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Ravizza D, Giunta M, Sala I, Bagnardi V, Tamayo D, de Roberto G, Trovato C, Bravi I, Soru P, Maregatti M, Pisa E, Bertani E, Bonomo G, Spada F, Nicola F. Gastric neuroendocrine tumors: 20-Year experience in a reference center. J Neuroendocrinol 2024; 36:e13440. [PMID: 39191460 DOI: 10.1111/jne.13440] [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: 04/11/2024] [Revised: 07/17/2024] [Accepted: 07/29/2024] [Indexed: 08/29/2024]
Abstract
Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (p value = .50) and complications rate (p value = .084). The median follow-up period was 5.8 years (range: 0.3-20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (p value = .006) and had larger lesions (p value <.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM. CLINICAL TRIAL REGISTRATION: Project code UID 2854.
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Affiliation(s)
- Davide Ravizza
- Division of Endoscopy, European Institute of Oncology, IRCCS, Milan, Italy
| | - Mariangela Giunta
- Division of Endoscopy, European Institute of Oncology, IRCCS, Milan, Italy
| | - Isabella Sala
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
| | - Darina Tamayo
- Data Management-Clinical Trial Office, Scientific Direction, European Institute of Oncology, IRCCS, Milan, Italy
| | | | - Cristina Trovato
- Division of Endoscopy, European Institute of Oncology, IRCCS, Milan, Italy
| | - Ivana Bravi
- Division of Endoscopy, European Institute of Oncology, IRCCS, Milan, Italy
| | - Pietro Soru
- Division of Endoscopy, European Institute of Oncology, IRCCS, Milan, Italy
| | | | - Eleonora Pisa
- Division of Pathology, European Institute of Oncology, IRCCS, Milan, Italy
| | - Emilio Bertani
- Digestive Surgery, European Institute of Oncology, IRCCS, Milan, Italy
| | - Guido Bonomo
- Division of Interventional Radiology, European Institute of Oncology, IRCCS, Milan, Italy
| | - Francesca Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy
| | - Fazio Nicola
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy
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Cavalcoli F, Rausa E, Ferrari D, Rosa R, Maccauro M, Pusceddu S, Sabella G, Cantù P, Vitellaro M, Coppa J, Mazzaferro V. Pathological Characteristics, Management, and Prognosis of Rectal Neuroendocrine Tumors: A Retrospective Study from a Tertiary Hospital. Diagnostics (Basel) 2024; 14:1881. [PMID: 39272666 PMCID: PMC11394532 DOI: 10.3390/diagnostics14171881] [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: 06/13/2024] [Revised: 08/22/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Rectal neuroendocrine tumors (rNENs) are rare, constituting 1-2% of rectal tumors, and are often asymptomatic, leading to challenges in early diagnosis. Current management guidelines recommend endoscopic resection for small lesions and surgical intervention for larger or high-risk tumors. This study aims to retrospectively analyze the pathological characteristics, management, and prognosis of rNEN patients. METHODS Data from the Neuroendocrine Tumor Registry at a tertiary hospital in Milan, Italy from 2005 to 2023 were retrospectively analyzed. Patient demographics, disease characteristics, pathology findings, treatment details, and surveillance data were collected. Statistical analyses included descriptive statistics, multivariable binary logistic regression, and Kaplan-Meier survival analysis. RESULTS Forty-five patients were included, 53.3% male with a mean age of 57.5 years. Most patients were asymptomatic, with incidental diagnosis during colonoscopy. Endoscopic excision was the primary treatment modality (77.8%), with surgical resection reserved for incomplete or inappropriate endoscopic resections. Disease progression occurred in 13 patients (28.9%), with tumor-related mortality of 22.2%. Kaplan-Meier analysis showed 5- and 10-year survival rates of 68.8% and 59.1%, respectively, with corresponding progression-free survival rates of 72.8% and 54.0%. Tumor stage was significantly associated with disease progression on multivariable analysis (OR = 7.230, p = 0.039). CONCLUSIONS This study highlights the heterogeneous presentation and prognosis of rNENs, with a substantial proportion diagnosed incidentally. Endoscopic management was predominantly utilized, aligning with current guidelines for localized tumors. Tumor stage emerged as a significant predictor of disease progression, emphasizing the importance of accurate staging for optimal management. Further research is warranted to refine management protocols and validate these findings.
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Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Davide Ferrari
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Roberto Rosa
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Marco Maccauro
- Departement of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Giovanna Sabella
- Department of the Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Paolo Cantù
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Jorgelina Coppa
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
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Serafin M, Jabłońska B, Senderek E, Majewska K, Mrowiec S. The Clinicopathological Characteristics and Surgical Treatment of Gastrointestinal Neuroendocrine Neoplasm-A 10-Year Single-Center Experience. J Clin Med 2024; 13:4892. [PMID: 39201037 PMCID: PMC11355324 DOI: 10.3390/jcm13164892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Gastrointestinal neuroendocrine neoplasms (GI-NENs) represent a diverse group of tumors, with surgical resection being the gold standard for treatment. Materials and Methods: A retrospective analysis was conducted on 63 patients (32 women, 31 men) who underwent surgery for GI-NENs at the Department of Digestive Tract Surgery from January 2013 to June 2023. Tumors were classified by stage (localized, regionally advanced, metastatic). Results: Clinical symptoms were reported by 42 (66.7%) patients, with abdominal pain being the most common symptom, affecting 28 (44.4%) patients. The majority of tumors (44, 69.8%) originated in the midgut. The most frequently performed surgery was right hemicolectomy, carried out on 33 (52.4%) patients. Radical tumor resection was performed in 35 (55.6%) patients. Postoperative complications occurred in 12 (19%) patients, with male gender identified as an independent predictive factor for complications (p = 0.04). Non-functioning tumors were more common (33, 52.4%), and most tumors were classified as grade 1 histopathologically (49, 77.8%). Distant metastases were present in 29 (46%) patients. The overall two-year survival rate was 94.9%, with a five-year survival rate also estimated at 94.9%. Conclusions: GI-NENs are often diagnosed at advanced stages, frequently with distant or lymph node metastases, and predominantly arise in the midgut. Despite low postoperative morbidity and mortality, male gender may be a predictor of postoperative complications. Overall, the prognosis for GI-NENs is favorable, reflected in high overall survival rates.
