Rare Cancer News & Clinical Trials

Pancreas (208 unread)

Permalink for 'Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation'

Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation

Posted: May 27th, 2024, 11:00pm UTC

Conditions: Neuroendocrine Tumors; MEN1 Mutation
Interventions: Biological: blood sample
Sponsors: Centre Hospitalier Universitaire Dijon
Recruiting

Evaluating ImmuNe Changes in the Evolution of Pre Type 1 Diabetes With Adult ONset

Posted: August 23rd, 2023, 11:00pm UTC

Conditions: Type 1 Diabetes; Type 1 Diabetes Mellitus Maturity Onset
Interventions: Genetic: High genetic risk for type 1 diabetes; Genetic: High gentic risk for Coeliac disease
Sponsors: Royal Devon and Exeter NHS Foundation Trust; University of Exeter
Completed

DOTATOC PET/CT for Imaging NET Patients

Posted: July 11th, 2018, 11:00pm UTC

Conditions: Neuroendocrine Tumors; Insulinoma; Gastrinoma; Glucagonoma; Vipoma; Pheochromocytoma; Paraganglioma; Neuroblastoma; Ganglioneuroma; Medullary Carcinoma; Pituitary Adenoma; Medulloblastoma; Merkel Cell Carcinoma; Small-cell Lung Cancer; Meningioma; Carcinoid
Interventions: Diagnostic Test: 68Ga-DOTATOC PET/CT; Diagnostic Test: 18F-FDG PET/CT
Sponsors: British Columbia Cancer Agency
Recruiting

Fluorodopa F 18 in Congenital Hyperinsulinism and Insulinoma

Posted: December 27th, 2013, 1:00am UTC

Conditions: Congenital Hyperinsulinism; Insulinoma
Interventions: Drug: Fluorodopa F 18
Sponsors: Cook Children's Health Care System
Recruiting

18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Subjects With Hyperinsulinemic Hypoglycemia

Posted: August 5th, 2013, 11:00pm UTC

Conditions: Congenital Hyperinsulinism (CHI); Beckwith-Wiedemann Syndrome; Insulinoma
Interventions: Drug: 18F-DOPA
Sponsors: Children's Hospital of Philadelphia
Available

Capecitabine, Temozolomide, and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors

Posted: February 2nd, 2012, 1:00am UTC

Conditions: Gastrinoma; Glucagonoma; Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Recurrent Pancreatic Cancer; Somatostatinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
Interventions: Drug: Capecitabine; Drug: Temozolomide; Biological: Bevacizumab
Sponsors: Shaheen Shagufta; National Cancer Institute (NCI)
Completed

Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

Posted: April 10th, 2008, 11:00pm UTC

Conditions: Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific
Interventions: Drug: everolimus; Drug: vatalanib; Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Procedure: ultrasound imaging
Sponsors: Mayo Clinic
Completed

Diagnosing and Treating Low Blood Sugar Levels

Posted: November 4th, 1999, 1:00am UTC

Conditions: Hypoglycemia; Insulinoma
Sponsors: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruiting

$Permalink for 'Refractory Hyperinsulinemic Hypoglycemia as a Complication of Roux-en-Y Gastric Bypass Surgery'$

Refractory Hyperinsulinemic Hypoglycemia as a Complication of Roux-en-Y Gastric Bypass Surgery

Fetched: October 16th, 2024, 2:02am UTC by Tawana Mazhude

Cureus. 2024 Sep 9;16(9):e69037. doi: 10.7759/cureus.69037. eCollection 2024 Sep.

ABSTRACT

This case involves a 45-year-old woman with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) surgery. After one year, she developed daily episodes of severe hypoglycemia, presenting with symptoms of palpitations, diaphoresis, and syncope. The patient was diagnosed with endogenous hyperinsulinemic hypoglycemia, a condition characterized by abnormally high insulin levels leading to low blood glucose, commonly associated with insulinoma. In rare instances, this can be due to nesidioblastosis, an overgrowth of pancreatic beta cells, which is more prevalent in individuals who have undergone bariatric surgery. Diagnostic evaluations included blood tests, abdominal computed tomography and magnetic resonance imaging, continuous glucose monitoring, and hepatic venous sampling to exclude insulinoma. This report details the diagnosis and unsuccessful treatment of endogenous hyperinsulinemic hypoglycemia following RYGB surgery. Interventions included dietary modifications (small, frequent, low-carbohydrate meals), medical management with acarbose 100 mg three times daily, diazoxide 150 mg three times daily, verapamil 40 mg twice daily, and surgical reversal of the RYGB. Ultimately, a percutaneous gastrostomy tube was placed for 24-hour continuous parenteral feeding. Despite these extensive treatment efforts, the patient continues to experience frequent hypoglycemic episodes four years after the bariatric procedure.

PMID:39391450 | PMC:PMC11464727 | DOI:10.7759/cureus.69037

Subtyping of pancreatic neuroendocrine tumors by transcription factors, hormones, histology, and patient outcome

Fetched: October 16th, 2024, 2:02am UTC by Elisa Moser

Pathologie (Heidelb). 2024 Oct 8. doi: 10.1007/s00292-024-01367-w. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) show pronounced heterogeneity in terms of hormone and transcription factor (TF) expression. TFs such as ARX and PDX1 are related to alpha- and beta-cell-type features, respectively, and partly associate with patient outcome. However, detailed studies correlating hormone expression, histology, and clinical data are lacking.

OBJECTIVE: The aim of this study was to identify subtypes of PanNETs that associate with histological, hormonal, and prognostic findings.

METHODS: A total of 185 resected PanNETs were divided into five subtypes (types A1, A2, B, C, and D) by cluster analysis based on expression of four TFs (ARX, PDX1, ISL1, and CDX2) and correlated to the expression of hormones and DAXX/ATRX as well as ALT activation status, histology, and progression-free survival.

RESULTS: Subgroup A1 (ISL1+/ARX+/PDX-/CDX2-) was most frequent (46%), followed by type B (18%; ISL1+/ARX-/PDX+/CDX2-), A2 (15%; ISL1+/ARX+/PDX+/CDX2-), C (15%; ISL1-/ARX-/PDX-/CDX2-), and D (5%; ISL1-/ARX-/PDX+/CDX2+). Subgroups A1 and A2 showed a strong association with a trabecular growth pattern and glucagon and pancreatic polypeptide (PP) expression (p < 0.001), while A2 was in addition associated with gastrin expression. Subgroup B was associated with insulin production (p < 0.001) and included all 17 insulinomas. Subgroup C was associated with solid morphology and expression of serotonin, calcitonin, and adrenocorticotropic hormone (ACTH). Subgroup D showed solid morphology, expression of ACTH, somatostatin, or serotonin and had the shortest disease-free survival (p < 0.01). ALT positivity was associated with poorer outcome in types A1 and A2 but not in other types.

CONCLUSION: PanNETs can be categorized into five subgroups based on different TF signatures, which associate strongly with histology, hormone production, functionality, and patient outcome.

PMID:39377913 | DOI:10.1007/s00292-024-01367-w

Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers

Fetched: October 16th, 2024, 2:02am UTC by Shin Ito

Cancer Sci. 2024 Oct 8. doi: 10.1111/cas.16365. Online ahead of print.

ABSTRACT

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

PMID:39377143 | DOI:10.1111/cas.16365

Case report: Novel germline c.587delA pathogenic variant in familial multiple endocrine neoplasia type 1

Fetched: October 16th, 2024, 2:02am UTC by Haotian Huang

Front Endocrinol (Lausanne). 2024 Sep 20;15:1467882. doi: 10.3389/fendo.2024.1467882. eCollection 2024.

ABSTRACT

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare genetic disease, characterized by co-occurrence of several lesions of the endocrine system. In MEN1, the pathogenic MEN1 gene mutations lead to the Abnormal expression of menin, a critical tumor suppressor protein. We here reported a case of a 14-year-old male with insulinoma and primary hyperparathyroidism. Genetic testing demonstrated a novel heterozygote variant c.587delA of MEN1, resulting in the substitution of the 196th amino acid, changing from glutamic acid to glycine, followed by a frameshift translation of 33 amino acids. An identical variant was identified in the proband's father, who was further diagnosed with hyperparathyroidism. To the best of our knowledge, this is the first report of MEN1 syndrome caused by the c.587delA MEN1 variant. Observations indicated that, despite sharing the same MEN1 gene change, family members exhibited diverse clinical phenotypes. This underscored the presence of genetic anticipation within the familial context.

PMID:39371924 | PMC:PMC11452907 | DOI:10.3389/fendo.2024.1467882

Permalink for 'Trends in Presentation and Management of Endogenous Hyperinsulinaemic Hypoglycaemia Over the Last Three Decades at a Tertiary Care Centre (1992-2022)'

Trends in Presentation and Management of Endogenous Hyperinsulinaemic Hypoglycaemia Over the Last Three Decades at a Tertiary Care Centre (1992-2022)

Fetched: October 16th, 2024, 2:02am UTC by Setu Gupta

Indian J Endocrinol Metab. 2024 Jul-Aug;28(4):363-369. doi: 10.4103/ijem.ijem_87_24. Epub 2024 Aug 28.

ABSTRACT

INTRODUCTION: Endogenous hyperinsulinaemic hypoglycaemia (EHH) is characterized by inappropriate insulin secretion from pancreatic beta cells despite low blood glucose concentrations. We aimed to evaluate the secular changes in presentation and management of EHH due to insulinoma/non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) at our centre.

METHODS: This was a single-centre ambispective study (2014-2022). The clinical, biochemical, hormonal and radiological parameters (n = 63) collected as part of this study were compared with our earlier studies (1992-2005, n = 31; and 2006-2013, n = 35) and with other centres across the world.

RESULTS: A total of 63 patients (39 males) with a preoperative diagnosis of EHH (insulinoma, n = 58; and NIPHS, n = 5) and a mean age of 40.7 years were studied. The mean lag time from the onset of symptoms to diagnosis decreased from 4.6 years during the first study period to 1.9 years during this study period. However, the majority presented with fasting hypoglycaemia of 98.4%, and both fasting and postprandial hypoglycaemia of 32%. Exclusive postprandial hypoglycaemia was present in 1.7% of insulinoma. A histopathological diagnosis of insulinoma was made in 52 patients and nesidioblastosis in two patients. Intraoperative ultrasonography (IOUS) and intraoperative palpation (IOP) yielded 100% sensitivity, while endoscopic ultrasonography (EUS) and 68Ga-DOTA-Exendin-4 positron emission tomography/computed tomography (PET/CT) yielded sensitivity of 86% and 85%, respectively, for localizing insulinoma. Resolution of hypoglycaemia was noted in 53 of 57 (93%) patients who underwent surgery with a preoperative diagnosis of insulinoma.

CONCLUSION: We observed a trend towards earlier diagnosis of EHH, increased patient numbers and availability of nuclear imaging techniques for preoperative localization in the last decade compared to earlier.

PMID:39371650 | PMC:PMC11451956 | DOI:10.4103/ijem.ijem_87_24

In Vitro and In Vivo Biocompatibility of Bacterial Cellulose

Fetched: October 16th, 2024, 2:02am UTC by Vincent-Daniel Girard

J Biomed Mater Res B Appl Biomater. 2024 Oct;112(10):e35488. doi: 10.1002/jbm.b.35488.

ABSTRACT

Bacterial cellulose is a unique biomaterial produced by various species of bacteria that offers a range of potential applications in the biomedical field. To provide a cost-effective alternative to soft-tissue implants used in cavity infills, remodeling, and subdermal wound healing, in vitro cytotoxicity and in vivo biocompatibility of native bacterial cellulose were investigated. Cytotoxicity was assessed using a metabolic assay on Swiss 3T3 fibroblasts and INS-1832/13 rat insulinoma. Results showed no cytotoxicity, whether the cells were seeded over or under the bacterial cellulose scaffolds. Biocompatibility was performed on Sprague-Dawley rats (males and females, 8 weeks old) by implanting bacterial cellulose membranes subcutaneously for 1 or 12 weeks. The explanted scaffolds were then sliced and stained with hematoxylin and eosin for histological characterization. The first series of results revealed acute and chronic inflammation persisting over 12 weeks. Examination of the explants indicated a high number of granulocytes within the periphery of the bacterial cellulose, suggesting the presence of endotoxins within the membrane, confirmed by a Limulus amebocyte lysate test. This discovery motivated the development of non-pyrogenic bacterial cellulose scaffolds. Following this, a second series of animal experiments was done, in which materials were implanted for 1 or 2 weeks. The results revealed mild inflammation 1 week after implantation, which then diminished to minimal inflammation after 2 weeks. Altogether, this study highlights that unmodified, purified native bacterial cellulose membranes may be used as a cost-effective biomedical device provided that proper endotoxin clearance is achieved.

PMID:39360852 | DOI:10.1002/jbm.b.35488

Permalink for 'Trends in endogenous insulin secretion capacity and anti-islet autoantibody titers in two childhood-onset slowly progressive insulin-dependent diabetes mellitus cases'

Trends in endogenous insulin secretion capacity and anti-islet autoantibody titers in two childhood-onset slowly progressive insulin-dependent diabetes mellitus cases

Fetched: October 16th, 2024, 2:02am UTC by Dai Suzuki

Clin Pediatr Endocrinol. 2024 Oct;33(4):238-243. doi: 10.1297/cpe.2024-0039. Epub 2024 Aug 13.

ABSTRACT

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is a subtype of type 1 diabetes. Although SPIDDM is not rare among Japanese children, there are few reports on endogenous insulin secretory capacity and anti-pancreatic islet autoantibodies in pediatric SPIDDM. We followed the trends in endogenous insulin secretory capacity and anti-pancreatic islet autoantibody titers in two pediatric SPIDDM cases over several years. Case 1 developed insulin deficiency eight months after diabetes diagnosis; as her insulinoma-associated antibody test result was positive, insulin therapy was initiated. Fourteen months after the diagnosis, she tested positive for glutamic acid decarboxylase autoantibodies (GADA) and was diagnosed with SPIDDM. Case 2 was mildly positive for GADA at the onset of diabetes, but became a high titer during the course of the disease. Fourteen months after the diagnosis of diabetes, he became mildly insulin deficient, and insulin therapy was initiated. However, his insulin secretory capacity was preserved for 60 mo after the onset. SPIDDM is generally indistinguishable from type 2 diabetes at diagnosis; therefore, repeated evaluation of the insulin secretory capacity and anti-islet autoantibodies facilitates early diagnosis and appropriate treatment, especially in nonobese children with type 2 diabetes.

PMID:39359664 | PMC:PMC11442699 | DOI:10.1297/cpe.2024-0039

Dexmedetomidine alleviates CoCl2-induced hypoxic cellular damage in INS-1 cells by regulating autophagy

Fetched: October 16th, 2024, 2:02am UTC by Jin Ha Park

Korean J Anesthesiol. 2024 Oct 2. doi: 10.4097/kja.24457. Online ahead of print.

ABSTRACT

BACKGROUND: Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic Î²-cell damage by regulating autophagy under hypoxia.

METHODS: INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. CoCl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine.

RESULTS: Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1.

CONCLUSIONS: Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice.

PMID:39355897 | DOI:10.4097/kja.24457

Proton Stereotactic Body Radiotherapy for Liver Metastases From Malignant Pancreatic Insulinoma

Fetched: October 16th, 2024, 2:02am UTC by Jake A Kloeber

JCEM Case Rep. 2024 Sep 27;2(10):luae175. doi: 10.1210/jcemcr/luae175. eCollection 2024 Oct.

ABSTRACT

Insulin-producing pancreatic tumors are a common subtype of neuroendocrine tumor. Standard of care includes surgical resection of the pancreatic tumor and medical management with somatostatin analogs. For patients with metastatic disease, tumor control and hypoglycemic symptom relief can be achieved through surgical resection of the tumor, hepatic artery embolization, radiofrequency ablation, or radioembolization using radioactive isotopes as well as with systemic therapy such as somatostatin analogs and everolimus. We present the case of a 74-year-old male with metastatic insulin-producing pancreatic carcinoma. After a long history of successfully controlling his hypoglycemic episodes post-liver wedge resection, bland embolizations subsequently failed to maintain control of the frequency and severity of his hypoglycemic symptoms. Stereotactic body radiotherapy (SBRT) with protons was used to achieve symptomatic control and led to partial radiographic response with complete resolution of his hypoglycemic episodes. This case demonstrates the potential utility of proton SBRT in metastatic insulinomas.

PMID:39346012 | PMC:PMC11427829 | DOI:10.1210/jcemcr/luae175

Permalink for 'Insulinoma-associated protein 1 (INSM1) immunohistochemical expression in normal, hyperplastic, and neoplastic canine neuroendocrine tissues'

Insulinoma-associated protein 1 (INSM1) immunohistochemical expression in normal, hyperplastic, and neoplastic canine neuroendocrine tissues

Fetched: October 16th, 2024, 2:02am UTC by Fu-Hua Yang

Vet Pathol. 2024 Sep 30:3009858241279127. doi: 10.1177/03009858241279127. Online ahead of print.

ABSTRACT

Insulinoma-associated protein 1 (INSM1), a recently identified neuroendocrine marker, is a transcriptional regulator with highly conserved INSM1 homologues in various species. This study investigated the immunohistochemical reactivity of the INSM1 antibody in 20 normal canine neuroendocrine tissues from various anatomical locations, 87 hyperplastic or neoplastic tissues of neuroendocrine origin, and 62 non-neuroendocrine neoplasms and compared the results with those of chromogranin A and synaptophysin in neuroendocrine neoplasms. Western blot was performed on fresh canine pituitary glands and canine parathyroid glands to confirm the specificity of the anti-INSM1 antibody. The results showed that the anti-INSM1 antibody could detect nuclear expression in normal canine neuroendocrine tissues, except for the parathyroid glands. INSM1 was detectable in 79/87 (91%) of the hyperplastic and neoplastic neuroendocrine lesions, but all parathyroid carcinomas and parathyroid adenomas (three samples each) were negative for INSM1. In contrast, INSM1 was detected in only one of 62 (2%) non-neuroendocrine neoplasms. The overall percentage of neuroendocrine neoplasms that immunolabeled positively for all three markers was 89%. In addition, the nuclear expression of INSM1 was easier to interpret than that of chromogranin A or synaptophysin. These findings confirm that INSM1 is a useful immunohistochemical marker for diagnosing canine neuroendocrine neoplasms, except for parathyroid neoplasms, and should be considered as part of immunohistochemistry panels to improve diagnostic capability.

PMID:39344951 | DOI:10.1177/03009858241279127

Adropin Is Expressed in Pancreatic Islet Cells and Reduces Glucagon Release in Diabetes Mellitus

Fetched: October 16th, 2024, 2:02am UTC by Ifrah I Ali

Int J Mol Sci. 2024 Sep 11;25(18):9824. doi: 10.3390/ijms25189824.

ABSTRACT

Diabetes mellitus affects 537 million adults around the world. Adropin is expressed in different cell types. Our aim was to investigate the cellular localization in the endocrine pancreas and its effect on modulating pancreatic endocrine hormone release in streptozotocin (STZ)-induced diabetic rats. Adropin expression in the pancreas was investigated in normal and diabetic rats using immunohistochemistry and immunoelectron microscopy. Serum levels of insulin, glucagon pancreatic polypeptide (PP), and somatostatin were measured using a Luminex^Â® Ï‡MAP (Magpix^Â®) analyzer. Pancreatic endocrine hormone levels in INS-1 832/3 rat insulinoma cells, as well as pancreatic tissue fragments of normal and diabetic rats treated with different concentrations of adropin (10^-6, 10^-9, and 10^-12 M), were measured using ELISA. Adropin was colocalized with cells producing either insulin, glucagon, or PP. Adropin treatment reduced the number of glucagon-secreting alpha cells and suppressed glucagon release from the pancreas. The serum levels of GLP-1 and amylin were significantly increased after treatment with adropin. Our study indicates a potential role of adropin in modulating glucagon secretion in animal models of diabetes mellitus.

PMID:39337311 | PMC:PMC11432804 | DOI:10.3390/ijms25189824

Insulinoma Unmasked: A Continuous Glucose Monitoring-Fueled Journey

Fetched: October 16th, 2024, 2:02am UTC by Andrijana Koceva

Curr Oncol. 2024 Sep 14;31(9):5452-5461. doi: 10.3390/curroncol31090403.

