Search Results (75)

Multiple endocrine neoplasia (MEN) syndromes are rare hereditary disorders characterized by the development of multiple endocrine and non-endocrine tumours with variable penetrance and age-dependent expression. Although uncommon, these syndromes are highly relevant from both biological and clinical perspectives, as they exemplify the direct link between germline genetic alterations and tumorigenesis. Early tumour detection is critical in MEN syndromes because many associated neoplasms—such as medullary thyroid carcinoma (MTC), pancreatic neuroendocrine tumours (NETs), pheochromocytomas, and parathyroid disease—may remain clinically silent for prolonged periods while retaining malignant potential. Delayed diagnosis is associated with advanced disease and worse outcomes, whereas early identification enables curative or organ-preserving interventions. This clinical challenge has driven the development of integrated diagnostic strategies combining genetic testing, biochemical markers, and imaging. Among these, genetic testing plays a pivotal role, providing definitive diagnosis, enabling family screening, and guiding risk-adapted surveillance. The aim of this review is to provide a comprehensive synthesis of genetically driven diagnostics in MEN syndromes, outlining the current state of the art and future directions in precision medicine. Full article

Background: Neuroendocrine tumours (NETs) are heterogeneous neoplasms with several treatment options. Response rates, disease progression, and haematological toxicities can limit the use of some indicated treatments. Case Presentation: A 73-year-old woman with a well-differentiated grade 2 pancreatic NET (Ki-67 18%) underwent surgical resection and later developed hepatic recurrence. First-line treatment with sunitinib plus octreotide achieved temporary disease stabilisation. Upon progression, peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE was initiated, resulting in stable disease but complicated by grade 3 thrombocytopenia. Two years later, PRRT retreatment was performed due to disease progression, which led to grade 4 thrombocytopenia. Further treatments with capecitabine and everolimus were limited by progression and significant thrombocytopenia. Therapy was switched to streptozocin plus 5-fluorouracil, which resulted in recovery of platelet counts, absence of haematological toxicity, and a sustained radiologic response until March 2025, when she presented with hepatic progression. FOLFOX chemotherapy was initiated but discontinued after one cycle due to severe thrombocytopenia. Deterioration in general condition ultimately led to supportive care and death in March 2026. Conclusions: This case highlights the risk of cumulative haematological toxicity with PRRT, particularly in retreatment settings. Careful patient selection and close monitoring are essential. Streptozocin-based chemotherapy may be an effective and well-tolerated alternative for patients with treatment-limiting toxicity. Full article

Background: Acute appendicitis in girls presenting with lower abdominal pain remains a frequent diagnostic dilemma because of the overlap in clinical presentation with gynaecological and non-surgical causes. This study aimed to evaluate the diagnostic performance of IL-6 and CD64 and to compare them with classical inflammatory markers and the Alvarado score. Methods: We conducted a prospective observational diagnostic-accuracy study over a three-year period (December 2022 to December 2025) at the First University Paediatric Surgery Clinic, General Hospital of Thessaloniki “Georgios Gennimatas”. Consecutive girls aged ≤16 years presenting with lower abdominal pain were included. The primary outcome was appendicitis (yes/no), defined by the final clinical diagnosis and, where applicable, intraoperative and/or histopathological confirmation. Diagnostic performance was assessed using ROC curves and AUCs with 95% confidence intervals estimated by the DeLong method. The prespecified primary regression model included the Alvarado score and IL-6; IL-6 was summarised on its original scale and log1p-transformed only for regression analyses to account for right-skewness. Additional multivariable models were exploratory. Results: Of 74 initially assessed cases, one was excluded (appendiceal neuroendocrine tumour, NET G1), yielding a final sample of 73 girls: 37 with appendicitis and 36 without appendicitis. IL-6 was higher in the appendicitis group (median 19.41 vs. 4.10 pg/mL) and showed moderate discrimination (AUC 0.696). CRP showed lower to borderline performance (AUC 0.595), whereas CD64 did not demonstrate useful discrimination (AUC 0.521). The Alvarado score had the highest discriminatory ability (AUC 0.885). In the subset with complete data, adding IL-6 to the Alvarado score did not materially improve discrimination. Conclusions: IL-6 showed moderate diagnostic performance as a standalone biomarker and may be useful as an adjunct, particularly when a clinical score is unavailable or unreliable. CD64 did not add meaningful diagnostic information in this setting. Larger, prespecified studies are required to determine clinically useful cut-offs and to clarify whether IL-6 offers incremental value beyond established clinical assessment. Full article

