Characteristics and prognosis of patients in Japan with viral marker-negative hepatocellular carcinoma.

BACKGROUND AND AIM: The characteristics and prognosis of patients with hepatitis virus marker-negative hepatocellular carcinoma (HCC) is not fully elucidated in Japan. We investigated the characteristics and prognosis of HCC patients in whom no markers for hepatitis virus infection were detected, in comparison with those of HCC patients with hepatitis virus infection. METHODS: Viral markers for hepatitis B and C virus (HBV and HCV) infection were measured in 1152 patients in whom initial HCC was diagnosed between 1991 and 2004. Patient characteristics, characteristics of HCC and survival were compared between patients in whom no marker was positive (viral marker-negative HCC) and those in whom chronic HBV or HCV infection was confirmed by viral markers (viral HCC). RESULTS: Overall, 119 patients (10.3%) were shown to have viral marker-negative HCC. Hepatocellular carcinoma was detected under surveillance in a significantly smaller percentage of patients with viral marker-negative HCC than of patients with viral HCC (P < 0.0001). The tumor was significantly larger (P < 0.0001) and vascular invasion was significantly more prevalent (P = 0.0003) in patients with viral marker-negative HCC than in those with viral HCC. The survival rate of patients with viral marker-negative HCC was significantly lower than that of patients with viral HCC (P = 0.0378). CONCLUSION: The patients with HCC in whom hepatitis viral infection had not been confirmed tended not to be under surveillance, resulting in the detection of HCC at more advanced stage and with a poorer prognosis. Efforts to identify patients without hepatitis virus infection who should be under surveillance for HCC will be necessary in the future.

Impact of surveillance on survival of patients with initial hepatocellular carcinoma: a study from Japan.

BACKGROUND & AIMS: We investigated trends in the prediagnostic surveillance of patients in whom hepatocellular carcinoma (HCC) was diagnosed, and evaluated the impact of these trends on early detection of HCC and on patient survival. METHODS: We evaluated 1641 patients in whom HCC initially was diagnosed during the period of 1968 to 2004. Patients were grouped by the year of diagnosis: 1968-1980 (n = 151), 1981-1990 (n = 409), 1991-2000 (n = 754), and 2001-2004 (n = 324). They also were classified according to whether they were in surveillance and its context before the diagnosis of HCC: patients undergoing follow-up evaluation in our center (group A), those followed up and referred by a primary care physician (group B), and those not in surveillance (group C). RESULTS: The percentage of patients in groups A and B increased markedly over time. Early stage HCC was significantly more prevalent in groups A and B than in group C, and the frequency of early stage HCC increased sequentially. The patient survival rate was highest in group A, followed by that in groups B and C in that order; patient survival improved sequentially. CONCLUSIONS: The percentage of patients undergoing in-center surveillance or referred by a primary care physician increased, resulting in increased early detection of HCC and improved patient survival.

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: comparison with pathology on resected specimen.

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings.

Computed tomographic demonstration of a fish bone in abdominal actinomycosis: report of a case.

A 53-year-old man who had the habit of consuming fish bones was referred to our clinic because of a suspected malignant abdominal wall tumor. Computed tomography (CT) showed a mass (10 x 5 cm) in continuity with the transverse abdominal muscle, containing a small calcification. A laparotomy was performed with a preoperative diagnosis of an inflammatory mass due to fish bone penetration from the sigmoid colon. A fish bone, measuring 2.3 cm in length, was detected within the tumor by specimen radiography. The pathological findings demonstrated actinomycotic colonies. We herein present the first case of a CT demonstration showing a fish bone in an abdominal mass which was pathologically confirmed to be actinomycosis. Evidence of the presence of a foreign body is valuable for diagnosing inflammatory nodules such as actinomycosis and differentiation from malignancies.

Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. RESULTS: Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. CONCLUSIONS: Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.

Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan.

OBJECTIVES: We retrospectively compared the usefulness of three different staging systems for hepatocellular carcinoma (HCC), the Cancer of the Liver Italian Program (CLIP) scoring system, the Barcelona Clinic Liver Cancer (BCLC) classification system, and the Japan Integrated Staging (JIS) system, in terms of patient distribution and survival rates. METHODS: Subjects were 1,508 patients diagnosed as having initial HCC during the period of 1976-2003. The disease was staged in all patients by means of the three staging systems, and the distribution of patients across stages and associated survival rates were compared between systems. In addition, comparisons were made on the basis of the time of diagnosis: 1976-1990 (n = 497) and 1991-2003 (n = 1,011). RESULTS: Patients were evenly distributed across stages within each staging system, and survival rates differed between stages except for BCLC C and D. During the period 1991-2003, when HCCs were smaller at diagnosis, JIS system is in particular yielded even distribution of patient across stages and marked differences in survival rates. CONCLUSIONS: Overall, the CLIP and the JIS scoring systems proved to be suitable for patients in Japan with HCC. The CLIP staging systems proved to be more suitable before 1991. In contrast, the JIS system was the most suitable after 1990, when early detection and early treatment of HCC became common. The JIS system is, therefore, the appropriate system in this era of early detection and treatment of HCC.

