Treatment of adrenal metastases after hepatic resection of a hepatocellular carcinoma.

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from a hepatocellular carcinoma (HCC). However, treatment of adrenal metastases has not been well characterized. METHODS: Of 562 patients who underwent hepatic resection for a HCC, 91 developed extrahepatic metastases. We reviewed the medical records of 10 patients with adrenal metastases (9 males and 1 female; mean age 63 years at the time of hepatic resection). RESULTS: The mean diameter of the primary tumors was 5 cm, and all were located in the right lobe of the liver. The mean interval from hepatic resection to recurrence was 18 months. Seven patients underwent treatment of intrahepatic recurrence. To treat the adrenal metastases, surgical resection was performed in 4 patients, and transcatheter arterial embolization was performed in 1 patient. The patients treated had no other extrahepatic metastases. The mean diameter of the resected adrenal tumors was 6 cm. There was no hospital mortality. With surgical resection, 1 patient has been alive 63 months after recurrence. CONCLUSIONS: Adrenal metastases from a HCC were often large at the time of diagnosis. Since surgical resection was a safe procedure, and some patients could be alive for a long time, it should be performed whenever possible.

Renal pelvic carcinoma producing granulocyte colony-stimulating factor: report of a case.

A 69-year-old man was admitted to our hospital because of anorexia and weight loss. Abdominal computed tomography showed an irregularly contoured mass in his left renal pelvis. The patient had a remarkable degree of leukocytosis with no obvious focus of infection. An enzyme immunoassay of the serum revealed a remarkably high concentration of granulocyte colony-stimulating factor (G-CSF). The patient died 6 weeks after admission without a resection of the renal pelvic tumor. At autopsy, the tumor involved the pancreas, stomach, and descending colon. The histopathologic diagnosis was squamous cell carcinoma with sarcomatous change. Immunohistochemical staining using anti-G-CSF antibody demonstrated immunoreactivity in the cancer cells. To our knowledge, this is the first case of renal pelvic carcinoma proven to produce G-CSF reported in English.

Virologic and biochemical changes and prognosis after liver resection for hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND/AIMS: During the natural course of hepatitis B virus (HBV) infection, clearance of HB e antigen (HBeAg) and HB surface antigen (HBsAg) occurs with remission of liver disease. We investigated the effects of postoperative changes in virologic and biochemical parameters on the prognosis after liver resection for HBV-related hepatocellular carcinoma (HCC). METHODS: We investigated the relationship between postoperative changes in virologic and biochemical parameters and the incidence of intrahepatic recurrence and the outcome during a 3-year period following surgery in 30 HCC patients with HBsAg. RESULTS: The incidence of intrahepatic recurrence of HCC was significantly higher in patients with acute postoperative exacerbation of hepatitis (p = 0.0084), a sustained high serum concentration of HBV DNA (> or = 5.0 mEq/ml, p = 0.001), and sustained expression of HBsAg after surgery (p = 0.0421). A high serum concentration of HBV DNA was significantly associated with a shorter survival time (p = 0.0447) and the cause of death was recurrence of HCC. CONCLUSION: Patients with acute postoperative exacerbation of hepatitis, sustained HBsAg expression, and sustained high serum concentrations of HBV DNA after surgery may require more intensive postoperative monitoring for HCC recurrence.

Large focal nodular hyperplasia of the liver: possible to evade surgical resection.

PURPOSE: Although recent advances in diagnostic imaging have allowed a number of patients with focal nodular hyperplasia (FNH) to avoid surgical treatment, the natural course of large FNH is still unknown. CASE REPORT: A 25-year-old man was admitted because of a large hepatic mass detected on routine examination in June 1998. The only laboratory abnormality was an elevated gamma-GTP. Computed tomography, angiography, positron emission tomography using F-18 fluorodeoxyglucose (FDG-PET), and scintigraphy using technetium-99m-galactosylneoglycoalbumin(99mTc-NGA) demonstrated a spoke-wheel appearance of vessels, normal hepatocytes, and no malignancy. Histologic findings on needle biopsy were consistent with FNH. After informed consent, the patient agreed to observation. Two years after the initial diagnosis, he has no symptoms, and there are no changes in the size or character of the lesion on computed tomography. DISCUSSION: Careful observation of patients with FNH is required because its natural course is unknown and these lesions can bleed or rupture.

Erythrocytosis caused by an erythropoietin-producing hepatocellular carcinoma.

