Search Results (182)

Pancreatic cystic lesions (PCLs) are increasingly detected due to widespread use of cross-sectional imaging. They encompass a heterogeneous group of lesions, ranging from benign pseudocysts and serous cystic neoplasms (SCNs) to premalignant mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs), as well as rare malignant entities such as solid pseudopapillary epithelial neoplasm (SPENs) and cystic pancreatic neuroendocrine tumors (cystic PanNETs). Management of PCLs depends on their malignant potential; therefore, an accurate classification is essential for optimizing treatment. This narrative review summarizes current knowledge on the epidemiology, imaging characteristics, diagnosis, and management of PCLs, highlighting the role of CT, MRI, MRCP, and endoscopic ultrasound. Recent advances in radiomics for lesion characterization and risk stratification, particularly in IPMNs, are discussed. Full article

Purpose: Zollinger–Ellison syndrome (ZES) is the most frequent, functional, malignant pancreatic neuroendocrine tumor syndrome (pNET), which is due to ectopic secretion of gastrin by a pNET/NET (i.e., gastrinomas) resulting in severe, refractory acid-peptic disease (ulcer, GERD). ZES has several unique management features, which lead to a number of unresolved controversies. Areas covered: Whereas both medical and surgical controversies exist, they have not been examined in detail for some time. This review contains an analysis of a number of the main current, medical controversies that are unresolved in ZES patients, including insights into the basis of these controversies and possible insights into their resolution from recent studies in patients with gastrinomas or from recent studies in other pNET syndromes or other neuroendocrine tumors (NETs). These include the following: controversies in the long-term control of acid secretion and acid antisecretory drug side-effects; controversies related to the difficulty in making the diagnosis of ZES; nonsurgical MEN1/ZES controversies related to the management of gastric carcinoids (Type II); nonsurgical MEN1/ZES controversies related to whether genotype–phenotype correlations exist in MEN1 patients including MEN1/ZES patients; nonsurgical MEN1/ZES controversies related to the roles of imaging/tumor localization in MEN1 patients for gastrinomas/pNETs in their initial/follow-up management; controversies related to the role of non-surgical tumor ablation for treatment of ZES/gastrinomas; and controversies related to medical treatment selection for advanced, metastatic disease in patients with ZES/gastrinomas/other malignant pNETs. Conclusions: In this paper, the basis for the development of each of these unique ZES-related controversies is discussed and insights into progress that could lead to their resolution are reviewed. Full article

Pancreatic neuroendocrine neoplasms (PanNENs) are a diverse group of cancers with varying clinical presentations and prognoses due to differences in morphology and clinical stage. Most are non-functional tumors that express somatostatin receptors (SSTRs). Several treatment options have been established for patients with locally advanced or metastatic PanNETs, but the optimal choice of treatment approach and the sequence of available therapies are not yet clearly defined and are currently being studied in multiple ongoing clinical trials. Additionally, new drugs are being researched for PanNET treatment, including immune checkpoint inhibitors, next-generation peptide receptor radionuclide therapy, and other targeted biological therapies. To improve treatment outcomes for patients with PanNETs, a multidisciplinary team should evaluate systemic treatment options. The aim of this article is to review currently available therapies and discuss new and emerging systemic treatment strategies for patients with advanced PanNETs. Full article

Neuroendocrine tumors (NETs) are heterogeneous neoplasms with different molecular characteristics and prognosis. Although slow-growing, NETs are often diagnosed at an advanced stage. The treatment choice depends on primary site, extent, grade, growth rate, somatostatin receptor status, functional status, performance status, and comorbidities. Precise knowledge of the biological and molecular features of NETs has led to the development of novel therapies. Therapeutic options include somatostatin analogs, multi-targeted tyrosine kinase inhibitors (e.g., sunitinib), or mammalian targets of rapamycin (mTOR) inhibitors (e.g., everolimus), telotristat ethyl, chemotherapy, and peptide-receptor radionuclide therapy. Pivotal studies that led to approval, treatment-related adverse events, and safety concerns, as demonstrated in clinical trials and real-world clinical practice. Questions, such as the optimal timing, selection, and sequence of therapies, and biomarkers that predict response to the novel agents in an individual patient, remain to be answered. We propose a stepwise approach for the management of advanced Gastro-entero-pancreatic (GEP)-NETs that utilizes a multidisciplinary team of experts. Biomarkers may assist in both the diagnosis and post-treatment follow-up in patients with GEP-NETs. The next decade of research on GEP-NETs is promising and should provide new insights into the molecular underpinnings of this disease, therapy selection, and the sequencing of the available therapies, along with the potential role of AL in NET pharmacotherapy. Full article

Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess the frequency and clinical relevance of germline DNA repair gene mutations in patients with pNENs, both with and without a family history of cancer. Germline DNA from 57 Polish patients with pNENs was analyzed using targeted next-generation sequencing to identify variants in a panel of DNA repair genes. Variant classification followed the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Germline mutations were identified in 14 patients (24.6%), both with and without a family history of malignancy. Two patients carried pathogenic variants in BRCA2 and CHEK2, while seven carried variants of uncertain significance (VUS). The identified variants have been implicated in various cancer types, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations. Full article

Background and Objectives: Pancreatic neuroendocrine tumors (PanNETs) are rare and heterogeneous neoplasms with variable clinical behavior. Despite advances in diagnosis and treatment, the optimal management strategy remains unclear. This present study aims to evaluate survival outcomes according to first-line therapy and tumor characteristics. Materials and Methods: We conducted a retrospective cohort study including adult patients with histologically confirmed PanNETs who were treated at a tertiary care center between January 2020 and January 2025. Patients were divided into two groups according to their first-line management: surgical resection or non-surgical treatment. Overall survival (OS) was assessed in the entire cohort, and disease-free survival (DFS) was evaluated in patients who underwent complete surgical resection (R0). Results: A total of 68 patients were included, of whom 46 (67.6%) underwent surgery as first-line treatment. In the non-surgical group, 45.5% received combined systemic therapy and somatostatin analogues (SSA), 36.4% received SSA alone, 4.5% systemic therapy alone, and 9.1% were managed with active surveillance. Patients who underwent surgery tended to have lower-grade tumors and earlier-stage disease. The OS rates were 96.5% at one year, 83.2% at three years, and 62.3% at five years, with a median OS of 179 months. Both surgical treatment and lower tumor grade were significantly associated with improved OS. Among patients who had R0 resection, DFS was 95.8% at one year and 84.3% at both three and five years. Lower-grade tumors were also associated with longer DFS. Conclusions: This study demonstrates that first-line surgical resection and lower tumor grade were significantly associated with better OS in patients with PanNETs. Among patients who underwent curative surgery, lower tumor grades were associated with improved DFS. Full article

Background: Pancreatic neuroendocrine neoplasia (PanNEN) comprises a spectrum, from well-differentiated (i.e., G1, G2) pancreatic neuroendocrine tumors (PanNETs) to poorly differentiated carcinomas (PanNECs). Therapeutic progress is limited by the lack of representative preclinical models. Patient-derived organoids (PDOs) offer potential as translational models, but evidence remains scattered. Methods: We conducted a systematic review of PubMed (Jan 2009–Aug 2025) for original studies reporting on PDOs from PanNEN patients. Eligible studies were screened using the Rayyan software and data extracted from PDO take rates, validation methods, and clinical applications. Results: Twelve studies were included for qualitative and quantitative analyses. PDOs were successfully generated from both PanNETs (G1–G3; n = 26) and PanNECs (n = 6), primarily derived from primary tumors, but several studies also included metastatic sites. Take rates ranged from 33% to 100%, for a cumulative 33 PDOs from 44 attempts (overall take rate: 75%). Validation consistently employed histology, immunohistochemistry, and molecular profiling, with several studies incorporating xenotransplantation or omics approaches. PDOs demonstrated variable culture durations, from short-term (<3 weeks) to long-term (>20 passages). Drug screening studies (n = 7) revealed heterogenous responses to standard agents and pathways (everolimus, sunitinib, and temozolomide) and identified novel vulnerabilities, including EZH2 dependency, PI3K/CDK4/6 synergy, and Bcl-2-linked sensitivities in PanNECs. One study provided evidence of concordance between PDO drug sensitivity and patient responses. Conclusions: Research into PanNEN organoids remains limited. However, PDOs can preserve key histological and molecular features, enable pharmacotyping, and uncover candidate biomarkers for therapy. Despite feasibility across subtypes, progress is constrained by variability in culture success. Standardization and prospective validation are essential to advance PDOs as tools for personalized medicine in PanNENs. Full article

