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AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Luigi Santacroce, MD, Department of Dentistry and Surgery, Section of General Surgery, Assistant Professor, Medical and Dentistry School, State University at Bari, Italy
Coauthor(s):
Silvia Gagliardi, MD, Consulting Staff, Department of Surgery, Medical Center Vita, Italy;
Mini R Abraham, MD, Consulting Staff, Midwestern Endocrinology, PA
Editors: Frederick H Ziel, MD, Chief of Endocrinology, Kaiser Permanente Woodland Hills, Associate Professor, Department of Internal Medicine, Division of Diabetes and Endocrinology, University of California at Los Angeles; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Romesh Khardori, MD, Chief, Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Professor, Southern Illinois University School of Medicine; Mark Cooper, MD, Head, Vascular Division, Baker Medical Research Institute; Professor of Medicine, Monash University; George T Griffing, MD, Professor of Medicine, Director of General Internal Medicine, St Louis University
Author and Editor Disclosure
Synonyms and related keywords:
alpha-cell tumor, alpha-cell adenoma, 4D syndrome, neuroendocrine tumor, islet cell pancreatic tumor, glucagon overproduction, diabetes mellitus, hypoaminoacidemia, weight loss, normochromic and normocytic anemia, necrolytic migrating erythema, NME, hyperglucagonemia, pancreas, octreotide, Sandostatin, peptide hormone, bioactive peptide, tumor of the pancreas, multiple endocrine neoplasia type 1, MEN I, islet cell tumor
Background
Glucagonoma is a rare neuroendocrine tumor with nearly exclusive pancreatic localization. Malignant glucagonomas are islet cell pancreatic tumors that are discovered because of the glucagonoma syndrome, because of local mass effects, or incidentally. Glucagonomas originate from the alpha2 cells of the pancreas. In 1942, Becker et al first described glucagonomas. Fewer than 250 cases of glucagonomas have been described in the literature. Unregulated production (overproduction) of peptide hormones and growth factors, which are not normally expressed in the tissue of origin, is characteristic of neuroendocrine tumors. Abnormal production of these bioactive peptides can lead to significant systemic toxic consequences and the promotion of further tumor growth. The origin of this pathology remained unknown until 1966, when McGavran assessed the radioimmunoassay (RIA) technique for glucagon. In 75-80% of cases, the glucagonoma starts in malignant form, and in 50% of these cases, metastasis exists at diagnosis. This tumor is characterized by glucagon overproduction, diabetes mellitus, hypoaminoacidemia, weight loss, normochromic and normocytic anemia, and a necrolytic migrating erythema (NME), which is the most characteristic clinical sign of this pathology. NME presents as a phlogistic damage of tissues in areas exposed to friction and pressure. Another feature of the syndrome that is noteworthy is the high rate of thromboembolic complications and consequent pulmonary embolisms; this is dangerous for many patients who can succumb to it. The correct recognition of NME is really important, because it may allow early detection either of glucagonoma or of extra-pancreatic glucagon-secreting tumors.
Glucagonomas not associated with the syndrome are diagnosed in various ways. The tumor may appear as a malignant pancreatic tumor discovered because of local growth, with or without metastases, or the tumor may be associated with insulinoma or gastrinoma. Glucagonoma may also occur as a single microadenoma found incidentally at autopsy in elderly patients. Glucagonoma very rarely is a member of multiple endocrine neoplasia type 1 (MEN I) syndromes, and, in such cases, it appears as a single lesion and is biologically inactive. Similar to other islet cell tumors, the primary and metastatic lesions are slow growing.
However, it is noteworthy that some cases of NME without glucagonoma have been reported. The role of hyponutrition, especially vitamins and minerals, has been suggested to be responsible of differentiation/proliferation modifications of keratinocytes in such patients.
