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Ma T, Wang H, Dai W, Shen P, Zhang J, Xie R. Historical trends in histological composition and cause specific mortality of small intestine tumors based on SEER database analysis. Sci Rep 2025; 15:18628. [PMID: 40436948 PMCID: PMC12120026 DOI: 10.1038/s41598-025-03046-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 05/19/2025] [Indexed: 06/01/2025] Open
Abstract
Small intestine tumors, though rare, have shown a concerning increase in incidence and mortality in recent years. This study aimed to investigate the historical trends in histological composition and causes of death among patients with small intestine tumors using the SEER database. A total of 18,234 patients diagnosed with primary small intestine cancer from 1992 to 2018 were included in this study. Demographic details, tumor characteristics, treatment modalities, and outcomes were collected. Cause-specific mortality was analyzed using Fine and Gray regression, with non-small intestine-specific deaths considered as competing risks. Small intestine-specific deaths were the leading cause of mortality, with adenocarcinoma and carcinoid tumors being the most common histological types. Heart disease emerged as a significant cause of death following diagnosis, surpassing small intestine-specific deaths after 5-6 years. The study revealed variations in mortality causes across histological subtypes and identified risk factors for small intestine-specific mortality, including age, tumor site, grade, and treatment modalities. The findings highlight the substantial impact of heart disease on the long-term survival of patients with small intestine tumors. This underscores the potential benefits of adopting comprehensive management strategies that integrate oncological and cardiological care to improve survival rates and quality of life. A multidisciplinary approach in oncocardiology may help address the complex needs of these patients and optimize clinical outcomes.
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Affiliation(s)
- Tianheng Ma
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Honggang Wang
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Weijie Dai
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Peng Shen
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Jialing Zhang
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China.
| | - Rui Xie
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China.
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Zhang XL, Jiang YY, Chang YY, Sun YL, Zhou Y, Wang YH, Dou XT, Guo HM, Ling TS. Endoscopic full-thickness resection: A definitive solution for local complete resection of small rectal neuroendocrine neoplasms. World J Gastroenterol 2025; 31:100444. [PMID: 40093679 PMCID: PMC11886531 DOI: 10.3748/wjg.v31.i10.100444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 12/11/2024] [Accepted: 02/10/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Recently, several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms (R-NENs). However, none of these methods can achieve 100% complete resection (CR), particularly in the vertical direction. Endoscopic full-thickness resection (EFTR) has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs. AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique. METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs, including 132 who underwent endoscopic submucosal dissection (ESD) and 28 who underwent EFTR. Lesions were categorized as < 1 cm, 1-2 cm, and > 2 cm in size. CR rate, en bloc resection rate, operation time, and complications were evaluated. Subgroup analyses and follow-up were also performed. RESULTS EFTR achieved 100% CR rates for lesions < 1 cm and 1-2 cm, compared with 67.0% and 50.0%, respectively, in the ESD group. En bloc resection and successful removal of the R-NENs were achieved in all patients. Meanwhile, EFTR showed performance comparable to ESD in terms of operation time, hospitalization cost, and postoperative adverse events, except for a one-day longer hospital stay. We also analyzed the invasion depth of R-NENs based on full-thickness specimens. The data showed that 80% of lesions (< 1 cm) and 85.7% of lesions (1-2 cm) had invaded the SM3 level or deeper at the time of resection. For ESD specimens, 46.6% (< 1 cm) and 89.3% (1-2 cm) of lesions had infiltrated more than 2000 μm beneath the muscularis mucosae. CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.
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Affiliation(s)
- Xiao-Long Zhang
- Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yang-Yang Jiang
- Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Ying-Ying Chang
- Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yu-Li Sun
- Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Ying Zhou
- Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yao-Hui Wang
- Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Xiao-Tan Dou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Hui-Min Guo
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Ting-Sheng Ling
- Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
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Lauricella E, Vilisova S, Chaoul N, Giglio A, D'Angelo G, Porta C, Cives M. The current status of somatostatin analogs in the treatment of neuroendocrine tumors and future perspectives. Expert Rev Neurother 2025; 25:245-258. [PMID: 39415322 DOI: 10.1080/14737175.2024.2417419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/13/2024] [Indexed: 10/18/2024]
Abstract
INTRODUCTION Somatostatin analogs (SSAs) were developed as antisecretory agents to palliate hormonal symptoms in patients with functioning neuroendocrine tumors (NETs). Their antiproliferative activity has been established in the phase 3 PROMID and CLARINET trials. SSAs currently represent the standard first-line therapy for the majority of well-differentiated G1/G2 gastroenteropancreatic NETs as well as for pulmonary NETs. AREAS COVERED An update on the clinical applications of established SSAs for the treatment of NETs is provided. Perspectives on emerging nonpeptide SSAs such as paltusotine and innovative formulations of octreotide (CAM2029) are included. EXPERT OPINION SSAs represent the cornerstone of treatment for both functioning and nonfunctioning NETs. While standard-dose SSAs have a defined place in the therapeutic algorithm of well-differentiated NETs, uncertainties remain on how to best integrate above-label doses of SSAs in the treatment sequence, particularly when tumor control is the goal. Octreotide and lanreotide appear to be clinically interchangeable, and no signs of superiority of one agent over the other has been observed so far. Whether SSAs may be exploited in the maintenance setting following more aggressive treatments, whether continuing SSAs beyond-progression after first-line therapy could be an effective treatment strategy, and whether new-generation SSAs such as pasireotide could overcome resistance to established SSAs are key areas of investigation.
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Affiliation(s)
- Eleonora Lauricella
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Sofija Vilisova
- Department of Oncology, Pauls Stradins Clinical University Hospital, Riga, Latvia
| | - Nada Chaoul
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Andrea Giglio
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Gabriella D'Angelo
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Camillo Porta
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Mauro Cives
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
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Sen T, Dotsu Y, Corbett V, Puri S, Sen U, Boyle TA, Mack P, Hirsch F, Aljumaily R, Naqash AR, Sukrithan V, Karim NA. Pulmonary neuroendocrine neoplasms: the molecular landscape, therapeutic challenges, and diagnosis and management strategies. Lancet Oncol 2025; 26:e13-e33. [PMID: 39756451 DOI: 10.1016/s1470-2045(24)00374-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/20/2024] [Accepted: 06/25/2024] [Indexed: 01/07/2025]
Abstract
Lung neuroendocrine neoplasms are a group of diverse, heterogeneous tumours that range from well-differentiated, low-grade neuroendocrine tumours-such as typical and atypical carcinoids-to high-grade, poorly differentiated aggressive malignancies, such as large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). While the incidence of SCLC has decreased, the worldwide incidence of other pulmonary neuroendocrine neoplasms has been increasing over the past decades. In addition to the standard histopathological classification of lung neuroendocrine neoplasms, the introduction of molecular and sequencing techniques has led to new advances in understanding the biology of these diseases and might influence future classifications and staging that can subsequently improve management guidelines in the adjuvant or metastatic settings. Due to the rarity of neuroendocrine neoplasms, there is a paucity of prospective studies that focus on the lungs, especially in rare, well-differentiated carcinoids and LCNECs. In contrast with the success of targeted therapies in non-small-cell lung cancer (NSCLC), high-grade neuroendocrine carcinomas of the lung often only have a few specific targetable gene alterations. Optimal therapy for LCNECs is not well defined and treatment recommendations are based on extrapolating guidelines for the management of patients with SCLC and NSCLC. This Review explores the epidemiology, diagnosis, and staging of lung neuroendocrine neoplasms to date. In addition, we focus on the evolving molecular landscape and biomarkers, ranging from tumour phenotypes to functional imaging studies and novel molecular biomarkers. We outline the various clinical outcomes, challenges, the treatment landscape, ongoing clinical trials, and future directions.
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Affiliation(s)
- Triparna Sen
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Yosuke Dotsu
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Virginia Corbett
- Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sonam Puri
- Division of Clinical Oncology, The Huntsman Cancer Institute at The University of Utah, Salt Lake City, UT, USA
| | - Utsav Sen
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Phil Mack
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Fred Hirsch
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Raid Aljumaily
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
| | - Abdul Rafeh Naqash
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
| | - Vineeth Sukrithan
- Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
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Debraine Z, Borbath I, Deprez P, Bosly F, Maiter D, Furnica RM. Long-term clinical and radiological outcomes of endoscopic ultrasound-guided radiofrequency ablation of benign insulinomas. Clin Endocrinol (Oxf) 2024; 101:485-490. [PMID: 37859570 DOI: 10.1111/cen.14981] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/26/2023] [Accepted: 10/01/2023] [Indexed: 10/21/2023]
Abstract
OBJECTIVE In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative nonsurgical treatment for pancreatic neuroendocrine tumours. The aim of our study was to assess the long-term follow-up of patients treated with EUS-RFA for a sporadic insulinoma in our centre in terms of efficacy, safety and risk of recurrence. DESIGN, PATIENTS AND MEASUREMENTS We retrospectively analysed the data of 11 patients with an insulinoma treated by EUS-RFA in our tertiary centre between June 2018 and April 2022. Clinical and biological, as well as imaging, follow-up was planned at 3, 6, 12 months and then annually. RESULTS In our series, there were nine women and two men with a median age of 65 years. All tumours were sporadic, with a mean size of 11 mm. The procedure allowed an immediate and complete symptomatic and biological remission in all patients without notable complications. Complete radiological resolution of the tumour after ablation was observed in seven patients, and persistence of an asymptomatic tumour residue was observed in four patients. During the mean follow-up period of 26 months, two patients presented a significant but asymptomatic increase of the tumour residue; a second EUS-RFA session was performed in one patient and the other patient is being closely monitored. CONCLUSIONS EUS-RFA treatment of benign insulinomas provides a long-term complete clinical resolution of hypoglycaemia. A long-term follow-up is essential if residual tumour persists after initial EUS-RFA treatment.
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Affiliation(s)
- Zoé Debraine
- Division of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Ivan Borbath
- Division of Hepatogastroenterology, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Pierre Deprez
- Division of Hepatogastroenterology, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Florence Bosly
- Division of Endocrinology, Clinique Vivalia, Arlon Hospital, Arlon, Belgium
| | - Dominique Maiter
- Division of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Raluca M Furnica
- Division of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
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Periferakis A, Tsigas G, Periferakis AT, Tone CM, Hemes DA, Periferakis K, Troumpata L, Badarau IA, Scheau C, Caruntu A, Savulescu-Fiedler I, Caruntu C, Scheau AE. Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias. Curr Issues Mol Biol 2024; 46:9721-9759. [PMID: 39329930 PMCID: PMC11430067 DOI: 10.3390/cimb46090578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/29/2024] [Accepted: 08/31/2024] [Indexed: 09/28/2024] Open
Abstract
Somatostatin is a peptide that plays a variety of roles such as neurotransmitter and endocrine regulator; its actions as a cell regulator in various tissues of the human body are represented mainly by inhibitory effects, and it shows potent activity despite its physiological low concentrations. Somatostatin binds to specific receptors, called somatostatin receptors (SSTRs), which have different tissue distributions and associated signaling pathways. The expression of SSTRs can be altered in various conditions, including tumors; therefore, they can be used as biomarkers for cancer cell susceptibility to certain pharmacological agents and can provide prognostic information regarding disease evolution. Moreover, based on the affinity of somatostatin analogs for the different types of SSTRs, the therapeutic range includes conditions such as tumors, acromegaly, post-prandial hypotension, hyperinsulinism, and many more. On the other hand, a number of somatostatin antagonists may prove useful in certain medical settings, based on their differential affinity for SSTRs. The aim of this review is to present in detail the principal characteristics of all five SSTRs and to provide an overview of the associated therapeutic potential in neoplasias.
