Juvenile hepatocellular carcinoma with congestive liver cirrhosis

A case of juvenile hepatocellular carcinoma (HCC) with congestive liver cirrhosis is reported. The patient was a 21-year-old woman. She had been diagnosed as having transposition of the great arteries, type 2, in 1978. She underwent the Mustard operation, but suffered from chronic heart failure. In 1995, she experienced abdominal pain and underwent examination. The laboratory data were normal, except for elevated total bilirubin (5.2mg/dl). Blood examinations were performed at frequent intervals, and the total bilirubin level fluctuated between 0.9 and 8.1mg/dl over the next 4 years, but the transaminase level remained normal. In 1999, she experienced abdominal pain again and was admitted to our hospital. Computed tomography showed four space-occupying lesions in the liver; 45mm, 20mm, 12mm, and 10mm in size. She was diagnosed as having HCC, and transcatheter arterial chemoembolization and percutaneous ethanol injection therapy were performed. Histology of the cancerous and the noncancerous liver tissue revealed HCC, moderately differentiated type, in cirrhotic liver with congestion. This patient had no background factors of liver disease, except for liver congestion, associated with the chronic heart failure. Because most patients with cardiac cirrhosis die of cardiac disease, only a small number of these patients develop liver failure. However, the incidence of HCC in patients with congestive liver disease is likely to increase in the future, as survival time is prolonged with the advances in treatment for chronic heart failure. Therefore, patients with congestive liver disease should be followed, taking into account the possibility of HCC.     

PBC-AIH overlap syndrome with concomitant ITP and Hashimoto’s disease with positivity for anti-centromere antibody

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimotos disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimotos disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6g/dl; -globulin (glb), 35.9%; total bilirubin (T-bil), 9.41mg/dl; direct bilirubin (D-bil), 7.52mg/dl; aspartate aminotransferase (AST), 957U/l; alanine aminotransferase (ALT), 651U/l; alkaline phosphatase (ALP), 595U/l; -guanosine triphosphate (GTP), 129U/l; IgG, 2620mg/dl; IgM, 223mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimotos disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.     

A Three-dimensional Analysis of Blood Vessels in Bronchioloalveolar Carcinoma

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 m thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08±1.10 m, 3.95±1.02 m, 5.04±1.56 m, and 6.11±2.23 m, the circumferences of those vessels seen as complete circles were 43.11±12.78 m, 43.71±12.87 m, 95.21±39.32 m, and 126.77±54.65 m; the lengths between vessel bifurcations were 13.28±3.08 m, 13.47±4.58 m, 24.91±9.66 m, and 41.82±28.08 m in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.     

Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice

Background d-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor- (TNF-) plays a pivotal role. We examined the effects of a highly selective adenosine A_2A receptor agonist (ATL-146e) on GalN/LPS-induced fulminant hepatic failure.Methods Mice were given an intraperitoneal dose of GalN (800mg/g body weight)/LPS (100ng/g body weight) with and without ATL-146e (0.01µg/kg) treatment. Liver injury was assessed biochemically and histologically. Also, TNF- levels in the serum were determined.Results The serum liver enzyme (ALT) level in vehicle-treated mice was 20960 ± 2800IU/ml and was reduced by 63% to 7800 ± 1670IU/ml by treatment with 0.01µg/kg per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum TNF- and greatly reduced inflammation assessed by histopathologic examination compared with control mice treated with GalN/LPS. ATL-146e also reduced lethality at 12h from 65% to 13%.Conclusion The present findings suggest that the highly selective adenosine A_2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF- secretion.     

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n=7; E-LAVAGE, n=5) or bolus (I-BOLUS, n=8; E-BOLUS, n=5), or went untreated (CONTROL, n=4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO₂ were observed in the lavage groups compared to the bolus groups and the controls. PaO₂ (mmHg) at 240 min posttreatment: I-LAVAGE=297±54, E-LAVAGE= 280±57; I-BOLUS=139±31; E-BOLUS=152±29; C=119±73 (mean± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.     

Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease

Canavan disease, an inherited leukodystrophy, is caused by mutationsin the aspartoacylase (ASPA) gene. It is most common among children of Ashkenazi Jewish descent but has been diagnosed in many diverse ethnic groups.Two mutations comprise the majority of mutant alleles in Jewish patients, while mutations in the ASPA gene among non-Jewish patients are different and more diverse. In the present study, the ASPA gene was analysed in 22 unrelated non-Jewish patients with Canavan disease, and 24 different mutations were found. Of these, 14 are novel, including five missense mutations (E24G, D68A, D249V, C152W, H244R), two nonsense mutations (Q184X, E214X), three deletions (923delT, 33del13, 244delA), one insertion mutation (698insC), two sequence variations in one allele ([10T>G; 11insG]), an elimination of the stop codon (941A>G, TAGTGG, X314W), and one splice acceptor site mutation (IVS1–2A>T). The E24G mutation resulted in substitution of an invariable amino acid residue (Glu) in the first esterase catalytic domain consensus sequence. The IVS1–2A>T mutation caused the retention of 40 nucleotides of intron 1 upstream of exon 2. The results of transient expression of the mutant ASPA cDNA containing these mutations in COS-7 cells and assays for ASPA activity of patient fibroblasts indicated that these mutations were responsible for the enzyme deficiency. In addition, patients with the novel D249V mutation manifested clinically at birth and died early. Also, patients with certain other novel mutations, including C152W, E214X, X314W, and frameshift mutations in both alleles, developed clinical manifestations at an earlier age than in classical Canavan disease.     

Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats

Background Gabexate mesilate, a synthetic protease inhibitor, is used to treat acute pancreatitis and disseminated intravascular coagulation because it inhibits various serine proteases; however, whether gabexate mesilate prevents acute liver failure has not yet been studied. The aim of the present study was to investigate the effect of gabexate mesilate in carbon tetrachloride (CCl₄)-induced liver injury in rats.Methods Acute hepatic failure was induced by administration of CCl₄ intragastrically to male Sprague–Dawley rats. The effects of gabexate mesilate were examined in terms of serum transaminase levels, liver histology, and the prognosis of rats.Results Gabexate mesilate treatment significantly decreased the elevation of serum transaminase levels and improved liver histology 24h after the administration of CCl₄ (0.2ml/100g rat weight). Plasma tumor necrosis factor- (TNF-) and interleukin-1 (IL-1) decreased significantly in the gabexate mesilate-treated rats compared with saline-treated rats. Gabexate mesilate treatment also significantly improved survival rate after a lethal dose of CCl₄ (0.5ml/100g rat weight) from 0% to 20%.Conclusions Gabexate mesilate treatment attenuated CCl₄-induced liver injury via a suppression of proinflammatory cytokine production. In addition, these investigations suggest that gabexate mesilate treatment may provide therapeutic strategies for human acute liver failure.     

α-Fetoprotein,tissue polypeptide antigen and ferritin in diagnosing primary hepatocellular carcinoma in patients with liver cirrhosis

Summary This study was undertaken in order to compare the usefulness of three indices of tumour proliferation in detecting primary hepatocellular carcinoma (HCC) and in differentiating this neoplasm from liver cirrhosis. In 10 patients with HCC and in 63 with liver cirrhosis serum -fetoprotein (AFP), tissue polypeptide antigen (TPA) and ferritin were assayed. Increased levels of AFP but not of TPA and ferritin were observed in HCC as compared to liver cirrhosis. The receiver-operating characteristic curves demonstrated that AFP is more discriminating between HCC and liver cirrhosis than the other two markers. Correlations between liver function tests and serum markers were observed in liver cirrhosis but not in HCC. We can conclude that AFP is more useful than TPA and ferritin in detecting HCC in patients with liver cirrhosis, owing to the high frequency of false positive results of the latter two indices in liver cirrhosis. Liver dysfunction is probably involved in increasing all these markers of malignancy, thus reducing the specificity of these tests.Abbreviations AFP -tetoprotein - TPA tissue polypeptide antigen - HCC primary hepatocellular carcinoma Partially supported by a grant of the Italian National Research Council, Special Project Oncology, contract 87.01.541.04. Under the auspices of the R. Farini association for gastroenterological research     

Anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus investigated with a three-dimensional electroanatomical mapping system

We studied the anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus in humans with a three-dimensional electroanatomical mapping system (CARTO, Biosense, Haifa, Israel). Fifteen patients with atrial flutter were studied. Thirteen patients had underlying heart disease. We investigated the anatomical structure of the isthmus with cross sections made from the three-dimensional right atrial map. The cross sections of the isthmus showed a concave shape in 7 patients (47%: group A), convex shape in 2 (13%: group B), and complex shape in 6 (40%: group C). The distance between the IVC and TA was 34 ± 17mm (group A), 25 ± 2mm (group B), 34 ± 16mm (group C), and 32 ± 15mm (Total), respectively. The distance between the top and bottom was 6 ± 5mm (group A), 3mm (group B), 6 ± 3mm (group C), and 6 ± 4mm (total), respectively. Seven of 15 patients exhibited an uneven surface of more than 5mm in depth and 4 of 15 patients had one of more than 10mm. The anatomical structure of the isthmus varies. To carry out precise catheter ablation, these variations should be taken into consideration to ensure an effective procedure.     

