Pancreatic Insulinoma Research Articles

Insulinoma with suspected mutant somatostatin receptor expression according to histological examination.

This case highlights the possibility of an insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression. Insulinoma is a pancreatic disease that causes hyperinsulinemic hypoglycemia. The first-line treatment is surgery; however, somatostatin derivatives are administered in cases where surgery is not a viable option and to prevent preoperative hypoglycemia. Here, we report a case in which preoperative examination indicated a potential tumor with low somatostatin receptor 2 (SSTR2) and SSTR5 expression, whereas postoperative pathological examination indicated strong SSTR expression. We report the case of a 69-year-old Japanese female who experienced hypoglycemia-like symptoms for a decade such as sweating, fatigue, hunger, and confusion with an increase in episode frequency per year. Dynamic computed tomography revealed a 13-mm diameter nodule and aberrant blood flow in the pancreatic tail. Subsequently, the patient was diagnosed with pancreatic insulinoma. A preoperative octreotide test did not relieve hypoglycemia, and no uptake of 111indium-pentetreotide was observed, suggesting an insulinoma with low SSTR expression. However, postoperative histological studies suggested that the intracellular domain of SSTRs were highly expressed, while the extracellular domain may be mutated. We present a rare case of insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression.

Pancreatic insulinomas: Our 15-year surgical experience.

Insulinomas are rare endocrine tumors of the pancreas. The majority are benign, sporadic, and solitary. Surgery is the only curative treatment. In this study, we present our experiences with the perioperative management of sporadic and benign pancreatic insulinomas. Patients who underwent surgery for pancreatic insulinoma in our clinic between 2008 and 2023 were retrospectively reviewed. Demographic data, preferred radiological methods, surgical procedures, and morbidity and mortality data were evaluated. Patients with malignant, invasive, or familial multiple endocrine neoplasia mutations were excluded from the study. Nineteen patients underwent surgery, with a median age of 49 years (range: 33-85). Symptoms related to hypoglycemia were the most commonly observed. The tumor location was identified preoperatively in 74% of cases using computed tomography. Palpation and intraoperative ultrasound identified the tumor location in 88% of patients. Enucleation (53%) were the most common surgical procedures. Pancreatic fistula occurred in three patients (17%). While serious morbidity was lower in patients who underwent enucleation, the rate of fistula formation was higher. The accurate localization of insulinomas plays a crucial role in determining the appropriate surgical procedure. With high success rates and lower morbidity, enucleation is the recommended procedure for suitable patients.

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

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. 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. 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. 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.

Challenges in Managing Insulinomas and Hyperparathyroidism in MEN1: A Clinical Case Study

Pancreatic insulinoma is an uncommon neuroendocrine tumor with an incidence of approximately 1 per million people annually. While the majority of insulinomas are sporadic, a minority are associated with Multiple Endocrine Neoplasia type 1 (MEN1), a rare genetic disorder transmitted in an autosomal dominant pattern. MEN1 is characterized by the presence of hyperplastic or adenomatous parathyroid glands, pancreatic islet cell tumors, and pituitary tumors. The disorder can also involve lesions in the duodenum, adrenal glands, thymus, and bronchi. We report a case of MEN1 presenting with multiple insulinomas in a 37-year-old male, who exhibited symptoms of intermittent hypoglycemia over a decade. Diagnostic workup included biochemical assays , and imaging studies that revealed elevated insulin and C-peptide levels and hypervascular pancreatic lesions, , and pathological findings consistent with MEN1. Surgical intervention involved the enucleation of insulinomas and distal pancreatectomy, followed by removal of parathyroid adenomas. The postoperative evolution was marked by the resolution of hypoglycemic episodes and the persistence of primary hyperparathyroidism. This case underscores the complexity of diagnosing and managing insulinomas within the context of MEN1. It highlights the importance of a multidisciplinary approach to treatment and the need for ongoing surveillance to address both endocrine manifestations and psychological impacts. The findings advocate for comprehensive management strategies and support systems to improve patient outcomes and quality of life.

