Despite growing interest in EUS-guided ablation for pNETs, the evidence base remains limited. Most studies are retrospective or observational, include relatively small cohorts, and vary in patient sel

The gap

Consensus across the literature

Supporting evidence — 3 representative gaps

• Mo1192 A CHANGING MAP OF GASTRIC CANCER IN THE UNITED STATES: 20- YEAR TRENDS REVEAL PERSISTENT AND EMERGING HIGH-RISK REGIONS (2026) · doi

  EUS imaging is useful not only for detection and characterization of small pNETs, but also for precise localization during laparoscopic/robotic surgery by performing EUS-guided tattooing preoperatively, using either sterile India ink or indocyanine green [12]. Although surgery is the mainstay for pNETs, other locally ablative therapies like EUS-guided radiofrequency ablation (EUS-RFA) have been described in a limited number of cases (N=61 patients with 73 tumors with the mean size of 16 mm, one third insulinomas) [13]. The overall effectiveness of 96%, for functional and non-functional pNETs, as well as the mild adverse events (13.7%) indicates the method might be reasonable for small pNETs, especially for patients unfit for surgery. Gastro-Entero-Pancreatic Neuroendocrine Tumors What is New in Gastroenterology and Hepatology 65 Targeting somatostatin receptors with similar agents for both imaging and therapy paved the way to theranostic applications and molecular targeting of these exotic tumors. Other studies targeted the C-X-C motif chemokine receptor 4 (CXCR4), because it is overexpressed in high-grade GEP-NETs and can be used as a therapeutic target, even in somatostatin receptor negative NETs. Other receptors are also targeted: glucagon-like peptide-1 (GLP-1) receptor for insulinoma, cholecystokinin 2 receptor (CCK2R) for gastric and pancreatic NETs, etc. [14]. Various other targeted radionuclides are currently assessed for both diagnosis and therapy (11Carbon, 212Lead, 177Lutetium, using innovative approaches: targeting with antagonists instead of agonists, alpha instead of beta particles, intra-arterial versus intravenous administration, combination therapy, etc. [14]. 55Cobalt, etc.), 166Holmium, 212Bismuth, 64Copper, 90Ytrium, gastro-entero-pancreatic neuroendocrine tumors, not being very frequent, are quite difficult lesions, but new developments in the diagnosis and management of these diseases give hope for a better therapeutic approach. CONSENT FOR PUBLICATION Not applicable. CONFLICT OF INTEREST The author confirms that this chapter contents have no conflict of interest. ACKNOWLEDGEMENTS Declared none. REFERENCES [1] Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31(7): 844-60. [http://dx.doi.org/10.1016/j.annonc.2020.03.304] [PMID: 32272208] [2] Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012; 61(1): 6-32. [http://dx.doi.org/10.1136/gutjnl-2011-300831] [PMID: 22052063] [3] Ma ZY, Gong YF, Zhuang HK, et al. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol 2020; 26(19): 2305-22. [http://dx.doi.org/10.3748/wjg.v26.i19.2305] [PMID: 32476795] [4] [5] Amin MB, Edge S, Greene F, Eds. AJCC Cancer Staging Manual. 2017. [http://dx.doi.org/10.1007/978-3-319-40618-3] Kunz PL, Reidy-Lagunes D, Anthony LB, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas 2013; 42(4): 557-77. [http://dx.doi.org/10.1097/MPA.0b013e31828e34a4] [PMID: 23591432] 66 What is New in Gastroenterology and Hepatology Săftoiu and Constantinescu [6] [7] [8] [9] Zhang MY, He D, Zhang S. Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment. World J Gastrointest Oncol 2020; 12(7): 705- 18. [http://dx.doi.org/10.4251/wjgo.v12.i7.705] [PMID: 32864039] Shah MH, Goldner WS, Halfdanarson TR, et al. NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018. J Natl Compr Canc Netw 2018; 16(6): 693-702. [http://dx.doi.org/10.6004/jnccn.2018.0056] [PMID: 29891520] Ito T, Jensen RT. Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management. Curr Opin Endocrinol Diabetes Obes 2017; 24(1): 15-24. [PMID: 27875420] I, Grozinsky-Glasberg S.

