Effect of endogenous hypergastrinemia on gallbladder volume and ejection fraction in patients with autoimmune gastritis

BACKGROUND: Gastrin has a cholecystokinetic action on gallbladder motility, and cholecystokinin and gastrin act directly on the smooth muscle of the gallbladder. The aim of this study was to investigate the effect of endogenous hypergastrinemia on gallbladder motility in patients with autoimmune gastritis. METHODS: Forty-one patients (29 females, 12 males; mean age, 46 years) with autoimmune gastritis and 29 healthy subjects (17 females, 12 males; mean age, 44.8 years) were enrolled in the study. Fasting and postprandial gallbladder volumes were measured ultrasonographically with the ellipsoid technique and the ejection fraction of the gallbladder was calculated from fasting and postprandial volumes. All subjects were investigated after 12 hours of fasting and 30 minutes after a standard test meal. RESULTS: The gallbladder ejection fraction (%) of the patients with autoimmune gastritis was lower than that of the control group (46.06±18.28% vs 55.03±14.67%, P=0.032). There was no difference between patients with autoimmune gastritis and the control group in terms of the mean fasting gallbladder volume (30.38±12.85 vs 29.27±9.91 cm 3 , P=0.189) and the mean postprandial gallbladder volume (15.67±8.32 vs 13.44±7.69 cm 3 , P=0.258). Logistic regression analysis of baseline parameters revealed that 'abdominal bloating' was a risk factor for the low gallbladder ejection fraction in autoimmune gastritis patients (P=0.045, F=4.40). In addition, logistic regression analysis of baseline parameters revealed that smoking (n=5, P=0.025, F=5.44) is a predictor of low gallbladder ejection fraction in patients with autoimmune gastritis.CONCLUSIONS: Patients with endogenous hypergastrinemia have a low gallbladder ejection fraction compared with healthy controls. This study shows that at least part of upper gastrointestinal symptoms observed in this patient population may be due to altered gallbladder motility.

Hypergastrinemia and recurrent type 1 gastric carcinoid in a young Indian male: Necessity for antrectomy?

Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the wide-spread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his young age.

Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia:A case report and review of literature

BACKGROUND Zollinger–Ellison syndrome(ZES)results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors,commonly referred to as gastrinomas.The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum.Here,we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma.CASE SUMMARY A 72-year-old woman presented with the typical clinical manifestations of ZES,including upper abdominal pain,significant watery diarrhea,and acidic liquid vomitus.Surprisingly,however,she did not have an increased level of serum gastrin.In addition,there was no evidence of gastrinoma or any other ulcerogenic tumor.Esophagogastroduodenoscopy was conducted to examine the upper digestive tract.Revised diagnoses were considered,and an individualized treatment plan was developed.The patient responded to antacid medication while experiencing intermittent,recurring bouts of ZES.18F-AlF-NOTAoctreotide positron emission tomography(18F-OC PET)/computed tomography(CT)helped locate the tumor.Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site.CONCLUSION This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia.18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.

Hypergastrinemia

Gastrin is an important hormone of the digestive system,which assists gastric acid secretion.It may be pathologically elevated in conditions such as Zollinger-Ellison syndrome,or due to common medications such as proton pump inhibitors.In this review we provide an overview of the pathophysiology and medical causes of hypergastrinemia,diagnostic testing and clinical consequences of chronic hypergastrinemia.

幽门螺杆菌感染和高胃泌素血症与结直肠癌的相关性研究

目的:探讨幽门螺杆菌(Helicobacter pylori)感染、高胃泌素血症和环氧合酶-2(cyclooxygenase-2,COX-2)与结直肠癌的相关性。方法:采用放射免疫分析法检测51例结直肠癌患者和43例非结直肠癌患者(对照组)血清中胃泌素的表达水平,ELISA法检测血清中抗幽门螺杆菌IgG的表达水平。给予结直肠癌患者口服塞来昔布6个月,分别于服药2、4和6个月时检测血清中胃泌素和抗幽门螺杆菌IgG的表达水平。结果:结直肠癌患者的幽门螺杆菌阳性率和血清胃泌素表达水平均明显高于对照组(P<0.05)。结直肠癌患者血清中胃泌素的表达水平与抗幽门螺杆菌IgG的表达量显著相关(r=0.662,P<0.001)。远端结肠与直肠癌患者幽门螺杆菌的阳性率显著高于近端结肠癌患者(P<0.05);同时,高胃泌素血症患者所占比率也明显高于近端结肠癌患者(P<0.05)。此外,随着Duke分期的升高,幽门螺杆菌阳性率与高胃泌素血症患者所占比率均同步升高。口服塞来昔布后,结直肠癌患者血清中幽门螺杆菌阳性率和血清胃泌素的表达水平均呈下降趋势,并且随着服药时间的延长进一步下降。结论:幽门螺杆菌感染诱导高胃泌素血症可能与结直肠癌的形成相关。选择性COX-2抑制剂塞来昔布可降低幽门螺杆菌阳性率和血清胃泌素的表达水平。

