Kazumichi Harada

Gastric emptying in OLETF rats not expressing CCK-A receptor gene

We have very recently demonstrated the lowacidity of gastric juice and the high susceptibility tothe development of gastric ulceration in OtsukaLong-Evans Tokushima Fatty (OLETF) rats not expressing CCK-A receptors. In the present study, gastricemptying in this strain was examined and compared withcontrol Long-Evans Tokushima Otsuka (LETO) rats. Gastricemptying was evaluated by the phenol red method. Gastric emptying 30 and 60 min after a liquidmeal in OLETF rats was significantly delayed compared tothat in control LETO rats. Intraperitoneal injection ofCCK-8 at a dose of 5 μg/kg significantly inhibited gastric emptying in control LETO rats, whereasthe same dose of CCK-8 failed to inhibit gastricemptying in OLETF rats. These results suggest for thefirst time that gastric emptying was suppressed in OLETF rats. We also confirmed with this mutant thatCCK delays gastric emptying through the CCK-Areceptors.

Gastric antisecretory and antiulcer actions of interleukin-1 : evidence for the presence of an immune-brain-gut axis

Increasing evidence suggests that interleukin-1 (IL-1), a cytokine mainly produced by activated monocytes/macrophages, has various biological actions in addition to its immunological activities. In the present study, we examined the effects of IL-1 on gastric secretion and gastric ulcer formation in rats. Gastric secretion was assessed in conscious pylorus-ligated rats weighing approximately 200 g. The peripheral injection of IL-1 resulted in a dose-related inhibition of gastric acid output. The central injection of IL-1 similarly reduced gastric acid secretion at 100 times smaller doses than peripherally injected IL-1, suggesting that this gastric antisecretory action of IL-1 is mediated by the central nervous system. In addition, it was found that this inhibitory effect of IL-1, either peripherally or centrally administered, was still evident at 8 h after injection, indicating the long-lasting property of this IL-1 action. On the basis of these antisecretory actions of IL-1, we determined whether or not pretreatment with IL-1 would prevent experimentally induced gastric ulcer formation. As expected, the central administration of IL-1 dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion restraint stress, a well-established ulcerogenic procedure. These results clearly demonstrated that IL-1 has potent antisecretory and antiulcer effects that are mediated by the central nervous system. Moreover, these findings suggest that there may exist an “immune–brain–gut” axis, which is involved in the regulation of gastric secretion and mucosal homeostasis, especially under certain pathophysiological conditions that activate the immune system to release various cytokines including IL-1.

Effects of submucosal administration of endothelin-3 on rat gastric mucosa

The present study was carried out to examine the effects of submucosal administration of endothelin on gastric mucosal integrity in rats. Injection of endothelin-3 into the submucosal space of the stomach induced gastric mucosal damage dose-dependently and site-specifically. The gastric injury was localized only at the injected site and the mucosal damage was associated with hemorrhage. Macroscopic and microscopic examinations revealed that mucosal injury had developed 15 min after endothelin application. Submucosal injection of either adrenalin or noradrenalin also induced gastric mucosal damage, but produced multiple gastric mucosal lesions; i.e., the macroscopic appearance of endothelin-induced gastric lesions differed from those produced by catecholamines. The endothelin-induced mucosal lesions were significantly inhibited by pretreatment with either atropine, pirenzepine, or ranitidine; or by vagotomy. In addition, NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, significantly enhanced the formation of gastric mucosal lesions. Thus, it appears that nitric oxide synthesis, possibly induced by endothelin, may play a role as an antiulcer mechanism in endothelin-induced gastric mucosal damage. Vagotomy and anti-cholinergic or antisecretory treatment significantly attenuated the severity of the mucosal lesions, suggesting that vagal cholinergic pathways and acid secretion may influence the development of the gastric mucosal damage induced by endothelin-3. These results suggest that endothelin-3 may play an important role in the development of gastric ulceration; the submucosal application of endothelin-3 in the gastric mucosa may be a useful experimental model for investigating acute gastric mucosal ulceration.

YAG Laser Therapy for Intractable Gastric Ulcer

At present a number of excellent therapeutic agents including H2-blocker antagonists have been developed for peptic ulcers. As a result, so-called intractable gastric ulcers have come to be encountered less frequently, though there are still some cases of gastric ulcer with repeated relapse and recrudescence that follow an intractable clinical course. We have been applying endoscopic local injection therapy for the treatment of intractable gastric ulcers for 20 years. Using this therapy, which consists of an injection of steroid solution and 0.5% Alantoine solution into the ulcer edge area and base, we have obtained favorable results. In the present study we used YAG laser irradiation in lieu of the injection of steroid solution for the treatment of intractable gastric ulcer and observed healing in all cases. In the following, our procedures are described, with a presentation of the cases.

