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A 62-year-old man had been followed up for chronic hepatitis B (HB) since 1973. Hepatocellular carcinoma (HCC) was detected in 1985, at the age of 42 years. Serum HB surface antigen and anti-HB envelope antibody were positive at that time. A right hepatic lobectomy was performed. In 1995, serum HB surface antigen had cleared spontaneously and liver function had normalized. In March 2005, at the age of 62 years, a 1.5-cm diameter hepatic mass was detected in the left lateral segment. At that time, he was seropositive only for anti-HB core antibody. A diagnosis of recurrent HCC was made, and partial hepatectomy was performed. Covalently closed circular HBV DNA was detected in both cancerous and noncancerous tissues by nested polymerase chain reaction (PCR). Cassette-ligation-mediated PCR showed that HBV DNA was integrated into the telomerase reverse transcriptase gene located on chromosome 5p15.

Interferon therapy suppresses the development of hepatocellular carcinoma (HCC) and tumor recurrence after a resection of HCC in patients with chronic hepatitis C. However, the value of a liver resection and which method is best for the treatment of HCC detected after successful interferon therapy remains to be clarified. The risk factors for tumor recurrence after a liver resection for HCC detected after successful interferon therapy were investigated to determine the appropriate operative method for such HCC.Risk factors including the clinicopathologic findings and the operative methods for tumor recurrence were evaluated by univariate and multivariate analyses in 24 patients who underwent liver resection for HCC detected after successful interferon therapy (sustained viral response or biochemical response).According to a univariate analysis, large tumor (2 cm, P = 0.0326), multiple tumors (P = 0.0372), nonanatomic resection (P = 0.0103), and positive surgical margin (5 mm of a free surgical margin, P = 0.0245) were possible risk factors for short tumor-free survival time after surgery. A multivariate analysis showed that large tumor (P = 0.0407), nonanatomic resection (P = 0.0215), and positive surgical margin (P = 0.0253) were independent risk factors for a short tumor-free survival time after surgery.An anatomic resection with an appropriate surgical margin (or = 5 mm of a free surgical margin) is recommended for patients with HCC detected after successful interferon therapy.

Background Clinically, portal vein embolization has been proven to be useful as a preoperative treatment for major hepatic surgeries with impaired liver function. However, its effects on the metabolism and elimination of various drugs after portal vein embolization or ligation remain to be elucidated. Materials and methods A portal vein branch that perfuses the central and left lobes of the liver of male Wistar rat was ligated, and changes in the weights of ligated and nonligated lobules as well as hepatic levels and activities of cytochrome P450 (CYP) isoforms, such as CYP3A2 and CYP2C11, were determined. To evaluate in vivo the effect of PVL on hepatic drug metabolism, the narcotic activity (sleep time) of midazolam, a specific substrate for CYP3A2, was measured. Results Although plasma levels of alanine aminotransferase and hepatic weight returned to basal levels at day 7 after the portal vein ligation, hepatic activities of CYP3A2 and CYP2C11 still remained low (53% and 54% of control levels, respectively), and returned to their initial levels after about day 14. The metabolism of midazolam was prolonged by approximately three times at day 7 after ligation and returned to basal levels at day 14. Conclusions Because hepatic CYP-dependent drug metabolism by CYP isoforms recovered more slowly than the apparent recovery of hepatic volume and plasma alanine aminotransferase levels, the therapeutics of drugs metabolized by the CYP isoforms should be used carefully in patients who receive major hepatectomy with portal vein branch embolization.

We examined the expression of mucin core protein 1 (MUC1) immunohistochemically in 186 surgical specimens of histopathologically nonmucinous hepatocellular carcinoma (HCC) and compared the clinicopathological features in patients with MUC1-positive HCC (MUC1-positive group) with those in patients with MUC1-negative HCC (MUC1-negative group).MUC1 immunoreactively was present in 85 of the 186 HCCs. Of the clinicopathological variables examined, the serum concentration of alpha-fetoprotein, tumor differentiation, bile duct invasion, lymph node metastasis, and cytokeratin 19 expression exhibited significant associations with MUC1 expression. Although cumulative and tumor-free survival rates were not different between the two groups, the percentage of patients with first recurrence of HCC in distant organs (distant metastasis) within 2 years after surgery was significantly higher in the MUC1-positive group than in the MUC1-negative group (P = 0.0104). The risk ratio of MUC1 positivity for this type of distant metastasis was 3.156 (95% confidence interval, 1.064-9.358).In patients with MUC1-positive HCC, careful follow-up is necessary, not only for intrahepatic recurrence but also for distant metastasis, after the resection of primary HCC.

