15-羟基前列腺素脱氢酶与胃癌发生关系的研究

NAD依赖性15-羟基前列腺素脱氢酶（15-PGDH）是前列腺素和相关廿烷类生物降解、灭活的关键酶，其表达缺失或减低可能与一些恶性肿瘤的发生、发展密切相关。目的：探讨15-PGDH在胃癌组织和癌旁组织中的表达及其与临床病理特征的关系，初步评价15-PGDH在胃癌发生、发展中的作用及其意义。方法：随机收集30例胃癌患者的癌组织、癌旁3cm和6cm的对照组织，以及10例胃息肉、萎缩性胃炎和健康志愿者正常胃黏膜组织标本，以免疫组化和Western blot法检测15-PGDH蛋白表达，半定量逆转录聚合酶链反应（RT-PCR）法检测其mRNA表达，并分析其临床病理特征。结果：癌组织中15-PGDH蛋白和mRNA表达显著低于癌旁3cm、癌旁6cm对照组织和正常胃黏膜（P均〈0.01），约1／3癌组织中15-PGDH表达缺失，胃息肉和萎缩性胃炎组织显著低于正常胃黏膜（P均〈0．01）；癌组织中15-PGDH蛋白表达量较癌旁3cm和6cm对照组织分别平均降低5．7倍和8．3倍，胃息肉和萎缩性胃炎组织较正常胃组织分别平均降低2．0倍和2．1倍；黏液腺癌中15-PGDH蛋白量显著低于高分化腺癌（只〈0．05），印戒细胞癌中15-PGDH蛋白和mRNA的表达均缺失：伴有远处转移组15-PGDH蛋白和mRNA表达显著低于无远处转移组（P〈0．05和P〈0．01）；Ⅳ期胃癌组织15-PGDH蛋白表达量显著低于Ⅰ期（P〈0．01），其mRNA表达在Ⅲ、Ⅳ期胃癌组织中显著低于Ⅰ、Ⅱ期胃癌（P均〈0．01）。结论：15-PGDH在胃癌组织中表达减少甚至缺失，在癌旁组织和胃癌前状态中表达减少；15-PGDH表达缺失或减少可能是胃癌发生、发展．以及胃癌浸润转移的重要机制之一。     

A rare case of iron deficiency

Giant lipomas of the stomach are very rare, accounting for less than 3% of all benign tumors of the stomach. A clear-cut endoscopic differentiation between gastric lipomas and other submucosal neoplasms is not feasible, because routine endoscopic gastric biopsies do not reach the submucosal layer. Gastric submucosal lipomas can cause gastric ulceration as in the case presented below and in rare instances this may in turn promote gastric cancer. Therefore, complete pretreatment diagnostic evaluation is needed. We present a 52-year-old man with a 6-month history of epigastric discomfort, early satiety, decreased appetite, and dyspepsia. His weight was noted to be stable and he was iron deficient (hemoglobin 11.5 g/dl and ferritin of 5 g/dl). His past history included a gastric ulcer found on endoscopy 5 years ago for which he was on omeprazole 40 mg once a day, hypertension, hypercholesterolemia, and diabetes. Clinical examination revealed central obesity with divarification of recti muscles. He underwent a colonoscopy that was normal, and an oesophago-gastro-duodenoscopy that revealed a smooth extrinsic indentation of the anterior aspect of the distal stomach at around 50 cm. Biopsies of this were normal. A computed tomography scan was obtained () that demonstrated a 14 by 15-cm fatty tumor arising from the distal stomach with a couple of 5-mm nodes adjacent to tumor and no distant metastasis representing either a lipoma, liposarcoma or gastrointestinal stromal tumours. He subsequently underwent a subtotal gastrectomy. Macroscopically, the antrum was distorted by a huge submucosal intramural tumor mass. The antral mucosa was stretched over its surface and bore a central 15-mm ulcer surrounded by a raised border (). Microscopic examination confirmed an ulcerated benign submucosal lipoma. Our patient was symptomatic with a large gastric lipoma that necessitated surgical excision. Following surgery his postoperative recovery was uneventful, and he was asymptomatic when reviewed 4 weeks later. This case demonstrates a rare case of gastric lipoma causing gastric epithelial ulceration leading to iron deficiency.     

