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Babapour S, Chen A, Li G, Phan L. Pancreatic Neuroendocrine Diagnostic Imaging Order and Reader Evaluation over Two Decades in a Tertiary Academic Center. Diagnostics (Basel) 2025; 15:960. [PMID: 40310338 PMCID: PMC12026277 DOI: 10.3390/diagnostics15080960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 03/03/2025] [Accepted: 03/04/2025] [Indexed: 05/02/2025] Open
Abstract
Background/Objective: Identifying patterns of diagnostic imaging workflow parallel to the influence of certain variables, such as pathology guidelines over time, provides valuable insight for clinical decision making. This study presents a recurring trend of initial imaging orders and follow-ups, up to the diagnosis of pancreatic neuroendocrine tumors (pNETs), across two decades, with scans which led to pathological investigation. Methods: Three readers evaluated common conventional imaging among initial and follow-up studies for lesion detection and localization. Inter-reader and intra-reader analyses were controlled as contributing factors to the imaging diagnostic trend. Results: Our results show that CT was the prominent initial scan in pNET workup, likely due to their wide availability, high spatial resolution, and rapid acquisition, with a sufficient detection rate throughout both decades, regardless of technical advances. However, MRI scans also gained soaring popularity, especially among syndromic patients, likely due to follow-up and anatomical surgery precision. Conclusions: Newer modalities may be eventually useful and only requested for pNETs staging and further treatment.
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Affiliation(s)
- Sara Babapour
- Radiological Sciences, Clinical Research, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; (A.C.); (G.L.); (L.P.)
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Hobeika C, Pfister M, Geller D, Tsung A, Chan A, Troisi RI, Rela M, Di Benedetto F, Sucandy I, Nagakawa Y, Walsh RM, Kooby D, Barkun J, Soubrane O, Clavien PA. Recommendations on Robotic Hepato-Pancreato-Biliary Surgery. The Paris Jury-Based Consensus Conference. Ann Surg 2025; 281:136-153. [PMID: 38787528 DOI: 10.1097/sla.0000000000006365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
OBJECTIVE To establish the first consensus guidelines on the safety and indications of robotics in Hepato-Pancreatic-Biliary (HPB) surgery. The secondary aim was to identify priorities for future research. BACKGROUND HPB robotic surgery is reaching the IDEAL 2b exploration phase for innovative technology. An objective assessment endorsed by the HPB community is timely and needed. METHODS The ROBOT4HPB conference developed consensus guidelines using the Zurich-Danish model. An impartial and multidisciplinary jury produced unbiased guidelines based on the work of 10 expert panels answering predefined key questions and considering the best-quality evidence retrieved after a systematic review. The recommendations conformed with the GRADE and SIGN50 methodologies. RESULTS Sixty-four experts from 20 countries considered 285 studies, and the conference included an audience of 220 attendees. The jury (n=10) produced recommendations or statements covering 5 sections of robotic HPB surgery: technology, training and expertise, outcome assessment, and liver and pancreatic procedures. The recommendations supported the feasibility of robotics for most HPB procedures and its potential value in extending minimally invasive indications, emphasizing, however, the importance of expertise to ensure safety. The concept of expertise was defined broadly, encompassing requirements for credentialing HPB robotics at a given center. The jury prioritized relevant questions for future trials and emphasized the need for prospective registries, including validated outcome metrics for the forthcoming assessment of HPB robotics. CONCLUSIONS The ROBOT4HPB consensus represents a collaborative and multidisciplinary initiative, defining state-of-the-art expertise in HPB robotics procedures. It produced the first guidelines to encourage their safe use and promotion.
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Affiliation(s)
- Christian Hobeika
- Department of Hepato-pancreato-biliary surgery and Liver transplantation, Beaujon Hospital, AP-HP, Clichy, Paris-Cité University, Paris, France
| | - Matthias Pfister
- Department of Surgery and Transplantation, University of Zurich, Zurich, Switzerland
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland
| | - David Geller
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Allan Tsung
- Department of Surgery, University of Virginia, Charlottesville, VA
| | - Albert Chan
- Department of Surgery, School of Clinical Medicine, University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Roberto Ivan Troisi
- Department of Clinical Medicine and Surgery, Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, Naples, Italy
| | - Mohamed Rela
- The Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Fabrizio Di Benedetto
- Hepato-pancreato-biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Iswanto Sucandy
- Department of Hepatopancreatobiliary and Gastrointestinal Surgery, Digestive Health Institute AdventHealth Tampa, Tampa, FL
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - R Matthew Walsh
- Department of General Surgery, Cleveland Clinic, Digestive Diseases and Surgery Institution, OH
| | - David Kooby
- Department of Surgery, Emory University School of Medicine, Atlanta, GA
| | - Jeffrey Barkun
- Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
| | - Olivier Soubrane
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, University of Zurich, Zurich, Switzerland
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland
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Hong X, Zhang X, Jiang R, Qiao S, Wang W, Zhang H, Wang J, Yin B, Li F, Ling C, Wang X, Zhao Y, Wu K, Wu W. A cross-species transcriptomic analysis reveals a novel 2-dimensional classification system explaining the invasiveness heterogeneity of pancreatic neuroendocrine tumor. Cancer Lett 2024:217131. [PMID: 39048044 DOI: 10.1016/j.canlet.2024.217131] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 07/02/2024] [Accepted: 07/18/2024] [Indexed: 07/27/2024]
Abstract
Pancreatic neuroendocrine tumors (PanNETs), the second most common type of primary pancreatic tumors, display notable heterogeneity in invasiveness. Current knowledge regarding genomic alterations, including DAXX/ATRX, MEN1 mutations, and copy number variations (CNVs), provides some insights into tumor invasiveness. However, the underlying reasons for the significant variation in invasiveness between insulinoma and other types of PanNETs remain unclear. To construct a comprehensive model for the stratification of prognosis, we employed analysis of both the well-established Rip1-Tag 2 (RT2) mouse model of PanNETs and human PanNETs with various functional types. Firstly, by applying single-cell and bulk RNA sequencing in PanNETs from different ages and strains of RT2 mice and human PanNETs, we introduced a 2-dimensional (2D) classification system. Based on the 2D classification system, human PanNETs were mainly classified as benign insulinomas or non-insulinomas subclusters. Non-insulinomas subtypes mainly included gastrinomas, glucagonomas, VIPomas, and NF-PanNETs, which all exhibited potential invasiveness. In addition, we discovered an enrichment of specific CNV patterns and mutations in corresponding human PanNET subclusters. Then we denoted somatic DAXX/ATRX as the 'second hit' and confounding factors for invasiveness. Finally, by combining the 2D system, DAXX/ATRX mutation status, and tumor diameter, a group of indolent PanNETs with minimal recurrence risk was identified. In conclusion, our current work constructed a comprehensive model to elucidate the heterogeneity of invasiveness in PanNETs and improve prognostic stratification.
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Affiliation(s)
- Xiafei Hong
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xingwu Zhang
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China; School of Medicine, Tsinghua University, Beijing, 100084, China
| | - Rui Jiang
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China; Department of General Surgery, Xuanwu Hospital Capital Medical University, Beijing, 100053, China
| | - Sitan Qiao
- BGI-Shenzhen, Shenzhen, 518083, China; The Chinese University of Hong Kong, Shatin, China
| | - Wenze Wang
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Hao Zhang
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Jingqiao Wang
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Bohui Yin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | | | - Chao Ling
- The Laboratory of Clinical Genetics, Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xianze Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
| | - Kui Wu
- BGI-Shenzhen, Shenzhen, 518083, China.
| | - Wenming Wu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
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Hoyos S, Posada-Moreno P, Guzman-Arango N, Chanci-Drago R, Chavez J, Andrés-Duarte A, Salazar-Ochoa S. Pancreatic neuroendocrine tumors: Are tumors smaller than 2 cm truly indolent? World J Gastrointest Oncol 2024; 16:1756-1762. [PMID: 38764809 PMCID: PMC11099423 DOI: 10.4251/wjgo.v16.i5.1756] [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: 12/20/2023] [Revised: 02/07/2024] [Accepted: 03/25/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PNETs) are relatively rare but rank as the second most common pancreatic neoplasm. They can be functional, causing early metabolic disturbances due to hormone secretion, or non-functional and diagnosed later based on tumor size-related symptoms. Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management; some practitioners advocate for surgical removal and others suggest observation due to the tumors' lower potential for malignancy. However, it is unclear whether managing these small tumors expectantly is truly safe. AIM To evaluate poor prognostic factors in PNETs based on tumor size (> 2 cm or < 2 cm) in surgically treated patients. METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín, Colombia. To assess patient survival, quarterly follow-ups were conducted during the first year after surgery, followed by semi-annual consultations at the hospital's hepatobiliary surgery department. Qualitative variables were described using absolute and relative frequencies, and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion. RESULTS The presence of lymph node involvement, neural involvement, and lymphovascular invasion were all associated with an increased risk of mortality, with hazard ratios of 5.68 (95%CI: 1.26-25.61, P = 0.024), 6.44 (95%CI: 1.43-28.93, P = 0.015), and 24.87 (95%CI: 2.98-207.19, P = 0.003), respectively. Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter. The recurrence rates between the two tumor groups were furthermore similar: 18.2% for tumors smaller than 2 cm and 21.4% for tumors larger than 2 cm. Patient survival was additionally comparable between the two tumor groups. CONCLUSION Tumor size does not dictate prognosis; lymph node and lymphovascular involvement affect mortality, which highlights that histopathological factors-rather than tumor size-may play a role in management.
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Affiliation(s)
- Sergio Hoyos
- Hepatobilary and Liver Transplant Unit, Hospital Pablo Tobon Uribe and Gastrohepathology Group Universidad de Antioquia, Medellin 050034, Antioquia, Colombia
| | - Pablo Posada-Moreno
- Department of General Surgery, Universidad Pontificia Bolivariana, Medellín 050034, Antioquia, Colombia
| | - Natalia Guzman-Arango
- Department of General Surgery, Universidad Pontificia Bolivariana, Medellín 050034, Antioquia, Colombia
| | - Romario Chanci-Drago
- Department of General Surgery, Universidad Pontificia Bolivariana, Medellín 050034, Antioquia, Colombia
| | - Jaime Chavez
- Hepatobilary and Liver Transplant Unit, Hospital Pablo Tobon Uribe and Gastrohepathology Group Universidad de Antioquia, Medellin 050034, Antioquia, Colombia
| | - Alvaro Andrés-Duarte
- Hepatobilary and Liver Transplant Unit, Hospital Pablo Tobon Uribe and Gastrohepathology Group Universidad de Antioquia, Medellin 050034, Antioquia, Colombia
| | - Santiago Salazar-Ochoa
- Department of General Surgery, Universidad Pontificia Bolivariana, Medellín 050034, Antioquia, Colombia
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Wu W, Cai S, Chen R, Fu D, Ge C, Hao C, Hao J, Huang H, Jian Z, Jin G, Li F, Li H, Li S, Li W, Li Y, Liang T, Liu X, Lou W, Miao Y, Mou Y, Peng C, Qin R, Shao C, Sun B, Tan G, Wang H, Wang L, Wang W, Wang W, Wei J, Wu H, Wu Z, Yan C, Yang Y, Yin X, Yu X, Yuan C, Zhao Y. Consensus of clinical diagnosis and treatment for non-functional pancreatic neuroendocrine neoplasms with diameter <2 cm. JOURNAL OF PANCREATOLOGY 2023; 6:87-95. [DOI: 10.1097/jp9.0000000000000139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2025] Open
Abstract
In clinical practice, pancreatic neuroendocrine neoplasms (pNENs) with a diameter smaller than 2 cm are commonly referred to as small pNENs. Due to their generally favorable biological characteristics, the diagnosis and treatment of small pNENs differ from other pNENs and are somewhat controversial. In response to this, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association have developed a consensus on the diagnosis and treatment of small pNENs, which is based on evidence-based medicine and expert opinions. This consensus covers various topics, including concepts, disease assessment, treatment selection, follow-up, and other relevant aspects.
