|
1
|
Butz F, Supper L, Reinhard L, Dukaczewska A, Jann H, Fehrenbach U, Müller-Debus CF, Skachko T, Pratschke J, Goretzki PE, Mogl MT, Dobrindt EM. Emergency surgery influences oncological outcome in small intestinal neuroendocrine tumors. Scand J Surg 2024; 113:303-313. [PMID: 39230104 DOI: 10.1177/14574969241271841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2024]
Abstract
BACKGROUND AND AIMS Patients with small intestinal neuroendocrine tumors (siNETs) frequently present emergently due to bowel ischemia or bowel obstruction. The influence of emergency surgery on the prognosis of siNET remains controversial. The aim of this study was to investigate the association between type of presentation (emergency/elective) and oncological outcome. METHODS Clinicopathological data of patients who underwent bowel resection and were treated due to siNET at the Charité - Universitätsmedizin Berlin, Germany were analyzed retrospectively. RESULTS A total of 165 patients underwent bowel resection for siNET. Of these, 22.4% (n = 37) were emergency and 77.6% (n = 128) were elective procedures. A preoperative known diagnosis was less common in patients with emergency surgery (48.6% vs 85.2%; p < 0.001) and complete resections of all tumor manifestations were performed less often (32.4% vs 50.8%; p = 0.049), while more completion operations had to be performed (24.3% vs 11.1%; p = 0.049). Overall survival (OS) and progression-free survival (PFS) of emergently operated patients were reduced (5-year OS: 85.2% vs 89.5% (p = 0.023); 5-year PFS: 26.7% versus 52.5% (p = 0.018)). In addition, emergency surgery was negatively associated with OS after multivariable regression analysis. CONCLUSION Emergency surgery in siNET patients is associated with adverse oncological outcomes including shorter OS and PFS. Prevention of emergency conditions should be emphasized in advanced disease.
Collapse
Affiliation(s)
- Frederike Butz
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Leonie Supper
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Lisa Reinhard
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Agata Dukaczewska
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Henning Jann
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Uli Fehrenbach
- Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Charlotte Friederike Müller-Debus
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Tatiana Skachko
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Peter E Goretzki
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Martina T Mogl
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Eva M Dobrindt
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| |
Collapse
|
|
2
|
Loree JM, Chan D, Lim J, Stuart H, Fidelman N, Koea J, Posavad J, Cummins M, Doucette S, Myrehaug S, Naraev B, Bailey DL, Bellizzi A, Laidley D, Boyle V, Goodwin R, Del Rivero J, Michael M, Pasieka J, Singh S. Biomarkers to Inform Prognosis and Treatment for Unresectable or Metastatic GEP-NENs. JAMA Oncol 2024; 10:1707-1720. [PMID: 39361298 DOI: 10.1001/jamaoncol.2024.4330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
Importance Evidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics. Objective To create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs. Methods A multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method. Findings A total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society. Conclusions and Relevance The study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.
Collapse
Affiliation(s)
- Jonathan M Loree
- BC Cancer, Vancouver Centre, Vancouver, British Columbia, Canada
| | - David Chan
- Northern Clinical School, University of Sydney, Sydney, Australia
- ENETS Centre of Excellence, Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Jennifer Lim
- St George Hospital, Sydney, New South Wales, Australia
- University of New South Wales, Sydney, New South Wales, Australia
- Garvan Institute of Medical Research, Sydney, New South Wales, Australia
| | - Heather Stuart
- University of British Columbia and BC Cancer Agency, Vancouver, British Columbia, Canada
| | | | - Jonathan Koea
- Te Whatu Ora Waitemata and the University of Auckland, Auckland, New Zealand
| | - Jason Posavad
- Canadian Neuroendocrine Tumours Society, Cornwall, Ontario, Canada
| | | | | | - Sten Myrehaug
- Odette Cancer Centre, Toronto, Ontario, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Boris Naraev
- Tampa General Hospital Cancer Institute, Tampa, Florida
| | - Dale L Bailey
- Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | | | - David Laidley
- Western University, London, Ontario, Canada
- Lawson Health Research Institute, London, Ontario, Canada
| | - Veronica Boyle
- School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Department of Oncology, Auckland City Hospital, Te Whatu Ora Tamaki Makaurau, Auckland, New Zealand
| | - Rachel Goodwin
- Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada
| | - Jaydi Del Rivero
- Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Michael Michael
- NET Unit and ENETS Centre of Excellence, Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Parkville, Victoria, Australia
| | - Janice Pasieka
- Section of General Surgery, Division of Endocrine Surgery and Surgical Oncology, Department of Surgery and Oncology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Simron Singh
- University of Toronto, Toronto, Ontario, Canada
- Sunnybrook Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
| |
Collapse
|
|
3
|
Ortigão R, Afonso LP, Pimentel-Nunes P, Dinis-Ribeiro M, Libânio D. Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:236-245. [PMID: 39022301 PMCID: PMC11250119 DOI: 10.1159/000530684] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 02/02/2023] [Indexed: 07/20/2024]
Abstract
INTRODUCTION/AIM Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA). METHODS The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed. RESULTS We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender (p = 0.030), type III/IV (p < 0.001), Ki-67 index >20% (p < 0.001), grade 2/3 (p < 0.001), invasion beyond the submucosa (p < 0.001), and presence of metastases (p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% (p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs). CONCLUSION Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET.
Collapse
Affiliation(s)
- Raquel Ortigão
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Luís Pedro Afonso
- Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
- RISE@CI-IPOP (Health Research Network, IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Unilabs Portugal, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Diogo Libânio
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
| |
Collapse
|
|
4
|
Zi M, Ma Y, Chen J, Pang C, Li X, Yuan L, Liu Z, Yu P. Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis. Cancer Med 2024; 13:e7011. [PMID: 38457192 PMCID: PMC10922030 DOI: 10.1002/cam4.7011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/29/2023] [Accepted: 01/31/2024] [Indexed: 03/09/2024] Open
Abstract
OBJECTIVE This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.
Collapse
Affiliation(s)
- Mengli Zi
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Yubo Ma
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Jinxia Chen
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Chuhong Pang
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Xiao Li
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Li Yuan
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Zhuo Liu
- Department of Colorectum surgeryZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
| | - Pengfei Yu
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
| |
Collapse
|
|
5
|
Grundmann N, Voigtländer S, Hakimhashemi A, Pape U, Meyer M, Müller‐Nordhorn J. Site-specific trends in gastroenteropancreatic neuroendocrine neoplasms in Bavaria, Germany. Cancer Med 2023; 12:19949-19958. [PMID: 37737059 PMCID: PMC10587981 DOI: 10.1002/cam4.6510] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 07/20/2023] [Accepted: 08/30/2023] [Indexed: 09/23/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms (NEN) are rare and heterogeneous epithelial tumors, occurring throughout the body. For gastroenteropancreatic (GEP)-NEN, rising incidence rates were reported for the last decades, with underlying causes remaining largely unexplained. We evaluated NEN trends stratifying by their histologic subtypes. METHODS Incident cases of GEP-NEN diagnosed between 2005 and 2019 were retrieved from the prospective, population-based Bavarian Cancer Registry. GEP-NEN were divided in their histologic subtypes, that is, neuroendocrine tumors (NET) G1, NET G2/G3, other NET versus small-cell neuroendocrine carcinoma (NEC), large-cell NEC, and other NEC. We calculated annual age-standardized incidence rates (ASIRs) per 100,000 persons for the total of GEP-NEN, NEN histologic subtypes, and tumor sites. We used an annual percentage change (APC) approach including a joinpoint analysis to investigate NEN incidence trends. RESULTS ASIR of GEP-NEN rose from 2.2 in 2005 to 4.8 in 2019, characterized by a significant increase until 2012 (APC 2005-2012: 10.1%), followed by modest rise (APC 2012-2019: 1.5%). In the last decade, this increase was mainly driven by the rise of NET G1 and G2/G3, while incidence for NEC declined. Over the study period, ASIR increased significantly for all GEP-sites except the colon. APCs were largest for the stomach, the appendix, the pancreas, and the rectum. CONCLUSIONS This study found a significant increase in the incidence of GEP-NET. Though this development may partially be attributable to the increased use of advanced detection techniques and changes in NEN classification, further research should also focus on the identification of NEN risk factors.
Collapse
Affiliation(s)
- Nina Grundmann
- Bavarian Cancer Registry, Bavarian Health and Food Safety AuthorityNurembergGermany
| | - Sven Voigtländer
- Bavarian Cancer Registry, Bavarian Health and Food Safety AuthorityNurembergGermany
| | - Amir Hakimhashemi
- Bavarian Cancer Registry, Bavarian Health and Food Safety AuthorityNurembergGermany
| | - Ulrich‐Frank Pape
- Department of Internal Medicine and Gastroenterology, Asklepios Tumour Centre Hamburg and Asklepios Hospital St. GeorgHamburgGermany
| | - Martin Meyer
- Bavarian Cancer Registry, Bavarian Health and Food Safety AuthorityNurembergGermany
| | | |
Collapse
|
|
6
|
Somnay K, Surpur S, Saini P, Gibson C, Luo J. Early Definitive Diagnosis and Management of Incidental Neuroendocrine Tumors Found on Gastrointestinal Endoscopy. Cureus 2023; 15:e44718. [PMID: 37674763 PMCID: PMC10479724 DOI: 10.7759/cureus.44718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 09/08/2023] Open
Abstract
Neuroendocrine tumors (NETs) are tumors that originate from neuroendocrine cells and can be found throughout the body but are most commonly seen in the gastrointestinal tract, pancreas, and lungs. There is an increase in the diagnosis of NETs due to advances in diagnostic modalities. Although mucosal tumors are easily visualized on upper GI endoscopic imaging, neuroendocrine tumors are often missed due to their deep mucosal origin with normal overlying mucosa. We first present the case of a 46-year-old woman with anemia and epigastric discomfort who was found to have an incidental submucosal mass in the duodenal bulb on esophagogastroduodenoscopy (EGD), which on endoscopic ultrasound (EUS) with a fine needle biopsy (FNB) showed a neuroendocrine tumor. Imaging with CT, however, failed to detect the presence of the mass in the duodenum. Furthermore, a DOTATATE scan showed only a nonspecific signal near the liver. The patient then underwent an EGD-guided, laparoscopic, robot-assisted transduodenal resection of the tumor, together with the removal of enlarged peritumoral lymph nodes. Pathology showed a well-differentiated neuroendocrine tumor of the duodenal bulb with metastasis to one lymph node, which was confirmed via immunohistochemistry staining. The second case is of a 51-year-old female who presented with occasional constipation and rectal pain and was found to have a rectal polypoid lesion on her colonoscopy, jumbo biopsies of which revealed a NET. An EUS done for staging and endoscopic mucosal resection (EMR) revealed a grade 1 well-differentiated NET on pathology, which was confirmed by immunohistochemistry staining. These cases stress the need for timely, definitive diagnosis and intervention. Here, we discuss the clinical features and investigations of neuroendocrine tumors for early diagnosis and management.