Effects of Piclamilast,a Selective Phosphodiesterase-4 Inhibitor,on Oxidative Burst of Sputum Cells From Mild Asthmatics and Stable COPD Patients

Oxidative stress associated with increased presence of neutrophils is an important feature of inflammatory airways diseases like asthma or chronic obstructive pulmonary disease. We studied the in vitro effect of piclamilast (RP73401), a selective phosphodiesterase (PDE)-4 inhibitor, compared to theophylline and prednisolone, on respiratory burst of sputum cells from mild asthmatics and COPD patients. Sputum cells were harvested from mild asthmatics and stable COPD patients and treated with piclamilast, theophylline or prednisolone. Respiratory burst was assessed by luminol-dependent chemoluminescence after stimulation with 10 M n-formyl-met-leu-phe (FMLP). Piclamilast inhibited FMLP-induced respiratory burst of sputum cells in a concentration-dependent manner (asthma: EC₅₀ approximately 100 nM, max. inhibition: 97.5±5% at 100 M; COPD: EC₅₀ approximately 1 M, max. inhibition: 70.6±4.5% at 100 M), whereas maximal inhibition observed with theophylline (asthma: max. inhib. 27±15%; COPD: 6±2%, both p < 0.05 vs. piclamilast) and prednisolone (asthma: 16±6%; COPD: 7.8±6.2%, both p < 0.05 vs. piclamilast) was weaker. Inhibition by piclamilast was largely reversed through pretreatment of cells with the adenylcyclase inhibitor SQ22536. We concluded that piclamilast, a selective PDE-4 inhibitor, attenuates the respiratory burst of sputum cells from mild asthmatics and COPD patients in vitro. These data underline the potential of PDE-4 inhibition as a novel therapeutic approach to inflammatory airway diseases like asthma or COPD.     

Characteristics of ischaemic human myocardium: a transoesophageal echocardiographic and voltammetric microelectrode study

Delayed local myocardial power development (primary asynchrony) has been suggested as a marker of ischaemic ventricular dysfunction in humans. However, to prove this, microcirculatory perfusion, microcirculatory oxygenation, and intrinsic mechanical function of the same asynchronous myocardial segment should be studied simultaneously before and after revascularisation. We performed a prospective intraoperative study of 15 patients (age 67 [SD 5] years) at baseline and 30min after left anterior descending artery grafting. Local tissue perfusion and oxygenation of the anterior left ventricular wall were quantified with a voltammetric microelectrode technique. Transesophageal M-mode echocardiograms and simultaneous high-fidelity left ventricular pressure were measured. Eight patients showed primary asynchrony and 7 did not. Patients with primary asynchrony had local mechanical depression with lower resting values of myocardial work and peak power which increased with surgery. In this group, resting perfusion consistently increased with surgery (32.1 [13] to 54 [31]mlmin^–1 100g^–1, P < 0.05). In the remaining patients, local work and power were normal, and resting perfusion was consistently higher (90 [9]Mlmin^–1 100g^–1, P < 0.05 vs primary asynchrony), and fell with surgery. Local tissue oxygen tension was similar in both groups (38 vs 44mmHg) and did not change with surgery. In patients with chronic coronary artery disease, microcirculatory perfusion, but not pO₂, is reduced in regions showing primary asynchrony and impaired mechanical function. Abnormalities in both mechanical function and perfusion normalise within 30min of revascularisation. These data provide further evidence that primary asynchrony is not only a marker of chronic ischemic ventricular dysfunction, but is associated with a modified contraction pattern in which normal oxygen tension coexists with reduced perfusion.     