  Keywords: neuroendocrine tumors http pmid pancreatic management pnets receptor nets guidelines imaging surgery targeting therapy targeted
• 1101 SURGICAL MANAGEMENT AND SMALL BOWEL TRANSPLANTATION IN PATIENTS UNDERWENT TOTAL ENTERECTOMY. TECHNICAL ASPECTS AND TREATMENT SPECIFIC OUTCOMES. (2026) · doi

  EUS imaging is useful not only for detection and characterization of small pNETs, but also for precise localization during laparoscopic/robotic surgery by performing EUS-guided tattooing preoperatively, using either sterile India ink or indocyanine green [12]. Although surgery is the mainstay for pNETs, other locally ablative therapies like EUS-guided radiofrequency ablation (EUS-RFA) have been described in a limited number of cases (N=61 patients with 73 tumors with the mean size of 16 mm, one third insulinomas) [13]. The overall effectiveness of 96%, for functional and non-functional pNETs, as well as the mild adverse events (13.7%) indicates the method might be reasonable for small pNETs, especially for patients unfit for surgery. Gastro-Entero-Pancreatic Neuroendocrine Tumors What is New in Gastroenterology and Hepatology 65 Targeting somatostatin receptors with similar agents for both imaging and therapy paved the way to theranostic applications and molecular targeting of these exotic tumors. Other studies targeted the C-X-C motif chemokine receptor 4 (CXCR4), because it is overexpressed in high-grade GEP-NETs and can be used as a therapeutic target, even in somatostatin receptor negative NETs. Other receptors are also targeted: glucagon-like peptide-1 (GLP-1) receptor for insulinoma, cholecystokinin 2 receptor (CCK2R) for gastric and pancreatic NETs, etc. [14]. Various other targeted radionuclides are currently assessed for both diagnosis and therapy (11Carbon, 212Lead, 177Lutetium, using innovative approaches: targeting with antagonists instead of agonists, alpha instead of beta particles, intra-arterial versus intravenous administration, combination therapy, etc. [14]. 55Cobalt, etc.), 166Holmium, 212Bismuth, 64Copper, 90Ytrium, gastro-entero-pancreatic neuroendocrine tumors, not being very frequent, are quite difficult lesions, but new developments in the diagnosis and management of these diseases give hope for a better therapeutic approach. CONSENT FOR PUBLICATION Not applicable. CONFLICT OF INTEREST The author confirms that this chapter contents have no conflict of interest. ACKNOWLEDGEMENTS Declared none. REFERENCES [1] Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31(7): 844-60. [http://dx.doi.org/10.1016/j.annonc.2020.03.304] [PMID: 32272208] [2] Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012; 61(1): 6-32. [http://dx.doi.org/10.1136/gutjnl-2011-300831] [PMID: 22052063] [3] Ma ZY, Gong YF, Zhuang HK, et al. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol 2020; 26(19): 2305-22. [http://dx.doi.org/10.3748/wjg.v26.i19.2305] [PMID: 32476795] [4] [5] Amin MB, Edge S, Greene F, Eds. AJCC Cancer Staging Manual. 2017. [http://dx.doi.org/10.1007/978-3-319-40618-3] Kunz PL, Reidy-Lagunes D, Anthony LB, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas 2013; 42(4): 557-77. [http://dx.doi.org/10.1097/MPA.0b013e31828e34a4] [PMID: 23591432] 66 What is New in Gastroenterology and Hepatology Săftoiu and Constantinescu [6] [7] [8] [9] Zhang MY, He D, Zhang S. Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment. World J Gastrointest Oncol 2020; 12(7): 705- 18. [http://dx.doi.org/10.4251/wjgo.v12.i7.705] [PMID: 32864039] Shah MH, Goldner WS, Halfdanarson TR, et al. NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018. J Natl Compr Canc Netw 2018; 16(6): 693-702. [http://dx.doi.org/10.6004/jnccn.2018.0056] [PMID: 29891520] Ito T, Jensen RT. Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management. Curr Opin Endocrinol Diabetes Obes 2017; 24(1): 15-24. [PMID: 27875420] I, Grozinsky-Glasberg S.