The Liver Cancer Study Group of Japan established a tumor-nodule-metastasis (TNM) staging system for mass-forming intrahepatic cholangiocarcinoma, with T determined by tumor number and size and vascular or serosal invasion. Serosal invasion is not considered in the designation established by the International Union Against Cancer.Sixty-three patients who underwent hepatic resection for mass-forming intrahepatic cholangiocarcinoma were investigated retrospectively, with the investigation including univariate and multivariate analyses of potential prognostic factors.By log-rank test, tumor size more than 3.0 cm, vascular invasion, lymph node metastasis, intrahepatic metastasis, and involved resection margin, but not serosal invasion, were associated significantly with poor prognosis. Even in patients with serosal invasion, the postoperative outcome was much better in those without than in those with vascular invasion. Multivariate analysis identified vascular invasion, lymph node metastasis, and an involved resection margin as independent prognostic factors. When serosal invasion was excluded from tumor staging, the 5-year survival rates became more clearly stratified: 100% in those with stage I disease, 62% in those with stage II, 25% in those with stage III, and 7% for patients with stage IV.Serosal invasion showed no survival impact after hepatic resection for mass-forming intrahepatic cholangiocarcinoma. When serosal invasion was omitted from the TNM staging proposed by the Liver Cancer Study Group of Japan, stratification of postoperative survival between stages was more effective.

Pancreatoduodenectomy can be difficult in patients with obstruction of the celiac axis because of the development of collateral arteries around the head of the pancreas. Bleeding from a pseudoaneurysm is a rare and serious complication of pancreatoduodenectomy. We report a case of a pseudoaneurysm of an enlarged dorsal pancreatic artery, which formed as a result of obstruction of the celiac axis after pancreatoduodenectomy. We assumed that a weakness in the wall of this dorsal pancreatic artery caused by the dissection led to the formation of the aneurysm. Although transcatheter arterial embolization (TAE) could not treat the aneurysm or stop bleeding from the aneurysm completely, it achieved transient hemostasis, whereby the patient's condition improved, making laparotomy safe. This case demonstrates that the dissection of arteries that have developed around the head of the pancreas must be considered in patients with obstruction of the celiac axis.

Aim: To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens. Methods: Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene. Results: CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation. Conclusion: These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis.

We investigated the correlation between serum concentrations of type IV collagen 7s domain (7s collagen) and changes in the volume of the nonembolized liver lobe after subsequent portal vein embolization (PVE).The relationship between the pre-embolization results of laboratory tests and the increase in the left lobe volume was evaluated in 32 patients who underwent preoperative PVE via the right portal vein.By 2 weeks after PVE, the mean volume of the left lobe had increased significantly (P0.001). The percent increase in the left lobe volume correlated negatively with the pre-embolization serum concentration of 7s collagen (r = -0.472, P = 0.0063). In three of four patients with high serum concentrations (8 ng/ml), the percent increase was less than 100% and right lobectomy was not performed. The serum 7s collagen concentration correlated with the histologic activity score (r = 0.469, P = 0.0061) and the histologic fibrosis score (r = 0.425, P = 0.0145).The serum concentration of 7s collagen may predict the efficacy of PVE. Performing PVE before right lobectomy may not be indicated in patients with high serum concentrations of 7s collagen because the increases in left lobe volume may be insufficient.

Ischemia-reperfusion injury is responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. Recently, it has been reported that mitochondrial K A T P channel openers have an effect on myocardial protection via a pharmacological preconditioning action. However, it remains unclear as to whether K A T P channel openers can reduce ischemia-reperfusion injury in the liver. The aim of this study was to determine the effects of the mitochondrial K A T P channel opener, nicorandil, on ischemia-reperfusion injury in the rat liver. Male Wistar rats were subjected to 73% ischemia for 45 minutes followed by 120 minutes of reperfusion. Nicorandil (3 mg/kg) was orally administered 60 minutes before hepatic ischemia. Nicorandil significantly decreased plasma levels of alanine aminotransferase and lactate dehydrogenase by about 50% and inhibited the remarkably increased TUNEL-positive hepatocytes after reperfusion. Some mediators associated with apoptosis were analyzed by Western blotting. Cytochrome-c and caspase-3 levels in the cytosol increased after reperfusion; nicorandil inhibited the release of cytochrome-c and activation of caspase-3. The expression of Bax and Bcl-2 was significantly increased after reperfusion, being slightly inhibited by the administration of nicorandil. These results suggest that the protective effects of nicorandil against hepatic ischemia-reperfusion injury correlate with the inhibition of mitochondrial cytochrome-c release and caspase-3 activation. These findings demonstrate that nicorandil may become a therapeutic drug for ischemia reperfusion-related liver injury.

