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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 NFPNETs, 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. [ABSTRACT FROM AUTHOR]

ObjectivesTo develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs).MethodsA 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.ResultsA 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.ConclusionA novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.

Insulinomas are functioning pancreatic neuroendocrine tumors (NETs). They secrete insulin, and hence, present with hypoglycemia. We report a case of insulinoma in a 16-year-old girl presenting as seizures. She was initially managed at a private clinic and later commenced on carbamazepine when convulsion persisted. Convulsions were generalized, associated with dizziness and altered sensorium, often preceded by hunger and physical exertion, but relieved by the intake of carbonated drinks and fruit juice. She was referred to the neurology clinic when seizures persisted, despite the use of anticonvulsant. She was later referred to the endocrine clinic on suspicion of insulinoma when her random blood glucose (BG) was found to be low during an episode of convulsion. She was moderately obese but other examination findings were normal. She had a 72-hour prolonged fast, which was terminated when hypoglycemia (BG = 2.2 mmol/L) ensued after 12 hours, with elevated serum insulin and C-peptide. Abdominal magnetic resonance imaging scan showed a pancreatic tumor suggestive of insulinoma. She subsequently had distal pancreatectomy performed with complete resolution of symptoms. Unusual presentation of insulinoma may delay diagnosis, resulting in wastage of resources with increased morbidities and mortality. [ABSTRACT FROM AUTHOR]

Insulinomas 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. This 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. A 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. Data 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Dogs can develop a tumour of the pancreas that produces too much insulin, which is called an 'insulinoma'. These tumours cause signs such as collapse at exercise and very low blood sugar. Insulinomas are difficult to cure because they spread to other tissues very commonly. The diagnosis of an insulinoma requires the demonstration of the simultaneous occurrence of low blood glucose levels and either normal or elevated blood insulin levels. The diagnostic imaging of insulinomas in dogs is preferably conducted by taking computed tomography scans. In general, the surgical treatment of insulinomas is the preferred therapy because it results in the best survival times, but many dogs also require medical treatment at some point. The prognosis of dogs with insulinomas is guarded, because clinical symptoms relating to low blood sugar almost always return due to tumour regrowth or spread. This review paper aims to provide a summary and update the current recommendations in the veterinary literature for the diagnosis, treatment and clinical outcome of insulinomas in dogs. The contents of this review are comprehensive and relevant to veterinarians that work at all levels and will inform and advance our understanding of insulinomas in dogs. The most common pancreatic tumour in dogs is the insulinoma. Canine insulinomas are considered to be malignant in more than 95% of the cases because they almost always tend to metastasise. The diagnosis of an insulinoma requires the demonstration of the simultaneous occurrence of hypoglycaemia and blood insulin levels that are within or above the high end of the reference interval. The staging of canine insulinomas is preferably conducted by contrast-enhanced computed tomography. In general, surgical treatment is the most effective because of it results in long survival times, but many dogs also require medical treatment at some point. The prognosis of canine insulinomas is guarded as clinical hypoglycaemia almost always returns due to metastasis or tumour regrowth. This review aims to provide a summary and update the current recommendations in the veterinary literature for the diagnosis, treatment and prognostication of canine insulinomas. [ABSTRACT FROM AUTHOR]

Introduction: Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs); however, the available data are limited. Our aim was to assess the efficacy of FOLFOX (association of 5-fluorouracil with oxaliplatin) in a large series of patients with advanced digestive NETs. Methods: All patients with advanced digestive well-differentiated NETs treated with at least 3 cycles of FOLFOX between January 2004 and December 2018 in 12 centers from the French Group of Endocrine Tumors were included. Tumor response rate according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria, progression free survival (PFS), and overall survival, as well as prognostic factors, were analyzed retrospectively. Results: One hundred fifty-five patients were included. Primary tumor locations were pancreas (n = 89), small intestine (n = 40), unknown with no evidence for lung primary (n = 13), stomach (n = 7), and rectum (n = 6). Median Ki-67 was 10%, and 65% of the tumors were grade 2. The partial response rate was 30% for pancreatic NETs, 12.5% for small intestine NETs, 38.5% for unknown primary NETs, 14% for gastric NETs, and 17% for rectal NETs. Significant prognostic factors for poor PFS after FOLFOX were progressive disease at the beginning of treatment (hazard ratio [HR] = 1.83, p = 0.007), hepatic involvement superior to 50% (HR = 2.67, p = 0.0001), and rectal primary tumor location (HR = 2.6, p = 0.0036). Among pancreatic NETs, insulinomas had a better median PFS (22 months) than other pancreatic NETs (9 months, p = 0.026) and showed a high rate (8/9) of serum glucose normalization. Conclusions: FOLFOX shows a promising antitumor activity in advanced digestive NETs. Rapid symptomatic response is observed in metastatic insulinomas. [ABSTRACT FROM AUTHOR]

