Local steroid injection into the artificial ulcer created by endoscopic submucosal dissection for gastric cancer: prevention of gastric deformity.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) of large gastric lesions results in an extensive artificial ulcer that can lead to marked gastric deformity. The aim of the current study was to evaluate therapeutic efficacy in the prevention of gastric deformity of local triamcinolone acetonide (TCA) injection into the extensive artificial ulcer following ESD. PATIENTS AND METHODS: A total of 45 patients who were diagnosed with early gastric cancer were enrolled. Patients were randomly assigned by the sealed-envelope randomization method to either local TCA injections (n = 21) or sham-control (n = 20) groups. Two clips were placed at the two maximum outer edges of the artificial ulcer after the lesion had been resected (Day 0). Local TCA injections were performed on postoperative Day 5 and Day 12. The distance between the two clips was measured by endoscopic measuring forceps on Days 5, 12, 30, and 60. Granulation formation and gastric deformity were evaluated by visual analog scale (VAS) on Days 30 and 60. RESULTS: Local TCA injection did not alter clip-to-clip distance on postoperative Day 60, and formation of flat granulation tissue over the ulcer was followed by regenerative mucosa without any gastric deformity. The sham-control group showed significant shortening of clip-to-clip distance compared with the local steroid-injected group and protruded forms of granulation tissue with mucosal convergence. Histological evaluation revealed prominent growth of neovessels, swelling, and marked increases in endothelial cells in the local steroid-injected group compared with the sham-control group. CONCLUSIONS: Local steroid injection into the floor of a post-ESD artificial ulcer promotes the formation of granulation tissue at an early stage of the healing process leading to regeneration of gastric mucosa without mucosal convergence or gastric deformity.

Association between cardiac function and pulmonary function in hypertensive patients.

OBJECTIVE: This study examined the association between cardiac function and pulmonary function in hypertensive patients. METHODS: Hypertensive patients without overt cardiovascular disease were enrolled (n=43; mean±SD age 71±9 years). Pulmonary function was measured by the percentage of predicted forced vital capacity (%FVC) and the ratio of 1 s forced expiratory volume (FEV1) to FVC (FEV1/FVC ratio). Left ventricular ejection fraction (LVEF) and the ratio of peak early diastolic transmitral flow (E) to peak early diastolic mitral annular velocity (e') (E/e' ratio) were assessed using echocardiography. RESULTS: Multiple linear regression analysis revealed that E/e' was independently associated with %FVC and that LVEF was independently associated with FEV1/FVC ratio. Both LVEF and FEV1/FVC ratio were significantly lower in hypertensive former or current smokers than in hypertensive never smokers. CONCLUSIONS: Subclinical cardiac dysfunction was independently associated with reduced pulmonary function in hypertensive patients. Hypertensive patients with decreased pulmonary function may need preventive care to prevent the progression of heart failure.

Differences in left ventricular diastolic dysfunction between eccentric and concentric left ventricular hypertrophy in hypertensive patients with preserved systolic function.

Left ventricular (LV) hypertrophy (LVH) may be eccentric or concentric (2 × LV posterior wall thickness relative to LV end-diastolic dimension ≤ 0.42 or > 0.42, respectively). The LV diastolic function between age-matched hypertensive patients with eccentric and concentric LVH was compared in the present study. Echocardiography was used to measure LV mass index (LV mass/body surface area; LVMI) as an index of LVH. LV diastolic function was assessed by measurements of peak early transmitral flow velocity (E)/peak late transmitral flow velocity (A) (the E/A ratio), peak early diastolic mitral annular velocity (e') and the E/e' ratio. Although LVMI, E/A and e' did not differ between the two groups, E/e' was significantly higher (worse) in patients with concentric LVH (13.4 ± 5.4) than in those with eccentric LVH (11.1 ± 3.6). Among hypertensive patients with LVH, those with concentric LVH may, therefore, have more severe LV diastolic dysfunction than those with eccentric LVH even if their LVMIs, which reflect the degree of LVH, are similar.

Aortic root dilatation as a marker of subclinical left ventricular diastolic dysfunction in patients with cardiovascular risk factors.