Background. In organ transplantation, several immunosuppressants are currently used to control graft rejection. Clinically, no single immunosuppressive agent can completely prevent posttransplantation immunoreaction; thus, combination therapy is usually performed. Novel agents with more powerful immunosuppressive activity and less toxicity need to be developed. Methods. Lewis rat livers were orthotopically transplanted into Brown-Norway recipients. FK778 was administered orally from day 0 to day 6 to prevent acute rejection and from day 7 to day 13 to rescue ongoing rejection. To assess the combined effects, recipients were treated with intramuscular injection of FK506 and oral administration of FK778 from day 0 to day 6. Blood chemistry and histopathologic findings were measured to determine the patient's general condition and the graft condition. Allospecific antibodies were measured using enzyme-linked immunosorbent assays. The FK778 trough concentration was examined by using high-performance liquid chromatography. Results. The acute immune response was suppressed by FK778 alone in a dose-dependent manner. The optimal FK778 dosage was determined to be 20 mg/kg per day, because adverse effects (weight loss and intestinal bleeding) occurred at 30 mg/kg per day. FK778 treatment from day 7 to day 13 rescued liver grafts from ongoing rejection. The intramuscular FK506 (0.125 mg/kg per day) injection and the oral FK778 (20 mg/kg per day) gavages suppressed acute liver graft rejection effectively and maintained better graft condition compared with monotherapy. Conclusions. FK778 treatment effectively prevented acute rejection and rescued ongoing rejection after liver transplantation. The optimal dosage was determined to be 20 mg/kg per day. Combination therapy with FK506 was more beneficial than FK778 monotherapy.

Background The prognosis of hepatocellular carcinoma originating in or mainly involving the caudate lobe (caudate HCC) is generally poor. We reviewed the clinicopathologic findings of patients who underwent liver resection of caudate HCC and correlated the outcome with the surgical strategy. Methods Records of 402 patients who underwent liver resection for HCC were reviewed. The patients were divided into 2 groups. One group consisted of 15 patients who underwent liver resection for caudate HCC. The other group included 387 patients with HCC in a site other than the caudate lobe. Results Anatomic resection of Couinaud segment I or IX (a partial caudate lobectomy), conforming to portal anatomy, was performed in 13 patients with caudate HCC, and segmentectomies of segments I and IX (a total caudate lobectomy) were performed in 2 patients with caudate HCC. The incidence of postoperative complications was similar in the caudate HCC group and HCC in other sites group, with no operative deaths in the caudate HCC group. Tumor-free survival and cumulative survival were similar in the 2 groups. However, among patients with caudate HCC, tumor-free and cumulative survival were lower in patients with than without microscopic portal venous involvement ( P Conclusions Partial caudate lobectomy (anatomic resection of segment I or IX) along the portal system is an appropriate procedure for caudate HCC, especially in patients with impaired liver function or a small HCC. Patients with caudate HCC who have microscopic portal venous involvement may require adjuvant therapy as early recurrence is likely.

To determine the predictive value of the preoperative serum concentration of type IV collagen 7s domain (7s collagen) for postoperative hepatic failure in patients undergoing liver resection for hepatocellular carcinoma.Clear and reliable criteria for predicting hepatic failure after liver resection are needed. The serum 7s collagen concentration correlates with the histologic degree of active hepatitis and hepatic fibrosis and may predict the regenerative potential of the liver.Potential risk factors for postoperative hepatic failure, including the serum 7s collagen concentration, were evaluated in 251 patients who underwent liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses.Hepatic failure developed postoperatively in 25 patients, 4 of whom died. The serum 7s collagen concentration correlated with the histologic degree of hepatitis activity and hepatic fibrosis. The serum 7s collagen concentration was a risk factor for postoperative hepatic failure by univariate analysis and was the only risk factor on multivariate analysis. No patient with a serum 7s collagen concentration12 ng/mL died of postoperative hepatic failure, and all 4 patients who died had a serum 7s collagen concentrationor=12 ng/mL.The preoperative serum 7s collagen concentration correlated independently with hepatic failure following liver resection for hepatocellular carcinoma. Patients whose serum 7s collagen isor=12 ng/mL are poor candidates for hepatic resection.

A 65-year-old Japanese man underwent radiofrequency ablation (RFA) therapy of a hepatocellular carcinoma. Hemobilia from the intrahepatic bile ducts adjacent to the tumor developed on the fifth day after the RFA therapy. Ultrasonograms and computed tomograms showed swelling of the gallbladder, which was filled with a clot, suggesting the diagnosis of hemocholecyst. The hemobilia resolved with conservative therapy, but a cholecystectomy was performed to manage postprandial abdominal pain. The resected gallbladder was filled with a clot, but injury or ulceration of the gallbladder was absent, suggesting that the hemocholecyst developed secondary to the hemobilia. Secondary hemocholecyst is a rare complication of RFA therapy. The number of cases of secondary hemocholecyst is likely to increase as hepatocentestic therapy becomes more common. Cholecystectomy is indicated for hemocholecyst because spontaneous liquefication and drainage of a clot in the gallbladder usually does not occur.

