[Hemobilia due to ruptured superior pancreaticoduodenal pseudoaneurysm after chemoradiotherapy for pancreatic head cancer: an autopsy case report].

A 78-year-old man came to our department because of obstructive jaundice, and was diagnosed as pancreatic head cancer. He underwent chemoradiation therapy. A metal stent was inserted into the common bile duct and the patient was followed up on an outpatient basis. The patient visited our emergency department 46 days after stent insertion due to abdominal pain. The patient was diagnosed with ruptured pseudoaneurysm of the superior pancreaticoduodenal artery by angiography and treated with coil embolization. He died due to sudden deterioration the next day. Pathological autopsy revealed that the cause of the ruptured pseudoaneurysm appeared to be vasculopathy due to radiation therapy.

Neoplastic seeding after radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: Neoplastic seeding reportedly occurs in up to 12.5% of patients treated with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study is to assess the incidence, risk factors, and prognosis of neoplastic seeding after RFA among a large number of patients with a long-term follow-up. METHOD: From February 1999 to December 2004, 1,031 patients underwent a total of 1,845 treatments with RFA for a total of 3,837 HCC nodules. The following variables were assessed to elucidate the risk factors of neoplastic seeding: age, sex, positivity for viral markers, tumor size, number of tumor nodules, number of RFA sessions, tumor location, percutaneous biopsy prior to RFA, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) levels, and the degree of tumor differentiation. RESULTS: Neoplastic seeding was detected in 33 patients (3.2% per patient) at intervals of 4.8-63.8 (median, 15.2) months after RFA. On multivariate logistic regression analysis, only the poor differentiation degree was associated with the risk of neoplastic seeding (P= 0.012). Of tumor factors, tumor size, and AFP, DCP, and AFP-L3 levels were significantly associated with the poor differentiation degree. The cumulative survival rates 1 and 2 yr after the detection of neoplastic seeding were 86% and 47%, respectively. CONCLUSION: Poor differentiation degree was the risk factor of neoplastic seeding after RFA for HCC. The surrogate markers for poor differentiation degree were larger tumor size and elevated tumor marker levels. Indication for RFA should be carefully considered for HCC patients under these conditions.

Extrahepatic metastasis of hepatocellular carcinoma: incidence and risk factors.

BACKGROUND: Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of growing importance as the survival of patients has been improved owing to advances in treatments to intrahepatic lesions. METHODS: To elucidate the incidence and risk factors of extrahepatic metastasis of HCC, we enrolled 1573 (1131 treatment-naïve and 442 previously treated on referral) patients with HCC without extrahepatic tumour spread treated at the authors' department between 1990 and 2003. Patients received medical treatment including percutaneous ablation and transcatheter arterial chemoembolization, and followed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) and tumour markers every 3-4 months. Extrahepatic metastasis was diagnosed by plain X-ray, CT, MRI and scintigraphy. Clinical parameters at the time of treatment to intrahepatic lesions were evaluated as a predictor of subsequent extrahepatic metastasis among the 1131 treatment-naïve patients by Cox's proportional hazard model. RESULTS: During the average observation period of 3.9 years, extrahepatic metastasis was diagnosed in 123 in the treatment-naïve and 53 in the patients treated previously. The incidence rate of extrahepatic metastasis, as detected during the lifetime after medical treatment of HCC, was approximately 13% at 5 years. Multivariate analysis with Cox proportional hazard model revealed that positivity for viral markers, lager tumour diameter, multiple tumour nodules, presence of vascular tumour invasion and elevated tumour markers were associated with the development of extrahepatic metastasis. CONCLUSION: The incidence of extrahepatic metastasis of HCC diagnosed during clinical course was not frequent. Advanced intrahepatic lesions, presence of vascular tumour invasion, elevated tumour markers and presence of viral hepatitis were risk factors for extrahepatic metastasis.

