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Vasoactive intestinal peptide secreting tumor (VIPoma) is a rare mostly malignant neuroendocrine tumor that is characterized by watery diarrhea, hypokalemia and achlorhydria due to the nonregulated increased secretion of VIP. VIPomas ar diagnosed by the presence of the most common symptoms, laboratory analysis of blood and stool, radiological imaging and immunohistochemical findings. Primary treatment includes fluid replacement, electrolyte balance correction, pharmacological treatment with somatostatin analogs, surgical resection and chemotherapy. This review aims to provide an insight into the latest research on VIPoma epidemiology, pathophysiology, diagnostics and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

VIPomas are generally rare functioning pancreatic neuroendocrine tumors (PanNETs) that cause watery diarrhea, hypokalemia, and achlorhydria. Due to their extreme rarity, the clinicopathological features and outcomes of VIPomas have not been well reported. This study aimed to determine the diagnostic and therapeutic characteristics and prognosis of VIPomas and to compare them with other PanNETs at a Japanese reference hospital. Medical records of 293 patients with PanNETs were collected. Patient and tumor characteristics and outcomes were retrospectively reviewed. This cohort had only 1.4% (four patients) of patients with VIPomas, and three of these patients changed from non-functioning (NF-) PanNETs during their disease course. Recurrences of hormonal symptoms were observed in all patients despite the initial controls, and all of them died from their disease, more specifically mainly from hormonal symptoms. Compared to the other PanNETs, VIPomas were all located at the pancreatic tail, were larger, and had a higher Ki-67 index and more metastasis. The median survival time was significantly shorter for patients with VIPoma than for those with NF-PanNET (5.9 vs. 26.7 years, p < 0.0001), insulinoma (21.8 years, p < 0.0001), and gastrinoma (12.3 years, p = 0.0325). This study presents the possibility of shifting from non-symptomatic to symptomatic VIPomas as they grow or of transforming from NF-PanNETs to VIPomas. VIPomas should be considered in patients with relatively large NF-PanNETs, especially those located in the pancreatic tail, when diarrhea is continuously observed. As hormonal symptoms are an important cause of death in VIPomas, long-term symptomatic control, which is relatively difficult, is of great significance.

Background: Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma., Objective: Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma., Methods: We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received., Results: Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025)., Conclusions: Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Vasoactive intestinal peptide-secreting tumors (VIPomas) are rare functioning neuroendocrine tumors often characterized by a difficult-to-control secretory syndrome and high potential to develop metastases. We hereby present the characteristics of 15 cases of VIPomas and provide a recent literature review., Methods: This was a retrospective data analysis of 15 patients with VIPoma from 3 different centers and literature research through PubMed database during the last 10 years., Results: Fifteen patients with VIPomas (9 with hepatic metastases at diagnosis) with watery diarrhea and raised VIP levels were studied. Ten patients (67%) had grade 2 tumors, 6 of 15 had localized disease and underwent potentially curative surgery, whereas the remaining 9 received multiple systemic therapies; 3 patients died during follow-up. The median overall survival was 71 months (range, 41-154 months). Patients who were treated with curative surgery (n = 7) had longer median overall survival compared with patients who were treated with other therapeutic modalities (44 vs 33 months)., Conclusions: The management of VIPomas is challenging requiring the application of multiple treatment modalities. Patients who underwent surgical treatment with curative intent appear to have higher survival rate. Central registration and larger prospective studies are required to evaluate the effect of currently employed therapies in these patients.

Purpose: Vasoactive intestinal peptide (VIP) secreting tumor (VIPoma) constitutes a rare functional neuroendocrine tumor that most often originates from pancreatic islet cells and presents as a sporadic, solitary neoplasm of the pancreas. The purpose of this study was to systematically review the literature of pancreatic VIPomas and report clinicopathologic data and treatment modalities for this rare entity., Methods: A systematic literature search was performed. The reviewed clinical series and case reports were included if they reported surgical treatment and also analyzed oncological outcomes on individual patients. Data extraction was performed using a standard registry pro-forma., Results: The search resulted in 53 case reports and 2 case series including 65 patients in total. Median age reported was 54 years. The predominant pancreatic location was the pancreatic tail. The most common clinical symptom was watery diarrhea. Serum VIP levels were remarkably elevated in all patients. Distal pancreatectomy with or without splenectomy was the most commonly applied surgical procedure. Overall survival associated with pancreatic VIPoma was 67.7%, recurrence rate 40.4% and relevant median disease-free interval was 16 months., Conclusions: VIPomas are functional tumors that secrete excessive amounts of VIP. Clinically, production of VIP causes refractory watery diarrhea, hypokalemia and achlorydria. As far as diagnosis is concerned, elevated VIP plasma levels are required. Moreover, the majority of VIPomas are malignant or have already metastasized on diagnosis. Despite recent research on the therapeutic strategies against pancreatic VIPoma, surgical resection appears as the only potentially curative approach.

