Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment

Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.

Early detection of pine wilt disease in Pinus tabuliformis in North China using a field portable spectrometer and UAV-based hyperspectral imagery

Background:Pine wilt disease(PWD)is a major ecological concern in China that has caused severe damage to millions of Chinese pines(Pinus tabulaeformis).To control the spread of PWD,it is necessary to develop an effective approach to detect its presence in the early stage of infection.One potential solution is the use of Unmanned Airborne Vehicle(UAV)based hyperspectral images(HIs).UAV-based HIs have high spatial and spectral resolution and can gather data rapidly,potentially enabling the effective monitoring of large forests.Despite this,few studies examine the feasibility of HI data use in assessing the stage and severity of PWD infection in Chinese pine.Method:To fill this gap,we used a Random Forest(RF)algorithm to estimate the stage of PWD infection of trees sampled using UAV-based HI data and ground-based data(data directly collected from trees in the field).We compared relative accuracy of each of these data collection methods.We built our RF model using vegetation indices(VIs),red edge parameters(REPs),moisture indices(MIs),and their combination.Results:We report several key results.For ground data,the model that combined all parameters(OA:80.17%,Kappa:0.73)performed better than VIs(OA:75.21%,Kappa:0.66),REPs(OA:79.34%,Kappa:0.67),and MIs(OA:74.38%,Kappa:0.65)in predicting the PWD stage of individual pine tree infection.REPs had the highest accuracy(OA:80.33%,Kappa:0.58)in distinguishing trees at the early stage of PWD from healthy trees.UAV-based HI data yielded similar results:the model combined VIs,REPs and MIs(OA:74.38%,Kappa:0.66)exhibited the highest accuracy in estimating the PWD stage of sampled trees,and REPs performed best in distinguishing healthy trees from trees at early stage of PWD(OA:71.67%,Kappa:0.40).Conclusion:Overall,our results confirm the validity of using HI data to identify pine trees infected with PWD in its early stage,although its accuracy must be improved before widespread use is practical.We also show UAV-based data PWD classifications are less accurate but comparable to those of ground-based data.We believe that these results can be used to improve preventative measures in the control of PWD.

Newly discovered endocrine functions of the liver

The liver,the largest solid visceral organ of the body,has numerous endocrine functions,such as direct hormone and hepatokine production,hormone metabolism,synthesis of binding proteins,and processing and redistribution of metabolic fuels.In the last 10 years,many new endocrine functions of the liver have been discovered.Advances in the classical endocrine functions include delineation of mechanisms of liver production of endocrine hormones[including 25-hydroxyvitamin D,insulin-like growth factor 1(IGF-1),and angiotensinogen],hepatic metabolism of hormones(including thyroid hormones,glucagon-like peptide-1,and steroid hormones),and actions of specific binding proteins to glucocorticoids,sex steroids,and thyroid hormones.These studies have furthered insight into cirrhosis-associated endocrinopathies,such as hypogonadism,osteoporosis,IGF-1 deficiency,vitamin D deficiency,alterations in glucose and lipid homeostasis,and controversially relative adrenal insufficiency.Several novel endocrine functions of the liver have also been unraveled,elucidating the liver’s key negative feedback regulatory role in the pancreaticαcell-liver axis,which regulates pancreaticαcell mass,glucagon secretion,and circulating amino acid levels.Betatrophin and other hepatokines,such as fetuin-A and fibroblast growth factor 21,have also been discovered to play important endocrine roles in modulating insulin sensitivity,lipid metabolism,and body weight.It is expected that more endocrine functions of the liver will be revealed in the near future.

Pathologic pancreatic endocrine cell hyperplasia

Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known.β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy,which is commonly caused by mutations in the islet ATP-sensitive potassium channel,and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors.An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence,the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium.Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia,elevated islet hormone levels,and pancreatic neuroendocrine tumors.Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

Tumors and cancers of the gastrointestinal tract and pancreas are commonly derived from precursor lesions so that understanding the physiological, cellular, and molecular mechanisms underlying the pathogenesis of precursor lesions is critical for the prevention and treatment of those neoplasms. Pancreatic neuroendocrine tumors(PNETs) can also be derived from precursor lesions. Pancreatic α cell hyperplasia(ACH), a specific and overwhelming increase in the number of α cells, is a precursor lesion leading to PNET pathogenesis. One of the 3 subtypes of ACH, reactive ACH is caused by glucagon signaling disruption and invariably evolves into PNETs. In this article, the existing work on the mechanisms underlying reactive ACH pathogenesis is reviewed. It is clear that the liver secretes a humoral factor regulating α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed.