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Ye X, Hua H, Hu C, Dai J, Wu C, Huai J, Shen Z. Endoscopic Ultrasound-Guided Fine Needle Acquisition for Evaluation of Pancreatic Neuroendocrine Tumors: A Meta-Analysis. J Clin Gastroenterol 2025; 59:310-320. [PMID: 39312536 DOI: 10.1097/mcg.0000000000002070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 08/05/2024] [Indexed: 09/25/2024]
Abstract
AIMS The aim of this meta-analysis was to assess the diagnostic performance of EUS-FNA/B in patients with panNETs. METHODS We conducted a computerized search of the MEDLINE and Embase databases to identify relevant articles. The primary outcomes involved grading concordance rate, diagnostic rate, and correlation coefficient (Cohen's κ) for FNA/B samples compared with surgical specimens. Secondary outcomes included sample adequacy, mean number of passes, and adverse events. RESULTS Forty-five studies involving 2978 patients were finally included. The pooled concordance rate between EUS-FNA/B and surgical grading was 0.77 (95% CI: 0.73-0.80; I2 =48.2%). A significantly higher level of concordance was observed in G1 subgroup (0.88, 95% CI: 0.84-0.91), whereas the G2 subgroup revealed the lowest level of agreement (0.59, 95% CI: 0.52-0.65; P < 0.001). Pooled diagnostic rate for FNA/B sampling was 0.83 (95% CI: 0.79-0.86; I2 =63.3%). In addition, FNB outperformed FNA in terms of sample adequacy (0.93 for FNB vs. 0.81 for FNA; P =0.007) and number of needle passes required (2.53 for FNB vs. 3.32 for FNA; P =0.013). Moreover, the overall level of agreement for grading was moderate (κ=0.59, 95% CI: 0.49-0.68; I2 =84.5%). There were a limited number of adverse events that had minor influence on patient outcomes (0.03, 95% CI: 0.02-0.05; I2 =19.2%). CONCLUSIONS EUS-FNA/B is a reliable approach for the diagnosis and preoperative grading of panNET, with FNB demonstrating superior performance compared with FNA.
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Affiliation(s)
- Xiaohua Ye
- Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Hongjun Hua
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Chunxiao Hu
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Jianying Dai
- Department of Research and Development, Hangzhou Yingjian Bioscience and technology Co., Ltd
| | - Chenjiao Wu
- Department of Gastroenterology, Digestive Endoscopy Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
| | - Jiaping Huai
- Department of Critical Care, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
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Massironi S, Gallo C, Coltro L, Dell'Anna G, Preatoni P, Danese S. Clinical and biological heterogeneity of Grade 2 digestive neuroendocrine neoplasms: prognostic significance of the 10% Ki-67 index cutoff and implications for treatment strategies. A longitudinal study. J Endocrinol Invest 2025:10.1007/s40618-025-02552-1. [PMID: 39969798 DOI: 10.1007/s40618-025-02552-1] [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: 12/21/2024] [Accepted: 02/10/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND Digestive neuroendocrine neoplasms (NENs) encompass a heterogeneous group of tumors with varying prognoses and clinical behaviors. Grade 2 (G2) tumors, defined by a Ki-67 index between 3% and 20%, are particularly challenging to manage due to their intermediate and variable biological behavior. Evidence suggests a distinct prognosis between G2 digestive NENs with a Ki-67 index < 10% and those with a Ki-67 index ≥ 10%. AIM To investigate the clinical and biological heterogeneity between Grade 1 (G1) and G2 digestive NENs, and within G2 tumors, with a focus on the prognostic significance of a 10% Ki-67 index cutoff. METHODS This study involved a combined retrospective and prospective analysis of patients with low-grade G1 and G2 digestive NENs managed at IRCCS San Gerardo Hospital in Monza, Italy, between January 2000 and May 2024. Data on patient demographics, tumor characteristics, treatment modalities, and survival outcomes were collected and potential differences were analyzed between G1, G2 with Ki-67 index < 10% and G2 with Ki-67 index ≥ 10%. RESULTS Out of a total of 113 enrolled patients, 69 (61%) had G1 tumors, and 44 (39%) had G2 tumors. Median tumor size at diagnosis was 19 mm (IQR: 12-25 mm), with primary lesions mainly localized in the pancreas (57% among G1 and 45% among G2). Most G1 tumors were diagnosed at stage I (29 patients, 42%), while the majority of G2 tumors were metastatic at diagnosis (24 patients, 54.5%). Patients with G1 tumors exhibited a slightly higher 5-year OS rate compared to G2 tumors (98.1% vs. 92.8% respectively, though not statistically significant), and a significantly longer median PFS (141 vs. 22 months, p = 0.0003). Within the G2 group, 31 patients (70%) had a Ki-67 index < 10%, while 13 (30%) had a Ki-67 index ≥ 10%, with comparable baseline characteristics. A Ki-67 index < 10% was associated with a significantly better median PFS (38 vs. 8 months for tumors with Ki-67 index ≥ 10% G2 tumors, p = 0.002). PFS after first-line medical therapy was significantly longer in patients with a Ki-67 index < 10%, compared to those with ≥ 10% (undefined vs. 16 months, p = 0.0085), as well as median post-surgical PFS (84 vs. 10.5 months, p < 0.0001). Multivariate analysis identified higher tumor grade, advanced stage at diagnosis, and absence of PRRT as independent predictors of worse outcomes. CONCLUSIONS The findings highlight the significant clinical heterogeneity within G2 digestive NENs. A Ki-67 index cutoff of 10% within G2 tumors may serve as a critical prognostic marker, with patients with a Ki-67 index < 10% exhibiting significantly better outcomes in terms of PFS. These results suggest that the Ki-67 index could play an essential role in guiding treatment strategies, emphasizing the need for personalized approaches in managing G2 digestive NENs.
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Affiliation(s)
- Sara Massironi
- Vita e Salute San Raffaele University, Milan, Italy.
- Gastroenterology Unit, Istituti Ospedalieri Bergamaschi, Zingonia (BG), Italy.
| | - Camilla Gallo
- Digestive and Interventional Endoscopy Unit, ASST GOM Niguarda, Milan, Italy
| | - Lorenzo Coltro
- Department of Medicine, Bicocca University of Milan, Milan, Italy
| | - Giuseppe Dell'Anna
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Paoletta Preatoni
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Silvio Danese
- Vita e Salute San Raffaele University, Milan, Italy
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
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Danek E, Kavnoudias H, McLean C, Gerstenmaier JF, Di Muzio B. Radiological Variability in Pancreatic Neuroendocrine Neoplasms: A 10-Year Single-Center Study on Atypical Presentations and Diagnostic Challenges. Biomedicines 2025; 13:496. [PMID: 40002909 PMCID: PMC11853254 DOI: 10.3390/biomedicines13020496] [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: 01/07/2025] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Pancreatic neuroendocrine neoplasms (PNENs) are rare but clinically significant tumors with variable radiological presentations that complicate diagnosis. While typical PNENs are well characterized, atypical features, such as cystic or hypoenhancing patterns, are less understood and can lead to diagnostic delays or misdiagnosis. This study aimed to evaluate atypical radiological presentations of PNENs, focusing on their impact on diagnostic pathways and differentiation from other pancreatic pathologies. Methods: A retrospective review was conducted of all PNEN cases diagnosed at a single tertiary center between 2010 and 2020. Cases with histopathological confirmation and available cross-sectional imaging were included. Radiological features were categorized as typical (solid and hyperenhancing) or atypical (cystic and hypoenhancing). Demographic, radiological, and pathological data were analyzed. Comparisons between typical and atypical PNENs were performed using descriptive and inferential statistics. Results: Among 77 PNEN cases, 39 met the inclusion criteria. Atypical radiological presentations were identified in 46% of cases, including cystic (18%) and hypoenhancing (28%) lesions. Hypoenhancing PNENs were significantly more likely to present with advanced disease (54% vs. 14% in typical PNENs, p = 0.016). In contrast, none of the cystic PNENs exhibited advanced disease. Atypical PNENs posed greater diagnostic challenges, with alternative diagnoses initially considered in 64% of hypoenhancing and 43% of cystic cases compared to 10% of typical PNENs (p = 0.0042). Conclusions: Atypical PNENs, particularly hypoenhancing lesions, present significant diagnostic challenges and are more likely to be associated with advanced disease. These findings highlight the need for improved recognition of atypical imaging patterns and more precise diagnostic strategies. However, the retrospective design and small cohort size limit the generalizability of our findings. Further multicenter studies are warranted to refine the imaging criteria and optimize the differentiation from other pancreatic neoplasms.
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Affiliation(s)
- Eleanor Danek
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Helen Kavnoudias
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Catriona McLean
- Department of Anatomical Pathology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Jan F. Gerstenmaier
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
| | - Bruno Di Muzio
- Department of Radiology, The Alfred Hospital, Melbourne, VIC 3004, Australia
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Ahn B, Park HJ, Kim HJ, Hong SM. Radiologic tumor border can further stratify prognosis in patients with pancreatic neuroendocrine tumor. Pancreatology 2024; 24:753-763. [PMID: 38796309 DOI: 10.1016/j.pan.2024.05.524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 04/30/2024] [Accepted: 05/14/2024] [Indexed: 05/28/2024]
Abstract
BACKGROUND AND OBJECTIVES Pancreatic neuroendocrine tumor (PanNET), although rare in incidence, is increasing in recent years. Several clinicopathologic and molecular factors have been suggested for patient stratification due to the extensive heterogeneity of PanNETs. We aimed to discover the prognostic role of assessing the tumor border of PanNETs with pre-operative computed tomography (CT) images and correlate them with other clinicopathologic factors. METHODS The radiologic, macroscopic, and microscopic tumor border of 183 surgically resected PanNET cases was evaluated using preoperative CT images (well defined vs. poorly defined), gross images (expansile vs. infiltrative), and hematoxylin and eosin-stained slides (pushing vs. infiltrative). The clinicopathologic and prognostic significance of the tumor border status was compared with other clinicopathologic factors. RESULTS A poorly defined radiologic tumor border was observed in 65 PanNET cases (35.5 %), and were more frequent in male patients (P = 0.031), and tumor with larger size, infiltrative macroscopic growth pattern, infiltrative microscopic tumor border, higher tumor grade, higher pT category, lymph node metastasis, lymphovascular and perineural invasions (all, P < 0.001). Patients with PanNET with a poorly defined radiologic tumor border had significantly worse overall survival (OS) and recurrence-free survival (RFS; both, P < 0.001). Multivariable analysis revealed that PanNET with a poorly defined radiologic border is an independent poor prognostic factor for both OS (P = 0.049) and RFS (P = 0.027). CONCLUSION Pre-operative CT-based tumor border evaluation can provide additional information regarding survival and recurrence in patients with PanNET.
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Affiliation(s)
- Bokyung Ahn
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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Gorai PK, Rastogi S, Bharti PS, Agarwal S, Pal S, Sharma MC, Kumar R, Nikolajeff F, Kumar S, Rani N. Deciphering pancreatic neuroendocrine tumors: Unveiling through circulating small extracellular vesicles. Heliyon 2024; 10:e29079. [PMID: 38596136 PMCID: PMC11002672 DOI: 10.1016/j.heliyon.2024.e29079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 03/27/2024] [Accepted: 03/29/2024] [Indexed: 04/11/2024] Open
Abstract
The survival rate over a five-year period for rare pancreatic neuroendocrine tumors (PanNET) is notably lower compared to other neuroendocrine tumors due to late-stage detection, which is a consequence of the absence of suitable diagnostic markers; therefore, there exists a critical need for an early-stage biomarker-specific to PanNETs. This study introduces a novel approach, investigating the impact of small extracellular vesicles (sEV) in PanNET growth and metastasis. As proof of concept, this study shows a correlation between sEV concentration in controls and PanNET. Notably, higher sEV concentrations were observed in PanNETs than in controls (p < 0.0001) with a sensitivity of 100%. Further, apparent differences were observed in the sEV concentrations between controls and grades 1 PanNET (p = 0.005). The expression of sEV markers was confirmed using CD63, TSG101, CD9, Flotillin-1, and GAD65 antibodies. Additionally, the expression of cancer marker BIRC2/cIAP1 (p = 0.002) and autophagy marker Beclin-1 (p = 0.02) were observed in plasma-derived sEVs and PanNET tissue. This study represents the first to indicate the increased secretion of sEV in PanNET patients' blood plasma, proposing potential function of sEV as a new biomarker for early-stage PanNET detection.
