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Kartik A, Armstrong VL, Stucky CC, Wasif N, Fong ZV. Contemporary Approaches to the Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2024; 16:1501. [PMID: 38672582 PMCID: PMC11048062 DOI: 10.3390/cancers16081501] [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: 02/20/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor's biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques.
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Affiliation(s)
| | | | | | | | - Zhi Ven Fong
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ 85054, USA
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Hentzen S, Mehta K, Al-Rajabi RMT, Saeed A, Baranda JC, Williamson SK, Sun W, Kasi A. Real world outcomes in patients with neuroendocrine tumor receiving peptide receptor radionucleotide therapy. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2023; 4:396-405. [PMID: 37455826 PMCID: PMC10344897 DOI: 10.37349/etat.2023.00141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 03/06/2023] [Indexed: 07/18/2023] Open
Abstract
Aim 177Lu-Dotatate (Lu-177), a form of peptide receptor radionuclide therapy (PRRT), was approved by Food and Drug Administration (FDA) for the treatment of somatostatin-receptor-positive neuroendocrine tumors (NETs) in 2018. Clinical trials prior to the FDA approval of Lu-177 showed favorable outcomes but there is limited published real world outcomes data. This study aims to describe and analyze real world outcomes of patients with NET who received Lu-177. Methods After obtaining institutional review board approval, retrospective evaluation was performed to analyze the efficacy of Lu-177 for somatostatin receptor-positive gastro-entero-pancreatic NETs (GEP-NETs) patients at the University of Kansas Cancer Center between June 2018 and September 2021. This study aims to determine the response rate to the treatment of the entire cohort and subgroups. Results A total of 65 patients received Lu-177 of which 58 completed treatment. The 58 patients had a median age of 61.5 years, 24 females and 34 males, 86% Caucasian and 12% black. The origins of NETs were primarily small bowel (n = 24) and pancreatic (n = 14). Pathology showed grades 1 (n = 21), 2 (n = 25), and 3 (n = 4) and were primarily well-differentiated tumors (n = 4). Among the cohort, 52 patients had imaging to assess response with 14 (26.9%) patients with partial response (PR), 31 (59.6%) with stable disease (SD), and 7 (13.5%) with progressive disease (PD). In a subset analysis, patients with non-functional disease (n = 29) had higher rates of PR 42.3% (compared to 11.5%, P = 0.0147) and higher disease control rate of 96% (compared to 78%, P = 0.042) than patients with functional disease (n = 29). Patients with non-functional disease had a lower PD of 3.85% (compared to 23%, P = 0.0147) than those with functional disease. Conclusions This real world outcomes analysis of NETs treated with Lu-177 shows improved PR when compared to the initial clinical trials and is promising for patients. In addition, patients with non-functional tumors were found to have a statistically significant improved response rate which has not been described in the literature before. If these study findings are validated in a larger cohort they may guide patient selection for Lu-177 therapy in the future.
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Affiliation(s)
- Stijn Hentzen
- Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Kathan Mehta
- Department of Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA
| | | | - Anwaar Saeed
- Department of Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA
| | | | - Stephen K. Williamson
- Department of Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA
| | - Weijing Sun
- Department of Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA
| | - Anup Kasi
- Department of Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA
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Nakao Y, Hayashi H, Yamashita YI, Takashi O, Matsumura K, Uemura N, Kitamura F, Itoyama R, Yusa T, Taki K, Miyata T, Higashi T, Nakagawa S, Okabe H, Imai K, Baba H. Risk factors for lymph node metastasis in patients with pancreatic neuroendocrine neoplasms. World J Clin Oncol 2022; 13:520-528. [PMID: 35949434 PMCID: PMC9244965 DOI: 10.5306/wjco.v13.i6.520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 10/24/2021] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although PNENs generally have a better prognosis than pancreatic cancers, some PNENs display malignant behavior including lymph node (LN) metastasis. Complete tumor resection can be the only potentially curative treatment for patients with resectable PNENs. However, the indications for LN dissection are still controversial. Over the last decade, minimally invasive surgery such as laparoscopic pancreatic surgery (LPS) has been increasingly performed for pancreatic tumors including PNENs.
AIM To investigate the risk factors for LN metastasis in PNENs and to select appropriate patients for limited surgery by LPS.
METHODS From April 2001 to December 2019, 92 patients underwent pancreatic resection for PNENs at Kumamoto University Hospital. Finally, 82 patients were enrolled in this study. Using perioperative factors, we examined the predictive factors for LN metastasis in PNENs.
RESULTS Among the 82 patients, the percentage of LN metastasis according to the pathological findings was 12% (10/82 cases). The median tumor size was 12 mm (range: 5-90 mm). The median tumor size in the LN-positive group (37 mm) was significantly larger than that in the LN-negative group (12 mm) (P = 0.0001). Multivariate analyses revealed that larger tumor size (≥ 20 mm) was an independent risk factor for LN metastasis (odds ratio 16.8, P = 0.0062). In patients with small tumors (≤ 10 mm), LN metastasis was not found.
CONCLUSION Larger tumor size (≥ 20 mm) is an independent risk factor for LN metastasis in PNENs. In smaller PNENs (≤ 10 mm), we may be able to choose limited surgery without LN dissection.
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Affiliation(s)
- Yosuke Nakao
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Yo-ichi Yamashita
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Ofuchi Takashi
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Kazuki Matsumura
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Norio Uemura
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Fumimasa Kitamura
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Rumi Itoyama
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Toshihiko Yusa
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Katsunobu Taki
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Tatsunori Miyata
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Takaaki Higashi
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-8556, Japan
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Ramage JK, Friend E, Randell J, KING B, Fernandez Ortega P, McNamara MG, Kaltsas G, Falconi M, Cwikla J, Capdevila J, Grozinsky‐Glasberg S, Mandair D, Gamper E, Srirajaskanthan R, O Weickert M, Gray D. Development of a quality of life questionnaire for patients with pancreatic neuroendocrine tumours (the PANNET module). J Neuroendocrinol 2022; 34:e13097. [PMID: 35156246 PMCID: PMC9285342 DOI: 10.1111/jne.13097] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 01/18/2022] [Indexed: 12/04/2022]
Abstract
Pancreatic neuroendocrine tumours (panNET) are heterogeneous neoplasms usually characterised by slow growth and secretion of hormones, which often cause symptoms. The effect of these symptoms on quality of life (QoL) has not previously been examined in detail. EORTC (European Organisation for Research and Treatment of Cancer) guidelines were followed in phases 1-3 to produce a potential module of questions usable for trials in panNET, focusing on three common types of panNET. For two less common types, a list of symptoms was constructed. Following an extensive literature search and phase 1a interviews with patients and healthcare workers, a long list of potential issues (169) was obtained. This list was shown to 12 patients from three countries in phase 1b interviews to check that no items were missed. The list was reduced to 57 issues. The list of issues was converted to questions, mainly from existing validated questions within the EORTC item library. The list of questions was then used in a phase 3 international study in eight countries using seven languages. A provisional module of 24 items is presented for use in nonfunctioning panNET, gastrinoma and insulinoma. This module increases knowledge concerning QoL in this condition and may be a useful adjunct in clinical trials. A phase 4 trial is being considered for validation of this questionnaire.
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Affiliation(s)
| | | | | | - Barbara KING
- Hampshire Hospitals NHS Foundation TrustBasingstokeUK
| | | | - Mairéad G. McNamara
- Division of Cancer SciencesUniversity of Manchester/The Christie NHS Foundation TrustManchesterUK
| | | | - Massimo Falconi
- Pancreatic Surgery UnitPancreas Translational & Clinical Research CenterIRCCS San Raffaele Scientific InstituteMilanItaly
| | | | - Jaume Capdevila
- Vall D’Hebron University HospitalVall Hebron Institute of Oncology (VHIO)BarcelonaSpain
| | | | | | - Eva Gamper
- Medical University of InnsbruckInnsbruckAustria
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Yazdanpanah O, Surapaneni S, Shanah L, Kabashneh S. Diagnosis and Management of Gastrointestinal Neuroendocrine Tumors: A Comprehensive Literature Review. Cureus 2021; 13:e14006. [PMID: 33884247 PMCID: PMC8053559 DOI: 10.7759/cureus.14006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation and the ability to synthesize and secrete variable hormones and monoamines. They are relatively rare, accounting for 2% of all malignancy cases in the United States. The most common system affected by NETs is the gastrointestinal tract. Clinical presentation depends on the organ being involved and the hormone being secreted. It can be variable from asymptomatic incidental findings on imaging to intestinal obstruction, or carcinoid syndrome (CS). Several biochemical testings are developed to help with the diagnosis of NETs including 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA). Computerized tomography (CT) scans and magnetic resonance imaging (MRI) are the most commonly used modalities to localize the primary tumor and evaluate for metastasis. However, radionuclide imaging using somatostatin receptor-based imaging techniques has improved accuracy to detect smaller neoplasm. Surgical removal is the mainstay of treatment for locoregional tumors. Several medical managements are available for non-respectable NETs which include SSAs, peptide receptor radionuclide therapy (PRRT), and platinum-based chemotherapy agents.
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Affiliation(s)
- Omid Yazdanpanah
- Internal Medicine, Wayne State University Detroit Medical Center, Detroit, USA
| | - Sarvani Surapaneni
- Internal Medicine, Wayne State University Detroit Medical Center, Detroit, USA
| | - Layla Shanah
- Internal Medicine, Wayne State University Detroit Medical Center, Detroit, USA
| | - Sohaip Kabashneh
- Internal Medicine, Wayne State University Detroit Medical Center, Detroit, USA
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Tanaka M, Heckler M, Mihaljevic AL, Probst P, Klaiber U, Heger U, Schimmack S, Büchler MW, Hackert T. Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2020; 28:1614-1624. [PMID: 32720049 DOI: 10.1245/s10434-020-08850-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 06/27/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy. PATIENTS AND METHODS The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed. RESULTS From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2 cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00-4.99, P < 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81-8.83, P < 0.001) was associated with worse OS. CONCLUSIONS LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.