The most common pancreatic tumour in dogs is the insulinoma. Canine insulinomas are considered to be malignant in more than 95% of the cases because they almost always tend to metastasise. The diagnosis of an insulinoma requires the demonstration of the simultaneous occurrence of hypoglycaemia and blood insulin levels that are within or above the high end of the reference interval. The staging of canine insulinomas is preferably conducted by contrast-enhanced computed tomography. In general, surgical treatment is the most effective because of it results in long survival times, but many dogs also require medical treatment at some point. The prognosis of canine insulinomas is guarded as clinical hypoglycaemia almost always returns due to metastasis or tumour regrowth. This review aims to provide a summary and update the current recommendations in the veterinary literature for the diagnosis, treatment and prognostication of canine insulinomas.

Background/objectives: Insulinomas 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., Methods: This 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., Results: A 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., Conclusions: Data 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., Competing Interests: Declaration of competing interest Ivo Boskoski is a consultant for Apollo Endosurgery, Cook Medical, BostonScientific, and Nitinotes. Guido Costamagna is a consultant for Cook Medical, Boston Scientific, and Olympus. All the other authors have nothing to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

PET imaging of the glucagon-like peptide-1 receptor (GLP-1R) using radiolabeled exendin is a promising imaging method to detect insulinomas. However, high renal accumulation of radiolabeled exendin could hamper the detection of small insulinomas in proximity to the kidneys and limit its use as a radiotherapeutic agent. Here, we report two new exendin analogues for GLP-1R imaging and therapy, designed to reduce renal retention by incorporating a cleavable methionine-isoleucine (Met-Ile) linker. We examined the renal retention and insulinoma targeting properties of these new exendin analogues in a nude mouse model bearing subcutaneous GLP-1R-expressing insulinomas. NOTA or DOTA was conjugated via a methionine-isoleucine linker to the C-terminus of exendin-4 (NOTA-MI-exendin-4 or DOTA-MI-exendin-4). NOTA- and DOTA-exendin-4 without the linker were used as references. The affinity for GLP-1R was determined in a competitive binding assay using GLP-1R transfected cells. Biodistribution of [ 68 Ga]Ga-NOTA-exendin-4, [ 68 Ga]Ga-NOTA-MI-exendin-4, [ 177 Lu]Lu-DOTA-exendin-4, and [ 177 Lu]Lu-DOTA-MI-exendin-4 was determined in INS-1 tumor-bearing BALB/c nude mice, and PET/CT was acquired to visualize renal retention and tumor targeting. For all tracers, dosimetric calculations were performed to determine the kidney self-dose. The affinity for GLP-1R was in the low nanomolar range (<11 nM) for all peptides. In vivo biodistribution revealed a significantly lower kidney uptake of [ 68 Ga]Ga-NOTA-MI-exendin-4 at 4 h post-injection (p.i.) (34.2 ± 4.2 %IA/g), compared with [ 68 Ga]Ga-NOTA-exendin-4 (128 ± 10 %IA/g). Accumulation of [ 68 Ga]Ga-NOTA-MI-exendin-4 in the tumor was 25.0 ± 8.0 %IA/g 4 h p.i., which was similar to that of [ 68 Ga]Ga-NOTA-exendin-4 (24.9 ± 9.3 %IA/g). This resulted in an improved tumor-to-kidney ratio from 0.2 ± 0.0 to 0.8 ± 0.3. PET/CT confirmed the findings in the biodistribution studies. The kidney uptake of [ 177 Lu]Lu-DOTA-MI-exendin-4 was 39.4 ± 6.3 %IA/g at 24 h p.i. and 13.0 ± 2.5 %IA/g at 72 h p.i., which were significantly lower than those for [ 177 Lu]Lu-DOTA-exendin-4 (99.3 ± 9.2 %IA/g 24 h p.i. and 45.8 ± 3.9 %IA/g 72 h p.i.). The uptake in the tumor was 7.8 ± 1.5 and 11.3 ± 2.0 %IA/g 24 h p.i. for [ 177 Lu]Lu-DOTA-MI-exendin-4 and [ 177 Lu]Lu-DOTA-exendin-4, respectively, resulting in improved tumor-to-kidney ratios for [ 177 Lu]Lu-DOTA-MI-exendin-4. The new exendin analogues with a Met-Ile linker showed 2-3-fold reduced renal retention and improved tumor-to-kidney ratios compared with their reference without the Met-Ile linker. Future studies should demonstrate whether [ 68 Ga]Ga-NOTA-MI-exendin-4 results in improved detection of small insulinomas in close proximity to the kidneys with PET/CT. [ 177 Lu]Lu-DOTA-MI-exendin-4 might open a window of opportunity for exendin-based radionuclide therapy.

