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Shahoud M, Abdin D, Ismail A, Ismail F, Azzawi T. Carcinoid tumor in a 10-year-old boy challenges in diagnosis and management: A rare case report. Int J Surg Case Rep 2025; 126:110811. [PMID: 39753072 PMCID: PMC11755083 DOI: 10.1016/j.ijscr.2024.110811] [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: 11/21/2024] [Revised: 12/23/2024] [Accepted: 12/28/2024] [Indexed: 01/15/2025] Open
Abstract
INTRODUCTION Lung cancer is a major cause of cancer-related deaths, with 2 million new cases annually. Bronchopulmonary neuroendocrine tumors (BP-NETs) comprise about 20 % of lung cancers, including typical carcinoid tumors (TC). While tobacco is a primary risk factor, non-tobacco factors also play a role. Typically, NETs affect individuals over 50, with typical carcinoids being rare in children. This report discusses a unique case of a typical carcinoid in a 10-year-old boy linked to environmental exposure. CASE PRESENTATION A 10-year-old boy presented with cough, dyspnea, hemoptysis, and recurrent pneumonia. Imaging revealed lobar collapse and a large mass in the right lower lobe. Surgical excision confirmed a carcinoid tumor with no lymph node metastasis. Post-surgery, the patient showed complete symptom resolution during follow-up. DISCUSSION Neuroendocrine tumors (NETs) are uncommon in children and can present with respiratory symptoms. This case highlights the importance of considering NETs in pediatric patients, particularly with environmental exposure. Timely diagnosis and surgical intervention led to a successful outcome, emphasizing the need for awareness of these tumors in younger populations. CONCLUSION This case report presents a rare typical carcinoid tumor in a 10-year-old boy, with successful surgical resection leading to complete symptom resolution. It highlights the need to recognize bronchopulmonary neuroendocrine tumors in children, particularly those with environmental exposure, and underscores the importance of ongoing follow-up for affected patients.
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Affiliation(s)
- Maya Shahoud
- University of Aleppo, Faculty of Medicine, Aleppo, Syria.
| | - Dania Abdin
- University of Aleppo, Faculty of Medicine, Aleppo, Syria.
| | - Ahmad Ismail
- University of Aleppo, Faculty of Medicine, Aleppo, Syria
| | - Fatima Ismail
- University of Aleppo, Faculty of Medicine, Aleppo, Syria
| | - Tameem Azzawi
- University of Aleppo, Faculty of Medicine, Aleppo, Syria
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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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Zhou Y, Li L, Wang H, Huang HX, Cao D, Ke NW, Su MG, Tian R. Heterogeneous Uptake of 68 Ga-DOTATATE and 18 F-FDG in Initial Diagnosed Neuroendocrine Tumors Patients : Which Patients Are Suitable for Dual-Tracer PET Imaging? Clin Nucl Med 2024; 49:516-520. [PMID: 38637950 DOI: 10.1097/rlu.0000000000005231] [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: 04/20/2024]
Abstract
PURPOSE This study was designed to assess the uptake heterogeneity in neuroendocrine tumor (NET) patients at initial diagnosis with dual-tracer PET imaging and the staging changes and prognostic value it brings to explore the indication of the use of dual-tracer PET. METHODS Fifty-one newly diagnosed patients with pathologically confirmed NET who underwent 18 F-FDG and 68 Ga-DOTATATE PET imaging between January 2020 and September 2022 were enrolled. Dual-tracer uptake patterns were classified into 3 groups: A. 68 Ga-DOTATATE positive and 18 F-FDG negative, B. 68 Ga-DOTATATE positive and 18 F-FDG positive, and C. 68 Ga-DOTATATE negative and 18 F-FDG positive. Descriptive statistics were used to evaluate the heterogeneity of dual-tracer uptake patterns among different grading (G) groups, between primary and metastatic lesions, and staging changes. Moreover, dual-tracer uptake patterns, grade, age, sex, and stage were compared with progression-free survival (PFS) by Cox regression. RESULTS In the different G groups, none of the patients with dual-tracer uptake pattern A had grade 3 histology, but 57% of patients with grade 1 disease had FDG avidity (25% of them resulting in dual-tracer uptake pattern C). Patients with no metastasis were well differentiated, but one of them presented with dual-tracer uptake pattern C. Different uptake patterns were also observed between primary and metastatic lesions, particularly 44% of patients with dual-tracer uptake pattern A of primary with FDG avidity of metastases. Moreover, 9 (17.6%) had new lesions detected by additional 18 F-FDG PET imaging, and 3 of them (5.9%) had clinical stage changed accordingly. The Cox regression test showed that the dual-tracer uptake patterns were significantly correlated with PFS by univariate and multivariate analyses ( P = 0.026 and 0.039, respectively), whereas the grade and stage did not correlate with survival (all P >0.05). CONCLUSION The current study has proven the uptake heterogeneity of the NET at initial diagnosis and demonstrated the staging and prognostic value of dual-tracer PET imaging. Our preliminary results have confirmed the importance of dual-tracer imaging modalities and concluded that dual-tracer PET imaging could be considered as prognostic tool for all patients with an initial diagnosis of NET.
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Affiliation(s)
- Yi Zhou
- From the Department of Nuclear Medicine, West China Hospital, Sichuan University, China
| | - Li Li
- From the Department of Nuclear Medicine, West China Hospital, Sichuan University, China
| | - Hui Wang
- From the Department of Nuclear Medicine, West China Hospital, Sichuan University, China
| | - He-Xiao Huang
- From the Department of Nuclear Medicine, West China Hospital, Sichuan University, China
| | - Dan Cao
- Division of Abdominal Tumor, Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Neng-Wen Ke
- Division of pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, China
| | - Ming-Gang Su
- From the Department of Nuclear Medicine, West China Hospital, Sichuan University, China
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Zi M, Ma Y, Chen J, Pang C, Li X, Yuan L, Liu Z, Yu P. Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis. Cancer Med 2024; 13:e7011. [PMID: 38457192 PMCID: PMC10922030 DOI: 10.1002/cam4.7011] [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: 09/25/2023] [Revised: 11/29/2023] [Accepted: 01/31/2024] [Indexed: 03/09/2024] Open
Abstract
OBJECTIVE This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.
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Affiliation(s)
- Mengli Zi
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Yubo Ma
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Jinxia Chen
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Chuhong Pang
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Xiao Li
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Li Yuan
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Zhuo Liu
- Department of Colorectum surgeryZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
| | - Pengfei Yu
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
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Wu Z, Shang G, Zhang K, Wang W, Fan M, Lin R. Combined the surgery, radiation, and chemotherapy for predicting overall survival in patients with gastroenteropancreatic neuroendocrine tumors. Int J Surg 2024; 110:01279778-990000000-00998. [PMID: 38241384 PMCID: PMC11020034 DOI: 10.1097/js9.0000000000001080] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/27/2023] [Indexed: 01/21/2024]
Abstract
BACKGROUND Over the last few decades, the annual global incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has steadily increased. Because of the complex and inconsistent treatment of GEP-NETs, the prognosis of patients with GEP-NETs is still difficult to assess. The study aimed to construct and validate the nomograms included treatment data for prediction overall survival (OS) in GEP-NETs patients. METHODS GEP-NETs patients determined from the Surveillance, Epidemiology, and End Results (SEER)-13 registry database (1992-2018) and with additional treatment data from the SEER-18 registry database (1975-2016). In order to select independent prognostic factors that contribute significantly to patient survival and can be included in the nomogram, multivariate Cox regression analysis was performed using the minimum value of Akaike information criterion (AIC) and we analyzed the relationship of variables with OS by calculating hazard ratios (HRs) and 95% CIs. In addition, we also comprehensively compared the nomogram using to predict OS with the current 7th American Joint Committee on Cancer (AJCC) staging system. RESULTS From 2004 to 2015, a total of 42,662 patients at diagnosis years with GEP-NETs were determined from the SEER database. The results indicated that the increasing incidence of GEP-NETs per year and the highest incidence is in patients aged 50-54. After removing cases lacking adequate clinicopathologic characteristics, the remaining eligible patients (n=7,564) were randomly divided into training (3,782 patients) and testing sets (3,782 patients). In the univariate analysis, sex, age, race, tumor location, SEER historic stage, pathology type, TNM, stage, surgery, radiation, chemotherapy, and CS tumor size were found to be significantly related to OS. Ultimately, the key factors for predicting OS were determined, involving sex, age, race, tumor location, SEER historic stage, M, N, grade, surgery, radiation, and chemotherapy. For internal validation, the C-index of the nomogram used to estimate OS in the training set was 0.816 (0.804-0.828). For external validation, the concordance index (C-index) of the nomogram used to predict OS was 0.822 (0.812-0.832). In the training and testing sets, our nomogram produced minimum AIC values and C-index of OS compared with AJCC stage. Decision curve analysis (DCA) indicated that the nomogram was better than the AJCC staging system because more clinical net benefits were obtained within a wider threshold probability range. CONCLUSION A nomogram combined treatment data may be better discrimination in predicting overall survival than AJCC staging system. We highly recommend to use our nomogram to evaluate individual risks based on different clinical features of GEP-NETs, which can improve the diagnosis and treatment outcomes of GEP-NETs patients and improve their quality of life.