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Affiliation(s)
- Priya Kumari Gorai
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| | - Simran Rastogi
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
| | | | - Shipra Agarwal
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Sujoy Pal
- Department of GI Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Mehar Chand Sharma
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | | | - Saroj Kumar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
- Department of Health Science, Lulea University of Technology, Sweden
| | - Neerja Rani
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
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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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Sripodok P, Kouketsu A, Kuroda K, Miyashita H, Sugiura T, Kumamoto H. Primary Oral Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN): A Rare Case Report and Review of the Literature. Head Neck Pathol 2024; 18:13. [PMID: 38393494 PMCID: PMC10891016 DOI: 10.1007/s12105-024-01613-w] [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: 11/21/2023] [Accepted: 01/10/2024] [Indexed: 02/25/2024]
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare tumors recently characterized by the presence of both neuroendocrine and non-neuroendocrine components within the same tumor tissue. Although MiNEN found their place in the WHO classification for various organs, this composite tumor in the head and neck region remains exceptionally rare. We present a case of primary oral MiNEN in a 64-year-old male located on the left side of lower gingiva. Biopsy raised suspicion of neuroendocrine carcinoma (NEC) and the patient underwent partial mandibulectomy. The resected specimen showed two distinct components of NEC and squamous cell carcinoma (SCC) with the confirmation of immunohistochemical markers. There has been no sign of recurrence nor metastasis 6 years after the surgery. In addition, we have conducted a review of published cases with potential relevance to this entity, resulting in five cases. The diverse terminology reinforces the need for a standardized classification system of oral/head and neck MiNENs.
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Affiliation(s)
- Pawat Sripodok
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan.
- Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
| | - Atsumu Kouketsu
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
| | - Kanako Kuroda
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
| | - Hitoshi Miyashita
- Department of Dentistry and Oral Surgery, Tohoku Medical and Pharmaceutical University Hospital, Miyagi, Japan
| | - Tsuyoshi Sugiura
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
| | - Hiroyuki Kumamoto
- Division of Oral Pathology, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
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Kim DH, Kim B, Chung DJ, Kim KA, Lee SL, Choi MH, Kim H, Rha SE. Predicting resection margin status of pancreatic neuroendocrine tumors on CT: performance of NCCN resectability criteria. Br J Radiol 2023; 96:20230503. [PMID: 37750830 PMCID: PMC10646654 DOI: 10.1259/bjr.20230503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 07/18/2023] [Accepted: 08/21/2023] [Indexed: 09/27/2023] Open
Abstract
OBJECTIVE To test the performance of the National Comprehensive Cancer Network (NCCN) CT resectability criteria for predicting the surgical margin status of pancreatic neuroendocrine tumor (PNET) and to identify factors associated with margin-positive resection. METHODS Eighty patients with pre-operative CT and upfront surgery were retrospectively enrolled. Two radiologists assessed the CT resectability (resectable [R], borderline resectable [BR], unresectable [UR]) of the PNET according to NCCN criteria. Logistic regression was used to identify factors associated with resection margin status. κ statistics were used to evaluate interreader agreements. Kaplan-Meier method with log-rank test was used to estimate and compare recurrence-free survival (RFS). RESULTS Forty-five patients (56.2%) received R0 resection and 35 (43.8%) received R1 or R2 resection. R0 resection rates were 63.6-64.2%, 20.0-33.3%, and 0% for R, BR, and UR diseases, respectively (all p ≤ 0.002), with a good interreader agreement (κ, 0.74). Tumor size (<2 cm, 2-4 cm, and >4 cm; odds ratio (OR), 9.042-18.110; all p ≤ 0.007) and NCCN BR/UR diseases (OR, 5.918; p = 0.032) were predictors for R1 or R2 resection. The R0 resection rate was 91.7% for R disease <2 cm and decreased for larger R disease. R0 resection and smaller tumor size in R disease improved RFS. CONCLUSION NCCN resectability criteria can stratify patients with PNET into distinct groups of R0 resectability. Adding tumor size to R disease substantially improves the prediction of R0 resection, especially for PNETs <2 cm. ADVANCES IN KNOWLEDGE Tumor size and radiologic resectability independently predicted margin status of PNETs.
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Affiliation(s)
- Dong Hwan Kim
- Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Bohyun Kim
- Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong Jin Chung
- Department of Radiology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyung Ah Kim
- Department of Radiology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Su Lim Lee
- Department of Radiology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Moon Hyung Choi
- Department of Radiology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hokun Kim
- Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Eun Rha
- Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Liu Z, Hu F, Guo S, Zhang P, Li G, Qin Y. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report. Open Life Sci 2023; 18:20220672. [PMID: 38035045 PMCID: PMC10685408 DOI: 10.1515/biol-2022-0672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 10/05/2023] [Accepted: 10/05/2023] [Indexed: 12/02/2023] Open
Abstract
Necrolytic migratory erythema (NME) is usually associated with paraneoplastic syndrome caused by functional pancreatic neuroendocrine tumor (PNET). Accurate diagnosis and effective treatment of NET-related NME is challenging due to its rarity and lack of typical clinical symptoms and specific pathological manifestations. Here we report a rare case of PNET with NME as the initial manifestation. 68Ga-DOTA-TATE PET/MR was used to detect the primary pancreatic and metastatic liver tumors. Finally, the patient was diagnosed as PNET via liver biopsy. After four cycles of standard capecitabine plus temozolomide chemotherapy combined with long-acting octreotide, the patient's skin lesions on both lower extremities improved only slightly, while tumors remained stable and unchanged in size. Then the patient was treated with surufatinib. Two months later, the skin lesions healed completely, and tumors responded significantly. This rare case suggests that surufatinib may be a promising therapy for patients with PNET-associated NME.
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Affiliation(s)
- Zhongan Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan430022, China
| | - Feng Hu
- Department of Dermatology, Wuhan No. 1 Hospital, Wuhan430022, China
| | - Shuang Guo
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan430022, China
| | - Peng Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan430022, China
| | - Guiling Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan430022, China
| | - You Qin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan430022, China
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10
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Zhong L, Pan Y, Han S, Qi Q, Liao H, Jiang Y, Shen J. The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma. Indian J Cancer 2023; 60:512-520. [PMID: 38206083 DOI: 10.4103/ijc.ijc_151_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 03/01/2021] [Indexed: 01/12/2024]
Abstract
PURPOSE The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. METHODS Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. RESULTS In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). CONCLUSIONS Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.
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Affiliation(s)
- Liping Zhong
- Department of Medical Oncology, Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Zhejiang, China
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11
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Jazeer M, Garusinghe C. Occurrence of Immune Thrombocytopenic Purpura Following Enucleation of a Neuroendocrine Tumor of the Head of the Pancreas. Cureus 2023; 15:e47109. [PMID: 38022022 PMCID: PMC10646959 DOI: 10.7759/cureus.47109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2023] [Indexed: 12/01/2023] Open
Abstract
Neuroendocrine tumors are growths occurring in various organs including the pancreas which contain endocrine tissue. Pancreatic neuroendocrine tumors are rare in occurrence with an incidence of <1 per 100,000 individuals. But the incidence is rising and the said tumors are becoming more common in the world. Herein we report a case of a 49-year-old female with a background history of poorly controlled type 2 diabetes mellitus for 7 years, dyslipidemia, and bronchial asthma for 19 years on regular inhaler therapy presenting with a history of back pain for 3 months duration. With serial investigations, she was found to have a neuroendocrine tumor involving the head of the pancreas with no local infiltration and distant metastases. Whipple's procedure was performed after which she developed thrombocytopenia from post-operative day 1 itself. Following this, she was diagnosed as having immune thrombocytopenic purpura and being managed with oral corticosteroids, after which she made a successful recovery from the acute condition but with multiple relapses from time to time.
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Affiliation(s)
- Mohamed Jazeer
- Internal Medicine, Teaching Hospital, Batticaloa, Batticaloa, LKA
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12
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Helderman NC, Suerink M, Kilinç G, van den Berg JG, Nielsen M, Tesselaar ME. Relation between WHO Classification and Location- and Functionality-Based Classifications of Neuroendocrine Neoplasms of the Digestive Tract. Neuroendocrinology 2023; 114:120-133. [PMID: 37690447 PMCID: PMC10836754 DOI: 10.1159/000534035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 08/21/2023] [Indexed: 09/12/2023]
Abstract
Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise of a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues is due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare the literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are, by definition, high grade and therefore constitute a separate entity from NETs. Moreover, the term NET is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding the current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.
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Affiliation(s)
- Noah C. Helderman
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Manon Suerink
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Gül Kilinç
- Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands
| | - José G. van den Berg
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Maartje Nielsen
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Margot E.T. Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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13
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Bocchini M, Tazzari M, Ravaioli S, Piccinini F, Foca F, Tebaldi M, Nicolini F, Grassi I, Severi S, Calogero RA, Arigoni M, Schrader J, Mazza M, Paganelli G. Circulating hsa-miR-5096 predicts 18F-FDG PET/CT positivity and modulates somatostatin receptor 2 expression: a novel miR-based assay for pancreatic neuroendocrine tumors. Front Oncol 2023; 13:1136331. [PMID: 37287922 PMCID: PMC10242108 DOI: 10.3389/fonc.2023.1136331] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 04/25/2023] [Indexed: 06/09/2023] Open
Abstract
Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are rare diseases encompassing pancreatic (PanNETs) and ileal NETs (SINETs), characterized by heterogeneous somatostatin receptors (SSTRs) expression. Treatments for inoperable GEP-NETs are limited, and SSTR-targeted Peptide Receptor Radionuclide Therapy (PRRT) achieves variable responses. Prognostic biomarkers for the management of GEP-NET patients are required. 18F-FDG uptake is a prognostic indicator of aggressiveness in GEP-NETs. This study aims to identify circulating and measurable prognostic miRNAs associated with 18F-FDG-PET/CT status, higher risk and lower response to PRRT. Methods Whole miRNOme NGS profiling was conducted on plasma samples obtained from well-differentiated advanced, metastatic, inoperable G1, G2 and G3 GEP-NET patients enrolled in the non-randomized LUX (NCT02736500) and LUNET (NCT02489604) clinical trials prior to PRRT (screening set, n= 24). Differential expression analysis was performed between 18F-FDG positive (n=12) and negative (n=12) patients. Validation was conducted by Real Time quantitative PCR in two distinct well-differentiated GEP-NET validation cohorts, considering the primary site of origin (PanNETs n=38 and SINETs n=30). The Cox regression was applied to assess independent clinical parameters and imaging for progression-free survival (PFS) in PanNETs. In situ RNA hybridization combined with immunohistochemistry was performed to simultaneously detect miR and protein expression in the same tissue specimens. This novel semi-automated miR-protein protocol was applied in PanNET FFPE specimens (n=9). In vitro functional experiments were performed in PanNET models. Results While no miRNAs emerged to be deregulated in SINETs, hsa-miR-5096, hsa-let-7i-3p and hsa-miR-4311 were found to correlate with 18F-FDG-PET/CT in PanNETs (p-value:<0.005). Statistical analysis has shown that, hsa-miR-5096 can predict 6-month PFS (p-value:<0.001) and 12-month Overall Survival upon PRRT treatment (p-value:<0.05), as well as identify 18F-FDG-PET/CT positive PanNETs with worse prognosis after PRRT (p-value:<0.005). In addition, hsa-miR-5096 inversely correlated with both SSTR2 expression in PanNET tissue and with the 68Gallium-DOTATOC captation values (p-value:<0.05), and accordingly it was able to decrease SSTR2 when ectopically expressed in PanNET cells (p-value:<0.01). Conclusions hsa-miR-5096 well performs as a biomarker for 18F-FDG-PET/CT and as independent predictor of PFS. Moreover, exosome-mediated delivery of hsa-miR-5096 may promote SSTR2 heterogeneity and thus resistance to PRRT.
