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Shamoon R, Elhassan O, Al-Emadi L, Zabara A, Petkar MA, Sayed S, Mohammad OH. Neuroendocrine carcinoma causing common bile duct obstruction: a case report. Oxf Med Case Reports 2025; 2025:omaf011. [PMID: 40162142 PMCID: PMC11952893 DOI: 10.1093/omcr/omaf011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 11/30/2024] [Accepted: 01/26/2025] [Indexed: 04/02/2025] Open
Abstract
A 46-year-old male with no comorbidities was referred to our hospital because of jaundice and elevated LFT markers. After further investigations, he underwent magnetic resonance cholangiopancreatography (MRCP), which revealed a hypo-enhancing periampullary mass measuring 15 mm in size causing common bile duct (CBD) dilatation of 12 mm in cross diameter with intrahepatic biliary obstruction, which explained the patient's symptoms. Side-view endoscopy was performed to obtain a specimen of the mass. Further histopathological workup revealed poorly differentiated neuroendocrine carcinoma (NEC). A multidisciplinary team (MDT) was conducted, and the patient was planned to undergo positron emission tomography-computed tomography (PET-CT) scan to investigate any further organ metastasis. Unfortunately, the patient missed his upcoming appointments and was lost to follow-up. Nevertheless, more research is needed to understand pathogenesis and the best course of management for small periampullary NETs.
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Affiliation(s)
- Richard Shamoon
- Department of Internal Medicine, Hazm Mebaireek General Hospital, Street 33, Industrial Area, Al-Rayyan, Doha, Qatar
| | - Osman Elhassan
- Department of Medical Education, Hamad Medical Corporation (HMC), C-Ring Road, Hamad Medical City, Doha, Qatar
| | - Lujain Al-Emadi
- Weill Cornell Medicine, Al-Luqta St, Education City, Al-Rayyan, Doha, Qatar
| | - Abdulwahab Zabara
- Department of Diagnostic Radiology, Hazm Mebaireek General Hospital, Street 33, Industrial Area, Al-Rayyan, Doha, Qatar
| | - Mahir A Petkar
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation (HMC), C-Ring Road, Hamad Medical City, Doha, Qatar
| | - Sarah Sayed
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation (HMC), C-Ring Road, Hamad Medical City, Doha, Qatar
| | - Osama H Mohammad
- Department of Internal Medicine, Hazm Mebaireek General Hospital, Street 33, Industrial Area, Al-Rayyan, Doha, Qatar
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Dong SC, Tang QY, Wang L, Fang F, Bai DS, Jin SJ, Zhou BH, Jiang GQ. Characteristics and risk differences of different tumor sizes on distant metastases of pancreatic neuroendocrine tumors: A retrospective study in the SEER database. Hepatobiliary Pancreat Dis Int 2025; 24:188-196. [PMID: 39019667 DOI: 10.1016/j.hbpd.2024.07.001] [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: 08/27/2023] [Accepted: 07/02/2024] [Indexed: 07/19/2024]
Abstract
BACKGROUND The rate of distant metastasis in patients with pancreatic neuroendocrine tumors (PNETs) is 20%-50% at the time of initial diagnosis. However, whether tumor size can predict distant metastasis for PNETs remains unknown up to date. METHODS We used Surveillance, Epidemiology, and End Results (SEER) population-based data to collect 6089 patients with PNETs from 2010 to 2019. The optimal cut-off point of tumor size to predict distant metastasis was calculated by Youden's index. Multivariate logistic regression analysis was used to figure out the association between tumor size and distant metastasis patterns. RESULTS The most common metastatic site was liver (27.2%), followed by bone (3.0%), lung (2.3%) and brain (0.4%). Based on an optimal cut-off value of tumor size (25.5 mm) for predicting distant metastasis determined by Youden's index, patients were categorized into groups of tumor size < 25.5 mm and ≥ 25.5 mm. Multivariate logistic regression analyses showed that, compared with < 25.5 mm, tumor size ≥ 25.5 mm was an independent risk predictor of overall distant metastasis [odds ratio (OR) = 4.491, 95% confidence interval (CI): 3.724-5.416, P < 0.001] and liver metastasis (OR = 4.686, 95% CI: 3.886-5.651, P < 0.001). CONCLUSIONS Tumor size ≥ 25.5 mm was significantly associated with more overall distant and liver metastases. Timely identification of distant metastasis for tumor size ≥ 25.5 mm may provide survival benefit for timely and precise treatment.
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Affiliation(s)
- Song-Chen Dong
- Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital, Yangzhou 225000, China
| | - Qi-Yun Tang
- Department of Geriatric Gastroenterology, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China; Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing 210029, China
| | - Lu Wang
- Center of Endoscopy, Northern Jiangsu People's Hospital, Yangzhou 225000, China
| | - Fang Fang
- Department of Gastrointestinal Surgery, Northern Jiangsu People's Hospital, Yangzhou 225000, China
| | - Dou-Sheng Bai
- Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital, Yangzhou 225000, China; Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225000, China
| | - Sheng-Jie Jin
- Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital, Yangzhou 225000, China; Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225000, China
| | - Bao-Huan Zhou
- Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital, Yangzhou 225000, China
| | - Guo-Qing Jiang
- Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital, Yangzhou 225000, China; Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225000, China.
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Merola E, Michielan A, Gabbrielli A. Commentary: Predicting histologic grades for pancreatic neuroendocrine tumors by radiologic image-based artificial intelligence: a systematic review and meta-analysis. Front Oncol 2025; 15:1456557. [PMID: 40231262 PMCID: PMC11994426 DOI: 10.3389/fonc.2025.1456557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 03/11/2025] [Indexed: 04/16/2025] Open
Affiliation(s)
- Elettra Merola
- Gastroenterology Unit, Giovan Battista (G.B.) Grassi Hospital (Azienda Sanitaria Locale (ASL) Roma 3), Rome, Italy
| | - Andrea Michielan
- Azienda Provinciale per i Servizi Sanitari (APSS), Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento, Italy
| | - Armando Gabbrielli
- Azienda Provinciale per i Servizi Sanitari (APSS), Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, Trento, Italy
- Center for Medical Sciences (CISMed), University of Trento, Trento, Italy
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Gao H, Zhang W, Li Z, Liu W, Liu M, Zhuo Q, Shi Y, Xu W, Zhou C, Qin Y, Xu J, Chen J, Yu X, Xu X, Ji S. Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide. BMC Cancer 2024; 24:1362. [PMID: 39511555 PMCID: PMC11542389 DOI: 10.1186/s12885-024-13117-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 10/28/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). METHOD Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. RESULTS In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001). CONCLUSION Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.
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Affiliation(s)
- Heli Gao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wuhu Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Zheng Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wensheng Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Mengqi Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Qifeng Zhuo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yihua Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wenyan Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Chenjie Zhou
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
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Kővári B, Carneiro F, Lauwers GY. Epithelial tumours of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:227-286. [DOI: 10.1002/9781119423195.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Casey M, Brown A, Romero-Hernandez F, Wang JJ, Ganjouei AA, Tozzi F, Rashidian N, Kirkwood K, Corvera C, Nakakura E, Alseidi A, Adam M. National practice patterns in the use of endoscopic ultrasound biopsy for resectable Pancreatic Neuroendocrine Tumors: Insights into the role of DOTATATE PET/CT in diagnosis. Am J Surg 2024; 235:115779. [PMID: 38811243 DOI: 10.1016/j.amjsurg.2024.115779] [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: 02/06/2024] [Revised: 04/30/2024] [Accepted: 05/23/2024] [Indexed: 05/31/2024]
Abstract
INTRODUCTION Pancreatic neuroendocrine tumors (PNETs) are typically diagnosed using endoscopic ultrasound-guided (EUS) biopsy, which can be associated with complications. Since 2016, DOTATATE PET/CT has emerged as an effective tool to localize and stage PNETs. METHODS Patients with PNETs who underwent R0 resections were identified from the 2004-2019 National Cancer Database PUF. Joinpoint regression and multivariable logistic regression were used to analyze trends in the use of biopsy. RESULTS Of 16,746 R0 resected PNET patients, 44 % underwent diagnostic biopsy. Joinpoint regression showed a significant increase in the use of biopsy from 2004 to 2019 (APC 1.80, p < 0.001). A higher percentage of patients diagnosed after DOTATATE approval underwent biopsy compared to those diagnosed before (48 % vs. 42 %, p < 0.001). Adjusted analysis showed diagnosis after 2016 was associated with increased odds of biopsy (OR = 1.67, p < 0.001). CONCLUSIONS Despite technologic advancement with DOTATATE PET/CT, there has been a significant increase in the proportion of resectable PNETs undergoing preoperative biopsy.
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Affiliation(s)
- Megan Casey
- School of Medicine, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Audrey Brown
- Department of Surgery, University of California, San Francisco, San Francisco, CA, 94143, USA
| | | | - Jaeyun Jane Wang
- Department of Surgery, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Amir Ashraf Ganjouei
- Department of Surgery, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Francesca Tozzi
- Department of General, HPB Surgery and Liver Transplantation, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium
| | - Nikdokht Rashidian
- Department of General, HPB Surgery and Liver Transplantation, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium
| | - Kimberly Kirkwood
- Division of Surgical Oncology, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Carlos Corvera
- Division of Surgical Oncology, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Eric Nakakura
- Division of Surgical Oncology, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Adnan Alseidi
- Division of Surgical Oncology, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Mohamed Adam
- Division of Surgical Oncology, University of California, San Francisco, San Francisco, CA, 94143, USA.
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Battistella A, Tacelli M, Mapelli P, Schiavo Lena M, Andreasi V, Genova L, Muffatti F, De Cobelli F, Partelli S, Falconi M. Recent developments in the diagnosis of pancreatic neuroendocrine neoplasms. Expert Rev Gastroenterol Hepatol 2024; 18:155-169. [PMID: 38647016 DOI: 10.1080/17474124.2024.2342837] [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: 10/21/2023] [Accepted: 04/10/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION Pancreatic Neuroendocrine Neoplasms (PanNENs) are characterized by a highly heterogeneous clinical and biological behavior, making their diagnosis challenging. PanNENs diagnostic work-up mainly relies on biochemical markers, pathological examination, and imaging evaluation. The latter includes radiological imaging (i.e. computed tomography [CT] and magnetic resonance imaging [MRI]), functional imaging (i.e. 68Gallium [68 Ga]Ga-DOTA-peptide PET/CT and Fluorine-18 fluorodeoxyglucose [18F]FDG PET/CT), and endoscopic ultrasound (EUS) with its associated procedures. AREAS COVERED This review provides a comprehensive assessment of the recent advancements in the PanNENs diagnostic field. PubMed and Embase databases were used for the research, performed from inception to October 2023. EXPERT OPINION A deeper understanding of PanNENs biology, recent technological improvements in imaging modalities, as well as progresses achieved in molecular and cytological assays, are fundamental players for the achievement of early diagnosis and enhanced preoperative characterization of PanNENs. A multimodal diagnostic approach is required for a thorough disease assessment.