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Affiliation(s)
- Michał Serafin
- Student Scientific Society, Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (M.S.); (E.S.)
| | - Beata Jabłońska
- Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (K.M.); (S.M.)
| | - Emila Senderek
- Student Scientific Society, Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (M.S.); (E.S.)
| | - Karolina Majewska
- Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (K.M.); (S.M.)
| | - Sławomir Mrowiec
- Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (K.M.); (S.M.)
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Dell’Unto E, Marasco M, Mosca M, Gallo C, Esposito G, Rinzivillo M, Pilozzi E, Orrù F, Campana D, Massironi S, Annibale B, Panzuto F. Clinical Outcome of Patients with Gastric, Duodenal, or Rectal Neuroendocrine Tumors after Incomplete Endoscopic Resection. J Clin Med 2024; 13:2535. [PMID: 38731064 PMCID: PMC11084244 DOI: 10.3390/jcm13092535] [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: 03/18/2024] [Revised: 04/16/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
Objectives: Our aim was to investigate the clinical outcome of patients with well-differentiated gastric, duodenal, and rectal neuroendocrine tumors after treatment with incomplete endoscopic resection due to the finding of microscopic positive resection margins (R1). Methods: This is a retrospective analysis of consecutive patients with type 1 gastric, non-ampullary non-functioning duodenal, or rectal neuroendocrine neoplasms with positive R1 margins after endoscopic resection. The rate of tumor recurrence and progression-free survival were considered to be the study's main endpoints. Statistical analysis was performed using MedCalc® v.17 software and a p-value of <0.05 was considered significant. A Cox proportional-hazard regression was performed to identify risk factors for disease recurrence/progression. Results: After evaluating 110 patients, a total of 58 patients were included in the final analysis (15 gastric NENs, 12 duodenal NENs, and 31 rectal NENs). After evidence of endoscopic R1 resection had been gathered, 26 patients (44.8%) underwent an endoscopic/surgical extension of the previous resection. Tumor progression (all local recurrences) occurred in five out of fifty-eight patients (8.6%) with a median PFS of 36 months. There were no tumor-related deaths. G2 grading and the gastric primary tumor site were the only features significantly associated with the risk of recurrence of the disease (HR: 11.97 [95% CI: 1.22-116.99], HR: 12.54 [95% CI: 1.28-122.24], respectively). Conclusions: Tumor progression rarely occurs in patients with microscopic positive margin excision (R1) after endoscopic resection and does not seem to affect patients' clinical outcomes.
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Affiliation(s)
- Elisabetta Dell’Unto
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence or Rome, 00189 Rome, Italy; (E.D.); (M.M.); (G.E.); (M.R.); (B.A.)
- Department of Medical, Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy
| | - Matteo Marasco
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence or Rome, 00189 Rome, Italy; (E.D.); (M.M.); (G.E.); (M.R.); (B.A.)
- Department of Medical, Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy
- PhD School in Translational Medicine and Oncology, Sapienza University of Rome, 00189 Rome, Italy
| | - Mirta Mosca
- Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy; (M.M.); (D.C.)
- Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria of Bologna, 40138 Bologna, Italy
| | - Camilla Gallo
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (C.G.); (S.M.)
| | - Gianluca Esposito
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence or Rome, 00189 Rome, Italy; (E.D.); (M.M.); (G.E.); (M.R.); (B.A.)
- Department of Medical, Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence or Rome, 00189 Rome, Italy; (E.D.); (M.M.); (G.E.); (M.R.); (B.A.)
| | - Emanuela Pilozzi
- Department of Clinical and Molecular Medicine, UOC Anatomic Pathology, Sant’Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy; (E.P.); (F.O.)
| | - Federica Orrù
- Department of Clinical and Molecular Medicine, UOC Anatomic Pathology, Sant’Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy; (E.P.); (F.O.)
| | - Davide Campana
- Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy; (M.M.); (D.C.)
- Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria of Bologna, 40138 Bologna, Italy
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (C.G.); (S.M.)
| | - Bruno Annibale
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence or Rome, 00189 Rome, Italy; (E.D.); (M.M.); (G.E.); (M.R.); (B.A.)
- Department of Medical, Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence or Rome, 00189 Rome, Italy; (E.D.); (M.M.); (G.E.); (M.R.); (B.A.)