ABSTRACT

Insulinomas are rare functional neuroendocrine tumors that are usually indolent and small. Due to their rarity, there is often a delay in disease recognition and diagnosis, and small tumor size makes their localization challenging. Glucose monitoring and dietary modification with or without pharmacotherapy are crucial during diagnostics, and surgery is the only definite treatment. Continuous glucose monitoring (CGM) systems can be a valuable tool in managing insulinoma patients. We present three patients with confirmed endogenous hyperinsulinemic hypoglycemia undergoing tumor localization, medical treatment, and surgery while wearing a CGM system. By accurately depicting glucose fluctuations, CGM can help prevent hypoglycemia, decrease hypoglycemia unawareness, track hypoglycemia frequency, aid in medical therapy dose titration, and confirm a cure after surgery.

PMID:39330031 | PMC:PMC11431697 | DOI:10.3390/curroncol31090403

Permalink for 'Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS-guided ethanol injection'

Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS-guided ethanol injection

Fetched: October 16th, 2024, 2:02am UTC by Kazuyuki Matsumoto

Endosc Ultrasound. 2024 May-Jun;13(3):193-195. doi: 10.1097/eus.0000000000000058. Epub 2024 May 31.

NO ABSTRACT

PMID:39318649 | PMC:PMC11419466 | DOI:10.1097/eus.0000000000000058

Type 1 diabetes, celiac disease, and autoimmune thyroiditis autoantibodies in population-based type 2 diabetes patients

Fetched: October 16th, 2024, 2:02am UTC by Lind Alexander

J Clin Transl Endocrinol. 2024 Sep 6;37:100367. doi: 10.1016/j.jcte.2024.100367. eCollection 2024 Sep.

ABSTRACT

AIMS: The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls.

METHODS: Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay.

RESULTS: GADA were detected in 46 % (88/191) of T1D and increased to 6.2 % (23/372) in T2D compared to 2.6 % (7/259) of controls (p = 0.0367). tTGA was low (1.1-2.6 %) and not different in between the study cohorts, nonetheless, in T1D tTGA was associated to islet autoantibodies. TPOA was more frequent in T1D, 27.1 % (53/191), compared to either T2D, 14.8 % (55/372; p = 0.0002) or controls, 14.3 % (37/259) (p = 0.0004). Overall, TPOA was more frequent in GADA positive (34.8 %; 8/23) than negative (13.5 %; 47/349; p = 0.0053) T2D individuals.

CONCLUSION: It's suggested that analyzing GADA and TPOA may refine the autoimmune landscape in individuals clinically classified as T2D.

PMID:39308768 | PMC:PMC11416225 | DOI:10.1016/j.jcte.2024.100367

Robotic Central Pancreatectomy

Fetched: October 16th, 2024, 2:02am UTC by Georg F Weber

Zentralbl Chir. 2024 Sep 17. doi: 10.1055/a-2404-3182. Online ahead of print.

ABSTRACT

Central pancreatectomy is an excellent alternative to left pancreatectomy for symptomatic benign or premalignant lesions of the pancreatic body or tail. A key advantage of this technique lies in the preservation of pancreatic parenchyma, resulting in a lower rate of postoperative diabetes mellitus. However, this procedure requires more complex reconstruction, which in turn is associated with an increased risk of morbidity.Insulinoma in the pancreatic body.Robot-assisted central pancreatectomy with pancreaticojejunostomy using a modified Blumgart technique.Central pancreatectomy is a generally rare and challenging pancreatic procedure, but clearly plays a significant role in modern pancreatic surgery due to its functional advantages. When appropriate and technically feasible, central pancreatectomy should be preferred to the alternative of left pancreatectomy and whenever possible, performed minimally invasively.

PMID:39288906 | DOI:10.1055/a-2404-3182

Hyperinsulinemic Hypoglycemia Due to an Insulinoma in a 2-Year-Old Child

Fetched: October 16th, 2024, 2:02am UTC by Lauren M Mitteer

JCEM Case Rep. 2024 Sep 16;2(9):luae161. doi: 10.1210/jcemcr/luae161. eCollection 2024 Sep.

ABSTRACT

Insulinomas are rare insulin-secreting tumors that most commonly affect adults. A 26-month-old child presented to her local emergency department with severe hypoglycemia. Initial workup was consistent with hyperinsulinemic hypoglycemia. Over the course of 10 months, multiple therapies for hyperinsulinism (HI) were trialed without significant benefit. Genetic testing for genes associated with HI was negative. At age 35 months, the patient was transferred to our center for further treatment. She underwent several imaging tests that revealed a lesion on her pancreas concerning for an insulinoma. The patient underwent surgical intervention to enucleate the lesion. Histopathological review of the specimen confirmed a benign, well-circumscribed insulinoma. A postoperative fasting test proved the patient was cured and she was discharged without the need for further glucose monitoring.

PMID:39286518 | PMC:PMC11402795 | DOI:10.1210/jcemcr/luae161

Permalink for 'Potential contribution of gut microbiota in the development of autoantibodies in T1D children carrying HLA-DRB1/DQB1 risk alleles: an experimental and in silico analysis'

Potential contribution of gut microbiota in the development of autoantibodies in T1D children carrying HLA-DRB1/DQB1 risk alleles: an experimental and in silico analysis

Fetched: October 16th, 2024, 2:02am UTC by Ata Shirizadeh

Immunogenetics. 2024 Sep 14. doi: 10.1007/s00251-024-01354-8. Online ahead of print.

ABSTRACT

This study aimed to investigate the prevalence of insulin autoantibody (IAA), glutamic acid decarboxylase antibody (GADA), and insulinoma-associated antigen-2 antibody (IA-2A) in type 1 diabetes (T1D) children based on the presence of predisposing HLA-II alleles. Additionally, to assess the sequence homology between autoantigens of islet cells and selected proteins derived from gut bacteria in terms of their binding capacities to HLA risk alleles, HLA-DRB1/DQB1 alleles were determined by PCR-SSOP in 111 T1D children (probands) along with 222 parents and 133 siblings. Autoantibodies were measured by ELISA, and in silico analysis was run as follows: protein extraction, homology and epitope prediction, peptide alignment, and HLA-peptide docking. Higher significant frequencies of DRB1*03:01, DQB1*02:01, and DQB1*03:02 alleles and DRB1*03:01 ~ DQB1*02:01 haplotype and lower frequencies of DRB1*11:01, DRB1*14:01, and DQB1*03:01 alleles were found in probands compared to parents and siblings. DRB1*11:01 ~ DQB1*03:01, DRB1*14:01 ~ DQB1*05:03, and DRB1*15:01-DQB1*06:02 haplotypes were significantly less frequent in the probands compared to parents. Out of 111 probands, 21 were seronegative, 90 tested positive for one autoantibody, and 15 showed the concurrent presence of three autoantibodies. Logistic regression analysis revealed that DRB1*04 ~ DQB1*03:02 haplotype was associated with the induction of GADA and IA-2A, while DRB1*11:01 ~ DQB1*03:01 was associated with seronegativity. Epitopes derived from GAD and gut bacteria showed strong binding capacities to HLA risk alleles. Due to the sequence similarities between gut bacteria-derived proteins and islet cell autoantigens and their potential for binding to HLA risk alleles, dysbiosis of gut microbiota can be considered another risk factor for the development of T1D, especially in genetically susceptible individuals.

PMID:39276210 | DOI:10.1007/s00251-024-01354-8

Signaling effect, combinations, and clinical applications of triciribine

Fetched: October 16th, 2024, 2:02am UTC by Shinichiro Takahashi

J Chemother. 2024 Sep 14:1-9. doi: 10.1080/1120009X.2024.2403050. Online ahead of print.

ABSTRACT

Triciribine (TCN) is a tricyclic nucleoside. Its synthesis was first described in 1971. Subsequent studies have indicated that TCN plays a role in inhibiting DNA synthesis and was revealed to possess a higher selectivity for Akt. Although a single dose of TCN demonstrated limited activity in solid tumors at the clinical level, combinations of TCN with various agents, such as specific inhibitors, tyrosine kinase inhibitor dasatinib, ErbB inhibitor tipifarnib, IGF1-R inhibitor NVP-AEW541, mTORC1 inhibitor RAD-001, TNF-related apoptosis-inducing ligand, PPARÎ³ agonist, 1,25(OH)2D3, gemcitabine, and paclitaxel, have been reported to be efficient against various malignancies such as pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumor, and hepatocellular carcinoma at the preclinical level. Other than malignancies, through Akt inhibition activity, TCN has also been demonstrated potential for treating lung injuries, including those encountered in COVID-19 infections.

PMID:39275964 | DOI:10.1080/1120009X.2024.2403050

UTRs and Ago-2/miR-335 Complex Restricts Amylin Translation in Insulinoma and Human Pancreatic beta-Cells

Fetched: October 16th, 2024, 2:02am UTC by Zhanar Kudaibergenova

Int J Mol Sci. 2024 Sep 5;25(17):9614. doi: 10.3390/ijms25179614.

ABSTRACT

Amylin promoter and transcriptional factors are well-established, inducible factors in the production of the main amyloidogenic pancreatic hormone, human islet amyloid peptide (hIAPP) or amylin. However, posttranscriptional mechanisms driving hIAPP expression in pancreas remain enigmatic, and hence were explored here. The translational assay revealed that both 5' and 3' untranslated regions (UTRs) of hIAPP restricted expression of the luciferase constructs only in constructs driven by the hIAPP promoter. Bioinformatics analysis revealed several putative seed sequences for a dozen micro RNAs (miRNAs) in hIAPP's 3' UTR. miR-182, miR-335, and miR-495 were the most downregulated miRNAs in stressed human islets exposed to endoplasmic reticulum (ER) or metabolic stressors, thapsigargin (TG) or high glucose (HG). Correspondingly, miR-335 mimics alone or in combination with miR-495 and miR-182 mimics significantly and potently (>3-fold) reduced hIAPP protein expression in HG-treated cultured human islets. siRNA-mediated silencing of Ago2 but not Ago1 significantly stimulated hIAPP expression and secretion from transfected, HG-treated human islets. Conversely, ectopic expression of Ago2 in hIAPP-expressing RIN-m5F cell line driven by CMV promoter reduced hIAPP intracellular protein levels. Collectively, the results point to a novel and synergistic role for hIAPP promoter, 5/3' UTRs and Ago-2/miR-335 complex in post-transcriptional regulation of hIAPP gene expression in normal and metabolically active Î²-cells.

PMID:39273561 | PMC:PMC11394793 | DOI:10.3390/ijms25179614

Laparoscopic enucleation of tumors embedded in the pancreatic head: Safety and feasibility

Fetched: October 16th, 2024, 2:02am UTC by Jiahao Wu

Asian J Surg. 2024 Sep 12:S1015-9584(24)01985-7. doi: 10.1016/j.asjsur.2024.09.001. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical treatment for a benign or low-grade malignant tumor in the pancreatic head remains a challenge at present. As an organ-sparing procedure, enucleation is ideal. However, it is still controversial whether laparoscopic enucleation (LapEN) can be safely performed for a pancreatic head tumor, especially a deeply embedded one.

METHODS: The cases who underwent LapEN of a pancreatic tumor from January 2014 to September 2022 in our hospital were collected and analyzed.

RESULTS: A total of 151 cases were collected. The incidence of pancreatic fistula (PF, grade B) was 21.9 %. No patient developed PF (grade C) or died. Compared with enucleating a tumor in the distal pancreas (N = 98), enucleating a tumor in the pancreatic head (N = 53) showed a longer operation time and a higher incidence of conversion. The cases with a tumor in the pancreatic head were then divided into the group with a deeply embedded tumor (N = 32) and the group with a superficial tumor (N = 21). The embedded group had a smaller tumor size and a higher proportion of insulinoma. There were no statistical differences in the parameters of operation time, blood loss and incidence of complications between the two groups. The outcomes of enucleating a tumor deeply embedded in the proximal and distal pancreas were further analyzed, which indicated no statistical differences in clinical parameters between the two groups.

CONCLUSION: LapEN of a tumor in the pancreatic head is feasible and safe, even for a deeply embedded tumor.

PMID:39271350 | DOI:10.1016/j.asjsur.2024.09.001

Permalink for 'Encapsulation of telmisartan inside insulinoma-cell-derived extracellular vesicles outperformed biomimetic nanovesicles in modulating the pancreatic inflammatory microenvironment'

Encapsulation of telmisartan inside insulinoma-cell-derived extracellular vesicles outperformed biomimetic nanovesicles in modulating the pancreatic inflammatory microenvironment

Fetched: October 16th, 2024, 2:02am UTC by Anjali Singh

J Mater Chem B. 2024 Sep 13. doi: 10.1039/d4tb00808a. Online ahead of print.

ABSTRACT

Diabetes mellitus (DM) is a chronic metabolic condition, characterized by hyperglycaemia, oxidative imbalance, pancreatic Î²-cell death, and insulin insufficiency. Angiotensin II (Ang II) increases oxidative stress, inflammation, and apoptosis, and Ang II type 1 receptor (AT1R) blockers (ARBs) can ameliorate inflammatory response and oxidative stress. However, like other small-molecule drugs, free ARBs show poor in vivo efficacy and dose-limiting toxicities. Hence, in this study, we developed nano-formulations of telmisartan (TEL), an ARB, by encapsulating it inside a murine insulinoma cell-derived extracellular vesicle (nanoTEL) and a bio-mimetic lipid nanovesicle (lipoTEL). Both nano-formulations showed spherical morphology and sustained release of TEL. In vitro, nanoTEL restored oxidative equilibrium, attenuated reactive oxygen species levels, enhanced the uptake of glucose analogue, and increased the expression of glucose transporter protein 4 better than lipoTEL. In a streptozotocin-induced murine model of diabetes, nanoTEL lowered blood glucose levels, improved glucose tolerance, and promoted insulin synthesis and secretion significantly better than lipoTEL. Moreover, nanoTEL was found superior in ameliorating the pancreatic inflammatory microenvironment by regulating NF-ÎºBp65, HIF-1Î±, and PPAR-Î³ expression; modulating IL-1Î², IL-6, tumor necrosis factor-Î±, IL-10, and IL-4 levels and inducing the polarization of macrophage from M1 to M2. Further, nanoTEL administration induced angiogenesis and promoted the proliferation of pancreatic cells to restore the structural integrity of the islets of Langerhans more efficiently than lipoTEL. These findings collectively suggest that nanoTEL outperforms lipoTEL in restoring the function of pancreatic Î²-cells by modulating the pancreatic inflammatory microenvironment and show potential for the treatment of DM.

PMID:39269191 | DOI:10.1039/d4tb00808a

A new potential cause of secondary hypertension

Fetched: October 16th, 2024, 2:02am UTC by Milos Mijalkovic

Front Cardiovasc Med. 2024 Aug 29;11:1458089. doi: 10.3389/fcvm.2024.1458089. eCollection 2024.

NO ABSTRACT

PMID:39267799 | PMC:PMC11390545 | DOI:10.3389/fcvm.2024.1458089

Permalink for 'Advanced esophagogastric junction mixed neuroendocrine-non-neuroendocrine neoplasm with long-term recurrence-free survival'

Advanced esophagogastric junction mixed neuroendocrine-non-neuroendocrine neoplasm with long-term recurrence-free survival

Fetched: October 16th, 2024, 2:02am UTC by Shunsuke Takenaka

Surg Case Rep. 2024 Sep 11;10(1):217. doi: 10.1186/s40792-024-02011-8.

ABSTRACT

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare malignant gastrointestinal tumor. The prognosis of patients with MiNEN is poor because of the high frequency of recurrence and metastases. We report a case of esophagogastric junction MiNEN (EGJ-MiNEN) with a long-term recurrence-free survival of 5.5 years.

CASE PRESENTATION: A 58-year-old male patient underwent thoracoscopic esophagectomy for esophagogastric junction adenocarcinoma. The patient's postoperative course was uneventful. R0 resection was achieved, and the pathological diagnosis of the surgical specimen was pT3N2M0 Stage IIIA (according to the Japanese Classification of Gastric Cancer, 4th edition). Based on the pathology results, the patient was treated with postoperative adjuvant therapy with oral S-1. The patient maintained recurrence-free survival for 5.5 years postoperatively. However, 6 years postoperatively, the patient visited our department with cachexia. Computed tomography (CT) revealed a large amount of ascites and pleural effusion. He rapidly developed a poor circulatory and respiratory status and died 16 days after admission. An autopsy revealed severe bloody ascites and pleural effusion, as well as numerous nodules on the pleura and mesentery. Immunohistochemistry of the nodules revealed positivity for chromogranin A, Synaptophysin A, neural cell adhesion molecule (NCAM or CD56), and insulinoma-associated protein 1 (INSM1). The specimen showed a mixture of adenocarcinoma and neuroendocrine cell carcinoma and was diagnosed as MiNEN. Retrospective immunostaining of the surgical specimen showed similar results, and we diagnosed the patient with recurrence of EGJ-MiNEN.

CONCLUSION: MiNEN has a poor prognosis; however, in some cases, long-term recurrence-free survival is achieved with radical resection and adjuvant chemotherapy.

PMID:39259237 | PMC:PMC11390994 | DOI:10.1186/s40792-024-02011-8

Permalink for 'A Case of Type 2 Diabetes Mellitus Revealed Transient Positivity of Glutamic Acid Decarboxylase (GAD) Antibodies Following Immunoglobulin Administrations'

A Case of Type 2 Diabetes Mellitus Revealed Transient Positivity of Glutamic Acid Decarboxylase (GAD) Antibodies Following Immunoglobulin Administrations

Fetched: October 16th, 2024, 2:02am UTC by Muneo Kawasumi

Cureus. 2024 Aug 9;16(8):e66485. doi: 10.7759/cureus.66485. eCollection 2024 Aug.

ABSTRACT

Glutamic acid decarboxylase (GAD) antibodies are frequently measured in diabetes care as islet-associated autoantibodies that are useful in the diagnosis of type 1 diabetes. However, GAD antibodies derived from other persons may contaminate immunoglobulin preparations, and there have been cases of transiently positive GAD antibodies after intravenous immunoglobulin (IVIg) in patients who were originally negative for GAD antibodies. Clinicians may be unaware of such contamination and misdiagnose some cases as type 1 instead of type 2 diabetes mellitus based on positivity for GAD antibodies. Herein, we present a case of type 2 diabetes mellitus that revealed transiently positive GAD antibodies following immunoglobulin administrations. A 68-year-old woman with a medical history of diabetes mellitus was admitted to our hospital for the treatment of Guillain-BarrÃ© syndrome, and IVIg was started on the day of admission. Blood tests on admission revealed negative for GAD antibodies but showed weak positivity on day one after IVIg. Afterward, GAD antibodies turned negative on day 72. Immunoglobulin preparations were revealed to have a high concentration of GAD antibodies. Based on changes in GAD antibody titers and all negativity for anti-insulinoma-associated antigen-2 (IA-2), insulin, and zinc transporter 8 (ZnT8) antibodies, the patient was diagnosed with type 2 diabetes mellitus rather than slowly progressive type 1 diabetes mellitus (SPIDDM). This case demonstrates that it is important for the medical clinician to be aware of the possible presence of GAD antibodies in immunoglobulin preparations and to measure antibody titers before and after their use for diagnosing the type of diabetes mellitus.

PMID:39247010 | PMC:PMC11380740 | DOI:10.7759/cureus.66485

LAPAROTOMIC RADIOFREQUENCY ABLATION OF PANCREATIC INSULINOMA

Fetched: October 16th, 2024, 2:02am UTC by Allan Rubens Zucolotto Cansi

Arq Bras Cir Dig. 2024 Aug 30;37:e1819. doi: 10.1590/0102-6720202400026e1819. eCollection 2024.

ABSTRACT

Insulinomas are rare neoplasms of the endocrine pancreas. Minimally invasive treatment options for insulinomas have gained prominence, replacing surgical resection due to its associated morbidity and mortality. Radiofrequency ablation (RFA) has emerged as a relevant treatment option. We present a case of a female patient with neuroglycopenic symptoms and severe hypoglycemic crises. The abdominal magnetic resonance imaging (MRI) showed a small nodular lesion in the pancreatic body. Laparotomy was performed, followed by RFA using a 15-mm active-tipped needle. No complications transpired, and no hypoglycemic episodes were observed during 12 months of follow-up.

