Minoru Ukida

Peritoneoscopy of the liver stained by intravenous injection of indocyanine green-experimental and clinical studies.

SummaryLiver surface patterns were observed by peritoneoscopy after intravenous injection of indocyanine green (ICG). The normal rat liver was diffusely stained dark greenish-brown 5 minutes after the injection of ICG 25 mg/kg body weight into the tail vein. Green spots persisted longer in the centrolobular area, clearly revealing lobular markings. This regional difference in hepatocyte staining suggested differing abilities of hepatocytes to take up or excrete ICG. This dyeing technique was applied to liver disease patients. The liver was diffusely stained light greenish-brown 5 minutes after the injection of ICG 5 mg/kg body weight. In patients, especially those with obscure lobular markings before ICG injection, lobules were clearly demarcated by reddish terminal portal veins against a green background. This simplified detection of lobular distortions. Prenodular patches (Kalk’s Bunteflecke) on the liver surface were stained green more intensely than surrounding areas, which supports the hypothesis that patches are composed of active hepatocytes.

Scanning electron microscopy of the bile ductule.

SummaryScanning electron microscopy of a liver biopsy specimen from a patient 6 months after the onset of acute hepatitis revealed a normal appearing bile ductule. The bile ductule was 13 μm in outer diameter and 1.5–2.7 μm in inner diameter. The ductular lumen was surrounded by two ductular cells and ampullary dilated at the canalicular side. In the lumen, intracytoplasmic diverticles were observed with an orifice d ameter of 0.9 μm. About 15 microvilli 0.4–0.6 μm in length and 0.1 μm in thickness were observed on 1 μm2 of luminal surface. The number of microvilli was calculated to be approximately 1,500 per ductular cell. A single cilium 0.15 μm in diameter at the base and 0.10 μm at the trunk, and 7–15 μm in length was found on each ductular cell. The cilium arose from p. recess at the canalicular side of the ductular cell, and the free-end was on the bile-duct side. The cilia seemed to play an important role in bile flow to the duct. Sometimes between the ductular cells at the edge of the basal portion a cell was intercalated with thin processes. Such thin processes were not observed on ductular cells.

Photodynamic therapy of rat liver cancer: Protection of the normal liver by indocyanine green

SummaryThe application of photodynamic therapy (PDT) to hepatocellular carcinoma (HCC) has been difficult because hematoporphyrin derivatives (HpD) accumulate not only in cancer cells but also in normal hepatocytes and, hence, laser irradiation causes injuries in both tissues. Protection of the normal liver tissue from laser phototoxicity was demonstrated using indocyanine green (ICG) as a protective agent. In vitro, argon laser irradiation decolored the green tint of ICG much faster in solutions containing HpD than those without, suggesting that ICG captured singlet oxygen from HpD. Degeneration of Chang hepatocytes induced by HpD and laser irradiation was prevented by an addition of ICG into the medium. In vivo, laser irradiation of the rat liver surface caused hyperemia when HpD was injected two days before, while the hyperemia was much milder in rats additionally receiving ICG injection 10 minutes before the irradiation. ICG injected into rat HCC accumulated only in the normal liver tissue. Laser irradiation of rat HCC preinjected with both HpD and ICG destroyed only the cancer tissue, while the surrounding liver tissue was preserved.Both in vitro and in vivo results suggest that ICG has a scavenger effect against excited oxygen and it might be used as a protective agent in PDT of HCC.

Scanning electron microscopy of a liver cavernous hemangioma

SummaryA 39-year-old female with a large cavernous hemangioma of the liver was successfully treated by ligation of the left hepatic artery. A wedge biopsy specimen of the hemangioma was obtained after the ligation and was examined by scanning electron microscopy. The hemangioma was demarcated from the surrounding normal liver parenchyma and had a labyrinth of caves 50–150 μm in diameter. The caves were separated by fibrous septa 20–40 μm in width. Endothelial cells of the caves were spindle-shaped and arranged in parallel. The surface property of the caves resembled that of the hepatic artery and differed from that of the portal vein or hepatic vein. These findings support that the cavernous hemangioma of the liver was supplied by the hepatic artery. The labyrinthine structure of the cavernous hemangioma may explain the long standing contrast enhancement of the hemangioma after hepatic arteriography.

Repeated Laparoscopy of 27 Patients with Chronic Non‐A, Non‐B Hepatitis Showing a Complete Response to IFN Therapy

The laparoscopies and liver histology results of 27 patients with chronic non‐A, non‐B hepatitis who had a complete response to the longterm administration of IFN‐alpha were studied. When comparing the liver surface before IFN therapy, code number 1 using Shimadas classification, i. e., whitish markings, increased from 14.0% to 57.9%, code number 2, i. e., dilated vessels, decreased from 34.9% to 10.6%, code number 4, i. e., reddish markings, decreased from 11.6% to 2.6%, and code number 7, i. e., patchy markings, decreased from 16.3% to 2.6%. Improvement of the liver edge dullness and a decrease of the liver consistency after the IFN therapy were also observed in 40. 7%, and 14. 8% of the patients, respectively. Liver histology after the therapy showed normal liver or liver fibrosis in chronic hepatitis patients, and liver cirrhosis with active hepatitis developed into liver cirrhosis without activity. The hepatitis activity index score decreased significantly after the therapy. The present report seems to be the first which describes detailed changes of the liver surface before and after IFN therapy in patients with chronic non‐A, non‐B hepatitis who had a complete response to the therapy