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Affiliation(s)
- Argyrios Periferakis
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Elkyda, Research & Education Centre of Charismatheia, 17675 Athens, Greece
- Akadimia of Ancient Greek and Traditional Chinese Medicine, 16675 Athens, Greece
| | - Georgios Tsigas
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Aristodemos-Theodoros Periferakis
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Elkyda, Research & Education Centre of Charismatheia, 17675 Athens, Greece
| | - Carla Mihaela Tone
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Daria Alexandra Hemes
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Konstantinos Periferakis
- Akadimia of Ancient Greek and Traditional Chinese Medicine, 16675 Athens, Greece
- Pan-Hellenic Organization of Educational Programs, 17236 Athens, Greece
| | - Lamprini Troumpata
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Ioana Anca Badarau
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Cristian Scheau
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Radiology and Medical Imaging, "Foisor" Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 030167 Bucharest, Romania
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, The "Carol Davila" Central Military Emergency Hospital, 010825 Bucharest, Romania
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, "Titu Maiorescu" University, 031593 Bucharest, Romania
| | - Ilinca Savulescu-Fiedler
- Department of Internal Medicine, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Constantin Caruntu
- Department of Physiology, The "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Dermatology, "Prof. N.C. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Andreea-Elena Scheau
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
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Van Ussel K, Leonard D, Watremez C, Robu CB. Anesthetic key points in a patient with a terminal ileum neuroendocrine tumor and a rare carcinoid left heart disease presented for non-cardiac surgery: case report. BMC Anesthesiol 2024; 24:265. [PMID: 39085758 PMCID: PMC11290185 DOI: 10.1186/s12871-024-02648-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/19/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period. CASE PRESENTATION We describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc. CONCLUSION Despite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients.
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Affiliation(s)
- Kevin Van Ussel
- Department of Anesthesiology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Av Hippocrate 10, Brussels, 1200, Belgium.
- , Brussels, Belgium.
| | - Daniel Leonard
- Department of Colorectal Surgery, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Christine Watremez
- Department of Anesthesiology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Av Hippocrate 10, Brussels, 1200, Belgium
| | - Cristina Bianca Robu
- Department of Anesthesiology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Av Hippocrate 10, Brussels, 1200, Belgium
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Modestino MR, Iacono O, Ferrentino L, Lombardi A, De Fortuna U, Verdoliva R, De Luca M, Guardasole V. How should we differentiate hypoglycaemia in non-diabetic patients? J Basic Clin Physiol Pharmacol 2024; 35:111-119. [PMID: 38619602 DOI: 10.1515/jbcpp-2024-0030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 03/10/2024] [Indexed: 04/16/2024]
Abstract
Hypoglycaemic syndromes are rare in apparently healthy individuals and their diagnosis can be a difficult challenge for clinicians as there are no shared guidelines that suggest how to approach patients with a suspect hypoglycaemic disorder. Since hypoglycaemia symptoms are common and nonspecific, it's necessary to document the Whipple Triad (signs and/or symptoms compatible with hypoglycaemia; relief of symptoms following glucose administration; low plasma glucose levels) before starting any procedure. Once the triad is documented, a meticulous anamnesis and laboratory tests (blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate and anti-insulin antibodies) should be performed. Results can guide the physician towards further specific tests, concerning the suspected disease. In this review, we consider all current causes of hypoglycaemia, including rare diseases such as nesidioblastosis and Hirata's syndrome, describe appropriate tests for diagnosis and suggest strategies to differentiate hypoglycaemia aetiology.
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Affiliation(s)
- Michele R Modestino
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
| | - Olimpia Iacono
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
| | - Laura Ferrentino
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
| | - Anna Lombardi
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
| | - Umberto De Fortuna
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
| | - Rita Verdoliva
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
| | - Mariarosaria De Luca
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
| | - Vincenzo Guardasole
- Department of Translational Medical Sciences, 165474 Federico II University Hospital , Napoli, Italy
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Criss CR, Makary MS. Liver-Directed Locoregional Therapies for Neuroendocrine Liver Metastases: Recent Advances and Management. Curr Oncol 2024; 31:2076-2091. [PMID: 38668057 PMCID: PMC11049250 DOI: 10.3390/curroncol31040154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 03/27/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
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 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.
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Affiliation(s)
- Cody R. Criss
- Department of Internal Medicine, OhioHealth Riverside Methodist Hospital, Columbus, OH 43214, USA;
| | - Mina S. Makary
- Division of Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43240, USA
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Bulj N, Tomasic V, Cigrovski Berkovic M. Managing end-stage carcinoid heart disease: A case report and literature review. World J Gastrointest Oncol 2024; 16:1076-1083. [PMID: 38577438 PMCID: PMC10989396 DOI: 10.4251/wjgo.v16.i3.1076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/26/2023] [Accepted: 01/24/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients' quality of life. Cardiovascular complications of GEP-NENs, primarily tricuspid and pulmonary valve disease, and right-sided heart failure, are the leading cause of death, even compared to metastatic disease. CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea, back pain, polyneuropathic leg pain, and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases. During the initial presentation, serum biomarkers were not evaluated, and the patient received five cycles of doxorubicin, which he did not tolerate well, so he refused further therapy and was lost to follow-up. After 10 years, he presented to the emergency room with signs and symptoms of right-sided heart failure. Panneuroendocrine markers, serum chromogranin A, and urinary 5-hydroxyindoleacetic acid were extremely elevated (900 ng/mL and 2178 µmol/L), and transabdominal ultrasound confirmed hepatic metastases. Computed tomography (CT) showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis. Furthermore, an Octreoscan showed lesions in the heart, thoracic spine, duodenum, and ascendent colon. A standard transthoracic echocardiogram confirmed findings of carcinoid heart disease. The patient was not a candidate for valve replacement. He started octreotide acetate treatment, and the dose escalated to 80 mg IM monthly. Although biochemical response and symptomatic improvement were noted, the patient died. CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors, usually with liver metastases, which manifests as right-sided heart valve dysfunction leading to right-sided heart failure. Carcinoid heart disease and tumor burden are major prognostic factors of poor survival. Therefore, they must be actively sought by available biochemical markers and imaging techniques. Moreover, imaging techniques aiding tumor detection and staging, somatostatin receptor positron emission tomography/CT, and CT or magnetic resonance imaging, should be performed at the time of diagnosis and in 3- to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery. Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered, while any delay can worsen right-sided ventricular failure.
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Affiliation(s)
- Nikola Bulj
- Department of Cardiology, University Hospital Centre “Sestre Milosrdnice,“ Zagreb 10000, Croatia
| | - Vedran Tomasic
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Centre “Sestre Milosrdnice,” Zagreb 10000, Croatia
| | - Maja Cigrovski Berkovic
- Department for Sport and Exercise Medicine, University of Zagreb Faculty of Kinesiology, Zagreb 10000, Croatia
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Isaiah S, Loots DT, van Furth AMT, Davoren E, van Elsland S, Solomons R, van der Kuip M, Mason S. Urinary markers of Mycobacterium tuberculosis and dysbiosis in paediatric tuberculous meningitis cases undergoing treatment. Gut Pathog 2024; 16:14. [PMID: 38475868 PMCID: PMC10936073 DOI: 10.1186/s13099-024-00609-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/29/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND The pathogenesis of tuberculous meningitis (TBM) involves infection by Mycobacterium tuberculosis in the meninges and brain. However, recent studies have shown that the immune response and inflammatory processes triggered by TBM can have significant effects on gut microbiota. Disruptions in the gut microbiome have been linked to various systemic consequences, including altered immunity and metabolic dysregulation. Inflammation caused by TBM, antibiotic treatment, and changes in host immunity can all influence the composition of gut microbes. This complex relationship between TBM and the gut microbiome is of great importance in clinical settings. To gain a deeper understanding of the intricate interactions between TBM and the gut microbiome, we report innovative insights into the development of the disease in response to treatment. Ultimately, this could lead to improved outcomes, management strategies and quality of life for individuals affected by TBM. METHOD We used a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to investigate metabolites associated with gut metabolism in paediatric participants by analysing the urine samples collected from a control group (n = 40), and an experimental group (n = 35) with confirmed TBM, which were subdivided into TBM stage 1 (n = 8), stage 2 (n = 11) and stage 3 (n = 16). FINDINGS Our metabolomics investigation showed that, of the 78 initially selected compounds of microbiome origin, eight unique urinary metabolites were identified: 2-methylbutyrlglycine, 3-hydroxypropionic acid, 3-methylcrotonylglycine, 4-hydroxyhippuric acid, 5-hydroxyindoleacetic acid, 5-hydroxyhexanoic acid, isobutyrylglycine, and phenylacetylglutamine as urinary markers of dysbiosis in TBM. CONCLUSION These results - which are supported by previous urinary studies of tuberculosis - highlight the importance of gut metabolism and of identifying corresponding microbial metabolites as novel points for the foundation of improved management of TBM patients.
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Affiliation(s)
- Simon Isaiah
- Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa
| | - Du Toit Loots
- Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa
| | - A Marceline Tutu van Furth
- Vrije Universiteit, Pediatric Infectious Diseases and Immunology, Amsterdam University Medical Centers, Emma Children's Hospital, De Boelelaan 1117, Amsterdam, The Netherlands
| | - Elmarie Davoren
- Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa
| | - Sabine van Elsland
- MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, UK
- Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Regan Solomons
- Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Martijn van der Kuip
- Vrije Universiteit, Pediatric Infectious Diseases and Immunology, Amsterdam University Medical Centers, Emma Children's Hospital, De Boelelaan 1117, Amsterdam, The Netherlands
| | - Shayne Mason
- Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa.
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Herrera-Martínez AD, Fuentes-Fayos AC, Sanchez-Sanchez R, Montero AJ, Sarmento-Cabral A, Gálvez-Moreno MA, Gahete MD, Luque RM. Does Telotristat Have a Role in Preventing Carcinoid Heart Disease? Int J Mol Sci 2024; 25:2036. [PMID: 38396713 PMCID: PMC10888480 DOI: 10.3390/ijms25042036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/18/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
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 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.
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Affiliation(s)
- Aura D. Herrera-Martínez
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Endocrinology and Nutrition Service, Reina Sofia University Hospital, 14004 Córdoba, Spain
| | - Antonio C. Fuentes-Fayos
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Córdoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Córdoba, Spain
- Reina Sofia University Hospital, 14004 Cordoba, Spain
| | - Rafael Sanchez-Sanchez
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Pathology Service, Reina Sofia University Hospital, 14004 Córdoba, Spain
| | - Antonio J. Montero
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Córdoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Córdoba, Spain
- Reina Sofia University Hospital, 14004 Cordoba, Spain
| | - André Sarmento-Cabral
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Córdoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Córdoba, Spain
- Reina Sofia University Hospital, 14004 Cordoba, Spain
| | - María A. Gálvez-Moreno
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Endocrinology and Nutrition Service, Reina Sofia University Hospital, 14004 Córdoba, Spain
| | - Manuel D. Gahete
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Córdoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Córdoba, Spain
- Reina Sofia University Hospital, 14004 Cordoba, Spain
| | - Raúl M. Luque
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain; (A.C.F.-F.); (R.S.-S.); (A.J.M.); (A.S.-C.); (M.A.G.-M.); (M.D.G.)