Neuroendocrine tumors (NETs) are a group of rare and heterogeneous malignancies that can develop in various organs. A significant number of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is functionally active and presents with symptoms related to the secretion of biologically active substances, leading to the development of distinct clinical syndromes. There are various therapeutic approaches for GEP-NETs, including curative surgery, palliative surgery, local-ablative and loco-regional therapies as well as systemic therapeutic options including peptide receptor radionuclide therapy, cytotoxic therapy, and molecularly targeted therapies. Specific supportive therapy of patients with NETs includes management or prevention of hormone-related clinical syndromes and paraneoplastic states. Supportive therapy plays a key role in NET treatment. Supportive therapy includes debulking surgery and interventional radiologic techniques to reduce tumour bulk or load, as well as systemic medical treatment options to manage or prevent hypersecretion syndromes and treatment-related side effects. Supportive therapies are a type of of comprehensive treatment addressing the patient as a whole person throughout the process of NET treatment. Therefore, supportive therapy also encompasses psychosocial support, expert nursing, nutritional support and management of cancer related pain.

Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications., (© 2018 Marshfield Clinic.)

The purpose of this study was to investigate the safety and efficacy of irreversible electroporation (IRE) for the management of unresectable pancreatic vasoactive intestinal peptide tumor (VIPoma) in a 34-year-old male patient. The initial symptom was watery diarrhea, which could not be stopped by fasting. Laboratory tests revealed high vasoactive intestinal peptide (VIP) hormone levels, hypokalemia, and metabolic acidosis. Computed tomography examination showed a 6.0 × 5.0-cm, contrast-enhanced lesion in the neck and body of the pancreas and obliteration of the portal vein. Pathological and immunohistochemical findings were indicative of pancreatic VIPoma. The patient was treated with octreotide and IRE, and had no obvious IRE-related complications, except for moderate pain at the puncture sites. The patient reported that the watery diarrhea had decreased gradually; moreover, the VIP hormone level was normalized 15 days after IRE. Computed tomography scans showed a large area of necrosis in the pancreatic lesion. The findings from this case indicated that IRE could be a feasible and safe technique in controlling pancreatic VIPoma; however, additional follow-up and findings from more cases are required to further confirm the efficacy of IRE ablation therapy for pancreatic VIPoma.

Despite their perceived rarity, gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rising in incidence and prevalence. The biology, natural history, and therapeutic options for GEP-NETs are heterogeneous: NETs arising in the pancreas can be distinguished from those arising elsewhere in the gastrointestinal tract, and therapy is dichotomized between these two groups. Somatostatin analogues are the mainstay of oncologic management of bowel NETs; everolimus, streptozocin, and sunitinib are approved to treat pancreatic NETs. There are significant differences in molecular genetics between pancreatic and extrapancreatic NETs, and studies are evaluating whether additional NET patients may benefit from targeted agents. We discuss the distinguishing features of these two groups of tumors, as well as the therapeutic implications of the distinction. We also examine the evolving therapeutic landscape and discuss the likelihood that treatment will be developed independently for pancreatic and extrapancreatic gastrointestinal NETs, with novel therapeutics effective for newly identified pathologically or molecularly defined subgroups.

Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.

Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behaviour and most important, in their response to certain anti-tumour treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We report a case of recurrent pancreatic VIPoma with liver and peritoneal metastases who has been surviving over 7 years by a successful treatment with a combination of surgical resection and loco-regional therapies. A 59-year-old female underwent distal pancreatectomy for pancreatic endocrine tumor. Five years after pancreatectomy, she had a recurrence of liver and peritoneal metastases with the symptoms by hypersecretion of VIP, and she underwent hepatectomy and peritoneal tumor resection. Seven months later, multiple liver metastases appeared and were treated with transcatheter arterial chemoembolization (TACE). Additionally radiofrequency ablation( RFA) for remnant viable lesion was performed. Seven years and eight months after primary panceatectomy and two years and six months after resection of the liver and peritoneal recurrences, she is now disease-free with good quality of life. The progression of well-differentiated pancreatic neuroendocrine carcinoma is usually slow. It is potentially useful in controlling of liver metastases to combine the loco-regional therapy like TACE and RFA with surgical resection.