幽门螺杆菌、高胃泌素血症对结肠腺瘤形成的作用

目的:探讨幽门螺杆菌(H.pylori)感染、血清胃泌素(GAS)与结肠腺瘤的相互关系.方法:采用放射免疫法(RIA)测定结肠腺瘤(n=48)及对照组(n=43)的血清胃泌素水平,用ELISA法检测H.pyloriIgG抗体.给予结肠腺瘤患者口服塞来昔布6mo,分别在2、4、6mo检测血清胃泌素及抗H.pyloriIgG抗体.结果:腺瘤组患者H.pylori感染阳性率、血清胃泌素水平明显高于对照组(P<0.05),结肠腺瘤组血清胃泌素水平与H.pyloriIgG抗体显著相关(r=0.854,P<0.001);远端结肠腺瘤患者H.pylori阳性率显著高于近端结肠(P<0.05),同时高胃泌素血症患者比例明显高于近端结肠(72.7%vs37.8%,P<0.05).口服塞来昔布后,H.pylori阳性率、血清胃泌素水平均趋向下降并且随着服药时间的延长进一步降低.结论:H.pylori感染可诱导高胃泌素血症与结肠腺瘤形成;COX-2可能介导胃泌素诱导的结肠腺瘤形成;口服COX-2抑制剂塞来昔布可以降低H.pylori阳性率及血清胃泌素水平,从而发挥抑制结肠腺瘤生长的作用.

幽门螺杆菌、高胃泌素血症对结直肠癌形成的影响

目的探讨H.pylori感染、高胃泌素血症与结直肠癌形成三者之间的相互关系及H.pylori在结直肠癌组织中的表达情况。方法采用放射免疫法(RIA)测定结直肠癌患者(51例)及对照组(43例)的血清胃泌素水平,用ELISA法检测H.pylori IgG抗体,用免疫组化的方法观察H.pylori在结直肠癌组织中的表达情况。结果肿瘤组患者H.pylori感染阳性率、血清胃泌素水平明显高于对照组(P<0.05),远端结肠与直肠患者H.pylori阳性率显著高于近端结肠患者(P<0.05),同时高胃泌素血症患者的比例明显高于近端结肠患者(77.8%vs.37.5%,80.0%vs.37.5%,P<0.05);并且随着肿瘤分期升高,二者比例均同步升高。此外,在结直肠癌组中,8例(15.7%)患者观察到H.pylori阳性表达,表现为模糊的颗粒状或粗杆状黏膜染色图形;而在对照组的结直肠组织中H.pylori未见表达。结论用免疫组化的方法可以证明H.pylori存在于结直肠癌组织中,尤其是血清H.pylori阳性并高胃泌素血症的患者;H.pylori感染可能诱导高胃泌素血症并与结直肠癌的形成有关。

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.

长期使用质子泵抑制剂所致高胃泌素血症及其对策

质子泵抑制剂的应用是酸相关疾病的标准治疗。但是,长期使用对胃食管反流征患者可能存在潜在危害,例如低酸反馈所致的高胃泌素血症,肠嗜银细胞的增殖,潜在的胃部肿瘤诱发作用,停药后的酸反跳,幽门螺杆菌感染者胃泌酸区胃炎发生率增加,高胃泌素血症所致的其它肿瘤等。人们正在研究这些潜在危害,评价长期使用质子泵抑制剂的风险-效益比,并提出对应策略。

