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Sena G, Currò G, Vescio G, Ammerata G, Amaddeo A, Rizzuto A. Surgical vs. Conservative Management of Patients with Nonfunctioning Pancreatic Neuroendocrine Tumors Smaller than 2 cm (NF-PANNETs < 2 cm) Systematic Review and Meta-Analysis. Cancers (Basel) 2025; 17:1649. [PMID: 40427145 PMCID: PMC12109734 DOI: 10.3390/cancers17101649] [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: 04/11/2025] [Revised: 05/08/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
INTRODUCTION There is no consensus on managing non-functioning pancreatic neuroendocrine tumors smaller than 2 cm (NF-PANNETs < 2 cm). Therefore, their treatment remains controversial. The aim of this study, by literature review and meta-analysis, is to establish the best management of NF-PANNETs < 2 cm based on overall survival (OS) and cancer-specific survival (CSS). MATERIALS AND METHODS An extensive online search was conducted using the MEDLINE, EMBASE, Google Scholar, Scopus, Web of Science, and Cochrane Central databases. All retrospective and prospective studies were included in this study, comparing the outcomes of surgical management vs. conservative management in patients with NF-PANNETs < 2 cm. The pooled odds ratio and 95% CI for survival were calculated. RESULTS Six studies were included in the quantitative analysis, with 2708 patients managed operatively and 985 managed conservatively. A pooled analysis of all the data demonstrated increased OS in patients managed operatively compared with those managed conservatively at five years (OR = 1.77, 95% CI: 0.96 to 2.58; p = 0.002). In contrast, the meta-analysis did not demonstrate increased CSS in patients undergoing surgical resection compared with conservative management (OR = 1.01, 95% CI: -5.25 to 7.27; p = 0.56). Furthermore, analysis demonstrated a high heterogeneity for OS (Q = 43.98, p < 0.001, tau2 = 0.46, I2 = 88.63%) and for CSS (Q = 22.81, p < 0.0001, tau2 = 1.72, I2 = 91.23%). CONCLUSION This systematic review and meta-analysis indicated that surgical management of NF-PANNETs < 2 cm improves overall survival (OS) but does not significantly enhance cancer-specific survival (CSS). There is variability in outcomes among studies, and while surgery may help some patients, the lack of clear CSS benefits and associated risks call for individualized decision-making. Therefore, a conservative approach with active surveillance may be more suitable for low-risk patients.
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Affiliation(s)
- Giuseppe Sena
- Department of General Surgery, “Renato Dulbecco” Hospital, Viale Europa, 88100 Catanzaro, Italy
| | - Giuseppe Currò
- Department of Health Science, “Magna Graecia” University, Viale Europa, 88100 Catanzaro, Italy
| | - Giuseppina Vescio
- Department of Surgical and Medical Science, “Magna Graecia” University, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (A.A.); (A.R.)
| | - Giorgio Ammerata
- Department of General Surgery, “Di Venere” Hospital, Via Ospedale Di Venere, 1, 70131 Bari, Italy;
| | - Angela Amaddeo
- Department of Surgical and Medical Science, “Magna Graecia” University, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (A.A.); (A.R.)
| | - Antonia Rizzuto
- Department of Surgical and Medical Science, “Magna Graecia” University, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (A.A.); (A.R.)
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Singh J, Gudmundsdottir H, Halfdanarson TR, Cleary SP, Kendrick ML, Truty MJ, Smoot RL, Nagorney DM, Vege SS. Pancreatic Neuroendocrine Tumors-A Descriptive Study of the Presenting Features in a 20-Year Surgical Resection Cohort at a Tertiary Institution. Pancreas 2025; 54:e423-e429. [PMID: 40314740 DOI: 10.1097/mpa.0000000000002452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 12/16/2024] [Indexed: 05/03/2025]
Abstract
OBJECTIVES Pancreatic neuroendocrine tumors (pNETs) are uncommon, comprising 3%-7% of pancreatic tumors. With increasing incidence due to advanced imaging techniques, there is a need for detailed characterization of these tumors. This study aims to describe the clinical features, diagnostic evaluations, and pathology characteristics of pNETs in a large cohort from a single tertiary center, and to compare these findings with other larger cohort studies. METHODS We conducted a retrospective analysis of 866 patients with pNETs who underwent surgical resection at Mayo Clinic, Rochester, from March 2000 to December 2019. Data on demographics, clinical presentation, laboratory tests, imaging, and pathology were extracted and analyzed. Descriptive statistics were used to summarize the data. RESULTS The cohort had a median age of 57 years. Nonfunctional tumors were much more prevalent (77.5%), with functional tumors primarily being insulinomas (75.9%). Common presenting symptoms included gastrointestinal (45.3%) and nongastrointestinal symptoms (30.7%). Chromogranin A levels were elevated in 57.5% of patients. Imaging revealed enhancing lesions in most cases, with computed tomography scans performed in 90.9% of patients. Endoscopic ultrasound (EUS) identified tumors in 98.1% of cases, with EUS-FNA showing a sensitivity of 82%. Ki-67 index, used in 58.1% of cases, indicated grade 2 tumors as the most common (55.9%). Metastasis was observed in 39.4% of patients at the time of diagnosis, predominantly in the liver. CONCLUSION This study provides a comprehensive description of pNET characteristics in a large surgical cohort. Findings highlight the predominance of nonfunctional tumors and the importance of imaging and EUS in diagnosis. The data can aid in inter-institutional comparisons and enhance understanding of pNETs, contributing to improved patient management and future research.
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Affiliation(s)
- Jassimran Singh
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA
| | | | | | - Sean P Cleary
- Department of Hepatobiliary and Pancreas Surgery, University of Toronto, Toronto, ON, Canada
| | | | - Mark J Truty
- Departments of Hepatobiliary and Pancreas Surgery
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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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Murase Y, Esaki M, Mizui T, Takamoto T, Nara S, Ban D, Hiraoka N, Shimada K. Optimal lymph node dissection area for pancreatic neuroendocrine neoplasms by tumor location, size, and grade. Surgery 2025; 180:109029. [PMID: 39740608 DOI: 10.1016/j.surg.2024.109029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 12/02/2024] [Accepted: 12/03/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND Lymph node dissection is required for many pancreatic neuroendocrine neoplasms. However, the need for such dissection has rarely been examined in detail by the tumor size, tumor location, or World Health Organization grading. The objective is to determine which characteristics of pancreatic neuroendocrine neoplasms require lymph node dissection, and to what extent lymph node dissection should be performed. METHODS A retrospective review was performed of patients who had undergone pancreatectomy with lymph node dissection between 2000 and 2022. Frequency of lymph node metastases stratified by tumor size and grade, and efficacy index (calculated by multiplying the frequency of metastasis to the lymph node station by the 5-year overall survival rate of patients with metastasis to that station) for each lymph node station were evaluated. RESULTS Among 130 patients, 29 (22.3%) had lymph node metastases. Tumors larger than 2 cm had a 33.3% lymph node metastasis rate, whereas grade 1 and grade 2 neuroendocrine tumors had rates of 2.4% and 31.8%, respectively. In grade 1 neuroendocrine tumor, for pancreatic head tumor, only peripancreatic head lymph node had an efficacy index of 5.0. Pancreatic body and tail tumor had no lymph node metastases. In grade 2 neuroendocrine tumor, for pancreatic head tumor, peripancreatic and superior mesenteric artery lymph nodes had efficacy indexes of 29.2 and 14.3, respectively. For pancreatic body tumor, peridistal pancreatic lymph node had an efficacy index of 27.3, whereas for pancreatic tail tumor, peridistal pancreatic lymph node and splenic hilum lymph node had an efficacy index of 27.8 and 7.1, respectively. CONCLUSION The optimal extent of lymph node dissection for pancreatic neuroendocrine neoplasms should be determined by considering both the tumor size and grade for each tumor location.
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Affiliation(s)
- Yoshiki Murase
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan.
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Nobuyoshi Hiraoka
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
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Tan Q, Liu L, Liu X, Tan C, Wang X. Prognosis of small pancreatic neuroendocrine neoplasms: Functionality matters. Am J Surg 2025:116302. [PMID: 40140248 DOI: 10.1016/j.amjsurg.2025.116302] [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: 12/14/2024] [Revised: 03/03/2025] [Accepted: 03/19/2025] [Indexed: 03/28/2025]
Abstract
BACKGROUND This study aimed to evaluate potential difference in clinicopathological characteristics, prognosis as well as the genetic bases between insulinomas and non-functional pancreatic neuroendocrine neoplasms (NF-PNENs). METHOD We analyzed data from 241 patients who underwent resection for PNENs measuring 1-2 cm at West China Hospital between 2002 and 2020. RESULTS NF-PNENs were more likely to show lymph node involvement (P < 0.001), perineural invasion (P = 0.025), and a more advanced tumor grade (P < 0.001). In multivariate analysis, NF-PNENs, when combined with lymph node metastasis and WHO G2/G3 grading, independently decreased recurrence-free survival [hazard ratio (HR), 4.72; P = 0.014]. Whole exome sequencing revealed that most of the top 20 somatic mutated genes (90 %, 36/40) between insulinomas and NF-PNENs are different. Besides, all copy number variant (CNV) patterns were present in NF-PNENs, whereas insulinomas were more likely to exhibit CNV amplification. CONCLUSION Insulinomas and small NF-PNENs exhibit distinct tumor biology, prognosis, and genetic backgrounds, which may inform changes in surgical management and postoperative follow-up strategies for these patients.
