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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.

Aim To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs). Background The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense. Methods Thirty-one MEN1 patients from the Groupe d’étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed. Results Indication for surgery was: Zollinger–Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0–433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13–110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8–98.3] and ten-year overall survival was 89.1% [CI 69.6–96.4]. After a mean follow-up of 151 months (range 0–433), the biochemical cure rate for MEN-1 related gastrinomas was 61%. Conclusion In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.

Chronic diarrhea is a common chief complaint in the pediatric population with a wide range of diagnostic differentials; as such, whilst suspecting common causes, less prevalent conditions tend to be overlooked, such as neuroendocrine tumor pathologies. VIPomas are characterized by hypersecretion of the vasoactive intestinal peptide (VIP), causing watery diarrhea, hypokalemia, and achlorhydria. Nonetheless, its low incidence rate in children makes it an easily unnoticed pathology. Herein, we report a case of a 14-year-old female patient and a review of relevant literature. The patient complained of 7-month history of watery diarrhea, multiple emetic episodes, and relevant past medical history of multiple hospitalizations. Chronic diarrheal disease work-up studies, including a high VIP scintigram, showed a lesion suggestive of a VIPoma-type neuroendocrine pancreatic tumor. A distal pancreatectomy was performed with a complete resolution of the symptoms. When faced with a pediatric patient presenting with chronic secretory diarrhea and whose work-up studies rule out the most common pathologies, the possible presence of a neuroendocrine tumor as VIPoma should be considered. J Med Cases. 2021;12(5):195-201 doi: https://doi.org/10.14740/jmc3535

We present the case of a 73-year-old female who underwent percutaneous cryoablation for recurrent life-threatening pancreatic vasoactive intestinal polypeptide-producing tumor (VIPoma) following a pancreaticoduodenectomy and chemotherapy 5 years earlier. She presented with profuse watery diarrhea causing severe electrolyte and acid-base abnormalities, along with acute kidney injury. Cryoablation was successful in treating her profound symptoms, completely reversing her clinical course. The patient has made a successful recovery for the last 1.5 years since the procedure.

A description of a rare clinical observation of pancreatic VIPoma is presented. Submitted literature review. The difficulties of preoperative diagnosis, as well as the effectiveness of surgical treatment are shown.

Background 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. Case presentation 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. Conclusions 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.

VIPoma is an unusual neuroendocrine neoplasm that autonomously secretes VIP. It is associated with secretory diarrhea and electrolyte disturbances. Herein we report a case of a male patient, who was hospitalized in the Department of Endocrinology in Hedi Chaker Hospital, Sfax, Tunisia. He presented VIPoma syndrome, with hepatic metastases at diagnosis. He had a history of chronic, watery diarrhea. He was dehydrated with many electrolytic disorders as hypokalemia, hyponatremia and metabolic acidosis. Abdominal CT scan showed a heterogeneous mass in the pancreatic head with multiple hepatic lesions. A high VIP hormone level was found. Histological study of a liver biopsy revealed hepatic metastases of neuroendocrine carcinoma. The patient received analogues of somatostatin and systemic chemotherapy, with a transient symptomatic relief. Sadly the patient was lost to follow-up.

Patient: Female, 33 Final Diagnosis: VIPoma Symptoms: Diarrhea Medication: — Clinical Procedure: Laparoscopy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: VIPomas are rare neuroendocrine tumors typically located in the pancreas. The majority of cases autonomously secret vasoactive intestinal polypeptide (VIP), which can result in profuse, refractory, watery diarrhea. The fluid and electrolyte imbalance can progress to dehydration and profound hypokalemia, resulting in the watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome. One previous case of a pancreatic VIPoma progressing to hypokalemic rhabdomyolysis has been described. Case Report: A 33-year-old woman presented with 3 months of progressive, refractory diarrhea and weakness. Her serum VIP level was elevated and imaging discovered a mass in the region of the pancreatic tail. Laparoscopic partial pancreatic resection was performed and a 3.7-cm diameter, solitary stage T2 N0 M0, well-differentiated carcinoma was removed. Conclusions: A high index of suspicion is important when diagnosing chronic diarrhea. Minimally invasive surgery is an option in the surgical treatment of pancreatic VIPoma.