Right trisectionectomy of the liver for intrahepatic cholangiocarcinoma with bile duct invasion in a Jehovah's Witness.

Intrahepatic cholangiocarcinoma (ICC) is well known to have a very poor prognosis. Aggressive surgical strategies in the treatment of ICC, including major hepatectomy, have been reported to afford patients the best chance for significant survival. Recent advancements in surgical techniques concerning live donor liver transplantation have dramatically improved the results of major hepatectomy. However, surgical treatment of biliary malignancy is complex and is known to increase the likelihood of blood transfusion. We describe a Jehovah's Witness patient with ICC and concomitant bile duct invasion who had a successful right trisectionectomy with bile duct resection, lymph node dissection, and Rouxen-Y hepatico-jejunostomy without blood transfusion. A multidisciplinary preparation was crucial in obtaining this positive outcome. Importantly, bloodless liver transection techniques with inflow clamping, meticulous dissection, and hemostasis should be utilized for major hepatectomy in a Jehovah's Witness. The success of this case may alert clinicians to consider a hepatectomy as a possible option in the treatment of ICC in a Jehovah's Witness.

Age-related comparison of the profiles of patients with hepatocellular carcinoma.

BACKGROUND/AIMS: It is not known whether the putative etiologic factors and clinical and pathological features of hepatocellular carcinoma differ between young adults and older patients. Therefore this study aims to evaluate whether the clinicopathological features in young patients with HCC significantly differ from those of elderly patients. METHODOLOGY: A total of 1014 consecutive patients with HCC were divided into two groups based on age. Among them, 73 patients younger than 50 years of age comprised the first group and 941 patients 50 years and older made up the second. Clinical, laboratory, and pathological characteristics were compared between the two age groups. RESULTS: The male: female ratio and the incidence of positive hepatitis B surface antigen were significantly higher in young patients than in elderly patients. Tumor size, pathological grading of the tumor, and the severity of liver disease did not differ between the two groups. Especially in those patients demonstrating positive antibody to hepatitis C virus, alanine aminotransferase was higher in the younger, and platelet count was lower. Younger patients also had a higher ratio of alcohol consumption compared to elderly patients. CONCLUSIONS: There were age-related differences in the clinicopathological characteristics of HCC patients. Concerning hepatocarcinogenesis, male and HBsAg positive patients were at high risk in young. Of the HCV-related HCC patients, heavy drinking may accelerate the progression from chronic hepatitis to cirrhosis and HCC.

Factors predisposing to poorly differentiated hepatocellular carcinoma and its recurrence.

BACKGROUND/AIMS: We investigated the clinical factors predisposing moderately or poorly differentiated hepatocellular carcinoma and analyzed which clinical and histological factors are associated with poorly differentiated hepatocellular carcinoma (HCC) recurrence. METHODOLOGY: Percutaneous fine-needle biopsy was taken from the liver tumor of 191 consecutive patients between January 1994 and September 1996. The histological degree of differentiation of hepatocellular carcinoma at the first time of initial treatment and at the time of second recurrence was classified according to the criteria of Edmondson and Steiner. RESULTS: At the time of the first therapy, 86 patients, 81, 24, and 0 patients had liver tumors classified as Edmondson (Ed), 1, 2, 3, and 4, respectively. The prognosis of patients with Ed-3/4 HCC was worse than and the tumor sizes were larger than that of Ed-1/2 HCC patients. Of the 167 patients classified as Ed-1/2 at the time of first therapy, HCC recurred in 95 of the patients during the mean follow-up period of 3.4 years. Multivariate analysis revealed that only tumor size (P=0.035) and TACE therapy (P=0.0009) were independently significant factors in predicting future Ed-3/4 or multiple HCC recurrence. CONCLUSIONS: Tumor size and TACE therapy were clinical predisposing factors for Ed-3/4 or multiple HCC recurrences.

A novel display of reconstruction computed tomography for the detection of small hepatocellular carcinoma.