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Córdoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Córdoba, Spain
- Reina Sofia University Hospital, 14004 Cordoba, Spain
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Flynn M, Noss C, Miller R, Adams C, Ruether D, Chan D, Pasieka J, Lithgow K. Use of perioperative telotristat in a patient with carcinoid heart disease. Endocrinol Diabetes Metab Case Rep 2024; 2024:23-0070. [PMID: 38377684 PMCID: PMC10895306 DOI: 10.1530/edm-23-0070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 01/31/2024] [Indexed: 02/22/2024] Open
Abstract
Summary Carcinoid heart disease is a rare complication of carcinoid syndrome, resulting in right-sided valvular heart disease and subsequent heart failure due to long-term exposure to vasoactive substances. The management of this condition is complex, often requiring surgical intervention. Current perioperative regimens entail the use of prophylactic somatostatin analogs to prevent carcinoid crisis; however, regimens vary widely among practitioners and evidence supporting their efficacy in this clinical setting is mixed. This case report describes the perioperative management of a 65-year-old man with carcinoid heart disease requiring tricuspid and pulmonary valve replacement surgery. As an adjunct to somatostatin analog therapy, the novel tyrosine hydroxylase inhibitor, telotristat, was initiated preoperatively. This combination resulted in normalization of preoperative urinary 5-HIAA levels. The patient successfully underwent tricuspid and pulmonic valve replacement without evidence of carcinoid crisis. This clinical case is the first published documenting the use of telotristat in the perioperative period in a patient with carcinoid syndrome and carcinoid heart disease and was associated with a good long-term outcome despite the high-risk nature of the case. Learning points Carcinoid crisis is a life-threatening complication of carcinoid syndrome, resulting in hemodynamic instability, bronchospasm, and arrhythmia. Cardiac surgical patients with carcinoid syndrome present a unique challenge as they are subject to physiologic conditions and medications which can potentiate intraoperative carcinoid crisis. Perioperative management of patients with carcinoid syndrome currently entails the use of prophylactic somatostatin analogs; however, these agents do not prevent carcinoid crisis in all cases. Telotristat, a tryptophan hydroxylase inhibitor, shows promise as an adjunctive therapy to somatostatin analogs to reduce the risk of intraoperative carcinoid crisis.
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Affiliation(s)
- Maria Flynn
- Department of Medicine, University of Calgary, Alberta, Canada
| | - Christopher Noss
- Department of Anesthesiology, Perioperative, and Pain Medicine, University of Calgary, Alberta, Canada
| | - Robert Miller
- Department of Cardiac Sciences, University of Calgary, Alberta, Canada
| | - Corey Adams
- Department of Cardiac Sciences, University of Calgary, Alberta, Canada
| | - Dean Ruether
- Department of Medicine, University of Calgary, Alberta, Canada
| | - Denise Chan
- Department of Radiology, University of Calgary, Alberta, Canada
| | - Janice Pasieka
- Department of Surgery, University of Calgary, Alberta, Canada
| | - Kirstie Lithgow
- Department of Medicine, University of Calgary, Alberta, Canada
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Ewang-Emukowhate M, Subramaniam K, Lam F, Hayes A, Mandair D, Toumpanakis C, Grossman A, Nair D, Caplin M. Plasma or serum 5-hydroxyindoleacetic acid can be used interchangeably in patients with neuroendocrine tumours. Scand J Clin Lab Invest 2023; 83:576-581. [PMID: 38112030 DOI: 10.1080/00365513.2023.2286645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/31/2023] [Accepted: 11/05/2023] [Indexed: 12/20/2023]
Abstract
5-hydroxyindole acetic acid, a metabolite of serotonin, is used in the diagnosis and monitoring of patients with neuroendocrine tumours, in particular patients with small intestinal neuroendocrine tumours associated with the carcinoid syndrome. Analysis of 5-hydroxyindole acetic acid was commonly performed in urine, but blood-based assays are now becoming available. The objective of this study was to assess how 5-hydroxyindole acetic acid compares in plasma and serum as a biochemical marker of neuroendocrine tumours. Twenty-four-hour urine, plasma and serum samples were obtained from 80 patients with neuroendocrine tumours and 30 healthy volunteers. We developed a liquid chromatography tandem mass spectrometry assay for plasma and serum 5-hydroxyindole acetic acid. Comparison was made between them, and their cut-off was determined using a receiver-operating characteristic curve. A close correlation was shown between plasma and serum 5-hydroxyindole acetic acid. At a cut-off of 135 nmol/l, a sensitivity of 91.2% with a specificity of 61.9% was obtained for both compared to the urinary assay. A statistically significant agreement was shown when plasma and serum 5-hydroxyindole acetic acid were compared with the currently used urine assay in patients with neuroendocrine tumours; κ = 0.675 (95% CI 0.49 to 0.86), p < 0.001 and healthy volunteers; 0.967 (95% CI 0.828 to 0.999), p = <0.001. In conclusion, 5-hydroxyindole acetic acid in plasma and serum were comparable, hence either sample type can be used interchangeably.
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Affiliation(s)
- Mfon Ewang-Emukowhate
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
- Department of Clinical Biochemistry, Royal Free Hospital, London, UK
| | | | | | - Aimee Hayes
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | | | | | | | - Devaki Nair
- Department of Clinical Biochemistry, Royal Free Hospital, London, UK
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
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15
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Jiang XT, Hu Y, Gong J, Guo SB. Clinical Value of Clip-and-Snare Assisted Endoscopic Submucosal Resection in Treatment of Rectal Neuroendocrine Tumors. Visc Med 2023; 39:140-147. [PMID: 37899795 PMCID: PMC10601530 DOI: 10.1159/000533393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 07/31/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction The aim of the study was to introduce a new endoscopic technology, clip-and-snare assisted endoscopic submucosal resection (CS-ESMR), for treatment of rectal neuroendocrine tumors (NETs) and then to investigate the therapeutic value of CS-ESMR. Methods In this retrospective study, 67 patients who underwent endoscopic treatment of rectal NETs from March 2017 to December 2021 were analyzed. According to the endoscopic resection methods (endoscopic mucosal resection [EMR], CS-ESMR, and endoscopic submucosal dissection [ESD]), the cases were divided into CS-ESMR group (27 cases), ESD group (31 cases), and EMR group (9 cases). The pathological R0 resection rate and the incidence of adverse events (bleeding and perforation) were compared among the three groups. Results There was a significant difference about the pathological R0 resection between the CS-ESMR group and the EMR group and between the CS-ESMR group and the ESD group (both p < 0.05). Compared with ESD group, the procedure time, intraoperative bleeding, and the cost of CS-ESMR group are significantly decreased (p < 0.001, p < 0.05, p < 0.001, respectively). Conclusion CS-ESMR may be a safe and effective treatment for rectal NETs with a diameter of less than 10 mm, without muscularis propria invasion and metastasis.
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Affiliation(s)
- Xin-Tong Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yang Hu
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jian Gong
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shi-Bin Guo
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Cavalcoli F, Gallo C, Coltro LA, Rausa E, Cantù P, Invernizzi P, Massironi S. Therapeutic Challenges for Gastric Neuroendocrine Neoplasms: Take It or Leave It? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1757. [PMID: 37893475 PMCID: PMC10608689 DOI: 10.3390/medicina59101757] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/23/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023]
Abstract
Background and Objectives: Gastric neuroendocrine neoplasms (gNENs) represent rare but increasingly recognized tumors. They are distinguished into three main clinical types (type-1, type-2, and type-3) according to gastrin level and at histological evaluation in well-differentiated G1, G2, or G3 lesions, as well as poorly-differentiated lesions. Small type-1 and type-2 neoplasms with low proliferation indices demonstrated excellent survival without progression during an extended follow-up period, and for these reasons, active endoscopic observation or endoscopic resection are feasible options. On the other hand, surgery is the treatment of choice for more aggressive type-3, G3, or infiltrating neoplasms. The present study aims to comprehensively review and compare the available therapeutic strategies for gNENs. Materials and Methods: A computerized literature search was performed using relevant keywords to identify all of the pertinent articles with particular attention to gNEN endoscopic treatment. Results: In recent years, different endoscopic resective techniques (such as endoscopic mucosal dissection, modified endoscopic mucosal resection, and endoscopic full-thickness resection) have been developed, showing a high rate of complete resection for advanced and more aggressive lesions. Conclusions: Overall, gNENs represent a heterogeneous group of lesions with varying behavior which require personalized management. The non-operative approach for small type-1 gNENs seems to be feasible and should be promoted. A step-up approach with minimally invasive endoscopic therapies might be proposed, particularly for type-1 gNEN. On the other hand, it is important to recognize the negative prognostic factors in order to identify those rare cases requiring more aggressive approaches. A possible therapeutic algorithm for localized gNEN management is provided.
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Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (F.C.); (P.C.)
| | - Camilla Gallo
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Lorenzo Andrea Coltro
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;
| | - Paolo Cantù
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (F.C.); (P.C.)
| | - Pietro Invernizzi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, ASST Monza, 20900 Monza, Italy
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El Gabry M, Arends S, Shehada SE, Lahner H, Kamler M, Wendt D, Spetsotaki K. Hedinger Syndrome-Lessons Learnt: A Single-Center Experience. J Cardiovasc Dev Dis 2023; 10:413. [PMID: 37887860 PMCID: PMC10607344 DOI: 10.3390/jcdd10100413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/26/2023] [Accepted: 09/28/2023] [Indexed: 10/28/2023] Open
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 ± 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.
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Affiliation(s)
- Mohamed El Gabry
- Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Centre, 45147 Essen, Germany; (M.E.G.); (M.K.); (D.W.)
| | - Sven Arends
- Department for Anesthesiology and Intensive Care Medicine, University of Duisburg-Essen, 45147 Essen, Germany;
| | - Sharaf-Eldin Shehada
- Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Centre, 45147 Essen, Germany; (M.E.G.); (M.K.); (D.W.)
| | - Harald Lahner
- Department of Endocrinology and Metabolism, University Hospitals Duisburg-Essen, 45147 Essen, Germany;
| | - Markus Kamler
- Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Centre, 45147 Essen, Germany; (M.E.G.); (M.K.); (D.W.)
| | - Daniel Wendt
- Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Centre, 45147 Essen, Germany; (M.E.G.); (M.K.); (D.W.)
- CytoSorbents Europe GmbH, 12587 Berlin, Germany
| | - Konstantina Spetsotaki
- Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Centre, 45147 Essen, Germany; (M.E.G.); (M.K.); (D.W.)
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Tsoli M, Koumarianou A, Angelousi A, Kaltsas G. Established and novel circulating neuroendocrine tumor biomarkers for diagnostic, predictive and prognostic use. Best Pract Res Clin Endocrinol Metab 2023; 37:101785. [PMID: 37336711 DOI: 10.1016/j.beem.2023.101785] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
Abstract
The management of neuroendocrine tumors (NETs) represents a clinical challenge due to heterogeneity of their clinical behaviour, molecular biology and response to treatment. Over the years, several circulating biomarkers have been developed for the early diagnosis and follow-up of NETs. The specific secretory products of tumors associated with a secretory syndrome (functioning tumors) may be used as diagnostic and/or prognostic biomarkers while the most common non-specific circulating biomarkers, that may be increased in both functioning and non-functioning tumors, are chromogranin A and the neuron specific enolase. However, the diagnostic accuracy as well as the prognostic and predictive value of these biomarkers are limited and novel techniques of multianalyte analysis of regulators of tumor biology have been developed. The NETest has been most extensively studied and proved to be useful in NET diagnosis, early detection of post-operative recurrence and prediction of response to treatment but further investigation establishing higher level of evidence is required for implementation in clinical practice.