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Affiliation(s)
- Qingquan Tan
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Li Liu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital / West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Xubao Liu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Chunlu Tan
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| | - Xing Wang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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López Gonzalez M, Hernando-Requejo O, Ciervide Jurío R, Montero Luis Á, Saiz Guisasola C, Sánchez Saugar E, Álvarez Rodríguez B, Chen-Zhao X, García-Aranda M, Valero Albarran J, Alonso Gutierrez R, García Cañamaque L, Prados S, Quijano Y, de Vicente E, Rubio C. Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis. Clin Transl Oncol 2025; 27:377-385. [PMID: 38907097 DOI: 10.1007/s12094-024-03538-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/24/2024] [Indexed: 06/23/2024]
Abstract
INTRODUCTION Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs. MATERIALS AND METHODS From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. RESULTS In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection. CONCLUSION SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.
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Affiliation(s)
- Mercedes López Gonzalez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain.
| | - Ovidio Hernando-Requejo
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Raquel Ciervide Jurío
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Ángel Montero Luis
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Carmen Saiz Guisasola
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Emilio Sánchez Saugar
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Beatriz Álvarez Rodríguez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Xin Chen-Zhao
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Mariola García-Aranda
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Jeannette Valero Albarran
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Rosa Alonso Gutierrez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
| | - Lina García Cañamaque
- Department of Nuclear Medicine, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Susana Prados
- Department of Gastroenterology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Yolanda Quijano
- Department of Surgery, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Emilio de Vicente
- Department of Surgery, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Carmen Rubio
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Oña 10, 28050, Madrid, Spain
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Katsuda H, Kobayashi M, Ito G, Kawamoto A, Krimura S, Sato H, Hirakawa A, Akahoshi K, Kudo A, Ohtsuka K, Okamoto R. Evaluating endoscopic ultrasound-guided tissue acquisition for diagnosis of small pancreatic neuroendocrine neoplasms. Endosc Int Open 2024; 12:E1379-E1385. [PMID: 39610940 PMCID: PMC11604306 DOI: 10.1055/a-2422-9363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 09/26/2024] [Indexed: 11/30/2024] Open
Abstract
Background and study aims Although small hypervascular tumors are suspected to be pancreatic neuroendocrine tumors (p-NENs), their diagnosis and treatment are challenging. This study evaluated the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosis of small p-NENs. Methods All p-NEN lesions that underwent EUS-TA at our hospital between April 2018 and December 2023 were retrospectively analyzed. The diagnostic sensitivity of EUS-TA and the concordance rate of grading with EUS-TA and surgical specimens were examined. The lesions were grouped by size. Results The diagnostic sensitivity of EUS-TA was analyzed for 82 lesions, of which 44 were compared with postoperative specimens for grading. The definitive diagnosis was neuroendocrine tumor (NET) in 75 lesions, neuroendocrine carcinoma in five lesions, and mixed neuroendocrine non-neuroendocrine neoplasm in two lesions. Thirty tumors were ≤10 mm, 30 were 10 to 20 mm, and 22 were >20 mm, and the diagnostic sensitivities were 96.7%, 96.7%, and 90.9%, respectively. Concordance rates for grading were 94.4%, 82.4%, and 77.8% for tumors ≤10 mm, 10 to 20 mm, and ≥20 mm, respectively, with Cohen's kappa coefficients of 0.64, 0.48, and 0.40, respectively. Conclusions EUS-TA showed adequate diagnostic sensitivity and grading agreement for p-NENs of all sizes, allowing for determination of appropriate treatment.
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Affiliation(s)
- Hiromune Katsuda
- Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Masanori Kobayashi
- Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Go Ito
- Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Ami Kawamoto
- Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Susumu Krimura
- Pathology, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Hiroyuki Sato
- Clinical Biostatistics, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Bunkyo-ku, Japan
| | - Akihiro Hirakawa
- Clinical Biostatistics, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Bunkyo-ku, Japan
| | - Keiichi Akahoshi
- Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Atsushi Kudo
- Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Kazuo Ohtsuka
- Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Japan
| | - Ryuichi Okamoto
- Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Japan
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Bispo M, Marques S, Fernandes A, Rodrigues-Pinto E, Vilas-Boas F, Rio-Tinto R, Devière J, on behalf of the Portuguese Pancreatic Club, specialized section of the Portuguese Society of Gastroenterology. Portuguese Pancreatic Club Perspective on the Surveillance Strategy for Pancreatic Neuroendocrine Tumours: When and How to Do It? GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:306-313. [PMID: 39360175 PMCID: PMC11444664 DOI: 10.1159/000535815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 11/24/2023] [Indexed: 10/04/2024]
Abstract
Background Pancreatic neuroendocrine tumours (pNETs) are a highly heterogeneous group of tumours with widely variable biological behaviour. The incidence of pNETs has risen exponentially over the last three decades, particularly for asymptomatic small pNETs (≤2 cm), due to the widespread use of cross-sectional imaging in clinical practice. Summary Current consensus guidelines suggest that incidentally discovered pNETs ≤2 cm can be selectively followed due to the overall low risk of malignancy. Nevertheless, the "watch-and-wait" management strategy for small asymptomatic pNETs is still not widely accepted due to the lack of long-term data on the natural history of these small lesions. Additionally, it is clear that a subset of small pNETs may show malignant behaviour. Key Message Given the non-negligible risk of malignancy even in small pNETs, it is of the utmost importance to identify other preoperative factors, other than size, that may help to stratify the risk of malignant behaviour and guide clinical management. In this article, the Portuguese Pancreatic Club reviews the importance of risk stratification of pNETs and presents an updated perspective on the surveillance strategy for sporadic well-differentiated pNETs.
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Affiliation(s)
- Miguel Bispo
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Susana Marques
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Alexandra Fernandes
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
| | - Eduardo Rodrigues-Pinto
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Filipe Vilas-Boas
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | | | - Jacques Devière
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Erasme University Hospital – Université Libre de Bruxelles, Brussels, Belgium
| | - on behalf of the Portuguese Pancreatic Club, specialized section of the Portuguese Society of Gastroenterology
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Erasme University Hospital – Université Libre de Bruxelles, Brussels, Belgium
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Brandl A, Lundon D, Siriwardena AK, Sochorova D, Ceelen W, Besselink M, Soreide K, Stättner S. Surgical management of pancreatic neuroendocrine tumors - An EYSAC and E-AHPBA international survey of current practice. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108544. [PMID: 39059195 DOI: 10.1016/j.ejso.2024.108544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/05/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024]
Abstract
INTRODUCTION Pancreatic neuroendocrine tumors (pNET) exhibit a wide spectrum of clinical behavior, which makes their assessment and management quite challenging. The purpose of this study was to comprehensively assess the existing treatment landscape for patients with pNET. MATERIALS AND METHODS The study was conducted with the support of the ESSO-EYSAC Research Academy in collaboration with the E-AHPBA. An online survey was distributed via email and social media to surgical networks across Europe and beyond (September 1-30, 2023). RESULTS Overall, 155 complete responses were obtained. A specialized NET tumor board was present at the institutions of 94 (61 %) of the study participants. The most frequently applied guidelines were from ENETS (n = 97; 63 %), NCCN (n = 74; 48 %), and ESMO (n = 53; 34 %). For resectability, similar criteria as in pancreatic ductal adenocarcinoma were used by 111 (72 %) participants, even though 116 (75 %) participants believed that pNET/pNEC should have their own resectability criteria. Most respondents used somatostatin analogues (n = 126; 81 %) and chemotherapy (n = 85; 55 %) as neoadjuvant treatments, followed by molecularly targeted agents (n = 45; 29 %) and PRRT (n = 37; 24 %). Only 17 (11 %) participants agreed/strongly agreed that the management of pNET/pNEC is sufficiently addressed in surgical education programs. CONCLUSION This international survey highlighted areas for improvement in the care of pNET, namely the lack of pNET-specific resectability criteria and educational programs addressing pNET management.
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Affiliation(s)
- Andreas Brandl
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Germany.
| | - Dara Lundon
- Department of Urology, Icahn School of Medicine at Mount Sinai Hospitals, New York, United States
| | - Ajith K Siriwardena
- Regional Hepato-Pancreato-Biliary Unit, Manchester Royal Infirmary, Manchester, UK
| | - Dana Sochorova
- Department of Surgery, Tomas Bata Regional Hospital, Zlin, Czech Republic
| | - Wim Ceelen
- Department of GI Surgery, Ghent University Hospital, and Cancer Research Institute Ghent (CRIG), Belgium
| | - Marc Besselink
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands
| | - Kjetil Soreide
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Stefan Stättner
- Department of General, Visceral and Vascular Surgery, Salzkammergutklinikum, Vöcklabruck, Austria
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Clarke CN, Ward E, Henry V, Nimmer K, Phan A, Evans DB. Impact of Regional Metastasis on Survival for Patients with Nonfunctional Pancreatic Neuroendocrine Tumors: A Systematic Review. Ann Surg Oncol 2024; 31:4976-4985. [PMID: 38652199 DOI: 10.1245/s10434-024-15249-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 03/19/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND Controversy exists regarding the benefit of lymphadenectomy for nonfunctional pancreatic neuroendocrine tumors (NF-PNET). PATIENTS AND METHODS MEDLINE/PubMed, EMBASE, and the Cochrane Library were searched for studies of pancreatic neuroendocrine tumors (PNET) published between 1990 and 2021. Studies of functional PNET were excluded. Reported incidence of lymph node metastasis (LNM) and survival analysis of either disease-free survival (DFS) or overall survival (OS) were required for inclusion. RESULTS Overall, 52 studies analyzing 24,608 PNET met the inclusion criteria. The reported LNM rate for NF-PNET ranged from 7 to 64 % (median 24.5%). Reported LNM rates ranged from 7 to 51% (median 11%) for NF-PNET< 2 cm in 14 studies and 29-47% (median 38%) in NF-PNET > 2 cm. In total, 19 studies (66%) reported LNM to have a negative impact on DFS. Additionally, 21 studies (60%) reported LNM to have a negative impact on OS. Two studies investigating the impact of lymphadenectomy (LND) found LND had the greatest impact for large, high-grade tumors. The overall quality of available evidence was low as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation System. CONCLUSIONS Published literature evaluating the impact of regional LNM and LND in PNET is confounded by heterogeneity in practice patterns and the retrospective nature of these cohort studies. Most studies suggest high rates of LNM in NF-PNET that negatively impact DFS and OS. Given the high rate of LNM in NF-PNET and its potential detrimental effect on DFS and OS, we recommend lymphadenectomy be completed for NF-PNET > 2 cm and strongly considered for NF-PNET < 2 cm.