Pathophysiology
Although the relationship between hyperglucagonemia and necrolytic migrating erythema is not clear, elevated glucagon serum levels can be found at the same time as this cutaneous manifestation of the disease. Glucagon is a peptidic hormone mostly produced from alpha2 cells of the pancreas and, in smaller amounts, from amine precursor uptake and decarboxylation (APUD) cells in gastric and duodenal mucosa. Three known forms of this hormone exist. The pancreatic form contains 29 amino acids and has a molecular weight of 3485 daltons; the gastric form contains 29 amino acids and has a molecular weight of 3500 daltons; and the enteric form, or enteroglucagon, contains a polypeptidic chain, has a high molecular weight, and is biologically and chemically different from other hormones but cross-reacts with them. Glucagon is secreted under the influence of various factors. The most important of these factors is the reduced blood concentration of glucose. Acetylcholine and catecholamines elevate serum levels of glucagon and somatostatin, and serotonin reduces these levels. Physiological glucagon activity includes (1) glycogenolysis activation with contemporary glycolysis inhibition and activation of the gluconeogenesis; (2) stimulation of lipolysis and catecholamines secretion; (3) inhibition of the gastric secreting activity, the pancreatic secreting activity, and the gastrointestinal motility; and (4) the stimulation of urinary excretion of water and phosphates as well as sodium, calcium, and magnesium ions. When glucagon production is due to a secreting tumor, it becomes independent and loses the feedback control mechanisms, and the subsequent increase of glucagon concentration in the blood causes the symptoms. Diabetes mellitus occurs in patients with glucagonoma because of the lack of equilibrium between insulin production and glucagon production, which occurs when high serum levels of glucagon and normal levels of insulin exist or when insulin production is reduced and a normal glucagon level is present. However, glucagon may not induce hyperglycemia directly unless metabolism of glucose by the liver is compromised directly. Another factor affecting glucagon secretion may be variation in the molecular species of glucagon that is present in each case and the biological potency of these molecular species of glucagon. Weight loss is due to the action of glucagon on the lipid and protein metabolism, increased caloric expenditure determined from the proteic catabolism, and the consequent increase of gluconeogenesis and ureagenesis. This mechanism is probably also responsible for the cases of anemia and hypoaminoacidemia observed in patients with glucagonoma. Thromboembolism, occasionally observed in patients, is attributable to the production of a molecule similar to coagulative factor X from tumoral cells. Although many theories about the pathogenesis of necrolytic migrating erythema exist, the process of pathogenesis is not explained with certainty. According to one of these theories, necrolytic migrating erythema can be caused by a tryptophan loss in cutaneous tissues because of the excess circulating glucagon; the amino acid tryptophan is responsible for niacin (PP or pellagra prevention vitamin) function, which regulates cell turnover, capillary tone, and maturation of the epidermis and mucosal epithelia.
According to another theory, necrolytic migrating erythema is related to the hypoalbuminemia due to glucagon excess; in fact, albumin acts as a carrier for essential fatty acids and zinc. This mineral carries out a fundamental role in the maintenance of the cutaneous trophism. Also, the mineral is responsible for the linoleic acid desaturation and, therefore, is involved in the prostaglandin synthesis, which could determine phlogistic damage of tissues in areas exposed to friction and pressure if it occurs in excess. necrolytic migrating erythema may also occur in areas of cutaneous trauma.
Frequency
International
Glucagonoma is a rare pathology. Incidence is probably 1% of all neuroendocrine tumors. From 1942, approximately 250 cases are described in the literature. Incidence of this pathology is estimated on an annual basis, with 1 case occurring in every 20 million people. This number is probably an underestimation of the actual occurrence because of the relative lack of specificity of the symptoms. An additional factor contributing to this underestimation is the time during which the tumors are clinically silent.
Mortality/Morbidity
Glucagonoma is a tumor with a slow rate of growth. Most of the cases start with nonspecific symptoms. In a report of patients with functional pancreatic tumors, the average delay of diagnosis was 3 years. Approximately 50% of cases have metastases at diagnosis. For patients with metastases at diagnosis, the prognosis is poor.
- The rate of survival after 5 years is not determined because of the small number of cases; however, a study reports an average survival time of 3.7 years in a group of 12 patients and of 4.9 years in a different group of 9 patients.
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- Like other islet cell neoplasms, glucagonoma may overproduce multiple hormones, and all of these can have clinical manifestations. Insulin is the second most common hormone secreted by these tumors. Others include (in order of frequency) adrenocorticotropic hormone (ACTH), pancreatic polypeptide, or parathyroid hormone (PTH) or substances with activity similar to PTH, such as gastrin, serotonin, vasoactive intestinal polypeptide (VIP), and melanocyte-stimulating hormone (MSH).
Race
No racial prevalence is known.
Sex
Frequency in males and females is nearly equal, although a greater frequency is reported in females.
Age
Most patients with glucagonoma are in the sixth decade of life, with a mean age of 55 years and an age range of 19-84 years.