Collapse
Affiliation(s)
- Kaumudi Somnay
- Gastroenterology, NewYork-Presbyterian Queens Hospital, New York City, USA
| | - Swapnil Surpur
- Internal Medicine, Jawaharlal Nehru Medical College, Belgaum, IND
| | - Prerna Saini
- Internal Medicine, Government Medical College, Patiala, IND
| | | | - Jean Luo
- Pathology, NewYork-Presbyterian Queens Hospital, New York City, USA
| |
Collapse
|
|
7
|
Emilsson L, Maret-Ouda J, Ludvigsson JF. Mortality in small bowel cancers and adenomas - A nationwide, population-based matched cohort study. Cancer Epidemiol 2023; 85:102399. [PMID: 37327506 DOI: 10.1016/j.canep.2023.102399] [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: 05/17/2023] [Revised: 06/06/2023] [Accepted: 06/11/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA), neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are neoplastic lesions of the small bowel while small bowel adenomas are precursors of SBA. AIM To examine mortality in patients diagnosed with SBA, small bowel adenomas, NET and GIST. METHODS We performed a population-based matched cohort study encompassing all individuals with SBA (n = 2289), adenomas (n = 3700), NET (n = 1884) and GIST (n = 509) in the small bowel diagnosed at any of Sweden's 28 pathology departments between 2000 and 2016 (the "ESPRESSO study"). Each case was matched by sex, age, calendar year and county of residence to up to 5 comparators from the general population. Through Cox regression we estimated hazard ratios (HRs) and 95% confidence intervals (95%CIs) for death and cause-specific death adjusting for education. RESULTS During follow-up until December 31, 2017, 1836 (80%) deaths occurred in SBA patients, 1615 (44%) in adenoma, 866 (46%) in NET and 162 (32%) in GIST patients. This corresponded to incidence rates of 295, 74, 80 and 62/1000 person-years respectively and adjusted HRs of 7.60 (95%CI=6.95-8.31), 2.21 (2.07-2.36), 2.74 (2.50-3.01) and 2.33 (1.90-2.87). Adjustment for education had a substantial impact on the HR for death in SBA but not for other neoplasias. The predominant cause of excess death was cancer in all groups. CONCLUSION This study confirms earlier findings of increased death rates in patients with SBA and NET in a modern study population. We also demonstrate a more than 2-fold increased risk of death in both GIST and the SBA precursor adenoma.
Collapse
Affiliation(s)
- Louise Emilsson
- Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway; Vårdcentralen Värmlands Nysäter and Centre for Clinical Research, County Council of Värmland, Värmland, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
| | - John Maret-Ouda
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; Department of Pediatrics, Örebro University Hospital, Sweden; Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| |
Collapse
|
|
8
|
Javed AA, Pulvirenti A, Razi S, Zheng J, Michelakos T, Sekigami Y, Thompson E, Klimstra DS, Deshpande V, Singhi AD, Weiss MJ, Wolfgang CL, Cameron JL, Wei AC, Zureikat AH, Ferrone CR, He J. Grading Pancreatic Neuroendocrine Tumors Via Endoscopic Ultrasound-guided Fine Needle Aspiration: A Multi-institutional Study. Ann Surg 2023; 277:e1284-e1290. [PMID: 35081574 PMCID: PMC9364076 DOI: 10.1097/sla.0000000000005390] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To identify factors associated with concordance between World Health Organization (WHO) grade on cytological analysis (c-grade) and histopathological analysis (h-grade) of surgical specimen in patients with PanNETs and examine trends in utilization and accuracy of EUS-FNA in preoperatively predicting grade. BACKGROUND WHO grading system is prognostic in pancreatic neuroendo-crine tumors (PanNETs). The concordance between c-grade and h-grade is reported to be between 50% and 92%. METHODS A multicenter retrospective study was performed on patients undergoing resection for PanNETs at four high-volume centers between 2010 and 2019. Patients with functional or syndrome-associated tumors, and those receiving neoadjuvant therapy were excluded. Factors associated with concordance between c-grade and h-grade and trends of utilization of EUS-FNA were assessed. RESULTS Of 869 patients included, 517 (59.5%) underwent EUS-FNA; 452 (87.4%) were diagnostic of PanNETs and WHO-grade was reported for 270 (59.7%) patients. The concordance between c-grade and h-grade was 80.4% with moderate concordance ( Kc = 0.52, 95% CI: 0.41-0.63). Significantly higher rates of concordance were observed in patients with smaller tumors (<2 vs. ≥2cm, 81.1% vs. 60.4%, P = 0.005). Highest concordance (98.1%) was observed in patients with small tumors undergoing assessment between 2015-2019 with a near-perfect concordance ( Kc = 0.88, 95% CI: 0.61-1.00). An increase in the utilization of EUS-FNA (56.1% to 64.1%) was observed over the last 2 decades ( P = 0.017) and WHO-grade was more frequently reported (44.2% vs. 77.6%, P < 0.001). However, concordance between c-grade and h-grade did not change significantly (P = 0.118). CONCLUSION Recently, a trend towards increasing utilization and improved diagnostic accuracy of EUS-FNA has been observed in PanNETs. Concordance between c-grade and h-grade is associated with tumor size with near-perfect agreement when assessing PanNETs <2cm in size.
Collapse
Affiliation(s)
- Ammar A. Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA
| | - Alessandra Pulvirenti
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Samrah Razi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jian Zheng
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - Yurie Sekigami
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Elizabeth Thompson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David S. Klimstra
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Vikram Deshpande
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Aatur D. Singhi
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | | | - John L. Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alice C. Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Amer H. Zureikat
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | |
Collapse
|
|
9
|
Factors Predicting Type I Gastric Neuroendocrine Neoplasia Recurrence: A Single-Center Study. Biomedicines 2023; 11:biomedicines11030828. [PMID: 36979807 PMCID: PMC10045191 DOI: 10.3390/biomedicines11030828] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/01/2023] [Accepted: 03/07/2023] [Indexed: 03/12/2023] Open
Abstract
Type I gastric neuroendocrine neoplasms (gNENs) are associated with atrophic gastritis and have a high recurrence rate, which means frequent endoscopies are required. The objective of this study was to identify factors predicting the local recurrence of type I gNENs. The clinical course and the pathological and biochemical data of patients with type I gNENs treated at Bnai Zion Medical Center between 2006 and 2022 were analyzed retrospectively. Twenty-seven type I gNENs were evaluated. The follow-up period was 41 months (range: 11–288 months). Recurrence of the tumor occurred in 13/27 (48%) patients after 35 months (median (M), interquartile range (IQR): 21–67.5). Serum gastrin levels were significantly higher in patients with recurrent disease versus patients with non-recurrent disease (788 vs. 394 ng/L; p = 0.047), while the Ki-67 index was significantly lower in patients with recurrent disease versus patients with non-recurrent disease (1% vs. 3.5%; p = 0.035). Tumor size, mitotic count, and serum chromogranin A levels did not correlate with recurrence. The present study emphasizes the role of gastrin in the pathogenesis of gNEN recurrence and highlights the debate regarding the ability of the Ki-67 index to predict the clinical course of this disease.
Collapse
|
|
10
|
Stiefel R, Lehmann K, Winder T, Siebenhüner AR. What have we learnt from the past - would treatment decisions for GEP-NET patients differ between 2012 to 2016 by the new recommendations in 2022? BMC Cancer 2023; 23:148. [PMID: 36782152 PMCID: PMC9926660 DOI: 10.1186/s12885-023-10567-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 01/19/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyse outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of European Society of Medical Oncology (ESMO) 2020 for GEP-NETs. METHODS Patients were included in this retrospective single-center analysis from 2012-2016. All patients suffering from a GEP-NET, who were screened, treated or evaluated at ENETS Center in Zurich, Switzerland were included in analysis. Patients with any other diagnosis of NET were not included. We used Kaplan Meier estimator as well as Cox regression to compare survival rates between different sites of localization, grades or stages and treatment sequences. RESULTS Overall, we identified 256 GEP-NETs, most in advanced stage (62%) and located in small intestine tract or pancreatic gland. Survival depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed early but also in advanced stages, usually followed by Somatostatine-Agonist modalities. In distant disease (Stage IV), we investigated a positive effect of PFS after treatment with Somatostatine Analogues (SSA) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21 - 0.97; p = 0.04) and systemic treatment (HR, 0.51; 95% CI, 0.26 - 0.99; p = 0.047) if patients underwent prior surgery or endoscopic resection. Kaplan Meier distributions predict shorter OS in distant disease (Stage IV), (Figure. 1; HR, 2.06; 95% CI, 1.46 - 2.89; log-rank test, p < 0.001). CONCLUSION This retrospective analysis presents a great overview of all patients', disease and treatment characteristics of GEP-NETs at ENETS Center in Zurich, Switzerland. We illustrated survival (PFS) depending on implemented therapies. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. The results of this project may define GEP-NET patients' selection for upcoming clinical prospective studies.
Collapse
Affiliation(s)
- Rahel Stiefel
- grid.414526.00000 0004 0518 665XMedical Oncology and Hematology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Kuno Lehmann
- grid.7400.30000 0004 1937 0650Department of Surgery and Transplantation, University Hospital and University of Zurich, Zurich, Switzerland
| | - Thomas Winder
- grid.413250.10000 0000 9585 4754Internal Medicine II, Hematology, Oncology and Gastroenterology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria ,grid.7400.30000 0004 1937 0650University of Zurich, Zurich, Switzerland
| | - Alexander R. Siebenhüner
- grid.7400.30000 0004 1937 0650Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland ,Clinic of Internal Medicine and Oncology, Cantonal Hospital Schaffhausen, Schaffhausen, Switzerland
| |
Collapse
|
|
11
|
Alsadik S, Gnanasegaran G, Chen L, Quigley AM, Mandair D, Toumpanakis C, Caplin M, Navalkissoor S. Single centre retrospective review of outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy in the treatment of progressive metastatic neuroendocrine tumours: Survival, toxicity, and prognostic factors. J Neuroendocrinol 2022; 34:e13210. [PMID: 36399420 DOI: 10.1111/jne.13210] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 10/17/2022] [Accepted: 10/18/2022] [Indexed: 11/30/2022]
Abstract
The aim of this study was to evaluate the efficacy and safety of 177 Lu-DOTATATE therapy in advanced metastatic disease. A retrospective analysis of 395 patients (180 female, 215 males, mean age 62) with progressive metastatic neuroendocrine tumours (NETs) who were treated with 177 Lu-DOTATATE was performed. Overall, 115 patients had less than four cycles and 280 completed four cycles of treatment. Progression-free survival (PFS) and overall survival (OS) was performed using Kaplan-Meier analysis. Analysis of survival predictors was performed using Cox regression model. Toxicity was defined using the Common Terminology Criteria for Adverse Events version 5 (CTCAE 5.0). The percentage of patients with liver and skeletal metastases were 91 and 57%, respectively. Median PFS and OS were calculated at 33 months (95% CI: 29-37 months) and 46 months (95% CI: 48-56 months), respectively. End of treatment response assessment was performed using cross sectional imaging demonstrated partial response in 22%, stable disease in 64% and progressive disease in 14% of patients. Overall, grade 3 and 4 bone marrow toxicity was seen in 8%. One patient (0.3%) developed irreversible grade 4 nephrotoxicity. Myelodysplastic disease was recorded in one patient (0.3%). Univariate analysis of PFS predictors showed that body mass index (BMI), baseline chromogranin A (CgA) >400 ng/l, baseline alkaline phosphatase (ALP) >130 mg/dl, liver tumour volume and overall tumour burden were significant. On multivariate analysis only Ki67, high CgA and low BMI retained significance. 177 Lu-DOTATATE is an effective treatment in advanced NETs with generally high-volume metastases. It is well-tolerated. Ki-67, CgA and BMI appear to be predictors for PFS.