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Affiliation(s)
- Callisia N Clarke
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Erin Ward
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Valencia Henry
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Kaitlyn Nimmer
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Alexandria Phan
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Doug B Evans
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
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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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Notake T, Shimizu A, Kubota K, Sugenoya S, Umemura K, Goto T, Yamada A, Fujinaga Y, Soejima Y. Usefulness of intratumoral perfusion analysis for assessing biological features of non-functional pancreatic neuroendocrine neoplasm. Langenbecks Arch Surg 2024; 409:38. [PMID: 38221590 DOI: 10.1007/s00423-023-03219-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/29/2023] [Indexed: 01/16/2024]
Abstract
PURPOSE Here, we evaluated the usefulness of intratumoral perfusion analysis using preoperative contrast-enhanced CT (E-CT) to assess biological features of non-functional pancreatic neuroendocrine neoplasms (NF-PanNENs). METHODS We retrospectively studied 44 patients who underwent curative surgery for NF-PanNENs. We used preoperative E-CT with compartment model analysis to calculate the tumor perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time), and K1/k2 (distribution volume). We assessed the association between perfusion parameters and biological features of NF-PanNENs, including the WHO classification tumor histopathological grade and prognosis after surgery. RESULTS Patients in this study had a neuroendocrine tumor (NET) G1 (n = 32) or NET G2 (n = 12). Neither NET G3 or NEC tumors were observed. Among perfusion parameters, K1 was the most accurate predictor of the high-grade tumor (AUC: 0.726). K1-low (< 0.028 s-1) was significantly associated with large tumors (≥ 20 mm) (p = 0.022), high mitotic index (p = 0.017), high Ki-67 index (p = 0.004), and lymphatic invasion (p = 0.025). Synchronous extra-pancreatic metastasis, including lymph node metastasis or liver metastasis, more frequently developed in K1-low patients than in K1-high patients (29% vs 4%, p = 0.025). Disease-free survival of patients with a K1-low tumor was poorer than that of patients with a K1-high tumor (p = 0.005). Furthermore, no patient with a K1-high tumor developed recurrence after initial surgery. CONCLUSION The perfusion parameters obtained using E-CT were significantly associated with biological features and prognosis of NF-PanNENs.
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Affiliation(s)
- Tsuyoshi Notake
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan.
| | - Akira Shimizu
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Koji Kubota
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Shinsuke Sugenoya
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Kentaro Umemura
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Takamune Goto
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Akira Yamada
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yasunari Fujinaga
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yuji Soejima
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
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13
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Irfan A, Gleason F, Reddy S, Heslin MJ, Rose JB. Resection Versus Observation for Small (≤2 cm) Pancreatic Neuroendocrine Tumors. Am Surg 2023; 89:4675-4680. [PMID: 36134675 DOI: 10.1177/00031348221129501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND We hypothesized that those patients with pancreatic neuroendocrine tumors (pNETs) ≤2 cm managed nonoperatively would have comparable disease progression to individuals undergoing an operation. METHODS Patients diagnosed with nonfunctional pNETs ≤ 2 cm who were evaluated at a single comprehensive cancer center from 2010 to 2017 were selected from a cancer registry database. Clinicopathologic variables were obtained via retrospective chart review. Primary outcomes were overall and disease specific survival. Variables were compared between the 2 groups using chi-square and independent t-test. RESULTS Fifty-two individuals had tumors ≤2 cm, of whom 75% had an operation, while 25% were observed. Each treatment arm had similar distributions of gender, race, and tumor location. The most common operation was distal pancreatectomy (n = 29) followed by pancreatoduodenectomy (n = 6). Nine patients had grade III postoperative complications and 4 had grade IV under Clavien-Dindo classification. The observation group was noted to have a mean disease progression interval of 80.9 months, while those who underwent an operation had a mean disease progression interval of 94.6 months (P = .246). CONCLUSIONS Overall disease progression in patients with pNETs ≤ 2 cm without evidence of metastasis at the time of presentation is not different between those who underwent operation compared to those observed.
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Affiliation(s)
- Ahmer Irfan
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Frank Gleason
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sushanth Reddy
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Martin J Heslin
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - J Bart Rose
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
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Gu W, Chen Y, Zhu H, Chen H, Yang Z, Mo S, Zhao H, Chen L, Nakajima T, Yu X, Ji S, Gu Y, Chen J, Tang W. Development and validation of CT-based radiomics deep learning signatures to predict lymph node metastasis in non-functional pancreatic neuroendocrine tumors: a multicohort study. EClinicalMedicine 2023; 65:102269. [PMID: 38106556 PMCID: PMC10725026 DOI: 10.1016/j.eclinm.2023.102269] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 09/26/2023] [Accepted: 09/26/2023] [Indexed: 12/19/2023] Open
Abstract
BACKGROUND Lymph node status is an important factor for the patients with non-functional pancreatic neuroendocrine tumors (NF-PanNETs) with respect to the surgical methods, prognosis, recurrence. Our aim is to develop and validate a combination model based on contrast-enhanced CT images to predict the lymph node metastasis (LNM) in NF-PanNETs. METHODS Retrospective data were gathered for 320 patients with NF-PanNETs who underwent curative pancreatic resection and CT imaging at two institutions (Center 1, n = 236 and Center 2, n = 84) between January 2010 and March 2022. RDPs (Radiomics deep learning signature) were developed based on ten machine-learning techniques. These signatures were integrated with the clinicopathological factors into a nomogram for clinical applications. The evaluation of the model's performance was conducted through the metrics of the area under the curve (AUC). FINDINGS The RDPs showed excellent performance in both centers with a high AUC for predicting LNM and disease-free survival (DFS) in Center 1 (AUC, 0.88; 95% CI: 0.84-0.92; DFS, p < 0.05) and Center 2 (AUC, 0.91; 95% CI: 0.85-0.97; DFS, p < 0.05). The clinical factors of vascular invasion, perineural invasion, and tumor grade were associated with LNM (p < 0.05). The combination nomogram showed better prediction capability for LNM (AUC, 0.93; 95% CI: 0.89-0.96). Notably, our model maintained a satisfactory predictive ability for tumors at the 2-cm threshold, demonstrating its effectiveness across different tumor sizes in Center 1 (≤2 cm: AUC, 0.90 and >2 cm: AUC, 0.86) and Center 2 (≤2 cm: AUC, 0.93 and >2 cm: AUC, 0.91). INTERPRETATION Our RDPs may have the potential to preoperatively predict LNM in NF-PanNETs, address the insufficiency of clinical guidelines concerning the 2-cm threshold for tumor lymph node dissection, and provide precise therapeutic strategies. FUNDING This work was supported by JSPS KAKENHI Grant Number JP22K20814; the Rare Tumor Research Special Project of the National Natural Science Foundation of China (82141104) and Clinical Research Special Project of Shanghai Municipal Health Commission (202340123).
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Affiliation(s)
- Wenchao Gu
- Department of Diagnostic and Interventional Radiology, University of Tsukuba, Faculty of Medicine, Ibaraki, Tsukuba, Japan
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Yingli Chen
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Haibin Zhu
- Key Laboratory of Carcinogenesis and Translational Research, Department of Radiology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Haidi Chen
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zongcheng Yang
- Department of Stomatology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Shaocong Mo
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Hongyue Zhao
- Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, China
| | - Lei Chen
- Department of Radiology, Minhang Branch, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Takahito Nakajima
- Department of Diagnostic and Interventional Radiology, University of Tsukuba, Faculty of Medicine, Ibaraki, Tsukuba, Japan
| | - XianJun Yu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Shunrong Ji
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - YaJia Gu
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jie Chen
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Wei Tang
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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15
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Regolo M, Cardaci N, Salmeri C, Laudani A, Colaci M, Ippolito M, Motta F, Magrì S, Parisi S, Torcitto AG, Malatino L. Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review. J Clin Med 2023; 12:6617. [PMID: 37892755 PMCID: PMC10607714 DOI: 10.3390/jcm12206617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 09/24/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient's survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs.
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Affiliation(s)
- Matteo Regolo
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Nicolas Cardaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Clara Salmeri
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Alfredo Laudani
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Michele Colaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Massimo Ippolito
- Nuclear Medicine Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Fabio Motta
- Pathological Anatomy Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Salvatore Magrì
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | - Stefanie Parisi
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | | | - Lorenzo Malatino
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
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16
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Elkelany OO, Karaisz FG, Davies B, Krishna SG. An Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their Management. Curr Oncol 2023; 30:7566-7580. [PMID: 37623030 PMCID: PMC10453483 DOI: 10.3390/curroncol30080549] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/25/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
The growing importance of advanced endoscopy in the diagnosis and treatment of pancreatic neuroendocrine neoplasms (PanNETs) necessitates a comprehensive understanding of various biochemical markers, genetic testing methods, radiological techniques, and treatment approaches that encompass multiple disciplines within and beyond gastrointestinal oncology. This review aims to highlight key aspects of these topics, with a specific focus on emerging EUS-guided procedures for the management of PanNETs.