Ultrasonic tissue characterization in patients with dilated cardiomyopathy: comparison with findings from right ventricular endomyocardial biopsy

Aim: The clinical usefulness of integrated backscatter (IB) imaging was compared with right ventricular endomyocardial biopsy for assessing myocardial damage in patients with dilated cardiomyopathy (DCM). Methods: We examined 15 patients with DCM and 20 healthy controls. In addition to the conventional M-mode echocardiographic parameters, we determined the cyclic variation in IB values (CV-IB) obtained from parasternal short axis views of the left ventricle just under the transducer for both the interventricular septum (IVS) and the left ventricular posterior wall (PW). The per cent fibrosis area (%) and the transverse diameter of myocytes (m) were measured in right ventricular endomyocardial biopsy specimens by computer image analysis. To analyze the relationship between pathological findings and CV-IB, we divided patients into four subgroups on the basis of the pathological characteristics of endomyocardial biopsy specimens as follows: degeneration dominant group (n=5), fibrosis dominant group (n=5), dilated phase hypertrophic cardiomyopathy (n=2), and mixed type (n=3). Results: CV-IB in the IVS and the PW was lower in patients with DCM (8.8 ± 2.9, 8.3 ± 2.7dB, respectively) than in normal subjects (14.4 ± 2.9, 13.6 ± 2.6dB, respectively). Biopsy findings showed a mean per cent fibrosis area of 24.0 ± 12.3%, and a mean myocyte diameter of 14.3 ± 2.9m in patients with DCM. CV-IB was correlated with both of these findings: per cent fibrosis area (r=–0.56 in IVS, r=–0.56 in PW) and myocyte diameter (r=0.67 in IVS, r=0.71 in PW). CV-IB was decreased in all DCM subgroups compared with normal subjects, but there was no significant difference between subgroups. Conclusions: CV-IB was correlated with both the extent of fibrosis in myocardial tissue and the myocyte diameter. These findings suggest that ultrasonic tissue characterization is a good indicator of the severity of fibrosis and myocyte atrophy in patients with DCM.     

Chemotherapy using 5-fluorouracil,mitoxantrone, and cisplatin for patients with advanced hepatocellular carcinoma: an analysis of 63 cases

Background We evaluated the anti-tumor efficacy and toxicity of 5-fluorouracil (5-FU), mitoxantrone, and cisplatin (FMP) in patients with advanced hepatocellular carcinoma (HCC), and conducted an analysis of the prognostic factors for response to such therapy and patient survival.Methods Sixty-three patients suffering from unresectable and non-embolizable HCC and who had objectively measurable tumors, adequate liver and renal function, and adequate bone-marrow reserve were enrolled in this study. The therapeutic regimen consisted of cisplatin 80mg/m² and mitoxantrone 6mg/m² intravenously on day 1, and 5-FU 450mg/m² per day continuous infusion for a period of 5 days. Univariate and multivariate analyses of patient and disease characteristics were used to identify factors predicting patient response and survival.Results The objective response was 23.8% (95% confidence interval [CI], 13.0–34.6%). The median survival for all 63 patients was 4.9 months (95% CI, 3.2–6.6 months). The median time to progression was 2.5 months (95% CI, 1.7–3.3 months). Multivariate analysis identified only performance status (P = 0.050) and liver tumor size (P = 0.012) as being significantly related to patient objective response. Independent variables associated with a better patient survival included: the absence of ascites (P = 0.003), a lower total bilirubin level (P = 0.026), and the patient being a positive chemotherapy responder (P = 0.009).Conclusions The response rate to an FMP regimen was still unsatisfactory, although a specific subgroup of patients (good performance status, smaller liver tumor mass, good liver reserve, and distant metastasis) may benefit from this regimen.     

Percutaneous radiofrequency ablation with cooled electrodes combined with hepatic arterial balloon occlusion in hepatocellular carcinoma

Background We have reported that percutaneous radiofrequency ablation (RFA) with balloon occlusion of the hepatic artery (balloon-occluded RFA), using an expandable electrode, increases the coagulation area. In this study, we investigated the efficacy of balloon-occluded RFA and balloon-microcatheter-occluded RFA, using a cool RF single electrode.Methods We studies 41 patients with 47 hepatocellular carcinoma (HCC) lesions. We treated 28 patients (32 nodules) with balloon-occluded RFA, 5 patients (6 nodules) with balloon-microcatheter-occluded RFA, and 8 patients (9 nodules) with standard RFA. Initial therapeutic efficacy was evaluated with dynamic computed tomography performed 1 week after one session of treatment.Results One session of treatment was done for 20 nodules (62.5%) in the balloon-occluded RFA group and for 4 nodules (66.7%) in the balloon-microcatheter-occluded RFA group. We compared the coagulation diameter for balloon-occluded RFA (7 nodules), balloon-microcatheter-occluded RFA (6 nodules), and standard RFA (9 nodules) after one application cycle (12min). The greatest dimension of the area coagulated by balloon-occluded RFA was significantly larger (greatest long-axis dimension, 47.6 ± 7.8mm; greatest short-axis dimension, 33.4 ± 7.5mm) than that coagulated by standard RFA (greatest long-axis dimension, 35.3 ± 4.7mm; greatest short-axis dimension, 25.9 ± 3.7mm; P = 0.002 for greatest long-axis dimension; P = 0.041 for greatest short-axis dimension). However, there was significant difference only in the greatest short-axis dimension of the area coagulated comparing balloon-microcatheter-occluded RFA and standard RFA.Conclusions We consider balloon-occluded RFA using a cool RF electrode to be superior to standard RFA for the treatment of HCC, especially when larger coagulation volumes are required.     

