Multiple focal fatty changes in the liver in patients with porphyria cutanea tarda: A case series and review of the literature.

Porphyria cutanea tarda (PCT) is commonly diagnosed in cases where multiple hyperechoic nodules are observed in the liver. Pathologically, these nodules associated with PCT are focal fatty deposits. We report here, seven cases of PCT with fatty changes over multiple foci in the liver. Furthermore, the characteristics of ultrasonography (US) findings of 32 previously reported cases are summarized. The US features of these nodules showed a homogenous hyperechoic or hyperechoic rim pattern, partial confluence, and no mass effect in the vascular structures. Because multiple hyperechoic liver nodules occasionally mimic malignancies, and because their diagnosis can be challenging, clinicians should consider checking urine porphyrin levels to rule out PCT when such nodules are observed on US.

Pilot Study of Hepatic Arterial Infusion Chemotherapy with Interferon-beta and 5-fluorouracil: A New Chemotherapy for Patients with Advanced Hepatocellular Carcinoma.

BACKGROUND/AIMS: The present pilot study aimed to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with interferon-beta (IFN-ß) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). METHODOLOGY: We studied 10 patients with advanced HCC and who were unresponsive to previous HAIC using low-dose 5-FU and cisplatin. The median age was 67 years. Eight patients had portal vein tumor thrombosis and four patients had extrahepatic metastasis. Using a drug delivery system, patients were treated with HAIC of IFN-ß (600 MIU/body, three times/week) and 5-FU (250 mg/body, five times/week). Chemotherapy was repeated consecutively for 2 weeks every 4 weeks. RESULTS: Six (60%) patients had a decrease in tumor markers alpha-fetoprotein (APP) or des-gamma-carboxy prothrombin (DCP). The median overall survival was 108 days and the 1-year survival rate was 10.0%. Univariate analysis showed two significant prognostic factors related to long-term survival for more than 60 days: a decrease in APP or DCP 4 weeks after treatment (P = 0.035) and no extra hepatic metastasis (P = 0.035). Severe hepatic injury was not observed. CONCLUSIONS: HAIC with IFN-ß and 5-PU exerts modest antitumor effects and poses no particular safety concerns. This may be a new promising strategy for treatment of advanced HCC.

Limitation of repeated radiofrequency ablation in hepatocellular carcinoma: proposal of a three (times) × 3 (years) index.

BACKGROUND AND AIM: Percutaneous radiofrequency ablation (RFA) has been shown to be a highly effective treatment for hepatocellular carcinoma (HCC). We investigated the controllability of HCC and explored the algorithm of therapeutic strategy for HCC in patients who met the RFA criteria. METHODS: We enrolled 472 patients with HCC who met the RFA criteria (≤ 3 nodules, ≤ 3 cm) and underwent RFA for initial therapy. Patients who underwent repeated RFA were evaluated retrospectively when HCC exceeded the RFA criteria, or the functional hepatic reserve progressed to Child-Pugh grade C. RESULTS: Overall survival rates were: 1 year, 96%; 3 years, 79%; and 5 years, 56%. In 5 years, 14% of patients progressed to Child-Pugh grade C. Meanwhile, 47% of patients exceeded the RFA criteria. Annually, 8% of patients deviated from the RFA criteria. The percentage of patients who were able to receive RFA significantly decreased at the fourth session compared with up to the third session. The survival rates decreased at the rate of 7% annually until the third year after the initial RFA. Afterwards, it shifted to a decrease at the rate of 12% annually. In a multivariate analysis, the presence of hepatitis C virus infection and the existence of a single tumor were identified as significant independent factors contributing to probabilities exceeding the RFA criteria. CONCLUSIONS: HCC was controlled by RFA up to three RFA treatments and 3 years from the initial therapy. On this basis, we propose a "three (times) × 3 (years) index" for considering a shift from RFA to other treatment modalities.

Late-evening snack with branched-chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma.

AIM: This prospective study was designed to examine whether consumption of a branched-chain amino acid (BCAA)-enriched nutrient mixture as a late-evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: An equal number (10) of 30 LC patients who had undergone RFA for HCC was randomly assigned to a standard diet group (control) group, a morning BCAA (M-BCAA) administration group, or a LES with BCAA (LES-BCAA) administration group. Liver function testing was performed and Child-Pugh scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12 weeks post-RFA. RESULTS: Compared to the control and M-BCAA groups, the LES-BCAA group experienced a rapid and significant improvement in albumin and total serum bilirubin levels and in CPS that began during the initial post-RFA period. These results indicate that LES with BCAA supplementation significantly improved the CPS of the LES-BCAA group at 4 and 12 weeks post-RFA. Although no patients experienced serious adverse effects, two patients who had been diagnosed with diabetes mellitus before undergoing RFA required blood sugar management to improve glycemic control and one subject withdrew due to supplement-induced vomiting. CONCLUSION: LES with BCAA supplementation significantly and rapidly improves liver functioning and CPS in LC patients who have undergone RFA for HCC. Control of blood sugar levels is necessary when calorie-containing BCAA is administrated to LC patients with impaired glucose tolerance.