Vasoactive intestinal polypeptide-secreting tumors (VIPoma) are a rare pancreatic neuroendocrine tumor that can cause chronic diarrhea with 1 case per 10 million people per year. Diagnosis is made based on a combination of laboratory evaluation (serum VIP level), imaging findings (functional positron emission tomography-computed tomography [PET-CT]), and histological analysis (chromogranin A stain). We present a case of a male with 6 months of diarrhea and malaise who was found to have significant kidney injury and hypokalemia requiring admission to the medical intensive care unit. Subsequent laboratory evaluation while admitted eventually showed a low stool osmotic gap (–11 mOsm/kg) consistent with secretory diarrhea, in addition to significantly elevated VIP levels at 940 pg/mL (normal

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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

Introduction: VIPoma is a neuroendocrine tumor that secrets vasoactive intestinal peptide and produces a well-defined clinical syndrome characterized by watery diarrhea, hypokalemia, hypochlorhydria and metabolic acidosis. The aim of this study to investigate clinical studies about diagnostic and therapeutic modalities of vipoma patients. In this retrospective study, all patients of vipoma were investigated. Clinical features, laboratory data at initial presentation, management and outcomes were collected. Subjects and Methods: The paper has written based on searching PubMed and Google Scholar to identify potentially relevant articles or abstracts. Categorical variables as percentage and continuous variables were reported as mean ± standard deviation (SD). Results: All the patients presented with watery diarrhea (30/30, 100%) and dehydration was reported in 33.3% of them. Prevalence of laboratory findings in these patients were assessed for hypokalaemia (25/30, 83.3%), metabolic acidosis (9/30, 33.6%), hypochloremia and achlorhydria (2/30, 6.6%). Elevated VIP levels have been seen in 73.3% patients with mean values of 882.85 ± 1134.87 pg/ml. Prevalence of diagnostic methods included CT scan in 19 patients (19/30, 63.3%), ultrasonography (15/50, 50%), and somatostatin receptor scintigraphy (8/30, 26.6%). Medical treatments included somatostatin and analogues in 18 patients (18/30, 60%). Surgery included less percentage of treatment in these patients. Conclusion: CT scan can be used as a reliable modality for diagnosis of vipoma and somatostatin analogues can be used as the most effective treatment in vipoma patients. Surveillance of these patients needs to close monitoring of patients via history, physical examination, laboratory and imaging.

Introduction Octreotide acetate subcutaneous injection is indicated to treat acromegaly and the symptoms of carcinoid tumors and vasoactive intestinal peptide tumors (VIPomas). This formative human factors study assessed the octreotide acetate pen injector and accompanying instructions for use (IFU) with self-trained participants. Methods The study enrolled patients with diagnoses of acromegaly, carcinoid tumors, or VIPomas and healthcare practitioners (HCPs) who treat patients with these diagnoses. The IFU provided a stepwise process with illustrations to train participants on using the pen injector. Participants familiarized themselves with the pen injector and the IFU before administering 2 unaided injections into skin-like pads; administering the full dose into the pad was considered a successful injection. The investigators evaluated each injection by performance measures—specific tasks necessary to safely and correctly administer the medication—and subjective measures, which included participant comments, feedback from questions, and suggestions for improvements. Results The study enrolled 11 participants—8 patients and 3 HCPs. Participants had a success rate of 100% for both injections. Errors included 1 participant priming the pen with the incorrect dose and 2 participants not holding the injector button for 10 s after the injection. Neither error led to a failed injection. To improve the IFU, participants suggested changing the order of wording on the priming step, clarifying illustrations of the plunger, and stronger indications to hold the injector button. Conclusion The octreotide pen injector and IFU were usable by self-trained participants. Participant errors and suggestions provided a foundation for recommendations to improve the IFU. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01739-1.

INTRODUCTION: In the past the inability to control the hormone-excess-state was the main determinant of survival in patients with Functional Neuroendocrine Neoplasm syndromes (F-NENs). This could prove especially difficult because the pharmacological armamentarium available until relatively recently was limited. In the last few years there have been a marked increase in the therapeutic strategies available which have opened new pharmacotherapeutic approaches, but have also generated some controversies, uncertainties and confusion. AREAS COVERED: In this perspective, the authors briefly review the different F-NENs that are established as well as those proposed; the rationale for approaching their treatment and why both an approach to controlling their hormone-excess-state and their malignant nature is required in most cases; the current recommended initial pharmacotheraputic approach to controlling the hormone-excess-state of the different F-NENs; the secondary approaches to controlling the hormone-excess-state if the initial approach fails or resistance develops; and the approach to deal with the malignant nature of the NEN per se. Also discussed are the controversies the new treatments have generated particularly related to the timing of the diagnosis of the F-NEN, as well as the sequences of secondary treatments, and the exact role of PRRT. EXPERT OPINION: Unfortunately, except for patients with insulinomas(>90-95%), gastrinomas(

Vasoactive intestinal peptide (VIP) secreting tumor (VIPoma) is a rare disease, presenting with profuse diarrhea, electrolyte imbalance, and possibly fatal outcome. The diagnosis and treatment are challenging, and no consensus guideline of management is available. The pediatric incidence remains unclear. This study comprises two pediatric case reports from a tertiary center and a literature-based case series investigating the characteristics among children. The two reported cases both presented with severe diarrhea and laboratory abnormalities, including electrolyte imbalance and elevated plasma VIP level. Case 1 received several imaging investigations, partial pancreatectomy, octreotide, and everolimus, reflecting her complicated and refractory course. Case 2 underwent total excision of suprarenal ganglioneuroblastoma, and the clinical response was significant. In both cases, varied degrees of symptomatic control, reduced plasma VIP level, and correction of electrolyte imbalance were achieved. A literature review-based case series analyzed 45 pediatric cases retrieved from the PubMed database until December 31, 2019. Demographics, clinical features, diagnostic modalities, treatments, and outcomes were presented.

