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Keywords = carcinoid syndrome

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20 pages, 2581 KiB  
Review
Nutritional Management of Functioning GEP-NENs
by Maribel del Olmo-García, Lorena Hernandez-Rienda, Maria Argente Pla and Juan F. Merino-Torres
Nutrients 2025, 17(13), 2175; https://doi.org/10.3390/nu17132175 - 30 Jun 2025
Viewed by 452
Abstract
Background: Functioning gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors that secrete biologically active hormones, leading to complex clinical syndromes such as carcinoid syndrome, VIPoma, glucagonoma, gastrinoma, insulinoma, and somatostatinoma. These syndromes frequently induce profound metabolic, gastrointestinal, and nutritional disturbances. Objective: This review aims [...] Read more.
Background: Functioning gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors that secrete biologically active hormones, leading to complex clinical syndromes such as carcinoid syndrome, VIPoma, glucagonoma, gastrinoma, insulinoma, and somatostatinoma. These syndromes frequently induce profound metabolic, gastrointestinal, and nutritional disturbances. Objective: This review aims to provide a comprehensive overview of the physiopathology of malnutrition in functioning GEP-NENs and to highlight nutritional and supportive care strategies, including how medical, surgical, and locoregional treatments can indirectly improve nutritional outcomes. Methods: We analyzed the current literature and clinical guidelines to identify key mechanisms of malnutrition across different functioning syndromes and their clinical manifestations. Nutritional recommendations and the impact of treatment modalities on nutritional status were summarized. Results: The pathophysiology of malnutrition in functioning NENs is multifactorial and syndrome-specific. Hormonal hypersecretion may cause diarrhea, electrolyte imbalances, catabolic states, steatorrhea, or hypoglycemia, among other effects. These lead to nutrient loss, malabsorption, or altered intake. Tailored dietary interventions, micronutrient supplementation (e.g., niacin, calcium, vitamin B12), and symptom-guided nutritional support are essential. Somatostatin analogs, PRRT, and cytoreductive approaches often contribute to symptom control, thereby enhancing nutritional status and patient quality of life. Conclusions: Malnutrition in functioning GEP-NENs is a significant clinical issue that requires early recognition and a multidisciplinary, individualized management plan. Integrating nutrition into the comprehensive care of these patients is essential to improve outcomes and quality of life. Full article
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15 pages, 1717 KiB  
Article
The Value of Repeat 5-HIAA Measurements as a Predictor of Carcinoid Heart Disease: A Prospective 5-Year Follow-Up Study in Patients with Small Intestinal Neuroendocrine Tumors
by Iiro Kostiainen, Piia Simonen, Katri Aaltonen, Riikka Lindén, Noora Karppinen, Daniel Gordin, Janne Rapola, Camilla Schalin-Jäntti and Niina Matikainen
Cancers 2024, 16(23), 3896; https://doi.org/10.3390/cancers16233896 - 21 Nov 2024
Cited by 2 | Viewed by 1061
Abstract
Background: Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. Methods: We measured [...] Read more.
Background: Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. Methods: We measured 5-HIAA and cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeated measurements, proBNP, vascular function, hepatic tumor load, and transthoracic echocardiography (TTE) at baseline and during the median 5-year follow-up. Of 65 patients with SI-NETs, 54 patients underwent a prospective follow-up. In addition, survival was evaluated during the median follow-up of 6 years. Results: At baseline, three patients had CHD. During the median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg score, Spearman’s ρ = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristic analysis with an AUC of 0.98 (95% CI: 0.94–1.00) and outperformed proBNP, chromogranin A (CgA), and individual serum 5-HIAA measurements (AUC = 0.75, 0.85, and 0.91, respectively). Minor changes in valve regurgitation were frequently detected but did not correlate with vascular function. Regurgitation increased or decreased in 29% of tricuspid and 30% of pulmonic valves. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) were associated with increased mortality in SI-NET patients. Conclusions: Cum-5-HIAA is a promising biomarker for CHD risk and outperformed other biomarkers. CHD and hepatic tumor load are the strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was low among the SI-NET patients, probably reflecting successful treatment regimens. Full article
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17 pages, 761 KiB  
Review
Exploring Carcinoid Syndrome in Neuroendocrine Tumors: Insights from a Multidisciplinary Narrative Review
by Matteo Marasco, Elena Romano, Giulia Arrivi, Daniela Prosperi, Maria Rinzivillo, Damiano Caruso, Paolo Mercantini, Michele Rossi, Antongiulio Faggiano and Francesco Panzuto
Cancers 2024, 16(22), 3831; https://doi.org/10.3390/cancers16223831 - 14 Nov 2024
Cited by 2 | Viewed by 2787
Abstract
Carcinoid syndrome (CS) is a rare condition associated with neuroendocrine tumors (NETs), particularly those originating in the gastrointestinal tract, which secrete bioactive substances like serotonin. The management of CS requires a multidisciplinary approach due to its complex clinical manifestations, including flushing, diarrhea, bronchospasm, [...] Read more.
