Shigeki Mizutani

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.

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.

Experimental liver cysts induced by 2-acetylaminofluorene

SummaryLiver cyst formation was studied serially in an experimental model in which rats were fed a diet containing 0.02% 2-acetylaminofluorene, a carcinogen, for 6 weeks, followed by a normal diet for 42 weeks. Cysts appeared in the portal tracts at the 12th week, by which time the intrahepatic bile ducts had also proliferated and dilated. Some of the dilated bile ducts were cavernous or multicystic and appeared to represent a transitional form between the bile duct dilatation and cystic formation. After 20 weeks cysts were observed in the majority of rats. The number and the size of cysts in the liver increased with time; after 40 weeks, there were up to 20 cysts as large as 15 mm in diameter. Carcinoma or cirrhosis did not develop in this model. Indocyanine green dye injected intravenously did not accumulate in the cysts, which denies the possibility of communication between cysts and the bile duct. Scanning electron microscopy demonstrated that the cysts were composed of a few intercommunicating cavities and were lined with epithelial cells similar to those of the intrahepatic bile duct, which had numerous microvilli and a central cilium. These observations suggest that liver cysts originate in the bile duct.

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.

Ranking of liver tests for differential diagnosis of liver parenchymal diseases

SummaryLiver function tests were ranked in the order useful to differentiate 8 liver parenchymal diseases in combination of tests by forward selection and backward elimination procedures in the likelihood method using a microcomputer. The orders were almost same in both procedures: indocyanine green plasma disappearance rate, glutamic pyruvic transaminase (GPT), zinc turbidity test, alkaline phosphatase, age, HBsAg, RA test, glutamic oxaloacetic transaminase (GOT)/GPT ratio, GOT, cholesterol, total protein, total bilirubin, albumin/globulin ratio and γ-globulin. The first 9 tests had almost all informations of all tests. The first likelihood diagnosis using the 9 tests was correct in 53% and the first or the second diagnosis was correct in 71 % of 444 cases of 8 liver parenchymal diseases. A score table of likelihood diagnosis using the 9 tests was presented for manual application to new cases.