- Department of Medical, Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy
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Gopakumar H, Jahagirdar V, Koyi J, Dahiya DS, Goyal H, Sharma NR, Perisetti A. Role of Advanced Gastrointestinal Endoscopy in the Comprehensive Management of Neuroendocrine Neoplasms. Cancers (Basel) 2023; 15:4175. [PMID: 37627203 PMCID: PMC10453187 DOI: 10.3390/cancers15164175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 08/15/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Neuroendocrine neoplasms (NENs), also called neuroendocrine tumors (NETs), are relatively uncommon, heterogenous tumors primarily originating in the gastrointestinal tract. With the improvement in technology and increasing use of cross-sectional imaging and endoscopy, they are being discovered with increasing frequency. Although traditionally considered indolent tumors with good prognoses, some NENs exhibit aggressive behavior. Timely diagnosis, risk stratification, and management can often be a challenge. In general, small NENs without local invasion or lymphovascular involvement can often be managed using minimally invasive advanced endoscopic techniques, while larger lesions and those with evidence of lymphovascular invasion require surgery, systemic therapy, or a combination thereof. Ideal management requires a comprehensive and accurate understanding of the stage and grade of the tumor. With the recent advancements, a therapeutic advanced endoscopist can play a pivotal role in diagnosing, staging, and managing this rare condition. High-definition white light imaging and digital image enhancing technologies like narrow band imaging (NBI) in the newer endoscopes have improved the diagnostic accuracy of traditional endoscopy. The refinement of endoscopic ultrasound (EUS) over the past decade has revolutionized the role of endoscopy in diagnosing and managing various pathologies, including NENs. In addition to EUS-directed diagnostic biopsies, it also offers the ability to precisely assess the depth of invasion and lymphovascular involvement and thus stage NENs accurately. EUS-directed locoregional ablative therapies are increasingly recognized as highly effective, minimally invasive treatment modalities for NENs, particularly pancreatic NENs. Advanced endoscopic resection techniques like endoscopic submucosal dissection (ESD), endoscopic submucosal resection (EMR), and endoscopic full-thickness resection (EFTR) have been increasingly used over the past decade with excellent results in achieving curative resection of various early-stage gastrointestinal luminal lesions including NENs. In this article, we aim to delineate NENs of the different segments of the gastrointestinal (GI) tract (esophagus, gastric, pancreatic, and small and large intestine) and their management with emphasis on the endoscopic management of these tumors.
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Affiliation(s)
- Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA;
| | - Vinay Jahagirdar
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; (V.J.); (J.K.)
| | - Jagadish Koyi
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; (V.J.); (J.K.)
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, USA;
| | - Hemant Goyal
- Department of Surgery, Center for Interventional Gastroenterology at UT (iGUT), The University of Texas Health Science Center, Houston, TX 77054, USA;
| | - Neil R. Sharma
- Advanced Interventional Endoscopy & Endoscopic Oncology (IOSE) Division, GI Oncology Tumor Site Team, Parkview Cancer Institute, 11104 Parkview Circle, Suite 310, Fort Wayne, IN 46845, USA;
| | - Abhilash Perisetti
- Division of Gastroenterology and Hepatology, Kansas City Veteran Affairs, Kansas City, MO 64128, USA
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Esposito G, Dell'Unto E, Ligato I, Marasco M, Panzuto F. The meaning of R1 resection after endoscopic removal of gastric, duodenal and rectal neuroendocrine tumors. Expert Rev Gastroenterol Hepatol 2023; 17:785-793. [PMID: 37497604 DOI: 10.1080/17474124.2023.2242261] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/26/2023] [Accepted: 07/25/2023] [Indexed: 07/28/2023]
Abstract
INTRODUCTION Well-differentiated gastric, duodenal, and rectal neuroendocrine neoplasms (NETs) are rare diseases usually managed by endoscopic treatment. Although several endoscopic techniques are available, the number of patients with incomplete (R1) resection is significant. AREAS COVERED This review focuses on the meaning of incomplete R1 findings after endoscopic resection in type I gastric NETs; nonfunctioning, non-ampullary duodenal NETs; and small rectal NETs. Data were identified by MEDLINE database search without publication date limitation. EXPERT OPINION An incomplete R1 finding may have no significant impact on a patient's clinical outcome, particularly in small G1 type I gastric NETs, which have an indolent course. A 'stepwise approach,' which uses more advanced endoscopic techniques, or minimally invasive surgery may be justified to achieve complete margin-free resection. This approach must balance the tumor features and the procedure-related risk of complications, particularly in the duodenum, where the role of deep endoscopic resections is limited due to the thin duodenal wall. Gastric and rectal NETs that are incompletely removed after initial resection are more easily amenable to deep endoscopic techniques. However, this might not be necessary for patients with comorbidities, elderly, or both due to the uncertainty of how R1 finding impacts a patient's clinical outcome.
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Affiliation(s)
- Gianluca Esposito
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Elisabetta Dell'Unto
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Irene Ligato
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Matteo Marasco
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Francesco Panzuto
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
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Chetcuti Zammit S, Sidhu R. Small bowel neuroendocrine tumours - casting the net wide. Curr Opin Gastroenterol 2023; 39:200-210. [PMID: 37144538 DOI: 10.1097/mog.0000000000000917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
PURPOSE OF REVIEW Our aim is to provide an overview of small bowel neuroendocrine tumours (NETs), clinical presentation, diagnosis algorithm and management options. We also highlight the latest evidence on management and suggest areas for future research. RECENT FINDINGS Dodecanetetraacetic acid (DOTATATE) scan can detect NETs with an improved sensitivity than when compared with an Octreotide scan. It is complimentary to small bowel endoscopy that provides mucosal views and allows the delineation of small lesions undetectable on imaging. Surgical resection is the best management modality even in metastatic disease. Prognosis can be improved with the administration of somatostatin analogues and Evarolimus as second-line therapies. SUMMARY NETs are heterogenous tumours affecting most commonly the distal small bowel as single or multiple lesions. Their secretary behaviour can lead to symptoms, most commonly diarrhoea and weight loss. Metastases to the liver are associated with carcinoid syndrome.
