vasoactive-intestinal-peptide and Neuroendocrine-Tumors

Vasoactive intestinal peptide-secreting tumors (VIPomas) are a group of rare neuroendocrine tumors, which cause a typical syndrome of watery diarrhea. Most of these tumors are found in the pancreas and are usually detected at a later stage. Although curative resection is not possible in most of these tumors, both symptom and tumor control can be achieved by a multidimensional approach, to enable a long survival of most patients. There are no clear-cut guidelines for the management of VIPomas because of the rarity of this neoplasm and lack of prospective data. In this review, we discuss the available evidence on the clinical features and management of these rare tumors.

Topics: Diarrhea; Humans; Magnetic Resonance Imaging; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Survival Analysis; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

Topics: Aged; Diabetes Mellitus, Type 2; Glucagon; Humans; Male; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatectomy; Pancreatic Neoplasms; Splenectomy; Treatment Outcome; Vasoactive Intestinal Peptide

A 53-year-old man presented with diarrhoea and hypokalaemia and was diagnosed with a neuroendocrine tumour of unknown origin with multiple liver metastases. Somatostatin analogues led to a reduction in the size of the tumours and improvement of his symptoms. However, after several years, the tumours grew in size, and the patient's clinical symptoms recurred. The patient underwent transcatheter arterial embolization (TAE) of the hepatic artery to treat the liver metastases. Immediately after embolization, the symptoms disappeared. Although the patient had an unresectable vasoactive intestinal polypeptide-producing neuroendocrine tumour, the endocrine symptoms were able to be controlled with chemotherapy and TAE, resulting in a long-term survival.

Topics: Combined Modality Therapy; Embolization, Therapeutic; Endosonography; Hepatic Artery; Humans; Liver Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide

Circulating markers of neuroendocrine tumours are useful tools in the diagnosis of these tumours. Laboratory tests for general biomarkers have acceptable sensitivity for the recognition of neuroendocrine tumours as these biologically active proteins are typically synthesized by all types of neuroendocrine cells. Measurement of chromogranin A is widely used not only in the diagnosis of neuroendocrine tumours but it may predict the prognosis of the diseases and the effect of the antitumor therapy. It is also a useful tool for the detection of residual tumours. Neurendocrine tumours represent a heterogeneous group of tumours with the ability to secrete several hormones and, therefore, measurement of these hormones can also serve as neuroendocrine cell type-specific markers in routine clinical practice. In this review the authors summarize the significance of tumour markers in the diagnosis of neuroendocrine tumours as well as in the management and follow-up of patients with this disease.. A vérben keringő, illetve a vizelettel ürülő neuroendokrin tumormarkerek vizsgálata kiemelt fontosságú diagnosztikai eszköz a neuroendokrin daganatok kórisméjének felállításában. Az általános neuroendokrin tumormarkerek olyan biológiailag aktív fehérjék, amelyek szintézisére minden neuroendokrin differenciálódást mutató sejt képes, ezért vizsgálatuk megfelelően érzékeny módszernek bizonyult e daganatok felismeréséhez. Az általános neuroendokrin tumormarkerek közül a legszélesebb körben a chromogranin A vizsgálata terjedt el. A legújabb eredmények szerint a chromogranin A szérumkoncentrációjának vizsgálata a kórjóslat megállapításában, a daganatellenes terápia hatékonyságának előrejelzésében, továbbá a daganatkiújulás észlelésében is fontos eszközként szolgál. Az általános tumormarker mellett a sejtspecifikus markerek is komoly jelentőséggel bírnak. Jelen közleményben a szerzők áttekintik a neuroendokrin tumormarkerek szerepét a daganatok diagnosztikájában, illetve a betegek kezelése és utánkövetése során. Orv. Hetil., 2014, 155(45), 1775–1782.

Topics: 5-Hydroxytryptophan; Biomarkers, Tumor; Chorionic Gonadotropin; Chromogranins; Glucagon; Humans; Hydroxyindoleacetic Acid; Insulin; Neoplasm, Residual; Neuroendocrine Tumors; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Population Surveillance; Predictive Value of Tests; Prognosis; Serotonin; Somatostatin; Vasoactive Intestinal Peptide

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms representing <5% of all pancreatic malignancies with an estimated incidence of 1-1.5 cases/100,000. PNETs are broadly classified as either functional or nonfunctional. Functional PNETs include insulinomas, gastrinomas, vasoactive intestinal peptideomas, glucagonomas, and somatostatinomas. The clinical manifestations associated with these tumors are the result of excessive hormonal secretion and action. The functional nature of these tumors makes pancreatic hormone testing critical not only for initial diagnosis but also for follow-up, because they are important tumor markers. Nonfunctional PNETs typically remain clinically silent until a substantial mass effect occurs. Although the majority of PNETs occur sporadically, it is important to recognize that these tumors may be associated with a variety of familial syndromes and in many cases genetic testing of PNET patients is warranted. This article familiarizes the reader with the clinical presentation and the biochemical, radiologic, and genetic testing indicated for diagnosis and follow-up of patients with PNET.

Topics: Gastrinoma; Gastrins; Glucagon; Glucagonoma; Hormones; Humans; Hypoglycemia; Insulinoma; Neuroendocrine Tumors; Pancreatic Neoplasms; Somatostatinoma; Vasoactive Intestinal Peptide; Vipoma

Topics: Antibodies, Monoclonal; Biomarkers; Biomarkers, Tumor; Carcinoid Tumor; Female; Graves Disease; Humans; Male; Neuroendocrine Tumors; Octreotide; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity; Vasoactive Intestinal Peptide

This review has focused on the unique role of radionuclide scintigraphy in characterization of hepatic mass lesions. Radionuclide scintigraphy, unlike most other imaging modalities, is based on specific physiological and biochemical properties of each pathological entity that affects the liver. Hepatic scintigraphy, with its widespread availability, noninvasive nature, and relatively low cost is a powerful adjunct to other imaging techniques in the investigation of hepatic mass lesions. We have reviewed clinical presentation and characteristic findings of most hepatic lesions and have described reported findings with all available imaging modalities with particular emphasis on hepatic scintigraphy (Table 1) as well as a suggested algorithm for workup of solid hepatic masses (Fig 6). Additionally, the role of newer, more specialized techniques including PET scanning, 123I-labeled VIP, and 111In-labeled DTPA-D-Phe-octreotide scanning are reviewed. Hepatic nuclear scintigraphy continues to play an important role in the management of patients with solid hepatic masses.

Topics: Algorithms; Carcinoma, Hepatocellular; Costs and Cost Analysis; Hemangioma, Cavernous; Humans; Indium Radioisotopes; Iodine Radioisotopes; Liver Diseases; Liver Neoplasms; Neuroendocrine Tumors; Octreotide; Pentetic Acid; Terbium; Tomography, Emission-Computed; Vasoactive Intestinal Peptide

Topics: Humans; Insulin; Multiple Endocrine Neoplasia Type 1; Mutation; Neuroendocrine Tumors; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

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.

Topics: Diarrhea; Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Retrospective Studies; Vasoactive Intestinal Peptide; Vipoma

Neuroendocrine tumors are rare, heterogeneous neoplasms that produce a wide variety of clinical symptoms. Diarrhea in neuroendocrine tumors is incredibly common and is usually benign in nature. We report two extreme cases of diarrhea in metastatic neuroendocrine tumors that threatened fatality and provide evidence for steroids as a novel agent in the management of vasoactive intestinal peptide tumors.. A 63-year-old Caucasian male with a grade 2 (Ki-67 17%) metastatic small bowel neuroendocrine tumor, and a 43-year-old female with a grade 2 (Ki-67 5%) metastatic pancreatic vasoactive intestinal peptide tumor. Both patients suffered life-threatening diarrhea despite extensive treatment modalities, including new systemic agents. This case explains how a lack of compliance and patient under-reporting of symptoms contributed to their challenging clinical course. Only steroids had a significant sustained effect on the diarrhea of the patient with vasoactive intestinal peptide tumor.. This report discusses two rare cases of life-threatening diarrhea in neuroendocrine tumors and stresses the importance of accurate clinical history taking, patient education, and compliance for symptom control. The report suggests steroids as a potential novel pharmaceutical option in the management of vasoactive intestinal peptide tumors; this is of great significance as it may provide a new approach to their management and potentially act as a life-saving agent in other oncology patients.

