Congenital disorder of glycosylation Ib (CDG-Ib) without gastrointestinal symptoms

Summary: We report a 7-year-old girl with hyperinsulinaemic hypoglycaemia and hepatomegaly due to congenital disorder of glycosylation (CDG) Ib without gastrointestinal symptoms. Oral mannose therapy produced clinical and biochemical normalization after 2 years of treatment.     

Endocrine tumours of the gastrointestinal tract. Peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy.     

Endocrine cells in the upper gastrointestinal tract in relation to gastrointestinal dysfunction in patients with familial amyloidotic polyneuropathy.

Gastrointestinal (GI) dysfunction is a common complication of familial amyloidotic polyneuropathy (FAP). In previous reports, a decreased content of small and large intestinal endocrine cells has been found in patients with FAP and it has been suggested that this may contribute to the development of GI disturbances. The aim of the present study was to investigate the endocrine cell content in the stomach and duodenum of FAP patients, and to correlate the findings with gastric emptying. Fifteen patients with FAP were included in the study. Twenty-eight subjects with macroscopically and histologically normal mucosa were used as controls for endocrine cell contents and 14 healthy subjects for gastric scintigraphy. The endocrine cells were identified by immunohistochemistry and quantified with image analysis. Gastric emptying time was detected by scintigraphy and endoscopy. The number of chromogranin A-immunoreactive (IR) cells was reduced in all investigated parts of the GI tract except bulbus duodeni. Gastrin/CCK cell content was reduced in duodenum, but tended to be increased in antrum of the stomach (P = 0.07). Otherwise, the content of all other endocrine cells types in the upper GI tract was reduced compared with controls. A correlation with malnutrition was found for gastric inhibitory polypeptide and secretin cell content in bulbus duodeni. Gastric scintigraphy disclosed delayed gastric emptying of solid food, but the finding was not correlated to the decreased content of neuroendocrine cells. The severity of endocrine cell depletion was not correlated to duration of GI disturbances. The present study showed that the endocrine cells of the stomach are affected in FAP patients and that the abnormalities in the upper GI endocrine cells occur early during the course of the disease.     

Endocrine tumours of the gastrointestinal tract. Management of metastatic endocrine tumours

Gastroenteropancreatic tumours are rare. They compromise a heterogenous class of neoplasm. If there is no hypersecretion syndrome, symptoms may be uncharacteristic and thus diagnosis occurs rather late after the first manifestations of the disease. The most important prognostic parameters are histological classification, the localisation of the primary, the tumour size and stage at diagnosis, and the presence or absence of metachronous or synchronous neoplasia. The article will focus on the importance of each of these parameters for the various treatment options in patients with metastatic disease.     

Endocrine system of the gastrointestinal tract. Pathophysiology with a clinical view

Present role of the hormones produced in the gastrointestinal tract is shown in this short overview. Selected actual information on glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and somatostatin is presented as an example in development of the knowledge of pathophysiology and of the possibilities in their clinical use. It is evident that hormones originating from the gastrointestinal tract are perspective not only in relationship to the explanation of pathophysiology of different diseases but they may be used more for diagnostic and therapeutic purposes.     

Endocrine tumours of the gastrointestinal tract. Biotherapy for metastatic endocrine tumours

Somatostatin analogues have been the mainstay of symptomatic management of patients with neuroendocrine tumours (NETs) for two decades with the main mechanism of action being inhibition of peptide release. Evidence base for interferon use is perhaps less clear. It may contribute to symptom control by abrogating peptide release, and there is some evidence that it has an anti-proliferative action. Combination of somatostatin analogues and interferon provides symptom control, mainly by effecting a reduction in the amount of circulating, physiologically active, peptide hormones. Treatment can also provide disease stabilisation in a proportion of patients. In a minority of patients treatment may lead to partial response.     

Endocrine tumours of the gastrointestinal tract. Surgical treatment of neuroendocrine metastases

Neuroendocrine tumors of the intestinal tract have low malignant potential but can result in decreased survival if they spread to the liver. The estimated 5-year survival of patients with liver metastases from neuroendocrine tumor is only 20%. Further, morbidity related to the Carcinoid Syndrome and other endocrine symptoms may also greatly reduce the quality of life. Treatment options for liver neuroendocrine tumor include long-acting somatostatin receptor antagonists (LAR), inteferon-alpha, chemotherapy and hepatic artery embolisation with and without chemotherapy. Surgical resection is feasible in select patients, but it may result in major morbidity and even mortality. In our series of 18 patients with liver neuroendocrine tumors, there was no operative mortality and acceptable morbidity. All 10 patients with the Carcinoid syndrome had complete amelioration of symptoms and the 5-year actuarial survival was 80%. Aggressive major surgery for liver neuroendocrine tumor metastases can be performed safely with acceptable mortality by experienced surgeons. Results have been similar for patients with gastrinoma and pancreatic neuroendocrine tumors. Surgical resection appears to result in outstanding long-term survival and amelioration of symptoms. It should be the first-line therapy for patients with liver neuroendocrine tumors in whom the tumor can be completely removed.     