Association between serum hepatocyte growth factor and survival in untreated hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is a common hepatic malignancy worldwide. Its nature of rapid growth results in a grave prognosis. Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, responsible for their proliferation. The aim of the present study was to investigate the prognostic roles of serum HGF in untreated HCC patients.Methods Fifty-five patients with inoperable HCC were studied. The diagnosis of HCC was based on either liver histopathology or imaging evidence of a liver mass, together with elevated serum alpha-fetoprotein. Serum HGF levels of the patients, at the time of diagnosis, were compared to those of 28 healthy controls. All patients received only palliative treatments and were followed up until they died. Comparison of survival curves between patients with a serum HGF level of 1.0ng/ml or more and those with lower serum HGF was performed, using the log-rank test. Data values are expressed as means and SD.Results Fifty-one men and four women with inoperable HCC were recruited. The mean age was 54.15 ± 15.34 years. The serum HGF levels in the inoperable HCC patients were significantly higher than those in the controls (0.58 ± 0.43 vs 0.14 ± 0.04ng/ml; P < 0.001). The patients mean survival time was 5.28 ± 6.73 months (range, 0.1–33 months). Serum HGF levels exhibited a negative correlation with the survival time (P = 0.032). In addition, HCC patients with serum HGF levels of 1.0ng/ml or more had a shorter survival time than the other HCC patients (P = 0.0025).Conclusions Patients with inoperable HCC had higher levels of serum HGF than the healthy controls, and serum HGF was negatively correlated with the survival time. Serum HGF levels of 1.0ng/ml or more in HCC patients are suggestive of a grave prognosis, indicating that HGF plays important and active roles in the disease progression. The detailed mechanisms need to be further investigated.     

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.     

Risk factors for the local recurrence of hepatocellular carcinoma after a single session of percutaneous radiofrequency ablation

Background Radiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electrode insertion.Methods From February 1999 to September 2001, we treated 104 HCC tumors with an expandable needle with four hooks. Ninety-nine of the 104 tumors were successfully treated by single-session RFA with a single electrode insertion. We investigated the relationships between pretreatment factors (tumor size, tumor staining, tumor capsule, and tumor location) and local recurrence in these 99 tumors.Results The mean size of the 99 tumors was 21.5mm in diameter (range, 10 to 33mm). The overall local recurrence rates were 9.7%, 15.4%, and 20.4%, at 1, 2, and 3 years, respectively. For small tumors (smaller than 25mm), the local recurrence rates at 1, 2, and 3 years were 4.0%, 8.0%, and 14.6%, respectively. The local recurrence rates were 21.1% and 32.3% at 1 and 2 years, respectively, for large tumors (25mm or larger), and at 3 years the rate was over 50% for tumors located close to the liver surface. Tumor size and tumor location relative to the liver surface were significantly associated with a higher local recurrence rate. However, other variables tested showed no significant relationship to the local recurrence rate.Conclusions This study demonstrated that both tumor size and location relative to the liver surface influence the local efficacy of single-session RFA with a single electrode insertion.     

Early Outcomes Following Alternative Treatment Strategies in the Management of the Acutely Ischemic Limb

The modem emergency management of the acutely ischemic limb has evolved considerably with the introduction of catheter-directed thrombolysis. Following preservation of life, the next goal of intervention in these emergency cases, whether with surgery or thrombolysis, is limb salvage. We report our own experience with both approaches in the early outcome of the emergency management of the acutely ischemic limb. This is a retrospective review of a tertiary-level vascular units experience. The inclusion criteria consisted of acute limb ischemia as defined by the guidelines of the Vascular Surgical Society of Great Britain and Ireland. Data acquisition used the hospitals inpatient enquiry system, and its operative and radiology databases. Analysis used the ² test and the Yates correction factor (p < 0.05). Patients: N=84. Events: 103. Median age: females, 82 yrs; males, 71 yrs. 17–91 yrs. Females vs. males > 70 years: ²=5.4, d.f.=1, 0.01 < p, 0.02) (²: p= 0.05). Seventy-one patients underwent preoperative angiography. Successful limb salvage was achieved in 75% of cases. Overall, the amputation and mortality rates were 16.5% and 13.1%, respectively. We initially treated 62% of events with surgery and 38% with thrombolysis. In those patients who underwent thrombolysis there, 31% went on to have reconstructive surgery. Thrombolytic treatment resulted in a limb salvage rate of 69%. Thrombolysis was discontinued in six cases due to complications. Significant differences in outcome were not demonstrable between the two treatment groups (²=1.1, d.f.=1, 0.5 < p < 0.1). Acute limb ischemia has significant morbidity and mortality rates. The use of catheter-directed thrombolysis offers the surgeon an alternative to emergency surgery. This approach does not demonstrate any increase in the rate of limb loss.     

Pulsed Doppler tissue imaging can help to identify patients with right ventricular infarction

This study was planned to assess whether tissue Doppler imaging is a useful method for the detection of the right ventricular myocardial infarction. Forty-eight patients with acute inferior myocardial infarction and 24 age- and sex-matched healthy controls were included in this study. Twenty-four patients had electrocardiographic signs of inferior myocardial infarction without right ventricular infarction (group I), and the other 24 patients had electrocardiographic signs of inferior myocardial infarction with right ventricular infarction (group II). From the echocardiographic apical four-chamber view, peak systolic, early diastolic, and late diastolic velocities of the tricuspid annulus at the right ventricular free wall were recorded with the use of pulsed-wave Doppler tissue imaging. The tricuspid annular peak tissue Doppler imaging systolic velocity was significantly lower in group I (14.03 ± 2.57cm/s, P 0.005) and in group II (8.50 ± 0.84cm/s, P 0.005) than in controls (16.63 ± 2.31cm/s). The tricuspid annular peak systolic (8.50 ± 0.84cm/s vs 16.63 ± 2.31cm/s) and peak early diastolic (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) velocities were significantly lower in group II than in group I, as compared with controls (P 0.001). Peak early diastolic velocity of tricuspid annulus (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) was significantly lower in group I than in controls (P 0.001); however, late diastolic velocity was significantly lower in group II (15.98 ± 5.08cm/s, P 0.05) than in group I (18.21 ± 2.63cm/s, P 0.05) and in controls (19.02 ± 5.29cm/s). The results of this study indicate that tricuspid annular peak systolic and early diastolic velocities are reduced in patients with right ventricular infarction. The velocity of the tricuspid annulus by tissue Doppler imaging is simple and can be used to distinguish whether patients with inferior myocardial infarction have right ventricular infarction.This study was presented at the XXIII. Congress of the European Society of Cardiology, Stockholm, Sweden, 1–5 September 2001     

Efficacy of mizoribine treatment in patients with SjÖgren’s syndrome: an open pilot trial

The aim of this study was to evaluate the efficacy and safety of mizoribine in patients with SjÖgrens syndrome. Forty patients with sicca syndrome, whose conditions were definitely diagnosed as SjÖgrens syndrome, were given mizoribine orally at a dosage of 150mg/day for 12 months. The percentage change in salivary secretion after 3, 6, and 12 months of the therapy increased to +112.2% (P 0.001), +119.9% (P 0.01), and +147.3% (P 0.001), respectively, compared with the baseline. Serum IgG levels decreased significantly throughout the study, and the level was 1969.4 ± 620.0mg/dl after treatment for 12 months compared with the pretreatment value of 2094.3 ± 746.6mg/dl (P 0.05). The patients assessment of clinical signs and symptoms on a 10-cm visual analog scale improved significantly from 7.2 ± 2.3cm at the start of the treatment to 5.0 ± 1.9cm after 12 months (P 0.001). There was a similar improvement in the physicians assessment using the 10-cm visual analog scale: 7.1 ± 1.6cm at the start of the treatment and 5.2 ± 1.9cm after 12 months (P 0.001). With regard to safety, no serious adverse reactions were observed. Although a controlled study would be required to clarify the efficacy of mizoribine, these preliminary observations indicate its efficacy for ameliorating glandular symptoms through improvements in immune abnormalities in patients with SjÖgrens syndrome.