Pancreatic neuroendocrine tumors: contemporary diagnosis and management.

Pancreatic neuroendocrine tumors (PNETs) are neoplasms that arise from the hormone producing cells of the islets of Langerhans, also known as pancreatic islet cells. PNETs are considered a subgroup of neuroendocrine tumors, and have unique biology, natural history and clinical management. These tumors are classified as 'functional' or 'non-functional' depending on whether they release peptide hormones that produce specific hormone- related symptoms, usually in established patterns based on tumor subtype. This manuscript will review pancreatic neuroendocrine tumor subtypes, syndromes, diagnosis, and clinical management.

[Type 1 diabetes as a mask of a neuroendocrine tumour of pancreas]. / Cukrzyca typu 1 jako maska neuroendokrynnego guza trzustki.

Neuroendocrine tumours of pancreas originating from pancreatic islet cells are uncommon neoplasms with clinical manifestation depending on a type of hormone secreted. Diabetes as a clinical sign of such a tumour has been reported many times and is not an uncommon finding but it is generally mild and makes only a part ofa whole pattern of symptoms. We report on a case of a malignant neuroendocrine pancreatic tumour in 19 years old patient, where diabetes, with a clinical course typical for type 1 diabetes, was the first and the main symptom of the disease.

Experiences with nonfunctioning neuroendocrine neoplasms of the pancreas.

AIM: We present our experiences in the treatment of nonfunctioning neuroendocrine neoplasms of the pancreas to define the natural history and to suggest proper management. METHOD: From August 1993 to June 2005, the medical records of 19 patients with the diagnosis of nonfunctioning neuroendocrine (islet cell) neoplasms of the pancreas were retrospectively reviewed with respect to patient characteristics, characteristics of neoplasms, surgical procedures, and long-term outcomes in the Yonsei University Medical Center, Seoul, Korea. RESULTS: The median age of the patients (10 males and 9 females) was 51 years. Abdominal pain and discomfort (58%) were the most frequent symptoms. Tumors with a median size of 3.5 cm were noted in the head of the pancreas in 9 patients and in the body or in the tail of the pancreas in 10 patients. Thirteen patients (68%) had neoplasms with malignant features. Twelve patients (63%) underwent surgical resection, and curative resection was performed in 10 patients (53%). Unresectable neoplasms (p=0.0055), distant metastases (p=0.0124), and macroinvasion to adjacent organs (p=0.024) had significantly adverse effects on the mean survival. Neither palliative surgery nor adjuvant chemoradiation therapy seemed to be effective. CONCLUSIONS: Early detection of nonfunctioning neuroendocrine neoplasms of the pancreas is important, and curative resection should be attempted for a good prognosis.

[Non-functional islet-cell tumor: analysis of 237 cases].

OBJECTIVE: To summarize the clinical aspects of nonfunctional islet-cell tumor (NIT) reported in Chinese periodicals. METHODS: Articles in Chinese on NIT were screened from the Chinese Bio-Medical Database (1981.1 - 1999.10). Data of epidemiology, clinical manifestations, diagnosis, defferential diagnosis, and treatment of NIT were analyzed. RESULTS: 60 articles and 237 cases of NIT were selected. The female to male ratio was 2.9:1. Abdominal mass was the most common clinical symptom. It was difficult for the pre-operative diagnosis of NIT and differentiation from pancreatic tumor or retroperitoneal mass. The malignant rate of NIT was 35%. The five-year survival rate of malignant NIT was 53.1%. CONCLUSION: NIT is rare. It occurs more often in female than in male. The preoperative diagnostic rate is rather low. The prognosis of malignant NIT is favorable. Active treatment is strongly recommended.

The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pancreatic islet pathology in Sprague-Dawley rats.

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on aged-related degenerative and proliferative changes of the endocrine pancreas in Sprague-Dawley (SD) rats. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Before each necropsy, glucose and serum insulin levels were measured. In addition to the routine histopathologic examination performed in both sexes, determination of 9 pancreatic islet stereologic parameters was done in males at 13, 26, and 53 weeks. In AL-fed rats, early changes in the islet morphology occurred, which resulted in a high incidence of islet fibrosis, focal hyperplasias and adenomas by two years. DR was dose-proportionally associated with decreased glucose and serum insulin levels, and delayed the onset, and decreased the incidence and severity of islet fibrosis and hyperplasia. Results of the stereology supported the histopathologic and clinical chemistry findings. It demonstrated that, compared to AL-fed rats, DR-fed rats had smaller pancreas, smaller pancreatic islets, smaller insulin secreting cell volumes, a lower degree of islet fibrosis and a lower islet cell BrdU labeling index, which correlated with a lower incidence of islet adenoma and carcinoma at study termination. Moderate and marked degrees of DR delayed the onset and severity of islet hyperplasia and fibrosis in a temporal- and dose-related manner. In contrast to marked DR, which dramatically prevented these changes, moderate DR delayed but not prevented onset of islet tumors. These findings support the concept that moderate DR results in a better-controlled animal model with a lower incidence or delayed onset of chronic spontaneous endocrine diseases in the rat bioassay.

