Endocrine tumours of the stomach

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.     

Endocrine tumours of the hindgut

Neuroendocrine tumours of the colon and rectum are rare but distinct with regard to clinical symptoms, diagnostic and therapeutic management and prognosis compared to other neuroendocrine tumours of the gut as well as ordinary colorectal cancer. Therapeutic algorithms are proposed depending mainly on analogous TNM categories and grading considering conventional and experimental surgical and non-surgical therapy. Colonic neuroendocrine tumours are often misdiagnosed as undifferentiated adenocarcinoma and are therefore not properly treated with adjuvant and additive chemotherapy. As most rectal neuroendocrine tumours are benign because of submucosal extension only, the size and infiltration depth correlates with lymph-node and distant metastases and therefore with the prognosis. It is unknown whether endoscopic ultrasound can improve the diagnostic accuracy compared to size-related conclusions, and therefore whether it can change therapeutic strategies and improve survival by modern rectal surgery.     

Endocrine tumors of the pancreas

A review of 33 patients operated on between 1951 and 1978 for endocrine tumors of the pancreas is presented. The series consists of 25 patients with hyperinsulinism, 6 with the Zollinger-Ellison syndrome, and 2 with the WDHA syndrome. Clinical features and diagnostic problems are discussed. A noticeable feature is that the average time lapse between onset of symptoms and final diagnosis in insulinoma patients has not been significantly reduced during the years covered by this review. This is in spite of the progress made in testing procedures and laboratory methods designed to diagnose hyperinsulinism. Resection of the tumor has been the preferred treatment in insulinoma patients, of whom 22 are still alive. Insulinomas were associated with other endocrinopathies in 3 cases. Patients with the Zollinger-Ellison syndrome had raised serum gastrin levels and increased basal acid output. Four patients are still alive. Two patients had other endocrinopathies. Both patients with the WDHA syndrome died shortly after the operation. One had biochemical evidence of multiple endocrinopathies.     

Endocrine tumors of the pancreas.

Neuroendocrine tumors of the pancreas are rare neoplasms of the heterogeneous group of neuroendocrine gastroenteropancreatic tumors that originate from totipotential stem cells or preexisting endocrine cells within the pancreas. Most neuroendocrine tumors of the pancreas are benign or show an indolent course of disease.A subset of them shows a very aggressive behavior, becomes highly malignant, and metastasizes early with life-limiting consequences. An effective disease-management includes the diagnostic approach with hormonal testing and localization and surgical treatment with histologic classification in combination with biotherapy, chemotherapy, or therapy with radionucleotides, de-pending on the individual behavior of the tumor. The primary goal is the improvement of symptoms leading to an acceptable quality of life in the individual patient.     

Cystic tumours of the pancreas

Pancreatic carcinoma accounts for the most dismal survival among all malignancies with 5-year survival rates approaching 5%. The reason for this, besides the inherent biologic nature of the disease, is the fact that the patients tend to present late in the disease. We present a review of the current published data on cystic neoplasms of the pancreas, which though rare, constitute an important subgroup of pancreatic neoplasms that have a better prognosis and are potentially curable lesions.     

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 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: 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 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.     

Islet tumours of the pancreas with intractable diarrhoea

This paper reports the association between severe, prolonged, watery diarrhoea and islet cell tumours of the pancreas. There appear to be significant differences between patients with these symptoms and those with the classical Zollinger-Ellison syndrome.     

Endocrine tumours, somatostatin and somatostatin receptors

Somatostatin blocks the release of numerous growth factors and is therefore a potent inhibitor of cell division and/or secretion. It exerts its effects through binding to somatostatin receptors. Five different subtypes of such receptors are identified (SSTR1 to SSTR5), having various tissue expression. The detection of their presence in tumours can be performed on histological sections and has potential therapeutic implications.     

Endocrine tumor arising in heterotopic gastric pancreas

We report the case of a 49-year-old caucasian woman, in whom an endocrine tumor arising in gastric heterotopic pancreas was diagnosed. The patient was treated surgically with a gastric wedge resection. Heterotopic pancreas is a benign anatomic condition, probably widely underdiagnosed because usually asymptomatic. The malignant transformation of aberrant pancreas is very rare and almost always in adenocarcinoma. The endocrine tumors developed in heterotopic pancreas are exceedingly rare. Of our knowledge, only four cases have been published and only one case in the gastric location similar to this reported case.