the conditioned medium revealed the release of a mass of glutamine from cortical cells in culture. L-Glutamine mimicked the conditioned medium in action promoting the viability of neurons. These findings suggest that the effect of plating density on neuronal cell viability is mediated at least in part by glutamine released from cultured cells.

The natural history of untreated hepatocellular carcinoma

AbstractBackground. Although early diagnosis and treatment of hepatocellular carcinoma (HCC) has become available through advances in diagnostic imaging and therapeutic modalities, there is still a need for recent data on the prognosis of untreated HCC. Therefore, we evaluated the natural history of patients with untreated HCC from various clinical viewpoints. Methods. Data from 70 untreated HCC patients (57 men, 13 women; aged 43–94 years) diagnosed from June 1992 to May 1997 at seven hospitals in Gunma Prefecture, Japan, were analyzed. Results. The overall mean survival was 5.3 ± 7.6 months from diagnosis to death. The median survival was 2.0 months from diagnosis to death; 12.0 months for tumor stage I, 6.8 months for tumor stage II, 8.6 months for tumor stage III, 2.0 months for tumor stage IV-A, and 2.0 months for tumor stage IV-B. According to clinical stage, the median length of survival of clinical stage I patients was 4.3 months; stage II, 4.3 months; and stage III, 1.4 months. In the 15 patients who refused any anti-cancer treatment, the median survival was 15.2 months and in the 55 patients who could not be given anti-cancer treatment because of poor liver function or advanced cancer the median survival was 1.6 months. The prognosis of patients with HCC complicated by portal thrombus was extremely poor. Multivariate analysis showed that portal thrombus and hypoalbuminemia were significant indicators of poor prognosis. Older patients with HCC had a poor prognosis, although the difference from prognosis in younger patients was not significant. Conclusions. Both tumor stage and clinical stage were correlated with duration of survival from diagnosis in these patients with HCC. The prognosis of untreated patients with HCC was extremely poor. All untreated patients died within 3 years of diagnosis.

APPEARANCE OF BETA-2-MICROGLOBULIN IN RAT HYPOTHALAMIC MAGNOCELLULAR NEURONS AFTER HYPOPHYSECTOMY

To clarify the relationship between neuronal cell degeneration and MHC class-I complex expression, we have immunohistochemically examined the distribution of beta(2)-microglobulin in the hypophysectomized rat hypothalamus. In the sham-operated control rats, positive stainings were distributed only in blood vessels in the hypothalamic areas where magnocellular neurons were localized. Three days after hypophysectomy, positive stainings appeared in a large number of magnocellular neurons in the paraventricular and supraoptic nuclei. Most of such beta(2)-microglobulin-positive cells were simultaneously stained with antivasopressin serum. The pattern of distribution of positive cells and the intensity of the stainings remained unchanged at least until the 14th day. These morphological findings suggest that the process of degeneration of hypothalamic magnocellular neurons after hypophysectomy is a useful model to investigate the role of MHC class I complex in the brain.