Mikio Shiomi

Gene expression analysis in colorectal cancer using practical DNA array filter

PURPOSE: We examined the usability of a newly developed, compact-sized DNA array filter for studying the gene expression pattern of individual colorectal cancer. METHODS: Complementary DNA probes were prepared from mRNA extracted from colonic cancer specimens and adjacent normal mucosa and then were labeled with chemiluminescence. These labeled probes were allowed to bind to the gene fragments on the filter. A specialized scanning charge-coupled device camera measured the intensity of each chemiluminescent spot, which is an indicator of the degree to which a specific gene is expressed. Gene expression image was quantified into intensity of signals by using computer software. RESULTS: Characteristic gene expression patterns were obtained from the colonic cancer cell line, RPMI4788, and the leukemia cell line, HL60, by using this compact-sized DNA array filter in the preliminary experiment. Up-regulation of nm23, TIMP1, VEGF, and cyclin E and down-regulation of some tumor suppressor genes (p53, TOSO, and SIVA),β-catenin, and metallothionein were observed in colonic cancer specimen when compared with those of normal mucosa. CONCLUSIONS: We have obtained unique gene expression patterns from colorectal cancer and normal tissue by using a newly developed compact-sized DNA array filter system. Collecting, storing, and analyzing of gene expression data from many samples of colorectal cancer will enable us to identify distinct subsets of patients based on molecular characteristics in the near future.

Two cases of histopathologically advanced (stage IV) early gastric cancers.

We report two cases of early gastric cancer with distant metastases (stage IV). At our institute 1428 cases of primary gastric cancer were resected between 1980 and 1997; 536 were diagnosed as early gastric cancer based on the resected specimens (304 cases of mucosal cancer, Tis – TNM classification – and 232 of submucosal cancer, T1). 528 of these 536 cases were classified as histological stage I, six as stage II, none as stage III and two as stage IV. The incidence of stage IV early gastric cancer was 0.14% of all gastric cancers and 0.37% of the early gastric cancers. The two patients with stage IV early gastric cancer were women. Both tumors were defined as early cancer because they were confined to the submucosa. One was a type 0 IIc + III early cancer, histologically classifiable as a small, moderately differentiated adenocarcinoma (tub2 according to the Japanese Classification of Gastric Carcinoma1,2, G2; TNM classification: ICD-0 C16), size 10 × 8 mm; the other was a surface spreading type 0 lic, classifiable as a signet-ring cell carcinoma (sig, G3), size 50 × 35 mm. Stage IV factors were N3 in the first and ovarian metastasis (Krukenberg tumor) in the second case.

Comparison of argon plasma coagulation and paravariceal injection sclerotherapy with 1% polidocanol in mucosa-fibrosing therapy for esophageal varices