Collapse
Affiliation(s)
- Shahad Alsadik
- Department of Nuclear Medicine, Royal Free Hospital, London, UK
| | | | - Luohai Chen
- Royal Free London NHS Foundation Trust; Department of Gastroenterology, London, United Kingdom. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ann-Marie Quigley
- Department of Nuclear Medicine, Royal Free London NHS foundation Trust, London, UK
| | - Dalvinder Mandair
- Neuroendocrine Unit, Royal Free London NHS foundation Trust, London, UK
| | | | - Martyn Caplin
- Neuroendocrine Unit, Royal Free London NHS foundation Trust, London, UK
| | - Shaunak Navalkissoor
- Department of Nuclear Medicine, Royal Free London NHS foundation Trust, London, UK
| |
Collapse
|
|
12
|
Wang Y, Cai H, Zhang Y, Zhuang J, Liu X, Guan G. A modified mTNM staging system based on lymph node ratio for colon neuroendocrine tumors: A recursive partitioning analysis. Front Surg 2022; 9:961982. [PMID: 36338645 PMCID: PMC9634476 DOI: 10.3389/fsurg.2022.961982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 09/27/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND In the current tumor-lymph node-metastasis (TNM) staging system for colon neuroendocrine tumors, lymph node status is divided into N1 and N0. An assessment of the lymph node ratio (LNR) and a proposal for a modified mTNM staging system were the objectives of this study. METHODS Selecting the optimal cut-off value of LNR was done using X-tile. A Cox regression model and the Kaplan-Meier method were performed to calculate patient cancer-specific survival in the Surveillance, Epidemiology and End Results cohort. Recursive partitioning analysis was used to improve TNM staging. RESULTS The study included 674 patients. The current TNM staging system showed inadequate discriminatory power between stage I and stage II patients (p = 0.088). The optimal cut-off value was determined as 0.6 for LNR. Based on multivariate Cox regression analysis, the modified mN classification could be classified into mN 0 (LNR = 0.00), mN 1 (LNR = 0.01-0.60), and mN 2 (LNR > 0.60), and was found to be an independent factor affecting prognosis (p < 0.001). Using the American Joint Committee on Cancer T and modified mN classifications, the modified mTNM system was constructed, and it exhibited better prognostic discriminatory power ability than the traditional TNM system (C-index: 0.587 vs. 0.665). CONCLUSIONS Our study determined that LNR is a prognostic factor in colon NET patients. In addition, to more accurately assess the prognosis of colon NET patients, we proposed a modified mTNM staging system.
Collapse
Affiliation(s)
- Ye Wang
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Huajun Cai
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yiyi Zhang
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jinfu Zhuang
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xing Liu
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China,Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Guoxian Guan
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China,Correspondence: Guoxian Guan
| |
Collapse
|
|
13
|
Kaur A, Wang S, Herbert J, Steinberg L, Kumar A. Analysis of Clinical Characteristics and Survival in Patients With Functional Neuroendocrine Tumors of Gastrointestinal Origin. Pancreas 2022; 51:1171-1178. [PMID: 37078942 DOI: 10.1097/mpa.0000000000002171] [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: 04/21/2023]
Abstract
OBJECTIVES Functional neuroendocrine tumors (FNETs) are characterized by excess secretion of disease-specific hormones. In this study, we attempted to define survival trends in patients with some of these uncommon tumors. METHODS Using the Surveillance, Epidemiology, and End Results database, 529 patients with FNETs (gastrinoma, insulinoma, glucagonoma, VIPoma, and somatostatinoma) were identified. We analyzed patient and tumor characteristics, overall survival, and cancer-specific survival. RESULTS Functional neuroendocrine tumors were found to be more predominant in White patients older than 50 years. Most common FNETs were gastrinoma (56.3%) and insulinoma (23.8%). Most FNETs were found in the pancreas, with the second most common location being the small bowel. Surgery was the primary modality of treatment, used in 55.8% of the cases. Median overall survival was 9.8 years (95% confidence interval [CI], 7.9-11.8) with a median cancer-specific survival of 18.5 years (95% CI, 12.8-24.2). In multivariate analysis, age >50 years (hazard ratio [HR], 2.7; 95% CI, 2.02-3.64), no surgical resection (HR, 1.88; 95% CI, 1.43-2.46), metastasis (HR, 3.0; 95% CI, 2.0-4.5), and poor differentiation were associated with poor survival. Site and histology did not have a significant impact on survival (P = 0.82 and 0.57 respectively). CONCLUSIONS Our study highlights the most important prognostic factors for gastrointestinal FNETs.
Collapse
Affiliation(s)
- Anahat Kaur
- From the Department of Hematology-Oncology, Albert Einstein College of Medicine-Jacobi Medical Center
| | - Shuai Wang
- Department of Internal Medicine, Albert Einstein College of Medicine-Jacobi Medical Center
| | - Joshua Herbert
- Department of Internal Medicine, Albert Einstein College of Medicine-Jacobi Medical Center
| | - Lewis Steinberg
- Department of Hematology-Oncology, Jacobi Medical Center, Bronx, NY
| | - Abhishek Kumar
- From the Department of Hematology-Oncology, Albert Einstein College of Medicine-Jacobi Medical Center
| |
Collapse
|
|
14
|
Chen J, Liu Y, Xu K, Ren F, Li B, Sun H. Establishment and validation of a clinicopathological prognosis model of gastroenteropancreatic neuroendocrine carcinomas. Front Oncol 2022; 12:999012. [PMID: 36226064 PMCID: PMC9549976 DOI: 10.3389/fonc.2022.999012] [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: 07/20/2022] [Accepted: 09/08/2022] [Indexed: 12/04/2022] Open
Abstract
Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are a rare, highly malignant subset of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, how to predict the prognosis of GEP-NECs by clinical features is still under study. This study aims to establish and validate a nomogram model of overall survival (OS) in patients with GEP-NECs for predicting their prognosis. Methods We selected patients diagnosed with GEP-NECs from the Surveillance, Epidemiology, and End Results (SEER) database and two Chinese hospitals. After randomization, we divided the data in the SEER database into the train cohort and the test cohort at a ratio of 7:3 and used the Chinese cohort as the validation cohort. The Cox univariate and multivariate analyses were performed to incorporate statistically significant variables into the nomogram model. We then established a nomogram and validated it by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, the area under the curve (AUC), and the decision curve analysis (DCA) curve. Results We calculated the nomogram C-index as 0.797 with a 95% confidence interval (95% CI) of 0.783–0.815 in the train cohort, 0.816 (95% CI: 0.794–0.833) in the test cohort and 0.801 (95% CI: 0.784–0.827) in the validation cohort. Then, we plotted the calibration curves and ROC curves, and AUCs were obtained to verify the specificity and sensitivity of the model, with 1-, 3- and 5-year AUCs of 0.776, 0.768, and 0.770, respectively, in the train cohort; 0.794, 0.808, and 0.799 in the test cohort; 0.922, 0.925, and 0.947 in the validation cohort. The calibration curve and DCA curves also indicated that this nomogram model had good clinical benefits. Conclusions We established the OS nomogram model of GEP-NEC patients, including variables of age, race, sex, tumor site, tumor grade, and TNM stage. This model has good fitting, high sensitivity and specificity, and good clinical benefits.
Collapse
Affiliation(s)
- Jing Chen
- Hebei Key Laboratory for Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China
| | - Yibing Liu
- The Third Bethune Clinical Medical College, Jilin University, Changchun, China
| | - Ke Xu
- Hebei Key Laboratory for Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China
| | - Fei Ren
- The Second Bethune Clinical Medical College, Jilin University, Changchun, China
| | - Bowen Li
- Hebei Key Laboratory for Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China
| | - Hong Sun
- Hebei Key Laboratory for Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China
- *Correspondence: Hong Sun,
| |
Collapse
|
|
15
|
Magi L, Prosperi D, Lamberti G, Marasco M, Ambrosini V, Rinzivillo M, Campana D, Gentiloni G, Annibale B, Signore A, Panzuto F. Role of [ 18F]FDG PET/CT in the management of G1 gastro-entero-pancreatic neuroendocrine tumors. Endocrine 2022; 76:484-490. [PMID: 35149933 PMCID: PMC9068639 DOI: 10.1007/s12020-022-03000-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 01/28/2022] [Indexed: 02/08/2023]
Abstract
PURPOSE Since the role of [18F]FDG PET/CT in low-grade gastroenteropancreatic (GEP) neuroendocrine neoplasia (NET) is not well established, this study was aimed to evaluate the role of [18F]FDG PET/CT in grade 1 (G1) GEP-NETs. METHODS This is a retrospective study including patients with G1 GEP-NETs who underwent [18F]FDG PET/CT. RESULTS 55 patients were evaluated, including 24 (43.6%) with pancreatic NETs and 31 (56.4%) with gastrointestinal NETs. At the time of diagnosis, 28 (51%) patients had metastatic disease, and 50 (91%) patients were positive by 68-Ga sstr PET/CT. Overall, 27 patients (49%) had positive findings on [18F]FDG PET/CT. Following [18F]FDG PET/CT, therapeutic management was modified in 29 (52.7%) patients. Progression-free survival was longer in patients with negative [18F]FDG PET/CT compared with positive [18F]FDG PET/CT (median PFS was not reached and 24 months, respectively, p = 0.04). This significance was particularly evident in the pancreatic group (p = 0.008). CONCLUSIONS Despite having low proliferative activity, approximately half of GEP-NETs G1 showed positive [18F]FDG PET/CT, with a corresponding negative impact on patients' clinical outcomes. These data are in favor of a more "open" attitude toward the potential use of [18F]FDG PET/CT in the diagnostic work-up of G1 GEP-NETs, which may be used in selected cases to detect those at higher risk for an unfavorable disease course.
Collapse
Affiliation(s)
- Ludovica Magi
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Daniela Prosperi
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189, Rome, Italy
| | - Giuseppe Lamberti
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Marasco
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
| | - Valentina Ambrosini
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
| | - Davide Campana
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Guido Gentiloni
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189, Rome, Italy
| | - Bruno Annibale
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Alberto Signore
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189, Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy.
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
| |
Collapse
|
|
16
|
Naheed S, Holden C, Tanno L, Pattini L, Pearce NW, Green B, Jaynes E, Cave J, Ottensmeier CH, Pelosi G. Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis. BMJ Open 2022; 12:e041961. [PMID: 35241462 PMCID: PMC8895948 DOI: 10.1136/bmjopen-2020-041961] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVES Ki-67, a marker of cellular proliferation, is associated with prognosis across a wide range of tumours, including gastroenteropancreatic neuroendocrine neoplasms (NENs), lymphoma, urothelial tumours and breast carcinomas. Its omission from the classification system of pulmonary NENs is controversial. This systematic review sought to assess whether Ki-67 is a prognostic biomarker in lung NENs and, if feasible, proceed to a meta-analysis. RESEARCH DESIGN AND METHODS Medline (Ovid), Embase, Scopus and the Cochrane library were searched for studies published prior to 28 February 2019 and investigating the role of Ki-67 in lung NENs. Eligible studies were those that included more than 20 patients and provided details of survival outcomes, namely, HRs with CIs according to Ki-67 percentage. Studies not available as a full text or without an English manuscript were excluded. This study was prospectively registered with PROSPERO. RESULTS Of 11 814 records identified, seven studies met the inclusion criteria. These retrospective studies provided data for 1268 patients (693 TC, 281 AC, 94 large cell neuroendocrine carcinomas and 190 small cell lung carcinomas) and a meta-analysis was carried out to estimate a pooled effect. Random effects analyses demonstrated an association between a high Ki-67 index and poorer overall survival (HR of 2.02, 95% CI 1.16 to 3.52) and recurrence-free survival (HR 1.42; 95% CI 1.01 to 2.00). CONCLUSION This meta-analysis provides evidence that high Ki-67 labelling indices are associated with poor clinical outcomes for patients diagnosed with pulmonary NENs. This study is subject to inherent limitations, but it does provide valuable insights regarding the use of the biomarker Ki-67, in a rare tumour. PROSPERO REGISTRATION NUMBER CRD42018093389.