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Affiliation(s)
- Martine Bocchini
- Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Marcella Tazzari
- Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Sara Ravaioli
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Filippo Piccinini
- Scientific Directorate, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Flavia Foca
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Michela Tebaldi
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Fabio Nicolini
- Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Ilaria Grassi
- Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Stefano Severi
- Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Raffaele Adolfo Calogero
- Molecular Biotechnology Center, Department of Biotechnology and Health Sciences, University of Turin, Turin, Italy
| | - Maddalena Arigoni
- Molecular Biotechnology Center, Department of Biotechnology and Health Sciences, University of Turin, Turin, Italy
| | - Joerg Schrader
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Massimiliano Mazza
- Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Giovanni Paganelli
- Nuclear Medicine and Radiometabolic Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
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Prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT in pancreatic neuroendocrine neoplasms. Eur Radiol 2023; 33:2713-2724. [PMID: 36378252 DOI: 10.1007/s00330-022-09235-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 10/07/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022]
Abstract
OBJECTIVES We aimed to evaluate the prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT (CER on PVP) and compare its prognostic performance to prevailing grading and staging systems in pancreatic neuroendocrine neoplasms (PanNENs). METHODS In this retrospective study, data on 465 patients (development cohort) who underwent upfront curative-intent resection for PanNEN were used to assess the performance of CER on PVP and tumor size measured by CT (CT-Size) in predicting recurrence-free survival (RFS) using Harrell's C-index and to determine their optimal cutoffs to stratify RFS using a multi-way partitioning algorithm. External data on 184 patients (test cohort) were used to validate the performance of CER on PVP in predicting RFS and overall survival (OS) and compare its predictive performance with those of CT-Size, 2019 World Health Organization classification system (WHO), and the 8th American Joint Committee on Cancer staging system (AJCC). RESULTS In the test cohort, CER on PVP showed C-indexes of 0.83 (95% confidence interval [CI], 0.74-0.91) and 0.84 (95% CI, 0.73-0.95) for predicting RFS and OS, respectively, which were higher than those for the WHO (C-index: 0.73 for RFS [p = .002] and 0.72 for OS [p = .004]) and AJCC (C-index, 0.67 for RFS [p = .002] and 0.58 for OS [p = .002]). CT-Size obtained C-indexes of 0.71 for RFS and 0.61 for OS. CONCLUSIONS CER on PVP showed superior predictive performance on postoperative survival in PanNEN than current grading and staging systems, indicating its potential as a noninvasive preoperative prognostic tool. KEY POINTS • In pancreatic neuroendocrine neoplasms, the tumor-to-parenchymal enhancement ratio on portal venous-phase CT (CER on PVP) showed acceptable predictive performance of postoperative outcomes. • CER on PVP showed superior predictive performance of postoperative survival over the current WHO classification and AJCC staging system.
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Ziogas IA, Rallis KS, Tasoudis PT, Moris D, Schulick RD, Del Chiaro M. Management and outcomes of mixed adenoneuroendocrine carcinoma of the ampulla of Vater: A systematic review and pooled analysis of 56 patients. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:682-687. [PMID: 36646615 DOI: 10.1016/j.ejso.2023.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 12/31/2022] [Accepted: 01/07/2023] [Indexed: 01/11/2023]
Abstract
BACKGROUND Tumors of mixed neuroendocrine and nonneuroendocrine histology are classified as collision, combined, or amphicrine and can occur in most organs, including the hepato-pancreato-biliary tract. Given the rarity of mixed adenoneuroendocrine carcinoma (MANEC) of the ampulla of Vater, the patient characteristics, management, and outcomes remain unclear. We sought to systematically review the worldwide literature on ampullary MANECs. METHODS Eligible studies were identified through a systematic search of the MEDLINE (via PubMed), Scopus, and Cochrane Library databases (end-of-search-date: January 5th, 2022), according to the PRISMA 2020 statement. RESULTS A total of 39 studies reporting on 56 patients with ampullary MANEC were included. The median age was 63.0 (interquartile range [IQR]: 51.0-69.0) years and 55.6% were male (n = 25/45). Most had combined tumors (64.4%; n = 29/45), followed by collision (24.4%; n = 11/45), and amphicrine tumors (11.1%; n = 5/45). More than half had lymph node metastasis (56.8%; n = 25/44), yet only 7.9% had distant metastasis (n = 3/38). Tumor resection (i.e., mostly pancreaticoduodenectomy) was performed in 96.3% (n = 52/54), followed by adjuvant chemotherapy in 61.8% (n = 21/34). Nearly half experienced disease recurrence (47.2%; n = 17/36) over a median follow-up of 12.0 (IQR: 3.0-16.0) months, and 42.1% (n = 16/38) died over a median follow-up of 12.0 (IQR: 4.0-18.0) months. The most common cause of death was disease progression/recurrence in 81.3% (n = 13/16). CONCLUSION Early diagnosis and management of ampullary MANEC is challenging yet crucial to improve outcomes since many patients are diagnosed at an advanced disease stage and have unfavorable outcomes. Multicenter granular data are warranted to further understand and improve outcomes in these patients.
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Affiliation(s)
- Ioannis A Ziogas
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA; Surgery Working Group, Society of Junior Doctors, Athens, Greece.
| | - Kathrine S Rallis
- Surgery Working Group, Society of Junior Doctors, Athens, Greece; Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Panagiotis T Tasoudis
- Surgery Working Group, Society of Junior Doctors, Athens, Greece; School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA; University of Colorado Cancer Center, Aurora, CO, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA; University of Colorado Cancer Center, Aurora, CO, USA
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16
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Ziogas IA, Tasoudis PT, Borbon LC, Sherman SK, Breheny PJ, Chandrasekharan C, Dillon JS, Bellizzi AM, Howe JR. Surgical Management of G3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Systematic Review and Meta-analysis. Ann Surg Oncol 2023; 30:148-160. [PMID: 36227392 DOI: 10.1245/s10434-022-12643-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 08/15/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are rare, aggressive tumors with poor prognosis. The World Health Organization 2017 and 2019 classifications further subdivided G3 NENs into G3 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Current guidelines favor medical management in most of these patients, and the role of surgical management is not well defined. We performed a systematic literature review and meta-analysis of surgical management versus nonsurgical management for G3 GEP NENs. MATERIALS AND METHODS A PRISMA-compliant systematic review of the MEDLINE, Embase, Scopus, and Cochrane Library databases (end-of-search date: 16 July 2021) was conducted. Individual patient survival data were reconstructed, and random-effects meta-analyses were performed. RESULTS Fourteen studies comprising 1810 surgical and 910 nonsurgical patients were systematically reviewed. Publication bias adjusted meta-analysis of 12 studies (1788 surgical and 857 nonsurgical patients) showed increased overall survival (OS) after surgical compared with nonsurgical management for G3 GEP NENs [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.31-0.53]. Subgroup meta-analyses showed increased OS after surgical management for both pancreatic and gastrointestinal primary sites separately. In another subgroup meta-analysis of G3 GEP NETs (not NECs), surgical management was associated with increased OS compared with nonsurgical management (HR 0.26, 95% CI 0.11-0.61). CONCLUSIONS Surgical management of G3 GEP NENs may provide a potential survival benefit in well-selected cases. Further research is needed to define which patients will benefit most from surgical versus nonsurgical management. The current literature is limited by inconsistent reporting of survival outcomes in surgical versus nonsurgical groups, tumor grade, differentiation, primary tumor site, and selection criteria for surgical and nonsurgical management.
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Affiliation(s)
- Ioannis A Ziogas
- Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | | | - Luis C Borbon
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Scott K Sherman
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Patrick J Breheny
- Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA, USA
| | | | - Joseph S Dillon
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Andrew M Bellizzi
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - James R Howe
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
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Development and validation of a combined nomogram model based on deep learning contrast-enhanced ultrasound and clinical factors to predict preoperative aggressiveness in pancreatic neuroendocrine neoplasms. Eur Radiol 2022; 32:7965-7975. [PMID: 35389050 DOI: 10.1007/s00330-022-08703-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/21/2022] [Accepted: 02/25/2022] [Indexed: 01/03/2023]
Abstract
OBJECTIVES This study aimed to develop and validate a combined nomogram model based on deep learning (DL) contrast-enhanced ultrasound (CEUS) and clinical factors to preoperatively predict the aggressiveness of pancreatic neuroendocrine neoplasms (PNENs). METHODS In this retrospective study, consecutive patients with histologically proven PNENs underwent CEUS examination at the initial work-up between January 2010 and October 2020. Patients were randomly allocated to the training and test sets. Typical sonographic and enhanced images of PNENs were selected to fine-tune the SE-ResNeXt-50 network. A combined nomogram model was developed by incorporating the DL predictive probability with clinical factors using multivariate logistic regression analysis. The utility of the proposed model was evaluated using receiver operator characteristic, calibration, and decision curve analysis. RESULTS A total of 104 patients were evaluated, including 80 (mean age ± standard deviation, 47 years ± 12; 56 males) in the training set and 24 (50 years ± 12; 14 males) in the test set. The DL model displayed effective image recognition with an AUC of 0.81 (95%CI: 0.62-1.00) in the test set. The combined nomogram model that incorporated independent clinical risk factors, such as tumor size, arterial enhancement level, and DL predictive probability, showed strong discrimination, with an AUC of 0.85 (95%CI: 0.69-1.00) in the test set with good calibration. Decision curve analysis verified the clinical usefulness of the combined nomogram. CONCLUSIONS The combined nomogram model could serve as a preoperative, noninvasive, and precise evaluation tool to differentiate aggressive and non-aggressive PNENs. KEY POINTS • Tumor size (odds ratio [OR], 1.58; p = 0.02), arterial enhancement level (OR, 0.04; p = 0.008), and deep learning predictive probability (OR, 288.46; p < 0.001) independently predicted aggressiveness of pancreatic neuroendocrine neoplasms preoperatively. • The combined model predicted aggressiveness better than the clinical model (AUC: 0.97 vs. 0.87, p = 0.009), achieving AUC values of 0.97 and 0.85 in the training set and the test set, respectively.
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Sedhai S, Mohammed F, Sahtiya S, Sanaullah S, Pritwani P, Saleem F, Abere A, Ghaffari MAZ. Pancreatic Neuroendocrine Tumor (PNET) Presenting as a Pseudocyst: A Case Report. Cureus 2022; 14:e29617. [DOI: 10.7759/cureus.29617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2022] [Indexed: 11/05/2022] Open
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Lee ONY, Tan KV, Tripathi V, Yuan H, Chan WWL, Chiu KWH. The Role of 68 Ga-DOTA-SSA PET/CT in the Management and Prediction of Peptide Receptor Radionuclide Therapy Response for Patients With Neuroendocrine Tumors : A Systematic Review and Meta-analysis. Clin Nucl Med 2022; 47:781-793. [PMID: 35485851 DOI: 10.1097/rlu.0000000000004235] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE The aim of this study was to identify and evaluate the role of 68 Ga-DOTA-somatostatin analog (SSA) PET/CT in guiding treatment for patients with neuroendocrine tumors (NETs) based on published literature, with specific focus on the ability of PET/CT to impact clinical management and predict peptide receptor radionuclide therapy (PRRT) response. PATIENTS AND METHODS A systematic literature search of articles up to December 2021 was performed using PubMed and Scopus. Eligible studies included ≥10 patients with confirmed or suspected NETs who had undergone pretreatment staging 68 Ga-DOTA-SSA PET/CT. A meta-analysis using the random-effects model was conducted to determine the overall change in management after PET/CT, whereas PET/CT-derived parameters that correlated with PRRT outcome were summarized from studies that assessed its predictive capabilities. RESULTS A total of 39 studies were included in this systemic review, of which 2266 patients from 24 studies were included for meta-analysis. We showed that PET/CT resulted in a change in clinical management in 36% (95% confidence interval, 31%-41%; range, 3%-66%) of patients. Fifteen studies consisting of 618 patients examined the prognostic ability of 68 Ga-DOTA-SSA PET/CT for PRRT. Of those, 8 studies identified a higher pretreatment SUV to favor PRRT, and 4 identified PET-based radiomic features for somatostatin receptor heterogeneity to be predictive of PRRT response. CONCLUSIONS Along with its diagnostic abilities, 68 Ga-DOTA-SSA PET/CT can impact treatment decision-making and may predict PRRT response in patients with NETs. More robust studies should be conducted to better elucidate the prognostic role of somatostatin receptor PET/CT in optimizing treatment for clinical outcome.
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Affiliation(s)
- Osher Ngo Yung Lee
- From the Edinburgh Medical School, The University of Edinburgh, Edinburgh, United Kingdom
| | - Kel Vin Tan
- Department of Oncology, The University of Oxford, Oxford, United Kingdom
| | - Vrijesh Tripathi
- Department of Mathematics and Statistics, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago
| | - Hui Yuan
- Department of Nuclear Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | | | - Keith Wan Hang Chiu
- Department of Diagnostic and Interventional Radiology, Kwong Wah Hospital, Hong Kong
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Prabandari NPSS, Wande IN, Mahartini NN. Recurrent Hypoglycemia in Baby with Insulinoma: A Case Report. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Insulinoma is a functional neuroendocrine tumor in the pancreas that can cause hypoglycemia due to endogenic hyperinsulinism. Insulinoma is a rare case with an incidence of 1–4 cases per million people each year. Insulinoma can occur at various ages and mostly occurs in adults with a predominance in women.
CASE REPORT: A baby boy aged 1 month 23 days was referred from Prof. Dr. W. Z. Johannes Hospital with the chief complaint was seizures. The results of the examination of blood glucose levels at Sanglah Hospital were 28 mg/dl. There were some episodes of normal blood glucose level in the patient after having some doses of glucose infusion therapy. However, it was only for a while, the blood glucose level came back low and induced the symptoms of the seizure (neuroglycopenia). The seizures stopped after having anticonvulsant therapy and blood glucose levels within normal limits. These symptoms were consistent with the Whipple triad in insulinoma. The patient has an elevated insulin level (92 IU/ml). Computed tomography scan of the abdomen with contrast showed a mass in the caudal part of the pancreas. The patient underwent a partial pancreatectomy. Histomorphology features showed pancreatic neuroendocrine tumors without metastases. Immunohistochemical results of Ki-67 showed well-differentiated neuroendocrine tumors grade 2.
