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Glucagonoma is a rare pancreatic neuroendocrine tumor (panNET) that can be characterized by increased secretion of glucagon and distinguishing symptoms - glucagonoma syndrome with a typical dermatosis, necrolytic migratory erythema, being its most common manifestation. While surgery and somatostatin analogs remain first-line therapeutic options in panNETs, radioligand therapy with [177Lu]Lu-DOTA-TATE is a recommended second-line palliative treatment in advanced, metastatic cases. However, its prospects and efficacy are still not vastly researched in less frequent neuroendocrine neoplasms. Here, we present an extraordinary case of a metastatic glucagonoma treated with [177Lu]Lu-DOTA-TATE used as a second-line treatment in progressive disease.

Abstract: Glucagonomas are rare types of pancreatic neuroendocrine tumors. They may present with a clinical entity called glucagonoma syndrome, which includes necrolytic migratory erythema as a skin component. Here we present a 26-year-old woman experiencing ongoing skin lesions, excessive weight loss, and nausea. She was diagnosed with metastatic glucagonoma. Her 68Ga-DOTATATE PET/CT showed increased uptake at the primary pancreatic lesion and hepatic metastases. She received 2 cycles of peptide receptor radionuclide therapy and had a partial response with a near-complete regression of her skin lesions., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Glucagonoma is a rare type of functional pancreatic neuroendocrine tumor that is characterized by distinctive clinical manifestations; among these, necrolytic migratory erythema represents the hallmark clinical sign of glucagonoma syndrome and is usually presented as the initial complaint of patients., Patient Concerns: A 30-year-old male patient was admitted to our hospital with a complaint of diffuse erythematous ulcerating skin rash for more than 10 months. He also complained of hyperglycemia and a weight loss of 15 kg in those months., Diagnosis: This patient underwent a contrast-enhanced computed tomography scan which showed a pancreatic body mass measuring approximately 6 cm with low density accompanied by partial calcification in plain scanning images and uneven enhancement in strengthening periods. In addition, laboratory tests indicated elevated fasting blood glucagon (1109 pg/mL, normal range: 50-150 pg/mL) levels. Glucagonoma syndrome was ultimately diagnosed in clinical., Intervention: Spleen-preserving distal pancreatectomy was conducted and postoperative pathology revealed the presence of glucagonoma., Outcomes: The patient recovered uneventfully with the glucagonoma syndrome disappeared soon after surgery, and the postoperative plasma glucagon decreased to a normal level. Follow-up showed no recurrence for 5 years since the surgery., Lessons: The treatment of glucagonoma should be directed according to the stage at which the disease is diagnosed. Surgery is currently the only method available to cure the tumor, although medications are given to patients who present with advanced glucagonoma and who are not candidates for operation. Multidisciplinary therapy and multimodality treatment are advised, although these have been systematically evaluated to a lesser degree.

Competing Interests: Competing interests: None declared.

Necrolytic migratory erythema (NEM) is associated with glucagonoma, an endocrine malignancy of the pancreas. It is a rare and a likely underrecognized paraneoplastic dermatitis. A 38-year-old woman presented to our clinic with a 3-year history of reocurring pruritic skin rashes with increasing intensity. The skin lesions presented with active annular borders, central scaling, and postinflammatory hyperpigmentation, but also with erosions, pustules, and crusted lesions. Multiple skin biopsies were taken. The workup of the patient revealed a tumor localized in the head of the pancreas, and glucagon serum levels were elevated. Clues to the diagnosis of NEM were the waxing and waning of serpiginous erythemas with active borders localized on extremities, intertriginous areas, and face. On histopathology, dyskeratosis in all layers of the epidermis were an early feature of NEM, and long-standing lesions typically showed psoriasiform hyperplasia with pallor and necrosis of upper epidermal layers. Clinicians and histopathologists need to be aware of the wide spectrum of skin manifestations in glucagonoma. Early diagnosis of the tumor is crucial for patients.