7122 Can endoscopic retrograde ileography alone assess the disease activity in crohn's disease ?

Background: The ileum is frequently affected site of the small intestine in Crohns disease (CD). However, precise evaluation of disease activity is sometimes difficult by small bowel enteroclysis (SBE) because of multiple overlapping loops. We have reported the usefulness of balloon occluded endoscopic retrograde ileography (ERIG) that is a combination of colonoscopic and radiological ileal examination for the evaluation of the disease activity not only in the colon but also in the distal ileum at one procedure (Taruishi M. et al. Radiology; in press). Aim: To evaluate weather ERIG alone can represent the disease activity of the whole small intestine without SBE information. Patients and Methods: Between May 1990 and May 1999, 50 times of both ERIG and SBE were performed within two weeks in 33 cases of known CD. Three cases were colitis, 12 were ileocolitis and 18 were ileitis type of CD. Written informed consent was obtained. Briefly, ERIG procedures were as follows. Total colonoscopy was performed, followed by intubation to the ileum. After a guide wire was introduced through the forceps channel into the ileum, only colonoscope was removed. Silicon balloon tube was inserted into the terminal ileum and fixed by the expanded balloon. After barium surfate and air was injected followed by several turning of position, double contrasted radiography was obtained. Disease activity was diagnosed independently on ERIG and SBE.We compared the disease activity assessed by ERIG with that by SBE. Results: Of 50 procedures, both ERIG and SBE revealed identical CD activity; active disease in 25 procedures and remission in 9. On the other hand, in 10 procedures ERIG showed active disease but SBE did not, and SBE showed active disease but ERIG did not in 6 procedures. ERIG could represent and evaluate the disease activity of whole small bowel in 44 (88%) of 50 procedures. The reasons to fail in evaluating the disease activity by ERIG alone were visualization of only short part of the distal ileum (less than about 100 cm) in 4 procedures, severe stricture in 1 procedure and active disease affected only in the jejunum and remission in the ileum in 1 procedure. Conclusion: Because most CD affected distal ileum, ERIG could represent the disease activity of CD not only in the colon but also in the whole small bowel, and assess it at one procedure without SBE.

⁎4539 Is high-frequency ultrasound probe a useful modality for invasion depth diagnosis of early gastric cancers?

Background: Precise preoperative invasion depth staging is essential to determine a therapeutic strategy for early gastric cancer, because endoscopic mucosal resection (EMR) is satisfactory for intramucosal cancers (m-ca) but gastrectomy is necessary for submucosal cancers (sm-ca). Recently, high-frequency ultrasound probe (HFUP) has become available and it enabled to provide high resolutional images especially for small and superficial gastric cancers. Aims: To clarify whether or not HFUP is useful for invasion depth diagnosis, we prospectively compared its accuracy with endoscopy. Patients and Methods: We prospectively studied 113 consecutive patients with 114 early gastric cancers (T1 stage), consisting of 81 mca and 33 sm-ca, that were subsequently treated by EMR (n=59) or gastrectomy (n=55) between Mar. 1995 and Sep. 1999. The criteria of invasion depth diagnosis were referred to the report for endoscopy (Sano T, et al. Dig Dis Sci 35, 1990) and for HFUP (Yasuda K, et al. Stomach and Intestine 27, 1992). The invasion depth was diagnosed prospectively based on these criteria. HFUP was performed by using 15 or 20 MHz probes. The macroscopic type was divided into Type I (protruded, n=4) and Type II (superficial, n=110). Type II was subdivided into following 3 types; superficial elevated (IIa, n=35), superficial depressed with ulceration (IIc Ul(+), n=26), superficial depressed without ulceration (IIcUl(-), n=42) and flat elevated with depression (IIa+IIc, n=7). Results: No significant difference was found in the overall accuracy between the two modalities, that were 77.8% in endoscopy and 73.7% in HFUP. However, HFUP could provide correct diagnosis in 9 (34.6%) of 26 cases misdiagnosed by endoscopy. Conversely, endoscopy did so in 10 (37.0%) of 27 cases incorrectly diagnosed by HFUP. Both modalities showed a significantly lower accuracy rate in type IIc Ul(+) than in the other macroscopic types (p

Characteristics of the gastric cancer in the aged (over 65 years old)

老年者の胃癌の特徴をみるため, 過去10年間, 当科に入院した胃癌症例を65歳以上の群 (A群) と65歳未満の群 (B群) の2群に分け, 以下の検討を行った.胃癌症例225例 (男160例, 女65例) を対象とし, これをA群120例, B群105例とに分け, 1) 各群平均年齢, 2) 性別, 年齢別構成, 3) 初発症状, 4) 発見動機, 5) 癌占居部位 (CMA分類), 6) 癌の大きさ, 7) 早期胃癌肉眼型分類, 8) 進行胃癌肉眼型分類, 9) 癌深達度, 10) 癌組織型分類-以上10項目について胃癌取扱い規約に基づき検討を行った. なお, 7)～10) までは, 手術例153例 (男112例, 女41例) について検討した.この結果, 1) 全症例の平均年齢は63.1歳, A群74.0歳, B群51.0歳であった. 2) 70歳～79歳の年齢層が最も多く, この年代では男性は女性の2倍以上を占める. 3) 初発症状では, 両群ともに腹痛が最も多く, ついで無症状例が多かった. 従って症状がなくとも積極的に胃の検査を行うべきである. 4) 発見動機では症状があって受診する例が両群ともに約40%にみられ最も多かった. 5) 癌占居部位では両群ともにM→A→C→CMAの順となっており, 各領域の比率は両群でほぼ同様である. 6) 癌の大きさではA群でB群より大きなものの多い傾向にあった. 7) 早期胃癌の手術例では両群ともにIIcが最も多かった (A群54.8%, B群71.2%). 8) 進行胃癌の手術例ではA群で限局型が, B群で浸潤型が多かった. 9) 早期癌手術例ではA群でmとsmがほぼ同率, B群ではmの率がsmに比し高かった. 進行癌では両群に大差はなかった. 10) 手術例での組織型はA群で分化型が, B群では未分化型が多く, 特にB群では印環細胞癌が多かった.