History
- Glucagonoma initially manifests with a nonspecific clinical scenario characterized, in most cases, by weight loss, diabetes mellitus, diarrhea, and stomatitis.
- The cutaneous lesions in this phase of the disease can easily be confused with nonspecific dermatitis, which occurs more often in patients with diabetes mellitus.
- Sometimes, poorly defined symptoms of this condition make it difficult to establish a correct differential diagnosis (eg, with a pancreatic adenocarcinoma that causes weight loss, the early stages of dyspepsia, and the later stages of jaundice).
Physical
- The most frequent clinical sign observed in patients with glucagonoma is necrolytic migrating erythema (NME), which is present in 80% of cases and is characterized by an erythematous and swollen area of skin.
- The symptoms that appear on the skin (in order of appearance) include maculopapular, ringed lesions and blisters that breach after a few days, and pustular evolution due to bacterial superinfection is possible. These lesions are often confluent, evolve in a period of 1-2 weeks, and are strongly pruritic and painful. They heal with hyperpigmentation.
- Initially, necrolytic migrating erythema occurs in areas of the skin that are subject to friction and pressure, such as the feet and legs, hands and forearms, buttocks, pubic area, groin area, and perineal area. Frequently, mucocutaneous lesions are observed as atrophic glossitis, commissural cheilitis, stomatitis, balanoposthitis or vulvovaginitis, and ungual and hair dystrophies.
- Beyond necrolytic migrating erythema, other symptoms often observed in glucagonoma are diabetes or glucose intolerance in 80-90% of cases and weight loss of 5-15 kg in most patients.
- Other symptoms that occur less frequently are venous thromboses (in approximately 40% of cases); intestinal motility alterations with diarrhea and abdominal pains (in approximately 20% of cases); anemia; scotomata and other optical disturbances; and psychical disturbances, eg, insomnia, depression, disorientation, lethargy, and bradylalia.
Causes
Causes of this pathology remain unknown, although some genetic factors could play an important role, especially in patients who have a family history of multiple endocrine neoplasia type 1 (MEN I) or Wermer syndrome.
Cirrhosis
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Paraneoplastic Syndromes
Other Problems to be Considered
Acrodermatitis enteropathica
Bacteremia
Burn injury
Essential fatty acid deficiency
Herpetic dermatitis
Kwashiorkor
Psoriasis
Pellagra
Renal failure
Zinc deficiency
Prolonged fasting
Hepatic failure
Use of danazol or oral contraceptive
Lab Studies
- Determining the level of glucagonemia by means of radioimmunoassay (RIA) test is mandatory. A positive test result for glucagonoma exceeds 1000 pg/mL (reference range is 50-200 pg/mL).
- Performing a fasting blood sugar, the glucose tolerance test, or both in order to establish the presence of diabetes is important.
- A CBC with differential count is important to evaluate the presence of anemia.
- Because some cases of glucagonoma can rarely be a part of multiple endocrine neoplasia type 1 (MEN I) syndrome, also check serum levels of fasting insulin, glucagon, prolactin, calcium, and VIP.
- Performing a study of the nutritional status of the patient is important to correct nutritional deficits; this test must evaluate the level of serum concentration of amino acids, zinc, and essential fatty acids.
- Determining the level of transaminases, bilirubinemia, and alkaline phosphatase is important in order to detect hepatic metastases.
- Recently, the serum level of chromogranin A has been proposed to be a type of sensitivity marker, although nonspecific, in determining the presence of glucagonoma.
- Stimulating tests with arginine, secretin, or tolbutamide, which rapidly stimulate plasmatic glucagon levels in patients affected by glucagonoma, are of little additional help.
- The detection of telomerase and the quantification of human telomerase reverse transcriptase protein subunit (hTERT) have been recently proposed to distinguish clinically benign from malignant endocrine tumors. In the reported cases, primary endocrine malignant tumour showed telomerase activity, and quantification of hTERT mRNA has been used in clinical practice to exclude malignancy.
Imaging Studies
- In patients with functioning islet cell tumors, the radiologist must localize the lesion.
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- Knowing the tumor size and location, especially with hepatic metastases, is fundamentally important when deciding treatment.
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- As with other endocrine tumors of the pancreas, the diagnosis requires localization by one of several modalities, including angiography, CT scan, or MRI study.
