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Lv HY, Liu MX, Hong WT, Li XW. Primary hepatic neuroendocrine tumor with a suspicious pulmonary nodule: A case report and literature review. World J Clin Oncol 2025; 16:101236. [PMID: 40130063 PMCID: PMC11866086 DOI: 10.5306/wjco.v16.i3.101236] [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: 09/08/2024] [Revised: 12/07/2024] [Accepted: 12/27/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare tumors originating from neuroendocrine cells. Due to lack of neuroendocrine symptoms and specific radiographic characteristics, PHNETs are challenging to differentiate from other liver tumors. CASE SUMMARY This case involved a 67-year-old male who was admitted with a discovered hepatic mass and a suspicious lung lesion. Primary hepatic carcinoma was initially speculated based on the characteristic magnetic resonance imaging findings. The patient underwent a laparoscopic right partial hepatectomy, and subsequent immunohistochemical examination revealed a HNET. To exclude other potential origins, a positron emission tomography-computed tomography scan and gastrointestinal endoscopy were performed, leading to a final diagnosis of PHNETs. Then we conducted a literature review using the PubMed database, identifying 99 articles and 317 cases related to PHNETs. The characteristics, diagnostic methods, and treatment of PHNETs have been described. Finally, we elaborate on the presumed origins, pathological grades, clinical features, diagnosed methods, and treatments associated with PHNETs. CONCLUSION The diagnosis of PHNETs was primarily an exclusionary process. A definitive diagnosis of PHNETs relied mainly on immunohistochemical markers (chromogranin A, synaptophysin, and cluster of differentiation 56) and exclusion of primary foci in other organs. Radical surgery was the preferred treatment for early-stage tumors.
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Affiliation(s)
- Hai-Yan Lv
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Mei-Xuan Liu
- Department of Burns and Wound Care Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Wen-Ting Hong
- Department of Nursing Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Xia-Wei Li
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Department of Cancer Center, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
- Harvard T.H. Chan School of Public Health, Harvard University, Cambridge, MA 02138, United States
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Ladenheim A, Zheng JX, Teklu A, Matsukuma K. PCSK2 can be Useful in a Panel Approach to Distinguish Foregut and Midgut Neuroendocrine Tumors. Int J Surg Pathol 2025; 33:76-84. [PMID: 39034588 DOI: 10.1177/10668969241260208] [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] [Indexed: 07/23/2024]
Abstract
INTRODUCTION A number of immunohistochemical stains have been examined for utility in establishing the site of origin for metastatic well-differentiated neuroendocrine tumors (NETs). In the gastrointestinal (GI) tract, distinguishing metastatic duodenal NETs from jejunoileal and other GI NETs is important for clinical work-up, prognosis, and therapy. A recent study indicated that prohormone convertase 2 (PCSK2 or PC2) had broad expression in small intestine and appendiceal NETs. Because the study did not include duodenal NETs, we examined PCSK2 expression in duodenal and other GI NETs. METHODS GI NETs (n = 69) and 13 corresponding lymph node metastases from stomach, duodenum, pancreas, ileum, appendix, and rectum were evaluated for the expression of PCSK2, along with ISL1, NKX2.2, CDX2, SATB2, and PAX8. Expression of each stain was evaluated using the H-score system, and differences in expression by site were evaluated by the chi square test. RESULTS PCSK2 was expressed at similar frequency in duodenal (50%), pancreatic (59%), and ileal NETs (40%). PCSK2 was infrequently expressed in stomach (0%), appendiceal (8%), and rectal (25%) NETs. However, incorporating PCSK2 into a panel including ISL1, NKX2.2, CDX2, and SATB2 allowed development of an algorithm which had 87% sensitivity and 93% specificity for classification of ileal NETs; and 68% sensitivity and 98% specificity for pancreaticoduodenal NETs. CONCLUSIONS In contrast to previous findings, PCSK2 does not show specificity for any particular GI site. An algorithmic approach incorporating the expression of PCSK2 with that of ISL1, NKX2.2, CDX2, and SATB2 is useful in discriminating pancreatic, duodenal, ileal, appendiceal, and rectal NETs.
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Affiliation(s)
- Alexander Ladenheim
- Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, Sacramento, CA, USA
| | - Jasper X Zheng
- Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, Sacramento, CA, USA
| | - Abebe Teklu
- Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, Sacramento, CA, USA
| | - Karen Matsukuma
- Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, Sacramento, CA, USA
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Tran CG, Sherman SK, Chandrasekharan C, Howe JR. Surgical Management of Neuroendocrine Tumor Liver Metastases. Hematol Oncol Clin North Am 2025; 39:37-53. [PMID: 39510676 DOI: 10.1016/j.hoc.2024.08.001] [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] [Indexed: 11/15/2024]
Abstract
Patients with neuroendocrine tumor liver metastases (NETLMs) may develop carcinoid syndrome, carcinoid heart disease, or other symptoms from overproduction of hormones. Hepatic resection and cytoreduction is the most direct treatment of NETLMs in eligible patients, and cytoreduction improves symptoms, may reduce the sequelae of carcinoid syndrome, and extends survival. Parenchymal-sparing procedures, such as ablation and enucleation, should be considered during cytoreduction to maximize treatment of multifocal tumors while preserving healthy liver tissue. For patients with large hepatic tumor burdens, high-grade disease, or comorbidities precluding surgery, liver-directed and systemic therapies can be used to palliate symptoms and improve progression-free survival.
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Affiliation(s)
- Catherine G Tran
- Department of Surgery, Division of Colorectal Surgery, University of Minnesota, Minneapolis, MN
| | - Scott K Sherman
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | | | - James R Howe
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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4
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Martinez Ponce JP, Ubysz O, Vanhecke T. Carcinoid Heart Disease: A Rare Complication of Metastatic Neuroendocrine Tumor. Cureus 2025; 17:e78148. [PMID: 40026979 PMCID: PMC11872146 DOI: 10.7759/cureus.78148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2025] [Indexed: 03/05/2025] Open
Abstract
Carcinoid heart disease (CHD), also known as Hedinger syndrome, is a rare but significant cardiac complication associated with metastatic neuroendocrine tumors (NETs). These tumors secret bioactive substances such as serotonin, leading to fibrotic changes primarily affecting the right-sided heart valves. A case study involving a 69-year-old male presented with a four-month history of diarrhea and a new systolic heart murmur. Transthoracic echocardiogram (TTE) results indicated a left ventricular ejection fraction (LVEF) of 60% to 65%, with severe tricuspid regurgitation and pulmonary valve stenosis. Elevated levels of 5-hydroxyindoleacetic acid (5-HIAA) were detected in a 24-hour urine test, and imaging revealed multiple hypoechoic masses in the liver and mesenteric masses adherent to the small intestine. Furthermore, a biopsy confirmed the diagnosis of a NET. Medical therapy like long-acting somatostatin injection and a peptide receptor radionuclide therapy was ineffective in reversing established valvular pathology, and the patient continued to experience clinical decline, suffering from right-sided heart failure. The patient was able to undergo combined tricuspid and pulmonary valve replacement, which resolved his symptoms. This case exemplifies the successful treatment of a rare syndrome leading to right heart failure.
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Affiliation(s)
| | - Oskar Ubysz
- Cardiology, Henry Ford Health, Grand Blanc, USA
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Bosch EM, Laskaratos FM, Sodergren M, Faiz O, Humphries A. The Role of Small-Bowel Endoscopy in the Diagnosis and Management of Small-Bowel Neuroendocrine Tumours. J Clin Med 2024; 13:6877. [PMID: 39598021 PMCID: PMC11594952 DOI: 10.3390/jcm13226877] [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: 09/24/2024] [Revised: 11/10/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024] Open
Abstract
Neuroendocrine tumours (NETs) are relatively rare neoplasms but represent one of the most frequent types of primary small-bowel tumours. Their incidence is rising, and this is most likely because of their more frequent early-stage detection, physician awareness, and increasing availability and use of imaging and small-bowel endoscopic techniques, such as video capsule endoscopy and device-assisted enteroscopy, which enable the detection, localisation, and histological sampling of previously inaccessible and underdiagnosed small-bowel lesions. This review summarises the role of small-bowel endoscopy in the diagnosis and management of small-bowel NETs to assist clinicians in their practice. Small-bowel endoscopy may play a complementary role in the diagnosis of these tumours alongside other diagnostic tests, such as biomarkers, conventional radiology, and functional imaging. In addition, small-bowel enteroscopy may play a role in the preoperative setting for the identification and marking of these tumours for surgical resection and the management of rare complications, such as small-bowel variceal bleeding, in cases of portal hypertension due to the encasement of mesenteric vessels in fibrotic small-bowel NETs.
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Affiliation(s)
- Elisabet Maristany Bosch
- St Mark’s National Bowel Hospital, Acton Lane, Park Royal, London NW10 7NS, UK; (E.M.B.); (A.H.)
| | - Faidon-Marios Laskaratos
- St Mark’s National Bowel Hospital, Acton Lane, Park Royal, London NW10 7NS, UK; (E.M.B.); (A.H.)
| | - Mikael Sodergren
- Department of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital, London W12 0TS, UK;
- Imperial Neuroendocrine Tumour Unit, ENETS Centre of Excellence, London W12 0TS, UK
- Imperial College London, London SW7 2AZ, UK;
| | - Omar Faiz
- Imperial College London, London SW7 2AZ, UK;
- Department of Surgery, St Mark’s National Bowel Hospital, Acton Lane, Park Royal, London NW10 7NS, UK
| | - Adam Humphries
- St Mark’s National Bowel Hospital, Acton Lane, Park Royal, London NW10 7NS, UK; (E.M.B.); (A.H.)
- Imperial College London, London SW7 2AZ, UK;
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Piscione M, Cammalleri V, Antonelli G, De Luca VM, Carpenito M, Gaudio D, Cocco N, Nenna A, Dominici C, Bianchi A, Grigioni F, Ussia GP. Cardiac Surgery and Transcatheter Intervention for Valvular Heart Disease in Carcinoid Syndrome: Risk Factors, Outcomes, and Evolving Therapeutic Strategies. J Cardiovasc Dev Dis 2024; 11:359. [PMID: 39590202 PMCID: PMC11594282 DOI: 10.3390/jcdd11110359] [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: 09/19/2024] [Revised: 10/24/2024] [Accepted: 11/03/2024] [Indexed: 11/28/2024] Open
Abstract
Carcinoid heart disease (CHD) affects right-sided valves and causes significant mortality and morbidity. Even though the pathophysiology of the disease is not entirely understood, it is known that chronic exposure to high levels of circulating serotonin is the main factor responsible for developing valvular heart disease. Cardiac imaging plays a critical role in the management of CHD, so the final diagnosis can be performed through multimodal imaging techniques and the measurement of biomarkers. Moreover, in observational studies, surgical treatment of carcinoid-induced valve disease has been found to improve outcomes. Despite advancements in pre-operative preparation in recent years, mortality rates remain high in elderly patients and those with multiple comorbidities due to the risk of intra-operative carcinoid crisis and high post-operative bleeding. In this comprehensive review, we will analyze the causes of carcinoid syndrome and how it can result in severe right heart failure. The role of different imaging modalities in detecting heart valve disease will be discussed together with the therapeutic options at our disposal, such as medical treatment, surgery, and the novel role of transcatheter intervention.
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Affiliation(s)
- Mariagrazia Piscione
- Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (M.P.); (G.A.); (V.M.D.L.); (D.G.); (F.G.); (G.P.U.)
| | - Valeria Cammalleri
- Unit of Cardiovascular Science, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (M.C.); (N.C.)
| | - Giorgio Antonelli
- Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (M.P.); (G.A.); (V.M.D.L.); (D.G.); (F.G.); (G.P.U.)
| | - Valeria Maria De Luca
- Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (M.P.); (G.A.); (V.M.D.L.); (D.G.); (F.G.); (G.P.U.)
| | - Myriam Carpenito
- Unit of Cardiovascular Science, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (M.C.); (N.C.)
| | - Dario Gaudio
- Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (M.P.); (G.A.); (V.M.D.L.); (D.G.); (F.G.); (G.P.U.)
| | - Nino Cocco
- Unit of Cardiovascular Science, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (M.C.); (N.C.)
| | - Antonio Nenna
- Department of Cardiovascular Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (A.N.); (C.D.)
| | - Carmelo Dominici
- Department of Cardiovascular Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (A.N.); (C.D.)
| | - Antonio Bianchi
- Internal Medicine, Endocrinology and Diabetes Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Department of Medical and Surgical Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy;
| | - Francesco Grigioni
- Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (M.P.); (G.A.); (V.M.D.L.); (D.G.); (F.G.); (G.P.U.)
- Unit of Cardiovascular Science, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (M.C.); (N.C.)
| | - Gian Paolo Ussia
- Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Rome, Italy; (M.P.); (G.A.); (V.M.D.L.); (D.G.); (F.G.); (G.P.U.)
- Unit of Cardiovascular Science, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy; (M.C.); (N.C.)
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Rudolph JJ, Agyei O, Telvizian T, Ghaneie A. Gastric Neuroendocrine Tumors and Pernicious Anemia: A Case Report and Literature Review. Cureus 2024; 16:e73553. [PMID: 39669826 PMCID: PMC11637537 DOI: 10.7759/cureus.73553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2024] [Indexed: 12/14/2024] Open
Abstract
Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, with the gastric (stomach) subtype (G-NETs) representing a significant clinical focus. Type 1 G-NETs are particularly noteworthy due to their relationship with autoimmune atrophic gastritis (AAG) and pernicious anemia (PA), conditions that impact vitamin B12 absorption. This report presents the case of a patient with a type 1 G-NET identified at the initial diagnosis of PA, demonstrating the connection between these conditions. In the literature review, we discuss the general mechanisms underlying PA, including its etiology, pathogenesis, clinical presentations, and diagnostic approaches. Emphasis is placed on the importance of recognizing and diagnosing this condition early, given the treatable nature of the associated gastric neuroendocrine dysregulation. Additionally, the report examines the broad spectrum of G-NETs, with a special emphasis on the characteristics of type 1 tumors. By considering recent developments in the field, we provide an overview of the current understanding of G-NET epidemiology, classification, clinical features, diagnosis, and management strategies.
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Affiliation(s)
| | - Obed Agyei
- Hematology and Medical Oncology, Lankenau Medical Center, Wynnewood, USA
| | - Talar Telvizian
- Hematology and Medical Oncology, Lankenau Medical Center, Wynnewood, USA
| | - Arezoo Ghaneie
- Hematology and Medical Oncology, Lankenau Medical Center, Wynnewood, USA
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Sakurai Y, Karaki H, Nakamura Y, Fukuda H, Okaya T, Oheda Y, Yokoyama Y, Hirai F, Abe M, Sugano I. A case of early-stage type 3 gastric neuroendocrine tumor in the upper body of the stomach: is endoscopic resection feasible? Clin J Gastroenterol 2024; 17:814-819. [PMID: 38865017 DOI: 10.1007/s12328-024-01999-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 06/03/2024] [Indexed: 06/13/2024]
Abstract
Although gastric neuroendocrine tumors (NETs) are uncommon compared with gastric carcinomas, the incidence of NETs has been recently increasing. Gastric NETs are classified into three subgroups, and among these, gastrin-independent sporadic type 3 gastric NETs have a poor prognosis because of frequent lymph node or distant metastasis. We experienced a case of an early-stage type 3 gastric NET associated with lymphovascular and submucosal invasion. In a 54 year-old woman, esophagogastroduodenoscopy performed during a health screening identified an elevated lesion of the upper body of the stomach. The results of immunohistochemical analyses of endoscopic biopsy specimens obtained from the lesion were positive for chromogranin A and synaptophysin, indicating an NET. Because the patient's serum gastrin level was normal and she had no predisposing conditions for NET development, the tumor was diagnosed as a type 3 gastric NET. The patient underwent local resection of the tumor and regional lymph node dissection. The resected specimen indicated a diagnosis of type 3 gastric NET with invasion into the submucosa and lymphatic duct. This is an extremely rare case of an early-stage type 3 gastric NET. Our discussion provides insight into the pathogenesis and development of these tumors and the appropriate therapeutic strategy.
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Affiliation(s)
- Yoichi Sakurai
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan.
| | - Hirokazu Karaki
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yusuke Nakamura
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Hiroyuki Fukuda
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Tomohisa Okaya
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yoshio Oheda
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yuya Yokoyama
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Futoshi Hirai
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Michikazu Abe
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Isamu Sugano
- Pathology Division, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
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Sharma A, Muralitharan M, Ramage J, Clement D, Menon K, Srinivasan P, Elmasry M, Reed N, Seager M, Srirajaskanthan R. Current Management of Neuroendocrine Tumour Liver Metastases. Curr Oncol Rep 2024; 26:1070-1084. [PMID: 38869667 PMCID: PMC11416395 DOI: 10.1007/s11912-024-01559-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] [Accepted: 05/22/2024] [Indexed: 06/14/2024]
Abstract
PURPOSE OF REVIEW This article aims to illustrate the current state of investigations and management of liver metastases in patients with Neuroendocrine Neoplasms. Neuroendocrine tumours (NETs) are rising in incidence globally and have become the second most prevalent gastrointestinal malignancy in UK and USA. Frequently, patients have metastatic disease at time of presentation. The liver is the most common site of metastases for gastro-enteropancreatic NETs. Characterisation of liver metastases with imaging is important to ensure disease is not under-staged. RECENT FINDINGS Magnetic resonance imaging and positron emission tomography are now becoming standard of care for imaging liver metastases. There is an increasing armamentarium of therapies available for management of NETs and loco-regional therapy for liver metastases. The data supporting surgical and loco-regional therapy is reviewed with focus on role of liver transplantation. It is important to use appropriate imaging and classification of NET liver metastases. It is key that decisions regarding approach to treatment is undertaken in a multidisciplinary team and that individualised approaches are considered for management of patients with metastatic NETs.
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Affiliation(s)
- Aditya Sharma
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K
| | | | - John Ramage
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Dominique Clement
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Krishna Menon
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Parthi Srinivasan
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Mohamed Elmasry
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Nick Reed
- Department of Oncology, Beatson Centre, G12 0YN, Glasgow, U.K
| | - Matthew Seager
- Department of Radiology, King's College Hospital, SE5 9RS, London, U.K
| | - Rajaventhan Srirajaskanthan
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K..
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K..
- Neuroendocrine Tumour Unit Institute of liver studies, King's College Hospital, SE5 9RS, London, U.K..
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10
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Tie SJ, Fan ML, Zhang JY, Yu J, Wu N, Su GQ, Xu Z, Huang WF. Clinical outcomes after endoscopic resection and the risk of lymph node metastasis in rectal neuroendocrine tumors: a single-center retrospective study. Surg Endosc 2024; 38:5178-5186. [PMID: 39043886 DOI: 10.1007/s00464-024-11088-z] [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: 05/06/2024] [Accepted: 07/14/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND AND AIM The incidence of rectal neuroendocrine tumors (R-NETs) has increased in recent years. However, the predictors of lymph node (LN) metastasis and clinical outcomes, particularly following endoscopic treatment, remain unclear. Our study aims to elucidate the potential risk factors for LN metastasis and the clinical outcomes of patients undergoing endoscopic resection in R-NETs. METHODS A total of 128 patients with R-NETs were retrospectively identified from a single center between June 2012 and December 2021. Risk factors for LN metastasis in R-NETs were analyzed using multivariate analysis. Additionally, the clinical outcomes of endoscopic resections in patients with R-NETs were assessed. RESULTS In our study, 128 patients with R-NETs were retrospectively analyzed. The risk factors for LN metastasis determined by multivariate analysis were tumor size and patient age at diagnosis. Among the 111 patients treated with endoscopic resection and with tumor margin records available, 92 underwent endoscopic submucosal dissection (ESD) and 19 underwent conventional endoscopic mucosal resection (EMR). There was no significant difference between the two groups regarding the positive rates of basal tumor margin and lateral tumor margin. Furthermore, 64 patients who underwent endoscopic resection for R-NETs were successfully followed up (range, 1.64-76.71 months), during which only one patient developed local recurrence. CONCLUSION Tumor size and age at diagnosis were predictors for LN metastasis of R-NETs. Both ESD and EMR are alternative techniques with a favorable prognosis for R-NETs, even in cases with positive resection margins. However, due to the relatively small number of patients undergoing EMR and missing data in follow-up protocols, definitive conclusions require further large-scale studies.
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Affiliation(s)
- Sheng-Jiao Tie
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Mei-Ling Fan
- Department of Gastroenterology, The Third Hospital of Xiamen, Xiamen, China
| | - Jin-Yan Zhang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Juan Yu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Na Wu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Guo-Qiang Su
- Department of Colorectal Cancer Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Zhong Xu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
| | - Wei-Feng Huang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
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Padmanabhan Nair Sobha R, Jensen CT, Waters R, Calimano-Ramirez LF, Virarkar MK. Appendiceal Neuroendocrine Neoplasms: A Comprehensive Review. J Comput Assist Tomogr 2024; 48:545-562. [PMID: 37574653 DOI: 10.1097/rct.0000000000001528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
ABSTRACT Appendiceal neuroendocrine neoplasm (NEN) is the most common adult appendiceal malignant tumor, constituting 16% of gastrointestinal NENs. They are versatile tumors with varying morphology, immunohistochemistry, secretory properties, and cancer genomics. They are slow growing and clinically silent, to begin with, or present with features of nonspecific vague abdominal pain. Most acute presentations are attributed clinically to appendicitis, with most cases detected incidentally on pathology after an appendectomy. Approximately 40% of them present clinically with features of hormonal excess, which is likened to the functional secretory nature of their parent cell of origin. The symptoms of carcinoid syndrome render their presence clinically evident. However, slow growing and symptomatically silent in its initial stages, high-grade neuroendocrine tumors and neuroendocrine carcinomas of the appendix are aggressive and usually have hepatic and lymph node metastasis at presentation. This review article focuses on imaging characteristics, World Health Organization histopathological classification and grading, American Joint Committee on Cancer/Union or International Cancer Control, European Neuroendocrine Tumor Society staging, European Neuroendocrine Tumor Society standardized guidelines for reporting, data interpretation, early-stage management protocols, and advanced-stage appendiceal NENs. Guidelines are also set for the follow-up and reassessment. The role of targeted radiotherapy, chemotherapy, and high-dose somatostatin analogs in treating advanced disease are discussed, along with types of ablative therapies and liver transplantation for tumor recurrence. The search for newer location-specific biomarkers in NEN is also summarized. Regarding the varying aggressiveness of the tumor, there is a scope for research in the field, with plenty of data yet to be discovered.
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Affiliation(s)
| | - Corey T Jensen
- From the Department of Radiology, University of Texas MD Anderson Cancer Center
| | - Rebecca Waters
- Department of Pathology and Lab Medicine MD Anderson Cancer Center, Houston, TX
| | | | - Mayur K Virarkar
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL
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Hartrampf PE, Serfling SE, Higuchi T, Bojunga J, Weich A, Werner RA. [Clinical significance of neuroendocrine tumors : Incidence, symptoms, diagnosis, stage, and prognostic factors and their influence on disease management]. RADIOLOGIE (HEIDELBERG, GERMANY) 2024; 64:536-545. [PMID: 38777918 DOI: 10.1007/s00117-024-01315-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/24/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Neuroendocrine neoplasms (NEN) are heterogenous with an increasing incidence in recent years. OBJECTIVES Overview on incidence, symptoms, diagnostics, grading, imaging and prognostic determinants, including factors having an impact on therapeutic management. METHODS Review on current literature, including original articles, reviews, guidelines and expert opinions. RESULTS NEN are mainly located in the gastrointestinal tract and their incidence has increased in recent years, mainly due to improved diagnostics, e.g., cross-sectional imaging. Clinical characteristics include hormone excess syndromes (carcinoid syndrome). Laboratory markers such as chromogranin A are commonly used as part of routine diagnostics, followed by endoscopic and endosonographic procedures, which also allow biopsies to be obtained. Tumor spread can be determined by contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) or somatostatin receptor (SSRT)-PET/CT (positron emission tomography). Prognostic factors include Ki67 index, type, and grading. Resection with curative intent is the therapy of choice. In a metastasized setting, SSRT-directed treatment approaches are favored, while in dedifferentiated NEN, conventional chemotherapy is needed. CONCLUSION A broad diagnostic armamentarium can be offered to NEN patients and the improved diagnostic procedures have most likely caused a raising incidence in recent years. Among others, prognostic factors are Ki67 and NEN subtypes; these clinical determinants also have an impact on patient management.
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Affiliation(s)
- Philipp E Hartrampf
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Sebastian E Serfling
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Takahiro Higuchi
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
- Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Jörg Bojunga
- Schwerpunkt Endokrinologie, Diabetologie und Ernährungsmedizin, Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Alexander Weich
- Medizinische Klinik und Poliklinik II, Lehrstuhl für Gastroenterologie, Universitätsklinikum Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Deutschland.