Pancreatic neuroendocrine tumours (PNET) are rare entities with an annual incidence of < 100,000. About 1 - 2 % of pancreatic neoplasias are neuroendocrine tumours. About one third of these tumours secrete biologically active substances that lead to development of specific clinical syndromes. PNET may occur sporadically or in association with hereditary syndromes, such as multiple endocrine neoplasia type 1 (MEN1). Among the functional PNET, insulinomas and gastrinomas are the most common entities. In contrast, vasoactive intetinale peptide (VIP)-secreting tumours, glucagonomas, serotonin-secreting carcinoid tumors, and tumours with secretion of ectopic hormones, such as calcitonin, are extremely rare. Once diagnosis has been established on the basis of clinical and laboratory findings, localization of the source of pathologic hormone secretion is warranted. Imaging methods frequently used for localization of PNET comprise anatomical imaging modalities, computed tomography, and magnetic resonance imaging, endoscopic ultrasound, selective arterial catheterization with hepatic venous sampling, DTPA-octreotid scintigraphy and DOTA-D-Phe(1)-Tyr(3)-octreotid positron emission tomography. Therapy is based on the specific tumour entity and the extent of the disease. In the majority of patients, even in the case of malignant disease, a surgical approach is warranted, eventually combined with a medical treatment., (© Georg Thieme Verlag KG Stuttgart · New York.)

Vasoactive intestinal peptide-producing tumour (VIPoma) or Verner-Morrison syndrome is a very rare neuroendocrine tumour. It occurs in less than ten percent of all pancreatic islet cell tumours, and about 70 percent to 80 percent of these tumours originate from the pancreas. Diagnosis is characteristically delayed. The first-line treatment is surgical. It may be curative in forty percent of patients with benign and non-metastatic disease. Palliative surgery is indicated in extensive disease, followed by conventional somatostatin analogue (octreotide) therapy. Somatostatin analogues improve hormone-mediated symptoms, reduce tumour bulk and prevent local and systemic effects. We present a female patient with VIPoma syndrome, which had metastasised to the liver at diagnosis. The patient underwent palliative Whipple procedure and subsequent cytoreductive radiofrequency ablations to her liver metastases. Unfortunately, after symptomatic improvement for three years, her disease progressed. Currently, she is on daily octreotide, achieving partial control of her symptoms.

Neuroendocrine tumors (NETs) are relatively rare neoplasms that often present as diagnostic dilemmas due to obscure or non-specific symptoms. The ability of carcinoid tumors to cause clinical symptoms by secretion of hormones or biogenic amines is best recognised in the form of the carcinoid syndrome. Although generally slow growing, a significant minority demonstrate aggressive tumor growth. Ten-twenty percent of pancreatic NETs may be associated with hereditary disorders such as multiple endocrine neoplasia-1 (MEN-1) and less frequently, Von Hippel Lindau, which should be considered in the investigation and management of these patients. A small percentage of NETs are associated with co-existing synchronous non-carcinoid neoplasm. The aim of this paper was to review the optimal management in patients with NETs. The therapeutic options which are reviewed, including the use of somatostatin analogues, the role of surgery, the use of chemotherapy, biotherapy using interferon, peptide receptor targeted therapy. In addition, the challenging interventional management of liver metastases is discussed, including the role of hepatic-artery embolization, radiofrequency ablation and the place of orthotoptic liver transplantation in selected patients. Authors have focused on the newest therapeutic modalities, e.g., radionuclide peptide receptor targeted therapy with Yttrium-90 and Lutetium-177, the newest somatostatin analogues such as pasireotide and angiogenic inhibitors. In conclusion, with the increasing number of investigative procedures and therapeutic options available to diagnose and treat carcinoid tumors, it is vital to have a multidisciplinary approach. Furthermore, additional scientific research and controlled clinical trials are needed to determine the efficacy of the many treatment options, which for these rare tumors can only be achieved by collaboration.

