Treatment of hepatocellular carcinoma with radiofrequency ablation: radiologic-histologic correlation during follow-up periods

To determine whether radiographic images after radiofrequency (RF)-induced coagulation necrosis are correlated with the pathologic effects, we evaluated the morphology and histologic characteristics of RF ablation lesions over a 6-month follow-up period and compared the results with those of radiologic studies. Thirty-three hepatocellular carcinoma (HCC) tumors with a maximum diameter of 3 cm or less were treated percutaneously by using RF ablation in 26 patients. Six treated tumors were resected 4 weeks after ablation; the remaining 27 treated tumors underwent a biopsy procedure by using an 18-gauge fine needle 3 days, 4 weeks, and 24 weeks after ablation. The excised or biopsied lesions were examined by using histologic methods; the findings were then compared with those of contrast-enhanced computed tomography (CT). Three days after ablation, a core of hypoattenuation surrounded by an enhanced/hemorrhagic rim was observed on the contrast-enhanced CT images. Hematoxylin-eosin-stained specimens were inconclusive as to whether or not cellular viability remained; however, cell viability as determined by the presence of histochemical (lactate-dehydrogenase, maleate-dehydrogenase, and the reduced form of nicotinamide-adenine dinucleotide phosphate [NADPH]-diaphorase) stains was absent, suggesting 100% cellular destruction in the ablated lesion. Four and 24 weeks after ablation, the sizes of the ablated lesions were progressively smaller on the CT images; the histochemical stains remained superior to the hematoxylin-eosin stains for obtaining a definite diagnosis of cell death. We conclude that irreversible cellular destruction, as determined by the absence of positive histochemical staining patterns, was useful for evaluating the pathologic thermal effect of RF ablation. These pathologic findings can be correlated with those of contrast-enhanced CT.     

Impact of Src homology 2-containing inositol 5'-phosphatase 2 on the regulation of insulin signaling leading to protein synthesis in 3T3-L1 adipocytes cultured with excess amino acids

Src homology 2-containing inositol 5'-phosphatase 2 (SHIP2) possesses 5'-phosphatase activity to specifically hydrolyze the phosphatidylinositol 3-kinase product PI(3,4,5)P3 in the regulation of insulin signaling. In the present study, we examined the impact of SHIP2 on the regulation of insulin signaling leading to protein synthesis in 3T3-L1 adipocytes cultured with standard and excess concentrations of amino acids. Insulin-induced translocation of PDK1 to the plasma membrane, phosphorylation of Akt and p70S6-kinase and ribosomal protein S6, increase in the amount of 4E-BP1 gamma-form, association of eIF4E with eIF4G, and protein synthesis were decreased by overexpression of wild-type SHIP2 by adenovirus-mediated gene transfer. The effect of SHIP2 overexpression on the regulation of insulin-induced phosphorylation of Akt and p70S6-kinase was somewhat augmented by the incubation with 5-fold excess concentrations of amino acids for 30 min. In contrast, the impact of SHIP2 expression was diminished in insulin-induced phosphorylation of p70S6-kinase and S6, but not of Akt, after the incubation for 16 h. Interestingly, incubation with the excess concentrations of amino acids for 30 min induced activation of phosphatidylinositol 3-kinase and phosphorylation of Akt, whereas phosphorylation of p70S6-kinase and S6 was decreased. Furthermore, although the exposure for longer time periods up to 24 h did not elicit phosphorylation of Akt, it markedly induced phosphorylation of p70S6-kinase and S6. These results indicate that SHIP2 plays an important role in the negative regulation of insulin signaling for the protein synthesis and that the impact of SHIP2 is altered, dependent on the acute or chronic exposure of excess concentrations of amino acids in culture.     

Prognosis of "masked" hypertension and "white-coat" hypertension detected by 24-h ambulatory blood pressure monitoring 10-year follow-up from the Ohasama study

OBJECTIVES: We sought to investigate the prognosis in subjects with "white-coat" hypertension (WCHT) and "masked" hypertension (MHT), in which blood pressure (BP) is lower in clinical measurements than during ambulatory monitoring. BACKGROUND: The prognostic significance of WCHT remains controversial, and little is known about MHT. METHODS: We obtained 24-h ambulatory BP and "casual" BP (i.e., obtained in clinical scenarios) values from 1,332 subjects (872 women, 460 men) > or =40 years old in a representative sample of the general population of a Japanese community. Survival and stroke morbidity were then followed up for a mean duration of 10 years. RESULTS: Composite risk of cardiovascular mortality and stroke morbidity examined using a Cox proportional hazards regression model for subjects with WCHT (casual BP > or =140/90 mm Hg, daytime BP <135/85 mm Hg; relative hazards [RH])1.28; 95% confidence interval [CI] 0.76 to 2.14) was no different from risk for subjects with sustained normal BP (casual BP <140/90 mm Hg, daytime BP <135/85 mm Hg). However, risk was significantly higher for subjects with MHT (casual BP <140/90 mm Hg, daytime BP > or =135/85 mm Hg; RH 2.13; 95% CI 1.38 to 3.29) or sustained hypertension (casual BP > or =140/90 mm Hg, daytime BP > or =135/85 mm Hg; RH 2.26; 95% CI 1.49 to 3.41) than for subjects with sustained normal BP. Similar findings were observed for cardiovascular mortality and stroke morbidity among subgroups by gender, use of antihypertensive medication, and risk factor level (all p for heterogeneity >0.2). CONCLUSIONS: Conventional BP measurements may not identify some individuals at high or low risk, but these people may be identifiable by the use of ambulatory BP.     