Carcinoid syndrome (CS) is a rare condition associated with neuroendocrine tumors (NETs), particularly those originating in the gastrointestinal tract, which secrete bioactive substances like serotonin. The management of CS requires a multidisciplinary approach due to its complex clinical manifestations, including flushing, diarrhea, bronchospasm, and carcinoid heart disease. Optimal care involves collaboration between several professional figures like oncologists, endocrinologists, gastroenterologists, surgeons, and dietitians. Currently, a wide range of treatments are available, focused on both symptom control and tumor burden reduction. Somatostatin analogs (SSAs) are the first-line therapy for symptom relief. Still, in patients with progressive disease or refractory CS, other options include targeted therapies, peptide receptor radionuclide therapy (PRRT), liver-directed therapies, and surgical resection, when feasible. Furthermore, management of complications related to prolonged serotonin release and malnutrition as a result of exocrine pancreatic insufficiency, post-surgical conditions, vitamin deficit, and chronic diarrhea often requires early detection to mitigate symptoms and improve the quality of life in these patients. The complexity of CS necessitates individualized care and continuous coordination among specialists to optimize outcomes and enhance patient well-being. Full article
(This article belongs to the Special Issue Neuroendocrine Tumors: From Diagnosis to Therapy)
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13 pages, 2308 KiB  
Review
Cardiac Surgery and Transcatheter Intervention for Valvular Heart Disease in Carcinoid Syndrome: Risk Factors, Outcomes, and Evolving Therapeutic Strategies
by Mariagrazia Piscione, Valeria Cammalleri, Giorgio Antonelli, Valeria Maria De Luca, Myriam Carpenito, Dario Gaudio, Nino Cocco, Antonio Nenna, Carmelo Dominici, Antonio Bianchi, Francesco Grigioni and Gian Paolo Ussia
J. Cardiovasc. Dev. Dis. 2024, 11(11), 359; https://doi.org/10.3390/jcdd11110359 - 7 Nov 2024
Cited by 1 | Viewed by 1294
Abstract
Carcinoid heart disease (CHD) affects right-sided valves and causes significant mortality and morbidity. Even though the pathophysiology of the disease is not entirely understood, it is known that chronic exposure to high levels of circulating serotonin is the main factor responsible for developing [...] Read more.
Carcinoid heart disease (CHD) affects right-sided valves and causes significant mortality and morbidity. Even though the pathophysiology of the disease is not entirely understood, it is known that chronic exposure to high levels of circulating serotonin is the main factor responsible for developing valvular heart disease. Cardiac imaging plays a critical role in the management of CHD, so the final diagnosis can be performed through multimodal imaging techniques and the measurement of biomarkers. Moreover, in observational studies, surgical treatment of carcinoid-induced valve disease has been found to improve outcomes. Despite advancements in pre-operative preparation in recent years, mortality rates remain high in elderly patients and those with multiple comorbidities due to the risk of intra-operative carcinoid crisis and high post-operative bleeding. In this comprehensive review, we will analyze the causes of carcinoid syndrome and how it can result in severe right heart failure. The role of different imaging modalities in detecting heart valve disease will be discussed together with the therapeutic options at our disposal, such as medical treatment, surgery, and the novel role of transcatheter intervention. Full article
(This article belongs to the Special Issue Risk Factors and Outcomes in Cardiac Surgery)
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10 pages, 787 KiB  
Article
Sarcopenia in Patients with Advanced Gastrointestinal Well-Differentiated Neuroendocrine Tumors
by Elena Romano, Michela Polici, Matteo Marasco, Francesco Lerose, Elisabetta Dell’Unto, Stefano Nardacci, Marta Zerunian, Elsa Iannicelli, Maria Rinzivillo, Andrea Laghi, Bruno Annibale, Francesco Panzuto and Damiano Caruso
Nutrients 2024, 16(14), 2224; https://doi.org/10.3390/nu16142224 - 11 Jul 2024
Cited by 5 | Viewed by 1866
Abstract
Background: Neuroendocrine neoplasms (NENs) are slow-growing tumors. Sarcopenia is defined as the loss of muscle mass, strength, and physical performance. First-line NEN therapy is somatostatin analogs, which could be responsible for malabsorption conditions, such as pancreatic exocrine insufficiency (EPI) with underlying sarcopenia. Aim: [...] Read more.