Relationship between Lens culinaris agglutinin-reactive alpha-fetoprotein and pathologic features of hepatocellular carcinoma.

AIM: We investigated pathological features of Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP-L3. METHODS: A total of 111 patients with HCC < or =5 cm in diameter who underwent hepatic resection were studied. Serum AFP-L3 concentration was measured within a month prior to surgery by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and expressed as AFP-L3 percentage of total AFP. AFP-L3 of 10% or higher was judged to be positive. Pathologic features of resected HCC specimens were evaluated and classified concerning growth pattern (expansive or infiltrative growth), capsule formation, capsule infiltration, septal formation, portal vein invasion, hepatic vein invasion, bile duct invasion, and intrahepatic metastasis. These macroscopic and microscopic findings were compared between AFP-L3-positive and negative HCC specimens. RESULTS: Thirty-three (29.7%) were positive for AFP-L3. The prevalence of HCC with infiltrative growth, with capsule infiltration, with septum formation, with portal vein invasion, and with hepatic vein invasion was significantly higher in AFP-L3-positive group (P=0.0121, 0.0290, 0.0442, 0.0314, and 0.0433, respectively). These pathologic features reportedly indicate the progression of the tumor. CONCLUSIONS: AFP-L3-positive HCC had several pathologic features of progressed state of HCC, which accounted for the AFP-L3 as an indicator of poor prognosis of HCC.

Gallstone pancreatitis: positive correlation between severe pancreatitis and passed stone.

BACKGROUND/PURPOSE: Little is known about whether the severity of pancreatitis depends upon persistent stone impaction or stone passage into the duodenum, and the role of endoscopic sphincterotomy (ES) has remained controversial. METHODS: This study reviewed our experience of 183 patients with gallstone pancreatitis, with special attention paid to the relationship between the severity of pancreatitis, the severity of coexisting biliary pathology, and the outcome. RESULTS: Sixteen patients (9%) had severe pancreatitis (SP) and the remaining 167 (91%) had mild pancreatitis (MP). All of the SP patients had pancreatic necrosis, and 6 of them developed multiple organ failure (MOF). No SP patients had stones impacted at the papilla of Vater or persistent stones and purulent bile in the bile duct (severe cholangitis). Most SP patients (94%) had stones in the gallbladder alone, suggesting stone passage into the duodenum. Of the 167 MP patients, on the other hand, 58 (35%) had severe cholangitis. Four patients (25%) with SP died of MOF. There were four deaths in the MP group (2%) and all in patients with coexisting severe cholangitis, 2 of whom were in septic shock at the time of admission. CONCLUSIONS: None of the SP patients had severe cholangitis. The positive correlation between SP and passed stone suggests that early ES should not be advocated for SP patients. MP patients with coexisting severe cholangitis are likely to benefit from ES.

Metabolic pre-conditioning of cultured cells in physiological levels of insulin: generating resistance to the lipid-accumulating effects of plasma in hepatocytes.

Understanding the regulation of hepatocyte lipid metabolism is important for several biotechnological applications involving liver cells. During exposure of hepatocytes to plasma, as is the case in extracorporeal bioartificial liver assist devices, it has been reported that hepatic-specific functions, e.g., albumin and urea synthesis and diazepam removal, are dramatically compromised and hepatocytes progressively accumulate cytoplasmic lipid droplets. We hypothesized that the composition of hepatocyte culture medium significantly affects lipid metabolism during subsequent plasma exposure. Rat hepatocytes were cultured in medium containing either physiological (50 microU/mL) or supra-physiological (500 mU/mL) insulin levels for 1 week and then exposed to human plasma supplemented with or without amino acids. We found that insulin's anabolic effects, such as stimulation of triglyceride storage, were carried over from the pre-conditioning to the plasma exposure period. While hepatocytes cultured in high insulin medium accumulated large quantities of triglycerides during subsequent plasma exposure, culture in low insulin medium largely prevented lipid accumulation. Urea and albumin secretion, as well as the ammonia removal rate, were largely unaffected by insulin but increased with amino acid supplementation. Thus, hepatocyte metabolism during plasma exposure can be modulated by medium pre-conditioning and supplements added to plasma.