幽门螺旋杆菌与胃癌

胃癌是世界上发病率为第二位的恶性肿瘤,日本的患者也很多。欧美胃癌发病率在短期间内有减少倾向,由此可以想象环境因素在胃癌发病中的重要作用,这种想法至今基本没有改变,但自从分离培养出幽门螺旋杆菌,该菌与胃癌发生尤为受人关注。本文主要阐述幽门螺旋杆菌与胃癌发病机制的关系。幽门螺旋杆菌的助催化剂——氨幽门螺旋杆菌有较强的尿素酶活性,分解胃内尿素产生氨。感染本菌人的胃液中氨浓度为0.01％,明显高于非感染者的0.005％。研究人员让大鼠自由饮用含有0.01％氨水。

Importance of gastrin in the pathogenesis and treatment of gastric tumors

In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.

Influence of gastric inhibitory polypeptide on pentagastrinstimulated gastric acid secretion in patients with type 2 diabetes and healthy controls

AIM： Gastric inhibitory polypeptide is secreted from intestinal K-cells in response to nutrient ingestion and acts as an incretin hormone in human physiology. While animal experiments suggested a role for GIP as an inhibitor of gastric secretion, the GIP effects on gastric acid output in humans are still controversial. METHODS： Pentagastrin was administered at an infusion rate of 1 μg . kg^-1 . h^-1 over 300 min in 8 patients with type 2 diabetes （2 female, 6 male, 54± 10 years, BMI 30.5 ± 2.2 kg/m^2; no history of autonomic neuropathy） and 8 healthy subjects （2/6, 46 ± 6 years., 28.9 ± 5.3 kg/ m^2）. A hyperglycaemic clamp （140 mg/dl） was performed over 240 min. Placebo, GIP at a physiological dose （1 pmol . kg^-1 . min^-1）, and GIP at a pharmacological dose （4 mol . kg^-1 . min^-1） were administered over 60 min each. Boluses of placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at the beginning of each infusion period, respectively. Gastric volume, acid and chloride output were analysed in 15-min intervals. Capillary and venous blood samples were drawn for the determination of glucose and total GIP. Statistics were carried out by repeated-measures ANOVA and one-way ANOVA. RESULTS： Plasma glucose concentrations during the hyperglycaemic clamp experiments were not different between patients with type 2 diabetes and controls. Steady-state GIP plasma levels were 61 ±8 and 79 ± 12 pmol/I during the low-dose and 327±35 and 327± 17 pmol/I during the high-dose infusion of GIP, in healthy control subjects and in patients with type 2 diabetes, respectively （P= 0.23 and p 0.99）. Pentagastrin markedly increased gastric acid and chloride secretion （P〈 0.001）. There were no significant differences in the rates of gastric acid or chloride output between the experimental periods with placebo or any dose of GIP. The temporal patterns of gastric acid and chloride secretion were similar in patients with type 2 diabetes and healthy controls （P= 0.86 and P= 0.61, respectively）. CONCLUSION： Pentagastrin-stimulated gastric acid secretion is similar in patients with type 2 diabetes and healthy controls. GIP administration does not influence gastric acid secretion at physiological or pharmacological plasma levels. Therefore, GIP appears to act as an incretin rather than as an enterogastrone in human physiology.

Neuroendocrine gastric carcinoma expressing somatostatin: A highly malignant, rare tumor

Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with yon Recklinghausen＇s neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.

Biochemically curative surgery for gastrinoma in multiple endocrine neoplasia type 1 patients

AIM： To search for the optimal surgery for gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. METHODS： Sixteen patients with genetically confirmed multiple endocrine neoplasia type 1 （MEN 1） and Zollinger-Ellison syndrome （ZES） underwent resection of both gastrinomas and duodenopancreatic neuroendocrine tumors （NETs） between 1991 and 2009. For localization of gastrinoma, selective arterial secretagogue injection test （SASI test） with secretin or calcium solution was performed as well as somatostatin receptor scintigraphy （SRS） and other imaging methods such as computed tomography （CT） or magnetic resonance imaging （MRI）. The modus of surgery for gastrinoma has been changed over time, searching for the optimal surgery： pancreaticoduodenectomy （PD） was first performed guided by localization with the SAST test, then local resection of duodenal gastrinomas with dissection of regional lymph nodes （LR）, and recently pancreas-preserving total duodenectomy （PPTD） has been performed for multiple duodenal gastrinomas. RESULTS： Among various types of preoperative localizing methods for gastrinoma, the SASI test was the most useful method. Imaging methods such as SRS or CT made it essentially impossible to differentiate functioning gastrinoma among various kinds of NETs. However, recent imaging methods including SRS or CT were useful for detecting both distant metastases and ectopic NETs; therefore they are indispensable for staging of NETs. Biochemical cure of gastrinoma was achieved in 14 of 16 patients （87.5%）; that is, 100% in 3 patients who underwent PD, 100% in 6 patients who underwent LR （although in 2 patients （33.3%） second LR was performed for recurrence of duodenal gastri- noma）, and 71.4% in 7 patients who underwent PPTD. Pancreatic NETs more than 1 cm in diameter were resected either by distal pancreatectomy or enucleations, and no hepatic metastases have developed postoperatively. Pathological study of the resected specimens revealed co-existence of pancreatic gastrinoma with duodenal gastrinoma in 2 of 16 patients （13%）, and G cell hyperplasia and/or microgastrinoma in the duodenal Brunner＇s gland was revealed in all of 7 duodenal specimens after PPTD. CONCLUSION： Aggressive resection surgery based on accurate localization with the SASI test was useful for biochemical cure of gastrinoma in patients with MEN 1.Imamura Metal. Curative resection of gastrinoma in MEN-1

