|
1
|
Ye X, Hua H, Hu C, Dai J, Wu C, Huai J, Shen Z. Endoscopic Ultrasound-Guided Fine Needle Acquisition for Evaluation of Pancreatic Neuroendocrine Tumors: A Meta-Analysis. J Clin Gastroenterol 2025; 59:310-320. [PMID: 39312536 DOI: 10.1097/mcg.0000000000002070] [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] [Received: 04/06/2024] [Accepted: 08/05/2024] [Indexed: 09/25/2024]
Abstract
AIMS The aim of this meta-analysis was to assess the diagnostic performance of EUS-FNA/B in patients with panNETs. METHODS We conducted a computerized search of the MEDLINE and Embase databases to identify relevant articles. The primary outcomes involved grading concordance rate, diagnostic rate, and correlation coefficient (Cohen's κ) for FNA/B samples compared with surgical specimens. Secondary outcomes included sample adequacy, mean number of passes, and adverse events. RESULTS Forty-five studies involving 2978 patients were finally included. The pooled concordance rate between EUS-FNA/B and surgical grading was 0.77 (95% CI: 0.73-0.80; I2 =48.2%). A significantly higher level of concordance was observed in G1 subgroup (0.88, 95% CI: 0.84-0.91), whereas the G2 subgroup revealed the lowest level of agreement (0.59, 95% CI: 0.52-0.65; P < 0.001). Pooled diagnostic rate for FNA/B sampling was 0.83 (95% CI: 0.79-0.86; I2 =63.3%). In addition, FNB outperformed FNA in terms of sample adequacy (0.93 for FNB vs. 0.81 for FNA; P =0.007) and number of needle passes required (2.53 for FNB vs. 3.32 for FNA; P =0.013). Moreover, the overall level of agreement for grading was moderate (κ=0.59, 95% CI: 0.49-0.68; I2 =84.5%). There were a limited number of adverse events that had minor influence on patient outcomes (0.03, 95% CI: 0.02-0.05; I2 =19.2%). CONCLUSIONS EUS-FNA/B is a reliable approach for the diagnosis and preoperative grading of panNET, with FNB demonstrating superior performance compared with FNA.
Collapse
Affiliation(s)
- Xiaohua Ye
- Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Hongjun Hua
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Chunxiao Hu
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Jianying Dai
- Department of Research and Development, Hangzhou Yingjian Bioscience and technology Co., Ltd
| | - Chenjiao Wu
- Department of Gastroenterology, Digestive Endoscopy Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
| | - Jiaping Huai
- Department of Critical Care, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
| |
Collapse
|
|
2
|
Debraine Z, Borbath I, Deprez P, Bosly F, Maiter D, Furnica RM. Long-term clinical and radiological outcomes of endoscopic ultrasound-guided radiofrequency ablation of benign insulinomas. Clin Endocrinol (Oxf) 2024; 101:485-490. [PMID: 37859570 DOI: 10.1111/cen.14981] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/26/2023] [Accepted: 10/01/2023] [Indexed: 10/21/2023]
Abstract
OBJECTIVE In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative nonsurgical treatment for pancreatic neuroendocrine tumours. The aim of our study was to assess the long-term follow-up of patients treated with EUS-RFA for a sporadic insulinoma in our centre in terms of efficacy, safety and risk of recurrence. DESIGN, PATIENTS AND MEASUREMENTS We retrospectively analysed the data of 11 patients with an insulinoma treated by EUS-RFA in our tertiary centre between June 2018 and April 2022. Clinical and biological, as well as imaging, follow-up was planned at 3, 6, 12 months and then annually. RESULTS In our series, there were nine women and two men with a median age of 65 years. All tumours were sporadic, with a mean size of 11 mm. The procedure allowed an immediate and complete symptomatic and biological remission in all patients without notable complications. Complete radiological resolution of the tumour after ablation was observed in seven patients, and persistence of an asymptomatic tumour residue was observed in four patients. During the mean follow-up period of 26 months, two patients presented a significant but asymptomatic increase of the tumour residue; a second EUS-RFA session was performed in one patient and the other patient is being closely monitored. CONCLUSIONS EUS-RFA treatment of benign insulinomas provides a long-term complete clinical resolution of hypoglycaemia. A long-term follow-up is essential if residual tumour persists after initial EUS-RFA treatment.
Collapse
Affiliation(s)
- Zoé Debraine
- Division of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Ivan Borbath
- Division of Hepatogastroenterology, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Pierre Deprez
- Division of Hepatogastroenterology, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Florence Bosly
- Division of Endocrinology, Clinique Vivalia, Arlon Hospital, Arlon, Belgium
| | - Dominique Maiter
- Division of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Raluca M Furnica
- Division of Endocrinology and Nutrition, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
| |
Collapse
|
|
3
|
Perry RR, Feliberti EC, Hughes MS. Management of Pancreatic Neuroendocrine Tumors: Surgical Strategies and Controversies. Endocr Pract 2024; 30:908-916. [PMID: 39032831 DOI: 10.1016/j.eprac.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 06/01/2024] [Accepted: 07/09/2024] [Indexed: 07/23/2024]
Abstract
OBJECTIVE Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors which are increasing in incidence. The management of these tumors continues to evolve. This review examines the current role of surgery in the treatment of these tumors. METHODS Studies published over the past 10 years were identified using several databases including PubMed, MEDLINE, and Science Direct. Search terms included PNETs, treatment, and surgery. Clinical practice guidelines and updates from several major groups were reviewed. RESULTS Surgery continues to have a major role in the treatment of sporadic functional and nonfunctional PNETs. Pancreas-sparing approaches are increasingly accepted as alternatives to formal pancreatic resection in selected patients. Options such as watch and wait or endoscopic ablation may be reasonable alternatives to surgery for non-functional PNETs < 2 cm in size. Surgical decision-making in multiple endocrine neoplasia type 1 patients remains complex and in some situations such as gastrinoma quite controversial. The role of surgery has significantly diminished in patients with advanced disease due to the advent of more effective systemic and liver-directed therapies. However, the optimal treatments and sequencing in advanced disease remain poorly defined, and it has been suggested that surgery is underutilized in these patients. CONCLUSIONS Surgery remains a major treatment modality for PNETs. Given the plethora of available treatments, ongoing controversies and the changing landscape, management has become increasingly complex. An experienced multidisciplinary team which includes surgery is essential to manage these patients.
Collapse
Affiliation(s)
- Roger R Perry
- Division of Surgical Oncology, Eastern Virginia Medical School, Norfolk, Virginia.
| | - Eric C Feliberti
- Division of Surgical Oncology, Eastern Virginia Medical School, Norfolk, Virginia
| | - Marybeth S Hughes
- Division of Surgical Oncology, Eastern Virginia Medical School, Norfolk, Virginia
| |
Collapse
|
|
4
|
Schramm M, Neppl C. [Challenges of cytopathological pancreas diagnostics]. PATHOLOGIE (HEIDELBERG, GERMANY) 2024; 45:19-27. [PMID: 38052744 DOI: 10.1007/s00292-023-01277-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/23/2023] [Indexed: 12/07/2023]
Abstract
The cytologic diagnostics of solid and cystic pancreatic lesions with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is an integral part of the clinical workup and the decision of a surgical versus a conservative approach. Cystic lesions are increasingly being diagnosed due to improved imaging and represent numerous neoplastic as well as non-neoplastic epithelial and non-epithelial entities, which differ in biological behavior and prognosis. In particular, the differentiation of mucinous and non-mucinous cysts is significant for further clinical management. Regressive cellular changes, gastrointestinal contaminants, and overlapping morphologic changes of reactively altered ductal epithelial cells and cells of well-differentiated neoplasms and preneoplasms are special challenges of cytological diagnostics. For a uniform cytological classification of findings, an internationally developed seven-level classification system has been published and co-published by the World Health Organization (WHO). This classification system takes into account both morphological findings and further procedures on cytological material such as next-generation sequencing and immunocytochemistry and is based on the WHO classification for pancreatic tumors. Against this background, important cytologic diagnostic criteria of various solid and cystic lesions relevant in clinical practice are presented in this article, considering diagnostic possibilities and pitfalls as well as differential diagnoses.
Collapse
Affiliation(s)
- Martin Schramm
- Institut für Pathologie und Funktionsbereich Zytopathologie, Medizinische Fakultät und Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.
| | - Christina Neppl
- Institut für Pathologie und Funktionsbereich Zytopathologie, Medizinische Fakultät und Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland
| |
Collapse
|
|
5
|
Javed AA, Zhu Z, Kinny-Köster B, Habib JR, Kawamoto S, Hruban RH, Fishman EK, Wolfgang CL, He J, Chu LC. Accurate non-invasive grading of nonfunctional pancreatic neuroendocrine tumors with a CT derived radiomics signature. Diagn Interv Imaging 2024; 105:33-39. [PMID: 37598013 PMCID: PMC10873069 DOI: 10.1016/j.diii.2023.08.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 08/21/2023]
Abstract
PURPOSE The purpose of this study was to develop a radiomics-signature using computed tomography (CT) data for the preoperative prediction of grade of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs). MATERIALS AND METHODS A retrospective study was performed on patients undergoing resection for NF-PNETs between 2010 and 2019. A total of 2436 radiomic features were extracted from arterial and venous phases of pancreas-protocol CT examinations. Radiomic features that were associated with final pathologic grade observed in the surgical specimens were subjected to joint mutual information maximization for hierarchical feature selection and the development of the radiomic-signature. Youden-index was used to identify optimal cutoff for determining tumor grade. A random forest prediction model was trained and validated internally. The performance of this tool in predicting tumor grade was compared to that of EUS-FNA sampling that was used as the standard of reference. RESULTS A total of 270 patients were included and a fusion radiomic-signature based on 10 selected features was developed using the development cohort (n = 201). There were 149 men and 121 women with a mean age of 59.4 ± 12.3 (standard deviation) years (range: 23.3-85.0 years). Upon internal validation in a new set of 69 patients, a strong discrimination was observed with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.71-0.90) with corresponding sensitivity and specificity of 87.5% (95% CI: 79.7-95.3) and 73.3% (95% CI: 62.9-83.8) respectively. Of the study population, 143 patients (52.9%) underwent EUS-FNA. Biopsies were non-diagnostic in 26 patients (18.2%) and could not be graded due to insufficient sample in 42 patients (29.4%). In the cohort of 75 patients (52.4%) in whom biopsies were graded the radiomic-signature demonstrated not different AUC as compared to EUS-FNA (AUC: 0.69 vs. 0.67; P = 0.723), however greater sensitivity (i.e., ability to accurately identify G2/3 lesion was observed (80.8% vs. 42.3%; P < 0.001). CONCLUSION Non-invasive assessment of tumor grade in patients with PNETs using the proposed radiomic-signature demonstrated high accuracy. Prospective validation and optimization could overcome the commonly experienced diagnostic uncertainty in the assessment of tumor grade in patients with PNETs and could facilitate clinical decision-making.
