One hundred years after the discovery of insulin and glucagon:the history of tumors and hyperplasias that hypersecrete these hormones

One century ago, in 1922, Frederick G Banting, Charles H Best, James B Collip and John J R Macleod first published their experiments resulting in the isolation of a hypoglycemic factor, named insulin, from a solution extract from a dog’s pancreas. One year later, in 1923, a hyperglycemic factor named glucagon was isolated by Charles P Kimball and John R Murlin. In the following years, it could be demonstrated that pancreatic islet alpha- and beta-cell neoplasms and hyperplasias could inappropriately secrete excessive amounts of these two hormones. This review is a sequel to the discovery of insulin and glucagon and introduces the history of this fascinating group of neuroendocrine neoplasms and hyperplasias of the pancreas.</p

Medical treatment of neuroendocrine neoplasms

Medical therapy of clinically nonfunctioning (nonsecreting) low grade (grade 1–2) neuroendocrine neoplasms consists of first-line first generation somatostatin analogs and second-line or third-line peptide receptor radiotherapy with radiolabeled beta-emitting somatostatin analogs, Everolimus, Sunitinib, and interferon-α. Second-generation somatostatin analogs like Pasireotide have no proven superiority over first-generation somatostatin analogs. Chemotherapy is usually reserved as second-line therapy in pancreatic neuroendocrine neoplasms and neuroendocrine carcinomas.</p

What Is Carcinoid Syndrome? A Critical Appraisal of Its Proposed Mediators:A critical appraisal of its proposed mediators

Carcinoid syndrome (CS) is a debilitating disease that affects approximately 20% of patients with neuroendocrine neoplasms (NEN). Due to the increasing incidence and improved overall survival of patients with NEN over recent decades, patients are increasingly suffering from chronic and refractory CS symptoms. At present, symptom control is hampered by an incomplete understanding of the pathophysiology of this syndrome. This systematic review is the first to critically appraise the available evidence for the various hormonal mediators considered to play a causative role in CS. Overall, evidence for the putative mediators of CS was scarce and often of poor quality. Based on the available literature, data are only sufficient to agree on the role of serotonin as a mediator of CS-associated diarrhea and fibrosis. A direct role for tachykinins and an indirect role of catecholamines in the pathogenesis of CS is suggested by several studies. Currently, there is insufficient evidence to link histamine, bradykinin, kallikrein, prostaglandins, or motilin to CS. To summarize, available literature only sufficiently appoints serotonin and suggests a role for tachykinins and catecholamines as mediators of CS, with insufficient evidence for other putative mediators. Descriptions of CS should be revised to focus on these proven hormonal associations to be more accurate, and further research is needed into other potential mediators.</p

Search for gamma‐ray emission from AGN with COMPTEL

The COMPTEL data (∼0.7–30 MeV) were searched for emission from AGN. Four sources have been detected so far: the quasars 3C 273, 3C 279, PKS 0528+134, and the radio galaxy Centaurus A. 3C 273 and 3C 279 were detected in CGRO observation period 3 with quite different spectral shapes. There is also evidence for 3C 273 at a weak flux level in observation period 11. The quasar PKS 0528+134 was detected above 3 MeV as part of a search for AGN already observed by EGRET. Cen A was seen up to 3 MeV by combining data from different observation periods

COMPTEL observations of the inner galaxy

This paper presents a first global study of COMPTEL observations of the inner Galaxy in the energy range 0.75–10 MeV. Preliminary findings demonstrate COMPTEL’s capabilities for mapping the observed gamma radiation and disentangling the contributions from point sources and diffuse emission

The interstellar oxygen-K absorption edge as observed by XMM-Newton

High resolution X-ray spectra of the Reflection Grating Spectrometer (RGS) on board the XMM satellite are used to resolve the oxygen K absorption edge. By combining spectra of low and high extinction sources, the observed absorption edge can be split in the true interstellar (ISM) extinction and the instrumental absorption. The detailed ISM edge structure closely follows the edge structure of neutral oxygen as derived by theoretical R-matrix calculations. However, the position of the theoretical edge requires a wavelength shift. In addition the detailed instrumental RGS absorption edge structure is presented. All results are verified by comparing to a subset of Chandra LETG-HRC observations.Comment: LaTeX2e A&A style, 10 pages, 12 postscript figures, accepted for publication in Astronomy and Astrophysic

Approach to the Patient: Insulinoma

Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with the Whipple triad: (1) symptoms, signs, or both consistent with hypoglycemia; (2) a low plasma glucose measured at the time of the symptoms and signs; and (3) relief of symptoms and signs when the glucose is raised to normal. Nonmetastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive." The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options.</p