Pancreatic Insulinoma Research Articles

SAT152 Retrospective Analysis Of HbA1c In Patients Diagnosed With Pancreatic Insulinoma Prior To- And After Surgical Excision

Abstract Disclosure: S.J. Lawless: None. A. McGrath: None. R. Campbell: None. D. O'Keeffe: None. M.J. Bell: None. Insulinomas are rare pancreatic tumours characterised by episodes of hyperinsulinaemic hypoglycaemia. Patients may develop secondary diabetes following surgical intervention for insulinoma. Glycated haemoglobin (HbA1c) is a reliable bio-marker for the diagnosis and prognosis of diabetes. HbA1c is a useful surrogate marker for insulinoma (1). A retrospective analysis of patients diagnosed with insulinoma and attending our service in Galway University Hospital (GUH) was performed. Data was collected using the electronic patient correspondence system to gather information from clinic letters, hospital and GP laboratory results were accessed on the Evolve laboratory system. Diagnostic criteria employed a 72-hour fast with plasma glucose levels of ≤2.2 mmol/L, with a corresponding insulin level ≥18 pmol/L and a c-peptide of <200 pmol/l. We analysed their HbA1c at initial presentation and longitudinally following treatment. There are currently six patients carrying a diagnosis of insulinoma attending our service. All of these patients have had surgical intervention. At diagnosis four of the six patients had a HbA1c taken. One patient was diagnosed prior to HbA1c being routinely available and another patient had initial investigations and management elsewhere. The average HbA1c at time of diagnosis was 27.75 mmol/mol (n=4) (reference range 20 to 42 mmol/mol). All insulinoma patients have their HbA1c monitored yearly as part of ongoing follow-up. HbA1c trends upwards with an average HbA1c 18-24 months post surgical excision of 36.25 mmol/mol (n=4). There is a tendency of increased HbA1c post-operatively with a mean increase in HbA1c of 8.5 mmol/mol over 18-24 months. Three of our six patients have developed diabetes on extended follow-up. The average time to diagnosis post-surgical resection was 5.5 years (n=3). HbA1c is a useful tool for monitoring for secondary diabetes post pancreatic surgery. While admitting our number of patients is low, it is interesting to observe the difference in HbA1c pre- and post-operatively in patients with insulinoma. 1.Vaidakis, Dennis, et al. "Pancreatic insulinoma: current issues and trends." Hepatobiliary & pancreatic diseases international: HBPD INT 9.3 (2010): 234-241. Presentation: Saturday, June 17, 2023

OR16-03 Epigenetic Studies Of Pancreatic Neuroendocrine Tumours (PNETs) Reveal Decreased DNA Hydroxymethylation In Non-functioning PNETs But Not Insulinomas