- NET Zentrum Würzburg, European Neuroendocrine Tumor Society (ENETS) Centers of Excellence (CoE), Würzburg, Deutschland.
| | - Rudolf A Werner
- Nuklearmedizin, Klinik für Radiologie und Nuklearmedizin, Goethe Universität Frankfurt, Universitätsklinikum, Frankfurt, Deutschland
- The Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA
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13
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Kim SJ, Lee J, Kim GW, Kim SY. The role of endoscopic ultrasonography for diagnosis of residual rectal neuroendocrine tumor. Surg Endosc 2024:10.1007/s00464-024-10963-z. [PMID: 38866946 DOI: 10.1007/s00464-024-10963-z] [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: 03/20/2024] [Accepted: 05/25/2024] [Indexed: 06/14/2024]
Abstract
BACKGROUND Endoscopic ultrasonography (EUS) is useful for assessing the depth and regional lymph node involvement in rectal neuroendocrine tumors (NETs). However, evidence regarding the effectiveness of EUS in identifying residual lesions in patients with incompletely resected NET is limited. We aimed to evaluate the efficacy of EUS in identifying residual rectal NETs and the clinical outcomes of salvage endoscopic treatment. METHODS We retrospectively reviewed the records of patients who were transferred to Chosun University Hospital and received salvage treatment for incompletely resected rectal NETs between January 2012 and October 2021. RESULTS This study included 68 incompletely resected rectal NET, of which 59 were margin-positive and 9 were margin-indeterminate. EUS detection (odds ratio (OR), 8.44; 95% confidence interval (CI), 1.18-41.35) and visual detection (OR, 7.00; 95% CI, 1.50-47.48) were associated with residual lesion in patients with incompletely resected NET. EUS detection of residual lesions showed a sensitivity of 94%, specificity of 71%, positive predictive value of 88%, negative predictive value of 83%, and accuracy of 87%. All patients underwent salvage treatment with band-ligation endoscopic mucosal resection (58.8%) and endoscopic submucosal dissection (41.2%). Residual NETs were diagnosed in 47 of 68 patients (69.1%), and no recurrence was noted during the follow-up period of 51.8 ± 22.9 months. CONCLUSIONS EUS is a more sensitive method than visual detection for evaluating residual rectal NETs. Salvage endoscopic treatment for incompletely resected NETs is safe and effective.
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Affiliation(s)
- Seong-Jung Kim
- Department of Internal Medicine, College of Medicine, Chosun University 309, Pilmun-Daero, Dong-Gu, Gwangju, 61452, Republic of Korea
| | - Jun Lee
- Department of Internal Medicine, College of Medicine, Chosun University 309, Pilmun-Daero, Dong-Gu, Gwangju, 61452, Republic of Korea.
| | - Gang-Woo Kim
- Department of Internal Medicine, College of Medicine, Chosun University 309, Pilmun-Daero, Dong-Gu, Gwangju, 61452, Republic of Korea
| | - So Yeong Kim
- Department of Preventive Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea
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14
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Yang H, Zhang Y, Li H, Zhang Y, Feng Y, Yang X, Chen Y. Efficacy and Safety of 225 Ac-DOTATATE in the Treatment of Neuroendocrine Neoplasms With High SSTR Expression. Clin Nucl Med 2024; 49:505-512. [PMID: 38498615 DOI: 10.1097/rlu.0000000000005149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2024]
Abstract
PURPOSE We aimed to evaluate the efficacy and safety of 225 Ac-DOTATATE targeted α therapy (TAT) in various neuroendocrine neoplasms (NENs) with high somatostatin receptor (SSTR) expression. PATIENTS AND METHODS This single-center prospective study included 10 patients with histologically diagnosed NENs that exhibited increased SSTR expression on 68 Ga-DOTATATE PET/CT imaging. All patients received 225 Ac-DOTATATE TAT. The primary end points were molecular imaging-based response and disease control rate (DCR), measured using the slightly modified Positron Emission Tomography Response Criteria in Solid Tumors 1.0. The secondary end points were adverse event profiles and clinical responses. The adverse event profile was determined according to the Common Terminology Criteria for Adverse Events version 5.0. Clinical response was assessed using the EORTC QLQ-C30 v3.0 (European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire version 3.0). RESULTS A molecular imaging-based partial response was observed in 40% of all patients, SD in 40%, PD in 20%, and DCR in 80%. The DCR was 83.3% (5/6) in patients who were previously treated with 177 Lu-DOTATATE. According to the EORTC QLQ-C30 v3.0 score, most symptoms improved after 225 Ac-DOTATATE treatment, with only diarrhea showing no improvement. Grade III/IV hematological, kidney, and liver toxicities were not observed. The median follow-up time was 14 months (7-22 months), and no deaths were reported. CONCLUSIONS This initial study suggests that 225 Ac-DOTATATE is a potentially promising option for treating NENs with elevated SSTR expression, with an acceptable toxicity profile and well-tolerated adverse effects.
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Affiliation(s)
| | | | | | | | | | - Xiqun Yang
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
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15
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Chi Y, Liu S, Zhang J, Li H, Yang L, Zhang X, Li H, Li Q, Wang N, Lu M, Zhuo M. Epidemiological characteristics of neuroendocrine neoplasms in Beijing: a population-based retrospective study. BMC Public Health 2024; 24:1396. [PMID: 38789981 PMCID: PMC11127419 DOI: 10.1186/s12889-024-18845-8] [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: 08/31/2023] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND The incidence of neuroendocrine neoplasms (NENs) is rising rapidly worldwide. However, there are few reports on these heterogeneous diseases in China. Our study aimed to explore the epidemiological characteristics of NENs in Beijing. METHODS We conducted a retrospective cohort study using population-based cancer surveillance data in Beijing, China. All data were extracted from the Beijing Cancer Registry with incidence dates from 1 January 1998 to 31 December 2018; the follow-up period was through 31 December 2021. Segi's world standard population was used to estimate the age-standardized rate. Survival was estimated using the Kaplan-Meier method. RESULTS From 1998 to 2018, the incidence of NENs in Beijing initially showed a significant increasing trend, from 1.07/100,000 to 3.53/100,000; this began to plateau after 2013. The age-specific incidence rate increased with age and peaked in the age group 70-74 years. The incidence in men was significantly higher than that in women (4.41/100,000 vs. 1.69/100,000). The most common sites of NENs were the lung (2.38/100,000) and rectum (0.14/100,000). Most NENs were diagnosed at a late stage. We found that NENs originating from the lung had worse overall survival than extrapulmonary NENs, and male patients had worse survival than female patients. CONCLUSIONS This study retrospectively analyzed the epidemiological characteristics of NENs in Beijing from 1998 to 2018. Our findings provide a reference regarding the epidemiological statistics of NENs in Beijing to contribute to the prevention, diagnosis, and treatment of these specific tumors.
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Affiliation(s)
- Yujia Chi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Shuo Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Jianwei Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Huichao Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Lei Yang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xi Zhang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Haoxin Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Qingyu Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Ning Wang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Ming Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Minglei Zhuo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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16
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Bolduan F, Wetzel A, Giesecke Y, Eichhorn I, Alenina N, Bader M, Willnow TE, Wiedenmann B, Sigal M. Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting. Front Endocrinol (Lausanne) 2024; 15:1331231. [PMID: 38694940 PMCID: PMC11061435 DOI: 10.3389/fendo.2024.1331231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 04/03/2024] [Indexed: 05/04/2024] Open
Abstract
A subset of neuroendocrine tumors (NETs) can cause an excessive secretion of hormones, neuropeptides, and biogenic amines into the bloodstream. These so-called functional NETs evoke a hormone-related disease and lead to several different syndromes, depending on the factors released. One of the most common functional syndromes, carcinoid syndrome, is characterized mainly by over-secretion of serotonin. However, what distinguishes functional from non-functional tumors on a molecular level remains unknown. Here, we demonstrate that the expression of sortilin, a widely expressed transmembrane receptor involved in intracellular protein sorting, is significantly increased in functional compared to non-functional NETs and thus can be used as a biomarker for functional NETs. Furthermore, using a cell line model of functional NETs, as well as organoids, we demonstrate that inhibition of sortilin reduces cellular serotonin concentrations and may therefore serve as a novel therapeutic target to treat patients with carcinoid syndrome.
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Affiliation(s)
- Felix Bolduan
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Digital Clinician Scientist Program, Berlin, Germany
| | - Alexandra Wetzel
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Yvonne Giesecke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Ines Eichhorn
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Natalia Alenina
- Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- German Center for Cardiovascular Research (DZHK), Berlin, Germany
| | - Michael Bader
- Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- German Center for Cardiovascular Research (DZHK), Berlin, Germany
- Charité - Universitätsmedizin Berlin, Berlin, Germany
- University of Lübeck, Institute for Biology, Lübeck, Germany
| | - Thomas E. Willnow
- Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Bertram Wiedenmann
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Michael Sigal
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
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Oda K, Murata T, Tsujimoto K, Tanaka F, Takahashi D, Saiki R, Hirabayashi Y, Tsunoda A, Saito K, Yuasa H, Imai H, Katayama K, Dohi K. A case of carcinoid syndrome probably exacerbated by hemodialysis in which prochlorperazine maleate was effective. CEN Case Rep 2024; 13:135-140. [PMID: 37606883 PMCID: PMC10982206 DOI: 10.1007/s13730-023-00814-6] [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: 10/21/2022] [Accepted: 07/31/2023] [Indexed: 08/23/2023] Open
Abstract
Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs due to liver metastasis of neuroendocrine carcinoma. We report the case of a patient with liver metastasis of neuroendocrine carcinoma who suffered from acute abdominal pain and diarrhea triggered by hemodialysis. Various differential diagnoses were considered, but we concluded these symptoms to be probably caused by exacerbation of carcinoid syndrome, as the serum 5HIAA level was markedly elevated, and a drug with anti-serotonin activity was effective. Prochlorperazine maleate, which has anti-serotonin activity, was effective for these symptoms, and the patient was able to continue maintenance hemodialysis, which contributed to his quality of life and prognosis. We speculated the mechanism of carcinoid exacerbation was that substances such as serotonin had entered the systemic circulation via the increased extrahepatic shunt of the portal venous blood flow, entering the inferior vena cava and that this condition had been triggered by hemodialysis via the same mechanism as portal systemic encephalopathy.
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Affiliation(s)
- Keiko Oda
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Tomohiro Murata
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
| | - Kayo Tsujimoto
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Fumika Tanaka
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Daisuke Takahashi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Ryosuke Saiki
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Yosuke Hirabayashi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Akira Tsunoda
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kanako Saito
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Hiroto Yuasa
- Department of Pathology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Hiroshi Imai
- Department of Pathology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kan Katayama
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Kaoru Dohi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
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18
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Choi JS, Kim MJ, Shin R, Park JW, Heo SC, Jeong SY, Park KJ, Ryoo SB. Risk Factor Analysis of Lymph Node Metastasis for Rectal Neuroendocrine Tumors: Who Needs a Radical Resection in Rectal Neuroendocrine Tumors Sized 1-2 cm? Ann Surg Oncol 2024; 31:2414-2424. [PMID: 38194045 DOI: 10.1245/s10434-023-14829-x] [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: 06/01/2023] [Accepted: 12/08/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND Rectal neuroendocrine tumors (NETs) have malignant potential, and lymph node (LN) or distant metastases can occur; however, treatment of NETs 1-2 cm in size is controversial. OBJECTIVE This study aimed to identify predictive factors for LN metastasis and prognostic factors for recurrence of rectal NETs, especially tumors 1‒2 cm in size. METHODS Between October 2004 and November 2020, 453 patients underwent endoscopic or surgical treatment for rectal NETs in Seoul National University Hospital. The data on these patients were prospectively collected in our database and reviewed retrospectively. In cases of local excision, we evaluated LN metastasis with radiologic imaging, including computed tomography or magnetic resonance imaging before treatment and during the follow-up periods. RESULTS LN metastasis was observed in 40 patients (8.8%). A higher rate of LN metastasis was observed in larger-sized tumors, advanced T stage, lymphovascular invasion (LVI), perineural invasion (PNI), and high tumor grade. In multivariable analysis, the significant risk factors for LN metastasis were tumor size (1 ≤ size < 2 cm: hazard ratio [HR] 64.07; size ≥2 cm: HR 102.37, p < 0.001) and tumor grade (G2: HR 3.63, p = 0.034; G3: HR 5.09, p = 0.044). In multivariable analysis for tumors 1-2 cm in size, the risk factor for LN metastasis was tumor grade (G2: HR 6.34, p = 0.013). CONCLUSIONS Tumor grade and size are important predictive factors for LN metastasis. In NETs 2 cm in size, tumor grade is also important for LN metastasis, and radical resection should be considered.
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Affiliation(s)
- Jin Sun Choi
- Department of Surgery, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Min Jung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Rumi Shin
- Department of Surgery, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
| | - Ji Won Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Seung Chul Heo
- Department of Surgery, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
| | - Seung-Yong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Kyu Joo Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
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19
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Sawaid IO, Samson AO. Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence. J Clin Med 2024; 13:1970. [PMID: 38610738 PMCID: PMC11012754 DOI: 10.3390/jcm13071970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 03/14/2024] [Accepted: 03/14/2024] [Indexed: 04/14/2024] Open
Abstract
Background: Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. Methods: First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Results: Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Conclusions: Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.
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Affiliation(s)
| | - Abraham O. Samson
- Azrieli Faculty of Medicine, Bar Ilan University, Safed 1311502, Israel;
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20
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Al-Darwish AS, Alsubaie WR, AlShammari W, AlaSheikh M, AlRashed M. Neuroendocrine tumor of the appendix masquerading as acute appendicitis with a mucocele on CT scan: a rare finding. Surg Case Rep 2024; 10:65. [PMID: 38499895 PMCID: PMC10948727 DOI: 10.1186/s40792-024-01870-5] [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: 01/31/2024] [Accepted: 03/14/2024] [Indexed: 03/20/2024] Open
Abstract
INTRODUCTION Neuroendocrine tumors (NETs) of the appendix are rare and are often discovered incidentally during surgery for acute appendicitis or other unrelated conditions (Modlin et al. in Gastroenterology 128:1717-1751, 2005, Alsaad et al. in Oncol Rep 16:1105-1109, 2006, Frilling et al. in Lancet Oncol 15:e8-e21, 2014). These tumors can range from asymptomatic incidental findings to clinically significant tumors with metastases (Alsaad et al. in Oncol Rep 16:1105-1109, 2006, Gomes et al. in World J Emerg Surg 10:60, 2015, Paiva et al. in Eur J Cancer 38:702-705, 2002, Burke et al. in Am J Surg Pathol. 9:661-674, 1985). This case report presents a rare case of a NET of the appendix presenting as acute appendicitis. CASE DESCRIPTION A 23-year-old male presented with right lower quadrant abdominal pain, nausea, and vomiting for 2 days. A CT scan revealed a mucocoele of the appendix. The patient underwent laparoscopic appendectomy, and the appendix was sent for histopathological examination. The final pathological report confirmed a NET of the appendix with a Ki-67 index of 1% and no lymphovascular invasion. Due to tumor invasion to the cecum and its large size (3-4 cm), the patient underwent right hemicolectomy. The final histopathology report of the resected specimen confirmed the diagnosis of NET of the appendix. DISCUSSION The clinical diagnosis of NETs of the appendix can be challenging due to their rarity and non-specific presentation. Symptoms of NETs of the appendix can mimic those of acute appendicitis, making it difficult to differentiate between the two conditions. Imaging studies, such as CT scans, can provide valuable information about the size and location of the tumor (Gomes et al. in World J Emerg Surg 10:60, 2015, Maggard et al. in Ann Surg 240:117-122, 2004, Burke et al. in Am J Surg Pathol. 9:661-674, 1985, Frilling et al. in Lancet Oncol 15:e8-e21, 2014). However, the definitive diagnosis is made through histopathological examination of the resected specimen. The treatment of NETs of the appendix depends on factors such as the size, location, and grade of the tumor. Small tumors confined to the appendix with no lymph-vascular invasion can be treated with appendectomy alone, while larger tumors or those that have spread beyond the appendix may require more extensive surgery, such as right hemicolectomy (Gomes et al. in World J Emerg Surg 10:60, 2015, Mestier et al. in Dig Liver Dis 52:899-911, 2020, Maggard et al. in Ann Surg 240:117-122, 2004, Burke et al. in Am J Surg Pathol. 9:661-674, 1985, Frilling et al. in Lancet Oncol 15:e8-e21, 2014, Pavel et al. in Neuroendocrinology 103:172-185, 2016). In some cases, additional treatments such as chemotherapy or radiation therapy may be recommended. CONCLUSION This case report emphasizes the importance of considering NETs of the appendix in the differential diagnosis of acute appendicitis. Imaging studies can provide valuable information, but the definitive diagnosis is made through histopathological examination. The treatment approach for NETs of the appendix depends on various factors and requires a multidisciplinary approach for optimal management.
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Affiliation(s)
- Abdullah S Al-Darwish
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia.
- Department of Surgery, Arryan Hospital, Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia.
| | - Waad Rashaid Alsubaie
- Department of Pathology, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
| | - Waleed AlShammari
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
- Department of Surgery, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Muath AlaSheikh
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
| | - Muath AlRashed
- Department of Surgery, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
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Guo X, Zhao X, Huang G, Yu Y. Advances in Endoscopic Diagnosis and Treatment of Gastric Neuroendocrine Neoplasms. Dig Dis Sci 2024; 69:27-35. [PMID: 37971578 DOI: 10.1007/s10620-023-08180-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 11/01/2023] [Indexed: 11/19/2023]
Abstract
Gastric neuroendocrine neoplasms refer to a group of diseases that are relatively rare. They can be classified into three subtypes based on their clinical and histopathological features, and there are significant differences in diagnosis, treatment, and prognosis among the different subtypes. The incidence of gastric neuroendocrine neoplasms has been increasing globally in recent years with the localized disease being particularly evident. Gastrointestinal endoscopy is of irreplaceable importance for the diagnosis and management of g-NENs. Endoscopy with biopsy is the gold standard for the diagnosis of g-NENs. Ultrasound endoscopy can assess the depth of tumor invasion and the presence of lymphatic metastases, which is important for the development of treatment strategies. Meanwhile, for some small and low-risk lesions, endoscopic surveillance or endoscopic resection has satisfactory therapeutic results and prognosis. This means that even though the incidence has increased, advances in endoscopic techniques have allowed more patients to adopt a relatively conservative treatment strategy. However, the criteria for patients suitable for endoscopic surveillance or endoscopic resection remain controversial.
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Affiliation(s)
- Xinrui Guo
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Xiaohan Zhao
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Gang Huang
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Yanbo Yu
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China.
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
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Kazi M, Patkar S, Saklani A. Simultaneous laparoscopic liver metastasectomy and intersphincteric resection for neuroendocrine tumor of the rectum by natural orifice specimen extraction surgery. JOURNAL OF MINIMALLY INVASIVE SURGERY 2023; 26:215-217. [PMID: 38098355 PMCID: PMC10728686 DOI: 10.7602/jmis.2023.26.4.215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 07/29/2023] [Accepted: 10/04/2023] [Indexed: 12/21/2023]
Abstract
Neuroendocrine tumors (NET) are relatively uncommon rectal neoplasms, and the liver is the most common site of distant metastasis. Simultaneous liver and colorectal resections by minimally invasive surgery and natural orifice specimen extraction are gaining popularity, reducing morbidity. We describe a case of rectal NET with liver metastasis operated simultaneously by laparoscopy with both specimens extracted via the anal canal. Transanal or transvaginal natural orifice specimen extraction surgery for suitable cases is underutilized and only isolated case reports for simultaneous resections exist.
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Affiliation(s)
- Mufaddal Kazi
- Department of Gastrointestinal Surgical Oncology, Tata Memorial Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Shraddha Patkar
- Department of Gastrointestinal Surgical Oncology, Tata Memorial Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Avanish Saklani
- Department of Gastrointestinal Surgical Oncology, Tata Memorial Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
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23
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Del Rivero J, Perez K, Kennedy EB, Mittra ES, Vijayvergia N, Arshad J, Basu S, Chauhan A, Dasari AN, Bellizzi AM, Gangi A, Grady E, Howe JR, Ivanidze J, Lewis M, Mailman J, Raj N, Soares HP, Soulen MC, White SB, Chan JA, Kunz PL, Singh S, Halfdanarson TR, Strosberg JR, Bergsland EK. Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline. J Clin Oncol 2023; 41:5049-5067. [PMID: 37774329 DOI: 10.1200/jco.23.01529] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 07/24/2023] [Indexed: 10/01/2023] Open
Abstract
PURPOSE To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
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Affiliation(s)
| | | | | | | | | | | | - Sandip Basu
- Bhabha Atomic Research Centre, Tata Memorial Hospital, Mumbai, India
| | | | | | | | | | | | | | | | | | | | - Nitya Raj
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | | | - Simron Singh
- Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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24
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Plachouris D, Eleftheriadis V, Nanos T, Papathanasiou N, Sarrut D, Papadimitroulas P, Savvidis G, Vergnaud L, Salvadori J, Imperiale A, Visvikis D, Hazle JD, Kagadis GC. A radiomic- and dosiomic-based machine learning regression model for pretreatment planning in 177 Lu-DOTATATE therapy. Med Phys 2023; 50:7222-7235. [PMID: 37722718 DOI: 10.1002/mp.16746] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 09/01/2023] [Accepted: 09/07/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND Standardized patient-specific pretreatment dosimetry planning is mandatory in the modern era of nuclear molecular radiotherapy, which may eventually lead to improvements in the final therapeutic outcome. Only a comprehensive definition of a dosage therapeutic window encompassing the range of absorbed doses, that is, helpful without being detrimental can lead to therapy individualization and improved outcomes. As a result, setting absorbed dose safety limits for organs at risk (OARs) requires knowledge of the absorbed dose-effect relationship. Data sets of consistent and reliable inter-center dosimetry findings are required to characterize this relationship. PURPOSE We developed and standardized a new pretreatment planning model consisting of a predictive dosimetry procedure for OARs in patients with neuroendocrine tumors (NETs) treated with 177 Lu-DOTATATE (Lutathera). In the retrospective study described herein, we used machine learning (ML) regression algorithms to predict absorbed doses in OARs by exploiting a combination of radiomic and dosiomic features extracted from patients' imaging data. METHODS Pretreatment and posttreatment data for 20 patients with NETs treated with 177 Lu-DOTATATE were collected from two clinical centers. A total of 3412 radiomic and dosiomic features were extracted from the patients' computed tomography (CT) scans and dose maps, respectively. All dose maps were generated using Monte Carlo simulations. An ML regression model was designed based on ML algorithms for predicting the absorbed dose in every OAR (liver, left kidney, right kidney, and spleen) before and after the therapy and between each therapy session, thus predicting any possible radiotoxic effects. RESULTS We evaluated nine ML regression algorithms. Our predictive model achieved a mean absolute dose error (MAE, in Gy) of 0.61 for the liver, 1.58 for the spleen, 1.30 for the left kidney, and 1.35 for the right kidney between pretherapy 68 Ga-DOTATOC positron emission tomography (PET)/CT and posttherapy 177 Lu-DOTATATE single photon emission (SPECT)/CT scans. Τhe best predictive performance observed was based on the gradient boost for the liver, the left kidney and the right kidney, and on the extra tree regressor for the spleen. Evaluation of the model's performance according to its ability to predict the absorbed dose in each OAR in every possible combination of pretherapy 68 Ga-DOTATOC PET/CT and any posttherapy 177 Lu-DOTATATE treatment cycle SPECT/CT scans as well as any 177 Lu-DOTATATE SPECT/CT treatment cycle and the consequent 177 Lu-DOTATATE SPECT/CT treatment cycle revealed mean absorbed dose differences ranges from -0.55 to 0.68 Gy. Incorporating radiodosiomics features from the 68 Ga-DOTATOC PET/CT and first 177 Lu-DOTATATE SPECT/CT treatment cycle scans further improved the precision and minimized the standard deviation of the predictions in nine out of 12 instances. An average improvement of 57.34% was observed (range: 17.53%-96.12%). However, it's important to note that in three instances (i.e., Ga,C.1 → C3 in spleen and left kidney, and Ga,C.1 → C2 in right kidney) we did not observe an improvement (absolute differences of 0.17, 0.08, and 0.05 Gy, respectively). Wavelet-based features proved to have high correlated predictive value, whereas non-linear-based ML regression algorithms proved to be more capable than the linear-based of producing precise prediction in our case. CONCLUSIONS The combination of radiomics and dosiomics has potential utility for personalized molecular radiotherapy (PMR) response evaluation and OAR dose prediction. These radiodosiomic features can potentially provide information on any possible disease recurrence and may be highly useful in clinical decision-making, especially regarding dose escalation issues.
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Affiliation(s)
- Dimitris Plachouris
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, Greece
| | | | - Thomas Nanos
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, Greece
| | | | | | | | | | | | | | | | | | - John D Hazle
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - George C Kagadis
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, Greece
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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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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Guccione L, Gough K, Drosdowsky A, Price T, Pavlakis N, Wyld D, Ransom D, Michael M, Schofield P. The unmet information needs, quality of life, and care experiences of patients with neuroendocrine tumours (NETs) at follow-up: 6 months from diagnosis. Support Care Cancer 2023; 31:577. [PMID: 37712997 PMCID: PMC10504214 DOI: 10.1007/s00520-023-08034-5] [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: 05/02/2023] [Accepted: 08/31/2023] [Indexed: 09/16/2023]
Abstract
OBJECTIVES To identify changes in the healthcare preferences, patient experiences, and quality of life of patients with NETs at 6-month follow-up, informing the design of supportive care services. METHODS This study presents 6-month follow-up data of a mixed-methods multi-site study. Demographic, clinical, and patient-reported outcome questionnaire data was collected. RESULTS High percentages of suboptimal experiences of care were reported. Patients reported less positive experiences with being involved in decisions about their care and treatment; their family or someone close to them having the opportunity to talk to their cancer doctor, or having their family or someone close to them receive all the information they need to help care for them at home. Patients also reported negative experiences for on the information about their cancer accessible online and the usefulness of the information they accessed. Differences between baseline and follow-up scores were mostly not significant apart from anxiety and sleep disturbance scales, CONCLUSIONS: Patients with NETs report difficulties in accessing and understanding written information that is persistent over time. PRACTICE IMPLICATIONS Outcomes will inform the design and development of an informational resource aimed at facilitating improved understanding for patients with NETs.
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Affiliation(s)
- Lisa Guccione
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Karla Gough
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Allison Drosdowsky
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Timothy Price
- Haematology and Oncology, The Queen Elizabeth Hospital, Woodville South, South Australia Australia
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales Australia
| | - David Wyld
- Department of Medical Oncology, Royal Brisbane and Women’s Hospital, Brisbane, QLD Australia
- Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - David Ransom
- Medical Oncology, Fiona Stanley Hospital, Murdoch, WA Australia
| | - Michael Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
- Upper Gastrointestinal Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Penelope Schofield
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
- Department of Psychology and Iverson Health Innovation Research Institute, Swinburne University, Melbourne, Australia
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Reinhard L, Mogl MT, Benz F, Dukaczewska A, Butz F, Dobrindt EM, Tacke F, Pratschke J, Goretzki PE, Jann H. Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors. Langenbecks Arch Surg 2023; 408:237. [PMID: 37332044 PMCID: PMC10277262 DOI: 10.1007/s00423-023-02956-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 05/23/2023] [Indexed: 06/20/2023]
Abstract
PURPOSE Neuroendocrine tumors of the small intestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3-20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading. METHODS Demographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively. RESULTS A total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3-9%) and G2 high (Ki67 10-20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases. CONCLUSION Lymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.
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Affiliation(s)
- Lisa Reinhard
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Martina T Mogl
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany.
| | - Fabian Benz
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Agata Dukaczewska
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Frederike Butz
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Eva Maria Dobrindt
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Peter E Goretzki
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Henning Jann
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Zheng X, Wu M, Li S, Er L, Deng H, Guo S, Liu Z. Clinicopathological characteristics of rectal multiple neuroendocrine neoplasms and literature review. BMC Surg 2023; 23:147. [PMID: 37264328 DOI: 10.1186/s12893-023-02050-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 05/21/2023] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms. METHODS This study retrospectively analyzed rectal neuroendocrine neoplasm patients diagnosed and treated at the Fourth Hospital of Hebei Medical University from February 2007 to May 2021. The clinicopathological characteristics of rectal multiple neuroendocrine neoplasms were summarized and analyzed in combination with 14 studies on rectal multiple neuroendocrine neoplasms. RESULTS The incidence of RM-NENs accounted for 3.8% of all R-NENs in this study. The number of tumors varied to some extent, the size of tumors was basically no more than 10 mm, and there were more G1 grade tumors. In the analysis of 46 cases with known lymph node metastasis, the difference in lymph node metastasis rate between the number of tumors < 8 and ≥ 8 was statistically significant (p = 0.002). CONCLUSIONS The incidence of rectal multiple neuroendocrine neoplasms accounted for 3.8% of all rectal neuroendocrine neoplasms. For rectal multiple neuroendocrine neoplasms, the lymph node metastasis rate was higher when the number of tumors was ≥ 8. The influence of the number of tumors on lymph node metastasis should be considered in the selection of treatment.
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Affiliation(s)
- Xiuli Zheng
- Department of Endoscopy, Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang'an District, Shijiazhuang, 050000, Hebei, China
| | - Mingli Wu
- Department of Endoscopy, Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang'an District, Shijiazhuang, 050000, Hebei, China.
| | - Shengmian Li
- Department of Gastroenterology, Fourth Hospital of Hebei Medical University, No.12 Jiankang Road, Chang'an District, Shijiazhuang, 050000, Hebei, China
| | - Limian Er
- Department of Endoscopy, Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang'an District, Shijiazhuang, 050000, Hebei, China
| | - Huiyan Deng
- Department of Pathology, Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang'an District, Shijiazhuang, 050000, Hebei, China
| | - Shuo Guo
- Department of Endoscopy, Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang'an District, Shijiazhuang, 050000, Hebei, China
| | - Zhihuan Liu
- Department of Endoscopy, Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Chang'an District, Shijiazhuang, 050000, Hebei, China
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Daraghmeh L, Shbaita S, Nassef O, Melhem L, Maqboul I. Non-specific Symptoms of Small Bowel Neuroendocrine Tumor and the Diagnostic Challenges: A Case Report. Cureus 2023; 15:e41080. [PMID: 37519565 PMCID: PMC10375939 DOI: 10.7759/cureus.41080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2023] [Indexed: 08/01/2023] Open
Abstract
Neuroendocrine tumors (NETs) are considered the most frequent tumors that affect the small bowels. Despite diagnostic modalities, the diagnosis of small bowel NETs is not straightforward and poses a high challenge to most physicians, due to poor accessibility to this area and the patient's non-specific presentations. We reported a case of a 60-year-old male patient, who presented with severe postprandial epigastric pain of one-month duration, loss of appetite, and weight loss. Investigations revealed no definite diagnosis. Therefore, exploratory laparoscopy was attempted along with multiple biopsies that led to the diagnosis of small bowel NET. We conclude that NETs require a high index of suspicion in patients with recurrent abdominal pain.
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Affiliation(s)
- Laith Daraghmeh
- Department of General Surgery, An-Najah National University Hospital, Nablus, PSE
| | - Sara Shbaita
- Faculty of Medicine, An-Najah National University, Nablus, PSE
| | - Omar Nassef
- Department of Radiology, An-Najah National University Hospital, Nablus, PSE
| | - Layan Melhem
- Department of Pathology, An-Najah National University Hospital, Nablus, PSE
| | - Iyad Maqboul
- Department of General Surgery, An-Najah National University Hospital, An-Najah National University, Nablus, PSE
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Bel Haj Yahia D, Bel Hadj Yahya M, Chelly I, Ksantini R, Jouini M, Kacem MJ. 21 years of evolution of primary hepatic neuroendocrine neoplasm in a patient with primary sclerosing cholangitis: A case report. Int J Surg Case Rep 2023; 106:108205. [PMID: 37075505 DOI: 10.1016/j.ijscr.2023.108205] [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: 02/20/2023] [Revised: 03/25/2023] [Accepted: 03/29/2023] [Indexed: 04/21/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Primary hepatic neuroendocrine neoplasms(PHNEN) are among the rarest primitive neuroendocrine neoplasms. Main prognostic factor is histological. We report an unusual case of a PHNEN with 21 years of evolution in the setting of a primary sclerosing cholangitis(PSC). CASE PRESENTATION A 40 year old man presented in 2001 with clinical signs of obstructive jaundice. CT-scan and MRI showed a 4 cm large hypervascular proximal hepatic mass evoking hepatocellular carcinoma(HCC) or cholangiocarcinoma. Exploratory laparotomy found an aspect of advanced chronic liver disease of the left lobe. Extemporaneous biopsy of a suspicious nodule showed signs of cholangitis. Left lobectomy was performed and postoperatively the patient received ursodeoxycholic-acid and biliary stenting. After 11 years of follow-up, jaundice reappeared with a stable hepatic lesion.A percutaneous liver biopsy was done. Pathology showed a G1 neuroendocrine tumor. Endoscopy, imagery and Octreoscan were normal, supporting the diagnosis of PHNEN. PSC was diagnosed on tumor-free parenchyma. The patient is on liver transplantation waiting list. CLINICAL DISCUSSION PHNENs are exceptional. Pathology findings, endoscopy and imagery are necessary to rule out an extra hepatic NEN with liver metastasis. While G1 NEN are known for their slow evolution, this 21 year latency is extremely rare. The presence of PSC adds to the complexity of our case. Surgical resection is recommended when possible. CONCLUSION This case showcases the extreme latency of some PHNEN as well as possible overlap with PSC. Surgery is the most recognized treatment. Liver transplantation seems to be necessary for us, as the rest of the liver shows signs of PSC.
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Affiliation(s)
- D Bel Haj Yahia
- The Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Surgery Department A, Rabta Hospital, Tunis, Tunisia
| | - M Bel Hadj Yahya
- The Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Radiology Department, National Institut Mongi Ben Hmida of Neurology of Tunis, Tunisia.
| | - I Chelly
- The Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Department of Pathology, Rabta Hospital Tunis, Tunisia
| | - R Ksantini
- The Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Surgery Department A, Rabta Hospital, Tunis, Tunisia
| | - M Jouini
- The Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Surgery Department A, Rabta Hospital, Tunis, Tunisia
| | - M J Kacem
- The Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Surgery Department A, Rabta Hospital, Tunis, Tunisia
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31
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Lee S, Jyala A, Ghazanfar H, Shin D, Patel H. Diagnostic Challenge of Small Bowel Neuroendocrine Tumor in a Young Female Patient. Cureus 2023; 15:e37925. [PMID: 37220442 PMCID: PMC10200070 DOI: 10.7759/cureus.37925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2023] [Indexed: 05/25/2023] Open
Abstract
Neuroendocrine tumors (NETs) are rare cancers arising from neuroendocrine cells and are characterized by their ability to secrete functional hormones causing distinctive hormonal syndromes. The incidence of NET has increased over the years, and small bowel neuroendocrine tumor (SBNET) is one of the most challenging to detect due to its varied presentation and poor accessibility with traditional endoscopic methods. Patients with SBNET present with variable hormonal symptoms, such as diarrhea, flushing, and nonspecific abdominal pain, which often delay the diagnosis. We present the case of a young patient who underwent multidisciplinary workups leading to a successful diagnosis of SBNET promptly. The patient was a 31-year-old female who presented to the emergency department with complaints of nausea, vomiting, and sudden-onset, severe, sharp abdominal pain. CT scan of her abdomen showed an area of irregular intraluminal soft tissue density suspicious for a mass in the mid-small bowel. The patient's initial enteroscopy was normal. A video capsule endoscopy showed a small bowel mass, which was consistent with SBNET confirmed by pathology later. This case emphasizes the importance of considering SBNET as a differential diagnosis in young patients with nonspecific symptoms of abdominal pain and highlights the role of multidisciplinary approaches in achieving prompt diagnosis and treatment.
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Affiliation(s)
- Somin Lee
- Internal Medicine, BronxCare Health System, Bronx, USA
| | | | | | - Dongmin Shin
- Internal Medicine, BronxCare Health System, Bronx, USA
| | - Harish Patel
- Gastroenterology, BronxCare Health System, Bronx, USA
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32
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Goo JJ, Baek DH, Kim HW, Lee HS, Lee JY, Park SB, Song GA, Lee SH, Lee JH. Clinical outcomes and risk factors associated with poor prognosis after endoscopic resection of 10-20 mm rectal neuroendocrine tumors: a multicenter, retrospective study of 10-year experience. Surg Endosc 2023:10.1007/s00464-023-09999-4. [PMID: 36947224 DOI: 10.1007/s00464-023-09999-4] [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: 12/01/2022] [Accepted: 02/27/2023] [Indexed: 03/23/2023]
Abstract
BACKGROUND The efficacy of endoscopic resection for of 10-20 mm rectal neuroendocrine tumor (NET) remains controversial. We aimed to evaluate the clinical outcomes and risk factors associated with poor prognosis after endoscopic resection of 10-20 mm rectal NET and to determine the optimal treatment. METHODS Patients who underwent endoscopic resection for rectal NET in four tertiary hospitals were enrolled, and data on with the clinical outcomes and risk factors related to poor prognosis were retrospectively analyzed. RESULTS A total of 105 patients who underwent endoscopic submucosal resection (ESD; n = 65, 61.9%), modified endoscopic mucosal resection (mEMR; n = 31, 29.5%), and conventional EMR (cEMR; n = 9, 8.6%) were enrolled. The mean follow-up period was 41.2 ± 21.9 months. In the morphologic findings, the mean diameter was 11.6 mm (range 10-19); the shape was sessile (50.5%) and mixed type (49.5%), and surface depression was observed in 41.9% of patients. In the histologic findings, 87.6% of patients had G1 and 12.4% G2 tumor grade, and 3.8% of patients had lymphovascular invasion. The overall en bloc and histologically complete (R0) resections were 99.1% and 76.2%, respectively. cEMR was a less-frequently developed R0 resection. In the univariate and multivariate analyses for R0 resection, only surface depression was significantly associated. Regional or distant organs metastasis during follow-up developed in three patients (2.9%) and was significantly associated with female sex, redness, G2 tumor grade, and non-ESD methods. CONCLUSION Patients who underwent endoscopic resection of 10-20 mm rectal NET had good prognosis; therefore, endoscopic resection can be considered as the first-line treatment, particularly for 10-14 mm rectal NET. However, the risk factors, such as female sex, redness, G2 tumor grade and non-ESD methods, were associated with regional or distant metastases during follow-up. Therefore, patients with these risk factors should be carefully monitored.
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Affiliation(s)
- Ja Jun Goo
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Dong Hoon Baek
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Hyung Wook Kim
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
| | - Hong Sub Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Jong Yoon Lee
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
| | - Su Bum Park
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Geun Am Song
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Sang Heon Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Jong Hoon Lee
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
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Popoviciu MS, Kaka N, Sethi Y, Patel N, Chopra H, Cavalu S. Type 1 Diabetes Mellitus and Autoimmune Diseases: A Critical Review of the Association and the Application of Personalized Medicine. J Pers Med 2023; 13:jpm13030422. [PMID: 36983604 PMCID: PMC10056161 DOI: 10.3390/jpm13030422] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/17/2023] [Accepted: 02/24/2023] [Indexed: 03/02/2023] Open
Abstract
Type 1 Diabetes Mellitus (T1DM) is a common hyperglycemic disease characterized by the autoimmune destruction of insulin-producing beta cells of the pancreas. Various attempts have been made to understand the complex interplay of genetic and environmental factors which lead to the development of the autoimmune response in an individual. T1DM is frequently associated with other autoimmune illnesses, the most common being autoimmune thyroid disorders affecting more than 90% of people with T1D and autoimmune disorders. Antithyroid antibodies are present in around 20% of children with T1D at the start of the illness and are more frequent in girls. Patients with T1DM often have various other co-existing multi-system autoimmune disorders including but not limited to thyroid diseases, parathyroid diseases, celiac disease, vitiligo, gastritis, skin diseases, and rheumatic diseases. It is a consistent observation in clinics that T1DM patients have other autoimmune disorders which in turn affect their prognosis. Concomitant autoimmune illness might affect diabetes care and manifest itself clinically in a variety of ways. A thorough understanding of the complex pathogenesis of this modern-day epidemic and its association with other autoimmune disorders has been attempted in this review in order to delineate the measures to prevent the development of these conditions and limit the morbidity of the afflicted individuals as well. The measures including antibody screening in susceptible individuals, early identification and management of other autoimmune disorders, and adoption of personalized medicine can significantly enhance the quality of life of these patients. Personalized medicine has recently gained favor in the scientific, medical, and public domains, and is frequently heralded as the future paradigm of healthcare delivery. With the evolution of the ‘omics’, the individualization of therapy is not only closer to reality but also the need of the hour.
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Affiliation(s)
| | - Nirja Kaka
- PearResearch, Dehradun 248001, India
- Department of Medicine, GMERS Medical College, Himmatnagar 383001, India
| | - Yashendra Sethi
- PearResearch, Dehradun 248001, India
- Department of Medicine, Government Doon Medical College, HNB Uttarakhand Medical Education University, Dehradun 248001, India
| | - Neil Patel
- PearResearch, Dehradun 248001, India
- Department of Medicine, GMERS Medical College, Himmatnagar 383001, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
- Correspondence:
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Vitale G, Carra S, Alessi Y, Campolo F, Pandozzi C, Zanata I, Colao A, Faggiano A. Carcinoid Syndrome: Preclinical Models and Future Therapeutic Strategies. Int J Mol Sci 2023; 24:ijms24043610. [PMID: 36835022 PMCID: PMC9961914 DOI: 10.3390/ijms24043610] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/27/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023] Open
Abstract
Carcinoid syndrome represents a debilitating paraneoplastic disease, caused by the secretion of several substances, occurring in about 10-40% of patients with well-differentiated neuroendocrine tumors (NETs). The main signs and symptoms associated with carcinoid syndrome are flushing, diarrhea, hypotension, tachycardia, bronchoconstriction, venous telangiectasia, dyspnea and fibrotic complications (mesenteric and retroperitoneal fibrosis, and carcinoid heart disease). Although there are several drugs available for the treatment of carcinoid syndrome, the lack of therapeutic response, poor tolerance or resistance to drugs are often reported. Preclinical models are indispensable tools for investigating the pathogenesis, mechanisms for tumor progression and new therapeutic approaches for cancer. This paper provides a state-of-the-art overview of in vitro and in vivo models in NETs with carcinoid syndrome, highlighting the future developments and therapeutic approaches in this field.
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Affiliation(s)
- Giovanni Vitale
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy
- Correspondence: ; Tel.: +39-02-6191-12023; Fax: +39-02-6191-13033
| | - Silvia Carra
- Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy
| | - Ylenia Alessi
- Endocrine Unit, University Hospital “Gaetano Martino” of Messina, 98125 Messina, Italy
| | - Federica Campolo
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Carla Pandozzi
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Isabella Zanata
- Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
| | - Annamaria Colao
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80138 Naples, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, 00189 Rome, Italy
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Pellegrino F, Granata V, Fusco R, Grassi F, Tafuto S, Perrucci L, Tralli G, Scaglione M. Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists. Tomography 2023; 9:217-246. [PMID: 36828370 PMCID: PMC9958666 DOI: 10.3390/tomography9010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 01/31/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes. Furthermore, they are primarily nonfunctioning, while, in the case of insulinomas, gastrinomas, glucagonomas, vipomas, and somatostatinomas, they produce hormones responsible for clinical syndromes. The GEP-NEN tumor grade and cell differentiation may result in different clinical behaviors and prognoses, with grade one (G1) and grade two (G2) neuroendocrine tumors showing a more favorable outcome than grade three (G3) NET and neuroendocrine carcinoma. Two critical issues should be considered in the NEN diagnostic workup: first, the need to identify the presence of the tumor, and, second, to define the primary site and evaluate regional and distant metastases. Indeed, the primary site, stage, grade, and function are prognostic factors that the radiologist should evaluate to guide prognosis and management. The correct diagnostic management of the patient includes a combination of morphological and functional evaluations. Concerning morphological evaluations, according to the consensus guidelines of the European Neuroendocrine Tumor Society (ENETS), computed tomography (CT) with a contrast medium is recommended. Contrast-enhanced magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is usually indicated for use to evaluate the liver, pancreas, brain, and bones. Ultrasonography (US) is often helpful in the initial diagnosis of liver metastases, and contrast-enhanced ultrasound (CEUS) can solve problems in characterizing the liver, as this tool can guide the biopsy of liver lesions. In addition, intraoperative ultrasound is an effective tool during surgical procedures. Positron emission tomography (PET-CT) with FDG for nonfunctioning lesions and somatostatin analogs for functional lesions are very useful for identifying and evaluating metabolic receptors. The detection of heterogeneity in somatostatin receptor (SSTR) expression is also crucial for treatment decision making. In this narrative review, we have described the role of morphological and functional imaging tools in the assessment of GEP-NENs according to current major guidelines.
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Affiliation(s)
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy
| | - Francesca Grassi
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80127 Naples, Italy
| | - Salvatore Tafuto
- S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
| | - Luca Perrucci
- Ferrara Department of Interventional and Diagnostic Radiology, Ospedale di Lagosanto, Azienda AUSL, 44023 Ferrara, Italy
| | - Giulia Tralli
- Department of Radiology, Ospedale Santa Maria della Misericordia, 45100 Rovigo, Italy
| | - Mariano Scaglione
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
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Zhuang X, Zhang S, Chen G, Luo Z, Hu H, Huang W, Guo Y, Ouyang Y, Peng L, Qing Q, Chen H, Li B, Chen J, Wang X. Risk factors and clinical outcomes of incomplete endoscopic resection of small rectal neuroendocrine tumors in southern China: a 9-year data analysis. Gastroenterol Rep (Oxf) 2022; 11:goac084. [PMID: 36632622 PMCID: PMC9825708 DOI: 10.1093/gastro/goac084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/07/2022] [Accepted: 11/29/2022] [Indexed: 01/09/2023] Open
Abstract
Background The histologically complete resection (CR) rate of small rectal neuroendocrine tumors (RNETs) is unsatisfactory at the first endoscopy. Risk factors and clinical outcomes associated with incomplete resection (IR) have not been explicitly elucidated. This study aims to explore the relevant factors of IR. Methods This retrospective study reviewed patients with small RNETs (≤10 mm) in eight centers from January 2013 to December 2021. Clinicopathological characteristics and clinical outcomes were compared between the CR and IR groups, and the polypectomy and advanced treatment groups. Results Of the 326 patients included, 83 (25.5%) were diagnosed with IR. Polypectomy (odds ratio [OR] = 16.86), a central depression (OR = 7.50), and treatment in the early period (OR = 2.60) were closely associated with IR. Further analysis revealed that an atypical hyperemic appearance (OR = 7.49) and treatment in the early period (OR = 2.54) were significantly associated with the inappropriate use of polypectomy (both P < 0.05). In addition, a total of 265 (81.3%) were followed up with a median follow-up period of 30.9 months. No death, metastasis, or recurrence was found during the follow-up period. Conclusions Polypectomy, a central depression, and treatment in the early period were risk factors for IR. Further, an atypical hyperemic appearance and treatment in the early period were significant predisposing factors for inappropriate choice of polypectomy. For histologically incompletely resected small RNETs, follow-up may be a safe and feasible alternative to rigorous salvage therapy.
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Affiliation(s)
| | | | - Guiquan Chen
- Department of Gastroenterology, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, P. R. China
| | - Zongqi Luo
- Department of Gastroenterology, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, P. R. China
| | - Huiqin Hu
- Department of Gastroenterology, Huizhou First Hospital, Huizhou, P. R. China
| | - Wenfeng Huang
- Department of Gastroenterology, Huizhou First Hospital, Huizhou, P. R. China
| | - Yu Guo
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Yongwen Ouyang
- Department of Digestive Diseases, The First People's Hospital of Foshan, Foshan, P. R. China
| | - Liang Peng
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, P. R. China
| | - Qing Qing
- Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China
| | - Huiting Chen
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P. R. China
| | - Bingsheng Li
- Corresponding authors. Bingsheng Li, Department of Gastroenterology, Huizhou First Hospital, Huizhou 516000, P. R. China. Tel: +86-752-2883877; ; Jie Chen, Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China. Tel: +86-21-64175590; ; Xinying Wang, Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Haizhu District, Guangzhou 510000, P. R. China. Tel: +86-20-62782273;
| | - Jie Chen
- Corresponding authors. Bingsheng Li, Department of Gastroenterology, Huizhou First Hospital, Huizhou 516000, P. R. China. Tel: +86-752-2883877; ; Jie Chen, Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China. Tel: +86-21-64175590; ; Xinying Wang, Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Haizhu District, Guangzhou 510000, P. R. China. Tel: +86-20-62782273;
| | - Xinying Wang
- Corresponding authors. Bingsheng Li, Department of Gastroenterology, Huizhou First Hospital, Huizhou 516000, P. R. China. Tel: +86-752-2883877; ; Jie Chen, Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China. Tel: +86-21-64175590; ; Xinying Wang, Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Haizhu District, Guangzhou 510000, P. R. China. Tel: +86-20-62782273;
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177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials. Cancers (Basel) 2022; 14:cancers14246022. [PMID: 36551507 PMCID: PMC9776442 DOI: 10.3390/cancers14246022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/31/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of 177 Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome. PATIENTS AND METHODS A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with ≥1 refractory sign/symptom to octreotide, and ≥1 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed. RESULTS Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, 1 (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2-63.2) median PFS was 33.0 months (95%CI: 27.1-48.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8% (95%CI: 76.1-94.1). Syndromic responders showed better survival than non-responders, with a 2-year OS of 93.9% (95%CI: 92.2-98.0) vs. 40.0% (95%CI: 6.6-73.4), respectively. A total of 233 adverse events were recorded. Grade 1-2 hematological toxicity was the most frequent. CONCLUSION The 177 Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS.
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Gonzáles-Yovera JG, Roseboom PJ, Concepción-Zavaleta M, Gutiérrez-Córdova I, Plasencia-Dueñas E, Quispe-Flores M, Ramos-Yataco A, Alcalde-Loyola C, Massucco-Revoredo F, Paz-Ibarra J, Concepción-Urteaga L. Diagnosis and management of small bowel neuroendocrine tumors: A state-of-the-art. World J Methodol 2022; 12:381-391. [PMID: 36186753 PMCID: PMC9516545 DOI: 10.5662/wjm.v12.i5.381] [Citation(s) in RCA: 6] [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: 03/06/2022] [Revised: 04/22/2022] [Accepted: 08/05/2022] [Indexed: 02/08/2023] Open
Abstract
This review provides an update on the epidemiology, pathophysiology, symptoms, diagnosis and treatment of neuroendocrine neoplasms (NENs) of the small bowel (SB). These NENs are defined as a group of neoplasms deriving from neuroendocrine cells. NENs are currently the most common primary tumors of the SB, mainly involving the ileum, making the SB the most frequently affected part of the gastrointestinal tract. SB NENs by definition are located between the ligament of Treitz and the ileocecal valve. They are characterized by small size and induce an extensive fibrotic reaction in the small intestine including the mesentery, resulting in narrowing or twisting of the intestine. Clinical manifestations of bowel functionality are related to the precise location of the primary tumor. The majority of them are non-functional NENs and generally asymptomatic; in an advanced stage, NENs present symptoms of mass effect by non-specific abdominal pain or carcinoid syndrome which appears in patients with liver metastasis (around 10%). The main manifestations of the carcinoid syndrome are facial flushing (94%), diarrhea (78%), abdominal cramps (50%), heart valve disease (50%), telangiectasia (25%), wheezing (15%) and edema (19%). Diagnosis is made by imaging or biochemical tests, and the order of request will depend on the initial diagnostic hypothesis, while confirmation will always be histological. All patients with a localized SB NEN with or without near metastasis in the mesentery are recommended for curative resection. Locoregional and distant spread may be susceptible to several therapeutic strategies, such as chemotherapy, somatostatin analogs and palliative resection.