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Affiliation(s)
- Wenming Wu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Shouwang Cai
- Department of Hepatobiliary Surgery, PLA General Hospital, Beijing 100853, China
| | - Rufu Chen
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Deliang Fu
- Department of Pancreatic Surgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Chunlin Ge
- Department of Hepatobiliary and Pancreatic Surgery, Hunnan Division of The First Hospital of China Medical University, Shenyang 110167, China
| | - Chunyi Hao
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jihui Hao
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Heguang Huang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510000, China
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital Affiliated to Navy Medical University (Second Military Medical University), Shanghai 200433, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Haimin Li
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
| | - Shengping Li
- Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Weiqin Li
- Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
| | - Yixiong Li
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xubao Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yi Miao
- Pancreas Centre, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yiping Mou
- Department of Gastrointestinal-Pancreatic Surgery, General Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
| | - Chenghong Peng
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Chenghao Shao
- Department of Pancreatic-biliary Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Bei Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
| | - Guang Tan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
| | - Huaizhi Wang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing 401147, China
| | - Lei Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Ji’nan 250012, China
| | - Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Junmin Wei
- Department of General Surgery, Beijing Hospital, Beijing 100730, China
| | - Heshui Wu
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Changqing Yan
- Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | - Yinmo Yang
- Department of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, China
| | - Xiaoyu Yin
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Pancreatic Cancer Institute Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Yupei Zhao
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
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Javed AA, Pulvirenti A, Razi S, Zheng J, Michelakos T, Sekigami Y, Thompson E, Klimstra DS, Deshpande V, Singhi AD, Weiss MJ, Wolfgang CL, Cameron JL, Wei AC, Zureikat AH, Ferrone CR, He J, Pancreatic Neuroendocrine Disease Alliance (PANDA). Grading Pancreatic Neuroendocrine Tumors Via Endoscopic Ultrasound-guided Fine Needle Aspiration: A Multi-institutional Study. Ann Surg 2023; 277:e1284-e1290. [PMID: 35081574 PMCID: PMC9364076 DOI: 10.1097/sla.0000000000005390] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To identify factors associated with concordance between World Health Organization (WHO) grade on cytological analysis (c-grade) and histopathological analysis (h-grade) of surgical specimen in patients with PanNETs and examine trends in utilization and accuracy of EUS-FNA in preoperatively predicting grade. BACKGROUND WHO grading system is prognostic in pancreatic neuroendo-crine tumors (PanNETs). The concordance between c-grade and h-grade is reported to be between 50% and 92%. METHODS A multicenter retrospective study was performed on patients undergoing resection for PanNETs at four high-volume centers between 2010 and 2019. Patients with functional or syndrome-associated tumors, and those receiving neoadjuvant therapy were excluded. Factors associated with concordance between c-grade and h-grade and trends of utilization of EUS-FNA were assessed. RESULTS Of 869 patients included, 517 (59.5%) underwent EUS-FNA; 452 (87.4%) were diagnostic of PanNETs and WHO-grade was reported for 270 (59.7%) patients. The concordance between c-grade and h-grade was 80.4% with moderate concordance ( Kc = 0.52, 95% CI: 0.41-0.63). Significantly higher rates of concordance were observed in patients with smaller tumors (<2 vs. ≥2cm, 81.1% vs. 60.4%, P = 0.005). Highest concordance (98.1%) was observed in patients with small tumors undergoing assessment between 2015-2019 with a near-perfect concordance ( Kc = 0.88, 95% CI: 0.61-1.00). An increase in the utilization of EUS-FNA (56.1% to 64.1%) was observed over the last 2 decades ( P = 0.017) and WHO-grade was more frequently reported (44.2% vs. 77.6%, P < 0.001). However, concordance between c-grade and h-grade did not change significantly (P = 0.118). CONCLUSION Recently, a trend towards increasing utilization and improved diagnostic accuracy of EUS-FNA has been observed in PanNETs. Concordance between c-grade and h-grade is associated with tumor size with near-perfect agreement when assessing PanNETs <2cm in size.
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Affiliation(s)
- Ammar A. Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA
| | - Alessandra Pulvirenti
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Samrah Razi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jian Zheng
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - Yurie Sekigami
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Elizabeth Thompson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David S. Klimstra
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Vikram Deshpande
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Aatur D. Singhi
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | | | - John L. Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alice C. Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Amer H. Zureikat
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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7
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Franchellucci G, Andreozzi M, Carrara S, De Luca L, Auriemma F, Paduano D, Calabrese F, Facciorusso A, Poletti V, Zerbi A, Lania AG, Bertuzzi AF, Spaggiari P, Pedicini V, Rodari M, Fusaroli P, Lisotti A, Ofosu A, Repici A, Mangiavillano B. Contrast Enhanced EUS for Predicting Solid Pancreatic Neuroendocrine Tumor Grade and Aggressiveness. Diagnostics (Basel) 2023; 13:239. [PMID: 36673049 PMCID: PMC9857765 DOI: 10.3390/diagnostics13020239] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/29/2022] [Accepted: 12/29/2022] [Indexed: 01/11/2023] Open
Abstract
Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.
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Affiliation(s)
- Gianluca Franchellucci
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
| | - Marta Andreozzi
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
- Department of Clinical Medicine and Surgery, ‘Federico II’ University of Naples, 80131 Naples, Italy
| | - Silvia Carrara
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Luca De Luca
- Endoscopic Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy
| | - Francesco Auriemma
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Danilo Paduano
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Federica Calabrese
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Valeria Poletti
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Andrea Gerardo Lania
- Endocrinology, Diabetology and Medical Andrology Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Alexia Francesca Bertuzzi
- Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Paola Spaggiari
- Department of Pathology, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Vittorio Pedicini
- Department of Interventional Radiology, Humanitas University, Humanitas Research Hospital IRCCS, 20089 Rozzano, Italy
| | - Marcello Rodari
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Italy
| | - Pietro Fusaroli
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40126 Imola, Italy
| | - Andrea Lisotti
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40126 Imola, Italy
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Benedetto Mangiavillano
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
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8
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Abstract
Neuroendocrine tumors (NETs) represent a heterogeneous group of tumors, with variable presentation based on the location of origin and degree of metastatic spread. There are no randomized control trials to guide surgical management; however, surgery remains the mainstay of treatment for most gastroenteropancreatic NETs based on retrospective studies. Metastatic disease is common at the time of presentation, particularly in the liver. There is a role for cytoreduction for improvement of both symptoms and survival. Robust prospective randomized data exists to support the use of medical therapies to improve progression-free and overall survival in patients with advanced, metastatic, and unresectable NETs.
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9
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Management of Small Nonfunctioning Pancreatic Neuroendocrine Neoplasms: Current Opinion and Controversies. J Clin Med 2022; 12:jcm12010251. [PMID: 36615051 PMCID: PMC9821009 DOI: 10.3390/jcm12010251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 12/31/2022] Open
Abstract
The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has increased due to the widespread use of high-resolution diagnostic imaging in screening programs. Most PNENs are slow-growing indolent neoplasms. However, a local invasion or metastasis can sometimes occur with PNENs, leading to a poor prognosis. The management of small, nonfunctioning PNENs remains under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgery remains a high-risk operation with a 28-30% morbidity and 1% mortality. Therefore, the decision on how to manage small PNENs is challenging. This review focuses on the management of small nonfunctioning PNENs. We also highlight the malignant potential of small PNENs according to tumor size, tumor grade, and tumor biomarker. Endoscopic-ultrasound-guided biopsy is recommended to evaluate the potential risk of malignancy. Furthermore, we discuss the current guidelines and future directions for the management of small PNENs.
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10
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Javed AA, Pulvirenti A, Zheng J, Michelakos T, Sekigami Y, Razi S, McIntyre CA, Thompson E, Klimstra DS, Deshpande V, Singhi AD, Weiss MJ, Wolfgang CL, Cameron JL, Wei AC, Zureikat AH, Ferrone CR, He J. A novel tool to predict nodal metastasis in small pancreatic neuroendocrine tumors: A multicenter study. Surgery 2022; 172:1800-1806. [PMID: 36192215 DOI: 10.1016/j.surg.2022.08.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/25/2022] [Accepted: 08/19/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Nonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. METHODS A multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. RESULTS Nodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71-7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03-1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63-0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. CONCLUSION Our model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.
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Affiliation(s)
- Ammar A Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. http://www.twitter.com/ammar_asrar
| | | | - Jian Zheng
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | - Yurie Sekigami
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Samrah Razi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Caitlin A McIntyre
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Elizabeth Thompson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - David S Klimstra
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Vikram Deshpande
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Aatur D Singhi
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | | | - John L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
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11
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Perinel J, Nappo G, Zerbi A, Heidsma CM, Nieveen van Dijkum EJM, Han HS, Yoon YS, Satoi S, Demir IE, Friess H, Vashist Y, Izbicki J, Muller AC, Gloor B, Sandini M, Gianotti L, Subtil F, Adham M. Sporadic nonfunctional pancreatic neuroendocrine tumors: Risk of lymph node metastases and aggressiveness according to tumor size: A multicenter international study. Surgery 2022; 172:975-981. [PMID: 35623953 DOI: 10.1016/j.surg.2022.04.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/25/2022] [Accepted: 04/06/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. METHODS Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999-2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. RESULTS Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46-2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. CONCLUSION In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.