An immunoglobulin-like antigen in human cell lines and sera of cancer patients.

Different sera from cancer patients were tested for the presence of C1-GMA, an antigen described by us, which was shared by HeLa-like human cell lines and gastric mucosa. Using the immunodiffusion test, dot-blotting and electrophoresis followed by immunoblotting, we failed to reveal the antigen in the sera of patients. However, an Ig-like 56-60 kD antigen was found in the sera of patients with ovary and stomach carcinoma and lymphoid tumors. The Ig-like antigen was also revealed in 2 out of 5 tested human cell lines of non-leukocyte origin (HEp-2 and E16-B).     

Measurement of immunoreactive gastrin in gastric mucosa.

A method for measurement of gastrin in gastric mucosa has been developed, and distribution of gastrin in the stomach of pig, dog, cat, rabbit, and man was examined. Measurable amounts of gastrin were found in corpus of all species, but the content in the antrum was considerably higher. The highest concentration of gastrin was seen in man. The borderline between corpus and antrum was abrupt, and in both parts of the stomach gastrin was evenly distributed. In 44 patients with duodenal ulcer the antral gastrin concentration was 21.3 mug eqv. per g mucosa, in 15 patients with prepyloric ulcer 23.0, in 10 patients with gastric ulcer 5.9, and in 16 patients with gastric carcinoma 7.9. The control group consisted of 10 healthy volunteers and 12 patients with minor abdominal complaints. Mean antral gastrin concentrations were 28.1 and 20.7 respectively. No significant relationship was observed between PAO and gastrin content of antral mucosa in any group.     

Lymphoepithelioma-like carcinoma of the stomach: a subset of gastric carcinoma with distinct clinicopathological features and high prevalence of Epstein-Barr virus infection.

BACKGROUND/AIMS: To evaluate the clinicopathological features of lymphoepithelioma-like carcinoma of stomach in Taiwan. METHODOLOGY: Of 379 patients with gastric adenocarcinoma, from 1993 to 1996, 6 of them with lymphoepithelioma-like carcinoma of stomach were retrospectively studied. RESULTS: Five patients were females and one patient was male. Their age ranged from 51-75 years with a mean age of 61.5 years. Endoscopically, 2 patients were initially diagnosed as early gastric cancer and the other 4 were diagnosed as advanced gastric cancer. Three patients had tumors located in the lower third of the stomach, while the other three tumors were located in the middle and upper third. Two tumors invaded into the serosal layer and the other four lesions were confined at submucosal and muscular layers. Using the in situ hybridization method, all 6 patients (100%) had positive nuclear Epstein-Barr virus-encoded small RNA signals in the tumor cells but not in the surrounding lymphoid stroma and non-neoplastic gastric mucosa. Helicobacter pylori was found in 4 (66.7%) of the cases. The mean follow-up period of the 6 patients was 27 months. Five patients were free of the disease. Lymph node involvement and mesenteric implantation was noted in one patient in which cancer recurred 1 year after gastrectomy. CONCLUSIONS: Lymphoepithelioma-like carcinoma of stomach in this study revealed a female predominance, preferential localization in the proximal part of the stomach, better prognosis, and a high association with Epstein-Barr virus infection.     