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Affiliation(s)
- Zenghong Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | | | | | | | | | - Rong Lin
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Assis AC, Tercioti V, Andreollo NA, Ferrer JAP, Coelho JDS, Lopes LR. GASTRIC NEUROENDOCRINE TUMOR: WHEN SURGICAL TREATMENT IS INDICATED? ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1768. [PMID: 37851754 PMCID: PMC10578147 DOI: 10.1590/0102-672020230050e1768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 08/17/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND Gastric neuroendocrine tumors are a heterogeneous group of neoplasms that produce bioactive substances. Their treatment varies according to staging and classification, using endoscopic techniques, open surgery, chemotherapy, radiotherapy, and drugs analogous to somatostatin. AIMS To identify and review cases of gastric neuroendocrine neoplasia submitted to surgical treatment. METHODS Review of surgically treated patients from 1983 to 2018. RESULTS Fifteen patients were included, predominantly female (73.33%), with a mean age of 55.93 years. The most common symptom was epigastric pain (93.3%), and the mean time of symptom onset was 10.07 months. The preoperative upper digestive endoscopy (UDE) indicated a predominance of cases with 0 to 1 lesion (60%), sizing ≥1.5 cm (40%), located in the gastric antrum (53.33%), with ulceration (60%), and Borrmann III (33.33%) classification. The assessment of the surgical specimen indicated a predominance of invasive neuroendocrine tumors (60%), with angiolymphatic invasion in most cases (80%). Immunohistochemistry for chromogranin A was positive in 60% of cases and for synaptophysin in 66.7%, with a predominant Ki-67 index between 0 and 2%. Metastasis was observed in 20% of patients. The surgical procedure most performed was subtotal gastrectomy with Roux-en-Y reconstruction (53.3%). Tumor recurrence occurred in 20% of cases and a new treatment was required in 26.67%. CONCLUSIONS Gastric neuroendocrine tumors have a low incidence in the general population, and surgical treatment is indicated for advanced lesions. The study of its management gains importance in view of the specificities of each case and the need for adequate conduct to prevent recurrences and complications.
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Affiliation(s)
| | - Valdir Tercioti
- Universidade Estadual de Campinas, Faculty of Medical Sciences, Department of Surgery and Gastro Center – Campinas (SP), Brazil
| | - Nelson Adami Andreollo
- Universidade Estadual de Campinas, Faculty of Medical Sciences, Department of Surgery and Gastro Center – Campinas (SP), Brazil
| | - José Antonio Possatto Ferrer
- Universidade Estadual de Campinas, Faculty of Medical Sciences, Department of Surgery and Gastro Center – Campinas (SP), Brazil
| | - João de Souza Coelho
- Universidade Estadual de Campinas, Faculty of Medical Sciences, Department of Surgery and Gastro Center – Campinas (SP), Brazil
| | - Luiz Roberto Lopes
- Universidade Estadual de Campinas, Faculty of Medical Sciences, Department of Surgery and Gastro Center – Campinas (SP), Brazil
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Bevere M, Masetto F, Carazzolo ME, Bettega A, Gkountakos A, Scarpa A, Simbolo M. An Overview of Circulating Biomarkers in Neuroendocrine Neoplasms: A Clinical Guide. Diagnostics (Basel) 2023; 13:2820. [PMID: 37685358 PMCID: PMC10486716 DOI: 10.3390/diagnostics13172820] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/14/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of diseases that are characterized by different behavior and clinical manifestations. The diagnosis and management of this group of tumors are challenging due to tumor complexity and lack of precise and widely validated biomarkers. Indeed, the current circulating mono-analyte biomarkers (such as chromogranin A) are ineffective in describing such complex tumors due to their poor sensitivity and specificity. In contrast, multi-analytical circulating biomarkers (including NETest) are emerging as more effective tools to determine the real-time profile of the disease, both in terms of accurate diagnosis and effective treatment. In this review, we will analyze the capabilities and limitations of different circulating biomarkers focusing on three relevant questions: (1) accurate and early diagnosis; (2) monitoring of disease progression and response to therapy; and (3) detection of early relapse.
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Affiliation(s)
- Michele Bevere
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
| | - Francesca Masetto
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
| | - Maria Elena Carazzolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
| | - Alice Bettega
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
| | - Anastasios Gkountakos
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
| | - Aldo Scarpa
- ARC-Net Research Center, University of Verona, 37134 Verona, Italy; (M.B.); (F.M.); (A.G.); (A.S.)
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
| | - Michele Simbolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy; (M.E.C.); (A.B.)
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Gherghe M, Lazar AM, Simion L, Irimescu IN, Sterea MC, Mutuleanu MD, Anghel RM. Standardized Uptake Values on SPECT/CT: A Promising Alternative Tool for Treatment Evaluation and Prognosis of Metastatic Neuroendocrine Tumours. Diagnostics (Basel) 2023; 13:318. [PMID: 36673128 PMCID: PMC9857822 DOI: 10.3390/diagnostics13020318] [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: 11/25/2022] [Revised: 01/04/2023] [Accepted: 01/13/2023] [Indexed: 01/17/2023] Open
Abstract
(1) Background: The aim of our study was to assess the feasibility of 99mTcEDDA/HYNIC-TOC SPECT/CT quantitative analysis in evaluating treatment response and disease progression in patients with NETs. (2) Methods: This prospective monocentric study evaluated 35 SPECT/CT examinations performed on 14 patients with neuroendocrine tumours who underwent a baseline and at least one follow-up 99mTcEDDA/HYNIC-TOC scan as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer’s administration, with the SPECT/CT performed 4 h post-injection. Images were analyzed by two experienced physicians and patients were classified into response categories based on their changes in SUV values. (3) Results: We evaluated 14 baseline studies and 21 follow-up scans, accounting for 123 lesions. A statistically positive correlation has been found between the SUVmax and SUVpeak values in tumoral lesions (p < 0.05). No correlation has been found between the SUV values and the ki67 proliferation index. Finally, 64.29% patients were classified as SD at the end of the study, with only 14.29% of patients exhibiting PD and 21.43% patients with PR. (4) Conclusions: The quantitative analysis of 99mTcEDDA/HYNIC-TOC SPECT/CT data in patients with neuroendocrine tumours could represent an alternative to 68Ga-DOTA-peptides PET/CT for the monitoring and prognosis of NETs.
