A case of vasoactive intestinal peptide-secreting tumor (VIPoma) arising from MEN1 inactivation which recurred 15 years after the initial resection.

Vasoactive intestinal peptide-secreting tumors (VIPomas) are extremely rare functional pancreatic neuroendocrine neoplasms (p-NENs) characterized by watery diarrhea, hypokalemia, and achlorhydria. Here, we report the case of a 51-year-old female patient with VIPoma that recurred after a long-term disease-free interval. This patient had been asymptomatic for approximately 15 years after the initial curative surgery for pancreatic VIPoma, with no metastasis. The patient underwent a second curative surgery for the locally recurrent VIPoma. Whole-exome sequencing of the resected tumor revealed a somatic mutation in MEN1, which is reportedly responsible not only for multiple endocrine neoplasia type 1 (MEN1) syndrome but also sporadic p-NENs. Symptoms were controlled with lanreotide before and after surgery. The patient is alive with no relapse following 14 months after surgery. This case demonstrates the importance of long-term observation of patients with VIPoma.

VIPoma: an unsuspecting culprit of severe secretory diarrhoea in a human immunodeficiency virus-infected patient.

A 35-year-old man with known human immunodeficiency virus experienced chronic diarrhoea for 18 months. He presented to multiple hospitals with profuse secretory diarrhoea and life-threatening electrolyte disturbances. Infectious and non-infectious aetiologies were considered, with focussed history and investigations ultimately leading to a diagnosis of VIPoma. Initiation of somatostatin analogue therapy followed by surgical resection led to complete resolution of symptoms and markedly improved quality of life.

[VIPoma of the Pancreas]. / VIPom des Pankreas.

VIPoma of the Pancreas Abstract. A 50-year old man was admitted for evaluation of progressive, chronic diarrhea with loss of weight and recurrent hypokalemia. Eventually, a neuroendocrine tumor of the pancreas secreting VIP (VIPoma) could be diagnosed. The patient was cured by a pancreaticoduodenectomy (Whipple procedure). With this case, we want to highlight the importance of a structured work-up in chronic diarrhea including thorough history and clinical assessment, laboratory tests and imaging studies.

Percutaneous Cryoablation of Recurrent Pancreatic Mass for Life-Threatening Pancreatic VIPoma Syndrome: A Case Report.

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.

Successful Treatment of Hypokalemic Rhabdomyolysis Caused by a Pancreatic VIPoma: A Case Report.

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.

Life-threating diarrhea and acute renal failure secondary to pancreatic VIPoma treated by surgery.

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.

Clinicopathological data and treatment modalities for pancreatic vipomas: a systematic review.

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.

Perioperative Hypotensive Crisis in an Adolescent with a Pancreatic VIPoma and MEN1-Gene Variant.

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.

[A Surgical Resected Case of VIPoma with Para-Aortic Lymph Node Involvement].

A 72-year-old woman had severe watery diarrhea and weight loss. Computed tomography demonstrated a 55mm tumor in pancreatic tail with enlargement of para-aortic lymph nodes. There was no apparent liver metastasis. Endoscopic ultrasound demonstrated a well-circumscribed heterogenous tumor, which was diagnosed neuroendocrine tumor by endoscopic ultrasound-guided fine needle aspiration biopsy. For suspected VIPoma with para-aortic lymph node involvement, distal pancreatectomy and para-aortic lymphadenectomy was performed. The tumor was diagnosed as VIPoma by immunohistochemistry. The diarrhea improved after surgery. No evidence of recurrence was detected after a follow-up of 11 months.

Pancreatic Neuroendocrine Tumor Secreting Vasoactive Intestinal Peptide and Dopamine With Pulmonary Emboli: A Case Report.