CONCLUSION: Based on clinical, physical examination, laboratory, and radiology findings, the patient was diagnosed with recurrent hypoglycemia due to insulinoma and improved with partial pancreatectomy.
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Chen HY, Pan Y, Chen JY, Liu LL, Yang YB, Li K, Yu RS, Shao GL. Quantitative analysis of enhanced CT in differentiating well-differentiated pancreatic neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Eur Radiol 2022; 32:8317-8325. [PMID: 35759016 DOI: 10.1007/s00330-022-08891-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 05/02/2022] [Accepted: 05/18/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To identify quantitative CT features for distinguishing well-differentiated pancreatic neuroendocrine tumors (PNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PNECs). MATERIALS AND METHODS Seventeen patients with PNECs and 131 patients with PNETs confirmed by biopsy or surgery were retrospectively included. General demographic (sex, age) and CT quantitative parameters (arterial/portal absolute enhancement, arterial/portal relative enhancement ratio, arterial/portal enhancement ratio) were collected. Univariate and multivariate logistic regression analyses were performed to confirm independent variables for differentiating PNECs from PNETs. Receiver operating characteristic (ROC) curves for each quantitative parameter were generated to determine their diagnostic ability. RESULTS PNECs had a much lower mean arterial/portal absolute enhancement value (19.5 ± 11.0 vs. 78.8 ± 47.2; 28.1 ± 15.8 vs. 77.0 ± 39.4), arterial/portal relative enhancement ratio (0.57 ± 0.36 vs. 2.03 ± 1.31; 0.80 ± 0.52 vs. 1.99 ± 1.13), and arterial/portal enhancement ratio (0.62 ± 0.27 vs. 1.22 ± 0.49; 0.74 ± 0.19 vs. 1.21 ± 0.36) than PNETs (all p < 0.001). After multivariable analysis, arterial absolute enhancement (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93, 0.99) and portal absolute enhancement (OR: 0.96, 95% CI: 0.92, 0.99) were independent factors for differentiating PNECs from PNETs. For each quantitative parameter, arterial lesion enhancement yielded the highest diagnostic performance, with an area under the curve (AUC) of 0.922 (95% CI: 0.867-0.960), followed by portal absolute enhancement. CONCLUSIONS Arterial/portal absolute enhancements were independent predictors with good diagnostic accuracy for differentiating between PNETs and PNECs. Quantitative parameters of enhanced CT can distinguish PNECs from PNETs. KEY POINTS • PNECs were hypovascular and had a much lower enhanced CT attenuation in both arterial and portal phases than well-differentiated PNETs. • Quantitative parameters derived from enhanced CT can be used to distinguish PNECs from PNETs. • Arterial absolute enhancement and portal absolute enhancement were independent predictive factors for differentiating between PNETs and PNECs.
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Affiliation(s)
- Hai-Yan Chen
- Department of Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China.,Institue of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Yao Pan
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88#, Hangzhou, 310009, China
| | - Jie-Yu Chen
- Department of Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China.,Institue of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Lu-Lu Liu
- Department of Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China.,Institue of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Yong-Bo Yang
- Department of Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China.,Institue of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Kai Li
- Department of Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China.,Institue of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Ri-Sheng Yu
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88#, Hangzhou, 310009, China.
| | - Guo-Liang Shao
- Institue of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, 310018, China. .,Department of Interventional Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China. .,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Qingchun Road 79#, Hangzhou, 310006, China.
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22
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Zhang XF, Xue F, Wu Z, Lopez-Aguiar AG, Poultsides G, Makris E, Rocha F, Kanji Z, Weber S, Fisher A, Fields R, Krasnick BA, Idrees K, Smith PM, Cho C, Beems M, Lyu Y, Maithel SK, Pawlik TM. Development and Validation of a Modified Eighth AJCC Staging System for Primary Pancreatic Neuroendocrine Tumors. Ann Surg 2022; 275:e773-e780. [PMID: 32511134 PMCID: PMC10188291 DOI: 10.1097/sla.0000000000004039] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system. BACKGROUND Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial. METHODS Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification. RESULTS The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts. CONCLUSION A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | | | | | - Flavio Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Zaheer Kanji
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Sharon Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Alexander Fisher
- 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
| | - Bradley A Krasnick
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - 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
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Yi Lyu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Timothy M Pawlik
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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23
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Wang H, Ding D, Qin T, Zhang H, Liu J, Zhao J, Wu CH, Javed A, Wolfgang C, Guo S, Chen Q, Zhao W, Shi W, Zhu F, Guo X, Li X, Peng F, He R, Xu S, Jin J, Wu Y, Nuer A, Edil B, Tien YW, Jin G, Zheng L, He J, Liu J, Liu Y, Wang M, Qin R. Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors. HPB (Oxford) 2022; 24:681-690. [PMID: 34836754 DOI: 10.1016/j.hpb.2021.10.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/15/2021] [Accepted: 10/27/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. METHODS We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. RESULTS Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). CONCLUSION These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.
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Affiliation(s)
- Hebin Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ding Ding
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Tingting Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Jun Liu
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong 250000, China
| | - Junfang Zhao
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Chien-Hui Wu
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei 10002, Taiwan
| | - Ammar Javed
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Christopher Wolfgang
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Shiwei Guo
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai 200433, China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
| | - Weihong Zhao
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Wei Shi
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong 250000, China
| | - Feng Zhu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xingjun Guo
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xu Li
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Feng Peng
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ruizhi He
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Simiao Xu
- Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jikuan Jin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Yi Wu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Abula Nuer
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Barish Edil
- Department of Surgery, University of Oklahoma, Oklahoma City, OK 73104, USA
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei 10002, Taiwan
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai 200433, China
| | - Lei Zheng
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jin He
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jianhua Liu
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
| | - Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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24
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Mitrovic-Jovanovic M, Grubor N, Milosevic S, Jankovic A, Stosic K, Ostojic S, Ninic A, Micev M, Djokic Kovac J. Total Pancreatectomy for Multicentric Cystic Neuroendocrine Tumor of the Pancreas: A Case Report. Diagnostics (Basel) 2022; 12:diagnostics12041003. [PMID: 35454051 PMCID: PMC9028915 DOI: 10.3390/diagnostics12041003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/12/2022] [Accepted: 04/12/2022] [Indexed: 02/01/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are uncommon pancreatic neoplasms with malignant potential, heterogeneous clinical behavior, as well as imaging appearance. These tumors represent less than 3% of all pancreatic neoplasms with typical CT presentation as solid, well-circumscribed, hypervascular lesions. Cystic PNET is a rare pancreatic tumor which is nowadays more often detected due to the widespread use of high-resolution cross-sectional imaging. They are mainly solitary lesions most commonly localized in the body and the tail of the pancreas. Due to cystic presentation these lesions often present a diagnostic challenge to both experienced radiologists and pathologists. Herein, we present a rare case of synchronous, multiple cystic and solid pancreatic neuroendocrine tumors, which due to their extensiveness required total dudenopancreatectomy with splenectomy. Histopathological findings confirmed microscopic and macroscopic cystic components as well as typical solid variants of neuroendocrine tumors along the entire pancreas.
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Affiliation(s)
- Milica Mitrovic-Jovanovic
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Centre of Serbia, Pasterova No. 2, 11000 Belgrade, Serbia; (S.M.); (A.J.); (K.S.); (J.D.K.)
- Correspondence: ; Tel.: +381-63-8064620
| | - Nikica Grubor
- Department for HBP Surgery, Clinic for Digestive Surgery, University Clinical Centre of Serbia, Koste Todorovica Street No. 6, 11000 Belgrade, Serbia; (N.G.); (S.O.); (A.N.)
- Department for Surgery with Anesthesiology, Faculty of Medicine, University of Belgrade, Dr Subotica No. 8, 11000 Belgrade, Serbia
| | - Stefan Milosevic
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Centre of Serbia, Pasterova No. 2, 11000 Belgrade, Serbia; (S.M.); (A.J.); (K.S.); (J.D.K.)
| | - Aleksandra Jankovic
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Centre of Serbia, Pasterova No. 2, 11000 Belgrade, Serbia; (S.M.); (A.J.); (K.S.); (J.D.K.)
| | - Katarina Stosic
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Centre of Serbia, Pasterova No. 2, 11000 Belgrade, Serbia; (S.M.); (A.J.); (K.S.); (J.D.K.)
| | - Slavenko Ostojic
- Department for HBP Surgery, Clinic for Digestive Surgery, University Clinical Centre of Serbia, Koste Todorovica Street No. 6, 11000 Belgrade, Serbia; (N.G.); (S.O.); (A.N.)
- Department for Surgery with Anesthesiology, Faculty of Medicine, University of Belgrade, Dr Subotica No. 8, 11000 Belgrade, Serbia
| | - Aleksandar Ninic
- Department for HBP Surgery, Clinic for Digestive Surgery, University Clinical Centre of Serbia, Koste Todorovica Street No. 6, 11000 Belgrade, Serbia; (N.G.); (S.O.); (A.N.)
| | - Marjan Micev
- Department for Pathology, Clinic for Digestive Surgery, University Clinical Centre of Serbia, Koste Todorovica Street No. 6, 11000 Belgrade, Serbia;
| | - Jelena Djokic Kovac
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Centre of Serbia, Pasterova No. 2, 11000 Belgrade, Serbia; (S.M.); (A.J.); (K.S.); (J.D.K.)
- Department for Radiology, Faculty of Medicine, University of Belgrade, Dr Subotica No. 8, 11000 Belgrade, Serbia
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25
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Appelstrand A, Bergstedt F, Elf AK, Fagman H, Hedenström P. Endoscopic ultrasound-guided side-fenestrated needle biopsy sampling is sensitive for pancreatic neuroendocrine tumors but inadequate for tumor grading: a prospective study. Sci Rep 2022; 12:5971. [PMID: 35396490 PMCID: PMC8993931 DOI: 10.1038/s41598-022-09923-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 03/30/2022] [Indexed: 11/10/2022] Open
Abstract
Accurate pretreatment grading of pancreatic neuroendocrine tumors (PanNETs) is important to guide patient management. We aimed to evaluate endoscopic ultrasound-guided fine needle biopsy sampling (EUS-FNB) for the preoperative diagnosis and grading of PanNETs. In a tertiary-center setting, patients with suspected PanNETs were prospectively subjected to 22-gauge, reverse-bevel EUS-FNB. The EUS-FNB samples (Ki-67EUS) and corresponding surgical specimens (Ki-67SURG) were analyzed with Ki-67 indexing and thereafter tumor grading, (GRADEEUS) and (GRADESURG) respectively. In total 52 PanNET-patients [median age: 66 years; females: 25/52; surgical resection 22/52 (42%)] were included. EUS-FNB was diagnostic in 44/52 (85%). In 42 available FNB-slides, the median neoplastic cell count was 1034 (IQR: 504-3667) with 32/42 (76%), 22/42 (52%), and 14/42 (33%) cases exceeding 500, 1000, and 2000 neoplastic cells respectively. Ki-67SURG was significantly higher compared to Ki-67EUS with a moderate correlation comparing Ki-67EUS and Ki-67SURG (Pearson r = 0.60, r2 = 0.36, p = 0.011). The GRADEEUS had a weak level of agreement (κ = 0.08) compared with GRADESURG. Only 2/12 (17%) G2-tumors were correctly graded in EUS-FNB-samples. EUS-guided fine needle biopsy sampling is sensitive for preoperative diagnosis of PanNET but biopsy quality is relatively poor. Therefore, the approach seems suboptimal for pretreatment grading of PanNET.
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Affiliation(s)
- Alexander Appelstrand
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Fredrik Bergstedt
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anna-Karin Elf
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Henrik Fagman
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.,Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Per Hedenström
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. .,Division of Medical Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, Medicinmottagningen, Sahlgrenska Sjukhuset, Blå Stråket 3, 413 35, Gothenburg, Sweden.