A randomized control trial of bi-monthly versus bi-weekly endoscopic variceal ligation of esophageal varices

Endoscopic variceal ligation (EVL) is a safe and simple procedure now being used on a widening scale. Yet most patients who undergo endoscopic treatment for esophageal varices eventually require additional treatment for recurrent varices. In this study, we investigated and compared the efficacy and long-term results of EVL performed in three treatments with a total of sixteen O-rings at two different intervals; bi-weekly (once every 2 wk: the conventional interval) and bi-monthly (once every 2 months). A total of 63 patients with esophageal varices were randomly assigned to groups receiving bi-weekly or bi-monthly EVL treatment. Optimal medical therapy was assessed by one medical doctor who was unaware of the patients' treatment assignments. Three parameters of treatment outcome were evaluated: the rate of recurrence, rate of additional treatment, and overall survival. The overall rates of variceal recurrence and additional treatment were both higher in the bi-weekly group than in the bi-monthly group (p < 0.001). In conclusion, EVL performed for the treatment of esophageal varices at bi-monthly intervals brought about better results than the same treatment performed at bi-weekly intervals. The treatments intercalated by the longer interval obtained a higher total eradication rate, lower recurrence rate, and lower rate of additional treatment.     

Effects of Okadaic Acid on Rat Colon

Effects of okadaic acid (OA) on mucosal damagewere examined in rat colon. OA was sprinkled on ratcolon mucosa under observation with anelectronic-endoscopic system, and OA was also applied tothe in vivo microscopic field. The OA-induced changesin transepithelialconductance (G_t) weremeasured by the Ussing voltage clamp technique. Byendoscopic observation, the luminal sprinkling of OA (60nmol/kg) evoked transient microthrombi in the submucosalvenule, which was followed by mucosal edema.Histological study after endoscopic observation showedsubmucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi werealso detected by in vivo microscopy. Byelectrophysiological study after endoscopic observationwith and without OA addition, the basal G_tvalues were 54 ± 6.2 and 36.2 ± 4.2 mS/cm²,respectively (P < 0.01). Furthermore in control rats,the serosal addition of OA evoked an increase inG_t in a concentration-dependent mannerwithout increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibitedOA-induced G_t change by 60%. These resultsindicate that OA evokes an increase in paracellularpermeability of epithelium. We conclude that thedeveloped microthrombi are the first key event of OA-induced mucosaldamage, followed by an increase in permeability in thesubmucosal venule and in the paracellular pathway of theepithelium.     

Treatment of asthma in smokers: A questionnaire survey in Japanese clinical practice

Background

Cigarette smoking in patients with asthma leads to poor symptom control. As patients who are current smokers have been excluded from enrollment in many clinical trials on asthma, there are few reports on the treatment in current smokers with asthma. In this study, we aimed to assess how respiratory physicians manage asthma in current smokers in Japan.

Sodium-glucose co-transporter-2 inhibitor-associated euglycemic diabetic ketoacidosis that prompted the diagnosis of fulminant type-1 diabetes: A case report

BACKGROUNDFulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by an abrupt onset and a rapid and complete functional loss of islet β cells. It is a very rare disease generally associated with ketoacidosis and the absence of circulating pancreatic islet-related autoantibodies. Diabetic ketoacidosis with normal blood glucose levels has been reported during sodium-glucose co-transporter 2 (SGLT2) inhibitor therapy.CASE SUMMARYThe patient was a 43-year-old woman that consulted a medical practitioner for malaise, thirst, and vomiting. Blood analysis showed high blood glucose levels (428 mg/dL), a mild increase of hemoglobin A1c (6.6%), and increased ketone bodies in urine. The patient was diagnosed with type 2 diabetes mellitus. The patient was initially treated with insulin, which was subsequently changed to an oral SGLT2 inhibitor. Antibodies to glutamic acid decarboxylase were negative. Four days after receiving oral SGLT2 inhibitor, she consulted at Mie University Hospital, complaining of fatigue and vomiting. Laboratory analysis revealed diabetic ketoacidosis with almost normal blood glucose levels. The endogenous insulin secretion was markedly low, and the serum levels of islet-related autoantibodies were undetectable. We made the diagnosis of FT1DM with concurrent SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis. The patient''s general condition improved after therapy with intravenous insulin and withdrawal of oral medication. She was discharged on day 14 with an indication of multiple daily insulin therapy.CONCLUSIONThis patient is a rare case of FT1DM that developed SGLT2 inhibitor-associated diabetic ketoacidosis with almost normal blood glucose levels. This case report underscores the importance of considering the diagnosis of FT1DM in patients with negative circulating autoantibodies and a history of hyperglycemia that subsequently develop euglycemic diabetic ketoacidosis following treatment with a SGLT2 inhibitor.     

Early upsurge in anti-HBs titer possibly caused by the immunomodulative, not by the mutagenetic effect of interferon and ribavirin

A patient with chronic hepatitis B and C undergoing treatment with interferon and ribavirin showed an upsurge in hepatitis B virus surface antibody (anti-HBs) titer, accompanied by a decrease in hepatitis B virus surface antigen (HBsAg) during the early treatment phase. Simultaneously, elevation of alanine aminotransferase (ALT) was observed. Subsequently, the hepatitis B virus (HBV) DNA titer decreased and HBV e antigen (HBeAg) to anti-HBe seroconversion occurred. The anti-HBs titer gradually returned to the pretreatment level after cessation of ribavirin treatment and HBV-DNA became undetectable. We found no nucleotide mutations in HBV-DNA that could explain the sudden elevation in anti-HBs titer. The appearance of anti-HBs was considered to be a break in immune tolerance against some epitopes in HBsAg, possibly the r epitope, stimulated by interferon/ribavirin treatment. The immunomodulatory effect of ribavirin might have caused this unexpected early immune response to HBsAg that preceded seroconversion to anti-HBe.