Collapse
Affiliation(s)
- Ammar A Javed
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Surgery, New York University Langone Hospital, New York City, New York 10016, USA
| | - Zhuotun Zhu
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Benedict Kinny-Köster
- Department of Surgery, New York University Langone Hospital, New York City, New York 10016, USA
| | - Joseph R Habib
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Satomi Kawamoto
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Ralph H Hruban
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Elliot K Fishman
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Christopher L Wolfgang
- Department of Surgery, New York University Langone Hospital, New York City, New York 10016, USA
| | - Jin He
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Linda C Chu
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
| |
Collapse
|
|
6
|
Ronot M, Soyer P. Can radiomics outperform pathology for tumor grading? Diagn Interv Imaging 2024; 105:3-4. [PMID: 37714731 DOI: 10.1016/j.diii.2023.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 09/01/2023] [Indexed: 09/17/2023]
Affiliation(s)
- Maxime Ronot
- Department of Radiology, Hôpital Beaujon, AP-HP, 92110, Clichy, France; Université Paris Cité, Faculté de Médecine, 75006, Paris, France.
| | - Philippe Soyer
- Université Paris Cité, Faculté de Médecine, 75006, Paris, France; Department of Diagnostic and Interventional Imaging, AP-HP, Hôpital Cochin, 75014, Paris, France
| |
Collapse
|
|
7
|
Zhu HB, Zhu HT, Jiang L, Nie P, Hu J, Tang W, Zhang XY, Li XT, Yao Q, Sun YS. Radiomics analysis from magnetic resonance imaging in predicting the grade of nonfunctioning pancreatic neuroendocrine tumors: a multicenter study. Eur Radiol 2024; 34:90-102. [PMID: 37552258 PMCID: PMC10791720 DOI: 10.1007/s00330-023-09957-7] [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: 08/09/2023]
Abstract
OBJECTIVES To explore the potential of radiomics features to predict the histologic grade of nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) patients using non-contrast sequence based on MRI. METHODS Two hundred twenty-eight patients with NF-PNETs undergoing MRI at 5 centers were retrospectively analyzed. Data from center 1 (n = 115) constituted the training cohort, and data from centers 2-5 (n = 113) constituted the testing cohort. Radiomics features were extracted from T2-weighted images and the apparent diffusion coefficient. The least absolute shrinkage and selection operator was applied to select the most important features and to develop radiomics signatures. The area under receiver operating characteristic curve (AUC) was performed to assess models. RESULTS Tumor boundary, enhancement homogeneity, and vascular invasion were used to construct the radiological model to stratify NF-PNET patients into grade 1 and 2/3 groups, which yielded AUC of 0.884 and 0.684 in the training and testing groups. A radiomics model including 4 features was constructed, with an AUC of 0.941 and 0.871 in the training and testing cohorts. The fusion model combining the radiomics signature and radiological characteristics showed good performance in the training set (AUC = 0.956) and in the testing set (AUC = 0.864), respectively. CONCLUSION The developed model that integrates radiomics features with radiological characteristics could be used as a non-invasive, dependable, and accurate tool for the preoperative prediction of grade in NF-PNETs. CLINICAL RELEVANCE STATEMENT Our study revealed that the fusion model based on a non-contrast MR sequence can be used to predict the histologic grade before operation. The radiomics model may be a new and effective biological marker in NF-PNETs. KEY POINTS The diagnostic performance of the radiomics model and fusion model was better than that of the model based on clinical information and radiological features in predicting grade 1 and 2/3 of nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Good performance of the model in the four external testing cohorts indicated that the radiomics model and fusion model for predicting the grades of NF-PNETs were robust and reliable, indicating the two models could be used in the clinical setting and facilitate the surgeons' decision on risk stratification. The radiomics features were selected from non-contrast T2-weighted images (T2WI) and diffusion-weighted imaging (DWI) sequence, which means that the administration of contrast agent was not needed in grading the NF-PNETs.
Collapse
Affiliation(s)
- Hai-Bin Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, 52 Fu Cheng Road, Hai Dian District, Beijing, 100142, China
| | - Hai-Tao Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, 52 Fu Cheng Road, Hai Dian District, Beijing, 100142, China
| | - Liu Jiang
- Department of Ultrasonography, Peking University First Hospital, Xi Cheng District, 100034, Beijing, China
- Department of Radiology, Peking University First Hospital, Xi Cheng District, Beijing, 100034, China
| | - Pei Nie
- Department of Radiology, Affiliated Hospital of Qingdao University, Shi Nan District, Qingdao, 266000, China
| | - Juan Hu
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, Wu hua District, Kunming, 650032, China
| | - Wei Tang
- Department of Radiology, Fudan University Shanghai Cancer Center, Xu Hui District, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Xu Hui District, Shanghai, 200032, China
| | - Xiao-Yan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, 52 Fu Cheng Road, Hai Dian District, Beijing, 100142, China
| | - Xiao-Ting Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, 52 Fu Cheng Road, Hai Dian District, Beijing, 100142, China
| | - Qian Yao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Hai Dian District, Beijing, 100142, China
| | - Ying-Shi Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, 52 Fu Cheng Road, Hai Dian District, Beijing, 100142, China.
| |
Collapse
|
|
8
|
Ghabi EM, Habib JR, Shoucair S, Javed AA, Sham J, Burns WR, Cameron JL, Ali SZ, Shin EJ, Arcidiacono PG, Doglioni C, Falconi M, Yu J, Partelli S, He J. Detecting Somatic Mutations for Well-Differentiated Pancreatic Neuroendocrine Tumors in Endoscopic Ultrasound-Guided Fine Needle Aspiration with Next-Generation Sequencing. Ann Surg Oncol 2023; 30:7720-7730. [PMID: 37488390 DOI: 10.1245/s10434-023-13965-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 07/03/2023] [Indexed: 07/26/2023]
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogenous behavior, whereby some small tumors are aggressive with a propensity for metastasis. Detection of somatic mutations associated with aggressive biology may help with patient stratification and surgical decision-making in patients with well-differentiated PanNETs. Using next-generation sequencing (NGS), we investigated the feasibility of detecting somatic mutations in endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) specimens and determining the mutational concordance between the EUS-FNA specimens and the primary tumors. METHODS Thirty-eight patients with well-differentiated, nonfunctioning PanNETs were obtained from two tertiary referral centers. Patient demographic characteristics and tumor, clinicopathologic features were collected. Tissue from both the EUS-FNA specimen and the primary tumor was extracted from archival tissue blocks. NGS using a panel of ten genes was performed on both samples. RESULTS In our series, the median age was 61.1 years. Tumors were predominantly left-sided (60.5%) and unifocal (94.7%). The median tumor size was 2.2 cm. NGS detected somatic mutations in 29% of primary tumors and 36.8% of EUS-FNA specimens. In primary tumors, DAXX/ATRX mutations were predominantly detected (63.6%). In EUS-FNA specimens, MEN1 mutations were predominantly detected (64.3%). Among non-wild-type specimens, mutational concordance was achieved in 31.6% of cases. In 11 patients with a detectable mutation in the primary tumor, a mutation was detected in the EUS-FNA specimen in 45.5% of cases, with a mutational concordance of 54.5%. CONCLUSIONS NGS can detect somatic mutations in EUS-FNA specimens of well-differentiated PanNETs. Efforts to improve detection sensitivity and mutational concordance are required to overcome current technical limitations.
Collapse
Affiliation(s)
- Elie M Ghabi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Joseph R Habib
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sami Shoucair
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ammar A Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jonathan Sham
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - William R Burns
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - John L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Syed Z Ali
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Eun Ji Shin
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita Salute San Raffaele University, Milan, Italy
| | - Claudio Doglioni
- Pathology Unit, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, ENETS Center of Excellence, Milan, Italy
| | - Massimo Falconi
- Pancreatic and Transplant Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, ENETS Center of Excellence, Milan, Italy
| | - Jun Yu
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Stefano Partelli
- Pancreatic and Transplant Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, ENETS Center of Excellence, Milan, Italy
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| |
Collapse
|
|
9
|
Regolo M, Cardaci N, Salmeri C, Laudani A, Colaci M, Ippolito M, Motta F, Magrì S, Parisi S, Torcitto AG, Malatino L. Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review. J Clin Med 2023; 12:6617. [PMID: 37892755 PMCID: PMC10607714 DOI: 10.3390/jcm12206617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 09/24/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient's survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs.
Collapse
Affiliation(s)
- Matteo Regolo
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Nicolas Cardaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Clara Salmeri
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Alfredo Laudani
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Michele Colaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Massimo Ippolito
- Nuclear Medicine Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Fabio Motta
- Pathological Anatomy Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Salvatore Magrì
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | - Stefanie Parisi
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | | | - Lorenzo Malatino
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| |
Collapse
|
|
10
|
Neyaz A, Crotty R, Rickelt S, Pankaj A, Stojanova M, Michelakos TP, Sekigami Y, Kontos F, Parrack PH, Patil DT, Heaphy CM, Ferrone CR, Deshpande V. Predicting recurrence in pancreatic neuroendocrine tumours: role of ARX and alternative lengthening of telomeres (ALT). Histopathology 2023; 83:546-558. [PMID: 37455385 DOI: 10.1111/his.14996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 05/11/2023] [Accepted: 06/04/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND While many pancreatic neuroendocrine tumours (PanNET) show indolent behaviour, predicting the biological behaviour of small nonfunctional PanNETs remains a challenge. Nonfunctional PanNETs with an epigenome and transcriptome that resemble islet alpha cells (ARX-positive) are more aggressive than neoplasms that resemble islet beta cells (PDX1-positive). In this study, we explore the ability of immunohistochemistry for ARX and PDX1 and telomere-specific fluorescence in situ hybridisation (FISH) for alternative lengthening of telomeres (ALT) to predict recurrence. METHODS Two hundred fifty-six patients with PanNETs were identified, and immunohistochemistry for ARX and PDX1 was performed. Positive staining was defined as strong nuclear staining in >5% of tumour cells. FISH for ALT was performed in a subset of cases. RESULTS ARX reactivity correlated with worse disease-free survival (DFS) (P = 0.011), while there was no correlation between PDX1 reactivity and DFS (P = 0.52). ALT-positive tumours (n = 63, 31.8%) showed a significantly lower DFS (P < 0.0001) than ALT-negative tumours (n = 135, 68.2%). ARX reactivity correlated with ALT positivity (P < 0.0001). Among nonfunctional tumours, recurrence was noted in 18.5% (30/162) of ARX-positive tumours and 7.5% (5/67) of ARX-negative tumours. Among WHO grade 1 and 2 PanNETs with ≤2 cm tumour size, 14% (6/43) of ARX-positive tumours recurred compared to 0 of 33 ARX-negative tumours and 33.3% (3/9) ALT-positive tumours showed recurrence versus 4.4% (2/45) ALT-negative tumours. CONCLUSION Immunohistochemistry for ARX and ALT FISH status may aid in distinguishing biologically indolent cases from aggressive small low-grade PanNETs, and help to identify patients who may preferentially benefit from surgical intervention.