Abstract Disclosure: K.A. English: None. A. Selberherr: None. O.A. Shariq: None. E. O'Neill: None. K.E. Lines: None. R.V. Thakker: None. Background: DNA methylation and hydroxymethylation (5hmC) are epigenetic alterations that can silence or maintain gene transcription, respectively. Pancreatic neuroendocrine tumours (PNETs), which can be hormone-secreting (e.g. insulinomas) or non-functioning (NF-PNETs), have a low mutational burden and are reported to be associated with DNA hypermethylation, but the role of 5hmC in PNETs is unknown. Aim: To determine the patterns of DNA 5hmC in NF-PNETs, insulinomas, and normal pancreatic islets. Methods: NF-PNETs (n=31, mean age 54 ± 13 years (y), 14 males (M), tumour grade (G) G1=15, G2=13, G3=3) and insulinomas (n=21, mean age 50 ± 21y, 9M, G1=17 and G2=4) were collected from patients who did not have a genetic syndrome associated with PNETs together with 14 normal pancreata (mean age 63 ± 12y, 11M). Samples were obtained following ethical approval from the Universities of Oxford and Vienna. DNA 5hmC was assessed by immunohistochemistry (IHC) and MethylationEPIC array (that interrogates 5hmC CpG sites). Multivariate analysis was used to determine variables associated with 5hmC. Transcriptome analysis was undertaken by RNA-Seq. Results: NF-PNETs had reduced 5hmC when compared to insulinomas (p<0.01) and to normal adjacent islets (p<0.001). Thus, 5hmC was ∼3 fold lower in NF-PNETs compared to normal adjacent islets (n=12; p<0.001), whilst 5hmC between insulinomas and normal adjacent islets (n=15) was not significantly different. Multivariate analysis confirmed this finding, with NF-PNETs being associated with lower 5hmC when controlled for patient age, sex and tumour grade (p<0.01). In normal pancreatic tissue 5hmC was ∼2 fold higher in normal islets when compared to exocrine tissue (51 islets assessed in total, range 1-9 islets/sample from 34 fields of 305,866um2 studied; p<0.001). MethylationEPIC array analysis, using DNA from NF-PNETs (n=5), insulinomas (n=4) and normal pancreatic tissue (n=7), revealed NF-PNETs and insulinomas to have a significant decrease in 5hmC compared to normal pancreatic tissue (p<0.001). Furthermore, subtype analysis revealed that NF-PNETs had lower 5hmC compared to insulinomas (0% vs 0.003%, adjusted p<0.08). To determine possible mechanisms underlying these differences in tumour subtype 5hmC, RNA-Seq analysis using NF-PNETs (n=7) and insulinomas (n=6) was performed. This revealed 79 genes to be differentially expressed (adjusted p<0.01), of which 33 were upregulated (including Calcium/Calmodulin Dependent Protein Kinase 2 Gamma (CAMK2G)); and 46 were down-regulated (including Glucagon Like peptide 1 receptor (GLP1R)) in NF-PNETs. Interestingly, CAMK2G and GLP1R are both involved in DNA 5hmC modulation via cAMP. Conclusions: DNA 5hmC, an epigenetic mechanism, is significantly lower in NF-PNETs when compared to normal islets and insulinomas and may involve dysregulation of cAMP-mediated signalling pathways. Presentation: Friday, June 16, 2023

The Broad Spectrum of Paediatric Pancreatic Disease: A Single-center 26-years Retrospective Review

BackgroundPaediatric pancreatic pathology and its management is rarely described. We present our experience. MethodsA retrospective case-note review of all patients with pancreatic disease from 1995 to 2021 was completed. Data are quoted as median (range). ResultsTwo hundred and twelve patients were identified with 75.9% presenting with pancreatitis. Referrals for pancreatitis increased during the study period and affected a wide age range (2 months–15.6 years).Acute pancreatitis (n = 118) (age 10.6 (0.18–16.3) years). The most common causes were idiopathic (n = 60, 50.8%) and biliary (n = 28, 23.8%). About 10% required treatment for complications or underlying biliary causes.Recurrent pancreatitis (n = 14) (11.6 (0.3–14.3) years). The most common cause was hereditary pancreatitis (n = 6, 42.9%). One patient required endoscopic drainage of pseudocyst.Chronic pancreatitis (n = 29) (16 (0.38–15.5) years). The underlying diagnosis was idiopathic (n = 14, 48.4%) or hereditary pancreatitis (n = 10, 34.5%). 13 patients required active management, including pancreaticojejunostomies (n = 5).Blunt Trauma (n = 34) was managed conservatively in 24 (70.5%). 6 patients required open surgery, but 4 were managed by either endoscopy or interventional radiology.Pancreatic tumours (n = 13) presented at 11.2 (2.3–16) years. Pathology included pancreaticoblastomas (n = 3), solid pseudopapillary tumours (n = 3), neuroendocrine tumours (n = 2), acinar cell cystadenoma (n = 1), intraductal papillary mucinous neoplasm (n = 1), pancreatic insulinoma (n = 1), pancreatic ductal adenocarcinoma (n = 1), and embryonal rhabdomyosarcoma (n = 1). Others (n = 4)Pancreatic cyst (n = 3) and annular pancreas (n = 1). ConclusionPaediatric pancreatic disease spans a wide spectrum of both benign and malignant disease and benefits from access to specialist medical, surgical, endoscopic, and interventional radiology expertise. Referrals for paediatric pancreatitis are increasing, but aetiology is different to that seen in adults. Level of EvidenceIV