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Affiliation(s)
- Anna Battistella
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Matteo Tacelli
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreato-biliary Endoscopy and EUS Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paola Mapelli
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Valentina Andreasi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Luana Genova
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco De Cobelli
- Vita-Salute San Raffaele University, Milan, Italy
- Radiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
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Dubash S, Barwick TD, Kozlowski K, Rockall AG, Khan S, Khan S, Yusuf S, Lamarca A, Valle JW, Hubner RA, McNamara MG, Frilling A, Tan T, Wernig F, Todd J, Meeran K, Pratap B, Azeem S, Huiban M, Keat N, Lozano-Kuehne JP, Aboagye EO, Sharma R. Somatostatin Receptor Imaging with [ 18F]FET-βAG-TOCA PET/CT and [ 68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study. J Nucl Med 2024; 65:jnumed.123.266601. [PMID: 38331457 PMCID: PMC10924162 DOI: 10.2967/jnumed.123.266601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 12/19/2023] [Accepted: 12/19/2023] [Indexed: 02/10/2024] Open
Abstract
There is a clinical need for 18F-labeled somatostatin analogs for the imaging of neuroendocrine tumors (NET), given the limitations of using [68Ga]Ga-DOTA-peptides, particularly with regard to widespread accessibility. We have shown that [18F]fluoroethyl-triazole-[Tyr3]-octreotate ([18F]FET-βAG-TOCA) has favorable dosimetry and biodistribution. As a step toward clinical implementation, we conducted a prospective, noninferiority study of [18F]FET-βAG-TOCA PET/CT compared with [68Ga]Ga-DOTA- peptide PET/CT in patients with NET. Methods: Forty-five patients with histologically confirmed NET, grades 1 and 2, underwent PET/CT imaging with both [18F]FET-βAG-TOCA and [68Ga]Ga-peptide performed within a 6-mo window (median, 77 d; range, 6-180 d). Whole-body PET/CT was conducted 50 min after injection of 165 MBq of [18F]FET-βAG-TOCA. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios at both lesion and regional levels by 2 unblinded, experienced readers. A randomized, blinded reading of both scans was also then undertaken by 3 experienced readers, and consensus was assessed at a regional level. The ability of both tracers to visualize liver metastases was also assessed. Results: A total of 285 lesions were detected on both imaging modalities. An additional 13 tumor deposits were seen in 8 patients on [18F]FET-βAG-TOCA PET/CT, and [68Ga]Ga-DOTA-peptide PET/CT detected an additional 7 lesions in 5 patients. Excellent correlation in SUVmax was observed between both tracers (r = 0.91; P < 0.001). No difference was observed between median SUVmax across regions, except in the liver, where the median tumor-to-background ratio of [18F]FET-βAG-TOCA was significantly lower than that of [68Ga]Ga-DOTA-peptide (2.5 ± 1.9 vs. 3.5 ± 2.3; P < 0.001). Conclusion: [18F]FET-βAG-TOCA was not inferior to [68Ga]Ga-DOTA-peptide in visualizing NET and may be considered in routine clinical practice given the longer half-life and availability of the cyclotron-produced fluorine radioisotope.
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Affiliation(s)
- Suraiya Dubash
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Tara D Barwick
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
- Department of Imaging, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Kasia Kozlowski
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Andrea G Rockall
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Sairah Khan
- Department of Imaging, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Sameer Khan
- Department of Imaging, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Siraj Yusuf
- Radiology and Nuclear Medicine Department, Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Angela Lamarca
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Richard A Hubner
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Mairéad G McNamara
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Tricia Tan
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Florian Wernig
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Jeannie Todd
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Karim Meeran
- Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Bhavesh Pratap
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Saleem Azeem
- Invicro-London, Imperial College London, London, United Kingdom; and
| | - Michael Huiban
- Invicro-London, Imperial College London, London, United Kingdom; and
| | - Nicholas Keat
- Invicro-London, Imperial College London, London, United Kingdom; and
| | - Jingky P Lozano-Kuehne
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
- Population Health Sciences Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle, United Kingdom
| | - Eric O Aboagye
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Rohini Sharma
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom;
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Marasco M, Magi L, Rogges E, Dell'Unto E, Rinzivillo M, Pilozzi E, Annibale B, Panzuto F. Utility of histopathological revision in the management of gastro-entero-pancreatic neuroendocrine neoplasia. Endocrine 2023; 82:435-441. [PMID: 37338723 PMCID: PMC10543798 DOI: 10.1007/s12020-023-03418-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 06/05/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND Histological evaluation and grading assessment are key points in the diagnostic work-up of gastroentero-pancreatic neuroendocrine neoplasms (GEP-NENs). AIM To analyze the impact of histopathological revision on the clinical management of patients with GEP-NEN. MATERIALS AND METHODS Patients referred to our Center of Excellence between 2015 and 2021 were included in this study. Immunohistochemical slides at the time of initial diagnosis were reviewed to assess tumor morphology, diagnostic immunohistochemistry, and Ki67. RESULTS 101 patients were evaluated, with 65 (64.4%) gastrointestinal, 25 (24.7%) pancreatic, and 11 (10.9%) occult neoplastic lesions suspected to be of GEP origin. The main changes resulting from the revision were: first Ki-67 assessment in 15.8% of patients, Ki-67 change in 59.2% of patients and grading modification in 23.5% of patients. An additional immunohistochemical evaluation was performed in 78 (77.2%) patients, leading to a confirmation of GEP origin in 10 of 11 (90.9%) of unknown primary site neoplastic lesions and an exclusion of NEN diagnosis in 2 (2%) patients. After histopathological revision, a significant modification in clinical management was proposed in 42 (41.6%) patients. CONCLUSIONS Histopathological revision in a referral NEN center is strongly advised in newly diagnosed GEP-NENs to properly plan prognostic stratification and therapeutic choice.
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Affiliation(s)
- Matteo Marasco
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Ludovica Magi
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Evelina Rogges
- Pathologic Morphological and Molecular Anatomy Unit, Sant'Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Elisabetta Dell'Unto
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Emanuela Pilozzi
- Pathologic Morphological and Molecular Anatomy Unit, Sant'Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Bruno Annibale
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy.
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10
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Chen Y, Liang Y, Cao L, Dong X, Sun D. Neuroendocrine differentiation: a risk fellow in colorectal cancer. World J Surg Oncol 2023; 21:89. [PMID: 36899368 PMCID: PMC9999536 DOI: 10.1186/s12957-023-02952-8] [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: 10/14/2022] [Accepted: 02/14/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND Neuroendocrine differentiation (NED) is often found in colorectal cancer (CRC) and may have unique biological behavior, which has not been previously delineated. Here, we explore the relationship between CRC, NED, and clinicopathological factors. We also offer a preliminary explanation of the mechanism underlying the malignant biological behavior of NED in CRC. METHODS Between 2013 and 2015, 394 CRC patients who underwent radical operations were selected for analysis. The relationship between NED and clinicopathological factors was analyzed. To further clarify the pivotal role of NED in CRC, we performed bioinformatic analyses and identified genes that may be involved in NED, which were obtained from in silico data from The Cancer Genome Atlas (TCGA) database. Then, we conducted functional enrichment analyses and confirmed the critical pathways for intensive study. Moreover, we detected the expression of key proteins by immunohistochemistry and analyzed the correlation of their expression with NED. RESULTS The statistical analysis showed that CRC with NED was positively correlated with lymph node metastasis. Through bioinformatic analysis, we found that chromogranin A (CgA) was positively correlated with invasion and lymph node metastasis. ErbB2 and PIK3R1, which are key proteins in the PI3K-Akt signaling pathway, were closely related to NED. Furthermore, we determined that the PI3K-Akt signaling pathway likely plays a critical role in the NED of CRC. CONCLUSIONS CRC with NED is associated with lymph node metastasis. The PI3K-Akt signaling pathway, which is closely related to CRC, may be the mechanism promoting the malignant biological behavior of CRC with NED.
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Affiliation(s)
- Yue Chen
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Yu Liang
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Lianqun Cao
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Xinxin Dong
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China
| | - Deyu Sun
- Department of Radiation Oncology Gastrointestinal and Urinary and Musculoskeletal Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, China.
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11
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Watanabe H, Fujishima F, Unno M, Sasano H, Suzuki T. Somatostatin Receptor 2 in 10 Different Types of Human Non-Neoplastic Gastrointestinal Neuroendocrine Cells. Pathol Res Pract 2023; 244:154418. [PMID: 36989844 DOI: 10.1016/j.prp.2023.154418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 03/16/2023] [Accepted: 03/16/2023] [Indexed: 03/19/2023]
Abstract
Somatostatin is known to inhibit the secretion of various hormones by acting on endocrine cells through the somatostatin receptor 2 (SSTR2). Immunohistochemical evaluation of SSTR2 has become increasingly important in clinical practice to determine treatment strategies for patients with a neuroendocrine tumor (NET). Gastrointestinal (GI) tracts contain various neuroendocrine cells that constitute a diffuse endocrine system and some NETs are derived from those cells. In addition, NETs have been well known to express a variable spectrum of proteins shared by their normal cell counterparts of the specific anatomical sites. Thus, we may derive the kinetics of SSTR2 expression of NETs, including de novo expression, from the SSTR2 expression of the corresponding normal neuroendocrine cells. Therefore, a detailed study on the distribution of SSTR2 in normal human neuroendocrine cells may contribute to understanding the expression of SSTR2 in GI-NETs. However, the detailed cellular localization of SSTR2 in non-neoplastic neuroendocrine cells remains unknown. Therefore, we immunolocalized SSTR2 in neuroendocrine cells of normal human GI tracts, including the stomach, duodenum, ileum, and rectum, obtained from 41 surgically resected tissue specimens. Double immunohistochemistry of SSTR2 and hormones or hormone-associated proteins was performed. In all GI neuroendocrine cells, cell types other than D- and EC-cells demonstrated a high percentage of SSTR2-positive cases or a high double-positive ratio. In particular, EC-cells showed lower SSTR2-positive ratios in all sites. Midgut NETs, which often produce serotonin, are excellent targets for somatostatin analogs and are positive for SSTR2. Thus, we speculated that EC-cell NETs might lead to the de novo expression of SSTR2. In addition, a previous report showed high SSTR2 expression in ECL-cell NETs and gastrinomas, which could be because they are derived from neuroendocrine cells with high SSTR2 expression. This study may contribute to understanding the expression of SSTR2 in GI-NETs.
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Affiliation(s)
- Hirofumi Watanabe
- Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan
| | | | - Michiaki Unno
- Department of Surgery, Tohoku University, Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Takashi Suzuki
- Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan
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12
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Marcal LP, Chuang HH, Tran Cao HS, Halperin DM. Pancreatic Neuroendocrine Tumors. ONCOLOGIC IMAGING : A MULTIDISCIPLINARY APPROACH 2023:197-217. [DOI: 10.1016/b978-0-323-69538-1.00014-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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13
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Liang W, Xu X, Liu Y, Cui J, Gao Y, Wang C, Zhuang Z, Zhang K, Xi H, Cai A, Wei B, Chen L. Defining the impact of platelet-to-lymphocyte ratio on patient survival with gastric neuroendocrine neoplasm: a retrospective cohort analysis. World J Surg Oncol 2022; 20:356. [DOI: 10.1186/s12957-022-02822-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 10/29/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN).
Methods
A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels.
Results
In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32–2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28–2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202–1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1–3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05).
Conclusion
The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.
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14
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Wu Z, Qiu X, Zhi Y, Shi X, Lv G. The risk and prognostic factors for G1 pancreatic neuroendocrine tumors: A retrospective analysis of the SEER database. Front Oncol 2022; 12:993524. [PMID: 36276109 PMCID: PMC9582835 DOI: 10.3389/fonc.2022.993524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/16/2022] [Indexed: 11/13/2022] Open
Abstract
Background Pancreatic neuroendocrine tumors (pNETs) are rare neuroendocrine neoplasms (NENs) for which little is known about their clinical features, treatment options, and survival prognosis. The purpose of this study is to evaluate the risk factors affecting the overall survival (OS) and cancer-specific survival (CSS) in patients with grade 1 pNETs (G1 pNETs) and to provide a new theoretical basis for clinical diagnosis and treatment. Methods A retrospective analysis of individuals with G1 pNETs registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. Risk factors affecting OS and CSS were analyzed using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model. Results A total of 751 patients were included, most of whom were white (77.2%) women (53.9%) under the age of 60 years (54.9%), of whom 66 died of pNETs (8.78%) and 34 died of other causes (4.52%). Patients who were older than 60 years at diagnosis (hazard ratio [HR] = 1.866, 95% confidence interval [CI]: 1.242-2.805) had worse OS. And stage in the regional extent (HR = 1.777, 95% CI: 1.006-3.137) or distance extent (HR = 4.540, 95% CI: 2.439-8.453) had worse OS. Patients who delayed treatment after diagnosis had shorter CSS (delayed treatment < 1 month: HR = 1.933, 95% CI: 0.863-4.333; delayed treatment ≥ 1 month: HR = 2.208; 95% CI:1.047-4.654). Patients with lymph node metastasis (HR = 1.989, 95% CI: 1.137-3.479) or distant metastasis (HR = 5.625, 95% CI: 1.892-16.726) had worse CSS. Acceptance of surgery can significantly improve the patient’s OS and CSS. OS (partial pancreatectomy [PP]: HR = 0.350, 95% CI: 0.182-0.672; pancreatectomy and duodenectomy [PD]: HR = 0.426, 95% CI: 0.222-0.815; total pancreatectomy [TP]: HR = 0.495, 95% CI: 0.193-1.267). CSS(PP: HR = 0.148, 95% CI: 0.0054-0.401; PD: HR = 0.332, 95% CI: 0.150-0.730; TP: HR = 0.69, 95% CI: 0.254-1.872). Conclusion Age and stage were identified as independent risk factors for OS. Delayed treatment, N stage and M stage were independent risk factors for CSS. Only surgery was identified as independent protective factors for OS and CSS.