Background. Although living-donor liver transplantation (LDLT) has been accepted for adult populations, the occurrence and pathogenesis of small-for-size syndrome remain highly controversial. Methods. Portal venous pressure (PVP) was measured in 79 cases of LDLT from anhepatic phase to day 14. PVP was monitored through a catheter inserted via the inferior mesenteric vein. In a separate series of seven cases of adult LDLT, the splenic artery was ligated following arterial reperfusion. Results. For days 2 to 4 and 9 to 11, recipients of small-for-size graft (

We investigated the incidence of recurrence after resection of small hepatocellular carcinomas (HCC) in patients infected with hepatitis C virus (HCV) to determine the appropriate surgical management of these patients. Sixty-one patients with anti-HCV antibody who underwent curative liver resection for small HCC (≦ 2.0 cm in greatest diameter) were categorized into two groups. Group 1 consisted of 27 patients with serum concentrations of type IV collagen 7S domain (7S collagen), a marker for hepatic fibrosis, < 8 ng/ml. Group 2 consisted of 34 patients with serum concentrations of 7S collagen ≧ 8 ng/ml. Serum concentration of 7S collagen correlated with the severity of active hepatitis and the degree of fibrosis in the noncancerous hepatic tissue, both of which are related to risk potential of hepatocarcinogenesis. Serum concentration of total bilirubin, aspartate aminotransferase activity, indocyanine green retention rate at 15 minutes, the proportion of patients who were Child-Pugh class B, and the proportion of patients with severe active hepatitis or cirrhosis (determined by histologic examination) were significantly higher in group 2 than in group 1. Platelet count was significantly lower in group 2. Tumor-free survival rates were not different between the groups. In group 1, nonanatomic resection was a risk factor for recurrence by univariate and multivariate analyses (odds ratio = 3.45, p = 0.040). In group 2, nonanatomic resection was not a risk factor for recurrence. In patients with small HCV-related HCC, anatomic resection is recommended when the serum concentration of 7S collagen is low (< 8 ng/ml) because the potential of hepatocarcinogenesis may be low even after the operation.

Background/Aims: Serum concentration of type IV collagen 7S domain (7S collagen) is a marker of hepatic fibrosis. We investigated the usefulness of measuring the serum 7S collagen concentration as a risk factor for recurrence after liver resection for hepatocellular carcinoma (HCC). Methods: The serum 7S collagen concentration was measured before liver resection for HCC in 219 patients. Group 1 included 102 patients with a high serum concentration of 7S collagen (≧8.0 ng/ml), and group 2 consisted of 117 patients with a low serum concentration of 7S collagen (Results: The results of liver function tests were better in group 2 than in group 1. The percentage of patients with cirrhosis or who underwent minor resection was higher in group 1 than in group 2. The percentage of patients with moderately or poorly differentiated HCC or portal invasion was higher in group 2 than in group 1. Univariate and multivariate analyses identified that a high serum concentration of 7S collagen (≧8.0 ng/ml) was an independent risk factor for recurrence. Conclusion: Measuring the serum 7S collagen concentration is useful to estimate the risk of recurrence after resection of HCC.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder characterized by extensively vascularized tumors and cysts in specific organs. Angiogenesis is a striking future of VHL disease with its characteristic cysts and well-vascularized tumors. The hypervascular nature of VHL lesions has been linked to the overproduciton of vascular endothelial growth factor (VEGF) through increased expression of hypoxia inducible factor-1alpha (HIF-1alpha). Here we describe a rare case of VHL disease with esophageal and gastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas, which, upon immunohistochemical examination, exhibited HIF-1alpha and VEGF expression. Rupture of esophageal varices was successfully treated with endoscopic injection sclerotherapy.

Background/Aims: The improvement of diagnostic modalities and operative techniques has resulted in prolonged survival for cancer patients, but has also led to the diagnosis of an increasing number of patients with synchronous hepatocellular carcinoma (HCC) and extrahepatic primary cancer. It is necessary to determine the optimal surgical strategies for synchronous HCC and gastric cancer. Methods: In this retrospective study, clinicopathologic findings, diagnostic methods, treatment and outcome were reviewed in 13 patients who underwent curative surgery for synchronous HCC and gastric cancer. Results: Twelve of the 13 patients were men older than 60 years. All patients had chronic hepatic disease, and hepatitis viral infection was detected in 9 patients. Examinations of the esophagus to search for esophageal varices before liver resection for HCC, and imaging studies to rule out liver metastasis before gastrectomy for gastric cancer can lead to the incidental finding of a synchronous carcinoma. The most frequent postoperative complication was massive ascites, which occurred in 4 patients who underwent lymph node dissection, 1 of whom died of perioperative hepatic failure. HCC recurred in 7 patients, 4 of whom died of their disease; only 1 patient died of recurrence of gastric cancer. Conclusion: Careful follow-up for recurrence of HCC is necessary because the most common cause of death in patients with synchronous carcinoma is recurrence of HCC.

A 63-year-old woman successfully underwent a graft replacement of the retrohepatic inferior vena cava with a ringed polytetrafluoroethylene graft for primary leiomyosarcoma of the inferior vena cava (IVC). Although anticoagulant had been administered, a thrombus was found in the IVC just cranial of the downstream anastomosis 67 months after the operation. The patient remained free of symptoms, and she had no evidence of any tumor recurrence. She underwent a complete resection with a prosthetic reconstruction for leiomyosarcoma of the IVC and has since been able to enjoy a reasonably long-term survival. The occurrence of thrombosis must be kept in mind in the long-term follow-up of such cases.

Background Bile leakage is one of the frequent and disturbing complications of hepatic resection. Study design Clinical records of the 363 patients who underwent hepatic resections without biliary reconstruction for hepatic cancers between January 1994 and June 2001 were reviewed. Postoperative bile leakage was defined as continuous drainage with a bilirubin concentration of 20 mg/dL or 1,500 mg/d lasting 2 days. Leakage that continued longer than 2 weeks or that required surgical intervention was defined as uncontrollable. Differences in incidence and frequency of uncontrollable leakage for the different types of hepatic resection, tumors, and underlying liver disease were investigated. Outcomes after treatment for uncontrollable bile leakage were also reviewed. Results Postoperative bile leakage occurred in 26 of 363 patients (7.2%). Although the incidence in patients with cholangiocellular carcinoma (3/9 [33%]) was higher (p = 0.03) than in patients with hepatocellular carcinoma, rates of occurrence were similar among the different types of hepatic resection and underlying liver disease. Eight of the 26 patients (31%) had uncontrollable leakage. Two patients required reoperation to control leakage; one of these developed hepatic failure and died 2 months after surgery. Four patients underwent endoscopic nasobiliary drainage 21 to 34 days after hepatectomy, and the leakage resolved within 3 to 21 days. Fibrin glue sealing was effective in two patients whose leaking bile ducts were not connected to the common bile duct. Conclusions Although meticulous surgical technique can minimize the risk of postoperative bile leakage, some instances of leakage are unavoidable. Nonsurgical treatments, such as nasobiliary drainage or fibrin glue sealing, are preferable to reoperation.

Background The prognosis of patients without nodal metastasis of oesophageal cancer is generally good, but recurrence develops in some cases. Methods Data on 88 consecutive patients with squamous oesophageal cancer who underwent three-field lymph node dissection from 1986 to September 1998 and who had no evidence of nodal disease were reviewed retrospectively. Disease status was based on histological examination of the section of each node with the largest surface area, stained with haematoxylin and eosin. Results The 3- and 5-year survival rates of patients without lymph node metastasis were 85 and 81 per cent respectively, better than in patients with metastasis. Twelve patients died from recurrence. Recurrence was haematogenous in nine patients and locoregional in three. Survival was worse in men, for patients with lesions located in the upper thoracic oesophagus, and in those with lymphatic or blood vessel invasion. Only the presence of lymphatic invasion correlated with survival on multivariate analysis (P = 0·04). Conclusion Although survival was generally good in patients without nodal metastasis from oesophageal cancer following three-field lymph node dissection, patients with lymphatic invasion remained at risk for haematogenous dissemination.

Although curative surgical resection provides the best chance of long-term survival for patients with intrahepatic cholangiocarcinoma, the presence of bile duct invasion decreases postoperative survival rates in patients with mass-forming intrahepatic cholangiocarcinoma. We carried out this study to determine a surgical strategy for patients with bile duct invasion of these tumors. Forty-one patients with mass-forming intrahepatic cholangiocarcinoma were classified as either having bile duct invasion (n= 26) or not having bile duct invasion (n= 15). Clinicopathologic findings, including postoperative outcomes, were compared between these two groups. Perineural invasion, lymphatic invasion, and a positive resection margin were more frequent in patients with ductal invasion. Patients with ductal invasion had lower survival rates than those without ductal invasion. Intraoperative frozen section examination of the bile duct stump to confirm a clear resection margin is required in patients with mass-forming tumors. Resection of the extrahepatic bile duct should be considered when tumor cells are identified at the surgical margin of the resected bile duct.

To clarify the variables related to survival after recurrence of resected hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV), we studied 17 clinicopathological factors in 99 patients with recurrence of HCC associated with HCV infection after hepatic resection. The 1-, 3-, and 5-year survival rates after first resection in these patients were 91%, 81%, and 49%, while after recurrence they were 81%, 51%, and 29%, respectively. Multivariate analysis showed that the following six variables were independent prognostic factors after recurrence: platelet count, albumin level, bilirubin level, number of hepatic lesions, distant metastasis, and any treatment at recurrence. A correlation between second hepatic resection (SHR) and liver function tests was seen in regard to albumin and total bilirubin values at recurrence. Indeed, hepatic function and progression of intrahepatic tumors at recurrence were significant prognostic factors after recurrence of HCC associated with HCV infection, while any treatment at recurrence was also a significant prognostic factor. Therefore, in order to improve prognosis after recurrence, we should actively treat the recurrent hepatic lesions whenever possible.