Mid-ventricular obstruction occurred in hypertrophic left ventricle of heterozygous Fabry's disease-Favorable effects of cibenzoline: A case report.

A 54-year-old woman visited our hospital because of palpitation and dizziness. Systolic ejection murmur, Levine IV/VI, was heard at the left sternal border and atrial gallop was auscultated at apex. Echocardiogram demonstrated diffuse hypertrophy of the left ventricular walls extending to the apex. The left ventricular walls increased symmetrically; the septal and the posterior wall measured approximately 26 mm and 30 mm in thickness, respectively. Apical two-chamber views revealed a narrow outflow of the left ventricular cavity at apex with a distinct convergence zone, where color flow Doppler imaging showed turbulent jet flow from mid to late systole. The leukocyte α-galactosidase A activity was lower than normal. Percutaneous endomyocardial biopsy showed specific change for Fabry's disease by electron microscopy. On cardiac catheterization, mid-ventricular resting pressure gradient of approximately 90 mmHg was shown. This pressure gradient dramatically disappeared after intravenous administration of 70 mg of cibenzoline. We describe a rare case of Fabry's disease that revealed diffuse hypertrophy having dynamic obstruction at mid-left ventricle, like mid-ventricular obstruction, and the administration of cibenzoline had beneficial effects on pressure gradient of mid-left ventricle.

Sustained upregulation of sodium taurocholate cotransporting polypeptide and bile salt export pump and downregulation of cholesterol 7α-hydroxylase in the liver of patients with end-stage primary biliary cirrhosis.

To examine the mRNA expression of hepatobiliary transporters in primary biliary cirrhosis (PBC) patients and to compare bile acid absorption, synthesis, and efflux in patients with non-end-stage and end-stage PBC, we obtained liver samples from PBC patients by percutaneous needle biopsy. End-stage PBC was defined as follows: histological stage IV; cirrhosis; serum total bilirubin, ≥4.0 mg/dl; and Child-Pugh Class C. The mRNA expression levels of sodium taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and hepatic cholesterol 7α-hydroxylase (CYP7A1) were significantly higher in the PBC patients than in the controls (P < 0.01). The mRNA levels of NTCP and BSEP were significantly higher in the end-stage PBC patients than in the controls (P < 0.01). However, hepatic CYP7A1 mRNA expression decreased significantly (by 70%) in the patients with end-stage PBC as compared to the controls and the patients with non-end-stage PBC (P < 0.01). The hepatic expression of transporters mediating bile acid influx and efflux showed sustained elevation, whereas that of the rate-limiting enzyme for bile acid biosynthesis was attenuated in the end-stage PBC patients. Thus, mechanisms may be present preventing the accumulation of toxic bile acids in the hepatocytes of end-stage PBC patients.

Spontaneous pericardial hematoma with familial amyloid polyneuropathy.

There are more than a few risks of hemorrhage complication in patients with amyloidosis. Although most cases with amyloidosis exhibit minor bleeding manifestations, they can be occasionally associated with life-threatening problems. To our knowledge, there are only a few cases of spontaneous pericardial hematoma associated with amyloidosis. We here report a patient who suddenly died of cardiac tamponade with massive pericardial hematoma 7 years after the diagnosis of familial amyloid polyneuropathy (FAP). A 69-year-old female with FAP with cardiogenic shock was admitted to our emergency room. Although she previously underwent permanent pacemaker implantation for atrial fibrillation with slow ventricular response, electrocardiogram showed a critical pacing failure. Emergent telemetry check revealed a sudden extreme increase of pacing capture threshold in the right ventricle. Maximum pacing voltage could not improve the critical condition, and she died 7 h after arrival. Autopsy showed a massive pericardial hematoma in the right ventricular free wall, and microscopic examination revealed typical amyloid deposition in the arterial wall of the pericardium. In this case, it is assumed that a sudden rupture of fragile pericardial vessels with amyloid deposition led to the lethal pericardial hematoma.

Budd-Chiari syndrome: two cases with different courses.