Background Pancreatic neuroendocrine tumors are rare, with rising incidence and limited clinicopathological studies. Methods Adult patients with pNET at a single tertiary care center were retrospectively evaluated. Results In total, 87 patients with histologically confirmed pNET who underwent resection were evaluated. 11% of patients had functioning pNETs: 9 insulinoma and 1 VIPoma. The majority (88.5%) were nonfunctioning. The most common surgical procedure performed was distal pancreatectomy with splenectomy (36.8%). 35.6% of cases were performed with minimally invasive surgery (MIS). MIS patients had fewer postoperative complications, shorter length of stay, and fewer ICU admissions.Disease-free survival (DFS) was unaffected by tumor size (p = 0.5) or lymph node status (p = 0.62). Patients with high-grade (G3) tumors experienced significantly shorter DFS (p = 0.02). Conclusions This series demonstrates that survival in patients with pNET is driven mostly by tumor grade, though overall most have long-term survival after surgical resection. Additionally, an MIS approach is efficacious in appropriately selected cases.

Vasoactive intestinal peptide (VIP)-secreting neuroendocrine tumors are an exceptionally rare cause of chronic diarrhea. We describe a 36-year-old woman presenting with a 2-year history of severe diarrhea and electrolyte derangements ultimately diagnosed with VIPoma.

Secretory tumors of vasoactive intestinal polypeptides (VIPomas) are rare neuroendocrine pancreatic neoplasms usually associated with secretory diarrhea. Most cases present themselves with diarrhea, weight loss, and hypokalemia. Although VIPoma patients share easily distinguishable symptoms, early diagnosis remains a challenge. Therefore, tumors are usually found in large proportions and with later staging. The presenting case portrays a unique situation where the tumor found was still in a small size, is worth reporting it to the current literature. The diagnosis was made through laboratory evaluation and imaging studies. The primary treatment consists of exeresis surgery, but cytoreductive surgery also can provide several benefits. This way is necessary to pay attention to diagnoses also in the ways of treatment.

Hypercalcemia is a clinical problem that is commonly seen in both the inpatient and outpatient settings. Overall, most common causes of hypercalcemia include hyperparathyroidism and malignancy. Our case report is the presentation of hypercalcemia in a patient eventually diagnosed with a vasoactive intestinal peptide tumor, a type of neuroendocrine tumor, without associated hyperparathyroidism.

Background. Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. In this report, we analyzed the clinical characteristics of functional PanNENs in a large cohort of Chinese patients and summarized our clinical experience in diagnosis and treatment. Methods. The retrospective analysis was performed in patients with a definite diagnosis of functional PanNENs hospitalized in Chinese PLA General Hospital between 2000 and 2020. The clinical characteristics, surgical information, and pathological findings were extracted from their medical records and were analyzed. Results. Totally, 286 patients (gender: male 103 and female 183; age: 45.55 ± 15.23 years old) were diagnosed with definite functional PanNENs. The most frequent functional PanNENs were insulinoma (266/286) followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone- (ACTH-) producing tumor (3/286), gastrinoma (2/286), and VIPoma (2/286). Nine patients were diagnosed with multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. The duration from symptoms’ onset to confirmed diagnosis was 3.67 ± 4.28 years. Two hundred and eighty patients with tumor localized in pancreatic or with limited metastasis underwent surgery. The symptoms associated with hormonal oversecretion were improved significantly after surgery. Five patients with unresectable metastases or tumor recurrence after surgery were administrated with systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms were also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized into NEN-G1 (41.95%), NEN-G2 (54.90%), NEN-G3 (3.15%), and NEC-G3 (0%). Conclusion. Patients with suspected functional PanNENs should have a systematic endocrine examination at diagnosis. Multidisciplinary collaborations are essential for precise diagnosis and tumor localization. A successful surgery or other targeted therapies can improve the prognosis of patients with such rare but complex disorders.