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Affiliation(s)
- Mirela Gherghe
- Nuclear Medicine Department, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania
- Nuclear Medicine Department, Institute of Oncology “Professor Doctor Alexandru Trestioreanu”, 022328 Bucharest, Romania
| | - Alexandra Maria Lazar
- Nuclear Medicine Department, Institute of Oncology “Professor Doctor Alexandru Trestioreanu”, 022328 Bucharest, Romania
| | - Laurentiu Simion
- Department of Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 1st Clinic of General Surgery and Surgical Oncology, Bucharest Oncology Institute, 022328 Bucharest, Romania
| | - Ionela-Nicoleta Irimescu
- Nuclear Medicine Department, Institute of Oncology “Professor Doctor Alexandru Trestioreanu”, 022328 Bucharest, Romania
| | - Maria-Carla Sterea
- Nuclear Medicine Department, Institute of Oncology “Professor Doctor Alexandru Trestioreanu”, 022328 Bucharest, Romania
| | - Mario-Demian Mutuleanu
- Nuclear Medicine Department, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania
- Nuclear Medicine Department, Institute of Oncology “Professor Doctor Alexandru Trestioreanu”, 022328 Bucharest, Romania
| | - Rodica Maricela Anghel
- Oncology Department, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania
- Radiotherapy Department, Institute of Oncology “Professor Doctor Alexandru Trestioreanu”, 022328 Bucharest, Romania
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Gisder DM, Overheu O, Keller J, Nöpel-Dünnebacke S, Uhl W, Reinacher-Schick A, Tannapfel A, Tischoff I. DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis. Pathobiology 2022; 90:71-80. [PMID: 35691289 DOI: 10.1159/000524920] [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: 06/24/2021] [Accepted: 05/01/2022] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published. METHODS We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2. RESULTS Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis. DISCUSSION/CONCLUSION Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.
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Affiliation(s)
| | - Oliver Overheu
- Department of Haematology and Oncology with Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Julia Keller
- Institute of Pathology, Ruhr Universität Bochum, Bochum, Germany
| | - Stefanie Nöpel-Dünnebacke
- Department of Haematology and Oncology with Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Waldemar Uhl
- Katholisches Klinikum Bochum gGmbH, Institute of General and Visceral Surgery, St. Josef-Hospital, Bochum, Germany
| | - Anke Reinacher-Schick
- Department of Haematology and Oncology with Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Andrea Tannapfel
- Institute of Pathology, Ruhr Universität Bochum, Bochum, Germany
| | - Iris Tischoff
- Institute of Pathology, Ruhr Universität Bochum, Bochum, Germany
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Weng Y, Ran J, Peng Y, Xiang Y, Xu L. Comparison of characteristics between true rectal neuroendocrine tumors and rectal hyperplastic polyps among patients with endoscope-diagnosed rectal neuroendocrine tumors. J Gastrointest Oncol 2022; 13:1121-1131. [PMID: 35837162 PMCID: PMC9274043 DOI: 10.21037/jgo-22-369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/27/2022] [Indexed: 11/06/2022] Open
Abstract
Background To explore the white light endoscopy and endoscopic ultrasonography (EUS) features of rectal hyperplastic polyps (rHP) misdiagnosed as rectal neuroendocrine neoplasms (rNENs). In rNENs with a diameter of 5-10 mm, the endoscopic findings are not typical and some of them are similar to rHP, so it is not uncommon to misdiagnose rNENs as rHP. However, misdiagnosis of rHP as rNENs has not been reported in the literature, which can alert clinicians to the existence of this possibility and avoid over-treatment. Methods We collected 245 cases of rectal submucosal tumor (SMT) diagnosed by endoscopy in our hospital from January 2015 to December 2020 and 103 patients with suspected rNENs identified through endoscopy. A retrospective analysis was conducted of the shape, color, vascular dilatation, and boundary on the surface of the lesion under white light endoscope, and the source, boundary, and echo characteristics of EUS. We also analyzed the endoscopic features of rHP misdiagnosed as rNENs. Endoscopic diagnosis and pathological diagnosis were reviewed by a senior endoscopic expert and pathologist respectively. The counting data were tested and analyzed by χ2 test and Fisher exact probability method. Results A total of 103 cases of rNENs were diagnosed by endoscope, among whom 75 cases were confirmed as rNENs (72.8%) and 8 cases as rHP (7.8%) by histopathology. There was no significant difference between rNENs and rHP in terms of gender, age, clinical manifestation, shape and color of lesions, dilatation of blood vessels on the surface, and location of lesions. Meanwhile, there were significant differences in whether the boundary of the lesion was clear under white light endoscopy, and the source, echo, and boundary of the lesion under EUS. Conclusions The morphology of some rHP is similar to rNENs under endoscopy. The boundary is clear under white light endoscopy and the source, echo, and boundary under EUS are helpful for the diagnosis of rNENs and rHP.
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Affiliation(s)
- Yan Weng
- Clinical College of Guiyang Medical University, Guiyang, China
| | - Jingxue Ran
- Clinical College of Guiyang Medical University, Guiyang, China
| | - Yongmei Peng
- Clinical College of Guiyang Medical University, Guiyang, China
| | - Yining Xiang
- Department of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Liangbi Xu
- Endoscopy Center of the Affiliated Hospital of Guizhou Medical University, Guiyang, China
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11
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Gherghe M, Lazăr AM, Stanciu AE, Mutuleanu MD, Sterea MC, Petroiu C, Galeș LN. The New Radiolabeled Peptide 99mTcEDDA/HYNIC-TOC: Is It a Feasible Choice for Diagnosing Gastroenteropancreatic NETs? Cancers (Basel) 2022; 14:2725. [PMID: 35681704 PMCID: PMC9179571 DOI: 10.3390/cancers14112725] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/23/2022] [Accepted: 05/26/2022] [Indexed: 02/04/2023] Open
Abstract
(1) Background: The aim of our study is to reveal the advantages and limitations of the use of 99mTcEDDA/HYNIC-TOC (Tektrotyd®, Polatom) in the diagnosis of gastroenteropancreatic neuroendocrine tumors and to compare our results with the values obtained for 111In-pentetreotide and 68Ga-DOTA-peptides, routinely used in medical practice. (2) Methods: This retrospective monocentric study included 173 patients with gastroenteropancreatic neuroendocrine tumors who underwent 99mTcEDDA/HYNIC-TOC scans as part of their clinical management. The examination protocol included a whole-body scan acquired 2 h after the radiotracer's administration, with the SPECT/CT performed 4 h post-injection. Physiological and abnormal uptake were established by two experienced physicians and, based on the obtained results, sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated. (3) Results: Our method presented a sensitivity of 90.5%, a specificity of 71.9%, and an accuracy of 84.3%, with a positive predictive value of 86.7% and a negative predictive value of 78.8%. (4) Conclusions: 99mTc-EDDA/HYNIC-TOC, a receptor-based radiopharmaceutical, could represent a competitor for 68Ga-labeled peptides in the diagnosis and management of patients with gastroenteropancreatic neuroendocrine tumors. Our results show a lower sensitivity (90.5%) than 68Ga-DOTA-peptides, but with great specificity, accuracy, positive, and negative predictive values.
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Affiliation(s)
- Mirela Gherghe
- Nuclear Medicine Department, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania; (M.G.); (M.-D.M.)
- Nuclear Medicine Department, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania; (M.-C.S.); (C.P.)
| | - Alexandra Maria Lazăr
- Nuclear Medicine Department, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania; (M.-C.S.); (C.P.)
| | - Adina Elena Stanciu
- Carcinogenesis and Molecular Biology Department, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania;
| | - Mario-Demian Mutuleanu
- Nuclear Medicine Department, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania; (M.G.); (M.-D.M.)