Consensus is lacking about the clinical importance of aortic root dilatation in assessment of the risk of cardiovascular disease. In this study, correlations between aortic root diameter and echocardiographic features of left ventricular (LV) diastolic function were investigated in 333 patients with at least one cardiovascular risk factor (hypertension, diabetes or dyslipidaemia) and preserved LV systolic function. Aortic root diameter was measured by M-mode echocardiography, and LV diastolic function was evaluated by measuring the peak velocity of early (E) and late (A) diastolic transmitral blood flow and peak early diastolic mitral annular velocity (E') by Doppler echocardiography. Linear regression analysis showed that, in men, age was not related to aortic root diameter but hypertension and LV hypertrophy were, whereas the converse was true in women. The parameters E, E/A ratio and E', were related to aortic root diameter in both sexes. Stepwise multiple regression analysis confirmed that E in women and E' in men were independently associated with aortic root diameter. It is concluded that aortic root dilatation might be a useful marker of subclinical LV diastolic dysfunction. Patients with preserved systolic function showing aortic root dilatation should, therefore, be given preventative therapy against LV diastolic heart failure.

Combination immunotherapy with OK-432, recombinant granulocyte-colony-stimulating factor and recombinant interleukin-2 for human hepatocellular carcinoma.

The antitumor effects of immunotherapy using streptococcal preparations (OK-432), recombinant granulocyte-colony-stimulating factor (rG-CSF) and recombinant interleukin-2 (rIL-2) were examined for human hepatocellular carcinoma (HCC). Following subcutaneous injection of OK-432 (2 KE) and rG-CSF (50-60 microg), low-dose intratumoral administration of OK-432 (3-12 KE) was performed. Thereafter, 2 x 10(5) JRU of rIL-2 was subcutaneously injected. This therapeutic regimen was repeated twice. Serum alpha-fetoprotein levels were markedly decreased in three of seven patients with HCC by this treatment. Post-therapeutic histological examination revealed that trabecular cords or pseudoglandular arrangements of tumor cells were completely disordered in all cases and that extensive infiltration of lymphocytes into the tumor stroma was present in five cases. The number of CD4- and CD57-positive cells among tumor-infiltrating lymphocytes after immunotherapy was significantly higher than that in patients without immunotherapy (P <0.01). These findings suggest that even a small intratumoral injection of OK-432 can induce extensive infiltration of helper/inducer and natural killer cells into the tumor stroma when combined with subcutaneous injection of OK-432, rG-CSF and rIL-2 and that these cells might play important roles in tumor cytotoxicity.

Frequency and significance of antibodies to P450IID6 protein in Japanese patients with chronic hepatitis C.

BACKGROUND/AIMS: The aims of the current study were to assess the frequency and the significance of antibodies to cytochrome P450IID6 protein (anti-P450IID6) in various diseases among Japanese patients. METHODS: Sera from 541 patients were tested by indirect immunofluorescence, and the specificity of anti-P450IID6 was ascertained by either enzyme immunoassay (ELISA) or Western blot using recombinant antigen or rat liver microsomes. RESULTS: Anti-P450IID6 was found in only 6 of 235 patients (2.6%) with chronic active hepatitis (CAH) positive for hepatitis C virus (HCV) antibody and quantitative HCV-RNA with genotypes II and IV. The predominant epitopes on immunoblots were 66 and 50KD, a 10KD band being the newly underfined microsomal antigen. Even in the patients negative for autoantibodies to nuclear antigens (ANA) by routine indirect immunofluorescence test, various ANA were detected by the newly developed recombinant ELISA. These patients were younger, with lower gamma-globulin and IgG levels than patients with autoimmune hepatitis. Three of five patients with anti-P450IID6 responded well to interferon therapy and one received prednisone when interferon was ineffective. Interestingly, only this patient was diagnosed as definite autoimmune hepatitis according to the criteria proposed by the International Autoimmune Hepatitis Group (IAHG). The other five patients who did not satisfy the IAHG criteria might be considered as CAH-C with autoimmune features. No autoimmune hepatitis patients positive for anti-P450IID6 were identified in the current study, indicating that the variant is very rare in Japan. CONCLUSIONS: Anti-P450IID6 in CAH-C patients in Japan is not as rare as expected. Anti-P450IID6 among Japanese patients has uncertain significance and precludes further characterization of CAH-C with autoimmune features, which might require interferon therapy.