Vasoactive intestinal peptide-producing tumors (VIPoma) usually originate in the pancreas and are characterized by diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). In adults, nonpancreatic VIPoma is very rare. Herein, we report an unusual case of VIP-producing pheochromocytoma marked by persistent shock, flushing, and watery diarrhea and high sensitivity to octreotide. A 53-year-old woman was hospitalized for sudden-onset hypertension with convulsions, which then rapidly evolved to persistent shock, flushing, and watery diarrhea. Abdominal computed tomography indicated a left adrenal mass, accompanied by bleeding; and marked elevations of both plasma catecholamine and VIP concentrations were documented via laboratory testing. Surprisingly, all clinical symptoms responded swiftly to octreotide treatment. Once surgically treated, hormonal levels normalized in this patient, and the clinical symptoms dissipated. Postoperative pathological and immunohistopathological studies confirmed a VIP-secreting pheochromocytoma with strong, diffuse positivity for somatostatin receptor type 2. During a 6-mo follow-up period, she seemed in good health and was symptom-free.

Background: Vasoactive intestinal peptide-secreting tumours (VIPomas) lead to high-volume secretory diarrhoea with hypokalaemia, as well as hyperglycaemia and hypercalcaemia. Diagnosis is often delayed. Case Description: We present a 13-year-old girl with a distal pancreatic VIPoma diagnosed on her second hospital presentation who became severely hypotensive on anaesthetic induction prior to tumour removal, likely due to the vasodilatory effect of supraphysiological VIP levels. Prior to the second surgical attempt, an octreotide infusion was started preoperatively to suppress systemic VIP levels and counter the potential for VIP-induced hypotension upon tumour manipulation, and the tumour was successfully resected. Hyperparathyroidism and history of GI tumour resection were subsequently identified in the father, and the two members were found to have a heterozygous variant of uncertain significance in the multiple endocrine neoplasia type 1 (MEN1) gene. However, as this family meets the diagnostic criteria for MEN1 clinically, ongoing surveillance for MEN1 tumours and genetic counseling for at-risk family members are required despite the non-pathogenic genetic result. Conclusion: This case highlights the importance of screening for a VIPoma in patients with high-volume secretory diarrhoea and preventing cardiovascular complications with perioperative VIP suppression. Furthermore, careful interpretation of genetic results within the clinical context is required.

The article shows that a significant proportion of neuroendocrine tumors of the pancreas are non-functional, i.e., not secreting into the blood a variety of gastrointestinal hormones and polypeptides and as a result, not accompanied by typical clinical manifestations. Unfortunately, often the scan search starts in the detection of distant metastases of neuroendocrine tumors and development of cancer cachexia. Noted that the diagnosis of neuroendocrine tumors of the pancreas is a highly complex task, the solution of which depends on the choice of treatment and its remote results. Currently, the only radical method of treatment of hormonally functioning tumors of the pancreas is surgical. It is indicated that symptomatic therapy can be considered as a stage of preoperative preparation of the patient. The indication for surgical treatment in this situation, along with the ineffectiveness of conservative treatment is the size of detectable formations of 2 cm or more, which is a risk factor of distant metastases. Stressed that according to modern views of patients with nonfunctioning neuroendocrine tumors of the pancreas are subject to surgical treatment. Given that in 70-92% of cases they are malignant, most often used distal or extensive pancreatoduodenal resection. Currently, noted that the large size of the tumors are not a contraindication to surgery and if the tumor dormant, to 1 cm, the possibility of a short observation. Any tumors found in the pancreas, needs to be taken out of the context, or if it is possible – is widely excised. The article examines the rational and integrated use of modern Arsenal of surgical and therapeutic methods, which enable significantly prolong life, improve its quality in patients with metastatic forms of neuroendocrine tumors of the pancreas.

