Laparoscopic Wedge Resection of the Stomach for Submucosal Tumor

We performed laparoscopic wedge resection of the stomach in two patients with submucosal gastric tumor. Three trocars were inserted in addition to a laparoscope. After the blood vessels surrounding the tumors had been ligated with ENDO CUPs, we used ENDO GIA (a linear endoscopic stapling device) four times and then wedge resection was performed. The operative time was 3h33m in Case 1 and 2.5h in Case 2, and bleeding was minimal in both cases. The postoperative courses were uneventful, and intestinal peristalsis recovered rapidly with minimal wound pain. These results suggest that laparoscopic wedge resection of the stomach, a radical procedure, is indicated for submucosal tumor of the stomach.     

Decreased L-selectin expression in CD34-positive cells from patients with chronic myelocytic leukaemia

Abnormal adhesive interaction between bone marrow stroma and progenitors, one of the causes of unregulated proliferation in chronic myelocytic leukaemia (CML), may be caused by some alterations in adhesion molecules on CML progenitors. We investigated the expression of adhesion molecules (CD44, VLA-5, VLA-4, LFA-1, ICAM-1, L-selectin and c-kit) on bone marrow CD34⁺⁺ cells from 16 CML patients by three-colour flow cytometry. The mean percentage of cells expressing L-selectin in the CD34⁺⁺CD38^{+  ∼  ++} fraction from untreated CML patients was significantly lower, and that in the CD34⁺⁺CD38⁻ fraction tended to be lower than that from normal controls. Among 11 CML patients treated with interferon-α (IFN-α), the mean percentage of the cells expressing L-selectin in the CD34⁺⁺CD38⁻ fraction from three patients with a low percentage of Ph¹(+) cells in bone marrow was significantly higher than that from five patients with a high percentage of Ph¹(+) cells. In addition, L-selectin expression rate was inversely correlated to the percentage of Ph¹(+) cells. There was no significant difference between the untreated patients and normal controls with regard to the expression rates of the other adhesion molecules in each CD34⁺⁺ fraction except LFA-1. These data suggest that decreased L-selectin expression in CML CD34⁺⁺ cells reflects one of the features of malignant CML progenitors.     

Association between β‐adrenoceptor gene polymorphisms and relative response to β2‐agonists and anticholinergic drugs in Japanese asthmatic patients

Background and objective: Whether β₂‐adrenoceptor gene (ADRB2) polymorphisms are associated with airway responsiveness to β₂‐agonist medications remains controversial, partly due to factors that may confound pharmacogenetic associations, including age, cigarette smoking and airway remodelling. To overcome these problems, we performed an analysis using parameters that reflected the specific bronchodilator response to β₂‐agonists. Methods: The increases in FEV₁ after inhalation of procaterol hydrochloride (ΔFEV₁ procaterol) or oxitropium bromide (ΔFEV₁ oxitropium), and after sequential inhalation of procaterol and oxitropium (total airway reversibility), were measured in 81 Japanese patients with moderate to severe asthma. Approximately 3 kb of the DNA sequence of the coding and 5′‐flanking regions of ADRB2 were genotyped by direct sequencing and PCR‐restriction fragment length polymorphism assay. Results: The mean age of the participants was 54 years, and 38 (47%) were smokers. Although ΔFEV₁ procaterol and ΔFEV₁ oxitropium adjusted for predicted FEV₁ were not associated with ADRB2 polymorphisms, the ratio of ΔFEV₁ procaterol to total airway reversibility was significantly associated with the ADRB2 A46G genotype (P < 0.05). Patients who were homozygous for the A46 allele (arginine at amino acid 16) were more responsive than carriers of the G46 (glycine 16) allele (P = 0.008). Multivariate linear regression analysis showed that ΔFEV₁ procaterol was correlated with the number of A46 alleles (P = 0.014), and also with total airway reversibility (P < 0.001) and smoking index in current smokers (P = 0.009). Conclusions: The ADRB2 A46G polymorphism was associated with a relatively greater bronchodilator responsiveness to β₂‐agonists even in elderly asthmatic patients and smokers.     

CONCURRENT GASTRIC AND COLONIC LOW‐GRADE MUCOSA‐ASSOCIATED LYMPHOID TISSUE LYMPHOMATA IN A PATIENT WITHOUT HELICOBACTER PYLORI INFECTION

Mucosa‐associated lymphoid tissue (MALT) lymphomata observed simultaneously in the stomach and colon are rare. We report concurrent gastric and colonic low‐grade MALT lymphomata that originated from the same clone in a 58‐year‐old Japanese man without Helicobacter pylori infection. Endoscopy showed multiple erosive lesions in the gastric body and antrum, and a single flat elevation with an irregular margin in the sigmoid colon. Histopathological findings of both lesions suggested low‐grade MALT lymphoma. Lymphoepithelial lesions were evident in the gastric lesions, but not in the colonic lesion. Southern blot analysis of lymphoma cells revealed the same immunoglobulin heavy‐chain rearrangement pattern. The chromosomal translocation t(11;18)(q21;q21) was also observed. After six courses of cyclophosphamide, doxorubicin, vincristine and predonisolone, the gastric lesions disappeared endoscopically, while the colonic lesion persisted. A sigmoidectomy was consequently performed. The chromosomal translocation may be related to the pathogenesis of the present MALT lymphoma case without H. pylori infection. It is interesting that the gastric and colonic lesions differed in response to treatment and in their endoscopic and histologic features, despite having the same origin.     

Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics

Background and objective:   Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC₄ synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known. This was an analysis of the pharmacokinetics of pranlukast in a population of adult asthmatics, and its effect on clinical responses. Other factors that may be related to the therapeutic effects of pranlukast, including LTC₄ synthase gene polymorphisms, were also investigated.
Methods:   The population pharmacokinetics of pranlukast was analysed in a one-compartment model, using data collected in 50 Japanese adults with moderate to severe asthma, who were treated with pranlukast, 225 mg bd for 4 days. In 32 of these patients, in whom the clinical response to pranlukast (increase in FEV₁ after 4 weeks of treatment) was measured in a previous study, a combined pharmacokinetic and pharmacogenetic analysis was performed.
Results:   Using the population pharmacokinetic model, the estimated the mean oral clearance (CL/F) of pranlukast was 16.4 L/h, and the inter-individual variability was 30.1%. Univariate and multivariate analyses showed that LTC₄ synthase polymorphisms, but not the CL/F of the drug, predicted an improvement in pulmonary function with pranlukast treatment ( P  < 0.05).
Conclusions:   There was marked inter-individual variability in the pharmacokinetics of pranlukast among adult asthmatics, but this had little impact on the clinical effectiveness of the drug.     

BRIEF COMMUNICATION: A rapid and simple method to quantify Helicobacter pylori adhesion to human gastric MKN-28 cells

A rapid and simple method to quantitatively analyse Helicobacter pylori adhesion to human gastric epithelial cells was developed by using an enzyme-linked immunosorbent assay. This method made it possible to quantitatively evaluate the adhesion activities of many different H. pylori strains at a time. Our studies indicate that this method is well suited for the quantitative analysis of H. pylori adhesion to gastric epithelial cells.