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Affiliation(s)
| | - Reena Sidhu
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, Sheffield, UK
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Metastasis Prevalence and Survival of Patients with T1-2 Gastric Neuroendocrine Tumor Treated with Endoscopic Therapy and Surgery. Dig Dis Sci 2022; 67:3228-3238. [PMID: 34272627 DOI: 10.1007/s10620-021-07143-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 06/21/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM The selection criteria and long-term outcomes of endoscopic therapy (ET) for gastric neuroendocrine tumors (G-NETs) remain controversial. METHODS Using Surveillance, Epidemiology, and End Results (SEER) Program database, we assessed the prevalence of metastasis of early G-NETs and long-term outcomes of ET in G-NET patients with good/moderate differentiation and no muscularis propria (MP) involvement. RESULTS A total of 2207 patients with stage T1 and T2 G-NETs were included. The depth of invasion into MP [odds ratio (OR) 4.581, 95% confidence interval (CI) 2.571-8.162; P < 0.001] and size of > 20 mm (OR 5.656, 95% CI 2.002-15.975; P = 0.001) were significantly associated with metastasis. The 5-year overall survival (OS) and cancer-specific survival (CSS) of the ET group were similar to the surgery group (91.11% vs. 91.09%, P = 0.750; 99.26% vs. 99.01%, P = 0.173). In the multivariable Cox proportional hazards regression models adjusting for age, gender, race, year of diagnosis, SEER region, depth of tumor invasion, site of cancer, tumor size, and chemotherapy, procedures employed (ET or surgery) had no significant impact on the OS [hazard ratio (HR) 1.189; 95%CI 0.721-1.961; P = 0.498] and CSS (HR 0.684; 95% CI 0.021-22.727; P = 0.832). CONCLUSIONS The long-term outcome of survival did not appear to differ between ET and surgery in G-NETs with good/moderate differentiation, ≤ 20 mm size, and no MP involvement.
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Survival effects of primary and metastatic surgical treatment in metastatic small intestinal tumors: A propensity score–matching study. PLoS One 2022; 17:e0270608. [PMID: 35749551 PMCID: PMC9231803 DOI: 10.1371/journal.pone.0270608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/13/2022] [Indexed: 11/25/2022] Open
Abstract
Objective To analyze the effects of primary tumor resection and metastatic lesion resection on the survival of metastatic small intestinal tumors. Methods The research subjects were patients with metastatic small bowel tumors identified from 2004 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching and Kaplan–Meier analyses were performed to analyze the effect of surgery on the prognosis. Results A total of 4,034 patients from the SEER database were analyzed. Both before and after the propensity score–matching analysis, the prognosis of patients who underwent primary tumor surgery and metastatic surgery was better than that of patients who did not undergo surgery; all were patients with metastatic small bowel adenocarcinoma (mSIA) or metastatic small intestinal neuroendocrine tumors (mSI-NETs) (all p < .005). Patients with mSIA and adequate lymph node dissection had a longer prognosis than mSIA patients with inadequate lymph node dissection, but this survival benefit was not present in mSI-NET patients. It made no difference in the prognosis of mSIA and mSI-NETs whether localized surgery or intestine-ectomy was performed. Patients with mSIA who underwent primary and metastatic excision plus chemotherapy had the best overall survival and cancer-specific survival rates, whereas mSI-NET patients who underwent primary and metastatic excision had the best overall survival and cancer-specific survival rates (all p < .001). Conclusion In these carefully selected patients, primary tumor resection and/or metastatic lesion resection significantly improved the survival rates for patients with mSIA and mSI-NETs. The mSIA patients with resectable primary tumors seemed to require a sufficient number of lymph node dissections more than the patients with well-differentiated mSI-NETs.
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Risk factors for metastasis and survival of patients with T1 gastric neuroendocrine carcinoma treated with endoscopic therapy versus surgical resection. Surg Endosc 2022; 36:6162-6169. [PMID: 35507062 PMCID: PMC9283353 DOI: 10.1007/s00464-022-09190-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 03/07/2022] [Indexed: 11/16/2022]
Abstract
Background Gastrectomy with lymphadenectomy is recommended for early gastric Neuroendocrine carcinoma (G-NEC). We attempted to determine the prevalence and risk factors of metastasis of T1 G-NEC and compare the long-term survival of patients after receiving endoscopic therapy (ET) and radical surgery. Methods In this study, 205 patients in total with T1 G-NEC were collected from the Surveillance Epidemiology and End Result database. Independent predictors of metastasis were identified by Logistic regression analysis, followed by the calculation of both cancer-specific survival (CSS) and overall survival (OS). Results Twenty-five patients (12.2%) were burdened with metastasis at initial diagnosis, with a prevalence of 5.2% (3/58) in mucosa lesions and 16.2% (16/99) in submucosa lesions (P = 0.045). No metastasis was detected in lesions with mucosa involvement and tumors ≦ 20 mm (0%, 0/49). The most significant risk factor for metastasis was tumors > 20 mm [odds ratio (OR) 18.64; 95% confidence interval (CI) 4.01–86.68; P < 0.001]. For patients with T1N0M0 G-NEC who received ET or surgery, the 10-year OS was similar between the mucosa extension and submucosa extension groups, which was 91.56% in ET group vs 87.50% in surgery group (P = 0.62) and 57.33% vs 77.83% (P = 0.11), respectively. In addition, the 10-year CSS was also similar between the mucosa extension and submucosa extension groups with 97.30% in ET vs 100% in surgery (P = 0.51) and 97.62% vs 86.49% (P = 0.65). Conclusions In G-NEC, tumors > 20 mm were considered as the most significant risk factor for metastasis. ET seemed adequate for the lesions with mucosa involvement and size ≦ 2 cm.