- Nuclear Medicine Department, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania; (M.-C.S.); (C.P.)
| | - Maria-Carla Sterea
- Nuclear Medicine Department, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania; (M.-C.S.); (C.P.)
| | - Cristina Petroiu
- Nuclear Medicine Department, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania; (M.-C.S.); (C.P.)
| | - Laurenția Nicoleta Galeș
- Oncology Department, University of Medicine and Pharmacy “Carol Davila” Bucharest, 050474 Bucharest, Romania;
- Oncology Department, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania
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12
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Feola T, Puliani G, Sesti F, Modica R, Centello R, Minotta R, Cannavale G, Di Meglio S, Di Vito V, Lauretta R, Appetecchia M, Colao A, Lenzi A, Isidori AM, Faggiano A, Giannetta E. Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case-control study. J Endocrinol Invest 2022; 45:849-857. [PMID: 35040099 DOI: 10.1007/s40618-021-01715-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 11/24/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs. METHODS We performed a retrospective case-control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors. RESULTS Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31-3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39-4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18-2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08-0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05-5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08-5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28-5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11-3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38-4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08-3.33, p = 0.026). CONCLUSION This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.
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Affiliation(s)
- T Feola
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
- Neuroendocrinology, Neuromed Institute, IRCCS, Pozzilli, Italy
| | - G Puliani
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
- Oncological Endocrinology Unit, Regina Elena National Cancer Institute, IRCCS, Rome, Italy
| | - F Sesti
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - R Modica
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - R Centello
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - R Minotta
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - G Cannavale
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - S Di Meglio
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - V Di Vito
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - R Lauretta
- Oncological Endocrinology Unit, Regina Elena National Cancer Institute, IRCCS, Rome, Italy
| | - M Appetecchia
- Oncological Endocrinology Unit, Regina Elena National Cancer Institute, IRCCS, Rome, Italy
| | - A Colao
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - A Lenzi
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - A M Isidori
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - A Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - E Giannetta
- Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy.
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Fang JM, Li J, Shi J. An update on the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:1009-1023. [PMID: 35431496 PMCID: PMC8968521 DOI: 10.3748/wjg.v28.i10.1009] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/26/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) arise from neuroendocrine cells found throughout the gastrointestinal tract and islet cells of the pancreas. The incidence and prevalence of GEP-NENs have been increasing each year due to higher awareness, improved diagnostic modalities, and increased incidental detection on cross-sectional imaging and endoscopy for cancer screening and other conditions and symptoms. GEP-NENs are a heterogeneous group of tumors and have a wide range in clinical presentation, histopathologic features, and molecular biology. Clinical presentation most commonly depends on whether the GEP-NEN secretes an active hormone. The World Health Organization recently updated the classification of GEP-NENs to introduce a distinction between high-grade neuroendocrine tumors and neuroendocrine carcinomas, which can be identified using histology and molecular studies and are more aggressive with a worse prognosis compared to high-grade neuroendocrine tumors. As our understanding of the biology of GEP-NENs has grown, new and improved diagnostic modalities can be developed and optimized. Here, we discuss clinical features and updates in diagnosis, including histopathological analysis, biomarkers, molecular techniques, and radiology of GEP-NENs. We review established diagnostic tests and discuss promising novel diagnostic tests that are currently in development or require further investigation and validation prior to broad utilization in patient care.
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Affiliation(s)
- Jiayun M Fang
- Department of Pathology & Clinical Labs, University of Michigan, Ann Arbor, MI 48109, United States
| | - Jay Li
- Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, United States
| | - Jiaqi Shi
- Department of Pathology & Clinical Labs, University of Michigan, Ann Arbor, MI 48109, United States
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14
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Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms. Cancers (Basel) 2022; 14:cancers14051119. [PMID: 35267427 PMCID: PMC8909424 DOI: 10.3390/cancers14051119] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 02/17/2022] [Accepted: 02/21/2022] [Indexed: 02/08/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.
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15
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Fu M, Yu L, Yang L, Chen Y, Chen X, Hu Q, Sun H. Gender differences in pancreatic neuroendocrine neoplasms: A retrospective study based on the population of Hubei Province, China. Front Endocrinol (Lausanne) 2022; 13:885895. [PMID: 36004340 PMCID: PMC9393376 DOI: 10.3389/fendo.2022.885895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE The aims of the present study were to investigate gender differences in the clinicopathological features, distant metastasis and prognosis of pancreatic neuroendocrine neoplasms (pNENs) in a Chinese population, and to identify any important gaps in the classification and management of pNENs relative to gender. METHODS Retrospective collection of the clinicopathological data of 193 patients with pathologically confirmed pNENs were analyzed and follow up was extended to observe the prognosis of the disease. Differences between genders in basic characteristics, clinical symptoms, comorbidities, and tumor parameters were analyzed. RESULTS There was no significant difference in females and males, however, moderately higher for females (52.8% vs. 47.2%), with the largest subgroup being 40~60 years of age (54.9%). Age at onset (P=0.002) and age at diagnosis (P=0.005) were both younger in females compared to males. Males lived more in urban areas and females lived more in rural areas (P=0.047). The proportion of smokers and alcohol drinkers was significantly higher in males than in females (P < 0.001). Non-functional pNENs were more frequent in males and functional pNENs in females (P=0.032). In women, functional status of the tumor was significantly associated with metastatic outcome (P=0.007) and functional tumors proved to be a protective factor compared to non-functional tumors (OR=0.090,95% CI: 0.011~ 0.752). There were no gender differences in tumor size, location, grade, stage or prognosis. CONCLUSIONS Gender differences in some clinicopathological features, and distant metastasis in patients with pNENs were identified, which suggested certain management details that justified emphasis based on gender.
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Affiliation(s)
- Mengfei Fu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Endocrinology, Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Li Yu
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liu Yang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Endocrinology, Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Yang Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Endocrinology, Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Xiao Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Endocrinology, Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Qinyu Hu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Endocrinology, Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Hui Sun
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Endocrinology, Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
- *Correspondence: Hui Sun,
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Yozgat A, Kekilli M, Altay M. Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours. World J Clin Cases 2021; 9:8627-8646. [PMID: 34734042 PMCID: PMC8546836 DOI: 10.12998/wjcc.v9.i29.8627] [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: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/24/2021] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide. The reason for the increase in the incidence of NETs is the detection of benign lesions, incidental detection due to the highest use of endoscopic and imaging procedures, and higher recognition rates of pathologists. There have been exciting developments regarding NET biology in recent years. Among these, first of all, somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis, hormone secretion, and proliferation. Subsequently, activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism. Finally, the importance of proangiogenic factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblastic growth factor, angiopoietin, and semaphorins) in the progression of NET has been determined. Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.
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Affiliation(s)
- Ahmet Yozgat
- Department of Gastroenterology, Ufuk University, Ankara, 06510, Turkey
| | - Murat Kekilli
- Department of Gastroenterology, Gazi University, Ankara 06560, Turkey
| | - Mustafa Altay
- Department of Endocrinology and Metabolism, University of Health Sciences Turkey, Keçiören Health Administration and Research Center, Ankara 06190, Turkey
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17
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Cukier M, Vergara R, Mendez-Rios JD, Castillo O, Barrera I, Tello E, El Achtar O, Loo Y, Tapia H, Perez G, Peña M. Neuroendocrine tumors in Panama: A nationwide database analysis. Mol Clin Oncol 2021; 15:157. [PMID: 34178328 PMCID: PMC8220651 DOI: 10.3892/mco.2021.2319] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 04/23/2021] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) comprise a heterogenous group of rare malignancies, which are increasing in incidence worldwide. To further understand the epidemiology of NETs in the Republic of Panama, the present study used two study groups, which included patients from several hospitals and clinics throughout the country, who were referred to the three largest national reference centers: The Complejo Hospitalario Metropolitano, Hospital Santo Tomas and Instituto Oncologico Nacional. These two groups comprised a retrospective cohort, which included cases reported between 2016 and 2017, and a second cohort, which was retrospective, but data were continuously collected from patients diagnosed with NETs between 2018 and 2019. Data from 157 patients with NETs reported that 83% of patients were in the 40-80 years old age group. The majority of cases (46%) presented as grade G1 tumors, while 29% were G3. Computerized tomography scans with contrast, and analysis of the Ki-67 biomarker and immunohistology markers (chromogranin A and synaptophysin) was performed in the majority of the cases. The results revealed that the most frequent anatomical sites for the primary tumor were the colorectum (17.2%), pancreas (12.7%) and stomach (12.1%), and the most frequent organ with metastasis was the liver, accounting for 34% of all cases. In conclusion, the present study is the first comprehensive study of NET in Panama to the best of our knowledge, which provides evidence of the demographic characteristics of the population, clinical features and overall survival for the affected population in this Central American country.
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Affiliation(s)
- Moises Cukier
- Department of Surgical Oncology, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
| | - Ruth Vergara
- Department of Pathology, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
| | - Jorge D Mendez-Rios
- Department of Genetics and Cytogenetics, Caja de Seguro Social, Panama City, Panama 0824, Republic of Panama.,Department of Genetics, School of Medicine, Universidad Interamericana de Panama, Panama City, Panama 0820, Republic of Panama
| | - Omar Castillo
- Department of Medical Oncology, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
| | - Irma Barrera
- Department of Pathology, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
| | - Eliecer Tello
- Department of General Surgery, Caja de Seguro Social, Panama City, Panama 0824, Republic of Panama
| | - Olivia El Achtar
- Department of Surgical Oncology, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
| | - Yong Loo
- Department of Medical Oncology, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
| | - Hector Tapia
- Department of Radiology and Interventionism, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
| | - Guadalupe Perez
- Department of Endocrinology, Caja de Seguro Social, Panama City, Panama 0824, Republic of Panama
| | - Maximino Peña
- Department of Gastroenterology, Instituto Oncologico Nacional, Panama City, Panama 0816, Republic of Panama
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Zhou B, Xiang J, Jin M, Zheng X, Li G, Yan S. High vimentin expression with E-cadherin expression loss predicts a poor prognosis after resection of grade 1 and 2 pancreatic neuroendocrine tumors. BMC Cancer 2021; 21:334. [PMID: 33789624 PMCID: PMC8010952 DOI: 10.1186/s12885-021-08062-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 03/18/2021] [Indexed: 02/08/2023] Open
Abstract
Background Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms with malignant behaviors that can develop from inert slow growth or low malignancy to aggressive metastasis during follow-up. Recently, vimentin and E-cadherin were shown to be prognostic markers in some malignant tumors but were not evaluated in pNETs. The aim of this study was to evaluate the expression and prognostic significance of vimentin and E-cadherin in grade 1 and 2 pNETs. Methods A retrospective review of 227 patients with grade 1 and 2 pNETs undergoing surgical resection was conducted. Tumor specimens were immunohistochemically stained for vimentin and E-cadherin. Correlations between vimentin and E-cadherin expression and other clinicopathological features were then analyzed. Furthermore, overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier and univariate and multivariate Cox regression methods. Results Among 227 patients, 55 (24.2%) harbored tumors with high vimentin expression, while 117 (51.5%) harbored tumors with loss of E-cadherin expression. Patients with high vimentin expression and loss of E-cadherin expression had significantly elevated risks of lymph node metastasis, distant metastasis, perineural invasion and an advanced American Joint Committee on Cancer (AJCC) stage compared with those with low vimentin expression and preserved E-cadherin expression, high vimentin expression and preserved E-cadherin expression, or low vimentin expression and loss of E-cadherin expression. Furthermore, multivariate analysis showed that high vimentin expression with loss of E-cadherin expression was an independent predictor of OS and DFS in patients with grade 1 and 2 pNETs who underwent resection (both P < 0.001). Conclusions The current study demonstrated that high vimentin expression with loss of E-cadherin expression was correlated with lymph node metastasis, distant metastasis, disease progression and a poor prognosis in patients with grade 1 and 2 pNETs who underwent resection.
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Affiliation(s)
- Bo Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Jie Xiang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ming Jin
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xiang Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Guogang Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Sheng Yan
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
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Smith-Palmer J, Leeuwenkamp OR, Virk J, Reed N. Lutetium oxodotreotide ( 177Lu-Dotatate) for the treatment of unresectable or metastatic progressive gastroenteropancreatic neuroendocrine tumors: a cost-effectiveness analysis for Scotland. BMC Cancer 2021; 21:10. [PMID: 33402120 PMCID: PMC7786468 DOI: 10.1186/s12885-020-07710-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 12/03/2020] [Indexed: 01/10/2023] Open
Abstract
Background Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogenous group of tumors. Findings from the phase III NETTER-1 trial showed that treatment of unresectable/metastatic progressive gastrointestinal (GI) NETs with 177Lu-Dotatate resulted in a significant improvement in progression-free survival (PFS) and overall survival (OS) compared with best supportive care (BSC) with high dose octreotide long-acting repeatable (LAR) 60 mg. A health economic analysis was performed using input data from clinical studies and data derived from an indirect comparison to determine the cost-effectiveness of 177Lu-Dotatate in the treatment of GI-NETs and pancreatic NETs (P-NETs) in Scotland. Methods Cost-effectiveness analysis was performed from the payer perspective using a three-state partitioned survival model. In the base case 177Lu-Dotatate was compared with BSC in gastrointestinal (GI)-NETs using clinical data from the NETTER-1 trial. A secondary analysis comparing 177Lu-Dotatate with BSC, everolimus or sunitinib in patients with P-NETs was also performed using hazard ratios inferred from indirect comparisons. The base case analysis was performed over a 20-year time horizon with an annual discount rate of 3.5% for both costs and clinical outcomes. Results For unresectable/metastatic progressive GI-NETs treatment with 177Lu-Dotatate led to a gain in quality-adjusted life expectancy of 1.33 quality-adjusted life years (QALYs) compared with BSC due to extended PFS and OS. Mean total lifetime costs were GBP 35,701 higher with 177Lu-Dotatate, leading to an incremental cost-effectiveness ratio (ICER) of GBP 26,830 per QALY gained. In analyses in patients with P-NETs 177Lu-Dotatate was associated with ICERs below GBP 30,000 per QALY gained in comparisons with BSC, sunitinib and everolimus. Conclusions Cost-effectiveness analyses demonstrated that, in Scotland, from the payer perspective, 177Lu-Dotatate at the set acquisition cost is a cost-effective treatment option for patients with unresectable or metastatic progressive GI-NETs or P-NETs.
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Affiliation(s)
- J Smith-Palmer
- Ossian Health Economics and Communications GmbH, Bäumleingasse 20, 4051, Basel, Switzerland.
| | - O R Leeuwenkamp
- Advanced Accelerator Applications/A Novartis company, Geneva, Switzerland
| | - J Virk
- Advanced Accelerator Applications/A Novartis company, London, UK
| | - N Reed
- Beatson Oncology Centre, Gartnavel General Hospital, Glasgow, UK
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20
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Titan AL, Norton JA, Fisher AT, Foster DS, Harris EJ, Worhunsky DJ, Worth PJ, Dua MM, Visser BC, Poultsides GA, Longaker MT, Jensen RT. Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors. JAMA Netw Open 2020; 3:e2024318. [PMID: 33146734 PMCID: PMC7643030 DOI: 10.1001/jamanetworkopen.2020.24318] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPORTANCE Although outcome of surgical resection of liver metastases from pancreatic neuroendocrine tumors (PNETs) has been extensively studied, little is known about surgery for locally advanced PNETs; it was listed recently by the European neuroendocrine tumor society as a major unmet need. OBJECTIVE To evaluate the outcome of patients who underwent surgery for locally aggressive PNETs. DESIGN, SETTING, AND PARTICIPANTS This retrospective single-center case series reviewed consecutive patients who underwent resection of T3/T4 PNETs at a single academic institution. Data collection occurred from 2003 to 2018. Data analysis was performed in August 2019. MAIN OUTCOMES AND MEASURES Disease-free survival (primary outcome) and overall mortality (secondary outcome) were assessed with Kaplan-Meier analysis. Recurrence risk (secondary outcome, defined as identification of tumor recurrence on imaging) was assessed with Cox proportional hazard models adjusting for covariates. RESULTS In this case series, 99 patients with locally advanced nondistant metastatic PNET (56 men [57%]) with a mean (SEM) age of 57.0 (1.4) years and a mean (SEM) follow-up of 5.3 (0.1) years underwent surgically aggressive resections. Of those, 4 patients (4%) underwent preoperative neoadjuvant treatment (including peptide receptor radionuclide therapy and chemotherapy); 18 patients (18%) underwent pancreaticoduodenectomy, 68 patients (69%) had distal or subtotal pancreatic resection, 10 patients (10%) had total resection, and 3 patients (3%) had other pancreatic procedures. Additional organ resection was required in 86 patients (87%): spleen (71 patients [71%]), major blood vessel (17 patients [17%]), bowel (2 patients [2%]), stomach (4 patients [4%]), and kidney (2 patients [2%]). Five-year disease-free survival was 61% (61 patients) and 5-year overall survival was 91% (91 patients). Of those living, 75 patients (76%) had an Eastern Cooperative Oncology Group score of less than or equal to 1 at last followup. Lymph node involvement (HR, 7.66; 95% CI, 2.78-21.12; P < .001), additional organ resected (HR, 6.15; 95% CI, 1.61-23.55; P = .008), and male sex (HR, 3.77; 95% CI, 1.68-8.97; P = .003) were associated with increased risk of recurrence. Functional tumors had a lower risk of recurrence (HR, 0.23; CI, 0.06-0.89; P = .03). Required resection of blood vessels was not associated with a significant increase recurrence risk. CONCLUSIONS AND RELEVANCE In this case series, positive lymph node involvement and resection of organs with tumor involvement were associated with an increased recurrence risk. These subgroups may require adjuvant systemic treatment. These findings suggest that patients with locally advanced PNETs who undergo surgical resection have excellent disease-free and overall survival.
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Affiliation(s)
- Ashley L. Titan
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Jeffrey A. Norton
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Andrea T. Fisher
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Deshka S. Foster
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - E. John Harris
- Department of Surgery, Stanford University Hospital, Stanford, California
| | | | - Patrick J. Worth
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Monica M. Dua
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Brendan C. Visser
- Department of Surgery, Stanford University Hospital, Stanford, California
| | | | | | - Robert T. Jensen
- Gastrointestinal Cell Biology Section, National Institutes of Health, Bethesda, Maryland
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Heinrich S, Watzka F, Lang H. Integrative Concepts for Liver Surgery. Visc Med 2020; 36:351-358. [PMID: 33178731 PMCID: PMC7590779 DOI: 10.1159/000511043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 08/20/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Surgery is the standard treatment for primary tumors and metastases. Due to improvements in surgical outcomes as well as the efficacy of systemic treatments, the role of surgery has changed in recent years. SUMMARY Liver surgery has become safe and efficient, with resectability being increased by multimodality concepts as well as staged liver resections and orthotopic liver transplantation. These concepts may be applied to primary liver tumors but also to selected patients with liver metastases from various diseases. In addition, even debulking surgery may be indicated for selected patients with endocrine metastases. While patient selection for liver resections was limited to clinical parameters in the past, histological and molecular characteristics have become increasingly important. Moreover, the response to regional or systemic chemotherapy has been demonstrated to be strong for a beneficial course of the disease even in advanced diseases. KEY-MESSAGES Due to the variety of available treatment options, optimal patient selection is crucial. Besides liver surgery, staged concepts as well as liver transplantation are curative tools for many patients.
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Affiliation(s)
| | | | - Hauke Lang
- General, Visceral and Transplantation Surgery, University Hospital, Mainz, Germany
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22
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Muscogiuri G, Barrea L, Feola T, Gallo M, Messina E, Venneri MA, Faggiano A, Colao A. Pancreatic Neuroendocrine Neoplasms: Does Sex Matter? Trends Endocrinol Metab 2020; 31:631-641. [PMID: 32223919 DOI: 10.1016/j.tem.2020.02.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 02/19/2020] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
Genetic and molecular disparities between men and women have a role in the differing incidence, pathophysiology, clinical signs, and treatment outcome of several cancers. Sex differences in cancer incidence are attributed to regulation at the genetic/molecular level and to sex hormones that in turn modulate gene expression in various cancers. Sex differences in the incidence of cancer, its aggressiveness, and the disease prognosis have been reported for several types of cancer but little is known for pancreatic neuroendocrine neoplasms (PNENs). The aim of this Opinion article is to provide an overview of sex differences in PNENs in terms of epidemiology, pathophysiology, treatment responses, prognosis, and survival. This overview might allow better tailoring of the management of PNENs.
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Affiliation(s)
- Giovanna Muscogiuri
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy.
| | - Luigi Barrea
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy
| | - Tiziana Feola
- Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy
| | - Marco Gallo
- Department of Medical Sciences, Oncological Endocrinology Unit, University of Turin, Turin, Italy
| | - Erika Messina
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Mary Anna Venneri
- Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy
| | | | - Annamaria Colao
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy
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Zlatopolskiy BD, Endepols H, Krasikova RN, Fedorova OS, Ermert J, Neumaier B. 11C- and 18F-labelled tryptophans as PET-tracers for imaging of altered tryptophan metabolism in age-associated disorders. RUSSIAN CHEMICAL REVIEWS 2020. [DOI: 10.1070/rcr4954] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The ageing of the world’s population is the result of increased life expectancy observed in almost all countries throughout the world. Consequently, a rising tide of ageing-associated disorders, like cancer and neurodegenerative diseases, represents one of the main global challenges of the 21st century. The ability of mankind to overcome these challenges is directly dependent on the capability to develop novel methods for therapy and diagnosis of age-associated diseases. One hallmark of age-related pathologies is an altered tryptophan metabolism. Numerous pathological processes including neurodegenerative and neurological diseases like epilepsy, Parkinson’s and Alzheimer’s diseases, cancer and diabetes exhibit marked changes in tryptophan metabolism. Visualization of key processes of tryptophan metabolic pathways, especially using positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI, can be exploited to early detect the aforementioned disorders with considerable accuracy, allowing appropriate and timely treatment of patients. Here we review the published 11C- and 18F-labelled tryptophans with respect to the production and also preclinical and clinical evaluation as PET-tracers for visualization of different branches of tryptophan metabolism.
The bibliography includes 159 references.
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Epithelial-Mesenchymal Transition Proteins in Neuroendocrine Neoplasms: Differential Immunohistochemical Expression in Different Sites and Correlation with Clinico-Pathological Features. Diagnostics (Basel) 2020; 10:diagnostics10060351. [PMID: 32481578 PMCID: PMC7345712 DOI: 10.3390/diagnostics10060351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/21/2020] [Accepted: 05/25/2020] [Indexed: 11/24/2022] Open
Abstract
The first step leading to metastasis, or for the acquisition of local invasiveness, involves changes in the phenotype of neoplastic cells in the primary tumor. The epithelial–mesenchymal transition (EMT) is a process that determines the acquisition of a form and a transcriptional program that are characteristic of mesenchymal cells, in epithelial cells. The factors involved in this process are E-cadherin and N-cadherin adhesion proteins and some transcription factors such as Slug and Twist. EMT is a site-specific mechanism that is also active in embryogenesis—embryonic cells are affected if invested in certain points, probably due to the signals emanating from the cells or groups of surrounding cells. It is known that neuroendocrine neoplasms have a biological behavior that differs in grading, staging, and site. The aim of our study was to investigate the immunohistochemical expression of EMT factors (Twist, Slug, and E-cadherin) in the neuroendocrine neoplasms of the gastrointestinal tract, the pancreas, and lungs, in 65 cases retrieved from the archives of the Department of Pathology, of three hospitals. The immunoscores were compared in each site and correlated with the clinico-pathological parameters. Statistical evaluation revealed an association between the higher Twist immunoscore and higher grading (p value < 0.0001) and staging (p value = 0.0055). Slug was detected only in pancreatic cases where its reduced expression was associated with a higher grading (p value = 0.0033). This data could be of diagnostic utility in the case of metastases from neuroendocrine neoplasm, to define the site of the primitive tumor when the traditional immunohistochemical panel is not sufficient. In summary, our results indicated, first that the EMT is also an active process in neuroendocrine neoplasms. To the best of our knowledge, this was the first study that evaluated the expression of EMT factors in neuroendocrine neoplasms of different districts.
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25
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Abrantes AM, Pires AS, Monteiro L, Teixo R, Neves AR, Tavares NT, Marques IA, Botelho MF. Tumour functional imaging by PET. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165717. [PMID: 32035103 DOI: 10.1016/j.bbadis.2020.165717] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/15/2020] [Accepted: 01/30/2020] [Indexed: 12/18/2022]
Abstract
Carcinogenesis is a complex multistep process, characterized by changes at different levels, both genetic and epigenetic, which alter cell metabolism. Positron emission tomography (PET) is a very sensitive image modality that allows to evaluate oncometabolism. PET functionalities are immense, since by labelling a molecule that specifically intervenes in a biochemical regulatory pathway of interest with a positron-emitting radionuclide, we can easily image that pathway. Thus, PET makes possible imaging several metabolic processes and assessing risk prediction, screening, diagnosis, response to therapy, metastization and recurrence. In this paper, we provide an overview of different radiopharmaceuticals developed for PET use in oncology, with a focus on brain tumours, breast cancer, hepatocellular carcinoma, neuroendocrine tumours, bladder cancer and prostate cancer because for these cancer types PET has been shown to be valuable. Most of the described tracers are just used in the research environment, with the aim to assess if these tracers could be able to offer an improvement concerning staging/restaging, characterization and stratification of different types of cancer, as well as therapeutic response assessment. In pursuit of personalized therapy, we briefly discuss the more established metabolic tracers and describe recent work on the development of new radiopharmaceuticals, aware that there will continue to exist diagnostic challenges to face modern cancer medicine.
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Affiliation(s)
- Ana Margarida Abrantes
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.
| | - Ana Salomé Pires
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.
| | - Lúcia Monteiro
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ricardo Teixo
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ana Rita Neves
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Project Development Office, Department of Mathematics and Computer Science, Eindhoven University of Technology (TU/e), NL-5612 AE Eindhoven, the Netherlands
| | - Nuno Tiago Tavares
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Inês Alexandra Marques
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Maria Filomena Botelho
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.
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26
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Kamieniarz L, Armeni E, O'Mahony LF, Leigh C, Miah L, Narayan A, Bhatt A, Cox N, Mandair D, Navalkissoor S, Caplin M, Toumpanakis C. Orbital metastases from neuroendocrine neoplasms: clinical implications and outcomes. Endocrine 2020; 67:485-493. [PMID: 31732922 DOI: 10.1007/s12020-019-02130-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 11/01/2019] [Indexed: 02/02/2023]
Abstract
PURPOSE Neuroendocrine neoplasms (NENs) may rarely metastasise to the orbit. Published data on epidemiology, incidence and preferred treatment is limited. We present the largest cohort of symptomatic and asymptomatic NEN patients with orbital metastases and data on epidemiological parameters, symptoms as well as diagnostic/treatment modalities used. METHODS We identified patients from our internal NEN database of patients who had also undergone Gallium68-DOTATATE PET (Ga68-DOTA). The diagnosis of orbital metastatic NEN was made on somatostatin receptor imaging and confirmed on a dedicated MRI of orbits. RESULTS We identified 27 patients of 994 patients evaluated with Ga68-DOTATATE PET imaging during their surveillance monitoring in our department; 15 female, average age at NEN diagnosis 53 years and orbital metastatic NEN diagnosis 59 years. The majority of NEN primaries originated from small bowel (18/27, 66.4%) or pancreas 4/27 (4/27, 14.8%). Hepatic with or without concomitant skeletal metastases were present in 23/27 (85%) of patients. Ocular symptoms and/or signs were evident in 11/27 (41%) of patients. 5/11 symptomatic patients underwent external beam radiotherapy (EBRT) resulting in complete symptoms resolution. The 5-year survival was estimated at 84.1%. CONCLUSIONS Orbital metastases of NEN have a relatively low prevalence, more commonly associated with small bowel primary. Extraocular muscles are primarily affected, irrespectively of liver disease burden. Survival does not seem to be affected. EBRT is an efficacious treatment modality for both symptom relief and tumour growth control. Administration of peptide receptor radionuclide therapy may occasionally induce temporary ocular symptoms, which resolve following treatment with a short course of steroids.
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Affiliation(s)
| | - Eleni Armeni
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, Pond Street, London, NW3 2QG, UK.
| | | | | | | | | | | | | | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
| | | | - Martyn Caplin
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
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Werner RA, Ilhan H, Lehner S, Papp L, Zsótér N, Schatka I, Muegge DO, Javadi MS, Higuchi T, Buck AK, Bartenstein P, Bengel F, Essler M, Lapa C, Bundschuh RA. Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy. Mol Imaging Biol 2019; 21:582-590. [PMID: 30014345 DOI: 10.1007/s11307-018-1252-5] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE Early identification of aggressive disease could improve decision support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-positron emission tomography (PET) before PRRT was analyzed. PROCEDURES Thirty-one patients with G1/G2 pNET were enrolled (G2, n = 23/31). Prior to PRRT with [177Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET computed tomography was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUVmean/max), imaging-based TF, and clinical parameters (Ki67, CgA) for prediction of both progression-free survival (PFS) and overall survival (OS) after PRRT were evaluated. RESULTS Within a median follow-up of 3.7 years, tumor progression was detected in 21 patients (median, 1.5 years) and 13/31 deceased (median, 1.9 years). In ROC analysis, the TF entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff = 6.7, AUC = 0.71, p = 0.02). Of note, increasing entropy could predict a longer survival (> 6.7, OS = 2.5 years, 17/31), whereas less voxel-based derangement portended inferior outcome (< 6.7, OS = 1.9 years, 14/31). These findings were supported in a G2 subanalysis (> 6.9, OS = 2.8 years, 9/23 vs. < 6.9, OS = 1.9 years, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using entropy (n = 31, p < 0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n = 31, p = 0.04). Ki67 was negatively associated with PFS (p = 0.002); however, SUVmean/max failed in prognostication (n.s.). CONCLUSIONS In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
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Affiliation(s)
- Rudolf A Werner
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Harun Ilhan
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Sebastian Lehner
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
- Ambulatory Healthcare Center Dr. Neumaier & Colleagues, Radiology, Nuclear Medicine, Radiation Therapy, Regensburg, Germany
| | - László Papp
- Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Imke Schatka
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Dirk O Muegge
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Mehrbod S Javadi
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Takahiro Higuchi
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
- Department of Bio Medical Imaging, National Cardiovascular and Cerebral Research Center, Suita, Japan
| | - Andreas K Buck
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Peter Bartenstein
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Frank Bengel
- Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany
| | - Markus Essler
- Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - Constantin Lapa
- Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Ralph A Bundschuh
- Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
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Katz LH, Levi Z, Twig G, Kark JD, Leiba A, Derazne E, Liphshiz I, Keinan-Boker L, Eisenstein S, Afek A. Risk factors associated with gastroenteropancreatic neuroendocrine tumors in a cohort of 2.3 million Israeli adolescents. Int J Cancer 2018; 143:1876-1883. [PMID: 29744856 DOI: 10.1002/ijc.31589] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Accepted: 04/16/2018] [Indexed: 12/27/2022]
Abstract
We investigated whether obesity and sociodemographic factors at adolescence are associated with incident gastroenteropancreatic neuroendocrine tumors (GEP-NET).Our cohort included 2.3 million Israeli adolescents examined at ages 16 to 19 years between 1967 and 2010. The baseline database included sex, country of birth, residential socioeconomic status (SES), body-mass index (BMI) and height. Participants were followed through linkage with the National Cancer Registry up to 2012. We identified 221 cases of GEP-NET (66 pancreatic, 52 gastric, 39 rectal, 27 appendiceal, 23 small bowel and 14 colonic). Immigration from the Former Soviet Union (FSU) was associated with the risk of small bowel and rectal NET's, [Hazard Ratio (HR) 4.79, 95% Confidence Interval (CI) 1.37-16.76 and 3.43, 95% CI 1.20-9.83, respectively].Height >75th percentile and BMI ≥ 85th percentile were associated with increased risk of gastric NET (HR 2.25 95% CI 1.14-4.42 and HR 2.38, 95% CI 1.19-4.75, respectively). Female sex was associated with appendiceal NET (HR 2.30, 95% CI 1.06-4.96) while male gender was associated with an increased risk for NET of the small bowel [HR 4.72 (95% CI 1.10-20.41)].In conclusion, our findings suggest different risk factor associations with the various GEP-NETS: immigrants from the FSU were at increased risk for small bowel and rectal NET; increased height and weight were associated with the risk of gastric NET and females were at increased risk for appendiceal NET. Further focus on the FSU population is indicated in addition to studies verifying the association of BMI and height with gastric NET.
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Affiliation(s)
- Lior H Katz
- The Gastroenterology Department, Sheba Medical Center, Tel-Hashomer, Israel
| | - Zohar Levi
- Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel.,The Gastroenterology Department, Rabin Medical Center, Petach Tikva, Israel
| | - Gilad Twig
- Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel.,The Israel Defense Forces Medical Corps.,The Dr. Pinchas Bornstein Talpiot Medical Leadership Program, Sheba Medical Center.,Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel
| | - Jeremy D Kark
- Hebrew University-Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem, Israel
| | - Adi Leiba
- The Israel Defense Forces Medical Corps
| | | | | | | | - Sapir Eisenstein
- Hebrew University-Hadassah School of Medicine, Jerusalem, Israel
| | - Arnon Afek
- Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel.,The general manager office, Tel Hashomer, Israel
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Pedraza-Arévalo S, Gahete MD, Alors-Pérez E, Luque RM, Castaño JP. Multilayered heterogeneity as an intrinsic hallmark of neuroendocrine tumors. Rev Endocr Metab Disord 2018; 19:179-192. [PMID: 30293213 DOI: 10.1007/s11154-018-9465-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Neuroendocrine tumors (NETs) comprise a complex and highly heterogeneous group of neoplasms that can arise all over the body, originating from neuroendocrine cells. NETs are characterized by a general lack of symptoms until they are in advanced phase, and early biomarkers are not as available and useful as required. Heterogeneity is an intrinsic, pivotal feature of NETs that derives from diverse causes and ultimately shapes tumor fate. The different layers that conform NET heterogeneity include a wide range of distinct characteristics, from the mere location of the tumor to its clinical and functional features, and from its cellular properties, to the core signaling and (epi)genetic components defining the molecular signature of the tumor. The importance of this heterogeneity resides in that it translates into a high variability among tumors and, hence, patients, which hinders a more precise diagnosis and prognosis and more efficacious treatment of these diseases. In this review, we highlight the significance of this heterogeneity as an intrinsic hallmark of NETs, its repercussion on clinical approaches and tumor management, and some of the possible factors associated to such heterogeneity, including epigenetic and genetic elements, post-transcriptional regulation, or splicing alterations. Notwithstanding, heterogeneity can also represent a valuable and actionable feature, towards improving medical approaches based on personalized medicine. We conclude that NETs can no longer be viewed as a single disease entity and that their diagnosis, prognosis and treatment must reflect and incorporate this heterogeneity.
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Affiliation(s)
- Sergio Pedraza-Arévalo
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Avenida Menéndez Pidal s/n, Edificio IMIBIC, 14004, Córdoba, Spain
- Department of Cell Biology, Physiology, and Immunology, Universidad de Córdoba, Córdoba, Spain
- Reina Sofia University Hospital, Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain
- Agrifood Campus of International Excellence (ceiA3), Córdoba, Spain
| | - Manuel D Gahete
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Avenida Menéndez Pidal s/n, Edificio IMIBIC, 14004, Córdoba, Spain
- Department of Cell Biology, Physiology, and Immunology, Universidad de Córdoba, Córdoba, Spain
- Reina Sofia University Hospital, Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain
- Agrifood Campus of International Excellence (ceiA3), Córdoba, Spain
| | - Emilia Alors-Pérez
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Avenida Menéndez Pidal s/n, Edificio IMIBIC, 14004, Córdoba, Spain
- Department of Cell Biology, Physiology, and Immunology, Universidad de Córdoba, Córdoba, Spain
- Reina Sofia University Hospital, Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain
- Agrifood Campus of International Excellence (ceiA3), Córdoba, Spain
| | - Raúl M Luque
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Avenida Menéndez Pidal s/n, Edificio IMIBIC, 14004, Córdoba, Spain.
- Department of Cell Biology, Physiology, and Immunology, Universidad de Córdoba, Córdoba, Spain.
- Reina Sofia University Hospital, Córdoba, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
- Agrifood Campus of International Excellence (ceiA3), Córdoba, Spain.
| | - Justo P Castaño
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Avenida Menéndez Pidal s/n, Edificio IMIBIC, 14004, Córdoba, Spain.
- Department of Cell Biology, Physiology, and Immunology, Universidad de Córdoba, Córdoba, Spain.
- Reina Sofia University Hospital, Córdoba, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
- Agrifood Campus of International Excellence (ceiA3), Córdoba, Spain.
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Chan MY, Ma KW, Chan A. Surgical management of neuroendocrine tumor-associated liver metastases: a review. Gland Surg 2018; 7:28-35. [PMID: 29629317 DOI: 10.21037/gs.2017.11.16] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Liver metastasis is common among patients who suffer from neuroendocrine tumors (NETs). Radical surgery is the standard treatment whenever possible but there is still controversies concerning the treatment strategies such as resection of the primary, role of debulking surgery, liver transplantation (LT) and neoadjuvant or adjuvant therapies. This article aims to review the current evidence available, together with some latest updates, focusing on the surgical management.
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Affiliation(s)
- Miu Yee Chan
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Ka Wing Ma
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Albert Chan
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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Huang YQ. Current progress in diagnosis and therapy of neuroendocrine neoplasms of the digestive system. Shijie Huaren Xiaohua Zazhi 2016; 24:2625-2636. [DOI: 10.11569/wcjd.v24.i17.2625] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of heterogeneous, biologically diverse, rare malignancies originated from the peptidergic neurons and neuroendocrine cells. In recent years, the incidence of NENs has been increasing gradually. They typically arise in the pancreas and gastrointestinal tract. Chromogranin A (CgA) has long been used as an important broad-spectrum marker for the identification of NENs. The diagnosis is based on histopathology demonstrating neuroendocrine features such as positive staining for chromogranin A and specific hormones such as gastrin, proinsulin, vasoactive intestinal peptide (VIP) and glucagon. In addition, radiological modalities including computed tomography (CT), positron emission tomography and computed tomography (PET/CT), magnetic resonance imaging (MRI), ultrasound (US), endoscopic ultrasound (EUS), and somatostatin receptor scintigraphy (SRS) can help establish a diagnosis. Surgery is still one of the cornerstones in the management of NENs. This article reviews the current progress in the diagnosis and therapy of NENs of the digestive system, including the pathological features and clinical diagnostic modalities for primary esophageal, gastric, duodenal, small intestinal, appendiceal, colonic, rectal, hepatic, gallbladder, extrahepatic bile duct, and pancreatic NENs, according to a revised system of classification, nomenclature and grading of NENs proposed by the fourth edition of "World Health Organization (WHO) classification of tumours of the digestive system" in 2010, and consensus of diagnosis and treatment of gastroenteropancreatic NENs (GEP-NENs) proposed by the Chinese Society of Clinical Oncology (CSCO) in 2013.
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