  Keywords: neuroendocrine tumors http pmid pancreatic management pnets receptor nets guidelines imaging surgery targeting therapy targeted
• Artificial Intelligence-Assisted Endoscopic Ultrasound-Guided Ablation of Pancreatic Neuroendocrine Tumors: Toward Precision Diagnosis, Risk Stratification, and Personalized Therapy (2026) · doi

  Despite growing interest in EUS-guided ablation for pNETs, the evidence base remains limited. Most studies are retrospective or observational, include relatively small cohorts, and vary in patient selection, tumor characteristics, ablation devices, energy settings, and follow-up protocols. Definitions of technical success, clinical response, radiological response, recurrence, and treatment failure are also inconsistent. These limitations make it difficult to determine the true durability of EUS-guided ablation, particularly for non- functioning pNETs, where long-term oncological control is harder to assess than symptom resolution in insulinomas [14-18]. The evidence supporting AI in this setting is even less mature. Although AI-assisted EUS and radiomics models have shown encouraging diagnostic and grading performance, most studies remain retrospective, single-center, and based on curated imaging datasets. External validation, prospective testing, real-time implementation, and assessment across different EUS platforms, operators, and institutions remain limited. Few studies have evaluated whether AI improves clinically meaningful outcomes, such as treatment selection, avoidance of unnecessary surgery, recurrence reduction, or earlier detection of residual disease [19-24,28-31]. Recent literature further highlights both the progress and the remaining evidence gaps in this field. Updated ENETS guidance provides contemporary management recommendations for non-functioning pNETs and reinforces the need for individualized decision-making in small lesions [32]. Recent prospective multicenter data also support the safety and effectiveness of EUS-radiofrequency ablation in selected functioning and non-functioning pNETs [33]. In parallel, emerging CT radiomics and machine-learning studies suggest potential value for non-invasive pNET grading [34], while externally validated multimodal AI models for solid pancreatic lesions provide stronger proof-of-concept for AI-assisted EUS diagnosis, although these findings should not be directly extrapolated to pNET-specific ablation selection without dedicated validation 2026 Salman et al. Cureus 18(5): e109721. DOI 10.7759/cureus.109721 8 of 11 [22]. Future research should therefore focus on multicenter prospective studies that combine standardized EUS image acquisition, EUS-guided tissue sampling, cross-sectional imaging, pathology, procedural data, and long-term follow-up. Dedicated pNET registries would be particularly valuable for developing and validating AI models that predict tumor grade, progression risk, ablation feasibility, recurrence, and need for surgery. Explainable AI systems will also be important to ensure that clinicians can understand, verify, and safely apply model outputs in real-world decision-making [19,24,28]. Recent evidence further supports the need for continued refinement of both EUS-guided ablation and AI- based risk assessment. A recent prospective international multicenter study reported encouraging safety and effectiveness of EUS-RFA for both functioning and non-functioning pNETs, supporting its role as an organ- preserving option in selected patients [33]. In parallel, recent radiomics and machine-learning studies continue to suggest that imaging-based AI models may help predict tumor grade and biological risk, although these approaches still require stronger external validation before routine clinical adoption [34]. From a therapeutic perspective, future trials should compare EUS-guided ablation with active surveillance and surgery in carefully defined patient groups, particularly small insulinomas and low-risk non-functioning pNETs. Standardized reporting of tumor characteristics, ablation technique, adverse events, radiological response, biochemical outcomes, quality of life, recurrence, and long-term survival will be essential. Ultimately, the goal should not be to replace clinical expertise, but to integrate AI into a precision- endoscopy pathway that improves consistency, safety, personalization, and long-term outcomes for patients with pNETs [15,18,24].

  Keywords: ablation pnets functioning guided recent evidence tumor recurrence long term models prospective risk small selection