Collapse
Affiliation(s)
- Salma Naheed
- Liverpool Head and Neck Centre, Department of Molecular & Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Chloe Holden
- Department of Oncology, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Lulu Tanno
- Cancer Sciences Unit, NIHR and CRUK Experimental Cancer Medicine Center and NIHR Biomedical Research Center Southampton, University of Southampton Faculty of Medicine, Southampton, UK
| | - Linda Pattini
- Department of Electronics, Information and Bioengineering, Polytechnic of Milan, Milano, Lombardia, Italy
| | - Neil W Pearce
- Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Bryan Green
- Department of Pathology, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Eleanor Jaynes
- Department of Cellular Pathology, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Judith Cave
- Department of Oncology, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Christian H Ottensmeier
- Cancer Sciences Unit, NIHR and CRUK Experimental Cancer Medicine Center and NIHR Biomedical Research Center Southampton, University of Southampton, Southampton, UK
| | - Giuseppe Pelosi
- Department of Oncology and Hemato-Oncology, University of Milan, Milano, Lombardia, Italy
| |
Collapse
|
|
17
|
Haslerud T. SPECT/CT in Neuroendrocrine Tumours. CLINICAL APPLICATIONS OF SPECT-CT 2022:95-118. [DOI: 10.1007/978-3-030-65850-2_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
18
|
Ciobanu OA, Martin S, Fica S. Perspectives on the diagnostic, predictive and prognostic markers of neuroendocrine neoplasms (Review). Exp Ther Med 2021; 22:1479. [PMID: 34765020 PMCID: PMC8576627 DOI: 10.3892/etm.2021.10914] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/23/2021] [Indexed: 12/15/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumors with different types of physiology and prognosis. Therefore, prognostic information, including morphological differentiation, grade, tumor stage and primary location, are invaluable and contribute to the formulation of treatment decisions. Biomarkers that are currently used, including chromogranin A (CgA), serotonin and neuron-specific enolase, are singular parameters that cannot be used to accurately predict variables associated with tumor growth, including proliferation, metabolic rate and metastatic potential. In addition, site-specific biomarkers, such as insulin and gastrin, cannot be applied to all types of NENs. The clinical application of broad-spectrum markers, as it is the case for CgA, remains controversial despite being widely used. Due to limitations of the currently available mono-analyte biomarkers, recent studies were conducted to explore novel parameters for NEN diagnosis, prognosis, therapy stratification and evaluation of treatment response. Identification of prognostic factors for predicting NEN outcome is a critical requirement for the planning of adequate clinical management. Advances in ‘liquid’ biopsies and genomic analysis techniques, including microRNA, circulating tumor DNA or circulating tumor cells and sophisticated biomathematical analysis techniques, such as NETest or molecular image-based biomarkers, are currently under investigation as potentially novel tools for the management of NENs in the future. Despite these recent findings yielding promising observations, further research is necessary. The present review therefore summarizes the existing knowledge and recent advancements in the exploration of biochemical markers for NENs, with focus on gastroenteropancreatic-neuroendocrine tumors.
Collapse
Affiliation(s)
- Oana Alexandra Ciobanu
- Department of Endocrinology and Diabetes, Elias Hospital, 011461 Bucharest, Romania.,Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 20021 Bucharest, Romania
| | - Sorina Martin
- Department of Endocrinology and Diabetes, Elias Hospital, 011461 Bucharest, Romania.,Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 20021 Bucharest, Romania
| | - Simona Fica
- Department of Endocrinology and Diabetes, Elias Hospital, 011461 Bucharest, Romania.,Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 20021 Bucharest, Romania
| |
Collapse
|
|
19
|
Rayes N, Denecke T. [Gastroenteropancreatic neuroendocrine tumors]. Radiologe 2021; 61:1129-1138. [PMID: 34727206 DOI: 10.1007/s00117-021-00929-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Neuroendocrine tumors (NET), or more generally neuroendocrine neoplasms (NEN), represent a very heterogeneous group of rare tumors with varying location which are only defined by their endocrine biology and secretion of synaptophysin and chromogranin A. They originate from mesoderm-derived stem cells. In the last few years, the incidence and prevalence of NEN have been steadily increasing. Classification is based on the affected organ, the proliferation rate and presence or absence of hormone production with typical symptoms. Diagnosis and treatment of these tumors is therefore very specific and requires an interdisciplinary approach. Treatment options include endoscopic or surgical resection, drug therapy for control of symptoms and proliferation, locoregional therapy and radionuclide therapy. Guidelines with algorithms for diagnostic workup and treatment are constantly updated.
Collapse
Affiliation(s)
- Nada Rayes
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Liebigstr. 20, 04103, Leipzig, Deutschland.
| | - Timm Denecke
- Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| |
Collapse
|
|
20
|
Zhang JY, Kunz PL. Making Sense of a Complex Disease: A Practical Approach to Managing Neuroendocrine Tumors. JCO Oncol Pract 2021; 18:258-264. [PMID: 34652954 DOI: 10.1200/op.21.00240] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous clinical entity with a broad range of grade, pace of disease, functional status, and primary sites. Pathologic classification, diagnostic modalities, and therapeutic options for NETs have evolved considerably in the past decade. In part driven by these advances, incidence and prevalence of NETs are rising in the United States and the practicing oncologist is likely to encounter these in the clinic. However, there are no clear lines of therapy for unresectable or metastatic NETs, and sequencing of systemic therapies depends on consideration of patient and tumor characteristics including extent of disease, grade, pace of growth, functional status, primary site, somatostatin receptor status, performance status, and comorbidities. Familiarity with ongoing clinical trials will guide therapeutic decision making as well. In this review, we seek to provide a framework to formulate and tailor an individualized treatment plan for each patient with a NET.
Collapse
Affiliation(s)
- Janie Y Zhang
- Division of Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT
| | - Pamela L Kunz
- Division of Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT
| |
Collapse
|
|
21
|
Albertelli M, Dotto A, Di Dato C, Malandrino P, Modica R, Versari A, Colao A, Ferone D, Faggiano A. PRRT: identikit of the perfect patient. Rev Endocr Metab Disord 2021; 22:563-579. [PMID: 32978685 PMCID: PMC8346456 DOI: 10.1007/s11154-020-09581-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Peptide receptor radionuclide therapy (PRRT) has been strengthened since the publication of NETTER-1. Nevertheless, the correct positioning in the therapeutic algorithm is debated, and no optimal sequence has yet been standardized. Possible criteria to predict the response to PRRT in neuroendocrine tumors (NET) have been proposed. The aim of this review is to define the perfect identity of the eligible patient who can mostly benefit from this therapy. Possible predictive criteria which have been analysed were: primary tumor site, grading, tumor burden, FDG PET and 68Ga-PET uptake. Primary tumor site and 68Ga-PET uptake do not play a pivotal role in predicting the response, while tumor burden, FDG PET uptake and grading seem to represent predictive/prognostic factors for response to PRRT. The heterogeneity in trial designs, patient populations, type of radionuclides, previous therapies and measurement of outcomes, inevitably limits the strength of our conclusions, therefore care must be taken in applying these results to clinical practice. In conclusion, the perfect patient, selected by 68Ga-PET uptake, will likely have a relatively limited liver tumor burden, a ki67 index <20% and will respond to PRRT irrespective to primary tumor. Nevertheless, we have mostly prognostic than predictive factors to predict the efficacy of PRRT in individual patients, while a promising tool could be the NETest. However, to date, the identikit of the perfect patient for PRRT is a puzzle without some pieces and still we cannot disregard a multidisciplinary discussion of the individual case to select the patients who will mostly benefit from PRRT.
Collapse
Affiliation(s)
- M Albertelli
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
| | - A Dotto
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
| | - C Di Dato
- Endocrinology, Department of Experimental Medicine, "Sapienza", University of Rome, Rome, Italy
| | - P Malandrino
- Endocrinology, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Medical Center, University of Catania, Catania, Italy
| | - R Modica
- Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Napoli, Napoli, Italy
| | - A Versari
- Nuclear Medicine, Azienda Ospedaliera Santa Maria Nuova-IRCCS Reggio Emilia, Reggio Emilia, Italy
| | - A Colao
- Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Napoli, Napoli, Italy
| | - D Ferone
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
| | - A Faggiano
- Endocrinology, Department of Experimental Medicine, "Sapienza", University of Rome, Rome, Italy.
- Depart. of Experimental Medicine, Division of Medical Physiopathology Sapienza University of Rome Viale del Policlinico 155, 00161, Rome, Italy.
| | | |
Collapse
|
|
22
|
Nguyen AH, O'Leary MP, De Andrade JP, Ituarte PG, Warner SG, Melstrom LG, Kessler J, Fong Y, Li D, Singh G. Presentation and survival of gastro-entero-pancreatic neuroendocrine tumors in young adults versus older patients. Am J Surg 2021; 223:939-944. [PMID: 34474917 DOI: 10.1016/j.amjsurg.2021.08.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/02/2021] [Accepted: 08/16/2021] [Indexed: 11/01/2022]
Abstract
BACKGROUND A minority of patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) is diagnosed at younger age. This population-based study explores the broad clinical and pathologic features of the youngest 5% of adult patients with GEP-NETs. METHODS A retrospective study of the National Cancer Database (NCDB) of patients with a primary GEP-NET was performed. Patients were stratified by age. Kaplan-Meier and multivariate Cox proportional hazards analyses were performed. RESULTS We identified 31,983 patients with a diagnosis of a GEP-NET and only 5% of patients were under the age of 35. Young patients were found to have greater proportions of localized, well differentiated disease. On multivariate analysis, young age, well differentiated histology, early stage, and surgical intervention were associated with lower risk of mortality. CONCLUSIONS Young patients with GEP-NETs tend to have earlier stage of presentation and well differentiated tumors, which may be most amenable to surgical intervention.
Collapse
Affiliation(s)
- Andrew H Nguyen
- Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Michael P O'Leary
- Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - James P De Andrade
- Department of Surgery, University of Iowa Health Care, 200 Hawkins Drive, Iowa City, IA, USA
| | - Philip G Ituarte
- Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Susanne G Warner
- Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Laleh G Melstrom
- Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Jonathan Kessler
- Department of Radiology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Daneng Li
- Department of Medical Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Gagandeep Singh
- Department of Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA.
| |
Collapse
|
|
23
|
Folkestad O, Wasmuth HH, Mjønes P, Fougner R, Hauso Ø, Fossmark R. Survival and Disease Recurrence in Patients with Duodenal Neuroendocrine Tumours-A Single Centre Cohort. Cancers (Basel) 2021; 13:cancers13163985. [PMID: 34439140 PMCID: PMC8391208 DOI: 10.3390/cancers13163985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/02/2022] Open
Abstract
Simple Summary Neuroendocrine tumours of the upper part of the small intestine are rare. They are slow growing but may spread to lymph nodes or other organs already when the tumours are small. Such tumours may be treated by endoscopic removal or by an operation. In the current study we present the treatment results of 32 patients with this rare tumour. We found that the long-term survival was long, and patients more often died from other diseases. The survival was associated with the growth rate of the tumours and whether all the tumour tissue could be removed. Endoscopic removal was sufficient for smaller tumours <10 mm, whereas a high proportion of tumours 10–20 mm have lymph node metastases that must be removed by an operation to make patients tumour free. None of the tumours that were perceived as cured after removal recurred after an average follow-up time of 4.8 years. Abstract Background: Duodenal neuroendocrine tumours (D-NETs) are rare but increasingly diagnosed. This study aimed to assess the overall survival and recurrence rate among patients treated for D-NETs. Methods: Patients with D-NETs were retrospectively reviewed with a median follow-up time of 4.8 years (range 0.0–17.2 years). Results: A total of 32 patients with median age 68.0 years were identified. Fifteen patients underwent surgery while ten patients underwent endoscopic treatment. Mean estimated overall survival for the entire population was 12.1 years (95% CI 9.5–14.7 years), while 5-year overall survival was 81.3%. Tumour grade G1 was associated with longer mean estimated survival compared to G2 tumours (13.2 years versus 4.4 years, p = 0.010). None of the 23 patients who underwent presumed radical endoscopic or surgical resection had disease recurrence during follow-up. Tumours <10 mm could be treated endoscopically whereas a high proportion of patients with tumours 10–20 mm should be considered for surgery. Conclusion: Patients with D-NETs had long overall survival, and mortality was more influenced by other diseases. Both endoscopic and surgical resections were effective as no recurrences were diagnosed during follow-up.
Collapse
Affiliation(s)
- Oddry Folkestad
- Department of Gastrointestinal Surgery, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway;
- Department of Gastrointestinal Surgery, Vestfold Hospital, 3103 Tønsberg, Norway
| | - Hans H. Wasmuth
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
| | - Patricia Mjønes
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Pathology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidun Fougner
- Department of Radiology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway;
| | - Øyvind Hauso
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Gastroenterology and Hepatology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Gastroenterology and Hepatology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Correspondence: ; Tel.: +47-7292-5164
| |
Collapse
|
|
24
|
Shah MH, Goldner WS, Benson AB, Bergsland E, Blaszkowsky LS, Brock P, Chan J, Das S, Dickson PV, Fanta P, Giordano T, Halfdanarson TR, Halperin D, He J, Heaney A, Heslin MJ, Kandeel F, Kardan A, Khan SA, Kuvshinoff BW, Lieu C, Miller K, Pillarisetty VG, Reidy D, Salgado SA, Shaheen S, Soares HP, Soulen MC, Strosberg JR, Sussman CR, Trikalinos NA, Uboha NA, Vijayvergia N, Wong T, Lynn B, Hochstetler C. Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:839-868. [PMID: 34340212 DOI: 10.6004/jnccn.2021.0032] [Citation(s) in RCA: 312] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.
Collapse
Affiliation(s)
- Manisha H Shah
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | - Pamela Brock
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Paxton V Dickson
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | | | | | | | | | - Jin He
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | - Arash Kardan
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | | | | | | | | | | | | | | | | | | | | | - Nikolaos A Trikalinos
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | | | - Beth Lynn
- National Comprehensive Cancer Network
| | | |
Collapse
|
|
25
|
Chevalier B, Dupuis H, Jannin A, Lemaitre M, Do Cao C, Cardot-Bauters C, Espiard S, Vantyghem MC. Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations. Front Endocrinol (Lausanne) 2021; 12:678869. [PMID: 34025587 PMCID: PMC8134657 DOI: 10.3389/fendo.2021.678869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 04/15/2021] [Indexed: 11/13/2022] Open
Abstract
Phakomatoses encompass a group of rare genetic diseases, such as von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC) and Cowden syndrome (CS). These disorders are due to molecular abnormalities on the RAS-PI3K-Akt-mTOR pathway for NF1, TSC and CS, and to hypoxia sensing for VHL. Phakomatoses share some phenotypic traits such as neurological, ophthalmological and cutaneous features. Patients with these diseases are also predisposed to developing multiple endocrine tissue tumors, e.g., pheochromocytomas/paragangliomas are frequent in VHL and NF1. All forms of phakomatoses except CS may be associated with digestive neuroendocrine tumors. More rarely, thyroid cancer and pituitary or parathyroid adenomas have been reported. These susceptibilities are noteworthy, because their occurrence rate, prognosis and management differ slightly from the sporadic forms. The aim of this review is to summarize current knowledge on endocrine glands tumors associated with VHL, NF1, TSC, and CS, especially neuroendocrine tumors and pheochromocytomas/paragangliomas. We particularly detail recent advances concerning prognosis and management, especially parenchyma-sparing surgery and medical targeted therapies such as mTOR, MEK and HIF-2 α inhibitors, which have shown truly encouraging results.
Collapse
Affiliation(s)
- Benjamin Chevalier
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
- University of Lille, Lille, France
| | - Hippolyte Dupuis
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
| | - Arnaud Jannin
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
- University of Lille, Lille, France
| | - Madleen Lemaitre
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
- University of Lille, Lille, France
| | - Christine Do Cao
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
| | - Catherine Cardot-Bauters
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
| | - Stéphanie Espiard
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
- University of Lille, Lille, France
- INSERM U1190, European Genomic Institute for Diabetes, Lille, France
| | - Marie Christine Vantyghem
- Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
- University of Lille, Lille, France
- INSERM U1190, European Genomic Institute for Diabetes, Lille, France
| |
Collapse
|
|
26
|
Tong Z, Wang L, Shi W, Zeng Y, Zhang H, Liu L, Zheng Y, Chen C, Xia W, Fang W, Zhao P. Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms. Front Med (Lausanne) 2021; 8:620988. [PMID: 34026777 PMCID: PMC8131504 DOI: 10.3389/fmed.2021.620988] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 04/06/2021] [Indexed: 02/06/2023] Open
Abstract
Background: Data on inter-tumoral heterogeneity and clonal evolution of pancreatic neuroendocrine neoplasms (panNENs) with liver metastasis are limited. The aim of this study was to explore different patterns of clonal evolution of pancreatic neuroendocrine neoplasms with liver metastasis and the possible distinctive signaling pathways involved between G2 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Methods: Tumor tissues of five patients (10 samples) with pancreatic neuroendocrine neoplasms with synchronous liver metastasis were analyzed using next-generation sequencing. PyClone, Gene Ontology, and Reactome pathway enrichment analysis were also applied. Results: Mutated genes varied in individuals, reflecting the inter-tumoral heterogeneity of panNENs. The distribution of subclones varied during tumor metastasis, and different clonal evolution patterns were revealed between NETs and NECs. Gene Ontology and Reactome analyses revealed that in both NETs and NECs, signaling pathways and biological processes shared similarities and differences in the primary and metastatic lesions. In addition, the signaling pathway features were different between NETs and NECs. In the primary lesions, epigenetic changes and post-transcriptional modifications participated in NETs, while FGFR signaling, EGFR signaling, and NTRK2 signaling were largely involved in NECs. Although DNA repair and TP53 regulation were both involved in the metastatic lesions, most of the signaling pathways and biological processes disrupted by the mutated genes were different. Conclusions: Our study revealed spatial inter-tumoral heterogeneity and temporal clonal evolution in PanNENs, providing potential therapeutic targets for further prospective clinical trials.
Collapse
Affiliation(s)
- Zhou Tong
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lin Wang
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | | | | | - Hangyu Zhang
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lulu Liu
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Zheng
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chunlei Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weiliang Xia
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weijia Fang
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Peng Zhao
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
27
|
Hasic Telalovic J, Pillozzi S, Fabbri R, Laffi A, Lavacchi D, Rossi V, Dreoni L, Spada F, Fazio N, Amedei A, Iadanza E, Antonuzzo L. A Machine Learning Decision Support System (DSS) for Neuroendocrine Tumor Patients Treated with Somatostatin Analog (SSA) Therapy. Diagnostics (Basel) 2021; 11:804. [PMID: 33925256 PMCID: PMC8145352 DOI: 10.3390/diagnostics11050804] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/23/2021] [Accepted: 04/26/2021] [Indexed: 01/10/2023] Open
Abstract
The application of machine learning (ML) techniques could facilitate the identification of predictive biomarkers of somatostatin analog (SSA) efficacy in patients with neuroendocrine tumors (NETs). We collected data from 74 patients with a pancreatic or gastrointestinal NET who received SSA as first-line therapy. We developed three classification models to predict whether the patient would experience a progressive disease (PD) after 12 or 18 months based on clinic-pathological factors at the baseline. The dataset included 70 samples and 15 features. We initially developed three classification models with accuracy ranging from 55% to 70%. We then compared ten different ML algorithms. In all but one case, the performance of the Multinomial Naïve Bayes algorithm (80%) was the highest. The support vector machine classifier (SVC) had a higher performance for the recall metric of the progression-free outcome (97% vs. 94%). Overall, for the first time, we documented that the factors that mainly influenced progression-free survival (PFS) included age, the number of metastatic sites and the primary site. In addition, the following factors were also isolated as important: adverse events G3-G4, sex, Ki67, metastatic site (liver), functioning NET, the primary site and the stage. In patients with advanced NETs, ML provides a predictive model that could potentially be used to differentiate prognostic groups and to identify patients for whom SSA therapy as a single agent may not be sufficient to achieve a long-lasting PFS.
Collapse
Affiliation(s)
- Jasminka Hasic Telalovic
- Computer Science Department, University Sarajevo School of Science and Technology, 71210 Sarajevo, Bosnia and Herzegovina;
| | - Serena Pillozzi
- Medical Oncology Unit, Careggi University Hospital, Largo Brambilla 4, 50134 Florence, Italy; (S.P.); (D.L.); (V.R.); (L.D.); (L.A.)
| | - Rachele Fabbri
- Department of Information Engineering, University of Florence, Via S. Marta 3, 50139 Florence, Italy; (R.F.); (E.I.)
| | - Alice Laffi
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141 Milan, Italy; (A.L.); (F.S.); (N.F.)
| | - Daniele Lavacchi
- Medical Oncology Unit, Careggi University Hospital, Largo Brambilla 4, 50134 Florence, Italy; (S.P.); (D.L.); (V.R.); (L.D.); (L.A.)
| | - Virginia Rossi
- Medical Oncology Unit, Careggi University Hospital, Largo Brambilla 4, 50134 Florence, Italy; (S.P.); (D.L.); (V.R.); (L.D.); (L.A.)
| | - Lorenzo Dreoni
- Medical Oncology Unit, Careggi University Hospital, Largo Brambilla 4, 50134 Florence, Italy; (S.P.); (D.L.); (V.R.); (L.D.); (L.A.)
| | - Francesca Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141 Milan, Italy; (A.L.); (F.S.); (N.F.)
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141 Milan, Italy; (A.L.); (F.S.); (N.F.)
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| | - Ernesto Iadanza
- Department of Information Engineering, University of Florence, Via S. Marta 3, 50139 Florence, Italy; (R.F.); (E.I.)
| | - Lorenzo Antonuzzo
- Medical Oncology Unit, Careggi University Hospital, Largo Brambilla 4, 50134 Florence, Italy; (S.P.); (D.L.); (V.R.); (L.D.); (L.A.)
| |
Collapse
|
|
28
|
Rinzivillo M, Prosperi D, Mazzuca F, Magi L, Iannicelli E, Pilozzi E, Franchi G, Laghi A, Annibale B, Signore A, Panzuto F. [ 18F]FDG-PET/CT and long-term responses to everolimus in advanced neuroendocrine neoplasia. J Endocrinol Invest 2021; 44:811-818. [PMID: 32767279 DOI: 10.1007/s40618-020-01378-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/30/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE This study aims to identify in patients with neuroendocrine neoplasia (NEN) the potential correlation between FDG-PET findings and responses to everolimus therapy to identify predictors of long-term efficacy. METHODS Retrospective analysis of patients with sporadic, advanced, progressive NEN treated with everolimus was performed based on the available data on FDG-PET patients obtained before commencing therapy. Data are expressed as the median (25-75th IQR). Risk factor analysis and survival analysis were performed by logistic regression and Cox proportional hazard regression and the determination of Kaplan-Meier curves, as appropriate. RESULTS Sixty-six patients were evaluated (NET G1 19.7%, NET G2 75.7%, and NET G3 4.6%), including 45.4% with positive FDG-PET findings. Overall, disease stabilization and a partial response were achieved for 71.2% and 6% of patients, respectively. A long-term response (> 24 months) was observed in 33% of patients. Ki67 was the only predictor of tumor progression (p = 0.03). No significant difference in clinical outcomes was observed between patients with positive or negative FDG-PET findings (median PFS was 24 months and 18 months, respectively, p = 0.337; the disease control rate was 83.3% and 70%, respectively, p = 0.245). CONCLUSIONS Everolimus is a valid therapeutic option for advanced, progressive, well-differentiated NEN, even in patients with positive FDG-PET findings.