PMID:39230119 | PMC:PMC11363906 | DOI:10.1590/0102-6720202400026e1819

Permalink for 'Intraoperative intermittently scanned continuous glucose monitoring in the management of patients with pancreatic insulinoma'

Intraoperative intermittently scanned continuous glucose monitoring in the management of patients with pancreatic insulinoma

Fetched: October 16th, 2024, 2:01am UTC by M Magliozzo

J Endocrinol Invest. 2024 Oct 14. doi: 10.1007/s40618-024-02472-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Insulinomas represent the most common functional pancreatic neuroendocrine tumors. Following preoperative localization, surgical excision is the curative treatment. It may be difficult to confirm a complete resection of insulinoma. We used intermittently scanned continuous glucose monitoring (isCGM) to record the fluctuation of interstitial glucose throughout surgery to help verify the tumor's complete surgical excision.

MATERIALS AND METHODS: In five individuals with insulinoma undergoing laparoscopic surgery we used the isCGM system (Freestyle Libre 2 Abbott) during tumor removal in order for the surgeon to understand "in real-time" the extent of tumor removal.

RESULTS: Two patients received no preoperative treatment, while three patients received medical treatment with either lanreotide (2 patients) or diazoxide (1 patient). In the non-treated patients, following tumor resection, there was a rapid interstitial glucose increase along with stabilized glucose levels thoroughly documented by intraoperative isCGM. Lanreotide treatment, on the other hand, resulted in only a minor increase in interstitial glucose. Finally, diazoxide-treated patients had a response that was intermediate between lanreotide-treated and non-treated patients.

CONCLUSION: Our findings suggest that isCGM is a useful tool to monitor the outcome of surgery during pancreatic insulinoma excision, assisting the surgical team in successfully removing the tumor. Despite the limited sample size, the results are promising, and, if validated in larger studies, they make us believe that the use of CGM systems has a definite benefit for becoming a standard in the surgical treatment of insulinomas.

PMID:39400889 | DOI:10.1007/s40618-024-02472-6

Permalink for 'Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases'

Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases

Fetched: September 3rd, 2024, 2:02am UTC by David Suster

Virchows Arch. 2024 Sep 3. doi: 10.1007/s00428-024-03904-7. Online ahead of print.

ABSTRACT

Insulinoma-associated protein 1 (INSM1) immunohistochemistry has been established as a sensitive and reliable immunohistochemical marker for detecting neuroendocrine differentiation in tumors across various organ systems. However, this marker has not been adequately investigated in primary thymic neuroendocrine tumors. We have studied a series of 27 cases of primary neuroendocrine carcinomas of the thymus, including 3 typical carcinoids, 18 atypical carcinoids, 4 large cell neuroendocrine carcinomas, and 2 small cell carcinomas. Immunostaining on whole tissue sections for INSM-1 was evaluated. Results of immunostaining for chromogranin and synaptophysin were also evaluated. 26/27 tumors (96%) demonstrated nuclear positivity for INSM1. 18 tumors (67%) showed strong and diffuse nuclear staining (3 +), 3 tumors (11%) moderate (2 +) nuclear staining, and 5 tumors (19%) showed weak (1 +) nuclear staining. The average percentage of tumor cells positive for INSM1 was 76%. Only one tumor, a small cell carcinoma, was negative. All tumors were positive for synaptophysin, and 26/27 (96%) were positive for chromogranin A. This study confirms that INSM1 immunohistochemistry is a sensitive marker of neuroendocrine differentiation in primary thymic neuroendocrine neoplasms and demonstrates similar performance characteristics compared to other organ systems. The nuclear staining with this marker offers the advantage of eliminating some of the ambiguity in the interpretation sometimes encountered with other markers. An added advantage is the consistent staining across the entire spectrum of neuroendocrine tumors of this organ.

PMID:39223347 | DOI:10.1007/s00428-024-03904-7

Permalink for 'Enucleation of insulinoma using laparoscopic distal pancreatectomy with a focus on vascular and splenic preservation: a case report'

Enucleation of insulinoma using laparoscopic distal pancreatectomy with a focus on vascular and splenic preservation: a case report

Fetched: September 3rd, 2024, 2:02am UTC by Luis F Marcial-Cuevas

J Surg Case Rep. 2024 Aug 30;2024(8):rjae561. doi: 10.1093/jscr/rjae561. eCollection 2024 Aug.

ABSTRACT

Insulinomas represent <10% of pancreatic tumors. It is a functional neuroendocrine tumor that can cause recurrent and severe episodes of loss of consciousness due to hypoglycemia. Surgical removal is the only curative treatment. The selection of the optimal surgical technique must be individualized for each patient. Currently, there are emerging innovations in less invasive techniques that reduce morbidity. We present the case of a 23-year-old woman who underwent enucleation of an insulinoma localized at the tip of the pancreatic tail after laparoscopic surgery, with a focus on vascular and splenic preservation. The tumor was safely identified during surgery and enucleated without injury to the spleen and adjacent vascular structures or postoperative complications.

PMID:39220171 | PMC:PMC11364455 | DOI:10.1093/jscr/rjae561

Permalink for 'Successful Localization by Hyperselective Arterial Calcium Injection Test for Surgical Resection of Insulinoma: A Case Report'

Successful Localization by Hyperselective Arterial Calcium Injection Test for Surgical Resection of Insulinoma: A Case Report

Fetched: September 3rd, 2024, 2:02am UTC by Momo Saito

J UOEH. 2024;46(3):263-269. doi: 10.7888/juoeh.46.263.

ABSTRACT

Surgery is the main treatment for insulinoma, and precise preoperative localization is important to determine the extent of resection and to rule out multiple lesions. The selective arterial calcium injection (SACI) test is instrumental in the localization of insulinoma. Here we report a patient in whom the exact location of pancreatic insulinoma could not be determined by the conventional SACI test, and thus surgery was replaced with oral diazoxide. The hyperselective SACI test subsequently localized the lesion accurately, allowing surgical resection of the pancreatic body and tail while preserving the pancreatic head. We recommend the use of the hyperselective SACI test when the conventional SACI test fails to accurately determine the location of insulinoma lesions within the pancreas.

PMID:39218663 | DOI:10.7888/juoeh.46.263

Management of functional neuroendocrine tumors

Fetched: September 1st, 2024, 2:02am UTC by Amr Wahba

Curr Probl Cancer. 2024 Oct;52:101130. doi: 10.1016/j.currproblcancer.2024.101130. Epub 2024 Aug 30.

ABSTRACT

Functional neuroendocrine neoplasms (NENs) are those associated with specific symptoms related to the hormonal secretion of the NENs. Although less than 25 % of NENs are functional at diagnosis,¹ the associated syndromes significantly increase the patient burden of disease. Management of hormonal NEN symptoms may involve tumor resection or other reduction strategies (e.g., chemotherapy, embolotherapy, etc), but also specific therapies directed at decreasing hormonal synthesis, secretion, or end-organ effects. In this review, we focus on specific symptomatic management of many of the NEN syndromes, which may be pursued in addition to management primarily directed at tumor bulk and growth. A continued focus on symptom management related to the hormonal secretions of NENs, in the context of other efforts to reduce tumor bulk and growth, could significantly improve patient wellbeing.

PMID:39213785 | DOI:10.1016/j.currproblcancer.2024.101130

Insulator-based dielectrophoresis-assisted separation of insulin secretory vesicles

Fetched: August 28th, 2024, 2:02am UTC by Mahta Barekatain

Elife. 2024 Aug 27;13:e74989. doi: 10.7554/eLife.74989.

ABSTRACT

Organelle heterogeneity and inter-organelle contacts within a single cell contribute to the limited sensitivity of current organelle separation techniques, thus hindering organelle subpopulation characterization. Here, we use direct current insulator-based dielectrophoresis (DC-iDEP) as an unbiased separation method and demonstrate its capability by identifying distinct distribution patterns of insulin vesicles from INS-1E insulinoma cells. A multiple voltage DC-iDEP strategy with increased range and sensitivity has been applied, and a differentiation factor (ratio of electrokinetic to dielectrophoretic mobility) has been used to characterize features of insulin vesicle distribution patterns. We observed a significant difference in the distribution pattern of insulin vesicles isolated from glucose-stimulated cells relative to unstimulated cells, in accordance with maturation of vesicles upon glucose stimulation. We interpret the difference in distribution pattern to be indicative of high-resolution separation of vesicle subpopulations. DC-iDEP provides a path for future characterization of subtle biochemical differences of organelle subpopulations within any biological system.

PMID:39190030 | PMC:PMC11349295 | DOI:10.7554/eLife.74989

Spontaneous Hypoglycemia in a Non-diabetic Patient: A Diagnostic and Therapeutic Conundrum

Fetched: August 28th, 2024, 2:02am UTC by Karnika Mahendiran

Cureus. 2024 Jul 26;16(7):e65467. doi: 10.7759/cureus.65467. eCollection 2024 Jul.

ABSTRACT

Hypoglycaemia is a medical emergency requiring an immediate intervention to prevent neuroglycopenic symptoms such as confusion, seizures, and coma. While evaluating for the cause of hypoglycemia, after excluding common causes like insulin use or sepsis, other causes involving endogenous hypoglycemia need to be evaluated. A cause to be considered is nesidioblastosis. This rare entity is also known as non-insulinoma pancreatogenous hypoglycemia syndrome. There have been instances where this disorder has been mistaken as insulinoma due to the characteristics shared by the two. Here, we present a case of a non-diabetic male experiencing symptoms of giddiness and palpitations for the past two years who had been extensively evaluated to rule out insulinoma and was diagnosed with nesidioblastosis.

PMID:39188435 | PMC:PMC11345124 | DOI:10.7759/cureus.65467

The outcomes of robotic-assisted enucleation for tumors located in uncinate process of pancreas in 16 cases

Fetched: August 27th, 2024, 2:03am UTC by W W Jin

Zhonghua Wai Ke Za Zhi. 2024 Aug 26;62(10):924-929. doi: 10.3760/cma.j.cn112139-20240316-00129. Online ahead of print.

ABSTRACT

Objective: To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas. Methods: This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People's Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age(M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m² (range:19.8 to 25.6 kg/m²). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results: In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay were 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor(n=3),insulinoma(n=2),introductal papillary mucinous neoplasm (n=5),solid pseudopapillary neoplasm (n=2),mucinous cystadenoma (n=1),serous cystadenoma (n=2),pseudocyst (n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion: Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.

PMID:39183017 | DOI:10.3760/cma.j.cn112139-20240316-00129

Permalink for 'Expression profiles of cadherin 17 and claudin 18.2 in comparison with peptide hormonal expression in pancreatic neuroendocrine tumours: Implications for targeted immunotherapy'

Expression profiles of cadherin 17 and claudin 18.2 in comparison with peptide hormonal expression in pancreatic neuroendocrine tumours: Implications for targeted immunotherapy

Fetched: August 25th, 2024, 2:01am UTC by Kahoko Maeda

Pathol Res Pract. 2024 Oct;262:155537. doi: 10.1016/j.prp.2024.155537. Epub 2024 Aug 12.

ABSTRACT

Cadherin 17 (CDH17) and claudin 18.2 (CLDN18.2) are highly selective markers of intestinal and gastric lineages and are expressed in adenocarcinomas of various organs. They have also been identified as potential targets for immunotherapy. Expression of CDH17 and CLDN18.2 has been observed in a subset of pancreatic neuroendocrine tumours (PanNETs). This study investigates the immunohistochemical expression of CDH17 and CLDN18 in PanNETs in comparison with hormonal expression profiles to provide baseline data for determining candidate indications for targeted therapy with CDH17 and CLDN18.2 in PanNETs, including insulinomas (n = 22), glucagonomas (n = 13), gastrinomas (n = 3), serotoninomas (n = 2) and PanNETs not otherwise specified (NOS) (n = 17). In the normal pancreas, CDH17 was expressed in the lateral membrane of ducts and some islet cells, whereas CLDN18 was occasionally expressed in the intercalated ducts and centroacinar cells. In PanNETs, CDH17 and CLDN18 was detected by membranous staining. CDH17 expression was observed in 10 to 17 (58.8 %) PanNETs NOS, 3 of 13 (23.1 %) glucagonomas, 1 of 3 (33.3 %,) gastrinomas, 1 of 2 (50 %) serotoninomas, and none of the insulinomas. According to predefined criteria, 7 of 17 (41.2 %) PanNETs NOS, 1 of 3 (33.3 %) gastrinomas, and 1 of 2 (50 %) serotoninomas were classified as CDH17-positive. There were no significant differences in clinicopathological features between CDH17-positive and CDH17-negative PanNETs, except for a higher tumour grade in the former (p<0.05). For CLDN18, expression was noted in 2 out of 3 (66.7 %) gastrinomas, one with focal staining and the other with diffuse staining. One of three (33.3 %) gastrinomas was classified as CLDN18-positive using predefined criteria. These findings suggest that a particular subset of PanNETs, including PanNET NOS, gastrinoma, and serotoninoma, may be potential candidates for CDH17-targeted immunotherapy. Additionally, gastrinoma may be a potential candidate for immunotherapy targeting CLDN18.2.

PMID:39178509 | DOI:10.1016/j.prp.2024.155537

18F-DOPA PET/MRI With Carbidopa for the Diagnosis of Hyperinsulinemic Hypoglycemia in an Adolescent Patient

Fetched: August 23rd, 2024, 2:02am UTC by Carine Anka

JCEM Case Rep. 2024 Aug 21;2(9):luae153. doi: 10.1210/jcemcr/luae153. eCollection 2024 Sep.

ABSTRACT

Hyperinsulinism due to focal or diffuse pancreatic lesions causing recurrent episodes of hypoglycemia is rare in mid-childhood. There is no consensus on the gold-standard imaging method to diagnose focal insulin-producing lesions beyond infancy. A 14-year-old boy with a complex medical history and refractory epilepsy, presented with blood glucose (BG) of 52 mg/dL (2.9 mmol/L) (normal reference range: 70-100 mg/dL [3.9-5.6 mmol/L]) and increased seizure frequency. He failed a fast within 4 hours, with BG of 48 mg/dL (2.7 mmol/L) and insulin level of 4.6 ÂµIU/mL (24.6 pmol/L) (diagnostic at the time of hypoglycemia >1.25 Î¼U/mL [8.7 pmol/L]). Conventional imaging studies showed no pancreatic lesion. Fluorine-18-L-dihydroxyphenylalanine positron emission tomography/magnetic resonance imaging (¹⁸F-DOPA-PET/MRI) scan premedicated with carbidopa demonstrated intense focal ¹⁸F-DOPA uptake in the distal pancreatic tail. He underwent distal pancreatectomy. Histopathology showed focal pancreatic islet cell hyperplasia, with more than 90% of the neuroendocrine islet cells being positive for chromogranin and synaptophysin, with no loss of p57 staining. Genetic studies were negative for mutations in ABCC8, KCNJ11, GCK, or GLUD1 genes, multiple endocrine neoplasia (MEN) type 1, and Beckwith-Wiedemann syndrome. BG normalized after surgery. Seizure frequency improved. This case highlights the utility of ¹⁸F-DOPA PET/MRI imaging in diagnosing focal hyperinsulinism beyond infancy.

PMID:39170749 | PMC:PMC11337120 | DOI:10.1210/jcemcr/luae153

A Case Report: Hypoglycaemic Unawareness Associated With Insulinoma

Fetched: August 21st, 2024, 2:02am UTC by Alamin Alkundi

Cureus. 2024 Jul 20;16(7):e64994. doi: 10.7759/cureus.64994. eCollection 2024 Jul.

ABSTRACT

Hypoglycaemic unawareness (HU) is more frequently described in relation to diabetics in the literature. We have noted that there is also an increasing reporting of HU in insulinoma cases. We report a hospital presentation for an incidental finding of hypoglycaemic unawareness in a gentleman in his fifties who was eventually diagnosed with insulinoma following biochemical studies, radiologic evaluation and histologic evaluation of an excised lesion between the pancreas and the spleen. We have reviewed existing literature evidence regarding the possible aetiologies and management options for this occurrence. More research studies to identify the epidemiology of this association and the determination of a protocol for increased detection of patients with insulinoma who display HU will need to be done.

PMID:39161528 | PMC:PMC11332653 | DOI:10.7759/cureus.64994

A Rare Case of Malignant Insulinoma Associated With Gastrointestinal Bleed

Fetched: August 20th, 2024, 2:02am UTC by William K Boateng

Cureus. 2024 Jul 19;16(7):e64894. doi: 10.7759/cureus.64894. eCollection 2024 Jul.

ABSTRACT

A gastrointestinal bleed (GIB) in the setting of metastatic insulinoma is a rare phenomenon. It appears that cases of metastatic insulinoma causing GIB are rare, often influenced by the tumor's location. Our case involves an 82-year-old male with dementia and a history of recurrent hypoglycemia, presenting with an episode of altered mental status. The patient exhibited hypoglycemia alongside a melena episode and anemia. Diagnostic criteria, including Whipple's triad, confirmed endogenous insulin production. Computed tomography (CT) showed a left paraaortic/retroperitoneal mass. Esophagogastroduodenoscopy (EGD) visualized an extrinsic mass at the gastric body, which caused an ulcerated surface that was treated with clipping and hemostasis. The patient's recurrent hypoglycemic episodes were treated with glucose, while his GIB was managed with hemostasis and clipping. However, the patient was not a surgical candidate, and further medical treatment was ceased by the family.

PMID:39156287 | PMC:PMC11330681 | DOI:10.7759/cureus.64894

A tale of two sisters - delayed diagnosis of genetic hyperinsulinaemic hypoglycaemia

Fetched: August 19th, 2024, 2:02am UTC by F Stringer

Endocrinol Diabetes Metab Case Rep. 2024 Aug 16;2024(3):24-0007. doi: 10.1530/EDM-24-0007. Print 2024 Jul 1.

ABSTRACT

SUMMARY: Congenital hyperinsulinism is the leading cause of persistent hypoglycaemia in infants and children; however, it is uncommon to be diagnosed in adulthood. We describe the cases of two sisters who presented with hyperinsulinaemic hypoglycaemia aged 47 and 57 years old, who were subsequently diagnosed with compound heterozygous likely pathogenic variants in the ABCC8 gene, a known cause of monogenic congenital hyperinsulinism. We discuss the typical presenting features, investigation findings, and treatment strategies for patients with this condition.

LEARNING POINTS: Congenital hyperinsulinism is a rare cause of hyperinsulinaemic hypoglycaemia diagnosed in adulthood. Clinical presentation is similar to an insulinoma, and imaging modalities may assist in differentiation. There are minimal medical therapies currently available for patients non-responsive to diazoxide (such as those with ABCC8 and KCNJ11 variants). Continuous glucose monitoring can be helpful in giving patients autonomy in managing their disease, as well as relieving anxiety and fear associated with hypoglycaemia.

PMID:39153498 | PMC:PMC11378141 | DOI:10.1530/EDM-24-0007

Permalink for 'ARX, PDX1, ISL1 and CDX2 expression distinguishes five subgroups of PanNETs with correlations to histology, hormone expression and outcome'

ARX, PDX1, ISL1 and CDX2 expression distinguishes five subgroups of PanNETs with correlations to histology, hormone expression and outcome

Fetched: August 16th, 2024, 2:01am UTC by Elisa Moser

Mod Pathol. 2024 Aug 13;37(11):100595. doi: 10.1016/j.modpat.2024.100595. Online ahead of print.