Background: Neuroendocrine neoplasms (NENs) are slow-growing tumors. Sarcopenia is defined as the loss of muscle mass, strength, and physical performance. First-line NEN therapy is somatostatin analogs, which could be responsible for malabsorption conditions, such as pancreatic exocrine insufficiency (EPI) with underlying sarcopenia. Aim: Evaluate the prevalence of sarcopenia in patients with NENs at diagnosis and during follow-up. Methods: A retrospective single-center study was conducted, including patients with advanced intestinal NENs G1/G2 (excluded pancreatic NENs). CT scans were analyzed at diagnosis and after 6 months of therapy, and the skeletal muscle index was assessed. Results: A total of 30 patients (F:M = 6:24) were enrolled, with the following primary tumor sites: 25 in the ileum, 1 stomach, 2 jejunum, and 2 duodenum. At diagnosis, 20 patients (66.6%) showed sarcopenic SMI values, and 10 patients (33.3%) showed non-sarcopenic SMI values. At follow-up, three more patients developed sarcopenic SMI values. Statistical significance in relation to the presence of sarcopenia was found in the group of patients with carcinoid syndrome (p = 0.0178), EPI (p = 0.0018), and weight loss (p = 0.0001). Conclusion: Sarcopenia was present in 2/3 of the patients with advanced intestinal NENs at the diagnosis and during the follow-up. It is reasonable to consider this condition to improve clinical outcomes. Full article
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21 pages, 1356 KiB  
Systematic Review
Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors
by Nektaria Papadopoulou-Marketou, Marina Tsoli, Eleftherios Chatzellis, Krystallenia I. Alexandraki and Gregory Kaltsas
Cancers 2024, 16(11), 2075; https://doi.org/10.3390/cancers16112075 - 30 May 2024
Cited by 8 | Viewed by 2272
Abstract
Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms. While the majority is sporadic, approximately 17% of PanNETs and a subset of LNETs develop in the context of monogenic familial tumor syndromes, especially multiple endocrine [...] Read more.
Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms. While the majority is sporadic, approximately 17% of PanNETs and a subset of LNETs develop in the context of monogenic familial tumor syndromes, especially multiple endocrine neoplasia type 1 (MEN1) syndrome. Other inherited syndromes associated with PanNETs include MEN4, von Hippel–Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). These syndromes are highly penetrant and their clinical manifestations may vary even among members of the same family. They are attributed to genetic mutations involving key molecular pathways regulating cell growth, differentiation, and angiogenesis. Pancreatic NETs in hereditary syndromes are often multiple, develop at a younger age compared to sporadic tumors, and are associated with endocrine and nonendocrine tumors derived from multiple organs. Lung NETs are not as common as PanNETs and are mostly encountered in MEN1 syndrome and include typical and atypical lung carcinoids. Early detection of PanNETs and LNETs related to inherited syndromes is crucial, and specific follow-up protocols need to be employed to optimize diagnosis and management. Genetic screening is recommended in childhood, and diagnostic screening starts often in adolescence, even in asymptomatic mutation carriers. Optimal management and therapeutic decisions should be made in the context of a multidisciplinary team in specialized centers, whereas specific biomarkers aiming to identify patients denoted to follow a more aggressive course need to be developed. Full article
(This article belongs to the Section Cancer Pathophysiology)
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16 pages, 687 KiB  
Review
Liver-Directed Locoregional Therapies for Neuroendocrine Liver Metastases: Recent Advances and Management
by Cody R. Criss and Mina S. Makary
Curr. Oncol. 2024, 31(4), 2076-2091; https://doi.org/10.3390/curroncol31040154 - 5 Apr 2024
Cited by 4 | Viewed by 3718
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such [...] Read more.
Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such as carcinoid syndrome, which can manifest as a constellation of symptoms significantly impacting patients’ quality of life. The prognosis of NETs is influenced by their tendency for metastasis, especially in cases involving the liver, where the estimated 5-year survival is between 20 and 40%. Although surgical resection remains the preferred curative option, challenges emerge in cases of neuroendocrine tumors with liver metastasis (NELM) with multifocal lobar involvement, and many patients may not meet the criteria for surgery. Thus, minimally invasive and non-surgical treatments, such as locoregional therapies, have surfaced. Overall, these approaches aim to prioritize symptom relief and aid in overall tumor control. This review examines locoregional therapies, encompassing catheter-driven procedures, ablative techniques, and radioembolization therapies. These interventions play a pivotal role in enhancing progression-free survival and managing hormonal symptoms, contributing to the dynamic landscape of evolving NELM treatment. This review meticulously explores each modality, presenting the current state of the literature on their utilization and efficacy in addressing NELM. Full article
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21 pages, 9770 KiB  
Article
Downregulation of Serotonergic System Components in an Experimentally Induced Cryptorchidism in Rabbits
by Francisco Jiménez-Trejo, Cristian Arriaga-Canon, Luis A. Herrera, Isabel Coronado-Mares, Rogelio Montiel-Manríquez, Isaac González-Santoyo, Wendy B. Pérez-Báez and Miguel Tapia-Rodríguez
Int. J. Mol. Sci. 2024, 25(6), 3149; https://doi.org/10.3390/ijms25063149 - 9 Mar 2024
Cited by 1 | Viewed by 2243
Abstract
Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis [...] Read more.
Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis syndrome (TDS), a complex pathology regarding the male reproductive system that apparently involves the interaction of both genetic and environmental harmful factors, mainly during embryonic development. Serotonin (5-HT) is an ancient molecule that participates in a broad range of body functions, and in recent years, its importance in reproduction has started to be elucidated. In male pathologies such as infertility, varicocele, erectile dysfunction, and primary carcinoid tumors, an increase in 5-HT concentration or its metabolites in the blood, semen, and urine has been directly related; nevertheless, the role of 5-HT in CO remains unknown. In the present work, our goal was to answer two important questions: (1) whether some serotonergic system components are present in adult male Oryctolagus cuniculus (chinchilla rabbit) and (2) if there are changes in their expression in an experimental model of CO. Using histological, molecular, and biochemical approaches, we found the presence of some serotonergic system components in the adult chinchilla rabbit, and we demonstrated that its expression is downregulated after CO was pharmacologically induced. Although we did not test the role of 5-HT in the etiology of CO, our results suggest that this indoleamine could be important for the regulation of steroidogenesis and spermatogenesis processes in the chinchilla rabbit during adulthood. Finally, in parallel experimental series, we found downregulation of kynurenine concentration in COI rabbits when compared to control ones, suggesting that CO could be affecting the kynurenine pathway and probably testicular immune privilege which in turn could lead to infertility/sterility conditions in this disorder. Full article
(This article belongs to the Special Issue New Sights into the Serotonin System, Obesity and Diabetes)
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13 pages, 5457 KiB  
Article
Does Telotristat Have a Role in Preventing Carcinoid Heart Disease?
by Aura D. Herrera-Martínez, Antonio C. Fuentes-Fayos, Rafael Sanchez-Sanchez, Antonio J. Montero, André Sarmento-Cabral, María A. Gálvez-Moreno, Manuel D. Gahete and Raúl M. Luque
Int. J. Mol. Sci. 2024, 25(4), 2036; https://doi.org/10.3390/ijms25042036 - 7 Feb 2024
Cited by 3 | Viewed by 1928
Abstract
Carcinoid heart disease (CHD) is a frequent and life-threatening complication in patients with carcinoid tumors. Its clinical management is challenging is some cases since serotonin-induced valve fibrosis leads to heart failure. Telotristat is an inhibitor of tryptophan-hydroxylase (TPH), a key enzyme in serotonin [...] Read more.