Role of gastrin-peptides in Barrett's and colorectal carcinogenesis

Gastrin is the main hormone responsible for the stimulation of gastric acid secretion;in addition,gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types.Gastrin synthesis and secretion are increased in certain situations,for example,when proton pump inhibitors are used.The impact of sustained hypergastrinemia is currently being investigated.In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates;although,this relationship is less clear in human beings.Higher gastrin levels have been shown to cause hyperplasia of several cell types;yet,the risk for developing cancer seems to be the same in normo-and hypergastrinemic patients.Some tumors also produce their own gastrin,which can act in an autocrine manner promoting tumor growth.Certain cancers are extremely dependent on gastrin to proliferate.Initial research focused only on the effects of amidated gastrins,but there has been an interest in intermediates of gastrin in the last few decades.These intermediates aren't biologically inactive;in fact,they may exert greater effects on proliferation and apoptosis than the completely processed forms.In certain gastrin overproduction states,they are the most abundant gastrin peptides secreted.The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production,levels,and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.

Gastric neuroendocrine tumor: A practical literature review

Gastric neuroendocrine tumors are gastric neoplasms originating from enterochromaffin type cells and are inserted in a larger group,named gastroenteropancreatic neuroendocrine tumors.They are considered rare and variable in terms of their clinical,morphological and functional characteristics and may be indolent or aggressive.They are classified into types I,II and III,according to their pathophysiology,behavior and treatment.Their diagnosis occurs,in most cases,incidentally during upper digestive endoscopies,presenting as simple gastric polyps.Most cases(type I and type II)are related to hypergastrinemia,can be multiple and are treated by endoscopic resection,whenever possible.The use of somatostatin analogs for tumor control may be one of the options for therapy,in addition to total or subtotal gastrectomy for selected cases.Adjuvant chemotherapy is only reserved for poorly differentiated neuroendocrine carcinomas.Although rare,gastric neuroendocrine tumors have an increasing incidence over the years,therefore deserving more comprehensive studies on its adequate treatment.The present study reviews and updates management recommendations for gastric neuroendocrine tumors.

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.

Diagnosis of Zollinger-Ellison syndrome:Increasingly difficult

In the present paper the increasing difficulty of diag-nosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the per-spective of clinical management.

Long term omeprazole therapy for reflux esophagitis:follow-up in serum gastrin levels,EC cell hyperplasia and neoplasia

AIM To evaluate the long-term safety ofomeprazole in patients of gastroesophagealreflux disease resistant to treatment with H2receptor antagonist.METHODS We prospectively followed 33patients on omeprazole therapy for severeerosive esophagitis for 5-8 years,with periodicgastrin levels,H.pylori infection,gastricbiopsies for incidence of ECL cell hyperplasia,carcinoids,gastric atrophy and neoplasia.Atotal 185 patient follow-up years and 137 gastricbiopsies were done.RESULTS Among the 33 patients,36% reachedtheir peak gastrin levels in an average of 8months to one year,then drifted Down slowlyover 1-2 year period to just above their baselinelevel,24% of the patients had a peak gastrinlevel above 400ng·L^1 and one patient had apeak level above 1000 ng·L^1.One patient had amild ECL cell hyperplasia which was self limitingand did not show any dysplastic changes.Eighteen percent of patients were positive forH.pylori infection.The gastric biopsies did notshow gastric atrophy,intestinal metaplasia orneoplastic changes.CONCLUSION In a series of 33 patients followed for 5 - 8 years on omeprazole therapy for severe reflux esophagitis, we did not observe any evidence of significant ECL cell hyperplasia, gastric atrophy, intestinal metaplasia, dysplasia or neoplastic changes.

Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach

Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract. It may coexist with other type of cancers,and if so,the tumors usually involve the stomach. The most common associated cancers are gastrointestinal carcinomas. We report a 65-year-old woman with a history of gastric gastrointestinal stromal tumor who had undergone subtotal segmental gastrectomy. New polypoid lesions were detected on a follow-up gastroscopy one year later. The lesions were biopsied and found to be carcinoid tumors. There was serum hypergastrinemia,and type 1 gastric carcinoid tumor was diagnosed. A total gastrectomy was performed. Pathologic examination revealed both carcinoid tumors and a recurrent gastrointestinal stromal tumor.