RITA/Registry of Industrial Toxicology Animal data: a comparative immunohistochemical study of 77 islet cell carcinomas in Sprague-Dawley and Wistar rats using antibodies against insulin, glucagon, somatostatin and gastrin.

UNLABELLED: The objective of this study was to investigate spontaneous islet cell carcinomas with particular reference to possible existing strain differences between Sprague Dawley (SD) and Wistar (W) rats in incidence and immunohistochemical staining pattern. Secondly the occurrence of somatostatin and/or gastrin-positive islet cell tumors should be tested. Islet cell adenocarcinomas (34 from SD, 43 from W-rats) were selected from the RITA-data base and company in-house data base out of an animal pool of 3915 (1681 SD, 2234 W-rats). They were untreated or sham-treated (vehicle) control animals from carcinogenicity studies and whole life-span experiments. Islet cell carcinomas occurred in a higher incidence in male rats (2.98% for SD, 3.23% for W) than in female rats (1.07% for SD, 0.63% for W). All specimens were immunohistologically stained with antibodies against insulin, glucagon, somatostatin and gastrin and, selected specimens with additional antibodies (pancreatic polypeptide, lipase, chymotrypsin, S100-protein, actin and cytokeratin). 94% (SD) and 93% (W), respectively, were insulin-positive and the mean staining intensity (on a scale ranging from 0-4) for insulin was 3.58 (SD) versus 3.37 (W). This high insulin staining incidence and intensity characterized most islet cell carcinomas as malignant insulinomas. 24% (SD) and 37% (W), respectively, were glucagon-positive. Except two tumors in W-rats with a focal strong glucagon expression, the mean staining intensity for glucagon was low (0.38 SD, 0.72 W). 38% (SD) and 44% (W), respectively, were somatostatin-positive, but except for five cases having a focal to multifocal, moderate to marked staining, only a few tumor cells were positive for somatostatin in the other cases and the mean staining intensity for somatostatin was low (0.50 SD, 0.84 W). 6% (SD) and 23% (W), respectively, were gastrin-positive, but only one case of a male Wistar rat exhibited a focal strong staining in parts of the tumor. The other cases showed only a few tumor cells which were positive for gastrin. The mean staining intensity for gastrin was low (0.06 SD, 0.35 W). In all tumors with marked glucagon, somatostatin or gastrin expression, the immunostaining for insulin was still predominating. Thus, insulin was the major hormone produced by most of the tumor cells. Five out of 77 tumors evaluated were immunohistologically negative with all applied antibodies. CONCLUSION: This study presents the first immunohistochemical survey on spontaneous islet cell carcinomas in SD and Wistar rats stained with antibodies against the endocrine pancreas hormones insulin, glucagon, somatostatin and gastrin. No major differences in incidence or immunohistochemical staining pattern between SD and W-rats could be detected. In contrast to SD rats, Wistar rats had multihormonal coexpression in 16.3%. The multihormonal appearance of the neoplasms is well comparable with the findings in other animal species and human insulinomas. Moreover, this is the first study in rats which reports five cases with a marked co-expression of somatostatin and one case with marked focal co-expression of gastrin in malignant islet cell adenocarcinomas.

Production and secretion of chromogranin A and pancreastatin by the human pancreatic carcinoma cell line QGP-1N on stimulation with carbachol.

Chromogranin A (CGA) is thought to be a precursor of pancreastatin (PST). Carbachol (Cch) stimulated the secretion of CGA and PST from QGP-1N cells derived from a human pancreatic islet cell tumor. Atropine inhibited the secretion of both. Sodium fluoride, phorbol ester, and calcium ionophore also stimulated the secretion of both. Cch (10(-5) M) stimulated inositol 1,4,5-trisphosphate production in QGP-1N cells. Stimulation with Cch increased the total amount of PST in the cells and the medium 1.7-fold and decreased the amount of CGA in the cells and medium. QGP-1N cells were labelled with [35S]methionine, and then CGA and PST in the cells and medium were immunoprecipitated with specific antisera, and separated by electrophoresis in polyacrylamide gel. Stimulation with Cch resulted in an increase in the intensity of PST-immunoreactive bands and a decrease in those of CGA-immunoreactive bands. Cch did not increase the cellular level of CGA messenger RNA. These results suggested that (1) the secretion of CGA and PST from QGP-1N cells is regulated mainly through muscarinic receptors coupled with activation of polyphosphoinositide breakdown by a G protein, with intracellular calcium ion and protein kinase C playing a role in the stimulus-secretion coupling and that (2) Cch may induce the secretion of PST and CGA and processing from CGA to PST.