胃癌及消化性溃疡患者胃窦粘膜胃肠激素的变化

目的探讨胃癌及消化性溃疡（ＰＵ）患者胃窦粘膜胃肠激素变化的意义．方法内镜及活检确诊的浅表性胃炎（ＣＳＧ）１０例，胃溃疡（ＧＵ）１５例，十二指肠溃疡（ＤＵ）１２例，胃癌（ＧＣ）６例．胃镜下取胃窦粘膜，用ＲＩＡ法测定胃泌素（Ｇａｓ）、生长抑素（ＳＳ）、Ｐ物质（ＳＰ）的含量，各组间进行比较．结果胃窦粘膜ＳＳ含量在ＧＵ，ＤＵ，ＣＳＧ，ＧＣ组分别为２５１ｐｇ／ｍｇ±１９４ｐｇ／ｍｇ（以下同），４７０±１７９，５３２±２１１及１２９３±５２３。其中ＧＵ组低于其余各组（Ｐ＜００５），而ＧＣ时则显著升高（Ｐ＜００１）．ＳＰ含量在ＤＵ组显著降低，与ＧＵ，ＣＳＧ，ＧＣ比较分别为４７９±１５７ｖｓ７６５±４１５，７８９±３９０及８０１±３４６，Ｐ＜００５；ＧＣ患者Ｇａｓ水平显著高于ＣＳＧ组，为４６４５±２９４４，ｖｓ２７６８±１５７２，Ｐ＜００１．结论胃粘膜中Ｇａｓ，ＳＳ，ＳＰ含量的变化可能在ＰＵ及胃癌的发病机理中起重要作用．     

The Peptic Gastric Ulcer — Histotopographic and Functional Investigations

Histotopographic studies of approximately 200 gastric ulcers using endoscopic biopsies show that the chronic gastric ulcer is found in mucosa containing only mucoid or intestinal glands. Furthermore, with few exceptions (prepyloric ulcer), this mucosa is usually inflamed. Since the ulcer is nearly always found at the border to the acid-producing mucosa, the localization is an indication of the extent of gastritis and of the maximal acid secretion capacity of the stomach. In patients with a gastric ulcer, normal body or antrum mucosa is found more rarely than in a corresponding control group.     

Effect of duodenal juice on pathogenesis of gastric ulcer

The purpose of the present study was to elucidate the effect of duodenal juice on development of gastric ulcer, in relation to changes of lipid composition and energy metabolism of the gastric mucosa in dogs. For regurgitation of duodenal juice and stagnation of gastric contents in the stomach, the duodenum was constricted below the papilla of Vater, accompanying with pyloroplasty and upper gastro-jejunostomy. Furthermore, to induce ischemia in the gastric mucosa, 0.5 ml of 1% formalin solution was injected into a descending branch of the left gastric artery. Three weeks later, U1 II-III gastric ulcer developed at the formalin injected area with severe gastritis but not with hyperacidity, and the histologic findings were similar to the one of a human gastric ulcer with hypoacidity. On assay of lipid composition in the gastric mucosa, lecithin decreased and both lysolecithin and NEFA increased, showing that lecithin of the gastric mucosa was decomposed by phospholipase A2 of the duodenal juice. In the gastric mucosa, ATP and energy charge decreased, and AMP and lactate increased, indicating that the energy metabolism was led to anaerobic glycolysis. These results revealed that the gastric mucosa becomes very fragile when duodenal juice regurgitates into the stomach and that gastric ulcer may develop even without hyperacidity when the microcirculation is disturbed in this condition.     

Atrophy of the corpus mucosa of the stomach simulating polyposis

We report on five cases of mucosal atrophy of the gastric body, under the aspect of a polyposis: These polyps showed intact mucosa with abundant fundic glands and were situated in the diffuse atrophic mucosa of the gastric body. Four of these cases were manifestations of type A gastritis, in one case the lesion surrounded a peptic ulcer. Laboratory findings of serologically analysed cases with type A gastritis showed elevated parietal cell antibodies in all cases, two of three cases showed a high level of gastrin, the values for vitamin B12 showed different levels; no patients revealed antibodies against the intrinsic factor, and no patient had pernicious anemia. The family history revealed three cases with cancer of the stomach on one side of the parents. It is important to biopsy polyps and the flat mucosa separately in order to verify this form of atrophy of the gastric mucosa and to also exclude small polypous tumors of the mucosa. Observation of the number of polyps allows a control of the extent of the atrophy of the mucosa.     

Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.     