Background and Objectives: Neuroendocrine neoplasms (NENs) are rare, mainly gastro-entero-pancreatic tumors with heterogeneous biology and multiple therapeutic options. Assessing treatment response remains challenging. Standard evaluation relies on RECIST 1.1, although its limitations are well recognized. Tumor growth rate (TGR), defined as the monthly percentage change in tumor size between two imaging assessments, has been proposed as a dynamic parameter to complement conventional criteria. This review explores the role of TGR in NEN. Results: Two different evaluations of TGR, once conducted between baseline diagnostic scan and a radiological assessment 12–24 weeks after (TGR0), and another conducted between baseline scan and a diagnostic evaluation three months after (TGR3m), proved to be well correlated to progression free survival (PFS) in G1 and low-G2 NEN, with cut off of 4%/month and 0.8%/month, respectively. Conclusions: TGR offers additional insights into tumor kinetics and may help refine treatment monitoring in NEN. While retrospective evidence supports its prognostic utility, prospective studies are required to validate TGR as a standard clinical tool. Full article

Background/Objectives: There is limited evidence on imaging characteristics and pathological grading of small pancreatic neuroendocrine tumors (PNENs). This study aimed to compare imaging features and histopathological diagnoses of PNENs based on tumor size. Methods: Patients with PNEN who underwent pathological diagnosis at Hiroshima University Hospital were retrospectively reviewed. Detection rates, imaging findings, and diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) were analyzed according to tumor size. Results: Among 107 patients with PNEN, 42 had tumors ≤10 mm, and 65 had tumors >10 mm. The detection rate for lesions ≤10 mm was 92.3% according to EUS and 83.3% according to contrast-enhanced CT, showing the superior sensitivity of EUS. Typical imaging features—well-defined margins, homogeneous internal structure, and early enhancement—were significantly more frequent in tumors ≤10 mm (p < 0.001). There were no significant differences in imaging findings between G1 and G2 tumors ≤10 mm. The diagnostic sensitivity of EUS-FNA was 91.2% for tumors ≤10 mm and 86.3% for tumors >10 mm, with no significant difference. However, the concordance rate between EUS-FNA and surgical histology for tumor grading was significantly higher in the ≤10 mm group (87.5% vs. 56.3%, p = 0.012). Discussion: In small PNENs (≤10 mm), imaging features are often typical but do not reliably determine tumor grade. In our cohort, EUS-FNA showed high diagnostic accuracy and provided essential pathological information to guide management, including the choice between surveillance and surgery. Full article

The recommended surgery for pancreatic tumors is dependent on the diagnosis. For pancreatic adenocarcinoma, duodenal, and ampullary adenocarcinoma, a Whipple pancreaticoduodenectomy with lymph node dissection is recommended. For small < 2 cm or non-imageable gastrinomas, duodenal transillumination, duodenotomy, duodenal tumor excision and adjacent lymphadenectomy is recommended. For large > 3 cm gastrinomas, a Whipple pancreaticoduodenectomy with adjacent lymph node dissection is recommended. For small 1–2 cm insulinomas, intraoperative ultrasound with enucleation is recommended. If the patient with gastrinoma, insulinoma, or multiple nonfunctional NETs occurs in the setting of MEN-1, a subtotal pancreatectomy with or without splenectomy with enucleation of pancreatic head tumors is recommended, with adjacent lymph node dissection. The detail of each procedure is described with illustrations. Full article

Endoscopic ultrasonography represents a crucial aspect of the diagnosis of pancreatic lesions. The echo-endoscopic features of pancreatic lesions, particularly their contrast behavior with the advent of Contrast-Enhanced EUS (CE-EUS) and Contrast Enhanced Harmonic-EUS (CH-EUS), can predict a lesion’s aggressiveness, depending on its nature. According to this, CH-EUS could be applied to structure an even more dedicated approach to patient care, for example, to ascertain eligibility for surgical intervention of a pancreatic ductal adenocarcinoma (PDAC) or the response to neoadjuvant chemotherapy in cases deemed borderline resectable. In addition to PDAC, other significant issues pertain to the management of small neuroendocrine tumors (NETs) and intraductal papillary mucinous neoplasms (IPMNs). In this context, CH-EUS can be crucial. The aim of this review is to underline the most recent evidence for EUS and CH-EUS applications in pancreatic lesion aggressiveness assessment and to focus on possible future research directions to further extend the application of CH-EUS in this field. Full article

Pancreatic neuroendocrine neoplasms (PNENs) are a diverse group of rare tumor subtypes, representing less than 2% of all pancreatic tumors. Often detected late in the clinical course, they are associated with high rates of morbidity and mortality. Hereditary syndromes such as multiple endocrine neoplasia type-1 and von Hippel–Lindau are associated with the development of PNENs, although only a small portion of total tumors have a genetic basis. This review aims to explore the recent advances in laboratory diagnostics, imaging modalities, medical management, and surgical approaches to hormone-producing PNENs (including some common, less common, and some rare subtypes), with the goal of assisting physicians in the integration of evidence-based information into their practice. Full article

