Islet Cell Carcinoma Research Articles

Evaluation of Neoplasia, Treatments, and Survival in Lizard Species.

Neoplasia has been reported in lizards, but more research is needed to accurately document the prevalence and prognosis of the various known neoplasms that affect lizards. This study reviewed medical records from an online database, the Exotic Species Cancer Research Alliance (ESCRA), and reviewed published literature to determine the prevalence of neoplasia, malignancy, metastasis, treatment strategies, and outcomes by species and sex. Records from 55 individual lizards, 20 different species, and 37 different tumors were identified. In the literature, 219 lizards, 59 species, and 86 unique tumors were identified from 72 published case reports. Potential signalment factors such as age, sex, and species were evaluated to see if they affected case outcome. Additional factors including neoplasia type, presence of metastasis, and types of pursued treatments were also evaluated. Statistical analysis was performed to determine whether a factor was significantly associated with animal death due to the identified neoplasia or with animal survival or death due to other causes (non-neoplastic outcomes). Komodo dragons and savannah monitors were more likely to die from neoplasia compared to other lizard species. Cases where the status of metastasis was unknown were significantly associated with death due to neoplasia. Having an unknown status of male versus female was significantly associated with non-neoplastic outcomes of death. Leukemia and islet cell carcinoma were significantly associated with death due to neoplastic causes. Chondrosarcoma, myxosarcoma, osteosarcoma, and squamous cell carcinoma were significantly associated with non-neoplastic outcomes of death. Surgery alone and radiation therapy alone each were significantly associated with non-neoplastic outcomes of death, while lizards not receiving treatment were significantly associated with death due to neoplasia. Benign neoplasia was significantly associated with non-neoplastic outcomes of death. These results will aid in the improved diagnosis and management of neoplasia in lizard species, as well as expanding our understanding of prognostic indicators of neoplasia in lizards.

P-08 Ectopic Cushing Syndrome in a patient with small cell lung cancer

Abstract Introduction Ectopic Cushing's syndrome (ECS) is a rare endocrine disorder caused by the autonomous secretion of ACTH from a tumor apart from the hypophysis. ECS is the second most common paraneoplastic syndrome associated with small cell lung cancer (SCLC). Due to the aggressive nature of the syndrome, ECS is difficult to diagnose. Most patients present electrolyte disturbances and muscle weakness rather than the typical clinical features of CS. Clinical Case A 70-year-old female patient hospitalized due to pleural effusion was referred for worsening hyperglycemia. She had no previous history of diabetes mellitus. She had a history of 90 pack-years of smoking and chronic obstructive pulmonary disease. The laboratory results were: fasting plasma glucose 216 mg/dl; creatinine, 0.81 mg/dl; sodium, 138 mmol/l; potassium, 3.1 mmol/l; HbA1c, 8.3%; Arterial blood gas analysis revealed metabolic alkalosis (pH 7.63, HCO3 53.6 meq/L). Due to resistant hypokalemia, the patient was evaluated for CS. The patient's ACTH level was 415.5 pg/ml and cortisol level was 63.44 μg/dl. Table 1 shows the tests perfomed for the diagnosis of CS. Pituitary MRG revealed no pathology. IPSS could not be performed as it is not available at our center. A suspicious mass in the right lung was observed on the thorax CT. The pathology of the cytology sample from the pleural effusion revealed SCLC. A chemotherapy regimen containing cisplatin was initiated. Intravenous potassium and acetazolamide treatment were administered for resistant hypokalemia. However, the patient died one month after diagnosis due to type 2 respiratory failure. Conclusion Ectopic secretion of ACTH accounts for 10–15% of CS. ECS is usually caused by mainly SCLC (45%), thymic carcinoma (15%), bronchial carcinoid (10%) and pancreas islet-cell carcinoma (10%). ECS is reported to occur in 1.6%–4.5% of patients with SCLC. IPSS is the most reliable examination for ECS. For ECS, surgery remains the optimal treatment. Some reports showed that metyrapone, ketoconazole and octreotide are effective but not widely used. In our case, the presence of resistant hypokalemia, metabolic alkalosis, and worsening hyperglycemia with the lack of classic clinical features of CS led us to suspect ECS. ECS has a higher incidence of hypokalemic alkalosis than other causes of Cushing's syndrome (>90% vs. 10%). Excessive amounts of adrenal steroids with the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase may cause this pathology. This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. In conclusion, although rare, in cases where conditions such as metabolic alkalosis, resistant hypokalemia, with the absence of classic clinical features of CS, the possibility of ectopic CS should be kept in mind.Table 1.Laboratory results of the patient

MORBIDITY AND MORTALITY OF BINTURONGS (ARCTICTIS BINTURONG) IN UNITED STATES ZOOLOGICAL INSTITUTIONS (1986-2019).