12450 Beyond the Surface: A Deep Dive into Pancreatic Insulinoma

Abstract Disclosure: S. Bhandari: None. R. Elhag: None. J. Singh: None. N. Rastogi: None. Background: Pancreatic neuroendocrine tumors (NET) are rare lesions that are typically sporadic, solitary and usually <2cm in diameter, with reported incidence of 4 cases per 1 million patients per year[1]. The most common hormone secreting NET are insulinomas. The hallmark of insulinomas is hypersecretion of insulin, leading to neuroglycopenic symptoms and uncontrolled sympathoadrenal activity. Clinical case: 51 years old female with no significant past medical history was referred to endocrine clinic by her primary care physician for hypoglycemia with a blood glucose level of 48 mg/dl. She reported an increased frequency of headaches and dizziness which began with intermittent fasting (10-12 hours) for past 6 months. These symptoms improved upon increasing meal frequency. Initial laboratory investigations revealed glucose of 54 mg/dl, normal HbA1c, and negative sulfonylurea panel. The patient had normal liver and kidney function with no malnutrition or malabsorption issues. Further work up showed C-peptide level 1.56 ng/ml (n 0.80-3.85ng/ml), insulin level 7.9 uIU/mL (n <18.4 uIU/mL), pro-insulin level significantly elevated at 77.6 pmol/L (n </= 18.8pmol/L) and beta hydroxybutyrate of 0.12 mmol/l (n 0.02-0.27mmol/l). Insulin like growth factor was normal. Insulin antibodies were negative, and pituitary hormones were within normal limits. Pancreatic ultrasound was normal. CT abdomen/pelvis showed a 0.8x1.1 cm homogenously hypervascular anterior pancreatic body soft tissue lesion consistent with NET. Patient was started on diazoxide and continuous glucose monitoring (CGM). She was referred to general surgery and underwent successful tumor resection. Insulinoma is suggested by Whipple's triad, which is presence of hypoglycemic symptoms, documented hypoglycemia and resolution of hypoglycemic symptoms after glucose administration. As clinical manifestations are non-specific, diagnosing an insulinoma is challenging and depends on collateral history and a high index of suspicion. The gold standard of diagnosis is supervised 72-hour fasting test with plasma glucose, insulin, C-peptide, and proinsulin level measurements. Medical management of insulinoma includes the use of diazoxide, calcium channel blockers, propranolol, and glucocorticoids. Surgery is definitive treatment for insulinomas, with cure rates ranging from 77 to 100%. Conclusion: Insulinomas are benign and curable in most cases but can be fatal if misdiagnosed. Incidental findings of hypoglycemia should warrant thorough diagnostic workup to facilitate timely diagnosis and management.

5104 Ectopic Insulinoma- a Rare Presentation of a Rare Tumor

Abstract Disclosure: O. Lavrynenko: None. A. DeMarsilis: None. C. Jiang: None. R. Middelbeek: None. H. Rosen: None. M.E. Patti: None. Background. Insulinoma is a rare, functioning neuroendocrine tumor (NET) typically localized within the pancreas, that secretes insulin, resulting in hypoglycemia. Ectopic insulinoma is even more rare than pancreatic insulinoma and is more difficult to diagnose. Case report. This 31-year-old previously healthy woman, who had an uncomplicated pregnancy and a healthy baby in October 2021, presented with intermittent hypoglycemia for more than 8 months. She denied any prior use of insulin or antidiabetic medications and was not currently taking any medications at all. There is no history of bariatric or other GI surgery. While nursing her baby in early 2022, she was noted to have a capillary blood glucose (BG) between 20-30 mg/dl, and reported both adrenergic and neuroglycopenic symptoms of hypoglycemia; these usually occurred in the morning or before lunch, especially if lunch was delayed. She wore a Libre CGM which revealed episodic hypoglycemia, which correlated with her timeline of symptoms. She reported weight gain of 8 lbs during this period. Laboratory data obtained after a 10-12 hour fast revealed hypoglycemia (venous glucose 39 mg/dL) with inappropriately high plasma insulin (42.3 mIU/ml), C- peptide (3.78 ng/ml), and proinsulin (99 pmol/L). Beta-hydroxybutyrate was 0.05 mmol/L (reference <0.28) and insulin autoantibody and sulfonylurea screen were negative. Various imaging modalities for localization revealed a solitary omental mass outside the pancreas consistent with extra-pancreatic insulinoma. No pancreatic lesion or other findings were observed with MRCP, CT C/A/P or endoscopic ultrasound. The patient underwent CT-guided biopsy of the omental mass, which confirmed a well-differentiated NET, consistent with insulinoma. Due to persistent hypoglycemia, she was started on corn starch and diazoxide. She subsequently underwent laparoscopic resection of the mass. Postoperative pathology revealed a well-differentiated NET staining positive for insulin, consistent with an extra-pancreatic insulinoma. Following surgical resection of the insulinoma, her hypoglycemia resolved even off corn starch and diazoxide. Conclusion. Ectopic insulinoma is a rare insulin-secreting NET. Only 28 ectopic insulinomas have been described in the literature to date1. We describe a patient with symptomatic hypoglycemia who was found to have an omental neuroendocrine tumor; hypoglycemia completely resolved after laparoscopic enucleation of the ectopic insulinoma. 1Fernando Guerrero-Pérez, Nuria Vialarrasa, Lidia V. Huanuco et. al. Ectopic Insulinoma: a systemic review: Reviews in Endocrine and Metabolic Disorders, 2023 Presentation: 6/1/2024