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15
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Merola E, Perren A, Rinke A, Zerbi A, McNamara MG, Arsenic R, Fazio N, de Herder W, Valle JW, Gress TM, Wiedenmann B, Pascher A, Pavel ME. High rate of Ki-67 increase in entero-pancreatic NET relapses after surgery with curative intent. J Neuroendocrinol 2022; 34:e13193. [PMID: 36306194 DOI: 10.1111/jne.13193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/06/2022] [Accepted: 07/27/2022] [Indexed: 11/29/2022]
Abstract
Neuroendocrine neoplasms (NENs) present with advanced disease at diagnosis in up to 28% of cases, precluding the possibility of curative-intent surgery. Histopathological heterogeneity of this disease can be observed inter-individually as well as intra-individually during disease course. The present study aimed to assess the frequency of Ki-67 change after radical surgery, in a series of patients with radically resected entero-pancreatic neuroendocrine tumors (EP-NETs). We present the analysis of a multicenter, retrospective, series of EP-NETs G1-G2 recurring after radical resection and with histological re-evaluation at disease recurrence (DR). The primary endpoint was the description of Ki-67 change at DR compared to time of surgery. The secondary endpoint was assessment of recurrence-free survival (RFS) rates. In total, 47 patients had a second histological evaluation and could be included in the present study. Median Ki-67 at surgery was 3% (range 1-15%) but, at DR, a significant increase in the value was observed (7%, range 1-30%; p < .01) and involved 66.0% of cases, with a corresponding increase in tumor grading in 34.0% (p = .05). Median RFS of the overall population was 40 months, and was worse when Ki-67 increased at DR vs. stable Ki-67 value (36 vs. 61 months, respectively; p = .02). In conclusion, in more than half of the cases with relapse after radical surgery, a higher proliferative index with a potentially more aggressive potential was observed. Therefore, histological reassessment should be considered on DR because tailored therapeutic strategies may be required for these patients.
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Affiliation(s)
- Elettra Merola
- Department of Medicine 1, Division of Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| | - Aurel Perren
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Anja Rinke
- Department of Gastroenterology, University Hospital Gießen and Marburg, Marburg, Germany, Department of Surgery, Charité Universitätsmedizin, Berlin, Germany
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Milan, Italy
| | - Mairéad G McNamara
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Ruza Arsenic
- Department of Pathology, Charité Universitätsmedizin, Berlin, Germany
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumours, European Institute of Oncology IEO, IRCCS, Milan, Italy
| | - Wouter de Herder
- Department of Internal Medicine, Sector of Endocrinology, Rotterdam, The Netherlands
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Thomas M Gress
- Department of Gastroenterology, University Hospital Gießen and Marburg, Marburg, Germany, Department of Surgery, Charité Universitätsmedizin, Berlin, Germany
| | - Bertram Wiedenmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité Universitätsmedizin, Berlin, Germany
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Germany
- Department of Surgery, Campus Virchow-Klinikum, Charité Universitätsmedizin, Berlin, Germany
| | - Marianne E Pavel
- Department of Medicine 1, Division of Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité Universitätsmedizin, Berlin, Germany
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16
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Syguła A, Ledwon A, Hasse-Lazar K, Jurecka-Lubieniecka B, Michalik B, Paliczka-Cieślik E, Zeman M, Chmielik E, Sczasny J, Jarzab B, Handkiewicz-Junak D. In patients with well-differentiated neuroendocrine tumours, there is no apparent benefit of somatostatin analogues after disease control by peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2022; 49:3841-3851. [PMID: 35503379 DOI: 10.1007/s00259-022-05792-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 04/03/2022] [Indexed: 12/13/2022]
Abstract
PURPOSE Peptide receptor radionuclide therapy (PRRT) and somatostatin analogues (SSAs) are commonly combined as primary treatment for neuroendocrine neoplasms (NEN), and SSAs given as maintenance. We sought to evaluate whether sequential therapy with PRRT followed by SSAs has progression or survival benefits in patients with NEN after disease control by PRRT. METHODS This prospective, randomised, single-centre study had as principal eligibility criteria: unresectable, locally advanced, or metastatic, histologically confirmed well-differentiated NEN; no symptoms/biochemical diagnosis of carcinoid syndrome; no SSAs or ≤ 3 months of SSAs before PRRT; and stable disease or partial or complete response after PRRT. Altogether, 115 patients were randomised 2:1 to an SSA group (n = 74) given octreotide acetate LAR every 4 weeks, or a control group (n = 41) receiving only best supportive care. Octreotide treatment was to stop upon intolerable toxicity or patient refusal, or, at physician/patient discretion, upon NEN progression. The primary endpoint was progression-free survival (PFS), the secondary endpoint, and overall survival (OS). RESULTS Median (25th-75th percentile) follow-up from the first PRRT activity to death or latest observation was 6.6 (3.18-10.22) years. During that time, 71/115 patients (62%) progressed, 52/74 (70%) in the SSA group, and 19/41 (46%) in the control group (p = 0.01). Eighty-eight/115 patients (76%) died, 58/74 (78%) in the SSA group, and 30/41 (73%) in the control group (p = 0.52). Median (95% CI) PFS was 4.7 (2.8-7.7) years in the SSA group, and 6.4 (4.1-not reached) years in controls. Overall, median OS was 6.6 years. Neither PFS nor OS differed between groups (p = 0.129, p = 0.985, respectively). CONCLUSIONS In patients with disease control after PRRT, subsequent SSA treatment appeared not to be associated with better PFS or OS. Whether to continue SSA administration upon progression after PRRT requires evaluation in a prospective, randomised, controlled multicentre study with a relatively homogeneous sample.
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Affiliation(s)
- Aleksandra Syguła
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland
| | - Aleksandra Ledwon
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland
| | - Kornelia Hasse-Lazar
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland
| | - Beata Jurecka-Lubieniecka
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland
| | - Barbara Michalik
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland
| | - Ewa Paliczka-Cieślik
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland
| | - Marcin Zeman
- The Oncologic and Reconstructive Surgery Clinic, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
| | - Ewa Chmielik
- Tumor Pathology Department, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
| | - Joanna Sczasny
- Radiology and Diagnostic Imaging Department, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
| | - Barbara Jarzab
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland
| | - Daria Handkiewicz-Junak
- Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland.
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Bodei L, Jayaprakasam VS, Kidd M, Gilardi L, Volterrani D, Paganelli G, Grana CM, Modlin IM. Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors. NUCLEAR ONCOLOGY 2022:933-974. [DOI: 10.1007/978-3-031-05494-5_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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18
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Abbas D, Abdallah M, Suryawanshi G, Osman K, McDonald N, Bilal M, Azeem N. Endoscopic Papillectomy Is Effective and Safe for Ampullary Neuroendocrine Tumors: A Comprehensive Review of the Available Literature. TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY 2022; 24:331-339. [DOI: 10.1016/j.tige.2022.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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19
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Patterns and predictors of pancreatic neuroendocrine tumor prognosis: Are no two leaves alike? Crit Rev Oncol Hematol 2021; 167:103493. [PMID: 34653597 DOI: 10.1016/j.critrevonc.2021.103493] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 02/20/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous; thus, individual prognostic prediction is important. Clinicopathological features, like TNM stage, grade, and differentiation, are independent clinical predictors. However, single predictors are insufficient, as patients sharing similar clinicopathological features usually show distinct prognoses. Accordingly, novel nomograms and risk stratifications have been developed for more accurate PanNET prognostic prediction. Moreover, the exploration of molecular mechanisms has identified novel prognostic predictors for PanNET. Multi-analyte assays of molecular biomarkers provide a deeper understanding of PanNET features; however, the priority, and the optimal combination of classic and novel predictors for PanNET prognosis prediction remain unclear. In this review, we summarized the patterns and predictors of PanNET prognosis and discussed their clinical utility; we emphasized that PanNET at different stages have different superior predictor, and that multi-analyte assays are more sensitive than mono-analyte biomarkers. Therefore, combined biomarkers improve the accuracy of surveillance and optimize decision-making in clinical practice.
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Folkestad O, Wasmuth HH, Mjønes P, Fougner R, Hauso Ø, Fossmark R. Survival and Disease Recurrence in Patients with Duodenal Neuroendocrine Tumours-A Single Centre Cohort. Cancers (Basel) 2021; 13:cancers13163985. [PMID: 34439140 PMCID: PMC8391208 DOI: 10.3390/cancers13163985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/02/2022] Open
Abstract
Simple Summary Neuroendocrine tumours of the upper part of the small intestine are rare. They are slow growing but may spread to lymph nodes or other organs already when the tumours are small. Such tumours may be treated by endoscopic removal or by an operation. In the current study we present the treatment results of 32 patients with this rare tumour. We found that the long-term survival was long, and patients more often died from other diseases. The survival was associated with the growth rate of the tumours and whether all the tumour tissue could be removed. Endoscopic removal was sufficient for smaller tumours <10 mm, whereas a high proportion of tumours 10–20 mm have lymph node metastases that must be removed by an operation to make patients tumour free. None of the tumours that were perceived as cured after removal recurred after an average follow-up time of 4.8 years. Abstract Background: Duodenal neuroendocrine tumours (D-NETs) are rare but increasingly diagnosed. This study aimed to assess the overall survival and recurrence rate among patients treated for D-NETs. Methods: Patients with D-NETs were retrospectively reviewed with a median follow-up time of 4.8 years (range 0.0–17.2 years). Results: A total of 32 patients with median age 68.0 years were identified. Fifteen patients underwent surgery while ten patients underwent endoscopic treatment. Mean estimated overall survival for the entire population was 12.1 years (95% CI 9.5–14.7 years), while 5-year overall survival was 81.3%. Tumour grade G1 was associated with longer mean estimated survival compared to G2 tumours (13.2 years versus 4.4 years, p = 0.010). None of the 23 patients who underwent presumed radical endoscopic or surgical resection had disease recurrence during follow-up. Tumours <10 mm could be treated endoscopically whereas a high proportion of patients with tumours 10–20 mm should be considered for surgery. Conclusion: Patients with D-NETs had long overall survival, and mortality was more influenced by other diseases. Both endoscopic and surgical resections were effective as no recurrences were diagnosed during follow-up.