Carcinoid heart disease (CHD) is a frequent and life-threatening complication in patients with carcinoid tumors. Its clinical management is challenging is some cases since serotonin-induced valve fibrosis leads to heart failure. Telotristat is an inhibitor of tryptophan-hydroxylase (TPH), a key enzyme in serotonin production. Telotristat use in patients with carcinoid syndrome and uncontrollable diarrhea under somatostatin analogs is approved, but its specific role in patients with CHD is still not clear. IN this context, we aimed to explore the effect of telotristat in heart fibrosis using a mouse model of serotonin-secreting metastasized neuroendocrine neoplasm (NEN). To this aim, four treatment groups (n = 10/group) were evaluated: control, monthly octreotide, telotristat alone, and telotristat combined with octreotide. Plasma serotonin and NT-proBNP levels were determined. Heart fibrosis was histologically evaluated after 6 weeks of treatment or when an individual mouse’s condition was close to being terminal. Heart fibrosis was observed in all groups. Non-significant reductions in primary tumor growth were observed in all of the treated groups. Feces volume was increased in all groups. A non-significant decrease in feces volume was observed in the octreotide or telotristat-treated groups, while it was significantly reduced with the combined treatment at the end of the study compared with octreotide (52 g reduction; p < 0.01) and the control (44.5 g reduction; p = 0.05). Additionally, plasma NT-proBNP decreased in a non-significant, but clinically relevant, manner in the octreotide (28.2% reduction), telotristat (45.9% reduction), and the octreotide + telotristat (54.1% reduction) treatment groups. No significant changes were observed in plasma serotonin levels. A similar non-significant decrease in heart valve fibrosis was observed in the three treated groups. In conclusion, Telotristat alone and especially in combination with octreotide decreases NT-proBNP levels in a mouse model of serotonin-secreting metastasized NEN, when compared with the control and octreotide, but its effect on heart valve fibrosis (alone and in combination) was not superior to octreotide in monotherapy. Full article
(This article belongs to the Special Issue Molecular Research of Gastrointestinal Disease)
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18 pages, 2590 KiB  
Review
Lung Carcinoids: A Comprehensive Review for Clinicians
by Dan Granberg, Carl Christofer Juhlin, Henrik Falhammar and Elham Hedayati
Cancers 2023, 15(22), 5440; https://doi.org/10.3390/cancers15225440 - 16 Nov 2023
Cited by 21 | Viewed by 5597
Abstract
Lung carcinoids are neuroendocrine tumors, categorized as typical or atypical carcinoids based on their histological appearance. While most of these tumors are slow-growing neoplasms, they still possess malignant potential. Many patients are diagnosed incidentally on chest X-rays or CT scans. Presenting symptoms include [...] Read more.