Dynamic relationship between urea and glutamine synthesis in the mechanism of ammonia detoxication: A tracer study using15NH4Cl in fulminant hepatic failure rats

SummaryFulminant hepatic failure (FHF) was produced in rats with intraperitoneal injection of Dgalactosamine.15NH4C1 (50 mg/kg of body weight) was injected into the rats via the tail vein. Arterial blood was drawn before and 5,15, 30, 60 min after the injection of15NH4C1.15N-ammonia, -urea, and-glutamine (amide and amino) were determined by gas chromatography and mass spectrometry. The plasma15N-ammonia level was higher but decreased more rapidly in the FHF rats than in the control rats. This suggests that in FHF rats, the systemic vascular pool of ammonia is enlarged and ammonia clearance from blood is increased. The incorporation of15N into urea was significantly different between the two groups. In FHF rats, the plasma urea-15N level rose 5 min after the injection, decreased at 15 min and was elevated again up to 60 min after injection. This biphasic change suggests that in FHF rats the incorporation of15N into the extrahepatic glutamine pool is accelerated up to 15 min and that after 30 min a larger volume of glutamine-amide-15N is transferred to the urea cycle.

The suppressive effect of a cytosolic calcium-ion chelator on the hepatocellular injury by oxidative stress

Abstract Previously, two different mechanisms were suggested to be involved in the hepatocellular injury caused by TBHP: peroxidation of the cell membrane lipids, and a disturbance of cytosolic calcium homeostasis. In this study, the cytosolic calcium-ion chelator BAPTA-AM suppressed the hepatocellular injury by TBHP at extracellular calcium-ion concentrations of 0, 1, and 3 mM, independent of peroxidation of the cell membrane lipids and the mitochondrial membrane potential. Therefore, a disturbance of cytosolic calcium homeostasis plays the major role in the hepatocellular injury caused by TBHP.

Peritoneoscopic Findings of Autoimmune Hepatitis

Abstract: To clarify the morphologic differences between hepatitis C virus (HCVI‐negative autoimmune hepatitis (AIH) and HCV‐positive AIH, peritoneoscopic findings were studied. Among twenty three patients with AIH according to the Japanese criteria (1992), 15 were HCV‐negative and 8 were HCV‐positive. The terms grooved depression, coarse depression, coarse elevation, coarse undulation, and round‐shaped reddish marking (RM) were used in this study to evaluate the peritoneoscopic findings. Grooved depressions, coarse depressions, coarse elevations, coarse undulations and round‐shaped RMs were all common findings (53%, 87%, 73%, 80%, and 80%, respectively) in HCV‐negative AIH patients, but they were less common (13%, 25%, 13%, 13%, and 0%, respectively) in HCV‐positive AIH patients. This study revealed that HCV‐negative AIH patients had different peritoneoscopic findings from HCV‐positive AIH patients. Thus HCV‐negative AIH may be typical AIH, and HCV‐positive AIH may essentially be a subset of type C chronic hepatitis.

A Case of Funnel Liver Induced by Dimethylformamide

Abstract: The laparoscopic and histological findings of a patient suffering from dimethylformamide (DMF) intoxication are discussed. A 20‐year‐old man was admitted to our department for further evaluation of a liver injury. A laparoscopy revealed that the liver was markedly deformed by a combination of depressions and protuberances, and this finding was compatible with the funnel liver reported by H. Kalk. After an intravenous injection of high dose indocyanine green, broad whitish depressions appeared as a non‐staining area and surrounding protuberances were stained a dark green color. A biopsy specimen taken from the site of the depression showed massive hepatic necrosis and a scar under the capsule. The histological diagnosis was a convalescent stage of toxic liver injury. The present report is apparently the first to consider the detailed laparoscopic findings of a liver injury induced by DMF.

Differential diagnosis of liver parenchymal diseases by likelihood method using 12 laboratory data and age

SummaryLiver parenchymal diseases were statistically diagnosed by likelihood method using 12 routine liver function tests and age. 444 cases of liver diseases were classified into 8 groups by histological diagnosis. A score diagnosis table was made from the data of these cases. For the likelihood diagnosis, data of each case were adapted to the score table and the probable diagnosis was calculated. Correct diagnosis rate of the first probable diagnosis was 50 % in all cases and that of the first and the second was 71%. Descending order of the correct diagnosis rate of the first diagnosis was fatty liver (76%), liver cirrhosis (67%), slight histological changes (61%), acute hepatitis (51%), alcoholic liver injury (48%), chronic aggressive hepatitis 2A (43%), chornic persistent hepatitis (40%) and chronic aggressive hepatitis 2B (26%). In conclusion, differential diagnosis of liver parenchymal diseases was made easily with the score table of 13 informations with a considerable success.