Background: Vasoactive intestinal peptide-secreting tumors (VIPoma) are rare neuroendocrine tumors (NETs) that present with a triad of profuse watery diarrhea, hypokalemia, and achlorhydria. The resulting renal impairment, electrolytes and acid-base imbalances pose a high risk of morbidity and mortality. We describe a case of life-threatening VIPoma crisis in an immunocompromised patient. Clinical Case: A 64-year-old man was intubated after he was brought in unconscious with tachypnea. Upon review, he had experienced persistent watery diarrhea for the past 6 months, with a weight loss of 18 kg. He had severe hypokalemia (potassium 1.9 mmol/L, n= 3.5-5.0), metabolic acidosis (blood gases pH 6.927, bicarbonate 4.8 mmol/L, base excess -25.9 mmol/L), and acute kidney injury (urea 47.9 mmol/L, creatinine 980umol/L). He continued to have electrolyte imbalances and acidosis due to persistent diarrhea, despite hydration and dialysis support. His biohazard screening results were positive for human immunodeficiency virus (HIV), with a CD4 count of 101 cells/µl. He was given courses of antibiotics for treating pathogenic infections; however, his septic workups were negative for infection, including HIV-related opportunistic infections. Later, pancreatic CT revealed a well-defined heterogeneously enhancing pancreatic head mass, size 6.8x5.2x7.5 cm. Further laboratory investigations confirmed the diagnosis of VIPoma, with elevated VIP levels (1600 pg/ml, n < 75). Eventually, subcutaneous octreotide was started, with resolution of the diarrhea and normalization of his electrolytes and renal function. After a 6-week hospital stay, he was discharged well with monthly octreotide and initiated on antiretroviral therapy (ART). After 3 months of ART, his CD4 count improved, and he remained diarrhea-free with octreotide. He is scheduled for tumor debulking surgery. Conclusion:This case highlights the importance of having a clinical suspicion of NETs, especially in immunocompromised patients. Further investigations and imaging studies to rule out noninfectious pathologies should be considered in patients who respond poorly to standard therapy. In VIPoma, somatostatin analog is an antisecretory treatment and it is highly effective for controlling diarrhea. High-dose octreotide up to 1500 µg/day has previously been studied for treatment of refractory diarrhoea in the setting of HIV infection² and it has been found to be helpful in reducing stool volume and frequency. Lastly, delays in the diagnosis and treatment of VIPoma in immunocompromised patients can be fatal. References1/ Hoffland J., Kaltsas G., de Herder W. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocrine Reviews, Volume 41, Issue 2, April 2020, Pages 371-403.2/ Farthing MJ. Octreotide in the treatment of refractory diarrhoea and intestinal fistulae. Gut 1994;35:S5-10.

OBJECTIVES: To document the existence of primary pancreatic secretinoma in patients with watery diarrhea syndrome (WDS) and achlorhydria and establish secretin as a diarrheogenic hormone. BACKGROUND: Vasoactive intestinal peptide (VIP) has been widely accepted as the main mediator of WDS. However, in 1968, Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors, WDS, and achlorhydria. During surgery on the first, a 24-year-old patient, they noticed distended duodenum filled with fluid and a dilated gallbladder containing dilute bile with high bicarbonate concentration. After excision of the tumor, WDS ceased and gastric acid secretion returned. The second, a 47-year-old, patient’s metastatic tumor extract given intravenously in dogs, produced significantly increased pancreatic and biliary fluid rich in bicarbonate. They suggested a secretin-like hormone of islet cell origin explains WDS and achlorhydria. These observations, however, predated radioimmunoassay, immunohistochemical staining, and other molecular studies. METHODS: The first patient’s tumor tissue was investigated for secretin and VIP. Using both immunohistochemistry and laser microdissection and pressure catapulting technique for RNA isolation and subsequent reverse transcription polymerase chain reaction, the expression levels of secretin, and VIP were measured. RESULTS: Immunoreactive secretin and its mRNA were predominantly found in the tumor tissue whereas VIP and its mRNA were scarce. CONCLUSIONS: The findings strongly support that the WDS and achlorhydria in this patient may have been caused by secretin as originally proposed in 1968 and that secretin may act as a diarrheogenic hormone.

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.

Pancreatic microadenomas are benign tumors of neuroendocrine origin less than 5 mm in size. Whereas most microadenomas are non-functional; a few rare functional pancreatic microadenomas have been described in the setting of multiple endocrine neoplasia type one (MEN-1). In this report, we describe a unique case of multiple functional microadenomas of the pancreatic head in a patient who presented with persistent secretory diarrhea, refractory hypokalemia, metabolic acidosis and elevated plasma vasoactive intestinal peptide (VIP) levels. Following extensive serologic, radiographic and endoscopic work up, our patient underwent open pancreaticoduodenectomy with subsequent resolution of diarrheal symptoms and electrolyte abnormalities on postoperative follow up.