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Affiliation(s)
- Marina Tsoli
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527, Greece.
| | - Anna Koumarianou
- Haematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, National and Kapodistrian University of Athens, 12462, Greece
| | - Anna Angelousi
- Unit of Endocrinology, First Department of Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527, Greece
| | - Gregory Kaltsas
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527, Greece
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Magi L, Marasco M, Rinzivillo M, Faggiano A, Panzuto F. Management of Functional Pancreatic Neuroendocrine Neoplasms. Curr Treat Options Oncol 2023; 24:725-741. [PMID: 37103745 PMCID: PMC10272249 DOI: 10.1007/s11864-023-01085-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2023] [Indexed: 04/28/2023]
Abstract
OPINION STATEMENT Functional pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous diseases in terms of both clinical and pathological aspects. These tumors secrete hormones or peptides, which may cause a wide variety of symptoms related to a clinical syndrome. The management of functional pNENs is still challenging for clinicians due to the need to control both tumor growth and specific symptoms. Surgery remains the cornerstone in the management of local disease because it can definitively cure the patient. However, when the disease is not resectable, a broad spectrum of therapeutic options, including locoregional therapy, somatostatin analogs (SSAs), targeted therapies, peptide-receptor radionuclide therapy (PRRT), and chemotherapy, are available. The present review summarizes the main key issues regarding the clinical management of these tumors, providing a specific highlight on their therapeutic approach.
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Affiliation(s)
- Ludovica Magi
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy
| | - Matteo Marasco
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via Di Grottarrossa 1035, 00189, Rome, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy.
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Via di Grottarossa 1035, 00189, Rome, Italy.
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Kwon J, Kim BH. Novel scoring system guiding the incorporation of adjuvant RT for neuroendocrine neoplasms treated with surgical resection followed by chemotherapy. J Cancer Res Clin Oncol 2023; 149:4419-4428. [PMID: 36114862 DOI: 10.1007/s00432-022-04351-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/06/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE This study aimed to investigate the role of adjuvant radiotherapy (RT) in neuroendocrine tumors (NET) treated with primary resection and systemic chemotherapy and guide to incorporate adjuvant RT based on individualized prediction. METHODS We identified 4324 eligible patients using the SEER database. The most common histology was small cell carcinoma (SCC), followed by neuroendocrine carcinoma and carcinoid tumor. As the patients treated with RT were not randomly assigned, we performed propensity score matching (PSM). RESULTS RT was administered to 1693 (39.2%) patients who had more unfavorable features [higher proportion of SCC, N2/3 stage, and poorly/undifferentiated (PD) tumors]. After PSM, old age, male sex, SCC, advanced T or N stage, PD tumors, large tumor size, and no use of RT were all significantly associated with a poor prognosis. After multivariate analysis, the survival benefit of RT was preserved (HR 0.82, 95% CI 0.73‒0.91, p < 0.001). Exploratory analysis suggested that primary site, PD tumors, SCC, tumor size < 2 cm, or LN negativity were the factors for which adjuvant RT appeared desirable. Further, we proposed a novel scoring system using aforementioned factors; site-thorax/genitourinary, PD tumor, tumor size < 2 cm, LN negativity. Based on individually calculated scores, we found that RT significantly increased survival in patients with scores of 2-4 but not in those with scores of 0-1. CONCLUSIONS Our study highlights the necessity of guiding adjuvant RT for these rare types of cancer. We proposed a novel scoring system to carefully recommend RT in selected patients.
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Affiliation(s)
- Jeanny Kwon
- Department of Radiation Oncology, Chungnam National University School of Medicine, Munhwa-ro 282, Jung-gu, Daejeon, 35015, Republic of Korea
| | - Byoung Hyuck Kim
- Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, Republic of Korea.
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Eshmuminov D, Studer DJ, Lopez Lopez V, Schneider MA, Lerut J, Lo M, Sher L, Musholt TJ, Lozan O, Bouzakri N, Sposito C, Miceli R, Barat S, Morris D, Oehler H, Schreckenbach T, Husen P, Rosen CB, Gores GJ, Masui T, Cheung TT, Kim-Fuchs C, Perren A, Dutkowski P, Petrowsky H, Thiis-Evensen E, Line PD, Grat M, Partelli S, Falconi M, Tanno L, Robles-Campos R, Mazzaferro V, Clavien PA, Lehmann K. Controversy Over Liver Transplantation or Resection for Neuroendocrine Liver Metastasis: Tumor Biology Cuts the Deal. Ann Surg 2023; 277:e1063-e1071. [PMID: 35975918 DOI: 10.1097/sla.0000000000005663] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND In patients with neuroendocrine liver metastasis (NELM), liver transplantation (LT) is an alternative to liver resection (LR), although the choice of therapy remains controversial. In this multicenter study, we aim to provide novel insight in this dispute. METHODS Following a systematic literature search, 15 large international centers were contacted to provide comprehensive data on their patients after LR or LT for NELM. Survival analyses were performed with the Kaplan-Meier method, while multivariable Cox regression served to identify factors influencing survival after either transplantation or resection. Inverse probability weighting and propensity score matching was used for analyses with balanced and equalized baseline characteristics. RESULTS Overall, 455 patients were analyzed, including 230 after LR and 225 after LT, with a median follow-up of 97 months [95% confidence interval (CI): 85-110 months]. Multivariable analysis revealed G3 grading as a negative prognostic factor for LR [hazard ratio (HR)=2.22, 95% CI: 1.04-4.77, P =0.040], while G2 grading (HR=2.52, 95% CI: 1.15-5.52, P =0.021) and LT outside Milan criteria (HR=2.40, 95% CI: 1.16-4.92, P =0.018) were negative prognostic factors in transplanted patients. Inverse probability-weighted multivariate analyses revealed a distinct survival benefit after LT. Matched patients presented a median overall survival (OS) of 197 months (95% CI: 143-not reached) and a 73% 5-year OS after LT, and 119 months (95% CI: 74-133 months) and a 52.8% 5-year OS after LR (HR=0.59, 95% CI: 0.3-0.9, P =0.022). However, the survival benefit after LT was lost if patients were transplanted outside Milan criteria. CONCLUSIONS This multicentric study in patients with NELM demonstrates a survival benefit of LT over LR. This benefit depends on adherence to selection criteria, in particular low-grade tumor biology and Milan criteria, and must be balanced against potential risks of LT.
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Affiliation(s)
- Dilmurodjon Eshmuminov
- Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Debora J Studer
- Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Victor Lopez Lopez
- Clinic and University Virgen de la Arrixaca Hospital, IMIB-Arrixaca, Murcia, Spain
| | - Marcel A Schneider
- Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Jan Lerut
- Institute for Experimental and Clinical Research (IREC), UCLouvain, Brussels, Belgium, Université Catholique Louvain (UCL), Brussels, Belgium
| | - Mary Lo
- Department of Surgery, University of Southern California, Keck School of Medicine, Los Angeles, CA
| | - Linda Sher
- Department of Surgery, University of Southern California, Keck School of Medicine, Los Angeles, CA
| | - Thomas J Musholt
- Clinic of General, Visceral- and Transplantation Surgery, University Medical Center Mainz, Mainz, Germany
| | - Oana Lozan
- Clinic of General, Visceral- and Transplantation Surgery, University Medical Center Mainz, Mainz, Germany
| | - Nabila Bouzakri
- Clinic of General, Visceral- and Transplantation Surgery, University Medical Center Mainz, Mainz, Germany
| | - Carlo Sposito
- Università degli Studi di Milano, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Rosalba Miceli
- Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS, Instituto Nazionale dei Tumori, Milan, Italy
| | - Shoma Barat
- South East Sydney Local Health District, Sydney, NSW, Australia
| | - David Morris
- South East Sydney Local Health District, Sydney, NSW, Australia
| | - Helga Oehler
- Department of General, Visceral, Transplantation and Thoracic Surgery, Goethe University Frankfurt, Frankfurt University Hospital, Frankfurt/Main, Germany
| | - Teresa Schreckenbach
- Department of General, Visceral, Transplantation and Thoracic Surgery, Goethe University Frankfurt, Frankfurt University Hospital, Frankfurt/Main, Germany
| | - Peri Husen
- Division of Transplant Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN
| | - Charles B Rosen
- Division of Transplant Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN
| | | | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tan-To Cheung
- University of Hong Kong Queen Mary Hospital, Hong Kong, China
| | - Corina Kim-Fuchs
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Aurel Perren
- Inselspital Bern, Institute of Pathology, Bern, Switzerland
| | - Philipp Dutkowski
- Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Henrik Petrowsky
- Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland
| | | | - Pål-Dag Line
- Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Michal Grat
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Stefano Partelli
- Pancreas Translational & Clinical Research Center, San Raffaele Hospital IRCCS, Vita-Salute University, Milan, Italy
| | - Massimo Falconi
- Pancreas Translational & Clinical Research Center, San Raffaele Hospital IRCCS, Vita-Salute University, Milan, Italy
| | - Lulu Tanno
- University Hospital Southampton, ENETS Center of Excellence, Southampton, UK
| | | | - Vincenzo Mazzaferro
- Università degli Studi di Milano, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Pierre-Alain Clavien
- Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Kuno Lehmann
- Department of Surgery & Transplantation, University Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
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Massironi S, Gallo C, Laffusa A, Ciuffini C, Conti CB, Barbaro F, Boskoski I, Dinelli ME, Invernizzi P. Endoscopic techniques for gastric neuroendocrine tumors: An update. World J Gastrointest Endosc 2023; 15:103-113. [PMID: 37034968 PMCID: PMC10080559 DOI: 10.4253/wjge.v15.i3.103] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 01/11/2023] [Accepted: 02/08/2023] [Indexed: 03/16/2023] Open
Abstract
Gastric neuroendocrine neoplasms (gNENs) are a rare type of gastric neoplasm, even if their frequency is increasing according to the latest epidemiologic revisions of the main registries worldwide. They are divided into three main subtypes, with different pathogeneses, biological behaviors, and clinical characteristics. GNEN heterogeneity poses challenges, therefore these neoplasms require different management strategies. Update the knowledge on the endoscopic treatment options to manage g-NENs. This manuscript is a narrative review of the literature. In recent years, many advances have been made not only in the knowledge of both the pathogenesis and the molecular profiling of gNENs but also in the endoscopic expertise towards innovative treatment options, which proved to be less aggressive without losing the capability of being radical. The endoscopic approach is increasingly applied in the field of gastrointestinal (GI) luminal neoplasms, and this is true not only for adenocarcinomas but also for gNENs. In particular, different techniques have been described for the endoscopic removal of suspected lesions, ranging from classical polypectomy (cold or hot snare) to endoscopic mucosal resection (both with "en bloc" or piecemeal technique), endoscopic submucosal dissection, and endoscopic full-thickness resection. GNENs comprise different subtypes of neoplasms with distinct management and prognosis. New endoscopic techniques offer a wide variety of approaches for GI localized neoplasms, which demonstrated to be appropriate and effective also in the case of gNENs. Correct evaluation of size, site, morphology, and clinical context allows the choice of tailored therapy in order to guarantee a definitive treatment.
