Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoid Tumor/drug therapy , Gastrointestinal Neoplasms/drug therapy , Pancreatic Neoplasms/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Benzamides , Carcinoid Tumor/metabolism , Endocrine Gland Neoplasms/drug therapy , Endocrine Gland Neoplasms/metabolism , Gastrointestinal Neoplasms/metabolism , Humans , Imatinib Mesylate , Pancreatic Neoplasms/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Receptors, Platelet-Derived Growth Factor/metabolismSubject(s)
Brachytherapy/methods , Carcinoid Tumor/radiotherapy , Carcinoid Tumor/secondary , Gastrointestinal Neoplasms/pathology , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Yttrium Radioisotopes/therapeutic use , Carcinoid Tumor/diagnostic imaging , Chemoembolization, Therapeutic , Female , Glass , Hepatic Artery , Humans , Liver Neoplasms/diagnostic imaging , Microspheres , Resins, Synthetic , Tomography, X-Ray Computed , Treatment Outcome , Yttrium Radioisotopes/administration & dosageABSTRACT
BACKGROUND: Glucagon-secreting endocrine pancreatic tumor is a rare disease, hence controlled studies on clinical management are lacking. In an attempt to assess the efficacy of diagnostic and therapeutic measures in patients with glucagonoma, a retrospective study was performed using the archives of a tertiary care center. PATIENTS AND METHODS: Records from 340 patients with endocrine pancreatic tumors were reassessed and 23 patients with malignant endocrine pancreatic tumor and elevated plasma glucagon levels were identified. RESULTS: About 7% of patients with histologically verified tumors fullfilled our criteria for glucagonoma. Only 22% of these patients had developed diabetes prior to the diagnosis of glucagonoma. Seventy eight percent had metastatic disease to the liver at diagnosis. Necrolytic migratory erythema was diagnosed or clinically suspected in 52%. Somatostatin receptor scintigraphy was positive in 95%. Nineteen patients received chemotherapy at some point, in 18 cases streptozotocin and 5 FU. With this treatment, objective radiological responses were seen in 50% of evaluable patients. Other treatment modalities used were interferon, somatostatin analogs, hepatic artery embolization, radio-frequency ablation of liver metastases, and radiolabeled somatostatin analogs. During the study period, 11 patients died at a median of 80 months from diagnosis whereas 11 patients are still alive after a median follow up of 52 months. One patient was lost to follow-up. CONCLUSIONS: Glucagonomas represent 7% of our comprehensive referral material of endocrine pancreatic tumors. Necrolytic migratory erythema was a common finding (52%) and diabetes less frequent at presentation than previously reported. Tumors were positive on somatostatin receptor scintigraphy and objective responses were seen to chemotherapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Erythema/complications , Glucagonoma/therapy , Pancreatic Neoplasms/therapy , Adult , Aged , Combined Modality Therapy , Erythema/diagnosis , Female , Glucagon/blood , Glucagonoma/complications , Glucagonoma/metabolism , Glucagonoma/mortality , Glucagonoma/pathology , Humans , Interferons , Liver Neoplasms/secondary , Male , Middle Aged , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Receptors, Somatostatin/metabolism , Retrospective Studies , Sex Factors , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. EXPERIMENTAL DESIGN: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m(2)) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of O(6)-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n=23) and compared with response to temozolomide. RESULTS: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with O(6)-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. CONCLUSIONS: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
Subject(s)
Bronchial Neoplasms/drug therapy , Carcinoid Tumor/drug therapy , Dacarbazine/analogs & derivatives , Neuroendocrine Tumors/drug therapy , Thyroid Neoplasms/drug therapy , Aged , Bronchial Neoplasms/diagnostic imaging , Bronchial Neoplasms/pathology , Carcinoid Tumor/diagnostic imaging , Carcinoid Tumor/pathology , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Female , Hematologic Diseases/chemically induced , Humans , Male , Middle Aged , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Retrospective Studies , Temozolomide , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/pathology , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
[Ca(2+)](i) oscillations were found in human osteoblast-like cells (hOB cells) exposed to high-lipid bovine serum albumin (BSA), but not when exposed to low-lipid BSA. These [Ca(2+)](i) oscillations were inhibited by heptanol and suramin, which implies that gap junctions and purinergic signalling may be important for these [Ca(2+)](i) oscillations. The high-lipid BSA preparation that was used contains arachidonic acid. [Ca(2+)](i) oscillations could be induced by low lipid albumin with arachidonic acid added. The albumin-bound lipids were also important for osteoblast growth since DNA synthesis and the total cell protein content was higher in hOB cells exposed to high-lipid BSA. The effect of arachidonic acid on hOB cell proliferation was bone-donor dependent; both stimulatory and inhibitory effects were observed. The physiological importance of albumin-bound lipids is unclear; given that albumin has only minimal contact with osteoblasts under normal conditions. Only when bone capillaries are disrupted, e.g. during a fracture, would significant amounts of albumin reach osteoblasts. Albumin-bound lipids could therefore contribute to stimulation of osteoblast proliferation during fracture healing.