Expression of variant CD44 containing variant exon v8-10 in gallbladder cancer.

We studied the Cd44v8-10 expression in gallbladder cancer immunohistochemically. Eighteen of 37 gallbladder cancer tissues expressed CD44v8-10. There were significant correlations between CD44v8-10 immunoreactivity and perineural invasion, venous invasion, and lymph node metastasis. Patients with CD44v8-10-positive tumors showed poor prognoses, whereas those with CD44v8-10-negative tumors had favorable prognoses. A multivariate analysis using the Cox regression model showed the immunoreactivity of CD44v8-10 to be an independent prognostic indicator of gallbladder cancer. The results suggest that CD44v8-10 expression may be a biologic marker of prognostic significance in gallbladder cancer.

Clinical significance of combined immunohistochemical detection of CD44v and sialyl LeX expression for colorectal cancer patients undergoing curative resection.

To evaluate their prognostic value, the expressions of CD44v and sialyl LeX (SLX) in colorectal cancers were studied immunohistochemically. Tissue specimens were reacted with monoclonal antibodies (mAb) CD44-1V and CSLEX-1. Of the 145 colorectal cancer patients undergoing curative resection, 59 (40.7%) were positive for mAb CD44-1V, and 40 (27.6%) were positive for mAb CSLEX-1. There was a significant correlation between the combined expression of SLX and CD44v8-10 and lymph node metastasis. The patients with tumors negative for CD44v8-10 and SLX had the most favorable prognoses. Conversely, the patients with tumors positive for both CD44v8-10 and SLX had a high recurrence rate and the poorest prognoses. In a multivariate analysis using the Cox regression model, the combined expression of SLX and CD44v8-10 emerged as an independent prognostic indicator. These results suggested that the combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance.

[Effective transcatheter arterial embolization for hepatic metastasis in a case of AFP producing gastric cancer].

We experienced a case of effective transcatheter arterial embolization (TAE) for hepatic metastasis in a AFP producing gastric cancer. A 51-year-old man with 2 type gastric cancer (H0) underwent subtotal gastrectomy (D2). The serum AFP level was 134.3 ng/ml, and AFP positive tumor cells were detected by PAP method. After the operation, the serum AFP level initially decreased but re-increased on the 7th postoperative month, and metastatic lesions of the liver were detected by CT scan. After the patient was treated 4 times by TAE, the serum AFP level returned within normal range and the metastatic tumors of the liver decreased markedly. Therefore liver resection was performed at the 28th month after the first operation. Total necrosis of metastatic liver lesions was confirmed. This patient has been well without recurrence signs for 10 years since operation. It is concluded that TAE should be used to treat hepatic metastasis in the case of an AFP producing gastric cancer.

[Liver resection in a case of multiple liver metastases of gastric cancer following hepatic arterial infusion chemotherapy].

A 61-year-old-man underwent subtotal gastrectomy (D2) for advanced gastric cancer with multiple liver metastases. After the operation, repeated hepatic arterial infusion chemotherapy was performed employing implantable catheter and port system with CDDP and MMC. The result was that the liver tumors showed a remarkable regression in size, and the serum CA 19-9 level decreased within normal range. But the tumor in the lateral segment grew and the CA 19-9 level increased again. There was no evidence of metastasis or recurrence except in the liver, and the metastatic tumors in right lobe became smaller by hepatic arterial infusion chemotherapy at this time. Therefore, lateral segment resection was performed for reductive surgery 14 months after the first operation. After that, the liver tumors did not grow and CA 19-9 kept within the normal range, while hepatic arterial infusion chemotherapy could be given. Thus, it seems that liver resection for reduction surgery following hepatic arterial infusion chemotherapy should be considered as a treatment for multiple liver metastases.

Predicting the viability of grafted livers in rats through a rapid and sensitive metabolic indicator assessed by 31P-NMR spectroscopy.

The present study was undertaken to clarify whether a correlation exists between the hepatic ratio of the beta-phosphorus moiety of ATP (beta-ATP) to inorganic phosphate (Pi), measured by 31P nuclear magnetic resonance spectroscopy 1 h after the reestablishment of portal blood flow, and the survival rate of rats following liver transplantation. This ratio was compared with the arterial ketone body ratio [AKBR (acetoacetate/3-hydroxybutyrate)], which is accepted as a reliable indicator of liver viability. After the transplantation of fresh livers, the 1-week survival rate was 92% and the beta-ATP/Pi ratio was 64% of the normal level. When the liver grafts were subjected to warm ischemia for 25 min or 45 min prior to harvesting, the 1-week survival rate decreased to 43% and 0%, respectively, and the beta-ATP/Pi ratio dropped to 31% and 18% of the normal level, respectively. On the other hand, the AKBR was about 25% of the normal level after transplantation of fresh livers, while it was 37% and 48% after transplantation with 25 min and 45 min of warm ischemia, respectively. However, 4 h after the reestablishment of portal blood flow, the AKBR correlated with the beta-ATP/Pi ratio in both the fresh graft group and the 45-min warm ischemic damage group. These results show that the beta-ATP/Pi ratio provides an accurate evaluation of a graft viability even at an extremely early stage following liver transplantation, and should prove useful for the early diagnosis of primary graft nonfunction after liver transplantation.

Expression of human nm23-H1 and nm23-H2 proteins in hepatocellular carcinoma.