Topics: Adult; Diarrhea; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Peptide receptor radionuclide therapy (PRRT) with the radiolabeled somatostatin analogue [Lutetium-177-DOTA0-Tyr3]octreotate (177Lu-DOTATATE) is widely applied for inoperable metastatic small intestinal and nonfunctioning pancreatic neuroendocrine tumors (pNETs). The aim of this study is to describe the safety and efficacy of the treatment of functioning pNETs.. Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gbq per cycle. Radiological (Response Evaluation Criteria in Solid Tumors 1.1), symptomatic, and biochemical response were analyzed retrospectively for all patients with a functioning pNET (insulinoma, gastrinoma, VIPoma, and glucagonoma) treated with 177Lu-DOTATATE. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module questionnaire.. Thirty-four patients with a metastatic functioning pNET (European Neuroendocrine Tumor Society grade 1 or 2) were included: 14 insulinomas, 5 VIPomas, 7 gastrinomas, and 8 glucagonomas. Subacute hematological toxicity, grade 3 or 4 occurred in 4 patients (12%) and a hormonal crisis in 3 patients (9%). PRRT resulted in partial or complete response in 59% of patients and the disease control rate was 78% in patients with baseline progression. 71% of patients with uncontrolled symptoms had a reduction of symptoms and a more than 80% decrease of circulating hormone levels was measured during follow-up. After PRRT, median progression-free survival was 18.1 months (interquartile range: 3.3 to 35.7) with a concurrent increase in QOL.. Treatment with 177Lu-DOTATATE is a safe and effective therapy resulting in radiological, symptomatic and biochemical response in a high percentage of patients with metastatic functioning pNETs. Hormonal crises occur relatively frequent and preventive therapy should be considered before and/or during PRRT.

Topics: Adult; Aged; Coordination Complexes; Female; Gastrins; Glucagon; Humans; Insulin; Lutetium; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Pancreas; Pancreatic Neoplasms; Quality of Life; Radiation Dosage; Radioisotopes; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Vasoactive Intestinal Peptide

Gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) are increasing in incidence, and accurate staging is important for selecting the appropriate treatment. (68)Ga-DOTATATE imaging is a promising approach for detecting GEPNETs and could help in selecting optimal therapeutic strategies. The aim of this study was to prospectively determine the clinical utility of (68)Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) in detecting unknown primary and metastatic GEPNETs.. One hundred thirty-one patients were enrolled in a prospective study of patients undergoing (68)Ga-DOTATATE PET/CT, (111)In-pentetreotide single-photon emission computed tomography (SPECT)/CT and multiphasic CT scan, and/or magnetic resonance imaging in a blinded fashion with comprehensive biochemical testing. The primary outcome measure was the detection of lesions by each imaging study.. (68)Ga-DOTATATE PET/CT imaging detected 95.1% of lesions (95% CI, 92.4% to 96.8%) with an average maximum standardized uptake value of 65.4 ± 47 (range, 6.9 to 244), anatomic imaging detected 45.3% of lesions (95% CI, 37.9% to 52.9%), and (111)In-pentetreotide SPECT/CT detected 30.9% of lesions (95% CI, 25.0% to 37.5%), with a significant difference between imaging modalities (P < .001). In four of 14 patients (28.6%), (68)Ga-DOTATATE PET/CT found a previously unknown primary tumor, and detected primary GEPNET, lymph node, and distant metastases correctly in 72 of 113 lesions (63.7%) when compared with histopathology, with 22.1% and 38.9% detected by using (111)In-pentetreotide SPECT/CT and anatomic imaging, respectively. On the basis of findings with (68)Ga-DOTATATE PET/CT, 43 of 131 patients (32.8%) had a change in management recommendation. In patients with carcinoid symptoms but negative biochemical testing, (68)Ga-DOTATATE PET/CT detected lesions in 65.2% of patients, 40% of which were detected neither by anatomic imaging nor by (111)In-pentetreotide SPECT/CT.. (68)Ga-DOTATATE PET/CT imaging provides important information for accurate staging of GEPNETs and selection of appropriate treatment interventions even in the absence of biochemical evidence of disease in symptomatic patients.

Topics: Adult; Aged; Aged, 80 and over; Chromogranin A; Female; Humans; Hydroxyindoleacetic Acid; Intestinal Neoplasms; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Neoplasms, Unknown Primary; Neuroendocrine Tumors; Organometallic Compounds; Pancreatic Neoplasms; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Positron-Emission Tomography; Prospective Studies; Somatostatin; Stomach Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Young Adult

Topics: Aged; Carcinoma, Pancreatic Ductal; Humans; Immunohistochemistry; Male; Neoplasms, Multiple Primary; Neuroendocrine Tumors; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