S1276 Epidemiology for Non-Surgical Local Ablative Intervention in Pancreatic Insulinoma

S1276 Epidemiology for Non-Surgical Local Ablative Intervention in Pancreatic Insulinoma

MDCT appearances of pancreatic insulinoma as well as the other well differentiated endocrine tumors

Introduction: Pancreatic endocrine tumors (PETs) are primarily well-differentiated tumors composed of cells that resemble normal islet cells but that arise from pancreatic ductal cells. They are classified as functioning or nonfunctioning according to their associated clinical symptoms; insulinomas, gastrinomas and glucagonomas are the most common function­ing PETs Case Report: A 36-years old man presented with a one-month history of fainting attacks and dizziness, symptoms of hypoglycemia such as hunger, sweating, palpitations, loss of consciousness and syncope. We tried abdominal enhanced spiral CT to localize the tumor, but that wasn’t successful. Therefore, we tried a new method of MD spiral CT scanning and localized the tumor. Discussion and Conclusion: Insulinomas are the commonest islet cell tumors of the pancreas, followed by gastrinomas. Preoperative localization is very helpful in planning the operation: it allows the surgeon to determine whether simple tumor resection or partial pancreatectomy is likely to be required.

MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response

Lack of efficient insulin secretion from the pancreas can lead to impaired glucose tolerance (IGT), prediabetes, and diabetes. We have previously identified two IGT-associated single nucleotide polymorphisms (SNPs) rs62212118 and rs13052524 located at two overlapping genes: MRPS6 and SLC5A3. In this study, we show that MRPS6 but not SLC5A3 regulates glucose-stimulated insulin secretion (GSIS) in primary human β-cell and a mouse pancreatic insulinoma β-cell line. Data mining and biochemical studies reveal that MRPS6 is positively regulated by the mitochondrial unfolded protein response (UPRmt), but feedback inhibits UPRmt. Disruption of such feedback by MRPS6 knockdown causes UPRmt hyperactivation in high glucose conditions, hence elevated ROS levels, increased apoptosis, and impaired GSIS. Conversely, MRPS6 overexpression reduces UPRmt, mitigates high glucose-induced ROS levels and apoptosis, and enhances GSIS in an ATF5-dependent manner. Consistently, UPRmt up-regulation or down-regulation by modulating ATF5 expression is sufficient to decrease or increase GSIS. The negative role of UPRmt in GSIS is further supported by analysis of public transcriptomic data from murine islets. In all, our studies identify MRPS6 and UPRmt as novel modulators of GSIS and apoptosis in β-cells, contributing to our understanding of the molecular and cellular mechanisms of IGT, prediabetes, and diabetes.

Anaesthetic challenges in surgical enucleation of pancreatic insulinoma

Insulinoma is a very rare tumour occurring in 1-4 persons per million per year. It is a functional endocrine tumour of the pancreas characterized by repeated attacks of hypoglycaemia presenting as adrenergic or neuroglycopenic symptoms. Surgical management of insulinoma is the mainstay of treatment which can be done by either laparoscopic or open approach. There is occurrence of rapid and wide fluctuations of blood glucose levels in the intraoperative as well as perioperative period. Intraoperative hypoglycaemia is critical due to masking of symptoms by the effect of anaesthesia and if not detected and treated promptly may lead to permanent neurological insult. We here-in describe the challenges of anaesthetic management in a case of functional pancreatic insulinoma undergoing open surgical enucleation with the help of intraoperative ultrasonography.

