VIP and Calcitonin-Producing Pancreatic Neuroendocrine Tumor with Watery Diarrhea: Clinicopathological Features and the Effect of Somatostatin Analogue

Context Pancreatic neuroendocrine tumor (pNET) secretes various peptide hormones; however, calcitonin hypersecretion is rare. Its clinicopathological significance and treatment is still controversial. Case report A 43 year-old Japanese man presented severe watery diarrhea and a large mass in the pancreatic tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0-100 pg/mL), and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL). There was no tumor in other endocrine organs. The resected tumor was composed of 80% calcitonin-positive cells and 10% VIP-positive cells. After the operation, the levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively, and diarrhea was improved. The mRNA of somatostatin receptor (SSTR) subtypes 2, 3 and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of normal pancreas, respectively. At 19 months after the operation, blood calcitonin was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver. With the treatment of long-acting somatostatin analogue, calcitonin was reduced to 803 pg/mL. The patient does not present endocrine symptom, and the size of the metastatic tumors appears stable. Conclusion From the world literature to date, co-secretion of VIP and calcitonin was documented in only 10 cases of pNET including the current case. Although VIP is a primary cause of diarrhea in these cases, high level of calcitonin may also influence on the clinical symptoms. Somatostatin analogue suppresses the levels of VIP and calcitonin, and the control proliferation is also expected when tumor cells express SSTRs

Axon terminal hypertrophy of striatal projection neurons with levodopa-induced dyskinesia priming

BackgroundA rat model of levodopa-induced dyskinesia (LID) showed enlarged axon terminals of striatal direct pathway neurons in the internal segment of the globus pallidus (GPi) with excessive gamma-aminobutyric acid (GABA) storage in them. Massive GABA release to GPi upon levodopa administration determines the emergence of LID.ObjectivesWe examined whether LID and axon terminal hypertrophy gradually develop with repeated levodopa treatment in Parkinsonian rats to examine if the hypertrophy reflects dyskinesia priming.Methods6-hydroxydopamine-lesioned hemiparkinsonian rats were randomly allocated to receive saline injections (placebo group, 14 days; n = 4), injections of 6 mg/kg levodopa methyl ester combined with 12.5 mg/kg benserazide (levodopa-treated groups, 3-day-treatment; n = 4, 7-day-treatment; n = 4, 14-day-treatment; n = 4), or injections of 6 mg/kg levodopa methyl ester with 12.5 mg/kg benserazide and 1 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin for 14 days (8-OH-DPAT-treated group; n = 4). We evaluated abnormal involuntary movement (AIM) scores and axon terminals in the GPi.ResultsThe AIM score increased with levodopa treatment, as did the hypertrophy of axon terminals in the GPi, showing an increased number of synaptic vesicles in hypertrophied terminals.ConclusionIncreased GABA storage in axon terminals of the direct pathway neurons represents the priming process of LID