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Affiliation(s)
- Oddry Folkestad
- Department of Gastrointestinal Surgery, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway;
- Department of Gastrointestinal Surgery, Vestfold Hospital, 3103 Tønsberg, Norway
| | - Hans H. Wasmuth
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
| | - Patricia Mjønes
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Pathology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidun Fougner
- Department of Radiology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway;
| | - Øyvind Hauso
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Gastroenterology and Hepatology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Gastroenterology and Hepatology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Correspondence: ; Tel.: +47-7292-5164
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21
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Lea D, Gudlaugsson EG, Skaland I, Lillesand M, Søreide K, Søreide JA. Digital Image Analysis of the Proliferation Markers Ki67 and Phosphohistone H3 in Gastroenteropancreatic Neuroendocrine Neoplasms: Accuracy of Grading Compared With Routine Manual Hot Spot Evaluation of the Ki67 Index. Appl Immunohistochem Mol Morphol 2021; 29:499-505. [PMID: 33758143 PMCID: PMC8354564 DOI: 10.1097/pai.0000000000000934] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 02/22/2021] [Indexed: 02/01/2023]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare epithelial neoplasms. Grading is based on mitotic activity or the percentage of Ki67-positive cells in a hot spot. Routine methods have poor intraobserver and interobserver consistency, and objective measurements are lacking. This study aimed to evaluate digital image analysis (DIA) as an objective assessment of proliferation markers in GEP-NENs. A consecutive cohort of patients with automated DIA measurement of Ki67 (DIA Ki67) and phosphohistone H3 (DIA PHH3) on immunohistochemical slides was analyzed using Visiopharm image analysis software (Hoersholm, Denmark). The results were compared with the Ki67 index from routine pathology reports (pathology Ki67). The study included 159 patients (57% males). The median pathology Ki67 was 2.0% and DIA Ki67 was 4.1%. The interclass correlation coefficient of the DIA Ki67 compared with the pathology Ki67 showed an excellent agreement of 0.96 [95% confidence interval (CI): 0.94-0.96]. The observed kappa value was 0.86 (95% CI: 0.81-0.91) when comparing grades based on the same methods. PHH3 was measured in 145 (91.2%) cases. The observed kappa value was 0.74. (95% CI: 0.65-0.83) when comparing grade based on the DIA PHH3 and the pathology Ki67. The DIA Ki67 shows excellent agreement with the pathology Ki67. The DIA PHH3 measurements were more varied and cannot replace other methods for grading GEP-NENs.
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Affiliation(s)
- Dordi Lea
- Departments of Pathology
- Gastrointestinal Translational Research Unit, Molecular Laboratory, Hillevåg, Stavanger University Hospital, Stavanger
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | | | | | | | - Kjetil Søreide
- Gastrointestinal Surgery
- Gastrointestinal Translational Research Unit, Molecular Laboratory, Hillevåg, Stavanger University Hospital, Stavanger
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Jon A. Søreide
- Gastrointestinal Surgery
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
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22
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Sakamoto A, Nozawa H, Sonoda H, Hinata M, Ishii H, Emoto S, Anzai H, Yokoyama Y, Murono K, Sasaki K, Kawai K, Ushiku T, Ishihara S. Rectal neuroendocrine tumor with extracapsular lymph node metastasis: a case report. Clin J Gastroenterol 2021; 14:1426-1430. [PMID: 34028785 DOI: 10.1007/s12328-021-01447-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 05/17/2021] [Indexed: 11/24/2022]
Abstract
The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor in patients with colorectal carcinoma. However, there is no English literature on neuroendocrine tumor (NET) with EX. We report a patient with rectal NET with extracapsular metastasis of a regional lymph node that was considered to be EX. A 51-year-old Japanese woman with diabetes was referred to our hospital for further examination of a submucosal tumor in the lower rectum. She was diagnosed as having rectal NET by immunohistochemical analysis of a biopsy, and underwent laparoscopic low anterior resection with lymph node dissection and covering ileostomy. Pathological findings of the resected specimen showed that the primary tumor was NET-G1 without any lymphatic or venous invasion. A single metastatic deposit was found near the capsule of a NET-negative regional lymph node. She has been free from recurrence for nine months without adjuvant treatments. Extracapsular metastasis of NET on a dissected lymph node in our case was considered to correspond to EX as defined for colorectal carcinoma. This rare case suggests that NET can disseminate to form EX in a similar manner to colorectal carcinoma.
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Affiliation(s)
- Akira Sakamoto
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Hiroaki Nozawa
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hirofumi Sonoda
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Munetoshi Hinata
- Department of Pathology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroaki Ishii
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Shigenobu Emoto
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroyuki Anzai
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yuichiro Yokoyama
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Koji Murono
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kazuhito Sasaki
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tetsuo Ushiku
- Department of Pathology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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23
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Shiozaki H, Shirai Y, Horiuchi T, Yasuda J, Furukawa K, Onda S, Gocho T, Shiba H, Ikegami T. Feasible laparoscopic distal pancreatectomy for pancreatic neuroendocrine tumors. Mol Clin Oncol 2021; 14:111. [PMID: 33903817 DOI: 10.3892/mco.2021.2273] [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: 10/10/2020] [Accepted: 02/15/2021] [Indexed: 11/05/2022] Open
Abstract
Pancreatic neuroendocrine tumor (PNET) cases are increasing; however, the treatment indication and procedure remain unestablished. The present study evaluated the indication, feasibility and safety of laparoscopic distal pancreatectomy (LDP) with our technique for PNET. A total of 13 patients with insulinoma and nonfunctional PNET <2 cm in diameter who underwent LDP and 13 patients with any size of PNET who underwent open distal pancreatectomy (ODP) between October 2009 and June 2019 were retrospectively reviewed and compared. The median age of patients was 45 (33-61) years, and 14 (54%) patients were male. The median follow-up periods were 70 months for the LDP group and 46 months for the ODP group. The tumor diameter of the patients who underwent LDP for PNET was 18±9 mm compared with 37±25 mm for those who underwent ODP. The operation time, estimated blood loss, and complication were 290.2±115 vs. 337±131 min (P=0.338), 122±172 vs. 649±693 ml (P=0.019) and 31 vs. 54% (P=0.234), respectively. Pancreatic fistula developed in 8% of patients who underwent LDP compared with 31% who underwent ODP (P=0.131). Notably, the postoperative hospitalization period was significantly shorter in the LDP group (11±7 vs. 21±13 days; P=0.022). Tumor grade of 2017 World Health Organization classification (G1/G2/G3/NEC/unknown) was 9/2/0/0/2 for the LDP group compared with 5/5/0/3/0 for the ODP group. Furthermore, lymph node metastasis was detected in only 1 patient who underwent ODP, for whom the maximum tumor diameter was 70 mm and was classified as G2. In addition, 2 patients in the ODP group developed postoperative lung and liver metastases. LDP for PNETs of <2 cm in selected patients can be safely performed; however, the extent of lymph node dissection needs to be clarified.
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Affiliation(s)
- Hironori Shiozaki
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Yoshihiro Shirai
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Takashi Horiuchi
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Jungo Yasuda
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Kenei Furukawa
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Shinji Onda
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Takeshi Gocho
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Hiroaki Shiba
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Toru Ikegami
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
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24
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Merola E, Zandee W, de Mestier L, Klümpen HJ, Makulik K, Geboes K, van Velthuysen ML, Couvelard A, Cros J, van Eeden S, Hoorens A, Stephenson T, Zajęcki W, de Herder W, Munir A. Histopathological Revision for Gastroenteropancreatic Neuroendocrine Neoplasms in Expert Centers: Does It Make the Difference? Neuroendocrinology 2021; 111:170-177. [PMID: 32155627 DOI: 10.1159/000507082] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/09/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND The correct histopathological diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is crucial for treatment selection and prognostication. It is also very challenging due to limited experience in nonexpert centers. Revision of pathology is standard of care for most patients who are referred to NEN expert centers. OBJECTIVES To describe the clinical impact of histopathological revision for GEP-NEN patients referred to an expert center. METHODS Retrospective multicenter analysis of all GEP-NENs receiving a histopathological revision in 6 European NEN expert centers (January 2016 to December 2016) to evaluate the impact on patient management. RESULTS 175 patients were included and 14.7% referred for a second opinion. Histological samples were 69.1% biopsies, 23.4% surgical specimens, and 7.5% endoscopic resections. Histopathological changes due to revision included first assessment of Ki67 in 8.6% of cases, change in grading in 11.4% (3.4% G1 to G2; 5.7% G2 to G1; 0.6% G2 to G3; 1.7% G3 to G2), definition of tumor invasion in 10.8%, additional immunohistochemical staining in 2.3%, diagnosis of mixed adenoneuroendocrine carcinoma in 3.4%, exclusion of NEN in 3.4%, first diagnosis of NEN in 2.3%, and tumor differentiation for G3 in 1.7%. The revision had a clinical impact in 36.0% of patients, leading to a new therapeutic indication in 26.3%. The indication to then perform a new imaging test occurred in 21.1% and recommendation to follow-up with no further treatment in 6.3%. CONCLUSIONS Histopathological revision in expert centers for NENs can change the diagnosis, with a significant clinical impact in about one third of patients.
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Affiliation(s)
- Elettra Merola
- Department of Gastroenterology, Azienda Provinciale Servizi Sanitari (APSS), Trento, Italy,
| | - Wouter Zandee
- Department of Internal Medicine, Sector of Endocrinology, Erasmus MC, Rotterdam, The Netherlands
| | - Louis de Mestier
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (APHP) and Paris 7 University, Clichy, France
| | - Heinz Josef Klümpen
- Department of Medical Oncology, Academic Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Karolina Makulik
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, Katowice, Poland
| | - Karen Geboes
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | | | - Anne Couvelard
- Department of Pathology, Beaujon/Bichat Hospital (APHP) and Université de Paris, Clichy, France
| | - Jérôme Cros
- Department of Pathology, Beaujon/Bichat Hospital (APHP) and Université de Paris, Clichy, France
| | - Susanne van Eeden
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - Anne Hoorens
- Department of Pathology, University Hospital Ghent, Ghent, Belgium
| | - Timothy Stephenson
- Department of Pathology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
| | - W Zajęcki
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, Katowice, Poland
| | - Wouter de Herder
- Department of Internal Medicine, Sector of Endocrinology, Erasmus MC, Rotterdam, The Netherlands
| | - Alia Munir
- Department of Endocrinology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
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25
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Shi H, Chen L, Zhang Q, Lin Y, Jiang C, Yao H, Hou X, Chen M, Lin R, Chen J. Concordance Between the Ki-67 Index Cutoff Value of 55% and Differentiation in Neuroendocrine Tumor and Neuroendocrine Carcinoma in Grade 3 Pancreatic Neuroendocrine Neoplasms. Pancreas 2020; 49:1378-1382. [PMID: 33122528 DOI: 10.1097/mpa.0000000000001693] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE In 2017 and 2019, the World Health Organization defined grade 3 neuroendocrine tumors (G3 NETs) and neuroendocrine carcinoma (G3 NEC) in the pancreas. The validity of this classification remains to be verified. METHODS Clinical data were collected and analyzed for 39 G3 pancreatic neuroendocrine neoplasms (PanNENs) patients between 2009 and 2018. RESULTS The tumor-node-metastasis stage (P = 0.0260), differentiation (P = 0.0115), and Ki-67 index (P = 0.0371) are prognostic factors for G3 PanNENs by Kaplan-Meier survival analysis. Among 39 patients, 18 had a Ki-67 index of less than 55% and well-differentiated morphology (G3 NET) and 16 had a Ki-67 index of 55% or greater and poorly differentiated morphology (G3 NEC). Grade 3 neuroendocrine tumor had a significant better prognosis than G3 NEC (median overall survival time, 25 months [95% confidence interval, 10.854-39.146 months] vs 12 months [95% confidence interval, 6.316-17.684 months], P = 0.0164). Based on Cox regression analyses, tumor-node-metastasis stage (P = 0.016) was identified as the independent prognostic factor for G3 PanNENs. CONCLUSIONS The upper Ki-67 index cutoff of 55% might be the best cutoff value to define G3 NETs and G3 NECs for G3 PanNENs. The World Health Organization 2017 and 2019 classification system for G3 PanNENs can identify high-risk patients with G3 PanNENs.