胃神经内分泌肿瘤的研究进展

胃神经内分泌肿瘤是临床较少见的一类肿瘤性病变,由于病例报道少,临床诊断率较低,在国内外尚无统一的诊疗方法。得益于内镜技术的发展以及临床上广泛应用的质子泵抑制剂,胃神经内分泌肿瘤的发病率和诊断率呈现上升的趋势。通过研究其发病机制,学者发现其发生与各种原因引起的高胃泌素血症密切相关。根据疾病的进展状态和临床表现,学者对胃神经内分泌肿瘤进行了分型和病理分级。临床上运用的诊断方法有胃镜、影像学、核医学、胃泌素、Cg A等检查。根据临床分型的不同,治疗手段也存在差异,如果疾病进展迅速且分级较高,则应积极行外科手术切除病灶加术后辅助化学药物治疗。其他更好的治疗方法还在不断探索中。

Gastric neuroendocrine neoplasms: A review

Gastric neuroendocrine neoplasms(g-NENs)or neuroendocrine tumors are generally slow-growing tumors with increasing incidence.They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features.Type 1 and 2 are gastrin dependent,whereas type 3 and 4 are sporadic.The reason for hypergastrinemia is atrophic gastritis in type 1,and gastrin releasing tumor(gastrinoma)in type 2 g-NEN.The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy.g-NENs are positively stained with chomogranin A and synaptophysin.Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis.It is crucial to discriminate between types of g-NENs,because the management,treatment and prognosis differ significantly between subtypes.Treatment options for g-NENs include endoscopic resection,surgical resection with or without antrectomy,medical treatment with somatostatin analogues,netazepide or chemotherapy regimens.Follow-up without excision is another option in appropriate cases.The prognosis of type 1 and 2 g-NENs are good,whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.

Successful type-oriented endoscopic resection for gastric carcinoid tumors: A case report

The standard treatment in Japan for gastric carcinoid has been gastrectomy with lymphadenectomy. This report describes the possibility of endoscopic treatment as an appropriate option for gastric carcinoid fulfilling certain conditions. A 46 year old woman underwent endoscopic mucosal resection for two 3 mm gastric carcinoids. The patient had hypergastrinemia with pernicious anemia and type A chronic atrophic gastritis, suggesting that the tumors were type Ⅰ in Rindi's classification. Both tumors were located in the mucosal layer with no cellular polymorphism and were chromogranin A positive. Neither tumor recurrence in the stomach nor distant metastases have been documented during the 5 years of follow-up. Although many type Ⅰ gastric carcinoids may be clinically indolent, reports on successful endoscopic treatment for this carcinoid have been scanty in the literature in Japan, presumably because of the hitherto surgical treatment stance for the disease. This report discusses how the size, number, depth and histological grading of the type Ⅰ gastric carcinoid could allow the correct identification of a benign or malignant propensity of anindividual tumor and how endoscopic resection could be a treatment of choice when these factors render it feasible. This stance could also obviate unnecessary surgical resection for more benign tumors.

胃神经内分泌肿瘤的分型和治疗研究进展

胃神经内分泌肿瘤(gastric neuroendocrine neoplasm,G-NENs)是一类起源于胃黏膜肠嗜铬细胞的一类罕见且可变的异质性肿瘤,是一种惰性肿瘤,也可以具有侵袭性和广泛转移等生物学行为。过去由于发生率低没有引起人们足够重视,随着上消化道内镜普及、技术的提高,越来越多的人认识到G-NENs,检出率提高,大多数G-NETs在行内窥镜检查时偶然发现单纯的胃息肉。2019年世界卫生组织WHO提出胃肠胰神经内分泌肿瘤分级分类的新三型分类。本文对G-NENs各亚型流行病学、临床分型、组织学分级以及治疗方法等最新进展进行综述,以期对今后的治疗提供参考。

从机制到治疗:自身免疫性萎缩性胃炎和1型胃神经内分泌肿瘤

自身免疫性萎缩性胃炎(autoimmune atrophic gastritis,AAG)是一种局限于胃底、胃体黏膜的器官特异性自身免疫性疾病,可合并或继发多种疾病,其中包括1型胃神经内分泌肿瘤(gastric neuroendocrine tumors,g-NETs)。1型g-NETs是在AAG发病基础上引起肠嗜铬样(enterochromaffin-like,ECL)细胞系列增生而导致的一种生长缓慢但易复发的罕见恶性肿瘤。近年来,由于诊断技术的进步以及医生对疾病意识的提高,两种疾病的发病率呈逐年上升的趋势,得到了临床医生的重视。本文从AAG和1型g-NETs的发病机制、诊断和治疗以及二者之间的区别和联系等方面展开综述,以期为临床医生提供借鉴。