Vipoma (Werner-Morrison syndrome)

Vipoma is a non-bile cell tumor of pancreatic islet cells secreting vasoactive intestinal peptide (VIP), leading to a syndrome of watery diarrhea, hypokalemia and achlorhydria (WDHA syndrome). The diagnosis is established by determining the serum VIP level, tumor localization is determined by CT and endoscopic ultrasound. Treatment of the vipoma is surgical resection.

What causes Vipoma?

Of these tumors, 50-75% are malignant and some of them can be quite large (7 cm). Approximately 6% of the vipoma develops as part of multiple endocrine neoplasia.

Vipoma is a tumor of the APUD system that produces an excessive amount of the vasoactive intestinal polypeptide. In 90% of cases, the tumor is localized in the pancreas, in 10% - has an extra-pancreatic localization (in the sympathetic trunk region). Approximately half the time the tumor is malignant.

In 1958 Werner and Morrison described the syndrome of aquatic diarrhea in a patient with a non-pellular cell tumor of the pancreas. Before this disease was a variant of the Zollinger-Ellison syndrome, its atypical ulcerative form with hypokalemia. Further studies have shown that the cause of the clinical manifestations in these cases is the secretion of non-gastrin, as in patients with ulcerogenic syndrome, and the vasoactive intestinal peptide (VIP), hence the name of the tumor is Vipoma. Sometimes this disease is called pancreatic cholera or according to the initial letters of English words: water diarrhea, hypokalemia, achlorhydria - WDHA-syndrome.

More than 70% of VIPs are malignant,% of which at the time of diagnosis already have hepatic metastases. In 20% of patients, the symptom complex may be the result of hyperplasia of the islet apparatus.

Excessive secretion of VIP stimulates the expressed excretion of the small intestine and pancreas of fluid and electrolytes, which do not have time to be absorbed in the large intestine. Clinically, this is expressed by profuse diarrhea - at least 700 ml / day, often exceeding 3-5 l, which leads to dehydration. The loss of potassium, bicarbonates and magnesium contributes to the development of acidosis, severe weakness and tetanic seizures. As a result of dehydration and hypokalemic nephropathy, azotemia occurs. Approximately half of the patients have hypo- and achlorhydria. Among other manifestations of the syndrome, hyperglycemia and hypercalcemia, not associated with an elevated level of parathyroid hormone, should be noted.

Vipoma occurs with periods of remission and exacerbation. The levels of VIPs in the blood, exceeding 80 pmol / l, should always be alarming regarding the tumor nature of the disease.

VIPoma are usually large, so they are well identified by angiography or by computed tomography.

Symptoms of VIPoma

The main symptoms of vipoma include prolonged, profuse, watery diarrhea (fasting volume of the stool is more than 750-1000 ml / day, and when eating more than 3000 ml / day) and signs of hypokalemia, acidosis and dehydration. In half the cases, diarrhea is constant; in others, the severity of diarrhea changes over a long period of time. In 33%, diarrhea lasted less than 1 year before the diagnosis, but in 25% of cases it lasted more than 5 years before the diagnosis was established. Lethargy, muscle weakness, nausea, vomiting and abdominal cramps are common. Hyperemia of the face like carcinoid syndrome occurs in 20% of patients during diarrhea attacks.

The main characteristic symptoms of the vipoma are:

• massive watery diarrhea; the amount of water lost per day can be about 4-10 liters. At the same time, sodium and potassium are lost simultaneously with water. Heavy dehydration, weight loss, hypokalemia develops. Diarrhea is caused by high secretion of sodium and water into the intestinal lumen under the influence of the vasoactive intestinal polypeptide;
• pain in the abdomen of an uncertain, diffuse nature;
• oppression of gastric secretion;
• blood flushes and paroxysmal reddening of the face (due to the expressed vasodilating effect of the vasoactive intestinal polypeptide); a non-permanent symptom is observed in 25-30% of patients;
• tendency to lower blood pressure; possible severe arterial hypotension;
• the enlargement of the gallbladder and the formation of stones in it (in connection with the development of pronounced atony of the gallbladder under the influence of the vasoactive intestinal polypeptide);
• convulsive syndrome (due to the loss of a large amount of magnesium in diarrhea);
• violation of glucose tolerance (a non-permanent symptom, is due to the increased disintegration of glycogen and increased secretion of glucagon under the influence of the vasoactive intestinal polypeptide).