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Affiliation(s)
- Julie Perinel
- Department of Digestive Surgery, E. Herriot Hospital, Hospices Civils de Lyon, Lyon Sud Faculty of Medicine, UCBL1, Lyon, France.
| | - Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS Rozzano, Milan, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Charlotte M Heidsma
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, The Netherlands
| | | | - Ho Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan; Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Ihsan Ekin Demir
- Department of Surgery, Technical University Munich Faculty of Medicine, Munchen, Germany
| | - Helmut Friess
- Department of Surgery, Technical University Munich Faculty of Medicine, Munchen, Germany
| | - Yogesh Vashist
- Medias Klinikum, Centre for Surgical Oncology, Burghausen, Germany
| | - Jakob Izbicki
- General, Visceral, and Thoracic Surgery Department, Clinic University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Beat Gloor
- University Hospital Bern Inselspital Bern, Switzerland
| | - Marta Sandini
- School of Medicine and Surgery, University of Milano-Bicocca and Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Luca Gianotti
- School of Medicine and Surgery, University of Milano-Bicocca and Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Fabien Subtil
- UCBLUMR CNRS 5558 - LBBE, Service de Biostatistiques, Hospices Civils de Lyon, France
| | - Mustapha Adham
- Department of Digestive Surgery, E. Herriot Hospital, Hospices Civils de Lyon, Lyon Sud Faculty of Medicine, UCBL1, Lyon, France
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12
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Molasy B, Zemła P, Mrowiec S, Grudzińska E, Kuśnierz K. Evaluation of Risk Factors for Distant and Lymph Node Metastasis of Pancreatic Neuroendocrine Tumors. Ther Clin Risk Manag 2022; 18:745-752. [PMID: 35937972 PMCID: PMC9346299 DOI: 10.2147/tcrm.s361332] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 05/30/2022] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Metastases of pancreatic neuroendocrine tumors (pNETs) can be found at the time of diagnosis in 20-50% of cases. Small asymptomatic tumors may be left for observation; however, they can metastasize. The aim of the study was to evaluate risk factors for distant and lymph node metastases of pNETs. PATIENTS AND METHODS One hundred and fourteen patients with postoperatively confirmed pNET were analyzed retrospectively in a single ENETS Center of Excellence. The relationship between location, size, differentiation of the tumor, and occurrence of lymph node and distant metastases was analyzed. RESULTS pNETs' location was pancreatic head - 38 (33.3%), body or tail - 68 (59.7%), and 8 (7.0%) involved the entire organ. Fifty-six (49.1%) tumors were graded G1, 50 (43.9%) G2, and 8 (7.0%) G3. Seventy-two (63.2%) tumors were ≥2 cm in diameter, and 42 (36.8%) <2 cm. Twenty-two (19.3%) patients had distant metastases and 47 (41.2%) had lymph node metastases. In ≥2 cm tumors distant and lymph node metastases were more frequent (p < 0.05). Distant metastases incidence was significantly higher in distally located tumors (p = 0.01) and in G2 and G3 tumors (p < 0.01). In 9.5% of <2cm tumors, distant metastases were present at diagnosis. CONCLUSION Distant metastases are more often found in larger, distally located pNETs grade G2 and G3, while a higher occurrence of lymph node metastases seems to be associated only with larger tumor size. A considerable number of tumors <2 cm in size have distant metastases already at the diagnosis, which might indicate the need for careful qualification of smaller lesions for observation.
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Affiliation(s)
- Bartosz Molasy
- Students’ Scientific Society of the Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
- Department of General Surgery, St Alexander Hospital, Kielce, Poland
| | - Patryk Zemła
- Students’ Scientific Society of the Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
| | - Sławomir Mrowiec
- Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
| | - Ewa Grudzińska
- Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
| | - Katarzyna Kuśnierz
- Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland
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13
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Ye J, Wu H, Li J, Liu C. Impact of Surgery on Non-Functional Pancreatic Neuroendocrine Tumors ≤2 cm: Analyses With Propensity Score–Based Inverse Probability of Treatment Weighting. Front Surg 2022; 9:890564. [PMID: 36071950 PMCID: PMC9442601 DOI: 10.3389/fsurg.2022.890564] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 06/23/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose The impact of surgery on non-functional pancreatic neuroendocrine tumors (NF-PNETs) ≤2 cm is controversial. This study sought to demonstrate the impact of surgery on the prognosis of NF-PNETs ≤2 cm with different biological behaviors. Methods Patients with NF-PNETs ≤2 cm from 2004 to 2015 in the Surveillance, Epidemiology, and End Results database were included in this study. An inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. Kaplan–Meier survival analysis and Cox proportional hazards regression were used to evaluate the effect of surgery on the prognosis. Results In the IPTW-adjusted Cox proportional hazards regression analysis, surgery improved the cancer-specific survival (CSS) in the overall cohort (hazard ratio [HR], 0.187; 95% confidence interval [CI], 0.102–0.343; p < 0.001), patients with poorly differentiated or undifferentiated tumor grades (HR, 0.238; 95% CI, 0.105–0.64; p < 0.001), patients with distant metastasis (HR, 0.102; 95% CI, 0.021–0.496; p = 0.005), and patients with local invasion (HR, 0.059; 95% CI, 0.005–0.683; p = 0.002). Surgery did not improve the CSS in patients with lymph node metastasis only (HR, 0.26; 95% CI, 0.0462–1.461; p = 0.126) or patients with well or moderate differentiation while without distant and lymph node metastasis (HR, 0.387; 95% CI, 0.146–1.028; p = 0.057). Conclusions Among patients with NF-PNETs ≤2 cm, different biological behaviors correlate with different prognostic impacts of surgery. As long as distant metastasis does not occur and the grade is well–moderately differentiated, these patients will not benefit from surgery no matter whether lymph node metastasis occurs or not. However, when local invasion appears in this group of patients, surgery should be performed. Moreover, patients with a tumor grade of poorly differentiated or undifferentiated or those with distant metastases may benefit from surgery.
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14
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Arra DASM, Ribeiro HSC, Henklain G, Barbosa A, Torres SM, Diniz AL, Godoy AL, Farias IC, Costa WL, Coimbra FJF. Surgery or active surveillance for pNETs < 2 cm: Preliminary results from a single center Brazilian cohort. J Surg Oncol 2022; 126:168-174. [DOI: 10.1002/jso.26931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 05/12/2022] [Accepted: 05/14/2022] [Indexed: 01/27/2023]
Affiliation(s)
| | | | | | | | | | | | | | | | - Wilson L. Costa
- A.C. Camargo Cancer Center Sao Paulo Brazil
- Department of Medicine/Epidemiology and Population Sciencies, Baylor College of Medicine Houston Texas USA
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15
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Comparative outcomes of pancreatic neuroendocrine neoplasms: A population-based analysis of the SEER database. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2181-2187. [DOI: 10.1016/j.ejso.2022.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/07/2022] [Accepted: 05/17/2022] [Indexed: 11/18/2022]
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16
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Are We Undertreating Black Patients with Nonfunctional Pancreatic Neuroendocrine Tumors? Critical Analysis of Current Surveillance Guidelines by Race. J Am Coll Surg 2022; 234:599-606. [PMID: 35380181 PMCID: PMC8988469 DOI: 10.1097/xcs.0000000000000105] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Pancreatic neuroendocrine tumor (PNET) survival outcomes differ by race. Current recommendations for surveillance of PNETs less than 2 cm in size are based on low malignant potential and low rates of lymph node metastases (LNM). We investigated whether these guidelines are universally applicable regardless of race. STUDY DESIGN A multi-institutional analysis of patients with resected, nonfunctional, sporadic PNETs was performed initially using the US Neuroendocrine Study Group dataset with the National Cancer Database as a validation dataset. Patients with distant metastatic disease were excluded from analysis. RESULTS A total of 453 (388 White and 65 Black) and 5,532 patients (4,772 White and 760 Black) were analyzed in the initial and validation datasets, respectively. White patients had a low incidence of LNM in tumors of less than 2 cm in both datasets (5% and 12%, respectively), which increased with tumor size. However, the incidence of LNM in Black patients was similar in the initial and validation datasets for tumors sized less than 2 cm (23% and 21%) and 2 to 3 cm (21% and 29%). Black patients had a significantly higher incidence of LNM in tumors less than 2 cm in size in the initial and validation datasets (p < 0.01) compared with White patients. CONCLUSIONS The current recommendation for surveillance of PNETs of less than 2 cm in size is likely based on a low rate of LNM seen in a predominantly White population. The incidence of LNM in Black patients with tumors less than 2 cm in size is clinically relevant and concerning. Current guidelines may not be universally applicable, and a more aggressive approach to resection in Black patients with small PNETs may be warranted.
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17
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Keihanian T, Othman M. Epidemiology, Pathogenesis, and Prognosis of Pancreatic Neuroendocrine Tumors. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:623-637. [DOI: 10.1007/978-3-030-41683-6_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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18
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Frey S, Mirallié E, Le Bras M, Regenet N. What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review. Cancers (Basel) 2021; 13:5954. [PMID: 34885063 PMCID: PMC8656750 DOI: 10.3390/cancers13235954] [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] [Received: 10/29/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a "wait and see" strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.
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Affiliation(s)
- Samuel Frey
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- L’institut du Thorax, Université de Nantes, CNRS, INSERM, CHU de Nantes, 44000 Nantes, France
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Eric Mirallié
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Maëlle Le Bras
- Endocrinologie, Diabétologie et Nutrition, L’institut du Thorax, CHU Nantes, 44000 Nantes, France;
| | - Nicolas Regenet
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
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19
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Tsilimigras DI, Pawlik TM. Pancreatic neuroendocrine tumours: conservative versus surgical management. Br J Surg 2021; 108:1267-1269. [PMID: 34519788 DOI: 10.1093/bjs/znab232] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 06/02/2021] [Indexed: 11/12/2022]
Affiliation(s)
- D I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - T M Pawlik
- Department of Surgery, Division of Surgical Oncology, Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
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20
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Zheng-Pywell R, Fang A, AlKashash A, Awad S, Reddy S, Vickers S, Heslin M, Dudeja V, Chen H, Rose JB. Prognostic Impact of Tumor Size on Pancreatic Neuroendocrine Tumor Recurrence May Have Racial Variance. Pancreas 2021; 50:347-352. [PMID: 33835965 PMCID: PMC8041062 DOI: 10.1097/mpa.0000000000001776] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE The incidence of pancreatic neuroendocrine tumors (PNETs) has increased over the last decade. Black patients have worse survival outcomes. This study investigates whether oncologic outcomes are racially disparate at a single institution. METHODS Retrospective analysis was performed on 151 patients with resected PNETs between 2010 and 2019. RESULTS More White males and Black females presented with PNETs (P = 0.02). White patients were older (65 years vs 60 years; P = 0.03), more likely to be married (P < 0.01), and had higher median estimated yearly incomes ($28,973 vs $17,767; P < 0.01) than Black patients. Overall and disease-free survival were not different. Black patients had larger median tumor sizes (30 mm vs 23 mm; P = 0.02). Tumor size was predictive of recurrence only for White patients (hazard ratio, 1.02; P = 0.01). Collectively, tumors greater than 20 mm in size were more likely to have recurrence (P = 0.048), but this cutoff was not predictive in either racial cohort independently. CONCLUSIONS Black patients undergoing curative resection of PNETs at our institution presented with larger tumors, but that increased size is not predictive of disease-free survival in this population.
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Affiliation(s)
- Rui Zheng-Pywell
- From the Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
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21
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Liu X, Chin W, Pan C, Zhang W, Yu J, Zheng S, Liu Y. Risk of malignancy and prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. Gland Surg 2021; 10:219-232. [PMID: 33633978 DOI: 10.21037/gs-20-582] [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] [Indexed: 12/14/2022]
Abstract
Background Small nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) ≤2 cm have variable biological features, and there is no gold standard treatment for their management. The present study aimed to evaluate the risk of malignancy of small NF-PNETs and their outcomes following curative resection. Methods Patients with NF-PNETs undergoing surgical resection at the First Affiliated Hospital, College of Medicine, Zhejiang University, between 2012 and 2017 were included. Clinicopathological characteristics, perioperative results, and prognosis were retrospectively analyzed. Results A total of 73 patients were identified, including 28 with small NF-PNETs and 45 large PNETs; 32.1% of NF-PNETs ≤2 cm underwent a parenchyma-sparing pancreas surgery, which was >6.7% in large NF-PNETs. No statistically significant differences in perioperative results, postoperative complications, and long-term outcomes were found between small tumors undergoing standard and parenchyma-sparing pancreatectomy. Eighteen small tumors (64.3%) developed a perioperative complication, with a clinically significant pancreatic fistula rate of 25%; however, only 2 patient needed reintervention. Small NF-PNETs in 3 patients were malignant. Multivariate logistic regression showed that grade ≥3 and lymphovascular invasion were independently related to malignancy in NF-PNETs. Conclusions Small NF-PNETs (≤2 cm) are not immune from potential malignancy. Surgical resection may be considered for small tumors and can provide favorable postoperative and long-term outcomes. Parenchyma-sparing pancreatectomy may be an alternative surgery for selected small local NF-PNETs.