Background: VIPoma is a rare neuroendocrine neoplasm that autonomously secretes vasoactive intestinal peptide. It is a syndrome of watery diarrhea, hypokalemia and achlorydia. Majority of VIPOmas have metastasized at the time of diagnosis.1Case: We report a case of a 36 year-old male initially presenting with non-pruritic, maculopapular rashes over the facial area. Upon consult with a primary care physician, he was prescribed with doxycycline. Few days after the intake of medication, he developed non-bloody, non-mucoid loose watery stools with increasing frequency during the subsequent days. Diarrhea was initially attributed to doxycycline. Hence, it was discontinued. However, despite its discontinuation, the previously noted watery diarrhea persisted for the next three months. This was accompanied by persistent hypokalemia despite sufficient electrolyte correction. On work up, thyroid function test and 5HIAA level were unremarkable. VIP level was elevated at 320 pg/mL (normal < 75 pg/mL). CT scan of the whole abdomen revealed a heterogeneously enhancing pancreatic tail mass measuring 4.0 x 6.6 x 4.1cm. Distal pancreatectomy with peripancreatic lymph node dissection and splenectomy were subsequently done. Frozen section revealed well-differentiated pancreatic neuroendocrine tumor. Immunohistochemical stains were positive for chromogranin and synaptophysin with 1% ki-67. Final staging for the VIPoma were as follows: WHO and ENETS histological classification low grade, G1; AJCC staging for PNET stage 1B; ENETS Classification Stage IIB. The patient’s aforementioned symptoms completely resolved post-operatively. Conclusion: The diagnosis of VIPoma is usually delayed due to its nonspecific manifestations. If it is left untreated, it may lead to renal failure and death. Hence, there should be a high index of suspicion for VIPoma in patients with chronic watery diarrhea and persistent hypokalemia. Reference: 1. Abu-Zaid, A., Azzam, A., Abudan, Z., Algouhi, A., Almana, H., Amin, T. Sporadic pancreatic vasoactive intestinal peptide-producing tumor (VIPoma) in a 47-year-old male. Hematol Oncol Stem Cell Ther. 2014; 7(3): 109-115.

Pancreatic neuroendocrine tumors represent less than 5% of all pancreatic tumors. They are a heterogeneous group of neoplasms with a diverse behavior and prognosis. Pancreatic vasoactive intestinal polypeptide tumor (VIPoma) is an exceptional tumor within this group due to its low incidence. The presence of pancreatic VIPoma should be clinically suspected in all patients with watery diarrhea, particularly when accompanied by a loss of potassium and bicarbonate and a pancreatic mass on imaging. There are other pathologies with similar symptoms; therefore, a correct differential diagnosis with an adequate treatment is essential for its management. We present the case of a 46-year-old patient who developed a prerenal kidney failure secondary to severe watery diarrhea after a diagnosis of pancreatic VIPoma. Thus, a resection was performed as the patient was rapidly deteriorating and required an intervention.

VIPomas are extremely rare tumors that secrete excessive vasoactive intestinal peptide (VIP). Symptoms include watery diarrhea, flushing, hypotension, and dehydration. Most VIPomas are sporadic but can be associated with multiple endocrine neoplasia type 1 (MEN1). Biochemical evaluation may show hypochloremic, hypokalemic metabolic acidosis. Diagnosis is confirmed with fasting VIP levels >200 pg/ml. Tumors may be localized with cross-sectional imaging with either computed tomography (CT) or magnetic resonance imaging (MRI). VIPomas are usually >2 cm and located in the body or tail of the pancreas. Surgical resection is indicated for isolated disease.

VIPomas, glucagonomas, and somatostatinomas are three rare kinds of neuroendocrine tumors with an estimated incidence of less than 1 per 10 million patient years. VIPomas are mainly localized in the pancreas and VIP secretion can cause severe diarrhea. Glucagonomas cause hyperglycemia, necrolytic migratory erythema, cachexia, and glottitis. The somatostatinoma syndrome is characterized by diabetes mellitus of recent onset, decreased gastric acid secretion, cholelithiasis, steatorrhea, and anemia/weight loss. Treatment of these neuroendocrine tumors is surgical if a radical resection is feasible. Metastatic tumor is treated symptomatically and often somatostatin analogues are very effective.

BACKGROUND The aim of this study was to explore the effect and possible mechanism of sodium valproate (VPA) on the cognitive function and the hippocampus of rats after convulsive status epilepticus (CES). MATERIAL AND METHODS A rat model of CES was established and the Morris water maze was used to observe changes in the cognitive function of the rats after the administration of VPA. Acute hippocampal slices were made to detect field excitatory postsynaptic potential. Western blot analysis was used to test for the expression of CaMKII and p-CaMKII. RESULTS (1) CSE caused no spatial reference memory (SFM) or spatial working memory (SWM) damage to 15-day-old (P15) rats, but caused significant SRM and SWM damage to 35-day-old (P35) rats. VPA damaged the SRM and SWM of P15 rats in both the CSE and control groups. However, VPA improved the memory damage caused by CSE in P35 rats. (2) VPA treatment in vivo increased the induced success rate and the sustainable time of long-term potentiation (LTP) in P35 rats, and also inhibited the expression of CaMKII and p-CaMKII in both P15 and P35 rats. CONCLUSIONS VPA significantly improved spatial cognitive dysfunction in a CSE model of P35 rats, and damaged the spatial memory of normal P15 and P35 rats. Improvements after administration of VPA were closely related to the increase of induced success rate and the prolongation of the sustainable time of LTP. VPA treatment in vivo, which inhibited expression and phosphorylation of CaMKII, showed no obvious inhibition on LTP, which may be related to the elution effect of VPA.