CONTEXT: The vasoactive intestinal peptide-secreting neuroendocrine tumor (VIPoma) is a very rare pancreatic tumor. We report the first case of a patient with VIPoma that co-secreted dopamine and had pulmonary emboli. CASE DESCRIPTION: A 67-year-old woman presented with 2 months of watery diarrhea, severe generalized weakness,6.8 kg of weight loss, a facial rash, and hypokalemia. Colonoscopy did not reveal the cause of the chronic diarrhea. Initial biochemical testing showed markedly elevated serum vasoactive intestinal peptide (VIP) and pancreatic polypeptide. Computed tomography scan of the abdomen and pelvis revealed a 5.4-cm distal pancreatic mass. Octreoscan showed an intense uptake in the area of the pancreatic mass. Incidental pulmonary emboli were found and treated. Additional biochemical testing revealed a markedly elevated urinary dopamine level. The patient received preoperative α-blockade and octreotide. She underwent a successful laparoscopic distal pancreatectomy. Postoperative urinary dopamine and pancreatic polypeptide were within normal limits. Serum VIP decreased by half but remained elevated. Pathology confirmed a grade 1 pancreatic neuroendocrine tumor without lymph node metastasis. The patient's symptoms resolved and no longer required octreotide. Metastatic workup including computed tomography, F18-fluorodeoxglucose positron emission tomography, and Ga68-DOTATATE scans were negative during 4 years of follow-up. CONCLUSIONS: VIPoma is a rare subtype of pancreatic neuroendocrine tumor that can secrete dopamine and can be associated with thromboembolism.

Ventricular fibrillation resulting from electrolyte imbalance reveals vipoma in MEN1 syndrome.

Sporadic VIPoma is an exceedingly rare tumor with an annual incidence of 1:10 million people worldwide, yet it is described in approximately 5 % of MEN1 patients. The majority of VIPomas are malignant and radical surgery is the best therapeutic option. A 58-year-old man presented with cardiocirculatory arrest due to ventricular fibrillation. The patient had a 3-month history of epigastric pain with diarrhea. After reanimation, laboratory data revealed severe hypokalemia and hypercalcemia. Further investigations showed hyperparathyroidism, left adrenal adenoma and pituitary microprolactinoma and genetic diagnosis of MEN1 syndrome was made. Abdominal computed tomography revealed a 45 × 30 mm mass of the pancreatic head and two hepatic lesions, which proved to be neuroendocrine after 68 Ga PET and needle biopsy. Vasoactive intestinal peptide (VIP) serum level had increased. Subsequently the patient underwent pylorus-preserving pancreaticoduodenectomy and hepatic resection. Intraoperative VIP returned to normal values. Histopathology confirmed a pancreatic VIPoma metastatic to the liver. The postoperative course was unremarkable and the patient is well with no evidence of disease at a 48 months follow-up. Even in case of anusual presentation, when two or more main clinical findings of MEN1 related tumors are present, unrespectively to the presence of MEN1 mutation, MEN1 syndrome should be suspected. Surgery in MEN1 pancreatic neuroendocrine tumors is indicated both to treat symptoms and to avoid oncological progression even in advanced cases.

VIPoma with multiple endocrine neoplasia type 1 identified as an atypical gene mutation.

A 47-year-old man presented with persistent diarrhoea and hypokalaemia. CT revealed 4 pancreatic tumours that appeared to be VIPomas, because the patient had an elevated plasma vasoactive intestinal polypeptide level. MRI showed a low-intensity area in the pituitary suggestive of a pituitary tumour, and a parathyroid tumour was detected by ultrasonography and 99Tc-MIBI scintigraphy. Given these results, the patient was diagnosed with multiple endocrine neoplasia type 1 (MEN1) and scheduled for surgery. MEN1 is an autosomal dominant disorder associated with MEN1 mutations. Genetic testing indicated that the patient had a MEN1 gene mutation; his 2 sons had the same mutations. Most MEN1 tumours are benign, but some pancreatic and thymic tumours could become malignant. Without treatment, such tumours would result in earlier mortality. Despite its rarity, we should perform genetic testing for family members of patients with MEN1 to identify mutation carriers and improve the patients' prognosis.

Intractable and dramatic diarrhea in liver transplantation recipient with vasoactive intestinal peptide-producing tumor after split liver transplantation: a case report.

Diarrhea after liver transplantation is a common complication. Vasoactive intestinal peptide-producing tumor (VIPoma) is a rare cause of watery diarrhea; 80% of such tumors occur in the pancreas, but it is rare in liver. Hypersecretion of vasoactive intestinal polypeptide can stimulate intestinal water and electrolyte secretion, and patients with VIPoma present with watery diarrhea, hypokalemia, and dehydration. Here we report on a 50-year-old man who presented with a 7-month history of watery diarrhea. He had undergone an orthotopic split-liver transplantation for hepatocellular carcinoma in November 2011. Two months after the liver transplantation, he presented with watery diarrhea, dehydration, and hypokalemia. Antibiotics, immunosuppressive drugs modification, antidiarrheal agents, antispasmodics, adsorbents, and fasting were alternately used to control the diarrhea, but his symptoms remained unchanged. A chromogranin examination, a marker of pancreatic neuroendocrine neoplasm, was positive in the third month of the diarrhea history and VIPoma was considered. Treatment with somatostatin immediately controlled the diarrhea, but the primary lesion could not be identified even after corresponding examinations were completed. In the ninth month of diarrhea, a 1 × 1-cm lesion was detected in the right liver by ultrasonography. Radiofrequency ablation was performed, and the diarrhea stopped. Seventeen months later, the chromogranin level decreased to normal and the patient was asymptomatic. Neither the recipient sharing the other liver portion nor the donor presented with any symptoms, so we wondered how the tumor occurred. It is possible that a small VIPoma lesion existed in the liver donor before the transplantation, and that the immunosuppressive drugs induced tumor development.

