Yasuhiro Kurumiya

Differential suppression of liver-specific genes in regenerating rat liver induced by extended hepatectomy

BACKGROUND/AIMS The function of the remnant liver is critical to survival of patients following an extended hepatectomy. The aim of this study was to determine whether proliferating hepatocytes in the remnant liver preserve the expression of liver-specific genes. METHODS Using regenerating rat livers after 30, 70, and 90% partial hepatectomy (PHx), Northern blot analyses were performed with probes for seven liver-specific genes, six growth-related genes, two housekeeping genes and two acute phase reactant protein genes. RESULTS During the regeneration after 90% PHx, the transcription of liver-specific genes showed three chronological patterns: transcription of serum albumin and cytochrome P450 2B decreased rapidly and reached a nadir at 6 to 24 h after PHx; those of apolipoprotein A-1, phosphoenolpyruvate carboxykinase and ornithine transcarbamylase decreased gradually until 24 to 48 h; those of UDP-glucuronosyltransferase and hepatocyte nuclear factor 4 did not show any changes until 48 h after PHx. In contrast, expression levels of all the growth-related genes and of housekeeping genes increased rapidly after PHx. After 30 and 70% PHx, expression of these genes changed in a similar manner to the 90% PHx case but to a lower extent. CONCLUSIONS Based upon the fractions of Ki-67 positive hepatocytes in remnant livers, we could estimate the degree of expression of each liver-specific gene in the proliferating hepatocytes. The serum albumin gene was completely suppressed, while that encoding UDP-glucuronosyltransferase was not affected. These results correlated well with the patterns of albumin and bilirubin in rat serum after PHx. Other liver-specific genes were moderately suppressed in proliferating hepatocytes. Thus, expression of liver-specific gene is differentially suppressed when hepatocytes enter a proliferation cycle. Those that are unaffected may be indispensable for maintaining the homeostasis of the living organism.

Active form of human hepatocyte growth factor is excreted into bile after hepatobiliary resection

BACKGROUND/AIMS We have shown that hepatocyte growth factor is excreted into bile after hepatectomy in patients with biliary tract carcinoma. However, it is not certain whether hepatocyte growth factor in bile is an active molecule or degradation products. METHODS Bile was obtained from five patients after hepatobiliary resection. Bile hepatocyte growth factor was purified on a heparin-Sepharose column and subjected to Western blotting. It was also tested for growth-stimulating activity with rat primary cultured hepatocytes. Biles from 50 patients who underwent various types of hepatobiliary resections were examined with respect to hepatocyte growth factor by an enzyme-linked immunosorbent assay. RESULTS Upon Western blotting following nonreducing electrophoresis, the purified bile hepatocyte growth factor showed an 85 kDa peptide corresponding to native hepatocyte growth factor. Under reducing conditions, it showed bands of a-subunit at 69 kDa and beta-subunit at 34 kDa with corresponding monoclonal antibodies. The purified bile hepatocyte growth factor stimulated the [3H]thymidine incorporation into primary cultured hepatocytes with a specific activity comparable to recombinant human hepatocyte growth factor. It was observed that the levels of bile hepatocyte growth factor increased after the various types of hepatobiliary resections, including bile duct resection without hepatectomy. CONCLUSIONS The human bile obtained after hepatobiliary resection contains active hepatocyte growth factor that can stimulate hepatocyte growth. Bile hepatocyte growth factor increased not only in hepatectomy but in bile duct resection. These results suggest that the biliary tract system may play an important role in the production of bile hepatocyte growth factor.

Recurrent fibrolamellar hepatocellular carcinoma with biliary invasion: Successful resection

A jaundiced 17-year-old man was diagnosed as having a local recurrence of fibrolamellar hepatocellular carcinoma 2 years and 4 months after left hepatic trisegmentectomy with total caudate lobectomy had been performed. The patient had a tumor occupying the upper part of the extrahepatic and intrahepatic bile ducts. Complete resection of the recurrent tumor was carried out. The patient remains well 3 years after the second surgery. Fibrolamellar hepatocellular carcinoma, a rare type of liver cancer, is a well defined disease entity with distinct clinical and histopathological features and a favorable prognosis. The good prognosis seems to warrant aggressive surgical intervention in patients with recurrences. Therefore, additional surgery for tumor recurrence should be considered. To our knowledge, this is the first report of a case in which a recurrent tumor of fibrolamellar hepatocellular carcinoma invaded the entire bile duct wall was successfully resected.

Laparoscopic Choledocolithotomy in Post-Gastrectomy Patients

はじめに: 胃切除後の胆管結石症の治療に際しては, 消化管再建のため経乳頭的アプローチが困難な例も多く, 手術的治療のウエイトが大きくなる. 方法: 腹腔鏡下手術を試みた胃切除の既往を有する胆管結石症19例の成績を検討した. 成績: 15例で腹腔鏡下切石に成功した. 既往胃手術の内容は幽門側胃切除B-I再建7例, B-II再建7例, 胃全摘Roux-Y再建5例であった. 開腹移行率はおのおの14%, 29%, 20%で術式との間に有意な関連は見られなかった. 胃疾患は良性11例, 悪性8例で開腹移行率は良性27%, 悪性13%でこれも有意差はなかった.胃手術から胆管結石手術までの期間の長さと開腹移行率の間にも関連は見られなかった. 術前にERCを施行しえたのは19例中6例で施行率はB-Iでは57%, B-IIでは29%, 胃全摘では0%であった. 腹腔鏡下に完遂できた症例での胆管結石の切石方法は経胆嚢管法が5例と胆管切開が10例であり, 術後在院日数はおのおの4.6日と12.7日であった. 結語: 胃切除後症例では癒着剥離に時間がかかるものの, 多くの症例で腹腔鏡下手術が可能であり, 試みるべき術式と考えられた.