PURPOSE: To evaluate the usefulness of the alternate display of arterial and equilibrium phase images (ADAEI) of 2 mm-pitch reconstruction computed tomography (CT) in the detection of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred and eleven nodules in 72 patients were confirmed as HCC by radiology, histology, or clinical course. Blinded to the outcome, we retrospectively reviewed the CT images obtained with dual-phase spiral CT (Radix Prima, Hitachi Medical, Tokyo, Japan) by ADAEI and by conventional display on cut films. Scanning for the arterial and equilibrium phases was initiated at 33 and 120 s, respectively, after starting the injection of contrast medium (iopamidol 3 ml/s) with a section thickness of 5 mm and a table feed speed of 5-7 mm/s. In ADAEI, all images were reconstructed with a 2-mm interval, and displayed on the monitor in an alternating fashion so that an image in the arterial phase was followed by the corresponding image in the equilibrium phase, and then by the next pair of images in the craniocaudal direction. RESULTS: All 20 HCC nodules larger than 20 mm in diameter were detected by both ADAEI and the conventional display (NS). On the other hand, detectability of smaller HCC nodules was 91/91 (100%) and 72/91 (79%), respectively (P<0.0001 by McNemar' test). False-positively identified HCC nodules, including those diagnosed as possible HCC, were 11 by ADAEI and eight by conventional display. CONCLUSION: The novel, alternate display, ADAEI of 2 mm-pitch reconstruction CT images was useful in detecting small HCC nodules while not requiring additional equipment or expense.

Evaluation of transcatheter arterial embolization prior to percutaneous tumor ablation in patients with hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Transcatheter arterial embolization (TAE) may reduce the risk of hepatocellular carcinoma (HCC) recurrence when performed before percutaneous tumor ablation (PTA), either percutaneous ethanol injection therapy (PEIT) or radiofrequency ablation (RFA). We conducted a randomized, controlled trial comparing the use of TAE combined with percutaneous ethanol injection therapy (TAE/PEIT) to the use of PEIT only to assess the effects on HCC recurrence and survival. We continued the study after the introduction of RFA and compared TAE combined with RFA (TAE/RFA) with RFA only. METHODS: Between March 1997 and April 2001, 42 HCC patients were enrolled who satisfied the following inclusion criteria: (1) uninodular HCC as determined by angiography under computed tomography, (2) arterial hypervascularity, and (3) no prior history of HCC treatment. Twenty-two patients were treated with TAE/PTA (PEIT, 12; RFA, 10) and 20 patients with PTA only (PEIT, 14; RFA, 6). RESULTS: There were four cases of local recurrence in the PTA-only group and none in the TAE/PTA group (P=0.043). The four patients with local recurrence were treated with PEIT. None of the patients treated with RFA showed local recurrence. The effect of TAE on overall recurrence was not significant (P=0.4179). In the multivariate analysis, prior TAE was not significant for survival (P=0.514). CONCLUSIONS: TAE has a limited use in suppressing local recurrence when performed before PEIT but not before RFA.

Factors affecting the prognosis of patients with hepatocellular carcinoma invading the portal vein--a retrospective analysis using 952 consecutive HCC patients.

BACKGROUND/AIMS: Hepatocellular carcinoma with portal venous invasion has a very poor prognosis. The aim of this study is to clarify the factors contributing to the survival of hepatocellular carcinoma patients with portal venous invasion. METHODOLOGY: Out of 952 patients with hepatocellular carcinoma admitted to Tokyo University hospital and its affiliated hospitals from 1987 to 1999, 53 patients developed portal venous invasion until December 2000. The main portal vein was invaded in 33 patients, and the first branch was invaded in the 20 patients. The factors contributing to the prognosis of hepatocellular carcinoma patients with portal venous invasion were determined by univariate and multivariate analyses using 19 clinicopathological parameters. RESULTS: Overall survival rates of the 53 patients at 6 months, and 1 and 2 years were 40%, 18%, and 12%, respectively. Univariate analysis indicated that the serum albumin level, Child classification, number of tumor foci, portal venous invasion-targeted irradiation, and percutaneous tumor ablation of the parenchymal main tumor were significant. Multivariate analysis showed that percutaneous tumor ablation (P = 0.033; risk ratio = 0.28) was the most important factor contributing to a favorable prognosis followed by number of tumor foci (P = 0.048; risk ratio = 0.41). CONCLUSIONS: This study showed the significance of treatment for the parenchymal main tumor in addition to portal venous invasion in patients with hepatocellular carcinoma involving portal venous invasion. Therefore, the efficacy of combined therapy using portal venous invasion-targeted irradiation and percutaneous tumor ablation for the parenchymal main tumor on survival of hepatocellular carcinoma patients with portal venous invasion is suggested.

Clinical features of patients with HCC who are negative for both HBV and HCV markers.

BACKGROUND/AIMS: The aim of this study is to clarify the clinical features of hepatocellular carcinoma that are negative for both hepatitis B surface antigen and anti-hepatitis C antibody. METHODOLOGY: Patients were classified according to viral markers: 45 patients (82%) had hepatitis B (B-HCC), 467 patients (82%) had hepatitis C (C-HCC), and 53 patients (9%) had neither hepatitis B nor hepatitis C (NBNC-HCC). Differences in clinical parameters among these three groups were analyzed. RESULTS: Patients with NBNC-HCC were older than B-HCC and C-HCC patients. The incidence of alcoholism in NBNC-HCC patients was higher than in C-HCC patients. Patients with NBNC-HCC had similar rates of positive antibody to hepatitis B core antigen as did patients with C-HCC. NBNC-HCC patients were further classified according to median age. The younger group showed a greater tendency towards alcoholism than did the aged group. Liver functioning in the younger group was worse than in the older group. The older group had larger tumors than the younger group. CONCLUSIONS: The livers of younger NBNC-HCC patients were more cirrhotic, possibly because of alcoholism. Older NBNC-HCC patients presented with larger tumors, possibly because they did not receive regular medical check-ups due to their relatively preserved liver function.

Congenital absence of portal vein with multiple hyperplastic nodular lesions in the liver.

Congenital absence of the portal vein is an extremely rare anomaly, in which enteric blood bypasses the liver and drains into the inferior vena cava. A 16-year-old girl was referred to our hospital presenting with liver tumor. Although she had suffered from galactosemia soon after birth, the galactosemia had improved spontaneously 1 year later. Between the ages of 8 and 12 years, chronic hepatitis with a mild elevation of aspartate transaminase (AST) and alanine transaminase (ALT) was observed, but liver tumor had not been detected on computed tomography (CT) in regular medical examinations. However, at age 16, liver tumors, 10 cm in diameter, were found. Abdominal angiography indicated complete absence of the portal vein, suggesting that enteric blood was bypassing the liver and draining into the inferior vena cava. In biopsy specimens obtained under ultrasonographic guidance, liver tumors were confirmed histologically as hyperplastic nodules. In addition to this case report, the clinical features of 25 reported cases of congenital absence of the portal vein are reviewed.

Hepatocellular carcinoma in elderly patients: beneficial therapeutic efficacy using percutaneous ethanol injection therapy.