Veterinary literature on diseases in binturong (Arctictis binturong) is often limited to case series or reports without population-level information. Morbidity and mortality data were collected from North American institutions through survey completion or submission of medical records. Responses included information about 74 individuals (37 males, 30 females, and 7 unknown neonates) representing 22 institutions, from 1986 to 2019. Antemortem data were available from 39 individuals, and postmortem data were available from 53 individuals. Eighteen individuals had both antemortem and postmortem records available. Age (mean ± SD) at death for adults (n = 41) was 15.2 ± 4.3 yr. Morbidity events were summarized by affected organ system; 160 events were reported. The systems with the most frequently reported events were gastrointestinal (33%; 53/160), integumentary (19%; 31/160), urinary (12%; 20/160), and musculoskeletal (19 [12%] of 160). Excluding neonates, primary causes of mortality included neoplasia (51%; 21/41), infectious or inflammatory diseases (24%; 10/41), and cardiovascular disease (17%; 7/41). Neoplasms (51%; 21/41) confirmed on histopathology included renal adenocarcinoma (47%; 10/21); mammary carcinoma (14%; 3/21); pancreatic islet cell carcinoma (2 [10%] of 21); and single instances of multicentric lymphoma, uterine carcinoma, and submucosal urethral adenoma. There were three additional cases of presumed neoplasia without histopathologic confirmation; masses were detected in the liver, heart base, and pancreas. Metastases were reported in 15 (71%) of 21 neoplasms. Although neoplasia and cardiovascular disease were common causes of mortality, they were rarely diagnosed antemortem. Neoplasia was often malignant and generally diagnosed after metastasis. Preventive medicine protocols with improved renal and cardiovascular evaluation are warranted and may result in earlier detection of subclinical disease in binturong.

Induction of a single dose of streptozotocin (50 mg) in rat model causes insulin resistance with type 2 diabetes mellitus.

Streptozotocin (STZ) is a broad-spectrum antibiotic that is toxic to the insulin-producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague-Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post-STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60-day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ was able to destroy the pancreatic insulin-producing beta cell, as evidenced by an increase in plasma glucose level, insulin resistance, and oxidative stress. Biochemical investigation indicates that STZ can generate diabetes complications through hepatocellular damage, elevated HbA1c, kidney damage, hyperlipidemia, cardiovascular damage, and impairment of the insulin-signaling pathway.

Socioeconomic Factors, Treatment Modality, and Survival in Islet Cell Carcinoma: A National Cancer Database Analysis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Factors Impacting Survival Outcomes of Islet Cell Carcinoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Ulcerated, tender nodules of the lower extremities

Ulcerated, tender nodules of the lower extremities

Perioperative outcomes in dogs and cats undergoing pancreatic surgery: 81 cases (2008-2019).

To identify and describe the type and frequency of perioperative factors in dogs and cats undergoing pancreatic surgery under referral care. Medical records from a small animal surgical referral practice were retrospectively reviewed to identify dogs and cats that underwent pancreatic surgery between 2008 and 2019. Inclusion criteria included complete medical record, histopathology results and follow-up of at least 14 days postoperatively or until death. Variables collected included signalment, history, presenting complaint, preoperative diagnostic results, intraoperative complications, surgical findings/procedures, postoperative complications and histopathology results. Cases were excluded if pertinent information or a histopathology report was missing from the medical record. The frequency of these variables was reported. There were 81 client-owned animals identified that met the inclusion criteria (57 dogs and 24 cats). The most common pancreatic procedure performed in dogs was partial pancreatectomy 63.2% (36/57) and in cats was pancreatic biopsy 62.5% (15/24). The most common histologic diagnosis in dogs was pancreatic islet cell carcinoma 50.9% (29/57) and in cats was pancreatitis 41.7% (10/24). The overall mortality rate was 13.6% (11/81), with a 10.5% (6/57) mortality rate in dogs and a 20.8% (5/24) mortality rate in cats. In this series of dogs and cats, pancreatic surgery under referral care carried a low to moderate mortality rate.