Introduction: Pancreatic Neuroendocrine Tumours (p-NETs) are an important disease entity and comprise of peptide-secreting tumours often with a functional syndrome. Accounting for a small percentage of all pancreatic tumours, they have a good overall survival rate when diagnosed early, with surgery being curative. The role of nuclear medicine in the diagnosis and treatment of these tumours is evident. However, the vast majority of patients will require extensive imaging in the form of conventional radiological techniques. It is important for clinicians to have a fundamental understanding of the p-NET appearances to aid prompt identification and to help direct management through neoplastic staging., Methods: This article will review the advantages and disadvantages of conventional radiological techniques in the context of p-NETs and highlight features that these tumours exhibit., Conclusion: Pancreatic neuroendocrine tumours are a unique collection of neoplasms that have markedly disparate clinical features but similar imaging characteristics. Most p-NETs are small and welldefined with homogenous enhancement following contrast administration, although larger and less welldifferentiated tumours can demonstrate areas of necrosis and cystic architecture with heterogeneous enhancement characteristics. Prognosis is generally favourable for these tumours with various treatment options available. However, conventional radiological techniques will remain the foundation for the initial diagnosis and staging of these tumours, and a grasp of these modalities is extremely important for physicians., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Glucagonoma is an extremely rare, glucagon-secreting neuroendocrine tumor of the pancreas. Only sparse data are available about the characteristics of this tumor in somatostatin receptor imaging and only for the situation of initial diagnosis. We present a series of 3 glucagonoma patients who underwent at least 1 Ga-DOTATATE PET/CT scan. All patients were diagnosed by either histology and/or elevated serum levels of glucagon. The presented cases suggest that somatostatin receptor-based imaging can probably be used for re-evaluation of disease status in patients with glucagonoma in a similar way as it is already established for neuroendocrine tumors of other origin.

Rationale: Glucagonoma is an uncommon disease but it has been associated with a pattern of symptoms defined as glucagonoma syndrome. These symptoms, if promptly recognized, could help to speed up the diagnosing process., Patient Concerns: We report a case of a 68-year-old woman with a pancreatic glucagonoma. Her symptoms at the onset were typical of the glucagonoma syndrome., Diagnoses: After a significant weight loss, she underwent a computer tomography scan of the abdomen, which showed a hypervascular lesion of the tail of the pancreas and hypervascular lesions of the liver. An ultrasound guided biopsy was performed and pathology was consistent with glucagonoma. Her blood glucagon levels were elevated., Outcomes: She was treated with chemotherapy and somatostatin analogs. After 4 years, the disease had a malignant transformation, and metastases suddenly started to grow up. She stopped being responsive to treatment and eventually passed away., Lessons: Due to its rarity, clinical diagnosis is challenging and generally it comes after a long interval since the onset of symptoms. Awareness of physicians and dermatologists of the characteristic necrolytic migratory erythema, and of the other symptoms, often leads to early diagnosis., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Necrolytic migratory erythema (NME) is a rare dermatological condition which presents a diagnostic challenge. Repeated negative skin biopsies and non-detection of any pancreatic tumor in conventional imaging modalities like a computed tomography (CT) scan and ultrasonogram (USG) make the diagnosis more difficult. By the time the diagnosis is made, the patient usually presents with metastasis. We present a rare case of difficult to diagnose NME, as repeated skin biopsies and conventional imaging modalities like CT and USG could not detect the underlying glucagonoma. A (68)Ga-DOTANOC positron emission tomography PET-CT was able to detect the underlying cause of NME as glucagonoma of the pancreas and the same investigation confirmed the absence of any metastasis elsewhere in the body. The tumor was excised and patient dramatically improved, and all skin lesions disappeared., (© 2012 Wiley Publishing Asia Pty Ltd.)

A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: The pancreatic neuroendocrine tumor (pNET) is relatively rare and generally felt to follow an indolent course. EUS has an important role in detection of pNET. This is a review of clinical and radiological presentation and pathologic reports of 22 patients with pNET., Patients and Methods: In this study we analyzed clinical and radiological presentations and pathologic reports of all relevant cases who were referred to Taleghani hospital for 3 years since 2008., Results: A total of 22 patients 28-74 years old (mean=49) were enrolled between 2008 and 2011. Among the total, 13 (59%) were male, 9 (41%) were female and 16 (72.7%) had functional tumors. The results of CT were negative in 12 (54%) cases but EUS was capable of detecting the lesions in these patients, cysts being found in 4 (19%) patients., Conclusion: EUS is a highly sensitive procedure for the localization of functional pNETs and especially insulinomas. Nonfunctional tumors were detected in more advanced and late stages and cystic lesions were more common in this group.

