Best practice & research. Clinical endocrinology & metabolism最新文献

Neuroendocrine tumours commonly metastasise to the liver, particularly those arising from the intestinal tract and pancreas. Whilst surgery offers the only approach with intent to cure, the vast majority of patients with neuroendocrine liver metastases are ineligible. Liver-directed interventional therapies seek to exploit the patho-anatomy of the blood supply of hepatic metastases to deliver therapy to liver deposits. This may involve percutaneous ablation, bland embolization, or the selective infusion of chemotherapeutics, targeted agents or radiolabelled embolic material. Retrospective case series evidence has characterised objective response rates, disease control rates, and longer-term outcomes associated with each approach. Recent advances in this field include ongoing comparative trials of different techniques, but more importantly, combinations of interventional liver-directed therapies and other systemic therapy in multimodal treatment concepts.

Gastro-enteropancreatic neuroendocrine tumours (GEP-NETs) represent a rare and highly heterogeneous entity with increasing incidence. Based on the results obtained from several trials performed in the last decade, various therapeutic options have been established for the treatment of patients with GEP-NETs. The options include somatostatin analogues, targeted therapies (sunitinib and everolimus), chemotherapy (with temozolomide or streptozocin-based regimens), and peptide receptor radionuclide therapy. The treatment choice is influenced by various clinico-pathological factors including tumour grade and morphology, the primary mass location, hormone secretion, the volume of the disease and the rate of tumour growth, as well as patient comorbidities and performance status. In this review, the efficacy and safety of treatment options for patients with GEP-NETs is discussed and the evidence to inform the best sequence of available therapies to control tumour growth, prolong patient survival, and to lower potential toxicity, while maintaining patient quality of life is explored.

Precision medicine describes a target-related approach to tailoring diagnosis and treatment of the individual patient. While this personalized approach is revoluzionizing many areas of oncology, it is quite late in the field of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), in which there are few molecular alterations to be therapeutically targeted. We critically reviewed the current evidence about precision medicine in GEP NENs, focusing on potential clinically relevant actionable targets for GEP NENs, such as the mTOR pathway, MGMT, hypoxia markers, RET, DLL-3, and some general agnostic targets. We analysed the main investigational approaches with solid and liquid biopsies. Furthermore, we reviewed a model of precision medicine more specific for NENs that is the theragnostic use of radionuclides. Overall, currently no true predictive factors for therapy have been validated so far in GEP NENs, and the personalized approach is based more on clinical thinking within a NEN-dedicated multidisciplinary team. However, there is a robust background to suppose that precision medicine, with the theragnostic model will yield new insights in this context soon.

Neuroendocrine neoplasms are a unique form of malignancies as they can be accompanied by specific functioning hormonal syndromes that can impair survival and quality of life in patients. Functioning syndromes are defined by the combination of specific clinical signs and symptoms in combination with inappropriately elevated circulating levels of hormones. Clinicians should remain vigilant for the presence of functioning syndromes in neuroendocrine neoplasm patients at presentation as well as during follow-up. The correct diagnostic work-up should be initiated in cases of clinical suspicion of a neuroendocrine neoplasm-associated functioning syndrome. Management of a functional syndrome includes options from supportive, surgical, hormonal and antiproliferative treatment modalities. Here, we review the patient and tumour characteristics for each functioning syndrome that should be taken into account when deciding the optimum treatment strategy in neuroendocrine neoplasm patients.

Histopathological classifications of neuroendocrine neoplasms (NEN) change regularly and the latest WHO classification published in 2022, which concerns all NEN in the body, attempts to standardize classifications in the different locations. Differentiation and proliferation mainly assessed by Ki-67 index are still the cornerstone of those classifications. However, many markers are now used for diagnostic (to check neuroendocrine differentiation, to identify the site of origin of a metastasis, to help separating high-grade neuroendocrine tumors/NET and neuroendocrine carcinoma/NEC), prognostic or theranostic purposes. NENs are often heterogeneous and this can lead to difficulties in classifications, biomarker and prognostic assessment. These different points are discussed successively in this review, insisting especially on the frequent digestive, gastro-entero-pancreatic (GEP) localizations.