ABSTRACT

Many pancreatic neuroendocrine tumors (PanNETs) fall into 2 major prognostic subtypes based on DAXX/ATRX-induced alternative lengthening of telomerase phenotype and alpha- and beta-cell-like epigenomic profiles. However, these PanNETs are still flanked by other PanNETs that do not fit into either subtype. Furthermore, despite advanced genotyping, PanNETs are generally not well-characterized in terms of their histologic and hormonal phenotypes. We aimed to identify new subgroups of PanNETs by extending the currently used transcription factor signatures and investigating their correlation with histologic, hormonal, molecular, and prognostic findings. One hundred eighty-five PanNETs (nonfunctioning 165 and functioning 20), resected between 1996 and 2023, were classified into 5 subgroups (A1, A2, B, C, and D) by cluster analysis based on ARX, PDX1, islet-1 (ISL1), and CDX2 expressions and correlated with trabecular vs solid histology, expression of insulin, glucagon, polypeptide (PP), somatostatin, serotonin, gastrin, calcitonin, adrenocorticotropic hormone (ACTH), DAXX/ATRX, MEN1, and alternative lengthening of telomerase status by fluorescence in situ hybridization, and disease-free survival. A1 (46%, ARX+/ISL1+/PDX1-/CDX2-) and A2 (15%, ARX+/ISL1+/PDX1+/CDX2-) showed trabecular histology and glucagon/PP expression, with A2 also showing gastrin expression. B (18%, PDX1+/ISL1+/ARX-/CDX2-) showed solid histology, insulin, and somatostatin expression (P < .001). It included all insulinomas and had the best outcome (P < .01). C (15%, ARX-/PDX1-/ISL1-/CDX2-) showed solid histology and frequent expression of serotonin, calcitonin, and ACTH. D (5%, PDX1+/CDX2+/ISL1-/ARX-) showed solid histology, expressed ACTH/serotonin, and was an independent poor prognosticator (P < .01). Differential expressions of ARX, PDX1, ISL1, and CDX2 stratified PanNETs into 5 subgroups with different histologies, hormone expressions, and outcomes. Subgroups A1 and A2 resembled the alpha-cell-like type, and subgroup B, the beta-cell-like type. Subgroup C with almost no transcription factor signature was unclear in cell lineage, whereas the PDX+/CDX2+ signature of subgroup D suggested a pancreatic/intestinal cell lineage. Assigning PanNETs to the subgroups may help establish the diagnosis, predict the outcome, and guide the treatment.

PMID:39147030 | DOI:10.1016/j.modpat.2024.100595

Pancreatic masses in children: a single-center experience over two decades

Fetched: August 16th, 2024, 2:01am UTC by Joyce J L H McRae

Eur J Pediatr. 2024 Oct;183(10):4467-4476. doi: 10.1007/s00431-024-05731-z. Epub 2024 Aug 15.

ABSTRACT

Pancreatic masses are extremely rare in pediatric patients, with limited data available. This lack of data makes the diagnosis and management of these tumors in children extremely challenging. Therefore, we aimed to describe the presentations, clinical course, and outcomes of children with pancreatic tumors at our center. A retrospective analysis was performed of all pediatric patients diagnosed with pancreatic masses between 2003 and 2022 in an academic freestanding children's hospital. Data including demographics, clinical presentation, workup, management, and subsequent morbidity and mortality were collected and aggregated. Furthermore, we reviewed cases of pancreatic tumor resections in the National Surgical Quality Improvement Program - Pediatric (NSQIP-P) database to identify common adverse outcomes and measures for quality improvement. In total, 17 patients were identified at our institution. Diagnoses included solid pseudopapillary (n = 9), gastrinoma (n = 1), rhabdomyosarcoma (n = 2), pancreatoblastoma (n = 2), and insulinoma (n = 1). Two patients did not have a histopathologic diagnosis and were excluded from subsequent analysis. Overall, 12 patients underwent surgical intervention, with the most common procedures being pancreaticoduodenectomy and distal pancreatectomy, and all 12 were known to be alive at last contact. There were 3 deaths, all due to complications related to metastatic disease. Furthermore, 30-day postoperative outcomes in the NSQIP-P dataset for pancreatic surgeries in pediatric patients are excellent, with negligible morbidity and no mortalities after the index surgery.

CONCLUSIONS: Children with pancreatic tumors amenable to surgical resection appear to have adequate long-term survival. Short-term outcomes at diagnosis are excellent and mainly appear to be influenced by the presence of metastatic disease at initial presentation.

WHAT IS KNOWN: â€¢ Pancreatic masses are a rare entity in children with limited data on their presentation, management and surgical outcomes. â€¢ Solid Pseudopapillary tumors are one of the most common pancreatic tumors in children with a fair prognosis after surgical intervention.

WHAT IS NEW: â€¢ Surgical management of pediatric patients with pancreatic tumors is safe and effective in patients who do not have aggressive tumor types or metastatic disease. â€¢ Our case series provides a notable cohort of these pancreatic tumors with insight into the presentation, management and outcomes of five of these tumor types.

PMID:39145888 | DOI:10.1007/s00431-024-05731-z

Robotic enucleation of pancreatic insulinoma

Fetched: August 16th, 2024, 2:01am UTC by P V Markov

Khirurgiia (Mosk). 2024;(8):64-68. doi: 10.17116/hirurgia202408164.

ABSTRACT

We demonstrate robot-assisted treatment of a patient with benign pancreatic insulinoma. A 31-year-old patient suffered from attacks of weakness, numbness of the fingertips and Â«turbidity of consciousnessÂ» for 2 years. These symptoms occurred on an empty stomach and regressed after eating. We found pancreatic insulinoma. The patient underwent robotic enucleation of pancreatic tumor. Surgery time was 145 min. Postoperative period proceeded without complications. Hyperglycemia up to 10.5 mmol/l on the first postoperative day was followed by normalization after 4 days. The patient was discharged in 6 days after surgery. Minimally invasive robotic enucleation of insulinoma minimizes surgical trauma and provides precise resection of tumor. The key aspect of safe enucleation is localization of tumor at a distance of at least 2 mm from the pancreatic duct.

PMID:39140945 | DOI:10.17116/hirurgia202408164

(68)Ga-DOTATATE PET/CT: How is it reliable in imaging of cases having clinical suspicion of insulinomas?

Fetched: August 14th, 2024, 2:02am UTC by Mostafa M Abdelkawi

Eur J Radiol. 2024 Oct;179:111669. doi: 10.1016/j.ejrad.2024.111669. Epub 2024 Aug 8.

ABSTRACT

PURPOSE: This retrospective study evaluates the value of ⁶⁸Ga-DOTATATE PET/CT in the diagnosis and localization of insulinomas, whether sporadic, malignant or MEN-1 associated insulinoma.

METHOD: The study included 43 patients, having clinical (symptomatic hypoglycemia) and/or laboratory suspicion of having insulinoma (72 h fasting test with serum insulin â‰¥18 pmol/L), with available pre-operative ⁶⁸Ga-DOTATATE PET/CT and CE-CT, and diagnosed with insulinoma confirmed by post-operative histopathology. Preoperative imaging was retrospectively analyzed by two radiologists who were blinded to the final diagnosis and to the results of other imaging modalities. Histopathology of specimen was considered the reference standard, and head-to-head comparison of preoperative CE-CT and PET imaging findings. Findings were classified as true positive (TP), true negative (TN), false positive (FP), and false negative (FN) for each modality. Based on these results, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CE-CT, and ⁶⁸Ga-DOTATATE PET/CT for the detection of insulinoma were calculated.

RESULTS: 43 patients (N = 43 patients, L = 56 lesions), out of these, 37 patients had benign sporadic insulinoma (N = 37, L = 42), only 3 patients had malignant sporadic insulinoma (N = 2, L = 9), and 3 patients had MEN-1 syndrome associated insulinoma (N = 3, L = 5). There was no significant statistical difference in sensitivity (P = 0.3058) and PPV (P = 0.5533) for insulinoma localization in the overall cohort with ⁶⁸Ga-DOTATATE PET/CT (87.5 %, 90.74 %) compared to CE-CT (80.36 %, 93.75 %).

CONCLUSION: ⁶⁸Ga-DOTATATE PET/CT is a non-invasive imaging modality that can identify most insulinomas. Still, it offers limited additional information when the tumor is localized by other anatomic imaging studies, so should be used as an adjunct when imaging studies fail to localize the tumor in insulinoma patients, especially when minimally invasive surgical is intended.

PMID:39137605 | DOI:10.1016/j.ejrad.2024.111669

Insulinoma presenting with anti-insulin antibodies

Fetched: August 13th, 2024, 2:02am UTC by Rikako Nakajima

Endocrinol Diabetes Metab Case Rep. 2024 Aug 12;2024(3):24-0062. doi: 10.1530/EDM-24-0062. Print 2024 Jul 1.

ABSTRACT

SUMMARY: An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 ÂµU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 ÂµU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies.

LEARNING POINTS: Insulinoma presenting with concomitant anti-insulin antibodies appears rare. Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome. Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.

PMID:39133227 | PMC:PMC11378122 | DOI:10.1530/EDM-24-0062

Diagnostic Challenges in Difficult-to-Localize Insulinomas: A Case Report and Review of Literature

Fetched: August 11th, 2024, 2:02am UTC by Nikica M Grubor

Diagnostics (Basel). 2024 Jul 25;14(15):1600. doi: 10.3390/diagnostics14151600.

ABSTRACT

Non-somatostatin receptor expressing hypovascular insulinomas can be challenging to prove through imaging. This case highlights the utility of a structured approach to molecular imaging in patients with confirmed endogenous hyperinsulinemia. A 54-year-old woman was admitted because of a sudden loss of consciousness. Her relative reported that she complained of dizziness, intense sweating, blurry vision, and upper extremity tingling before becoming unresponsive for 20 min, after which the patient had little recollection of the event. She experienced similar episodes of shorter duration, trouble recalling everyday events, and unintentional weight gain of over 10 kg during the previous two years. Abdominal magnetic resonance imaging (MRI) and multidetector computerized tomography (MDCT) were unremarkable. Selective arterial calcium stimulation significantly increased hepatic venous insulin concentrations when the superior mesenteric and gastroduodenal arteries were stimulated. Technetium-99m (99mTc) octreotide single-photon emission computed tomography (SPECT) did not localize the lesion. Gallium-68 DOTA-Exendin-4 PET/CT acquisition was performed. A single intense 2 cm hyperperfused pancreatic lesion was located anteriorly in the head of the pancreas. Earlier targeted PET/CT imaging and recognition of significant neuropsychiatric symptoms attributable to the patient's hypoglycemic state might have accelerated the resolution of her condition and obviated the need for unnecessary testing.

PMID:39125476 | PMC:PMC11311322 | DOI:10.3390/diagnostics14151600

Characteristics, therapy, and outcome of rare functioning pancreatic neuroendocrine neoplasms

Fetched: August 11th, 2024, 2:02am UTC by Max B Albers

Sci Rep. 2024 Aug 9;14(1):18507. doi: 10.1038/s41598-024-68290-1.

ABSTRACT

Functioning pancreatic neuroendocrine neoplasms other than insulinomas and gastrinomas (rf-pNENs) are exceptionally rare tumours. Thus, their characteristics and long-term prognosis have not been well defined. This article aims to present data and experience from a single institution concerning this topic. Twelve of 216 (5.5%) patients with pNENs operated between 2002 and 2022 in the ENETS Centre of Excellence Marburg had rf-pNENs and their data were retrospectively analysed. We identified three vasoactive intestinal polypeptide producing pNENs, four glucagonomas and five calcitoninomas. The tumour could be visualised by preoperative imaging in all 12 patients, and six patients had distant metastases at the time of diagnosis. The tumour was located in the pancreatic tail in nine patients and the median tumour size was 82 (range 12-220) mm. Eleven patients underwent tumour resections (two robotic, nine conventional), nine of which were R0. After a median follow-up of 75 (range 1-247) months, six patients were alive, five of whom had no evidence of disease. All patients who remained disease-free had an initial R0 resection of the primary tumour and no initial liver involvement. This study sheds light on the distinct characteristics and outcomes of these exceedingly rare tumours, offering insights for improved understanding and management.

PMID:39122816 | PMC:PMC11316089 | DOI:10.1038/s41598-024-68290-1

A case of insulinoma misidentified as schizophrenia due to its manifestation in neuropsychiatric symptoms

Fetched: August 6th, 2024, 2:02am UTC by Tomoyuki Haba

Diabetol Int. 2024 Apr 21;15(3):611-615. doi: 10.1007/s13340-024-00722-9. eCollection 2024 Jul.

ABSTRACT

Insulinomas can present with neuroglycopenic symptoms suggesting neuropsychiatric disorders, delaying diagnosis and treatment. We recently treated a 65-year-old woman with insulinoma who was misdiagnosed at her nearby psychiatric clinic as having schizophrenia because of personality changes and memory impairment; she was treated with brexpiprazole, which was discontinued due to persistence of the symptoms. Despite her relatively low casual plasma glucose (70 mg/dL), the physician at the psychiatric clinic did not investigate the possibility of hypoglycemia, partly because her HbA1c level (5.2%) was within normal range. After skipping lunch one day, she was found by her family to be unable to communicate properly. She was transported to the emergency room of our hospital, where intermittently scanning continuous glucose monitoring (isCGM) use permitted detection of the hypoglycemia and led to a diagnosis of insulinoma and successful resection. A 72-h fasting test established hyperinsulinemic hypoglycemia. Contrast-enhanced computed-tomography and endoscopic ultrasonography together with selective arterial calcium stimulation test revealed an insulin-secreting tumor in the tail of the pancreas. Surgical resection of the tumor corrected her glucose and insulin levels as well as eliminated the insulinoma neuropsychiatric symptoms. Pathological examination showed that the tumor was positive for chromogranin A, synaptophysin and insulin. It is, therefore, important for physicians to be aware that insulinomas can manifest as neuroglycopenic symptoms and to consider the possibility of hypoglycemia by careful medical interview and isCGM, especially when patients suspected of psychiatric disorders do not show the expected response to antipsychotic drugs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-024-00722-9.

PMID:39101165 | PMC:PMC11291769 | DOI:10.1007/s13340-024-00722-9

Pioneering robotic-assisted surgery for insulinoma during pregnancy: The first case report and literature review

Fetched: August 6th, 2024, 2:02am UTC by Voraboot Taweerutchana

Heliyon. 2024 Jul 6;10(14):e34239. doi: 10.1016/j.heliyon.2024.e34239. eCollection 2024 Jul 30.

ABSTRACT

INTRODUCTION: Insulinoma during pregnancy is a rare condition with vague clinical symptoms, making diagnosis challenging. The standard treatment for insulinoma is surgical tumor removal, preferably using a minimally invasive method. However, there have been no recorded examples of employing a robotic platform in pregnant women with insulinoma. In this report, we present the first successful case of robotic enucleation for insulinoma during pregnancy.

CASE PRESENTATION: A 30-year-old pregnant woman presented with recurrent hypoglycemic symptoms throughout her first trimester that were relieved by food intake. After confirming endogenous hyperinsulinemia, an abdominal magnetic resonance imaging scan was performed to locate the tumor. A well-defined 2-cm mass was found in the pancreatic body. Robotic enucleation was performed at week 18 of gestation, and the patient experienced relief from hypoglycemic episodes postoperatively. Her blood glucose levels returned to normal, and she had an uneventful pregnancy. The patient eventually delivered a healthy baby via cesarean section without any complications.

CONCLUSIONS: For a subset of pregnant individuals with insulinoma, a minimally invasive approach as robotic-assisted surgery is safe and feasible. This innovative technique has the potential to both mothers and fetuses.

PMID:39100462 | PMC:PMC11296031 | DOI:10.1016/j.heliyon.2024.e34239

Permalink for 'Comprehensive analysis of single-cell transcriptomics and genetic factors reveals the mechanisms and preventive strategies for the progression from pulmonary fibrosis to lung cancer'

Comprehensive analysis of single-cell transcriptomics and genetic factors reveals the mechanisms and preventive strategies for the progression from pulmonary fibrosis to lung cancer

Fetched: August 4th, 2024, 2:02am UTC by Jinghua Gu

Int Immunopharmacol. 2024 Oct 25;140:112803. doi: 10.1016/j.intimp.2024.112803. Epub 2024 Aug 1.

ABSTRACT

BACKGROUND: Pulmonary fibrosis (PF) leads to excessive deposition of fibrous connective tissue in the lungs, increasing the risk of lung cancer due to the enhanced activity of fibroblasts (FBs). Fibroblast-mediated collagen fiber deposition creates a tumor-like microenvironment, laying the foundation for tumorigenesis. Clinically, numerous cases of lung cancer induced by pulmonary fibrosis have been observed. In recent years, the study of nucleotide point mutations, which provide more detailed insights than gene expression, has made significant advancements, offering new perspectives for clinical research.

METHODS: We initially employed Mendelian randomization to ascertain that the initial stage of lung cancer induced by PF belongs to small cell lung cancer (SCLC). Subsequently, pulmonary neuroendocrine cells (PNECs) were identified by using pseudo-time series analysis as cell clusters with carcinogenic potential. We categorized FBs into four groups according to their cellular metabolism, and then analyzed the cellular communication between FBs and PNECs, as well as changes in intracellular pathways of PNECs. Additionally, we examined the characteristic genome of FBs which is significantly associated with PF and investigated the impact of FBs on immune cells in the PF microenvironment. Finally, we explored strategies for preventing the progression from PF to lung cancer.

RESULTS: The genetic features of cells with carcinogenic potential in PF tissues were revealed, characterized by upregulation of Achaete-Scute Family BHLH Transcription Factor 1 (ASCL1), Homeobox B2 (HOXB2), Teashirt Zinc Finger Homeobox 2 (TSHZ2), Insulinoma-associated 1 (INSM1), and reduced activity of RE1 Silencing Transcription Factor (REST). FBs characterized by high glycolysis and low tricarboxylic acid (TCA) cycling played a key role in the progression of PF. The microenvironment of PF resembles the tumor microenvironment, providing a conducive immunosuppressive environment for the occurrence of cancer cells. In dendritic cells, rs9265808 is a susceptibility locus for progression from pulmonary fibrosis to lung cancer, mutations at this locus increase the expression of Complement Factor B (CFB), and excessive activation of the complement pathway is a crucial factor leading to lung cancer development in patients with pulmonary fibrosis. Ensuring adequate nutritional supply and physical function is one of the effective measures to prevent progression from pulmonary fibrosis to lung cancer.

CONCLUSION: CFB promotes lung cancer occurrence by inducing the accumulation and polarization of a large number of monocytes/macrophages in the lungs, driving disease progression by reducing the physical fitness of patients with pulmonary fibrosis.

PMID:39094357 | DOI:10.1016/j.intimp.2024.112803

Spontaneous Hypoglycaemia due to Insulin Autoimmune Syndrome in Six Cases, Response to Steroid Therapy and Rituximab

Fetched: August 2nd, 2024, 2:02am UTC by Chandar M Batra

Indian J Endocrinol Metab. 2024 May-Jun;28(3):295-301. doi: 10.4103/ijem.ijem_378_23. Epub 2024 Jun 26.

ABSTRACT

INTRODUCTION: Dr. Hirata of Japan first described insulin autoimmune syndrome (IAS) in 1970. Seven hundred ninety-five cases of this rare syndrome have been reported from Japan and China and 29 from India. IAS has the following characteristic features 1) severe spontaneous attacks of hyperinsulinemic hypoglycaemia, 2) high total immunoreactive insulin levels, 3) elevated insulin autoantibody (IAA) titres, 4) no prior exposure to exogenous insulin, and 5) no pathological abnormalities of the pancreatic islet cells.

METHODS: We treated six cases of IAS with high doses of prednisolone for 4-6 weeks and then gradually reduced the doses. Diagnosis of IAS was established by documenting Whipple's triad of symptoms and signs of hypoglycaemia, blood sugar <55 mg/dl, improvement of symptoms with dextrose infusion, inappropriately increased insulin levels >3 uU/ml, C-peptide levels >0.6 ng/ml, and increased titres of anti-insulin autoantibodies. Insulinoma and non-pancreatic tumours were ruled out by CECT (contrast-enhanced computerised tomography) or MRI (magnetic resonance imaging) of the abdomen and if necessary endoscopic ultrasonography and gallium 68 Dotanoc PET (positron enhanced tomography). Autoimmune screening and serum electrophoresis were done to rule out multiple myeloma. Monitoring of the patient's blood sugars was done by the laboratory, glucometer readings, and a freestyle libre glucose monitoring system.