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11
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Deprez PH, Moons LMG, OʼToole D, Gincul R, Seicean A, Pimentel-Nunes P, Fernández-Esparrach G, Polkowski M, Vieth M, Borbath I, Moreels TG, Nieveen van Dijkum E, Blay JY, van Hooft JE. Endoscopic management of subepithelial lesions including neuroendocrine neoplasms: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2022; 54:412-429. [PMID: 35180797 DOI: 10.1055/a-1751-5742] [Citation(s) in RCA: 171] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
1: ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape), but EUS alone is not able to distinguish among all types of SEL.Strong recommendation, moderate quality evidence. 2: ESGE suggests providing tissue diagnosis for all SELs with features suggestive of gastrointestinal stromal tumor (GIST) if they are of size > 20 mm, or have high risk stigmata, or require surgical resection or oncological treatment.Weak recommendation, very low quality evidence. 3: ESGE recommends EUS-guided fine-needle biopsy (EUS-FNB) or mucosal incision-assisted biopsy (MIAB) equally for tissue diagnosis of SELs ≥ 20 mm in size.Strong recommendation, moderate quality evidence. 4: ESGE recommends against surveillance of asymptomatic gastrointestinal (GI) tract leiomyomas, lipomas, heterotopic pancreas, granular cell tumors, schwannomas, and glomus tumors, if the diagnosis is clear.Strong recommendation, moderate quality evidence. 5: ESGE suggests surveillance of asymptomatic esophageal and gastric SELs without definite diagnosis, with esophagogastroduodenoscopy (EGD) at 3-6 months, and then at 2-3-year intervals for lesions < 10 mm in size, and at 1-2-year intervals for lesions 10-20 mm in size. For asymptomatic SELs > 20 mm in size that are not resected, ESGE suggests surveillance with EGD plus EUS at 6 months and then at 6-12-month intervals.Weak recommendation, very low quality evidence. 6: ESGE recommends endoscopic resection for type 1 gastric neuroendocrine neoplasms (g-NENs) if they grow larger than 10 mm. The choice of resection technique should depend on size, depth of invasion, and location in the stomach.Strong recommendation, low quality evidence. 7: ESGE suggests considering removal of histologically proven gastric GISTs smaller than 20 mm as an alternative to surveillance. The decision to resect should be discussed in a multidisciplinary meeting. The choice of technique should depend on size, location, and local expertise.Weak recommendation, very low quality evidence. 8: ESGE suggests that, to avoid unnecessary follow-up, endoscopic resection is an option for gastric SELs smaller than 20 mm and of unknown histology after failure of attempts to obtain diagnosis.Weak recommendation, very low quality evidence. 9: ESGE recommends basing the surveillance strategy on the type and completeness of resection. After curative resection of benign SELs no follow-up is advised, except for type 1 gastric NEN for which surveillance at 1-2 years is advised.Strong recommendation, low quality evidence. 10: For lower or upper GI NEN with a positive or indeterminate margin at resection, ESGE recommends repeating endoscopy at 3-6 months and another attempt at endoscopic resection in the case of residual disease.Strong recommendation, low quality evidence.
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Affiliation(s)
- Pierre H Deprez
- Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Leon M G Moons
- Divisie Interne Geneeskunde en Dermatologie, Maag-, Darm- en Leverziekten, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands
| | - Dermot OʼToole
- Neuroendocrine Tumor Service, ENETS Centre of Excellence, St. Vincent's University Hospital and Department of Clinical Medicine, Trinity College Dublin, University of Dublin St. James's Hospital, Dublin, Ireland
| | - Rodica Gincul
- Service de Gastroentérologie et Endoscopie Digestive, Hôpital Privé Jean Mermoz, Lyon, France
| | - Andrada Seicean
- Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Pedro Pimentel-Nunes
- Department of Gastroenterology, Portuguese Oncology Institute of Porto; Department of Surgery and Physiology, Center for Research in Health Technologies and Information Systems (CINTESIS), Faculty of Medicine, University of Porto, Portugal
| | | | - Marcin Polkowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Center for Postgraduate Medical Education, and Department of Oncological Gastroenterology, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Michael Vieth
- Institut of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Ivan Borbath
- Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Tom G Moreels
- Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Els Nieveen van Dijkum
- Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, The Netherlands
| | - Jean-Yves Blay
- Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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12
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Carvão J, Dinis-Ribeiro M, Pimentel-Nunes P, Libânio D. Neuroendocrine Tumors of the Gastrointestinal Tract: A Focused Review and Practical Approach for Gastroenterologists. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 28:336-348. [PMID: 34604465 PMCID: PMC8443956 DOI: 10.1159/000512089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 10/01/2020] [Indexed: 02/05/2023]
Abstract
Neuroendocrine tumors (NETs) are rare tumors derived from the neuroendocrine cell system, and more commonly found in the gastrointestinal (GI) tract. Over the last decades, the incidence of GI-NETs has been steadily increasing, partly due to the expanding indications for endoscopy. Most patients with NETs are asymptomatic, and their NETs are noticed during screening examinations; thus, endoscopists are on the frontline of the diagnosis of GI-NETs. Since GI-NETs are less frequent than other malignancies, the natural history, diagnosis, and management of these tumors may not be fully understood. In this review, we aim to update the endoscopist on key clinical features and management of patients with gastric, duodenal, and rectal NETs.
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Affiliation(s)
- Joana Carvão
- Gastroenterology Department, Hospital Central do Funchal, Funchal, Portugal
- *Joana Isabel Jardim Carvão, Department of Gastroenterology, Hospital Central do Funchal, Avenida Luís de Camões nº 57, PT–9004-514 Funchal (Portugal),
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
- Surgery and Physiology Department, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Diogo Libânio
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
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13
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Klemm N, Lu-Cleary D, Chahal D, Trasolini R, Lam E, Donnellan F. Endoscopic Management of Diminutive Duodenal Neuroendocrine Tumors. J Gastrointest Cancer 2021; 52:448-453. [PMID: 33471257 DOI: 10.1007/s12029-020-00577-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2020] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Although duodenal neuroendocrine tumors (dNETs) are rare, the incidence, particularly for lesions ≤ 10 mm, continues to rise with the advent of widely available, high-quality endoscopy. Given their rarity and controversy regarding prognostication factors, limited guidelines exist for resection of well-differentiated, ≤ 20-mm dNETs. Importantly, lesions ≤ 10 mm in a duodenal location are ideal for consideration of endoscopic management given both morbidity and technical challenges associated with surgery and their accessibility to a wide range of endoscopic techniques. OBJECTIVES The primary objective of this study was to demonstrate the safety and efficacy of the endoscopic resection of dNETs <10 mm in a case series and literature review. METHODS We performed a literature review and present a series of nine cases to demonstrate the viability of endoscopic resection for diminutive dNETs as an alternative to surgery. RESULTS Our case series included nine well-differentiated diminutive dNETs in seven patients, the majority resected using endoscopic mucosal resection (EMR), 67%, and there was no residual disease at follow-up. The literature review of 178 patients demonstrated that EMR was the most used method of resection of diminutive dNETs, 81%, compared to endoscopic submucosal dissection, 19%. The most common complication was intraoperative bleeding in 9.55%, and only 2.25% of patients had recurrence. CONCLUSION While complications may arise with endoscopic resection of diminutive dNETs, they are usually managed endoscopically and compare favorably with the literature on surgical complication rates and typically result in shorter hospitalizations.