Background/aims: Arterial stimulation and venous sampling (ASVS) is a catheter-based diagnostic technique used to identify the localization of an insulinoma or gastrinoma. The aim of this study was to clarify the clinical significance of ASVS for glucagonomas., Methodology: Eight patients with pancreatic hypervascular tumors and elevated serum glucagon levels in the peripheral blood were enrolled. Pancreatic angiography was performed and a bolus dose of calcium was injected into a suitable artery. Hepatic venous blood samples were then obtained to measure concentrations of glucagon and insulin. All patients underwent surgical resection, and the resected specimens were investigated immunohistochemically., Results: Compared to insulin, the glucagon levels stabilized after calcium stimulation in four patients, with a 1.2-fold increase or decrease. In the remaining four patients, there was a 1.6- to 5.8-fold increase in glucagon levels. The peak value of glucagon was observed at 90s or 120s which was slower than the insulin peak observed in patients with insulinoma. The patients with elevated glucagon levels during ASVS exhibited positive immunostaining of glucagon in resected specimens., Conclusions: Increase in glucagon after calcium stimulation was observed in patients with glucagonomas. ASVS for glucagonomas may be useful in determining the most suitable surgical procedure.

Background: Surgery for pancreatic endocrine tumors (PETs) with blood vessel involvement is controversial., Hypothesis: Resection of PETs with major blood vessel involvement can be beneficial., Design: The combined databases of the National Institutes of Health and Stanford University hospitals were queried., Main Outcome Measures: Operation, pathologic condition, complications, and disease-free and overall survival., Results: Of 273 patients with PETs, 46 (17%) had preoperative computed tomography evidence of major vascular involvement. The mean size for the primary PET was 5.0 cm. The involved major vessel was as follows: portal vein (n = 20), superior mesenteric vein or superior mesenteric artery (n = 16), inferior vena cava (n = 4), splenic vein (n = 4), and heart (n = 2). Forty-two of 46 patients had a PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n = 7) or resection (n = 35). Resections included distal or subtotal pancreatectomy in 23, Whipple in 10, and total in 2. Eighteen patients had concomitant liver resection: 10 wedge resection and 8 anatomic resections. Nine patients had vascular reconstruction: each had reconstruction of the superior mesenteric vein and portal vein, and 1 had concomitant reconstruction of the superior mesenteric artery. There were no deaths, but 12 patients had complications. Eighteen patients (41%) were immediately disease free, and 5 recurred with follow-up, leaving 13 (30%) disease-free long term. The 10-year overall survival was 60%. Functional tumors were associated with a better overall survival (P < .001), and liver metastases decreased overall survival (P < .001)., Conclusion: These findings suggest that surgical resection of PETs with vascular abutment/invasion and nodal or distant metastases is indicated.

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., (© 2011 Blackwell Publishing Ltd.)

The glucagonoma syndrome is a rare disorder, characterized by necrolytic migratory erythema, elevated serum glucagon levels, abnormal glucose tolerance, weight loss, and anemia in association with a glucagon-secreting alpha-cell tumor of the pancreas. We present a 67-year-old diabetic patient with extensive cutaneous lesions, weight loss, and poor glycemic control. The clinical investigation revealed a pancreatic glucagonoma with resolution of the cutaneous and systemic features after surgical removal. The dermatologic and endocrine approach to this syndrome is discussed here. Early recognition and treatment may prevent metastatic disease and ensure its cure with resolution of the cutaneous and catabolic manifestations.

Objective: To describe a patient with a histologically proven pancreatic glucagonoma, noted incidentally during a follow-up visit for high aminotransferase levels, and to evaluate its autonomy with a standard 75-g oral glucose tolerance test., Methods: We present the results of a 2-hour oral glucose tolerance test, with plasma glucagon and blood glucose levels measured every 30 minutes after an oral glucose load. In addition, we provide a brief review of the literature on the diagnosis and management of glucagonomas and the importance of long-term surveillance., Results: In our patient, who had a 1-year history of impaired fasting glucose, plasma glucagon levels were persistently suppressed to within the normal range after oral glucose challenge. Octreotide scintigraphy revealed abnormal uptake in the pancreatic tail, and a 2.8-cm mass was removed at laparoscopic distal pancreatectomy. Immunohistochemical staining of the tumor tissue showed intense reactivity for glucagon. Plasma glucagon levels were reduced to <50 pg/mL postoperatively, and scintigraphic study at 4-month follow-up showed no residual uptake at the previous tumor site or elsewhere., Conclusion: Glucagon-secreting pancreatic tumors are extremely rare. A substantially elevated plasma level of glucagon is usually seen in patients with metastatic tumors. In the early stage of a glucagonoma, however, the plasma glucagon level may be only modestly elevated and may still be susceptible to normal negative feedback inhibition. We demonstrated plasma glucagon complete suppressibility after oral glucose challenge in a patient with a glucagonoma, the first such report in the literature.