A case of erythrocytosis caused by a hepatocellular carcinoma (HCC) that produced erythropoietin (Epo) is described. A 64-year-old man, with a huge HCC tumor in the right lobe of the liver, showed a high concentration of hemoglobin and increased levels of serum Epo, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II). Right lobectomy of the liver was performed. Histological findings of the specimen showed a moderately differentiated HCC. The existence of Epo was confirmed immunohistochemically only in the tumor tissue and not in the normal liver tissue. Erythrocytosis disappeared and the serum levels of Epo, AFP, and PIVKA-II returned to the normal range after the operation. Within 2 months after the operation, recurrent tumors appeared in the remnant liver, and the patient died 13 months after the operation.

Preoperative portal vein embolization improves prognosis after right hepatectomy for hepatocellular carcinoma in patients with impaired hepatic function.

BACKGROUND: Percutaneous transhepatic portal vein embolization (PTPE) increases the safety of subsequent major hepatectomy. The aim of this study was to determine the effect of PTPE on long-term prognosis after hepatectomy in patients with hepatocellular carcinoma (HCC). METHODS: Seventy-one patients with HCC underwent right hepatectomy between 1984 and 1998. Preoperative PTPE was performed in 33 patients (group 1) and was not used in 38 patients (group 2). Outcome after operation was compared between the groups. The patients were further divided according to the median tumour diameter (cut-off 6 cm) and indocyanine green retention rate at 15 min (ICGR15) (cut-off 13 per cent). RESULTS: The cumulative survival rate was significantly higher in group 1 than in group 2 in patients with an ICGR15 of at least 13 per cent. Tumour-free survival rates were similar in both groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were more frequently subjected to further treatment. CONCLUSION: Preoperative PTPE improves the prognosis after right hepatectomy for HCC in patients with impaired hepatic function, although it does not prevent tumour recurrence.

Portal vein stenting to treat portal vein tumor thrombus in hepatocellular carcinoma.

Tumor thrombus in the portal vein is refractory to therapy and a serious negative prognostic factor in hepatocellular carcinoma. We describe herein the case of a patient in whom an expandable metallic stent was successfully employed to treat portal vein tumor thrombus by restoring blood flow. An expandable metallic stent was implanted in a patient with severe main portal vein stenosis caused by tumor thrombus protruding from the left portal vein branch. Immediately after stent placement, the stenotic lesion was effectively dilated, the portal blood flow restored, and portal hypertension relieved. Angiography, computed tomography, and doppler ultrasonography done 2 months after the stent placement revealed continued patency of the portal vein. Thus, intraportal placement of an expandable metallic stent appears to be an effective treatment for major portal vein tumor

Successful treatment of a hepatic abscess that formed secondary to fish bone penetration by percutaneous transhepatic removal of the foreign body: report of a case.

We describe herein the case of a hepatic abscess that developed secondary to fish bone penetration which was successfully treated without laparotomy. A 61-year-old man was admitted to our hospital with a high fever that had persisted for 2 weeks in spite of medication. Abdominal ultrasonography (AUS) and computed tomography (CT) of the abdomen revealed a hepatic abscess with a linear calcified foreign body and gas. Percutaneous abscess drainage was performed under ultrasonographic guidance. After drainage, the patient became afebrile, and AUS and CT findings demonstrated that the abscess cavity had decreased in size, but still contained the foreign body. Under ultrasonographic guidance and fluoroscopy, we inserted endoscopic forceps into the sinus tract and succeeded in removing the foreign body from the liver. It was found to be a fish bone that was 2.8 cm long and 0.3 cm wide.

Serum endothelin-1 and hepatocyte growth factor levels in patients with obstructive jaundice.

BACKGROUND/AIMS: Endothelin-1, a potent vasoconstrictive peptide, is known to modulate changes in local circulation. Additionally, hepatocyte growth factor, a potent mitogen for hepatocytes, is increased in various liver diseases. The present study examined changes in serum endothelin-1 and hepatocyte growth factor levels in patients with obstructive jaundice before and after percutaneous transhepatic cholangio drainage. METHODOLOGY: Endothelin-1 and hepatocyte growth factor levels were measured by enzyme-linked immunosorbent assay using sera from 16 patients with obstructive jaundice before and after percutaneous transhepatic cholangio drainage. RESULTS: Serum endothelin-1 levels decreased rapidly in the good bilirubin decrease group after biliary drainage. Endothelin-1 levels decreased 1 week after drainage but then increased gradually in the worse bilirubin decrease group. Serum hepatocyte growth factor levels decreased gradually after biliary drainage, and were higher in the worse bilirubin decrease group than in the good bilirubin decrease group throughout the study. CONCLUSIONS: These results suggest that endothelin-1 may be associated with the microcirculatory disturbance in obstructive jaundice and prolonged cholestasis. Measurement of hepatocyte growth factor levels in patients with obstructive jaundice before percutaneous transhepatic cholangio drainage may be an early clinical predictor of the subsequent rate of decrease of the serum bilirubin concentration.