Objective: To discuss our experience in diagnosing and treating pancreatic vasoactive intestinal peptide-secreting tumors (VIPomas) by summarizing clinical information of 4 patients., Method: Clinical manifestations, laboratory examination, imaging features, surgical findings, and pathological findings of 4 patients with VIPoma admitted in our hospital from 1991 to the present are discussed., Results: Watery diarrhea and hypokalemia were the main clinical manifestations. Hepatic metastasis occurred in 2 patients. The pancreatic body and tail were the main locations of lesions. Two tumors were shown in the pancreatic body and tail in 1 patient. Two patients with hepatic metastases received a combination therapy of octreotide, surgery, and chemotherapy, which resulted in symptom improvement and normalization of the serum potassium values. Distal pancreatic resection and second resection of hepatic metastatic lesions were performed in 1 patient. Resection of the pancreatic body and tail was done in 1 patient, and pancreatoduodenectomy was performed in another patient. Laparotomy was done in 1 patient because of invasion of the superior mesenteric vein and duodenum., Conclusions: Typical symptoms play an important role in the diagnosis of VIPoma. Octreotide therapy has advanced the preoperative electrolyte management, and the combination of octreotide, chemotherapy, and surgery may be helpful in metastatic disease.

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension in young children. We report the case of a 2-year-old girl with severe undernutrition, chronic watery diarrhea, and gastrointestinal bleeding because of a congenital intrahepatic arterioportal fistula. Radiographic embolization and surgical ligation of the left hepatic artery were attempted, with no resolution of the symptoms. So, a left lobectomy was performed, with excellent results and prompt disappearance of the diarrhea. Hepatectomy should be considered as a definitive and reliable therapy for congenital IAPF.

Most vasoactive intestinal peptide (VIP)-producing tumours are from epithelial origin. Tumours derived from the sympathetic nervous system can produce VIP as well. We report here the case of a Verner-Morrison syndrome in a 40-year-old woman revealing a metastatic ganglioneuroblastoma. The diarrhea resolved after the resection of primary tumour and liver metastases. Neuroblastic tumours occur extremely rarely in adults. Thus, the management of these tumours is poorly defined in adults.

The neuroendocrine tumors (NET) of the pancreas are very rare lesions with frequency of about 3 to 10 per 1 000 000 inhabitants. The neuroendocrine tumors composes a heterogeneous group of tumors. The gastro-entero-pancreatic tumors (GEP) constitute 70% of all NET and 2% of all digestive system tumors. There have been several attempts to classify those lesions and since 2000 exists WHO classification which divides NET according to malignancy and histologic structure. The most often NET of the pancreas are insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma. There is a recommendation to assay hormonal activity, measure concentration of specific peptides, biogenic amines and hormones produced by NET cells to establish diagnosis. Those tests are useful in monitoring treatment and in prognostication course of the disease. Imaging methods especially useful in localization GEP-NET are: ultrasound (US), endoscopic ultrasound (EUS), somatostatin receptor scintigraphy (SRS), computer tomography (CT), magnetic resonance (MR) and angiography. The most sensitive method in preoperative diagnosis seems to be EUS or less accessible intra ductal ultrasonography (IDUS). Surgical treatment depends on progression of disease as well as on localization of tumor and consists in both radical methods and palliative operations. The gold standard in pharmacological treatment are somatostatin analogs which can induce long-term remission even in inoperable lesions. Although NET of pancreas are very rare. they are still important diagnostic and therapeutic problem and requires interdisciplinary co-operation. The neuroendocrine tumors should be treated in centers with highest rank of references.

Functional pancreatic endocrine tumors other than gastrinoma and insulinoma are quite rare. Some of these tumors may be part of multiple endocrine neoplasia type one (MEN-1) syndrome or phakomatoses. Depending on their cell type, functional pancreatic endocrine tumors may cause distinct clinical endocrine syndromes, such as the 'glucagonoma syndrome', Verner-Morrison syndrome and the 'somatostatinoma syndrome'. The significant progress made in recent years, especially in the field of imaging procedures, has brought about great improvement in the identification and differentiation of these neoplasms. Currently, the only curative treatment for islet cell tumors is complete surgical resection. The medical treatment of endocrine pancreatic tumours consists of somatostatin analogues, chemotherapy, and interferon-alpha. The purpose of this manuscript is to provide an overview of the contemporary etiopathogenesis, diagnosis and treatment of rare pancreatic endocrine tumors.

Neuroendocrine tumors (NET) of the gastrointestinal tract are rare and constitute 0.5-1% of all human malignancies. Based on their endocrine secretion, they are functional active or inactive. They are further classified into fore-, mid-, or hindgut tumors. The recently published WHO-classification grouped the tumors according to their tumor size, angioinvasion and Ki-67 index. NET are mainly diagnosed in an advanced tumor stadium because of the paucity of symptoms or when symptoms occur due to endocrine hypersecretion. NET are diagnosed serologically by their hormone secretion and by measuring Chromogranin A levels. They are further detected by CT, MRI or endoscopy including endoscopic ultrasound. Many NET have somatostatin receptors on their surface and can be diagnosed by somatostatin receptor scintigrafy with high sensitivity and specificity. Only by surgery NET can be cured. Because many tumors are diagnosed late, medical options are of utmost importance. Symptom control can be established by somatostatin analogues and interferon-ot. Diazoxid can further inhibit insulin secretion, proton pump inhibitors are the therapy of choice for acid hypersecretion in Zollinger-Ellison syndrome. Advanced neuroendocrine cancers can be treated with chemotherapy. Recently, radio receptor therapy with 90Y-DOTA Octreotid and 177Lu-DOTA Octreotate was established in advanced neuroendocrine cancers and is further evaluated in studies. Net of the gastrointestinal tract should be treated in a multidisciplinary approach with gastroenterologists, surgeons and experts in nuclear medicine. An overview about epidemiology, clinical features, diagnostic methods and therapy of NET of the gastrointestinal tract will is provided in this article.

Functional pancreatic endocrine tumors other than gastrinoma and insulinoma are quite rare. The principles of management include the diagnosis and management of the functional hormonal syndrome, and management of the potentially malignant tumor. Optimally, control of the hormonal syndrome is achieved preoperatively to stabilize the patient status for the operation, however, resection may be an important part of the control of the hormonal syndrome. Ultimately, the only curative treatment for these neoplasms is complete tumour resection, when feasible.

Background/aims: VIPoma is a rare pancreatic endocrine tumor (PET) which secretes excessive amounts of VIP (Vasoactive Intestinal Peptide) that causes a special clinical syndrome characterized by secretory diarrhea, hypokalemia and achlorhydria. Among a total number of 76 patients (pts) with PETs, we present in this study 11 pts with VIPoma syndrome focusing on our diagnostic and therapeutic approach, in parallel with a brief review of the literature., Methodology: Eleven pts (7 males and 4 females), aged from 2 to 83 years (mean age 53.1 years) were included. The diagnosis was based upon compatible clinical features and serum VIP values and was supported by the estimation of other peptides and neuroendocrine markers such as gastrin, pancreatic polypeptide and chromogranin-A (CgA). In 10/11 pts, diagnosis was confirmed histopathologically. The primary or metastatic lesions were located by conventional imaging methods or by OCTREOSCAN or Endoscopic Ultrasound (EUS). The follow-up period ranged from 2.5-13.5 years (mean 4.8 years)., Results: Chronic secretory diarrhea, which persisted despite fasting, was the main symptom in all pts of our study. VIP levels at the time of diagnosis were more than 3 or 10 times the upper normal limit in 7/11 (63.6%) or 4/11 (36.4%) pts, respectively. The primary lesion was detected by CT scan or MRI in 6/11 (54.5%), with EUS or abdominal angiography in 4/11 (36.4%). OCTREOSCAN revealed a solitary lesion in the right hepatic lobe, not detected by all the previous studies, while it detected, as a whole, the primary lesion in 10/11 (91%), and the metastases in 3/4 (75%) pts. In 7/11 (63.6%) the primary lesion was located in the pancreas, whereas in the rest it was in the duodenum or retroperitoneum. A surgical resection was possible in 7/11 (63.6%) pts, while pts with metastatic disease already or poorly differentiated tumors also received additional treatment with somatostatin analogues and chemotherapy. Liver metastases and poor differentiation of tumors seemed to be negative prognostic factors., Conclusions: Clinical suspicion, early diagnosis and precise management may affect survival and improve the quality of life of patients. Also, surgical treatment, as extensive as possible, in combination with somatostatin analogues or chemotherapy when necessary, may also result in prolonged survival, also in patients with advanced disease.