Observations on the histology of the gastric mucosa in chronic gastric ulcer

Histologic changes were studied in the gastric mucosa of 18 patients with a chronic, lesser curve, gastric ulcer. Biopsies were taken approximately 2 cm from the ulcer margin, and from the opposite wall of the stomach body. Morphologic appearances noted in the active phase of ulceration were found to persist during the healing process (12 patients) and, on follow-up study, at 6 to 10 weeks (5 patients). The ulcer failed to heal in 6 patients, 5 were treated surgically and another refused operation; all had persisting gastritis. Twelve patients had been treated with carbenoxolone, which did not appear to influence histology. The ability of the ulcer to heal in the presence of continuing gastritis, the persistence of gastritis after the ulcer healed and the lack of difference in the surrounding mucosa between healed and unhealed ulcers indicate that the relationship between the two lesions is uncertain.     

Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients: effects of aspirin and paracetamol.

The distribution of mucosal PGE2-like activity was determined by bioassay technique in the body and antrum of the stomach and in the duodenum of healthy subjects and duodenal ulcer patients before and after administration of aspirin, paracetamol, or histamine. In healthy subjects, the oxyntic, antral and duodenal mucosa was found to be capable of generating large amounts of PGE2, which were not significantly different from those found in duodenal ulcer patients. No correlation was found between the generation of PGE2 and gastric acid secretory status or serum gastrin level. Aspirin-and to a much lesser extent, paracetamol-caused a dramatic reduction in the ability of the gastric mucosa to biosynthesis PGE2 and this was accompanied by marked side-effects and injury to the gastric mucosa. Administration of histamine caused small but significant reduction in the biosynthesis of PGE2 but it was accompanied by marked mucosal damage. This study indicates that the gastric and duodenal mucosa is capable of generating PGE2-like activity which may be involved in the mechanism that protects the mucosa against the damage caused by aspirin.     

Prevalence of Helicobacter pylori infection in advanced gastric carcinoma

BACKGROUND: [corrected] There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS: To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's classification METHODS: A prospective controlled study enrolled 56 patients from "Hospital Universitário", Federal University of Rio Grande do Norte, Natal, RN, Brazil, with advanced gastric cancer, treated from February 2000 to March 2003. Immediately after partial gastrectomy, the resected stomach was opened and several mucosal biopsy samples were taken from the gastric tumor and from the adjacent mucosa within 4 cm distance from the tumor margin. Tissue sections were stained with hematoxylin and eosin. Lauren's classification for gastric cancer was used, to analyse the prevalence of H. pylori in intestinal or diffuse carcinomas assessed by the urease rapid test, IgG by ELISA and Giemsa staining. H. pylori infected patients were treated with omeprazole, clarithromycin and amoxicillin for 7 days. Follow-up endoscopy and serology were performed 6 months after treatment to determine successful eradication of H. pylori in non-tumor tissue. Thereafter, follow-up endoscopies were scheduled annually. Chi-square and MacNemar tests with 0.05 significance were used. RESULTS: Thirty-four tumors (60.7%) were intestinal-type and 22 (39.3%) diffuse type carcinomas. In adjacent non-tumor gastric mucosa, chronic gastritis were found in 53 cases (94.6%) and atrophic mucosa in 36 patients (64.3%). All the patients with atrophic mucosa were H. pylori positive. When examined by Giemsa and urease test, H. pylori positive rate in tumor tissue of intestinal type carcinomas was higher than that in diffuse carcinomas. In tumor tissues, 34 (60.7%) H. pylori-positive in gastric carcinomas were detected by Giemsa method. H. pylori was observed in 30 of 56 cases (53.5%) in tissues 4 cm adjacent to tumors. This difference was not significant. Eradication of H. pylori in non-tumor tissue of gastric remnant led to a complete negativity on the 12th postoperative month CONCLUSIONS: The data confirmed the hypothesis of a high prevalence of H. pylori in tumor tissue of gastric advanced carcinomas and in adjacent non-tumor mucosa of operated stomachs. The presence of H. pylori was predominant in the intestinal-type carcinoma.     