Background: Radiofrequency ablation (RFA) has been used to treat various abdominal tumors including pancreatic tumors. Multiple approaches such as laparoscopic, open, and percutaneous have been used for pancreatic tissue ablation. More recently, endoscopic ultrasound (EUS)-guided RFA has emerged as a new technique for pancreatic tissue ablation. The role of EUS-RFA in management of pancreatic lesions is still not well-established. In this study, our aim is to assess efficacy and safety of EUS-RFA for management of pancreatic lesions., Methods: MEDLINE, Scopus, and Cochrane Library databases were searched to identify studies reporting EUS-RFA of pancreatic lesions with outcomes of interest. Studies with <5 patients were excluded. Clinical success was defined as symptom resolution, decrease in tumor size, and/or evidence of necrosis on radiologic imaging. Efficacy was assessed by the pooled clinical response rate whereas safety was assessed by the pooled adverse events rate. Heterogeneity was assessed using I 2 . Pooled estimates and the 95% CI were calculated using random-effect model., Results: Ten studies (5 retrospective and 5 prospective) involving 115 patients with 125 pancreatic lesions were included. 152 EUS-RFA procedures were performed. The lesions comprised of 37.6% non-functional neuroendocrine tumors (NFNETs), 15.4% were insulinomas, 26.5% were pancreatic cystic neoplasms (PCNs), and 19.7% were pancreatic adenocarcinomas. The majority were present in the pancreatic head (40.2%), 38.3% in the body, 11.2% in the tail, and 10.3% in the uncinate process. Pooled overall clinical response rate was 88.9% (95% CI: 82.4-93.7, I 2 =38.1%). Pooled overall adverse events rate was 6.7% (95% CI: 3.4-11.7, I 2 =34.0%). The most common complication was acute pancreatitis (3.3%) followed by pancreatic duct stenosis, peripancreatic fluid collection, and ascites (2.8%) each. Only one case of perforation was reported with pooled rate of (2.1%)., Discussion: This study demonstrates that EUS-RFA is an effective treatment modality for pancreatic lesions, especially functional neuroendocrine tumors such as insulinomas., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-20-84/coif). The authors have no conflicts of interest to declare., (2022 Translational Gastroenterology and Hepatology. All rights reserved.)

Background: Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) has recently been proposed as a local treatment for functional pancreatic neuroendocrine neoplasms in patients unfit for surgery, in order to obtain clinical syndrome regression. Data on the safety and long-term effectiveness of this approach are scarce, and EUS-RFA procedures are not standardized., Case Summary: The present case series reports 3 elderly patients with a pancreatic insulinoma and comorbidities, locally treated by EUS-guided RFA with clinical success in terms of hypoglycemic symptoms. RFA procedures were performed during deep sedation, under EUS control with a 19 G needle, an electrode 5-mm in size at a power of 30 W and multiple RFA applications during the same session in order to treat the whole area of the lesions. Immediate relief of symptoms was evident in 2 patients after the first EUS-RFA, while in the third patient a second endoscopic treatment was needed. All 3 patients are symptom-free without need of medications after 24 mo of follow-up with imaging follow-up showing no disease recurrence. A single adverse event of intraprocedural bleeding occurred, which was successfully treated endoscopically., Conclusion: EUS-RFA represents an effective and safe alternative to surgery for the treatment of insulinomas in elderly patients at high surgical risk. However, larger multicenter studies with longer follow-up are needed in order to better assess its safety and clinical success., Competing Interests: Conflict-of-interest statement: The authors have note conflicts of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)