Troubleshooting ViPo

For diagnosis, the presence of secretory diarrhea is necessary (osmolarity of the stool almost corresponds to the osmolality of the plasma, and the double sum of Na and K concentrations in the stool determines the osmolarity of the stool). Other causes of secretory diarrhea and, in particular, abuse of laxatives should be avoided. In such patients, serum VIP levels should be measured (best during diarrhea). A significant increase in the level of VIPs suggests a diagnosis, but moderate increases can be seen in the syndrome of the small intestine and inflammatory diseases. Patients with elevated levels of VIP need to conduct research (endoscopic ultrasound and scintigraphy with octreotide and arteriography) for diagnosis of tumor localization and metastases.

Electrolytes should be determined and a general blood test performed . Hyperglycemia and a decrease in glucose tolerance are observed in less than 50% of patients. Hypercalcemia develops in half of the patients.

Diagnostic criteria of the vipoma

• duration of diarrhea not less than 3 weeks;
• daily volume of stool not less than 700 ml or 700 g;
• fasting for 3 days does not reduce the daily volume of stool less than 0.5 liters (during starvation, loss of water and electrolytes must be supplemented with intravenous administration of an isotonic solution of table salt and electrolytes);
• hypo- or achlorhydria of gastric juice;
• high content of vasoactive intestinal polypeptide in the blood;
• detection of a pancreatic tumor with computer or magnetic resonance imaging (less often sonography).

[1], [2], [3], [4], [5], [6]

The examination program for vipome

1. General analysis of blood, urine.
2. Feces analysis : coprocytogram, measurements of stool volume per day.
3. LHC: content of sodium, potassium, chlorine, calcium, magnesium, glucose, total protein and protein fractions, aminotransferases.
4. Examination of gastric secretion.
5. Sample with fasting for 3 days.
6. FEGDS.
7. Ultrasound of the abdominal cavity organs.
8. Determination of the content of the vasoactive intestinal polypeptide in the blood.
9. Computer or magnetic resonance imaging of the pancreas.

Treatment of the vipoma

First of all, transfusion of liquids and electrolytes is required. It is necessary to replenish bicarbonate in connection with the loss of it with a stool to prevent acidosis. Since there are significant losses of water and electrolytes with feces, rehydration with continuous intravenous infusions can become difficult.

Octreotide usually controls diarrhea, but it may be necessary to administer large doses of the drug. Respondents noted the positive effect of the use of octreotide prolonged action of 20-30 mg intramuscularly once a month. Patients taking octreotide should additionally take pancreatic enzymes, because octreotide suppresses the secretion of pancreatic enzymes.

Resection of the tumor is effective in 50% of patients with a localized process. When metastasizing the tumor, resection of the entire visible tumor can provide a temporary decrease in symptoms. The combination of streptozocin and doxorubicin can reduce diarrhea and tumor volume if objective improvement is observed (50-60%). Chemotherapy is ineffective.

Medicamentous and preoperative treatment of the vipoma is a massive transfusion of fluid and electrolytes, sometimes using glucocorticoids. Chemotherapy for malignant metastasizing WIPO is performed with streptozotocin. The latter to a greater or lesser degree causes remission of the process in 50% of patients.

Surgical treatment of the vipoma is effective only with a radical removal of the entire functioning tumor tissue, which is not always possible. In the absence of a tumor with obvious clinical and laboratory manifestations of the disease, distal resection of the pancreas is recommended.