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26
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Sutton TL, Pommier RF, Mayo SC, Gilbert EW, Papavasiliou P, Babicky M, Gerry J, Sheppard BC, Worth PJ. Similar Outcomes in Minimally Invasive versus Open Management of Primary Pancreatic Neuroendocrine Tumors: A Regional, Multi-Institutional Collaborative Analysis. Cancers (Basel) 2022; 14:cancers14061387. [PMID: 35326539 PMCID: PMC8946133 DOI: 10.3390/cancers14061387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 02/28/2022] [Accepted: 03/04/2022] [Indexed: 11/16/2022] Open
Abstract
In pancreatic neuroendocrine tumors (PNETs), the impact of minimally invasive (MI) versus open resection on outcomes remains poorly studied. We queried a multi-institutional pancreatic cancer registry for patients with resected non-metastatic PNET from 1996−2020. Recurrence-free (RFS), disease-specific survival (DSS), and operative complications were evaluated. Two hundred and eighty-two patients were identified. Operations were open in 139 (49%) and MI in 143 (51%). Pancreaticoduodenectomy was performed in 77 (27%, n = 23 MI), distal pancreatectomy in 184 (65%, n = 109 MI), enucleation in 13 (5%), and total pancreatectomy in eight (3%). Median follow-up was 50 months. Thirty-six recurrences and 13 deaths from recurrent disease yielded 5-year RFS and DSS of 85% and 95%, respectively. On multivariable analysis, grade 1 (HR 0.07, p < 0.001) and grade 2 (HR 0.20, p = 0.002) tumors were associated with improved RFS, while T3/T4 tumors were associated with worse RFS (OR 2.78, p = 0.04). MI resection was not associated with RFS (HR 0.53, p = 0.14). There was insufficient mortality to evaluate DSS with multivariable analysis. Of 159 patients with available NSQIP data, incisional surgical site infections (SSIs), organ space SSIs, Grade B/C pancreatic fistulas, reoperations, and need for percutaneous drainage did not differ by operative approach (all p > 0.2). Nodal harvest was similar for MI versus open distal pancreatectomies (p = 0.16) and pancreaticoduodenectomies (p = 0.28). Minimally invasive surgical management of PNETs is equivalent for oncologic and postoperative outcomes.
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Affiliation(s)
- Thomas L. Sutton
- Department of Surgery, Division of General Surgery, Oregon Heath & Science University (OHSU), Portland, OR 97239, USA; (T.L.S.); (E.W.G.); (B.C.S.)
| | - Rodney F. Pommier
- Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Oregon Heath & Science University (OHSU), Portland, OR 97239, USA; (R.F.P.); (S.C.M.)
| | - Skye C. Mayo
- Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Oregon Heath & Science University (OHSU), Portland, OR 97239, USA; (R.F.P.); (S.C.M.)
| | - Erin W. Gilbert
- Department of Surgery, Division of General Surgery, Oregon Heath & Science University (OHSU), Portland, OR 97239, USA; (T.L.S.); (E.W.G.); (B.C.S.)
| | | | - Michele Babicky
- The Oregon Clinic, Center for Advanced Surgery, Portland, OR 97213, USA; (M.B.); (J.G.)
| | - Jon Gerry
- The Oregon Clinic, Center for Advanced Surgery, Portland, OR 97213, USA; (M.B.); (J.G.)
| | - Brett C. Sheppard
- Department of Surgery, Division of General Surgery, Oregon Heath & Science University (OHSU), Portland, OR 97239, USA; (T.L.S.); (E.W.G.); (B.C.S.)
| | - Patrick J. Worth
- Department of Surgery, Division of General Surgery, Oregon Heath & Science University (OHSU), Portland, OR 97239, USA; (T.L.S.); (E.W.G.); (B.C.S.)
- Correspondence: ; Tel.: +1-503-346-0243; Fax: +1-503-494-8884
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27
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Hsiao TH, Wu CC, Tseng HH, Chen JH. Synchronous but separate neuroendocrine tumor and high-grade dysplasia/adenoma of the gall bladder: A case report. World J Clin Cases 2022; 10:2322-2329. [PMID: 35321155 PMCID: PMC8895191 DOI: 10.12998/wjcc.v10.i7.2322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/22/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gall bladder neuroendocrine tumors (GB-NETs) are rare, accounting for less than 0.5% of all NETs. They usually lack specific symptoms and are difficult to diagnose preoperatively. In most cases, GB-NETs are incidentally found after cholecystectomy for large polyps or cholelithiasis, causing acute or chronic cholecystitis. The coexistence of GB-NET and GB adenocarcinoma is very rare.
CASE SUMMARY We report a case of synchronous but separate GB-NET and adenoma with high-grade dysplasia in a patient who had undergone surgery for a progressively growing GB polypoid lesion. To the best of our knowledge, simultaneous separation of NETs and cancer in the GB has not been reported.
CONCLUSION Coexistent GB carcinoid tumor and adenocarcinoma is rare. A surveillance program is needed for these large GB polyps.
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Affiliation(s)
- Tsung-Hsien Hsiao
- Division of Gastroenterology and Hepatology, Taipei Tzu Chi Hospital, New Taipei City 231, Taiwan
| | - Chao-Chuan Wu
- Department of Surgery, Taipei Tzu Chi Hospital, New Taipei City 231, Taiwan
| | - Hui-Hwa Tseng
- Department of Pathology, Taipei Tzu Chi Hospital, New Taipei City 231, Taiwan
| | - Jiann-Hwa Chen
- Division of Gastroenterology and Hepatology; Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
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Havasi A, Sur D, Cainap SS, Lungulescu CV, Gavrilas LI, Cainap C, Vlad C, Balacescu O. Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers. Int J Mol Sci 2022; 23:1109. [PMID: 35163032 PMCID: PMC8834851 DOI: 10.3390/ijms23031109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/10/2022] [Accepted: 01/18/2022] [Indexed: 12/17/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.
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Affiliation(s)
- Andrei Havasi
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania; (A.H.); (C.C.)
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
- MedEuropa Radiotherapy Center, 410191 Oradea, Romania
| | - Daniel Sur
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania; (A.H.); (C.C.)
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
| | - Simona Sorana Cainap
- Department of Mother and Child, Pediatric Cardiology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
| | | | - Laura-Ioana Gavrilas
- Department of Bromatology, Hygiene, Nutrition, University of Medicine and Pharmacy “Iuliu Hatieganu”, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Calin Cainap
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania; (A.H.); (C.C.)
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
| | - Catalin Vlad
- Department of Surgery, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34–36, Republicii Street, 400015 Cluj-Napoca, Romania;
- Department of Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 8, Victor Babes Street, 400012 Cluj-Napoca, Romania
| | - Ovidiu Balacescu
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta’’, 400015 Cluj-Napoca, Romania
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Yang Z, Zhang D, Shi G. Reappraisal of a 2-cm Cutoff Size for the Management of Nonfunctional Pancreatic Neuroendocrine Tumors: A Population-Based Study. Front Endocrinol (Lausanne) 2022; 13:928341. [PMID: 35923628 PMCID: PMC9339804 DOI: 10.3389/fendo.2022.928341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 05/31/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Expectant observation and aggressive surgery are both recommended for small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). However, the optimal management of small NF-PanNETs remains disputable due to the heterogeneous clinical behavior. METHODS Patients who were diagnosed with pancreatic neuroendocrine neoplasms (PanNENs) between 2000 and 2018 were identified from the surveillance, epidemiology, and end results (SEER) database and reviewed retrospectively. Tumor aggressiveness was defined as poor differentiation, lymph node involvement, liver involvement, and advanced stage. The best cutoff of tumor size associated with tumor aggressiveness was determined through the receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to identify prognostic factors in patients with tumors of ≤2 cm. RESULTS A total of 5,172 patients with PanNENs were enrolled, including 1,760 (34.0%) tumors ≤2 cm and 3,412 (66.0%) tumors >2 cm. A 2.5-cm cutoff size was found to be associated with a satisfactory ability in predicting tumor aggressiveness. On multivariate analysis, age, gender, ethnicity, tumor grade, tumor number, and stage were independent prognostic factors for overall survival (OS) in patients with tumors less than or equal to 2 cm in size. A total of 1,621 patients were diagnosed with NF-PanNETs according to the WHO classification, of whom 1,350 underwent surgery, 271 performed active observation. The OS was significantly better in the surgery group compared to the observation group regardless of propensity score analysis. Additionally, a total of 407 patients were selected based on the multivariate Cox regression analysis, of whom 46 underwent observation, 361 underwent surgery, and the OS was comparable. CONCLUSION Expectant observation may be a reasonable alternative to aggressive surgical resection in highly selected small NF-PanNET patients. Also, the decision to observe versus surgery should not only be based on tumor size alone but also take into account other important clinicopathological factors.
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Kim HJ, Lee KH, Shim HJ, Hwang EC, Choi YD, Bang H, Cho SH, Chung IJ, Hwang JE, Lee MA, Bae WK. Prognostic Significance of the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Neuroendocrine Carcinoma. Chonnam Med J 2022; 58:29-36. [PMID: 35169557 PMCID: PMC8813653 DOI: 10.4068/cmj.2022.58.1.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 11/25/2022] Open
Abstract
Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.
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Affiliation(s)
- Hyeon-Jong Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Kang Han Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Hyun Jeong Shim
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Eu Chang Hwang
- Department of Urology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Yoo-Duk Choi
- Department of Pathology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Hyunjin Bang
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Sang Hee Cho
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Ik-Joo Chung
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
- Immunotherapy Innovation Center, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Jun Eul Hwang
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Woo Kyun Bae
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
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31
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Adnan A, Basu S. Discordance between Histopathological grading and Dual Tracer PET-CT findings ( 68Ga-DOTATATE and FDG) in metastatic Neuroendocrine Neoplasms and outcome of 177Lu-DOTATATE PRRT: does in-vivo molecular PET imaging perform better from 'prediction of tumour biology' viewpoint? J Nucl Med Technol 2021; 50:248-255. [PMID: 34876476 DOI: 10.2967/jnmt.121.261998] [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: 01/23/2021] [Accepted: 08/05/2021] [Indexed: 11/16/2022] Open
Abstract
Background and Aim: Discordance between histopathological grading and dual tracer PET-CT (68Ga-DOTATATE and FDG) findings in neuroendocrine tumours (NETs), though not typical, can be encountered in real-world scenario. The aim of this study was to assess patients with discordance between WHO 2017 grade predicted molecular PET-CT imaging and the actual dual tracer PET-CT findings (by exploring their histopathological, immunohistochemical and molecular imaging characteristics), with a view to identifying the prognostic determinants effecting outcome in a peptide receptor radionuclide therapy (PRRT) set-up. Methods: Thirty six patients of histopathologically proven inoperable, locally advanced/metastatic NETs, referred for PRRT were included in this study. The cohort was divided into two broad population groups: (a) those with discordance (between WHO 2017 grade predicted molecular imaging and the dual tracer PET-CT findings) and (b) control (showing both FDG and 68Ga-DOTATATE uptake). The cohort was divided based on dual tracer PET-CT into: (i) metabolically FDG non-avid and SSTR expressing tumors, (ii) metabolically active and non-68Ga-DOTATATE concentrating (SSTR expressing) and (iii) matched imaging characteristics with WHO 2017 grading system (showing both FDG and 68Ga-DOTATATE concentrating disease) for statistical analysis. Statistical analyses were done on SPSS 23.0. Descriptive statistics was used to analyze categorical data, multivariate analysis was used to assess the correlation between different variables with progression free survival (PFS) and overall survival (OS). Kaplan-Meier was used for survival analysis to calculate median survival and to analyze the survival based on WHO 2017 grading and dual tracer PET. Cox proportional hazards regression analysis was used to determine predictors of survival (OS and PFS). Results: In the entire cohort (n = 36), 24 patients (66.7%) showed discordance whereas 12 patients (33.3%) were in the control group. Among the patients showing discordance: 14 patients (38.9%) had metabolically inactive and SSTR expressing disease and remaining 10 patients (27.8%) had FDG concentrating and SSTR non-expressing disease. Those in the control group, 12 patients (33.3%) had intermediate grade NETs and showed matched (68Ga-DOTATATE and FDG concentrating lesions) disease. Multivariate analysis in patients with discordant findings demonstrated significant correlation of dual tracer PET with overall survival while no significant correlation could be established between WHO grade and overall survival in the discordant subgroups. No significant correlation could be appreciated between PFS and either dual tracer PET or WHO grading. The Kaplan-Meier survival analysis and Cox proportional hazards regression analysis demonstrated dual tracer PET-CT imaging to be significant prognostic determinant and predictor of outcome respectively. Conclusion: In summary, in NET patients with discordance between the two parameters, dual tracer PET-CT with FDG and 68Ga-DOTATATE performed better than WHO grading, differentiation status and immunohistochemistry in prognosticating and predicting outcome.
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Affiliation(s)
| | - Sandip Basu
- RADIATION MEDICINE CENTRE (BARC), Tata Memorial Hospital Annexe; Homi Bhabha National Institute, India
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Gamal GH. The utility of 18F-FDG PET/CT in the diagnosis, staging of non-functioning pancreatic neuroendocrine tumors. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-021-00617-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The non-functional PNETs are often discovered incidentally, they are commonly malignant and commonly present at a late stage with large size. We evaluate in this study the usefulness of 18F-FDG PET/CT in the detection and staging of non-functioning PNETs.