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- The selective angiographic study of the coeliac tripod localizes with high reliability the center of the tumor, which usually appears as a hypervascular prominent area, and simultaneously characterizes hepatic metastases.
- The CT scan and MRI study of the pancreas help to characterize the precise site of the tumor (usually localized in the pancreatic tail in 86-88% of cases) that in 95% of cases appears as a single mass of diameter that varies from 1-30 cm.
- Abdominal CT scan is helpful to localize the tumor and metastatic disease. Thus, the combination of CT scan and angiography provides an acceptable preoperative assessment.
- MRI is useful in characterizing islet cell tumors, which have marked increased signal intensity on T2-weighted images. Gadolinium enhancement in the nonnecrotic or nondegenerated areas of the tumor shows a characteristic pattern that allows differentiation of islet cell tumors from the more common pancreatic adenocarcinoma, which is hypovascular and has a lower signal intensity on T2 images.
- Metaiodobenzylguanidine (MIBG) scintigraphy may be helpful in detecting the primary tumor.
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- Recently, the positron emission tomography (PET) technique and scintigraphic study with indium In 111 octreotide (In-111-D-PHE1-octreotide) or with 11C-L-dopa have been used, but, because of the small number of patients with glucagonoma, estimating the real reliability of these imaging techniques is not possible. However, because the lymph node metastasizes and the primary tumor in the pancreatic tail cannot be observed with ultrasound, CT scan, or angiography, this diagnostic tool might only be useful in selected patients. Practically all glucagonomas studied have been somatostatin receptor positive.
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- Endoscopic ultrasound is another useful modality that can be used in early localization of the tumor.
Procedures
- Correctly performing a biopsy of the skin during an advanced phase of the disease allows for a diagnosis of necrolytic migrating erythema. Different stages of the cutaneous lesions may be present simultaneously. Performing repetitive, multiple, and random sampling of the lesions is very helpful for diagnosis.
- Based on radiological features, a Tru-cut biopsy or laparotomy could be performed in order to obtain histologic samples.
Histologic Findings
Usually, glucagonomas arise from alpha2 cells of the pancreatic islets and grossly appear as a single mass. In approximately 80% of cases, glucagonoma is a carcinoma, and it is an adenoma in 20% of cases. Although the tumor is more frequently localized in the tail of the pancreas, finding it in other areas of the organ is not rare. Glucagonoma is rarely found in a gastric or duodenal location. The tumor appears as a solid mass that is well demarcated from the surrounding parenchyma and capsulated, with a rich vascular network that differentiates it from pancreatic adenocarcinomas. The tumor cells are occasionally organized in nests and strands and appear strongly glucagon-positive on immunohistochemical staining. Recently, a strong cellular affinity for beta-cellulin, a new member of the family of epidermal growth factors (EGFs), has been reported. Electron microscopy shows secretory granules and an extended rough endoplasmic reticulum (RER).
Small blisters seem to be the basic damage to the skin and contain acantholytic epidermal cells, neutrophils, and lymphocytes. The surrounding epidermis is usually intact, and the dermis contains a lymphocytic perivascular infiltrate. Skin samples from the areas with early necrolytic migrating erythema show lymphocytic infiltration of the dermis, while examination of the epidermis shows focal dyskeratosis and lymphocytes. Later, lymphocytic infiltration of the dermis with neutrophils and eosinophils can be found, while the epidermis shows diffuse parakeratosis, acanthosis, loss of the granular layer, and necrosis of the superficial layers.
Staging
No detailed or generally accepted staging system for glucagonoma exists.
Medical Care
Currently, active drugs used to treat glucagonoma do not exist, although some drugs can cause partial regression of a neoplastic mass or improvements in the symptoms of necrolytic migrating erythema.
- In the literature, good results are obtained with doxorubicin and streptozotocin (5-fluorouracil [5-FU] and streptozotocin) via selective damage of islets cells.
- Long-acting octreotide, analogous to human somatostatin, causes necrolytic migrating erythema (NME) symptom regression in some patients and not in other patients.
- Remission of glucagonoma through treatment with dacarbazine is described in a single patient.
Surgical Care
Once a glucagonoma is identified, optimal management is surgical resection, which is the only curative therapy.
- In some patients, removal of the tumor may reverse symptoms.
- Patients with liver metastases and severe symptoms caused by tumor bulk or hormone-release syndromes may benefit from procedures that reduce hepatic arterial blood flow to metastases, including hepatic arterial occlusion with embolization or with chemoembolization that causes a necrosis of the metastases without damaging the healthy hepatic parenchyma, which is supplied from the portal circulation. This treatment may also be combined with systemic chemotherapy in selected patients.
- Multimodal therapeutic interventions including liver transplantation are reported, but the results need further studies to confirm and validate such time and cost expensive procedure.
- Beyond neoplasm removal, resect healthy surrounding parenchyma and locoregional lymph nodes, which can occasionally be metastatic or, more rarely, the primary site of the tumor.
- Several authors have reported clinical palliation of symptoms from surgical debulking of the tumor.
Consultations
Mucocutaneous lesions, endocrine disturbances, and optical and psychical disturbances may be very helpful for differential diagnosis, therapy, and needed consultations (from dermatologists, neurologists, endocrinologists, and ophthalmologists).
Diet
In patients with glucagonoma, providing a supplemental protein supply in order to furnish amino acids is useful. This can be administrated intravenously in the more severe cases. Essential fatty acids (ie, administering olive oil), zinc, vitamins, and minerals are also helpful.
Activity
Mild exercise is usually not harmful in patients with glucagonoma.
Worldwide, the only drug considered for the treatment of glucagonomas is octreotide. Antiproliferative drugs may be useful for patients with diffuse metastases to palliate symptoms.
Drug Category: Antisecretory agents
Include drugs with a multitude of endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides.
| Drug Name | Octreotide (Sandostatin) |
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| Description | Synthetic analog of the hypothalamic peptide somatostatin that inhibits the secretion of both pituitary and GI hormones, inducing an increase of intestinal absorption of water and electrolytes, a decrease in pancreatic and gastric acid secretions, and a delay of intestinal transit time. Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion, and has a multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides. |
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| Adult Dose | 100 mcg SC tid/qid
Administer IV over 5 min in emergencies |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers may need dosage adjustments |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | Adverse effects are primarily related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counter-regulatory hormones (ie, insulin, glucagon, GH), hypoglycemia or hyperglycemia may be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; because of inhibition of TSH secretion, hypothyroidism may also occur; exercise caution in patients with renal impairment; cholelithiasis may occur |
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Drug Category: Antineoplastic agents
Inhibit cell growth and differentiation.
| Drug Name | Doxorubicin (Adriamycin, Rubex) |
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| Description | May be helpful for palliation of symptoms for patients with progressive disease. Dosage is related to body surface area. |
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| Adult Dose | 60-75 mg/m2 IV single dose q3-4wk, maximum cumulative dose 550 mg/m2 or 400 mg/m2 with previous or concomitant treatment (eg, daunorubicin, cyclophosphamide, irradiation of cardiac region) |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severe CHF; cardiomyopathy; impaired cardiac function; preexisting myelosuppression; previous treatment with complete cumulative doses of doxorubicin, idarubicin, and/or daunorubicin |
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| Interactions | May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin |
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| Pregnancy | D - Unsafe in pregnancy
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| Precautions | May cause nausea and reddish stain of urine (not blood in urine) in the short term and toxicity of heart, oral mucosa, hair (alopecia), and hematopoietic system; extravasation may occur, resulting in severe tissue necrosis; caution in patients with impaired hepatic function |
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| Drug Name | Fluorouracil (Adrucil) |
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| Description | Useful for palliation of symptoms in patients with progressive disease. |
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| Adult Dose | 15 mg/kg/d IV (continuous 24 h infusion) for 5 consecutive d |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; potentially serious infection; bone marrow depression |
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| Interactions | Allopurinol decreases toxicity; cimetidine increases plasma levels |
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| Pregnancy | D - Unsafe in pregnancy
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| Precautions | Nausea, oral and GI ulcers; may depress immune system and cause bone marrow suppression; caution in severe renal impairment, adjust dose |
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| Drug Name | Streptozocin (Zanosar) |
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| Description | Helpful for palliation of symptoms for patients with progressive disease. Dosage is related to body surface area. Sometimes, may cause complete remission of disease. Administration must be suspended only when desired response or toxicity occurs. May induce severe nephrotoxic effects. |
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| Adult Dose | 500 mg/m2 IV for 5 consecutive d q4-6wk |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severe renal impairment |
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| Interactions | Loop diuretics, aminoglycosides, and amphotericin B may enhance nephrotoxicity |
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| Pregnancy | X - Contraindicated in pregnancy
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| Precautions | Streptozocin-induced nephrotoxicity may be irreversible and lead to death; may cause hypoglycemia and hyperglycemia; caution in diabetic patients |
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| Drug Name | Dacarbazine (DTIC-Dome) |
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| Description | Although administration in patients with glucagonoma is not established, it may be helpful for palliation of symptoms for patients in whom surgery is not feasible. Complete remission of disease was reported in only one patient. |
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| Adult Dose | 300 mg/m2 IV for 5 consecutive d q3-4wk |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severe chronic hepatic impairment |
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| Interactions | None reported |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | May depress immune system and cause bone marrow suppression; caution in severe renal impairment, adjust dose |
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Further Inpatient Care
- For inpatients, psychotherapeutic intervention may be very helpful when comorbid depression is present.