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Affiliation(s)
- Masayuki Tanaka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.,Department of Surgery, Keio University, School of Medicine, Tokyo, Japan
| | - Max Heckler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - André L Mihaljevic
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Ulla Klaiber
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Ulrike Heger
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Simon Schimmack
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
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7
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Bu J, Youn S, Kwon W, Jang KT, Han S, Han S, You Y, Heo JS, Choi SH, Choi DW. Prognostic factors of non-functioning pancreatic neuroendocrine tumor revisited: The value of WHO 2010 classification. Ann Hepatobiliary Pancreat Surg 2018. [PMID: 29536058 PMCID: PMC5845613 DOI: 10.14701/ahbps.2018.22.1.66] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Backgrounds/Aims Various factors have been reported as prognostic factors of non-functional pancreatic neuroendocrine tumors (NF-pNETs). There remains some controversy as to the factors which might actually serve to successfully prognosticate future manifestation and diagnosis of NF-pNETs. As well, consensus regarding management strategy has never been achieved. The aim of this study is to further investigate potential prognostic factors using a large single-center cohort to help determine the management strategy of NF-pNETs. Methods During the time period 1995 through 2013, 166 patients with NF-pNETs who underwent surgery in Samsung Medical Center were entered in a prospective database, and those factors thought to represent predictors of prognosis were tested in uni- and multivariate models. Results The median follow-up time was 46.5 months; there was a maximum follow-up period of 217 months. The five-year overall survival and disease-free survival rates were 88.5% and 77.0%, respectively. The 2010 WHO classification was found to be the only prognostic factor which affects overall survival and disease-free survival in multivariate analysis. Also, pathologic tumor size and preoperative image tumor size correlated strongly with the WHO grades (p<0.001, and p<0.001). Conclusions Our study demonstrates that 2010 WHO classification represents a valuable prognostic factor of NF-pNETs and tumor size on preoperative image correlated with WHO grade. In view of the foregoing, the preoperative image size is thought to represent a reasonable reference with regard to determination and development of treatment strategy of NF-pNETs.
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Affiliation(s)
- Jiyoung Bu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sangmin Youn
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kee Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sanghyup Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sunjong Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Younghun You
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seong Ho Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Wook Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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8
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Ricci C, Casadei R, Taffurelli G, Pacilio CA, Campana D, Ambrosini V, Donatella S, Minni F. Sporadic Small (≤20 mm) Nonfunctioning Pancreatic Neuroendocrine Neoplasm: is the Risk of Malignancy Negligible When Adopting a More Conservative Strategy? A Systematic Review and Meta-analysis. Ann Surg Oncol 2017; 24:2603-2610. [DOI: 10.1245/s10434-017-5946-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Indexed: 12/18/2022]
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ElGuindy YM, Javadi S, Menias CO, Jensen CT, Elsamaloty H, Elsayes KM. Imaging of secretory tumors of the gastrointestinal tract. Abdom Radiol (NY) 2017; 42:1113-1131. [PMID: 27878636 DOI: 10.1007/s00261-016-0976-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Gastrointestinal secretory tumors, or gastroenteropancreatic neuroendocrine tumors, encompass a wide array of endocrine cell tumors. The significance of these tumors lies in their ability to alter physiology through hormone production as we well as in their malignant potential. Functioning tumors may present earlier due to symptomatology; conversely, non-functioning tumors are often diagnosed late as they reach large sizes, causing symptoms secondary to local mass effect. Imaging aids in the diagnosis, staging, and prognosis and provides key information for presurgical planning. Although most of these tumors are sporadic, some are associated with important syndromes and associations, knowledge of which is critical for patient management. In this article, we provide an overview of secretory and neuroendocrine tumors of the GI tract and pancreas.
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Izumi H, Yazawa N, Furukawa D, Masuoka Y, Yamada M, Mashiko T, Kawashima Y, Ogawa M, Kawaguchi Y, Mine T, Hirabayashi K, Nakagohri T. Laparoscopic splenopancreatectomy for an endocrine tumor with cystic changes: a case report. Clin Case Rep 2017; 5:328-332. [PMID: 28265400 PMCID: PMC5331262 DOI: 10.1002/ccr3.844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 11/19/2016] [Accepted: 01/09/2017] [Indexed: 11/25/2022] Open
Abstract
The biological behavior of a cystic pancreatic endocrine neoplasm is less aggressive than that of pancreatic neuroendocrine neoplasms, and its prognosis is better. Limited surgery should be considered for cystic pancreatic endocrine neoplasms that are not accompanied preoperatively by lymph node or distant metastasis.
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Affiliation(s)
- Hideki Izumi
- Department of Gastrointestinal Surgery Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Naoki Yazawa
- Department of Gastrointestinal Surgery Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Daisuke Furukawa
- Department of Gastrointestinal Surgery Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Yoshihito Masuoka
- Department of Gastrointestinal Surgery Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Misuzu Yamada
- Department of Gastrointestinal Surgery Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Taro Mashiko
- Department of Gastrointestinal Surgery Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Yohei Kawashima
- Department of Internal Medicine Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Masami Ogawa
- Department of Internal Medicine Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Yoshiaki Kawaguchi
- Department of Internal Medicine Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Tetsuya Mine
- Department of Internal Medicine Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Kenichi Hirabayashi
- Department of Pathology Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
| | - Toshio Nakagohri
- Department of Gastrointestinal Surgery Tokai University School of Medicine 143 Shimokasuya Isehara Kanagawa 259-1193 Japan
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11
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Taki K, Hashimoto D, Nakagawa S, Ozaki N, Tomiyasu S, Ohmuraya M, Arima K, Kaida T, Higashi T, Sakamoto K, Sakata K, Okabe H, Nitta H, Hayashi H, Chikamoto A, Beppu T, Takamori H, Hirota M, Baba H. Significance of lymph node metastasis in pancreatic neuroendocrine tumor. Surg Today 2017; 47:1104-1110. [PMID: 28229300 DOI: 10.1007/s00595-017-1485-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 01/11/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE Pancreatic neuroendocrine tumor (PNET) is relatively rare and has a generally better prognosis than does pancreatic cancer. However, as its prognosis in patients with lymph node metastasis (LNM) is unclear, lymph node dissection for PNET is controversial. Our study aimed to clarify the significance of LNM in PNET. METHODS We retrospectively examined 83 PNET patients who underwent pancreatic resections with lymph node dissection at Kumamoto University Hospital, Saiseikai Kumamoto Hospital, and Kumamoto Regional Medical Center from April 2001 to December 2014. Their clinicopathological parameters were analyzed by the absence or presence of LNM, and with regard to the disease-free survival (DFS) and overall survival (OS). A predictive score of LNM was also made using the age, tumor size, primary tumor location, and tumor function. RESULTS Although the 5-year OS was 74.8% for LNM+ and 94.6% for LNM- (P = 0.002), LNM was not an independent risk factor for the OS in a multivariate analysis. However, tumors larger than 1.8 cm were found to be an independent prognostic factor, and the cut-off value for the predictive score was 1.69. CONCLUSIONS Although LNM was not an independent prognostic factor, lymph node dissection is recommended for patients whose predictive score is larger than 1.69.