Ethanol Extract of Myrtle (Myrtus communis L.) Berries as a Remedy for Streptozotocin-Induced Oxidative Stress in Rats.

Streptozotocin (STZ) is an antitumor antibiotic indicating in the treatment of metastatic islet cell carcinoma of the pancreas. It is also used as a tool to create experimental diabetes models. The STZ exposure at a high dose causes severe damage to cells of humans and other mammals. The goal of the present study was to assess the protective effects of the ethanol extract of the Myrtle (Myrtus communis L.) berries, which is a well-known medicinal plant due to its rich phenolic content and beneficial effects on health, against STZ-induced oxidative stress in the diabetic rats.Diabetes was induced by STZ (40mg/kg, i.p.) in the rats. After diabetes induction, a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and blood glucose levels as well asa significant decrease in superoxide dismutase (SOD) activities and glutathione (GSH) levels was observed. The rats were treated to three different ethanol extracts of Myrtle berries (0.25, 0.5, and 1g/kg) by oral gavage for 14days. At the end of the experiment, ALT, AST, MDA, and blood glucose levels of the rats significantly decreased while significant increases in GSH levels and SOD activities were observed.We believe that our findings may contribute to the development of new drugs in the treatment of many global disorders due to the antioxidant activity of the ethanol extract of Myrtus communis L. berries.

Do Canine Pancreatic Neuroendocrine Neoplasms Resemble Human Pancreatic Neuroendocrine Tumours? A Comparative Morphological and Immunohistochemical Investigation

Although canine pancreatic neuroendocrine neoplasms (PanNENs) have been proposed as a model for the counterpart human neoplasms, the type or grade of human PanNEN that they resemble is unclear. PanNENs in animals are classified as adenoma or carcinoma, whereas in humans they are classified as pancreatic neuroendocrine tumour (PanNET) if well-differentiated, or as pancreatic neuroendocrine carcinoma (PanNEC) if poorly differentiated. We evaluated 16 canine primary PanNENs and two metastases histologically and immunohistochemically, and graded them using the animal and human grading systems. All neoplasms had local or vascular invasion and were classified as pancreatic islet cell carcinomas according to the current WHO classification. The Ki-67 index was low in all cases (0.01-1.50%). All had cytoplasmic expression of synaptophysin and insulin but were immunonegative for glucagon, confirming a functional diagnosis of canine insulinoma. Membranous expression of SSTR2A and nuclear expression of ATRX, but no p53 expression, was found in all neoplasms. One primary tumour was diagnosed as a mixed neuroendocrine-non-neuroendocrine neoplasm, which is the first report of this neoplasm in dogs. The other 15 primary tumours and both metastatic tumours were graded as PanNET G1, according to the human WHO classification. We conclude that canine PanNENs share well-differentiated histomorphology, SSTR2A expression and absence of nuclear p53 immunolabelling with human PanNETs G1. However, they differ in ATRX gene expression and functionality, and seem to have a worse prognosis than human PanNETs G1, although their generally low Ki-67 index precludes more precise assessment of prognosis. Membranous SSTR2A expression renders canine PanNENs potentially amenable to treatment with somatostatin analogues or SSTR targeted in-vivoimaging methods.