This is a rare case of a patient with type 1 multiple endocrine neoplasia (MEN-1) syndrome. The case is further unusual in that the glucagonoma debuted with two synchronic pancreatic masses at the time of diagnosis and with pulmonary metastases as the primary site of metastasis and not the more usual site of the liver.

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET. GRS was directly compared with SRS. If lesions were visible on GRS but not detectable by SRS, other imaging modalities (MRI, CT) and follow-up were used for verification. Of the 60 evaluable patients, 51 had carcinoid tumours, 3 gastrinomas, 2 glucagonomas, 1 insulinoma and 3 paragangliomas. The overall tumour-detection rate was 73.7% for GRS and 82.1% for SRS. In the 11 patients with negative SRS, GRS was positive in 6 (54.5%). Based on the number of tumour sites detected and the degree of uptake, GRS performed better than SRS in 13 patients (21.7%), equivalent images were obtained in 18 cases (30.0%) and SRS performed better in 24 (40.0%) cases. In six of the SRS positive patients, 18 additional sites of tumour involvement could be detected. Overall, GRS detected additional tumour sites in 20% of the patients. Localisation of the primary tumours or their functional status had no influence on the outcome of imaging. GRS should be performed in selected patients as it may provide additional information in patients with NET with equivocal or absent somatostatin uptake.

Objective: To report the diagnostic difficulties encountered in a case of glucagonoma., Methods: We provide a literature review and present the clinical findings, pertinent laboratory data, and results of related studies in a patient with a glucagonoma., Results: A 54-year-old-man, with no relevant history of endocrine disorders, presented to the hospital with a 5-year history of recurrent stomatitis and glossitis, a more recent weight loss of 11.5 kg, and recurrent pruritic maculae on the scalp in conjunction with raised erythematous maculae in the scrotal region and perineum that gradually migrated to the distal extremities, becoming bullous and painful. The patient was hospitalized, and because of the dermatologic findings suggestive of necrolytic migratory erythema, the presence of a glucagonoma was suspected. His blood glucose levels were in the normal range. Glucagon levels were found to be elevated, and imaging studies confirmed the presence of an enlarged mass in the pancreatic tail, without evidence of extension to surrounding structures. Liver metastatic lesions were also excluded. After surgical removal of the tumor, the skin and oral mucosal lesions disappeared spontaneously. The histologic appearance and immunohistochemical staining results confirmed the diagnosis of a glucagonoma. Subsequently, all related symptoms resolved, and the glucagon levels normalized., Conclusion: The diagnosis of glucagonoma is often delayed. Clinicians should be aware of the unusual initial manifestations of this tumor and the potential for less than a full spectrum of the characteristic features of the glucagonoma syndrome.

Necrolytic migratory erythema (NME) is a rare paraneoplastic dermatologic condition. Its underlying cause is usually a pancreatic islet cell tumour with marked glucagon secretion. The glucagonoma syndrome is characterised by pancreatic neuroendocrine neoplasm, NME, and diabetes mellitus. We present a case of glucagonoma syndrome in a 58-year-old woman with a history of recurrent cutaneous manifestations who was referred for surgical resection of a pancreatic neoplasm after the NME was finally diagnosed. We discuss diagnostic methods, differential diagnosis, and therapeutic management of this disease.

Glucagonoma is a rare pancreatic endocrine tumor that is often both well developed and malignant at detection. In the case of metastatic spread the patient has a poor long-term prognosis. We hope to familiarize dermatologists and other specialists with this rare and potentially fatal disorder because early recognition of necrolytic migratory erythema, a clinical feature that may appear in patients with glucagonoma, can lead to possible cure, whereas delayed identification of the disease is associated with metastatic disease and a poor prognosis. We report the case of a 57-year-old patient with a metastatic glucagon-producing tumor; necrolytic migratory erythema was diagnosed and was successfully treated by a multimodal intervention including liver transplantation. Currently, 72 months after transplantation, our patient is in complete remission, which has been verified by somatostatin receptor scintigraphy monitoring, computed tomographic scanning and glucagon serum control. Increased awareness of the clinical symptoms and visible polymorphic mucocutaneous and nonspecific histopathologic features of glucagonoma syndrome is needed to avoid unnecessary delay in the diagnosis of this syndrome.