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Affiliation(s)
- Osama O. Elkelany
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Fred G. Karaisz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Benjamin Davies
- College of Medicine, The Ohio State University, Columbus, OH 43201, USA
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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17
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Lin J, Huang H. Observational study of surgical resection in small non-functional pancreatic neuroendocrine tumors: AS SEER-based study. Sci Rep 2023; 13:12824. [PMID: 37550460 PMCID: PMC10406806 DOI: 10.1038/s41598-023-39980-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 08/03/2023] [Indexed: 08/09/2023] Open
Abstract
The potential benefits of surgical resection for small non-functional pancreatic neuroendocrine tumors (NF-PNETs) in terms of survival remain uncertain. This study aimed to evaluate the impact of surgical treatment on patients with NF-PNETs. Using SEER data, we identified 1102 patients from 2004 to 2015 with well and moderately differentiated pancreatic neuroendocrine tumors (PNETs). The associations between continuous variables and receipt of surgery were assessed using Wilcoxon rank-sum tests. Kaplan-Meier survival curves for OS were compared using the log-rank test. We compared outcomes in patients who received surgical resection with those in patients who did not, using a univariable Cox model with inverse probability weighting according to the propensity score and propensity-score matching. Among the cohort of 1102 patients, a majority of 965 individuals (87%) underwent surgical intervention. Upon conducting univariate analysis, we observed that surgical treatment significantly prolonged patients' survival [HR = 0.41, 95% CI [0.26-0.65] P < 0.001]. However, the old [HR = 3.27, 95% CI (2.24-4.76), P 0.001], male gender [HR = 1.82, 95% CI (1.23-2.68), P = 0.003], and moderately well-differentiated factors [HR = 1.71, 95% CI (1.04-2.80), P = 0.034] were found to potentially decrease patients' survival time. In the multivariate analysis, male gender [HR = 1.73, 95% CI (1.15-2.61), P = 0.009] and the old factor [HR = 3.52, 95% CI (2.33-5.31), P < 0.001] emerged as influential predictors with higher hazard ratios. Notably, surgical treatment remained a significant factor associated with improved overall survival [HR = 0.53, 95% CI (0.33-0.84), P = 0.007]. Propensity-score matching and inverse probability weighting were employed as analytical techniques. The univariate analysis results showed favorable outcomes in the weight group [HR = 0.48, 95% CI (0.29-0.78), P = 0.003] and matched group [HR = 0.44, 95% CI (0.22-0.85), P = 0.015], respectively. Survival analysis further confirmed that surgical treatment contributed to increased overall survival (log rank, P < 0.05) in both the matching and weight groups. Patients diagnosed with small, non-functioning pancreatic neuroendocrine tumors who undergo surgical intervention exhibit improved overall survival (OS) outcomes. Therefore, surgery is strongly recommended for this patient population.
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Affiliation(s)
- Jiajing Lin
- Department of General Surgery, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, 350001, People's Republic of China
| | - Heguang Huang
- Department of General Surgery, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, 350001, People's Republic of China.
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18
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Sulciner ML, Clancy TE. Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2023; 15:2006. [PMID: 37046665 PMCID: PMC10093271 DOI: 10.3390/cancers15072006] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones. A wide range of clinical behavior can be seen, with the primary prognostic indicator being tumor grade as defined by the Ki67 proliferation index and mitotic index. Surgery is the primary treatment modality for PNETs. While functional PNETs should undergo resection for symptom control as well as potential curative intent, nonfunctional PNETs are increasingly managed nonoperatively. There is increasing data to suggest small, nonfunctional PNETs (less than 2 cm) are appropriate follow with nonoperative active surveillance. Evidence supports surgical management of metastatic disease if possible, and occasionally even surgical management of the primary tumor in the setting of widespread metastases. In this review, we highlight the evolving surgical management of local and metastatic PNETs.
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Affiliation(s)
| | - Thomas E. Clancy
- Division of Surgical Oncology, Department of Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Zhang WH, Xu JF, Hu YH, Qin Y, Chen J, Yu XJ, Xu XW, Ji SR. The Surgical and Therapeutic Activities of Non-Functional Pancreatic Neuroendocrine Tumors at a High-Volume Institution. Cancers (Basel) 2023; 15:1955. [PMID: 37046616 PMCID: PMC10093673 DOI: 10.3390/cancers15071955] [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: 02/06/2023] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND This study aimed to summarize the surgical and therapeutic activities of non-functional pancreatic neuroendocrine tumors (NF-PanNETs) and perform survival analyses of a 15-year single-institutional cohort of NF-PanNETs. METHODS In total, 1001 patients with neuroendocrine neoplasms treated at Fudan University Shanghai Cancer Center were screened for inclusion, and 509 patients with NF-PanNETs from 2006 to 2020 were included. For time trend analyses, the 15-year study period was randomly divided into three periods. Survival analyses used the Kaplan-Meier method and Cox regression models. RESULTS The total number of resected NF-PanNETs increased over the 15-year study period, from 5 resections in 2006 to 94 resections in 2020. A significant decrease in the tumor size was observed, from a mean of 4.0 cm to 3.3 cm, and to 3.0 cm in the most recent period (p = 0.006). Minimally invasive techniques gradually increased from 3.5% to 12.9%, and finally to 46.4% in the most recent period (p < 0.001). In non-metastatic and resected tumors, the tumor size (p < 0.001), positive lymph node (p < 0.001), adjuvant treatment (p = 0.048), and tumor grade (p < 0.001) were independent prognostic factors for recurrence-free survival (RFS). The microvascular invasion (p = 0.024) and tumor grade (p = 0.013) were independent prognostic factors for overall survival (OS). A malignant transformation from NET into neuroendocrine carcinoma was observed. CONCLUSIONS An increasing number of NF-PanNETs resection and minimally invasive surgery was shown. In non-metastatic and resected tumors NF-PanNETs, tumor size, positive lymph node, adjuvant treatment, and tumor grade were independent predictors of RFS. Microvascular invasion and tumor grade were independent prognostic factors for OS.
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Affiliation(s)
- Wu-Hu Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; (W.-H.Z.); (J.-F.X.); (Y.-H.H.); (Y.Q.); (X.-J.Y.); (X.-W.X.)
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jun-Feng Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; (W.-H.Z.); (J.-F.X.); (Y.-H.H.); (Y.Q.); (X.-J.Y.); (X.-W.X.)
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yu-Heng Hu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; (W.-H.Z.); (J.-F.X.); (Y.-H.H.); (Y.Q.); (X.-J.Y.); (X.-W.X.)
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; (W.-H.Z.); (J.-F.X.); (Y.-H.H.); (Y.Q.); (X.-J.Y.); (X.-W.X.)
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; (W.-H.Z.); (J.-F.X.); (Y.-H.H.); (Y.Q.); (X.-J.Y.); (X.-W.X.)
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xiao-Wu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; (W.-H.Z.); (J.-F.X.); (Y.-H.H.); (Y.Q.); (X.-J.Y.); (X.-W.X.)
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Shun-Rong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; (W.-H.Z.); (J.-F.X.); (Y.-H.H.); (Y.Q.); (X.-J.Y.); (X.-W.X.)
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China;
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
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20
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Williams JK, Schwarz JL, Keutgen XM. Surgery for metastatic pancreatic neuroendocrine tumors: a narrative review. Hepatobiliary Surg Nutr 2023; 12:69-83. [PMID: 36860243 PMCID: PMC9944533 DOI: 10.21037/hbsn-22-238] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 10/10/2022] [Indexed: 01/18/2023]
Abstract
Background and Objective Pancreatic neuroendocrine tumors (PanNETs) are derived from the islet cells of the pancreas and have been increasing in incidence. Most of these tumors are nonfunctional although some can secrete hormones and lead to hormone-specific clinical syndromes. Surgery is the mainstay of treatment for localized tumors, however, surgical resection is controversial in metastatic PanNETs. This narrative review seeks to summarize the current literature surrounding surgery, specifically in the controversial area of metastatic PanNETs, review current treatment paradigms, and understand the benefits of surgery in this group of patients. Methods Authors searched PubMed using the terms "surgery pancreatic neuroendocrine tumor", "metastatic neuroendocrine tumor", and "liver debulking neuroendocrine tumor" from January 1990 to June 2022. Only English language publications were considered. Key Content and Findings There is no consensus among the leading specialty organizations regarding surgery for metastatic PanNETs. When considering surgery for metastatic PanNETs, tumor grade and morphology, location of the primary tumor, extra-hepatic or extra-abdominal disease, as well as liver tumor burden and metastatic distribution should be considered. Because the liver is the most common site of metastasis and liver failure is the most common cause of death in patients with hepatic metastases, attention is centered here on debulking and other ablative techniques. Liver transplantation is rarely used for hepatic metastases but could be beneficial in a small subset of patients. Retrospective studies have demonstrated improvement in survival and symptoms after surgery for metastatic disease, but the lack of prospective randomized control trials significantly limits analysis of surgical benefits in patients with metastatic PanNETs. Conclusions Surgery is the standard of care for localized PanNETs, while it remains controversial in metastatic disease. Many studies have shown a survival and symptomatic benefit to surgery and liver debulking in select groups of patients. However, most of the studies on which recommendations are based in this population are retrospective in nature and are subject to selection bias. This presents an opportunity for future investigation.