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Affiliation(s)
- Sara Massironi
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Camilla Gallo
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Alice Laffusa
- Interventional Endoscopy Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Cristina Ciuffini
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore di Roma, Center for Endoscopic Research Therapeutics and Training (CERTT), Roma 00168, Italy
| | - Clara Benedetta Conti
- Interventional Endoscopy Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Federico Barbaro
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore di Roma, Center for Endoscopic Research Therapeutics and Training (CERTT), Roma 00168, Italy
| | - Ivo Boskoski
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore di Roma, Center for Endoscopic Research Therapeutics and Training (CERTT), Roma 00168, Italy
| | - Marco Emilio Dinelli
- Interventional Endoscopy Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Pietro Invernizzi
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
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Joolharzadeh P, Rodriguez M, Zaghlol R, Pedersen LN, Jimenez J, Bergom C, Mitchell JD. Recent Advances in Serum Biomarkers for Risk Stratification and Patient Management in Cardio-Oncology. Curr Cardiol Rep 2023; 25:133-146. [PMID: 36790618 PMCID: PMC9930715 DOI: 10.1007/s11886-022-01834-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/31/2022] [Indexed: 02/16/2023]
Abstract
PURPOSE OF REVIEW Following significant advancements in cancer therapeutics and survival, the risk of cancer therapy-related cardiotoxicity (CTRC) is increasingly recognized. With ongoing efforts to reduce cardiovascular morbidity and mortality in cancer patients and survivors, cardiac biomarkers have been studied for both risk stratification and monitoring during and after therapy to detect subclinical disease. This article will review the utility for biomarker use throughout the cancer care continuum. RECENT FINDINGS A recent meta-analysis shows utility for troponin in monitoring patients at risk for CTRC during cancer therapy. The role for natriuretic peptides is less clear but may be useful in patients receiving proteasome inhibitors. Early studies explore use of myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and others as novel biomarkers in CTRC. Biomarkers have potential to identify subclinical CTRC and may reveal opportunities for early intervention. Further research is needed to elucidate optimal biomarkers and surveillance strategies.
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Affiliation(s)
- Pouya Joolharzadeh
- General Medical Sciences, Washington University School of Medicine, St. Louis, MO, USA
| | - Mario Rodriguez
- Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Cardio-Oncology Center of Excellence, Washington University School of Medicine, St. Louis, MO, USA
| | - Raja Zaghlol
- Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Cardio-Oncology Center of Excellence, Washington University School of Medicine, St. Louis, MO, USA
| | - Lauren N Pedersen
- Cardio-Oncology Center of Excellence, Washington University School of Medicine, St. Louis, MO, USA
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA
| | - Jesus Jimenez
- Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Cardio-Oncology Center of Excellence, Washington University School of Medicine, St. Louis, MO, USA
| | - Carmen Bergom
- Cardio-Oncology Center of Excellence, Washington University School of Medicine, St. Louis, MO, USA
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA
| | - Joshua D Mitchell
- Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
- Cardio-Oncology Center of Excellence, Washington University School of Medicine, St. Louis, MO, USA.
- Alvin J. Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA.
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24
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Stiefel R, Lehmann K, Winder T, Siebenhüner AR. What have we learnt from the past - would treatment decisions for GEP-NET patients differ between 2012 to 2016 by the new recommendations in 2022? BMC Cancer 2023; 23:148. [PMID: 36782152 PMCID: PMC9926660 DOI: 10.1186/s12885-023-10567-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 01/19/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyse outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of European Society of Medical Oncology (ESMO) 2020 for GEP-NETs. METHODS Patients were included in this retrospective single-center analysis from 2012-2016. All patients suffering from a GEP-NET, who were screened, treated or evaluated at ENETS Center in Zurich, Switzerland were included in analysis. Patients with any other diagnosis of NET were not included. We used Kaplan Meier estimator as well as Cox regression to compare survival rates between different sites of localization, grades or stages and treatment sequences. RESULTS Overall, we identified 256 GEP-NETs, most in advanced stage (62%) and located in small intestine tract or pancreatic gland. Survival depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed early but also in advanced stages, usually followed by Somatostatine-Agonist modalities. In distant disease (Stage IV), we investigated a positive effect of PFS after treatment with Somatostatine Analogues (SSA) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21 - 0.97; p = 0.04) and systemic treatment (HR, 0.51; 95% CI, 0.26 - 0.99; p = 0.047) if patients underwent prior surgery or endoscopic resection. Kaplan Meier distributions predict shorter OS in distant disease (Stage IV), (Figure. 1; HR, 2.06; 95% CI, 1.46 - 2.89; log-rank test, p < 0.001). CONCLUSION This retrospective analysis presents a great overview of all patients', disease and treatment characteristics of GEP-NETs at ENETS Center in Zurich, Switzerland. We illustrated survival (PFS) depending on implemented therapies. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. The results of this project may define GEP-NET patients' selection for upcoming clinical prospective studies.
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Affiliation(s)
- Rahel Stiefel
- grid.414526.00000 0004 0518 665XMedical Oncology and Hematology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Kuno Lehmann
- grid.7400.30000 0004 1937 0650Department of Surgery and Transplantation, University Hospital and University of Zurich, Zurich, Switzerland
| | - Thomas Winder
- grid.413250.10000 0000 9585 4754Internal Medicine II, Hematology, Oncology and Gastroenterology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria ,grid.7400.30000 0004 1937 0650University of Zurich, Zurich, Switzerland
| | - Alexander R. Siebenhüner
- grid.7400.30000 0004 1937 0650Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland ,Clinic of Internal Medicine and Oncology, Cantonal Hospital Schaffhausen, Schaffhausen, Switzerland
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25
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The Role of Somatostatin Analogues in the Control of Diarrhea and Flushing as Markers of Carcinoid Syndrome: A Systematic Review and Meta-Analysis. J Pers Med 2023; 13:jpm13020304. [PMID: 36836538 PMCID: PMC9959441 DOI: 10.3390/jpm13020304] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 01/27/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND Somatostatin analogues (SSAs) are the cornerstone of treatment for carcinoid syndrome (CS)-related symptoms. The aim of this systematic review and meta-analysis is to evaluate the percentage of patients achieving partial (PR) or complete response (CR) with the use of long-acting SSAs in patients with CS. METHODS A systematic electronic literature search was conducted in PubMed, Cochrane, and Scopus to identify eligible studies. Any clinical trials reporting data on the efficacy of SSAs to alleviate symptoms in adult patients were considered as potentially eligible. RESULTS A total of 17 studies reported extractable outcomes (PR/CR) for quantitative synthesis. The pooled percentage of patients with PR/CR for diarrhea was estimated to be 0.67 (95% confidence interval (CI): 0.52-0.79, I2 = 83%). Subgroup analyses of specific drugs provided no evidence of a differential response. With regards to flushing, the pooled percentage of patients with PR/CR was estimated to be 0.68 (95% CI: 0.52-0.81, I2 = 86%). Similarly, no evidence of a significant differential response in flushing control was documented. CONCLUSIONS We estimate there is a 67-68% overall reduction in symptoms of CS associated with SSA treatment. However, significant heterogeneity was detected, possibly revealing differences in the disease course, in management and in outcome definition.
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26
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Liu M, Wei L, Liu W, Chen S, Guan M, Zhang Y, Guo Z, Liu R, Xie P. Trends in incidence and survival in patients with gastrointestinal neuroendocrine tumors: A SEER database analysis, 1977-2016. Front Oncol 2023; 13:1079575. [PMID: 36776304 PMCID: PMC9909535 DOI: 10.3389/fonc.2023.1079575] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 01/04/2023] [Indexed: 01/27/2023] Open
Abstract
Objectives We aimed to determine trends in incidence and survival in patients with gastrointestinal neuroendocrine tumors (GI-NETs) from 1977 to 2016, and then analyze the potential risk factors including sex, age, race, grade, Socioeconomic status (SES), site, and stage. Methods Data were obtained from Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier survival analysis, relative survival rates (RSRs), and Cox proportional risk regression model were used to evaluate the relationship between these factors and prognosis. Results Compared with other sites, the small intestine and rectum have the highest incidence, and the appendix and rectum had the highest survival rate. The incidence was higher in males than in females, and the survival rate in males was close to females. Blacks had a higher incidence rate than whites, but similar survival rates. Incidence and survival rates were lower for G3&4 than for G1 and G2. Age, stage, and grade are risk factors. Conclusions This study described changes in the incidence and survival rates of GI-NETs from 1977 to 2016 and performed risk factor analyses related to GI-NETs.
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Affiliation(s)
- Miao Liu
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Lingge Wei
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Wei Liu
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Shupeng Chen
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Meichao Guan
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Yingjie Zhang
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Ziyu Guo
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Ruiqi Liu
- Department of Nuclear Medicine, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Peng Xie
- Department of Nuclear Medicine, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei, China,*Correspondence: Peng Xie,
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Balancing carcinoid crisis and right ventricular dysfunction during tricuspid and pulmonic valve replacement for carcinoid heart disease: A case report. Int J Surg Case Rep 2023; 102:107855. [PMID: 36610355 PMCID: PMC9829749 DOI: 10.1016/j.ijscr.2022.107855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 12/19/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Carcinoid tumors are rare malignancies of neuroendocrine origin that can manifest with a constellation of systemic symptoms including right-sided cardiac involvement. Many patients with carcinoid heart disease require valve replacement, but intraoperative management of carcinoid syndrome varies within the literature. CASE PRESENTATION A 72-year-old man with carcinoid syndrome underwent tricuspid and pulmonic valve replacement with multiple episodes of carcinoid crisis intraoperatively as well as right ventricular dysfunction after cardiopulmonary bypass. CLINICAL DISCUSSION Octreotide is the mainstay in prevention and treatment of intraoperative carcinoid crisis, but reported dosages and timing varies significantly. The use of exogenous catecholamines is also controversial as they are thought to paradoxically worsen carcinoid symptoms. Our patient was managed successfully with both an octreotide infusion and intermittent boluses, as well as exogenous catecholamines for right ventricular support during and after cardiopulmonary bypass. CONCLUSION The management of carcinoid syndrome in patients undergoing valve surgery for carcinoid heart disease is dependent on timely prevention and treatment of carcinoid crisis and effective mitigation of right ventricular dysfunction.
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Zhao F, Huang L, Wang Z, Wei F, Xiao T, Liu Q. Epidemiological trends and novel prognostic evaluation approaches of patients with stage II-IV colorectal neuroendocrine neoplasms: A population-based study with external validation. Front Endocrinol (Lausanne) 2023; 14:1061187. [PMID: 36817582 PMCID: PMC9928741 DOI: 10.3389/fendo.2023.1061187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/16/2023] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE This study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification. METHODS Among all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital's independent cohort of 62 patients with CRNENs was used as the external validation cohort. RESULTS In the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90-5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient. CONCLUSION Over the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.