The role of polyamines in growth factor induced DNA synthesis in cultured rat hepatocytes.

BACKGROUND/AIMS: Hepatocyte growth factor and transforming growth factor-alpha are growth factors with important roles in hepatocyte proliferation. The polyamines, putrescine, spermidine, and spermine are widely distributed in many different cells and play an essential role in cell growth and differentiation. The present study examined the role of polyamine in this growth promoting factor-induced hepatocyte proliferation, in primary cultured rat hepatocytes. METHODOLOGY: Hepatocytes were isolated from rats by the collagenase perfusion method. Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were measured as the release of 14CO2 from L-[-14C]ornithine and S-adenosyl-L-[carboxyl14C]methionine, respectively. The concentration of polyamine was analyzed by high performance liquid chromatography. RESULTS: When transforming growth factor-alpha and hepatocyte growth factor were added to the hepatocyte culture simultaneously, ornithine decarboxylase activity, S-adenosylmethionine decarboxylase activity, polyamine concentration and DNA synthesis increased additively. The increase in DNA synthesis caused by transforming growth factor-alpha, hepatocyte growth factor, or both was completely inhibited by alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The inhibition was reversed by exogenous spermidine or spermine, but not by putrescine. CONCLUSIONS: Increased spermidine or spermine levels are essential for hepatocyte proliferation in cultured rat hepatocytes.

Portal serum human hepatocyte growth factor levels after partial hepatectomy.

BACKGROUND/AIMS: We investigated whether or not hepatocyte growth factor increases in portal serum via an endocrine mode after partial hepatectomy in humans. METHODOLOGY: Portal blood was sampled through a catheter inserted through the umbilical vein to the portal trunk during surgery in 17 patients. Serum human hepatocyte growth factor levels were determined by enzyme-linked immunosorbent assay. RESULTS: Human hepatocyte growth factor levels were higher in portal than in peripheral serum throughout the study. Portal and peripheral serum human hepatocyte growth factor levels without complications increased rapidly and reached a maximum level 1 day after partial hepatectomy. The maximal level of portal and peripheral serum human hepatocyte growth factor was 1.20 and 1.00 ng/ml, respectively. In the case of hepatic failure after partial hepatectomy, portal and peripheral serum human hepatocyte growth factor levels markedly increased and reached 9.31 ng/ml and 6.78 ng/ml 2 days before death, respectively. CONCLUSIONS: These results suggest that hepatocyte growth factor increases in portal serum via an endocrine mode after partial hepatectomy in humans. Furthermore, measurement of the portal and peripheral serum human hepatocyte growth factor levels may be useful for the clinical evaluation of patients with post-operative hepatic failure.

Mirizzi syndrome caused by xanthogranulomatous cholecystitis: report of a case.

Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory disease of the gallbladder. In severe cases, inflammation extends to adjacent structures, and XGC is sometimes confused with a malignant neoplasm. We recently diagnosed XGC as the preoperative cause of Mirizzi syndrome in a patient based on the clinical course. The patient was admitted because of obstructive jaundice, with gallbladder carcinoma as the suspected cause. The gallbladder was swollen with gallstones and the serum level of carbohydrate antigen 19-9 (CA19-9) was 3070 U/ml at admission. A percutaneous transhepatic cholangiodrainage (PTCD) was done, and the common hepatic duct as well as the right and left hepatic ducts were found to be obstructed. Later, the CA19-9 level and swelling of the gallbladder decreased and the obstruction of the bile ducts disappeared. A cholecystectomy was performed and the intraoperative pathohistological diagnosis of chronic cholecystitis was made from frozen sections. The pathohistological diagnosis of XGC was made from paraffin-embedded sections. Mirizzi syndrome such as that seen in our patient is a rare complication of XGC. XGC occasionally causes extensive inflammation; thus, performing a conventional cholecystectomy can be unsafe. However, in our opinion, a total, not subtotal, cholecystectomy should be done whenever possible because the incidence of gallbladder carcinoma accompanied with XGC is higher than that with ordinary cholecystitis or gallstones.

