Search Results (32)

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

Pancreatic neuroendocrine neoplasms (pNENs) represent approximately 2% of all solid pancreatic tumors. The incidence of pNENs has been increasing in the last decade. The clinical manifestations of pNENs range from hormone secretion syndromes in functioning neoplasms (F-pNENs) to local infiltration or distant metastases in late-stage diagnoses or incidental findings in small non-functioning neoplasms (NF-pNENs). While surgery is the gold-standard treatment for larger and more aggressive tumors, small and low-grade tumors (G1) may be followed-up due to the indolent course of disease. Recently, endoscopic ultrasound (EUS)-guided ablative techniques, such as ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA), have emerged as promising options for loco-regional ablations in selected cases. Despite promising safety profile and efficacy, high-quality evidence is needed to support their widespread adoption. This article reviews the current state of EUS-guided locoregional therapies, patient selection criteria, procedural details, and associated risks. Full article

Background: Neuroendocrine neoplasms are a rare and heterogeneous group of neoplasms. Small-sized (≤2 cm) pancreatic neuroendocrine tumors (PanNETs) are of particular interest as they are often associated with aggressive behavior, with no specific prognostic or progression markers. Methods: This article describes a clinical case characterized by a progressive growth of nonfunctional PanNET requiring surgical treatment in a patient with a germline FANCD2 mutation, previously not reported in PanNETs. The patient underwent whole exome sequencing and single-cell RNA sequencing. Results: The patient underwent surgical treatment. We confirmed the presence of the germline mutation FANCD2 and also detected the germline mutation WNT10A. The cellular composition of the PanNET was analyzed using single-cell sequencing, and the main cell clusters were identified. We analyzed the tumor genomics, and used the data to define the effect the germline FANCD2 mutation had. Conclusions: Analysis of the mutational status of patients with PanNET may provide additional data that may influence treatment tactics, refine the plan for monitoring such patients, and provide more information about the pathogenesis of PanNET. PanNET research using scRNA-seq data may help in predicting the effect of therapy on neuroendocrine cells with FANCD2 mutations. Full article

Radiofrequency ablation (RFA) under endoscopic ultrasound (EUS) guidance has been developed and utilized over the last decade to provide the loco-regional treatment of solid and cystic pancreatic neoplastic lesions. The advantage of this approach relies on the close proximity of the EUS transducer to the target pancreatic lesion, which, coupled with the development of specifically designed RFA ablation devices, has made the procedure minimally invasive, with a clear reduction in adverse events as compared to the high morbidity of the surgical approach. EUS-RFA has been applied so far to pancreatic functional and non-functional neuroendocrine neoplasms, pancreatic ductal adenocarcinoma or metastases to the pancreas, and pancreatic neoplastic cysts. Excluding neuroendocrine tumors, for other indications, most of these procedures have been performed in patients who refused surgery or were at high surgical risk. More studies evaluating EUS-RFA in selected patients, not at surgical risk, are gradually becoming available and will pave the road to extend the indications for this therapeutic approach, also in association with other oncological therapies. The present manuscript will critically review the available evidence in the field of the EUS-guided RFA of solid and cystic pancreatic neoplasms. Full article

The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor’s biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques. Full article

This study aimed to evaluate the optimal extent of lymphadenectomy in patients with nonfunctioning pancreatic neuroendocrine neoplasms. We retrospectively analyzed the clinicopathological data of patients with nonfunctioning pancreatic neuroendocrine neoplasms who underwent surgical resection. We investigated the frequency of metastases at each lymph node station according to tumor location and analyzed the factors contributing to poor overall survival (OS) and disease-free survival (DFS). Overall, data of 84 patients were analyzed. Among patients with pancreatic head tumors, metastases at stations 8, 13, and 17 were found in one (3.1%), four (12.5%), and three (9.3%) patients, respectively. However, none of the other stations showed metastases. For pancreatic body and tail tumors, metastases only at station 11 were found in two (5.1%) patients. Additionally, multivariate DFS and OS analyses showed that lymph node metastasis was the only independent prognostic factor. In conclusion, lymph node metastasis near the primary tumor was the only independent factor of poor prognosis in patients with nonfunctioning pancreatic neuroendocrine neoplasms after undergoing curative surgery. Peri-pancreatic lymphadenectomy might be recommended for nonfunctioning pancreatic neuroendocrine neoplasms. Full article

A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient’s survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs. Full article

Pancreatic neuroendocrine neoplasms (pNENs) are a heterogeneous group of tumors derived from multiple neuroendocrine origin cell subtypes. Incidence rates for pNENs have steadily risen over the last decade, and outcomes continue to vary widely due to inability to properly screen. These tumors encompass a wide range of functional and non-functional subtypes, with their rarity and slow growth making therapeutic development difficult as most clinically used therapeutics are derived from retrospective analyses. Improved molecular understanding of these cancers has increased our knowledge of the tumor biology for pNENs. Despite these advances in our understanding of pNENs, there remains a dearth of models for further investigation. In this review, we will cover the current field of pNEN models, which include established cell lines, animal models such as mice and zebrafish, and three-dimensional (3D) cell models, and compare their uses in modeling various disease aspects. While no study model is a complete representation of pNEN biology, each has advantages which allow for new scientific understanding of these rare tumors. Future efforts and advancements in technology will continue to create new options in modeling these cancers. Full article