Collapse
Affiliation(s)
- Azfar Neyaz
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Rory Crotty
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Steffen Rickelt
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Boston, MA, USA
| | - Amaya Pankaj
- Massachusetts General Hospital Cancer Center, Boston, MA, USA
| | | | | | - Yurie Sekigami
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Filippos Kontos
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Paige H Parrack
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Deepa T Patil
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Christopher M Heaphy
- Department of Medicine, Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA
| | | | - Vikram Deshpande
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| |
Collapse
|
|
11
|
Ahmed TM, Kawamoto S, Hruban RH, Fishman EK, Soyer P, Chu LC. A primer on artificial intelligence in pancreatic imaging. Diagn Interv Imaging 2023; 104:435-447. [PMID: 36967355 DOI: 10.1016/j.diii.2023.03.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 03/06/2023] [Indexed: 06/18/2023]
Abstract
Artificial Intelligence (AI) is set to transform medical imaging by leveraging the vast data contained in medical images. Deep learning and radiomics are the two main AI methods currently being applied within radiology. Deep learning uses a layered set of self-correcting algorithms to develop a mathematical model that best fits the data. Radiomics converts imaging data into mineable features such as signal intensity, shape, texture, and higher-order features. Both methods have the potential to improve disease detection, characterization, and prognostication. This article reviews the current status of artificial intelligence in pancreatic imaging and critically appraises the quality of existing evidence using the radiomics quality score.
Collapse
Affiliation(s)
- Taha M Ahmed
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Satomi Kawamoto
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Ralph H Hruban
- Sol Goldman Pancreatic Research Center, Department of Pathology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Elliot K Fishman
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Philippe Soyer
- Université Paris Cité, Faculté de Médecine, Department of Radiology, Hôpital Cochin-APHP, 75014, 75006, Paris, France, 7501475006
| | - Linda C Chu
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
| |
Collapse
|
|
12
|
Pyo JS, Kim NY, Min KW, Oh IH, Lim DH, Son BK. Diagnostic Accuracy of ki-67 Labeling Index in Endoscopic Ultrasonography-Fine-Needle Aspiration Cytology and Biopsy of Pancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2023; 13:2756. [PMID: 37685294 PMCID: PMC10487187 DOI: 10.3390/diagnostics13172756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/06/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). METHODS Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. RESULTS The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713-0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681-0.794) and 0.839 (95% CI, 0.738-0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590-0.917) and 0.998 (95% CI, 0.987-1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145-489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. CONCLUSIONS Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.
Collapse
Affiliation(s)
- Jung-Soo Pyo
- Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (J.-S.P.); (K.-W.M.)
| | - Nae Yu Kim
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
| | - Kyueng-Whan Min
- Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (J.-S.P.); (K.-W.M.)
| | - Il Hwan Oh
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
| | - Dae Hyun Lim
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
| | - Byoung Kwan Son
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
| |
Collapse
|
|
13
|
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
|
|
14
|
Contrast Enhanced EUS for Predicting Solid Pancreatic Neuroendocrine Tumor Grade and Aggressiveness. Diagnostics (Basel) 2023; 13:diagnostics13020239. [PMID: 36673049 PMCID: PMC9857765 DOI: 10.3390/diagnostics13020239] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/29/2022] [Accepted: 12/29/2022] [Indexed: 01/11/2023] Open
Abstract
Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.
Collapse
|
|
15
|
Management of Small Nonfunctioning Pancreatic Neuroendocrine Neoplasms: Current Opinion and Controversies. J Clin Med 2022; 12:jcm12010251. [PMID: 36615051 PMCID: PMC9821009 DOI: 10.3390/jcm12010251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 12/31/2022] Open
Abstract
The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has increased due to the widespread use of high-resolution diagnostic imaging in screening programs. Most PNENs are slow-growing indolent neoplasms. However, a local invasion or metastasis can sometimes occur with PNENs, leading to a poor prognosis. The management of small, nonfunctioning PNENs remains under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgery remains a high-risk operation with a 28-30% morbidity and 1% mortality. Therefore, the decision on how to manage small PNENs is challenging. This review focuses on the management of small nonfunctioning PNENs. We also highlight the malignant potential of small PNENs according to tumor size, tumor grade, and tumor biomarker. Endoscopic-ultrasound-guided biopsy is recommended to evaluate the potential risk of malignancy. Furthermore, we discuss the current guidelines and future directions for the management of small PNENs.
Collapse
|
|
16
|
Tacelli M, Bina N, Crinò SF, Facciorusso A, Celsa C, Vanni AS, Fantin A, Antonini F, Falconi M, Monica F, Capurso G, Arcidiacono PG, Barresi L. Reliability of grading preoperative pancreatic neuroendocrine tumors on EUS specimens: a systematic review with meta-analysis of aggregate and individual data. Gastrointest Endosc 2022; 96:898-908.e23. [PMID: 35863518 DOI: 10.1016/j.gie.2022.07.014] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 07/02/2022] [Accepted: 07/08/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related to the Ki-67 index, which defines tumor grading. The criterion standard for the assessment of grading of PanNETs is EUS-guided FNA (EUS-FBAFNA) or EUS-guided fine-needle biopsy sampling (EUS-FNB). Because data on diagnostic accuracy of EUS-FNA and EUS-FNB are heterogeneous, we aimed to analyze the variability in concordance between EUS grading and surgical grading. METHODS The MEDLINE, SCOPUS, and EMBASE databases were searched until November 2021 to identify studies reporting the concordance rate between EUS grading and surgical grading. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled events were calculated using a random-effects model and expressed in terms of pooled prevalence rates. A multivariate meta-regression was performed to find possible sources of heterogeneity. Where available, individual data were analyzed. RESULTS Twenty-six studies with 864 patients undergone EUS-FNA or EUS-FNB and surgical resection for PanNETs were included. The pooled estimate rate for the overall concordance of EUS grading and surgical grading was 80.3% (95% confidence interval, 75.6-85.1). Undergrading (EUS grading < surgical grading) was significantly more frequent with respect to overgrading (14.7% vs 3.5%, P < .001). Individual data analysis showed that among nonconcordant patients, the median Ki-67 difference was 3% (interquartile range, 2-6.15). The type of World Health Organization classification adopted and the median lesion diameter were significantly associated with heterogeneity at meta-regression. CONCLUSIONS EUS is an accurate technique in defining grading in patients with PanNETs, but a margin of error still exists, which should be the focus of future studies to minimize the risk of over- and/or undertreatment.
Collapse
Affiliation(s)
- Matteo Tacelli
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Niccolò Bina
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy; Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Stefano Francesco Crinò
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, University Hospital of Verona, Verona, Italy
| | - Antonio Facciorusso
- Department of Medical and Surgical Sciences, Gastroenterology Unit, University of Foggia, Foggia, Italy
| | - Ciro Celsa
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Andrea Sbrozzi Vanni
- Gastroenterology and Diagnostic and Operative Digestive Endoscopy, San Camillo Forlanini Hospital, Rome, Italy
| | | | - Filippo Antonini
- Gastroenterology and Digestive Endoscopy Unit, Augusto Murri Hospital, Polytechnic University of Marche, Fermo, Italy
| | - Massimo Falconi
- Vita-Salute San Raffaele University, Milan, Italy; Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Fabio Monica
- Gastroenterology and Digestive Endoscopy, "Cattinara" Academic Hospital, Trieste, Italy
| | - Gabriele Capurso
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | | |
Collapse
|
|
17
|
Huang XT, Xie JZ, Huang CS, Li JH, Chen W, Liang LJ, Yin XY. Development and validation of nomogram to predict lymph node metastasis preoperatively in patients with pancreatic neuroendocrine tumor. HPB (Oxford) 2022; 24:2112-2118. [PMID: 36127226 DOI: 10.1016/j.hpb.2022.08.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/29/2022] [Accepted: 08/31/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND Routine lymphadenectomy in pancreatic neuroendocrine tumors (pNETs) is debated. There lacks accurate model to predict lymph node metastasis (LNM) preoperatively in pNETs. Therefore, this study aimed at developing a nomogram in predicting LNM in pNETs preoperatively. METHODS Patients undergoing surgery from Surveillance, Epidemiology, and End Results (SEER) database (design cohort, n = 2742) and First Affiliated Hospital of Sun Yat-sen University (validation cohort, n = 136) were enrolled. Nomogram was developed based on risk factors determined by logistic regression analyses. The performance of nomogram was evaluated by area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis. RESULTS In design cohort, 915 of 2742 patients had LNM. Tumor in the pancreatic head, T stage, and tumor size were significantly associated with LNM (all p < 0.05). Prediction of nomogram was accurate with AUC of 0.776 in design cohort and 0.622 in validation cohort. The nomogram showed good agreement between prediction and observation in the design and validation cohort. Based on nomogram-predicted risk, patients with higher risk of LNM had worse overall survival over patients with lower risk of LNM (log-rank p < 0.001). CONCLUSIONS The novel nomogram could accurately predict LNM in pNET preoperatively. For patients with high risk of LNM, lymphadenectomy was recommended.
Collapse
Affiliation(s)
- Xi-Tai Huang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China
| | - Jin-Zhao Xie
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China
| | - Chen-Song Huang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China
| | - Jian-Hui Li
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China
| | - Wei Chen
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China
| | - Li-Jian Liang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China
| | - Xiao-Yu Yin
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China.
| |
Collapse
|
|
18
|
Iabichino G, Di Leo M, Arena M, Rubis Passoni GG, Morandi E, Turpini F, Viaggi P, Luigiano C, De Luca L. Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:4943-4958. [PMID: 36160644 PMCID: PMC9494936 DOI: 10.3748/wjg.v28.i34.4943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 06/29/2022] [Accepted: 08/22/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors derived from the neuroendocrine cell system, which that have increased in incidence and prevalence in recent years. Despite improvements in radiological and metabolic imaging, endoscopy still plays a pivotal role in the number of GEP-NENs. Tumor detection, characterization, and staging are essential in management and treatment planning. Upper and lower gastrointestinal (GI) endoscopy is essential for correct localization of the primary tumor site of GI NENs. Endoscopic ultrasonography (EUS) has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors. Correct staging and histological diagnosis have important prognostic implications. Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall. Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.