BACKGROUND: The expression of nm23-H1 and nm23-H2 proteins in 25 hepatocellular carcinomas was studied immunohistochemically. METHODS: Tissue specimens were reacted with anti-human nm23-H1 and nm23-H2 monoclonal antibodies (MoAb) (H1-229 and H2-206, respectively) and then stained by the biotin-streptoavidin complex method. RESULTS: Adjacent nontumorous tissues were intensely stained with nm23-H1 and nm23-H2. Of the 25 hepatocellular carcinomas, 60% were positive for MoAb H1-229, and 68% were positive for MoAb H2-206. These immunoreactivities were most common in the cytoplasm of tumor cells. There was no significant correlation between the expression of nm23-H1 protein and tumor size, Edmondson's histopathologic classification, or invasion of the capsule. However, the authors observed an inverse relationship between nm23-H1 expression and intrahepatic metastases of hepatocellular carcinomas. There was no significant correlation between the expression of nm23-H2 protein and clinicopathologic findings. Only a short survival period was observed in patients with hepatocellular carcinoma with reduced nm23-H1 or nm23-H2 proteins. CONCLUSIONS: The results suggest that nm23-H1 protein plays a role in the suppression of intrahepatic metastasis of hepatocellular carcinoma and that the combined expression of nm23-H1 is associated with favorable prognosis.

[Phagocytic activity of rat Kupffer cells--the measurement method in vitro and the effect of hepatocytes upon the phagocytic activity].

The measurement method of the phagocytic activity of Kupffer cells (=KC) was investigated and the effect of hepatocytes (=HC) upon the phagocytic activity of KC was studied in vitro. Phagocytic activity of KC was measured by the uptake rate of 59Fe by KC (2 x 10(6)) incubated with chondroitin sulfate 59Fe for 24 hours (=phagocytic activity rate:PAR). When KC were co-cultured with HC (2 x 10(5), 5 x 10(5), 1 x 10(6) cells) for 24 hours, the PAR increased in proportion to the increase in number of HC (4.13, 5.37, 6.28%), comparing with that of KC alone (3.36%). And when KC were cultured with the supernate of HC (5 x 10(5)) which were cultured for 24 hours, this PAR (4.15%) was superior to that of KC alone, but didn't exceed that of KC co-cultured with HC (5 x 10(5)). The PAR was remarkably suppressed by the inhibitor of glycolysis (NaF), but was not suppressed so much by the inhibitor of oxidative phosphorylation (NaN3). The measurement method of phagocytic activity of KC in vitro was established, and it was proved that the PAR was enhanced by co-cultured HC and the supernate of cultured HC, and depended on glycolytic metabolism.

The infiltration of bile duct carcinoma along the bile duct wall.

The infiltration of extrahepatic bile duct carcinoma along the bile duct wall was studied in 29 resection cases. Histologically, spreading took place by mucosal infiltration in one case, mucosal and transmural in three, and transmural in 25. The average microscopic infiltrating distance from the gross margin of the tumor (ID) was 16.8 mm towards the liver, 6.5 mm towards the duodenum. The ID of the infiltrating type in the gross appearance of the tumor and the ID of the tubular adenocarcinoma in the histological cellular type tended to be long. The severer the invasion of the carcinoma to the lymphatic vessels, the longer the ID. The result indicated that most bile duct carcinomas have a tendency for long infiltration along the wall. An exceedingly wide resection involving hepatectomy is advisable for treatment.

Experience with intrahepatic cholangiojejunostomy for unresectable carcinoma of the hepatic hilus.

An intrahepatic cholangiojejunostomy at segment III or segment IV (surgical bypass) was performed for 13 unresectable hepatic hilar carcinoma patients after reduction of jaundice. Compared with the result of external biliary drainage alone, the 30-day mortality rate was 1/13 in the surgical bypass group and 4/12 in the external biliary drainage group. The incidence of postoperative cholangitis in each group was 3/13, 6/17 and the mean survival rate was 155 days, 96 days. It was concluded that intrahepatic cholangiojejunostomy for unresectable hepatic hilar carcinoma, contributed to a temporary return to normal life, gave better results than external biliary drainage.

[The clinical and pathologic correlations in acute cholangitis].

The liver histology of acute cholangitis was studied in order to determine whether microscopic changes correspond to clinical status. Patients with acute cholangitis were divided into mild cholangitis (1st group, n = 18) and severe cholangitis (2nd, 3rd and 4th groups) accompanied by hypotension. The 2nd group consisted of 6 surviving patients who underwent liver biopsy during hypotension. The 3rd group consisted of 3 non-surviving patients with biopsy during hypotension. The 4th group consisted of 7 patients with biopsy during autopsy. The frequency of endotoxemia, gram negative bacteremia, disseminated intravascular coagulopathy and hepatic failure were significantly higher in severe cholangitis than in mild cholangitis. The incidence of neutrophilic infiltration in the sinusoid and microabscess in lobule were significantly higher in severe cholangitis than in mild one. The incidence of portal thrombosis and massive necrosis of hepatic cells were also significantly higher in severe cholangitis, especially in the 3rd and 4th groups. It was suggested that the neutrophilic infiltration in the sinusoid and microabscess in lobules which proved the existence of endotoxemia or bacteremia were characteristic findings in severe cholangitis.