BACKGROUND: The age of patients with hepatocellular carcinoma (HCC) has been increasing worldwide. The objective of this study was to assess the efficacy and safety of percutaneous ethanol injection therapy (PEIT) in elderly patients with HCC. METHODS: The authors retrospectively analyzed 653 patients who were treated with PEIT between 1985 and 1997. One hundred thirty-seven patients were age > or = 70 years, 90 of 137 patients (66%) were male, and 106 of 137 patients (77%) were positive for hepatitis C virus antibodies. Both survival rates and standardized mortality ratios (SMRs) related to the causes of death were compared between patients age > or = 70 years and patients age < 70 years. RESULTS: With the exception of greater maximum tumor size in elderly patients age > or = 70 years, the clinical features of tumors and underlying liver disease were similar to those of patients age < 70 years The survival rates after PEIT in patients age > or = 70 years were 83%, 52%, and 27% at 1 year, 3 years, and 5 years, respectively. These results were comparable to the rates for patients age < 70 years (1 year, 90%; 3 years, 65%; and 5 years, 40%). In addition, there was no difference in mortality from extrahepatic disease between the two groups (9.8% for patients age > or = 70 years vs. 9.4% for patients age < 70 years; P > 0.999). The SMR of patients age > or = 70 years who died of causes related to extrahepatic disease (SMR, 0.56; 95% confidence interval [95%CI], 0.18-1.30) was lower compared with the SMR of patients age < 70 years (SMR, 1.75; 95%CI, 1.07-2.71). The SMR of patients age > or = 70 years who died of causes related to liver disease (SMR, 115; 95%CI, 84.1-153.0) was similar to that of patients age < 70 years (SMR, 120; 95%CI, 103.0-138.0). CONCLUSIONS: These results provide support for the treatment of patients with HCC age > or = 70 years by tumor ablation using PEIT.

Hepatic volumetry to predict adverse events in percutaneous ablation of hepatocellular carcinoma.

BACKGROUND/AIMS: This study aimed to clarify the relation of hepatic volumetry to adverse events after percutaneous transhepatic ablation for hepatocellular carcinoma. METHODOLOGY: One hundred and forty-nine patients with hepatocellular carcinoma who underwent percutaneous ablation sessions with complete ablation of cancer nodules, underwent volume measurement of the entire liver, tumor, and ablated area using computed tomography. The parenchymal ablation rate was calculated: (ablated volume-tumor volume)/(entire liver volume-tumor volume) x 100 (%). Other clinical parameters were also analyzed to determine their relationship to adverse events. RESULTS: The median adjusted liver volume was 591 mL/body surface area (m2) (range: 300 to 1197 mL/m2). The median parenchymal ablation rate was 2.3% (range: 0.2% to 20.2%). Adverse events were observed in 17 patients after percutaneous ablation: liver abscess in 3, hepatic infarction in 3, portal vein thrombus in 3, hemobilia in 1, pleural effusion and/or ascites in 6, and gastric ulcer in 1. Multivariate analysis showed that Child B or C (P = 0.0009), adjusted liver volume < 600 mL/m2 (P = 0.0004), and parenchymal ablation rate > 5% (P = 0.0320) were independent risk factors for adverse events. CONCLUSIONS: Measurement of liver volume and parenchymal ablation rate are useful to predict the presence of percutaneous ablation-related adverse events.

Nonsurgical treatment of hepatocellular carcinoma: from percutaneous ethanol injection therapy and percutaneous microwave coagulation therapy to radiofrequency ablation.

Treatment of hepatocellular carcinoma (HCC) is different from that of other solid tumors, in that surgery plays a limited role while nonsurgical therapies are very instrumental. At our institute, 90% of previously untreated patients have received image-guided percutaneous tumor ablations, such as percutaneous ethanol injection therapy (PEIT), percutaneous microwave coagulation therapy (PMCT) and radiofrequency ablation (RFA). We performed PEIT in 756 patients with HCC. Their survival rates were 89% at 1 year, 64% at 3 years, 39% at 5 years, and 18% at 10 years. With PMCT, survival rates of 122 new patients with HCC were 90% at 1 year, 87% at 2 years, and 68% at 3 years. We performed RFA in 324 patients. RFA required fewer treatment sessions and a shorter hospital stay than PEIT or PMCT to achieve complete necrosis of the lesions. By virtue of their local curability, minimal effect on liver function, and easy repeatability for recurrence, image-guided percutaneous tumor ablations, especially RFA, will be increasingly important in the treatment of HCC.