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Affiliation(s)
| | - Pela J Roseboom
- Division of Emergency Medicine, Regional Academic Hospital of Trujillo, Trujillo 13011, Peru
| | | | | | | | - María Quispe-Flores
- Division of Endocrinology, Guillermo Almenara Irigoyen National Hospital, Lima 12590, Peru
| | - Anthony Ramos-Yataco
- Division of Internal Medicine, Ricardo Cruzado Rivarola Hospital, Ica 110301, Peru
| | | | | | - José Paz-Ibarra
- Department of Medicine, School of Medicine, National University of San Marcos, Lima 15001, Peru
| | - Luis Concepción-Urteaga
- Division of Internal Medicine, School of Medicine, National University of Trujillo, Trujillo 13011, Peru
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Pang S, Zong Y, Zhang K, Zhao H, Wang Y, Wang J, Liu C, Wu Y, Li P. Multiple rectal neuroendocrine tumors: An analysis of 15 cases and literature review. Front Oncol 2022; 12:996306. [PMID: 36185313 PMCID: PMC9515498 DOI: 10.3389/fonc.2022.996306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 08/24/2022] [Indexed: 12/07/2022] Open
Abstract
Multiple neuroendocrine tumors (M-NETs) are rare in the rectum and there is no consensus on their characteristics and treatments. Here, we report 15 cases of rectal M-NETs and review the previous literature. We discuss the clinical characteristics, endoscopic features and pathological features of rectal M-NETs, aiming to analyze the treatments and follow-up strategies in combination with these characteristics. We retrospectively reviewed and analyzed the data of 15 patients with rectal M-NETs who were diagnosed and treated at Beijing Friendship Hospital, Capital Medical University. Their clinical data, endoscopic findings, pathological features and treatments were analyzed. Follow-up evaluations and literature review were performed. In all, 14 male (93.3%) and 1 female (6.7%) were recruited. The average age at diagnosis was 55.7 years. The clinical manifestations include asymptomatic in 9 patients (60.0%), defecation habits changes in 2 patients (13.3%), anal distension in 2 patients (13.3%), and abdominal distension in 2 patient (13.3%). The largest tumor diameter ≤10mm was found in 13 patients (86.7%) and >10mm in 2 patients (13.3%). All of the lesions originated from the mucous or submucosa layer. WHO grades were all NET G1. The number of tumors diagnosed by pathology in 13 patients was consistent with that observed by endoscopy, while more lesions were observed by pathology than endoscopy in two patients. Lymph node metastasis occurred in 1 patient (6.7%), and vascular or lymphatic invasion occurred in 9 patients (60.0%). Among the 13 patients with the largest tumor diameter being ≤10mm, lymphovascular invasion occurred in 8 patients (61.5%). And among the 2 patients with the largest tumor diameter of >10mm, lymphovascular invasion occurred in 1 patient (50.0%). 14 patients underwent endoscopic resection and 1 underwent surgical excision. Postoperative follow-up was achieved in 13 patients and no recurrence or metastasis was found. The true number of rectal M-NETs may be more than seen under endoscopy. Rectal M-NETs is associated with a high risk of metastasis; therefore, treatment and surveillance strategies should be more radical than single lesion.
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Affiliation(s)
- Shu Pang
- Department of General Practice, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ye Zong
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Kun Zhang
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Haiying Zhao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yongjun Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Junxiong Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chuntao Liu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yongdong Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- *Correspondence: Yongdong Wu, ; Peng Li,
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- *Correspondence: Yongdong Wu, ; Peng Li,
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Sipilä LJ, Seppä K, Aavikko M, Ravantti J, Heikkinen S, Aaltonen LA, Pitkäniemi J. Sex-specific familial aggregation of cancers in Finland. Sci Rep 2022; 12:15126. [PMID: 36068325 PMCID: PMC9448814 DOI: 10.1038/s41598-022-19039-1] [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: 06/20/2022] [Accepted: 08/23/2022] [Indexed: 12/24/2022] Open
Abstract
Despite the fact that the effect of sex on the occurrence of cancers has been studied extensively, it remains unclear whether sex modifies familial aggregation of cancers. We explored sex-specific familial aggregation of cancers in a large population-based historical cohort study. We combined cancer and population registry data, inferring familial relationships from birth municipality-surname-sex (MNS) combinations. Our data consisted of 391,529 incident primary cancers in 377,210 individuals with 319,872 different MNS combinations. Cumulative sex-specific numbers of cancers were compared to expected cumulative incidence. Familial cancer risks were similar between the sexes in our population-wide analysis. Families with concordant cancer in both sexes exhibited similar sex-specific cancer risks. However, some families had exceptionally high sex-specific cumulative cancer incidence. We identified six families with exceptionally strong aggregation in males: three families with thyroid cancer (ratio between observed and expected incidence 184.6; 95% credible interval (95% CI) 33.1–1012.7, 173.4 (95% CI 65.4–374.3), and 161.4 (95% CI 29.6–785.7), one with stomach (ratio 14.4 (95% CI 6.9–37.2)), colon (ratio 15.5 (95% CI 5.7–56.3)) cancers and one with chronic lymphocytic leukaemia (ratio 33.5 (95% CI 17.2–207.6)). Our results imply that familial aggregation of cancers shows no sex-specific preference. However, the atypical sex-specific aggregation of stomach cancer, colon cancer, thyroid cancer and chronic lymphocytic leukaemia in certain families is difficult to fully explain with present knowledge of possible causes, and could yield useful knowledge if explored further.
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Affiliation(s)
- Lauri J Sipilä
- Department of Medical and Clinical Genetics, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.,Applied Tumor Genomics Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.,Finnish Cancer Registry, Unioninkatu 22, 00130, Helsinki, Finland
| | - Karri Seppä
- Finnish Cancer Registry, Unioninkatu 22, 00130, Helsinki, Finland
| | - Mervi Aavikko
- Department of Medical and Clinical Genetics, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.,Applied Tumor Genomics Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.,Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
| | - Janne Ravantti
- Department of Medical and Clinical Genetics, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.,Applied Tumor Genomics Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.,Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014, Helsinki, Finland
| | - Sanna Heikkinen
- Finnish Cancer Registry, Unioninkatu 22, 00130, Helsinki, Finland
| | - Lauri A Aaltonen
- Department of Medical and Clinical Genetics, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland.,Applied Tumor Genomics Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014, Helsinki, Finland
| | - Janne Pitkäniemi
- Finnish Cancer Registry, Unioninkatu 22, 00130, Helsinki, Finland. .,Health Sciences Unit, Faculty of Social Sciences (Health Sciences), Tampere University, Tampere, Finland. .,Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland. .,Institute for Statistical and Epidemiological Cancer Research, Finnish Cancer Registry, Unioninkatu 22, 00130, Helsinki, Finland.
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Chang D, González APG, Migaly J. Management of neuroendocrine tumors of the rectum. SEMINARS IN COLON AND RECTAL SURGERY 2022. [DOI: 10.1016/j.scrs.2022.100901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Agarwal P, Mohamed A. Systemic Therapy of Advanced Well-differentiated Small Bowel Neuroendocrine Tumors Progressive on Somatostatin Analogues. Curr Treat Options Oncol 2022; 23:1233-1246. [PMID: 35939200 DOI: 10.1007/s11864-022-00998-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2022] [Indexed: 11/30/2022]
Abstract
OPINION STATEMENT Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors whose management requires a nuanced and multi-disciplinary approach in order to control symptoms, halt tumor growth, and improve survival outcomes. Of late, the treatment landscape of NENs has advanced considerably as a result of several pivotal clinical trials, which have established somatostatin analogues as first-line therapy for advanced, metastatic, well-differentiated neuroendocrine tumors (NETs). However, an evolving classification system as well as an increased understanding of distinct clinical, molecular, and biologic features contribute to complexity in management. In particular, there remains limited randomized prospective data in the somatostatin analogue (SSA)-refractory setting for patients with primary tumors that originate in the small bowel. For well-differentiated small bowel neuroendocrine tumors (SBNETs), treatment beyond SSAs includes radionuclide therapy, targeted agents, liver-directed therapy, and to a lesser extent, cytotoxic chemotherapy. In the current era, selection of these agents is largely based on expert opinion in the context of patient and tumor characteristics without definitive data on the preferred order of agents to administer. In this review, we aim to describe the treatment landscape of metastatic SBNETs beyond SSAs and provide an overview of novel treatments which are currently under clinical evaluation.
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Affiliation(s)
- Parul Agarwal
- Hematology/Oncology, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, PCAM 10 South Pavilion, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA
| | - Amr Mohamed
- Department of Medical Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Lakeside, Cleveland, OH, 44106, USA.
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Rare Case of Neuroendocrine Tumor of Common Bile Duct Identified With Somatostatin Receptor But Not With Glucose Transporter Imaging. Clin Nucl Med 2022; 47:e715-e717. [PMID: 35961371 DOI: 10.1097/rlu.0000000000004342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ABSTRACT Neuroendocrine tumors (NETs) are heterogeneous group of tumors arising from enterochromaffin cells. Neuroendocrine tumors are most commonly found in bowel and pancreatic tissue. Because of paucity of enterochromaffin cells in biliary tract, NETs of bile duct are very rare. Most of the neoplasms in the extrahepatic bile duct are adenocarcinomas; only 0.2% to 0.3% of NETs arise from the bile duct. Cases reported in the literature of biliary carcinoid are diagnosed postoperatively on histopathologic evaluation. We hereby demonstrate a rare presentation of CBD NET identified preoperatively on somatostatin receptor but not on glucose transporter imaging, confirmed by histopathology and immunohistochemistry to be grade 2 NET (Ki-67, 20%).
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Wang Y, Huang B, Fu Q, Wang J, Ye M, Hu M, Qu K, Liu K, Hu X, Wei S, Sun K, Xiao W, Zhang B, Li H, Li J, Zhang Q, Liang T. Comprehensive Clinical Analysis of Gallbladder Neuroendocrine Neoplasms: A Large-Volume Multicenter Study During One Decade. Ann Surg Oncol 2022; 29:7619-7630. [PMID: 35849293 DOI: 10.1245/s10434-022-12107-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 06/05/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study aimed to comprehensively investigate the clinicopathologic characteristics and therapeutic situations of gallbladder neuroendocrine neoplasms (GB-NENs) in the real world via a multicenter, large-scale cohort study. METHODS The study searched for patients in 143 hospitals in China and enrolled 154 patients with GB-NENs diagnosed in 40 hospitals between 2004 and 2021. Clinicopathologic characteristics and therapeutic approaches were analyzed retrospectively. RESULTS The median age at the initial diagnosis of the patients with GB-NENs was 63 years (range 33-83 years), and 61.7% of the patients were women. Tumor-node-metastasis staging classified 92 patients as stage 3 or above. Based on the 2019 World Health Organization classification, 96 cases (62.3%) were confirmed pathologically as poorly differentiated neuroendocrine carcinomas, 13 cases (8.4%) as well-differentiated neuroendocrine tumors, and 45 cases as mixed neuroendocrine-non-neuroendocrine neoplasms. The liver was the most frequent metastatic site. Immunohistochemistry showed that synaptophysin was most frequently positive (80.4%), followed by chromogranin A (61.7%), and CD56 (58.4%). Computed tomography and magnetic resonance imaging showed more common clear boundaries (25/39 cases) and invasive growth features (27 cases). None of these cases had an accurate diagnosis before surgery, with a misdiagnosis rate of 100%. Surgical resection is the main treatment, and platinum-based chemotherapeutic regimens were preferred as adjuvant therapies for patients with GB-NENs. The available survival data for 74 patients showed an overall survival rate of 59% at 1 year, 33% at 3 years, and 29% at 5 years. No significant difference was found between the patients treated with and those treated without adjuvant chemotherapy. CONCLUSIONS Gallbladder neuroendocrine neoplasms have high malignancy and a poor prognosis. Importantly, this large-scale cohort study significantly improves our understanding of GB-NENs and will benefit the exploration of its mechanism and treatment modes. Further investigation is necessary to explore the management of this disease.
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Affiliation(s)
- Yangyang Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Bingfeng Huang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qihan Fu
- Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China.,Zhejiang University Cancer Center, Hangzhou, China.,Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianing Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mao Ye
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Manyi Hu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kai Qu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Kai Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China
| | - Xiao Hu
- Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shumei Wei
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ke Sun
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenbo Xiao
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Bo Zhang
- Department of General Surgery, Shenzhen University Luohu People's Hospital, Shenzhen, China
| | - Haijun Li
- Department of General Surgery, Shenzhen University Luohu People's Hospital, Shenzhen, China
| | - Jingsong Li
- The Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.,Research Center for Healthcare Data Science, Zhejiang Lab, Hangzhou, China
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. .,Zhejiang University Cancer Center, Hangzhou, China.
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. .,Zhejiang University Cancer Center, Hangzhou, China.
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Comparison between endoscopic mucosal resection with a cap and endoscopic submucosal dissection for rectal neuroendocrine tumors. BMC Surg 2022; 22:248. [PMID: 35761304 PMCID: PMC9238094 DOI: 10.1186/s12893-022-01693-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/14/2022] [Indexed: 11/22/2022] Open
Abstract
Background The aim of this study is to evaluate and compare the safety and efficacy of endoscopic mucosal resection with a cap (EMR-c) with those of endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (R-NETs) ≤ 15 mm in diameter, and to analyze the risk factors of incomplete resection. Methods A total of 122 patients who underwent EMR-c or ESD for R-NETs at the Fourth Hospital of Hebei Medical University between February 2007 and December 2020 were invovled in this study. The clinical outcomes of two groups were compared and evaluated. Results A total of 122 patients with 128 R-NETs underwent endoscopic resection (EMR-c, 80; ESD, 48). In terms of duration of operation, EMR-c was significantly shorter than ESD (p < 0.001). Univariate analysis and multivariate analysis suggested that tumor diameter ≥ 8 mm was an independent risk factor for incomplete resection in patients with R-NETs in this study. Conclusions Both EMR-c and ESD were safe and effective treatments for R-NETs ≤ 15 mm in diameter. In addition, tumor diameter ≥ 8 mm was an independent risk factor for incomplete resection.
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Yamada S, Kijima N, Kinoshita M, Shinzaki S, Sato K, Kido K, Hirayama R, Kagawa N, Takehara T, Morii E, Kishima H. Cerebellopontine angle metastasis of a neuroendocrine tumor mimicking vestibular schwannoma: A case report. Surg Neurol Int 2022; 13:264. [PMID: 35855178 PMCID: PMC9282763 DOI: 10.25259/sni_117_2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 05/30/2022] [Indexed: 12/26/2022] Open
Abstract
Background: Neuroendocrine tumors (NETs) are uncommon neoplasms arising from neuroendocrine cells and are rarely associated with intracranial metastases. Case Description: We discuss the case of a 74-year-old woman with a right CPA tumor. She had a history of retroperitoneal NET, but was diagnosed with vestibular schwannoma due to a right-sided hearing loss and a right CPA tumor along the VII and VIII nerves. After a 3-year follow-up, she presented with repetitive vomiting, a 1-month history of gait instability, and a 3-month history of general fatigue. Brain imaging revealed tumor growth and edematous changes in the right cerebellum. She underwent retrosigmoid craniotomy and partial resection. Histopathological examination revealed metastatic NET. She underwent stereotactic radiosurgery for residual lesion and, at 11 months of follow-up, the lesion was confirmed to have shrunk on magnetic resonance imaging (MRI). Conclusion: This is the first case to report the natural course of cerebellopontine metastasis of a NET. The differential diagnosis of CPA tumors is diverse, and, in our case, we suspected a vestibular schwannoma because of the typical symptoms and imaging features. However, the tumor grew relatively faster than expected and showed intratumoral hemorrhage during the 3-year follow-up. Therefore, in patients with a history of a NET, a careful follow-up is advisable even for lesions highly suspected to be another benign tumor on MRI. Careful follow-up imaging and appropriate treatment strategies were useful to manage the brain metastasis. Although NETs metastasizing to the CPA are extremely rare, this possibility should be considered when patients with NETs have intracranial lesions.
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Affiliation(s)
- Shuhei Yamada
- Department of Neurosurgery, Graduate School of Medicine, Suita, Osaka, Japan,
| | - Noriyuki Kijima
- Department of Neurosurgery, Graduate School of Medicine, Suita, Osaka, Japan,
| | - Manabu Kinoshita
- Department of Neurosurgery, Graduate School of Medicine, Suita, Osaka, Japan,
| | - Shinichiro Shinzaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Suita, Osaka, Japan,
| | - Kazuaki Sato
- Department of Pathology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
| | - Kansuke Kido
- Department of Pathology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
| | - Ryuichi Hirayama
- Department of Neurosurgery, Graduate School of Medicine, Suita, Osaka, Japan,
| | - Naoki Kagawa
- Department of Neurosurgery, Graduate School of Medicine, Suita, Osaka, Japan,
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Suita, Osaka, Japan,
| | - Eiichi Morii
- Department of Pathology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan
| | - Haruhiko Kishima
- Department of Neurosurgery, Graduate School of Medicine, Suita, Osaka, Japan,
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Costanzo A, Canziani M, Ferrari CC, Bertocchi V, Cutaia S, Bucci EO, Uslenghi E, Ferretti A, De Luca M, Ceriani F. An apparent primitive mass of the mesentery: A case report. Medicine (Baltimore) 2022; 101:e29464. [PMID: 35713456 PMCID: PMC9276447 DOI: 10.1097/md.0000000000029464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/26/2022] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Neuroendocrine tumours (NETs) are rare tumors. 55% of NETs originate in the gastrointestinal tract and the liver is the most common site of distant metastases. Serum chromogranin A is the most common biomarker for assessing the extent of disease and monitoring treatment; carcinoid syndrome occurs in 19% of NETs and is characterized by chronic diarrhea or flushing. Primary mesenteric NETs are rare and have been described only in case reports in literature; our case is an apparent primary mesenteric NETs with a surgical program to remove the mesenteric mass and subrenal interaortocaval and retrocaval lymphadenectomies. PATIENT CONCERNS A 73-year old man came to us because he had been experiencing abdominal pain for a year and he had recently developed diabetes mellitus. He was an active smoker with arterial hypertension. DIAGNOSIS After a computed tomography scan and 68 Gallium-positron emission tomography, a diagnosis of what appeared to be a primary mesenteric NET with retrocaval and interaortocaval lymph nodes was made. Laparoscopic biopsy showed NET G2 positive for serotonin, chromogranin A, synaptophysin. INTERVENTIONS The intraoperative finding of a primitive ileum-NET changed the surgical program. We removed the mesenteric mass with the lymph nodes of the superior mesenteric vessel and the middle distal ileum along with the cecum. OUTCOMES The postoperative course was normal, and the patient was discharged on the seventh postoperative day without signs of short bowel syndrome. Follow-up at 6 months revealed no evidence of short bowel syndrome or disease progression. CONCLUSION 68 Gallium-positron emission tomography does not show NETs smaller than 0.5 mm. Accurate palpation of the intestine is essential during surgery for NETs for two reasons: to find the primitive, and because of the risk of multiple intestinal primitives.
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Affiliation(s)
| | | | | | | | - Saro Cutaia
- General Surgery Department, IRCCS MultiMedica, Italy
| | | | | | - Andrea Ferretti
- Inter-Hospital Division of Pathology, IRCCS MultiMedica, Castellanza (Va) Italy
| | - Marco De Luca
- Inter-Hospital Division of Pathology, IRCCS MultiMedica, Castellanza (Va) Italy
| | - Fabio Ceriani
- General Surgery Department, IRCCS MultiMedica, Italy
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Cha B, Shin J, Ko WJ, Kwon KS, Kim H. Prognosis of incompletely resected small rectal neuroendocrine tumor using endoscope without additional treatment. BMC Gastroenterol 2022; 22:293. [PMID: 35681149 PMCID: PMC9185951 DOI: 10.1186/s12876-022-02365-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/30/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND In recent years, the incidence of rectal neuroendocrine tumors (NET)s has markedly increased due to the widespread use of screening colonoscopy. However, many patients are referred from local clinics after undergoing conventional endoscopic mucosal resection (EMR) for polyps without perceived NET, with a pathological report of incomplete resection. We evaluated the prognosis of incompletely resected small rectal NET without additional endoscopic resection for small rectal NET less than 10 mm in diameter present within the submucosal layer showing good prognosis, due to its rare metastatic potential. METHODS We retrospectively reviewed patients from 2008 to 2018 at a single center who had had small rectal NET (located in the rectum from the anal verge to 20 cm in proximity) and had undergone 'incomplete resection' using endoscopy with a positive deep margin or with a very small safe deep margin (< 100 um). A small rectal NET was defined as a tumor ≤ 10 mm in diameter, without lymph node nor distant metastasis, and with low grade (G1) according to the WHO grading system. RESULTS Of 267 patients who were diagnosed with small rectal NET, 77 were diagnosed with incomplete resection or possible remnant NET. Of those, 55 patients (55/77, 71.4%) were referred from local clinics post EMR diagnosed as polyps. The rate of histologically incomplete resection was highest in endoscopic submucosal dissection (11/21, 52.4%) and lowest in surgical resection (0/9, 0%), while endoscopic submucosal resection with band ligation showed an incomplete resection rate of 4.4% (5/113). After exclusion of 36 patients, namely 21 patients had undergone additional surgical (n = 6) or endoscopic (n = 15) resection and 25 patients who were lost during the follow-up period of 2 years, 31 patients had undergone surveillance with endoscopic evaluation or either a biopsy or radiological evaluation for distant metastasis during a median follow-up duration of 2 years. None of the incompletely resected small rectal NET patients showed local or distant metastasis. CONCLUSION Incomplete resection of small rectal NET with G1 grade has a good prognosis without additional treatment.
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Affiliation(s)
- Boram Cha
- Department of Internal Medicine, Digestive Disease Center, Inha University School of Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon, 400-711, Republic of Korea
| | - Jongbeom Shin
- Department of Internal Medicine, Digestive Disease Center, Inha University School of Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon, 400-711, Republic of Korea
| | - Weon Jin Ko
- Department of Internal Medicine, Digestive Disease Center, Inha University School of Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon, 400-711, Republic of Korea
| | - Kye Sook Kwon
- Department of Internal Medicine, Digestive Disease Center, Inha University School of Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon, 400-711, Republic of Korea
| | - Hyungkil Kim
- Department of Internal Medicine, Digestive Disease Center, Inha University School of Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon, 400-711, Republic of Korea.
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Gupta S, Allegretti JR. Mimics of Crohn's Disease. Gastroenterol Clin North Am 2022; 51:241-269. [PMID: 35595413 DOI: 10.1016/j.gtc.2021.12.006] [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] [Indexed: 02/21/2023]
Abstract
Crohn's disease is a chronic inflammatory disease that can affect any portion of the gastrointestinal tract. Associated symptoms can vary based on the severity of disease, extent of involvement, presence of extraintestinal manifestations, and development of complications. Diagnosis is based on a constellation of findings. Many diseases can mimic Crohn's disease and lead to diagnostic conundrums. These include entities associated with the gastrointestinal luminal tract, vascular disease, autoimmune processes, various infections, malignancies and complications, drug- or treatment-induced conditions, and genetic diseases. Careful consideration of possible causes is necessary to establish the correct diagnosis.
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Affiliation(s)
- Sanchit Gupta
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, 850 Boyslton Street, Suite 201, Chestnut Hill, MA 02467, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, 850 Boyslton Street, Suite 201, Chestnut Hill, MA 02467, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
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Papaefthymiou A, Laskaratos FM, Koffas A, Manolakis A, Gkolfakis P, Coda S, Sodergren M, Suzuki N, Toumpanakis C. State of the Art in Endoscopic Therapy for the Management of Gastroenteropancreatic Neuroendocrine Tumors. Curr Treat Options Oncol 2022; 23:1014-1034. [PMID: 35511346 DOI: 10.1007/s11864-022-00986-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2022] [Indexed: 12/13/2022]
Abstract
OPINION STATEMENT Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) comprise a heterogeneous group of slow growing tumors arising from the neuroendocrine cells of the gastrointestinal (GI) tract. Although they are considered relatively rare, their incidence is rising and it is believed that the more frequent use of endoscopy and imaging studies have at least in part contributed to the increased diagnosis especially of localized neoplasms. The management of these neoplasms should be guided by a multidisciplinary NEN team following appropriate staging investigations. Localized neoplasms of the GI tract may be suitable for endoscopic therapy, while patients with pancreatic NENs, unsuitable for surgery, should be considered for endoscopic ultrasound (EUS)-guided ablation. In this review, we discuss the evidence regarding endoscopic resection of luminal NENs and EUS-guided therapy of pancreatic NENs. The efficacy, safety, and other longer-term outcomes of these techniques are summarized. In conclusion, this review of endoscopic therapies for localized NENs may be a useful guide for NEN clinicians and endoscopists who are considering these therapeutic options for the management of focal GEP NENs.
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Affiliation(s)
- Apostolis Papaefthymiou
- Department of Gastroenterology, General University Hospital of Larisa, Mezourlo, 41110, Larisa, Greece.,First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124, Thessaloniki, Macedonia, Greece
| | | | - Apostolos Koffas
- Department of Gastroenterology, General University Hospital of Larisa, Mezourlo, 41110, Larisa, Greece
| | - Anastasios Manolakis
- Department of Gastroenterology, General University Hospital of Larisa, Mezourlo, 41110, Larisa, Greece
| | - Paraskevas Gkolfakis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, 1070, Brussels, Belgium
| | - Sergio Coda
- Digestive Diseases Centre, Barking Havering and Redbridge University Hospitals NHS Trust, London, UK
| | - Mikael Sodergren
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Noriko Suzuki
- Wolfson Unit for Endoscopy, St Mark's Hospital and Academic Institute, London, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit (ENETS Centre of Excellence) Centre for Gastroenterology, Royal Free Hospital, London, UK
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