Collapse
Affiliation(s)
- M Rinzivillo
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy
| | - D Prosperi
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - F Mazzuca
- Medical Oncology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
- Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
| | - L Magi
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy
| | - E Iannicelli
- Radiology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
- Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
| | - E Pilozzi
- Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
- Pathology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - G Franchi
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - A Laghi
- Radiology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
- Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
| | - B Annibale
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy
- Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
| | - A Signore
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
- Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
| | - F Panzuto
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy.
| |
Collapse
|
|
29
|
Mandair D, Khan MS, Lopes A, Furtado O'Mahony L, Ensell L, Lowe H, Hartley JA, Toumpanakis C, Caplin M, Meyer T. Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors. J Clin Endocrinol Metab 2021; 106:872-882. [PMID: 33180939 DOI: 10.1210/clinem/dgaa822] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined. OBJECTIVE This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs. PATIENTS AND METHODS CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. RESULTS The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P < .01) for PanNETs and 5.88 (P < .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P < .03) and 5.09 (P < .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P < .01), whereas 2 or greater CTCs had an HR of 2.25 (P < .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P < .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P < .06). CONCLUSIONS The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.
Collapse
Affiliation(s)
- Dalvinder Mandair
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Mohid S Khan
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
- Department of Gastroenterology, University Hospital of Wales, Cardiff, Wales, UK
| | - Andre Lopes
- Cancer Research UK & UCL Cancer Trials Centre, University College London, London
| | | | - Leah Ensell
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Helen Lowe
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - John A Hartley
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | | | - Martyn Caplin
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Tim Meyer
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
- Department of Oncology, Royal Free Hospital, London, UK
| |
Collapse
|
|
30
|
Klimov S, Xue Y, Gertych A, Graham RP, Jiang Y, Bhattarai S, Pandol SJ, Rakha EA, Reid MD, Aneja R. Predicting Metastasis Risk in Pancreatic Neuroendocrine Tumors Using Deep Learning Image Analysis. Front Oncol 2021; 10:593211. [PMID: 33718106 PMCID: PMC7946991 DOI: 10.3389/fonc.2020.593211] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/18/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The prognosis of patients with pancreatic neuroendocrine tumors (PanNET), the second most common type of pancreatic cancer, varies significantly, and up to 15% of patients develop metastasis. Although certain morphological characteristics of PanNETs have been associated with patient outcome, there are no available morphology-based prognostic markers. Given that current clinical histopathology markers are unable to identify high-risk PanNET patients, the development of accurate prognostic biomarkers is needed. Here, we describe a novel machine learning, multiclassification pipeline to predict the risk of metastasis using morphological information from whole tissue slides. METHODS Digital images from surgically resected tissues from 89 PanNET patients were used. Pathologist-annotated regions were extracted to train a convolutional neural network (CNN) to identify tiles consisting of PanNET, stroma, normal pancreas parenchyma, and fat. Computationally annotated cancer or stroma tiles and patient metastasis status were used to train CNN to calculate a region based metastatic risk score. Aggregation of the metastatic probability scores across the slide was performed to predict the risk of metastasis. RESULTS The ability of CNN to discriminate different tissues was high (per-tile accuracy >95%; whole slide cancer regions Jaccard index = 79%). Cancer and stromal tiles with high evaluated probability provided F1 scores of 0.82 and 0.69, respectively, when we compared tissues from patients who developed metastasis and those who did not. The final model identified low-risk (n = 76) and high-risk (n = 13) patients, as well as predicted metastasis-free survival (hazard ratio: 4.71) after adjusting for common clinicopathological variables, especially in grade I/II patients. CONCLUSION Using slides from surgically resected PanNETs, our novel, multiclassification, deep learning pipeline was able to predict the risk of metastasis in PanNET patients. Our results suggest the presence of prognostic morphological patterns in PanNET tissues, and that these patterns may help guide clinical decision making.
Collapse
Affiliation(s)
- Sergey Klimov
- Department of Biology, Georgia State University, Atlanta, GA, United States
- Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, United States
| | - Yue Xue
- Department of Pathology, Northwestern University, Chicago, IL, United States
| | - Arkadiusz Gertych
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Faculty of Biomedical Engineering, Silesian University of Technology, Zabrze, Poland
| | - Rondell P Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
| | - Yi Jiang
- Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, United States
| | - Shristi Bhattarai
- Department of Biology, Georgia State University, Atlanta, GA, United States
| | - Stephen J Pandol
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Emad A Rakha
- Department of Cellular Pathology, University of Nottingham, Nottingham, United Kingdom
| | - Michelle D Reid
- Department of Pathology, Emory University, Atlanta, GA, United States
| | - Ritu Aneja
- Department of Biology, Georgia State University, Atlanta, GA, United States
| |
Collapse
|
|
31
|
Muniraj T, Aslanian HR. Pancreatic Neuroendocrine Tumors. GERIATRIC GASTROENTEROLOGY 2021:1933-1951. [DOI: 10.1007/978-3-030-30192-7_81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
32
|
Panzuto F, Massironi S, Partelli S, Campana D, Rinzivillo M, Invernizzi P, Andreasi V, Lamberti G, Falconi M. Gastro-entero-pancreatic neuroendocrine neoplasia: The rules for non-operative management. Surg Oncol 2020; 35:141-148. [PMID: 32877883 DOI: 10.1016/j.suronc.2020.08.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/26/2020] [Accepted: 08/17/2020] [Indexed: 02/05/2023]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with favorable pathological and clinical features may be considered as indolent lesions, and therefore be amenable to conservative management. According to the primary tumor site, different non-aggressive approaches, based on endoscopic resection or simple active surveillance, can be proposed to selected patients fulfilling specific criteria. Tumor size, Ki67 proliferative index and depth of invasion are markers that can be used in order to identify these subjects. Patients with type I gastric NENs <1 cm as well as those with non-ampullary duodenal NENs <1 cm with no associated syndrome can be safely managed by endoscopic resection. On the other hand, an active surveillance approach is preferred over surgery for patients with asymptomatic, non-functioning pancreatic NENs ≤2 cm without dilation of the main pancreatic duct or bile duct. As far as NENs of the appendix are concerned, appendectomy should be considered as curative when a R0 resection has been achieved in the presence of a tumor ≤1.5 cm, graded as G1 and without lymphovascular invasion. Finally, G1 rectal NENs ≤1 cm without invasion of the muscular layer can be safely treated by endoscopic resection. Therefore, surgeons should be aware of the existence of indolent GEP-NENs, in order to avoid unnecessary operations with associated postoperative complications.
Collapse
Affiliation(s)
- Francesco Panzuto
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy.
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute - Vita-Salute San Raffaele University, Milan, Italy
| | - Davide Campana
- Division of Oncology, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Valentina Andreasi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute - Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Lamberti
- Division of Oncology, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute - Vita-Salute San Raffaele University, Milan, Italy
| |
Collapse
|
|
33
|
Rindi G, Wiedenmann B. Neuroendocrine neoplasia of the gastrointestinal tract revisited: towards precision medicine. Nat Rev Endocrinol 2020; 16:590-607. [PMID: 32839579 DOI: 10.1038/s41574-020-0391-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2020] [Indexed: 02/06/2023]
Abstract
Over the past 5 years, a number of notable research advances have been made in the field of neuroendocrine cancer, specifically with regard to neuroendocrine cancer of the gastrointestinal tract. The aim of this Review is to provide an update on current knowledge that has proven effective for the clinical management of patients with these tumours. For example, for the first time in the tubular gastrointestinal tract, well-differentiated high-grade (grade 3) tumours and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are defined in the WHO classification. This novel classification enables efficient identification of the most aggressive well-differentiated neuroendocrine tumours and helps in defining the degree of aggressiveness of MiNENs. The Review also discusses updates to epidemiology, cell biology (including vesicle-specific components) and the as-yet-unresolved complex genetic background that varies according to site and differentiation status. The Review summarizes novel diagnostic instruments, including molecules associated with the secretory machinery, novel radiological approaches (including pattern recognition techniques), novel PET tracers and liquid biopsy combined with DNA or RNA assays. Surgery remains the treatment mainstay; however, peptide receptor radionuclide therapy with novel radioligands and new emerging medical therapies (including vaccination and immunotherapy) are evolving and being tested in clinical trials, which are summarized and critically reviewed here.
Collapse
Affiliation(s)
- Guido Rindi
- Università Cattolica del Sacro Cuore, Rome, Italy.
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
| | - Bertram Wiedenmann
- Charité, Campus Virchow Klinikum and Charité Mitte, University Medicine Berlin, Berlin, Germany
| |
Collapse
|
|
34
|
Kimura T, Sugimoto M, Takagi T, Suzuki R, Konno N, Asama H, Sato Y, Irie H, Nakamura J, Takasumi M, Hashimoto M, Kato T, Kofunato Y, Kimura T, Yamada S, Hashimoto Y, Marubashi S, Hikichi T, Ohira H. Pancreatic Neuroendocrine Neoplasm Invading the Entire Main Pancreatic Duct Diagnosed by a Preoperative Endoscopic Biopsy. Intern Med 2020; 59:1991-1996. [PMID: 32448838 PMCID: PMC7492121 DOI: 10.2169/internalmedicine.4546-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 03/27/2020] [Indexed: 11/06/2022] Open
Abstract
A 78-year-old man was referred to our hospital for a detailed examination of a pancreatic tumor that filled the main pancreatic duct (MPD). The histological diagnosis of the endoscopic biopsy specimen was neuroendocrine tumor (NET) G3. The patient subsequently underwent total pancreatectomy. The histological diagnosis of the surgical specimen was also NET G3. This is the first report of a NET that occupied the MPD and was diagnosed by a preoperative endoscopic biopsy through the papilla of Vater. This case is a good example of a histopathological diagnostic method for pancreatic tumors invading the entire MPD.