According to the WHO classification of tumors, neuroendocrine neoplasms (NENs) of the esophagus are esophageal “epithelial neoplasms with neuroendocrine differentiation, including well-differentiated neuroendocrine tumours (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs)—an umbrella category including mixed adenoneuroendocrine carcinoma (MANEC)” [...] Full article

Background: Pituitary neuroendocrine tumours (PitNETs) are clinically and biologically heterogeneous neoplasms that remain challenging to diagnose, prognosticate, and treat. Although recent WHO classifications using transcription-factor-based markers have refined pathological categorisation, histopathology alone still fails to predict tumour behaviour or support individualised therapy. Objective: This systematic review aimed to evaluate how machine learning (ML) and knowledge extraction approaches can complement pathology by integrating multi-dimensional omics datasets to generate predictive and clinically meaningful insights in PitNETs. Methods: The review followed the PRISMA 2020 statement for systematic reviews. Searches were conducted in PubMed, Google Scholar, arXiv, and SciSpace up to June 2025 to identify omics studies applying ML or computational data integration in PitNETs. Eligible studies included original research using genomic, transcriptomic, epigenomic, proteomic, or liquid biopsy data. Data extraction covered study design, ML methodology, data accessibility, and clinical annotation. Study quality and validation strategies were also assessed. Results: A total of 726 records were identified. After the reviewing process, 98 studies met inclusion criteria. PitNET research employed unsupervised clustering or regularised regression methods reflecting their suitability for high-dimensional omics datasets and the limited sample sizes. In contrast, deep learning approaches were rarely implemented, primarily due to the scarcity of large, clinically annotated cohorts required to train such models effectively. To support future research and model development, we compiled a comprehensive catalogue of all publicly available PitNET omics resources, facilitating reuse, methodological benchmarking, and integrative analyses. Conclusions: Although omics research in PitNETs is increasing, the lack of standardised, clinically annotated datasets remains a major obstacle to the development and deployment of robust predictive models. Coordinated efforts in data sharing and clinical harmonisation are required to unlock its full potential. Full article

Background/Objectives: Insulinomas are rare insulin-secreting pancreatic neuroendocrine tumours (pNETs). Preoperative tumour localisation can usually be achieved by computed tomography (CT), magnetic resonance imaging, or positron emission tomography (PET)-CT. However, cross-sectional imaging can be negative, defining an insulinoma as occult and thus hampering surgical resection. Methods: All patients who underwent minimally invasive (MI) surgery for an insulinoma at the University Medical Center Hamburg-Eppendorf since 2017 were analysed. Clinicopathological parameters and diagnostic and operative approaches were assessed. A literature search of the MI resection of occult insulinomas was conducted. Results: Of eight patients with MI-resected insulinomas, two (25%) had negative preoperative imaging. Mean tumour size was 17.2 ± 13.3 mm. Patients underwent distal pancreatectomy (DP), enucleation, and pancreatic head resection (PHR) in 62.5% (5/8), 25.0% (2/8), and 12.5% (1/8) of cases, respectively. One patient had a major postoperative complication (Clavien–Dindo ≥ 3a). Twenty-four studies reporting on 140 occult insulinomas were identified. Occult insulinomas were more frequent in females, often located in the distal pancreas and G1-differentiated. Glucagon-Like Peptide-1 Receptor/PET-CT most frequently localised the conventionally non-visible insulinomas (positive in 67/76, 88.2%). Enucleation, DP, PHR and other resections were conducted in 47/94 (50.0%), 40/94 (42.6%), 4/94 (4.3%), and 3 (3.2%) of the reported cases. MI resection was reported in 10 of 19 (52.6%) specified resections. Conclusions: Insulinomas can be undetectable in cross-sectional and functional imaging. Surgical exploration with intraoperative ultrasound should be considered when clinical presentation and biochemical findings are highly suggestive for insulinoma. Minimally invasive and parenchyma sparing resection is feasible even for occult insulinomas and should always be considered. Full article