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Affiliation(s)
- Xi Liu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Wenjie Chin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Chenggeng Pan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Weichen Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Jun Yu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Yuanxing Liu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
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22
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Cloyd JM, Poultsides GA. The Landmark Series: Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2020; 28:1039-1049. [PMID: 32948965 DOI: 10.1245/s10434-020-09133-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 08/29/2020] [Indexed: 12/23/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous group of neoplasms arising from pancreatic islet cells that remain relatively rare but are increasing in incidence worldwide. While significant advances have been made in recent years with regard to systemic therapies for patients with advanced disease, surgical resection remains the standard of care for most patients with localized tumors. Although formal pancreatectomy with regional lymphadenectomy is the standard approach for most PNETs, pancreas-preserving approaches without formal lymphadenectomy are acceptable for smaller tumors at low risk for lymph node metastases. Furthermore, observation of small, asymptomatic, low-grade PNETs is a safe, initial strategy and is generally recommended for tumors < 1 cm in size. In this Landmark Series review, we highlight the critical studies that have defined the surgical management of PNETs.
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Affiliation(s)
- Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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23
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Weilin M, Xu H, Yang L, Wenqi C, Huanyu W, Wentao Z, Dayong J, Wenchuan W, Dansong W, Tiantao K, Lei Z, Wenhui L, Xuefeng X. Propensity score-matched analysis of clinical outcome after enucleation versus regular pancreatectomy in patients with small non-functional pancreatic neuroendocrine tumors. Pancreatology 2020; 20:169-176. [PMID: 31941586 DOI: 10.1016/j.pan.2019.12.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 10/19/2019] [Accepted: 12/11/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The effectiveness of enucleation in treatment for low-grade (G1, G2) small (≤2 cm) non-functional pancreatic neuroendocrine tumors (sNF-pNETs) remains controversial. This study investigated short- and long-term outcome of enucleation comparing with regular pancreatectomy in patients with sNF-pNETs. METHODS The clinical data of patients with sNF-pNETs who underwent surgery in our hospital from January 2000 to December 2017 were retrospectively collected. Short- and long-term outcomes of two operations were analyzed. The propensity score matching (PSM) was performed to reduce potential selection bias. RESULTS A total of 123 patients with sNF-pNETs were enrolled with 62 males, 69 G1, and median age was 56.91 ± 10.04 years old. During the follow-up period (mean 87 ± 58.1 months), 9(7.32%) disease progressed (recurrence or metastasis) and 2 died (1.62%), 5-years OS was 100%, 5-years DFS was 91.4%. Both lymph node metastasis (p = 0.117) and pathological grade (p = 0.050) were not prognostic factors for sNF-pNETs. The propensity score-matched cohort comprised 27 patients with enucleation and 44 patients with regular pancreatectomy. Enucleation was noninferior to regular pancreatectomy in terms of DFS, before or after PSM. The surgical duration (P < 0.01) and blood loss (P < 0.01) significantly decreased in enucleation compared with regular pancreatectomy. The other postoperative complications tended to occur in regular pancreatectomy than in enucleation, but no statistically significant difference (all p > 0.05). CONCLUSION Enucleation seems to be an effective option for the treatment of sNF-pNETs with a lower total rate of postoperative complications and similar long-term prognosis, compared with regular pancreatectomy.
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Affiliation(s)
- Mao Weilin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Han Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lv Yang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chen Wenqi
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wang Huanyu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhou Wentao
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jin Dayong
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wu Wenchuan
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wang Dansong
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kuang Tiantao
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhang Lei
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lou Wenhui
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Xu Xuefeng
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
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24
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Assi HA, Mukherjee S, Kunz PL, Machiorlatti M, Vesely S, Pareek V, Hatoum H. Surgery Versus Surveillance for Well-Differentiated, Nonfunctional Pancreatic Neuroendocrine Tumors: An 11-Year Analysis of the National Cancer Database. Oncologist 2019; 25:e276-e283. [PMID: 32043766 DOI: 10.1634/theoncologist.2019-0466] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (panNETs) are a rare group of tumors that make up 2%-3% of pancreatic tumors. Recommended treatment for panNETs generally consists of resection for symptomatic or large asymptomatic tumors; however, optimal management for localized disease is still controversial, with conflicting recommendations in established guidelines. Our study aim is to compare surgical intervention versus active surveillance in nonmetastatic panNETs by size of primary tumor. MATERIALS AND METHODS Using the National Cancer Database, we identified 2,004 patients diagnosed with localized well-differentiated, nonfunctional panNETs (NF-panNETs) between 2004 and 2015. Patients' clinicopathologic characteristics, treatment modalities, and overall survival (OS) were analyzed using frequency statistics, chi-square, and Kaplan-Meier curves. The objective of the study is to assess the outcome of surgical resection versus nonoperative management in patients with panNETs with different tumor sizes. RESULTS Tumor sizes were divided into three categories: <1 cm, 1-2 cm, and >2 cm. The number of patients with tumor size <1 cm, 1-2 cm, and >2 cm was 220 (11%), 794 (39.6%), and 990 (49.4%), respectively. Overall, 1,781 underwent surgical resection, whereas 223 patients did not. Median follow-up was 25.9 months. After adjusting for covariates, surgical resection was associated with improved OS in patients with tumor size 1-2 cm (hazard ratio [HR] = 0.37) and >2c m (HR = 0.30) but not <1 cm (HR = 2.81). Independent prognostic factors were age at diagnosis, Charlson-Deyo comorbidity score, stage, tumor location, and surgical resection. Higher tumor grade was not associated with worse OS. CONCLUSION Our findings suggest that active surveillance is potentially a safe approach for NF-panNETs <1 cm. Larger tumors likely need active intervention. Intermediate-grade tumors did not result in worse survival outcome compared with low-grade tumors. Future studies might consider prospective randomized clinical trials to validate our findings. IMPLICATIONS FOR PRACTICE The present study seeks to address the discrepancy in treatment recommendations in the management of nonfunctional pancreatic neuroendocrine tumors (NF-panNETs) by evaluating whether surgical resection is associated with improved overall survival in different tumor size groups as well as elucidating independent prognostic factors in patients with NF-panNETs. Data from the National Cancer Database were reviewed. This study's findings suggest that active surveillance is potentially a safe approach for NF-panNETs <1 cm. Larger tumors likely need active intervention. Independent prognostic factors include age at diagnosis, Charlson-Deyo comorbidity score, stage, tumor location, and surgical resection. These findings will help guide medical and surgical oncologists when formulating treatment plans for patients with small NF-panNETs.
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Affiliation(s)
- Hussein A Assi
- Department of Hematology/Oncology, Stephenson Cancer Center, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Sarbajit Mukherjee
- Department of Medicine, Roswell Park Comprehensive Cancer, University of Buffalo, Buffalo, New York, USA
| | - Pamela L Kunz
- Department of Hematology/Oncology, Stanford Cancer Institute, Stanford University Medical Center, Stanford, California, USA
| | - Michael Machiorlatti
- Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Sara Vesely
- Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Vipul Pareek
- Department of Hematology/Oncology, Stephenson Cancer Center, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Hassan Hatoum
- Department of Hematology/Oncology, Stephenson Cancer Center, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
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25
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Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study: Association Francophone de Chirurgie Endocrinienne & Groupe d'Etude des Tumeurs Endocrines. Ann Surg 2019; 268:158-164. [PMID: 28263205 PMCID: PMC6012055 DOI: 10.1097/sla.0000000000002191] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Objective: To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET). Background: Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinical outcome are poorly defined, and management is still controversial for small NF-PET. Methods: Clinical outcome and tumor progression were analyzed in 46 patients with MEN1 with 2 cm or smaller NF-PET who did not have surgery at the time of initial diagnosis. Survival data were analyzed using the Kaplan-Meier method. Results: Forty-six patients with MEN1 were followed prospectively for 10.7 ± 4.2 (mean ± standard deviation) years. One patient was lost to follow-up and 1 died from a cause unrelated to MEN1. Twenty-eight patients had stable disease and 16 showed significant progression of pancreaticoduodenal involvement, indicated by increase in size or number of tumors, development of a hypersecretion syndrome, need for surgery (7 patients), and death from metastatic NF-PET (1 patient). The mean event-free survival was 13.9 ± 1.1 years after NF-PET diagnosis. At last follow-up, none of the living patients who had undergone surgery or follow-up had evidence of metastases on imaging studies. Conclusions: Our study shows that conservative management for patients with MEN1 with NF-PET of 2 cm or smaller is associated with a low risk of disease-specific mortality. The decision to recommend surgery to prevent tumor spread should be balanced with operative mortality and morbidity, and patients should be informed about the risk-benefit ratio of conservative versus aggressive management when the NF-PET represents an intermediate risk.
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26
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Bartolini I, Bencini L, Bernini M, Farsi M, Calistri M, Annecchiarico M, Moraldi L, Coratti A. Robotic enucleations of pancreatic benign or low-grade malignant tumors: preliminary results and comparison with robotic demolitive resections. Surg Endosc 2019; 33:2834-2842. [PMID: 30421079 DOI: 10.1007/s00464-018-6576-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 11/02/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND The incidental detection of benign to low-grade malignant small pancreatic neoplasms increased in the last decades. The surgical management of these patients is still under debate. The aim of this paper is to evaluate the safety and feasibility of robotic enucleations and to compare the outcomes with non-parenchymal sparing robotic resections. METHODS The study included a total of 25 patients. Nine of them underwent a robotic enucleation (EN Group) and 16 patients received a robotic demolitive resection (DR Group). Perioperative and medium-term outcomes were compared between the two groups. RESULTS Patients' baseline characteristics were similar in the two groups except for presence of symptoms and tumor size, due to the inclusion criteria. Operative time was significantly shorter and postoperative results were better for EN group, including a significant shorter hospitalization (5 vs. 8 days, p = 0.027), reduced pancreatic leaks (22% vs. 50%, p = 0.287) and a better preservation of glandular function (100% vs. 62.5%, p = 0.066). Mortality rate was zero in both groups, with all patients free from disease at a median follow-up of 18 months. CONCLUSIONS The risks of under/overtreatment remain still unavoidable for benign to low-grade malignant small pancreatic neoplasms. Simple enucleation should be performed whenever oncological appropriate, to achieve the best postoperative outcomes. The adoption of robotic technique might widen the indications for parenchymal sparing, minimally invasive surgery.
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Affiliation(s)
- Ilenia Bartolini
- Department of Oncology, Division of Surgical Oncology and Robotics, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy.
