Hyperthermic isolated liver perfusion with melphalan and bevacizumab.

Whereas surgical resection is the only curative treatment for liver tumors, effective treatment for isolated unresectable lesions when there is tumor progression in spite of several lines of chemotherapy remains to be found. We report herein two cases of patients treated by a 1-hour Hyperthermic Isolated Liver Perfusion (HILP) with a combination of melphalan and bevacizumab leading to complete response. The first patient had liver metastases secondary to previously resected malignant glucagonoma and the second, recurrent hepatocellular carcinoma. We used bevacizumab in association with melphalan for HILP because of the additional effect of an anti-VEGF antibody in these highly vascularized tumors and its locally restricted delivery to the isolated hepatic vascular compartment despite of its classic contraindication in association with surgery. The protocol was approved by the Ethics Committee. Enhanced CT scans during follow-up showed complete tumor necrosis as early as the second postoperative day. Patients had 27 and 7 months disease-free survival and 48 and 41 months overall survival after HILP, for neuroendocrine liver metastases and HILP plus liver transplantation for HCC respectively. Under very specific conditions, bevacizumab in HILP can provide excellent tumor response in hopeless clinical cases of liver tumors.

Pancreatic glucagonoma presenting as a pulmonary mass.

Glucagonoma is an uncommon disease, a neuroendocrine tumour that develops from glucagon-producing pancreatic cells. They are usually slow-growing, but generally advanced at diagnosis, and metastatic disease is virtually incurable. Liver is the most common site of metastatic disease. We present the case of a 48-year-old man with a glucagonoma being diagnosed from a pulmonary mass. This case had no liver affection in the whole evolution of the disease, and showed a particularly aggressive course, with very little response to all therapies administered, and a survival from diagnosis of just 16 months.

Glucagonoma with two pancreatic masses and pulmonary metastases as debut of MEN-1.

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.

Metastatic glucagonoma: treatment with liver transplantation.

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.

[Glucagonoma: a recent series of 7 cases]. / Le glucagonome: à propos d'une série récente de 7 cas.

We report a series of 7 glucagonoma patients seen between 1994 and 2001, 5 males and 2 females, aged 32-69 years, with: necrolytic migratory erythema (NME) (n = 2), liver metastases (n = 3), jaundice (n = 1) and 1 case of familial history of multiple endocrine neoplasia. The diagnosis combined histology and hyperglucagonemia; 6 patients developed metastasis (5 initially); during the follow-up 3 developed a necrolytic erythema migraticum (NEM) worsening the general status. Somatostatin receptor scanning was highly positive in all. Four patients were operated, 5 received chemotherapy (2 OR and 2 SD), 3 had chemoembolization (1 transient improvement). Somatostatin was efficient on general status or skin lesions in all patients. Two died and 5 are alive with a follow up ranging from 12 to 60 months. We want to emphasize on the higher frequency than expected of this disease, the frequency of NEM, the efficacy of SMS on NEM and general status and on the fairly good prognosis. The high uptake of SMS by tumors on scanning could rise hopes about radioconjugate therapy.

Spinal metastasis as the initial manifestation of a nonsecretory glucagonoma.

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.

Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases: outcomes of an aggressive approach.

BACKGROUND: Pancreatic islet cell cancers are often characterized by the presence of endocrinopathies, an indolent clinical course, and a propensity for hepatic metastases. Hepatic metastases are associated with a negative impact on survival. The role of concurrent resections of pancreatic islet cell cancers and the hepatic metastases has not been defined. METHODS: The records of all consecutive patients undergoing concurrent resections of pancreatic islet cell cancers and their hepatic metastases between 1980 and 1998 were reviewed. Outcomes regarding overall progression-free and symptom-free survival and perioperative morbidity and mortality were assessed. RESULTS: All 23 patients underwent distal pancreatectomy and splenectomy. Six major (> or = 3 segments) and 17 minor (c3 segments) partial hepatectomies were performed. Complete gross resection of cancer (R0/R1) were performed in 9 patients and debulking resections (R2) (<10% residual tumor volume) in 14 patients. There were no perioperative deaths. Major complications occurred in 4 patients (18%). Overall, progression-free, and symptom-free survival was 71% (median: 76 months), 5% (median: 21 months), and 24% (median: 26 months), respectively, at 5 years. Conclusions. These data support aggressive concurrent resection of the pancreatic islet cell cancers and synchronic hepatic metastases when technically feasible. Because disease progression is frequent and the major cause of death, investigations of adjuvant and adjunctive therapies are warranted.

Is glucagonoma of the pancreas a curable disease?

BACKGROUND: Glucagonomas are rare neuroendocrine tumors of the pancreas. Because of its rarity, its natural history is not well understood. AIM: We evaluated the natural history of glucagonomas treated at a tertiary care cancer center. METHODS: A retrospective analysis of 12 patients during 1970 to 2000 was performed. Six patients (50%) had a tumor located in the head of the pancreas. RESULTS: Abdominal pain (83%) and weight loss (75%) were the most common symptoms. Median tumor size was 6 cm (range 0.04-10). Seven patients (58%) had liver metastases. Five patients (42%) underwent curative resection. Overall median survival was 66 mo, and 5-yr overall survival was 66%. Five-yr overall survival was 83% for patients who had resection versus 50% for the non-resected patients (p = 0.04). Patients who were disease-free had a complete resection of the primary tumor and no liver involvement. CONCLUSIONS: Glucagonomas generally present with liver metastases at the time of diagnosis. Cure is only possible if the disease is localized and completely resected.

[Glucagon-secreting malignant neuroendocrine tumor of the pancreas]. / Maligner neuroendokriner Pankreastumor mit Glukagonproduktion.

BACKGROUND: Glucagonoma is a rare pancreatic tumor of islet alpha 2 cells. Fewer than 200 cases have been reported worldwide, with an estimated incidence of 1 in 20 million. In general, the disease is characterized by a well-defined clinical syndrome which typically shows as necrotic migratory erythema of the skin, weight loss, diabetes mellitus, anemia, cheilosis and stomatitis. Since pancreatic glucagonomas are predominantly located in the tail and findings of radiographic or sonographic examination can remain unspecific, patients often present already metastasis when diagnosis is first established. CASE REPORT: We report the case of a 67-year-old man with an extended malignant glucagonoma of the pancreas infiltrating already the hilus of the spleen and, additionally, presenting metastatic lesions in the liver and the left adrenal gland. A monohormonal expression of glucagon could be ascertained by serological and immunohistochemical analysis. The special feature of this case is that the tumor was not associated with the characteristic skin rash. CONCLUSION: An unclear migratory erythema combined with diabetes mellitus and stomatitis/cheilosis should lead to the differential diagnosis of glucagonoma. Isolated glucagonomas are very difficult to find out and often diagnosed already presenting metastasis.

Scintigraphic long-term follow-up of a patient with metastatic glucagonoma.

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.

Pancreatic endocrine tumours.

Gastrointestinal endocrine neoplasms are rare tumours that have been classified by the peptides they secrete and the resulting clinical syndromes. The incidence of these tumours is estimated to be less than 1-1.5 cases/100,000 of the general population. These gastrointestinal endocrine cells are characterized by similar cytochemical and ultrastructural characteristics, contain amines and they are capable of uptake of amine precursors to amines or peptides. The function of these cells is the neuroendocrine regulation of normal homeostatic mechanisms including vasomotor tone as well as carbohydrate, calcium and electrolyte metabolism. Each amine precursor uptake and decarboxylation cell normally synthesizes, stores and secretes its single amine or polypeptide and is responsive to its environment for stimulation or suppression in the related clinical syndrome.

Treatment of metastatic glucagonoma to the liver: case report and literature review.

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.