Pancreatic islet cell tumors in adolescents and young adults

BackgroundPancreatic islet cell tumors are rare in adolescents, and most studies published to date focus on older patients. We utilized a national database to describe the histology and clinical pattern of pancreatic islet cell tumors in adolescent and young adult (AYA) patients, and to compare AYAs to older adults. We hypothesized that AYAs with pancreatic islet cell tumors would have better overall survival. MethodsThe National Cancer Data Base (NCDB, 1998–2012) was queried for AYA patients (15–39 years) with a pancreatic islet cell tumor diagnosis. Demographics, tumor characteristics, treatment modalities, and outcomes were abstracted and compared to adults (≥40 years). Results383 patients (56.4% female, 65% non-Hispanic Whites) were identified, with a median age of 27 (IQR 16–34) years. Islet cell carcinoma was the most common histology. Of patients with known stage of disease, 49% presented with early stage (I or II). Seventy percent of patients underwent surgical resection, including local excision 44%, Whipple procedure 37.5%, or total pancreatectomy 19%. Chemotherapy was utilized in 27% and radiotherapy in 7%. All-cause mortality was 36%. AYA patients underwent more extensive resections (p = 0.001) and had lower mortality rates (p < 0.001), with no differences in tumor stage or use of adjuvant therapies, when compared to adults. ConclusionsAYA patients with pancreatic islet cell tumors had comparable utilization of adjuvant therapies but underwent more extensive resections and demonstrated a higher overall survival rate than adult counterparts. Further investigation into approaches to earlier diagnosis and tailoring of multimodality therapy of these neoplasms in the AYA population is needed. Levels of evidencePrognostic Study, Level II — retrospective study.

Mixed ductal-acinar cell carcinoma of the pancreas: A case report.

Mixed carcinoma of the pancreas is defined as the concurrent existence of pancreatic ductal carcinoma, acinar cell carcinoma, and/or islet cell carcinoma within the same neoplasm. We herein report a rare case of mixed ductal-acinar cell carcinoma in a 74-year-old man who was undergoing treatment for hypertension and diabetes at another hospital. After an abrupt worsening of his blood glucose control, the patient was referred to our hospital for further evaluation. Abdominal contrast-enhanced computed tomography and magnetic resonance imaging revealed a tumor with a multilocular cystic lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography revealed obstruction of the main pancreatic duct and dilation of the dorsal pancreatic duct; in addition, adenocarcinoma was detected in the pancreatic juice cytology. Based on the abovementioned findings, the patient was diagnosed with carcinoma of the pancreatic head and underwent subtotal stomach-preserving pancreaticoduodenectomy. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with mixed ductal-acinar cell carcinoma. The patient was prescribed TS-1 as postoperative adjuvant chemotherapy upon discharge. However, treatment was discontinued 2 months later due to marked general malaise, and the patient succumbed to tumor recurrence in the residual pancreas 12 months after the surgery.

Management of Neuroendocrine Tumors of the Pancreas

Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies, with differences in prognosis and effective therapies. Traditionally, NETs have been characterized by tumor grade, site of primary tumor, functional status, and presence of underlying familial syndrome. However, increased feasibility and use of next-generation sequencing and other methodologies have revealed new genomic and epigenetic aberrations. In the past decade, treatment options available for metastatic well-differentiated gastroenteropancreatic NETs have expanded, with the approval of antiangiogenic and mTOR-directed targeted therapies, and our armamentarium of active therapies is likely to further increase. Optimal surgical therapy both for nonfunctional and functional PNETs has become more personalized and strategic to optimize long-term quality of life time. Management of localized metastatic PNET has become a true multidisciplinary management opportunity that all treating physicians should use. Peptide receptor radioligand therapy is an emerging treatment that uses functional imaging to personalize dosimetry to the tumor and avoid nephrotoxicity. Nevertheless, there is a critical need for further biomarkers, particularly multianalyte biomarkers, to aid in prognostication and predict efficacy of therapies. This review contains 1 figure, 1 table, and 72 references. Key Words: carcinoid tumor, islet cell carcinoma, neuroendocrine tumors, pancreatic, surgical management, medical management, metastatic, localized.

Management of Neuroendocrine Tumors of the Pancreas

Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies, with differences in prognosis and effective therapies. Traditionally, NETs have been characterized by tumor grade, site of primary tumor, functional status, and presence of underlying familial syndrome. However, increased feasibility and use of next-generation sequencing and other methodologies have revealed new genomic and epigenetic aberrations. In the past decade, treatment options available for metastatic well-differentiated gastroenteropancreatic NETs have expanded, with the approval of antiangiogenic and mTOR-directed targeted therapies, and our armamentarium of active therapies is likely to further increase. Optimal surgical therapy both for nonfunctional and functional PNETs has become more personalized and strategic to optimize long-term quality of life time. Management of localized metastatic PNET has become a true multidisciplinary management opportunity that all treating physicians should use. Peptide receptor radioligand therapy is an emerging treatment that uses functional imaging to personalize dosimetry to the tumor and avoid nephrotoxicity. Nevertheless, there is a critical need for further biomarkers, particularly multianalyte biomarkers, to aid in prognostication and predict efficacy of therapies. This review contains 1 figure, 1 table, and 72 references. Key Words: carcinoid tumor, islet cell carcinoma, neuroendocrine tumors, pancreatic, surgical management, medical management, metastatic, localized.