- Department of Surgery and Translational Medicine, Hepatobiliary Surgery Unit, University of Florence-AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy.
| | - Lapo Bencini
- Department of Oncology, Division of Surgical Oncology and Robotics, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy
| | - Marco Bernini
- Department of Oncology, Division of Oncologic and Reconstructive Breast Surgery, Breast Unit, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy
| | - Marco Farsi
- Department of Oncology, Division of Surgical Oncology and Robotics, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy
| | - Massimo Calistri
- Department of Oncology, Division of Surgical Oncology and Robotics, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy
| | - Mario Annecchiarico
- Department of Oncology, Division of Surgical Oncology and Robotics, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy
| | - Luca Moraldi
- Department of Oncology, Division of Surgical Oncology and Robotics, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy
| | - Andrea Coratti
- Department of Oncology, Division of Surgical Oncology and Robotics, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy
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27
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Partelli S, Mazza M, Andreasi V, Muffatti F, Crippa S, Tamburrino D, Falconi M. Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: Limitations to apply guidelines into real life. Surgery 2019; 166:157-163. [DOI: 10.1016/j.surg.2019.04.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/20/2019] [Accepted: 04/07/2019] [Indexed: 12/20/2022]
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28
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Cui Y, Khanna LG, Saqi A, Crapanzano JP, Mitchell JM, Sethi A, Gonda TA, Kluger MD, Schrope BA, Allendorf J, Chabot JA, Poneros JM. The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors. Clin Endosc 2019; 53:213-220. [PMID: 31302988 PMCID: PMC7137561 DOI: 10.5946/ce.2019.068] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 04/06/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/AIMS The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratify PNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NFPNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. METHODS We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NFPNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. RESULTS There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordance was the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028) were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumor size >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. CONCLUSION NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs with intermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUSFNA can be monitored without surgical intervention, up to tumor size 20 mm.
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Affiliation(s)
- YongYan Cui
- Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Lauren G Khanna
- Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA
| | - Anjali Saqi
- Department of Pathology and Cell Biology, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - John P Crapanzano
- Department of Pathology and Cell Biology, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - James M Mitchell
- Department of Pathology and Cell Biology, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Amrita Sethi
- Division of Digestive and Liver Diseases, Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Tamas A Gonda
- Division of Digestive and Liver Diseases, Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Michael D Kluger
- Department of Surgery, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - Beth A Schrope
- Department of Surgery, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - John Allendorf
- Department of Surgery, New York University Winthrop Hospital, Mineola, NY, USA
| | - John A Chabot
- Department of Surgery, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
| | - John M Poneros
- Division of Digestive and Liver Diseases, Department of Medicine, New York Presbyterian Columbia University Irving Medical Center, New York, NY, USA
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29
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Lopez-Aguiar AG, Ethun CG, Zaidi MY, Rocha FG, Poultsides GA, Dillhoff M, Fields RC, Idrees K, Cho CS, Abbott DE, Cardona K, Maithel SK. The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management. Surgery 2019; 166:15-21. [PMID: 31072670 DOI: 10.1016/j.surg.2019.03.008] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 02/17/2019] [Accepted: 03/03/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUND Management of <2-cm pancreatic neuroendocrine tumors is controversial. Although often indolent, the oncologic heterogeneity of these tumors particularly related to lymph node metastases poses challenges when deciding between resection versus surveillance. METHODS We analyzed all patients who underwent resection of primary nonfunctional <2-cm with curative-intent at 8 institutions of the US Neuroendocrine Tumor Study Group from 2000 to 2016. Pancreatic neuroendocrine tumors with poor differentiation and Ki-67 > 20% were excluded. Our primary aim was to create a lymph node risk score that predicted lymph node metastases accurately for <2-cm pancreatic neuroendocrine tumors, utilizing readily available preoperative data. RESULTS Of 695 patients with resected pancreatic neuroendocrine tumors, 309 were <2 cm. Of these small pancreatic neuroendocrine tumors, 25% were proximal (head/uncinate), 23% had a Ki-67 > 3%, and only 8% were moderately differentiated. Also, only 9% of all <2-cm pancreatic neuroendocrine tumors were lymph node (+). Indeed lymph node positivity was associated with worse 5-year recurrence-free survival compared with lymph node (-) disease (80% vs 96%; P = .007). Factors known preoperatively to be associated with lymph node metastases were proximal location (odds ratio 4.0; P = .002) and Ki-67 ≥3% (odds ratio 2.7; P = .05). Moderate differentiation was not associated with lymph node (+) disease. Location and Ki-67 were assigned a value weighted by their odds ratio: (distal= 1, proximal= 4, and Ki-67 < 3% = 1 and Ki-67 ≥ 3% = 3), which formed a lymph node risk score ranging 1-7. Scores were categorized into low (1-2), intermediate (3-4), and high (5-7) risk groups. Incidence of lymph node metastases increased progressively based on risk group, with low = 3.2%, intermediate = 13.8%, and high = 20.5%. Only 3.4% of pancreatic neuroendocrine tumors with a Ki-67 < 3% in the distal pancreas were lymph node (+) compared with 21.4% of pancreatic neuroendocrine tumors with a Ki-67 ≥ 3% in the head/uncinate. CONCLUSION This simple and novel lymph node risk score utilizes readily available preoperative factors (tumor location and Ki-67) to stratify risk of lymph node metastases accurately s for < 2-cm pancreatic neuroendocrine tumors and may help guide management strategy.
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Affiliation(s)
- Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Cecilia G Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Mohammad Y Zaidi
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Flavio G Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, WA
| | | | - Mary Dillhoff
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St. Louis, MO
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Clifford S Cho
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Daniel E Abbott
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
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30
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Hopper AD, Jalal M, Munir A. Recent advances in the diagnosis and management of pancreatic neuroendocrine tumours. Frontline Gastroenterol 2019; 10:269-274. [PMID: 31290854 PMCID: PMC6583562 DOI: 10.1136/flgastro-2018-101006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 09/12/2018] [Accepted: 09/14/2018] [Indexed: 02/06/2023] Open
Abstract
The incidence of pancreatic neuroendocrine tumours (PNET) is rising mainly due to the increased use of cross-sectional imaging. Although many PNETs are asymptomatic and non-functioning, the overall 5-year survival is still less than 50%. In this article, we review the advances in diagnosis, classification and staging of PNET that have evolved with the development of new cross-sectional imaging methods and biopsy techniques. With accurate classification, evidence-based, individualised prognostic outcomes and treatments are able to be given which are also discussed.
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Affiliation(s)
- Andrew D Hopper
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Mustafa Jalal
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Alia Munir
- Department of Endocrinology, Royal Hallamshire Hospital, Sheffield, UK
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31
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Oleinikov K, Dancour A, Epshtein J, Benson A, Mazeh H, Tal I, Matalon S, Benbassat CA, Livovsky DM, Goldin E, Gross DJ, Jacob H, Grozinsky-Glasberg S. Endoscopic Ultrasound-Guided Radiofrequency Ablation: A New Therapeutic Approach for Pancreatic Neuroendocrine Tumors. J Clin Endocrinol Metab 2019; 104:2637-2647. [PMID: 31102458 DOI: 10.1210/jc.2019-00282] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 04/03/2019] [Indexed: 02/07/2023]
Abstract
CONTEXT Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is rapidly emerging as feasible therapy for patients with pancreatic neuroendocrine tumors (pNETs) in selected cases, as a result of its favorable safety profile. OBJECTIVE To assess the feasibility, safety, and efficacy of EUS-RFA in a cohort of patients with functional and nonfunctional pNETs (NF-pNETs). DESIGN Data on pNET patients treated with EUS-RFA between March 2017 and October 2018 at two tertiary centers was retrospectively analyzed. RESULTS The cohort included 18 adults (eight women, 10 men), aged 60.4 ± 14.4 years (mean ± SD), seven insulinoma patients, and 11 patients with NF-pNETs. Twenty-seven lesions with a mean diameter of 14.3 ± 7.3 mm (range 4.5 to 30) were treated. Technical success defined as typical postablative changes on a surveillance imaging was achieved in 26 out of 27 lesions. Clinical response with normalization of glucose levels was observed in all (seven of seven) insulinoma cases within 24 hours of treatment. Overall, there were no major complications 48 hours postprocedure. No clinically significant recurrences were observed during mean follow-up of 8.7 ± 4.6 months (range 2 to 21 months). CONCLUSIONS EUS-guided RFA of pNETs is a minimally invasive, safe, and technically feasible procedure for selected patients.
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Affiliation(s)
- Kira Oleinikov
- Neuroendocrine Tumor Unit, Endocrinology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Alain Dancour
- Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Julia Epshtein
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Department of Gastroenterology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Ariel Benson
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Department of Gastroenterology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Haggi Mazeh
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Ilanit Tal
- Neuroendocrine Tumor Unit, Endocrinology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Shay Matalon
- Institute of Gastroenterology, Assaf Harofeh Medical Center, Zrifin, Israel
| | - Carlos A Benbassat
- Institute of Endocrinology, Assaf Harofeh Medical Center, Zrifin, Israel
| | - Dan M Livovsky
- Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Eran Goldin
- Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - David J Gross
- Neuroendocrine Tumor Unit, Endocrinology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Harold Jacob
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Department of Gastroenterology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Endocrinology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- European Neuroendocrine Tumor Society (ENETS) Centre of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
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Abstract
Small (<2 cm) sporadic neuroendocrine pancreatic neoplasms (pNENs) are a heterogeneous group of neoplasms, which can be separated into functionally active or non-functional tumors. Functionally active pNENs release various hormones, such as insulin, gastrin, glucagon and vasoactive intestinal hormones and therefore lead to severe symptoms independent of their size. The main symptoms include hypoglycemia, coma (insulinoma), diarrhea (gastrinoma, VIPoma), intestinal ulcers (gastrinoma) and hyperglycemia (glucagonoma). Asymptomatic inactive pNENs do not cause a hormonal syndrome even though in immunohistochemistry they are positive for various hormones and endocrine markers (e.g. chromogranin and synaptophysin). Non-active small pNENs are increasingly being found because of the widespread use of high-resolution imaging and are named incidental pNENs. The current therapy algorithms of small functionally active and non-functional pNENs are very different and include besides non-operative management and surveillance (wait and see strategy) of non-active pNENs (G1, low G2), all minimally invasive, open and robotic techniques of pancreas resection. Until today almost all recommendations of surgical and nonsurgical therapy algorithms have been established based on retrospective data.
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Sauvanet A. Gastroenteropancreatic neuroendocrine tumors: Role of surgery. ANNALES D'ENDOCRINOLOGIE 2019; 80:175-181. [PMID: 31079831 DOI: 10.1016/j.ando.2019.04.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Natural history of gastroenteropancreatic (GEP) Neuroendocrine tumors (NETs) is better and better known so indications of surgery are presently selective. Surgical resection, but also endoscopic resection and observation, can be proposed for gastric NETs according to presentation, size and grade. For small bowel NETs, resection is frequently needed but should obtain the best compromise between radicality and postoperative functional disorders. Appendiceal NETs are frequently diagnosed by appendectomy for appendicitis, but some patients at high risk for lymph node metastasis and recurrence should be reoperated for radical resection. Rectal NETs are often diagnosed incidentally; the smallest (<1cm) can be resected endoscopically but the most aggressive need a oncological proctectomy. Pancreatic NETs represent a wide spectrum, ranging from fully benign tumors to very aggressive ones. Insulinomas are mostly benign, responsible for incapacitating symptoms despite medical treatment, and should ideally be treated by parenchyma sparing resection, mainly enucleation. Conversely, symptoms of gastrinomas are efficiently treated medically but their resection needs an oncological approach. Nonfunctioning PNETs are more and more frequently and incidentally discovered. According to their size, presentation and patient's characteristics, they need a resection (oncological or parenchyma-sparing) or a close observation.