Neuroendocrine neoplasms are rare and heterogenous group of tumors with varying degrees of clinical presentations and involvement of multiple organ systems in the body. In the modern clinical practice somatostatin receptor molecular imaging and targeted radioligand therapy plays a vital role in the diagnosis and management of the disease. Several new and promising radiotracers for NET imaging and theranostics, belonging to various groups and classes are being studied and investigated. This exponential growth of radiotracers poses concerns about the indication, clinical benefit, and safety profile of the agents. We discuss the basis behind these radiotracers clinical use, receptor targeting and intra and inter tumor heterogeneity. Furthermore, role of dual tracer imaging, combination therapy and potential applications of dosimetry in predicting treatment outcome and safety profile is reviewed. Individualized precision medicine with better tumor characterization, maximum therapeutic benefit and minimum toxicity is the way forward for future medicine.

Neuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously considered uncommon, such as bone metastases, or even very rare, such as brain, orbital and cardiac metastases, are more frequently found in daily practice. Due to the great heterogeneity of these neoplasms, there is a lack of high-quality evidence on the management of patients with these types of metastases. The aim of this review is to provide the current state of the art, reviewing neuroendocrine neoplasm specific studies and useful information from other tumor types and to propose a treatment recommendation with algorithms to consider in daily clinical practice.

Neuroendocrine tumors (NETs) are relatively rare neoplasms displaying heterogeneous clinical behavior, ranging from indolent to aggressive forms. Patients diagnosed with NETs usually receive a varied array of treatments, including somatostatin analogs, locoregional treatments (ablation, intra-arterial therapy), cytotoxic chemotherapy, peptide receptor radionuclide therapy (PRRT), and targeted therapies. To maximize therapeutic efficacy while limiting toxicity (both physical and economic), there is a need for accurate and reliable tools to monitor disease evolution and progression and to assess the effectiveness of these treatments. Imaging morphological methods, primarily relying on computed tomography (CT) and magnetic resonance imaging (MRI), are indispensable modalities for the initial evaluation and continuous monitoring of patients with NETs, therefore playing a pivotal role in gauging the response to treatment. The primary goal of assessing tumor response is to anticipate and weigh the benefits of treatments, especially in terms of survival gain. The World Health Organization took the pioneering step of introducing assessment criteria based on cross-sectional imaging. This initial proposal standardized the measurement of lesion sizes, laying the groundwork for subsequent criteria. The Response Evaluation Criteria in Solid Tumors (RECIST) subsequently refined and enhanced these standards, swiftly gaining acceptance within the oncology community. New treatments were progressively introduced, targeting specific features of NETs (such as tumor vascularization or expression of specific receptors), and achieving significant qualitative changes within tumors, although associated with minimal or paradoxical effects on tumor size. Several alternative criteria, adapted from those used in other cancer types and focusing on tumor viability, the slow growth of NETs, or refining the existing size-based RECIST criteria, have been proposed in NETs. This review article aims to describe and discuss the optimal utilization of CT and MRI for assessing the response of NETs to treatment; it provides a comprehensive overview of established and emerging criteria for evaluating tumor response, along with comparative analyses. Molecular imaging will not be addressed here and is covered in a dedicated article within this special issue.

Neuroendocrine tumors (NETs) represent a heterogeneous group of malignancies that arise from neuroendocrine cells dispersed throughout the organs/tissues of the body. Treatment of advanced/metastatic disease varies depending on tumor origin and grade. Somatostatin analogs (SSA) have been the mainstay first-line treatment in the advanced/metastatic setting for tumor control and managing hormonal syndromes. Treatments beyond SSAs have expanded to include everolimus (mTOR inhibitor), tyrosine kinase inhibitors (TKI) (e.g., sunitinib), and peptide receptor radionuclide therapy (PRRT) with the choice of therapy to some extent dictated by the anatomic origin of the NETs. This review will focus on emerging systemic treatments for advanced/metastatic NETs, particularly TKIs, and immunotherapy.

The SARS-CoV-2 pandemic has had an unprecedented effect on global health, mortality and healthcare provision. Diabetes has emerged as a key disease entity over the pandemic period, influencing outcomes from COVID-19 but also a tantalising hypothesis that the virus itself may be inducing diabetes. An uptick in diabetes cases over the pandemic has been noted for both type 1 diabetes (in children) and type 2 diabetes but understanding how this increase in incidence relates to the pandemic is challenging. It remains unclear whether indirect effects of the pandemic on behaviour, lifestyle and health have contributed to the increase; whether the virus itself has somehow mediated new-onset diabetes or whether other factors such as stress hyperglycaemic of steroid treatment during COVID-19 infection have played a roll. Within the myriad possibilities are some real challenges in interpreting epidemiological data, assigning diabetes type and understanding what in vitro data are telling us. In this review article we address the issue of newly-diagnosed diabetes during the pandemic, reviewing both epidemiological and basic science data and bringing together both strands of this emerging story.