Worldwide, patients with hepatitis B virus (HBV) number as many as 280 million. HBV infection is a risk factor for hepatocellular carcinoma (HCC), 1 most effectively treated by resection. Recent progress in the preoperative evaluation of liver function, surgical procedures, and perioperative management has improved the results of liver resection. 2,3 However, resection in patients with chronic liver disease still can lead to postoperative hepatic failure, resulting in decompensation and death. The Child-Pugh classification 4 has been used frequently to evaluate preoperative liver function. Risk factors for postoperative hepatic failure have been studied by many investigators, and various new methods have been proposed for evaluating preoperative liver function. 3,5–12 After undergoing liver resection for HBV-related HCC, some patients again develop hepatitis. Four years ago, we treated an HBV carrier and who underwent right lobectomy for HCC and 6 weeks later developed fatal acute hepatic failure with remarkably increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (≥3,000 IU/L). The patient had well-preserved liver function before surgery and was discharged from the hospital 4 weeks after surgery. Although acute hepatic failure has been reported to occur from reactivation of HBV replication after liver transplantation, 13 whether reactivation of HBV replication occurs after liver resection is not known, nor is the relation of such an event to postoperative hepatitis. In the present study, we retrospectively studied the incidence of postoperative hepatitis. Beginning in 1994, we also prospectively investigated reactivation of HBV replication after liver resection and factors that might be associated with reactivation.

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.

22歳,男性.平成11年9月20日に交通事故のため,大阪府下の救命センターに搬送された. IIIB型肝外傷による腹腔内出血と診断され,肝動脈塞栓術が施行された.術後発熱が続くため胆嚢炎と診断,同月24日に胆摘術が施行された.しかし発熱は遷延し, 29日に発熱の原因と考えられたS5, S6の挫滅肝の非定型的部分切除が行われた.術後ドレーンより胆汁痩がみられ,保存治療で軽快せず,平成12年3月7日に当院転院となった. 瘻孔造影でS7肝内胆管が描出され,後枝の損傷による胆汁瘻と診断し, 4月5日に再々開腹した.肝門部で後枝胆管の肝側断端を確認しえたため胆道造影を施行し,肝管走行を確認した後に肝右葉切除を施行した.切除肝重量は425g. 術後経過は良好で,術3週後に軽快退院した. 肝外傷では胆管損傷を伴うことも多いため,胆道造影を行った後に,可能な限り定型的な肝切除を行うことが望ましいと思われた.

Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.

The presence of small additional hepatocellular carcinomas (HCCs) undetectable before hepatic resection is a crucial topic for hepatic surgeons. We assessed the incidence of pathologically diagnosed multiple HCCs in 267 patients who underwent hepatic resection for HCC. Ninety-five additional HCC nodules were detected in 72 of the patients (27%). The survival rate of these 72 patients was significant worse than for the 195 with single nodular HCC (p = 0.0013). Twenty-one (22%) were detected before surgery, 29 (31%) during surgery, and 45 (47%) on pathologic examination after surgery. The mean nodule diameters for each group were 2.1, 1.0, and 0.9 cm, respectively (p0.0001). None of the 21 nodules detected before surgery was well differentiated, whereas 30 of the 74 nodules in the other two groups were well-differentiated. Although the mean nodule diameter of the well-differentiated HCC group was the smallest, there was no significant difference among the three groups assigned according to tumor differentiation (p = 0.2355). Altogether, 9 of 16 patients with additional nodules detected before surgery (56%) and 49 of 59 with additional nodules detected during or after surgery (88%) had cirrhosis of the liver. The odds ratio for detecting a new HCC nodule during or after surgery in the presence of cirrhosis was 5.444 (p = 0.0087). Improvement in the detection of small additional HCC nodules before and during surgery and meticulous follow-up after surgery are necessary for patients with cirrhosis. For patients without cirrhosis, surgical treatment may be performed according to the results of preoperative imaging studies.

The frequency of lymph node (LN) metastasis in patients undergoing surgery for hepatocellular carcinoma (HCC) has rarely been studied. We evaluated the clinicopathologic characteristics and outcomes of six patients with nodal metastases from HCC among a total of 504 patients who underwent hepatic resection for HCC in our department over a 16-year period. The nodal metastases were diagnosed preoperatively in two patients. The average diameter of the resected tumors was 7.8 cm and all were confirmed as poorly differentiated HCC. All of the six patients had intrahepatic metastatic nodules and five also had portal vein invasion. One patient underwent limited resection, and the other five underwent bisegmentectomy. All of the regional LNs were removed in one patient, while only enlarged LNs were removed in the other five. One patient died of postoperative liver failure and the others all died later of intrahepatic or nodal recurrence. Our findings suggest that the prognosis of patients with nodal metastasis from HCC is generally poor, even if hepatic resection with regional LN dissection is performed.