Collapse
Affiliation(s)
| | - Milena Di Leo
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Monica Arena
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | | | | | - Francesca Turpini
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Paolo Viaggi
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Carmelo Luigiano
- Gastroenterology Section, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria 89124, Italy
| | - Luca De Luca
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| |
Collapse
|
|
19
|
Takikawa T, Kikuta K, Hamada S, Kume K, Miura S, Yoshida N, Tanaka Y, Matsumoto R, Ikeda M, Kataoka F, Sasaki A, Hayashi H, Hatta W, Ogata Y, Nakagawa K, Unno M, Masamune A. A New Preoperative Scoring System for Predicting Aggressiveness of Non-Functioning Pancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2022; 12:diagnostics12020397. [PMID: 35204488 PMCID: PMC8870938 DOI: 10.3390/diagnostics12020397] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/01/2022] [Accepted: 02/01/2022] [Indexed: 12/04/2022] Open
Abstract
The management of non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) is still controversial. This study aimed to develop a new scoring system for treatment decisions at initial diagnosis based on the identification of the predictive factors for aggressive NF-PanNENs. Seventy-seven patients who had been pathologically diagnosed with NF-PanNENs were enrolled. We retrospectively reviewed 13 variables that could be assessed preoperatively. Univariate and multivariate stepwise logistic regression analyses were performed to identify factors for the aggressiveness of NF-PanNENs, and a scoring system was developed by assigning weighted points proportional to their β regression coefficient. Tumor size > 20 mm on contrast-enhanced computed tomography, tumor non-vascularity, and Ki-67 labeling index ≥5% on endoscopic ultrasound-guided fine-needle aspiration specimens were identified as independent factors for predicting the aggressiveness of NF-PanNENs. The new scoring system, developed using the identified factors, had an excellent discrimination ability, with area under the curve of 0.92 (95% CI, 0.85–0.99), and good calibration (p = 0.72, Hosmer-Lemeshow test). Ten-year overall survival rates in low-risk (0 point), intermediate-risk (1 to 2 points), and high-risk (3 to 4 points) groups were 100%, 90.9%, and 24.3%, respectively. This new scoring system would be useful for treatment decisions and prognostic prediction at initial diagnosis.
Collapse
Affiliation(s)
- Tetsuya Takikawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Kazuhiro Kikuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Shin Hamada
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Kiyoshi Kume
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Shin Miura
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Naoki Yoshida
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Yu Tanaka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Ryotaro Matsumoto
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Mio Ikeda
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Fumiya Kataoka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Akira Sasaki
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Hidehiro Hayashi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Yohei Ogata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
| | - Kei Nakagawa
- Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan; (K.N.); (M.U.)
| | - Michiaki Unno
- Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan; (K.N.); (M.U.)
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan; (T.T.); (K.K.); (S.H.); (K.K.); (S.M.); (N.Y.); (Y.T.); (R.M.); (M.I.); (F.K.); (A.S.); (H.H.); (W.H.); (Y.O.)
- Correspondence: ; Tel.:+81-22-717-7171; Fax: +81-22-717-7177
| |
Collapse
|
|
20
|
Kasai Y, Masui T, Nakakura EK, Nakano K, Sato A, Uchida Y, Yogo A, Nagai K, Anazawa T, Hope TA, Kim GE, Whitman J, Le BK, Takaori K, Bergsland EK, Hatano E, Uemoto S. Preoperative risk stratification of lymph node metastasis for non-functional pancreatic neuroendocrine neoplasm: An international dual-institutional study. Pancreatology 2022; 22:123-129. [PMID: 34736838 DOI: 10.1016/j.pan.2021.10.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 09/29/2021] [Accepted: 10/25/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND /Objectives: Although the presence of lymph node metastasis (LNM) defines malignant potential, preoperative prediction of LNM has not been established for non-functional pancreatic neuroendocrine neoplasm (NF-PNEN). We sought to develop a prediction system using only preoperatively available factors that would stratify the risk of LNM for NF-PNEN. METHODS We retrospectively reviewed patients who underwent R0/1 resection of NF-PNEN at Kyoto University (2007-2019) and the University of California, San Francisco (2010-2019). Risk stratification of LNM was developed using preoperative factors by the logistic regression analysis. Long-term outcomes were compared across the risk groups. RESULTS A total of 131 patients were included in this study. Lymph nodes were pathologically examined in 116 patients, 23 (20%) of whom had LNM. Radiological tumor size [1.5-3.5 cm (odds ratio: 13.5, 95% confidence interval: 1.77-398) and >3.5 cm (72.4, 9.06-2257) against ≤1.5 cm], <50% cystic component (8.46 × 10^6, 1.68 × 10^106-), and dilatation of main pancreatic duct ≥5 mm (31.2, 3.94-702) were independently associated with LNM. When patients were classified as the low-risk (43 patients), intermediate-risk (44 patients), and high-risk groups (29 patients), proportions of LNM differed significantly across the groups (0%, 14%, and 59%, respectively). Recurrence-free survival (RFS) of the low- and intermediate-risk groups were significantly better than that of the high-risk group (5-year RFS rates of 92.2%, 85.4%, and 47.1%, respectively). CONCLUSIONS The prediction system using preoperative radiological factors stratifies the risk of LNM for NF-PNEN. This stratification helps to predict malignant potential and determine the surgical procedure and necessity of regional lymphadenectomy.
Collapse
Affiliation(s)
- Yosuke Kasai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Surgery, University of California, San Francisco, USA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Eric K Nakakura
- Department of Surgery, University of California, San Francisco, USA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA
| | - Kenzo Nakano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Asahi Sato
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuichiro Uchida
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akitada Yogo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Thomas A Hope
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA
| | - Grace E Kim
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA; Department of Pathology, University of California, San Francisco, USA
| | - Julia Whitman
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA
| | - Bryan K Le
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA
| | - Kyoichi Takaori
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Emily K Bergsland
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA; Department of Medicine, University of California, San Francisco, USA
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| |
Collapse
|
|
21
|
Tacelli M, Petrone MC, Capurso G, Muffatti F, Andreasi V, Partelli S, Doglioni C, Falconi M, Arcidiacono PG. Diagnostic accuracy of EUS-FNA in the evaluation of pancreatic neuroendocrine neoplasms grading: Possible clinical impact of misclassification. Endosc Ultrasound 2021; 10:372-380. [PMID: 34677159 PMCID: PMC8544016 DOI: 10.4103/eus-d-20-00261] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background and Objectives Prognosis of pancreatic neuroendocrine neoplasms (PanNENs) mostly depend on tumor stage and grade, determined by Ki-67 labeling index. EUS-FNA is considered the gold-standard technique to obtain it. The aims of our study were to establish diagnostic accuracy of preoperative EUS-FNA Ki-67 evaluation considering final pathological assessment on surgical specimen as gold standard and to investigate the possible impact on prognosis of misclassification. Methods This is a retrospective study from a prospectively collected database. EUS-FNA grading (eG) and surgical one (sG) measured according to Ki-67 proliferative index values, according to 2017 WHO classification, were compared. eG-sG correlation was evaluated by Spearman index. Logistic regression investigated factors associated with misclassification. Prognostic difference in terms of progression-free survival was evaluated by Kaplan Meier method. Results One hundred and twelve PanNENs patients enrolled. In 13.4% of patients (15/112) EUS-FNA "undergraded" patients (eG1 vs. sG2), while in 12.5% (n = 14) it "overgraded" PanNENs (eG2 to sG1). No misclassifications in G3 patients. In patients with tumors <20 mm (n = 44), 2 (4.5%) eG1 and 10 (22.7%) eG2 were finally classified respectively as G2 and G1 at surgical histology. No factors, as i.e. the lesions' size or their morphological aspect, were associated with misclassification. In overgraded PanNENs, no progression occurred, while in patients correctly classified/undergraded the progression rate was 14.3%. Conclusions This is the largest cohort of surgical PanNENs with preoperative EUS-FNA grading evaluation. Despite an acceptable eG-sG correlation, about 25% of patients are misclassified. Clinical impact of misclassification should be carefully considered especially in small tumors undergoing observation.
Collapse
Affiliation(s)
- Matteo Tacelli
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Maria Chiara Petrone
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Gabriele Capurso
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Francesca Muffatti
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Valentina Andreasi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Claudio Doglioni
- Department of Pathology, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Paolo Giorgio Arcidiacono
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| |
Collapse
|
|
22
|
Shirali AS, Pieterman CRC, Lewis MA, Hyde SM, Makawita S, Dasari A, Thosani N, Ikoma N, McCutcheon IE, Waguespack SG, Perrier ND. It's not a mystery, it's in the history: Multidisciplinary management of multiple endocrine neoplasia type 1. CA Cancer J Clin 2021; 71:369-380. [PMID: 34061974 DOI: 10.3322/caac.21673] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/12/2021] [Accepted: 03/30/2021] [Indexed: 12/11/2022] Open
Affiliation(s)
- Aditya S Shirali
- Department of Surgical Oncology, Section of Surgical Endocrinology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Carolina R C Pieterman
- Department of Surgical Oncology, Section of Surgical Endocrinology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mark A Lewis
- Department of Medicine, Intermountain Healthcare, Murray, Utah
| | - Samuel M Hyde
- Department of Obstetrics and Gynecology-Cancer Genetics, Northwestern Memorial Hospital, Chicago, Illinois
| | - Shalini Makawita
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Arvind Dasari
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Nirav Thosani
- Division of Gastroenterology, Hepatology, and Nutrition, McGovern Medical School, UTHealth, Houston, Texas
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ian E McCutcheon
- Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Steven G Waguespack
- Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Nancy D Perrier
- Department of Surgical Oncology, Section of Surgical Endocrinology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
23
|
Zhang J, Chen J, Li J, Yang X. Application Value of Ultrasound-Guided Fine Needle Aspiration Cytological Examination and Ultrasound Evaluation. JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS 2021. [DOI: 10.1166/jmihi.2021.3760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
In this paper, chronic inflammatory cell infiltration was seen during this period. The reason for the false-positive result may be the atypical proliferation of cells caused by chronic inflammatory stimulation with malignant cytology. 12 cases of false negative results, including 2
cases of type I nodules, 10 cases of type III nodules, postoperative histology and pathology were papillary carcinoma, there are many reasons for false negative results, including the size of the nodules, the puncture operator, the technical level, internal tissue composition and properties
of the nodules all affect the accuracy of puncture and cytopathology results. The satisfaction of puncture specimens of each group was calculated and compared. For thyroid nodules with the maximum diameter ≤5 mm, the satisfaction rate of puncture specimens was 87.2%, and the diagnostic
sensitivity and accuracy of ultras guided fine needle aspiration biopsy were relatively low. Cytological results were in poor agreement with postoperative histological and pathological results, so it was recommended to take active follow-up for thyroid nodules with the maximum diameter ≤5
mm to reduce unnecessary puncture. The overall puncture success rate is relatively high, ≤10 mm low-echo nodules or even ≤5 mm nodules can be cytological puncture, especially the kind of close to the capsule, trachea and recurrent laryngeal nerve nodules, for the largest diameter of
>5 mm, the satisfaction rate of puncture specimens is relatively high is 93.2%. Moreover, the sensitivity and accuracy of ultrasound guided fine needle aspiration biopsy were relatively high, and the cytological results were in good agreement with the postoperative histological and pathological
results. Therefore, it was feasible to confirm the diagnosis of suspected malignant nodules by ultrasound. The diagnostic in each group and the consistency between cytological diagnosis and histological diagnosis were analyzed by comparing the histological and pathological results after surgery.
