Glucagonoma of pancreas GCGN is an epidemiology: islet A cell tumor (tumor cells secrete excessive amounts of glucagon). This disease is extremely rare, accounting for 1% of neuroendocrine tumors, with an annual prevalence of 0. 01/100,000 to 0. 1/1 million, age of onset 50D60 years, slightly more women than men, and more common in menopausal women. Most of the tumors are located in the tail of the pancreas (1/2), 1/4 in the body of the pancreas, and less in the head of the pancreas, most of them are malignant (68%), and any skin mucosal damage during the course of the disease often suggests malignancy. Malignant disease progresses slowly, at least one year, and the average time from onset to definitive diagnosis is 5 years. It is usually solitary, with a diameter of 1.5 to 3 cm and a maximum of 5 cm or more. About 70% of the tumors have metastasized during the time of diagnosis Common metastatic sites are liver (mostly cystic solid) and local lymph nodes, followed by bone, lung, and adrenal gland.
History: Becker et al. first described this disease in 1942 and recognized that the tumor originated from pancreatic islet A cells. 1966 McGavran
In 1966, McGavran measured serum glucagon by radioimmunoassay and reported the first case of glucagonoma. In 1971, Wilkinson first used the name necrolytic migratoryerytherma (NME) to describe the skin manifestations of patients with glucagonoma. In 1974, Mallision named a series of typical symptoms (such as mild diabetes mellitus, migratory necrolytic dermatitis, linguitis, stomatitis, anemia and loss of body mass) produced by glucagonoma as glucagonoma syndrome.
Pathology: The tumor tissue secretes a large amount of glucagon (requiring zinc participation), causing excessive catabolism of carbohydrates, proteins, fats and other nutrients, resulting in nutritional disorders. By activating liver phosphorylase to promote glycogenolysis, it can raise blood glucose. In addition, glucagon inhibits the exocrine secretion of the pancreas, thereby inhibiting the secretion and release of pancreatic enzymes, which can also elevate blood glucose and manifest as diabetes. Types: (1) GCGN with skin syndrome, with typical necrotizing erythema (2) GCGN without skin syndrome, with only mild diabetes mellitus and elevated serum glucagon concentration (3) GCGN with multiple syndromes.
IV. Clinical manifestations:GCGN syndrome (glucagonoma syndrome, GCGNS) or quadruple syndrome
(1) Necrolytic loosening wandering erythema (NME) is the most characteristic skin manifestation of glucagonoma syndrome, and the incidence of skin lesions is 68%-90%. The mechanism of occurrence may be: 1) elevated glucagon promotes catabolism and gluconeogenesis, resulting in hypoaminoacidemia and skin malnutrition; 2) tumor synthesis of large amounts of glucagon requires large amounts of zinc consumption; 3) elevated glucagon induces epidermal production of large amounts of arachidonic acid and its products causing inflammatory skin damage. Therefore, the skin lesions can be effectively treated by controlling blood glucose and intravenous infusion of multiple amino acids as well as zinc supplementation. The lesions are found on the trunk or on areas prone to pressure and friction. They begin as erythematous patches, followed by blistering, central necrosis, oozing, and scabbing. As the edges spread outward, the center begins to heal and the scabs eventually fall off, leaving pigmentation. The whole body lesion changes from one to another, recurrent, often co-existing erythema, blistering, crusting, pigmentation and other forms, patients often come to the first consultation because of skin diseases, easier to misdiagnose, dermatological diagnosis: 1 eczema 2 herpes-like dermatitis 3 class aspergillosis
(2) diabetes mellitus, due to hyperglycemia and glucagon stimulation of pancreatic islet B cells to secrete increased insulin, so the symptoms of diabetes mellitus are mostly mild, and generally do not occur ketoacidosis, so it is easy to misdiagnose as type II diabetes mellitus.
(3) Wasting 90% of the patients lose more than 5kg, accompanied by malnutrition, hypoproteinemia and severe reduction of plasma amino acid level. The reasons are 1) glucagon inhibits digestive secretion, resulting in digestion and malabsorption; 2) primary tumor foci and metastases grow and consume; 3) very few of them combine with amine and amine precursor uptake and other endocrine tumors of decarboxylation system, which affect protein and fat metabolism.
(4) Anemia manifests as weakness, discomfort, pale conjunctiva, etc. There may also be obvious hepatosplenomegaly. This anemia is a normal pigmented normocytic anemia and the patient’s serum iron, vitamin B12 and folic acid saline are normal on average. Reasons: 1) The pro-catabolic effect of glucagon causes blood amino acid deficiency and malnutrition; 2) The late wasting effect of malignant disease; 3) Glucagon may have the effect of inhibiting red blood cell production.
(5) 30% of patients may eventually develop thrombotic lesions, mainly deep vein thrombosis and pulmonary embolism, but also cerebral artery and renal artery thrombosis have been reported. About 50% of deaths are attributed to this.
(6) Other conditions such as: 1) tongue inflammation, stomatitis, oral pain as a result of damage to the oral mucosa, the incidence is about 30%; 2) about 20
percent of patients develop psychiatric and neurological symptoms, such as depression, dementia, agitation, sensory hypersensitivity, insomnia, ataxia or muscle weakness; 3) gastrointestinal symptoms such as diarrhea, anorexia, usually without nausea, vomiting; 4) diabetic symptoms.
V. Auxiliary tests
1 The normal range of serum glucagon measured by radioimmunoassay is 50-150 pg/ml, and generally exceeds 1000 pg/ml in GCGN, but glucagon can also be mildly elevated, not exceeding 500 pg/ml in renal failure, burns, bacteremia, Cushing’s syndrome, hypoglycemia, liver failure and severe stress.
2 B ultrasound and CT are the first choice for tumor and metastasis localization, and MRI is also commonly used.
3 Selective visceral arteriography (abdominal aortography) has become the gold standard for the diagnosis of glucagonoma and is an invasive test. It shows high blood supply lesions.
4 CT-guided fine-needle aspiration biopsy, which is the most accurate, is not commonly used in clinical practice because of the complexity and invasiveness of the operation.
5 Blood amino acid profile analysis shows a general decrease in amino acid concentration 6 Serum protein level, blood glucose, urine glucose, blood routine, coagulation function, cholesterol, blood potassium, calcium level, CEA, CA199.
VI. Diagnosis
1. NME 2. Serum glucagon (<1 000 pg/ ml) 3. Imaging 4.
Characteristic secretory granules can be seen on electron microscopy, but some tumors contain a large number of atypical granules. Therefore, electron microscopy is not significant to identify what kind of endocrine tumor. 5. Immunohistochemistry shows that the tumor is positive for anti-insulin serum. It can be the most effective method for diagnosis and differential diagnosis. 6. Postoperative pathology.
VII. Treatment
1 Drugs 1) Growth inhibitors to inhibit secretion of islet alpha cells and reduce serum glucagon levels 2) Amino acid and fatty acid protein nutritional support 3) Hypoglycemic agents 4) Hormonal symptomatic treatment of NME 5) Oral zinc 6) Prophylactic use of anticoagulants to prevent thrombosis.
2) Surgery is the only way to cure GCGN, either pancreatic tail or pancreaticoduodenectomy.
3 Chemotherapy generally uses streptozotocin, azulfiram, 5-FU, etc. Some literature reports that azulfiram has better efficacy.
There are foreign reports of total pancreatectomy and liver transplantation.
5, tumor vascular embolization (TACE).
VIII. Prognosis
If treated properly, most patients have a good prognosis, with a survival period of about 3-7 years or even longer. Many patients finally die not from the tumor itself, but from complications, the most common being thrombosis, sepsis and gastrointestinal bleeding.