To the Editor: Endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) are widely used for esophageal varices treatment. However, recurrence of esophageal varices has sometimes been observed after these treatments. Especially, a high rate of recurrence associated with EVL1 was reported. In Japan, therefore, in addition to these treatments, mucosafibrosing therapy, by paravariceal injection sclerotherapy, was performed for complete disappearance of esophageal varices.2 In this study, we evaluated the efficacy, complications, and recurrence of esophageal varices after mucosa-fibrosing therapy with argon plasma coagulation (APC) compared with these features after paravariceal injection sclerotherapy using 1% polidocanol (PD). The study was retrospective. Forty-nine patients with esophageal varices exhibiting the red color sign (high-risk group,3 according to the criteria of the Japan Society for Portal Hypertension and Esophago-Gastric varices4) were evaluated. In the initial sessions, we performed endoscopic injection sclerotherapy (EISL),5 and immediately after the EISL procedure, EVL was also performed for esophageal varices (EISL/EVL therapy). One week after the initial EISL/EVL therapy, all patients underwent follow-up endoscopy. The patients with esophageal varices greater than F2 volume underwent additional EVL therapy. The additional EVL therapy was performed until the volume of varices became less than F1 volume. After the sessions, the patients with esophageal varices of F1 or F0 volume underwent mucosafibrosing therapy with APC or 1% PD. The 49 patients were divided into two groups; (1) the APC group and (2) the 1% PD group, in which patients received mucosa-fibrosing therapy by paravariceal injection sclerotherapy of 1% PD. APC therapy was performed only when the APC equipment was available (i.e., in April 1999, February 2000, March 2000, and October 2001; the equipment was rented from AMCO; during these periods 1% PD therapy was not performed). All data values are expressed as means SD. Statistical analysis to compare unpaired variables was performed using two-tailed Student’s t-test. The 2 test or Fisher’s exact test was used to compare categorical data. Intervals until the first recurrence were plotted by the Kaplan-Meier method, and compared by Wilcoxon test. A P values of less than 0.05 was considered statistically significant. The characteristics of the two groups are shown in Table 1. Thirteen of 15 patients in the APC group and 30 of 34 patients in the 1% PD group received prophylactic treatment. All candidates for prophylactic treatment were regarded as being at high risk for variceal hemorrhage. Four patients in the APC group (stage II, 3; stage III, 1) and 11 patients in the 1% PD group (stage I, 2; stage II, 9) had concomitant hepatoma. No significant differences of characteristics were found between the two groups. Endoscopic APC (gas flow, 1.6 l/min; power setting, 50W) was used to promote circumferential fibrosis of the esophageal mucosa from the esophagogastric junction to 5cm proximally (Fig. 1A–D). After the treatment, patients underwent endoscopy every 3 months until the end of follow-up. We defined recurrence as being greater than F1 volume or the appearance of the red color sign. Comparisons of the results of the APC group and the 1% PD group are shown in Table 2. There was no significant difference in the number of O-rings or in the volume of 5% ethanolamine oleate with iopamidol (5% EOI) between the two groups. The number of treatment sessions required to eradicate the varices was significantly lower in the APC group than in the 1% PD group (total, 2.2 0.5 vs 2.8 0.5; mucosa-fibrosing therapy, 1.1 0.3 vs 1.6 0.6; P 0.05). The 1and 2-year cumulative recurrencefree rates in the APC group (93.3% and 84%) were not This article is based on a study first reported in the Japanese Journal of Portal Hypertension (2002;8:180–4) by S Matsui, M Kudo, R Nakaoka, and M Shiomi. “Effect of mucosa-fibrosing therapy with argon plasma coagulation on esophageal varices”. Table 1. Characteristics of patients

Repeated hepatic arterial chemoembolization therapy for management of a patient with metastatic carcinoid tumors of the liver

The symptoms associated with these hernias vary from pain to cough or shortness of breath; occasionally they may be found incidentally during a workup for other diseases. Radiological investigation is the main method of diagnosing these lesions. Computed tomographic, sonographic, and hepatobiliary scanning have all been used (6–8). Most patients will benefit from surgery, especially if they are symptomatic, and some will be managed conservatively just like our patient. In conclusion, hepatic herniation into contiguous organs has been described but herniation into the rectus muscle is a rare phenomenon.

WEGENER’S GRANULOMATOSIS COMPLICATED WITH APHTHOID COLITIS

A 58‐year‐old man was admitted with upper abdominal pain and high fever. There was no abnormality on chest X‐ray, abdominal ultrasonography, abdominal CT and upper gastrointestinal endoscopy. Antineutrophil cytoplasmic antibodies (C‐ANCA) titers were high and a chest CT scan depicted multiple nodules in the bilateral lungs. A diagnosis of Wegener’s granulomatosis was therefore made. Three weeks after admission, diarrhea and bloody stool developed. Colonoscopy revealed many aphthoid lesions surrounded by redness in the entire colon. Although the biopsy from aphtha did not show vasculitis or granuloma, the aphthoid lesions were suspected as a complication of Wegener’s granulomatosis. As a result of predonisolone medication (60 mg/day), the plasma C‐reactive protein (CRP) and high fever improved promptly. In conclusion, although colonic involvement in a patient with Wegener’s granulomatosis is extremely rare, it is important to keep in mind that colonic lesions might be due to vasculitis in ANCA‐positive disease, such as Wegener’s granulomatosis.