[Diagnosis and surgical treatment for pancreatic vasoactive intestine polypeptide tumor].

OBJECTIVE: To explore the diagnosis and surgical treatment for pancreatic vasoactive intestine polypeptide tumor (VIPoma). METHODS: Clinical data of 7 patients with VIPoma from Xiangya Hospital, Central South University between January 1990 and July 2011 were collected and analyzed retrospectively. RESULTS: The different operation modes were selected according to the location of VIPomas, and the postoperative symptoms of all 7 patients were gradually relieved and cured. The follow up showed that life spans of the above-mentioned patients were 3-6 years. CONCLUSION: The incidence of pancreatic VIPoma is low but it is easy to misdiagnose. The excision for the tumor is the most effective therapy. Combining with somatostatin, intervention and other effective strategies, the life quality of patients can be improved and long-term survival may be achieved.

Sporadic pancreatic vasoactive intestinal peptide-producing tumor (VIPoma) in a 47-year-old male.

VIPoma is an exceedingly unusual neuroendocrine neoplasm that autonomously secretes vasoactive intestinal polypeptide (VIP). Its reported incidence is approximately 1 per 10 million individuals per year. Herein, we report the case of sporadic pancreatic VIPoma in a 47-year-old male who presented with a six-month history of chronic, plentiful, watery diarrhea. On physical examination, the patient looked sick, lethargic and had signs of dehydration. Laboratory investigations revealed high VIP hormone level (989pg/mL), hypokalemia, hypercalcemia, hyperglycemia, high blood urea nitrogen, high creatinine, and metabolic acidosis on arterial blood gas. Contrast-enhanced computed tomography (CT) scan showed a 3.1×3.3×4.7cm, well-defined, enhancing lesion involving the pancreatic tail with a cystic component. Moreover, a 5.7×6.1×6.8cm metastatic hepatic lesion was identified. The patient underwent distal pancreatectomy with splenectomy, hepatic lesion resection, and lymph node dissection. Histopathological and immunohistochemical examination of the pancreatic and hepatic lesions revealed neuroendocrine tumor (VIPoma). Postoperatively, the patient received radiofrequency ablation for the hepatic lesion. A post-operative six-month follow-up showed significant symptomatic relief, reduced VIP hormone level (71pg/mL) and normalized electrolyte and acid-base profiles. However, a magnetic resonance imaging (MRI) scan showed a small residual metastatic liver lesion which was considered for hepatic artery embolization (HAE). The patient is still alive with a residual hepatic disease at 18months. We also present a brief literature review on VIPoma.

[New considerations in the surgical treatment of pancreatic neuroendocrine tumours]. / A hasnyálmirigy neuroendokrin tumorok sebészi kezelésének újabb szempontjai.

Except insulinomas, pancreatic neuroendocrine tumours are malignant in more than 50% of cases. Treatment of these tumours should be directed against the tumours and the excess of hormones produced by the tumours. Surgical treatment may reduce the mortality and morbidity of patients and, in case of localized lesions, may result in a definitive cure. The aim of this review is to summarize novel developments in the surgical treatment of pancreatic neuroendocrine tumours, including those related to metastatic diseases and MEN1 syndrome.

The current management of pancreatic neuroendocrine tumors.

PanNETs constitute a rare and heterogeneous group of pancreatic neoplasms whose overall prognosis is better than the more common pancreatic adenocarcinoma. Although surgery is the only treatment that provides a cure, many adjuvant therapies have been explored with some new, exciting, targeted therapies just approved for PanNETs. With growing interest in this type of neoplasm, an increasing number of clinical trials and natural history studies should shed light on the best management for these patients.