Polyamine metabolism in the rat liver after orthotopic liver transplantation.

We examined the polyamine metabolism in liver transplanted after cold ischemia and effects of putrescine administration on liver injury, liver regeneration, and survival rate after orthotopic liver transplantation in the rat. Male Wistar rats were used as donors and recipients. Grafts were stored in Euro-Collins solution for 6 h at 4 degrees C. Orthotopic liver transplantation was performed by the three cuff technique. The activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase elevated and peaked 4 h after liver transplantation. Hepatic ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities were also elevated and peaked 8 h after the operation. In agreement with the increases in ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities, the putrescine content increased and spermidine content decreased in the transplanted liver. Putrescine administrated intraperitoneally improved the survival rate, decreased serum transaminase level and increased the [3H]thymidine incorporation into the liver DNA. These findings suggest that both biosynthetic and biodegradative pathways are stimulated in liver transplantation, resulting in the increase in the formation of putrescine from ornithine and from spermidine, and that putrescine administration improve the survival rate by protecting the damaged graft after cold ischemia and reperfusion and by stimulating liver regeneration.

Increased spermidine or spermine level is essential for hepatocyte growth factor-induced DNA synthesis in cultured rat hepatocytes.

BACKGROUND/AIMS: Hepatocyte growth factor is a potent mitogen for mature hepatocytes and seems to act as a trigger for liver regeneration. Hepatocyte growth factor was first purified from human and rabbit plasma and rat platelets. Additionally, putrescine, spermidine, and spermine are widely distributed in many different cells; intracellular concentrations of these polyamines are closely related to cell proliferation. The present study examined whether polyamine metabolism is involved in hepatocyte growth factor-induced DNA synthesis in primary cultured rat hepatocytes. METHODS: Hepatocytes were isolated from rats by the collagenase perfusion method. Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were measured as the release of 14CO2 from L-[1-14C]ornithine and S-adenosyl-L-[carboxyl-14C]methionine, respectively. RESULTS: alpha-Difluoromethylornithine inhibited hepatocyte growth factor-induced DNA synthesis by only 21%. On the other hand, methylglyoxal bis(guanylhydrazone) completely inhibited hepatocyte growth factor-induced DNA synthesis to nontreated control level. The inhibitory effect of methylglyoxal bis(guanylhydrazone) on hepatocyte growth factor-induced DNA synthesis was reversed by exogenously added spermidine or spermine. CONCLUSIONS: Spermidine or spermine is essential for hepatocyte growth factor-induced DNA synthesis in primary cultured rat hepatocytes.

The effect of hepatic ischemia-reperfusion on polyamine metabolism in some organs of the rat.

Hepatic ischemia was produced by clamping the portal venous and hepatic arterial blood supply to the left lateral and median lobes of the rat liver. Hepatic ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities in ischemic and nonischemic regions were increased and, respectively, peaked by 6 hr and 3 hr after 1 hr of hepatic ischemia. Hepatic putrescine contents in ischemic and nonischemic regions were increased and peaked by 6 hr. However, hepatic spermidine and spermine were not increased. an increase in ODC activity was also observed in the spleen and the kidney after 1 hr of hepatic ischemia. [3H]thymidine incorporation into DNA was observed in the liver and the spleen--however it was not observed in the kidney--after hepatic ischemia.

Increase in ornithine decarboxylase activity caused by hepatocyte growth factor in primary cultured adult rat hepatocytes.

The effect of hepatocyte growth factor on ornithine decarboxylase activity was studied in primary cultured adult rat hepatocytes. Ornithine decarboxylase activity was increased 3 hr after the addition of hepatocyte growth factor and remained at a high level until 12 hr; thereafter it decreased, and it returned to the control level by 24 hr. Enzyme activity began to increase with 1 ng/ml hepatocyte growth factor and reached its maximum with 5 ng/ml hepatocyte growth factor. When insulin or epidermal growth factor was added with hepatocyte growth factor, enzyme activity was further stimulated. The level of ornithine decarboxylase messenger RNA did not increase with addition of hepatocyte growth factor. The half-time of ornithine decarboxylase activity was prolonged about twofold by hepatocyte growth factor treatment. These results suggest that hepatocyte growth factor treatment of cells enhanced ornithine decarboxylase activity posttranslationally.