Background: Pancreatic neuroendocrine tumors (PanNETs) are relatively rare neoplasms with heterogeneous behavior, ranging from indolent to aggressive disease. The evolution of nuclear medicine has allowed the development of an efficient and advanced toolkit for the diagnosis and treatment of PanNETs. Case: A 45-year-old woman was diagnosed with a grade 1 PanNET and multiple liver metastases. She underwent distal pancreatectomy with splenectomy, extended liver resection, and radiofrequency ablation (RFA). Surgical planning was guided by [^99mTc]Tc-EDDA/HYNIC-TOC SPECT/CT (single-photon emission computed tomography/computed tomography) and preoperative [^99mTc]Tc-mebrofenin-based functional liver volumetry. Functional liver volumetry based on dynamic [^99mTc]Tc-mebrofenin SPECT/CT facilitated precise surgical planning and reliable assessment of the efficacy of parenchymal modulation, thereby aiding in the prevention of post-hepatectomy liver failure. Liver fibrosis was non-invasively evaluated using two-dimensional shear wave elastography (2D-SWE). Tumor progression was monitored using somatostatin receptor scintigraphy, chromogranin A, and contrast-enhanced CT. Recurrent disease was treated with somatostatin analogues (SSAs) and [¹⁷⁷Lu]Lu-DOTA-TATE peptide receptor radionuclide therapy (PRRT). Despite progression to grade 3 disease (Ki-67 from 1% to 30%), the patient remains alive 53 months post-diagnosis, in complete remission, with an ECOG (Eastern Cooperative Oncology Group) status of 0. Conclusions: Functional imaging played a pivotal role in guiding therapeutic decisions throughout the disease course. This case not only underscores the clinical utility of advanced nuclear imaging but also illustrates the dynamic nature of pancreatic neuroendocrine tumors. The transition from low-grade to high-grade disease highlights the need for further studies on tumor progression mechanisms and the potential role of adjuvant therapies in managing PanNETs. Full article

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represent a challenging disease. Their large heterogeneity limits the possibility of providing accurate risk assessments or standardizing the most effective therapies for these patients. In recent years, artificial intelligence (AI), and in particular machine learning approaches, have shown real promise in addressing these complexities. By analyzing large volumes of clinical, imaging, and pathological data, AI-based tools can significantly improve the accuracy of survival predictions and guide more tailored treatment strategies. In this narrative review, we examine the potential applications of AI to develop effective prognostic models in GEP-NENs, and how these models may help clinicians in predicting survival and optimizing patient management. While early results are encouraging, important limitations remain, since available data stem from small, retrospective datasets, sometimes lacking external validation, and concerns around transparency and ethics still represent an open issue. Addressing these gaps will be key to moving from research applications to practical tools that can support everyday clinical decision-making. Full article

Background/Objectives: Pancreatic neoplasms, including adenocarcinoma, pancreatic neuroendocrine tumors (pNETs), intraductal papillary mucinous neoplasms (IPMNs), and high-grade cystic lesions, often require surgical resection as a form of curative treatment. However, comorbidities and high-risk features may preclude surgery. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a minimally invasive alternative with proven cytoreductive efficacy in solid tumors. This case series evaluates the safety and efficacy of EUS-RFA in patients with various unresectable, non-metastatic pancreatic neoplasms. Methods: A retrospective review was conducted on eight patients who underwent EUS-RFA at our institutions between July 2021 and February 2025. All patients were deemed unsuitable surgical candidates due to comorbidities such as advanced age, cardiovascular disease, renal insufficiency, and COPD or due to patient resistance to surgical intervention. EUS-RFA was performed using a 19-gauge RFA needle (Taewoong Corporation). Follow-up imaging was conducted 3 to 6 months after the completion of RFA treatment. Results: All eight patients demonstrated a good to excellent response in terms of tumor size reduction. The most notable response was observed in a patient with pNET, resulting in complete resolution from 15.6 × 12.0 mm to 0.0 × 0.0 mm after two RFA treatments. Other neoplasms, including pancreatic adenocarcinoma and intraductal papillary mucinous neoplasms (IPMNs), also demonstrated significant reductions. Mild post-procedure complications, including pancreatitis and abdominal pain, were noted in three cases. Conclusions: EUS-RFA is a promising alternative for managing unresectable pancreatic neoplasms in high-risk patients. Our findings support its use across various tumor types with favorable outcomes and minimal complications, reinforcing its role in expanding therapeutic options beyond surgery. Full article