Background: This study aimed to summarize the surgical and therapeutic activities of non-functional pancreatic neuroendocrine tumors (NF-PanNETs) and perform survival analyses of a 15-year single-institutional cohort of NF-PanNETs. Methods: In total, 1001 patients with neuroendocrine neoplasms treated at Fudan University Shanghai Cancer Center were screened for inclusion, and 509 patients with NF-PanNETs from 2006 to 2020 were included. For time trend analyses, the 15-year study period was randomly divided into three periods. Survival analyses used the Kaplan–Meier method and Cox regression models. Results: The total number of resected NF-PanNETs increased over the 15-year study period, from 5 resections in 2006 to 94 resections in 2020. A significant decrease in the tumor size was observed, from a mean of 4.0 cm to 3.3 cm, and to 3.0 cm in the most recent period (p = 0.006). Minimally invasive techniques gradually increased from 3.5% to 12.9%, and finally to 46.4% in the most recent period (p < 0.001). In non-metastatic and resected tumors, the tumor size (p < 0.001), positive lymph node (p < 0.001), adjuvant treatment (p = 0.048), and tumor grade (p < 0.001) were independent prognostic factors for recurrence-free survival (RFS). The microvascular invasion (p = 0.024) and tumor grade (p = 0.013) were independent prognostic factors for overall survival (OS). A malignant transformation from NET into neuroendocrine carcinoma was observed. Conclusions: An increasing number of NF-PanNETs resection and minimally invasive surgery was shown. In non-metastatic and resected tumors NF-PanNETs, tumor size, positive lymph node, adjuvant treatment, and tumor grade were independent predictors of RFS. Microvascular invasion and tumor grade were independent prognostic factors for OS. Full article

Background: Pancreatic neuroendocrine neoplasms (pNENs) are often detected as large primary lesions, even with distant metastases, and their prognosis may be difficult to predict. Methods: In this retrospective study, we retrieved data of patients treated for a large pNEN in our Surgical Unit (1979–2017) to evaluate the possible prognostic role of clinic-pathological features and surgery. Cox-proportional hazard regression models were used to find possible associations among some variables (clinical features, surgery, and histology) and survival at univariate and multivariate analyses. Results: Among 333 pNENs, we identified 64 patients (19%) with a lesion > 4 cm. Patients’ median age was 61 years, median tumor size was 6.0 cm, and 35 (55%) patients had distant metastases at diagnosis. There were 50 (78%) nonfunctioning pNENs, and 31 tumors localized in the body/tail region of the pancreas. Overall, 36 patients underwent a standard pancreatic resection (with 13 associated liver resection/ablation). Regarding histology, 67% of pNENs were N1, and 34% were grade 2. After a median follow-up of 48 months (up to 33 years), 42 patients died of disease. Median survival after surgery was 79 months, and six patients experienced recurrence (median DFS 94 months). At multivariate analysis, distant metastases were associated with a worse outcome, while having undergone radical tumor resection was a protective factor. Conclusions: In our experience, about 20% of pNENs have a size > 4 cm, 78% are nonfunctioning, and 55% show distant metastases at diagnosis. Nevertheless, a long-term survival of more than five years may be achieved after surgery. Full article

Pancreatic neuroendocrine neoplasms (pNEN) are rare and heterogeneous tumors. Previous investigations have shown that autophagy can be a target for cancer therapy. This study aimed to determine the association between the expression of autophagy-associated gene transcripts and clinical parameters in pNEN. In total, 54 pNEN specimens were obtained from our human biobank. The patient characteristics were retrieved from the medical record. RT-qPCR was performed to assess the expression of the autophagic transcripts BECN1, MAP1LC3B, SQSTM1, UVRAG, TFEB, PRKAA1, and PRKAA2 in the pNEN specimens. A Mann–Whitney U test was used to detect differences in the expression of autophagic gene transcripts between different tumor characteristics. This study showed that G1 sporadic pNEN have a higher expression of autophagic genes compared to G2. Lymphatic and distant metastasis occurred significantly more often in pNEN with a decreased expression of the autophagic genes. Within sporadic pNEN, the insulinomas express higher levels of autophagic transcripts than gastrinomas and non-functional pNEN. MEN1-associated pNEN show a higher expression of autophagic genes than sporadic pNEN. In summary, a decreased expression of autophagic transcripts distinguishes metastatic from non-metastatic sporadic pNEN. The significance of autophagy as a molecular marker for prognosis and therapy decisions needs to be further investigated. Full article