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Affiliation(s)
- Jelani K Williams
- Division of General Surgery and Surgical Oncology, Department of Surgery, University of Chicago Medicine, Chicago, IL, USA
| | - Jason L Schwarz
- Division of General Surgery and Surgical Oncology, Department of Surgery, University of Chicago Medicine, Chicago, IL, USA
| | - Xavier M Keutgen
- Division of General Surgery and Surgical Oncology, Department of Surgery, University of Chicago Medicine, Chicago, IL, USA
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21
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Roesel R, Bernardi L, Bonino MA, Popeskou SG, Garofalo F, Cristaudi A. Minimally-invasive versus open pancreatic enucleation: systematic review and metanalysis of short-term outcomes. HPB (Oxford) 2023:S1365-182X(23)00053-9. [PMID: 36958987 DOI: 10.1016/j.hpb.2023.02.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 01/05/2023] [Accepted: 02/20/2023] [Indexed: 03/25/2023]
Abstract
BACKGROUND Minimally Invasive Pancreatic Enucleation, either laparoscopic or robot-assisted, is rarely performed. The aim of this study was to offer the current available evidence about the outcomes of minimally invasive pancreatic enucleations and explore the possible advantage of this approach over traditional surgery. METHODS PubMed (MEDLINE), Cochrane Library and Embase (ELSEVIER) medical databases were searched for articles published from January 1990 to March 2022. Studies which included more than 10 cases of minimally-invasive pancreatic enucleation were included. Data on the outcomes were synthetized and meta-analyzed when appropriate. RESULTS Twenty studies published between 2009 and 2022 with a total of 552 patients were included in the systematic review: three hundred fifty-one patients (63.5%) had a laparoscopic intervention, two hundred and one (36.5%) robot-assisted with a cumulative incidence of conversion rate of 5%. Minimally-invasive surgery was performed in 63% of cases on the body/tail of the Pancreas and in 37% of the cases on the head/uncinate process of the Pancreas. The cumulative post-operative 30 days - mortality rate was 0.2% and the major postoperative morbidity (Clavien-Dindo III-IV-V) 35%. Clinically relevant pancreatic fistula was observed in 17% of the patients. Compared with the standardized open approach (n: 366 patients), mean length of hospital stay was significantly reduced in patients undergoing minimally invasive pancreatic enucleation (2.45 days, p = 0.003) with a favorable trend for post-operative major morbidity (Clavien-Dindo III-IV) (- 24% RR, p: 0.13). Operative time, blood loss and clinically relevant pancreatic fistula rate were comparable between the two groups. One hundred and fourteen robot-assisted enucleations entered in a subgroup analysis with comparable results to open surgery. CONCLUSION Minimally-Invasive approach for pancreatic enucleation is safe, feasible and offers short-term clinical outcomes comparable with open surgery. The potential benefit of robotic surgery will need to be verified in further studies.
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Affiliation(s)
- Raffaello Roesel
- Department of Visceral Surgery, University Hospital of Geneva (HUG), Rue Gabrielle-Perret Gentil 4, Geneve, Switzerland.
| | - Lorenzo Bernardi
- Department of Visceral Surgery, Hospital of Lugano (EOC), Via Tesserete 46, 6900 Lugano, Switzerland
| | - Marco A Bonino
- Department of Visceral Surgery, University Hospital of Geneva (HUG), Rue Gabrielle-Perret Gentil 4, Geneve, Switzerland
| | - Sotirios G Popeskou
- Department of Visceral Surgery, Hospital of Lugano (EOC), Via Tesserete 46, 6900 Lugano, Switzerland
| | - Fabio Garofalo
- Department of Visceral Surgery, Hospital of Lugano (EOC), Via Tesserete 46, 6900 Lugano, Switzerland
| | - Alessandra Cristaudi
- Department of Visceral Surgery, Hospital of Lugano (EOC), Via Tesserete 46, 6900 Lugano, Switzerland
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22
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Nanno Y, Toyama H, Matsumoto I, Uemura J, Asari S, Goto T, Lee D, Murakami T, Komatsu S, Yanagimoto H, Kido M, Ajiki T, Okano K, Takeyama Y, Fukumoto T. Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2023; 30:3493-3500. [PMID: 36795254 DOI: 10.1245/s10434-023-13193-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 01/14/2023] [Indexed: 02/17/2023]
Abstract
BACKGROUND Optimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation. METHODS In this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels. RESULTS Of all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7-22.2) and MPD involvement (OR 16.8, 95% CI 1.6-174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy. CONCLUSIONS This combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.
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Affiliation(s)
- Yoshihide Nanno
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hirochika Toyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Ippei Matsumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
| | - Jun Uemura
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Sadaki Asari
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tadahiro Goto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Dongha Lee
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
| | - Tomomasa Murakami
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Shohei Komatsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hiroaki Yanagimoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masahiro Kido
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tetsuo Ajiki
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Yoshifumi Takeyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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23
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Uttinger KL, Reibetanz J, Diers J, Baum P, Pietryga S, Hendricks A, Schütze L, Baumann N, Wiegering V, Lock J, Dischinger U, Seyfried F, Fassnacht M, Germer CT, Wiegering A. Volume-outcome relationship in adrenal surgery from 2009-2017 in Germany-a retrospective study. Eur J Endocrinol 2023; 188:6979716. [PMID: 36651160 DOI: 10.1093/ejendo/lvac013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/30/2022] [Accepted: 12/08/2022] [Indexed: 01/11/2023]
Abstract
OBJECTIVE Adrenal resections are rare procedures of a heterogeneous nature. While recent European guidelines advocate a minimum annual caseload for adrenalectomies (6 per surgeon), evidence for a volume-outcome relationship for this surgery remains limited. DESIGN A retrospective analysis of all adrenal resections in Germany between 2009 and 2017 using hospital billing data was performed. Hospitals were grouped into three tertiles of approximately equal patient volume. METHODS Descriptive, univariate, and multivariate analyses were applied to identify a possible volume-outcome relationship (complications, complication management, and mortality). RESULTS Around 17 040 primary adrenal resections were included. Benign adrenal tumors (n = 8,213, 48.2%) and adrenal metastases of extra-adrenal malignancies (n = 3582, 21.0%) were the most common diagnoses. Six hundred and thirty-two low-volume hospitals performed an equal number of resections as 23 high-volume hospitals (median surgeries/hospital/year 3 versus 31, P < .001). Complications were less frequent in high-volume hospitals (23.1% in low-volume hospitals versus 17.3% in high-volume hospitals, P < .001). The most common complication was bleeding in 2027 cases (11.9%) with a mortality of 4.6% (94 patients). Overall in-house mortality was 0.7% (n = 126). Age, malignancy, an accompanying resection, complications, and open surgery were associated with in-house mortality. In univariate analysis, surgery in high-volume hospitals was associated with lower mortality (OR: 0.47, P < .001). In a multivariate model, the tendency remained equal (OR: 0.59, P = .104). Regarding failure to rescue (death in case of complications), there was a trend toward lower mortality in high-volume hospitals. CONCLUSIONS The annual caseload of adrenal resections varies considerably among German hospitals. Our findings suggest that surgery in high-volume centers is advantageous for patient outcomes although fatal complications are rare.
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Affiliation(s)
- Konstantin L Uttinger
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
- Department of Visceral, Transplant, Thoracic and Vascular Surgery at Leipzig University Hospital, 04103 Leipzig, Germany
| | - Joachim Reibetanz
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Johannes Diers
- Department of Internal Medicne, Marienkrankenhaus, 22087 Hamburg, Germany
| | - Philip Baum
- Department of Thoracic Surgery, Thoraxklinik at Heidelberg University Hospital, 62196 Heidelberg, Germany
| | - Sebastian Pietryga
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Anne Hendricks
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Leon Schütze
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Nikolas Baumann
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Verena Wiegering
- Department of Pediatrics, Ped. Hematology, Oncology and Stem Cell Transplantation, at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Johann Lock
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Ulrich Dischinger
- Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital Würzburg, 97080 Würzburg, Germany
| | - Florian Seyfried
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
| | - Martin Fassnacht
- Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital Würzburg, 97080 Würzburg, Germany
- Comprehensive Cancer Center Mainfranken, University of Würzburg Medical Center, 97080 Würzburg, Germany
| | - Christoph-Thomas Germer
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
- Comprehensive Cancer Center Mainfranken, University of Würzburg Medical Center, 97080 Würzburg, Germany
| | - Armin Wiegering
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery at Würzburg University Hospital, 97080 Würzburg, Germany
- Comprehensive Cancer Center Mainfranken, University of Würzburg Medical Center, 97080 Würzburg, Germany
- Department of Biochemistry and Molecular Biology, University of Würzburg, 97080 Würzburg, Germany
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24
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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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25
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Nießen A, Schimmack S, Lewosinska M, Hinz U, Bechtiger FA, Hackert T, Büchler MW, Strobel O. Lymph node metastases and recurrence in pancreatic neuroendocrine neoplasms. Surgery 2022; 172:1791-1799. [PMID: 36180252 DOI: 10.1016/j.surg.2022.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 08/09/2022] [Accepted: 08/19/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND The impact of lymph node metastasis on survival in pancreatic neuroendocrine neoplasms as well as their best surgical treatment is controversial. We aimed to determine the frequency and prognostic impact of lymph node involvement in pancreatic neuroendocrine neoplasms. METHODS Patients undergoing pancreatic resections for pancreatic neuroendocrine neoplasms between 2001 and 2019 were retrospectively analyzed based on a prospective database. Clinicopathological parameters and perioperative outcome were assessed. Overall and disease-free survival was analyzed. Subgroup analysis was performed for sporadic, nonfunctional pancreatic neuroendocrine neoplasms without distant metastases and ≥4 analyzed lymph nodes. RESULTS Of 605 surgically resected pancreatic neuroendocrine neoplasms, 55% were G1, 36% were G2, and 9% were G3 differentiated. At the time of resection, 34% of patients had lymph node metastasis, and 16% had distant metastases. For subgroup analysis, 314 patients were analyzed. Lymph node metastases occurred in 36% of patients and were most frequent in G3 patients (67%). An increase in tumor size and advancement was associated with higher rates of lymph node metastasis, and disease-free survival was significantly impaired. Significant differences in disease-free survival were observed between 1 and 3 (5-year disease-free survival 52%) and ≥4 positive lymph nodes (5-year disease-free survival 28%), as well as when G3 tumors were excluded. In multivariable analysis, grading, tumor stage, and especially lymph node metastases as well as the proposed pN1 and pN2 categories were confirmed as independent predictors of recurrence. CONCLUSION The presence and extent of lymph node involvement has considerable prognostic impact in pancreatic neuroendocrine neoplasms. This study, for the first time, validated the proposed pN2 stage for well-differentiated pancreatic neuroendocrine neoplasms.