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Affiliation(s)
- Alain Sauvanet
- Department of HPB surgery, pôle des maladies de l'appareil digestif (PMAD), université Paris Diderot, hôpital Beaujon, AP-HP, 100, boulevard du Général-Leclerc, 92110 Clichy, France.
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Maker AV, Tran TB, Coburn N, Fong ZV, Cardona K, Newell P, Morris-Stiff G, Chavin K, Mansour J. Does attending a Delphi consensus conference impact surgeon attitudes? Survey results from the Americas HepatoPancreatoBiliary Association consensus conference on small asymptomatic pancreatic neuroendocrine tumors. HPB (Oxford) 2019; 21:524-530. [PMID: 30442562 DOI: 10.1016/j.hpb.2018.10.001] [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: 08/09/2018] [Revised: 10/02/2018] [Accepted: 10/05/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Management of asymptomatic small well-differentiated (panNET) <2 cm remains controversial. A consensus conference was held on this topic. The impact of attending the conference and participating in the audience response survey on surgeon's clinical approach to pancreatic neuroendocrine tumors was assessed. METHODS Audience members were surveyed using a smartphone real-time response system at the beginning and end of the conference. RESULTS The majority of 75 attendees underwent fellowship training, and 30% had >10 years experience as attending surgeons. Previously published consensus statements on the topic were considered insufficient to guide surgical practice by 82% of attendees, and over 96% desired additional data. After review of the data, consensus statements, and decision-making process, a significant number of participants changed their opinions regarding indications for tissue biopsy (p = 0.001), size thresholds for excision (p = 0.002), and regional lymph node dissection (p = 0.002) independent of whether a consensus was reached by the content-expert panel. CONCLUSIONS This represented the first Delphi process consensus on the topic, and the survey confirmed the topic as well-chosen and timely. Attendees changed opinions on management of panNET regardless of whether formal consensus was reached. Therefore, statements of consensus combined with presentation of literature and live discussion served to impact attendees' approach to this disease.
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Affiliation(s)
- Ajay V Maker
- Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA.
| | - Thuy B Tran
- Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Natalie Coburn
- Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, ON, USA
| | - Zhi V Fong
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | | | - Philippa Newell
- Department of Surgery, Providence Portland Medical Center, Portland, OR, USA
| | | | - Kenneth Chavin
- Department of Surgery, University Hospitals, Cleveland, OH, USA
| | - John Mansour
- Department of Surgery, UT Southwestern, Dallas, TX, USA
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Concomitant pancreatic neuroendocrine tumors in hereditary tumor syndromes: who, when and how to operate? JOURNAL OF PANCREATOLOGY 2019. [DOI: 10.1097/jp9.0000000000000016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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36
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Deguelte S, de Mestier L, Hentic O, Cros J, Lebtahi R, Hammel P, Kianmanesh R. Sporadic pancreatic neuroendocrine tumor: Surgery of the primary tumor. J Visc Surg 2018; 155:483-492. [PMID: 30448206 DOI: 10.1016/j.jviscsurg.2018.08.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The management of patients with sporadic pancreatic neuroendocrine tumors (PNET) is multi-disciplinary and often, multimodal. Surgery has a large part in treatment because it is the only potentially curative therapeutic modality if resection can be complete. The update reviews the operative indications and the different surgical techniques available (including parenchymal-sparing surgery) to treat the primary lesion according to patient status, preoperative work-up and whether the tumor is functioning or not. The place of observation for "small" non-functional sporadic PNET is also discussed.
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Affiliation(s)
- S Deguelte
- Service de chirurgie generale, digestive et endocrinienne, hôpital Robert-Debré, université de Reims Champagne-Ardenne, 51100 Reims, France
| | - L de Mestier
- Service de gastroenterologie-pancréatologie, hôpital Beaujon, université Denis Diderot, AP-HP Clichy, 92110 Paris 7, France
| | - O Hentic
- Service de gastroenterologie-pancréatologie, hôpital Beaujon, université Denis Diderot, AP-HP Clichy, 92110 Paris 7, France
| | - J Cros
- Service d'anatomie pathologique, hôpital Beaujon, université Denis Diderot, AP-HP, Clichy, 92110 Paris 7, France
| | - R Lebtahi
- Service of médecine nucléaire, hôpital Beaujon, université Denis Diderot, AP-HP, Clichy, 92110 Paris 7, France
| | - P Hammel
- Service de gastroenterologie-pancréatologie, hôpital Beaujon, université Denis Diderot, AP-HP Clichy, 92110 Paris 7, France
| | - R Kianmanesh
- Service de chirurgie generale, digestive et endocrinienne, hôpital Robert-Debré, université de Reims Champagne-Ardenne, 51100 Reims, France.
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Raoof M, Jutric Z, Melstrom LG, Lee B, Li D, Warner SG, Fong Y, Singh G. Prognostic significance of Chromogranin A in small pancreatic neuroendocrine tumors. Surgery 2018; 165:760-766. [PMID: 30447803 DOI: 10.1016/j.surg.2018.10.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 10/03/2018] [Accepted: 10/15/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The incidence of nonfunctional pancreatic neuroendocrine tumors ≤2cm is rising. The biologic behavior of these tumors is variable; thus, their management remains controversial. Chromogranin A upregulation is a useful diagnostic biomarker of neuroendocrine tumors; however, the prognostic significance of Chromogranin A is unclear. The objective of this study was to determine whether Chromogranin A levels have prognostic value in pancreatic neuroendocrine tumor patients and may help guide management. METHODS We evaluated the National Cancer Database over a 10-year period (2004-2013). Patients with pancreatic neuroendocrine tumors measuring ≤2cm, without distant metastases, were identified and categorized as Chromogranin A high (>420ng/mL) or Chromogranin A low (≤420ng/mL), and those lacking data on Chromogranin A levels were excluded from the study. Univariate and multivariate analyses were performed using Cox proportional hazards model. Cut-point determination was performed using the Contal and O'Quigley method. RESULTS Of the 445 eligible patients, 352 (79%) were Chromogranin A low and 93 (21%) were Chromogranin A high. Median Chromogranin A level was 71ng/mL (interquartile range, 24-294ng/mL). Chromogranin levels were associated with clinical nodal status and grade. Furthermore, on multivariate analysis, Chromogranin A levels (Chromogranin A high versus Chromogranin A low) independently predicted overall survival after controlling for tumor size, grade, clinical nodal status, and academic status of the facility (hazard ratio: 7.90, 95%CI: 2.34-26.69, P = .001). The greatest benefit of surgical resection was noted in patients in the Chromogranin A high subgroup (log-rank P <.001). CONCLUSION Serum Chromogranin A levels can be incorporated in surgical decision-making for patients with small pancreatic neuroendocrine tumors. Patients in the Chromogranin A low group can be considered for observation, whereas patients in the Chromogranin A high group should be strongly considered for resection.
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Affiliation(s)
- Mustafa Raoof
- Department of Surgery, City of Hope National Medical Center, Duarte, CA
| | - Zeljka Jutric
- Department of Surgery, University of California, Irvine, CA
| | - Laleh G Melstrom
- Department of Surgery, City of Hope National Medical Center, Duarte, CA
| | - Byrne Lee
- Department of Surgery, City of Hope National Medical Center, Duarte, CA
| | - Daneng Li
- Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Susanne G Warner
- Department of Surgery, City of Hope National Medical Center, Duarte, CA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, CA
| | - Gagandeep Singh
- Department of Surgery, City of Hope National Medical Center, Duarte, CA.
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Natural History of Small Pancreatic Lesions Suspected to Be Nonfunctioning Pancreatic Neuroendocrine Tumors. Pancreas 2018; 47:1357-1363. [PMID: 30308537 DOI: 10.1097/mpa.0000000000001187] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are a rare disease but have been diagnosed more frequently than before. The aim of this study was to evaluate the natural course of small NF-PNETs. METHODS We performed a retrospective analysis of patients with incidentally found small NF-PNETs (<20 mm) from 1999 to 2015. The patients who were recommended surveillance were included. RESULTS There were 69 patients with small NF-PNETs with a mean size of 10.9 (standard deviation [SD], 3.1) mm. The average follow-up period was 52.2 (SD, 38.7) months. The changes in tumor size were as follows: increased (13.0%), sustained (84.1%), and decreased (2.9%). Eighteen were evaluated with grade 1 NF-PNETs and 1 with grade 2 among the obtained tissues. Thirteen patients underwent surgery after an average 32.9 (SD, 42.6) months later. There were 7 patients of Ia, 1 of Ib, 2 of IIa, and 1 of IIb according to the pathologic stages. Two patients received reoperation for recurrent tumors, and 2 patients showed distant metastasis after surgery, but no disease-related death occurred. CONCLUSIONS Most of the small NF-PNETs did not increase in size and seldom showed metastasis. The wait-and-see strategy can be used for NF-PNETs less than 2 cm.
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Exploring the surgical landscape of pancreatic neuroendocrine neoplasia in Austria: Results from the ASSO pNEN study group. Eur J Surg Oncol 2018; 45:198-206. [PMID: 30262324 DOI: 10.1016/j.ejso.2018.08.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 08/09/2018] [Accepted: 08/24/2018] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Pancreatic neuroendocrine neoplasia (pNEN) show increasing incidence and management is complex due to biological heterogeneity. Most publications report isolated high-volume single-centre data. This Austrian multi-centre study on surgical management of pNENs provides a comprehensive real-life picture of quality indicators, recurrence-patterns, survival factors and systemic treatments. METHODS Retrospective, national cohort-study from 7 medium-/high-volume centres in Austria, coordinated under the auspices of the Austrian Society of Surgical Oncology (ASSO). RESULTS Two-hundred patients underwent resection for pNEN, 177 had non-functioning tumours and 31 showed stage 4 disease. Participating centres were responsible for 2/3 of pNEN resections in Austria within the last years. The mean rate of completeness of variables was 98.6%. Ninety-days mortality was 3.5%, overall rate of complications was 42.5%. Morbidity did not influence long-term survival. The 5-year overall-survival (OS) was 81.3%, 10-year-OS 52.5% and 5-year recurrence-free-survival (RFS) 69.8%. Recurrence was most common in the liver (68.1%). Four out of five patients with recurrence underwent further treatment, most commonly with medical therapy or chemotherapy. Multivariable analysis revealed grading (HR:2.7) and metastasis (HR:2.5) as significant factors for relapse. Tumours-size ≥2 cm (HR:5.9), age ≥60 years (HR:3.1), metastasis (HR:2.3) and grading (HR:2.0) were associated with OS. Tumours <2 cm showed 93.9% 10-year-OS, but 33% had G2/G3 grading, 12.5% positive lymph-nodes and 4.7% metastasis at diagnosis, each associated with significant worse survival. CONCLUSION Resection of pNENs in Austria is performed with internationally comparable safety. Analysed factors allow for risk-stratification in clinical treatment and future prospective trials. A watch-and-wait strategy purely based on tumour-size cannot be recommended.