Results
Thirty patients with non-functioning PNETs were involved in this prospective study over a period starting from September 2016 to March 2021. Age ranged from 33 to 79 years. 18F-FDG PET/CT detected 26 patients had SUV max ≥ 2.5 of primary lesions and 4 lesions had SUV max < 2.5. There was no statistical significant between the site of the lesions and the type of grading of the tumors. 32 distant metastatic lesions were detected which show SUVmax ≥ 2.5 and only 9%where below 2.5. Of 30 patients, 4 patients (13.3%) of well differentiated tumor had altered their clinical strategies according to the results of PET/CT examinations. 18F-FDG PET/CT upstaged 1 patient with stage IB and 3 patients with IIA and B to stage IV.
Conclusion
The increased use of 18F-FDG PET/CT in the investigation of patient with PNETs allows for more accurate staging and therefore more appropriate management decision.
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33
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Alvarez Fallas ME, Pedraza-Arevalo S, Cujba AM, Manea T, Lambert C, Morrugares R, Sancho R. Stem/progenitor cells in normal physiology and disease of the pancreas. Mol Cell Endocrinol 2021; 538:111459. [PMID: 34543699 PMCID: PMC8573583 DOI: 10.1016/j.mce.2021.111459] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 03/19/2021] [Accepted: 09/13/2021] [Indexed: 02/08/2023]
Abstract
Though embryonic pancreas progenitors are well characterised, the existence of stem/progenitor cells in the postnatal mammalian pancreas has been long debated, mainly due to contradicting results on regeneration after injury or disease in mice. Despite these controversies, sequencing advancements combined with lineage tracing and organoid technologies indicate that homeostatic and trigger-induced regenerative responses in mice could occur. The presence of putative progenitor cells in the adult pancreas has been proposed during homeostasis and upon different stress challenges such as inflammation, tissue damage and oncogenic stress. More recently, single cell transcriptomics has revealed a remarkable heterogeneity in all pancreas cell types, with some cells showing the signature of potential progenitors. In this review we provide an overview on embryonic and putative adult pancreas progenitors in homeostasis and disease, with special emphasis on in vitro culture systems and scRNA-seq technology as tools to address the progenitor nature of different pancreatic cells.
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Affiliation(s)
- Mario Enrique Alvarez Fallas
- Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Sergio Pedraza-Arevalo
- Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Ana-Maria Cujba
- Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Teodora Manea
- Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Christopher Lambert
- Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Rosario Morrugares
- Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain; Departamento de Biologia Celular, Fisiologia e Inmunologia, Universidad de Cordoba, Cordoba, Spain; Hospital Universitario Reina Sofia, Cordoba, Spain
| | - Rocio Sancho
- Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK; Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany.
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Chang A, Sherman SK, Howe JR, Sahai V. Progress in the Management of Pancreatic Neuroendocrine Tumors. Annu Rev Med 2021; 73:213-229. [PMID: 34669433 DOI: 10.1146/annurev-med-042320-011248] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous and orphan group of neoplasms that vary in their histology, clinical features, prognosis, and management. The treatment of PNETs is highly dependent on the stage at presentation, tumor grade and differentiation, presence of symptoms from hormonal overproduction or from local growth, tumor burden, and rate of progression. The US Food and Drug Administration has recently approved many novel treatments, which have altered decision making and positively impacted the care and prognosis of these patients. In this review, we focus on the significant progress made in the management of PNETs over the past decade, as well as the active areas of research. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Amy Chang
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA; ,
| | - Scott K Sherman
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa, Iowa City, Iowa 52242, USA; ,
| | - James R Howe
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa, Iowa City, Iowa 52242, USA; ,
| | - Vaibhav Sahai
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA; ,
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35
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Broadbent R, Wheatley R, Stajer S, Jacobs T, Lamarca A, Hubner RA, Valle JW, Amir E, McNamara MG. Prognostic factors for relapse in resected gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis. Cancer Treat Rev 2021; 101:102299. [PMID: 34662810 DOI: 10.1016/j.ctrv.2021.102299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 09/02/2021] [Accepted: 09/05/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Gastroenteropancreatic neoplasms (GEP-NENs)can potentially be cured through surgical resection, but only 42-57% achieve 5-year disease-free survival.There is a lack of consensus regarding the factorsassociated withrelapse followingresection ofGEP-NENs. METHODS Asystematic review identified studies reporting factors associated with relapse in patients with GEP-NENs following resection of a primary tumour. Meta-analysis was performed to identify the factors prognostic for relapse-free survival (RFS)oroverall survival (OS). RESULTS 63 studies comprising 13,715 patients were included; 56 studies reported on pancreatic NENs (12,418 patients), 24 reported on patients with grade 1-2 tumours (4,735 patients). Median follow-up was 44.2 months, median RFS was 32 months. Pooling of multivariable analyses of GEP-NENs (all sites and grades) found the following factors predicted worse RFS (all p values < 0.05): vascular resection performed, metastatic disease resected, grade 2 disease, grade 3 disease, tumour size > 20 mm, R1 resection, microvascular invasion, perineural invasion, Ki-67 > 5% and any lymph node positivity. In a subgroup of studies comprising exclusively of grade 1-2 GEP-NENs, R1 resection, perineural invasion, grade 2 disease, any lymph node positivity and tumour size > 20 mm predicted worse RFS (all p values < 0.05). Few OSdata were available for pooling; in univariableanalysis(entire cohort), grade 2 predicted worse OS (p = 0.007), whileR1 resectiondid not (p = 0.14). CONCLUSIONS The factors prognostic for worse RFS following resection of a GEP-NEN identified in this meta-analysis could be included in post-curative treatment surveillance clinical guidelines and inform the stratification and inclusion criteria of future adjuvant trials.
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Affiliation(s)
- Rachel Broadbent
- University of Manchester, Division of Cancer Sciences, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Roseanna Wheatley
- University of Manchester, Division of Cancer Sciences, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Sabrina Stajer
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Timothy Jacobs
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Angela Lamarca
- University of Manchester, Division of Cancer Sciences, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Richard A Hubner
- University of Manchester, Division of Cancer Sciences, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Juan W Valle
- University of Manchester, Division of Cancer Sciences, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Eitan Amir
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Mairéad G McNamara
- University of Manchester, Division of Cancer Sciences, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK.
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Maharjan CK, Ear PH, Tran CG, Howe JR, Chandrasekharan C, Quelle DE. Pancreatic Neuroendocrine Tumors: Molecular Mechanisms and Therapeutic Targets. Cancers (Basel) 2021; 13:5117. [PMID: 34680266 PMCID: PMC8533967 DOI: 10.3390/cancers13205117] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 10/08/2021] [Accepted: 10/09/2021] [Indexed: 12/16/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are unique, slow-growing malignancies whose molecular pathogenesis is incompletely understood. With rising incidence of pNETs over the last four decades, larger and more comprehensive 'omic' analyses of patient tumors have led to a clearer picture of the pNET genomic landscape and transcriptional profiles for both primary and metastatic lesions. In pNET patients with advanced disease, those insights have guided the use of targeted therapies that inhibit activated mTOR and receptor tyrosine kinase (RTK) pathways or stimulate somatostatin receptor signaling. Such treatments have significantly benefited patients, but intrinsic or acquired drug resistance in the tumors remains a major problem that leaves few to no effective treatment options for advanced cases. This demands a better understanding of essential molecular and biological events underlying pNET growth, metastasis, and drug resistance. This review examines the known molecular alterations associated with pNET pathogenesis, identifying which changes may be drivers of the disease and, as such, relevant therapeutic targets. We also highlight areas that warrant further investigation at the biological level and discuss available model systems for pNET research. The paucity of pNET models has hampered research efforts over the years, although recently developed cell line, animal, patient-derived xenograft, and patient-derived organoid models have significantly expanded the available platforms for pNET investigations. Advancements in pNET research and understanding are expected to guide improved patient treatments.
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Affiliation(s)
- Chandra K. Maharjan
- Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;
| | - Po Hien Ear
- Department of Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (P.H.E.); (C.G.T.); (J.R.H.)
| | - Catherine G. Tran
- Department of Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (P.H.E.); (C.G.T.); (J.R.H.)
| | - James R. Howe
- Department of Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (P.H.E.); (C.G.T.); (J.R.H.)
| | - Chandrikha Chandrasekharan
- Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;
| | - Dawn E. Quelle
- Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA
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Imaging of Pancreatic Neuroendocrine Neoplasms. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18178895. [PMID: 34501485 PMCID: PMC8430610 DOI: 10.3390/ijerph18178895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 08/16/2021] [Accepted: 08/22/2021] [Indexed: 12/25/2022]
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) represent the second most common pancreatic tumors. They are a heterogeneous group of neoplasms with varying clinical expression and biological behavior, from indolent to aggressive ones. PanNENs can be functioning or non-functioning in accordance with their ability or not to produce metabolically active hormones. They are histopathologically classified according to the 2017 World Health Organization (WHO) classification system. Although the final diagnosis of neuroendocrine tumor relies on histologic examination of biopsy or surgical specimens, both morphologic and functional imaging are crucial for patient care. Morphologic imaging with ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) is used for initial evaluation and staging of disease, as well as surveillance and therapy monitoring. Functional imaging techniques with somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) are used for functional and metabolic assessment that is helpful for therapy management and post-therapeutic re-staging. This article reviews the morphological and functional imaging modalities now available and the imaging features of panNENs. Finally, future imaging challenges, such as radiomics analysis, are illustrated.
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Huang J, Chen J, Xu M, Zheng Y, Lin M, Huang G, Xie X, Xie X. Contrast-Enhanced Ultrasonography Findings Correlate with Pathologic Grades of Pancreatic Neuroendocrine Tumors. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:2097-2106. [PMID: 33934943 DOI: 10.1016/j.ultrasmedbio.2021.02.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/22/2021] [Accepted: 02/17/2021] [Indexed: 06/12/2023]
Abstract
The correlation of sonographic findings with pathologic grades of pancreatic neuroendocrine tumors (PNETs) remains unclear. This study aimed to evaluate the usefulness of sonographic features in diagnosing the pathologic grade of PNETs. Conventional and contrast-enhanced ultrasonography findings of PNETs diagnosed by surgical pathology from July 2010 to June 2020 were retrospectively reviewed. Sonographic features were compared among three pathologic grades of PNETs according to the World Health Organization 2010 classification. Ordinal regression models were constructed to evaluate the usefulness of the sonographic features in diagnosing the pathologic grade of PNETs. This study enrolled 93 participants with PNETs: 50 grade 1, 31 grade 2 and 12 grade 3. Multivariate ordinal regression analysis suggested that tumor size ≥2 cm (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.020-0.606; p = 0.011), dilation of the main pancreatic duct (OR, 0.103; 95% CI, 0.025-0.430; p = 0.002), hepatic metastases (OR, 0.250; 95% CI, 0.072-0.869; p = 0.029) and hyper-enhancement in arterial phase (OR, 4.676; 95% CI, 1.656-13.206; p = 0.004) were significantly associated with the pathologic grades of PNETs. The accuracy of the ordinal logistic regression model in identifying grade 1, 2 and 3 PNETs was 77.4%, 67.7% and 90.3%, respectively. The findings suggest that sonographic features, including tumor size, pancreatic duct dilation and hepatic metastasis, as well as the enhancement level in arterial phase, may help identify different pathologic grades of PNETs.
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Affiliation(s)
- Jingzhi Huang
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ming Xu
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanling Zheng
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Manxia Lin
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guangliang Huang
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoyan Xie
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaohua Xie
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Wang M, Ding D, Qin T, Wang H, Liu Y, Liu J, Liu J, Zhang H, Zhao J, Wu CH, Javed A, Wolfgang C, Guo S, Chen Q, Zhao W, Shi W, Zhu F, Guo X, Li X, He R, Xu S, Edil B, Tien YW, Jin G, Zheng L, He J, Qin R. New staging classification for pancreatic neuroendocrine neoplasms combining TNM stage and WHO grade classification []. Cancer Lett 2021; 518:207-213. [PMID: 34271105 DOI: 10.1016/j.canlet.2021.07.018] [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: 04/28/2021] [Revised: 06/25/2021] [Accepted: 07/10/2021] [Indexed: 10/20/2022]
Abstract
AJCC TNM stage and WHO grade (G) are two widely used staging systems to guide clinical management for pancreatic neuroendocrine neoplasms (panNENs), based on clinical staging and pathological grading information, respectively. We proposed to integrate TNM stage and G grade into one staging system (TNMG) and to evaluate its clinical application as a prognostic indicator for panNENs. Accordingly, 5254 patients diagnosed with panNENs were used to evaluate and to validate the applicability of TNMG to panNENs. The predictive accuracy of TNMG system was compared with that of each separate staging/grading system. We found that TNM stage and G grade were independent risk factors for survival in both the Surveillance, Epidemiology, and End Result (SEER) and multicenter series. The interaction effect between TNM stage and G grade was significant. Twelve subgroups combining the TNM stage and G grade were proposed in the TNMG stage, which were classified into five stages TNMG. According to the TNMG staging classification in the SEER series, the estimated median survival for stages I, II, III, IV, and V were 203, 174, 112, 61, and 8 months, respectively. The predictive accuracy of TNMG stage was higher than that of TNM stage and G grade used independently. The TNMG stage classification was more accurate in predicting panNEN patient's prognosis than either the TNM stage or G grade.