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Affiliation(s)
- Huiying Shi
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Luohai Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou
| | - Qin Zhang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Yuan Lin
- Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chen Jiang
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Hailing Yao
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Xiaohua Hou
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Minhu Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou
| | - Rong Lin
- From the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Jie Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou
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26
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Caroli-Bottino A, Mauricio AS, N Pannain VL. CD57 as a routine neuroendocrine marker for liver metastasis. INDIAN J PATHOL MICR 2020; 63:38-43. [PMID: 32031120 DOI: 10.4103/ijpm.ijpm_119_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background The characterization of hepatic metastases as having neuroendocrine origins is essential and the main markers currently used are chromogranin A (CgA) and synaptophysin (Syn). However, these markers may exhibit certain limitations, and the use of CD56 and CD57 can also be considered, although, due to low specificity, their use is discouraged. Aim This study sought to compare the immunohistochemical expression of these markers in hepatic metastases of neuroendocrine neoplasms (NEN). Materials and Methods Eighteen samples, were used for immunohistochemical staining with CgA, Syn, CD56, and CD57 antibodies. The immunostaining reactions were compared according to its intensity (I), the percentage of labeled cells (P), and a final score (I × P). Statistical agreement between the markers was also evaluated. Results CD57 was expressed in the highest number of cases and also showed the most intense expression. CgA showed the highest number of cases with more than 80% positively stained area (72.2%), followed by CD57 (61.1%). The highest average score (I × P) was obtained for CD57 (9.1 ± 4.1). The best indices of agreement were between CgA and CD57 with respect to positivity (P = 0.021) and score (P = 0.014). According to the primary site, stomach/duodenum, lungs, and undetermined subgroups showed the highest average scores for CD57, followed by CgA. For the small bowel subgroup, the highest average score was obtained for CgA, followed by CD57. Conclusion Our results highlight the importance of CD57 in the evaluation of hepatic metastases of NEN and indicate that this marker should be included with CgA and Syn in routine diagnostic panels.
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Affiliation(s)
- Adriana Caroli-Bottino
- Medical Faculty, Department of Pathology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, Ilha do Fundão, Rio de Janeiro - RJ, Brazil
| | - Almir S Mauricio
- Medical Faculty, Department of Pathology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, Ilha do Fundão, Rio de Janeiro - RJ, Brazil
| | - Vera L N Pannain
- Medical Faculty, Department of Pathology, Federal University of Rio de Janeiro, Rua Rodolpho Paulo Rocco, Ilha do Fundão, Rio de Janeiro - RJ, Brazil
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27
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Shimai S, Yamamoto K, Sofuni A, Tsuchiya T, Ishii K, Tanaka R, Tonozuka R, Honjo M, Mukai S, Fujita M, Nagai K, Asai Y, Matsunami Y, Kurosawa T, Kojima H, Honma H, Minami H, Yamaguchi H, Itoi T. Three Cases of Ampullary Neuroendocrine Tumor Treated by Endoscopic Papillectomy: A Case Report and Literature Review. Intern Med 2020; 59:2369-2374. [PMID: 32611953 PMCID: PMC7644498 DOI: 10.2169/internalmedicine.4568-20] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
We herein report three cases of patients with an ampullary neuroendocrine tumor (NET), who underwent endoscopic papillectomy (EP). No tumor recurrence or metastasis was detected in the patients for more than two years after EP. Generally, surgical resection is recommended for ampullary NETs by the European Neuroendocrine Tumor Society. However, as EP is less invasive than surgical resection, there are some reports of low-grade small ampullary NETs curatively treated by EP with long-term follow-up. We consider that EP may be a curative treatment for small and low-grade ampullary NETs without regional or distant metastasis.
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Affiliation(s)
- Satoshi Shimai
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Kenjiro Yamamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Atsushi Sofuni
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Takayoshi Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Kentaro Ishii
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Reina Tanaka
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Ryosuke Tonozuka
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Mitsuyoshi Honjo
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Shuntaro Mukai
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Mitsuru Fujita
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Kazumasa Nagai
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Yasutsugu Asai
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Yukitoshi Matsunami
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Takashi Kurosawa
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Hiroyuki Kojima
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Hirotoshi Honma
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | - Hiroto Minami
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
| | | | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Japan
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28
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Kövesdi A, Kurucz PA, Nyírő G, Darvasi O, Patócs A, Butz H. Circulating miRNA Increases the Diagnostic Accuracy of Chromogranin A in Metastatic Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2020; 12:cancers12092488. [PMID: 32887459 PMCID: PMC7565801 DOI: 10.3390/cancers12092488] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/24/2020] [Accepted: 08/27/2020] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Despite its varying sensitivity and decreased specificity, chromogranin A (CgA) is the most widely used biomarker for neuroendocrine tumors. The most common factor affecting its diagnostic accuracy is the use of proton pump inhibitors (PPIs). Our aim was to investigate circulating miRNA expression profiles in pancreatic neuroendocrine tumors (pNET) and pheochromocytomas/paragangliomas (PPGL) to find miRNAs which could be used as biomarkers along with CgA in these patients. MiRNA expression profiles were determined with next generation sequencing and validated by quantitative real time PCR in 74 samples obtained from patients and healthy volunteers treated with PPI. We observed a global downregulation of miRNAs in NET compared to controls. A set of miRNAs in combination with CgA resulted in the best discrimination of pNET irrespective of PPI treatment and a combination of miRNAs increased the diagnostic utility of CgA even in pNET patients with low CgA. Abstract Chromogranin A (CgA) is the most widely accepted biomarker for neuroendocrine tumors (NET) but its diagnostic accuracy is dependent on tumor type and the use of proton-pump inhibitors (PPI). We investigated the diagnostic value of circulating miRNAs along with CgA in pancreatic neuroendocrine tumors (pNET). 74 serum samples from patients with pNET (n = 25, nonfunctioning), pheochromocytoma/paraganglioma (PPGL, n = 20), healthy individuals with normal CgA (n = 29) including 10 samples from 5 healthy individuals with and without current PPI treatment were collected. MiRNA expression profiles were determined using next-generation sequencing, followed by validation with individual TaqMan assays. A global downregulation of miRNAs was observed in patients with NET compared to controls. MiRNA expression of 33 miRNAs was able to discriminate tumor samples from controls. No miRNA alone could be considered as an applicable biomarker for pNET or PPGL. However, using a logistic model, the combination of a set of miRNAs increased the discriminatory role of CgA irrespective of PPI treatment. In pNET patients with normal CgA level our regression model yielded high (89.4%) diagnostic accuracy (AUC: 0.904, sensitivity: 66.6%, specificity: 96.5%). A set of miRNAs increased the diagnostic utility of CgA in pNET even in patients with low CgA.
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Affiliation(s)
- Annamária Kövesdi
- 2nd Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary;
| | - Petra Anna Kurucz
- Department of Laboratory Medicine, Semmelweis University, 1089 Budapest, Hungary; (P.A.K.); (H.B.)
| | - Gábor Nyírő
- Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, 1088 Budapest, Hungary;
| | - Ottó Darvasi
- Hereditary Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, 1089 Budapest, Hungary;
| | - Attila Patócs
- Department of Laboratory Medicine, Semmelweis University, 1089 Budapest, Hungary; (P.A.K.); (H.B.)
- Hereditary Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, 1089 Budapest, Hungary;
- Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary
- Correspondence:
| | - Henriett Butz
- Department of Laboratory Medicine, Semmelweis University, 1089 Budapest, Hungary; (P.A.K.); (H.B.)
- Hereditary Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, 1089 Budapest, Hungary;
- Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary
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29
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Owens R, Gilmore E, Bingham V, Cardwell C, McBride H, McQuaid S, Humphries M, Kelly P. Comparison of different anti-Ki67 antibody clones and hot-spot sizes for assessing proliferative index and grading in pancreatic neuroendocrine tumours using manual and image analysis. Histopathology 2020; 77:646-658. [PMID: 32617996 DOI: 10.1111/his.14200] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/16/2020] [Accepted: 06/26/2020] [Indexed: 01/06/2023]
Abstract
AIMS Ki67 proliferative index (PI) is essential for grading gastroenteric and pancreatic neuroendocrine tumours (GEP NETs). Analytical and preanalytical variables can affect Ki67 PI. In contrast to counting methodology, until now little attention has focused on the question of clone equivalence and the effect of hot-spot size on Ki67 PI in GEP NETs. Using manual counting and image analysis, this study compared the Ki67 PI achieved using MM1, K2 and 30-9 to MIB1, a clone which has been validated for, and is referenced in, guidelines relating to assessment of Ki67 PI in GEP NETs. METHODS AND RESULTS Forty-two pancreatic NETs were each immunohistochemically stained for the anti-Ki67 clones MIB1, MM1, K2 and 30-9. Ki67 PI was calculated manually and by image analysis, the latter using three different hot-spot sizes. In manual comparisons using single hot-spot high-power fields, non-MIB1 clones overestimated Ki67 PI compared to MIB1, resulting in grading discordances. Image analysis shows good agreement with manual Ki67 PI but a tendency to overestimate absolute Ki67 PI. Increasing the size of tumour hot-spot from 500 to 2000 cells resulted in a decrease in Ki67 PI. CONCLUSION Different anti-Ki67 clones do not produce equivalent PIs in GEP NETs, and clone selection may therefore affect patient care. Increasing the hot-spot size decreases the Ki67 PI. Greater standardisation in terms of antibody clone selection and hot-spot size is required for grading GEP NETs. Image analysis is an effective tool for assisting Ki67 assessment and allows easier standardisation of the size of the tumour hot-spot.
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Affiliation(s)
- Roisin Owens
- Department of Cellular Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK
| | - Elaine Gilmore
- Precision Medicine Centre of Excellence, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Victoria Bingham
- Precision Medicine Centre of Excellence, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Christopher Cardwell
- Centre for Public Health, Institute of Clinical Sciences, Queen's University, Belfast, Northern Ireland, UK
| | - Hilary McBride
- Department of Cellular Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK
| | - Stephen McQuaid
- Precision Medicine Centre of Excellence, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Matthew Humphries
- Precision Medicine Centre of Excellence, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Paul Kelly
- Department of Cellular Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK
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30
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Neuroendocrine carcinoma arising from Barrett's esophageal adenocarcinoma: a case report. Clin J Gastroenterol 2020; 13:1028-1035. [PMID: 32852724 DOI: 10.1007/s12328-020-01210-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 08/12/2020] [Indexed: 12/12/2022]
Abstract
Neuroendocrine carcinoma in Barrett's esophagus is rare and its developmental mechanisms remain unclear. Neuroendocrine carcinoma arising in Barrett's esophagus with adenocarcinoma was detected at an early stage and resected by endoscopic submucosal dissection. Detailed pathological examination revealed that the neuroendocrine carcinoma originated via differentiation of the preexisting adenocarcinoma. A 79-year-old man presented with a flat protruding lesion in the esophagogastric junction. Esophagogastroduodenoscopy revealed a red flat 10-mm protruding lesion in the Barrett's epithelium and a shallow depression at the distal end. Narrow band imaging with magnification showed that the blood vessels in the protrusion were dilated and meandered irregularly, while those in the depression were small and did not form a network; the blood vessels were missing in some parts of the depression. Well-differentiated adenocarcinoma was diagnosed after analysis of the biopsy specimen of the protrusion, and endoscopic submucosal dissection was performed. The pathological diagnosis was neuroendocrine carcinoma with an adenocarcinoma component.