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Affiliation(s)
- Fuqiang Zhao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liling Huang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China
| | - Zhijie Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fangze Wei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tixian Xiao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Qian Liu,
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Mohamed A, Wu S, Hamid M, Mahipal A, Cjakrabarti S, Bajor D, Selfridge JE, Asa SL. Management of Appendix Neuroendocrine Neoplasms: Insights on the Current Guidelines. Cancers (Basel) 2022; 15:295. [PMID: 36612291 PMCID: PMC9818268 DOI: 10.3390/cancers15010295] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/19/2022] [Accepted: 12/26/2022] [Indexed: 01/03/2023] Open
Abstract
Appendiceal neuroendocrine neoplasms (ANENs) usually present as incidental findings at the time of appendectomy for acute appendicitis. They are rare, accounting for only 0.5-1% of intestinal neoplasms; they are found in 0.3-0.9% of all appendectomy specimens. They are usually sporadic tumors. There are several histological types including well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Histologic differentiation and the grade of well-differentiated NETs correlate with clinical behavior and prognosis. Management varies based on differentiation, aggressiveness, and metastatic potential. There is debate about the optimal surgical management for localized appendiceal NETs that are impacted by many factors including the tumor size, the extent of mesoappendiceal spread, lymphovascular invasion and perineural involvement. In addition, the data to guide therapy in metastatic disease are limited due to the paucity of these tumors. Here, we review the current advances in the management of ANENs within the context of a multidisciplinary approach to these tumors.
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Affiliation(s)
- Amr Mohamed
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sulin Wu
- Department of Internal Medicine, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
- Department of Medical Genetics, Center for Human Genetics, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Mohamed Hamid
- Department of Stem Cell Biology and Regenerative Medicine, City of Hope Beckman Research Institute, Duarte, CA 91010, USA
| | - Amit Mahipal
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sakti Cjakrabarti
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - David Bajor
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - J. Eva Selfridge
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sylvia L. Asa
- Department of Pathology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
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Yao J, Bergsland E, Aggarwal R, Aparicio A, Beltran H, Crabtree JS, Hann CL, Ibrahim T, Byers LA, Sasano H, Umejiego J, Pavel M. DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms. Oncologist 2022; 27:940-951. [PMID: 35983951 PMCID: PMC9632312 DOI: 10.1093/oncolo/oyac161] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 07/01/2022] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis. METHODS This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the potential for therapeutic targeting of DLL3, and ongoing studies of DLL3-targeting therapies. Classification, incidence, pathogenesis, and current management of NEN are reviewed to provide biological context and illustrate the unmet clinical needs. DISCUSSION DLL3 is overexpressed in many NENs, implicated in tumor progression, and is typically associated with poor clinical outcomes, particularly in patients with NEC. Targeted therapies using DLL3 as a homing beacon for cytotoxic activity mediated via several different mechanisms (eg, antibody-drug conjugates, T-cell engager molecules, CAR-Ts) have shown promising clinical activity in small-cell lung cancer (SCLC). DLL3 may be a clinically actionable target across NEN. CONCLUSIONS Current treatment options for NEN do not provide sustained responses. DLL3 is expressed on the cell surface of many NEN types and is associated with poor clinical outcomes. Initial clinical studies targeting DLL3 therapeutically in SCLC have been promising, and additional studies are expanding this approach to the broader group of NEN.
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Affiliation(s)
- James Yao
- Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Emily Bergsland
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Rahul Aggarwal
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Ana Aparicio
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Himisha Beltran
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Judy S Crabtree
- Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Christine L Hann
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Toni Ibrahim
- Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, IRCSS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Lauren A Byers
- Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | | | - Marianne Pavel
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
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El Bakouri A, El wassi A, Eddaoudi Y, Bouali M, EL Hattabi K, Bensardi F, Fadil A. Fortuitous discovery of an early neuroendocrine tumor during appendicular peritonitis. Ann Med Surg (Lond) 2022; 82:104735. [PMID: 36268349 PMCID: PMC9577830 DOI: 10.1016/j.amsu.2022.104735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/18/2022] [Accepted: 09/18/2022] [Indexed: 11/27/2022] Open
Abstract
Introduction Neuroendocrine tumors of the small bowel are rare but represent the most frequent histological type at this level; their incidence is increasing thanks to the evolution of diagnostic means.Intestinal NETs, developed at the expense of enterochromaffin cells of the embryological midgut, are frequently associated with mesenteric lymph node dissemination and distant metastasis (liver, peritoneum). Materials and methods We report a case of Incidental discovery of a small bowel neuroendocrinetumor during appendicular peritonitis in the department of Emergency visceral surgery P35 of the ibn rochd hospital in casablanca. Results Our patient Our patient was admitted to the emergency room for generalized abdominal pain with an appendicular symptomatology evolving five days before days the consultation with clinical examination: conscious patient stable on the hemodynamic and respiratory plan The examination noted generalized abdominal defense the hernial orifices were free The biological work-up revealed a hb 13 g/dL; hyperleukocytosis with predominantly PNN at 18,300 elements/mm3,CRP was elevated to 190, renal function was normal urea 5 mmol/L creatinemia 9 mg/l an abdominal ultrasound showed a 9 mm appenndix perforated at its tip with moderate peritoneal effusion.the patient were operated in the emergency room, approached by laparotomy with the exploration we found a swollen and inflamed appenndix perforated at the level of its tip with moderate peritoneal effusion with false membranes in all the peritoneal cavity with the presence of a polyp localized at 2 m from the duodenojejunal flexur .the patient benefited from a retrograde appendectomy with peritoneal cleansing and a resection of the polyp with 1cm on each side with a Grele-grele anastomosis with the examination of the anapathomopathologist: aspect compatible with a well differentiated neuroendocrine tumor of grade 2. Conclusion Digestive NETs are rare tumors, but their incidence has increased significantly in recent years. This is due to a better knowledge of these tumors, whose diagnosis is becoming easier with the advent of new morphological and biological techniques.The intestinal location is the most frequent. The digestive surgeon must therefore be familiar with its management. An update of knowledge and collaboration between surgeons, anatomopathologists, radiologists and oncologists are necessary, Whatever their location, these tumors are on the one hand capable of producing and secreting amines and on the other hand they are characterized by a common phenotype, expression of general endocrine markers (specific neuron enolase, chromogranin) or specific endocrine markers and expression of peptide receptors such as somastotatin receptors.These tumors are most often diagnosed incidentally during the workup of aspecific digestive disorders or during hormonal hypersecretion syndrome or rarely by a complication.
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Affiliation(s)
- Abdelilah El Bakouri
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
| | - anas El wassi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Yassine Eddaoudi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Mounir Bouali
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Khalid EL Hattabi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Fatimazahra Bensardi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Abdelaziz Fadil
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
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Management of Carcinoid Syndrome and Carcinoid Crisis in the Perioperative Environment. J Perianesth Nurs 2022; 37:975-978. [DOI: 10.1016/j.jopan.2022.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 08/30/2022] [Indexed: 11/05/2022]
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Sobash PT, Ullah A, Karim NA. Survival Benefit of Adjuvant Chemotherapy in Pulmonary Carcinoid Tumors. Cancers (Basel) 2022; 14:cancers14194730. [PMID: 36230651 PMCID: PMC9564155 DOI: 10.3390/cancers14194730] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/19/2022] [Accepted: 09/26/2022] [Indexed: 11/16/2022] Open
Abstract
Pulmonary carcinoid tumors are a rare subtype of neuroendocrine cell tumor found in approximately 1–2% of lung cancers. Management is primarily through surgical resection, with limited benefit of adjuvant therapy in the clinical setting. Genomic profiling is in the nascent stages to molecularly classify these tumors, but there are promising insights for future targeted therapy. A total of 80 abstracts were analyzed for further review with 11 included in our final analysis. Only 4 of the 11 reviewed in depth provided statistical analysis. We evaluated PFS, OS, 1- and 5-year survival as mentioned in the studies. Nodal and KI67 status were also analyzed. Based on the current literature, there is no definitive evidence that adjuvant chemotherapy after resection confers a survival benefit in typical or atypical carcinoids.
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Affiliation(s)
- Philip T. Sobash
- Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA
| | - Asad Ullah
- Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Nagla Abdel Karim
- Inova Schar Cancer Institute, University of Virginia, Fairfax, VA 22031, USA
- Correspondence: or
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Shin JE, Youn SY, Kim Y, Lee M, Park SJ. Case 2: A 66-Year-Old Man With Chronic Watery Diarrhea. J Korean Med Sci 2022; 37:e221. [PMID: 35916044 PMCID: PMC9344035 DOI: 10.3346/jkms.2022.37.e221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 06/24/2022] [Indexed: 11/20/2022] Open
Affiliation(s)
- Ji Eun Shin
- Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital Catholic University of Korea, Suwon, Korea
| | - Seo Yeon Youn
- Department of Radiology, Healthcare System Gangnam Center, Seoul National University College of Medicine, Seoul, Korea
| | - Younghoon Kim
- Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - MyungAh Lee
- Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea
| | - Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea.
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Grozinsky‐Glasberg S, Davar J, Hofland J, Dobson R, Prasad V, Pascher A, Denecke T, Tesselaar MET, Panzuto F, Albåge A, Connolly HM, Obadia J, Riechelmann R, Toumpanakis C. European Neuroendocrine Tumor Society (ENETS) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease. J Neuroendocrinol 2022; 34:e13146. [PMID: 35613326 PMCID: PMC9539661 DOI: 10.1111/jne.13146] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/17/2022] [Accepted: 04/18/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Simona Grozinsky‐Glasberg
- Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology and Metabolism, Hadassah Medical Organization and Faculty of MedicineHebrew University of JerusalemJerusalemIsrael
| | - Joseph Davar
- Carcinoid Heart Disease Clinic, Department of CardiologyRoyal Free Hospital & University College LondonLondonUK
| | - Johannes Hofland
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of ExcellenceErasmus MC and Erasmus Cancer InstituteRotterdamThe Netherlands
| | - Rebecca Dobson
- Department of CardiologyLiverpool Heart and Chest HospitalLiverpoolUK
| | - Vikas Prasad
- Department of Nuclear MedicineUniversity UlmUlmGermany
| | - Andreas Pascher
- Department of General, Visceral and Transplantation SurgeryUniversity Hospital MuensterMuensterGermany
| | - Timm Denecke
- Department of Diagnostic and Interventional RadiologyLeipzig University Medical CenterLeipzigGermany
| | | | - Francesco Panzuto
- Digestive Disease Unit, Department of Medical‐Surgical Sciences and Translational MedicineSapienza University of Rome, ENETS Center of ExcellenceRomeItaly
| | - Anders Albåge
- Department of Cardiothoracic Surgery and Anesthesiology, University Hospital, and Department of Surgical SciencesUppsala UniversityUppsalaSweden
| | - Heidi M. Connolly
- Department of Cardiovascular DiseasesMayo ClinicRochesterMinnesotaUSA
| | | | | | - Christos Toumpanakis
- Centre for Gastroenterology, Neuroendocrine Tumour Unit, ENETS Centre of ExcellenceRoyal Free HospitalLondonUK
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Perioperative Carcinoid Crisis: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14122966. [PMID: 35740631 PMCID: PMC9221110 DOI: 10.3390/cancers14122966] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/06/2022] [Accepted: 06/13/2022] [Indexed: 01/05/2023] Open
Abstract
Simple Summary Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication for patients with neuroendocrine tumors (NET). Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting the use of perioperative octreotide to prevent CC. The aim of our meta-analysis was to evaluate the existing evidence characterizing CC and the efficacy of prophylactic octreotide. We found that CC occurs frequently in patients having midgut NETs surgery, specifically those with NET liver metastasis, and is associated with worse postoperative outcomes. Our findings did not show a decreased risk in CC with prophylactic octreotide and questioned the advantage of routine prophylactic octreotide. Abstract Background: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide. Methods: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000–2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models. Results: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06–0.36]). Liver metastasis (odds ratio 2.85 [1.49–5.47]) and gender (male 0.58 [0.34–0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03–4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32–1.66]). Notably, there was no standard prophylactic octreotide strategy used. Conclusions: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC.