Lung carcinoids are neuroendocrine tumors, categorized as typical or atypical carcinoids based on their histological appearance. While most of these tumors are slow-growing neoplasms, they still possess malignant potential. Many patients are diagnosed incidentally on chest X-rays or CT scans. Presenting symptoms include cough, hemoptysis, wheezing, dyspnea, and recurrent pneumonia. Endocrine symptoms, such as carcinoid syndrome or ectopic Cushing’s syndrome, are rare. Surgery is the primary treatment and should be considered in all patients with localized disease, even when thoracic lymph node metastases are present. Patients with distant metastases may be treated with somatostatin analogues, chemotherapy, preferably temozolomide-based, mTOR inhibitors, or peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Most patients have an excellent prognosis. Poor prognostic factors include atypical histology and lymph node metastases at diagnosis. Long-term follow-up is mandatory since metastases may occur late. Full article
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16 pages, 4608 KiB  
Case Report
Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review
by Matteo Regolo, Nicolas Cardaci, Clara Salmeri, Alfredo Laudani, Michele Colaci, Massimo Ippolito, Fabio Motta, Salvatore Magrì, Stefanie Parisi, Alfredo Gaetano Torcitto and Lorenzo Malatino
J. Clin. Med. 2023, 12(20), 6617; https://doi.org/10.3390/jcm12206617 - 19 Oct 2023
Cited by 1 | Viewed by 2782
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Neuroendocrine Tumors: Etiology, Diagnosis, and Therapy)
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13 pages, 1999 KiB  
Article
Hedinger Syndrome—Lessons Learnt: A Single-Center Experience
by Mohamed El Gabry, Sven Arends, Sharaf-Eldin Shehada, Harald Lahner, Markus Kamler, Daniel Wendt and Konstantina Spetsotaki
J. Cardiovasc. Dev. Dis. 2023, 10(10), 413; https://doi.org/10.3390/jcdd10100413 - 1 Oct 2023
Cited by 2 | Viewed by 2387
Abstract
Background: Hedinger syndrome (HS) or carcinoid heart disease (CD) is a rare and challenging manifestation of malignant neuroendocrine tumours (NETs) involving the heart. We aimed to report our experience with surgical strategies and midterm results in HS patients. Methods: Eleven patients (58 ± [...] Read more.
Background: Hedinger syndrome (HS) or carcinoid heart disease (CD) is a rare and challenging manifestation of malignant neuroendocrine tumours (NETs) involving the heart. We aimed to report our experience with surgical strategies and midterm results in HS patients. Methods: Eleven patients (58 ± 11 (range 41 to 79 years); 5 females) with HS who underwent cardiac surgery in our department between 07/2005 and 05/2023 were analysed. Results: All patients showed a New York Heart Association (NYHA) class III–IV and in all the tricuspid valve (TV) was involved. Four patients received a TV replacement, and three TV reconstruction. Recently, to preserve the geometry and function of the compromised right ventricle (RV), we have applied the TV “bio-prosthesis in native-valve” implantation technique with the preservation of the valve apparatus (tricuspid valve implantation: TVI) in four cases. Concomitant procedures included pulmonary valve replacement in four, pulmonary implantation in one, and aortic valve replacement in three cases. To treat RV failure, we adapted a combined TandemHeart®-CytoSorb® haemoperfusion strategy in Patient #10 and venoarterial extracorporeal membrane oxygenation (V-A ECMO) support avoidance, after experiencing an ECMO-induced carcinoid-storm-related death in Patient #8. Mortality at 30 days was 18% (2/11). The median follow up was 2 ± 2.1 years (range 1 month to 6 years) with an overall mortality during the follow-up period of 72.7% (8/11). Conclusions: HS surgery, despite being a high-risk procedure, can efficiently prolong survival, and represents a safe and feasible procedure. However, patient selection seems to be crucial. Further follow up and larger cohorts are needed. Full article
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15 pages, 1008 KiB  
Review
Urinary 5-Hydroxyindolacetic Acid Measurements in Patients with Neuroendocrine Tumor-Related Carcinoid Syndrome: State of the Art
by Roberta Elisa Rossi, Elisabetta Lavezzi, Simona Jaafar, Giacomo Cristofolini, Alice Laffi, Gennaro Nappo, Silvia Carrara, Alexia Francesca Bertuzzi, Silvia Uccella, Alessandro Repici, Alessandro Zerbi and Andrea Gerardo Antonio Lania
Cancers 2023, 15(16), 4065; https://doi.org/10.3390/cancers15164065 - 11 Aug 2023
Cited by 4 | Viewed by 2115
Abstract
Carcinoid syndrome (CS), mostly associated with small intestinal neuroendocrine tumors (SI-NETs) or lung-related NETs, is characterized by symptoms related to hormonal secretion and long-term complications, including carcinoid heart disease (CHD), which is potentially life-threatening. In the early stages of the disease, symptoms are [...] Read more.