Further Outpatient Care
- Psychotherapeutic intervention may be very helpful when comorbid depression is present.
In/Out Patient Meds
- Preoperative preparation may require a period of total parenteral nutrition (TPN) because of the severe weight loss. Antibiotics, steroids, amino acids, and zinc supplementation may improve severe skin rash. Octreotide is also useful to help improve the perioperative condition of these patients. Prophylaxis for venous thrombosis and administrating low-dose heparin subcutaneously are mandatory treatments for all patients during the perioperative period.
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- In patients for whom surgery is not feasible, consider administering streptozotocin and doxorubicin or streptozotocin and 5-FU.
Complications
- The main complication of glucagonoma is hepatic metastasis or metastasis of the locoregional lymph nodes.
Prognosis
- Prognosis is poor. Survival after 5 years is unpredictable because of the small number of patients with glucagonoma; however, a study reports survival of 3.7 years in a group of 12 patients and 4.9 years in a group of 9 other patients.
Medical/Legal Pitfalls
- The main medicolegal problems related to the treatment of glucagonoma are the toxic effects of antiproliferative drugs and the consequences of surgical procedures. For this reason, always obtain an informed consent to any procedure or treatment, explaining all procedures and their possible complications.
| Media file 1:
A section of a glucagonoma mass with several fiber bundles and solid cellular strands (125 X). Courtesy of Professor Pantaleo Bufo, University of Foggia, Italy. |
 |  View Full Size Image | |
Media type: Photo
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| Media file 2:
A section of a glucagonoma mass with irregular aspects of fiber bundles and cellular strands (400 X). Courtesy of Professor Pantaleo Bufo, University of Foggia, Italy. |
 | View Full Size Image | |
Media type: Photo
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- Adam DN, Cohen PD, Ghazarian D. Necrolytic migratory erythema: case report and clinical review. J Cutan Med Surg. Jul-Aug 2003;7(4):333-8. [Medline].
- Akerstrom G, Hellman P, Hessman O, Osmak L. Surgical treatment of endocrine pancreatic tumours. Neuroendocrinology. 2004;80 Suppl 1:62-6. [Medline].
- Baton O, Eggenspieller P, Bechade D, et al. [Median pancreatectomy for early glucagonoma]. Gastroenterol Clin Biol. Mar 2005;29(3):308-10. [Medline].
- Bhathena SJ, Higgins GA, Recant L. Glucagonoma and glucagonoma syndrome. In: Unger RH, Orci L , eds. Glucagon. New York, NY: Elsevier Science;1981:413.
- Clouse ME, Perry L, Stuart K, Stokes KR. Hepatic arterial chemoembolization for metastatic neuroendocrine tumors. Digestion. 1994;55 Suppl 3:92-7. [Medline].
- Du Jardin P, Cools P, Van der Stighelen Y. Necrolytic migratory erythema: first symptom of a glucagonoma. A case report. Acta Chir Belg. Aug 2004;104(4):468-70. [Medline].
- Echenique-Elizondo M, Elorza JL, De Delas JS. Migratory necrolytic erythema and glucagonoma. Surgery. Apr 2003;133(4):449-50. [Medline].
- Grant CS. Surgical management of malignant islet cell tumors. World J Surg. Jul-Aug 1993;17(4):498-503. [Medline].
- Koike N, Hatori T, Imaizumi T, et al. Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus. J Hepatobiliary Pancreat Surg. 2003;10(1):101-5. [Medline].
- Moattari AR, Cho K, Vinik AI. Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses. Surgery. Sep 1990;108(3):581-7. [Medline].
- Moertel CG, Johnson CM, McKusick MA, et al. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med. Feb 15 1994;120(4):302-9. [Medline].
- Montenegro F, Lawrence GD, Macon W, Pass C. Metastatic glucagonoma. improvement after surgical debulking. Am J Surg. Mar 1980;139(3):424-7. [Medline].
- National Cancer Institute. NCI/PDQ Physician Statement: In Islet Cell Carcinoma. 2000. [Full Text].
- Pautrat K, Bretagnol F, de Muret A, de Calan L. [Recurrent glucagonoma 20 years after surgical resection]. Gastroenterol Clin Biol. Dec 2003;27(12):1163-5. [Medline].
- Pujol RM, Wang CY, el-Azhary RA, et al. Necrolytic migratory erythema: clinicopathologic study of 13 cases. Int J Dermatol. Jan 2004;43(1):12-8. [Medline].
- Remes-Troche JM, Garcia-de-Acevedo B, Zuniga-Varga J, et al. Necrolytic migratory erythema: a cutaneous clue to glucagonoma syndrome. J Eur Acad Dermatol Venereol. Sep 2004;18(5):591-5. [Medline].
- Tomassetti P, Migliori M, Corinaldesi R, Gullo L. Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR. Aliment Pharmacol Ther. May 2000;14(5):557-60. [Medline].
- Vinik AI, Perry RR. Neoplasms of the gastroenteropancreatic endocrine system. In: Holland JF, et al, eds. Cancer Medicine. 4th ed. Philadelphia, Pa: Lippincott William & Wilkins;1998.
- Wang L, Zhao YP, Lee CI, Liao Q. Diagnosis and treatment of malignant pancreatic endocrine tumour. Chin Med Sci J. Jun 2004;19(2):130-3. [Medline].
- Xu Q, Chen WH, Huang QJ. Spiral CT localization of pancreatic functioning islet cell tumors. Hepatobiliary Pancreat Dis Int. Nov 2004;3(4):616-9. [Medline].
- Zhang M, Xu X, Shen Y, et al. Clinical experience in diagnosis and treatment of glucagonoma syndrome. Hepatobiliary Pancreat Dis Int. Aug 2004;3(3):473-5. [Medline].
- el Darouty M, Abu el Ela M. Necrolytic migratory erythema without glucagonoma in patients with liver disease. J Am Acad Dermatol. Jun 1996;34(6):1092-3. [Medline].
- Nakashima H, Komine M, Sasaki K, et al. Necrolytic migratory erythema without glucagonoma in a patient with short bowel syndrome. J Dermatol. 2006;33(8):557-62. [Medline].
- Krause W. Skin diseases in consequence of endocrine alterations. Aging Male. 2006;9(2):81-95. [Medline].
- Jabbour SA, Davidovici BB, Wolf R. Rare syndromes. Clin Dermatol. 2006;24(4):299-316. [Medline].
- Radny P, Eigentler TK, Soennichsen K, et al. Metastatic glucagonoma: treatment with liver transplantation. J Am Acad Dermatol. 2006;54(2):344-7. [Medline].
- Kovacs RK, Korom I, Dobozy A, Farkas G, Ormos J, Kemeny L. Necrolytic migratory erythema. J Cutan Pathol. 2006;33(3):242-5. [Medline].
- Marko PB, Miljkovic J, Zemljic TG. Necrolytic migratory erythema associated with hyperglucagonemia and neuroendocrine hepatic tumors. Acta Dermatovenerol Alp Panonica Adriat. 2005;14(4):161-4, 166. [Medline].
- Tomita T, Masuzaki H, Noguchi M, et al. GPR40 gene expression in human pancreas and insulinoma. Biochem Biophys Res Commun. 2005;338(4):1788-90. [Medline].
- Schanz S, Schaefer J, Fierlbeck G. Glucagonoma presenting with necrolytic migratory erythema: the Glucagonoma syndrome. Gastroenterology. 2005;129(6):1816, 2131. [Medline].
- Cruz-Bautista I, Lerman I, Perez-Enriquez B, et al. Diagnostic challenge of glucagonoma: case report and literature review. Endocr Pract. 2006;12(4):422-6. [Medline].
Glucagonoma excerpt Article Last Updated: Feb 9, 2007
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