Confirmed and presumed canine insulinomas and their presumed metastases are most conspicuous in the late arterial phase in a triple arterial phase CT protocol.

Arterial enhancement is the commonly described characteristic of canine insulinomas in contrast-enhanced computed tomography (CECT). However, this finding is also reported as inconsistent. The main aim of this single-center retrospective observational study was to describe the contrast enhancement (CE) pattern of canine presumed and confirmed insulinomas and presumed metastases in three consecutive (early, mid, and late) arterial phases. Included dogs had a medical-record-based clinical or cytological/histopathological diagnosis of insulinoma and quadruple-phase CECT.The arterial phases were identified according to published literature. The arterial enhancement of confirmed and presumed lesions was assessed using a visual grading score. Twelve dogs with a total of 17 pancreatic nodules were analyzed. Three dogs had multiple pancreatic nodules and nine had solitary findings. Four insulinomas were histopathologically confirmed. Late arterial phase (LAP) images demonstrated the largest number of pancreatic nodules reaching the highest enhancement scores (n=13, 76%). All analyzed dogs had CT evidence of arterially enhancing nodules in the liver (n=12), seven in the hepatic, splenic, or colic lymph nodes, and three in the spleen. Three out of five sampled livers and three lymph nodes were metastatic. All sampled spleens were benign. Avid arterial enhancement was the most dominant feature of canine presumed and confirmed insulinomas and presumed metastases in quadruple-phase CECT. The highest enhancement scores were observed primarily in LAP, followed by MAP. Authors, therefore, recommend including LAP in the standard CT protocol for dogs with suspected pancreatic insulinomas.

A case of frequent hypoglycemic attacks successfully controlled with capecitabine plus temozolomide and 177Lu-DOTATATE peptide receptor radionuclide therapy in a patient with recurrent pancreatic insulinoma.

A 59-year-old woman with metastatic pancreatic insulinoma, having undergone several treatment regimens including sunitinib, everolimus, lanreotide and streptozocin plus 5-fluorouracil, was admitted to our hospital because of frequent hypoglycemic attacks. These were refractory to medical treatment using diazoxide and required frequent daily intravenous glucose infusions. She was started on capecitabine and temozolomide (CAPTEM), followed by initiation of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT). The frequency of hypoglycemic attacks decreased after treatment began and she was discharged on day 58 post-admission, without requiring daily glucose infusions. CAPTEM and PRRT were continued without any major adverse events. Computed tomography revealed shrinkage of primary and metastatic lesions, an anti-tumor effect that continued 8months after treatment was initiated. Hypoglycemic attacks caused by insulinomas are often refractory to conventional therapy; however, combination treatment using CAPTEM and PRRT has demonstrated a positive and significant response, successfully restoring glycemic control.

Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.

Rab26 is known to regulate multiple membrane trafficking events, but its role in insulin secretion in pancreatic β cells remains unclear despite it was first identified in the pancreas. In this study, we generated Rab26-/- mice through CRISPR/Cas9 technique. Surprisingly, insulin levels in the blood of the Rab26-/- mice do not decrease upon glucose stimulation but conversely increase. Deficiency of Rab26 promotes insulin secretion, which was independently verified by Rab26 knockdown in pancreatic insulinoma cells. Conversely, overexpression of Rab26 suppresses insulin secretion in both insulinoma cell lines and isolated mouse islets. Islets overexpressing Rab26, upon transplantation, also failed to restore glucose homeostasis in type 1 diabetic mice. Immunofluorescence microscopy revealed that overexpression of Rab26 results in clustering of insulin granules. GST-pulldown experiments reveal that Rab26 interacts with synaptotagmin-1 (Syt1) through directly binding to its C2A domain, which interfering with the interaction between Syt1 and SNAP25, and consequently inhibiting the exocytosis of newcomer insulin granules revealed by TIRF microscopy. Our results suggest that Rab26 serves as a negative regulator of insulin secretion, via suppressing insulin granule fusion with plasma membrane through sequestering Syt1.