Ultrasound-guided fine needle aspiration biopsy can be used more effectively in clinical practice.
Collapse
Affiliation(s)
- Jingcheng Zhang
- Tongxiang Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, 314500, China
| | - Jili Chen
- Tongxiang Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, 314500, China
| | - Juanjuan Li
- Tongxiang Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, 314500, China
| | - Xuechen Yang
- Tongxiang Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, 314500, China
| |
Collapse
|
|
24
|
Ellison EC. Commentary: Small nonfunctional pancreatic neuroendocrine tumors (NF-PNETS): Resect or enucleate ? The case for an individualized approach. Am J Surg 2021; 222:27-28. [DOI: 10.1016/j.amjsurg.2021.01.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 01/07/2021] [Indexed: 01/29/2023]
|
|
25
|
Pulvirenti A, Yamashita R, Chakraborty J, Horvat N, Seier K, McIntyre CA, Lawrence SA, Midya A, Koszalka MA, Gonen M, Klimstra DS, Reidy DL, Allen PJ, Do RKG, Simpson AL. Quantitative Computed Tomography Image Analysis to Predict Pancreatic Neuroendocrine Tumor Grade. JCO Clin Cancer Inform 2021; 5:679-694. [PMID: 34138636 DOI: 10.1200/cci.20.00121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
PURPOSE The therapeutic management of pancreatic neuroendocrine tumors (PanNETs) is based on pathological tumor grade assessment. A noninvasive imaging method to grade tumors would facilitate treatment selection. This study evaluated the ability of quantitative image analysis derived from computed tomography (CT) images to predict PanNET grade. METHODS Institutional database was queried for resected PanNET (2000-2017) with a preoperative arterial phase CT scan. Radiomic features were extracted from the primary tumor on the CT scan using quantitative image analysis, and qualitative radiographic descriptors were assessed by two radiologists. Significant features were identified by univariable analysis and used to build multivariable models to predict PanNET grade. RESULTS Overall, 150 patients were included. The performance of models based on qualitative radiographic descriptors varied between the two radiologists (reader 1: sensitivity, 33%; specificity, 66%; negative predictive value [NPV], 63%; and positive predictive value [PPV], 37%; reader 2: sensitivity, 45%; specificity, 70%; NPV, 72%; and PPV, 47%). The model based on radiomics had a better performance predicting the tumor grade with a sensitivity of 54%, a specificity of 80%, an NPV of 81%, and a PPV of 54%. The inclusion of radiomics in the radiographic descriptor models improved both the radiologists' performance. CONCLUSION CT quantitative image analysis of PanNETs helps predict tumor grade from routinely acquired scans and should be investigated in future prospective studies.
Collapse
Affiliation(s)
- Alessandra Pulvirenti
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Rikiya Yamashita
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Jayasree Chakraborty
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kenneth Seier
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Caitlin A McIntyre
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sharon A Lawrence
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Abhishek Midya
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Maura A Koszalka
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - David S Klimstra
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Diane L Reidy
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Peter J Allen
- Department of Surgery, Hepatopancreatobiliary Service, Duke, University School of Medicine, Durham, NC
| | - Richard K G Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amber L Simpson
- School of Computing, Queen's University, Kingston, ON, Canada
| |
Collapse
|
|
26
|
Nakano A, Hayano K, Tochigi T, Mashiko T, Masuoka Y, Yamamoto S, Ozawa S, Nakagohri T. Prediction of non-functioning pancreatic neuroendocrine tumor grades with fractal analysis of preoperative contrast-enhanced computed tomography images. Eur J Radiol 2021; 141:109803. [PMID: 34090111 DOI: 10.1016/j.ejrad.2021.109803] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 04/26/2021] [Accepted: 05/26/2021] [Indexed: 11/30/2022]
Abstract
PURPOSE To assess intra-tumoral heterogeneity (ITH) via fractal analysis of preoperative contrast-enhanced computed tomography (CT) images to predict pathological grades in non-functioning pancreatic neuroendocrine tumors (NF-PNETs) and verify its impact on patient survival. METHODS This retrospective study enrolled 40 patients with NF-PNET resected in our institution during a period from July 2005 to December 2018, except functioning tumors, unidentified tumors in CT, patients without preoperative contrast-enhanced CT. CT images were analyzed using plugin software for calculating fractal dimension (FD), and the maximum value was denoted as "FDmax," and compared with pathological grades and patient survival between G1 and G2/3 group separating according to two different Ki-67 index thresholds (3% and 5%). All CT images were acquired in three-phases and arterial phase images were examined. RESULTS Ki-67 index and FDmax showed a direct correlation with significance (p < 0.01). The mean FDmax of the G2/3 tumor group was significantly higher than that of the G1 tumor group (p < 0.01 in both 3% and 5% thresholds). In the ROC analysis, FDmax showed 0.773 of AUC, and cut-off value of 1.036 reported 62.5 % sensitivity, 90.0 % specificity, 86.2 % PPV, and 70.6 % NPV to distinguish G2/3 patients. The high-FD (≥1.036) group showed a significantly shorter disease-free survival (DFS) than the low-FD group (p = 0.0128). In multivariate analysis of prognostic factors, high FD was the only significant factor for DFS (HR, 5.793; 95 % CI: 1.213-27.664; p = 0.028). CONCLUSIONS The tumor's FDmax using CE-CT analysis might be a potential biomarker for preoperative prediction of G2/3 tumors, and predicting recurrence.
Collapse
Affiliation(s)
- Akira Nakano
- Department of Surgery, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
| | - Koichi Hayano
- Department of Frontier Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba 260-8677, Japan.
| | - Toru Tochigi
- Department of Frontier Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba 260-8677, Japan.
| | - Taro Mashiko
- Department of Surgery, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
| | - Yoshihito Masuoka
- Department of Surgery, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
| | - Seiichiro Yamamoto
- Department of Surgery, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
| | - Soji Ozawa
- Department of Surgery, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
| | - Toshio Nakagohri
- Department of Surgery, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
| |
Collapse
|
|
27
|
Fernandez CJ, Agarwal M, Pottakkat B, Haroon NN, George AS, Pappachan JM. Gastroenteropancreatic neuroendocrine neoplasms: A clinical snapshot. World J Gastrointest Surg 2021; 13:231-255. [PMID: 33796213 PMCID: PMC7993001 DOI: 10.4240/wjgs.v13.i3.231] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/17/2021] [Accepted: 03/02/2021] [Indexed: 02/06/2023] Open
Abstract
Our understanding about the epidemiological aspects, pathogenesis, molecular diagnosis, and targeted therapies of neuroendocrine neoplasms (NENs) have drastically advanced in the past decade. Gastroenteropancreatic (GEP) NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors. Most NENs are well-differentiated, and slow growing. Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin, glucagon, vasoactive intestinal polypeptide, gastrin, somatostatin, adrenocorticotropin, growth hormone releasing hormone, parathyroid hormone-related peptide, serotonin, histamine, and 5-hydroxy indole acetic acid (5-HIAA). Biomarkers such as pancreatic polypeptide, human chorionic gonadotrophin subunits, neurotensin, ghrelin, and calcitonin are used in the diagnosis of non-functional NENs. 5-HIAA levels correlate with tumour burden, prognosis and development of carcinoid heart disease and mesenteric fibrosis, however several diseases, medications and edible products can falsely elevate the 5-HIAA levels. Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs. Emerging novel biomarkers include circulating tumour cells, circulating tumour DNA, circulating micro-RNAs, and neuroendocrine neoplasms test (NETest) (simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood). NETest has high sensitivity (85%-98%) and specificity (93%-97%) for the detection of gastrointestinal NENs, and is useful for monitoring treatment response, recurrence, and prognosis. In terms of management, surgery, radiofrequency ablation, symptom control with medications, chemotherapy and molecular targeted therapies are all considered as options. Surgery is the mainstay of treatment, but depends on factors including age of the individual, location, stage, grade, functional status, and the heredity of the tumour (sporadic vs inherited). Medical management is helpful to alleviate the symptoms, manage inoperable lesions, suppress postoperative tumour growth, and manage recurrences. Several molecular-targeted therapies are considered second line to somatostatin analogues. This review is a clinical update on the pathophysiological aspects, diagnostic algorithm, and management of GEP NENs.
Collapse
Affiliation(s)
- Cornelius J Fernandez
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, United Kingdom
| | - Mayuri Agarwal
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, United Kingdom
| | - Biju Pottakkat
- Department of Surgical Gastroenterology, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Puducherry 605006, India
| | - Nisha Nigil Haroon
- Department of Endocrinology and Internal Medicine, Northern Ontario School of Medicine, Sudbury P3E 2C6, Ontario, Canada
| | - Annu Susan George
- Department of Medical Oncology, VPS Lakeshore Hospital, Cochin 682040, Kerala, India
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, PR2 9HT, Preston, The University of Manchester, Oxford Road M13 9PL, Manchester Metropolitan University, All Saints Building M15 6BH, Manchester, United Kingdom
| |
Collapse
|
|
28
|
Kitada T, Masui T, Kasai Y, Uchida Y, Ogiso S, Ito T, Ishii T, Seo S, Katsuragawa H, Uemoto S. A subcentimeter duodenal neuroendocrine neoplasm with a liver metastasis upgraded to G3: a case report. Surg Case Rep 2021; 7:72. [PMID: 33742297 PMCID: PMC7979845 DOI: 10.1186/s40792-021-01155-1] [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: 01/21/2021] [Accepted: 03/10/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis. CASE PRESENTATION The patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the "hot spot" and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy. CONCLUSIONS This case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy.