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Affiliation(s)
- Anna Nießen
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany. https://twitter.com/anna_niessen
| | - Simon Schimmack
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Magdalena Lewosinska
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Ulf Hinz
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Fabiola A Bechtiger
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Markus W Büchler
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany
| | - Oliver Strobel
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Germany; Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Austria.
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26
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Abe K, Kitago M, Iwasaki E, Yagi H, Abe Y, Hasegawa Y, Hori S, Tanaka M, Nakano Y, Kitagawa Y. Reconsideration of operative indications in pancreatic neuroendocrine neoplasms. World J Surg Oncol 2022; 20:366. [PMID: 36397094 PMCID: PMC9673351 DOI: 10.1186/s12957-022-02834-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/05/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. METHODS In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. RESULTS Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0-100.0, p = 0.001 and OR 8.7, 95% CI 1.5-52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5-23) tumor size for a median of 34 (range 2.4-114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0-3.33) per year. CONCLUSION Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.
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Affiliation(s)
- Kodai Abe
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Eisuke Iwasaki
- Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Shutaro Hori
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Masayuki Tanaka
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yutaka Nakano
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
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Tan Q, Chengzhi X, Chen Y. The management of small nonfunctional pancreatic neuroendocrine tumors: It's time to define the high-risk features. J Surg Oncol 2022; 126:1135-1136. [PMID: 36004442 DOI: 10.1002/jso.27025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 07/11/2022] [Accepted: 07/14/2022] [Indexed: 11/10/2022]
Affiliation(s)
- Qingquan Tan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiang Chengzhi
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yonghua Chen
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Wu Z, Qiu X, Zhi Y, Shi X, Lv G. The risk and prognostic factors for G1 pancreatic neuroendocrine tumors: A retrospective analysis of the SEER database. Front Oncol 2022; 12:993524. [PMID: 36276109 PMCID: PMC9582835 DOI: 10.3389/fonc.2022.993524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/16/2022] [Indexed: 11/13/2022] Open
Abstract
Background Pancreatic neuroendocrine tumors (pNETs) are rare neuroendocrine neoplasms (NENs) for which little is known about their clinical features, treatment options, and survival prognosis. The purpose of this study is to evaluate the risk factors affecting the overall survival (OS) and cancer-specific survival (CSS) in patients with grade 1 pNETs (G1 pNETs) and to provide a new theoretical basis for clinical diagnosis and treatment. Methods A retrospective analysis of individuals with G1 pNETs registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. Risk factors affecting OS and CSS were analyzed using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model. Results A total of 751 patients were included, most of whom were white (77.2%) women (53.9%) under the age of 60 years (54.9%), of whom 66 died of pNETs (8.78%) and 34 died of other causes (4.52%). Patients who were older than 60 years at diagnosis (hazard ratio [HR] = 1.866, 95% confidence interval [CI]: 1.242-2.805) had worse OS. And stage in the regional extent (HR = 1.777, 95% CI: 1.006-3.137) or distance extent (HR = 4.540, 95% CI: 2.439-8.453) had worse OS. Patients who delayed treatment after diagnosis had shorter CSS (delayed treatment < 1 month: HR = 1.933, 95% CI: 0.863-4.333; delayed treatment ≥ 1 month: HR = 2.208; 95% CI:1.047-4.654). Patients with lymph node metastasis (HR = 1.989, 95% CI: 1.137-3.479) or distant metastasis (HR = 5.625, 95% CI: 1.892-16.726) had worse CSS. Acceptance of surgery can significantly improve the patient’s OS and CSS. OS (partial pancreatectomy [PP]: HR = 0.350, 95% CI: 0.182-0.672; pancreatectomy and duodenectomy [PD]: HR = 0.426, 95% CI: 0.222-0.815; total pancreatectomy [TP]: HR = 0.495, 95% CI: 0.193-1.267). CSS(PP: HR = 0.148, 95% CI: 0.0054-0.401; PD: HR = 0.332, 95% CI: 0.150-0.730; TP: HR = 0.69, 95% CI: 0.254-1.872). Conclusion Age and stage were identified as independent risk factors for OS. Delayed treatment, N stage and M stage were independent risk factors for CSS. Only surgery was identified as independent protective factors for OS and CSS.
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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: 5] [Impact Index Per Article: 1.7] [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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30
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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: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [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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31
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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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32
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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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Zhang XF, Xue F, Wu Z, Lopez-Aguiar AG, Poultsides G, Makris E, Rocha F, Kanji Z, Weber S, Fisher A, Fields R, Krasnick BA, Idrees K, Smith PM, Cho C, Beems M, Lyu Y, Maithel SK, Pawlik TM. Development and Validation of a Modified Eighth AJCC Staging System for Primary Pancreatic Neuroendocrine Tumors. Ann Surg 2022; 275:e773-e780. [PMID: 32511134 PMCID: PMC10188291 DOI: 10.1097/sla.0000000000004039] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system. BACKGROUND Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial. METHODS Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification. RESULTS The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts. CONCLUSION A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | | | | | - Flavio Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Zaheer Kanji
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Sharon Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Alexander Fisher
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Ryan Fields
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Bradley A Krasnick
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Paula M Smith
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Cliff Cho
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Yi Lyu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Timothy M Pawlik
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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Nießen A, Bechtiger FA, Hinz U, Lewosinska M, Billmann F, Hackert T, Büchler MW, Schimmack S. Enucleation Is a Feasible Procedure for Well-Differentiated pNEN-A Matched Pair Analysis. Cancers (Basel) 2022; 14:cancers14102570. [PMID: 35626174 PMCID: PMC9139922 DOI: 10.3390/cancers14102570] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 02/05/2023] Open
Abstract
The extent of surgical resection in the treatment of pancreatic neuroendocrine neoplasms (pNEN) is still controversial. This study aimed to evaluate the outcomes of enucleation for well-differentiated non-functional (nf) pNEN. Patients undergoing enucleation (2001−2020) were analyzed. Clinicopathological parameters, perioperative outcomes and survival were assessed. The analysis was performed as a nested case-control study and matched-pair analysis with formal resection. Sixty-one patients undergoing enucleation were identified. Compared to patients undergoing formal resection, enucleation was associated with a significantly shorter median length of operative time (128 (IQR 95−170) versus 263 (172−337) minutes, p < 0.0001) and a significantly lower rate of postoperative diabetes (2% versus 21%, p = 0.0020). There was no significant difference in postoperative pancreatic fistula rate (18% versus 16% type B/C, p = 1.0), Clavien−Dindo ≥ III complications (20% versus 26%, p = 0.5189), readmission rate (12% versus 15%, p = 0.6022) or length of hospital stay (8 (7−11) versus 10 (8−17) days, p = 0.0652). There was no 30-day mortality after enucleation compared to 1.6% (n = 1) after formal resection. 10-year overall survival (OS) and disease-free survival (DFS) was similar between the two groups (OS: 89% versus 77%, p = 0.2756; DFS: 98% versus 91%, p = 0.0873). Enucleation presents a safe surgical approach for well-differentiated nf-pNEN with good long-term outcomes for selected patients.
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35
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Zhang Z, Wang F, Li Z, Ye Z, Zhuo Q, Xu W, Liu W, Liu M, Fan G, Qin Y, Zhang Y, Chen X, Yu X, Xu X, Ji S. Value of lymphadenectomy in patients with surgically resected pancreatic neuroendocrine tumors. BMC Surg 2022; 22:160. [PMID: 35538535 PMCID: PMC9088076 DOI: 10.1186/s12893-022-01595-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 04/05/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Although some factors that predict the prognosis in pancreatic neuroendocrine tumor (pNET) have been confirmed, the predictive value of lymph node metastasis (LNM) in the prognosis of pNETs remains conflicting and it is not clear whether regional lymphadenectomy should be performed in all grades of tumors. METHODS We included pNET patients undergoing surgery in Shanghai pancreatic cancer institute (SHPCI). The risk factors for survival were investigated by the Kaplan-Meier method and Cox regression model. We evaluated the predictors of LNM using Logistic regression. RESULTS For 206 patients in the SHPCI series, LNM was an independent prognostic factor for entire cohort suggested by multivariate Cox regression analysis. LNM (P = 0.002) predicted poorer overall survival (OS) in grade 2/3 cohort, but there is no significant association between LNM and OS in grade 1 cohort. Grade (P < 0.001) and size (P = 0.049) predicted LNM in entire cohort. Grade (P = 0.002) predicted LNM while regardless of size in grade 2/3 cohort. CONCLUSIONS Based on our own retrospective data obtained from a single center series, LNM seems to be associated with poorer outcome for patients with grade 2/3 and/or grade 1 > 4 cm tumors. On the other way, LNM was seems to be not associated with prognosis in patients with grade 1 tumors less than 4 cm. Moreover, tumor grade and tumor size seem to act as independent predictors of LNM. Thus, regional lymphadenectomy should be performed in grade 2/3 patients but was not mandatory in grade 1 tumors < 4 cm. It is reasonable to perform functional sparing surgery for grade 1 patients or propose a clinical-radiological monitoring.