RESULTS: Remission of hypoglycaemic episodes, hyperglycaemic episodes, and marked reduction of serum insulin and insulin autoantibodies in four out of six patients with diet therapy and steroids. Two patients resistant to steroids were treated with rituximab successfully. Patient 6 developed serious complications of cytomegalovirus and Pneumocystis carnii after rituximab, which were treated successfully.

CONCLUSION: A careful history including recent infections, medications, and vaccinations provides vital clues in the evaluation. An increased awareness of IAS will prevent unnecessary and costly investigations and surgery. Although it is often self-remitting, steroids are contributory in severe cases. Immunosuppressives are used successfully in cases refractory to steroids. Continuous glucose monitoring system (CGMS), by freestyle libre glucose monitoring system, provided real-time blood sugar values, total time in hypoglycaemia, and total time in the range (TIR), which proved very valuable in managing IAS patients. Low CGMS values should be corroborated clinically and with laboratory or glucometer values.

PMID:39086578 | PMC:PMC11288520 | DOI:10.4103/ijem.ijem_378_23

Diagnostic Modalities, Management Considerations, and Outcomes of Insulinoma: A Case Series from a Tertiary Care Centre

Fetched: August 2nd, 2024, 2:02am UTC by Anirudh J Shetty

Indian J Endocrinol Metab. 2024 May-Jun;28(3):279-288. doi: 10.4103/ijem.ijem_359_23. Epub 2024 Jun 26.

ABSTRACT

INTRODUCTION: Insulinomas are rare, usually sporadic, and typically benign pancreatic neuroendocrine tumours. Pre-operative localization is challenging and evidence on comparative analysis of anatomic and scintigraphic modalities for pre-operative tumour localization is limited, even in contemporary series.

METHODS: The current study was designed to study the clinical features and management challenges of insulinomas managed at a tertiary care centre. Clinical features, diagnosis, imaging techniques, surgical procedures, and outcomes details were collated. Pre-operative imaging techniques (CT/MRI, nuclear scintigraphy) were compared with intraoperative and histopathological findings to assess their accuracy of localization.

RESULTS: Thirty-seven patients (15 females [42%]; median age 36 years [IQR 28-49]) were included in the study. In four patients (10.8%), the tumour occurred in the setting of multiple endocrine neoplasia type 1 (MEN 1) while the remaining were sporadic. The sensitivity of pre-operative localization was 61.5% (multiphasic CT), 66.6% (multiphasic MRI), 100% (68Ga Exendin-4 PET-CT), and 91.6% (EUS). Three patients with normal multiphasic CT had localization on 68Ga Exendin-4 PET-CT. The positive predictive value (PPV) of both Exendin-PET-CT and EUS was similar at 91.6% and 91.6%, respectively. All patients (except one with nesidioblastosis), who underwent enucleation or partial pancreatic resection, were cured.

CONCLUSION: 68Ga Exendin-4 PET-CT based is a non-invasive imaging modality that has high sensitivity and PPV and can be used as a first-line imaging modality. The overall prognosis of these tumours is good with high cure rates attained following surgical resection.

PMID:39086573 | PMC:PMC11288522 | DOI:10.4103/ijem.ijem_359_23

Permalink for 'Restoring physiological parameters of the pancreas and kidney through treatment with a polymeric nano-formulation of C-peptide and lisofylline combination in diabetic nephropathy'

Restoring physiological parameters of the pancreas and kidney through treatment with a polymeric nano-formulation of C-peptide and lisofylline combination in diabetic nephropathy

Fetched: August 1st, 2024, 2:03am UTC by Arihant Kumar Singh

Nanoscale. 2024 Aug 29;16(34):16058-16074. doi: 10.1039/d4nr02010c.

ABSTRACT

Diabetic nephropathy (DN) is a progressive kidney disorder that develops as a complication of diabetes due to long-term exposure to elevated blood glucose levels (BGLs). In this case, an intervention of therapeutic moieties is needed to target the specific elements involved in diabetes to prevent/delay the deterioration of kidney function. Therefore, the present study focused on designing and evaluating a potent nano-formulation of a combination of C-peptide (CPep) and the anti-diabetic drug lisofylline (LSF) to prevent streptozotocin (STZ)-induced DN. As a strategic intervention, an LSF-oleic acid prodrug (LSF-OA) was initially synthesized and further encapsulated in an in-house-synthesized cationic polymer [(mPEG-b-P(CB-{g-DMDP}-co-LA)); mPLM] to prepare polymeric nano-complexes of CPep via electrostatic interaction, possessing a size of 218.6 Â± 14.4 nm and zeta potential of +5.2 mV together with stability for 30 days at 25 Â°C. mPLM-LSF-OA-CPep nanoparticles demonstrated hemocompatibility with RBCs and exhibited potent anti-oxidant activity by reducing nitrite levels, inducing the release of anti-oxidant GSH and protecting metabolically stressed rat kidneys and murine insulinoma cells from apoptosis. In vivo pharmacokinetics depicted an increase in tÂ½ and mean residence time in rats, which further improved the BGL and renal conditions and reduced plasma IL-6 and TNF-Î± levels in the STZ-induced DN animal model when treated with mPLM-LSF-OA-CPep compared to free LSF and CPep. Moreover, an increase in the plasma insulin level and detection of proliferative marker cells in pancreatic islets suggested the regeneration of Î²-cells in diabetic animals.

PMID:39082128 | DOI:10.1039/d4nr02010c

Clinicopathological Features of Pediatric Insulinoma: A Single-Centre Study

Fetched: July 31st, 2024, 2:01am UTC by Feng Tian

Br J Hosp Med (Lond). 2024 Jul 30;85(7):1-13. doi: 10.12968/hmed.2024.0259. Epub 2024 Jul 26.

ABSTRACT

Aims/Background: Insulinoma is an extremely rare condition in pediatric patients. This study aims to examine the pathological and clinical characteristics of pediatric insulinoma. Methods: A retrospective, single-center study was conducted involving five pediatric patients diagnosed with insulinoma. The study involved evaluating the postoperative status of the patients during follow-up and analyzing their clinical manifestations, diagnostic work-up, pathological findings, and therapeutic approaches. Results: The study cohort comprised four males and one female, aged between 4 and 9 years. Common symptoms included dizziness and fatigue. The insulinomas were located in various parts of the pancreas: two in the head, one in the neck, one in the body, and one in the tail. After undergoing subtotal pancreatectomy, four patients experienced no side effects during a follow-up period of 41 to 153 months. One patient, who underwent an incomplete pancreatic resection, required ongoing postoperative treatment with 150 mg Creon due to pancreatic enzyme deficiency. Postoperative pathological results indicated that all cases were low-grade neuroendocrine tumours, classified as grade 1 (G1) or grade 2 (G2). Two cases exhibited capsule invasion, and one case showed microvascular invasion. Despite these invasions, no recurrences or metastases have been observed to date. Conclusion: Surgical resection is a viable treatment option for pediatric insulinoma, yielding a favorable prognosis. The presence of capsular and microvascular invasions does not seem to affect the overall prognosis in these cases.

PMID:39078892 | DOI:10.12968/hmed.2024.0259

Sweet Saboteur: Insulinoma Presenting As Recurrent Hypoglycemic Seizures

Fetched: July 30th, 2024, 2:02am UTC by Jayaram Saibaba

Cureus. 2024 Jun 26;16(6):e63205. doi: 10.7759/cureus.63205. eCollection 2024 Jun.

ABSTRACT

Insulinoma, a rare neuroendocrine tumor of the pancreas, often presents diagnostic challenges due to its diverse clinical manifestations. We present the case of a 25-year-old female with recurrent hypoglycemic seizures and neuroglycopenic symptoms, ultimately diagnosed with insulinoma. Despite an initial asymptomatic period, the patient experienced progressively worsening symptoms over three years, culminating in eight episodes of generalized tonic-clonic seizures per week. Biochemical investigations during hypoglycemic episodes revealed elevated C-peptide and insulin levels, consistent with endogenous hyperinsulinemia. Imaging studies, including contrast-enhanced computed tomography (CECT) and Ga-DOTATATE scan, confirmed a hyper-enhancing lesion in the distal body of the pancreas, indicative of insulinoma. Histopathological examination (HPE) further corroborated the diagnosis. Prompt recognition and surgical excision led to the complete resolution of symptoms and improved long-term prognosis. This case underscores the importance of considering insulinoma in young individuals presenting with recurrent hypoglycemic episodes and highlights the significance of early diagnosis and intervention in preventing morbidity and mortality associated with this condition.

PMID:39070407 | PMC:PMC11277182 | DOI:10.7759/cureus.63205

The Influence of BMP6 on Serotonin and Glucose Metabolism

Fetched: July 28th, 2024, 2:02am UTC by Marina MileÅ¡eviÄ‡

Int J Mol Sci. 2024 Jul 18;25(14):7842. doi: 10.3390/ijms25147842.

ABSTRACT

Previous studies have suggested a potential role of bone morphogenetic protein 6 (BMP6) in glucose metabolism, which also seems to be regulated by serotonin (5-hydroxytryptamine, 5HT), a biogenic amine with multiple roles in the organism. In this study, we explored possible interactions between BMP6, serotonin, and glucose metabolism regulation. The effect of BMP6 or 5HT on pancreatic Î²-cells has been studied in vitro using the INS-1 832/13 rat insulinoma cell line. Studies in vivo have been performed on mice with the global deletion of the Bmp6 gene (BMP6-/-) and included glucose and insulin tolerance tests, gene expression studies using RT-PCR, immunohistochemistry, and ELISA analyses. We have shown that BMP6 and 5HT treatments have the opposite effect on insulin secretion from INS-1 cells. The effect of BMP6 on the 5HT system in vivo depends on the tissue studied, with no observable systemic effect on peripheral 5HT metabolism. BMP6 deficiency does not cause diabetic changes, although a mild difference in insulin tolerance test between BMP6-/- and WT mice was observed. In conclusion, BMP6 does not directly influence glucose metabolism, but there is a possibility that its deletion causes slowly developing changes in glucose and serotonin metabolism, which would become more expressed with ageing.

PMID:39063084 | PMC:PMC11276723 | DOI:10.3390/ijms25147842

Estimation of Individual Positive Anti-Islet Autoantibodies from 3 Screen ICA Titer

Fetched: July 28th, 2024, 2:02am UTC by Eiji Kawasaki

Int J Mol Sci. 2024 Jul 11;25(14):7618. doi: 10.3390/ijms25147618.

ABSTRACT

The 3 Screen ICA ELISA is a novel assay capable of simultaneously measuring autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), making it a valuable tool for screening type 1 diabetes. Despite its advantages, it cannot specify which individual autoantibodies are positive or negative. This study aimed to estimate individual positive autoantibodies based on the 3 Screen ICA titer. Six hundred seventeen patients with type 1 diabetes, simultaneously measured for 3 Screen ICA and three individual autoantibodies, were divided into five groups based on their 3 Screen ICA titer. The sensitivities and contribution rates of the individual autoantibodies were then examined. The study had a cross-sectional design. Sixty-nine percent (424 of 617) of patients with type 1 diabetes had 3 Screen ICA titers exceeding the 99th percentile cut-off level (20 index). The prevalence of GADA ranged from 80% to 100% in patients with a 3 Screen ICA over 30 index and 97% of patients with a 3 Screen ICA â‰¥300 index. Furthermore, the prevalence of all individual autoantibodies being positive was 0% for â‰¤80 index and as high as 92% for â‰¥300 index. Significant associations were observed in specific titer groups: the 20-29.9 index group when all the individual autoantibodies were negative, the 30-79.9 index group when positive for GADA alone or IA-2A alone, the 30-299.9 index group when positive for ZnT8A alone, the 80-299.9 index group when positive for both IA-2A and ZnT8A, the 300-499.9 index group when positive for both GADA and ZnT8A, and the â‰¥300 index group when positive for all individual autoantibodies. These results suggest that the 3 Screen ICA titer may be helpful in estimating individual positive autoantibodies.

PMID:39062856 | PMC:PMC11277171 | DOI:10.3390/ijms25147618

Permalink for 'Preparation and characterization of amidated pectin-gelatin-oxidized tannic acid hydrogel films supplemented with in-situ reduced silver nanoparticles for wound-dressing applications'

Preparation and characterization of amidated pectin-gelatin-oxidized tannic acid hydrogel films supplemented with in-situ reduced silver nanoparticles for wound-dressing applications

Fetched: July 28th, 2024, 2:02am UTC by Ilyas Benkhira

Int J Biol Macromol. 2024 Oct;277(Pt 1):134158. doi: 10.1016/j.ijbiomac.2024.134158. Epub 2024 Jul 24.

ABSTRACT

Wound dressings play a crucial role in protecting injured tissues and promoting the healing process. Traditional fabrication of antibacterial wound dressings can be complex and may involve toxic components. In this study, we developed an innovative hydrogel film (AP:GE@OTA/Ag) composed of amidated pectin (AP), gelatin (GE), oxidized tannic acid (OTA) at varying concentrations, and in-situ reduced silver nanoparticles (AgNPs). FTIR and XRD analyses confirmed that crosslinking occurs via interactions between OTA quinone groups and free amino groups in AP and GE. TEM imaging demonstrated the well-dispersed AgNPs with an average particle size of 58.64 nm, while the TG measurements indicated the enhancement of the thermal stability compared to AP:GE films. The AP:GE@OTA/Ag films exhibited superior fluid uptake ability (90.96 % at 2 h), water retention capacity (91.69 % at 2 h), and water vapor transmission rate (1903.29 g/m²/day), alongside improved tensile strength (38 MPa). Additionally, these films showed excellent cytocompatibility and sustained potent antimicrobial activity against S. aureus and E. coli with low AgNPs loadings of 1.02 Â± 0.13 Î¼g/cm². NIT-1 mouse insulinoma cells demonstrated robust proliferation when cultured with the prepared dressings. These films significantly accelerated wound repair in a skin excision model, indicating their potential clinical applications for wound healing.

PMID:39059528 | DOI:10.1016/j.ijbiomac.2024.134158

Stereotactic Body Radiation Therapy for Symptomatic Pancreatic Insulinoma: Two-Case Report and Literature Review

Fetched: July 27th, 2024, 2:02am UTC by Agnieszka Namysl-Kaletka

Curr Oncol. 2024 Jul 22;31(7):4123-4132. doi: 10.3390/curroncol31070307.

ABSTRACT

Insulinoma is the most common functional neuroendocrine tumor of the pancreas, with the main clinical symptom being hypoglycemia. The standard treatment is surgery, but some patients are not eligible for surgery, while in those operated on, the risk of perioperative complications is up to 30%. Diazoxide treatment to prevent hypoglycemia is effective only in 50% of patients. To prevent tumor growth and hormonal excess, stereotactic radiotherapy may be an alternative to surgical treatment. In our paper, we present two cases of patients with insulinoma treated successfully with stereotactic body radiation therapy (SBRT).

PMID:39057179 | PMC:PMC11275479 | DOI:10.3390/curroncol31070307

Permalink for 'Ghrelin Improves Glucolipotoxicity-Induced Pancreatic Î²-Cellular Dysfunction and Apoptosis by Inhibiting Endoplasmic Reticulum Stress-Induced IRE1/JNK Pathway'

Ghrelin Improves Glucolipotoxicity-Induced Pancreatic Î²-Cellular Dysfunction and Apoptosis by Inhibiting Endoplasmic Reticulum Stress-Induced IRE1/JNK Pathway

Fetched: July 27th, 2024, 2:02am UTC by Xin-Ying Li

Discov Med. 2024 Jul;36(186):1370-1377. doi: 10.24976/Discov.Med.202436186.127.

ABSTRACT

BACKGROUND: Glucose and fatty acid overload-induced glucolipid toxicity of pancreatic Î²-cells is associated with the development of diabetes. Endoplasmic reticulum stress (ERS) plays an essential role in this process. Ghrelin, a peptide secreted by the pancreas, negatively correlates with oxidative stress. The study aimed to investigate ghrelin's role in glycolipid-induced Î²-cell dysfunction and its possible mechanism.

METHODS: Mouse insulinoma Î²-cell, NIT-1 cells, were stimulated with high fat and high glucose to induce glucolipid toxicity. High fat and high glucose-induced NIT-1 cells were treated with acylated ghrelin (AG) or [d-Lys3]-growth hormone releasing peptide (GHRP)-6. Flow cytometry and Cell Counting Kit-8 (CCK-8) assay were performed to assess apoptosis and cell viability. The protein expression related to apoptosis, inositol-requiring kinase 1 (IRE1)/c-Jun N-terminal kinase (JNK) signaling, and ERS were investigated using western blot. Enzyme-linked immunosorbent assay (ELISA) was adopted to examine insulin's synthesis and secretion levels.

RESULTS: Ghrelin treatment improved cell viability while inhibiting cell glucolipotoxicity-induced NIT-1 cell apoptosis. Ghrelin can promote the synthesis and secretion of insulin in NIT-1 cells. Mechanistically, ghrelin attenuates ERS and inhibits the IRE1/JNK signaling pathway in NIT-1 cells induced by glucolipotoxicity.

CONCLUSION: Ghrelin improves Î²-cellular dysfunction induced by glucolipotoxicity by inhibiting the IRE1/JNK pathway induced by ERS. It could be an effective treatment for Î²-cellular dysfunction.

PMID:39054708 | DOI:10.24976/Discov.Med.202436186.127

Permalink for 'EBV-positive small cell neuroendocrine carcinoma of nasopharynx as a probably unique subtype of neuroendocrine carcinoma: a clinicopathologic study of three cases and literature review'

EBV-positive small cell neuroendocrine carcinoma of nasopharynx as a probably unique subtype of neuroendocrine carcinoma: a clinicopathologic study of three cases and literature review

Fetched: July 27th, 2024, 2:02am UTC by Ying Chen

Diagn Pathol. 2024 Jul 24;19(1):101. doi: 10.1186/s13000-024-01526-w.

ABSTRACT

BACKGROUND: There is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs.

MATERIALS AND METHODS: Herein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language.

RESULT: The 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases.

CONCLUSION: EBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.

PMID:39049067 | PMC:PMC11267672 | DOI:10.1186/s13000-024-01526-w

Permalink for 'A cross-species transcriptomic analysis reveals a novel 2-dimensional classification system explaining the invasiveness heterogeneity of pancreatic neuroendocrine tumor'

A cross-species transcriptomic analysis reveals a novel 2-dimensional classification system explaining the invasiveness heterogeneity of pancreatic neuroendocrine tumor

Fetched: July 27th, 2024, 2:02am UTC by Xiafei Hong

Cancer Lett. 2024 Jul 22:217131. doi: 10.1016/j.canlet.2024.217131. Online ahead of print.

ABSTRACT

Pancreatic neuroendocrine tumors (PanNETs), the second most common type of primary pancreatic tumors, display notable heterogeneity in invasiveness. Current knowledge regarding genomic alterations, including DAXX/ATRX, MEN1 mutations, and copy number variations (CNVs), provides some insights into tumor invasiveness. However, the underlying reasons for the significant variation in invasiveness between insulinoma and other types of PanNETs remain unclear. To construct a comprehensive model for the stratification of prognosis, we employed analysis of both the well-established Rip1-Tag2 (RT2) mouse model of PanNETs and human PanNETs with various functional types. Firstly, by applying single-cell and bulk RNA sequencing in PanNETs from different ages and strains of RT2 mice and human PanNETs, we introduced a 2-dimensional (2D) classification system. Based on the 2-D classification system, human PanNETs were mainly classified as benign insulinomas or non-insulinomas subclusters. Non-insulinomas subtypes mainly included gastrinomas, glucagonomas, VIPomas, and NF-PanNETs, which all exhibited potential invasiveness. In addition, we discovered an enrichment of specific CNV patterns and mutations in corresponding human PanNET subclusters. Then we denoted somatic DAXX/ATRX as the 'second hit' and confounding factors for invasiveness. Finally, by combining the 2D system, DAXX/ATRX mutation status, and tumor diameter, a group of indolent PanNETs with minimal recurrence risk was identified. In conclusion, our current work constructed a comprehensive model to elucidate the heterogeneity of invasiveness in PanNETs and improve prognostic stratification.