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31
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Heidsma CM, Tsilimigras DI, Rocha F, Abbott DE, Fields R, Smith PM, Poultsides GA, Cho C, van Eijck C, van Dijkum EN, Maithel SK, Pawlik TM. Clinical relevance of performing endoscopic ultrasound-guided fine-needle biopsy for pancreatic neuroendocrine tumors less than 2 cm. J Surg Oncol 2020; 122:1393-1400. [PMID: 32783272 DOI: 10.1002/jso.26158] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 07/28/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND We sought to define the diagnostic yield and concordance rates between endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) and surgical pathology specimen following resection of pancreatic neuroendocrine tumors (pNET) less than 2 cm. METHODS Patients with a pNET less than 2 cm who underwent EUS-FNA were identified using a multi-institutional international database. Tumor differentiation, and Ki-67 index, as determined through EUS-FNA were examined and concordance rates between EUS-FNA and the surgical pathology were assessed. RESULTS Among 628 patients with a pNET less than 2 cm, 57.2% of patients had an EUS-FNA performed. Patients who underwent EUS had slightly smaller size tumors (1.3 vs 1.4 cm), and the pNETs were less likely to be functional (15.3% vs 26.8%) or symptomatic (48.5% vs 56.5%) (both P < .05). Among 314 patients with a pNET less than 2 cm who had an EUS-FNA performed at the time of diagnosis, 243 (73.2%) had the diagnosis confirmed by preoperative EUS-FNA. Tumor differentiation and Ki-67 could be determined by EUS-FNA in only 26.4% and 20.1% of patients, respectively. Concordance rate between EUS-FNA and pathology was high relative to tumor differentiation (92.7%) and Ki-67 (81.0%). CONCLUSION Tumor differentiation and Ki-67 index could be determined by EUS-FNA in only 26.4% and 20.1% of cases, respectively. Further studies should focus on EUS techniques to optimize diagnostic yield and cell extraction in the preoperative setting.
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Affiliation(s)
- Charlotte M Heidsma
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.,Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Flavio Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Daniel E Abbott
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Ryan Fields
- Department of Surgery, Washington University School of Medicine, St Louis, Wisconsin
| | - Paula M Smith
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | | | - Cliff Cho
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Casper van Eijck
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Elisabeth Nieveen van Dijkum
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
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32
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Megdanova-Chipeva VG, Lamarca A, Backen A, McNamara MG, Barriuso J, Sergieva S, Gocheva L, Mansoor W, Manoharan P, Valle JW. Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs). Cancers (Basel) 2020; 12:E1988. [PMID: 32708210 PMCID: PMC7409353 DOI: 10.3390/cancers12071988] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/19/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023] Open
Abstract
Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.
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Affiliation(s)
- Vera G. Megdanova-Chipeva
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Department of Radiotherapy and Medical Oncology, University Hospital “Queen Yoanna” ISUL, 1000 Sofia, Bulgaria;
- Department of Nuclear Medicine, Radiotherapy and Medical Oncology, Medical University—Sofia, 1000 Sofia, Bulgaria
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Alison Backen
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Mairéad G. McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Jorge Barriuso
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Sonia Sergieva
- Nuclear Medicine Department, SBALOZ, Sofia grad, 1000 Sofia, Bulgaria;
| | - Lilia Gocheva
- Department of Radiotherapy and Medical Oncology, University Hospital “Queen Yoanna” ISUL, 1000 Sofia, Bulgaria;
- Department of Nuclear Medicine, Radiotherapy and Medical Oncology, Medical University—Sofia, 1000 Sofia, Bulgaria
| | - Was Mansoor
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Prakash Manoharan
- Department of Radiology and Nuclear Medicine, The Christie NHS Foundation Trust, Manchester M204BX, UK;
| | - Juan W. Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
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33
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Begum N, Maasberg S, Pascher A, Plöckinger U, Gress TM, Wurst C, Weber F, Raffel A, Krausch M, Holzer K, Bartsch DK, Musholt TJ, Keck T, Anlauf M, Rinke A, Pape UF, Goretzki PE. Long-term outcome of surgical resection in patients with gastroenteropancreatic neuroendocrine neoplasia: results from a German nation-wide multi-centric registry. Langenbecks Arch Surg 2020; 405:145-154. [PMID: 32372309 DOI: 10.1007/s00423-020-01868-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 03/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy. MATERIALS AND METHODS This is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999-2012). It focuses on patients without distant metastases (limited disease, LD, stage I-IIIB). RESULTS Data of 2239 patients with NEN were recorded. Median age was 59 years, the gender ratio was 1:1.3 (f:m). A total of 986 patients (44%) had LD, and the 5-year survival rate (5 years) was 77% for all and 90% for patients with LD. A total of 1635 patients (73%) received a surgical therapy (1st to 6th line); the 5 and 10 ysr were 83/65% after and 59/35% without surgery for all patients (p < .001). The resection margins in the LD patients were 76%, 16%, and 3% for R0, R1 and R2, respectively. The 10 ysr was 84%, 59% and 42% for R0, R1 and R2 resections, respectively (p = .021 R0/R1, p < .001 R0/R2). The R0 resection rate was 75% for G1/G2 NET and 67% for G3 NEC. CONCLUSION The rate of complete tumour resection (R0) in LD is independent of tumour grading, and R0 resection is the key determinant of long-term survival, as demonstrated by the 10 ysr. of 84%. All NEN patients with limited disease should be considered for operation, if possible, as the best 10-year survival is shown after an R0 resection.
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Affiliation(s)
- Nehara Begum
- Department for General-, Visceral- and Minimalinvasive Surgery, Agaplesion Evangelisches Klinikum Schaumburg, Obernkirchen, Germany.
| | - Sebastian Maasberg
- Department for Internal Medicine and Gastroenterology, Asklepios Hospital St. Georg, Lohmühlenstrasse 5, Hamburg, Germany.,Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charite, University Medicine Berlin, Berlin, Germany
| | - Andreas Pascher
- Department General-, Visceral- and Transplant Surgery, University Hospital Münster, Münster, Germany
| | - Ursula Plöckinger
- Centre of Metabollism: Endocrinology, Diabetes and Metabolism, Campus Virchow Clinic, Charite University-Medicine Berlin, Berlin, Germany
| | - Thomas M Gress
- Department of Gastroenterology and Endocrinology, University Hospital Marburg (UKGM), Marburg, Germany
| | - Christine Wurst
- Department of Surgery, Klinikum Crailsheim, Crailsheim, Germany
| | - Frank Weber
- Department of General-, Visceral- and Transplantation Surgery, Division of Endocrine Surgery, Medical Faculty, University Duisburg-Essen, Duisburg, Germany
| | - Andreas Raffel
- Department for General-, Visceral- and Endocrine Surgery, Marienhospital Gelsenkirchen, Gelsenkirchen, Germany
| | - Markus Krausch
- Department for General-, Visceral- and Endocrine Surgery, Marienhospital Gelsenkirchen, Gelsenkirchen, Germany
| | - Katharina Holzer
- Department of Visceral-, Thoracic- and Vascular Surgery, Section of Endocrine Surgery, University Hospital Marburg (UKGM), Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, University Hospital Marburg (UKGM), Marburg, Germany
| | - Thomas J Musholt
- Department of General, Visceral and Transplantation Surgery, Section of Endocrine Surgery, University Medicine Mainz, Mainz, Germany
| | - Tobias Keck
- Department of General Surgery, University Hospital Schleswig-Holstein, Lübeck, Germany
| | | | - Anja Rinke
- Department of Gastroenterology and Endocrinology, University Hospital Marburg (UKGM), Marburg, Germany
| | - Ulrich-Frank Pape
- Department for Internal Medicine and Gastroenterology, Asklepios Hospital St. Georg, Lohmühlenstrasse 5, Hamburg, Germany.,Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charite, University Medicine Berlin, Berlin, Germany
| | - Peter E Goretzki
- Department of General, Visceral and Transplant Surgery, Section of Endocrine Surgery, Charite, University Medicine Berlin, Berlin, Germany
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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.
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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
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35
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Xu X, Honda K, Miura N, Hori S, Le Blanc S, Bergmann F, Gaida MM, Volkmar M, Schimmack S, Hackert T, Strobel O, Felix K. Actinin-4 splice variant - a complementary diagnostic and prognostic marker of pancreatic neuroendocrine neoplasms. J Cancer 2020; 11:2318-2328. [PMID: 32127958 PMCID: PMC7052930 DOI: 10.7150/jca.37503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 01/02/2020] [Indexed: 11/05/2022] Open
Abstract
Introduction: For pathological diagnosis of pancreatic neuroendocrine neoplasms (pNENs) the routinely used immunohistochemical markers are chromogranin A (CgA) and synaptophysin (Syn). Their ability as prognostic markers is not well established. A splice variant of actinin-4 (Actn-4sv) was recently found to be an excellent biomarker of neuroendocrine neoplasms of the lung. We aimed to investigate the expression of Actn-4sv in pNENs and evaluate its quality as a biomarker of pNENs. Methods: Paraffin-embedded and frozen tissues specimens from 122 pNENs were analyzed. Western blots were performed to prove and compare the relative amount of Actn-4sv expression in pNENs tissue homogenates. For comparison pancreatic ductal adenocarcinoma (PDAC) and normal pancreatic tissues were analyzed in parallel. Immunohistochemistry (IHC) of paraffin sections of pNENs for Actn-4sv were performed and compared to the classic neuroendocrine markers CgA and Syn. Correlations were calculated between the staining intensity and distribution of Actn-4sv and staging, grading and afflicted lymph nodes respectively. Results: Actn-4sv was expressed in 88.5% (108/122) of pNENs, but not in normal pancreatic tissues (0/14) or PDAC (0/14). Compared to CgA and Syn, Actn-4sv was not detectable in islet cells of the normal pancreas. Staining intensity of Actn-4sv on pNENs negatively correlated to the histological grading (Spearman r=-0.4990, p<0.0001) and staging (r = -0.2581, p = 0.0041) but no correlation to afflicted lymph nodes was found. A significantly better overall survival was observed for pNEN patients with higher expression of Actn-4sv (hazard ratio 2.7; log-rank test p= 0.0349). Conclusions: The expression of Actn-4sv may be an important prognostic factor for patients with pNENs. Its expression correlates with the grading and staging of the tumors.
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Affiliation(s)
- Xiaojun Xu
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Kazufumi Honda
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan
| | - Nami Miura
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan
| | - Shutaro Hori
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan
- Surgery Division, Eiju General Hospital, Taito-ku, Tokyo, Japan
| | - Solange Le Blanc
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Frank Bergmann
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Matthias M. Gaida
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
- Institute of Pathology, University Medical Center Mainz, Mainz, Germany
| | - Michael Volkmar
- Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Simon Schimmack
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Klaus Felix
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
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36
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Ebbers SC, Braat AJAT, Moelker A, Stokkel MPM, Lam MGEH, Barentsz MW. Intra-arterial versus standard intravenous administration of lutetium-177-DOTA-octreotate in patients with NET liver metastases: study protocol for a multicenter, randomized controlled trial (LUTIA trial). Trials 2020; 21:141. [PMID: 32024533 PMCID: PMC7003409 DOI: 10.1186/s13063-019-3888-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 11/05/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Lutetium-177-DOTA-octreotate (177Lu-DOTATATE) significantly increases survival and response rates in patients with grade I and grade II neuroendocrine tumors (NETs). However, survival and response rates are significantly lower in patients with bulky liver metastases. Increasing the tumor-absorbed dose in liver metastases may improve response to 177Lu-DOTATATE. The LUTIA (Lutetium Intra-Arterial) study aims to increase the tumor-absorbed dose in liver metastases by intra-arterial (IA) administration of 177Lu-DOTATATE, compared to conventional intravenous (IV) administration. METHODS A multicenter, within-patient randomized controlled trial (RCT) in 26 patients with progressive, liver-dominant, unresectable grade I or grade II NET will be conducted. Patients with bilobar bulky disease will be randomly allocated to receive IA treatment into either the left or the right hepatic artery. Using this approach, one liver lobe will be treated intra-arterially (first-pass effect), while the contralateral lobe will receive an intravenous treatment as a second-pass effect. The primary endpoint of this study is the difference in tumor-to-non-tumor ratio of 177Lu-DOTATATE uptake between the two liver lobes on post-treatment SPECT/CT (IA versus IV). Secondary endpoints include absorbed dose in both liver lobes, tumor response, dose-response relationship, toxicity, uptake in extrahepatic lesions, and renal uptake. DISCUSSION This multicenter, within-patient RCT will investigate whether IA administration of 177Lu-DOTATATE results in a higher activity concentration in liver metastases compared to IV administration. TRIAL REGISTRATION ClinicalTrials.gov, NCT03590119. Registered on 17 July 2018.
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Affiliation(s)
- Sander C Ebbers
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Arthur J A T Braat
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Adriaan Moelker
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Marcel P M Stokkel
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Maarten W Barentsz
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
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Minon M, Soriano C, Morland D, Walter T, Lepage C, Tabarin A, Deblock M, Rousset P, Barbe C, Hoeffel C, Cadiot G. Prospective comparison of whole-body MRI with diffusion-weighted and conventional imaging for the follow-up of neuroendocrine tumors. Endocrine 2020; 67:243-251. [PMID: 31564038 DOI: 10.1007/s12020-019-02095-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 09/13/2019] [Indexed: 02/03/2023]
Abstract
AIM To determine whether whole-body magnetic resonance imaging is valuable in staging of neuroendocrine tumors by comparison with the conventional imaging defined by the combination of computed tomography and somatostatin receptor scintigraphy. METHODS This study concerned the patients included in the multicenter prospective study NCT02786303 with the following inclusion criteria: well-differentiated gastroenteropancreatic neuroendocrine tumors or of unknown primary, and computed tomography, whole-body magnetic resonance imaging and somatostatin receptor scintigraphy performed within 6 weeks. Results of the conventional imaging were compared with those of magnetic resonance imaging. Discrepancies between the conventional imaging and magnetic resonance imaging were evaluated by reviewing medical records. RESULTS Thirty-one patients (17 men and 14 women) were prospectively included. Complete concordance between the magnetic resonance imaging and the conventional imaging results was observed in 25 patients and discrepancies in 6. Whole-body magnetic resonance imaging detected more liver lesions than the conventional imaging did but standard imaging set was more effective in the detection of bone and peritoneum lesions than magnetic resonance imaging. Detecting more lesions had no impact on therapeutic management. CONCLUSIONS Whole-body magnetic resonance imaging including diffusion weighted may be a valuable alternative to computed tomography and somatostatin receptor scintigraphy. Further studies should compare whole-body MRI to the 68Ga PET/CT.
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Affiliation(s)
- Maximilien Minon
- Department of Radiology, Robert-Debré University Hospital, Reims, France.
| | - Clothilde Soriano
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France
| | - David Morland
- Department of Nuclear Medicine, Institut Jean-Godinot, Biophysics laboratory, UFR Medecine, Université de Reims Champagne-Ardenne (URCA), Reims, France
- CRESTIC, EA 3804, Université de Reims Champagne-Ardenne (URCA), Reims, France
| | - Thomas Walter
- Department of Digestive Oncology, Edouard Herriot Hospital, Lyon, France
| | - Côme Lepage
- Gastroenterology & Digestive Oncology, University Hospital Le Bocage, Dijon, France
| | - Antoine Tabarin
- Department of Endocrinology, Diabetology and Nutrition, Haut-Lévêque Hospital, Pessac, France
| | - Mathilde Deblock
- Department of Medical Oncology, Lorraine Cancer Institute, Vandoeuvre-les-Nancy, France
| | - Pascal Rousset
- Radiology Department, Lyon Sud University Hospital, Hospices Civils de Lyon, Lyon, France
| | - Coralie Barbe
- Clinical Research Coordination Unit, Robert-Debré University Hospital, Reims, France
| | - Christine Hoeffel
- Department of Radiology, Robert-Debré University Hospital, Reims, France
- CRESTIC, EA 3804, Université de Reims Champagne-Ardenne (URCA), Reims, France
| | - Guillaume Cadiot
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France
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Saadeh H, Abdullah N, Erashdi M, Sughayer M, Al-Kadi O. Histopathologist-level quantification of Ki-67 immunoexpression in gastroenteropancreatic neuroendocrine tumors using semiautomated method. J Med Imaging (Bellingham) 2019; 7:012704. [PMID: 31824983 DOI: 10.1117/1.jmi.7.1.012704] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 11/18/2019] [Indexed: 11/14/2022] Open
Abstract
The role of Ki-67 index in determining the prognosis and management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has become more important yet presents a challenging assessment dilemma. Although the precise method of Ki-67 index evaluation has not been standardized, several methods have been proposed, and each has its pros and cons. Our study proposes an imaging semiautomated informatics framework [semiautomated counting (SAC)] using the popular biomedical imaging tool "ImageJ" to quantify Ki-67 index of the GEP-NETs using camera-captured images of tumor hotspots. It aims to assist pathologists in achieving an accurate and rapid interpretation of Ki-67 index and better reproducibility of the results with minimal human interaction and calibration. Twenty cases of resected GEP-NETs with Ki-67 staining that had been done for diagnostic purposes have been randomly selected from the pathology archive. All of these cases were reviewed in a multidisciplinary cancer center between 2012 and 2019. For each case, the Ki-67 immunostained slide was evaluated and five camera-captured images at 40 × magnification were taken. Prints of images were used by three pathologists to manually count the tumor cells. The digital versions of the images were used for the semiautomated cell counting using ImageJ. Statistical analysis of the Ki-67 index correlation between the proposed method and the MC revealed strong agreement on all the cases evaluates ( n = 20 ), with an intraclass correlation coefficient of 0.993, "95% CI: 0.984 to 0.997." The results obtained from the SAC are promising and demonstrate the capability of this methodology for the development of reproducible and accurate semiautomated quantitative pathological assessments. ImageJ features are investigated carefully and accurately fine-tuned to obtain the optimal sequence of steps that will accurately calculate Ki-67 index. SAC is able to accurately grade all the cases evaluated perfectly mating histopathologists' manual grading, providing reliable and efficient solution for Ki-67 index assessment.
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Affiliation(s)
- Heba Saadeh
- The University of Jordan, King Abdullah II School for IT, Computer Science Department, Amman, Jordan
| | - Niveen Abdullah
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Al-Jubeiha, Amman, Jordan
| | - Madiha Erashdi
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Al-Jubeiha, Amman, Jordan
| | - Maher Sughayer
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Al-Jubeiha, Amman, Jordan
| | - Omar Al-Kadi
- The University of Jordan, King Abdullah II School for IT, Information Technology Department, Amman, Jordan
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Cai JS, Chen HY, Lu YF, Yu RS. A prognostic nomogram in patients with distant metastasis of pancreatic neuroendocrine tumors: a population-based study. Future Oncol 2019; 16:4369-4379. [PMID: 31802701 DOI: 10.2217/fon-2019-0545] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: Prognostic factors in patients with distant metastatic pancreatic neuroendocrine tumors (PNETs) remain uncertain. The purpose of our study is to establish a nomogram to predict survival outcomes in patients with metastatic PNETs. Methods: A total of 878 patients diagnosed with PNETs in the Surveillance, Epidemiology and End Results database between 2004 and 2016 were retrospectively identified. The Kaplan-Meier survival analysis with log-rank test was used to analyze survival outcomes. The nomogram was established after a univariate and multivariate Cox analysis. Results: The independent prognostic variables, including age, tumor grade and primary site surgery were applied to develop a nomogram. The original concordance index was 0.773 (95% CI: 0.751-0.795), and the bias-corrected concordance index was 0.769 (95% CI: 0.748-0.791). The internal calibration curves showed well consistency and veracity in predicting cancer-specific survival probabilities. Conclusion: A nomogram was constructed and verified to predict survival outcomes in patients with distant-stage PNETs.
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Affiliation(s)
- Jin-Song Cai
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Hai-Yan Chen
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Yuan-Fei Lu
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Ri-Sheng Yu
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
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Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013-2015. Br J Cancer 2019; 121:966-972. [PMID: 31649320 PMCID: PMC6889414 DOI: 10.1038/s41416-019-0606-3] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 09/21/2019] [Accepted: 10/01/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities. METHODS Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013-2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology. RESULTS A total of 15,222 NENs were identified, with an ASR (2013-2015 combined) of 8.6 per 100,000 (95% CI 8.5-8.7); 4.6 per 100 000 (95% CI, 4.5-4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9-75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs. CONCLUSION Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement.
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The multidisciplinary team for gastroenteropancreatic neuroendocrine tumours: the radiologist's challenge. Radiol Oncol 2019; 53:373-387. [PMID: 31652122 PMCID: PMC6884929 DOI: 10.2478/raon-2019-0040] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 07/15/2019] [Indexed: 02/07/2023] Open
Abstract
Background Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a heterogeneous group of tumours. An effective diagnosis requires a multimodal approach that combines evaluation of clinical symptoms, hormonelevels, radiological and nuclear imaging, and histological confirmation. Imaging plays a critical role in NETs diagnosis, prognosis and management, so the radiologists are important members of the multidisciplinary team. During diagnostic work-up two critical issues are present: firstly the need to identify tumor presence and secondly to define the primary site and assess regional and distant metastases. Conclusions The most appropriate imaging technique depends on the type of neuroendocrine tumour and the availability of specialized imaging techniques and expertise. There is no general consensus on the most efficient imaging pathway, reflecting the challenge in reliably detection of these tumours.
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Algashaamy K, Garcia-Buitrago M. Multifocal G1-G2 gastric neuroendocrine tumors: Differentiating between Type I, II and III, a clinicopathologic review. World J Clin Cases 2019; 7:2413-2419. [PMID: 31559277 PMCID: PMC6745311 DOI: 10.12998/wjcc.v7.i17.2413] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 07/26/2019] [Accepted: 08/20/2019] [Indexed: 02/05/2023] Open
Abstract
Gastric neuroendocrine tumors (gNETs) are a rare entity that is increasing in incidence. Different pathophysiological processes can lead to the development of these tumors, appropriate histological analysis is necessary to differentiate between grade 1 (G1) and grade 2 (G2) tumors as this will impact the management of these patients based on their increased risk of lymph node and distant metastases. To provide a comprehensive clinicopathologic review of multifocal gastric neuroendocrine tumors, with particular emphasis on G1 and G2 tumors and differentiating between types I, II and II and risk stratification based upon immunohistochemical profile. This review is based on peer-reviewed literature and the authors’ experience. gNETs are a heterogenous group of tumors that is rising in incidence. These lesions while arise from the same cell type, they have different etiologies. Identifying the type of gNETs is a collective effort of clinical and pathologic correlation. The correct grading and staging of these lesions are of paramount significance, due its impact on patient management and prognosis.
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Affiliation(s)
- Khaled Algashaamy
- Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
| | - Monica Garcia-Buitrago
- Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
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Farooqui ZA, Chauhan A. Neuroendocrine Tumors in Pediatrics. Glob Pediatr Health 2019; 6:2333794X19862712. [PMID: 31384627 PMCID: PMC6647200 DOI: 10.1177/2333794x19862712] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 05/14/2019] [Accepted: 05/15/2019] [Indexed: 12/23/2022] Open
Abstract
Neuroendocrine cells are dispersed diffusely throughout many organ systems in the body and hence neuroendocrine tumors (NETs) can arise from almost anywhere in the body. NETs are considered rare tumors, and the current incidence is reported to be about 6 cases in 100 000 in adults and about 2.8 cases per million in the pediatric age group. Despite the indolent nature of these tumors, they have the potential for metastasis and significant morbidity. NETs can be asymptomatic at the time of diagnosis or can present with flushing, diarrhea, wheezing, weight loss, and fatigue among other symptoms. Due to the ambiguity of presenting symptoms, it is not uncommon for NETs to be diagnosed late in the disease course. Despite low incidence, the prevalence of the disease is high since patients live for many years and sometimes decades. Early detection of well-differentiated NETs has excellent outcomes with the majority of early-stage diseases being cured with surgical resection alone. There have been recent advancements in the management of metastatic progressive NETs with approval of peptide receptor radionuclide therapy, telotristat, and everolimus. Awareness of these rare tumors and its management is crucial for optimal management. This article will focus on pediatric NETs and current advances in its management.