Background and Objectives: Neuroendocrine neoplasms are heterogeneous tumours arising from endocrine gland cells and the neuroendocrine system. Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) constitute two-thirds of this tumour group. This study was aimed at investigating the relationship between histone deacetylase enzymes (HDAC) and glutamine synthetase (GS) positivity, and ⁶⁸Ga-DOTATATE PET/CT data and their effect on prognosis in gastroenteropancreatic neuroendocrine tumours. Materials and Methods: Twenty-seven patients with Grade 1 and Grade 2 well-differentiated neuroendocrine tumours, diagnosed by biopsy and admitted to our nuclear medicine clinic for staging were included in the study. Results: There was no statistically significant correlation between HDAC and GS positivity in tumours and DOTATATE SUVmax value on PET/CT. There was no significant correlation between HDAC and GS positivity or negativity in the tumour and the presence or absence of metastasis on PET/CT. There was no statistically significant relationship between HDAC and GS positivity and survival. There was a statistically significant correlation between DOTATATE SUVmax value on PET/CT and survival (p = 0.039). Conclusions: According to the results of the present study, overall survival rates decreased in patients with high ⁶⁸Ga-DOTATATE uptake on PET/CT and therefore, patients with high SUVmax on PET/CT should be followed closely and their prognosis may be poor. In addition, although not statistically significant, the mortality rate is higher in patients with HDAC-positive tumours compared to in patients with HDAC-negative tumours; thus, it should be kept in mind that the prognosis of such patients may also be poor. According to the results of the present study, GS levels were generally negative in NETs. In addition, there was no statistically significant relationship between GS levels and survival. Full article

Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour (pNET) cells and the metabolic remodelling occurring in the presence and absence of glucose. pNET cell lines (BON-1 and QGP-1) and the non-malignant pancreatic α-TC1 cell line were used as models. Results showed that pNET cells responded differently to glucose deprivation than α-TC1 cells. Specifically, pNET cells upregulated the GCGR in the absence of glucose, while α-TC1 cells did so in high-glucose conditions, allowing the glucagon-related pERK1/2 activation under these conditions in pNET cells. Glucagon enhanced cancerous features in pNET BON-1 cells under glucose-deprived and hyperglucagonemia-compatible concentrations. In the α-TC1 cell line, glucagon modulated cell features under high-glucose and physiological glucagon levels. NMR exometabolome analysis revealed differences in metabolic processes based on glucose availability and glucagon stimulation across cell lines, highlighting amino acid metabolism, glycolysis, and gluconeogenesis. The expression of metabolic genes was consistent with these findings. Interestingly, QGP-1 and α-TC1 cells produced glucose in no-glucose conditions, and glucagon upregulated glucose production in α-TC1 cells. This suggests that gluconeogenesis may be beneficial for some pNET subsets, pointing out novel metabolism-based strategies to manage pNETs, as well as a step forward in endocrinology and systemic metabolism. The association between GCGR expression and malignancy and a negative correlation between glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) expression was observed, indicating a biological role of glucagon in pNETs that deserves to be explored. Full article

Objectives: The aim of this study was to investigate the treatment patterns and outcomes in two propensity score-matched cohorts of patients with neuroendocrine tumours (NETs) treated with first-line somatostatin analogue (SSA). Methods: Metastatic NET patients treated with first-line SSA (2009–2022) were retrospectively examined. First-line lanreotide vs. octreotide cohorts were matched 1:1 by propensity scores for demographics, tumour characteristics, and diagnosis year. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan–Meier analysis and the Cox proportional hazards model. Results: Among 441 patients, 310 were matched (155 in both the octreotide and lanreotide groups). First-line SSA was monotherapy (63.5%) or combination with other medications (36.5%). A total of 77% of second-line patients (188/244) maintained their initial SSA medication in combination with other therapies. Radioligand therapy with lanreotide (N = 72; 29.5%) or octreotide (N = 70; 28.7%) was the most common second-line treatment. First-line lanreotide and octreotide cohorts had similar median PFS (15.5; 95% CI: 13.6–19.1 vs. 14.0; 95% CI: 12.0–15.8 months), despite octreotide having a 36% higher likelihood of moving to the second line than lanreotide (95% CI: 1.05–1.76, p = 0.018). Multiple metastases (HR = 1.45; p = 0.004, 95% CI: 1.13–1.87) and Ki-67 > 20% (HR = 2.34; p < 0.001, 95% CI: 1.43–3.83) were significantly associated with the worst PFS. First-line lanreotide patients had a median OS of 10.4 years (95% CI: 7.5-NA) and octreotide 9.2 years (95% CI: 7.3-NA) (p = 0.537). Bone metastases increased death risk by 91% (p = 0.014; 95% CI: 1.14–3.20). Conclusions: SSA monotherapy is the main first-line treatment and most subsequent treatments include SSA with additional medications. Cohorts had similar PFS/OS, but octreotide demonstrated a 36% significantly higher likelihood of moving to the second-line treatment. Full article