Liver Mass: When in Doubt Think Carcinoid or Islet Cell Carcinoma

Few differentials for liver lesions include hepatocellular carcinoma, cholangiocarcinoma, hepatic adenoma, hepatic hemangioma, hepatic cysts and metastases. Carcinoids and islet cell carcinomas are normally not in the differential due to their rarity in comparison to the other conditions. Since these tumors are slow growing, the liver has time to adapt; hence patients present with minimal symptoms and large masses on imaging. It is imperative to have both carcinoid and islet cell carcinoma on top of the list for differentials when an incidental asymptomatic liver lesion is seen. 66-year-old male previously treated with ABVD for Hodgkin's lymphoma in 1999 presented with back pain. He denied flushing, chills, fever, diarrhea and lightheadedness. Physical exam was benign. Pertinent laboratory data revealed creatinine of 3.1, potassium of 5.3 and mildly elevated alkaline phosphatase. Three-phase CT of the abdomenshowed two masses in the liver (Figure 1): a 22 cm mass in the right lobe and a 2.5 cm mass in the left lobe. There was also a 4 cm mass in the right kidney. Initially, the liver lesions were thought to be metastases from the kidney. However, biopsy of the kidney mass revealed renal cell carcinoma while biopsy of the largest liver lesion was consistent with neuroendocrine carcinoma. To classify the etiology of the neuroendocrine carcinoma, whole body imaging with SPECT and octreotide scan was performed. A large 19 cm mass and two small lesions were noted in the right lobe of the liver. Lymph node adjacent to the third portion of the duodenum demonstrated abnormal uptake and it was presumed that the duodenum was the primary source of the neuroendocrine carcinoma. Lesions in the liver were likely metastases. The patient was treated with an ablation for renal cell carcinoma and started on somatostatin for neuroendocrine carcinoma of the duodenum. Differentiating carcinoids and islet cell carcinomas poses a diagnostic challenge for pathologists as both entities share the same histology and often immune staining can yield mixed results. It is very important as specialists to have both these diseases in the differential and make the correct diagnosis by taking into consideration the primary site involved along with the presence of 5-HIAA. Even with risk factors for other etiologies, a biopsy should be performed with further testing as indicated to make the correct diagnosis. Identifying the correct diagnosis further helps optimize treatment.2368 Figure 1. Aymptomatic Liver Lesion

Spontaneous adrenocorticotropic hormone (ACTH) normalisation due to tumour regression induced by metyrapone in a patient with ectopic ACTH syndrome: case report and literature review

BackgroundEctopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is caused by tumours releasing ACTH. Ectopic ACTH-producing tumour regression is rarely induced using steroidogenesis inhibitors. We presented a case of EAS in which ACTH production by a lung tumour was reduced by metyrapone (MTP) and also reviewed previous cases of ectopic ACTH production suppressed via steroidogenesis inhibition.Case presentationA 71-year-old female with general fatigue, central obesity and impaired glucose tolerance was diagnosed with Cushing’s syndrome due to elevated ACTH (192.9 pg/mL; normal range, 7.2–63.3 pg/mL), cortisol (73.1 μg/dL; 6.4–21.0 μg/dL) and 24-h urinary free cortisol (UFC) (6160 μg/day; 11.2–80.3 μg/day) levels. Chest computed tomography identified a solid 26.6 × 22.9 × 30.0 mm tumour with a cavity in the upper lobe of the left lung. There was no adrenal gland enlargement. Tumour markers were not significantly elevated; ACTH levels were not suppressed by 8-mg dexamethasone. A corticotropin-releasing hormone stimulation test revealed blunted ACTH response (basal ACTH, 204.6 pg/mL; highest ACTH level during the 120-min stimulation test, 214.0 pg/mL). She was diagnosed with EAS due to a lung lesion. MTP treatment was started to reduce cortisol production. ACTH levels and cortisol and UFC levels were normalised and the ACTH-producing lung tumour was ablated after MTP treatment. In several reported cases, plasma ACTH levels reduced during steroidogenesis inhibitor treatment for EAS. Among the 10 patients, three cases of pheochromocytoma, one of thymic carcinoid and one of islet cell carcinoma were reported. In four cases, the tumour was not detected. In our case, the pathology of the lung tumour was unknown because of lack of tumour cells in biopsy. The patients were treated with ketoconazole (KTZ) and/or MTP and exhibited ACTH and cortisol/UFC suppression, but tumour regression was observed only in our case.ConclusionMTP and/or KTZ may reduce ACTH and cortisol production. The tumour spontaneously regressed after MTP treatment, indicating that MTP may reduce the tumour size without surgery. The mechanisms of therapeutic effects of steroidogenesis inhibitors and prognosis of spontaneous remission should be elucidated further via molecular biology studies.