Objective: To discuss the experiences of diagnosis and treatment for vasoactive intestinal peptide-secreting-tumors (VIPoma) by summarizing clinical informations of 15 patients with VIPoma., Methods: To analyze Clinical manifestations, laboratory examinations, imaging features, operation, pathological findings and follow up survey of 15 patients, among them 1 case from our hospital and the other 14 cases were searched in chinese biological and medical literature database from Jan 1987 to Dec 2002., Results: The main clinical manifestation include periodical secretory watery diarrhea, hypokalemia, achlorhydria, in addition, periodical backache, skin rash, and polyps of colon were presented in the case in our hospital. The immunohistochemical expression of many kinds of digestive hormone including VIP presented positive; All clinical symptoms of which except polyps disappeared after operation, elevated VIP data in serum also markedly decreased. Part resection of superior mesenteric vein was performed in the same patient., Conclusions: VIPoma is rare. Typical symptoms and the serum value of VIP were keys to diagnosis, the operation is the most effective means for treatment. Resection of tumor, Radiofrequency tissue ablation, liver transplantation can be selected for metastatic VIPoma in the liver.

All pancreatic neuroendocrine tumors derive from Langerhans islet cells and have a low incidence. Half of them are functioning tumors that produce diverse hormones and occasionally cause serious clinical endocrine syndromes. They may be malignant, but they have a better survival, if compared to pancreatic ductal adenocarcinoma. Insulinoma, gastrinoma, glucagonoma, VIPoma (VIP=vasoactive intestinal peptide), somatostatinoma and ACTHoma are functioning tumors and they may also be part of Multiple Endocrine Neoplasia type I (MEN 1) syndrome and of von Hippel-Lindau disease. Diagnosis of non-functioning tumors is usually late, when they reach a big size and have even developed nodal and hepatic metastases. Nowadays, there are effective medical treatments for the medical problems secondary to excessive hormone production. For example, the hypergastrinemia typical of the Zollinger-Ellison syndrome in gastrinoma, can be adequately managed. Surgical resection is the most advisable therapy for pancreatic endocrine tumors, especially when they are small, when long time survival is better. Pre and intra operative imagenology is a great aid to locate these tumors. There are several surgical alternatives, according to the tumor size and location within the pancreas. Furthermore, palliative therapy can be used in disseminated disease. Treatment success is the result of a multidisciplinary medical team work of endocrinologists, surgeons, gastroenterologists, pathologists and geneticists.

Background: Malignant tumors of the pancreas are uncommon in children and adolescents and only recently have the most common tumor types been well characterized. As a result, the treatment approach to these patients has yet to be standardized, and much of the information available in the literature, particularly with regard to the role of chemotherapy and radiation, is anecdotal., Methods: A retrospective review was undertaken of all patients less than 21 years of age with malignant pancreatic tumors who were cared for at Memorial Sloan-Kettering since 1967., Results: Seventeen patients were identified. The pathologic types were pancreatoblastoma, 5; solid pseudopapillary tumor, 7; acinar cell carcinoma, 1; nonfunctioning pancreatic endocrine neoplasm, 1; malignant VIPoma, 1; and PNET, 2. A complete resection of the primary tumor was achieved in 82%, and 12 of 15 are alive, 10 with no evidence of disease. Chemotherapy or radiation were used in selected cases., Conclusions: Unlike malignant pancreatic tumors in adults, tumors in children and adolescents usually are resectable, and long-term survival is likely. However, the risk of recurrence for pancreatoblastoma is high. The roles of chemotherapy and radiation remain undefined., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Despite their rare occurrence, gastroenteropancreatic neuroendocrine tumors have been in the centre of interest because of the wide scale and variability of clinical signs and symptoms associated with oversecretion of different hormones. In the present review the authors summarize epidemiological data, pathologic findings, clinical symptoms, as well as diagnostic and therapeutic methods presently available for the management of patients with gastroenteropancreatic neuroendocrine tumors. In addition to surgical treatment and receptor-specific radionuclide therapy used in cases with surgically noncurable tumors, the therapeutic use of somatostatin analogues in recent years has resulted an important advance in the management of patients with these tumors. Somatostatin analogues alone or in combination with other pharmacological therapies may be used effectively for elimination of symptoms of hormonal oversection and, in a number of cases, for diminishing tumor progression.