PMID:39048044 | DOI:10.1016/j.canlet.2024.217131

Reg2 treatment is protective but the induced Reg2 autoantibody is destructive to the islets in NOD mice

Fetched: July 23rd, 2024, 2:02am UTC by Yi-Han Zhou

Biochem Pharmacol. 2024 Sep;227:116444. doi: 10.1016/j.bcp.2024.116444. Epub 2024 Jul 20.

ABSTRACT

Regenerating family protein 2 (Reg2) is a trophic factor which stimulates Î²-cell replication and resists islet destruction. However, Reg2 also serves as an islet autoantigen, which makes it complicated to judge the effectiveness in treating diabetes. How Reg2 treatment behaves in non-obese diabetic (NOD) mice is to be investigated. NOD mice were treated with recombinant Reg2 protein, Complete Freund's adjuvant (CFA) + PBS and CFA+Reg2 vaccinations, CFA+PBS- and CFA+Reg2-immunized antisera, and single chain variable fragment (scFv)-Reg2 and mIgG2a-Reg2 antibodies. Glycemic level, bodyweight, serum Reg2 antibody titer, glucose tolerance, and insulin secretion were determined. Islet morphological characteristics, insulitis, cell apoptosis, islet cell components, and T cell infiltration were analyzed by histological examinations. The autoantigenicity of constructed Reg2C and Reg2X fragments was determined in healthy BALB/c mice, and the bioactivity in stimulating cell proliferation and survival was assessed in insulinoma MIN6 cells. Reg2 administration alleviated diabetes in NOD mice with improved glucose tolerance and insulin secretion but elevated serum Reg2 autoantibodies. Histomorphometry showed reduced inflammatory area, TUNEL signal and CD8 + T cell infiltration, and increased Î²-cell proportion in support of the islet-protective effect of Reg2 treatment. CFA+PBS and CFA+Reg2 immunizations prevented diabetic onset and alleviated insulitis while injections of the antisera offered mild protections. Antibody treatments accelerated diabetic onset without increasing the overall incidence. Reg2C fragment depletes antigenicity, but reserves protective activity in streptozotocin (STZ)-treated MIN6 cells. In conclusion, Reg2 treatment alleviates type 1 diabetes (T1D) by preserving islet Î²-cells, but induces Reg2 autoantibody production which poses a potential risk of accelerating diabetic progression.

PMID:39038551 | DOI:10.1016/j.bcp.2024.116444

Decreased islet amyloid polypeptide staining in the islets of insulinoma patients

Fetched: July 20th, 2024, 2:02am UTC by Chisaki Ishibashi

Islets. 2024 Dec 31;16(1):2379650. doi: 10.1080/19382014.2024.2379650. Epub 2024 Jul 19.

ABSTRACT

Islet amyloid polypeptide (IAPP) is a factor that regulates food intake and is secreted from both pancreatic islets and insulinoma cells. Here, we aimed to evaluate IAPP immunohistochemically in islets or insulinoma cells in association with clinical characteristics. We recruited six insulinoma patients and six body mass index-matched control patients with pancreatic diseases other than insulinoma whose glucose tolerance was confirmed to be normal preoperatively. IAPP and IAPP-insulin double staining were performed on pancreatic surgical specimens. We observed that the IAPP staining level and percentage of IAPP-positive beta cells tended to be lower (p = 0.1699) in the islets of insulinoma patients than in those of control patients, which might represent a novel IAPP expression pattern under persistent hyperinsulinemia and hypoglycemia.

PMID:39028826 | PMC:PMC11262209 | DOI:10.1080/19382014.2024.2379650

INSM1 expression in neuroendocrine tumors in a tertiary care hospital

Fetched: July 19th, 2024, 2:02am UTC by Kundhavai Chandrasekaran

J Cancer Res Ther. 2024 Apr 1;20(3):811-816. doi: 10.4103/jcrt.jcrt_2329_22. Epub 2023 May 2.

ABSTRACT

AIM: Neuroendocrine tumors are heterogenous group of neoplasms that includes benign and malignant tumors that originate from neuroendocrine or nonneuroendocrine organs. Insulinoma-associated protein 1 (INSM1) is a zinc finger transcription factor originally isolated from subtraction library of human insulinoma. The main aim was to study the INSM1 expression in a spectrum of neuroendocrine tumors and a limited spectrum of nonneuroendocrine tumors.

MATERIALS AND METHODS: A total of 100 cases of which 57 neuroendocrine neoplasms and 43 nonneuroendocrine neoplasms were included in the study. Immunohistochemistry (IHC) was done and expression patterns of INSM1 were analyzed. Pituitary adenoma, medullary carcinoma of thyroid, pheochromocytoma lung, gastrointestinal, and pancreatic neuroendocrine tumors were the neuroendocrine tumors that were included in the study. Papillary carcinoma of thyroid, gastrointestinal adenocarcinoma, lung adenocarcinoma, and squamous cell carcinoma were the nonneuroendocrine tumors that were included in the study. Depending upon the tissue availability, comparison of INSM1 with synaptophysin and chromogranin was also done in few neuroendocrine tumors.

RESULTS: All the 57 neuroendocrine tumors showed positive expression for INSM1 and all the nonneuroendocrine tumors were negative for INSM1. This study is statistically significant.

CONCLUSION: Our study suggests that INSM1 is a diagnostic marker for neuroendocrine tumors with high degree of sensitivity and specificity. The study is significant and suggests that INSM1- IHC shows nuclear positivity in a spectrum of neuroendocrine tumors. Being a nuclear marker, interpretation is easy and more reliable than the cytoplasmic markers. INSM1 has a stronger positivity than synaptophysin and chromogranin in the present study especially for small cell carcinoma lung. Hence, INSM1 may be included in the routine panel for neuroendocrine tumors along with synaptophysin and chromogranin.

PMID:39023587 | DOI:10.4103/jcrt.jcrt_2329_22

A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia: A Case Report

Fetched: July 19th, 2024, 2:02am UTC by Sindhu C Pokhriyal

Cureus. 2024 Jun 17;16(6):e62527. doi: 10.7759/cureus.62527. eCollection 2024 Jun.

ABSTRACT

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disease characterized by the diffuse proliferation of neuroendocrine cells in the bronchial epithelium. It is considered a preinvasive precursor to carcinoid tumors and usually presents with obstructive symptoms. We present the case of a 71-year-old female, non-smoker, with a past medical history of asthma, osteoarthritis, allergic rhinitis, and hyperlipidemia who was referred to the pulmonology clinic in view of incidental chest CT findings of multiple pulmonary nodules. Physical examination and labs were unremarkable. CT of the chest showed scattered multiple noncalcified pulmonary nodules with a 10 mm dominant nodule in the inferior right middle lobe and several subcentimeter hypodensities in the left and right lobes of the lung. A PET scan confirmed the CT findings along with no abnormal hypermetabolic activity to suggest malignancy. The patient was followed up in the pulmonology clinic at six months, 12 months, and then 18 months. At 18 months owing to a slight increase in the size of the largest lung nodule, a CT-guided biopsy done was conclusive of a carcinoid. The tumor cells were positive for synaptophysin, chromogranin, insulinoma-associated protein 1 (INSM-1), and thyroid transcription factor 1 (TTF-1). The Ki-67 (Keil) index was <1%. A video-assisted thoracic surgery with right middle lobectomy along with mediastinal lymph node dissection was then done, and the patient was found to have stage pT1aN0 typical carcinoid tumor (1.0 cm), with multiple carcinoid tumors and neuroendocrine hyperplasia, consistent with DIPNECH. She has been under clinical follow-up for over three years at present and continues to be asymptomatic with complete remission following surgery. DIPNECH primarily affects middle-aged, non-smoking females who present with cough and dyspnea, and diagnosis is often delayed due to clinical features overlapping with those of obstructive lung disease. Imaging shows lung nodules, ground-glass opacities, and/or mosaic attenuation. Due to the rarity of the conditions, there are no established clinical trials, and therefore, there is a need to establish guidelines.

PMID:39022484 | PMC:PMC11253604 | DOI:10.7759/cureus.62527

Effect of recurrent severe insulin-induced hypoglycemia on the cognitive function and brain oxidative status in the rats

Fetched: July 15th, 2024, 2:02am UTC by Mahvash Nikpendar

Diabetol Metab Syndr. 2024 Jul 15;16(1):161. doi: 10.1186/s13098-024-01410-z.

ABSTRACT

BACKGROUND: Episodes of recurrent or severe hypoglycemia can occur in patients with diabetes mellitus, insulinoma, neonatal hypoglycemia, and medication errors. However, little is known about the short-term and long-term effects of repeated episodes of acute severe hypoglycemia on the brain, particularly in relation to hippocampal damage and cognitive dysfunction.

METHODS: Thirty-six wistar rats were randomly assigned to either the experimental or control group. The rats were exposed to severe hypoglycemia, and assessments were conducted to evaluate oxidative stress in brain tissue, cognitive function using the Morris water maze test, as well as histopathology and immunohistochemistry studies. The clinical and histopathological evaluations were conducted in the short-term and long-term.

RESULTS: The mortality rate attributed to hypoglycemia was 34%, occurring either during hypoglycemia or within 24 h after induction. Out of the 14 rats monitored for 7 to 90 days following severe/recurrent hypoglycemia, all exhibited clinical symptoms, which mostly resolved within three days after the last hypoglycemic episode, except for three rats. Despite the decrease in catalase activity in the brain, the total antioxidant capacity following severe insulin-induced hypoglycemia increased. The histopathology findings revealed that the severity of the hippocampal damage was higher compared to the brain cortex 90 days after hypoglycemia. Memory impairments with neuron loss particularly pronounced in the dentate gyrus region of the hippocampus were observed in the rats with severe hypoglycemia. Additionally, there was an increase in reactive astrocytes indicated by GFAP immunoreactivity in the brain cortex and hippocampus.

CONCLUSION: Recurrent episodes of severe hypoglycemia can lead to high mortality rates, memory impairments, and severe histopathological changes in the brain. While many histopathological and clinical changes improved after three months, it seems that the vulnerability of the hippocampus and the development of sustained changes in the hippocampus were greater and more severe compared to the brain cortex following severe and recurrent hypoglycemia. Furthermore, it does not appear that oxidative stress plays a central role in neuronal damage following severe insulin-induced hypoglycemia. Further research is necessary to assess the consequences of repeated hypoglycemic episodes on sustained damage across various brain regions.

PMID:39004753 | PMC:PMC11247731 | DOI:10.1186/s13098-024-01410-z

Permalink for 'Repair Effect of Umbilical Cord Mesenchymal Stem Cells Embedded in Hydrogel on Mouse Insulinoma 6 Cells Injured by Streptozotocin'

Repair Effect of Umbilical Cord Mesenchymal Stem Cells Embedded in Hydrogel on Mouse Insulinoma 6 Cells Injured by Streptozotocin

Fetched: July 14th, 2024, 2:02am UTC by Jia Yang

Polymers (Basel). 2024 Jun 28;16(13):1845. doi: 10.3390/polym16131845.

ABSTRACT

Umbilical cord mesenchymal stem cells (UC-MSCs) possess the capabilities of differentiation and immune modulation, which endow them with therapeutic potential in the treatment of type 2 diabetes mellitus (T2DM). In this study, to investigate the repair mechanism of UC-MSCs in hydrogel on pancreatic Î²-cells in diabetes, mouse insulinoma 6 (MIN-6) cells damaged by streptozotocin (STZ) in vitro were used in co-culture with UC-MSCs in hydrogel (UC-MSCs + hydrogel). It was found that UC-MSCs + hydrogel had a significant repair effect on injured MIN-6 cells, which was better than the use of UC-MSCs alone (without hydrogel). After repair, the expression of superoxide dismutase (SOD) and catalase (CAT) as well as the total antioxidant capacity (T-AOC) of the repaired MIN-6 cells were increased, effectively reducing the oxidative stress caused by STZ. In addition, UC-MSCs + hydrogel were able to curb the inflammatory response by promoting the expression of anti-inflammatory factor IL-10 and reducing inflammatory factor IL-1Î². In addition, the expression of both nuclear antigen Ki67 for cell proliferation and insulin-related genes such as Pdx1 and MafA was increased in the repaired MIN-6 cells by UC-MSCs + hydrogel, suggesting that the repair effect promotes the proliferation of the injured MIN-6 cells. Compared with the use of UC-MSCs alone, UC-MSCs + hydrogel exhibit superior antioxidant stress resistance against injured MIN-6 cells, better proliferation effects and a longer survival time of UC-MSCs because the porous structure and hydrophilic properties of the hydrogel could affect the growth of cells and slow down their metabolic activities, resulting in a better repair effect on the injured MIN-6 cells.

PMID:39000700 | PMC:PMC11244345 | DOI:10.3390/polym16131845

Chronic Epinephrine-Induced Endoplasmic Reticulum and Oxidative Stress Impairs Pancreatic Î²-Cells Function and Fate

Fetched: July 14th, 2024, 2:02am UTC by Ran Zhang

Int J Mol Sci. 2024 Jun 27;25(13):7029. doi: 10.3390/ijms25137029.

ABSTRACT

Epinephrine influences the function of pancreatic Î²-cells, primarily through the Î±2A-adrenergic receptor (Î±2A-AR) on their plasma membrane. Previous studies indicate that epinephrine transiently suppresses insulin secretion, whereas prolonged exposure induces its compensatory secretion. Nonetheless, the impact of epinephrine-induced Î±2A-AR signaling on the survival and function of pancreatic Î²-cells, particularly the impact of reprogramming after their removal from sustained epinephrine stimulation, remains elusive. In the present study, we applied MIN6, a murine insulinoma cell line, with 3 days of high concentration epinephrine incubation and 2 days of standard incubation, explored cell function and activity, and analyzed relevant regulatory pathways. The results showed that chronic epinephrine incubation led to the desensitization of Î±2A-AR and enhanced insulin secretion. An increased number of docked insulin granules and impaired Syntaxin-2 was found after chronic epinephrine exposure. Growth curve and cell cycle analyses showed the inhibition of cell proliferation. Transcriptome analysis showed the occurrence of endoplasmic reticulum stress (ER stress) and oxidative stress, such as the presence of BiP, CHOP, IRE1, ATF4, and XBP, affecting cellular endoplasmic reticulum function and survival, along with UCP2, OPA1, PINK, and PRKN, associated with mitochondrial dysfunction. Consequently, we conclude that chronic exposure to epinephrine induces Î±2A-AR desensitization and leads to ER and oxidative stress, impairing protein processing and mitochondrial function, leading to modified pancreatic Î²-cell secretory function and cell fate.

PMID:39000139 | PMC:PMC11241606 | DOI:10.3390/ijms25137029

Serotonin Influences Insulin Secretion in Rat Insulinoma INS-1E Cells

Fetched: July 14th, 2024, 2:02am UTC by Yeong-Min Yoo

Int J Mol Sci. 2024 Jun 21;25(13):6828. doi: 10.3390/ijms25136828.

ABSTRACT

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine that plays a critical role in insulin secretion, energy metabolism, and mitochondrial biogenesis. However, the action of serotonin in insulin production and secretion by pancreatic Î² cells has not yet been elucidated. Here, we investigated how exogenous nanomolar serotonin concentrations regulate insulin synthesis and secretion in rat insulinoma INS-1E cells. Nanomolar serotonin concentrations (10 and 50 nM) significantly increased insulin protein expression above the constant levels in untreated control cells and decreased insulin protein levels in the media. The reductions in insulin protein levels in the media may be associated with ubiquitin-mediated protein degradation. The levels of membrane vesicle trafficking-related proteins including Rab5, Rab3A, syntaxin6, clathrin, and EEA1 proteins were significantly decreased by serotonin treatment compared to the untreated control cells, whereas the expressions of Rab27A, GOPC, and p-caveolin-1 proteins were significantly reduced by serotonin treatment. In this condition, serotonin receptors, GÎ±q-coupled 5-HT2b receptor (Htr2b), and ligand-gated ion channel receptor Htr3a were significantly decreased by serotonin treatment. To confirm the serotonylation of Rab3A and Rab27A during insulin secretion, we investigated the protein levels of Rab3A and Rab27A, in which transglutaminase 2 (TGase2) serotonylated Rab3A but not Rab27A. The increases in ERK phosphorylation levels were consistent with increases in the expression of p-Akt. Also, the expression level of the Bcl-2 protein was significantly increased by 50 and 100 nM serotonin treatment compared to the untreated control cells, whereas the levels of Cu/Zn-SOD and Mn-SOD proteins decreased. These results indicate that nanomolar serotonin treatment regulates the insulin protein level but decreases this level in media through membrane vesicle trafficking-related proteins (Rab5, Rab3A, syntaxin6, clathrin, and EEA1), the Akt/ERK pathway, and Htr2b/Htr3a in INS-1E cells.

PMID:38999937 | PMC:PMC11241493 | DOI:10.3390/ijms25136828

$Permalink for '68Ga-NODAGA-Exendin-4 PET/CT Findings in a Case of Metastatic Insulinoma With Refractory Hypoglycemia Controlled by 90Y Transarterial Radioembolization'$

68Ga-NODAGA-Exendin-4 PET/CT Findings in a Case of Metastatic Insulinoma With Refractory Hypoglycemia Controlled by 90Y Transarterial Radioembolization

Fetched: July 6th, 2024, 2:02am UTC by Rahime Åžahin

Clin Nucl Med. 2024 Aug 1;49(8):e392-e393. doi: 10.1097/RLU.0000000000005266.

ABSTRACT

Metastatic insulinomas can cause recurrent hypoglycemia requiring continuous IV glucose infusion. Various medical and chemotherapeutic treatment options are used to reduce the patient's risk of death due to hypoglycemia. Treatment-resistant hepatic metastatic insulinomas may benefit clinically from 90Y transarterial radioembolization therapy. In this case, we present a case of liver metastatic insulinoma that achieved clinical improvement after 2 cycles of 90Y microspheres transarterial radioembolization, and the presence of active metastases was demonstrated with 68Ga-NODAGA-exendin-4 PET/CT imaging.

PMID:38967509 | DOI:10.1097/RLU.0000000000005266

Implications of noncoding regulatory functions in the development of insulinomas

Fetched: July 4th, 2024, 2:02am UTC by Mireia Ramos-RodrÃguez

Cell Genom. 2024 Aug 14;4(8):100604. doi: 10.1016/j.xgen.2024.100604. Epub 2024 Jul 2.

ABSTRACT

Insulinomas are rare neuroendocrine tumors arising from pancreatic Î² cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in Î² cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of Î² cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations.

PMID:38959898 | DOI:10.1016/j.xgen.2024.100604

Permalink for 'Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors'

Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors

Fetched: July 3rd, 2024, 2:02am UTC by Shuangyang Mo

Front Endocrinol (Lausanne). 2024 Jun 17;15:1383814. doi: 10.3389/fendo.2024.1383814. eCollection 2024.

ABSTRACT

OBJECTIVES: To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs).

METHODS: A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed.

RESULTS: A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts.

CONCLUSION: A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.

PMID:38952387 | PMC:PMC11215175 | DOI:10.3389/fendo.2024.1383814

Pancreatic Insulinoma Masquerading as Neurological Disease: Diagnosis and Treatment of a Rare Tumor

Fetched: July 2nd, 2024, 2:02am UTC by Seun A Arowolo

Cureus. 2024 May 30;16(5):e61378. doi: 10.7759/cureus.61378. eCollection 2024 May.

ABSTRACT

Insulinomas are rare functional pancreatic neuroendocrine tumors that typically manifest with classic hypoglycemic symptoms, such as diaphoresis, palpitations, and tremors. Although infrequent, neuroglycopenic symptoms associated with insulinomas have been reported, often leading to delayed diagnoses. Here, we present the case of a 31-year-old male with pancreatic insulinoma who experienced recurrent episodes of seizures and confusion preceded by diaphoresis, tremors, and palpitations. During these episodes, he was found to be hypoglycemic. Comprehensive evaluations, including brain and abdominal imaging, as well as biochemical and serological testing, were conducted. The findings confirmed a diagnosis of pancreatic insulinoma. The patient underwent surgical resection of the tumor, and a biopsy confirmed the insulinoma diagnosis. He remained asymptomatic during subsequent follow-ups.