BACKGROUND: Maximal safe resection is the objective of most neuro-oncological operations. Intraoperative magnetic resonance imaging (iMRI) may guide the surgeon to improve the extent of safe resection. There is limited evidence comparing the impact of iMRI on the rates of further resection between tumour types. AIM: To investigate the impact of iMRI on the rate of further resection following visualisation of residual tumour. METHODS: A retrospective cohort study identified all intracranial tumour operations performed in the 1.5 T iMRI machine of a single centre (2007–2023). Patients were identified using SurgiNet and were grouped according to their histopathological diagnosis in accordance with the WHO 2021 classification. The primary outcome was the rate of reoperation due to iMRI visualisation of residual tumours. RESULTS: A total of 574 cases were identified, including 152 low-grade gliomas (LGG), 108 high-grade gliomas (HGG), 194 pituitary neuroendocrine tumours (PitNETs), 15 metastases, and 6 meningiomas. Further resection following iMRI visualisation occurred in 45% of LGG cases, 47% of HGG cases, 29% of PitNET cases, and no meningioma or metastasis cases. Chi-square analysis showed that the rate of further resection after iMRI use across 2018–2023 was significantly higher than that across 2007–2012 (46% versus 33%, p = 0.036). CONCLUSION: Intraoperative MRI for guiding further resection was most useful in cases of LGG and HGG, possibly reflecting the difficulty of differentiating these tumour types from normal brain tissue. In addition, there was increased reliance on iMRI over time, which may represent our surgeons becoming accustomed to its use. Full article

Neuroendocrine tumours (NETs) are relatively rare neoplasms but represent one of the most frequent types of primary small-bowel tumours. Their incidence is rising, and this is most likely because of their more frequent early-stage detection, physician awareness, and increasing availability and use of imaging and small-bowel endoscopic techniques, such as video capsule endoscopy and device-assisted enteroscopy, which enable the detection, localisation, and histological sampling of previously inaccessible and underdiagnosed small-bowel lesions. This review summarises the role of small-bowel endoscopy in the diagnosis and management of small-bowel NETs to assist clinicians in their practice. Small-bowel endoscopy may play a complementary role in the diagnosis of these tumours alongside other diagnostic tests, such as biomarkers, conventional radiology, and functional imaging. In addition, small-bowel enteroscopy may play a role in the preoperative setting for the identification and marking of these tumours for surgical resection and the management of rare complications, such as small-bowel variceal bleeding, in cases of portal hypertension due to the encasement of mesenteric vessels in fibrotic small-bowel NETs. Full article