Background: Surgeons are always concerned about the localization of pancreatic functioning islet cell tumor. If the tumor is accurately localized before operation, resection of the pancreatic body and tail without intention can be avoided. The purpose of this study was to evaluate spiral CT localization of pancreatic functioning islet cell tumors and CT techniques., Methods: CT manifestations in 6 patients with clinically and pathologically proved pancreatic functioning islet cell tumors were analyzed retrospectively., Results: In 4 patients with insulinomas and 2 patients with glucagonomas, 5 were localized accurately by CT before surgery and 1 was detected retrospectively. The enhancement of tumors was greater than that of normal pancreas in arterial phase and pancreatic parenchymal phase. Four patients showed mild high-density and 2, iso-density in the portal venous phase., Conclusion: Spiral CT multi-phase enhanced scan with 1.5 ml/kg contrast agent and 2-5 mm slice width can localize functioning islet cell tumors accurately.

The glucagonoma syndrome is a rare disease in which a typical skin disorder, necrolytic migratory erythema, is often one of the first presenting symptoms. Weight loss and diabetes mellitus are two other prevalent characteristics of this syndrome. Necrolytic migratory erythema belongs to the recently recognized family of deficiency dermatoses of which zinc deficiency, necrolytic acral erythema and pellagra are also members. It is typically characterized on skin biopsies by necrolysis of the upper epidermis with vacuolated keratinocytes. In persistent hyperglucagonemia, excessive stimulation of basic metabolic pathways results in diabetes mellitus at the expense of tissue glycogen stores, and muscle and fat mass. Multiple (essential) nutrient and vitamin B deficiencies develop, which contribute to the dermatosis. In addition, glucagonomas may produce various other products, like pancreatic polypeptide, that add to the catabolic effects of glucagon.

Necrolytic migratory erythema (NME) is a cutaneous manifestation of the glucagonoma syndrome. We present a case with a pancreatic glucagon-secreting tumour, skin eruption and a good response to treatment., (Copyright 2004 European Academy of Dermatology and Venereology)

Introduction: Particular problems in MEN 1 syndrome come from the morphological identification of pancreatic tumors because of their are often small [<1 cm] and multiple [89% of the cases]. However intraoperatively it could be difficult to identify with palpation the tumors described by preoperative investigations and to decide the most suitable surgical treatment. The authors describe one case recently observed to underline and update the correct management., Case Report: A 34 year old woman was admitted for the surgical treatment of an insulinoma. Polimenorrea, hypercalcemia and familiarity for MEN 1 syndrome were also present. A CT scan showed the tumors in the body and tail of the pancreas [diameter 0.5-1 cm]. MRI described only a small mass in pancreatic head. A calcium angiography was positive for insulin secretion after calcium infusion in hepatic and gastroduodenal artery, and for glucagon secretion after infusion in splenic artery. An intraoperative ultrasonography discovered three nodules that were enucleated. They were one insulinoma and two glucagonomas respectively. After enucleation glycemia became immediately normal., Conclusion: To avoid wide surgical resections [es. left pancreatectomy] we suggest a conservative treatment [multiple enucletion with or without a pancreatic-jejunum side-to-side anastomosis] with a meticulous preoperative and intraoperative evaluation of all pancreatic nodules.

Background: Necrolytic Migratory Erythema (NME) is a rarely encountered dermatologic condition. It is the characteristic feature of a paraneoplastic syndrome associated with neuroendocrine pancreatic tumors. A case of NME initially diagnosed and treated as psoriasis is reviewed. A review of the current literature regarding NME is also included., Objective: The purpose of this report is to familiarize dermatologists with a rare and potentially fatal disorder. Early recognition of NME can lead to possible cure, while delayed identification of the disease is associated with metastatic disease and a poor prognosis for the patient., Conclusion: When evaluating the patient who presents with a dermatitis and weight loss, it is important to exercise great caution. The differential diagnosis should be re-evaluated in a disease that is not responsive to first-line therapy before further treatment is considered.

Glucagonomas are rare functional endocrine tumors of the pancreas that classically present with symptoms of glucagon excess, including rash, hyperglycemia, diarrhea, and weight loss. Metastatic disease at presentation is common but is often limited to the liver and regional lymph nodes. We describe an unusual case of a patient with glucagonoma who presented with a pathologic vertebral fracture. This tumor had no evidence of active hormone secretion but tested positive for glucagon by immunohistochemical staining.

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.

Glucagonomas are relatively rare, and can be difficult to differentiate from other pancreatic tumors. A 62-year-old woman who had suffered from diabetes mellitus was hospitalized for further evaluation of a space-occupying lesion in the head of the pancreas and tumors in the liver. F-18 fluorodeoxyglucose positron emission tomography revealed accumulation of isotope corresponding to a tumor of the pancreas with a standardized uptake value of 4.3, and tumors in the liver with standardized uptake values of 2.4 and 2.8. The serum glucagon level was high (1,170 pg/ml) and the secretin tolerance test was negative. She was diagnosed with glucagonoma with a high serum glucagon level and clinical findings. It is suggested that glucagonoma may be one of the tumors which show high uptake of F-18 fluorodeoxyglucose.

Two years after resection of a pancreatic glucagonoma, scintigraphy with 111indium-labeled octreotide revealed hepatic metastases in a 48-yr-old man. Hepatic metastases were also visualized by CT, whereas an additional lesion in the chest was seen only by scintigraphy. A total of 11 follow-up examinations over 46 months proved somatostatin receptor scintigraphy to monitor reliably somatostatin receptor expression, growth and dissemination of glucagonoma metastases, and to indicate therapeutic readjustment if necessary. The survival time of the patient is now >75 months, in comparison with a mean survival time of 59 months reported for metastatic glucagonoma.

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.

Unlabelled: The usefulness of 111In-pentetreotide scintigraphy in the diagnosis of neuroendocrine tumors was evaluated., Material and Method: 39 patients with clinical or biochemical suspicion of neuroendocrine tumors were studied. 29 patients underwent surgery and diagnosis was confirmed by anatomopathology findings (7 mixed tumors, 6 carcinoids, 3 insulinomas, 3 pheocromocytomas, 2 glucagonomas, 2 medullary thyroid carcinomas, 1 gastrinoma and 5 metastatic lesions). In 10 patients who did not undergo surgery, the diagnostic criteria were based on a 6 month follow-up. 111In-pentetreotide scintigraphy and computed tomography (CT) were performed in all of the patients., Results: The scintigraphy correctly detected 58% of the primary tumors while the CT was positive in only 45% of the cases. Both techniques detected metastasis in 5 patients., Conclusion: 111In-pentetreotide scintigraphy is a useful technique to diagnose those tumors that have somatostatin receptors. In our series, the sensitivity of this method was higher than the CT.

Glucagonoma, a rare neuroendocrine pancreatic tumour, is frequently malignant and often accompanied by hepatic metastases. Our aim was to consider the different treatments of metastatic glucagonoma to the liver and their results. A case of glucagonoma with metachronous, small, multiple and bilobar liver metastases is reported. Combined treatment with octreotide and hepatic arterial chemoembolization was applied with good results in terms of symptom relief, plasma glucagon levels and regression of hepatic metastases. Survival rates were also improved. Based on our experience, glucagonoma with metachronous, multiple, diffuse and bilobar hepatic metastases should be treated with octreotide plus hepatic arterial chemoembolization with improved outcome and prognosis.

Objective: This study evaluates the diagnostic and therapeutic implications of somatostatin-receptor scintigraphy in the management of patients with proven or high clinical suspicion of gastroenteropancreatic endocrine tumors., Methods: Forty-one patients were studied by planar and tomographic imaging at 4 h and 24 h after 111In-pentetreotide injection. Scintigraphic findings were compared with computed tomography, and in several patients also with ultrasound, angiography, biopsy, and/or surgery, when performed., Results: Among 23 patients with carcinoid tumor, three of nine primary tumors were initially identified by scintigraphy. Unsuspected mesenteric metastases found on scintigraphy in three patients led to octreotide treatment. Scintigraphic detection of multiple metastases in a patient with thyroid metastasis of bronchial carcinoid spared her an unnecessary total thyroidectomy. Among 18 patients with 19 islet-cell tumors, scintigraphy detected three of five insulinomas, whereas computed tomography identified only one. Receptor positivity in an islet-cell tumor (vipoma?) with no metastases on the scan led to surgical removal of the primary tumor. Receptor-positive metastases of gastrinoma (two of three patients), glucagonoma (two of three patients), and parathyroid hormone-related peptide-producing tumor (one patient) led to octreotide treatment. Nonvisualization of metastases of a glucovipoma led to chemotherapy., Conclusions: Somatostatin-receptor scintigraphy contributes to the management of patients with gastroenteropancreatic tumors in the following ways: 1) localization of a primary occult tumor, allowing surgical removal; 2) staging of the disease for optimal therapy-surgical excision or systemic treatment; and 3) identification of receptor status of the metastases for octreotide treatment or chemotherapy.