PMID:38947643 | PMC:PMC11214572 | DOI:10.7759/cureus.61378

Diagnostics and Imaging for Pancreatic Neuroendocrine Tumors

Fetched: June 30th, 2024, 2:02am UTC by Joseph Tobias

Surg Clin North Am. 2024 Aug;104(4):883-890. doi: 10.1016/j.suc.2024.02.015. Epub 2024 Mar 23.

ABSTRACT

Pancreatic neuroendocrine tumors originate from hormone-producing islet cells and have a propensity to metastasize to the liver once they reach 2 cm in size. Their diagnosis relies upon a combination of computed tomography, MRI, DOTATATE PET, and endoscopic ultrasound with or without tissue biopsy. Biochemical work-up is driven by patient symptoms of hormone excess.

PMID:38944506 | DOI:10.1016/j.suc.2024.02.015

Hypoglycemia in non-diabetic in-patients at a teaching referral hospital in Iran

Fetched: June 28th, 2024, 2:02am UTC by Fateme Ziamanesh

J Diabetes Metab Disord. 2023 Dec 30;23(1):759-763. doi: 10.1007/s40200-023-01346-7. eCollection 2024 Jun.

ABSTRACT

PURPOSE: This study aims to investigate comorbidities, clinical features, laboratory values, and diagnoses in non-diabetic patients experiencing hypoglycemic episodes.

METHODS: A retrospective observational study was conducted at Shariati Hospital in Iran from 2016 to 2023. Seventy-four non-diabetic patients admitted with a diagnosis of hypoglycemia were included, while patients with diabetes were excluded. Demographic data, symptoms, and biochemical assessments were obtained from the hospital information system. Hypoglycemic episodes were identified based on low measured blood glucose, recorded medications for hypoglycemia treatment, or recorded codes indicating hypoglycemia. Hypoglycemia was defined as blood glucose below 70 mg/dL (3.9 mmol/L) along with two other criteria of the Whipple triad. Statistical analysis was performed using SPSS software (version 26).

RESULTS: Among the enrolled patients, 63.5% were female, and 13.5% were elderly (â‰¥ 65 years). The most common comorbidities observed were cardiovascular disease (20.3%), psychological disorders (20.3%), hypothyroidism (14.9%), and hypertension (8.1%). The prevalent symptoms included weakness, loss of consciousness, sweating, palpitations, dizziness, and tremors. Non-diabetic hypoglycemia was caused by factitious disorders, insulinoma, organ failure, and infection, respectively.

CONCLUSION: Due to the diverse range of clinical symptoms, hypoglycemia in non-diabetic patients may be diagnosed late, leading to misdiagnoses such as psychological disorders or seizures. It is crucial to consider the possibility of hypoglycemia in non-diabetic patients and determine its underlying cause. Given the poor prognosis associated with hypoglycemia, timely interventions are essential.

PMID:38932802 | PMC:PMC11196425 | DOI:10.1007/s40200-023-01346-7

Permalink for 'Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance'

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

Fetched: June 28th, 2024, 2:02am UTC by Mara Carsote

Int J Mol Sci. 2024 Jun 8;25(12):6349. doi: 10.3390/ijms25126349.

ABSTRACT

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies (n = 7) included MEN1-related insulinomas (n = 2) or MEN1-associated PHP (n = 2) or analyses of genetic profile (n = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, p < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). MEN1 pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline MEN1 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: CDC73 gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified (n = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome (n = 1). Normocalcemic and mildly symptomatic hyperparathyroidism (n = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.

PMID:38928056 | PMC:PMC11203827 | DOI:10.3390/ijms25126349

Recurrent Hypoglycemia After Total Gastrectomy: A Case Report and Literature Analysis

Fetched: June 27th, 2024, 2:02am UTC by Yue Zhang

Am J Case Rep. 2024 Jun 26;25:e943144. doi: 10.12659/AJCR.943144.

ABSTRACT

BACKGROUND Hypoglycemia is a common complication following total gastrectomy, primarily caused by dumping syndrome and severe malnutrition, with late dumping syndrome being particularly significant. However, for recurrent fasting hypoglycemia, the possibility of insulinoma should be considered. Hypoglycemia caused by insulinoma can lead to severe consequences, including seizures and even death. Thus, it is crucial to differentially diagnose hypoglycemia occurring after total gastrectomy. CASE REPORT In this report, we present the case of a 36-year-old Chinese woman who underwent total gastrectomy for gastric cancer and subsequently received chemotherapy. Four months after surgery, she began experiencing recurrent seizures, and multiple tests confirmed hypoglycemia. A series of laboratory and imaging examinations ultimately led to a diagnosis of insulinoma. After surgical resection of the tumor, the patient's hypoglycemic symptoms resolved, and pathology results confirmed an insulinoma. CONCLUSIONS This case report highlights the rapid weight loss and severe hypoglycemia observed in a patient only 4 months after total gastrectomy for gastric cancer. Although dumping syndrome was initially suspected based on the clinical course, the final diagnosis turned out to be insulinoma. The case underscores the importance of comprehensive evaluation and appropriate diagnostic investigations for patients experiencing hypoglycemia after total gastrectomy. Furthermore, the case suggests that the increased levels of enteroglucagon following changes in the gastrointestinal tract resulting from total gastrectomy may promote the development of insulinomas. This case report also contributes to the existing literature regarding atypical presentations of insulinomas and their association with gastric resection.

PMID:38918938 | PMC:PMC11334087 | DOI:10.12659/AJCR.943144

The selective serotonin reuptake inhibitors, sertraline and paroxetine, improve islet beta-cell mass and function in vitro

Fetched: June 20th, 2024, 2:03am UTC by Toczyska Klaudia

Diabetes Obes Metab. 2024 Sep;26(9):3606-3617. doi: 10.1111/dom.15701. Epub 2024 Jun 18.

ABSTRACT

AIMS: To investigate the effects of the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine at therapeutically relevant concentrations on beta-cell mass and function.

METHODS: Viability was quantified in mouse insulinoma (MIN6) beta cells and mouse islets after 48-h exposure to sertraline (1-10 Î¼M) or paroxetine (0.01-1 Î¼M) using the Trypan blue exclusion test. The effects of therapeutic concentrations of these SSRIs on insulin secretion were determined by static incubation and perifusion experiments, while islet apoptosis was investigated by Caspase-Glo 3/7 assay, TUNEL staining and quantitative PCR analysis. Finally, proliferation of MIN6 and mouse islet beta cells was assessed by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay and immunofluorescence.

RESULTS: Sertraline (0.1-1 Î¼M) and paroxetine (0.01-0.1 Î¼M) were well tolerated by MIN6 beta cells and islets, whereas 10 Î¼M sertraline and 1 Î¼M paroxetine were cytotoxic. Exposure to 1 Î¼M sertraline and 0.1 Î¼M paroxetine significantly potentiated glucose-stimulated insulin secretion from mouse and human islets. Moreover, they showed protective effects against cytokine- and palmitate-induced apoptosis of islets, they downregulated cytokine-induced Stat1 and Traf1 mRNA expression, and they significantly increased proliferation of mouse beta cells.

CONCLUSIONS: Our data demonstrate that sertraline and paroxetine act directly on beta cells to enhance glucose-stimulated insulin secretion and stimulate beta-cell mass expansion by increasing proliferation and decreasing apoptosis. These drugs are therefore likely to be appropriate for treating depression in people with type 2 diabetes.

PMID:38888050 | DOI:10.1111/dom.15701

Permalink for 'Inhibition of endoplasmic reticulum stress and excessive autophagy by Jiedu Tongluo Tiaogan Formula via a CaMKKÎ²/AMPK pathway contributes to protect pancreatic Î²-cells'

Inhibition of endoplasmic reticulum stress and excessive autophagy by Jiedu Tongluo Tiaogan Formula via a CaMKKÎ²/AMPK pathway contributes to protect pancreatic Î²-cells

Fetched: June 18th, 2024, 2:02am UTC by Qi Zhang

J Ethnopharmacol. 2024 Oct 28;333:118440. doi: 10.1016/j.jep.2024.118440. Epub 2024 Jun 15.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of Î² cells.

AIM OF THE STUDY: We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used.

MATERIALS AND METHODS: The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 Î¼g/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin-eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining.

RESULT: 28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic Î²-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKÎ²/AMPK pathway.

CONCLUSIONS: The present study findings show that JTTF may protects Î²-cells by inhibiting the CaMKKÎ²/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM.

PMID:38885916 | DOI:10.1016/j.jep.2024.118440

Permalink for 'Insulinoma-Associated Protein-1 Expression in Lymphoepithelial Carcinoma of the Thymus: A Potential Pitfall for Diagnosis With Neuroendocrine Carcinomas of the Thymus'

Insulinoma-Associated Protein-1 Expression in Lymphoepithelial Carcinoma of the Thymus: A Potential Pitfall for Diagnosis With Neuroendocrine Carcinomas of the Thymus

Fetched: June 18th, 2024, 2:02am UTC by David I Suster

Arch Pathol Lab Med. 2024 Jun 17. doi: 10.5858/arpa.2024-0045-OA. Online ahead of print.

ABSTRACT

CONTEXT.â€”: Insulinoma-associated protein-1 (INSM1) is a recently developed immunohistochemical marker claimed to be highly specific and sensitive for the diagnosis of neuroendocrine malignancies. Recent studies, however, have demonstrated that this marker can also be expressed in non-neuroendocrine neoplasms including squamous cell carcinoma of the thymus.

OBJECTIVE.â€”: To examine INSM1 expression in lymphoepithelial thymic carcinomas.

DESIGN.â€”: Thirty-four cases of lymphoepithelial carcinoma of the thymus were examined by immunohistochemistry or in situ hybridization for INSM1, synaptophysin, chromogranin, CD5, CD117, Epstein-Barr virus-encoded small ribonucleic acid (EBER), and Ki-67. Basic clinical information was abstracted from the medical record.

RESULTS.â€”: The patients were 14 women and 20 men, aged 20 to 85 years. The tumors arose in the anterior mediastinum without any previous history or evidence of malignancy at other sites. Immunohistochemical staining showed moderate to strong positivity of the tumor cells for INSM1 in 65% of cases (22 of 34), focal weak positivity in 20% (7 of 34), and negative staining in 5 cases. Chromogranin staining was focally and weakly positive in 1 case, and synaptophysin showed only focal weak positivity in scattered tumor cells in 12 cases. No significant correlation could be identified between the pattern and intensity of staining for INSM1 and staining for CD5, CD117, and Ki-67.

CONCLUSIONS.â€”: INSM1 positivity in lymphoepithelial carcinoma of the thymus may represent a pitfall for diagnosis, particularly in small biopsy samples. Awareness of this finding may be of importance to avoid misdiagnosis of neuroendocrine malignancy.

PMID:38884541 | DOI:10.5858/arpa.2024-0045-OA

Insulinoma Unmasked Post Sleeve Gastrectomy With Incidental Renal Cell Carcinoma: A Rare Case

Fetched: June 18th, 2024, 2:02am UTC by Yashika Goel

Cureus. 2024 May 15;16(5):e60395. doi: 10.7759/cureus.60395. eCollection 2024 May.

ABSTRACT

Insulinoma is a functional pancreatic neuroendocrine tumor (pNET). Usually benign and solitary, these tumors present with recurrent episodes of hypoglycemia due to insulin hypersecretion. It's a rare cause of post bariatric surgery hypoglycemia and hence poses a diagnostic challenge. Here, we report the first case of a 53-year-old male with insulinoma unmasked post sleeve gastrectomy with incidental renal cell carcinoma (RCC). He presented with symptoms of Whipple's triad after two months of sleeve gastrectomy done for morbid obesity. On further inquiry, the patient gave a history of an asymptomatic peripancreatic neuroendocrine tumor (NET) for the past 11 years. With a suspicion of insulinoma, biochemical workup followed by non-invasive imaging like GA-68 DOTA and CT triphasic abdomen scan was done to guide the diagnosis of an insulinoma which also detected a second primary tumor in the right kidney, likely to be a malignant RCC. Following pancreatic mass excision with radical nephrectomy for right renal mass, histopathology (HPE) and immunohistochemistry (IHC) confirmed the diagnosis of an insulinoma and a right renal clear cell carcinoma. The patient was discharged with no further episodes of hypoglycemia. Hence, persistent hypoglycemia post bariatric surgery could be an indication of a hidden insulinoma and this possibility of synchronous tumors should be kept in mind when dealing with rare tumors like insulinoma.

PMID:38883112 | PMC:PMC11179045 | DOI:10.7759/cureus.60395

Differences in intratumor innate lymphoid cell composition between orthotopic and spontaneous pancreatic mouse models

Fetched: June 18th, 2024, 2:02am UTC by Sara Lamorte

Methods Cell Biol. 2024;188:153-169. doi: 10.1016/bs.mcb.2024.04.001. Epub 2024 Apr 24.

ABSTRACT

Pancreatic cancer remains an unmet medical need. Late diagnosis and the lack of efficient treatment significantly impact the prognosis of patients suffering from pancreatic cancer. Improving patient outcomes requires a deeper comprehension of the tumor ecosystem. To achieve this, a thorough exploration of the tumor microenvironment using pre-clinical models that accurately replicate human disease is imperative, particularly in understanding the dynamics of immune cell subsets. Surprisingly, the impact of model variations on the composition of the tumor microenvironment has been largely neglected. In this study, we introduce an orthotopic model of pancreatic ductal adenocarcinoma and a spontaneous model of insulinoma. Our findings reveal striking differences in the innate lymphoid cell infiltrate, highlighting the importance of considering model-specific influences when investigating the tumor microenvironment.

PMID:38880522 | DOI:10.1016/bs.mcb.2024.04.001

Laparoscopic insulinoma enucleation for an uncinate lesion

Fetched: June 15th, 2024, 2:02am UTC by Georgina E Riddiough

ANZ J Surg. 2024 Jun 14. doi: 10.1111/ans.19106. Online ahead of print.

ABSTRACT

How I do laparoscopic insulinoma enucleation. This article discusses a laparoscopic approach for insulinoma enucleation, an approach which offers all the advantages of a laparoscopic approach and which can also be adapted to other pancreatic lesions requiring enucleation.

PMID:38873968 | DOI:10.1111/ans.19106

Well-differentiated G1 and G2 pancreatic neuroendocrine tumors: a meta-analysis of published expanded DNA sequencing data

Fetched: June 14th, 2024, 2:02am UTC by Kirstine Ã˜ster Andersen

Front Endocrinol (Lausanne). 2024 May 29;15:1351624. doi: 10.3389/fendo.2024.1351624. eCollection 2024.

ABSTRACT

INTRODUCTION: Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in MEN1 as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.

METHODS: A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25^th of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.

RESULTS: Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was MEN1, with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in MEN1, VHL, CHEK2, BRCA2, PTEN, CDKN1B, and/or MUTYH) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The MEN1 point mutations/indels were distributed throughout MEN1. Overall, DAXX (16%, 37/225) and ATRX-variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. DAXX mutations occurred more frequently in PNETs with MEN1 mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.

DISCUSSION: The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).

PMID:38868744 | PMC:PMC11167081 | DOI:10.3389/fendo.2024.1351624

Permalink for 'A Systematic Review of the Accuracy of Insulin and C-peptide Secretion Ratios During the Oral Glucose Tolerance Test to Diagnose Insulinoma'

A Systematic Review of the Accuracy of Insulin and C-peptide Secretion Ratios During the Oral Glucose Tolerance Test to Diagnose Insulinoma

Fetched: June 13th, 2024, 2:02am UTC by Fransiskus Mikael Chandra

J ASEAN Fed Endocr Soc. 2024;39(1):79-83. doi: 10.15605/jafes.039.01.16. Epub 2024 Feb 5.

ABSTRACT

BACKGROUND: Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is a 72-hour fasting test which is inconvenient and inefficient as it requires hospitalization. Research has found that measurement of insulin and C-peptide during OGTT may help diagnose insulinoma. We aimed to assess the diagnostic value of OGTT in diagnosing insulinoma.

METHODOLOGY: The literature search was conducted on 19 August 2022 using several databases (MEDLINE, Scopus, Embase, and ScienceDirect). All studies that measured OGTT as diagnostic tools in diagnosing insulinoma and 72-hour fasting test as reference standard were included. The quality assessment of the selected studies was based on the Centre of Evidence-Based Medicine University of Oxford and the Quality Assessment of Diagnostic Accuracy-2 tool (QUADAS-2). Analysis of the included studies was performed qualitatively. This study was registered on PROSPERO (CRD42022360205).

RESULTS: A total of two case-control studies (106 patients) were included, which were at risk of bias and low concern of applicability. Both studies demonstrated that the combination of insulin and C-peptide levels measured during OGTT had high specificity, sensitivity, positive predictive value, and negative predictive value in diagnosing insulinoma compared to the reference standard. A logistic regression model of 8.305 - (0.441 Ã— insulin 2-h/0-h) - (1.679 Ã— C-peptide 1-h/0-h) >0.351 has the highest diagnostic value in one study (AUC 0.97, Sensitivity 86.5%, Specificity 95.2%, PPV 94.1, NPV 88.9).

CONCLUSION: The measurement of 0-h and 2-h insulin and C-peptide levels during 2-h OGTT was found in two small case-control studies with a total of 106 patients to have good sensitivity and specificity. However, due to these limitations, future research is still needed to validate the potential use of OGTT for the diagnosis of insulinoma.

PMID:38863915 | PMC:PMC11163310 | DOI:10.15605/jafes.039.01.16

Permalink for 'Bisphenol a accelerates the glucolipotoxicity-induced dysfunction of rat insulinoma cell lines: An implication for a potential risk of environmental bisphenol a exposure for individuals susceptible to type 2 diabetes'

Bisphenol a accelerates the glucolipotoxicity-induced dysfunction of rat insulinoma cell lines: An implication for a potential risk of environmental bisphenol a exposure for individuals susceptible to type 2 diabetes

Fetched: June 7th, 2024, 2:02am UTC by Chengmeng Huang

Toxicol In Vitro. 2024 Aug;99:105866. doi: 10.1016/j.tiv.2024.105866. Epub 2024 Jun 4.

ABSTRACT

Epidemiological studies have suggested a correlation between bisphenol A (BPA) and type 2 diabetes (T2DM). The effects of BPA on Î²-cell dysfunction may reveal the risks from an in vitro perspective. We used the rat insulinoma (INS-1) cell lines (a type of Î²-cells) to set up normal or damaged models (DM), which were exposed to various concentrations of BPA (0.001, 0.01, 0.1, 1, 10 and 100 Î¼M). An increase in reactive oxygen species (ROS) and apoptosis, and a decrease in cell viability were observed in INS-1 cells exposed to high doses of BPA for 48 h. Interestingly, exposure to lower doses of BPA for 24 h resulted in increased ROS levels and apoptosis rates in INS-1 in the DM group, along with decreased cell viability, suggesting that BPA exerts toxicity to INS-1 cells, particularly to the DM group. Insulin levels and Glut2 expression, glucose consumption, intracellular Ca²⁺ and insulin secretion were increased in INS-1 cells after 48 h exposure to high dose of BPA. Stronger effects were observed in the DM group, even those exposed to low doses of BPA for 24 h. Moreover, BPA inhibited high glucose-stimulated insulin secretion in these cells. Our research suggests that low doses of BPA exacerbate the dysfunction caused by glucolipotoxicity, implying environmental BPA exposure poses a risk for individuals with prediabetes or T2DM.

PMID:38844119 | DOI:10.1016/j.tiv.2024.105866

Permalink for '[(18)F]FB(ePEG12)12-exendin-4 noninvasive imaging of insulinoma negative for insulin immunostaining on specimen from endoscopic ultrasonography-guided fine needle aspiration: a case report with review of literature'

[(18)F]FB(ePEG12)12-exendin-4 noninvasive imaging of insulinoma negative for insulin immunostaining on specimen from endoscopic ultrasonography-guided fine needle aspiration: a case report with review of literature

Fetched: June 6th, 2024, 2:02am UTC by Daisuke Otani

Endocr J. 2024 Jun 5. doi: 10.1507/endocrj.EJ24-0187. Online ahead of print.