To present our experience of 93 neuroendocrine tumors (NETs) in the pancreas and peripancreatic region, with emphasis on how resectability affects long-term survival and the impact of functional status on the survival outcome.. Ninety-three patients with NETs in the pancreas and peripancreatic region were included to compare the clinical features between functional and nonfunctional NETs. Prognostic factors were determined by univariate and multivariate analyses.. There were 39 functional (41.9%) and 54 nonfunctional NETs (58.1%). According to World Health Organization (WHO) tumor categories, there were 57 well-differentiated tumors (61.3%), 26 well-differentiated carcinomas (28%), and 10 poorly differentiated carcinomas (10.8%). Univariate analysis showed that functional status of the tumor, tumor stage, lymph node status, and pathological classification were prognostic factors for both disease-free survival and disease-specific survival. Resectability did not influence the survival outcome, with the resectable and unresectable groups demonstrating a 5-year disease-specific survival of 86.4% and 65.6%, respectively (P = 0.210). Only the WHO pathological classification was an independent prognostic factor after multivariate analysis.. Irresectability does not necessarily preclude long-term survival for both functional and nonfunctional NETs. It is the WHO pathological classification, instead of hormonal functional status, that is an independent prognostic factor and has impact on the survival outcome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Differentiation; Chi-Square Distribution; Child; Disease-Free Survival; Female; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Insulin Secretion; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neuroendocrine Tumors; Odds Ratio; Pancreatectomy; Pancreatic Neoplasms; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Time Factors; Treatment Outcome; Vasoactive Intestinal Peptide; Young Adult

Pancreatic polypeptide (PP) islet cell tumors are usually not associated with a distinct clinical syndrome, although some reports suggest that they can cause a watery diarrhea syndrome similar to vasoactive intestinal polypeptide (VIP) cell tumors. We report the case of a young woman with an unusual presentation of a pancreatic neuroendocrine tumor mainly secreting PP. The patient developed a reversible hypokalemic rhabdomyolysis very likely secondary to the presence of the tumor. The myopathy resolved following the restoration of normokaliemia using potassium supplementation and a partial laparoscopic pancreasectomy. Isolated cases of hypokalemic rhabdomyolysis induced by intestinal diseases have been described in literature but these did not include gastroenteropancreatic neoplasms. We suggest that pancreatic neuroendocrine tumors should be added to the list of intestinal diseases capable of producing hypokalemic myopathy.

Topics: Adult; Diagnosis, Differential; Diarrhea; Female; Humans; Hypokalemia; Indium Radioisotopes; Neuroendocrine Tumors; Octreotide; Pancreas; Pancreatic Neoplasms; Pancreatic Polypeptide; Radionuclide Imaging; Rhabdomyolysis; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide

Human adenocarcinomas of the gastroenteropancreatic system overexpress vasoactive intestinal peptide (VIP) receptors and therefore represent logical diagnostic targets for receptor scintigraphy. Using iodine-123 labelled VIP, the newly employed diagnostic procedure termed VIP receptor scintigraphy (VIP-RS) appears to detect tumour tissue, especially pancreatic metastatic tumours, in almost all cases. So far, however, only a single centre has demonstrated convincing positive results. The aim of this study was to compare the sensitivity and specificity of VIP-RS with those of computer tomography (CT) and transabdominal ultrasound in patients with extensive pancreatic metastatic adenocarcinomas and neuroendocrine tumours. VIP was radiolabelled with carrier-free 123I using the chloramine T-method and preparative high-performance liquid chromatography for purification. Patients with metastatic pancreatic (n=12) and colorectal (n=3) carcinomas (adenocarcinoma: n=13, neuroendocrine tumour: n=2) were studied by VIP-RS, CT, ultrasound and, in one case, also by radioligand receptor autoradiography. Carrier-free radioiodinated VIP of maximum specific radioactivity maintained a high biological activity as determined by cAMP formation in receptor-expressing tumour cell lines. Intravenous injection of 123I-VIP did not cause any side-effects. Biodistribution, determined over 24 h, was high in the lungs and low in abdominal organs. Although all patients had extensive metastatic disease as evidenced by CT and ultrasound, VIP-RS was unable to detect either primaries or metastases in these patients. Only in two patients could a significant uptake of radiolabel be detected in organs directly infiltrated by the primary. To exclude false-negative findings, tumour tissue in one patient with a large primary, undetectable by VIP-RS, was analysed by radioligand receptor autoradiography and shown to be receptor positive. Moreover, in vitro receptor determinations showed that pancreatic carcinomas usually have fewer VIP receptors than the normal tissues to which they metastasize, like the liver. It is concluded that VIP can be radioactively labelled with maximum specific radioactivity while maintaining biological activity. Intravenous administration leads to a biodistribution almost identical to that reported previously. However, in contrast to these reports, very low sensitivity and specificity were observed for the detection of pancreatic cancers. In retrospect, these findings are

Topics: Adenocarcinoma; Adult; Aged; Colorectal Neoplasms; Female; Humans; Iodine Radioisotopes; Liver; Male; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Radionuclide Imaging; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide