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Pavlidis ET, Galanis IN, Pavlidis TE. Critical considerations for the management of gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms and pure neuroendocrine carcinomas. World J Gastrointest Oncol 2024; 16:4559-4564. [PMID: 39678788 PMCID: PMC11577359 DOI: 10.4251/wjgo.v16.i12.4559] [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: 08/10/2024] [Revised: 09/25/2024] [Accepted: 10/18/2024] [Indexed: 11/12/2024] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal (GI) tract and have high degrees of malignancy, and the frequency of these tumors has been increasing. They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis. The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms, which are generally slow-growing lesions. The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal, followed by gastric, mainly in the gastroesophageal junction. Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis. Liquid biopsy may contribute to early detection and timely diagnosis. Ultrasonography, either endoscopic or abdominal, is a technique that contributes to a diagnosis; additionally, contrast-enhanced ultrasonography is very helpful in follow-up appointments. Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67. The genetic profile can be valuable in diagnosis and gene therapy. Surgical resection with wide lymphadenectomy, whenever possible, and adjuvant chemotherapy constitute the main therapeutic management strategies. Targeted therapy and immunotherapy achieve encouraging results.
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Affiliation(s)
- Efstathios T Pavlidis
- The 2nd Department of Propaedeutic Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Ioannis N Galanis
- The 2nd Department of Propaedeutic Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Theodoros E Pavlidis
- The 2nd Department of Propaedeutic Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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Saegusa Y, Akabane S, Shimomura M, Okuda H, Yano T, Mochizuki T, Inoue W, Yamaguchi M, Yamaguchi S, Sentani K, Yamauchi M, Tokumo K, Ohdan H. Successful outcome achieved with adjuvant chemotherapy with irinotecan plus cisplatin in rectal neuroendocrine carcinoma: a case report. Surg Case Rep 2024; 10:220. [PMID: 39294428 PMCID: PMC11411022 DOI: 10.1186/s40792-024-02010-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 08/26/2024] [Indexed: 09/20/2024] Open
Abstract
BACKGROUND Rectal neuroendocrine carcinomas (NECs) are rare and associated with poorer prognoses compared to conventional adenocarcinomas. The efficacy of adjuvant chemotherapy for resectable rectal NECs remains uncertain. Herein, we present a case of rectal NEC successfully treated with postoperative chemotherapy using irinotecan plus cisplatin. CASE PRESENTATION A 48-year-old woman with a history of endometrial cancer presented with an intramural rectal tumour detected on follow-up imaging. Colonoscopy revealed a 30 mm submucosal tumour, and laparoscopic low anterior resection was performed. Histopathological examination showed poorly differentiated atypical cells with solid growth patterns. Metastasis from the uterine cancer was ruled out due to histological differences between the primary uterine tumour and the rectal lesion, as well as the absence of hormone receptor immunohistochemical expression. Further immunohistochemical analysis revealed diffuse CD56 positivity, a high mitotic rate (> 20/10 high power fields) and a Ki-67 labelling index exceeding 70%. Based on these findings, a diagnosis of rectal NEC, T3N0M0, Stage IIB (UICC 8th edition), was established. Given the aggressive nature of the tumour evidenced by a high Ki-67 labelling index, adjuvant chemotherapy comprising six cycles of irinotecan plus cisplatin was administered to mitigate the risk of recurrence. At the 3-year follow-up, the patient was free of disease recurrence. CONCLUSION This case highlights the importance of multidisciplinary surgical interventions followed by adjuvant chemotherapy in managing rectal NECs.
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Affiliation(s)
- Yoshitaka Saegusa
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shintaro Akabane
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
| | - Manabu Shimomura
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Okuda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Takuya Yano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tetsuya Mochizuki
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Wako Inoue
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Mizuki Yamaguchi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shinji Yamaguchi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Clinical Oncology, Hiroshima University Hospital, Hiroshima, Japan
| | - Kentaro Tokumo
- Department of Clinical Oncology, Hiroshima University Hospital, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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Gefen R, Emile SH, Horesh N, Garoufalia Z, Freund MR, Wexner SD. When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database. Tech Coloproctol 2024; 28:56. [PMID: 38772962 PMCID: PMC11108916 DOI: 10.1007/s10151-024-02927-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 04/03/2024] [Indexed: 05/23/2024]
Abstract
BACKGROUND Rectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy. METHODS A retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004-2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group. RESULTS A total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006). CONCLUSIONS Neoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.
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Affiliation(s)
- R Gefen
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Department of General Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - S H Emile
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Colorectal Surgery Unit, Mansoura University Hospital, Mansoura University, Mansoura, Egypt
| | - N Horesh
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Department of Surgery and Transplantations, Sheba Medical Center, Ramat Gan, Israel
| | - Z Garoufalia
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
| | - M R Freund
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA
- Department of General Surgery, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - S D Wexner
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA.
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Chacchi-Cahuin R, Despott EJ, Lazaridis N, Rimondi A, Fusai GK, Mandair D, Anderloni A, Sciola V, Caplin M, Toumpanakis C, Murino A. Endoscopic Management of Gastro-Entero-Pancreatic Neuroendocrine Tumours: An Overview of Proposed Resection and Ablation Techniques. Cancers (Basel) 2024; 16:352. [PMID: 38254841 PMCID: PMC10814323 DOI: 10.3390/cancers16020352] [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: 11/22/2023] [Revised: 01/06/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
A literature search of MEDLINE/PUBMED was conducted with the aim to highlight current endoscopic management of localised gastro-entero-pancreatic NETs. Relevant articles were identified through a manual search, and reference lists were reviewed for additional articles. The results of the research have been displayed in a narrative fashion to illustrate the actual state-of-the-art of endoscopic techniques in the treatment of NETs. Localised NETs of the stomach, duodenum and rectum can benefit from advanced endoscopic resection techniques (e.g., modified endoscopic mucosal resection, endoscopic full thickness resection, endoscopic submucosal dissection) according to centre expertise. Radiofrequency thermal ablation can be proposed as an alternative to surgery in selected patients with localised pancreatic NETs.
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Affiliation(s)
- Rocio Chacchi-Cahuin
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Edward J. Despott
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Nikolaos Lazaridis
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Alessandro Rimondi
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Giuseppe Kito Fusai
- Department of HPB Surgery and Liver Transplant, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Valentina Sciola
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy;
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Alberto Murino
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
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Al-Toubah T, Strosberg J, Hallanger-Johnson J, El-Haddad G. Targeted radionuclide therapy in endocrine-related cancers: advances in the last decade. Front Endocrinol (Lausanne) 2023; 14:1187870. [PMID: 38053729 PMCID: PMC10694449 DOI: 10.3389/fendo.2023.1187870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 10/26/2023] [Indexed: 12/07/2023] Open
Abstract
Targeted radionuclide therapy plays an increasingly important role in managing endocrine-related tumors and significantly advances the therapeutic landscape for patients with these diseases. With increasing FDA-approved therapies and advances in the field, come an increased knowledge of the potential for long-term toxicities associated with these therapies and the field must develop new strategies to increase potency and efficacy while individualizing the selection of patients to those most likely to respond to treatment. Novel agents and modalities of therapy are also being explored. This review will discuss the current landscape and describe the avenues for growth in the field currently being explored.
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Affiliation(s)
- Taymeyah Al-Toubah
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
| | - Jonathan Strosberg
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
| | - Julie Hallanger-Johnson
- Department of Head and Neck - Endocrine Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
| | - Ghassan El-Haddad
- Department of Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
- Department of Nuclear Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
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Duan X, Zhao M, Yin X, Mi L, Shi J, Li N, Han X, Han G, Wang J, Hou J, Yin F. Molecular typing and mutational characterization of rectal neuroendocrine neoplasms. Cancer Med 2023; 12:16207-16220. [PMID: 37387515 PMCID: PMC10469650 DOI: 10.1002/cam4.6281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 06/03/2023] [Accepted: 06/12/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. METHODS The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets. RESULTS C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFβ signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000). CONCLUSIONS This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.
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Affiliation(s)
- Xiaoling Duan
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Man Zhao
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Xiaolei Yin
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Lili Mi
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Jianfei Shi
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Ning Li
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Xin Han
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Guangjie Han
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Jinfeng Wang
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Jiaojiao Hou
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Fei Yin
- Department of GastroenterologyThe Fourth Affiliated Hospital of Hebei Medical UniversityShijiazhuangChina
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Sorbye H, Grande E, Pavel M, Tesselaar M, Fazio N, Reed NS, Knigge U, Christ E, Ambrosini V, Couvelard A, Tiensuu Janson E. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for digestive neuroendocrine carcinoma. J Neuroendocrinol 2023; 35:e13249. [PMID: 36924180 DOI: 10.1111/jne.13249] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 02/20/2023] [Accepted: 02/20/2023] [Indexed: 03/06/2023]
Abstract
This ENETS guidance paper, developed by a multidisciplinary working group, provides up-to-date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11-12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first-line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second-line treatment. Immunotherapy plays a minor role in biomarker-unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease.
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Affiliation(s)
- Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital and Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Enrique Grande
- Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Margot Tesselaar
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | | | - Ulrich Knigge
- Departments of Surgery and Clinical Endocrinology, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Emanuel Christ
- Department of Endocrinology, Diabetes and Metabolism, ENETS Center of Excellence, University Hospital of Basel, Basel, Switzerland
| | - Valentina Ambrosini
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Anne Couvelard
- Department of Pathology, AP-HP Bichat Hospital, Université Paris Cité, Paris, France
| | - Eva Tiensuu Janson
- Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden
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Pavlidis ET, Pavlidis TE. Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update. World J Clin Cases 2022; 10:9573-9587. [PMID: 36186187 PMCID: PMC9516923 DOI: 10.12998/wjcc.v10.i27.9573] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/16/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
The prevalence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing, and despite recent advances in their therapy, it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors. These tumors present many challenges concerning the molecular basis and genomic profile, pathophysiology, clinicopathological features, histopathologic classification, diagnosis and treatment. There has been an ongoing debate on diagnostic criteria and clinical behavior, and various changes have been made over the last few years. Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors (NETs). The diagnosis and management have changed over the past decade. Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools. Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents (64Cu-DOTATATE or 68Ga-DOTATATE) replacing enough octreoscan, has improved further the current diagnostic imaging. Promising results provide targeted therapies with biological agents, new drugs, chemotherapy and immunotherapy. However, the role of surgery is important, since it is the cornerstone of management. Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge. Endoscopy offers novel options not only for diagnosis but also for interventional management. The therapeutic option should be individualized based on current multidisciplinary information.
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Affiliation(s)
- Efstathios Theodoros Pavlidis
- Department of 2nd Surgical Propedeutic, Hippocration Hospital, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
| | - Theodoros Efstathios Pavlidis
- Department of 2nd Surgical Propedeutic, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
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