ATP6AP2 is robustly expressed in pancreatic β cells and neuroendocrine tumors, and plays a role in maintaining cellular viability

ATP6AP2, also known as (pro)renin receptor, has been shown to be expressed in several tissues including pancreatic β cells. Whereas ATP6AP2 plays an important role in regulating insulin secretion in mouse pancreatic β cells, the expression profiles and roles of ATP6AP2 in human pancreatic endocrine cells and neuroendocrine tumor cells remain unclear. Here in this study, we investigated the expression profiles of ATP6AP2 in pancreatic endocrine cells, and found that ATP6AP2 is robustly expressed in pancreatic insulinoma cells as well as in normal β cells. Although ATP6AP2 was also expressed in low-grade neuroendocrine tumors, it was not or faintly detected in intermediate- and high-grade neuroendocrine tumors. Knockdown experiments of the Atp6ap2 gene in rat insulinoma-derived INS-1 cells demonstrated decreased cell viability accompanied by a significant increase in apoptotic cells. Taken together, these findings suggest that ATP6AP2 plays a role in maintaining cellular homeostasis in insulinoma cells, which could lead to possible therapeutic approaches for endocrine tumors.

The potential oncogenic effect of tissue-specific expression of JC polyoma T antigen in digestive epithelial cells.

JC polyoma virus (JCPyV), a ubiquitous polyoma virus that commonly infects people, is identified as the etiologic factor for progressive multifocal leukoencephalopathy and has been closely linked to various human cancers. Transgenic mice of CAG-loxp-Laz-loxp T antigen were established. T-antigen expression was specifically activated in gastroenterological target cells with a LacZ deletion using a cre-loxp system. Gastric poorly-differentiated carcinoma was observed in T antigen-activated mice using K19-cre (stem-like cells) and PGC-cre (chief cells), but not Atp4b-cre (parietal cells) or Capn8-cre (pit cells) mice. Spontaneous hepatocellular and colorectal cancers developed in Alb-cre (hepatocytes)/T antigen and villin-cre (intestinal cells)/T antigen transgenic mice respectively. Gastric, colorectal, and breast cancers were observed in PGC-cre/T antigen mice. Pancreatic insulinoma and ductal adenocarcinoma, gastric adenoma, and duodenal cancer were detected in Pdx1-cre/T antigen mice. Alternative splicing of T antigen mRNA occurred in all target organs of these transgenic mice. Our findings suggest that JCPyV T antigen might contribute to gastroenterological carcinogenesis with respect to cell specificity. Such spontaneous tumor models provide good tools for investigating the oncogenic roles of T antigen in cancers of the digestive system.