Pancreatic neuroendocrine neoplasms (PanNENs) are rare neoplasms arising from islets of the Langerhans in the pancreas. They can be divided into two groups, based on peptide hormone secretion, functioning and nonfunctioning PanNENs. The first group is characterized by different secreted peptides causing specific syndromes and is further classified into subgroups: insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma and tumors producing serotonin and adrenocorticotrophic hormone. Conversely, the second group does not release peptides and is usually associated with a worse prognosis. Today, although the efforts to improve the therapeutic approaches, surgery remains the only curative treatment for patients with PanNENs. The development of high-throughput techniques has increased the molecular knowledge of PanNENs, thereby allowing us to understand better the molecular biology and potential therapeutic vulnerabilities of PanNENs. Although enormous advancements in therapeutic and molecular aspects of PanNENs have been achieved, there is poor knowledge about each subgroup of functioning PanNENs.Therefore, we believe that combining high-throughput platforms with new diagnostic tools will allow for the efficient characterization of the main differences among the subgroups of functioning PanNENs. In this narrative review, we summarize the current landscape regarding diagnosis, molecular profiling and treatment, and we discuss the future perspectives of functioning PanNENs. Full article

Non-invasive characterization of pancreatic masses aids in the management of pancreatic lesions. Intravoxel incoherent motion-diffusion kurtosis imaging (IVIM-DKI) and machine learning-based texture analysis was used to differentiate pancreatic masses such as pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine tumor (pNET), solid pseudopapillary epithelial neoplasm (SPEN), and mass-forming chronic pancreatitis (MFCP). A total of forty-eight biopsy-proven patients with pancreatic masses were recruited and classified into pNET (n = 13), MFCP (n = 6), SPEN (n = 4), and PDAC (n = 25) groups. All patients were scanned for IVIM-DKI sequences acquired with 14 b-values (0 to 2500 s/mm²) on a 1.5T MRI. An IVIM-DKI model with a 3D total variation (TV) penalty function was implemented to estimate the precise IVIM-DKI parametric maps. Texture analysis (TA) of the apparent diffusion coefficient (ADC) and IVIM-DKI parametric map was performed and reduced using the chi-square test. These features were fed to an artificial neural network (ANN) for characterization of pancreatic mass subtypes and validated by 5-fold cross-validation. Receiver operator characteristics (ROC) analyses were used to compute the area under curve (AUC). Perfusion fraction (f) was significantly higher (p < 0.05) in pNET than PDAC. The f showed better diagnostic performance for PDAC vs. MFCP with AUC:0.77. Both pseudo-diffusion coefficient (D*) and f for PDAC vs. pNET showed an AUC of 0.73. ADC and diffusion coefficient (D) showed good diagnostic performance for pNET vs. MFCP with AUC: 0.79 and 0.76, respectively. In the TA of PDAC vs. non-PDAC, f and combined IVIM-DKI parameters showed high accuracy ≥ 84.3% and AUC ≥ 0.84. Mean f and combined IVIM-DKI parameters estimated that the IVIM-DKI model with TV texture features has the potential to be helpful in characterizing pancreatic masses. Full article

The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has increased due to the widespread use of high-resolution diagnostic imaging in screening programs. Most PNENs are slow-growing indolent neoplasms. However, a local invasion or metastasis can sometimes occur with PNENs, leading to a poor prognosis. The management of small, nonfunctioning PNENs remains under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgery remains a high-risk operation with a 28–30% morbidity and 1% mortality. Therefore, the decision on how to manage small PNENs is challenging. This review focuses on the management of small nonfunctioning PNENs. We also highlight the malignant potential of small PNENs according to tumor size, tumor grade, and tumor biomarker. Endoscopic-ultrasound-guided biopsy is recommended to evaluate the potential risk of malignancy. Furthermore, we discuss the current guidelines and future directions for the management of small PNENs. Full article

Pancreatic neuroendocrine neoplasms (panNENs) are part of a large family of tumors arising from the neuroendocrine system. PanNENs show low–intermediate tumor grade and generally high somatostatin receptor (SSTR) expression. Therefore, panNENs benefit from functional imaging with ⁶⁸Ga-somatostatin analogues (SSA) for diagnosis, staging, and treatment choice in parallel with morphological imaging. This narrative review aims to present conventional imaging techniques and new perspectives in the management of panNENs, providing the clinicians with useful insight for clinical practice. The ⁶⁸Ga-SSA PET/CT is the most widely used in panNENs, not only fr diagnosis and staging purpose but also to characterize the biology of the tumor and its responsiveness to SSAs. On the contrary, the ¹⁸F-Fluordeoxiglucose (FDG) PET/CT is not employed systematically in all panNEN patients, being generally preferred in G2–G3, to predict aggressiveness and progression rate. The combination of ⁶⁸Ga-SSA PET/CT and ¹⁸F-FDG PET/CT can finally suggest the best therapeutic strategy. Other radiopharmaceuticals are ⁶⁸Ga-exendin-4 in case of insulinomas and ¹⁸F-dopamine (DOPA), which can be helpful in SSTR-negative tumors. New promising but still-under-investigation radiopharmaceuticals include radiolabeled SSTR antagonists and ¹⁸F-SSAs. Conventional imaging includes contrast enhanced CT and multiparametric MRI. There are now enriched by radiomics, a new non-invasive imaging approach, very promising to early predict tumor response or progression. Full article