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Affiliation(s)
- Katsunobu Taki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Nobuyuki Ozaki
- Department of Surgery, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Minami-ku, Kumamoto, 861-4193, Japan
| | - Shinjiro Tomiyasu
- Department of Surgery, Kumamoto Regional Medical Center, 5-16-10 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan
| | - Masaki Ohmuraya
- Institute of Resources Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan
| | - Kota Arima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Takaaki Higashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Keita Sakamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Kazuya Sakata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Toru Beppu
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hiroshi Takamori
- Department of Surgery, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Minami-ku, Kumamoto, 861-4193, Japan
| | - Masahiko Hirota
- Department of Surgery, Kumamoto Regional Medical Center, 5-16-10 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
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Busquets J, Ramírez-Maldonado E, Serrano T, Peláez N, Secanella L, Ruiz-Osuna S, Ramos E, Lladó L, Fabregat J. Surgical treatment of non-functioning pancreatic neuroendocrine tumours based on three clinical scenarios. Cir Esp 2016; 94:578-587. [PMID: 27863693 DOI: 10.1016/j.ciresp.2016.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Revised: 07/21/2016] [Accepted: 07/29/2016] [Indexed: 10/20/2022]
Abstract
INTRODUCTION The treatment of patients with non-functioning pancreatic neuroendocrine tumours (NFPNET) is resection in locally pancreatic disease, or with resectable liver metastases. There is controversy about unresectable liver disease. METHODS We analysed the perioperative data and survival outcome of 63 patients who underwent resection of NFPNET between 1993 and 2012. They were divided into 3 scenarios: A, pancreatic resection (44patients); B, pancreatic and liver resection in synchronous resectable liver metastases (12patients); and C, pancreatic resection in synchronous unresectable liver metastases (6patients). The prognostic factors for survival and recurrence were studied. RESULTS Distal pancreatectomy (51%) and pancreaticoduodenectomy (38%) were more frequently performed. Associated surgery was required in 44% of patients, including synchronous liver resections in 9patients. Two patients received a liver transplant during follow-up. According to the WHO classification they were distributed into G1: 10 (16%), G2: 45 (71%), and G3: 8 (13%). The median hospital stay was 11days. Postoperative morbidity and mortality were 49% and 1.6%, respectively. At the closure of the study, 43 (68%) patients were still alive, with a mean actuarial survival of 9.6years. The WHO classification and tumour recurrence were risk factors of mortality in the multivariate analysis. The median actuarial survival by scenarios was 131months (A), 102months (B), and 75months (C) without statistically significant differences. CONCLUSIONS Surgical resection is the treatment for NFPNET without distant disease. Resectable liver metastases in well-differentiated tumours must be resected. The resection of the pancreatic tumour with unresectable synchronous liver metastasis must be considered in well-differentiated NFPNET. The WHO classification grade and recurrence are risk factors of long-term mortality.
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Affiliation(s)
- Juli Busquets
- Servicio de Cirugía General y Digestivo, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España.
| | - Elena Ramírez-Maldonado
- Servicio de Cirugía General y Digestivo, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
| | - Teresa Serrano
- Servicio de Anatomía Patológica, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
| | - Núria Peláez
- Servicio de Cirugía General y Digestivo, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
| | - Luís Secanella
- Servicio de Cirugía General y Digestivo, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
| | - Sandra Ruiz-Osuna
- Servicio de Radiodiagnóstico, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
| | - Emilio Ramos
- Servicio de Cirugía General y Digestivo, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
| | - Laura Lladó
- Servicio de Cirugía General y Digestivo, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
| | - Juan Fabregat
- Servicio de Cirugía General y Digestivo, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona, España
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Zhu LM, Tang L, Qiao XW, Wolin E, Nissen NN, Dhall D, Chen J, Shen L, Chi Y, Yuan YZ, Ben QW, Lv B, Zhou YR, Bai CM, Chen J, Song YL, Song TT, Lu CM, Yu R, Chen YJ. Differences and Similarities in the Clinicopathological Features of Pancreatic Neuroendocrine Tumors in China and the United States: A Multicenter Study. Medicine (Baltimore) 2016; 95:e2836. [PMID: 26886644 PMCID: PMC4998644 DOI: 10.1097/md.0000000000002836] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria. This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based on WHO/ENETS criteria. The clinicopathological features of PNETs of Chinese and US patients were compared. Univariate and multivariate analyses were performed to find associations between survival and patient demographics, tumor grade and stage, and other clinicopathological characteristics. A total of 977 (527 Chinese and 450 US) patients with PNETs were studied. In general, Chinese patients were younger than US patients (median age 46 vs 56 years). In Chinese patients, insulinomas were the most common (52.2%), followed by nonfunctional tumors (39.7%), whereas the order was reversed in US patients. Tumor grade distribution was similar in the 2 countries (G1: 57.5% vs 55.0%; G2: 38.5% vs 41.3%; and G3: 4.0% vs 3.7%). However, age, primary tumor size, primary tumor location, grade, and stage of subtypes of PNETs were significantly different between the 2 countries. The Chinese nonfunctional tumors were significantly larger than US ones (median size 4 vs 3 cm) and more frequently located in the head/neck region (54.9% vs 34.8%). The Chinese and US insulinomas were similar in size (median 1.5 cm) but the Chinese insulinomas relatively more frequently located in the head/neck region (48.3% vs 26.1%). Higher grade, advanced stage, metastasis, and larger primary tumor size were significantly associated with unfavorable survival in both countries. Several clinicopathological differences are found between Chinese and US PNETs but the PNETs of both countries follow a similar natural history. The WHO tumor grading and ENETS staging criteria are applicable to both Chinese and US patients.