SPECT/CT with 99mTc-Tectrotide in the diagnosis of insulinoma

BACKGROUND: Insulinoma is a pancreatic neuroendocrine tumor that manifests by impaired carbohydrate metabolism with the development of hypoglycemic syndrome. The instrumental methods used at the present stage do not always make it possible to identify a tumor; moreover, the data obtained often contradict each other. Thus, the search for new possibilities of visualization of insulinoma is relevant.AIM: Evaluation of diagnostic effectiveness of scintigraphy with single-photon emission computed tomography combined with X-ray computed tomography (SPECT/CT) with 99mTc-Tectrotide for insulinoma in a Russian cohort of patients.MATERIALS AND METHODS: A single-centre (Endocrinology Research Centre of the Ministry of Health of the Russia), experimental, single-stage, controlled study. In the years 2017–2021 patients with pancreatic insulinoma (group 1) and hyperinsulinemic hypoglycemia of a different genesis (group 2) with negative or contradictory results of the 1st line imaging methods (ultrasound, magnetic resonance imaging (MRI), computed tomography (CT)) were included. All participants underwent the whole-body scintigraphy and low-dose SPECT/CT with 99mTc-Tectrotide (500–900 MBq). The studies were performed on a tomograph of the SPECT/GE Discovery NM/CT 670 using low-energy high-resolution collimators (LEHR) in the «whole body» mode.RESULTS: In the group 1 (n=21), according to the results of a pathomorphological study, the presence of 26 insulin-producing tumors was confirmed. Group 2 included 9 patients. According to the SPECT/CT with 99mTc-Tectrotide, 14 tumors were diagnosed in group 1 out of 26 insulin-producing tumors of the pancreas, and negative results were obtained in group 2 in 100% of cases. Thus, the sensitivity and specificity of the method were: 54%, 95% CI [33%; 73%] and 100%, 95% CI [68%; 100%], respectively.CONCLUSION: SPECT/CT with 99mTc-Tectrotide can detect insulinoma in 54% of cases with negative or contradictory results of 1st-line imaging methods (ultrasound, MRI, CT). This study can be effectively used as an alternative to SPECT/CT with 111In-octreotide, as a 2nd-line method for topical search for an insulin-producing pancreatic tumor.

Safety and efficacy of endoscopic ultrasound-guided radiofrequency ablation for pancreatic insulinoma: A single-center experience

Background/objectivesInsulinomas are rare, functioning pancreatic neuroendocrine neoplasms (pNEN), whose gold standard therapy is surgical resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a recent technique that has emerged as a minimally invasive therapeutic option for patients with pancreatic lesions not eligible for surgery. In this study, we aimed to describe a series of patients with unresectable pancreatic insulinoma treated with EUS-RFA. MethodsThis is a single-center, retrospective study including all consecutive patients with functioning pancreatic insulinoma undergoing EUS-RFA for surgical unfitness or surgery refusal, between March 2017 and September 2021. Technical success (i.e., complete mass ablation), adverse event rate and severity, clinical and radiologic outcomes (i.e., symptom remission with a normal concentration of blood glucose, and the presence of intralesional necrosis), and post-procedural follow-up were assessed. ResultsA total of 10 patients (mean age: 67.1 ± 10.1years; F:M 7:3) were included. The mean size of insulinoma was 11.9 ± 3.3 mm. Technical success and clinical remission were achieved in 100% of patients. Only one (10%) patient was successfully treated with two RFA sessions. Two procedure-related early adverse events occurred, including two (20%) cases of mild abdominal pain. No major complications were observed. The complete radiologic response within 3 months after EUS-RFA was observed in all patients (100%). After a median follow-up of 19.5 (range12–59) months, symptom remission and persistent euglycemia were assessed in all the patients. ConclusionsData from this case series suggest that EUS-RFA is a feasible and safe therapeutic approach for pancreatic insulinomas in patients unwilling or unable to undergo surgery with medium-term efficacy.

Left hemiparesis and urinary incontinence as presentation of pancreatic Insulinoma in a young female. A Case report and review of literature

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

Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI). Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis. Primary outcome was safety. Secondary outcomes were clinical efficacy, hospital stay, and recurrence rate after EUS-RFA. Using propensity score matching, 89 patients were allocated in each group (1:1), and were evenly distributed in terms of age, sex, Charlson comorbidity index, American Society of Anesthesiologists score, body mass index, distance between lesion and main pancreatic duct, lesion site, size, and grade. Adverse event (AE) rate was 18.0% and 61.8% after EUS-RFA and surgery, respectively (P < .001). No severe AEs were observed in the EUS-RFA group compared with 15.7% after surgery (P< .0001). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (P= .160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median, 23 months; interquartile range, 14-31 months vs 37 months; interquartile range, 17.5-67 months in the surgical group; P < .0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group; P < .0001). Fifteen lesions (16.9%) recurred after EUS-RFA and underwent a successful repeat EUS-RFA (11 patients) or surgical resection (4 patients). EUS-RFA is safer than surgery and highly effective for the treatment of PI. If confirmed in a randomized study, EUS-RFA treatment can become first-line therapy for sporadic PI.