Collapse
Affiliation(s)
- Tomoya Kitada
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Yosuke Kasai
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Yuichiro Uchida
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takashi Ito
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hiroyuki Katsuragawa
- Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| |
Collapse
|
|
29
|
Crinò SF, Ammendola S, Meneghetti A, Bernardoni L, Conti Bellocchi MC, Gabbrielli A, Landoni L, Paiella S, Pin F, Parisi A, Mastrosimini MG, Amodio A, Frulloni L, Facciorusso A, Larghi A, Manfrin E. Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors. Pancreatology 2021; 21:443-450. [PMID: 33390343 DOI: 10.1016/j.pan.2020.12.015] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 12/09/2020] [Accepted: 12/21/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens. METHODS Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed. RESULTS Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482). CONCLUSION Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.
Collapse
Affiliation(s)
- Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy.
| | - Serena Ammendola
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | - Anna Meneghetti
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | | | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Luca Landoni
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Federico Pin
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Alice Parisi
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | | | - Antonio Amodio
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Luca Frulloni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Antonio Facciorusso
- Digestive Endoscopy Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| |
Collapse
|
|
30
|
Ishii T, Katanuma A, Toyonaga H, Chikugo K, Nasuno H, Kin T, Hayashi T, Takahashi K. Role of Endoscopic Ultrasound in the Diagnosis of Pancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2021; 11:diagnostics11020316. [PMID: 33672085 PMCID: PMC7919683 DOI: 10.3390/diagnostics11020316] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 02/10/2021] [Indexed: 12/16/2022] Open
Abstract
Although pancreatic neuroendocrine neoplasms (PNENs) are relatively rare tumors, their number is increasing with advances in diagnostic imaging modalities. Even small lesions that are difficult to detect using computed tomography or magnetic resonance imaging can now be detected with endoscopic ultrasound (EUS). Contrast-enhanced EUS is useful, and not only diagnosis but also malignancy detection has become possible by evaluating the vascularity of tumors. Pathological diagnosis using EUS with fine-needle aspiration (EUS-FNA) is useful when diagnostic imaging is difficult. EUS-FNA can also be used to evaluate the grade of malignancy. Pooling the data of the studies that compared the PNENs grading between EUS-FNA samples and surgical specimens showed a concordance rate of 77.5% (κ-statistic = 0.65, 95% confidence interval = 0.59–0.71, p < 0.01). Stratified analysis for small tumor size (2 cm) showed that the concordance rate was 84.5% and the kappa correlation index was 0.59 (95% confidence interval = 0.43–0.74, p < 0.01). The evolution of ultrasound imaging technologies such as contrast-enhanced and elastography and the artificial intelligence that analyzes them, the evolution of needles, and genetic analysis, will further develop the diagnosis and treatment of PNENs in the future.
Collapse
Affiliation(s)
- Tatsuya Ishii
- Correspondence: ; Tel.: +81-11-681-8111; Fax: +81-11-685-2967
| | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Paik WH, Lee HS, Lee KJ, Jang SI, Lee WJ, Hwang JH, Cho CM, Park CH, Han J, Woo SM, Jeong S, Chon HK, Kim TN, Lee JK, Han JH, Yoon JH, Kim YT, Cho JH. Malignant potential of small pancreatic neuroendocrine neoplasm and its risk factors: A multicenter nationwide study. Pancreatology 2021; 21:208-214. [PMID: 33281058 DOI: 10.1016/j.pan.2020.11.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/24/2020] [Accepted: 11/24/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.
Collapse
Affiliation(s)
- Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Hee Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyong Joo Lee
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju, South Korea
| | - Sung Ill Jang
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Woo Jin Lee
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Chang Min Cho
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Chang-Hwan Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea
| | - Jimin Han
- Division of Gastroenterology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, South Korea
| | - Sang Myung Woo
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
| | - Seok Jeong
- Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea
| | - Hyung Ku Chon
- Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, South Korea
| | - Tae Nyeun Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
| | - Jun Kyu Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, South Korea
| | - Joung-Ho Han
- Department of Internal Medicine, Chungbuk National University College of Medicine, Chungbuk National University Hospital, Cheongju, South Korea
| | - Jai Hoon Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Seoul Hospital, Seoul, South Korea
| | - Yong-Tae Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.
| | - Jae Hee Cho
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
| |
Collapse
|
|
32
|
Ji S, Liu M, Xia H, Ye Z, Xu X, Yu X, Zhuo Q. Management of Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An Analysis of the US Surveillance, Epidemiology, and End Results Database. Pancreas 2021; 50:e8-e10. [PMID: 33370038 DOI: 10.1097/mpa.0000000000001705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Shunrong Ji
- Department of Pancreatic Surgery Fudan University Shanghai Cancer Center Shanghai, China Department of Oncology Shanghai Medical College Fudan University Shanghai, China Shanghai Pancreatic Cancer Institute Shanghai, China Pancreatic Cancer Institute Fudan University Shanghai, China ;
| | | | | | | | | | | | | |
Collapse
|
|
33
|
Albertelli M, Grillo F, Lo Calzo F, Puliani G, Rainone C, Colao AAL, Faggiano A. Pathology Reporting in Neuroendocrine Neoplasms of the Digestive System: Everything You Always Wanted to Know but Were Too Afraid to Ask. Front Endocrinol (Lausanne) 2021; 12:680305. [PMID: 33967966 PMCID: PMC8104083 DOI: 10.3389/fendo.2021.680305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 04/07/2021] [Indexed: 12/14/2022] Open
Abstract
During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals.
Collapse
Affiliation(s)
- Manuela Albertelli
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI) and Centre of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
- IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Federica Grillo
- IRCCS Ospedale Policlinico San Martino, Genova, Italy
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy
- *Correspondence: Federica Grillo,
| | - Fabio Lo Calzo
- Department of Clinical Medicine and Surgery, Division of Endocrinology, Federico II University, Naples, Italy
- Internal Medicine Unit, Frangipane Hospital, Ariano Irpino, Italy
| | - Giulia Puliani
- Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy
- Oncological Endocrinology Unit, Regina Elena National Cancer Institute, Roma, Italy
| | - Carmen Rainone
- Department of Clinical Medicine and Surgery, Division of Endocrinology, Federico II University, Naples, Italy
| | - Annamaria Anita Livia Colao
- Department of Clinical Medicine and Surgery, Division of Endocrinology, Federico II University, Naples, Italy
- UNESCO Chair for Health Education and Sustainable Development, Federico II University, Naples, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Roma, Italy
| | | |
Collapse
|
|
34
|
Paiella S, Landoni L, Rota R, Valenti M, Elio G, Crinò SF, Manfrin E, Parisi A, Cingarlini S, D'Onofrio M, Scarpa A, Lawlor RT, Bernardoni L, Capelli P, Nessi C, Miotto M, Gabbrielli A, Bassi C, Salvia R. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases. Endoscopy 2020; 52:988-994. [PMID: 32498099 DOI: 10.1055/a-1180-8614] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology. METHODS Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA. RESULTS EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen's κ = 0.59, 95 % confidence interval [CI] 0.34 - 0.78). Spearman's rho for Ki-67 in tumors ≤ 20 mm and > 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 - 0.83; rho = 0.59, 95 %CI 0.35 - 0.75). The Bland - Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements. CONCLUSIONS Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.
Collapse
Affiliation(s)
- Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Luca Landoni
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Roberta Rota
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Matteo Valenti
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Giovanni Elio
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Alice Parisi
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Sara Cingarlini
- Oncology Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Mirko D'Onofrio
- Radiology Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy.,ARC-Net Applied Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Rita Teresa Lawlor
- ARC-Net Applied Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Paola Capelli
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Chiara Nessi
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Marco Miotto
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| |
Collapse
|
|
35
|
Sadowski SM, Pieterman CRC, Perrier ND, Triponez F, Valk GD. Prognostic factors for the outcome of nonfunctioning pancreatic neuroendocrine tumors in MEN1: a systematic review of literature. Endocr Relat Cancer 2020; 27:R145-R161. [PMID: 32229700 PMCID: PMC7304521 DOI: 10.1530/erc-19-0372] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prognostic factors for risk stratification are limited. This systematic review aims to establish the current state of evidence regarding prognostic factors in MEN1-related NF-pNETs. We systematically searched four databases for studies assessing prognostic value of any factor on NF-pNET progression, development of distant metastases, and/or overall survival. In- and exclusion, critical appraisal and data-extraction were performed independently by two authors according to pre-defined criteria. Thirteen studies (370 unique patients) were included. Prognostic factors investigated were tumor size, timing of surgical resection, WHO grade, methylation, p27/p18 expression by immunohistochemistry (IHC), ARX/PDX1 IHC and alternative lengthening of telomeres. Results were complemented with evidence from studies in MEN1-related pNET for which data could not be separately extracted for NF-pNET and data from sporadic NF-pNET. We found that the most important prognostic factors used in clinical decision making in MEN1-related NF-pNETs are tumor size and grade. NF-pNETs <2 cm may be managed with watchful waiting, while surgical resection is advised for NF-pNETs ≥2 cm. Grade 2 NF-pNETs should be considered high risk. The most promising and MEN1-relevant avenues of prognostic research are multi-analyte circulating biomarkers, tissue-based molecular factors and imaging-based prognostication. Multi-institutional collaboration between clinical, translation and basic scientists with uniform data and biospecimen collection in prospective cohorts should advance the field.
Collapse
Affiliation(s)
- S M Sadowski
- Endocrine Surgery, Surgical Oncology Program, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - C R C Pieterman
- Department of Surgical Oncology, Section of Surgical Endocrinology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - N D Perrier
- Department of Surgical Oncology, Section of Surgical Endocrinology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - F Triponez
- Thoracic and Endocrine Surgery and Faculty of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - G D Valk
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| |
Collapse
|
|
36
|
Satturwar SP, Pantanowitz JL, Manko CD, Seigh L, Monaco SE, Pantanowitz L. Ki-67 proliferation index in neuroendocrine tumors: Can augmented reality microscopy with image analysis improve scoring? Cancer Cytopathol 2020; 128:535-544. [PMID: 32401429 DOI: 10.1002/cncy.22272] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 02/18/2020] [Accepted: 03/11/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND The Ki-67 index is important for grading neuroendocrine tumors (NETs) in cytology. However, different counting methods exist. Recently, augmented reality microscopy (ARM) has enabled real-time image analysis using glass slides. The objective of the current study was to compare different traditional Ki-67 scoring methods in cell block material with newer methods such as ARM. METHODS Ki-67 immunostained slides from 50 NETs of varying grades were retrieved (39 from the pancreas and 11 metastases). Methods with which to quantify the Ki-67 index in up to 3 hot spots included: 1) "eyeball" estimation (EE); 2) printed image manual counting (PIMC); 3) ARM with live image analysis; and 4) image analysis using whole-slide images (WSI) (field of view [FOV] and the entire slide). RESULTS The Ki-67 index obtained using the different methods varied. The pairwise kappa results varied from no agreement for image analysis using digital image analysis WSI (FOV) and histology to near-perfect agreement for ARM and PIMC. Using surgical pathology as the gold standard, the EE method was found to have the highest concordance rate (84.2%), followed by WSI analysis of the entire slide (73.7%) and then both the ARM and PIMC methods (63.2% for both). The PIMC method was the most time-consuming whereas image analysis using WSI (FOV) was the fastest method followed by ARM. CONCLUSIONS The Ki-67 index for NETs in cell block material varied by the method used for scoring, which may affect grade. PIMC was the most time-consuming method, and EE had the highest concordance rate. Although real-time automated counting using image analysis demonstrated inaccuracies, ARM streamlined and hastened the task of Ki-67 quantification in NETs.