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Affiliation(s)
- Li-Ming Zhu
- From the Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (L-MZ, X-WQ, Y-LS, T-TS, C-ML, Y-JC); Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY (LT); Markey Cancer Center, University of Kentucky, Lexington, KY (EW); Department of Surgery (NNN); Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA (DD); Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (JC); Department of Gastrointestinal Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute (LS); Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing (YC); Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai (Y-ZY, Q-WB); Department of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou (BL); Department of Endocrinology, the Third Hospital of Hebei Medical University, Shijiazhuang (Y-RZ); Department of Oncology (C-MB); Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (JC); and Division of Endocrinology and Carcinoid and Neuroendocrine Tumor Center, Cedars-Sinai Medical Center, University of California Los Angeles, Los Angeles, CA (RY)
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Jahan A, Yusuf MA, Loya A. Fine-Needle Aspiration Cytology in the Diagnosis of Pancreatic Neuroendocrine Tumors: A Single-Center Experience of 25 Cases. Acta Cytol 2015; 59:163-8. [PMID: 25895934 DOI: 10.1159/000381173] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Accepted: 02/24/2015] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Pancreatic neuroendocrine tumors (Pan NETs) are rare but are being increasingly diagnosed. The objective of this retrospective study was to share our experience of fine-needle aspiration (FNA), including endoscopic ultrasound-guided FNA with rapid on-site evaluation (ROSE), with the use of immunohistochemical (IHC) markers in the diagnosis of Pan NET. STUDY DESIGN A total of 25 cases of Pan NET diagnosed on pancreatic FNA between 2008 and 2013 were identified from our hospital database. Clinical history, radiology, cytomorphological features, and IHC performed were reviewed. RESULTS The mean age of our patient group was 52 years; 15/25 were male. Most presented with abdominal pain and the majority of the lesions were in the pancreatic body, the largest being 14 cm in size. Based on the 2010 World Health Organization criteria, cases were further graded as follows: 21 cases were grade 1, 2 cases were grade 2 and 2 cases were grade 3. Proliferation marker Ki-67 was utilized in 6 cases for definitive grading. Of the 25 cases, 23 were diagnosed as nonfunctional while 2 were functional; 1 patient had MEN-1 syndrome and 1 had von Recklinghausen's syndrome. CONCLUSIONS Our data suggests that FNA, with ROSE and IHC markers, is highly sensitive and specific for diagnosing Pan NET.
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Affiliation(s)
- Amna Jahan
- Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
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15
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Grozinsky-Glasberg S, Mazeh H, Gross DJ. Clinical features of pancreatic neuroendocrine tumors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:578-85. [DOI: 10.1002/jhbp.226] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 01/14/2015] [Indexed: 12/18/2022]
Affiliation(s)
- Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Department of Medicine; Hadassah-Hebrew University Medical Center; P.O.B. 12000 Jerusalem 91120 Israel
| | - Haggi Mazeh
- Department of Surgery; Hadassah-Hebrew University Medical Center; Jerusalem Israel
| | - David J. Gross
- Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Department of Medicine; Hadassah-Hebrew University Medical Center; P.O.B. 12000 Jerusalem 91120 Israel
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Luo G, Liu Z, Guo M, Jin K, Xiao Z, Liu L, Xu J, Zhang B, Liu C, Huang D, Hu S, Ni Q, Long J, Yu X. (18)F-FDG PET/CT can be used to detect non-functioning pancreatic neuroendocrine tumors. Int J Oncol 2014; 45:1531-1536. [PMID: 25096059 DOI: 10.3892/ijo.2014.2570] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 07/17/2014] [Indexed: 11/05/2022] Open
Abstract
18F-Fluorodeoxyglucose positron emission tomo-graphy and computed tomography (18F-FDG PET/CT) has limited value in well-differentiated neuroendocrine tumors. The value of 18F-FDG PET/CT in non-functioning pancreatic neuroendocrine tumors, which are often poorly differentiated, malignant, and present at an advanced stage, was also thought to be limited. This study was performed to evaluate the clinical value of 18F-FDG PET/CT in assessing non-functioning pancreatic neuroendocrine tumors. From January 2010 to February 2014, a comparable large cohort of patients (31 cases) with non-functioning pancreatic neuroendocrine tumors from Shanghai Cancer Center underwent 18F-FDG PET/CT scans. Demographics and clinical characteristics were retrospectively collected and analyzed for all the patients. Twenty-eight of 31 (90.3%) patients with non-functioning endocrine pancreatic tumors had an elevated 18F-FDG uptake (SUVmax ≥2.5). In addition, 18F-FDG PET/CT visualized 38 of 42 (90.5%) distant metastatic lesions. The 18F-FDG uptake had significant association with tumor size (P=0.012) and TNM stage (P=0.004). The application of 18F-FDG PET/CT has changed the management of 8 cases (8/31, 25.8%). In conclusion, 18F‑FDG PET/CT plays an important role in detecting and staging non-functioning pancreatic neuroendocrine tumors.