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Affiliation(s)
- Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Ding Ding
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Tingting Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Hebin Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin, 130021, China
| | - Jianhua Liu
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China
| | - Jun Liu
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong, 250000, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Junfang Zhao
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Chien-Hui Wu
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei, 10002, Taiwan
| | - Ammar Javed
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Christopher Wolfgang
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Shiwei Guo
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai, 200433, China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin, 130021, China
| | - Weihong Zhao
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China
| | - Wei Shi
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong, 250000, China
| | - Feng Zhu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Xingjun Guo
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Xu Li
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Ruizhi He
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Simiao Xu
- Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Barish Edil
- Department of Surgery, University of Oklahoma, Oklahoma City, OK, 73104, USA
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei, 10002, Taiwan
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai, 200433, China
| | - Lei Zheng
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Jin He
- Departments of Surgery and Oncology, the Pancreatic Cancer Precision Medicine Center of Excellence Program, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
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Frank V, Shariati S, Budai BK, Fejér B, Tóth A, Orbán V, Bérczi V, Kaposi PN. CT texture analysis of abdominal lesions – Part II: Tumors of the Kidney and Pancreas. IMAGING 2021; 13:25-36. [DOI: 10.1556/1647.2021.00020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
AbstractIt has been proven in a few early studies that radiomic analysis offers a promising opportunity to detect or differentiate between organ lesions based on their unique texture parameters. Recently, the utilization of CT texture analysis (CTTA) has been receiving significant attention, especially for response evaluation and prognostication of different oncological diagnoses. In this review article, we discuss the unique ability of radiomics and its subfield CTTA to diagnose lesions in the pancreas and kidney. We review studies in which CTTA was used for the classification of histology grades in pancreas and kidney tumors. We also review the role of radiogenomics in the prediction of the molecular and genetic subtypes of pancreatic tumors. Furthermore, we provide a short report on recent advancements of radiomic analysis in predicting prognosis and survival of patients with pancreatic and renal cancers.
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Affiliation(s)
- Veronica Frank
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
| | - Sonaz Shariati
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
| | - Bettina Katalin Budai
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
| | - Bence Fejér
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
| | - Ambrus Tóth
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
| | - Vince Orbán
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
| | - Viktor Bérczi
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
| | - Pál Novák Kaposi
- Department of Radiology, Medical Imaging Centre, Semmelweis University, Faculty of Medicine, Budapest, Hungary
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Półtorak-Szymczak G, Budlewski T, Furmanek MI, Wierzba W, Sklinda K, Walecki J, Mruk B. Radiological Imaging of Gastro-Entero-Pancreatic Neuroendocrine Tumors. The Review of Current Literature Emphasizing the Diagnostic Value of Chosen Imaging Methods. Front Oncol 2021; 11:670233. [PMID: 34211845 PMCID: PMC8239281 DOI: 10.3389/fonc.2021.670233] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 04/14/2021] [Indexed: 02/03/2023] Open
Abstract
Despite development of radiologic imaging, detection and follow-up of neuroendocrine neoplasms (NENs) still pose a diagnostic challenge, due to the heterogeneity of NEN, their relatively long-term growth, and small size of primary tumor. A set of information obtained by using different radiological imaging tools simplifies a choice of the most appropriate treatment method. Moreover, radiological imaging plays an important role in the assessment of metastatic lesions, especially in the liver, as well as, tumor response to treatment. This article reviews the current, broadly in use imaging modalities which are applied to the diagnosis of GEP-NETs, (the most common type of NENs) and put emphasis on the strengths and limitations of each modality.
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Affiliation(s)
- Gabriela Półtorak-Szymczak
- Department of Radiology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland
| | - Tadeusz Budlewski
- Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland.,Department of Nuclear Medicine, Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland
| | - Mariusz Ireneusz Furmanek
- Department of Radiology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland
| | - Waldemar Wierzba
- Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland.,University of Humanities and Economics, Lodz, Poland
| | - Katarzyna Sklinda
- Department of Radiology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland
| | - Jerzy Walecki
- Department of Radiology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland
| | - Bartosz Mruk
- Department of Radiology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Warsaw, Poland
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Rodriguez-Freixinos V, Thawer A, Capdevila J, Ferone D, Singh S. Advanced Pancreatic Neuroendocrine Neoplasms: Which Systemic Treatment Should I Start With? Curr Oncol Rep 2021; 23:80. [PMID: 33937962 DOI: 10.1007/s11912-021-01071-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE OF REVIEW Pancreatic neuroendocrine neoplasms (panNENs) often present as advanced disease and there is little data to guide treatment sequencing in the advance disease setting. Therefore, we aim to provide a comprehensive summary of the current evidence supporting the use of systemic treatment for patients with diagnosis of advanced and metastatic panNENs, as well as to provide strategies for treatment selection and address challenges for treatment selection and sequencing of therapy. RECENT FINDINGS Substantial advances have been made and many clinical trials have been performed over the past two decades expanding therapeutic options available for patients with advanced panNETs. Available systemic treatments for patients with well-differentiated pancreatic neuroendocrine tumors include somatostatin receptors ligands (SRLs), traditional cytotoxic chemotherapy regimens, peptide receptor radiotherapy (PRRT), and biologically targeted therapies, whereas patients with poorly differentiated neurodocrine carcinomas have more limited treatment options. Despite these advances, no clear guidelines exist to support the best sequence of treatments, not only the first-line, but also subsequent lines of therapy in patients with panNENs. Advances in molecular research and discovery of biomarkers for response allowing a more personalized approach to the multimodality therapy of panNENs are still limited. Understanding the impact of previous therapies on subsequent treatment efficacy and toxicity is also an ongoing research question. In the absence of definite predictive markers and paucity of comparative randomized trials, along with the heterogeneity of this patient population, systemic therapy selection in advanced non-resectable disease should be patient centered and often require evaluation within a multidisciplinary setting. The specific clinical context of the patient, with assessment of individual patient clinical and pathological features, somatostatin receptors imaging, and goals of treatment must all be considered when deciding on systemic therapy in the patient. Additional research is needed to address the gap in knowledge regarding optimal sequencing and timing of therapies and to provide individual care.
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Affiliation(s)
- Victor Rodriguez-Freixinos
- Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
| | - Alia Thawer
- Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Jaume Capdevila
- Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VIHO), Barcelona, Spain
| | - Diego Ferone
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Endocrinology, Department of Internal Medicine and Medical Specialties (DIMI) and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy
| | - Simron Singh
- Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
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Gopalakrishnan G, Srinivas BH, Pottakkat B, Gnanasekaran S, Kalayarasan R. Perforated High-Grade Mixed Neuroendocrine Nonneuroendocrine Neoplasm of Cecum: Unusual Presentation of Rare Disease. Gastrointest Tumors 2021; 8:128-133. [PMID: 34307311 DOI: 10.1159/000512237] [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: 08/09/2020] [Accepted: 09/21/2020] [Indexed: 11/19/2022] Open
Abstract
Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) are rare neoplasms of the gastrointestinal tract, where the neuroendocrine as well as the nonneuroendocrine components each comprise at least 30% of the tumor. Of all cases of colorectal malignancies, MiNENs constitute around 3-9.6%, with only a few cases reported to be arising in the cecum. Since majority present with nonspecific clinical and radiological findings, its diagnosis preoperatively is almost impossible and these are usually diagnosed after histopathological examination of the resected specimen. Owing to the rarity of these tumors as well as lack of complete molecular characterization, optimal treatment remains unestablished. We, here, report a rare case of MiNENs of the cecum infiltrating the right psoas muscle and presenting with perforation for which right hemicolectomy and en bloc excision of the involved psoas muscle was done followed by adjuvant chemotherapy.
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Affiliation(s)
- Gunasekaran Gopalakrishnan
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | | | - Biju Pottakkat
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Senthil Gnanasekaran
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Raja Kalayarasan
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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Chu H, Shi Y, Liu J, Huang D, Zhang J, Dou C. Update in clinical management for gallbladder neuroendocrine carcinoma. Medicine (Baltimore) 2021; 100:e25449. [PMID: 33832150 PMCID: PMC8036038 DOI: 10.1097/md.0000000000025449] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 03/10/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Gallbladder neuroendocrine carcinoma (GB-NEC) is rare and there are few reports at present. We sought to review the current knowledge of GB-NEC and provide recommendations for clinical management. METHODS A systemic literature research was conducted in the websites of Pubmed, Medline, Web of Science, CNKI, Wanfang Data using the keywords including gallbladder combined with neuroendocrine carcinoma or neuroendocrine tumor or neuroendocrine neoplasm. Two reviewers independently screened the articles by reading the title, abstract and full-text. RESULTS In computed tomography (CT) and magnetic resonance imaging (MRI) examination, a well-defined margin, gallbladder replacing type with larger hepatic and lymphatic metastases could be helpful for differential diagnosis of GB-NEC and gallbladder adenocarcinoma (GB-ADC). Older age, unmarried status, large tumor size (>5 cm), positive margins, and distant Surveillance, Epidemiology and End result (SEER) stage are independently associated with poor survival. Surgical resection remains as the preferred and primary treatment. The potential survival benefit of lymphadenectomy for patients remains controversial. Platinum-based postoperative adjuvant chemotherapy may improve the survival. The efficacy of other treatments including immunotherapy, targeted therapy and somatostatin analogue needs further investigation. CONCLUSION Typical imaging features could be helpful for preoperative diagnosis. Age, margin status, tumor size, marital status, histopathologic subtype and SEER stage may be independent predictors for the survival. Remarkable advances regarding the treatment for GB-NEC have been achieved in recent years. Further studies are needed to investigate the survival benefit of lymphadenectomy for patients with GB-NEC.
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Affiliation(s)
- Hongwu Chu
- Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou
- Qingdao University, Qingdao
| | - Ying Shi
- Obstetrics and Gynecology, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Junwei Liu
- Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou
| | - Dongsheng Huang
- Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou
| | - Jungang Zhang
- Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou
| | - Changwei Dou
- Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou
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Tidjane A, Boudjenan N, Bengueddach A, Kadri A, Ikhlef N, Benmaarouf N, Tabeti B. Pure large cell neuroendocrine carcinoma of the gallbladder, is surgical relentlessness beneficial? A case report and literature review. Int Cancer Conf J 2021; 10:127-133. [PMID: 33425643 PMCID: PMC7778705 DOI: 10.1007/s13691-020-00461-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 11/17/2020] [Indexed: 01/04/2023] Open
Abstract
Pure large cell neuroendocrine carcinoma of the gallbladder is a rare disease. However, the prognosis of this aggressive tumor is poor with short survival after diagnosis. We are describing in this manuscript a case of pure large cell neuroendocrine carcinoma in which survival exceeded 26 months, after performing two curative surgeries. We are reporting the case of a 68-year-old woman with a history of recovered right breast carcinoma and operated 6 years later for a completely asymptomatic gallbladder tumor of 31 mm. In this case, curative surgery was performed allowing monobloc resection of the gallbladder and the hepatic segments IVb and V, a lymph node dissection was performed to. The histological examination of the specimen and immunohistochemistry confirms that the tumor was a grade 3 pure large cell neuroendocrine carcinoma of gallbladder with lymph node invasion, the hepatic and biliary surgical margins were free. Postoperative adjuvant chemotherapy was administered and the evolution was eventless until the discovery at 20 months of a lymph node considered being metastatic recurrence. A second surgery was performed allowing removal of three lymph nodes. This time, a different protocol of chemotherapy was administered to our patient who remains alive and without recurrence at 26 months from her first surgery. Surgical relentlessness with free margins resections associated with appropriate chemotherapy probably improves the survival of patients suffering from this rare and aggressive tumor.