Collapse
Affiliation(s)
- Swati P Satturwar
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | | | - Christopher D Manko
- Department of Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Lindsey Seigh
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Sara E Monaco
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Liron Pantanowitz
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
37
|
Bian Y, Zhao Z, Jiang H, Fang X, Li J, Cao K, Ma C, Guo S, Wang L, Jin G, Lu J, Xu J. Noncontrast Radiomics Approach for Predicting Grades of Nonfunctional Pancreatic Neuroendocrine Tumors. J Magn Reson Imaging 2020; 52:1124-1136. [PMID: 32343872 DOI: 10.1002/jmri.27176] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 04/05/2020] [Accepted: 04/06/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Endoscopic ultrasound-guided fine-needle aspiration is associated with the accurate determination of tumor grade. However, because it is an invasive procedure there is a need to explore alternative noninvasive procedures. PURPOSE To develop and validate a noncontrast radiomics model for the preoperative prediction of nonfunctional pancreatic neuroendocrine tumor (NF-pNET) grade (G). STUDY TYPE Retrospective, single-center study. SUBJECTS Patients with pathologically confirmed PNETs (139) were included. FIELD STRENGTH/SEQUENCE 3T/breath-hold single-shot fast-spin echo T2 -weighted sequence and unenhanced and dynamic contrast-enhanced T1 -weighted fat-suppressed sequences. ASSESSMENT Tumor features on contrast MR images were evaluated by three board-certified abdominal radiologists. STATISTICAL TESTS Multivariable logistic regression analysis was used to develop the clinical model. The least absolute shrinkage and selection operator method and linear discriminative analysis (LDA) were used to select the features and to construct a radiomics model. The performance of the models was assessed using the training cohort (97 patients) and the validation cohort (42 patients), and decision curve analysis (DCA) was applied for clinical use. RESULTS The clinical model included 14 imaging features, and the corresponding area under the curve (AUC) was 0.769 (95% confidence interval [CI], 0.675-0.863) in the training cohort and 0.729 (95% CI, 0.568-0.890) in the validation cohort. The LDA included 14 selected radiomics features that showed good discrimination-in the training cohort (AUC, 0.851; 95% CI, 0.758-0.916) and the validation cohort (AUC, 0.736; 95% CI, 0.518-0.874). In the decision curves, if the threshold probability was 0.17-0.84, using the radiomics score to distinguish NF-pNET G1 and G2/3, offered more benefit than did the use of a treat-all-patients or treat-none scheme. DATA CONCLUSION The developed radiomics model using noncontrast MRI could help differentiate G1 and G2/3 tumors, to make the clinical decision, and screen pNETs grade. LEVEL OF EVIDENCE 4 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:1124-1136.
Collapse
Affiliation(s)
- Yun Bian
- Department of Radiology, Changhai Hospital, Shanghai, China
| | - Zengrui Zhao
- Jiangsu Key Laboratory of Big Data Analysis Technique, Nanjing University of Information Science and Technology, Nanjing, China
| | - Hui Jiang
- Department of Pathology, Changhai Hospital, Shanghai, China
| | - Xu Fang
- Department of Radiology, Changhai Hospital, Shanghai, China
| | - Jing Li
- Department of Radiology, Changhai Hospital, Shanghai, China
| | - Kai Cao
- Department of Radiology, Changhai Hospital, Shanghai, China
| | - Chao Ma
- Department of Radiology, Changhai Hospital, Shanghai, China
| | - Shiwei Guo
- Department of Pancreatic Surgery, Changhai Hospital, Shanghai, China
| | - Li Wang
- Department of Radiology, Changhai Hospital, Shanghai, China
| | - Gang Jin
- Department of Pancreatic Surgery, Changhai Hospital, Shanghai, China
| | - Jianping Lu
- Department of Radiology, Changhai Hospital, Shanghai, China
| | - Jun Xu
- Jiangsu Key Laboratory of Big Data Analysis Technique, Nanjing University of Information Science and Technology, Nanjing, China
| |
Collapse
|
|
38
|
Hofland J, Kaltsas G, de Herder WW. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocr Rev 2020; 41:bnz004. [PMID: 31555796 PMCID: PMC7080342 DOI: 10.1210/endrev/bnz004] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 02/28/2020] [Indexed: 02/07/2023]
Abstract
Neuroendocrine neoplasms constitute a diverse group of tumors that derive from the sensory and secretory neuroendocrine cells and predominantly arise within the pulmonary and gastrointestinal tracts. The majority of these neoplasms have a well-differentiated grade and are termed neuroendocrine tumors (NETs). This subgroup is characterized by limited proliferation and patients affected by these tumors carry a good to moderate prognosis. A substantial subset of patients presenting with a NET suffer from the consequences of endocrine syndromes as a result of the excessive secretion of amines or peptide hormones, which can impair their quality of life and prognosis. Over the past 15 years, critical developments in tumor grading, diagnostic biomarkers, radionuclide imaging, randomized controlled drug trials, evidence-based guidelines, and superior prognostic outcomes have substantially altered the field of NET care. Here, we review the relevant advances to clinical practice that have significantly upgraded our approach to NET patients, both in diagnostic and in therapeutic options.
Collapse
Affiliation(s)
- Johannes Hofland
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus MC Cancer Center, Erasmus MC, Rotterdam, The Netherlands
| | - Gregory Kaltsas
- 1st Department of Propaupedic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Wouter W de Herder
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus MC Cancer Center, Erasmus MC, Rotterdam, The Netherlands
| |
Collapse
|
|
39
|
Howe JR, Merchant NB, Conrad C, Keutgen XM, Hallet J, Drebin JA, Minter RM, Lairmore TC, Tseng JF, Zeh HJ, Libutti SK, Singh G, Lee JE, Hope TA, Kim MK, Menda Y, Halfdanarson TR, Chan JA, Pommier RF. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors. Pancreas 2020; 49:1-33. [PMID: 31856076 PMCID: PMC7029300 DOI: 10.1097/mpa.0000000000001454] [Citation(s) in RCA: 231] [Impact Index Per Article: 46.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.
Collapse
Affiliation(s)
- James R. Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Claudius Conrad
- Department of Surgery, St. Elizabeth Medical Center, Tufts University School of Medicine, Boston, MA
| | | | - Julie Hallet
- Department of Surgery, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Jeffrey A. Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Rebecca M. Minter
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | | | - Herbert J. Zeh
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Steven K. Libutti
- §§ Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
| | - Gagandeep Singh
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Jeffrey E. Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A. Hope
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA
| | - Michelle K. Kim
- Department of Medicine, Mt. Sinai Medical Center, New York, NY
| | - Yusuf Menda
- Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Jennifer A. Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Rodney F. Pommier
- Department of Surgery, Oregon Health & Sciences University, Portland, OR
| |
Collapse
|
|
40
|
Hackeng WM, Morsink FHM, Moons LMG, Heaphy CM, Offerhaus GJA, Dreijerink KMA, Brosens LAA. Assessment of ARX expression, a novel biomarker for metastatic risk in pancreatic neuroendocrine tumors, in endoscopic ultrasound fine-needle aspiration. Diagn Cytopathol 2019; 48:308-315. [PMID: 31846235 PMCID: PMC7079001 DOI: 10.1002/dc.24368] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 11/26/2019] [Accepted: 12/04/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The transcription factors ARX and PDX1, and alternative lengthening of telomeres (ALT) were recently described as prognostic markers for resected non-functional pancreatic neuroendocrine tumors (PanNETs). ALT positive tumors with ARX expression relapse most often. Currently, tumor size is the only preoperative marker used to decide whether or not to operate, thus additional preoperative prognostic markers are needed. Therefore, it is critical to assess the performance of these biomarkers on preoperative cytologic specimens. METHODS Endoscopic fine-needle aspiration cellblock material and corresponding surgical specimens of 13 patients with PanNETs were assessed for histology, immunohistochemical staining of ARX, PDX1, Synaptophysin, Ki67, and telomere-specific fluorescence in situ hybridization to detect ALT, and then associated with clinicopathological features. Scoring for ARX and PDX1 was performed blinded by two independent observers. RESULTS Of the 13 surgical specimens, 8 were ARX+/PDX1-, 2 ARX-/PDX1+, and 3 ARX+/PDX1+. Concordance between cytologic and surgical specimens for ARX protein expression was 100%, whereas concordance for PDX1, ALT, and WHO tumor grade was 85%, 91%, and 73%, respectively. There was a perfect inter-observer agreement in ARX and PDX1 scoring. CONCLUSION ARX can reliably be determined in cytologic specimens and has low inter-observer variability. For cytology, false-positive PDX1 expression was observed, possibly due to contamination or sampling, while ALT had a false-negative case due to incomplete sampling. As previously observed, tumor grade is underestimated in cytologic specimens. Thus, ARX and ALT are the most promising markers to predict metastatic behavior in PanNETs, thereby warranting further validation in larger studies.
Collapse
Affiliation(s)
- Wenzel M Hackeng
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Folkert H M Morsink
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Leon M G Moons
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Christopher M Heaphy
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - G Johan A Offerhaus
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Koen M A Dreijerink
- Department of Endocrinology and Internal Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| |
Collapse
|
|
41
|
Cui Y, Khanna LG, Saqi A, Crapanzano JP, Mitchell JM, Sethi A, Gonda TA, Kluger MD, Schrope BA, Allendorf J, Chabot JA, Poneros JM. The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors. Clin Endosc 2019; 53:213-220. [PMID: 31302988 PMCID: PMC7137561 DOI: 10.5946/ce.2019.068] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 04/06/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/AIMS The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratify PNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NFPNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. METHODS We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NFPNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. RESULTS There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordance was the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028) were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumor size >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. CONCLUSION NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs with intermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUSFNA can be monitored without surgical intervention, up to tumor size 20 mm.