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Affiliation(s)
- Natasha Klemm
- Department of Medicine, University of British Columbia, 319-630 Broadway East, Vancouver, BC, V5T 0J1, Canada.
| | - Destiny Lu-Cleary
- Faculty of Medicine, University of British Columbia, 119-2190 West 7th, Vancouver, BC, V6K 4K7, Canada
| | - Daljeet Chahal
- Division of Gastroenterology Fellowship, University of British Columbia, Vancouver, BC, Canada.,Gordon and Leslie Diamond Health Centre, Vancouver General Hospital, 5153-2775 Laurie St., Vancouver, BC, V5Z 1M9, Canada
| | - Roberto Trasolini
- Division of Gastroenterology Fellowship, University of British Columbia, Vancouver, BC, Canada.,Gordon and Leslie Diamond Health Centre, Vancouver General Hospital, 5153-2775 Laurie St., Vancouver, BC, V5Z 1M9, Canada
| | - Eric Lam
- Division of Gastroenterology, St. Paul's Hospital, 770-1190 Hornby St., Vancouver, BC, V6Z 2K5, Canada
| | - Fergal Donnellan
- Gordon and Leslie Diamond Health Centre, Vancouver General Hospital, 5153-2775 Laurie St., Vancouver, BC, V5Z 1M9, Canada.,Division of Gastroenterology, Vancouver General Hospital, Vancouver, BC, Canada
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14
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Cho HJ, Jang JY, Jeong SY, Kang IC, Lee SH, Choi SH. Robotic limited local resection of duodenal juxta-ampullary neoplasms. Int J Med Robot 2020; 17:e2192. [PMID: 33125798 DOI: 10.1002/rcs.2192] [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: 08/08/2020] [Revised: 09/28/2020] [Accepted: 10/26/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The unique and complex anatomical location of duodenal juxta-ampullary neoplasms complicates selection of the appropriate surgical strategy. For benign or borderline tumours, surgical local resection can be an appropriate treatment option, and robotic surgical systems can help perform minimally invasive local resection of these lesions. METHODS Between December 2014 and December 2019, 10 patients who underwent robotic local resections for duodenal juxta-ampullary tumours were reviewed. RESULTS All patients successfully underwent robotic local resection of the duodenum, preserving the ampulla of Vater without conversion. The mean tumour size was 2.2 cm. Final pathology consisted of gastrointestinal stromal tumour, neuroendocrine tumour, low grade and high grade dysplasia, ectopic pancreas, and well-differentiated adenocarcinoma (T1a). There were no postoperative complications or recurrences. CONCLUSION With accurate preoperative diagnosis and careful selection of patients, local resection of the duodenum for juxta-ampullary benign or borderline tumours using robotic surgical system is an attractive treatment option.
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Affiliation(s)
- Hye Jung Cho
- Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jae Young Jang
- Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea
| | - Sung Yub Jeong
- Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea
| | - In Cheon Kang
- Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea
| | - Sung Hwan Lee
- Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea
| | - Sung Hoon Choi
- Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea
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15
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Yu YJ, Li YW, Shi Y, Zhang Z, Zheng MY, Zhang SW. Clinical and pathological characteristics and prognosis of 132 cases of rectal neuroendocrine tumors. World J Gastrointest Oncol 2020; 12:893-902. [PMID: 32879666 PMCID: PMC7443838 DOI: 10.4251/wjgo.v12.i8.893] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/26/2020] [Accepted: 07/19/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neuroendocrine tumors (NETs) frequently occur in the gastrointestinal tract, lung, and pancreas, and the rectum and appendix are the sites with the highest incidence. Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract, including the stomach, intestine, appendix, colon, and rectum. The pathological changes and clinical symptoms of NETs are not specific, and therefore they are frequently misdiagnosed. AIM To investigate the clinical symptoms, pathological characteristics, treatment, and prognosis of rectal neuroendocrine tumors (RNETs) by analyzing the clinical and pathological data of 132 RNET cases at our hospital. METHODS All RNETs were graded according to Ki-67 positivity and mitotic events. The tumors were staged as clinical stages I, II, III, and IV according to infiltrative depth and tumor size. COX proportional hazard model was used to assess the main risk factors for survival. RESULTS These 132 RNETs included 83 cases of G1, 21 cases of G2, and 28 cases of G3 (neuroendocrine carcinoma) disease. Immunohistochemical staining showed that 89.4% of RNETs were positive for synaptophysin and 39.4% positive for chromogranin A. There were 19, 85, 23, and 5 cases of clinical stages I, II, III, and IV, respectively. The median patient age was 52.96 years. The diameter of tumor, depth of invasion, and pathological grade were the main reference factors for the treatment of RNETs. The survival rates at 6, 12, 36, and 60 mo after operation were 98.5%, 94.6%, 90.2%, and 85.6%, respectively. Gender, tumor size, tumor grade, lymph node or distant organ metastasis, and radical resection were the main factors associated with prognosis of RNETs. Multivariate analysis showed that tumor size and grade were independent prognostic factors. CONCLUSION The clinical symptoms of RNETs are not specific, and they are easy to misdiagnose. Surgery is the main treatment method. The grade and stage of RNETs are the main indices to evaluate prognosis.