VIPoma is a rare neuroendocrine tumor (NET) with a high potential to develop hepatic metastases and poor prognosis. The primitive tumor is nonsymptomatic and usually localized within the pancreas. Liver metastasis drives the prognosis and induces profuse watery diarrhea or renal failure. We herein present severe renal failure or diarrhea in two patients hospitalized in intensive care justifying emergency treatment of liver metastasis. The two patients experienced severe diarrhea due to a hypersecretion of vasoactive intestinal peptide (VIP) from liver metastasis released into the blood circulation. Therapeutic management was discussed and liver transarterial chemoembolization (TACE) was performed with chemotherapy-loaded embospheres, which cause necrosis of tumor lesions. TACE controlled the hormonal syndrome and made patients eligible for curative surgery. Tumor necrosis occurred and VIP levels collapsed. Surgery was performed in one of the two cases after TACE and the patient was considered in remission. Both patients were still alive after 3 years of follow up. Thus, TACE is feasible and appears to be an effective emergency treatment in patients with a VIP-hormonal syndrome due to liver metastases. Despite the biological disorder due to the hormonal secretion, an aggressive approach is warranted in VIP liver metastasis.

Malignant-functioning pancreatic neuroendocrine tumors (mFpNETs) are rare. Research analyzing the presentation, biological behavior, and patient outcomes of these tumors is limited.We used the Surveillance, Epidemiology, and End Results database to identify patients with malignant insulinomas, gastrinomas, glucagonomas, vasoactive intestinal peptide secreting tumors (VIPomas), somastatinomas, and mixed islet cell tumors (MICTs). The primary endpoint of this study was to identify factors affecting survival.We identified 401 patients with mFpNETs. Between histologic subtypes, there were significant differences in sex and age, and in tumor size, grade, location, and stage. Median survival time for insulinomas was 12.7 years; gastrinomas, 10.2 years; glucagonomas, 7.7 years; VIPomas, 7.9 years; and MICTs, 3.4 years. Multivariable analysis showed that histology (insulinoma, gastrinoma, and VIPoma; P = .009), absence of distant metastases (P = .002), age50 years (P = .001), surgical intervention (P = .001), and stage I/II disease (P = .011) were independently associated with prolonged survival. Subgroup analysis demonstrated that removal of the primary tumor in stage IV mFpNETs was associated with significantly prolonged survival (P = .01).mFpNETs are rare tumors that commonly present at an advanced stage despite hormonal secretion. Primary tumor resection is associated with longer survival in stages I-III as well as stage IV tumors.

Pancreatic neuroendocrine tumors are a rare group of neoplasms that arise from multipotent stem cells in the pancreatic ductal epithelium. Although they comprise only 1% to 2% of pancreatic neoplasms, their incidence is increasing. Most pancreatic neuroendocrine tumors are nonfunctioning, but they can secrete various hormones resulting in unique clinical syndromes. Clinicians must be aware of the diverse manifestations of this disease, as the key step to management of these rare tumors is to first suspect the diagnosis.

The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The pancreatic islet cells were first described in 1869 by Paul Langerhans. In 1924, Seale Harris was the first to describe endogenous hyperinsulinism/insulinoma. In 1942 William Becker and colleagues were the first to describe the glucagonoma syndrome. The first description of gastrinoma by Robert Zollinger and Edwin Ellison dates from 1955. The first description of the VIPoma syndrome by John Verner and Ashton Morrison dates from 1958. In 1977, the groups of Lars-Inge Larsson and Jens Rehfeld, and of Om Ganda reported the first cases of somatostatinoma. But only in 2013, Jens Rehfeld and colleagues described the CCK-oma syndrome. The most recently updated WHO classification for gastrointestinal neuroendocrine tumours dates from 2010.

Vasoactive intestinal peptideoma (VIPoma) is a rare pancreatic endocrine tumor associated with a well-defined clinical syndrome characterized by watery diarrhea, hypokalemia and metabolic acidosis. In adults, VIPoma is most commonly found in the pancreas, with 80% of the tumors occurring in the body and tail and 20% occurring in the pancreatic head. VIPomas can represent a significant diagnostic challenge due to their nonspecific clinical presentation, which can result in the misdiagnosis of a VIPoma as another condition, such as laxative overdose or a carcinoid secreting tumor. Surgical clearance of the tumor is the first-line treatment, even in cases with metastasis. The present study describes the case of a patient who presented with chronic watery diarrhea and hypokalemia due to a tumor in the pancreatic head, which was confirmed to contain immunoreactive vasoactive intestinal polypeptide via immunohistochemistry. A hepatic metastasis lesion was diagnosed following computed tomography. Stable control of symptoms was achieved after surgery and drug treatment. The study additionally reviews the clinical, histological, radiological and diagnostic features of the condition, as well as the therapeutic modalities that can be used to treat VIPoma in the pancreatic head with hepatic metastasis.