Neuroendocrine tumors often manifest an excess production of hormones that create severe metabolic abnormalities resulting in significant patient morbidity, independent of the tumor burden itself. VIPomas are rare neuroendocrine tumors arising from the pancreas and are associated with secretory diarrhea and electrolyte disturbances. We present a patient with VIPoma and hepatic metastases who had greater than 10 loose stools a day for 4 yr since diagnosis, despite debulking surgery, multiple antidiarrheal medications, large doses of octreotide, and targeted radioisotope injections. The patient required several hospitalizations for treatment of dehydration and electrolyte disturbances, despite receiving daily intravenous fluids at home. Hepatic artery embolization (HAE) immediately stopped the patient's diarrhea and provided a return to normal formed stools without any other symptom-support measures. One year after HAE, the patient remains asymptomatic and has returned to a productive life. HAE can be a very effective and durable treatment modality for patients with metastatic VIPomas (or other neuroendocrine tumors) and who are clinically symptomatic from the effects of hormone hypersecretion.

Islet cell tumors of the pancreas are rare, indolent, neuroendocrine tumors. Approximately 50% of the patients diagnosed with these tumors present with symptoms related to various biologically active hormones that are secreted by these neoplasms. Currently, the only curative treatment for islet cell tumors is complete surgical resection. Management of metastatic disease is conservative. Initial treatment of these tumors includes expectant observation and medical management of symptoms with clinical monitoring and serial CT scans to assess tumor growth. Patients with rapidly progressive disease, with local symptoms caused by tumor bulk, or with uncontrolled symptoms related to hormone secretion require more aggressive medical or surgical intervention. The somatostatin analogue octreotide may help control hormone secretion and stabilize tumor growth. Patients refractory to octreotide with tumor predominantly in the liver are potential candidates for mechanical ablative techniques, such as hepatic arterial embolization. Radiofrequency ablation and cryosurgical techniques may also be useful, although specific data are limited. Surgical resection of metastatic disease may offer palliative relief of symptoms related to hormone secretion in carefully selected patients. Chemotherapy may be used for palliation when ablative techniques have failed or when significant extrahepatic disease is present. Streptozicin-based combinations remain the first line standard, but major objective responses are less common than had been previously thought. Because of the overall modest success of current chemotherapeutic regimens, patients with advanced disease in need of treatment should be encouraged to enroll in clinical trials testing newer antineoplastic agents or newer treatment strategies.

Objective: To compare the efficacy of a reduced osmolarity oral rehydration salts (ORS) solution (75 mmol/L of sodium [Na], 20 mmol/L of potassium [K], 65 mmol/L of chloride, 10 mmol/L of citrate, and 75 mmol/L of glucose; osmolarity, 245 mosm/L) with that of the standard World Health Organization (WHO) ORS solution., Design: A multicenter, double-blind, randomized, controlled clinical trial conducted in children with acute diarrhea in 5 developing countries to measure mean stool output in the 24 hours after randomization, proportion of children who required unscheduled intravenous therapy, proportion of children who vomited in the first 24 hours, and diarrhea duration after randomization., Results: A total of 675 children who ranged in age from 1 to 24 months and who had acute diarrhea and dehydration were enrolled in the trial; 341 were randomized to receive reduced osmolarity ORS solution, and 334 were randomized to receive the WHO ORS solution. The mean (SE) stool output (g/kg) in the first 24 hours (reduced osmolarity ORS solution vs WHO ORS solution = 114 [4] vs 125 [5]) and during the total study period (reduced osmolarity ORS solution vs WHO ORS solution = 320 [18] vs 331 [18]) were comparable. The proportion of children who vomited in the first 24 hours (reduced osmolarity ORS solution vs WHO ORS solution = 58% vs 62%) and the diarrhea duration in the 2 treatment groups, compared by log rank test, were similar. The proportion of children who required unscheduled intravenous therapy was significantly lower in children who received reduced osmolarity ORS solution (10%) as compared with those who received the WHO ORS solution (15%; odds ratio = 0.6, 95% confidence interval = 0.4-1.0). There was no significant difference in the incidence of hyponatremia (serum Na <130 mmol/L) at 24 hours between the 2 treatment groups (11% in reduced osmolarity ORS solution group vs 9% in the WHO ORS solution group; odds ratio = 1.3; 95% confidence interval = 0.8-2.2). The frequency of patients with serum Na <125 mmol/L at 24 hours was 13 of 341 (4%) in children who were treated with reduced osmolarity ORS solution versus 7 of 334 (2%) in children who received the WHO ORS solution., Conclusions: Treatment with reduced osmolarity ORS solution was associated with a 33% reduction in the need for unscheduled intravenous therapy and had no apparent effect on stool output and illness duration when compared with treatment with the standard WHO ORS solution. Children with acute diarrhea, therefore, may benefit from a reduced osmolarity ORS solution. The results of trials that examine the efficacy and safety of reduced osmolarity ORS solution in adult patients with cholera have to be taken into consideration before consensus on composition of oral rehydration formulation can be reached.