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Christ E, Wild D, Refardt J. Molecular Imaging in neuroendocrine neoplasias. Presse Med 2022; 51:104115. [PMID: 35131317 DOI: 10.1016/j.lpm.2022.104115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 01/11/2022] [Accepted: 01/28/2022] [Indexed: 12/16/2022] Open
Abstract
Molecular imaging, which uses molecular targets due to the overexpression of specific peptide hormone receptors on the tumour surface, has become an indispensable diagnostic technique. Neuroendocrine neoplasms (NENs) especially differentiated NENs or neuroendocrine tumours (NETs) are a rare group of heterogeneous tumours, characterized by the expression of hormone receptors on the tumour cell surface. This property makes them receptive to diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Amongst the known hormone receptors, somatostatin receptors (SSTR) are expressed on the majority of NETs and are therefore the most relevant receptors for theranostic approaches. Current research aims to medically upregulate their expression, while other focuses are on the use of different radiopeptides (64Cu and 67Cu) or somatostatin-antagonists instead of the established somatostatin agonists. The GLP-1 receptor is another clinically relevant target, as GLP-1-R imaging has become the new standard for the localisation of insulinomas. For staging and prognostic evaluation in dedifferentiated NENs, 18F-FDG-imaging is useful, but lacks a therapeutic counterpart. Further options for patients with insufficient expression of SSTR involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4). New targets such as the glucose-dependant insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs recently and await further evaluation. For medullary thyroid cancer 18-F-DOPA imaging is standard, however this technique is rather second line for other NENs. In this area, the discovery of minigastrin, which targets the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut NENs, may improve future management. This review aims to provide an overview of the most commonly used functional imaging modalities for theranostics in NENs today and in the possible future.
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Affiliation(s)
- Emanuel Christ
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
| | - Damian Wild
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
| | - Julie Refardt
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
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Siebenhüner AR, Langheinrich M, Friemel J, Schaefer N, Eshmuminov D, Lehmann K. Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors-Need for a Conductor. Cancers (Basel) 2022; 14:1478. [PMID: 35326628 PMCID: PMC8946777 DOI: 10.3390/cancers14061478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/28/2022] [Accepted: 03/10/2022] [Indexed: 12/11/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a vast growing disease. Over 50% of these tumors are recognized at advanced stages with lymph node, liver, or distant metastasis. An ongoing controversy is the role of surgery in the metastatic setting as dedicated systemic treatments have emerged recently and shown benefits in randomized trials. Today, liver surgery is an option for advanced pNETs if the tumor has a favorable prognosis, reflected by a low to moderate proliferation index (G1 and G2). Surgery in this well-selected population may prolong progression-free and overall survival. Optimal selection of a treatment plan for an individual patient should be considered in a multidisciplinary tumor board. However, while current guidelines offer a variety of modalities, there is so far only a limited focus on the right timing. Available data is based on small case series or retrospective analyses. The focus of this review is to highlight the right time-point for surgery in the setting of the multimodal treatment of an advanced pancreatic neuroendocrine tumor.
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Affiliation(s)
- Alexander R. Siebenhüner
- Clinic for Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland
- ENETS Center of Excellence Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
| | - Melanie Langheinrich
- Department of Visceral Surgery, University Hospital Greifswald, Ferdinand-Sauerbruch-Strasse, D-17475 Greifswald, Germany;
| | - Juliane Friemel
- Institute for Pathologie, University Bern, Murtenstrasse 31, CH-3008 Bern, Switzerland;
| | - Niklaus Schaefer
- Department of Nuclear Medicine, University Hospital Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland;
| | - Dilmurodjon Eshmuminov
- Department of Surgery and Transplantation, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
| | - Kuno Lehmann
- ENETS Center of Excellence Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
- Department of Surgery and Transplantation, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
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Zhang D, Lu L, Zhu HJ, Xiao Y, Han XL, Du SD, Xue HD, Liu QX, Zhu ZH, Hu MM, Zhai X, Xing XP, Lu ZL. Somatostatin Treatment for Ectopic ACTH Syndrome due to Pancreatic Neuroendocrine Tumors: Review of the Literature. Int J Endocrinol 2022; 2022:6283706. [PMID: 35265125 PMCID: PMC8901294 DOI: 10.1155/2022/6283706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 01/21/2022] [Accepted: 02/01/2022] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVES To analyze and summarize the effect of SSA treatment on EAS due to p-NETs (EAS-p-NETs). METHODS Thirteen patients with EAS-p-NETs treated with SSAs at our center or described in the literature were included in this study. Clinical characteristics, laboratory data, imaging studies, histopathologic results, the effect of SSA treatment, and the prognosis of these EAS-p-NET patients were evaluated. RESULTS Four males and 9 females with an average age of 42.9 years were included in the study. The mean duration of follow-up was 38.8 ± 28.2 months. As one of the combined treatment measures, SSAs controlled the levels of ACTH and cortisol in 9 of the 13 patients (69.2%). Partial response was observed in 3 patients (23.1%), stable disease in 2 patients (15.4%), and progressive disease in 6 patients (46.2%). The median time to tumor progression was 24 months, and the median overall survival was 61 months. The side effects of SSA treatment included temporary mild abdominal pain, diarrhea, gallstones, and cholecystitis. CONCLUSIONS As a supplemental therapy, SSA treatment led to clinical and biochemical improvement with a good safety profile in patients exhibiting EAS-p-NET with metastasis. However, tumor progression was inhibited by SSA treatment in only a few patients. Combined with other treatments, SSAs may improve the prognosis of patients with EAS-p-NETs.
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Affiliation(s)
- Da Zhang
- Department of Endocrinology, Air Force Medical Center, People's Liberation Army, Beijing 100142, China
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Lin Lu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Hui-Juan Zhu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Yu Xiao
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Xian-Lin Han
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Shun-Da Du
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Hua-Dan Xue
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Qing-Xing Liu
- Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Zhao-Hui Zhu
- Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Ming-Ming Hu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Xiao Zhai
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Xiao-Ping Xing
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Zhao-Lin Lu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [DOI: - merola e, michielan a, rozzanigo u, et al.therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: state-of-the-art and future perspectives.world j gastrointestinal surgery, volume 14 number 2 february 27, 2022, doi: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/16/2025] Open
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [PMID: 35317548 PMCID: PMC8908345 DOI: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 10/18/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.
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Affiliation(s)
- Elettra Merola
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Andrea Michielan
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Umberto Rozzanigo
- Department of Radiology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Marco Erini
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Sandro Sferrazza
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Stefano Marcucci
- Department of Surgery, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Sartori
- Department of Pathology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Trentin
- Department of Medical Oncology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Giovanni de Pretis
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Franca Chierichetti
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
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Maxwell JE, Naraev B, Halperin DM, Choti MA, Halfdanarson TR. Shifting Paradigms in the Pathophysiology and Treatment of Carcinoid Crisis. Ann Surg Oncol 2022; 29:3072-3084. [PMID: 35165817 DOI: 10.1245/s10434-022-11371-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 01/16/2022] [Indexed: 11/18/2022]
Abstract
Carcinoid crisis is a potentially fatal condition characterized by various symptoms, including hemodynamic instability, flushing, and diarrhea. The incidence of carcinoid crisis is unknown, in part due to inconsistency in definitions across studies. Triggers of carcinoid crisis include general anesthesia and surgical procedures, but drug-induced and spontaneous cases have also been reported. Patients with neuroendocrine tumors (NETs) and carcinoid syndrome are at risk for carcinoid crisis. The pathophysiology of carcinoid crisis has been attributed to secretion of bioactive substances, such as serotonin, histamine, bradykinin, and kallikrein by NETs. The somatostatin analog octreotide has been considered the standard of care for carcinoid crisis due to its inhibitory effect on hormone release and relatively fast resolution of carcinoid crisis symptoms in several case studies. However, octreotide's efficacy in the treatment of carcinoid crisis has been questioned. This is due to a lack of a common definition for carcinoid crisis, the heterogeneity in clinical presentation, the paucity of prospective studies assessing octreotide efficacy in carcinoid crisis, and the lack of understanding of the pathophysiology of carcinoid crisis. These issues challenge the classical physiologic model of carcinoid crisis and its common etiology with carcinoid syndrome and raise questions regarding the utility of somatostatin analogs in its treatment. As surgical procedures and invasive liver-directed therapies remain important treatment modalities in patients with NETs, the pathophysiology of carcinoid crisis, potential benefits of octreotide, and efficacy of alternative treatment modalities must be studied prospectively to develop an effective evidence-based treatment strategy for carcinoid crisis.
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Affiliation(s)
- Jessica E Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Boris Naraev
- Banner MD Anderson Cancer Center, Phoenix, AZ, USA
| | - Daniel M Halperin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Thorvardur R Halfdanarson
- Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA. .,Mayo Clinic Cancer Center, Rochester, MN, USA.
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Carcinoid Crisis: A Misunderstood and Unrecognized Oncological Emergency. Cancers (Basel) 2022; 14:cancers14030662. [PMID: 35158931 PMCID: PMC8833591 DOI: 10.3390/cancers14030662] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/22/2022] [Accepted: 01/26/2022] [Indexed: 01/25/2023] Open
Abstract
Carcinoid Crisis represents a rare and extremely dangerous manifestation that can occur in patients with Neuroendocrine Tumors (NETs). It is characterized by a sudden onset of hemodynamic instability, sometimes associated with the classical symptoms of carcinoid syndrome, such as bronchospasm and flushing. Carcinoid Crisis seems to be caused by a massive release of vasoactive substances, typically produced by neuroendocrine cells, and can emerge after abdominal procedures, but also spontaneously in rare instances. To date, there are no empirically derived guidelines for the management of this cancer-related medical emergency, and the available evidence essentially comes from single-case reports or dated small retrospective series. A transfer to the Intensive Care Unit may be necessary during the acute setting, when the severe hypotension becomes unresponsive to standard practices, such as volemic filling and the infusion of vasopressor therapy. The only effective strategy is represented by prevention. The administration of octreotide, anxiolytic and antihistaminic agents represents the current treatment approach to avoid hormone release and prevent major complications. However, no standard protocols are available, resulting in great variability in terms of schedules, doses, ways of administration and timing of prophylactic treatments.