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Affiliation(s)
- Guopei Luo
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Zuqiang Liu
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Meng Guo
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Kaizhou Jin
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Zhiwen Xiao
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Liang Liu
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Jin Xu
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Bo Zhang
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Chen Liu
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Dan Huang
- Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Silong Hu
- Department of Nuclear Medicine, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Quanxing Ni
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Jiang Long
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
| | - Xianjun Yu
- Department of Pancreatic and Hepatobiliary Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
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Wong J, Fulp WJ, Strosberg JR, Kvols LK, Centeno BA, Hodul PJ. Predictors of lymph node metastases and impact on survival in resected pancreatic neuroendocrine tumors: a single-center experience. Am J Surg 2014; 208:775-780. [PMID: 24997491 DOI: 10.1016/j.amjsurg.2014.04.003] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Revised: 03/23/2014] [Accepted: 04/18/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Staging for pancreatic neuroendocrine tumors (PNET) considers tumor size and lymph node (LN) status; however, correlation with survival remains unclear. METHODS A single-institution database of patients with resected PNET was analyzed. RESULTS Of the 150 patients, incidentally discovered PNET was the most common presentation (42%). One hundred thirteen patients (75%) had LN data, 32 (28%) with positive LN (LN+). Procedure and tumor size did not predict LN+. Perineural invasion (P = .016) and lymphovascular (P < .001) invasion, however, were more common in LN+. Multivariate analysis showed poor/moderate differentiation predicted LN+. Median follow-up was 52 months and median overall survival was 225 months. Fifty-two patients (35%) developed recurrence and median disease-free survival (DFS) was 74 months. Only poor/moderate differentiation affected DFS. CONCLUSIONS PNET has an unclear prognosis based on variables factored into stage. In this study, tumor size did not predict LN+; furthermore, LN+ did not impact overall survival or DFS. Tumor differentiation appears to be more important in determining prognosis.
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Affiliation(s)
- Joyce Wong
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
| | - William J Fulp
- Department of Biostatistics, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
| | - Jonathan R Strosberg
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
| | - Larry K Kvols
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
| | - Barbara A Centeno
- Department of Pathology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
| | - Pamela J Hodul
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
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18
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Kishi Y, Shimada K, Nara S, Esaki M, Hiraoka N, Kosuge T. Basing Treatment Strategy for Non-functional Pancreatic Neuroendocrine Tumors on Tumor Size. Ann Surg Oncol 2014; 21:2882-8. [DOI: 10.1245/s10434-014-3701-y] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Indexed: 02/06/2023]
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Shrikhande SV, Sirohi B, Goel M, Barreto SG. Pancreatic neuroendocrine tumors. Indian J Gastroenterol 2013; 32:3-17. [PMID: 23054950 DOI: 10.1007/s12664-012-0257-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 09/04/2012] [Indexed: 02/04/2023]
Abstract
Pancreatic neuroendocrine tumors (pancreatic NETs) are rare, low- to intermediate-grade neoplasms thought to arise from the pancreatic islets. Recent advances in pathology and our understanding of the biological behavior of this group of tumors has resulted in changes in their nomenclature and how we treat them. This review puts into perspective our current understanding of pancreatic NETs in terms of their incidence, pathology, and management.
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Affiliation(s)
- Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, India.
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Abstract
This chapter describes the possibility of using peptide receptor radionuclide therapy (PRRT) as neoadjuvant treatment. PRRT is acknowledged to be a palliative treatment. Recently it has been reported that tumor size decrease followed by surgical intervention might be achieved in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs labeled with beta emitters. Such outcome of therapy has been described in a relatively small group of patients. In those patients, the treatment enabled total or partial excision of the tumor, also with liver metastases. Reduction of tumor dimensions or total excision of the tumor corresponded with prolongation of overall survival. The discussed papers on this subject differ in details of treatment (utilization of various isotopes, total activity of the isotope, or combination with radiosensitizing chemotherapy). The chapter presents a brief review of recently published manuscripts.
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Kim MJ, Choi DW, Choi SH, Heo JS, Park HJ, Choi KK, Jang KT, Sung JY. Surgical strategies for non-functioning pancreatic neuroendocrine tumours. Br J Surg 2012; 99:1562-8. [PMID: 23027073 DOI: 10.1002/bjs.8892] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The purpose of this study was to identify management strategies for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) by analysis of surgical outcomes at a single institution. METHODS Archived records of patients with NF-PNETs who underwent surgery between 1994 and 2010 were reviewed. RESULTS Among 125 patients, the median tumour size was 2·5 (range 0·15-20·5) cm. Of the 51 NF-PNETs with a diameter of no more than 2 cm, 12 (24 per cent) were diagnosed as carcinoma. Overall 20 patients (16·0 per cent) had metastases to the lymph nodes. The minimum size of the tumour with lymph node metastasis was 1·2 cm. Having a NF-PNET of 2 cm or larger significantly increased the probability of a poorly differentiated carcinoma (P = 0·006), and having a NF-PNET of at least 2·5 cm significantly increased the probability of lymph node metastasis (P = 0·048). The 5-year cumulative survival rate after curative resection was 89·7 per cent. During a median follow-up of 31·5 months, there were 27 recurrences (23·1 per cent) and 13 disease-specific deaths (11·1 per cent) among the 117 patients who had an R0 resection. All patients who underwent repeat operations were alive without additional recurrence after a mean(s.d.) follow-up of 27·1(18·0) months. CONCLUSION Curative surgery should be performed for control of primary NF-PNETs. Lymph node dissection for NF-PNETs of 2·5 cm or larger and at least node sampling for tumours with a diameter of 1 cm or more are recommended. Debulking surgery should be considered for advanced tumours.