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Lee L, Ito T, Jensen RT. Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 2018; 18:837-860. [PMID: 29973077 PMCID: PMC6283410 DOI: 10.1080/14737140.2018.1496822] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Recently, there have been a number of advances in imaging pancreatic neuroendocrine tumors (panNETs), as well as other neuroendocrine tumors (NETs), which have had a profound effect on the management and treatment of these patients, but in some cases are also associated with controversies. Areas covered: These advances are the result of numerous studies attempting to better define the roles of both cross-sectional imaging, endoscopic ultrasound, with or without fine-needle aspiration, and molecular imaging in both sporadic and inherited panNET syndromes; the increased attempt to develop imaging parameters that correlate with tumor classification or have prognostic value; the rapidly increasing use of molecular imaging in these tumors and the attempt to develop imaging parameters that correlate with treatment/outcome results. Each of these areas and the associated controversies are reviewed. Expert commentary: There have been numerous advances in all aspects of the imaging of panNETs, as well as other NETs, in the last few years. The advances are leading to expanded roles of imaging in the management of these patients and the results being seen in panNETs/GI-NETs with these newer techniques are already being used in more common tumors.
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Affiliation(s)
- Lingaku Lee
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
| | - Tetsuhide Ito
- c Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital International University of Health and Welfare 3-6-45 Momochihama , Sawara-Ku, Fukuoka , Japan
| | - Robert T Jensen
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
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41
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Hirose Y, Sakata J, Endo K, Takahashi M, Saito R, Imano H, Kido T, Yoshino K, Sasaki T, Wakai T. A 0.8-cm clear cell neuroendocrine tumor G1 of the gallbladder with lymph node metastasis: a case report. World J Surg Oncol 2018; 16:150. [PMID: 30037336 PMCID: PMC6057040 DOI: 10.1186/s12957-018-1454-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Accepted: 07/19/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Neuroendocrine tumors (NETs) of the gallbladder are rare and generally considered low-grade malignancies. We herein describe a case of a patient with a 0.8-cm clear cell NET G1 of the gallbladder with nodal involvement. CASE PRESENTATION A 65-year-old man with no medical history indicative of von Hippel-Lindau (VHL) disease underwent laparoscopic cholecystectomy for cholecystolithiasis. There was a 0.8-cm tumor in the neck of the gallbladder. Histologic examination revealed nests or trabecular growth of clear cells with small round-to-oval nuclei. Immunohistochemically, tumor cells showed positivity for chromogranin A and synaptophysin; Ki-67 index was < 1.0%. Based on the World Health Organization 2010 classification, we made a diagnosis of clear cell variant of NET G1 without VHL disease. The tumor invaded the muscular layer and had no extension to the perimuscular connective tissue but had metastasized to a cystic duct node. A radical second resection with regional lymphadenectomy of the gallbladder was performed, and there was no metastasis on histology. After the definitive surgery, he was followed up for 10 months without adjuvant therapy and is alive and well with no evidence of recurrence. CONCLUSIONS Our experience suggests that, even when smaller than 1 cm, NET G1 of the gallbladder can metastasize. When NET G1 is incidentally identified in the gallbladder of a surgical specimen, detailed pathologic examination of the cystic duct node, when found, should be performed to guide whether a radical second resection with regional lymphadenectomy is appropriate.
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Affiliation(s)
- Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510 Japan
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510 Japan
| | - Kazuhiko Endo
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Masato Takahashi
- Department of Diagnostic Pathology, Akita Kousei Medical Center, Akita, Japan
| | - Reijiro Saito
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Hiroshi Imano
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Tomoki Kido
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Kei Yoshino
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Toshiki Sasaki
- Department of Diagnostic Pathology, Akita Kousei Medical Center, Akita, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510 Japan
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Bartolini I, Bencini L, Risaliti M, Ringressi MN, Moraldi L, Taddei A. Current Management of Pancreatic Neuroendocrine Tumors: From Demolitive Surgery to Observation. Gastroenterol Res Pract 2018; 2018:9647247. [PMID: 30140282 PMCID: PMC6081603 DOI: 10.1155/2018/9647247] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 05/29/2018] [Accepted: 07/04/2018] [Indexed: 02/07/2023] Open
Abstract
Incidental diagnosis of pancreatic neuroendocrine tumors (PanNETs) greatly increased in the last years. In particular, more frequent diagnosis of small PanNETs leads to many challenging clinical decisions. These tumors are mostly indolent, although a percentage (up to 39%) may reveal an aggressive behaviour despite the small size. Therefore, there is still no unanimity about the best management of tumor smaller than 2 cm. The risks of under/overtreatment should be carefully evaluated with the patient and balanced with the potential morbidities related to surgery. The importance of the Ki-67 index as a prognostic factor is still debated as well. Whenever technically feasible, parenchyma-sparing surgeries lead to the best chance of organ preservation. Lymphadenectomy seems to be another important prognostic issue and, according to recent findings, should be performed in noninsulinoma patients. In the case of enucleation of the lesion, a lymph nodal sampling should always be considered. The relatively recent introduction of minimally invasive techniques (robotic) is a valuable option to deal with these tumors. The current management of PanNETs is analysed throughout the many available published guidelines and evidences with the aim of helping clinicians in the difficult decision-making process.
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Affiliation(s)
- Ilenia Bartolini
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| | - Lapo Bencini
- Department of Oncology, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Matteo Risaliti
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| | - Maria Novella Ringressi
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| | - Luca Moraldi
- Department of Oncology, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Antonio Taddei
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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Shatveryan GA, Karagyozyan GA, Chardarov NK, Bagmet NN, Ratnikova NP. [Surgical management of non-functioning pancreatic neuroendocrine tumors]. Khirurgiia (Mosk) 2018:4-9. [PMID: 29376950 DOI: 10.17116/hirurgia201814-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
AIM To analyze immediate and long-term results of surgical treatment of patients with non-functioning pancreatic neuroendocrine tumors (pNETs). MATERIAL AND METHODS Outcomes in 21 patients with non-functioning pNETs were retrospectively analyzed. RESULTS Long-term results were followed-up in 18 (85%) cases, median follow-up was 39 months. Postoperative mortality was 4.7%. The incidence of postoperative complications Clavien-Dindo degree IIIA and over was 20.8%, overall 5-year survival - 89%, desease-free 5-year survival - 78%. CONCLUSION At present time surgical intervention remains the only radical method of non-functioning pNETs management. Threshold tumor dimension should be 15 mm that determines surgical intervention or active surveillance. From an oncological point of view tumor enucleation is permissible only in case of small dimensions (up to 2 cm) and full confidence in low degree of malignancy. Lymphadenectomy should be performed in all cases in standard fashion because lymph node involvement is reliably poor prognostic sign.
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Affiliation(s)
- G A Shatveryan
- Liver, biliary and pancreatic surgery department, Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - G A Karagyozyan
- Liver, biliary and pancreatic surgery department, Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - N K Chardarov
- Liver, biliary and pancreatic surgery department, Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - N N Bagmet
- Liver, biliary and pancreatic surgery department, Petrovsky Russian Research Center for Surgery, Moscow, Russia
| | - N P Ratnikova
- Liver, biliary and pancreatic surgery department, Petrovsky Russian Research Center for Surgery, Moscow, Russia
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44
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Mills L, Drymousis P, Vashist Y, Burdelski C, Prachalias A, Srinivasan P, Menon K, Cotoi C, Khan S, Cave J, Armstrong T, Weickert MO, Izbicki J, Schrader J, Frilling A, Ramage JK, Srirajaskanthan R. Tumour diameter is not reliable for management of non-secreting pancreatic neuroendocrine tumours. Endocr Connect 2017; 6:876-885. [PMID: 29150545 PMCID: PMC5704448 DOI: 10.1530/ec-17-0293] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 10/25/2017] [Indexed: 12/20/2022]
Abstract
Small non-functioning pancreatic NETs (pNETs) ≤2 cm can pose a management dilemma in terms of surveillance or resection. There is evidence to suggest that a surveillance approach can be considered since there are no significant radiological changes observed in lesions during long-term follow-up. However, other studies have suggested loco-regional spread can be present in ≤2 cm pNETs. The aim of this study was to characterise the prevalence of malignant features and identify any useful predictive variables in a surgically resected cohort of pNETs. 418 patients with pNETs were identified from 5 NET centres. Of these 227 were included for main analysis of tumour characteristics. Mean age of patients was 57 years, 47% were female. The median follow-up was 48.2 months. Malignant features were identified in 38% of ≤2 cm pNETs. ROC analysis showed that the current cut-off of 20 mm had a sensitivity of 84% for malignancy. The rate of malignant features is in keeping with other surgical series and challenges the belief that small pNETs have a low malignant potential. This study does not support a 20 mm size cut-off as being a solitary safe parameter to exclude malignancy in pNETs.
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Affiliation(s)
- Logan Mills
- Institute of Liver StudiesKing's College Hospital, London, UK
| | | | - Yogesh Vashist
- Department of GeneralVisceral and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Burdelski
- Department of GeneralVisceral and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany
| | | | | | - Krishna Menon
- Department of SurgeryKing's College Hospital, London, UK
| | - Corina Cotoi
- Department of HistopathologyKing's College Hospital, London, UK
| | - Saboor Khan
- Department of SurgeryUniversity Hospitals Coventry and Warwickshire, Coventry, UK
| | - Judith Cave
- Department of OncologyUniversity Hospital, Southampton, UK
| | | | - Martin O Weickert
- Department of EndocrinologyUniversity Hospitals Coventry and Warwickshire, Coventry, UK
| | - Jakob Izbicki
- Department of GeneralVisceral and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany
| | - Joerg Schrader
- Departments of Gastroenterology and Department of GeneralVisceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - John K Ramage
- Institute of Liver StudiesKing's College Hospital, London, UK
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Moyana TN, Macdonald DB, Martel G, Pyatibrat S, Lee G, Capitano M. Pancreatic Neuroendocrine Tumors Complicated by Sinistral Portal Hypertension: Insights into Pathogenesis. J Pancreat Cancer 2017; 3:71-77. [PMID: 30631846 DOI: 10.1089/crpc.2017.0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Purpose: To investigate the association between pancreatic neuroendocrine tumors (panNETs) and sinistral portal hypertension (SPH) and provide insights into the pathogenesis. Methods: A retrospective review of panNETs was conducted from our institution for 12 years. Medical imaging findings were analyzed to determine any association with splenic vein thrombosis (SVT) at diagnosis. The cases were further selected based on the criteria for SPH, namely, (1) presence of SVT, (2) gastric varices, (3) patent portal vein, and (4) normal liver function tests. Results: There were 61 patients with panNETs and 8 (8/61) had SVT and gastric varices at diagnosis. Four (4/8) met the strict criteria for SPH while the other four had more conventional portal hypertension. The four with SPH had large tumors located in the tail with splenic vein invasion and three of four presented with bleeding gastric varices. All four patients underwent surgical resection. Mean follow-up was 8.5 years and the hematemesis never recurred. The other four patients (four of eight) with gastric varices had unresectable disease and all died after a mean survival of 29 months. Conclusion: PanNETs appear to be more commonly associated with SVT and SPH compared with other tumors. This could be related to their relatively indolent nature and their intrinsic vascularity. From a surgical viewpoint, the decision to operate depends on many factors including but not limited to the size/stage, grade, and functionality of the tumor and comorbidities. These considerations notwithstanding, the association between panNETs and SPH suggests that there is benefit in timely resection of panNETs located in the tail.