We report two cases of Budd-Chiari syndrome. Case 1: A 57-year-old man presented with leg edema and esophageal varices. Cavography showed obstruction of the inferior vena cava with antiphospholipid syndrome. Further, the patient showed positive serology for hepatitis C virus and consumed large quantities of alcohol. Percutaneous transluminal angioplasty was performed on this patient and anticoagulants administered; leg edema and esophageal varices were ameliorated although liver biopsy showed cirrhosis without evident congestion. More than 9 months since the diagnosis, restenosis of the inferior vena cava has not occurred. Case 2: A 73-year-old woman presented abdominal pain but no edema or varices. Cavography showed membranous obstruction of the inferior vena cava which required no therapy. Manifestation of portal hypertension was not present and liver function was maintained although liver biopsy showed obvious congestion. These cases showed untypical features against histopathology, and careful observation will be required for emergence of hepatocellular carcinoma.

Combination therapy of lamivudine and adefovir in Japanese patients with chronic hepatitis B.

PURPOSE: This study aimed to clarify the long-term efficacy of the lamivudine treatment in Japanese patients with chronic hepatitis B either with or without lamivudine resistance or with or without adefovir add-on treatment. METHODS: We followed 110 patients who received lamivudine for more than 12 months, including 67 hepatitis B e antigen (HBeAg)-positive and 43 HBeAg-negative patients. RESULTS: The median follow-up after the onset of lamivudine was 48 (range = 12-86) months. In all the patients with or without lamivudine resistance, the level of alanine aminotransferase (ALT) normalization decreased from 70.0% at 1 year to 36.4% at 5 years and the loss of serum HBV DNA level decreased from 72.7% at 1 year to 31.8% at 5 years. Sixty patients (54.6%) developed a lamivudine-resistant mutation, and this occurrence was more frequently observed in those who were HBeAg-positive (P < 0.01), those with a low level of ALT (P < 0.05), and those with a high level of serum HBV DNA (P < 0.01). Thirty-six of 60 patients received adefovir in addition to lamivudine to treat breakthrough hepatitis. A Cox proportional hazards model analysis revealed the level of baseline HBV DNA to be the best predictive factor for the virus recrudescence (risk ratio = 0.466, 95% confidence interval [CI]: 0.246-0.842, P = 0.011) and the breakthrough hepatitis (risk ratio = 0.444, 95% CI: 0.218-0.879, P = 0.019). We carefully monitored the efficacy of this treatment both in patients who received adefovir and in those who did not since the beginning of the lamivudine treatment. The normalization level of ALT was 61.4% at 5 years and the loss of serum HBV DNA was 61.4% at 5 years since lamivudine was started. A histologic improvement was observed in patients with ALT levels less than two times the upper limit of normal at the time of a second liver biopsy. CONCLUSIONS: Although the efficacy of lamivudine is limited because of breakthrough hepatitis, adefovir was used as a salvage treatment of patients with lamivudine-resistant chronic hepatitis B. In addition, lamivudine was used for the treatment of Japanese patients with chronic hepatitis B with or without lamivudine resistance, and was found to be useful regarding the long-term virologic and biochemical responses.

In-hospital outcomes of primary percutaneous coronary interventions performed at hospitals with and without on-site coronary artery bypass graft surgery.

BACKGROUND: Primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is performed in hospitals without on-site coronary artery bypass graft surgery in the ;real world'. However, data on the in-hospital outcomes of primary PCI performed at hospitals with and without on-site cardiac surgery are still lacking in Japan. METHODS AND RESULTS: In the present study, 2,230 AMI patients were enrolled in the AMI-Kyoto Multi-Center Risk Study between January 2000 and December 2005. Of these, 1,817 patients underwent primary PCI. Excluding patients without adequate data, we retrospectively compared clinical background, coronary risk factors, angiographic findings, acute results of primary PCI and in-hospital prognosis between patients undergoing primary PCI in hospitals without on-site cardiac surgery (without surgery group, n=792) and those in hospitals with (with surgery group, n=993). The without surgery group had higher prevalence of previous myocardial infarction, Killip class>or=3 at admission and multivessels as a culprit lesion than the with surgery group. The without surgery group was more likely to have lower frequency of stent usage and lower thrombolysis in myocardial infarction flow grade just after PCI, whereas it was more likely to have intra-aortic balloon pumping and temporary pacing during procedures. The overall in-hospital mortality did not differ between the 2 groups. On multivariate analysis, in AMI patients undergoing primary PCI, Killip class>or=3 at admission, multivessels or left main trunk (LMT) as culprit lesions, number of diseased vessels>or=2 or diseased LMT, and age were the independent predictors of the in-hospital mortality, but the presence of on-site cardiac surgery was not. CONCLUSIONS: These results suggest that in-hospital outcomes in AMI patients undergoing primary PCI at hospitals without on-site cardiac surgery are comparable to those at hospitals with on-site cardiac surgery in Japan.