Update on the pathologic approach to the diagnosis of gastritis, gastric atrophy, and Helicobacter pylori and its sequelae

Biopsy sampling of the gastric mucosa at diagnostic endoscopy provides information that cannot be obtained otherwise. The most common indication for gastric biopsy is the need to know whether the patient is infected with Helicobacter pylori or not and whether the stomach is gastritic or not. Microscopic examination of gastric biopsy specimens gives, in addition to H. pylori status, information about the grade, extent, and topography of gastritis- and atrophy-related alterations in the gastric mucosa. This information provides further possibilities for the assessment of risk and likelihood of various gastric disorders. The presence of atrophy (loss of mucosal glands) results in failures in secretory functions of the corresponding mucosa and leads to errors in the homeostasis of normal gastric physiology. The grade of atrophy of the corpus mucosa linearly correlates with peak and maximal output of acid. The presence of advanced (moderate or severe) corpus atrophy indicates an extremely hypochlorhydric or achlorhydric stomach in which, for example, ordinary peptic ulcer is unlikely or impossible in spite of a possible H. pylori infection. Some well characterized and common topographic phenotypes of H. pylori gastritis and atrophic gastritis can be delineated as follows: Predominance or restriction of the H. pylori-related inflammation in antrum, in association with a nonatrophic corpus mucosa--of which phenotype is the most common--and with an increased risk of peptic ulcer disease, duodenal ulcer in particular ("duodenal ulcer phenotype" of gastritis); the presence of atrophic gastritis in corpus of the stomach ("corpus predominant gastritis"), which indicates a low risk of peptic ulcer and a reduction in the capacity of the patient to secrete acid; the occurrence of advanced atrophic gastritis and intestinal metaplasia multifocally in the stomach (advanced "multifocal atrophic gastritis"), which are features of a gastritis type and which also indicate a low acid secretion capacity and an increased risk of gastric neoplasias ("gastric cancer phenotype of gastritis"), suggesting a need for a careful exclusion of concomitant presence of small focal neoplastic or dysplastic lesions; and the presence of normal and healthy gastric mucosa, which indicates an extremely low risk of both peptic ulcer disease or gastric cancer and, therefore, is a finding of high clinical relevance. The presence of duodenal or gastric ulcer in conjunction with normal, healthy gastric mucosa suggests either aspirin or nonsteroidal antiinflammatory drugs to be the most likely cause of the ulcer.     

Should we worry about gastric cancer in duodenal ulcer patients?

In three patients with active duodenal ulcer, carcinoma of the stomach was detected early during routine endoscopic examination. In all patients subtotal gastrectomy was performed, and pathological examination of the resected stomach revealed carcinoma confined to the mucosa. We review evidence for and against any association between gastric carcinoma and peptic ulcer disease.     

Effects of Cyanoacrylate on the Gastric Mucosa of Dogs –Endoscopic and Histopathological Studies for Sclerotherapy of Gastric Varices–

Abstract: The effect of cyanoacrylate tissue adhesive (C. A.) on the gastric mucosa of dogs was investigated endoscopically and histopathologically. When C. A. was applied to the surface of the gastric mucosa, the endoscopic findings the next day showed local redness at the applied site (Fig. 1-a) and histopathology revealed degenerative changes in the gastric mucosa (Fig. 1-b). When C. A. was endoscopically injected into the gastric mucosa, the endoscopic findings revealed a submucosal tumor-like lesion (Fig. 2-a). One day after treatment, the endoscopic findings showed a hemorrhagic erosion on the surface of the lesion (Fig. 2-b). An histopathological examination of the resected stomach revealed C. A. in the submucosal layer (Fig. 3-a, 3-b) and the lymph duct around the muscularis mucosa with severe acute inflammation (Fig. 4-a, 4-b). One week after treatment, a deep ulcer (Ul-IV) was observed (Fig. 5, 6) and a histopathological examination of the resected specimen revealed C. A. at the site of the ulcer and inflammatory cell infiltration by fibroblasts and giant cells (Fig. 7-a, 7-b). One month after treatment, the ulcer had healed and was replaced by a scar (Fig. 8). Histopathological examination of the resected stomach revealed C. A. in both the muscularis mucosa and the submucosa and also inflammatory cell infiltration by giant cells in addition to the fibrosis (Fig. 9). When using endoscopic sclerotherapy with C. A., it should be kept in mind that there is the possibility of such a lesion occurring as demonstrated by our study.     