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Affiliation(s)
- Zheng Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Fei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Zheng Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Zeng Ye
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Qifeng Zhuo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Wenyan Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Wensheng Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Mengqi Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Guixiong Fan
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China
| | - Yue Zhang
- The First People's Hospital of Changzhou, Changzhou City, Jiangsu Province, People's Republic of China
| | - Xuemin Chen
- The First People's Hospital of Changzhou, Changzhou City, Jiangsu Province, People's Republic of China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China.
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China.
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
- Shanghai Pancreatic Cancer Institute, Shanghai, People's Republic of China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, People's Republic of China.
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[Surgery of pancreatic neuroendocrine neoplasms: state of the art]. Chirurg 2022; 93:745-750. [PMID: 35499762 DOI: 10.1007/s00104-022-01641-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2022] [Indexed: 10/18/2022]
Abstract
Pancreatic neuroendocrine neoplasms (pNEN) have a rising incidence and are increasingly diagnosed at early and thus potentially resectable stages. Due to the rarity of these neoplasms the recommendations of currently available guidelines are mainly based on retrospective data. Surgical and oncological treatment of these rare diseases should only be performed at specialized centers. In cases of resectability without indications of diffuse metastases, complete resection with curative intent should be the treatment of choice. For small nonfunctional pNENs < 2 cm watch and wait strategies are recommended as an alternative to surgical treatment. Recent data, however, also showed an increased survival even of small (1-2 cm) pNENs after resection. For benign insulinomas and small nonfunctional well-differentiated pNENs parenchyma-sparing procedures, such as enucleation and segmental resection are available. The question of the influence of lymph node metastases on long-term disease-free survival and overall survival and consequently the role of systematic lymphadenectomy is still a matter of debate. In pNENs > 2 cm formal resection with lymphadenectomy is considered the gold standard. Minimally invasive and robotic-assisted procedures are of increasing importance also for formal pancreatic resection.
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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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Cai Y, Liu Z, Jiang L, Ma D, Zhou Z, Ju H, Zhu Y. Patterns of Lymph Node Metastasis and Optimal Surgical Strategy in Small (≤20 mm) Gastroenteropancreatic Neuroendocrine Tumors. Front Endocrinol (Lausanne) 2022; 13:871830. [PMID: 35937823 PMCID: PMC9350735 DOI: 10.3389/fendo.2022.871830] [Citation(s) in RCA: 0] [Impact Index Per Article: 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: 02/08/2022] [Accepted: 05/24/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Regional lymph node metastasis (LNM) is crucial for planning additional lymphadenectomy, and is directly correlated with poor prognosis in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the patterns of LNM for small (≤20 mm) GEP-NETs remain unclear. This population-based study aimed at evaluating LNM patterns and identifying optimal surgical strategies from the standpoint of lymph node dissemination. METHODS This retrospective cohort study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database for 17,308 patients diagnosed as having localized well-differentiated GEP-NETs ≤ 20 mm between January 1, 2004, and December 31, 2017. The patterns of LNM were characterized in 6,622 patients who underwent extended resection for adequate lymph node harvest. RESULTS Of 6,622 patients with localized small GEP-NETs in the current study, 2,380 (36%) presented with LNM after regional lymphadenectomy. Nodal involvement was observed in approximately 7.4%, 49.1%, 13.6%, 53.7%, 13.8%, 7.8%, and 15.4% of gastric (g-), small intestinal (si-), appendiceal (a-), colonic (c-), rectal (r-), non-functional pancreatic (nfp-), and functional pancreatic (fp-) NETs ≤ 20 mm. Patients with younger age, larger tumor size, and muscularis invasion were more likely to present with LNM. Additional lymphadenectomy conferred a significant survival advantage in NETs (≤10 mm: HR, 0.47; 95% CI, 0.33-0.66; p < 0.001; 11-20 mm: HR, 0.54; 95% CI, 0.34-0.85; p = 0.008) and fp-NETs ≤ 20 mm (HR, 0.08; 95% CI, 0.02-0.36; p = 0.001), as well as g-NETs (HR, 0.39; 95% CI, 0.16-0.96; p = 0.041) and c-NETs of 11-20 mm (HR, 0.07; 95% CI, 0.01-0.48; p = 0.007). Survival benefits of additional lymphadenectomy were not found in a-NETs, r-NETs, and nfp-NETs with a small size. CONCLUSIONS Given the increased risk for nodal metastasis, primary tumor resection with regional lymphadenectomy is a potential optimal surgical strategy for si-NETs and fp-NETs ≤ 20 mm, as well as g-NETs and c-NETs of 11-20 mm. Local resection is an appropriate and reliable surgical approach for a-NETs, r-NETs, and nfp-NETs ≤ 20 mm.
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Affiliation(s)
| | | | | | | | | | - Haixing Ju
- *Correspondence: Yuping Zhu, ; Haixing Ju,
| | - Yuping Zhu
- *Correspondence: Yuping Zhu, ; Haixing Ju,
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Tan Q, Wang X, Li Y, Liu Y, Liu X, Ke N. Prognostic Factors of Small Non-Functional Pancreatic Neuroendocrine Tumors and the Risk of Lymph Node Metastasis: A Population-Level Study. Front Endocrinol (Lausanne) 2022; 13:907415. [PMID: 35873006 PMCID: PMC9299363 DOI: 10.3389/fendo.2022.907415] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/04/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Small non-functional neuroendocrine tumors (NF-PNETs) are a heterogeneous subset of tumors with controversy regarding their optimal management. We aimed to analyze the prognostic factors of patients with small NF-PNETs and create a risk score for lymph node metastasis (LNM). METHODS Data of 751 patients with NF-PNETs ≤ 2 cm were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate survival analysis was performed to analyze the prognostic factors. Logistic regression was used to identify risk factors for LNM. RESULTS Of the 751 patients, 99 (13.2%) were confirmed to have LNM. In multivariate survival analysis, LNM (hazard ratio [HR], 2.12; 95% CI, 1.04-4.32, p = 0.040) was independently associated with disease-specific survival. Logistic regression identified that tumor location in the head of the pancreas (odds ratio [OR], 4.33; 95% CI, 2.75-6.81; p < 0.001), size ≥ 1.5-2 cm (OR, 1.84; 95% CI, 1.17-2.87; p = 0.009), and grade III-IV (OR, 7.90; 95% CI, 1.79-34.90; p = 0.006) were independent risk factors of LNM. According to the OR value, the risk of LNM was scored as follows: a score of 1 for tumors located in the body/tail of the pancreas and 4 for those located in the head; a score of 1 for tumors <1 cm and 2 for those ≥1.5-2 cm; and a score of 1 for tumors with grade I-II and 8 for those with grade III-IV. Finally, the median score for this cohort was 4, with an interquartile range of 3-6. Therefore, patients were classified as three groups based on the risk score system: a total score of 1-3 for low risk, 4-6 for intermediate risk (OR, 2.98; 95% CI, 1.59-5.60; p = 0.001), and 7-14 for high risk (OR, 8.94; 95% CI, 4.50-17.7; p < 0.001), with an incidence of LNM 5.0%, 13.5%, and 31.8%, respectively (p < 0.001). CONCLUSION Surgical resection with regional lymphadenectomy is recommended for small NF-PNETs with malignant potential of LNM. A risk score for LNM based on tumor grade, location, and size may preoperatively predict LNM of small NF-PNETs and guide clinical practice.
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Affiliation(s)
- Qingquan Tan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xing Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yichen Li
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yingyi Liu
- The First Clinical College, Chongqing Medical University, Chongqing, China
| | - Xubao Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xubao Liu, ; Nengwen Ke,
| | - Nengwen Ke
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xubao Liu, ; Nengwen Ke,
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Zhu J, Fu C, Zhang Y, Zhou X, Xiao W, Li Y. Observation Versus Resection for Small, Localized, and Nonfunctional Pancreatic Neuroendocrine Tumors: A Propensity Score Matching Study. Pancreas 2022; 51:56-62. [PMID: 35195596 DOI: 10.1097/mpa.0000000000001959] [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] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The best treatment modalities for small (1-2 cm), localized, and nonfunctional pancreatic neuroendocrine tumors remain controversial. Therefore, we aimed to evaluate whether surgical resection provides survival benefit over observation in those patients. METHODS From 1973 to 2015, all eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching (1:2) method was performed. The primary endpoints evaluated were overall survival (OS) and cancer-specific survival (CSS). RESULTS We identified 681 patients, of which 122 and 559 patients received observation and resection, respectively. Propensity score-matched patients who underwent surgery (n = 183) had significantly improved OS (P = 0.008) compared with matched patients who underwent observation (n = 106), but there was no difference in CSS (P = 0.310). On multivariate analysis, resection could improve OS but not CSS. Besides, poorly differentiated/undifferentiated tumor had a worse OS and CSS. Subgroup analysis showed that patients 60 years and older who underwent resection could achieve a longer OS and CSS. CONCLUSIONS This disease exhibits a very good prognosis. Patients undergoing resection were associated with comparable 5-year CSS but longer 5-year OS compared with those receiving observation. Elderly patients (≥60) may obtain benefit from surgery, whereas the treatment of younger patients should be individualized.