われわれが切除した肝細胞癌562例のうち1998年7月までに臨床的に肺転移を来たした23例を肺転移巣切除8例 (肺切群) と非切除15例 (非肺切群) に分け各群の臨床像を比較した.肺転移時に残肝再発を併存した症例は肺切群, 非肺切群でそれぞれ5例, 10例であった. このうち非肺切群3例には追加治療を行いえなかった. 肺転移までの期間, 肺転移巣の局在に差はなかったが, その個数は肺切群では全例countableで, 非肺切群では3例がuncountableであった.肝切除後累積生存率および肺転移後累積生存率とも肺切群が良好であった (p=0.0447, p=0.0020).また, 非肺切群死亡11例中3例が肺転移に起因する癌死であったが, 肺切群死亡4例の死因は肺転移によるものでなかった.肺転移巣数がcountableで, 残肝再発の制御されている肝癌切除後肺転移例に対して肺切除を行うべきであると考える.

We treated 30 patients with hepatocellular carcinoma (HCC) by laparoscopic microwave coagulation therapy (LMCT) and 5 patients with hepatic tumors by laparoscopic hepatectomy (LH). LMCT : The HCC was between 10 and 35 mm in longest diameter. After observation of the surface of the liver during laparoscopy as usual, the lesions were punctured with a electrode needle, coagulated with 60 to 80 W for 45 seconds. The efficacy of LMCT was evaluated by dynamic CT or dynamic MRI. After LMCT, 3 lesions of 3 patients were thought to be coagulated insufficiently and additional therapy was needed. The lesions of the other patients seemed to be coagulated sufficiently. LH : We treated 5 patients by LH under general anesthesia. The longest diameters of tumors were between 13 mm and 45 mm. All tumors were located at the edge of the liver. We coagulated the surrounding tissues around the tumors with the above mentioned method and resected the coagulated lesions with Laparoscopic Coagulating Shears System. The bleeding were few and no serious complications were not found. Conclusions : Laparoscopic treatment for HCC was useful but the indication was restricted by location of HCC.

Erythrocyte deformability is an important factor in the microcirculation. The deformability in patients with chronic liver disease is less than normal. We studied changes in erythrocyte deformability in 32 patients undergoing liver resection for hepatocellular carcinoma with underlying chronic liver disease to investigate whether the measurement of deformability gives information useful for postoperative management. We measured erythrocyte deformability as erythrocyte transit time (ETT) before and after resection, as well as the erythrocyte adenosine triphosphate level, mean corpuscular volume, mean corpuscular hemoglobin concentration, and indices of liver function. The 15-minute indocyanine green retention rate (ICGR15) was measured before resection. Correlations between the change in deformability and these values were evaluated, as was correlation with the scale of the operation and with the occurrence of postoperative complications. Mean ETT was higher in the patients before resection than in healthy volunteers. ETT was correlated with serum high density lipoprotein-cholesterol (p0.05). The incidence of postoperative complications was higher (p = 0.001) in the patients (group A) with ETT increased during the first 3 postoperative days by/=1 SD of the mean of the preoperative value than in patients (group B) with less change. Of the 12 patients whose ICGR15 value was/=20%, all 9 patients in group A had postoperative complications. The increase in ETT (decrease in erythrocyte deformability) is associated with the development of postoperative complications. The measurement of erythrocyte deformability gives information useful for postoperative management, and special monitoring for postoperative complications is necessary in patients with the increase soon after liver resection.

In an attempt to define better surgical strategies for patients with hepatocellular carcinoma (HCC), we conducted a retrospective analysis of 452 patients who underwent hepatic resection at our institute during a period of 15 years. The patients were divided into two groups: group A, comprising 188 patients who underwent hepatic resection before 1988, and group B, comprising 264 patients after 1989. These groups were compared clinicopathologically. The percentage of patients with Child's A disease but without cirrhosis, in group A was lower. The diameter of the resected tumor was larger in group A, and major hepatic resections and curative operations were more frequently performed in group A. In group B, there was less blood loss, the specimen weighed less, and the hospital mortality was lower. Although the tumor-free survival rates were similar between the two groups, the survival rate in group B was significantly better. While even minor hepatic resection accompanied by a lower rate of surgical margin-free surgery has contributed to making hepatic resection safer, it has not improved the tumor-free survival rate. Conversely, recent advances in imaging modalities used during follow-up for the early detection of recurrence and for planning multimodality treatment have contributed to increasing the survival rate.

We treated 2 patients with hepatocellular carcinoma by laparoscopic partial hepatectomy. The longest diameters of the tumors were 25 mm and 30 mm. The both tumors were located at the edge of segment 3 in the liver. After observation of the surface of the liver during laparoscopy as usual, we punctured the surrounding tissues around the tumors with electrode needle and coagulated 80 W for 45 seconds with microwave tissue coagulator. And resected the coagulated lesions with Laparoscopic Coagulating Shears System. The bleeding were few and no serious complications were not found. The resected specimens showed that the tumors were completely resected. Laparoscopic partial hepatectomy was useful for hepatocellular carcinoma located at the edge of the liver.