Relation of obesity to acute myocardial infarction in Japanese patients.

BACKGROUND: It remains uncertain whether obesity is an independent risk factor for coronary heart disease in young adults, as well as adults, in Japan. METHODS AND RESULTS: In the present study, 1,260 cases of acute myocardial infarction (AMI) and 3,775 community controls were recruited from the AMI-Kyoto Multi-Center Risk Study and Kyoto Citizen's Health and Nutrition Study, respectively. Obesity and other risk factors were retrospectively examined between cases and controls in each subgroup of young males (20-40 years), middle-aged males or females (40-60 years), older males or females (60-80 years), and very old males or females (80-100 years). In young, middle-aged, and older males, as well as in older females, cases had a higher body mass index (BMI) than controls. In young males, as well as in middle-aged and older females, cases had a higher prevalence of smoking than controls. Except for very old males, the prevalences of hypercholesterolemia, hypertension, and diabetes mellitus were higher in each subgroup of cases than in controls. Multivariate logistic regression analysis revealed that obesity (BMI >or=25) was an independent risk for AMI in young and middle-aged males, but not in females, whereas smoking was an independent risk for AMI in middle-aged and older females as well as in older males. CONCLUSIONS: Obesity is significantly associated with AMI, independent of the classic coronary risk factors, in young and middle-aged males. These findings support the current emphasis on controlling obesity to prevent coronary events in young Japanese male adults.

Postoperative recurrence in hepatocellular carcinoma: Comparison between percutaneous ethanol injection and radiofrequency ablation.

AIM: Recently percutaneous ethanol injection (PEI) turned into percutaneous radiofrequency ablation (PRFA), and it has become widely used for the treatment of hepatocellular carcinoma (HCC). The present study was to compare the incidence in postoperative HCC recurrence between these two therapeutic approaches. METHODS: One hundred and sixty-eight first-time HCC in patient cases were chosen for PEI (n=94) and PRFA (n=74). The localized recurrence rate based on the operator's experience in percutaneous treatment for HCC (on <5 years versus >/=5 years experience) was examined. RESULTS: The PRFA group demonstrated a significantly lower localized recurrence rate within 2 years than the PEI group (8% and 22%, respectively, P<0.01). The local recurrence rate of HCC within 2 years after PEI was significantly lower in those for whom the operator's experience was more than 5 years compared to those for whom it was less than 5 years (12% versus 24%, respectively, P<0.05). In contrast, after PRFA there was no significant difference between these two groups of <5 years and of >/=5 years experience (8% versus 8%, respectively, P=0.98). CONCLUSION: The present study demonstrated that PRFA resulted in a lower rate of local recurrence in comparison to conventional PEI, regardless of the operator's experience.

[Uremic pericarditis complicating cardiac tamponade: a case report].

A 29-year-old man developed diabetes mellitus in 1983 and diabetic nephropathy which gradually worsened from 1998. He was admitted to our hospital for initiation of peritoneal dialysis in May 2002. However, the efficiency of dialysis was not sufficient to improve elevated levels of blood urea nitrogen and serum creatinine. His body weight and cardiothoracic index by chest roentgenography gradually increased starting 9 days after admission. To improve the efficiency of dialysis, we tried to increase the dialysis fluid. Nevertheless, the efficiency of peritoneal dialysis remained low, and the patient complained of nausea 14 days after admission. Hypotension suddenly occurred 16 days after admission. Echocardiography showed massive pericardial effusion and collapse of the right ventricle. The diagnosis was cardiac tamponade. We performed cardiac centesis and pericardial drainage which revealed bloody pericardial effusion. Urgent hemodialysis was performed. The differential diagnosis of cardiac tamponade was established. After hemodialysis, the amount of pericardial effusion decreased, the gastro-intestinal symptoms disappeared, and the blood urea nitrogen and serum creatinine levels decreased. We speculated that the cause of cardiac tamponade was uremic pericarditis after ruling out infectious disease, collagen disease, malignant disease, and aortic dissection. Cardiac tamponade due to uremic pericarditis has become very rare since hemodialysis was developed.

Hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV tests but positive liver tissue HCV RNA.

A 70-year-old woman was admitted to our hospital because of a liver tumor. Laboratory data revealed mild liver dysfunction. Neither serum anti-HCV antibody nor HCV-RNA was detected. Computed tomography revealed a tumor lesion measuring 2 cm in diameter within the liver. Histological examination of the tumor revealed moderately differentiated hepatocellular carcinoma while the non-tumorous liver tissue demonstrated liver cirrhosis. By the RT-PCR method, HCV-RNA was detected from the non-tumorous liver tissue. We herein report a very rare case of hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV findings, but positive finding for liver tissue HCV RNA.