Insulinoma in Patients with Diabetes- A Systematic Review of Previously Reported Cases

Abstract Introduction: Paradoxical co-existence of insulinoma and diabetes is extremely rare. Although a few case reports addressed this association, a comprehensive study elucidating this relationship has been lacking. We performed a systematic review of published cases of insulinoma in diabetes. Methods: We conducted a literature search using PubMed and Google Scholar, employing various combinations of the following terms: ‘insulinoma’, ‘diabetes’, ‘nesidioblastosis’, ‘endogenous hyperinsulinism’, ‘hypoglycaemia’, and ‘hyperglycaemia’ (from January 1900 to January 30, 2024). Exclusion criteria included non-English publications, duplicate articles, reports lacking sufficient data, cases of endogenous hyperinsulinemic hypoglycaemia other than insulinoma, and inaccessible articles. Statistical analysis was performed using appropriate methods. Results: Sixty patients were considered for the final analysis. Mean age was 61 ± 15 years (range: 17–96 years) with a slight female preponderance; 88.3% had type-2 diabetes with a median duration of 8 years. The median delay in diagnosis of insulinoma was 6 months. Median blood glucose varied from 30.5 mg/dL to 235 mg/dL, with a mean HbA1c of 5.6 ± 1.3% (range: 2.9%–8.2%). Critical sampling data were available in 75% of cases. The median size of the insulinoma was 2 cm. Furthermore, 5.2% of insulinomas were extra-pancreatic. Among pancreatic insulinomas, 14.5% were multi-focal. One-third of cases were malignant. Surgical resection was done in 70.9% of cases, while 40% received drug therapy and 12.7% received both, with 20.7% overall mortality. Malignant insulinoma (P = 0.007), micro-angiopathic (P = 0.018) and macro-angiopathic complications (P = 0.039), and other co-morbidities (P = 0.009) were associated with unfavourable prognosis, while being overweight and obese (P = 0.020) at presentation was associated with favourable prognosis. Conclusion: This first systematic review provides insights into the uniqueness of insulinoma in diabetes.

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

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.

Aggressive Metastatic Insulinoma in a Patient of Diabetes Mellitus with Documentation on Dual-Tracer PET-CT ([68Ga]Ga-DOTATATE and [18F]FDG): Clinical Benefits with Combined Chemo-PRRT Approach

AbstractInsulinoma is a relatively uncommon pancreatic neuroendocrine tumor, with approximately 10% of the cases being malignant. Diabetes mellitus (DM) with concurrent insulinoma is very rare and the diagnosis of such condition is easily missed as it can be misconstrued as improved glycemic control. Therefore, persistent hypoglycemic symptoms even after stopping antidiabetic medications may be considered for insulinoma. Herein, we present a patient with DM and pancreatic insulinoma with extensive hepatic and skeletal metastases on dual-tracer positron emission tomography/computed tomography (PET/CT) ([68Ga]Ga-DOTATATE and [18F]fluorodeoxyglucose). Given the extensive disease, the patient was treated with a combination of peptide receptor radionuclide therapy (PRRT) and chemotherapy (capecitabine and temozolomide). During therapy, patient showed early clinical and imaging response for insulinoma leading to unmasking of poor glycemic control necessitating requirement of insulin administration for DM. The patient did not experience any life-threatening hypoglycemia during the chemo-PRRT treatment and showed an improvement in quality of life. Unfortunately, the disease progressed at the 4th cycle, 10 months after the initiation of PRRT. We conclude that combined chemo-PRRT may be considered an effective treatment option for patients with metastatic insulinoma and DM owing to its favorable imaging response and effective symptom control.