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Affiliation(s)
- Yong-Jun Yu
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Yu-Wei Li
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Yang Shi
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Zhao Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Min-Ying Zheng
- Department of Pathology, Tianjin Union Medical Center, Tianjin 300121, China
| | - Shi-Wu Zhang
- Department of Pathology, Tianjin Union Medical Center, Tianjin 300121, China
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16
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Park SG, Lee BE, Kim GH, Park JW, Lee MW, Kim SJ, Choi CW, Lee S, Park DY. Risk factors for lymph node metastasis in duodenal neuroendocrine tumors: A retrospective, single-center study. Medicine (Baltimore) 2019; 98:e15885. [PMID: 31169696 PMCID: PMC6571284 DOI: 10.1097/md.0000000000015885] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Duodenal neuroendocrine tumors (NETs) are rare, and risk factors associated with lymph node (LN) metastasis are still not well defined. The aim of this study was to investigate risk factors of LN metastasis in duodenal NETs based on the final histopathologic results and clinical follow-up data.This study included a total of 44 duodenal NETs in 38 patients who underwent endoscopic or surgical resection between January 2008 and December 2015. Diagnosis of duodenal NETs was confirmed based on immunohistochemical staining of chromogranin A, synaptophysin, and CD56; the clinicopathologic records were collected at the time of the initial diagnosis of duodenal NETs.Most duodenal NETs were small (≤1 cm in 33 tumors), World Health Organization (WHO) grade G1 (in 32 tumors), limited to the mucosa and/or submucosa (in 40 tumors), and located at the duodenal bulb (in 32 tumors). Of 44 tumors, lymphovascular invasion was present in 4 (9.1%), and among 38 patients, LN metastasis was detected in 4 (10.5%). LN metastases were significantly associated with the non-bulb location, tumor size >10 mm, tumor invasion into the muscularis propria or deeper, WHO grade G2, and lymphovascular invasion. During the mean follow-up period of 54.5 months (range, 24-123 months), recurrence occurred in 1 patient.Non-bulb location, tumor size >10 mm, invasion beyond the submucosa, WHO grade G2, and lymphovascular invasion are risk factors of LN metastasis in duodenal NETs. These findings can help clinicians choose the appropriate therapeutic modality for duodenal NETs.
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Affiliation(s)
- Sang Gyu Park
- Department of Internal Medicine, Pusan National University School of Medicine
| | - Bong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine
- Biomedical Research Institute, Pusan National University Hospital, Busan
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine
- Biomedical Research Institute, Pusan National University Hospital, Busan
| | - Joon Woo Park
- Department of Internal Medicine, Pusan National University School of Medicine
| | - Moon Won Lee
- Department of Internal Medicine, Pusan National University School of Medicine
- Biomedical Research Institute, Pusan National University Hospital, Busan
| | - Su Jin Kim
- Department of Internal Medicine, Pusan National University School of Medicine
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan
| | - Cheol Woong Choi
- Department of Internal Medicine, Pusan National University School of Medicine
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan
| | - Sojeong Lee
- Department of Pathology, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Do Youn Park
- Department of Pathology, Pusan National University School of Medicine, Busan, Republic of Korea
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17
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Lv Y, Han X, Xu XF, Ji Y, Zhou YH, Sun HC, Zhou J, Fan J, Lou WH, Huang C. Risk factors affecting prognosis in metachronous liver metastases from WHO classification G1 and G2 gastroenteropancreatic neuroendocrine tumors after initial R0 surgical resection. BMC Cancer 2019; 19:335. [PMID: 30961559 PMCID: PMC6454726 DOI: 10.1186/s12885-019-5457-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 03/12/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Here we describe the treatments and prognosis for metachronous metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) after initial R0 surgical resection at a large center in China. METHODS The clinicopathological data and survival outcomes for 108 patients (median age, 54.0 years) with metachronous hepatic metastatic GEP-NETs disease who were initially treated using R0 surgical resection between August 2003 and July 2014 were analyzed using one-way comparisons, survival analysis, and a predictive nomogram. RESULTS Fifty-five (50.9%) patients had pancreatic NETs and 92 (85.2%) had G2 primary tumors. For treatment of the hepatic metastases, 48 (44.4%) patients received liver-directed local treatment (metastasectomy, radiofrequency ablation, transcatheter arterial chemoembolization, etc.), 15 (13.9%) received systemic treatment (interferon, somatostatin analogs, etc.), and 45 (41.7%) received both treatments. Multivariable analyses revealed that OS was associated with hepatic tumor number (P < 0.001), treatment modality (P = 0.045), and elevated Ki-67 index between the metastatic and primary lesions (P = 0.027). The predictive nomogram C-index was 0.63. CONCLUSIONS A higher Ki-67 index in metastases compared to primary tumor was an independent factor for poor prognosis. Local treatment was associated with prolonged survival of hepatic metastatic GEP-NET patients. Optimal treatment strategies based on clinicopathological characteristics should be developed.