Background: Sarcopenia is a muscle disease that occur across a lifetime. It is commonly described in the aging population but can occur earlier in life in patients with cancer. Previous studies demonstrated sarcopenia is highly prevalent in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). In solid organ cancers, such as colorectal or pancreatic cancer, the presence of sarcopenia is associated with surgical complications. It is unknown if sarcopenia in patients with GEP-NETs is a risk factor for surgical complications. Methods: A multicentre retrospective study was performed in patients with a recently diagnosed GEP-NET and surgery to the primary tumour. CT scans were analysed for body composition analyses to assess for the presence of sarcopenia. Data regarding surgical procedures and complications were collected. Any major surgical complication was considered as Clavien–Dindo score ≥ 3. Results: This study included 180 patients, with 83 being male (46%) with a median age of 62 years (IQR 54–69). Most patients (n = 138, 77%) had a small intestinal NET, while 36 patients (20%) had pancreatic NETs. Sarcopenia was present in 109 patients (61%). In 43 patients (24%), surgical complications were recorded, and 21 complications (49%) were considered as major. Any type of surgical complication was not statistically different between patients without sarcopenia (n = 17, 24%) and with sarcopenia (n = 26, 24%)—a p-value of 0.36. This was the same for major complications; between patients without sarcopenia (n = 5, 24%) and with sarcopenia (n = 16, 76%)—a p-value of 0.18. Conclusions: Sarcopenia is highly prevalent in patients with a recently diagnosed GEP-NET, but this is not associated with major surgical complications. Future studies should include pathophysiological mechanisms that could be used to identify the causes of sarcopenia, its effect on quality of life and other oncological outcomes. Full article

Therapeutic options for pituitary neuroendocrine tumours (PitNETs) refractory to temozolomide are scarce. Immune checkpoint inhibitors (ICIs), particularly inhibitors of the programmed cell death-1 (PD-1) pathway and its ligand (PD-L1), have been experimentally used in aggressive or metastatic PitNETs. We aimed to study the therapeutic usefulness of anti-PD-1 drugs in patients with aggressive or metastatic PitNETs. Published cases and case series involving patients with PitNETs treated with PD-1/PD-L1 inhibitors were reviewed. Demographic data, clinical–pathological features, previous therapies, drug dosage and posology, and the best radiological and biochemical responses, as well as survival data, were evaluated. We identified 29 cases of aggressive (n = 13) or metastatic (n = 16) PitNETs treated with PD-1/PD-L1 inhibitors. The hypersecretion of adrenocorticotropic hormone (ACTH) was documented in eighteen cases (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to using ICIs. Overall, a positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen of twenty-nine cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 of the 17 functioning PitNET cases with available data (64.7%). The median survival of patients treated with ICIs was 13 months, with a maximum of 42 months in two ACTH-secreting tumours. Among 29 patients with PitNETs treated with PD-1/PD-L1 inhibitors, the positive radiological and biochemical response rates were 62.1% and 64.7%, respectively. Altogether, these data suggest a promising role of ICIs in patients with aggressive or metastatic PitNETs refractory to other treatment modalities. Full article

Post-operative tumour progression in patients with non-functioning pituitary neuroendocrine tumours is variable. The aim of this study was to use machine learning (ML) models to improve the prediction of post-operative outcomes in patients with NF PitNET. We studied data from 383 patients who underwent surgery with or without radiotherapy, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree, showed superior performance in predicting tumour progression when compared with parametric statistical modelling using logistic regression, with SVM achieving the highest performance. The strongest predictor of tumour progression was the extent of surgical resection, with patient age, tumour volume, and the use of radiotherapy also showing influence. No features showed an association with tumour recurrence following a complete resection. In conclusion, this study demonstrates the potential of ML models in predicting post-operative outcomes for patients with NF PitNET. Future work should look to include additional, more granular, multicentre data, including incorporating imaging and operative video data. Full article

This review article explores the evolving landscape of Molecular Radiotherapy (MRT), emphasizing Peptide Receptor Radionuclide Therapy (PRRT) for neuroendocrine tumours (NETs). The primary focus is on the transition from β-emitting radiopharmaceuticals to α-emitting agents in PRRT, offering a critical analysis of the radiobiological basis, clinical applications, and ongoing developments in Targeted Alpha Therapy (TAT). Through an extensive literature review, the article delves into the mechanisms and effectiveness of PRRT in targeting somatostatin subtype 2 receptors, highlighting both its successes and limitations. The discussion extends to the emerging paradigm of TAT, underlining its higher potency and specificity with α-particle emissions, which promise enhanced therapeutic efficacy and reduced toxicity. The review critically evaluates preclinical and clinical data, emphasizing the need for standardised dosimetry and a deeper understanding of the dose-response relationship in TAT. The review concludes by underscoring the significant potential of TAT in treating SSTR2-overexpressing cancers, especially in patients refractory to β-PRRT, while also acknowledging the current challenges and the necessity for further research to optimize treatment protocols. Full article