Collapse
Affiliation(s)
- Tomoya Kimura
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Mitsuru Sugimoto
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Tadayuki Takagi
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Rei Suzuki
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Naoki Konno
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Hiroyuki Asama
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Yuki Sato
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Hiroki Irie
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Jun Nakamura
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
- Department of Endoscopy, Fukushima Medical University Hospital, Japan
| | - Mika Takasumi
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Minami Hashimoto
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
- Department of Endoscopy, Fukushima Medical University Hospital, Japan
| | - Tsunetaka Kato
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Yasuhide Kofunato
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, School of Medicine, Fukushima Medical University, Japan
| | - Takashi Kimura
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, School of Medicine, Fukushima Medical University, Japan
| | - Shoki Yamada
- Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Japan
| | - Yuko Hashimoto
- Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Japan
| | - Shigeru Marubashi
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, School of Medicine, Fukushima Medical University, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| |
Collapse
|
|
35
|
Small Bowel Tumors – Case Series Analysis: Prognostic Factors and Survivals. Indian J Surg 2020. [DOI: 10.1007/s12262-020-02092-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
|
|
36
|
Chen X, Guo C, Cui W, Sun K, Wang Z, Chen X. CD56 Expression Is Associated with Biological Behavior of Pancreatic Neuroendocrine Neoplasms. Cancer Manag Res 2020; 12:4625-4631. [PMID: 32606955 PMCID: PMC7306468 DOI: 10.2147/cmar.s250071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 05/20/2020] [Indexed: 12/28/2022] Open
Abstract
Purpose CD56 is a neural cell adhesion molecule that plays a role in the cohesiveness of neuroendocrine cells. The aim of this study was to explore the biological values of CD56 expression in pancreatic neuroendocrine neoplasms (PNENs) and its role in predicting PNENs grades. Patients and Methods A total of 138 patients with histological-proven PNENs was included (66 G1, 46 G2 and 26 G3). The clinicopathological characteristics, including mitosis count, ki67 index, chromogranin A (CgA), synaptophysin (Syn) and CD56 expression, were evaluated. We assessed the diagnostic performance of markers in predicting PNEN G3 and the association between CD56 expression and risk of G3 or organs invasion. Results Lack of CD56 immunoreaction (CD56-) was more common in PNEN G3 than G1/G2 (31% vs 0–2%, p < 0.01). The sizes of CD56- tumors were larger than CD56 positive tumors in PNEN G3 (p < 0.01). The odds ratio (OR) of CD56- expression was 13.6 [95% confidence interval (CI): 2.1–88.1] in predicting PNEN G3. The OR of CD56- expression was 6.5 (95% CI: 1.1–38.6) and 31.9 (95% CI: 1.09–938.3) in predicting organs invasion and neuroendocrine carcinoma in PNEN G3, respectively. Tumor size (area under the curve [AUC] = 0.77 and size+CD56- expression [AUC = 0.84]) had acceptable performance in predicating PNEN G3. Conclusion Lack of CD56 immunoreaction may be a predictor and biological behavior marker for PNEN G3.
Collapse
Affiliation(s)
- Xin Chen
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 2100029, People's Republic of China
| | - Chuangen Guo
- Department of Radiology, The First Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310003, People's Republic of China
| | - Wenjing Cui
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 2100029, People's Republic of China
| | - Ke Sun
- Department of Pathology, The First Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310003, People's Republic of China
| | - Zhongqiu Wang
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 2100029, People's Republic of China
| | - Xiao Chen
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 2100029, People's Republic of China
| |
Collapse
|
|
37
|
Kniepeiss D, Schemmer P. Transplantation bei Lebermetastasen neuroendokriner Tumoren – Heilung oder Palliation? JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2020; 13:54-58. [DOI: 10.1007/s41969-019-00087-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
|
|
38
|
Abstract
OBJECTIVE There is a scarcity of prognostic tools for small intestine neuroendocrine tumors (SI-NETs) and inconsistencies in currently available grading and staging systems. Nomograms are being proposed to address these limitations. However, none is specific to the US population. This study proposed a concise nomogram for SI-NETs using US population-based data. METHODS Patients with SI-NETs (2004-2015) were selected from the Surveillance, Epidemiology, and End Results database. Variables selected were age, sex, race, tumor grade, primary tumor size, and TNM staging. Cox regression parameter estimates were used to generate nomogram scores. RESULTS A total of 2734 patients were selected: 2050 for nomogram development and 684 for internal validation. Prognosticators, age (P < 0.0001), primary tumor size >3 cm (P < 0.0022), tumor grade (P < 0.0001), depth of invasion ≥T3 (P < 0.0280), and distant metastasis (P < 0.0001) were used to develop the nomogram. Nomogram scores ranges from 10 to 80 points with an area under the curve of 0.76, which remained consistently high during internal validation (area under the curve, 0.75). CONCLUSIONS This Surveillance, Epidemiology, and End Results database nomorgram is a concise prognostic tool that demonstrated high predictive accuracy.
Collapse
|
|
39
|
Wang H, Lin Z, Li G, Zhang D, Yu D, Lin Q, Wang J, Zhao Y, Pi G, Zhang T. Validation and modification of staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma. BMC Cancer 2020; 20:188. [PMID: 32138704 PMCID: PMC7059325 DOI: 10.1186/s12885-020-6634-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Accepted: 02/14/2020] [Indexed: 12/13/2022] Open
Abstract
Background The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful tumor–node–metastasis (TNM) staging system for poorly differentiated pancreatic neuroendocrine carcinomas (pNECs). Methods An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients), and a modified system based on the analysis of the 7th AJCC classification was proposed. Results In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI) = 0.73–2.06, P = 0.44; HR for stage III =2.20, 95% CI =1.06–4.56, P = 0.03; HR for stage IV =4.95, 95% CI =3.20–7.65, P < 0.001). The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. Conclusions The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.
Collapse
Affiliation(s)
- Haihong Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhenyu Lin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Guiling Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Dejun Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Dandan Yu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qili Lin
- School of Business and Administration, Jiangxi University of Finance and Economics, Nanchang, China
| | - Jing Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ye Zhao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Guoliang Pi
- Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| |
Collapse
|
|
40
|
Hacking SM, Sajjan S, Lee L, Ziemba Y, Angert M, Yang Y, Jin C, Chavarria H, Kataria N, Jain S, Nasim M. Potential Pitfalls in Diagnostic Digital Image Analysis: Experience with Ki-67 and PHH3 in Gastrointestinal Neuroendocrine Tumors. Pathol Res Pract 2020; 216:152753. [DOI: 10.1016/j.prp.2019.152753] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 11/11/2019] [Accepted: 11/17/2019] [Indexed: 11/28/2022]
|
|
41
|
Kiritani S, Arita J, Matsumura M, Nishioka Y, Kudo H, Ichida A, Ishizawa T, Akamatsu N, Kaneko J, Hasegawa K. Repeat hepatectomy for patients with recurrent neuroendocrine liver metastasis: Comparison with first hepatectomy. Surgery 2020; 167:404-409. [PMID: 31635827 DOI: 10.1016/j.surg.2019.08.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 08/06/2019] [Accepted: 08/20/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND The value of repeat hepatectomy for intrahepatic recurrence after curative resection of neuroendocrine liver metastasis (NELM) remains unclear. The aim of this retrospective cohort study was to determine the significance of repeat hepatectomy for recurrent NELM. METHODS Patients who underwent hepatectomy for NELM between 1994 and 2016 were identified. The indications for a first hepatectomy were adequate liver remnant volume and no extrahepatic metastasis. The diagnosis of recurrent NELM was based on radiographic examinations. The indications for a repeat hepatectomy were the same as those for the first hepatectomy. Clinicopathologic factors, short-term survival, and long-term survival were investigated using clinical records. RESULTS Forty-four patients enrolled in this study. Thirty-three patients among them underwent a curative hepatectomy, and 28 of them developed recurrence. Of them, 16 patients underwent a repeat hepatectomy. The overall survival of the repeat hepatectomy cohort (n = 16) was significantly better than that of the no repeat hepatectomy cohort (n = 12) (P < .001). The progression free survival after the first hepatectomy (n = 44) and that after repeat hepatectomy (n = 16) were similar (P = .546). No significant difference was seen between the frequency of major complications (Clavien-Dindo score ≥ 3a) after the first and repeat hepatectomy (P = .279). No repeat hepatectomy (hazard ratio [HR] 5.0, P = .036) was identified as an independent predictive factor of a poor outcome among the recurrent cohort, along with the presence of multiple nodules (HR 26.2, P = .008) and a CA19-9 level ≥40 U/mL (HR 11.2, P = .012). CONCLUSIONS A repeat hepatectomy is feasible in selected patients with recurrent NELM.
Collapse
Affiliation(s)
- Sho Kiritani
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Masaru Matsumura
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yujiro Nishioka
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hiroki Kudo
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Akihiko Ichida
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Takeaki Ishizawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
| |
Collapse
|
|
42
|
Clift AK, Kidd M, Bodei L, Toumpanakis C, Baum RP, Oberg K, Modlin IM, Frilling A. Neuroendocrine Neoplasms of the Small Bowel and Pancreas. Neuroendocrinology 2020; 110:444-476. [PMID: 31557758 PMCID: PMC9175236 DOI: 10.1159/000503721] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 09/24/2019] [Indexed: 12/12/2022]
Abstract
The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeutic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.
Collapse
Affiliation(s)
- Ashley Kieran Clift
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Mark Kidd
- Wren Laboratories, Branford, Connecticut, USA
| | - Lisa Bodei
- Department of Nuclear Medicine, Memorial Sloan Kettering Cancer Centre, New York, New York, USA
| | - Christos Toumpanakis
- Centre for Gastroenterology/Neuroendocrine Tumour Unit, Royal Free Hospital, London, United Kingdom
| | - Richard P Baum
- Theranostics Centre for Molecular Radiotherapy and Precision Oncology, Zentralklinik, Bad Berka, Germany
| | - Kjell Oberg
- Department of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Irvin M Modlin
- Yale University School of Medicine, New Haven, Connecticut, USA
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom,
| |
Collapse
|
|
43
|
Jiang S, Zhao L, Xie C, Su H, Yan Y. Prognostic Performance of Different Lymph Node Staging Systems in Patients With Small Bowel Neuroendocrine Tumors. Front Endocrinol (Lausanne) 2020; 11:402. [PMID: 32733379 PMCID: PMC7358303 DOI: 10.3389/fendo.2020.00402] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 05/19/2020] [Indexed: 12/11/2022] Open
Abstract
Background: The prognostic significance of the lymph node (LN) classification for small bowel neuroendocrine tumors (SBNETs) remains unknown. The aim of the present study was to evaluate and compare the prognostic assessment of different LN staging systems. Methods: Patients with SBNETs were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The X-tile program was used to determine the cutoff value of the resected lymph nodes (RLNs), negative lymph nodes (NLNs), lymph node ratio (LNR), and the log odds of positive lymph nodes (LODDS). Survival analyses were performed using Kaplan-Meier curves with log-rank test. Logistic regression analysis was used to evaluate the differences between different periods. Univariate and multivariate Cox proportional hazards models were used to assess the prognostic value of different LN staging systems on cause-specific survival (CSS). The relative discriminative abilities of the different LN staging systems were assessed using the Akaike information criterion (AIC) and the Harrell consistency index (HCI). Result: A total of 3,680 patients were diagnosed with SBNETs between 1988 and 2014 from the SEER database. A significant difference over time (1988-1999 vs. 2000-2014) was seen in age (P <0.001), tumor differentiation (P <0.001), T stage (P <0.001), and RLN (P <0.001) subgroups. Multivariate Cox survival analysis identified that LN status stratified by the number of RLNs, NLNs, LNR, and LODDS all predicted CSS in patients with SBNETs (all P <0.05), whereas the number of positive lymph nodes (PLNs) failed (P = 0.452). When assessed using categorical variables, LODDS staging systems showed the best prognostic performance (HCI: 0.766, AIC: 7,575.154) in the whole population. Further analysis based on different RLNs after eliminating the missing data showed that when the RLNs are <12, the LODDS (HCI: 0.769, AIC: 1,088.731) maintained the best prognostic performance as well when the RLNs are ≥12 (HCI: 0.835, AIC: 825.692). Among patients with LNR scores of 0 or 1, there was a residual heterogeneity of outcomes that were better stratified and characterized by the LODDS. Conclusion: LODDS was a better predicator of survival when LN status was stratified as a categorical variable and should be considered when assessing the prognosis of patients with SBNETs to allow a more reliable means to stratify patient survival.