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Affiliation(s)
- Terence N Moyana
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - D Blair Macdonald
- Department of Medical Imaging, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - Guillaume Martel
- Division of Hepatobiliary Surgery, The Ottawa Hospital and University of Ottawa, Ottawa, Canada
| | - Sergey Pyatibrat
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - Goo Lee
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - Mario Capitano
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
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Moyana TN, Macdonald DB, Martel G, Pyatibrat S, Lee G, Capitano M. Pancreatic Neuroendocrine Tumors Complicated by Sinistral Portal Hypertension: Insights into Pathogenesis. J Pancreat Cancer 2017; 3:71-77. [PMID: 30631846 PMCID: PMC5933486 DOI: 10.1089/pancan.2017.0017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Purpose: To investigate the association between pancreatic neuroendocrine tumors (panNETs) and sinistral portal hypertension (SPH) and provide insights into the pathogenesis. Methods: A retrospective review of panNETs was conducted from our institution for 12 years. Medical imaging findings were analyzed to determine any association with splenic vein thrombosis (SVT) at diagnosis. The cases were further selected based on the criteria for SPH, namely, (1) presence of SVT, (2) gastric varices, (3) patent portal vein, and (4) normal liver function tests. Results: There were 61 patients with panNETs and 8 (8/61) had SVT and gastric varices at diagnosis. Four (4/8) met the strict criteria for SPH while the other four had more conventional portal hypertension. The four with SPH had large tumors located in the tail with splenic vein invasion and three of four presented with bleeding gastric varices. All four patients underwent surgical resection. Mean follow-up was 8.5 years and the hematemesis never recurred. The other four patients (four of eight) with gastric varices had unresectable disease and all died after a mean survival of 29 months. Conclusion: PanNETs appear to be more commonly associated with SVT and SPH compared with other tumors. This could be related to their relatively indolent nature and their intrinsic vascularity. From a surgical viewpoint, the decision to operate depends on many factors including but not limited to the size/stage, grade, and functionality of the tumor and comorbidities. These considerations notwithstanding, the association between panNETs and SPH suggests that there is benefit in timely resection of panNETs located in the tail.
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Affiliation(s)
- Terence N. Moyana
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - D. Blair Macdonald
- Department of Medical Imaging, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - Guillaume Martel
- Division of Hepatobiliary Surgery, The Ottawa Hospital and University of Ottawa, Ottawa, Canada
| | - Sergey Pyatibrat
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - Goo Lee
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
| | - Mario Capitano
- Department of Pathology and Lab Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
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Guo J, Zhao J, Bi X, Li Z, Huang Z, Zhang Y, Cai J, Zhao H. Should surgery be conducted for small nonfunctioning pancreatic neuroendocrine tumors: a systemic review. Oncotarget 2017; 8:35368-35375. [PMID: 28430639 PMCID: PMC5471061 DOI: 10.18632/oncotarget.15685] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 02/16/2017] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND The incidence of nonfunctioning pancreatic neuroendocrine tumors smaller than 2cm has increased remarkably in the last two decades. Controversies exist regarding whether surgery should be conducted for this group of tumors. METHODS MEDLINE, EMBASE and CENTRAL were search until 2017/01/17. Studies with comparative results between operation and observation group were included. Primary outcomes were overall survival and disease specific survival. Secondary outcomes were disease progression and surgical death and complications. RESULTS 6 studies with a total of 1861 patients were identified. No randomized controlled trials were found. Survival rate was high (97-100%) and no patients died because of the disease in 5 of the 6 studies, with no difference between operation and observation group. Disease progression was compared in 3 of the 6 studies. 2 studies reported minimal disease progression (0-3.5%) and no significant difference between operation and observation group. Perioperative deaths were rare (0-3%), but complications were common (33-46%). None of the 46 patients who crossed over form observation to operation group had disease recurrence after resection. CONCLUSION Small NF-PNETs without distant metastasis, lymph node metastasis and local invasion on imaging studies can be observed without increase in death and disease progression.
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Affiliation(s)
- Jingfei Guo
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jianjun Zhao
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyu Bi
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhiyu Li
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yefan Zhang
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianqiang Cai
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Paiella S, Impellizzeri H, Zanolin E, Marchegiani G, Miotto M, Malpaga A, De Robertis R, D'Onofrio M, Rusev B, Capelli P, Cingarlini S, Butturini G, Davì MV, Amodio A, Bassi C, Scarpa A, Salvia R, Landoni L. Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors. World J Gastroenterol 2017; 23:3092-3098. [PMID: 28533666 PMCID: PMC5423046 DOI: 10.3748/wjg.v23.i17.3092] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 01/30/2017] [Accepted: 03/31/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To establish the ability of magnetic resonance (MR) and computer tomography (CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors (PanNET) in a caseload of a tertiary referral center. METHODS Patients submitted to surgery for PanNET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination (MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman (BA) and Mountain-Plot (MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok (PB) regression analysis was used to check the agreement between MR and CT. RESULTS Our study population consisted of 292 patients. Seventy-nine (27.1%) were functioning PanNET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning- PanNET, respectively. Limits of agreement (LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-PanNET, no statistical significance was found in the size estimation rate of MR and CT (P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology. CONCLUSION MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of PanNET.
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Bar-Moshe Y, Mazeh H, Grozinsky-Glasberg S. Non-functioning pancreatic neuroendocrine tumors: Surgery or observation? World J Gastrointest Endosc 2017; 9:153-161. [PMID: 28465781 PMCID: PMC5394721 DOI: 10.4253/wjge.v9.i4.153] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 10/23/2016] [Accepted: 01/14/2017] [Indexed: 02/05/2023] Open
Abstract
Incidentally detected, sporadic, nonfunctional pancreatic neuroendocrine tumors are increasingly diagnosed on imaging studies performed for unrelated purposes. Although their resection is usually recommended, controversy still exists regarding their optimal management, due to their highly variable and difficult to predict biologic behavior. Recently, several studies and guidelines advocated an expectant management approach in small size, low grade, incidentally diagnosed nonfunctional pancreatic neuroendocrine tumors. The aim of this study is to review and summarize the available literature addressing nonfunctional pancreatic neuroendocrine tumors, with an emphasis on surgical management controversies.
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Yang G, Ji M, Chen J, Chen R, Chen Y, Fu D, Hou B, Huang H, Jiang L, Jin K, Ke N, Li Y, Li Y, Liang H, Liu A, Luo J, Ni Q, Shao C, Shen B, Sheng W, Song B, Sun J, Tan C, Tan H, Tang Q, Tang Y, Tian X, Wang J, Wang J, Wang W, Wang W, Wu Z, Xu J, Yan Q, Yang N, Yang Y, Yin X, Yu X, Yuan C, Zeng S, Zhang G, Zhang R, Zhou Z, Zhu Z, Shao C. Surgery management for sporadic small (≤2 cm), non-functioning pancreatic neuroendocrine tumors: a consensus statement by the Chinese Study Group for Neuroendocrine Tumors (CSNET). Int J Oncol 2017; 50:567-574. [PMID: 28035372 DOI: 10.3892/ijo.2016.3826] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 12/12/2016] [Indexed: 11/05/2022] Open
Abstract
The incidence of small (≤2 cm), non-functioning pancreatic neuroendocrine tumors (NF-pNETs) increased in the last decades. Before making appropriate strategy for patients with NF-pNETs ≤2 cm, pathological confirmation is vital. Incidentally diagnosed, sporadic small NF-pNETs may bring aggressive behavior and poor prognosis, such as extrapancreatic extension, lymph nodal metastasis, distant metastasis and recurrence, even causing disease-related death. Understanding and formulating an appropriate strategy for the patients with sporadic small, non-functioning pancreatic neuroendocrine tumors have been controversial for some time. Although several studies have reported that patients with NF-pNETs ≤2 cm had less rate of malignant behavior compared with larger ones (>2 cm); and the surgery approach may leading to surgery-related pancreatic complications; but there is still a lack of level I evidence to convince surgeons to abandon all cases with sporadic small NF-pNETs. Based on an updated literature search and review, the members of the Chinese Study Group for Neuroendocrine Tumors (CSNET) from high-volume centers have reached a consensus on the issue of the management strategy for the sporadic small NF-pNETs. We recommend that, except for some selected patients with NF-pNETs <1 cm, incidentally discovered and unacceptable surgical risks, all others with NF-pNETs ≤2 cm should undergo tumor resection with lymph node dissection or at least lymph node sampling and careful postoperative surveillance.
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Affiliation(s)
- Guang Yang
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Meng Ji
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Rufu Chen
- Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospial, Southern Medical University, Guangzhou, Guangdong, P.R. China
| | - Deliang Fu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, P.R. China
| | - Baohua Hou
- Department of General Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P.R. China
| | - Heguang Huang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, P.R. China
| | - Liming Jiang
- Department of Radiology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, Beijing, P.R. China
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Nengwen Ke
- Department of Hepatobiliary and Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Ying Li
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing, P.R. China
| | - Yong Li
- Department of General Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P.R. China
| | - Houjie Liang
- Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China
| | - An'an Liu
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jie Luo
- Department of Pathology, China-Japan Friendship Hospital, Beijing, P.R. China
| | - Quanxing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Chengwei Shao
- Department of Radiology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Boyong Shen
- Department of General Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Weiqi Sheng
- Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai, P.R. China
| | - Bin Song
- Department of Pancreatic Surgery, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jian Sun
- Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Chunlu Tan
- Department of Hepatobiliary and Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Huangying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, P.R. China
| | - Qiyun Tang
- Department of Gastroenterology, Jiangsu People's Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Yingmei Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming, Yunnan, P.R. China
| | - Xiaodong Tian
- Department of General Surgery, Peking University First Hospital, Beijing, P.R. China
| | - Jian Wang
- Department of Biliary and Pancreatic Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Jie Wang
- Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Wei Wang
- Department of General Surgery, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, P.R. China
| | - Wei Wang
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
| | - Zheng Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Qiang Yan
- Department of Surgery, Huzhou Central Hospital, Huzhou, Zhejiang, P.R. China
| | - Ning Yang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Yinmo Yang
- Department of General Surgery, Peking University First Hospital, Beijing, P.R. China
| | - Xiaoyu Yin
- Department of Biliary and Pancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Peking University, Beijing, P.R. China
| | - Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
| | - Guochao Zhang
- Department of General Surgery, China-Japan Friendship Hospital, Beijing, P.R. China
| | - Renchao Zhang
- Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, P.R. China
| | - Zhiwei Zhou
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
| | - Zhaohui Zhu
- Department of Nuclear Medicine, Peiking Union Medical College Hospital, Beijing, P.R. China
| | - Chenghao Shao
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
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