Detective flow imaging endoscopic ultrasound for localizing pancreatic insulinomas that are undetectable with other imaging modalities.

Detective flow imaging endoscopic ultrasound for localizing pancreatic insulinomas that are undetectable with other imaging modalities.

Induction of islet autoimmunity to defective ribosomal product of the insulin gene as neoantigen after anti-cancer immunotherapy leading to autoimmune diabetes.

The autoimmune response in type 1 diabetes (T1D), in which the beta cells expressing aberrant or modified proteins are killed, resembles an effective antitumor response. Defective ribosomal protein products in tumors are targets of the anti-tumor immune response that is unleashed by immune checkpoint inhibitor (ICI) treatment in cancer patients. We recently described a defective ribosomal product of the insulin gene (INS-DRiP) that is expressed in stressed beta cells and targeted by diabetogenic T cells. T1D patient-derived INS-DRiP specific T cells can kill beta cells and are present in the insulitic lesion. T cells reactive to INS-DRiP epitopes are part of the normal T cell repertoire and are believed to be kept in check by immune regulation without causing autoimmunity. T cell autoreactivity was tested using a combinatorial HLA multimer technology measuring a range of epitopes of islet autoantigens and neoantigen INS-DRiP. INS-DRiP expression in human pancreas and insulinoma sections was tested by immunohistochemistry. Here we report the induction of islet autoimmunity to INS-DRiP and diabetes after ICI treatment and successful tumor remission. Following ICI treatment, T cells of the cancer patient were primed against INS-DRiP among other diabetogenic antigens, while there was no sign of autoimmunity to this neoantigen before ICI treatment. Next, we demonstrated the expression of INS-DRiP as neoantigen in both pancreatic islets and insulinoma by staining with a monoclonal antibody to INS-DRiP. These results bridge cancer and T1D as two sides of the same coin and point to neoantigen expression in normal islets and insulinoma that may serve as target of both islet autoimmunity and tumor-related autoimmunity.

Endoscopic Ultrasound-Guided Radiofrequency Ablation as Therapeutic Approach for Pancreatic Insulinoma

Insulinoma is one of the most prevalent form of functional neuroendocrine tumor of the pancreas (PNET) that often manifests with debilitating symptomatic hypoglycemia. When conventional imaging fails to detect the lesion, endoscopic ultrasound (EUS) have proven to be of value to determine the preoperative localisation as well as with biochemical sampling via fine needle aspiration of the suspected lesion. Surgical resection has been the standard care for these pancreatic neuroendocrine tumors. However, with recent advancements, endoscopicultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a promising and less invasive therapeutic approach that carries a favourable outcome and a low risk of complications. We report eda patient with symptomatic pancreatic insulinoma who was treated with EUS-RFA.

Enucleation of a solitary pancreatic tail insulinoma: a case report and review of the literature

Introduction: Insulinomas are the most common pancreatic neuroendocrine tumors. They secrete insulin and result in endogenous hyperinsulinaemic hypoglycemia. The diagnosis of insulinoma was classically based on the fulfillment of Whipple’s triad; hypoglycaemia (plasma glucose <50mg/dL), neuroglycopaenic symptoms, and the prompt relief of such symptoms with the administration of glucose. Preoperative localization of the insulinoma will help to plan the type of surgery necessary, either enucleation or pancreatic resection, and also decide on the approach, either open or laparoscopic. Case description: A 53-year-old farmer presented with neuroglycopenia symptoms with biochemical evidence of endogenous hyperinsulinaemic hypoglycemia during the mixed meal test. Imaging evidence in the form of CT and MRI showed a benign, approximately 1cm, solitary pancreatic tail insulinoma. Intraoperative ultrasonography confirmed the findings and the patient underwent enucleation of the tumor. Histology revealed a grade 2 pancreatic neuroendocrine tumor with confirmation of an insulinoma on immunohistochemistry. Conclusion: Pancreatic insulinomas, a rare pancreatic tumor, the commonest of the pNET present with neuroglycopenia. Diagnosis entails biochemical confirmation of endogenous hyperinsulinaemic hypoglycemia on a 72-hour prolonged fasting test. Noninvasive imaging in the form of CT as the first line, followed by MRI is used for localization and assessment of resectability. EUS and ASVS are additional invasive imaging in diagnostic difficulty. Enucleation and intraoperative ultrasonography is the treatment of choice for small, benign, pancreatic insulinomas.