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Affiliation(s)
- M J Kim
- Department of Surgery, Jeju National University Hospital, School of Medicine, Jeju National University, Jeju, Korea
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22
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Tsutsumi K, Ohtsuka T, Mori Y, Fujino M, Yasui T, Aishima S, Takahata S, Nakamura M, Ito T, Tanaka M. Analysis of lymph node metastasis in pancreatic neuroendocrine tumors (PNETs) based on the tumor size and hormonal production. J Gastroenterol 2012; 47:678-85. [PMID: 22350698 DOI: 10.1007/s00535-012-0540-0] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2011] [Accepted: 12/19/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Because of the rarity and variety of pancreatic neuroendocrine tumors (PNETs), there have been few reports regarding the indication for lymph node dissection in patients with these tumors. This study aimed to evaluate the risk of lymph node metastasis of PNETs based on the tumor size and hormonal production. METHODS Data for a total of 66 patients who had PNETs resected at our department between 1987 and 2010 were retrospectively studied. The clinicopathological features, including the disease-specific survival rate, were assessed based on the status of lymph node metastasis at the time of initial surgical resection. Then the cut-off point of tumor size to predict lymph node metastasis was estimated. RESULTS There were 12 patients (18%) with lymph node metastasis. The frequency of lymph node metastasis tended to be higher in gastrinomas than that in other tumors (43 vs. 15%; P = 0.08). The size of PNETs with lymph node metastasis was significantly larger than that of the PNETs without metastasis (P = 0.04). The postoperative survival rate in the PNET patients with lymph node metastasis was significantly lower than that in the patients without metastasis (P < 0.0001). Only 2 (8%) of 26 PNETs with a tumor size of <15 mm had lymph node metastasis, and both of these were gastrinomas. On the other hand, 10 (25%) of the remaining 40 PNETs with a tumor size of ≥15 mm had lymph node metastasis. Notably, there were no PNETs with lymph node metastasis in 22 non-gastrinomas with a tumor size of <15 mm. CONCLUSIONS Non-gastrinomas with a tumor size of ≥15 mm and all gastrinomas would be an indication for pancreatectomy with lymph node dissection.
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Affiliation(s)
- Kosuke Tsutsumi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan
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Li J, Luo G, Fu D, Jin C, Hao S, Yang F, Wang X, Yao L, Ni Q. Preoperative diagnosis of nonfunctioning pancreatic neuroendocrine tumors. Med Oncol 2011; 28:1027-1031. [PMID: 20623205 DOI: 10.1007/s12032-010-9611-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2010] [Accepted: 06/18/2010] [Indexed: 01/27/2023]
Abstract
The aim of this study is to summarize the experience of preoperative diagnosis for nonfunctioning pancreatic neuroendocrine tumors (NFPNETs). The medical records of patients with NFPNETs were identified from 2001 to 2009 in a single center. They were all reviewed and analyzed for their demographics, clinical presentation, preoperative laboratory evaluation and radiographic characterization. Twenty-six patients (11 men and 15 women) in the past 8 years were diagnosed with NFPNETs. Almost all patients had the normal level of exocrine tumor markers. Although it was not difficult to find tumors by traditional imaging modalities including CT and MRI, the misdiagnosis rate was as high as 81.2%. Perfusion CT was helpful to predict the biological behavior of tumors and even identified NFPNETs as benign or malignant. The preoperative diagnosis for NFPNETs can be confirmed by one or the combination of CgA, perfusion CT, FNA-EUS, PET and octreoscans. NFPNETs should be aroused suspicion of normal exocrine tumor markers and relative specific imaging appearance, which can be proved by one or the combination of CgA, perfusion CT, FNA-EUS, PET and octreoscans.
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Affiliation(s)
- Ji Li
- Department of Pancreatic Surgery, General Surgery, Huashan Hospital, and Pancreatic Disease Institute, Fudan University, 200040, Shanghai, China
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The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant. Langenbecks Arch Surg 2011; 396:1145-56. [PMID: 21523447 DOI: 10.1007/s00423-011-0794-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2011] [Accepted: 03/23/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are increasing in incidence and prevalence. This reflects greater clinical awareness, effective imaging, and increasing pathological diagnostic recognition. Although the identification and treatment of clinical neuroendocrine syndromes are established, there is confusion when a NEN has no discernible clinical symptoms. DISCUSSION Nonfunctional tumors are usually diagnosed incidentally and at a later stage largely because either they do not secrete a bioactive product or do so, but in a form that is either inactive or in quantities that have no discernible effect. Nevertheless, the histopathology is indistinguishable from functional NENs, and tumors exhibit somatostatin receptor expression, and positive immunohistochemistry for neuroendocrine cell markers (CgA, NSE/synaptophysin). Similarly, their rates of growth and metastatic behavior are, like other NENs, predictably based on staging and grading (mitotic rate and Ki67 expression). Both types are diagnosed biochemically (CgA) and by imaging in an identical fashion with computed tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, and endoscopic ultrasound. NENs, irrespective of function or bioactive secretory profile, respond with equal efficacy to the same regimen of surgery or antitumor drugs (e.g., somatostatin analogs with or without tyrosine kinase inhibitors/antiangiogenics or cytotoxics) depending on grade. Given the efficacy of somatostatin analogs in increasing progression free survival, nonfunctional NENs should be managed identically to symptomatic NENs. The consideration of NENs as functional or nonfunctional is an archaic clinical concept that should be discarded since the tumors are indistinguishable at a cellular, biological, and morphological level. All current evidences indicate that their diagnosis and treatment should follow the same common principles.