Collapse
Affiliation(s)
- YongYan Cui
- Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Lauren G Khanna
- Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA
| | - Anjali Saqi
- Department of Pathology and Cell Biology, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - John P Crapanzano
- Department of Pathology and Cell Biology, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - James M Mitchell
- Department of Pathology and Cell Biology, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Amrita Sethi
- Division of Digestive and Liver Diseases, Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Tamas A Gonda
- Division of Digestive and Liver Diseases, Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Michael D Kluger
- Department of Surgery, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Beth A Schrope
- Department of Surgery, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - John Allendorf
- Department of Surgery, New York University Winthrop Hospital, Mineola, NY, USA
| | - John A Chabot
- Department of Surgery, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - John M Poneros
- Division of Digestive and Liver Diseases, Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| |
Collapse
|
|
42
|
Ren S, Chen X, Wang J, Zhao R, Song L, Li H, Wang Z. Differentiation of duodenal gastrointestinal stromal tumors from hypervascular pancreatic neuroendocrine tumors in the pancreatic head using contrast-enhanced computed tomography. Abdom Radiol (NY) 2019; 44:867-876. [PMID: 30293109 DOI: 10.1007/s00261-018-1803-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To determine useful contrast-enhanced computed tomography (CE-CT) features in differentiating duodenal gastrointestinal stromal tumors (duodenal GISTs) from hypervascular pancreatic neuroendocrine tumors in the pancreatic head (pancreatic head NETs). METHODS Seventeen patients with pathologically confirmed duodenal GISTs and 25 with pancreatic NETs underwent preoperative CE-CT. CT image analysis included tumor size, morphology, and contrast enhancement. Receiver operating characteristic curves were performed, and cutoff values were calculated to determine CT findings with high sensitivity and specificity. RESULTS CT imaging showed duodenal GISTs with higher frequencies of tumor central location close to the duodenum and a predominantly solid tumor type when compared with pancreatic head NETs (p < 0.05 for both). Duodenal GISTs were larger than pancreatic head NETs (3.3 ± 0.9 cm vs. 2.5 ± 1.1 cm, p = 0.03). Duodenal GISTs had significantly lower CT attenuation values (112.9 ± 17.9HU vs. 137.4 ± 32.1HU, p < 0.01) at the arterial phase and higher CT attenuation values at the delayed phase (94.3 ± 7.9HU vs. 84.9 ± 10.4HU, p < 0.01) when compared with pancreatic head NETs. A CT attenuation value of ≤ 135 HU at the arterial phase (30 s) was 76% sensitive, 94.1% specific, and 83.3% accurate for the diagnosis of duodenal GISTs, while a CT attenuation value of ≥ 89.5 HU at the delayed phase (120 s) was 93.3% sensitive, 81.8% specific, and 76.2% accurate for the diagnosis of duodenal GISTs. CONCLUSION Tumor central location, size, texture, and contrast enhancement are valuable characteristics for the differentiation between duodenal GISTs and hypervascular pancreatic head NETs during preoperative examination.
Collapse
Affiliation(s)
- Shuai Ren
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China
| | - Xiao Chen
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China
| | - Jianhua Wang
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China
| | - Rui Zhao
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China
| | - Lina Song
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China
| | - Hui Li
- Department of Pathology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu Province, China
| | - Zhongqiu Wang
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China.
| |
Collapse
|
|
43
|
Ren S, Chen X, Wang Z, Zhao R, Wang J, Cui W, Wang Z. Differentiation of hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinoma using contrast-enhanced computed tomography. PLoS One 2019; 14:e0211566. [PMID: 30707733 PMCID: PMC6358067 DOI: 10.1371/journal.pone.0211566] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 01/16/2019] [Indexed: 12/14/2022] Open
Abstract
Hypovascular pancreatic neuroendocrine tumors (hypo-PNETs) are often misdiagnosed as pancreatic ductal adenocarcinoma (PDAC). However, the treatment options and prognosis of PNETs and PDAC are substantially different. This retrospective study differentiated hypo-PNETs from PDAC using contrast-enhanced CT (CE-CT). Clinical data and CE-CT findings, including tumor location, size, boundary, pancreatic duct dilatation, local invasion or metastases, tumor contrast enhancement, and tumor-to-pancreas enhancement ratio, were compared between 39 PDACs and 18 hypo-PNETs. At CT imaging, hypo-PNETs showed a higher frequency of a well-defined margin and lower frequencies of pancreatic duct dilatation and local invasion or metastasis when compared with PDAC (p < 0.05 for all). The mean attenuation of hypo-PNETs at the arterial and portal venous phase was significantly higher than that of PDAC (p < 0.001, p = 0.003, respectively). Similar results were observed in tumor-to-pancreas enhancement ratio. Tumor attenuation and tumor-to-pancreas enhancement ratio at the arterial phase showed the largest area under the curve (AUC) of 0.888 and 0.812 with 83.3–88.9% of sensitivity and 61.6–77.0% of specificity. Pancreatic duct dilatation, local invasion or metastasis, and tumor attenuation at the portal venous phase also showed acceptable AUC (0.703–0.748). Thus CE-CT features, especially the enhancement degree at the arterial phases, may be useful for differentiating hypo-PNETs from PDAC using CE-CT.
Collapse
Affiliation(s)
- Shuai Ren
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiao Chen
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhonglan Wang
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Rui Zhao
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianhua Wang
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Wenjing Cui
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhongqiu Wang
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- * E-mail:
| |
Collapse
|
|
44
|
Sigel CS. Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms. Cancer Cytopathol 2018; 126:980-991. [PMID: 30485690 DOI: 10.1002/cncy.22073] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 09/18/2018] [Accepted: 09/18/2018] [Indexed: 02/01/2023]
Abstract
Two-thirds of neuroendocrine neoplasms arising in the human body originate from the gastrointestinal system or pancreas. Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous, comprising both well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The clinical presentation, molecular characteristics, and behavior are distinct for NETs and NECs. Fine-needle aspiration is an important modality for the primary diagnosis and staging of these neoplasms and can provide information of prognostic and therapeutic significance. Our evolving understanding of neuroendocrine neoplasm biology has led to several iterations of classification. In this review, new concepts and issues most relevant to cytology diagnosis of gastroenteropancreatic neuroendocrine neoplasms are discussed, such as newer detection methods that aid in diagnosis and staging, recent changes in World Health Organization classification, practical issues related to grading these neoplasms on cytology, guidelines for diagnostic reporting, and panels of immunohistochemical stains for the diagnosis of metastasis. The current understanding of genetic and epigenetic events related to tumor development and potential applications for cytology also are presented as they relate to prognostication and recent therapeutic advances.
Collapse
Affiliation(s)
- Carlie S Sigel
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| |
Collapse
|
|
45
|
Choi JH, Park DH, Kim MH, Hwang HS, Hong SM, Song TJ, Lee SS, Seo DW, Lee SK. Outcomes after endoscopic ultrasound-guided ethanol-lipiodol ablation of small pancreatic neuroendocrine tumors. Dig Endosc 2018; 30:652-658. [PMID: 29575213 DOI: 10.1111/den.13058] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 03/13/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Little is known about the standard care of small (<2 cm in diameter) pancreatic neuroendocrine tumors (PNET). The aim of the present study was to determine the clinical outcomes of small PNET after endoscopic ultrasound (EUS)-guided ethanol-lipiodol ablation (EUS-ELA). METHODS In this prospective cohort study, consecutive patients who underwent EUS-ELA for PNET were enrolled and were followed for ≥3 years. Treatment efficacy was the primary outcome measure. RESULTS In total, 33 patients who had 40 pathologically confirmed PNET (<2 cm in diameter) were enrolled for final analysis. A total of 63 EUS-ELA sessions were successfully carried out (mean, 1.9 sessions per patient, 1.6 sessions per tumor), which included 40 initial sessions and 23 repeated sessions owing to incomplete ablation. Median actual volume of ethanol-lipiodol mixture injected per session was 1.1 mL (IQR 0.8-1.9 mL). Complete ablation was achieved in 24 of 40 tumors (60%) with one (18 tumors, 45%) or two (24 tumors, 60%) sessions of EUS-ELA. Lipiodol retention within tumor had better treatment outcomes (P = 0.004). Rate of procedure-related adverse events was 3.2%. No malignancy or lymph node metastasis was discovered during a median follow up of 42 months (IQR 39-46 months). CONCLUSIONS We found that EUS-ELA was a safe and effective alternative option in the management of PNET <2.0 cm in diameter; 60% of patients achieved complete ablation. Lipiodol retention within tumor may be a useful early predictor of treatment effectiveness. Trial registered at ClinicalTrials.gov (NCT 01902238).
Collapse
Affiliation(s)
- Jun-Ho Choi
- Department of Internal Medicine, Dankook University College of Medicine, Dankook University Hospital, Cheonan, Korea
| | - Do Hyun Park
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Myung-Hwan Kim
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hee Sang Hwang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Tae Jun Song
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sang Soo Lee
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Dong-Wan Seo
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sung Koo Lee
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| |
Collapse
|
|
46
|
Lee L, Ito T, Jensen RT. Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 2018; 18:837-860. [PMID: 29973077 PMCID: PMC6283410 DOI: 10.1080/14737140.2018.1496822] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Recently, there have been a number of advances in imaging pancreatic neuroendocrine tumors (panNETs), as well as other neuroendocrine tumors (NETs), which have had a profound effect on the management and treatment of these patients, but in some cases are also associated with controversies. Areas covered: These advances are the result of numerous studies attempting to better define the roles of both cross-sectional imaging, endoscopic ultrasound, with or without fine-needle aspiration, and molecular imaging in both sporadic and inherited panNET syndromes; the increased attempt to develop imaging parameters that correlate with tumor classification or have prognostic value; the rapidly increasing use of molecular imaging in these tumors and the attempt to develop imaging parameters that correlate with treatment/outcome results. Each of these areas and the associated controversies are reviewed. Expert commentary: There have been numerous advances in all aspects of the imaging of panNETs, as well as other NETs, in the last few years. The advances are leading to expanded roles of imaging in the management of these patients and the results being seen in panNETs/GI-NETs with these newer techniques are already being used in more common tumors.
Collapse
Affiliation(s)
- Lingaku Lee
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
| | - Tetsuhide Ito
- c Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital International University of Health and Welfare 3-6-45 Momochihama , Sawara-Ku, Fukuoka , Japan
| | - Robert T Jensen
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
| |
Collapse
|
|
47
|
Implementation of Current ENETS Guidelines for Surgery of Small (≤2 cm) Pancreatic Neuroendocrine Neoplasms in the German Surgical Community: An Analysis of the Prospective DGAV StuDoQ|Pancreas Registry. World J Surg 2018; 43:175-182. [DOI: 10.1007/s00268-018-4751-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|