Endocrine tumours of the gastrointestinal tract: Chemotherapy

Malignant neuroendocrine tumours are less sensitive to chemotherapy than other epithelial malignancies. If chemotherapy is considered, tumours of pancreatic origin have a higher sensitivity than tumours from the gastrointestinal tract ('carcinoids'). Chemotherapy with streptozocin combinations and with dacarbazine should be considered in patients with progressive malignant neuroendocrine tumours of the pancreas. A favourable response to chemotherapy can be expected in up to 60% of patients receiving a combination of streptozocin plus doxorubicin, and in up to 40% of patients receiving dacarbazine. A survival benefit has been shown for streptozocin combinations. Treatment regimens are effective in functioning and non-functioning tumours. The response to treatment cannot be predicted. Poorly differentiated neuroendocrine tumours, independent of their origin, respond to a combination of etoposide plus cisplatin. Chemotherapy is, however, almost ineffective in patients with well-differentiated neuroendocrine tumours originating in the gastrointestinal tract ('carcinoids').     

Endocrine control of appetite: gastrointestinal hormonal effects on CNS appetitive structures.

Permanent semi-microelectrodes were implanted in the ventromedial hypothalamus (VMH), lateral hypothalamus (LH), amygdala (AMYG), medial forebrain bundle (MFB), anterior hypothalamus (AH), inferior colliculus (IC), and caudate nucleus (CN). Average evoked responses were recorded simultaneously from the above sites in freely behaving rats before and after administration of pentagastrin (100 microgram/kg), secretin 1 microgram/kg or cholecystokinin octapeptide (CCK-OP) (1 microgram/kg) in search of satiety signal. Gastrin and secretin had little effect while it appears that CCK may perform a regulatory function in a neurohumoral feedback mechanism.     

Endocrine tumours of the gastrointestinal tract. Transplantation in the management of metastatic endocrine tumours

Patients with neuroendocrine tumours often present with synchronous liver metastases or develop hepatic metastases in the course of their disease. A complete removal of liver metastases with an intention to cure may be accomplished by liver resection or, if hepatic disease is disseminated or hormonal symptoms and pain cannot be controlled medically, by total hepatectomy and transplantation. The indications for orthotopic liver transplantation for metastatic neuroendocrine tumour disease should be anchored in a multimodal and multidisciplinary therapeutic approach. Approximately, 120-130 cases of orthotopic liver transplantation for neuroendocrine tumours have been published so far, but follow-up after transplantation has been limited, and most reports comprise a small number of patients. After considering published studies and data, some recommendations may be given, although these are based on a low level of evidence. After excluding extrahepatic tumour manifestations by imaging procedures and diagnostic laparoscopy, the indication should be chosen restrictively. Few prognostic markers, for example age below 50 years and absence of concurrent extensive surgery, were identified by multivariate analysis in a large retrospective analysis. The prognostic impact of primary tumour localisation is still controversial. However, further indicators of favourable long-term prognosis are needed. Tumour biology characterised by Ki67 and E-cadherin expression may help to identify patients with a favourable outcome so that patient selection can be improved, but this needs further evaluation in larger patient cohorts. Orthotopic liver transplantation for patients with remission of disease or stable disease under medical treatment, and orthotopic liver transplantation for palliative reasons, should be restricted to selected individual cases.     

功能性消化不良胃肠动力障碍与胃肠激素的关系

功能性消化不良(functional dyspepsia,FD)是一种常见的症候群,占消化疾病患者的20％～40％。根据罗马Ⅱ体系标准,FD的诊断应符合以下四个条件:①持续性或反复性以上腹部为中心的疼痛或不适;②经内镜等常规检查排除与症状有关的器质性疾病;③症状与排便和(或)粪便性状改变无关:④上述症状在近12个月内至少出现12周,但无需连续。FD按临床表现分为3种亚型。①溃疡样消化不良型,以上腹部疼痛为主;②动力障碍样消化不良型,以上腹部不适     

Endocrine cells in the upper gastrointestinal tract in relation to gastrointestinal dysfunction in patients with familial amyloidotic polyneuropathy

Gastrointestinal (GI) dysfunction is a common complication of familial amyloidotic polyneuropathy (FAP). In previous reports, a decreased content of small and large intestinal endocrine cells has been found in patients with FAP and it has been suggested that this may contribute to the development of GI disturbances. The aim of the present study was to investigate the endocrine cell content in the stomach and duodenum of FAP patients, and to correlate the findings with gastric emptying.

Fifteen patients with FAP were included in the study. Twenty-eight subjects with macroscopically and histologically normal mucosa were used as controls for endocrine cell contents and 14 healthy subjects for gastric scintigraphy. The endocrine cells were identified by immunohis-tochemistry and quantified with image analysis. Gastric emptying time was detected by scintigraphy andendoscopy.

The number of chromogranin A-immunoreactive (IR) cells was reduced in all investigated parts of the GI tract except bulbus duodeni. Gastrin/CCK cell content was reduced in duodenum, but tended to be increased in antrum of the stomach (P=0.07). Otherwise, the content of all other endocrine cells types in the upper GI tract was reduced compared with controls. A correlation with malnutrition was found for gastric inhibitory polypeptide and secretin cell content in bulbus duodeni. Gastric scintigraphy disclosed delayed gastric emptying of solid food, but the finding was not correlated to the decreased content of neuroendocrine cells. The severity of endocrine cell depletion was not correlated to duration of GI disturbances.

The present study showed that the endocrine cells of the stomach are affected in FAP patients and that the abnormalities in the upper GI endocrine cells occur early during the course of the disease.     

功能性胃肠病研究之我见

一、历程回顾 在1970年代开始胃肠动力障碍等FGID关系研究之前，人们对。FGID的认识一直没有太大进展。但后来的研究发现肠道动力紊乱与FGID症状间并无明显关系。因此，其他一些潜在机制受到重视，如内脏敏感性增高，感染、内分泌、脑肠肽、免疫，浅表黏膜炎症的影响等。这些研究的基本思路是将FGID看成是消化道本身的问题，是针对周围，即消化