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SAKURAI K, TSUKAMOTO T, SHIMIZU S, KODAI S, KANAZAWA A, YAMAMOTO S, YAMASHITA Y, ARIMOTO Y, NISHIGUCHI Y. A case of neuroendocrine carcinoma originating from the pancreas with multiple liver metastasis resected after chemotherapy with etoposide and cisplatin. ACTA ACUST UNITED AC 2011. [DOI: 10.2958/suizo.26.563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Yu TC. Pancreatic neuroendocrine tumour (PNET) occurring with Guillian-Barré syndrome (Re: ANZ J. Surg. 2010; 80: 297). ANZ J Surg 2010; 80:951. [DOI: 10.1111/j.1445-2197.2010.05395.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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DiNorcia J, Lee MK, Reavey PL, Genkinger JM, Lee JA, Schrope BA, Chabot JA, Allendorf JD. One hundred thirty resections for pancreatic neuroendocrine tumor: evaluating the impact of minimally invasive and parenchyma-sparing techniques. J Gastrointest Surg 2010; 14:1536-46. [PMID: 20824378 DOI: 10.1007/s11605-010-1319-3] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2010] [Accepted: 08/09/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increasingly, surgeons apply minimally invasive and parenchyma-sparing techniques to the management of pancreatic neuroendocrine tumor (PNET). The aim of this study was to evaluate the impact of these approaches on patient outcomes. METHODS We retrospectively collected data on patients with PNET and compared perioperative and pathologic variables. Survival was analyzed using the Kaplan-Meier method. Factors influencing survival were evaluated using a Cox proportional hazards model. RESULTS One hundred thirty patients underwent resection for PNET. Traditional resections included 43 pancreaticoduodenectomies (PD), 38 open distal pancreatectomies (DP), and four total pancreatectomies. Minimally invasive and parenchyma-sparing resections included 25 laparoscopic DP, 11 central pancreatectomies, five enucleations, three partial pancreatectomies, and one laparoscopic-assisted PD. Compared to traditional resections, the minimally invasive and parenchyma-sparing resections had shorter hospital stays. By univariate analysis of neuroendocrine carcinoma, liver metastases and positive resection margins correlated with poor survival. There was an increase in minimally invasive or parenchyma-sparing resections over the study period with no differences in morbidity, mortality, or survival. CONCLUSION In this series, there has been a significant increase in minimally invasive and parenchyma-sparing techniques for PNET. This shift did not increase morbidity or compromise survival. In addition, minimally invasive and parenchyma-sparing operations yielded shorter hospital stays.
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Affiliation(s)
- Joseph DiNorcia
- College of Physicians and Surgeons, Department of Surgery, Columbia University, 161 Fort Washington Avenue, Suite 820, New York, NY 10032, USA
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Yagnik VD, Yagnik BD. Re: Pancreatic neuroendocrine tumour (PNET) occurring with Guillian-Barré syndrome (ANZ J. Surg. 2010; 80: 297). ANZ J Surg 2010; 80:568. [PMID: 20795981 DOI: 10.1111/j.1445-2197.2010.05384.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Current World Literature. Curr Opin Support Palliat Care 2010; 4:111-20. [DOI: 10.1097/spc.0b013e32833a1dfc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Barreto SG, Shukla PJ, Shrikhande SV. Tumors of the Pancreatic Body and Tail. World J Oncol 2010; 1:52-65. [PMID: 29147182 PMCID: PMC5649906 DOI: 10.4021/wjon2010.04.200w] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2010] [Indexed: 12/11/2022] Open
Abstract
Tumors of the pancreatic body and tail are uncommon. They have a propensity to present late and often attain a large size with local invasion before they produce any clinical symptoms. The current review aims at comprehensively analysing these tumors with respect to their pathology, presentation, the investigation of these tumors, and finally the latest trends in their surgical and medical management.
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Affiliation(s)
- Savio George Barreto
- Department of General and Digestive Surgery, Flinders Medical Centre, Adelaide - South Australia
| | - Parul J Shukla
- Department of Gastrointestinal Surgical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Shailesh V Shrikhande
- Department of Gastrointestinal Surgical Oncology, Tata Memorial Hospital, Mumbai, India
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Kaemmerer D, Prasad V, Daffner W, Hörsch D, Klöppel G, Hommann M, Baum RP. Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor. World J Gastroenterol 2009; 15:5867-70. [PMID: 19998512 PMCID: PMC2791284 DOI: 10.3748/wjg.15.5867] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Pancreatic endocrine tumors are rare but are among the most common neuroendocrine neoplasms of the abdomen. At diagnosis many of them are already advanced and difficult to treat. We report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman, who received neoadjuvant peptide receptor radionuclide therapy (PRRT) as first-line treatment. This resulted in a significant downstaging of the tumor and allowed its subsequent complete surgical removal. Follow-up for eighteen months revealed a complete remission. This is the first report on neoadjuvant PRRT in a neuroendocrine neoplasm with subsequent successful complete resection.
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