症例は52歳の男性. 1990年10月左腎癌の診断のもと左腎摘出術をうけ, 術後インターフェロンを投与された. 1996年10月検診の上部消化管造影検査にて異常陰影を指摘され, 精査の結果胃癌と診断された. 11月18日開腹すると胃角部に3×2cmのIII+IIc類似進行癌を認め, さらに空腸起始部に6×9cmの腫瘤を認めた. 胃癌に対し胃幽門側切除術, D2リンパ節郭清を, 小腸腫瘍に対し口側断端を十二指腸第4部とした小腸部分切除術を行った. 再建は空腸断端を十二指腸第2部に側側吻合したのち, BillothII法による胃空腸吻合を行った. 病理組織診断は胃癌は高分化型管状腺癌, 小腸腫瘍はmalignantlymphoma of mucosa-associated lymphoid tissueであった. 術後VEPA療法を施行し術1年7か月後の現在, 再発の徴候なく健在である.

We investigated morphological and functional changes after portal vein occlusion in rats. Portal branches for the median and left lateral lobes were ligated, after which the lobes were examined micromorphologically. After embolization of the same branches, regenerative capacity was evaluated in normal livers and in livers with CCl4-induced cirrhosis. Indocyanine green elimination, antithrombin III activity, and Kupffer cell density were also investigated. In another set of rats, the embolized lobes were resected 0, 2, 4, or 7 days after portal vein embolization (PVE), and endotoxin was injected intravenously 48h after each hepatectomy. In the ligated lobes, apoptotic hepatocytes were detected mainly around a widespread necrotic area on day 2, and among normal hepatocytes on day 7. In the nonembolized livers of control rats, increases were noted in liver weight, ornithine decarboxylase (ODC) activity, DNA synthesis, and mitosis of hepatocytes. In the cirrhotic livers, ODC activity was stimulated in a fashion similar to that seen in control liver, but DNA synthesis and weight change was delayed, although not significantly. On days 2, 4, 7, and 14 PVE, Kupffer cell density was about twice that seen in rats before PVE. Endotoxin-induced liver injury was slight if the rats had received PVE 4-7 days before the hepatectomy.

Hepatocellular carcinoma (HCC) is often associated with chronic liver disease, such as hepatitis or cirrhosis, and this association may limit the use of surgery as a therapy, and if surgery is pursued, may give rise to postoperative hepatic failure. We evaluated the outcome in patients with HCC given preoperative portal vein embolization (PVE) before they underwent major hepatectomy. After PVE, portal pressure increased significantly. Two weeks after PVE, both the volume of the non-embolized lobe and the 15-min indocyamine green retention rate (ICG R15) were significantly increased. The prognostic score, calculated on the basis of age, ICG R15, and the resection rate, was significantly decreased. The operative mortality rate was significantly lower in patients who underwent PVE before surgery than in patients who did not receive PVE. The cumulative survival rate of the PVE patients, even those with cirrhosis of the liver, was significantly higher. Prior PVE appears to allow more extensive major hepatectomy and to lessen the risk of this invasive surgery. However, patients in whom the portal pressure immediately after PVE was more than 30cm H2O and/or whose prognostic score exceeded 50 points developed postoperative hepatic failure. These features should be kept in mind when it is decided whether surgery is indicated. Nevertheless, preoperative PVE appears to be a beneficial procedure for patients undergoing major hepatectomy, particularly those with chronic liver disease.

We investigated the relationships between alcohol consumption, the degree of malignancy evaluated histologically, and tumor-free survival rates.In 80 male patients with the hepatitis C virus and small hepatocellular carcinomas (diameter of main tumor, 3.0 cm or less), 38 patients had drunk 86 gm or more of ethanol per day for at least 10 years until the detection of hepatocellular carcinoma (group 1), whereas the remaining 42 patients were nondrinkers or occasional drinkers (group 2).Differences in the results of liver function tests between the groups were not statistically significant. The operative methods used in the groups were comparable. The proportion of well-differentiated hepatocellular carcinoma was lower in group 1 than in group 2 (p0.0001). The prevalences of extracapsular invasion, portal tumor thrombi, and intrahepatic metastasis were higher in group 1 than in group 2 (p = 0.0085, p = 0.0319, and p = 0.0428, respectively). The tumor-free survival rate after operation was lower in group 1 than in group 2(p = 0.041 by the log-rank test; p = 0.032 by the generalized Wilcoxon test).These findings indicate that in group 1, even though tumors were small, the carcinomas were advanced and the outcomes after surgery were poor, suggesting that alcohol affects the grade of malignancy of this disease.