Abstract #1323855: Endoscopic Ultrasound: A Modality With High Sensitivity to Diagnose Pancreatic Insulinoma

An insulinoma is a rare endocrine tumor of the pancreas that causes hypoglycemia through its inappropriate secretion of insulin. Insulinomas are usually benign tumors. Symptoms of hypoglycemia include both adrenergic and neuroglycopenic symptoms. Whipple’s triad should be confirmed as part of diagnostic work-up, but be aware that over time, hypoglycemia unawareness may develop and potentially confound the clinical picture. Early localization of the disease is essential to prevent fatal hypoglycemia.

Effect of chronic exposure to ketohexoses on pancreatic β-cell function in INS-1 rat insulinoma cells.

Glucotoxicity, impaired insulin secretion, suppression of insulin gene expression, and apoptosis, in pancreatic β-cells caused by chronic hyperglycemia is a key component of the pathogenesis of type 2 diabetes. Recently, it has been reported that rare sugar d-allulose has antihyperglycemic and antihyperlipidemic effects in diabetic rats. However, the direct effects of rare sugars including d-allulose on pancreatic β-cell function are unclear. In this study, we investigated whether chronic exposure to ketohexoses causes glucotoxicity, suppression of insulin gene expression, and apoptosis, in INS-1 rat pancreatic insulinoma cells. d-Fructose, d-tagatose, l-allulose, and l-sorbose treatment for 1-week reduced insulin gene expression, whereas d-allulose, d-sorbose, l-fructose, and l-tagatose did not. All ketohexoses were transported into INS-1 cells, but were not metabolized. In addition, the ketohexoses did not induce apoptosis and did not affect glucose metabolism. These results suggest that long-term administration of d-allulose, d-sorbose, l-fructose, and l-tagatose does not affect pancreatic β-cell function.

Enucleation of pancreatic insulinomas: early- and long-term results of open surgery in 43 yearsТ experience in a single center

Enucleation of pancreatic insulinomas: early- and long-term results of open surgery in 43 yearsТ experience in a single center

EUS-guided radiofrequency ablation of pancreatic/peripancreatic tumors and oligometastatic disease: an observational prospective multicenter study.

Background and study aims Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an emerging and minimally invasive technique that seems promising for treatment of focal pancreatic and peripancreatic lesions. Our aim was to prospectively evaluate the feasibility, safety, and technical and clinical success of pancreatic and extra-pancreatic EUS-RFA. Patients and methods We prospectively collected clinical and technical data for all patients who underwent EUS-RFA at two Belgian academic centers from June 2018 to February 2022. Feasibility, adverse events (AEs), and follow-up were also assessed. Results Twenty-nine patients were included, accounting for 35 lesions: 10 non-functioning neuroendocrine tumors (29 %), 13 pancreatic insulinomas (37 %), one adenocarcinoma (3 %), and 11 intra-pancreatic and extra-pancreatic metastatic lesions (31 %). Technical success was achieved in 100 % of cases, with a median of three power applications per lesion (interquartile range 2). The majority of patients (59 %) presented no collateral effects, three (10.3 %) developed non-severe acute pancreatitis, and four (14 %) had mild abdominal pain. At 6 months follow-up (n = 25), 36 % of patients showed radiological complete response, 16 % presented a significant partial response and 48 % showed < 50 % decrease in diameter. At 12 months (n = 20), 30 % showed complete necrosis and 15 % > 50 % decrease in diameter. Hypoglycemia related to insulinoma was immediately corrected in all 13 cases, with no recurrence during follow-up. Conclusions EUS-RFA is feasible, safe, and effective for treatment of pancreatic and peripancreatic tumors. Larger and longer multicenter prospective studies are warranted to establish its role in management of focal pancreatic lesions and oligometastatic disease. Symptomatic insulinoma currently represent the best indication.