Effects of glutamine-containing total parenteral nutrition on phagocytic activity and anabolic hormone response in rats undergoing gastrectomy

AIM: To investigate the effect of glutamine (Gln)-containing parenteral nutrition on phagocytic activity and to elucidate the possible roles of Gln in the secretion of anabolic hormones and nitrogen balance in rats undergoing a gastrectomy. METHODS: Rats with an internal jugular catheter were divided into 2 experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN (control), and in the other group, 25% of the total amino acid nitrogen was replaced with Gin. After receiving TPN for 3 d, one-third of the rats in each experimental group were sacrificed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 and 3 d, respectively, after surgery. Plasma, peritoneal lavage fluid (PLF), and urine samples were collected for further analysis. RESULTS: The Gln group had fewer nitrogen losses 1 and 2 d after surgery (d1, 16.6±242.5 vs-233.4±205.9 mg/d, d2, 31.8±238.8 vs-253.4±184.6 mg/d, P<0.05). There were no differences in plasma growth hormone (GH) and insulin-like growth factor-1 levels between the 2 groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Gln group than in the control group 1 d after surgery (A 1185±931 vs323±201, P<0.05). There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the 2 groups at the baseline or on the postoperative days. No significant differences in interleukin-1β or interleukin-6 concentrations in PLF were observed between the 2 groups. However, tumor necrosis factor-α level in PLF was significantly lower in the Gln group than in the control group on postoperative d 3. CONCLUSION: TPN supplemented with Gln can improve the nitrogen balance, and enhance macrophage phagocytic activity at the site of injury. However, Gin supplementation has no effect on phagocytic cell activity in the systemic circulation, GH and insulin-like growth factor-1 might not be responsible for attenuating nitrogen losses in rats with a partial gastrectomy.

Pernicious anemia: What are the actual diagnosis criteria?

A gastric intrinsic factor output under 200 U/h after pentagastrin stimulation (N > 2000 U/h) is specific for pernicious anemia. The other findings are either variable or non specific. Serum intrinsic factor antibodies, considered as specific in general practice, are present only in half of the patients with pernicious anemia. In their absence, since the disappearance of the Schilling tests, the gastric tubage currently used for the study of gastric acid secretion, is obligatory for the simultaneous study of intrinsic factor output. This study is important to eliminate another disease much more frequent than pernicious anemia, the protein bound to cobalamin malabsorption was observed in achlorhydric simple atrophic gastritis in the presence of intrinsic factor secretion.

Gastric carcinoids:Between underestimation and overtreatment

Gastric carcinoids(GCs),which originate from gastric enterochromaffin-like(ECL) mucosal cells and account for 2.4% of all carcinoids,are found increasingly in the course of upper gastrointestinal tract endoscopy.Current nosography includes those occurring in chronic conditions with hypergastrinemia,as the type 1 associated with chronic atrophic gastritis,and the type 2 associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1,and type 3,which is unrelated to hypergastrinemia and is frequently malignant,with distant metastases.The optimal clinical approach to GCs remains to be elucidated,depending upon type,size and number of carcinoids.While there is agreement concerning the treatment of type 3 carcinoids,for types 1 and 2,current possibilities include simple surveillance,endoscopic polypectomy,surgical excision,associated or not with surgical antrectomy,or total gastrectomy.Moreover,the recent introduction of somatostatin analogues represents a therapeutic option of possibly outstanding relevance.

EFFECTS OF ELECTRO-ACUPUNCTURE ON SOMATOSTATIN AND PANCREATIC POLYPEPTIDE IN ISCHEMIC CEREBROVASCULAR DISEASES

The levels of somatostatin(SS)in CSF and blood and pancreatic polypeptide(PP)inplasma were measured by radioimmunoassay in 64 patients with acute ischemiccerebrovascular diseases(ICVD),randomly divided into two groups:group 1(n=31,bothelectro-acupuncture and routine treatments given)and group 2(n=33,routine treatment)and 26 non-ICVD patients were used as controls.The points of electro-acupuncture wereQuchi(LI 12),Waiguan(SJ 5)and Huantiao(GB 30)and Zusanli(St 36).After a courseof treatment,the SS levels in plasma and CSF were significantly increased in the patientsof group 1 with good result and their plasma PP level had no significant change.In thepatients with poor result,however,the PP level was significantly decreased.The resultssuggested that electro-acupuncture might play an active role in alleviating the SSmetabolic disturbance in CNS of ICVD patients.