P-43 Pancreatic insulinoma with delayed challenging diagnosis by 68Ga-DOTATATE PET/CT scan: Case report

Abstract Introduction Insulinoma (I) is most common neuroendocrine pancreatic tumor with an incidence of 0.1-0.3/100000(1). It is faintly more in females and can develop at any age(2). Usually benign, sporadic, less than 2 cm, solitary and in 10% of cases is multiple and happens as a component of multiple endocrine neoplasia syndrome type I (MEN–I)(3). Nonspecific symptoms may lead to delayed or misdiagnosis. Improper insulin secretion causes clinical features of hypoglycemia(2). Laboratory verification, localization followed by surgical removal are the main steps management. Localization may be difficult and delayed as here. Clinical Case A female of 58 years old with episodes of sweating, palpitation and tremor improved by drinking sweets, weight gain and denied any drugs intake. No personal or family history of diabetes or antidiabetic drugs. Body weight was 87 kg. Investigations during the attack showed low plasma glucose of 36 mg/dL, high serum insulin of 94.8 mIU/L (1.7 - 31), elevated C-peptide of 10.6 ng/mL (0.9-4). Cortisol and thyroid function are normal. Abdominal ultrasound (US), CT scan and MRI are normal. Due to failure of localization of Insulinoma, treatment by diazoxide started with no response. Octreotide long-acting repeatable (Octreotide LAR) 20 mg monthly injection was initiated and increased to 30 mg monthly with good improvement and less attacks. After three years, the patient developed abdominal pain and abdominal US showed multiple gall stones. The patient was advised to do 68Ga-DOTATATE PET/CT Scan, which revealed distal pancreatic mass of 26 mm (Figure1A and B). Distal pancreatectomy and cholecystectomy had been done with smooth postoperative period normal normal plasma glucose, insulin and c-peptide with no further hypoglycemia, histopathological examination confirmed Insulinoma (Figure 2A and B). Hypoglycemic symptoms of I, whether neuroglycopenic or sympathoadrenal are precipitated by fasting or exercise and could precede diagnosis by months and even years(3). Insulinoma, should be suggested when patient has typical Whipple's triad, high insulin, c-peptide and proinsulin during the attack(3). Weight gain noted in about 18% of cases(4). Modalities used to localize Insulinoma include trans-abdominal US, CT scan, MRI, EUS (endoscopic ultrasound), intraoperative US, intraoperative palpation and arteriography. An American study considered 68Ga-DOTATATE PET/CT as an adjuvant tool for diagnosis with 90% detection rate (5). A 90-95% of cases are benign, patients have high survival with complete resolution of symptoms after excision with only 5.4% recurrences(6). Malignant I limited to pancreas and responsive to chemotherapy has 5 years survival rate after resection and 19 months for recurrent tumors(6). Conclusion Insulinoma should be considered in patients with typical clinical and laboratory finding. Follow up, assessment and different imaging techniques are main steps in management with teamwork.Figure 1.68Ga-DOTATATE PET/CT Scan68Ga-DOTATATE PET/CT Scan revealed distal pancreatic mass of 26 mm

Robotic enucleation of pancreatic insulinoma

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 «turbidity of consciousness» 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.

Mismatched pre and postoperative diagnosis in pancreatic insulinomas: how leopard effect does not affect survival in a 20-year follow-up experience

Mismatched pre and postoperative diagnosis in pancreatic insulinomas: how leopard effect does not affect survival in a 20-year follow-up experience

A case of pancreatic glans insulinoma with low C-peptide level

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Dr. Allen Oldfather Whipple (1881-1963): Namesake of the pancreaticoduodenectomy.