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Vemuri KR, Balcerek MI, McGowan TE, Love A, Chapman PR. VIPoma:
an unsuspecting culprit of severe secretory diarrhoea in a human immunodeficiency virus‐infected patient. Intern Med J 2022; 52:125-129. [DOI: 10.1111/imj.15655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 06/16/2021] [Accepted: 06/29/2021] [Indexed: 11/27/2022]
Affiliation(s)
- Kanthi R. Vemuri
- Department of Infectious Diseases Royal Brisbane and Women's Hospital Brisbane Queensland Australia
- Herston Infectious Diseases Institute (HeIDI) Metro North Hospitals and Health Services Brisbane Queensland Australia
| | - Matthew I. Balcerek
- Department of Endocrinology and Diabetes Royal Brisbane and Women's Hospital Brisbane Queensland Australia
| | - Tom E. McGowan
- Department of Infectious Diseases Royal Brisbane and Women's Hospital Brisbane Queensland Australia
| | - Amanda Love
- Department of Endocrinology and Diabetes Royal Brisbane and Women's Hospital Brisbane Queensland Australia
| | - Paul R. Chapman
- Department of Infectious Diseases Royal Brisbane and Women's Hospital Brisbane Queensland Australia
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How Many Times Can One Go Back to the Drawing Board before the Accurate Diagnosis and Surgical Treatment of Glucagonoma? Diagnostics (Basel) 2022; 12:diagnostics12010216. [PMID: 35054383 PMCID: PMC8774529 DOI: 10.3390/diagnostics12010216] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/12/2022] [Accepted: 01/14/2022] [Indexed: 02/04/2023] Open
Abstract
Glucagonomas are neuroendocrine tumors (NETs) that arise from the alpha cells of the pancreatic islets. They are typically slow-growing tumors associated with abnormal glucagon secretion, resulting in one or more non-specific clinical features, such as necrolytic migratory erythema (NME), diabetes, diarrhea, deep vein thrombosis, weight loss, and depression. Here, we report the case of a 44-year-old male with a history of diabetes mellitus, presenting with a pruritic and painful disseminated cutaneous eruption of erythematous plaques, with scales and peripheral pustules, misdiagnosed as disseminated pustular psoriasis and treated for 2 years with oral retinoid and glucocorticoids. During this period, the patient complained of weight loss of 32 kg and diarrhea and developed deep vein thrombosis. These symptoms, together with an inadequate response to therapy of the skin lesions, led to the reassessment of the initial diagnosis. Laboratory tests confirmed elevated plasma glucagon levels (>1000 pg/mL) and computed tomography (CT) scans revealed a 35/44 mm tumor in the pancreatic tail. Due to considerable disease complications and the COVID-19 pandemic, the surgical removal of the tumor was delayed for nearly 2 years. During this time, somatostatin analogue therapy efficiently controlled the glucagonoma syndrome and likely prevented tumor progression. As in other functional pancreatic NETs, the early clinical recognition of hormonal hypersecretion syndrome and the multidisciplinary approach are the keys for best patient management.
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Trends in Incidence and Survival of Patients with Pancreatic Neuroendocrine Neoplasm, 1987-2016. JOURNAL OF ONCOLOGY 2022; 2021:4302675. [PMID: 34976056 PMCID: PMC8716229 DOI: 10.1155/2021/4302675] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 11/11/2021] [Indexed: 01/27/2023]
Abstract
Background Pancreatic neuroendocrine neoplasm (pNEN), with the lowest 5-year survival rates in neuroendocrine tumors (NETs), exerts great threat to human health. Because large-scale population research aimed at pNEN is rare, we aimed to explore the tendencies and differences of changes in incidences and survival rates of pNEN in each decade from 1987 to 2016 and evaluate the impacts of age, sex, race, socioeconomic status (SES), and grade. Methods Data on pNEN cases from 1987 to 2016 were extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier, Cox proportional hazards regression analyses, and relative survival rates (RSRs) were used to identify risk factors for pNEN. Results The incidence and survival duration of pNEN increase every decade due to medical developments. The disparities of long-term survival in different age, sex, and grade groups expanded over time while that in race and SES groups narrowed. Older age and higher grade are independent risk factors for poorer survival. Females have lower incidence and longer survival than males. Prognosis of Black patients and poor (medium and high poverty) patients improved. Conclusions This study depicted changes in incidence and survival rates of pNEN over the past three decades and evaluated potential risk factors related to pNEN, benefiting future prediction of vulnerable and clinical options.
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Whiley PJ, Balasooriya J, Wake RJ. A case of metastatic neuroendocrine disease and cholecystitis: surgical remedy and management of carcinoid crisis. J Surg Case Rep 2021; 2021:rjab543. [PMID: 34909171 PMCID: PMC8666200 DOI: 10.1093/jscr/rjab543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/10/2021] [Accepted: 11/13/2021] [Indexed: 11/16/2022] Open
Abstract
The report presents a case of a 70-year-old male with a known mesenteric neuroendocrine tumour and metastases to the liver diagnosed with acute cholecystitis. During surgery, the patient developed a carcinoid crisis with mixed distributive and cardiogenic shock involving systemic vasodilation and arrhythmia. During surgical procedures, carcinoid crisis can be precipitated by tumours that secrete a pathological shower of vasoactive mediators. Somatostatin analogues are utilized to control carcinoid syndrome and are routinely used peri-operatively. However, no standard infusion regimen exists. The case raises the suggestion that metastatic liver neuroendocrine disease may confound the diagnosis of cholecystitis, complicates the management of acute surgical presentations and highlights the need for agreement on octreotide therapy for surgical patients with carcinoid tumours.
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Affiliation(s)
- Phillip J Whiley
- Australian National University Medical School, Canberra, ACT, Australia
| | | | - Rudyard J Wake
- Division of General Surgery, The Canberra Hospital, ACT, Australia
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Baron E, Szymanski C, Hergault H, Lepère C, Dubourg O, Hauguel-Moreau M, Mansencal N. Progression of Carcinoid Heart Disease in the Modern Management Era. J Am Heart Assoc 2021; 10:e020475. [PMID: 34816734 PMCID: PMC9075379 DOI: 10.1161/jaha.120.020475] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Background The development of carcinoid heart disease (CaHD) is still relatively unclear. It is difficult to define an optimal follow‐up for patients without any cardiac involvement at baseline. The aim of this study was to assess the prevalence and natural history of CaHD by annual echocardiographic examinations. Methods and Results We studied 137 consecutive patients (61±12 years, 53% men) with proven digestive endocrine tumor and carcinoid syndrome between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right‐sided and left‐sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CaHD. An increase of 25% of the score was considered to be significant. Mean follow‐up was 54±45 months. Prevalence of CaHD was 27% at baseline and 32% at 5‐year follow‐up. Disease progression was reported in 28% of patients with initial CaHD followed up for >2 years (n=25). In patients without any cardiac involvement at baseline, occurrence of disease was 21%. CaHD occurred >5 years from the initial echocardiographic examination in 42% of our cases, especially in patients presenting with new recurrence of a digestive endocrine tumor. An increase of urinary 5‐hydroxyindoleacetic acid by 25% during follow‐up was identified as an independent predictor of CaHD occurrence during follow‐up (hazard ratio [HR], 5.81; 95% CI, 1.19–28.38; P=0.03), as well as a maximum value of urinary 5‐hydroxyindoleacetic acid >205 mg/24 h during follow‐up (HR, 8.41; 95% CI, 1.64–43.07; P=0.01). Conclusions Our study demonstrates that in patients without initial CaHD, cardiac involvement may occur late and is related to serotonin. Our data emphasize the need for cardiologic follow‐up in patients with recurrence of the tumor process.
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Affiliation(s)
- Emilie Baron
- Department of Cardiology Ambroise Paré HospitalAssistance Publique-Hôpitaux de Paris (AP-HP)Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou raresUniversité de Versailles-Saint Quentin (UVSQ) Boulogne France
| | - Catherine Szymanski
- Department of Cardiology Ambroise Paré HospitalAssistance Publique-Hôpitaux de Paris (AP-HP)Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou raresUniversité de Versailles-Saint Quentin (UVSQ) Boulogne France.,INSERM U-1018CESPTeam 5 (EpReC, Renal and Cardiovascular Epidemiology)UVSQ Villejuif France
| | - Hélène Hergault
- Department of Cardiology Ambroise Paré HospitalAssistance Publique-Hôpitaux de Paris (AP-HP)Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou raresUniversité de Versailles-Saint Quentin (UVSQ) Boulogne France
| | - Céline Lepère
- Department of Gastroenterology and Digestive Oncology European Georges Pompidou HospitalAP-HP Paris France
| | - Olivier Dubourg
- Department of Cardiology Ambroise Paré HospitalAssistance Publique-Hôpitaux de Paris (AP-HP)Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou raresUniversité de Versailles-Saint Quentin (UVSQ) Boulogne France.,INSERM U-1018CESPTeam 5 (EpReC, Renal and Cardiovascular Epidemiology)UVSQ Villejuif France
| | - Marie Hauguel-Moreau
- Department of Cardiology Ambroise Paré HospitalAssistance Publique-Hôpitaux de Paris (AP-HP)Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou raresUniversité de Versailles-Saint Quentin (UVSQ) Boulogne France.,INSERM U-1018CESPTeam 5 (EpReC, Renal and Cardiovascular Epidemiology)UVSQ Villejuif France
| | - Nicolas Mansencal
- Department of Cardiology Ambroise Paré HospitalAssistance Publique-Hôpitaux de Paris (AP-HP)Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou raresUniversité de Versailles-Saint Quentin (UVSQ) Boulogne France.,INSERM U-1018CESPTeam 5 (EpReC, Renal and Cardiovascular Epidemiology)UVSQ Villejuif France
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de Ponthaud C, Menegaux F, Gaujoux S. Updated Principles of Surgical Management of Pancreatic Neuroendocrine Tumours (pNETs): What Every Surgeon Needs to Know. Cancers (Basel) 2021; 13:5969. [PMID: 34885079 PMCID: PMC8656761 DOI: 10.3390/cancers13235969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/25/2021] [Accepted: 11/25/2021] [Indexed: 02/07/2023] Open
Abstract
Pancreatic neuroendocrine tumours (pNETs) represent 1 to 2% of all pancreatic neoplasm with an increasing incidence. They have a varied clinical, biological and radiological presentation, depending on whether they are sporadic or genetic in origin, whether they are functional or non-functional, and whether there is a single or multiple lesions. These pNETs are often diagnosed at an advanced stage with locoregional lymph nodes invasion or distant metastases. In most cases, the gold standard curative treatment is surgical resection of the pancreatic tumour, but the postoperative complications and functional consequences are not negligible. Thus, these patients should be managed in specialised high-volume centres with multidisciplinary discussion involving surgeons, oncologists, radiologists and pathologists. Innovative managements such as "watch and wait" strategies, parenchymal sparing surgery and minimally invasive approach are emerging. The correct use of all these therapeutic options requires a good selection of patients but also a constant update of knowledge. The aim of this work is to update the surgical management of pNETs and to highlight key elements in view of the recent literature.
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Affiliation(s)
- Charles de Ponthaud
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
| | - Fabrice Menegaux
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
| | - Sébastien Gaujoux
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
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Alvarez-Villegas D, Giménez-Milà M, Sbraga F, Camprubí I, Gil A, Valchanov K, Shayan H, Castillo J, Weiner MM. Dealing With the Right Side: Carcinoid Heart Disease. J Cardiothorac Vasc Anesth 2021; 36:2793-2802. [PMID: 34863651 DOI: 10.1053/j.jvca.2021.10.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 10/19/2021] [Indexed: 11/11/2022]
Affiliation(s)
- David Alvarez-Villegas
- Department of Anesthesia and Critical Care,Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Marc Giménez-Milà
- Department of Anesthesia and Critical Care,Hospital Clínic Barcelona, Universitat de Barcelona, Barcelona, Spain.
| | - Fabrizio Sbraga
- Department of Cardiovascular Surgery and Transplantation, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Immaculada Camprubí
- Department of Anesthesia and Critical Care,Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Albert Gil
- Department of Anesthesia and Critical Care,Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Kamen Valchanov
- Department of Anesthesia,Royal Columbian Hospital, New Westminster, British Columbia, Canada
| | - Hossain Shayan
- Department of Cardiac Surgery, Royal Columbian Hospital, New Westminster, British Columbia, Canada
| | - Javier Castillo
- Heart & Lung Institute, Bayamon Medical Center, Bayamon, Puerto Rico
| | - Menachem M Weiner
- Department of Anesthesiology, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY
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