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Affiliation(s)
- Anisse Tidjane
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU-1st November 1954, Department of Medicine, University of Oran 1, B.P 1510 El Menaouer, 31000 Oran, Algeria
| | - Nabil Boudjenan
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU-1st November 1954, Department of Medicine, University of Oran 1, B.P 1510 El Menaouer, 31000 Oran, Algeria
| | - Aicha Bengueddach
- Department of Oncology, EHU-1st November 1954, Department of Medicine, University of Oran 1, Oran, Algeria
| | - Amin Kadri
- Laboratoire d’Anatomie Pathologique Dr. Kadri, Oran, Algeria
| | - Nacim Ikhlef
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU-1st November 1954, Department of Medicine, University of Oran 1, B.P 1510 El Menaouer, 31000 Oran, Algeria
| | - Noureddine Benmaarouf
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU-1st November 1954, Department of Medicine, University of Oran 1, B.P 1510 El Menaouer, 31000 Oran, Algeria
| | - Benali Tabeti
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU-1st November 1954, Department of Medicine, University of Oran 1, B.P 1510 El Menaouer, 31000 Oran, Algeria
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Lam AKY, Ishida H. Pancreatic neuroendocrine neoplasms: Clinicopathological features and pathological staging. Histol Histopathol 2021; 36:367-382. [PMID: 33305819 DOI: 10.14670/hh-18-288] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The nomenclature and classification of pancreatic neuroendocrine neoplasms has evolved in the last 15 years based on the advances in knowledge of the genomics, clinical behaviour and response to therapies. The current 2019 World Health Organization classification of pancreatic neuroendocrine neoplasms categorises them into three groups; pancreatic neuroendocrine tumours (PanNETs)(grade 1 grade 2, grade 3), pancreatic neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) based on the mitotic rate, Ki-67 index, morphological differentiation and/or co-existing tissue subtype. PanNETs are also classified into non-functional NET, insulinoma, gastrinoma, VIPoma, glucagonoma, somatostatinoma, ACTH-producing NET and serotonin producing NET based on hormone production and clinical manifestations. A portion of the cases were associated with genetic syndromes such as multiple neuroendocrine neoplasia 1 (MEN 1), neurofibromatosis and Von Hippel-Lindau syndrome. In view of the distinctive pathology and clinical behaviour of PanNENs, the current 8th AJCC/UICC staging system has separated prognostic staging grouping for PanNETs from the pancreatic neuroendocrine carcinomas or MiNENs. Pancreatic neuroendocrine carcinomas and MiNENs are staged according to the prognostic stage grouping for exocrine pancreatic carcinoma. The new stage grouping of PanNETs was validated to have survival curves separated between different prognostic groups. This refined histological and staging would lead to appropriate selections of treatment strategies for the patients with pancreatic neuroendocrine neoplasms.
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Affiliation(s)
| | - Hirotaka Ishida
- School of Medicine, Griffith University, Gold Coast, QLD, Australia
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Yoo J, Kim SH, Jeon SK, Bae JS, Han JK. Added value of [ 68Ga]Ga-DOTA-TOC PET/CT for characterizing pancreatic neuroendocrine neoplasms: a comparison with contrast-enhanced CT and/or MRI in a large study cohort. Eur Radiol 2021; 31:7734-7745. [PMID: 33787974 DOI: 10.1007/s00330-021-07859-0] [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: 10/31/2020] [Revised: 02/14/2021] [Accepted: 03/10/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVES To investigate an additional value of [68Ga]Ga-DOTA-TOC PET/CT for characterizing suspected pancreatic neuroendocrine neoplasms (NENs) in a large study cohort. METHODS This retrospective study included 167 patients who underwent [68Ga]Ga-DOTA-TOC PET/CT for suspected pancreatic NENs detected by contrast-enhanced CT (n = 153) and/or MRI (n = 85). Two board-certified radiologists independently reviewed CT and/or MRI as well as [68Ga]Ga-DOTA-TOC PET/CT and scored the probability of NEN on a 5-point scale. Radiologists' diagnostic performances with and without [68Ga]Ga-DOTA-TOC PET/CT were compared using pathologic findings as the standard of reference. RESULTS All 167 patients were pathologically diagnosed with NENs (n = 131) or non-NENs (n = 36) by surgery (n = 93) or biopsy (n = 74). The non-NEN group included focal pancreatitis (n = 7), gastrointestinal stromal tumor (n = 6), serous cystadenoma (n = 5), metastatic renal cell carcinoma (n = 4), intrapancreatic accessory spleen (n = 4), ductal adenocarcinoma (n = 3), solid pseudopapillary neoplasm (n = 2), intraductal papillary mucinous carcinoma (n = 1), adenosquamous carcinoma (n = 1), schwannoma (n = 1), paraganglioma (n = 1), and solitary fibrous tumor (n = 1). Radiologists' diagnostic performance significantly improved after the addition of [68Ga]Ga-DOTA-TOC PET/CT (AUC of CT: 0.737 vs. 0.886 for reviewer 1 [p = 0.0004]; 0.709 vs. 0.859 for reviewer 2 [p = 0.0002], AUC of MRI: 0.748 vs. 0.872 for reviewer 1 [p = 0.023]; 0.670 vs. 0.854 for reviewer 2 [p = 0.001]). [68Ga]Ga-DOTA-TOC PET/CT significantly improved sensitivity (CT: 87.4% vs. 96.6% for reviewer 1 [p = 0.001]; 74.8% vs. 92.5% for reviewer 2 [p = 0.0001], MRI: 86.9% vs. 98.4% for reviewer 1 [p = 0.016]; 70.5% vs. 91.8% for reviewer 2 [p = 0.002]). CONCLUSIONS [68Ga]Ga-DOTA-TOC PET/CT provided an additional value over conventional CT or MRI for the characterization of suspected pancreatic NENs. KEY POINTS • [68Ga]Ga-DOTA-TOC PET/CT could provide additional value over conventional CT and/or MRI for the exact characterization of suspected pancreatic NENs by increasing AUC values and sensitivity. • Diagnostic improvement was significant, especially in NENs showing an atypical enhancement pattern. • The inter-observer agreement was improved when [68Ga]Ga-DOTA-TOC PET/CT was added to CT and/or MRI.
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Affiliation(s)
- Jeongin Yoo
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 110-744, Korea
| | - Se Hyung Kim
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 110-744, Korea. .,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea. .,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea.
| | - Sun Kyung Jeon
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 110-744, Korea
| | - Jae Seok Bae
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 110-744, Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul, 110-744, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea
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Nieto EP, Zhou JY, Blanco MR, Szafranska J, Cabús SS. Unclassifiable pancreatic tumour. A case report. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:559-561. [PMID: 33746027 DOI: 10.1016/j.gastrohep.2021.02.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 02/02/2021] [Accepted: 02/04/2021] [Indexed: 11/19/2022]
Affiliation(s)
- Elena Pareja Nieto
- Hospital de la Santa Creu i Sant Pau. Carrer de Sant Quintí, 89, 08041 Barcelona.
| | - Jinghuang Ye Zhou
- Hospital de la Santa Creu i Sant Pau. Carrer de Sant Quintí, 89, 08041 Barcelona
| | | | - Justyna Szafranska
- Hospital de la Santa Creu i Sant Pau. Carrer de Sant Quintí, 89, 08041 Barcelona
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Hori T, Kuriyama K, Yamamoto H, Harada H, Yamamoto M, Yamada M, Yazawa T, Sasaki B, Tani M, Sato A, Katsura H, Kamada Y, Tani R, Aoyama R, Sasaki Y, Iwasa Y, Zaima M. Adrenocorticotropic hormone-dependent hypercortisolism caused by pancreatic neuroendocrine carcinoma: A thought-provoking but remorseful case of delayed diagnosis. Int J Surg Case Rep 2021; 81:105729. [PMID: 33714002 PMCID: PMC7957145 DOI: 10.1016/j.ijscr.2021.105729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/01/2021] [Accepted: 03/03/2021] [Indexed: 11/18/2022] Open
Abstract
Diagnosis of functioning neuroendocrine neoplasms (NENs) in the pancreas is challenging. Adrenocorticotropic hormone (ACTH) regulates adrenal cortisol production. Functioning NENs may cause hypercortisolism as a result of ectopic ACTH secretion. Systematic endocrine examination and functional imaging studies are vital. Making a precise diagnosis enables appropriate treatment of NENs. Introduction and importance Definitive diagnosis of functioning neuroendocrine neoplasms (NENs) in the pancreas is challenging. Adrenocorticotropic hormone (ACTH) regulates adrenal cortisol production. Ectopic ACTH secretion by functioning NENs may cause hypercortisolism. Presentation of case A 62-year-old woman who was receiving medications for hypertension and hyperlipidemia was referred to our hospital because of abnormal blood tests. Diabetes mellitus was initially diagnosed. Dynamic computed tomography and endoscopic ultrasound revealed a 35-mm diameter hypovascular tumor in the distal pancreas and multiple liver metastases. Endoscopic ultrasound-guided fine-needle aspiration resulted in a diagnosis of neuroendocrine carcinoma. The patient developed pancreatic leakage progressing to peritonitis, abscess formation, pleural effusion, and ascites after the fine-needle aspiration biopsy. Her clinical condition deteriorated to a septic state, necessitating emergency surgery comprising distal pancreatectomy, intraperitoneal lavage, and drainage. Wound healing was protracted and accompanied by ongoing high white blood cell counts and neutrophilia. She also developed a gastric ulcer postoperatively. Systematic endocrine investigations were performed because hypercortisolism caused by a functioning NEN was suspected. Eventually, a definitive diagnosis of an ACTH-producing NEN in the pancreas was made. Systemic chemotherapy was proposed; however, the patient and her family opted for palliative treatment only. She died 42 days after the initial diagnosis. Clinical discussion We here present a patient with ACTH-dependent hypercortisolism attributable to a pancreatic NEN who died of progressive cancer after a delay in definitive diagnosis. Conclusion Detailed investigation, including systematic endocrine examination and functional imaging studies, are important for precise diagnosis of, and appropriate treatment for, NENs.
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Affiliation(s)
- Tomohide Hori
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Katsutoshi Kuriyama
- Department of Hepatobiliary Pancreatic Medicine, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Hidekazu Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Hideki Harada
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Michihiro Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Masahiro Yamada
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Takefumi Yazawa
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Ben Sasaki
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Masaki Tani
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Asahi Sato
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Hikotaro Katsura
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Yasuyuki Kamada
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Ryotaro Tani
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Ryuhei Aoyama
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Yudai Sasaki
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Yoko Iwasa
- Department of Diagnostic Pathology, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
| | - Masazumi Zaima
- Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan.
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Kaur J, Mogulla S, Malik A, Garg S. Unusual Presentation of a Sphenoidal Sinus Neuroendocrine Tumor: A Case Report and Review of Literature. Cureus 2021; 13:e13689. [PMID: 33833913 PMCID: PMC8019145 DOI: 10.7759/cureus.13689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Neuroendocrine tumors (NETs) have a heterogeneous pathology and indolent behavior, with the most common location being the gastrointestinal tract and then the lungs. The head and neck are rare sites of NET presentation with varied clinical signs and symptoms, which occasionally delay the diagnosis, thereby leading to an advanced stage at presentation. We present a rare case of paranasal sinus small cell neuroendocrine tumor and perform a review of the literature. A 71-year-old man presented with continuous bleeding from the left nostril and nasal congestion without any prior medical history. Clinical examination revealed nasal congestion, rhinorrhea, postnasal drip, and active bleeding. The laboratory data were within normal limits. Imaging studies showed a left sphenoid sinus mass extending to the left ethmoid sinus with a break in the cribriform plate encephalocele. An enlarged lymph node measuring 2.2 cm was noted in the left neck and supraclavicular region. The evaluation through stereotactic endoscopic sinus surgery and biopsy revealed left nasopharyngeal, sphenoid sinus, and ethmoid sinus masses. Pathologic biopsy findings were consistent with high-grade, malignant, small, round blue cell tumors. Immunohistochemical analysis confirmed high-grade small cell neuroendocrine carcinoma. The patient was diagnosed with stage IV (TXN2bM0, T: tumor size, N: lymph node, M: metastasis) high-grade neuroendocrine tumor of the left paranasal sinus. He was treated with concurrent chemoradiation therapy with two cycles of etoposide and cisplatin and radiation therapy with proton beam radiation therapy followed by two cycles of adjuvant etoposide cisplatin chemotherapy. The patient showed a good response to the treatment, as confirmed using imaging. He is currently being regularly followed up with serial imaging.
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Affiliation(s)
- Jasmeet Kaur
- Internal Medicine, Saint Joseph Mercy Oakland Hospital, Pontiac, USA
| | - Swathi Mogulla
- Internal Medicine, Saint Joseph Mercy Oakland Hospital, Pontiac, USA
| | - Ambreen Malik
- Internal Medicine, Saint Joseph Mercy Oakland Hospital, Pontiac, USA
| | - Sandeep Garg
- Hematology and Medical Oncology, Saint Joseph Mercy Oakland Hospital, Pontiac, USA
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