Helicobacter pylori cagA, iceA and vacA genotypes in patients with gastric cancer in Taiwan

AIM:Helicobacter pylori(Hpylori)has been linked to chronicgastritis,peptic ulcer,gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remainscontroversial.The aim of this study was to investigate theHpylori vacA alleles,cagA and iceA in patients with gastriccancer in Taiwan.METHODS:Patients with gastric cancer,peptic ulcer andchronic gastritis were enrolled in this study.We obtainedbiopsy specimens from the stomach at least 2 cm awayfrom the tumor margin in patients with gastric cancer,andfrom the antrum of stomach in patients with peptic ulceror chronic gastritis.DNA extraction and polymerase chainreaction were used to detect the presence or absence ofcagA and to assess the polymorphism of vacA and iceA.RESULTS:A total of 168 patients(gastric ulcer:77,duodenalulcer:66,and chronic gastritis:25)were found to havepositive PCR results of the biopsy specimens from patientswith peptic ulcer and chronic gastritis.We found positivecagA(139/168,83%),m2(84/168,50%)and iceA1(125/168,74%)strains in the majority of patients.In patients withgastric cancer,the vacA sla and slc subtypes were lesscommonly found than those in non-cancer patients(35/66 vs127/168,P=0.0001 for sla and 13/66 vs93/168,P<0.0001for slc).In the middle region,the ml T strain in patientswith gastric cancer was more than that of non-cancer patients(23/66 vs33/168,P=0.02).CONCLUSION:In Taiwan,Hpyloriwith positive vacA sla,cagA and iceAl strains are found in the majority of patientswith gastric cancer or non-cancer patients.In patients withgastric cancer,the vacA sla and slc subtypes are lessand mlT is more than in patients with peptic ulcer andchronic gastritis.     

Helicobacter pylori cagA, iceA and vacA genotypes in patients with gastric cancer in Taiwan

AIM: Helicobacter pylori (H pylori ) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma. The link of genotypes of H pylori to gastric cancer remains controversial. The aim of this study was to investigate the H pylori vacA alleles, cagA and iceA in patients with gastric cancer in Taiwan. METHODS: Patients with gastric cancer, peptic ulcer and chronic gastritis were enrolled in this study. We obtained biopsy specimens from the stomach at least 2 cm away from the tumor margin in patients with gastric cancer, and from the antrum of stomach in patients with peptic ulcer or chronic gastritis. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA. RESULTS: A total of 168 patients (gastric ulcer: 77, duodenal ulcer: 66, and chronic gastritis: 25) were found to have positive PCR results of the biopsy specimens from patients with peptic ulcer and chronic gastritis. We found positive cagA (139/168, 83%), m2 (84/168, 50%) and iceA1 (125/168, 74%) strains in the majority of patients. In patients with gastric cancer, the vacA s1a and s1c subtypes were less commonly found than those in non-cancer patients (35/66 vs 127/168, P = 0.0001 for s1a and 13/66 vs 93/168, P<0.0001 for s1c). In the middle region, the m1T strain in patients with gastric cancer was more than that of non-cancer patients (23/66 vs 33/168, P = 0.02). CONCLUSION: In Taiwan, H pylori with positive vacA s1a, cagA and iceA1 strains are found in the majority of patients with gastric cancer or non-cancer patients. In patients with gastric cancer, the vacA s1a and s1c subtypes are less and m1T is more than in patients with peptic ulcer and chronic gastritis.