Allen O. Whipple was an American surgeon who popularized the pancreaticoduodenectomy (Whipple procedure) for periampullary cancer, which remains the gold standard for pancreatic tumor resections. Whipple was educated at Princeton University (B.S., 1904) and Columbia University College of Physicians and Surgeons (M.D., 1908). He swiftly ascended the academic ranks, culminating in his appointment as Professor of Surgery at Columbia and Director of Surgical Services at Presbyterian Hospital in 1921. Whipple published three criteria (Whipple's triad) for evaluating hyperinsulinism secondary to pancreatic insulinoma. He also revived interest in portocaval anastomosis to reduce portal hypertension, determining it to be a consequence of liver disease. During his 40-year career, Whipple introduced the concept of multidisciplinary teams and prospective data collection. He also shaped the structure of surgical training as President of the American Surgical Association and Chairman of the American Board of Surgery. Beyond the walls of the operating room, Whipple was a Renaissance Man whose childhood in Persia (Iran) engendered a lifelong interest in the region's art, culture, history, and medicine. Dr. Allen Oldfather Whipple is remembered as a pioneering physician and surgeon beloved by those who trained under him.

Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic β cells

Impeding or reducing human amylin aggregation and/or its toxicity can be key to preventing pancreatic islet amyloidosis and β-cell loss in patients with Type 2 Diabetes Mellitus (T2DM). Here, Punica granatum (pomegranate) peel, Sideritis raeseri (ironwort) and Aronia melanocarpa (chokeberry) leaf extracts, were tested for their novel anti-aggregative and antitoxic properties in human amylin (hIAPP) treated rat pancreatic insulinoma (INS) cells. The protein aggregation (Th-T) assay revealed an inhibitory trend of all three plant extracts against amylin aggregates. In agreement with this finding, pomegranate peel and ironwort extracts effectively prevented the transition of hIAPP from disordered, random coil structures into aggregation prone β-sheet enriched molecular assemblies, revealed by CD spectroscopy. Consistent with their anti-aggregative action, all three extracts prevented, to various degrees, reactive oxygen species (ROS) accumulation, mitochondrial stress, and, ultimately, apoptosis of INS cells. Collectively, the results from this study demonstrate effectiveness of natural products to halt hIAPP aggregation, redox stress, and toxicity, which could be exploited as novel therapeutics against amylin-derived islet amyloidosis and β-cell stress in T2DM.

Ethanol Ablation for Benign Insulinoma: Intraoperative and Endoscopic Approaches

IntroductionEthanol ablation can be utilized to manage insulinoma. We aimed to analyze our outcomes of endoscopic ultrasound (EUS) and intraoperative ultrasound (IOUS) guided Ethanol ablation of insulinoma. MethodsA single institution retrospective review of adults undergoing Ethanol ablation of benign pancreatic insulinoma (2007-2022) was performed. Outcomes were categorized as resolution of hypoglycemia, improvement, or no change at last follow-up. ResultsA total of 16 patients underwent Ethanol ablation of benign insulinoma (N = 8 EUS, N = 8 IOUS): median age was 68 y, 8 (50%) were females, and 2 (12.5%) were associated with multiple endocrine neoplasia type-1. Median insulinoma size was 12 (range 7, 25) mm. Ethanol ablation was preferred over resection to avoid pancreaticoduodenectomy when it was not possible to enucleate the tumor in 10 (62.5%) patients while the rest underwent ablation due to being poor surgical candidates or because of a history of previous pancreatic resection. The median follow-up (interquartile range) was 43 (19.5, 81.5) mo. Resolution of hypoglycemia occurred in 11 patients (5 EUS, 6 IOUS), while the rest (3 EUS, 2 IOUS) experienced improvement in the severity and frequency of hypoglycemia. A single patient underwent resection following a previous ablation for symptomatic hypoglycemia 5 y after EUS guided ablation. ConclusionsEthanol ablation provides an alternative therapeutic option for patients with insulinoma. Both EUS and IOUS guided approaches are associated with a favorable resolution rate although EUS guided ablation may require multiple procedures to optimize outcomes.