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Affiliation(s)
- Yang Lv
- 0000 0004 1755 3939grid.413087.9Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
| | - Xu Han
- 0000 0004 1755 3939grid.413087.9Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
| | - Xue-Feng Xu
- 0000 0004 1755 3939grid.413087.9Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
| | - Yuan Ji
- 0000 0004 1755 3939grid.413087.9Department of Pathology, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
| | - Yu-Hong Zhou
- 0000 0004 1755 3939grid.413087.9Department of Oncology, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
| | - Hui-Chuan Sun
- 0000 0004 1755 3939grid.413087.9Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
- 0000 0004 0369 313Xgrid.419897.aKey Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Beijing, China
| | - Jian Zhou
- 0000 0004 1755 3939grid.413087.9Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
- 0000 0004 0369 313Xgrid.419897.aKey Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Beijing, China
| | - Jia Fan
- 0000 0004 1755 3939grid.413087.9Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
- 0000 0004 0369 313Xgrid.419897.aKey Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Beijing, China
| | - Wen-Hui Lou
- 0000 0004 1755 3939grid.413087.9Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
| | - Cheng Huang
- 0000 0004 1755 3939grid.413087.9Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Rd, Shanghai, 200032 China
- 0000 0004 0369 313Xgrid.419897.aKey Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Beijing, China
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18
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Lv Y, Pu N, Mao WL, Chen WQ, Wang HY, Han X, Ji Y, Zhang L, Jin DY, Lou WH, Xu XF. Development of predictive prognostic nomogram for NECs of rectum on population-based exploration. Endocr Connect 2018; 7:/journals/ec/aop/ec-18-0353.xml. [PMID: 30352397 PMCID: PMC6215795 DOI: 10.1530/ec-18-0353] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 09/20/2018] [Indexed: 12/12/2022]
Abstract
AIM We aim to investigate the clinical characteristics of the rectal NECs and the prognosis-related factors and construct a nomogram for prognosis prediction. METHODS The data of 41 patients and 1028 patients with rectal NEC were retrieved respectively from our institution and SEER database. OS or PFS were defined as the major study outcome. Variables were compared by Chi2 test, t-test when appropriate. Kaplan-Meier analysis with log-rank test was used for survival analysis and the cox regression analysis were applied. The nomogram integrating risk factors for predicting OS was constructed by R to achieve superior discriminatory ability. Predictive utility of the nomogram was determined by concordance index (C-index) and calibration curve. RESULTS In the univariate and multivariate analysis, tumor differentiation, N stage, M stage and resection of primary site were identified as independent prognostic indicators. The linear regression relationship was found between the value of Ki-67 index and the duration of OS (P<0.05). Furthermore, the independent prognostic factors were added to formulate prognostic nomogram. The constructed nomogram showed good performance according to the C-index. CONCLUSIONS Contrary to WHO classification guideline, we found that the rectal NEC disease are heterogeneous and should be divided as different categories according to the pathological differentiation. Besides, the nomogram formulated in this study showed excellent discriminative capability to predict OS for those patients. More advanced predictive model for this disease is required to assist risk stratification via the formulated nomogram.
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Affiliation(s)
- Yang Lv
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Ning Pu
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Wei-lin Mao
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-qi Chen
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Huan-yu Wang
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Xu Han
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of PathologyZhongshan Hospital, Fudan University, Shanghai, China
| | - Lei Zhang
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Da-yong Jin
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Hui Lou
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
| | - Xue-feng Xu
- Department of General SurgeryZhongshan Hospital, Fudan University, Shanghai, China
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Wang HM, Liang CM, Wu CK, Chiu YC, Chou YP, Wu KL, Huang CC, Chuah SK, Tai WC, Lu LS. Metachronous duodenal neuroendocrine neoplasms after endoscopic mucosal resection. ADVANCES IN DIGESTIVE MEDICINE 2017. [DOI: 10.1002/aid2.12071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Hsin-Ming Wang
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
| | - Chih-Ming Liang
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
| | - Cheng-Kun Wu
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
| | - Yi-Chun Chiu
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
- Chang Gung University College of Medicine; Taoyuan Taiwan
| | - Yeh-Pin Chou
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
- Chang Gung University College of Medicine; Taoyuan Taiwan
| | - Keng-Liang Wu
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
- Chang Gung University College of Medicine; Taoyuan Taiwan
| | - Chao-Cheng Huang
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
- Chang Gung University College of Medicine; Taoyuan Taiwan
- Department of Pathology; Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
- Biobank and Tissue Bank; Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
- Chang Gung University College of Medicine; Taoyuan Taiwan
| | - Wei-Chen Tai
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
- Chang Gung University College of Medicine; Taoyuan Taiwan
| | - Lung-Sheng Lu
- Division of Hepato-gastroenterology; Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital; Kaohsiung Taiwan
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20
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Shen C, Chen H, Chen H, Yin Y, Han L, Chen J, Tang S, Yin X, Zhou Z, Zhang B, Chen Z. Surgical treatment and prognosis of gastric neuroendocrine neoplasms: a single-center experience. BMC Gastroenterol 2016; 16:111. [PMID: 27613657 PMCID: PMC5016962 DOI: 10.1186/s12876-016-0505-5] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Accepted: 07/29/2016] [Indexed: 02/05/2023] Open
Abstract
Background Gastric neuroendocrine neoplasms (G-NENs) are uncommon, and data on their management is limited. We here investigated the clinicopathological characteristics, surgical and survival outcomes in G-NENs among Chinese. Moreover, we will discuss their prognostic value. Methods From existing databases of the West China Hospital, we retrospectively identified 135 consecutive patients who were surgically treated and pathologically diagnosed as G-NENs from January 2009 to August 2015. Results This entire cohort comprised 98 males and 37 females, with a median age of 60 years. Twenty-five patients underwent endoscopic resection, while 110 patients underwent open/laparoscopic surgery. Thirty-nine patients had neuroendocrine tumor G1 (NET G1), seven patients had neuroendocrine tumor G2 (NET G2), 69 patients had neuroendocrine carcinoma G3 (NEC G3) and 20 patients had mixed adenoneuroendocrine carcinoma (MANEC). The median survival was not achieved for both NET G1 and NET G2 versus 19 months (range 3–48) for NEC G3 and 10.5 months (range 3–45) for MANEC. The 3-year survival rates for stage I, II, III, and IV were 91.1 %, 78.6 %, 51.1 % and 11.8 %, respectively (P < 0.001). As for the prognostic analysis, both surgical margin and the newly updated World Health Organization (WHO) classification were independent predictors of overall survival (OS). Conclusions G-NENs are a kind of rare tumors, and patients with NET G3 and MANEC have unfavorable prognosis even surgically treated. Moreover, surgical margin and the new 2010 WHO criteria are closely associated with OS for G-NENs.
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Affiliation(s)
- Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Huijiao Chen
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Haining Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Luyin Han
- Intensive Care Unit, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiaju Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Sumin Tang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Zongguang Zhou
- Institute of Digestive Surgery and State key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Zhixin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
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