The incidence of VIPoma is approximately one per 10 million population. Thus in the Czech Republic this rare disease should be diagnosed once per year. The authors present their experience with the diagnosis and treatment of patient born in 1956, who suffered since 1990 from diarrhoea, at first episodically. In 1992-1994 the diarrhoea was profuse, caused dehydration, hypokalaemia and severe metabolic acidosis without an increase of the anion gap. As a result of dehydration the patient developed acute renal insufficiency. Due to hypokalaemia he developed paroxysmal atrial fibrillation. The diagnosis was based on the clinical finding and later confirmed on laboratory examination by a high VIP serum concentration. For treatment of diarrhoea Sandostatin was used. The tumour was located only after a scan with 123I-VIP in the cauda of the pancreas. Scintigraphy with labelled octreotide, similarly as other imaging methods (sono, X-ray and CT) were not effective. In 1994 left-sided hemipancreatectomy was performed. Although the patient was operated four years after the onset of the disease, no secondaries were detected. After surgery the diarrhoea stopped and no further treatment was necessary.

This report describes two patients with pancreatic cholera caused by vasoactive intestinal polypeptide (VIP)-producing tumors, which originated in the pancreas and showed metastases in both hepatic lobes at time of diagnosis. However, the two tumors displayed remarkably disparate clinical courses. Due to the protracted but progressive course over more than 10 years, a multifaceted therapeutic approach was performed to control symptoms and to improve quality of life. The long-acting somatostatin analog octreotide was the most effective treatment for relieving symptoms and correcting fluid and electrolytes disturbances. The effects of complementary treatments, including systemic chemotherapy and hyperselective chemoembolization, as well as concurrent application of octreotide and prednisolone or interferon with respect to clinical symptoms, VIP levels, and tumor growth are reviewed. Our experience, although small, emphasizes the need for an expert, well-planned, adaptive, and multidisciplinary approach in the care of these complex patients.

The aim of this review article is to analyze the diagnostic approach, presentation and therapeutic modalities in patients with liver metastasis from endocrine tumors. The paper shows the "state of the art" of therapeutic approaches with emphasis on the roll of different surgery, radio and chemotherapy, arterial embolization and other palliative procedures. The overall results of each of this modalities are also shown.

Purpose/objectives: To review the pathophysiology and clinical treatment of VIPomas, neuroendocrine tumors that secrete vasoactive intestinal polypeptide, and VIPoma syndrome., Data Sources: Published clinical treatments and case studies in the medical literature and case study data from a patient's medical record., Data Synthesis: VIPomas are rare neuroendocrine tumors that cause a syndrome of life-threatening symptoms. Clinical management is complex, yet little information is available in the medical and nursing literature to guide the clinician., Conclusions: Information about the pathophysiology and management of the disease may facilitate care of these patients., Implications for Nursing Practice: A case study presentation provides an example of the care required by one patient with VIPoma. The nurse has an important role in assessing, educating, and caring for the patient with VIPoma. Interventions include managing complex fluid and electrolyte imbalances, chemotherapy administration and management of side effects, activity and rest alterations, safety issues, altered social roles, and educational needs regarding medications, central lines, and follow-up care.

The authors intend to contribute to the knowledge of this complex and in part not fully defined subject of apudomas, in particular with regard to classification criteria and physiopathological aspects. After having examined the characteristics of these neoplasias (probably common embryonal origin, similar radioimmunological, immunohistochemical and ultrastructural characteristics, the capacity to convert amine precursors into amines), the authors focus on the most significant aspect of these carcinoids which, in the light of current knowledge, possess varying but undisputed degrees of biological aggressiveness. They also highlight the importance of the gastroenteric tract as an organ with an endocrine function and lastly affirm the value of the classification which, using the pancreas as the reference organ, distinguishes endocrine neoplasias in this tract into entopic and ectotopic examples.

Functional islet cell tumors cause recognizable clinical syndromes based on the peptide products they secrete (Table 1). Frequently, the diagnosis of these tumors is delayed. A high index of suspicion coupled with the use of appropriate biochemical and provocative tests should lead to earlier diagnosis. A suggested management plan for patients suspected of having an islet cell tumor is shown in Fig. 1. Earlier diagnosis coupled with advances in preoperative and intraoperative localization techniques have resulted in an increased number of patients being cured.