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.

RATIONALE Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited by SSTR-based imaging such as In octreotide scintigraphy and Ga DOTATATE positron emission tomography (PET)/computed tomography (CT), which are considered standard for initial evaluation of NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of "false-positive" physiologic uptake of these tracers in the pancreatic head - a common site of neuroendocrine tumor (NET) involvement. We present false positive uptake on Ga DOTATATE PET/CT along with false positive CT findings. Role of other imaging modalities is discussed. PATIENT CONCERNS A 78-year-old woman presented with a year-long history of diarrhea. DIAGNOSIS Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL (normal

Background The goals of resection of functional neuroendocrine tumors (NETs) are two-fold: Oncological benefit and symptom control. The interaction between the two is not well understood. Methods All patients with functional NETs of the pancreas, duodenum, and ampulla who underwent curative-intent resection between 2000 and 2016 were identified. Using Cox regression analysis, factors associated with reduced recurrence-free survival (RFS) were identified. Results Two-hundred and thirty patients underwent curative-intent resection. Fifty-three percent were insulinomas, 35% gastrinomas, and 12% were other types. Twenty-one percent had a known genetic syndrome, 23% had lymph node (LN) positivity, 80% underwent an R0 resection, and 14% had no postoperative symptom improvement (SI). Factors associated with reduced RFS included noninsulinoma histology, the presence of a known genetic syndrome, LN positivity, R1 margin, and lack of SI. On multivariable analysis, only the failure to achieve SI following resection was associated with reduced RFS. Considering only those patients with an R0 resection, failure to achieve SI was associated with worse 3-year RFS compared with patients having SI (36% vs 80%; P = 0.006). Conclusions Failure to achieve symptomatic improvement after resection of functional NETs is associated with worse RFS. These patients may benefit from short-interval surveillance imaging postoperatively to assess for earlier radiographical disease recurrence.

To evaluate the outcome of duodenopancreatic reoperations in patients with multiple endocrine neoplasia type 1 (MEN1). MEN1 patients who underwent reoperations for duodenopancreatic neuroendocrine neoplasms (dpNENs) were retrieved from a prospective database and retrospectively analyzed. Twelve of 101 MEN1 patients underwent up to three reoperations, resulting in a total of 18 reoperations for dpNEN recurrence. Patients initially underwent either formal pancreatic resections (n = 7), enucleations (n = 3), or duodenotomy with lymphadenectomy for either NF-pNEN (seven patients), Zollinger–Ellison syndrome (ZES, three patients), organic hyperinsulinism (one patient) or VIPoma (one patient). Six patients had malignant dpNENs with lymph node (n = 5) and/or liver metastases (n = 2). The indication of reoperations was NF-pNEN (five patients), ZES (five patients), organic hyperinsulinism (one patient), and recurrent VIPoma (one patient). Median time to first reoperation was 67.5 (range 6–251) months. Five patients required a second duodenopancreatic reoperation for 60–384 months after initial surgery, and one patient underwent a third reoperation after 249 months. The rate of complications (Clavien–Dindo ≥3) was 28%. Four patients required completion pancreatectomy. Six patients developed pancreoprivic diabetes. After a median follow-up of 18 (6–34) years after initial surgery, ten of 12 patients are alive, one died of metastatic pancreatic VIPoma, and one died of metastatic thymic NEN. Reoperations are frequently necessary for dpNEN in MEN1 patients, but are not associated with an increased perioperative morbidity in specialized centers. Organ-sparing resections should be preferred as initial duodenopancreatic procedures to maintain pancreatic function and avoid completion pancreatectomy.

Vasoactive intestinal polypeptide-secreting tumors (VIPomas) are rare neuroendocrine tumors that often present as watery diarrhea, hypokalemia, and achlorhydria or hypochlorhydria. In this study, we present our institutional experience of diagnosis and treatment of VIPomas, along with a review of the Chinese literature since 1980. Patient #1, diagnosed in 1984 and with intact clinical records, shows the natural history of this disease. Patient #2, diagnosed in 2015, shows the results of evaluation by nuclear medicine techniques and the outcomes of standardized treatment. Comprehensive review of 41 cases allows evaluation of clinical characteristics, treatments and outcomes of pancreatic VIPoma patients. All patients presented with watery diarrhea. The average stool volume reached 3247 mL per day. Average serum VIP level was 839.3 ng/L. Twelve of the 41 cases were reported to have metastases at diagnosis. Somatostatin receptor scintigraphy and 18FDG PET-CT are efficient methods for detection of VIPoma. Surgical excision can promptly alleviate hormonal symptoms.

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.