Collapse
Affiliation(s)
- Sujing Jiang
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lihao Zhao
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Congying Xie
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Huafang Su
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ye Yan
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- *Correspondence: Ye Yan
| |
Collapse
|
|
44
|
Lepage C. Épidémiologie des tumeurs neuroendocrines intestinales. ONCOLOGIE 2020. [DOI: 10.3166/onco-2019-0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Les données disponibles concernant l’incidence et les facteurs pronostiques des tumeurs neuroendocrines (TNE) digestives sont souvent fragmentaires. Les TNE digestives sont rares et représentent environ 1 % des cancers digestifs. En France, l’incidence des TNE digestives malignes est estimée à 1,1/100 000 chez l’homme et à 0,9/100 000 chez la femme. L’incidence augmente au cours du temps. Du fait de leur longue survie, les TNE constituent, après le cancer colorectal, le cancer digestif dont la prévalence est la plus élevée. La plupart des TNE sont bien différenciées, les carcinomes neuroendocrines peu différenciés représentent moins de 20 % des TNE digestives. Parmi les TNE bien différenciées intestinales, les localisations les plus fréquentes sont l’intestin grêle et le colorectal. Plus de la moitié des TNE sont diagnostiquées au stade métastatique, principalement au niveau hépatique. Le degré de différenciation, le grade histologique, la localisation du primitif et le stade sont les principaux facteurs pronostiques. Les taux de survie relative à cinq ans étaient de 4,5 % pour les tumeurs peu différenciées versus plus de 55 % pour les TNE bien différenciées.
Collapse
|
|
45
|
Lee L, Ito T, Jensen RT. Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies. Expert Rev Anticancer Ther 2019; 19:1029-1050. [PMID: 31738624 PMCID: PMC6923565 DOI: 10.1080/14737140.2019.1693893] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 11/13/2019] [Indexed: 02/06/2023]
Abstract
Introduction: Recent advances in diagnostic modalities and therapeutic agents have raised the importance of prognostic factors in predicting overall survival, as well as predictive factors for surgical outcomes, in tailoring therapeutic strategies of patients with pancreatic neuroendocrine neoplasms (panNENs).Areas covered: Numerous recent studies of panNEN patients report the prognostic values of a number of clinically related factors (clinical, laboratory, imaging, treatment-related factors), pathological factors (histological, classification, grading) and molecular factors on long-term survival. In addition, an increasing number of studies showed the usefulness of various factors, specifically biomarkers and molecular makers, in predicting recurrence and mortality related to surgical treatment. Recent findings (from the last 3 years) in each of these areas, as well as recent controversies, are reviewed.Expert commentary: The clinical importance of prognostic and predictive factors for panNENs is markedly increased for both overall outcome and post resection, as a result of recent advances in all aspects of the diagnosis, management and treatment of panNENs. Despite the proven prognostic utility of routinely used tumor grading/classification and staging systems, further studies are required to establish these novel prognostic factors to support their routine clinical use.
Collapse
Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, 20892-1804, USA
- Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan
| | - Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, Fukuoka, 814-0001, Japan
| | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, 20892-1804, USA
| |
Collapse
|
|
46
|
Zhang S, Tong YX, Zhang XH, Zhang YJ, Xu XS, Xiao AT, Chao TF, Gong JP. A novel and validated nomogram to predict overall survival for gastric neuroendocrine neoplasms. J Cancer 2019; 10:5944-5954. [PMID: 31762804 PMCID: PMC6856574 DOI: 10.7150/jca.35785] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 08/23/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND This study aims to develop and validate an effective nomogram to estimate the individual outcome of patients with Gastric neuroendocrine neoplasms (G-NENs). METHODS A total of 260 patients diagnosed with G-NENs at two medical centers were included, with 156 patients allocated as training set and 104 patients as validation. Predictive nomogram was constructed based on multivariate analyses using RMS package in R version. The predictive accuracy and discriminative ability were analyzed by C-index, risk group stratification and calibration curve, which was compared with other predictive systems for G-NENs. RESULTS In multivariate analysis, age, Ki-67, mitoses, neutrophil to lymphocyte ratio, serum tumor marker and distant metastasis were significantly associated with overall survival. The constructed prognostic nomogram demonstrated a good calibration and discrimination value with 0.884 and 0.852 C-indices in training and validation dataset. Compare to World Health Organization (WHO) grading system (C-indices=0.760 and 0.732) and American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (C-indices=0.747 and 0.811), the nomogram displayed a better predictive accuracy. CONCLUSIONS The novel prognostic nomogram showed superior predictive value in overall survival of G-NENs. It might be a useful tool for clinicians in estimating individual survival in G-NENs patients.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Jian Ping Gong
- Department of Gastrointestinal Surgery Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Jie Fang Ave, No. 1095 Wuhan, China
| |
Collapse
|
|
47
|
Okubo Y. Gangliocytic paraganglioma: An overview and future perspective. World J Clin Oncol 2019; 10:300-302. [PMID: 31572665 PMCID: PMC6766464 DOI: 10.5306/wjco.v10.i9.300] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 08/17/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023] Open
Abstract
Gangliocytic paraganglioma (GP) is rare neuroendocrine tumor (NET) with a good prognosis that commonly arising from duodenum. Although the tumor is characterized by its unique triphasic cells (epithelioid, spindle, and ganglion-like cells), the proportions of these three tumor cells vary widely from case to case, and occasionally, morphological and immunohistochemical similarities are found between GP and NET G1 (carcinoid tumors). Further, GP accounts for a substantial number of duodenal NETs. Therefore, GP continues to be misdiagnosed, most often as NET G1. However, GP has a better prognosis than NET G1, and it is important to differentiate GP from NET G1. In this article, I wish to provide up-to-date clinicopathological information to help oncologists gain better insight into the diagnosis and clinical management of this tumor.
Collapse
Affiliation(s)
- Yoichiro Okubo
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| |
Collapse
|
|
48
|
Algashaamy K, Garcia-Buitrago M. Multifocal G1-G2 gastric neuroendocrine tumors: Differentiating between Type I, II and III, a clinicopathologic review. World J Clin Cases 2019; 7:2413-2419. [PMID: 31559277 PMCID: PMC6745311 DOI: 10.12998/wjcc.v7.i17.2413] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 07/26/2019] [Accepted: 08/20/2019] [Indexed: 02/05/2023] Open
Abstract
Gastric neuroendocrine tumors (gNETs) are a rare entity that is increasing in incidence. Different pathophysiological processes can lead to the development of these tumors, appropriate histological analysis is necessary to differentiate between grade 1 (G1) and grade 2 (G2) tumors as this will impact the management of these patients based on their increased risk of lymph node and distant metastases. To provide a comprehensive clinicopathologic review of multifocal gastric neuroendocrine tumors, with particular emphasis on G1 and G2 tumors and differentiating between types I, II and II and risk stratification based upon immunohistochemical profile. This review is based on peer-reviewed literature and the authors’ experience. gNETs are a heterogenous group of tumors that is rising in incidence. These lesions while arise from the same cell type, they have different etiologies. Identifying the type of gNETs is a collective effort of clinical and pathologic correlation. The correct grading and staging of these lesions are of paramount significance, due its impact on patient management and prognosis.
Collapse
Affiliation(s)
- Khaled Algashaamy
- Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
| | - Monica Garcia-Buitrago
- Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
| |
Collapse
|
|
49
|
Felder S, Jann H, Arsenic R, Denecke T, Prasad V, Knappe-Drzikova B, Maasberg S, Wiedenmann B, Pavel M, Pascher A, Pape UF. Gastric neuroendocrine neoplasias: manifestations and comparative outcomes. Endocr Relat Cancer 2019; 26:751-763. [PMID: 31272081 PMCID: PMC6686747 DOI: 10.1530/erc-18-0582] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 07/04/2019] [Indexed: 12/15/2022]
Abstract
Although gastric neuroendocrine neoplasias (gNEN) are an orphan disease, their incidence is rising. The heterogeneous clinical course powers the ongoing discussion of the most appropriate classification system and management. Prognostic relevance of proposed classifications was retrospectively analysed in 142 patients from a single tertiary referral centre. Baseline, management and survival data were acquired for statistical analyses. The distribution according to the clinicopathological typification was gNEN-1 (n = 86/60.6%), gNEN-2 (n = 7/4.9%), gNEN-3 (n = 24/16.9%) and gNEN-4 (n = 25/17.6%), while hypergastrinemia-associated gNEN-1 and -2 were all low-grade tumours (NET-G1/2), formerly termed sporadic gNEN-3 could be subdivided into gNEN-3 with grade 1 or 2 and gNEN-4 with grade 3 (NEC-G3). During follow-up 36 patients died (25%). The mean overall survival (OS) of all gNEN was 14.2 years. The OS differed statistically significant across all subgroups with either classification system. According to UICC 2017 TNM classification, OS differed for early and advanced stages, while WHO grading indicated poorer prognosis for NEC-G3. Cox regression analysis confirmed the independent prognostic validity of either classification system for survival. Particularly careful analysis of the clinical course of gNEN-1 (ECLomas, gastric carcinoids) confirmed their mostly benign, but recurrent and extremely slowly progressive behaviour with low risk of metastasis (7%) and an efficient long-term control by repetitive endoscopic procedures. Our study provides evidence for the validity of current classifications focusing on typing, grading and staging. These are crucial tools for risk stratification, especially to differentiate gNEN-1 as well as sporadic gNET and gNEC (gNEN-3 vs -4).
Collapse
Affiliation(s)
- S Felder
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - H Jann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - R Arsenic
- Institut für Pathologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - T Denecke
- Klinik für Radiologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - V Prasad
- Klinik für Nuklearmedizin, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Nuklearmedizin, Universitätklinikum Ulm, Ulm, Germany
| | - B Knappe-Drzikova
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - S Maasberg
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
| | - B Wiedenmann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - M Pavel
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Medizinische Klinik 1, Gastroenterologie, Pneumologie und Endokrinologie, Universitätsklinikum der Friedrich-Alexander Universität Erlangen, Erlangen, Germany
| | - A Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uinversitätsklinikum Münster, Münster, Germany
| | - U F Pape
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
- Correspondence should be addressed to U F Pape:
| |
Collapse
|
|
50
|
Automated quantification of Ki-67 index associates with pathologic grade of pulmonary neuroendocrine tumors. Chin Med J (Engl) 2019; 132:551-561. [PMID: 30807354 PMCID: PMC6416093 DOI: 10.1097/cm9.0000000000000109] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Background: Classification of the pulmonary neuroendocrine tumor (pNET) categories is a step-wise process identified by the presence of necrosis and number of mitoses per 2 mm2. In neuroendocrine tumor pathology, Ki-67 was first described as a prognostic factor in the pancreas and incorporated into the grading system of digestive tract neuroendocrine neoplasms in the 2010 WHO classification. However, the significance of Ki-67 in pNETs was still a controversial issue. This study was to investigate the potentially diagnostic value of Ki-67 in pNETs. Methods: We retrieved 159 surgical specimens of pNETs, including 35 typical carcinoids (TCs), 2 atypical carcinoid (ACs), 28 large-cell neuroendocrine carcinomas (LCNECs), 94 small-cell lung cancers (SCLCs). Manual conventional method (MCM) and computer-assisted image analysis method (CIAM) were used to calculate the Ki-67 proliferative index. In CIAM, 6 equivalent fields (500 × 500 μm) at 10× magnification were manually annotated for digital image analysis. Results: The Ki-67 index among the 4 groups with ranges of 0.38% to 12.66% for TC, 4.34% to 29.48% for AC, 30.67% to 93.74% for LCNEC, and 40.71% to 96.87% for SCLC. The cutoff value of Ki-67 index to distinguish low grade with high grade was 30.07%. For the univariate survival analyses in pNETs, both the overall survival and progression-free survival correlated with Ki-67 index. In addition, the Ki-67 index performed by CIAM was proved to be of great positive correlation with MCM. Conclusions: Ki-67 index counted by CIAM is a reliable method and can be a useful adjunct to classify the low- and high-grade NETs.
Collapse
|