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Affiliation(s)
| | - Aman Chauhan
- Markey Cancer Center, Lexington, KY, USA
- University of Kentucky, Lexington, KY, USA
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Peptide Receptor Radionuclide Therapy Combined With Chemotherapy in Patients With Neuroendocrine Tumors. Clin Nucl Med 2019; 44:e329-e335. [DOI: 10.1097/rlu.0000000000002532] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Skalický A, Vištejnová L, Dubová M, Malkus T, Skalický T, Troup O. Mixed neuroendocrine-non-neuroendocrine carcinoma of gallbladder: case report. World J Surg Oncol 2019; 17:55. [PMID: 30902091 PMCID: PMC6429764 DOI: 10.1186/s12957-019-1598-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 03/13/2019] [Indexed: 02/06/2023] Open
Abstract
Background Mixed neuroendocrine-non-neuroendocrine tumors (MINEN) of the gallbladder are extremely rare; indeed, the English expert literature reports a mere handful of case reports and case series on this topic. According to the WHO classification of 2010, MINEN are considered to be tumors consisting of two major components, neuroendocrine and non-neuroendocrine, each of which hosts at least 30% of the total cellular population. To date, the etiology and pathogenesis of MINEN have not been precisely determined and the non-specific symptoms generally result in late diagnosis (mainly in the terminal stages of the condition) and contribute to the generally poor prognosis. As far as the management of the disease is concerned, radical surgery plays a crucial role; however, the significance of surgical debulking and biological therapy applying somatostatin analogues has not yet been determined. Case presentation A 56-year-old female was referred to our department for a rapidly progressing tumor in the subhepatic area along with the infiltration of S5 and S6 liver segments. With regard to preoperative findings, the tumor appeared as operable, although, during the surgery, an extensive involvement of the hepatoduodenal ligament by the tumor through the lymph nodes was revealed. Due to acute perioperative bleeding from the necrotic tumor, we decided to perform modified resection. Histologically, the tumor was confirmed as MINEN of gallbladder, where the neuroendocrine component was dominant over the non-neuroendocrine component. Six weeks after the discharge, the patient underwent a follow-up CT revealing large recurrence of the disease. Thereafter, the patient was started on systemic therapy with etoposide and carboplatin in combination with somatostatin analogues. Thirteen months after the surgery, the patient is in good clinical condition, and while a recently performed PET/MRI scan revealed a hepatic lesion and hilar lymphadenopathy in full regression, there was a spread of small peritoneal and pleural metastases. The patient remains in the follow-up care. Conclusions The occurrence of mixed neuroendocrine-non-neuroendocrine neoplasms is extremely rare. Radical surgery remains the only potentially effective approach to the cure of this disease. The role of biological therapy and debulking in the management of the disease has not yet been precisely defined. In our experience, both of these methods have the potential to positively influence overall survival rates and the postoperational quality of life of patients.
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Affiliation(s)
- Adam Skalický
- Department of Surgery and Biomedical Center, Faculty of Medicine and University Hospital in Pilsen, Charles University in Prague, 304 60, Pilsen, Czech Republic.
| | - Lucie Vištejnová
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 304 60, Pilsen, Czech Republic
| | - Magdaléna Dubová
- Šikl's Department of Pathology, Faculty of Medicine and University Hospital in Pilsen, Charles University, 305 99, Pilsen, Czech Republic
| | - Tomáš Malkus
- Department of Imaging Methods, University Hospital in Pilsen, 304 60, Pilsen, Czech Republic
| | - Tomáš Skalický
- Department of Surgery and Biomedical Center, Faculty of Medicine and University Hospital in Pilsen, Charles University in Prague, 304 60, Pilsen, Czech Republic
| | - Ondřej Troup
- Faculty of Medicine in Pilsen, Charles University, 301 00, Pilsen, Czech Republic
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Fujimoto A, Sasaki M, Goto O, Maehata T, Ochiai Y, Kato M, Nakayama A, Akimoto T, Kuramoto J, Hayashi Y, Kameyama K, Yahagi N. Treatment Results of Endoscopic Mucosal Resection with a Ligation Device for Duodenal Neuroendocrine Tumors. Intern Med 2019; 58:773-777. [PMID: 30449790 PMCID: PMC6465016 DOI: 10.2169/internalmedicine.1517-18] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Objective The vertical margin of neuroendocrine tumors (NETs) removed by endoscopic mucosal resection (EMR) is often tumor-positive. We examine the treatment results of endoscopic mucosal resection with a ligation device (EMR-L) for the removal of duodenal NETs located in the submucosal layer without metastasis. EMR-L can be performed with less technical skill, and the ligation device reduces the rate of positive vertical margin. Methods Ten consecutive patients with 10 duodenal NETs resected by EMR-L were enrolled. All of the lesions were located in the submucosal layer, were assessed to be free of metastasis, and were confirmed to be NETs pathologically by an endoscopic biopsy. The endoscopic results, pathological results, and prognosis were all examined. Results The en bloc resection rate and endoscopic complete resection rate were both 100%. Complete resection was achieved pathologically in 7 lesions (70.0%). The vertical margins were negative in all cases. Lymphatic vessel invasion was observed in three patients, all of whom underwent additional surgery with lymph node dissection (one of them also exhibited blood vessel invasion and a positive horizontal margin). No evidence of residual tumors or lymph node metastasis was observed in any of the patients. No recurrence was observed in any of the 10 patients (mean follow-up period: 18.6 months). One patient (10.0%) experienced intraoperative bleeding. Perforation occurred in 1 patient (10.0%), but the condition was managed well by conservative therapy. Conclusion EMR-L was an acceptable method for endoscopically resecting submucosal duodenal NETs, and the NETs resected by EMR-L were tumor-negative in the vertical margins.
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Affiliation(s)
- Ai Fujimoto
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Motoki Sasaki
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Osamu Goto
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Tadateru Maehata
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Yasutoshi Ochiai
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Motohiko Kato
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Atsushi Nakayama
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Teppei Akimoto
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
| | - Jyunko Kuramoto
- Department of Diagnostic Pathology, Keio University Hospital, Japan
| | - Yuichiro Hayashi
- Department of Diagnostic Pathology, Keio University Hospital, Japan
| | - Kaori Kameyama
- Department of Diagnostic Pathology, Keio University Hospital, Japan
| | - Naohisa Yahagi
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Japan
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Selberherr A, Koperek O, Riss P, Scheuba C, Kaderli R, Perren A, Niederle B. Neuroendocrine Liver Metastasis-a Specific Set of Markers to Detect Primary Tumor Sites. Endocr Pathol 2019; 30:31-34. [PMID: 30456697 DOI: 10.1007/s12022-018-9558-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The diagnosis of neuroendocrine neoplasia (NEN) is often made at an advanced stage of disease, including hepatic metastasis. At this point, the primary may still be unknown and sometimes cannot even be detected by functional imaging, especially in very small tumors of the pancreas (pan) and small intestinal (si) entities. The site of the primary may be based on biopsy specimens of the liver applying a specific set of markers. Specimens of liver metastases from 87 patients with NENs were studied. In retrospect, 50 patients had si and 37 pan NENs. Tissue samples were evaluated by immunohistochemistry. The markers applied were insulin gene enhancer protein Islet-1 (ISL-1), homeobox protein CDX-2 (CDX2), thyroid transcription factor 1 (TTF-1), and serotonin. Positive stains for CDX2 were documented in 43 (86%) and for serotonin in 45 (90%) of 50 siNENs. Three panNENs were positive for CDX2 and one for serotonin, respectively. ISL-1 was negative throughout in siNENs and also negative in 8 of 50 panNENs (21.6%). TTF-1 was negative in more than 90% of the specimens of either entity. Immunohistochemical markers in liver metastasis can lead the way to the site of the primary NEN. They should always be used in combined clusters.
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Affiliation(s)
- Andreas Selberherr
- Section "Endocrine Surgery", Division of General Surgery, Department of Surgery, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - Oskar Koperek
- Department of Pathology, Medical University, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Philipp Riss
- Section "Endocrine Surgery", Division of General Surgery, Department of Surgery, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Christian Scheuba
- Section "Endocrine Surgery", Division of General Surgery, Department of Surgery, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Reto Kaderli
- Section "Endocrine Surgery", Division of General Surgery, Department of Surgery, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Aurel Perren
- Institute of Pathology, University of Bern, Murtenstrasse 31, 3012, Bern, Switzerland
| | - Bruno Niederle
- Section "Endocrine Surgery", Division of General Surgery, Department of Surgery, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
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Zhang C, Huang Y, Long J, Yao X, Wang J, Zang S, Qu W, Wang F. Serum chromogranin A for the diagnosis of gastroenteropancreatic neuroendocrine neoplasms and its association with tumour expression. Oncol Lett 2019; 17:1497-1504. [PMID: 30675205 PMCID: PMC6341841 DOI: 10.3892/ol.2018.9795] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 10/03/2018] [Indexed: 01/26/2023] Open
Abstract
The aim of the present study was to assess the clinical value of serum chromogranin A (CgA) levels in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and to compare them with tumour expression of CgA. A total of 109 consecutive patients with confirmed GEP-NENs were enrolled in this prospective study between December 2012 and August 2016, including 73 patients with primary or recurrent GEP-NENs and 36 patients with GEP-NENs that were treated following surgery. Furthermore, 30 patients with benign gastrointestinal diseases and 30 healthy volunteers served as control groups. Serum CgA levels were measured by ELISA, using different reference values, in order to evaluate its diagnostic efficacy. Serum neuron-specific enolase was also measured to evaluate its diagnostic efficacy and analyse its association with serum CgA levels. The levels of CgA, synaptophysin and neural cell adhesion molecule 1 in the tumour tissue were assessed by immunohistochemical assays. The results indicated that serum CgA levels were significantly higher in patients with GEP-NENs compared with the control groups (P<0.05). No association was observed between serum CgA levels and tumour grade (G1, G2 and G3), but serum CgA levels differed significantly between patients with GEP-NENs of different origins (P<0.05). A serum CgA cut-off value of 85.3 ng/ml was associated with high sensitivity (64.4%) and specificity (92.7%). Different reference values were recommended for NENs of different origins, with serum CgA cut-off values of 96.72, 51.13 and 86.19 ng/ml for the stomach, intestines and pancreas, respectively. The serum CgA levels were consistent with the CgA expression in the tumour. In conclusion, serum CgA may serve as a circulating pathological biomarker for the diagnosis of GEP-NENs. The use of different reference values for different tumour origins may improve the diagnostic efficacy of CgA for GEP-NENs. A cut-off value of 85.3 ng/ml is recommended in the Chinese population.
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Affiliation(s)
- Chuan Zhang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Yue Huang
- Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Jiang Long
- Department of Pancreas Surgery, Fudan University Shanghai Cancer Centre, Shanghai 200032, P.R. China
| | - Xiaochen Yao
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Jun Wang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Shimin Zang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Wei Qu
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
| | - Feng Wang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
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Barry L, McFadden DW. Gastrointestinal Carcinoid Tumors. SHACKELFORD'S SURGERY OF THE ALIMENTARY TRACT, 2 VOLUME SET 2019:939-950. [DOI: 10.1016/b978-0-323-40232-3.00080-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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50
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Choe J, Kim KW, Kim HJ, Kim DW, Kim KP, Hong SM, Ryu JS, Tirumani SH, Krajewski K, Ramaiya N. What Is New in the 2017 World Health Organization Classification and 8th American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Neoplasms? Korean J Radiol 2018; 20:5-17. [PMID: 30627018 PMCID: PMC6315069 DOI: 10.3348/kjr.2018.0040] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Accepted: 07/09/2018] [Indexed: 12/12/2022] Open
Abstract
The diagnosis and management of pancreatic neuroendocrine neoplasms (NENs) have evolved significantly in recent years. There are several diagnostic and therapeutic challenges and controversies regarding the management of these lesions. In this review, we focus on the recent significant changes and controversial issues regarding the diagnosis and management of NENs and discuss the role of imaging in the multidisciplinary team approach.
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Affiliation(s)
- Jooae Choe
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kyung Won Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kyu Pyo Kim
- Department of Oncology, 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
| | - Jin-Sook Ryu
- Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sree Harsha Tirumani
- Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Katherine Krajewski
- Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Nikhil Ramaiya
- Department of Imaging, UH Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA
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