Endocrine neoplasms are rare tumors that have traditionally been imaged with ultrasound, CT, magnetic resonance imaging, and angiography. Additional imaging modalities are now available. Endoscopic ultrasound is a new imaging approach to islet cell tumors of the pancreas, in which they typically appear round, homogeneous, and slightly hypoechoic compared with the pancreatic parenchyma. Carcinoid tumors can now be localized with 111In octreotide scintigraphy, which binds to the somatostatin receptors in the tumor. Pheochromocytomas have a distinctive appearance on magnetic resonance imaging, but important advances have occurred using 131I metaiodobenzylguanidine (MIBG). 131I MIBG scanning has a high diagnostic accuracy in detecting pheochromocytoma, with sensitivity greater than 90%. The various tumors and recent advances in their imaging are discussed.

A 54-year-old woman was admitted to our department for assessment of a tumor of the pancreas found incidentally on abdominal ultrasonography. Examination revealed a hypovascular 1-cm sized tumor in the body of the pancreas. Surgical examination revealed that the tumor was solitary and located in the pancreas body, with no invasion to the adjacent organs iof lymph node involvement. Distal pancreatectomy, preserving the spleen, was performed. Histologically, the tumor was a glucagonoma with evident ductular and tubular structures, suggesting that its site of origin was ductal epithelia.

A 52-year-old man with a past history of a pituitary adenoma and hyperparathyroidism due to a parathyroid adenoma was admitted because of a solitary tumour of the pancreas revealed by ultrasonography. His family history was unremarkable. Plasma glucagon levels were slightly elevated (280 ng/l, normal range, 40-180 ng/l) with decreased plasma amino acid levels. Plasma glucagon levels disclosed an exaggerated response during an arginine infusion test and paradoxical elevation during a 75 g oral glucose tolerance test. Endoscopic ultrasonography revealed a monolocular cystic mass of about 3 cm in diameter in the body of the pancreas. A pancreatic tumour was diagnosed before surgery as a cystic glucagonoma. Intra-operative ultrasonography showed one cystic mass in the body of pancreas and two other solid tumours, about 1 cm and 0.5 cm in diameter, in the tail of the pancreas. Histologically, all three tumours showed neoplastic epithelial cells with round nuclei forming cords and/or a ribbon-like arrangement. They showed positive staining for Grimelius' silver stain and immunopositive cells for glucagon. Genetic analysis of the main cystic tumour revealed loss of heterozygosity (LOH) on chromosome 11. After the operation, the responses of plasma glucagon to arginine infusion and oral glucose became normal. Here we describe the usefulness of these provocation tests for early diagnosis and post-operative follow-up in a rare cystic glucagonoma associated with multiple endocrine neoplasia type 1 (MEN 1) which had LOH on chromosome 11.

Unlabelled: Neuroendocrine tumor cells frequently overexpress somatostatin receptors at their cell surfaces. To evaluate the possibility of using the somatostatin analog 111In-DTPA-D-Phe1-octreotide for radiation therapy, we studied the binding and subsequent internalization of 111In into three types of cultured human neuroendocrine tumor cells., Methods: Primary cultures of gastric carcinoid, midgut carcinoid and glucagonoma cells were incubated with 111In-DTPA-D-Phe1-octreotide and cell-surface bound, internalized and released 111In activity was measured. Electron microscopic autoradiography was also performed., Results: All three cell types specifically (80%-95%) bound 111In-DTPA-D-Phe1-octreotide and internalized 111In. After 1 hr pulse incubation with 111In-DTPA-D-Phe1-octreotide, there was an initial decrease in intracellular 111In to about 50% during the subsequent 6-hr incubation. Almost no further release was observed during the remaining 18-42 hr studied. Autoradiography showed that the internalized 111In was found in the cytoplasm and nucleus in the midgut carcinoid cells., Conclusion: Indium-111 DTPA-D-Phe1-octreotide might be useful for radiation therapy of patients with surgically incurable tumors having high somatostatin receptor densities.