Carcinoid syndrome (CS), mostly associated with small intestinal neuroendocrine tumors (SI-NETs) or lung-related NETs, is characterized by symptoms related to hormonal secretion and long-term complications, including carcinoid heart disease (CHD), which is potentially life-threatening. In the early stages of the disease, symptoms are non-specific, which leads to delayed diagnoses. The availability of reliable tumor markers is crucial for a prompt diagnosis and proper management. This review summarizes available evidence on the role of 24 h urinary 5-hydroxyindolacetic acid (24u5HIAA), which is the urinary breakdown metabolite of serotonin, in the diagnosis/follow-up of NET-related CS, with a focus on its potential prognostic role, while eventually attempting to suggest a timeline for its measurement during the follow-up of NET patients. The use of 24u5HIAA is an established biomarker for the diagnosis of NETs with CS since it shows a sensibility and specificity of 100% and 85–90%, respectively. The downside of 24u5-HIAA is represented by the need for 24 h urine collection and the risk of confounding factors (foods and medication), which might lead to false positive/negative results. Moreover, 24u5HIAA is useful in the follow-up of NETs with CS since a shorter double time correlates to a higher risk of disease progression/disease-specific mortality. Furthermore, an elevation in 24u5-HIAA is correlated with a dismal prognosis because it is associated with an increased likelihood of CHD development and disease progression/mortality. Other potentially interesting biochemical markers have been proposed, including plasmatic 5HIAA, although further standardization and prospective studies are required to define their role in the management of NETs. Meanwhile, 24u5HIAA remains the most accurate CS biomarker. Full article
(This article belongs to the Special Issue Biomarkers for Neuroendocrine Neoplasms)
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15 pages, 4294 KiB  
Article
Conventional Transarterial Chemo embolization Using Streptozocin in Patients with Unresectable Neuroendocrine Liver Metastases
by Audrey Fohlen, Remi Beaudouin, Arnaud Alvès, Karine Bouhier-Leporrier, Christophe Pasik and Jean-Pierre Pelage
Cancers 2023, 15(16), 4021; https://doi.org/10.3390/cancers15164021 - 8 Aug 2023
Cited by 1 | Viewed by 1541
Abstract
Background: The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. Patients and Methods: A total of 52 patients with predominant liver disease were [...] Read more.
Background: The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. Patients and Methods: A total of 52 patients with predominant liver disease were treated with cTACE using an emulsion of streptozocin, Lipiodol and embolization particles. A sequential approach was favored in patients with high liver tumor burden. Clinical, biological and radiological responses were evaluated using carcinoid symptoms, biomarkers and mRecist criteria, respectively. Results: A total of 127 procedures were performed with a sequential approach in 65% of patients. All patients received streptozocin and Lipiodol. Carcinoid syndrome was improved in 69% of patients after treatment (p = 0.01). Post-embolization syndrome was reported in 78% of patients. At the end of all cTACE, objective response and non-progressive disease were 32% and 70%, respectively. Progression-free survival was 18.3 ± 13.3 months (median 14.9) and median overall survival (OS) from start of treatment was 74 months. The OS at 1 year, 2 years, 3 years and 5 years was 91% (IC = 84–99%), 84% (CI = 72–95%), 69% (CI = 53–84%) and 63% (C = 46–81%), respectively. Conclusions: cTACE using streptozocin is an effective and well-tolerated palliative option for patients with neuroendocrine liver metastases, associated with prolonged survival and delayed time to progression. Full article
(This article belongs to the Section Cancer Therapy)
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Review
A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management
by Qamar Sultana, Jill Kar, Amogh Verma, Shreya Sanghvi, Nirja Kaka, Neil Patel, Yashendra Sethi, Hitesh Chopra, Mohammad Amjad Kamal and Nigel H. Greig
J. Clin. Med. 2023, 12(15), 5138; https://doi.org/10.3390/jcm12155138 - 5 Aug 2023
Cited by 50 | Viewed by 18425
Abstract
Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or [...] Read more.
Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs—both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)—have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide therapy (PRRT), which add to the growing evidence supporting the possibility of treatment beyond complete resection. As the incidence of NENs is on the rise in the United States and several other countries, physicians are more likely to see these cases, and their better understanding may support earlier diagnosis and tailoring treatment to the patient. We have compiled clinically significant evidence for NENs, including relevant changes to clinical practice that have greatly updated our diagnostic and therapeutic approach for NEN patients. Full article
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