ABSTRACT

Insulinomas are the most common functional pancreatic neuroendocrine neoplasm; when treatment is delayed, they induce hyperinsulinemic hypoglycemia, which is life-threatening. As surgical resection is the only curative treatment for insulinoma, preoperative localization is crucial; however, localization based on conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging is often inconclusive. Somatostatin receptor-targeted imaging is another option for detecting pancreatic neuroendocrine neoplasms but has low sensitivity and is not specific for insulinoma. The clinical application of other localizing approaches such as selective arterial calcium stimulation and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is limited by their being invasive and/or technically complex. Moreover, an EUS-FNA specimen of an insulinoma may be negative on insulin immunostaining. Thus, a noninvasive and clinically practical insulinoma-specific diagnostic tool to discriminate insulinomas with high accuracy is anticipated. Glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged in the effort to fulfill this need. We recently developed the novel fluorine-18-labeled exendin-4-based probe conjugated with polyethylene glycol, [¹⁸F]FB(ePEG12)12-exendin-4 (¹⁸F-exendin-4) for positron emission tomography (PET) imaging and reported its clinical benefit in a case of insulinoma in the pancreatic tail. We report here a case of insulinoma in the pancreatic head in which an EUS-FNA specimen was negative on insulin immunostaining while precise preoperative localization and conclusive evidence for curative enucleation was provided by ¹⁸F-exendin-4 PET/CT (Japan Registry of Clinical Trials; jRCTs051200156).

PMID:38839345 | DOI:10.1507/endocrj.EJ24-0187

Identification of Ppy-lineage cells as a novel origin of pancreatic ductal adenocarcinoma

Fetched: June 6th, 2024, 2:02am UTC by Ofejiro Blessing Pereye

J Pathol. 2024 Aug;263(4-5):429-441. doi: 10.1002/path.6295. Epub 2024 Jun 4.

ABSTRACT

The Ppy gene encodes pancreatic polypeptide (PP) secreted by PP- or Î³-cells, which are a subtype of endocrine cells localised mainly in the islet periphery. For a detailed characterisation of PP cells, we aimed to establish PP cell lines. To this end, we generated a mouse model harbouring the SV40 large T antigen (TAg) in the Rosa26 locus, which is expressed upon Ppy-promoter-mediated Cre-loxP recombination. Whereas Insulin1-CreERT-mediated TAg expression in beta cells resulted in insulinoma, surprisingly, Ppy-Cre-mediated TAg expression resulted in the malignant transformation of Ppy-lineage cells. These mice showed distorted islet structural integrity at 5 days of age compared with normal islets. CK19⁺ duct-like lesions contiguous with the islets were observed at 2 weeks of age, and mice developed aggressive pancreatic ductal adenocarcinoma (PDAC) at 4 weeks of age, suggesting that PDAC can originate from the islet/endocrine pancreas. This was unexpected as PDAC is believed to originate from the exocrine pancreas. RNA-sequencing analysis of Ppy-lineage islet cells from 7-day-old TAg⁺ mice showed a downregulation and an upregulation of endocrine and exocrine genes, respectively, in addition to the upregulation of genes and pathways associated with PDAC. These results suggest that the expression of an oncogene in Ppy-lineage cells induces a switch from endocrine cell fate to PDAC. Our findings demonstrate that Ppy-lineage cells may be an origin of PDAC and may provide novel insights into the pathogenesis of pancreatic cancer, as well as possible therapeutic strategies. Â© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

PMID:38837231 | DOI:10.1002/path.6295

Permalink for 'Super paramagnetic iron oxide contrast-enhanced magnetic resonance imaging was useful in differentiating an insulinoma from an accessory spleen: a case report with review of literature'

Super paramagnetic iron oxide contrast-enhanced magnetic resonance imaging was useful in differentiating an insulinoma from an accessory spleen: a case report with review of literature

Fetched: June 3rd, 2024, 2:02am UTC by Ema Toyokuni

Endocr J. 2024 Aug 8;71(8):809-815. doi: 10.1507/endocrj.EJ24-0142. Epub 2024 May 31.

ABSTRACT

When a neuroendocrine tumor with abundant blood flow is located in the pancreatic tail, it is difficult to distinguish it from accessory spleen. The patient was a 71-year-old woman who was admitted with impaired consciousness and hypoglycemia, raising suspicion of insulinoma. The selective arterial calcium injection test suggested a lesion in the pancreatic tail. Contrast-enhanced computed tomography and magnetic resonance imaging (MRI) showed a mass in the splenic hilum; however, its continuity with the pancreas was unclear. Contrast-enhanced MRI using super paramagnetic iron oxide (SPIO) showed no SPIO uptake in the splenic hilar mass. SPIO contrast-enhanced MRI is considered useful for differentiating pancreatic endocrine tumors from paraspleen tumors.

PMID:38825447 | DOI:10.1507/endocrj.EJ24-0142

Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status

Sci Rep. 2024 May 31;14(1):12521. doi: 10.1038/s41598-024-63525-7.

ABSTRACT

Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to the lysosome and the mitochondrial turnover in both mouse embryonic fibroblast (MEF) and in mouse insulinoma cells (MIN6) as a model of pancreatic Î² cells. Resveratrol (RESV), an activator of SIRT1 activity, promotes TSC2 deacetylation and its translocation to the lysosome, inhibiting mTORC1 activity. An improvement in mitochondrial turnover was also observed in cells treated with RESV, associated with an increase in the fissioned mitochondria, positive autophagic and mitophagic fluxes and an enhancement of mitochondrial biogenesis. This study proves that TSC2 in its deacetylated form is essential for regulating mTORC1 signalling and the maintenance of the mitochondrial quality control, which is involved in the homeostasis of pancreatic beta cells and prevents from several metabolic disorders such as Type 2 Diabetes Mellitus.

PMID:38822085 | PMC:PMC11143182 | DOI:10.1038/s41598-024-63525-7

Permalink for 'Use of Translational Science, Continuous Glucose Monitoring in the Primary Care Setting for Management of Nesidioblastosis: A Case Report and Literature Review'

Use of Translational Science, Continuous Glucose Monitoring in the Primary Care Setting for Management of Nesidioblastosis: A Case Report and Literature Review

Fetched: June 1st, 2024, 2:01am UTC by Karuna Manandhar

Cureus. 2024 Apr 30;16(4):e59388. doi: 10.7759/cureus.59388. eCollection 2024 Apr.

ABSTRACT

Nesidioblastosis is a term used to describe histologic changes in the pancreatic cell, which are defined by beta cell hypertrophy and the formation of ductoinsular complexes. It is a disease previously most extensively identified in neonates and is a rare cause of endogenous hypoglycemia in the adult population. However, with increasing numbers of gastric bypass surgeries for the management of obesity in recent years, there has been a growing number of populations with post-gastric bypass surgery-related nesidioblastosis. Here, we will present a case of a 60-year-old female with a history of Roux-en-Y gastric bypass (RYGB) surgery who initially presented with loss of consciousness and episodes of suspected hypoglycemia. Insulinoma was ruled out, supporting the diagnosis of adult onset RYGB-associated nesidioblastosis.This article was previously presented as a poster presentation at the 2023 Research Symposium, International Conference on Health Disparities, on September 8, 2023.

PMID:38817472 | PMC:PMC11139435 | DOI:10.7759/cureus.59388

Permalink for 'Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer: Identification, prognosis and survival, genetic and epigenetic factors'

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer: Identification, prognosis and survival, genetic and epigenetic factors

Fetched: May 30th, 2024, 2:02am UTC by Mohamed Wishahi

World J Clin Cases. 2024 May 6;12(13):2143-2146. doi: 10.12998/wjcc.v12.i13.2143.

ABSTRACT

Neuroendocrine prostate cancer (NEPC) shows an aggressive behavior compared to prostate cancer (PCa), also known as prostate adenocarcinoma. Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer. NEPC may arise de novo or develop following androgen deprivation therapy (ADT). NEPC that arise following ADT has the nomenclature "treatment-emerging/induced NEPC (t-NEPC)". t-NEPC would be anticipated in castration resistant prostate cancer (CRPC) and metastatic PCa. t-NEPC is characterized by low or absent androgen receptor (AR) expression, independence of AR signaling, and gain of neuroendocrine phenotype. t-NEPC is an aggressive metastatic tumor, develops from PCa in response to drug induced ADT, and shows very short response to conventional therapy. t-NEPC occurs in 10%-17% of patients with CRPC. De novo NEPC is rare and is accounting for less than 2% of all PCa. The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated. Sphingosine kinase 1 plays a significant role in t-NEPC development. Although neuroendocrine markers: Synaptophysin, chromogranin A, and insulinoma associated protein 1 (INSM1) are expressed in t-NEPC, they are non-specific for diagnosis, prognosis, and follow-up of therapy. t-NEPC shows enriched genomic alteration in tumor protein P53 (TP53) and retinoblastoma 1 (RB1). There are evidences suggest that t-NEPC might develop through epigenetic evolution. There are genomic, epigenetic, and transcriptional alterations that are reported to be involved in development of t-NEPC. Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC. PCa is resistant to immunotherapy, and at present there are running trials to approach immunotherapy for PCa, CRPC, and t-NEPC.

PMID:38808339 | PMC:PMC11129135 | DOI:10.12998/wjcc.v12.i13.2143

Malignant Insulinoma

Fetched: May 28th, 2024, 2:01am UTC by Sindhu Kishore

AACE Clin Case Rep. 2024 Jan 23;10(3):119-120. doi: 10.1016/j.aace.2024.01.004. eCollection 2024 May-Jun.

NO ABSTRACT

PMID:38799047 | PMC:PMC11127596 | DOI:10.1016/j.aace.2024.01.004

Permalink for 'Previously undiagnosed genetic disease in adult patient with hepatic masses and reported history of congenital hyperinsulinism'

Previously undiagnosed genetic disease in adult patient with hepatic masses and reported history of congenital hyperinsulinism

Fetched: May 24th, 2024, 2:02am UTC by Jacob Kuzy

BMJ Case Rep. 2024 May 22;17(5):e259355. doi: 10.1136/bcr-2023-259355.

ABSTRACT

Glycogen storage disease type 1A (GSD1A), also known as Von Gierke's disease, is a rare autosomal recessive disorder affecting glycogen metabolism in the liver. It most commonly presents in infancy with hypoglycaemia and failure to thrive, but cases have been reported as undiagnosed until adulthood. A woman in her early 20s with diabetes mellitus presented with right upper quadrant pain and was found to have several haemorrhagic hepatic adenomas. This patient had insulin-dependent diabetes since a pancreatectomy at age 9 months due to continued episodes of hypoglycaemia and suspected insulinoma. During the hospital stay, the hepatic adenomas were embolised, but significant lactic acidosis and hypoglycaemia continued. Further workup revealed a chronic lactic acid level, during several hospital stays, of above 5 mmol/L. After cytology of hepatic tissue ruled out hepatocellular carcinoma, the patient was discharged and recommended to follow-up for genetic testing, which confirmed the diagnosis of GSD1A.

PMID:38782444 | DOI:10.1136/bcr-2023-259355

Clinical Presentation, Diagnosis, and Management of Hyperinsulinemic Hypoglycemia in Adults: A Single-center Experience

Fetched: May 21st, 2024, 2:02am UTC by Giulia Cordenos

Endocr Metab Immune Disord Drug Targets. 2024 May 17. doi: 10.2174/0118715303322628240509094537. Online ahead of print.

ABSTRACT

INTRODUCTION: Hyperinsulinemic Hypoglycemia (HH) is a rare condition characterized by inappropriately elevated insulin levels in the presence of low glucose levels. A proper diagnostic framework is fundamental to avoid patients undergoing unnecessary diagnostic and therapeutic invasive procedures.

OBJECTIVE: The study aimed to assess the clinical presentation, diagnostic work-up, and treatment of a single-center cohort of patients affected by HH.

METHODS: We conducted a retrospective analysis of data collected from January 2000-2023.

RESULTS: Our study included 104 patients: 81 (58% F) affected by insulinoma, 11 (91% F) by autoimmune hypoglycemia, 7 (71% M) by post-gastric surgery hypoglycemia, and 5 (80% F) by factitious hypoglycemia. HH was more frequent in females (63 F vs. 41 M, p-value 0.039). The median age at diagnosis was lower in insulinoma than in the autoimmune group (52.7 vs. 63.7 y, p < 0.001). During the hypoglycemic event, insulin and C-peptide levels were significantly higher in autoimmune hypoglycemia than in insulinoma (insulin 324.6 vs. 36.4 Î¼U/ml, p-value 0.033; C-peptide 14.25 vs. 3.99 ng/ml, p-value 0.003). Specifically, C-peptide levels <9.6 ng/ml and insulin levels <75 Î¼U/ml exhibited 97.3% vs. 93.4% sensitivity and 80% vs. 90% specificity for insulinoma diagnosis, respectively. Regarding insulinoma, the sensitivity of localizing imaging was 88% for Endoscopic Ultrasound (EUS), 86% for Magnetic Resonance Imaging (MRI), 82% for Computed Tomography (CT) scan, 52% for nuclear imaging, and 100% for angiography with the Doppman test. Among insulinoma patients, 79% received surgical treatment while 4% radiofrequency ablation. Symptomatic remission occurred in 100% of cases.

CONCLUSION: We have confirmed insulinoma as the primary cause of HH. The autoimmune form should be suspected when insulin and C-peptide levels are markedly elevated.

PMID:38766827 | DOI:10.2174/0118715303322628240509094537

Permalink for 'SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway'

SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway

Fetched: May 21st, 2024, 2:02am UTC by Guangchun Jiang

J Cell Mol Med. 2024 May;28(10):e18397. doi: 10.1111/jcmm.18397.

ABSTRACT

Malignant insulinoma is an extremely rare type of functioning pancreatic neuroendocrine tumour with a high degree of malignancy and a high incidence of metastasis. However, it is still unclear how malignant insulinomas develop and metastasize. Serum amyloid P component (SAP), a member of the pentraxin protein family, is an acute-phase protein secreted by liver cells. The role of SAP in insulinoma and the related mechanism are still unknown. To determine the effect of SAP on insulinoma, we crossed Rip1-Tag2 mice, which spontaneously develop insulinoma, and SAP knockout (KO) mice to generate Rip1-Tag2;SAP^-/- mice. We found that SAP deletion significantly promoted the growth, invasion and metastasis of malignant insulinoma through C-X-C motif chemokine ligand 12 (CXCL12) secreted by cancer-associated fibroblasts (CAFs). Further study showed that SAP deletion promoted CXCL12 secretion by CAFs through the CXCR4/p38/ERK signalling pathway. These findings reveal a novel role and mechanism of SAP in malignant insulinoma and provide direct evidence that SAP may be a therapeutic agent for this disease.

PMID:38766687 | PMC:PMC11103456 | DOI:10.1111/jcmm.18397

Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease

Fetched: May 21st, 2024, 2:02am UTC by Eiji Kawasaki

World J Diabetes. 2024 May 15;15(5):935-944. doi: 10.4239/wjd.v15.i5.935.

ABSTRACT

BACKGROUND: In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice.

AIM: To investigate the frequency of anti-islet autoantibodies in AITD patients.

METHODS: Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D (n = 18), AITD with phenotypic type 2 diabetes (T2D) (n = 81), and AITD without diabetes (n = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups.

RESULTS: The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, the frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% vs 5.0%, P < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 Â± 66.4 vs 308.1 Â± 66.4 index). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves' disease and Hashimoto's thyroiditis in any of the groups.

CONCLUSION: Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

PMID:38766435 | PMC:PMC11099373 | DOI:10.4239/wjd.v15.i5.935

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia: A Promising Supportive Therapy

Fetched: May 18th, 2024, 2:01am UTC by Rong-Rong Li

Chin Med Sci J. 2024 Jun 30;39(2):102-110. doi: 10.24920/004329.

ABSTRACT

Objective To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia. Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events. Results The study population consisted of 24 cases of insulinoma patients, 7 males and 17 females, aged 46.08Â±14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51Â±3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 (interquartile range [IQR]: 2.50-2.90) mmol/L. The patients' weight increased by 0.38 (IQR: 0.05-0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30-5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60-2.90) mmol/L; P < 0.001]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L; P < 0.001). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L; P < 0.001], but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose. Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

PMID:38755752 | DOI:10.24920/004329

The Medical and Surgical Management of Recurrent Multicenter Insulinomatosis Without Known Genetic Predisposition

Fetched: May 17th, 2024, 2:01am UTC by Erin Jaquillard

ACG Case Rep J. 2024 May 13;11(5):e01350. doi: 10.14309/crj.0000000000001350. eCollection 2024 May.

ABSTRACT

Insulinomas are rare neuroendocrine tumors characterized by episodic hypoglycemia. Typically, insulinomas are benign, solitary, intrapancreatic, and measure less than 2 cm in diameter. When insulinomas are multicenter or recurrent, they are often associated with genetic conditions such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, or von Hippel-Lindau disease. Most insulinomas can be resolved with surgery. Multicenter and recurrent insulinomas, known as insulinomatosis, may require additional medical and surgical management. We report a distinctive case involving recurrent multicenter insulinomatosis devoid of any identified genetic familial predisposition. The patient's complex medical history spans nearly 2 decades, marked by unsuccessful attempts at resolution through surgical enucleation and noninvasive medical management, culminating in the decision for total pancreatectomy.

PMID:38746622 | PMC:PMC11093572 | DOI:10.14309/crj.0000000000001350

Giant parathyroid adenoma and hungry bone syndrome in MEN1 syndrome: A case report

Fetched: May 14th, 2024, 2:02am UTC by Jeremy Hugh Yen-Hey Lau

Radiol Case Rep. 2024 May 3;19(8):2959-2964. doi: 10.1016/j.radcr.2024.04.024. eCollection 2024 Aug.

ABSTRACT

An 18-year-old male with multiple endocrine neoplasm type 1 (MEN1) syndrome presented with hyperparathyroidism. Parathyroidectomy was performed. Patient complained of bone pain afterwards, multiple imaging modalities revealed features of osteitis fibrosa cystica and biochemical profile showed features of hungry bone syndrome. Incidental suspicious pancreatic lesion was initially revealed by ¹⁸F-FDG PET/CT scan while MRI further characterized the possibility of insulinoma. Ultimately, the patient was diagnosed of MEN1 syndrome by genetic test. This case report demonstrates the utilization of various imaging modalities such as ultrasound, Tc^99m-sestamibi parathyroid scintigraphy, bone scintigraphy, CT, PET/CT and MRI, which leads to ultimately the diagnosis of MEN1 syndrome.

PMID:38737174 | PMC:PMC11087690 | DOI:10.1016/j.radcr.2024.04.024

Pioglitazone Phases and Metabolic Effects in Nanoparticle-Treated Cells Analyzed via Rapid Visualization of FLIM Images

Fetched: May 12th, 2024, 2:01am UTC by Biagio Todaro

Molecules. 2024 May 4;29(9):2137. doi: 10.3390/molecules29092137.

ABSTRACT

Fluorescence lifetime imaging microscopy (FLIM) has proven to be a useful method for analyzing various aspects of material science and biology, like the supramolecular organization of (slightly) fluorescent compounds or the metabolic activity in non-labeled cells; in particular, FLIM phasor analysis (phasor-FLIM) has the potential for an intuitive representation of complex fluorescence decays and therefore of the analyzed properties. Here we present and make available tools to fully exploit this potential, in particular by coding via hue, saturation, and intensity the phasor positions and their weights both in the phasor plot and in the microscope image. We apply these tools to analyze FLIM data acquired via two-photon microscopy to visualize: (i) different phases of the drug pioglitazone (PGZ) in solutions and/or crystals, (ii) the position in the phasor plot of non-labelled poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), and (iii) the effect of PGZ or PGZ-containing NPs on the metabolism of insulinoma (INS-1 E) model cells. PGZ is recognized for its efficacy in addressing insulin resistance and hyperglycemia in type 2 diabetes mellitus, and polymeric nanoparticles offer versatile platforms for drug delivery due to their biocompatibility and controlled release kinetics. This study lays the foundation for a better understanding via phasor-FLIM of the organization and effects of drugs, in particular, PGZ, within NPs, aiming at better control of encapsulation and pharmacokinetics, and potentially at novel anti-diabetics theragnostic nanotools.

PMID:38731628 | PMC:PMC11085555 | DOI:10.3390/molecules29092137

Rare Cancer News & Clinical Trials » Pancreas

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