A Review on Microfluidic Paper-Based Analytical Devices for Glucose Detection.

Glucose, as an essential substance directly involved in metabolic processes, is closely related to the occurrence of various diseases such as glucose metabolism disorders and islet cell carcinoma. Therefore, it is crucial to develop sensitive, accurate, rapid, and cost effective methods for frequent and convenient detections of glucose. Microfluidic Paper-based Analytical Devices (μPADs) not only satisfying the above requirements but also occupying the advantages of portability and minimal sample consumption, have exhibited great potential in the field of glucose detection. This article reviews and summarizes the most recent improvements in glucose detection in two aspects of colorimetric and electrochemical μPADs. The progressive techniques for fabricating channels on μPADs are also emphasized in this article. With the growth of diabetes and other glucose indication diseases in the underdeveloped and developing countries, low-cost and reliably commercial μPADs for glucose detection will be in unprecedentedly demand.

Prediabetes linked to excess glucagon in transgenic mice with pancreatic active AKT1.

Protein kinase B/AKT has three isoforms (AKT1-3) and is renowned for its central role in the regulation of cell growth and proliferation, due to its constitutive activation in various cancers. AKT2, which is highly expressed in insulin-responsive tissues, has been identified as a primary regulator of glucose metabolism as Akt2 knockout mice (Akt2(-/-)) are glucose-intolerant and insulin-resistant. However, the role of AKT1 in glucose metabolism is not as clearly defined. We previously showed that mice with myristoylated Akt1 (AKT1(Myr)) expressed through a bicistronic Pdx1-TetA and TetO-MyrAkt1 system were susceptible to islet cell carcinomas, and in this study we characterized an early onset, prediabetic phenotype. Beginning at weaning (3 weeks of age), the glucose-intolerant AKT1(Myr) mice exhibited non-fasted hyperglycemia, which progressed to fasted hyperglycemia by 5 months of age. The glucose intolerance was attributed to a fasted hyperglucagonemia, and hepatic insulin resistance detectable by reduced phosphorylation of the insulin receptor following insulin injection into the inferior vena cava. In contrast, treatment with doxycycline diet to turn off the transgene caused attenuation of the non-fasted and fasted hyperglycemia, thus affirming AKT1 hyperactivation as the trigger. Collectively, this model highlights a novel glucagon-mediated mechanism by which AKT1 hyperactivation affects glucose homeostasis and provides an avenue to better delineate the molecular mechanisms responsible for diabetes mellitus and the potential association with pancreatic cancer.

Osseous metaplasia within a canine insulinoma

An 11-year-old male castrated mixed-breed dog was presented for exercise intolerance, tetraparesis, and persistent hypoglycemia. Abdominal ultrasound examination revealed 2 nodules within the right limb of the pancreas. Cytology from one nodule was consistent with a carcinoma of neuroendocrine origin, with a primary differential diagnosis of insulinoma. Histologic evaluation and immunohistochemistry for synaptophysin and insulin confirmed the diagnosis of insulinoma. Additionally, there was a solitary nodule of mineralized compact bone composing approximately 60% of the mass. To the authors' knowledge, this is the first report of osseous metaplasia within an insulinoma (islet cell carcinoma).

Will Detection of MicroRNA Biomarkers in Blood Improve the Diagnosis and Survival of Patients With Pancreatic Cancer?

Will Detection of MicroRNA Biomarkers in Blood Improve the Diagnosis and Survival of Patients With Pancreatic Cancer?