ABSTRACT
Pancreatic neuroendocrine neoplasms (panNENs) are rare relatively malignancies that, despite their frequently slow-growing pattern, have the ability to metastasize. Metastatic and/or advanced insulinomas and glucagonomas are functioning panNENs emerging from the pancreas displaying unique peculiarities, depending on their hormonal syndromes and increased malignant potential. Advanced insulinomas management follows usually the panNENs therapeutic algorithm, but some distinctions are well advised together with aiming to control hypoglycemias that occasionally can be severe and refractory to treatment. When first-generation somatostatin analogues (SSAs) fail to control hypoglycemia syndrome, second-generation SSAs and everolimus have to be considered for exploiting their hyperglycemic effect. There is evidence that everolimus is still effective after rechallenge retaining its hypoglycemic effect independently of its antitumor effect that seems to be mediated by different molecular pathways. Peptide receptor radionuclide therapy (PRRT) constitutes a promising therapeutic option for both its antisecretory and antitumoral action. Similarly, advanced and/or metastatic glucagonomas management also follows the panNENs therapeutic algorithm, but the clinical syndrome has to be addressed by aminoacid infusion and by first-generation SSAs to improve the patient performance status. PRRT seems to be an effective treatment when surgery and SSAs fail. The application of these therapeutic modalities has been shown to be efficacious in controlling the manifestations of the secretory syndrome and prolonging the overall survival of patients suffering from these malignancies.
Subject(s)
Glucagonoma , Hypoglycemia , Insulinoma , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Insulinoma/drug therapy , Everolimus/therapeutic use , Glucagonoma/drug therapy , Somatostatin , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Neuroendocrine Tumors/pathology , Hypoglycemia/drug therapyABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Glucagonoma/diagnostic imaging , Necrolytic Migratory Erythema/physiopathology , Liver Neoplasms/secondary , Glucagonoma/drug therapy , Glucagonoma/surgery , Psoriasis/physiopathology , Tomography, Spiral Computed/methods , Pancreatectomy/methodsSubject(s)
Amino Acids/administration & dosage , Glucagonoma/diagnosis , Glucagonoma/drug therapy , Necrolytic Migratory Erythema/drug therapy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/drug therapy , Biopsy , Female , Humans , Infusions, Intravenous , Middle Aged , Necrolytic Migratory Erythema/diagnosis , Necrolytic Migratory Erythema/pathology , Skin/pathologySubject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Glucagonoma/complications , Necrolytic Migratory Erythema/etiology , Octreotide/therapeutic use , Pancreatic Neoplasms/complications , Antineoplastic Agents, Hormonal/administration & dosage , Female , Glucagonoma/drug therapy , Humans , Injections, Subcutaneous , Middle Aged , Necrolytic Migratory Erythema/pathology , Octreotide/administration & dosage , Pancreatic Neoplasms/drug therapySubject(s)
Glucagonoma/diagnosis , Necrolytic Migratory Erythema/drug therapy , Octreotide/therapeutic use , Adrenalectomy , Female , Glucagonoma/drug therapy , Humans , Middle Aged , Necrolytic Migratory Erythema/diagnosis , Necrolytic Migratory Erythema/pathology , Pancreatic Neoplasms/drug therapy , Paraneoplastic Syndromes/therapy , Prednisone/therapeutic useABSTRACT
PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas. They may cause a clinical syndrome due to hormone overproduction. Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.
Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Glucagonoma/drug therapy , Hypercalcemia/chemically induced , Octreotide/adverse effects , Pancreatic Neoplasms/drug therapy , Female , Humans , Middle AgedSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Diabetes Mellitus/etiology , Glucagonoma/secondary , Liver Neoplasms/secondary , Pancreatic Neoplasms/pathology , Aged , Carboplatin/administration & dosage , Etoposide/administration & dosage , Glucagonoma/complications , Glucagonoma/drug therapy , Humans , Liver Neoplasms/complications , Liver Neoplasms/drug therapy , Male , Octreotide/administration & dosage , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/drug therapy , Weight LossSubject(s)
Antineoplastic Agents/therapeutic use , Diabetes Mellitus, Type 1/drug therapy , Indoles/therapeutic use , Neuroendocrine Tumors/drug therapy , Pancreatic Neoplasms/drug therapy , Pyrroles/therapeutic use , Animals , Glucagonoma/drug therapy , Humans , Insulinoma/drug therapy , Mice , Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors , SunitinibABSTRACT
OBJECTIVE: Glucagonoma is a pancreatic neuroendocrine tumour that arises from alpha cells in the pancreas and is often accompanied by a characteristic clinical syndrome. DESIGN: In this report, we present the cumulative experience and clinical characteristics of six patients diagnosed with glucagonoma and the glucagonoma syndrome and treated at our centre during the past 25 years. RESULTS: Although the course of the disease was variable, some features were similar. The median age at diagnosis was 53·5 years; the median time from onset of symptoms to diagnosis was 39 months. Presenting symptoms were as follows: weight loss 5/6 (83%), necrotizing migratory erythema (NME) 5/6 (83%), diabetes mellitus 4/6 (66%) and diarrhoea, weakness and thrombosis 2/6 (33%). Plasma glucagon was elevated in all patients upon diagnosis (range 200-10,000 pm; N < 50). Skin biopsy was diagnostic only in 1/6 specimens obtained, even after revision. Metastatic disease developed in all patients; 4/6 initially presented with hepatic metastasis. All patient symptoms responded to somatostatin analogue therapy. In 4/6, the NME responded to amino acid solutions. Other modes of therapy were as follows: surgery in 3/6 patients, peptide receptor radioligand therapy with (90) Y-DOTATOC (PRRT) in 3/6 patients (two responses) and chemotherapy in three patients (two responded). Four out of six patients died of the disease, and median survival time was 6·25 years (range 2-11) from diagnosis and 8 years (range 8-16) from initial symptoms. Five-year survival was 66%. CONCLUSION: Our data indicate that somatostatin analogues and an aggressive surgical approach offer symptom relief and tumour control. Among other available treatment modalities, PRRT seems to hold the most promise.
Subject(s)
Glucagonoma/diagnosis , Glucagonoma/therapy , Necrolytic Migratory Erythema , Pancreatic Neoplasms , Endocrine Gland Neoplasms/diagnosis , Endocrine Gland Neoplasms/therapy , Glucagonoma/diagnostic imaging , Glucagonoma/drug therapy , Glucagonoma/surgery , Humans , Middle Aged , Necrolytic Migratory Erythema/diagnosis , Necrolytic Migratory Erythema/therapy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Radionuclide Imaging , Retrospective Studies , Somatostatin/therapeutic use , Survival Rate , Syndrome , Treatment OutcomeSubject(s)
Diabetes Mellitus/etiology , Glucagonoma/complications , Pancreatic Neoplasms/complications , Adult , Alopecia/etiology , Anemia/etiology , Antineoplastic Agents, Hormonal/therapeutic use , Biomarkers, Tumor/blood , Chromogranin A/blood , Combined Modality Therapy , Female , Glossitis/etiology , Glucagon/blood , Glucagonoma/diagnosis , Glucagonoma/drug therapy , Glucagonoma/surgery , Humans , Hyperglycemia/etiology , Necrolytic Migratory Erythema/etiology , Octreotide/therapeutic use , Pancreatectomy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Weight LossABSTRACT
Malignant glucagonoma is an exceptional pancreatic endocrine tumour, with frequent dermatologic symptoms, diabetes and degradation of the general health status. Prognosis is unfavourable when liver metastases are present due to the usual inefficiency of chemotherapy. We report here an observation of a patient who was treated for a glucagonoma with multiple liver metastases, migratory necrolytic erythema, dilated cardiomypathy and diabetes that dramatically improved after a dacarbazin-based chemotherapy, allowing subsequent surgical resection of the primary. The patient was still alive and asymptomatic without progressive disease nearly two years after surgery.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cardiomyopathy, Dilated/complications , Glucagonoma/drug therapy , Liver Neoplasms/drug therapy , Adult , Dacarbazine/administration & dosage , Female , Fluorouracil/administration & dosage , Glucagonoma/pathology , Glucagonoma/surgery , Humans , Liver Neoplasms/secondary , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgeryABSTRACT
The glucagonoma syndrome is a rare disease in which a typical skin lesion, necrolytic migratory erythema, is often one of the presenting symptoms. A 68-year-old woman developed erythematous polycyclic migratory lesions with advancing scaling borders and crusts over several years. Skin biopsies, laboratory studies and imaging confirmed the diagnosis of necrolytic migratory erythema as part of a glucagonoma syndrome.
Subject(s)
Ciprofloxacin/administration & dosage , Erythema/diagnosis , Erythema/drug therapy , Glucagonoma/diagnosis , Glucagonoma/drug therapy , Administration, Oral , Aged , Anti-Infective Agents/administration & dosage , Female , Humans , Necrosis/diagnosis , Necrosis/drug therapy , Syndrome , Treatment OutcomeABSTRACT
Endocrine pancreatic tumours (EPTs) are uncommon tumours occurring in approximately 1 in 100,000 of the population, representing 1-2% of all pancreatic neoplasms. Some of the tumours may be part of multiple endocrine neoplasia type one (MEN-1) syndrome or von Hippel-Lindau (vHL) disease. EPTs are classified as functioning or non-functioning tumours on the basis of their clinical manifestation. The biochemical diagnosis of EPT is based on hormones and amines released. Besides specific markers such as insulin, there are also general tumour markers such as chromogranin A, which is the most valuable marker and has been reported to be increased in plasma in 50-80% of patients with EPTs and correlates with tumour burden. The location of endocrine tumours of the pancreas includes different techniques, from endoscopic investigations to scintigraphy (e.g. somatostatin receptor scintigraphy) and positron emission tomography. The medical treatment of endocrine pancreatic tumours consists of chemotherapy, somatostatin analogues and alpha-interferon. None of these can cure a patient with malignant disease. In future, therapy will be custom-made and based on current knowledge of tumour biology and molecular genetics.
Subject(s)
Carcinoma, Neuroendocrine/drug therapy , Carcinoma, Neuroendocrine/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Biopsy, Needle , Carcinoma, Neuroendocrine/epidemiology , Carcinoma, Neuroendocrine/genetics , Female , Gastrinoma/drug therapy , Gastrinoma/epidemiology , Gastrinoma/pathology , Glucagonoma/drug therapy , Glucagonoma/epidemiology , Glucagonoma/pathology , Humans , Immunohistochemistry , Incidence , Insulinoma/drug therapy , Insulinoma/epidemiology , Insulinoma/pathology , Male , Molecular Biology , Neoplasm Staging , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/genetics , Prognosis , Risk Assessment , Somatostatinoma/drug therapy , Somatostatinoma/epidemiology , Somatostatinoma/pathology , Survival Rate , Treatment Outcome , Zollinger-Ellison Syndrome/drug therapy , Zollinger-Ellison Syndrome/epidemiology , Zollinger-Ellison Syndrome/pathologySubject(s)
Erythema/etiology , Glucagonoma/diagnosis , Glucagonoma/drug therapy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/drug therapy , Somatostatin/analogs & derivatives , Antineoplastic Agents/therapeutic use , Glucagonoma/complications , Humans , Male , Middle Aged , Pancreatic Neoplasms/complications , Peptides, Cyclic/therapeutic use , Somatostatin/therapeutic use , SyndromeABSTRACT
The development of malignancies after solid organ transplantation represents an increasing clinical problem complicating the long-term follow-up of transplant recipients. In this case report the authors describe the rare triple combination of a simultaneous hepatocellular carcinoma with a glucagonoma and a splenic hamartoma in a renal allograft recipient. It is not only the first published report of a glucagonoma occurring after renal transplantation but serves also as an illustration of the therapeutic decision making in the setting of the immune-compromised host. This case report also illustrates the different imaging modalities that can be used for the diagnosis of neuroendocrine tumors.
Subject(s)
Kidney Transplantation/methods , Neoplasms/diagnosis , Neoplasms/surgery , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Female , Glucagonoma/diagnosis , Glucagonoma/drug therapy , Glucagonoma/surgery , Hamartoma/diagnosis , Hamartoma/drug therapy , Hamartoma/surgery , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Middle Aged , Neoplasms/drug therapy , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/drug therapy , Neoplasms, Multiple Primary/surgery , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Splenic Neoplasms/diagnosis , Splenic Neoplasms/drug therapy , Splenic Neoplasms/surgeryABSTRACT
Glucagonomas are rare tumors originating in alpha-cells of the pancreas. The most common clinical presentation is the association of diabetes mellitus, necrolytic erythema, weight loss and anemia. The diagnosis of pancreatic tumor is usually made by abdominal computed tomography and/or endoscopic ultrasonography. Indium-labeled octreotide scanning is useful for the localization of most neuroendocrine tumors and their metastases. Glucagon release can be confirmed by a high concentration of plasma glucagon. We report the case of a 74-year-old patient who had a glucagonoma with particular presentation of neurological impairment and weight loss. The diagnosis was confirmed by usual imaging procedures and plasma glucagon level. Medical treatment was started with long-acting repeatable octreotide (Sandostatin(R) LAR). After a one-year follow-up, the patient remained well. The original presentation and benefit of a new, long-acting somatostatin analog for the treatment of inoperable glucagonoma are discussed.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Glucagonoma/drug therapy , Octreotide/therapeutic use , Pancreatic Neoplasms/drug therapy , Aged , Diabetes Mellitus, Type 2/complications , Glucagonoma/complications , Humans , Male , Pancreatic Neoplasms/complications , Treatment OutcomeABSTRACT
Somatostatin analogs and alpha-interferon induce good responses as single drugs in the treatment of endocrine pancreatic tumors. We examined the efficacy and tolerability of the combination of alpha-interferon and somatostatin analogs in 16 patients with metastatic endocrine pancreatic tumors. All patients except one had received prior treatment and were in a progressive state. Doses of alpha-interferon and somatostatin analogs were individually titrated. The alpha-interferon doses varied between 9 and 25 million units per week and were combined with 100-1500 microg of octreotide or 6000 microg of lanreotide daily. Radiological response was seen in 3 of 16 (19%) patients (median duration 23 mo). Biochemical response was seen in 10 of 16 (62.5%) patients (median duration 22 mo). All three patients previously progressing on both alpha-interferon and somatostatin analog as single drugs achieved a stabilization of the disease when treated with the combination (median duration 10 mo). Seven of eight (88%) patients previously progressing on alpha-interferon treatment benefited from the combination with biochemical partial response or stabilization. All six patients previously progressing during somatostatin analog treatment achieved biochemical partial response or stabilization. More than 80% of patients who progressed during previous treatment with either drug benefited from the combined treatment, which also was well tolerated. Thus, a combination of alpha-interferon and somatostatin analogs may be considered for patients previously progressing on treatment with alpha-interferon or somatostatin analogs. However, in this study, the value of sequential treatment has not been evaluated.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gastrinoma/drug therapy , Glucagonoma/drug therapy , Pancreatic Neoplasms/drug therapy , Somatostatin/analogs & derivatives , Adult , Aged , Female , Gastrinoma/diagnostic imaging , Gastrinoma/pathology , Glucagonoma/diagnostic imaging , Glucagonoma/pathology , Humans , Interferon-alpha/administration & dosage , Male , Middle Aged , Octreotide/administration & dosage , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Peptides, Cyclic/administration & dosage , Somatostatin/administration & dosage , Tomography, Emission-ComputedABSTRACT
BACKGROUND: The thyroid gland and the adrenal glands are the most common sites of endocrine carcinomas (see Part I of this review, Med Klin 2000;95: 20-5, Nr. 1). Less frequent are endocrine malignancies of the gastrointestinal tract (gastrinomas, insulinomas, glucagonomas, carcinoids and others). TREATMENT: Because of the rarity and missing prospective studies as well as radiotherapy and chemotherapy resistance of these tumors, generally accepted conventional therapy guidelines for these endocrine carcinomas do not exist. Surgery and radionucleotide treatment should be considered as first line therapy. Somatostatin analogs (octreotide) are frequently used as well. Chemotherapy is usually not effective. Common substances are streptozotocin, 5-fluorouracil, doxorubicin, dacarbazine and cyclophosphamide.
Subject(s)
Antineoplastic Agents/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Neoplasms, Hormone-Dependent/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Carcinoid Tumor/drug therapy , Dose-Response Relationship, Drug , Gastrinoma/drug therapy , Gastrointestinal Neoplasms/diagnosis , Glucagonoma/drug therapy , Humans , Insulinoma/drug therapy , Neoplasms, Hormone-Dependent/diagnosis , Octreotide/therapeutic use , Somatostatin/analogs & derivativesABSTRACT
Glucagonomas, like other neuroendocrine tumors, express somatostatin receptors in more than 80% of cases. Unfortunately, because of the rarity of these tumors, the sensitivity and specificity of somatostatin analog (octreotide) imaging have not been established. Nonetheless, there have been limited reports in the literature supporting the use of indium In-111 DTPA N-terminal D-phenylalanine (D-PHE1) octreotide for glucagonoma imaging and may be most beneficial as an adjuvant to conventional imaging for tumor staging and therapeutic decision making. Current therapeutic applications of octreotide focus on stabilization of disease in tumors expressing somatostatin receptors, and tumor destruction, using beta-emitting isotopes. In this report, imaging of a glucagonoma with In-111 DTPA-D-PHE1 octreotide scintigraphy is described in a 51-year-old woman examined for a large palpable abdominal mass.