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Affiliation(s)
- Jisheng Zhu
- From the Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
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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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Ito T, Masui T, Komoto I, Doi R, Osamura RY, Sakurai A, Ikeda M, Takano K, Igarashi H, Shimatsu A, Nakamura K, Nakamoto Y, Hijioka S, Morita K, Ishikawa Y, Ohike N, Kasajima A, Kushima R, Kojima M, Sasano H, Hirano S, Mizuno N, Aoki T, Aoki T, Ohtsuka T, Okumura T, Kimura Y, Kudo A, Konishi T, Matsumoto I, Kobayashi N, Fujimori N, Honma Y, Morizane C, Uchino S, Horiuchi K, Yamasaki M, Matsubayashi J, Sato Y, Sekiguchi M, Abe S, Okusaka T, Kida M, Kimura W, Tanaka M, Majima Y, Jensen RT, Hirata K, Imamura M, Uemoto S. JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis. J Gastroenterol 2021; 56:1033-1044. [PMID: 34586495 PMCID: PMC8531106 DOI: 10.1007/s00535-021-01827-7] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/13/2021] [Indexed: 02/04/2023]
Abstract
Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters-diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel-Lindau (VHL) disease-and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of "neuroendocrine tumor" (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan.
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan.
| | - Toshihiko Masui
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Izumi Komoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Ryuichiro Doi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Robert Y Osamura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Akihiro Sakurai
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masafumi Ikeda
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Koji Takano
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Hisato Igarashi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Akira Shimatsu
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Kazuhiko Nakamura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yuji Nakamoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Susumu Hijioka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Koji Morita
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yuichi Ishikawa
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Nobuyuki Ohike
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Atsuko Kasajima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Ryoji Kushima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Motohiro Kojima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Hironobu Sasano
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Satoshi Hirano
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Nobumasa Mizuno
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Taku Aoki
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Takeshi Aoki
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Takao Ohtsuka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Tomoyuki Okumura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yasutoshi Kimura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Atsushi Kudo
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Tsuyoshi Konishi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Ippei Matsumoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Noritoshi Kobayashi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Nao Fujimori
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yoshitaka Honma
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Chigusa Morizane
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Shinya Uchino
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Kiyomi Horiuchi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masanori Yamasaki
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Jun Matsubayashi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yuichi Sato
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masau Sekiguchi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Shinichi Abe
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Takuji Okusaka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Mitsuhiro Kida
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Wataru Kimura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masao Tanaka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yoshiyuki Majima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Robert T Jensen
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Koichi Hirata
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masayuki Imamura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Shinji Uemoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
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Frequency of Neuroendocrine Tumor Studies: Using Latent Dirichlet Allocation and HJ-Biplot Statistical Methods. MATHEMATICS 2021. [DOI: 10.3390/math9182281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background: Neuroendocrine tumors (NETs) are severe and relatively rare and may affect any organ of the human body. The prevalence of NETs has increased in recent years; however, there seem to be more data on particular types, even though, despite the efforts of different guidelines, there is no consensus on how to identify different types of NETs. In this review, we investigated the countries that published the most articles about NETs, the most frequent organs affected, and the most common related topics. Methods: This work used the Latent Dirichlet Allocation (LDA) method to identify and interpret scientific information in relation to the categories in a set of documents. The HJ-Biplot method was also used to determine the relationship between the analyzed topics, by taking into consideration the years under study. Results: In this study, a literature review was conducted, from which a total of 7658 abstracts of scientific articles published between 1981 and 2020 were extracted. The United States, Germany, United Kingdom, France, and Italy published the majority of studies on NETs, of which pancreatic tumors were the most studied. The five most frequent topics were t_21 (clinical benefit), t_11 (pancreatic neuroendocrine tumors), t_13 (patients one year after treatment), t_17 (prognosis of survival before and after resection), and t_3 (markers for carcinomas). Finally, the results were put through a two-way multivariate analysis (HJ-Biplot), which generated a new interpretation: we grouped topics by year and discovered which NETs were the most relevant for which years. Conclusions: The most frequent topics found in our review highlighted the severity of NETs: patients have a poor prognosis of survival and a high probability of tumor recurrence.
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Abstract
Surgical management of pancreatic neuroendocrine tumors (PNETS) is steadily evolving and is influenced by multiple factors. Sporadic PNETs are generally managed more aggressively than those occurring in the background of hereditary syndromes, and functioning PNETs are almost always resected if they are not metastatic. Localized nonfunctioning PNETs less than 2 cm can often be observed. Surgical resection for localized PNET greater than 2 cm comprises parenchymal sparing pancreas resections, such as enucleations, or formal anatomic resection, such as distal pancreatectomy or pancreaticoduodenectomy. PNETs commonly metastasize to the liver, and several systemic and liver-directed options to treat hepatic metastases are available.
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Ha S, Song KB, Hong S, Shin D, Park Y, Kwon J, Lee W, Jun E, Lee JH, Hwang DW, Kim SC. The clinicopathologic and operative characteristics of patients with small nonfunctioning pancreatic neuroendocrine tumors. ANZ J Surg 2021; 91:E484-E492. [PMID: 34291544 DOI: 10.1111/ans.17055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 06/13/2021] [Accepted: 06/17/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND Incidentally detected, small nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed on imaging modalities. This retrospective investigation evaluated the clinicopathologic characteristics and perioperative and oncologic outcomes in patients with small NF-PNETs undergoing curative resection. METHODS The medical records of 444 patients who underwent pancreatic resection for NF-PNETs at a single, large-volume institution between January 2000 and December 2018 were retrospectively reviewed. Patients were divided into those with small (≤2 cm) and large (>2 cm) tumors based on the largest tumor diameter on preoperative computed tomography (CT). Outcomes were also evaluated in subgroups of patients with small NF-PNET who did and did not undergo lymphadenectomy. RESULTS Of the 444 patients with NF-PNETs, 195 (43.9%) had small (≤2 cm) and 249 (56.1%) had large (>2 cm) NF-PNETs. The rate of parenchyma-preserving surgery (14.4% vs. 7.2%, p = 0.014) and the ratio of spleen preservation for left-sided pancreatectomy (65.6% vs. 38.3%, p < 0.001) were higher in the small NF-PNET group. Size on CT >2 cm (p < 0.001, hazard ratio [HR]: 5.836, 95% confidence interval [CI]: 2.474-13.769), presence of perineural invasion (p < 0.001, HR: 3.025, 95% CI: 1.640-5.577), World Health Organization (WHO) Grade 2 (p = 0.007, HR: 2.861, 95% CI: 1.325-6.176), and WHO Grade 3 (p < 0.001, HR: 11.537, 95% CI: 5.282-25.199) were independent predictors of disease-free survival (DFS). DFS did not differ significantly in patients with small NF-PNETs who did and did not undergo lymphadenectomy (p = 0.886). CONCLUSIONS Assessment of long-term oncologic outcomes suggests that surgical resection may cure small NF-PNETs. Minimally invasive surgery and organ-preserving surgery are acceptable treatment options for select patients with small NF-PNETs. The effect on survival outcomes of lymph node dissection for small NF-PNETs remains unclear.
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Affiliation(s)
- SuHyeon Ha
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Dakyum Shin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Jaewoo Kwon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
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Ge L, Li H, Dong L, Shang G, Wang W, Li Y, Qi L, Zhao J, Peng D, Tong G. Nomogram for predicting survival of patients with metastatic nonfunctioning pancreatic neuroendocrine tumors: A SEER based study. Medicine (Baltimore) 2021; 100:e26347. [PMID: 34232169 PMCID: PMC8270631 DOI: 10.1097/md.0000000000026347] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 06/01/2021] [Indexed: 01/04/2023] Open
Abstract
More attention has been placed on nonfunctioning pancreatic neuroendocrine tumors due to the increase in its incidence in recent years. Whether tumor resection at the primary site of metastatic NFpNET is effective remains controversial. Moreover, clinicians need a more precise prognostic tool to estimate the survival of these patients.Patients with metastatic NFpNET were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were identified using a multivariate Cox regression model and included in the nomogram. Coarsened exact matching analysis was used to balance the clinical variables between the non-surgical and surgical groups in our study.A total of 1464 patients with metastatic nonfunctioning pancreatic neuroendocrine tumors (NFpNETs) were included in our cohort. Multivariate analysis identified age, sex, tumor size, differentiated grade, lymph node metastases, resection of primary tumors, and marital status as independent predictors of metastatic NFpNET. The nomogram showed excellent accuracy in predicting 1-, 3-, and 5-year overall survival, with a C-index of 0.812. The calibration curve revealed good consistency between the predicted and actual survival.Coarsened exact matching analysis using SEER data indicated the survival advantages of resection of primary tumors. Our study is the first to build a nomogram model for patients with metastatic NFpNETs. This predictive tool can help clinicians identify high-risk patients and more accurately assess patient survival times.
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Beane JD, Borrebach JD, Billderback A, Onuma AE, Adam MA, Zureikat AH, Pitt HA. Small pancreatic neuroendocrine tumors: Resect or enucleate? Am J Surg 2021; 222:29-34. [DOI: 10.1016/j.amjsurg.2020.12.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 11/24/2020] [Accepted: 12/04/2020] [Indexed: 12/18/2022]
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Shiozaki H, Shirai Y, Horiuchi T, Yasuda J, Furukawa K, Onda S, Gocho T, Shiba H, Ikegami T. Feasible laparoscopic distal pancreatectomy for pancreatic neuroendocrine tumors. Mol Clin Oncol 2021; 14:111. [PMID: 33903817 DOI: 10.3892/mco.2021.2273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 02/15/2021] [Indexed: 11/05/2022] Open
Abstract
Pancreatic neuroendocrine tumor (PNET) cases are increasing; however, the treatment indication and procedure remain unestablished. The present study evaluated the indication, feasibility and safety of laparoscopic distal pancreatectomy (LDP) with our technique for PNET. A total of 13 patients with insulinoma and nonfunctional PNET <2 cm in diameter who underwent LDP and 13 patients with any size of PNET who underwent open distal pancreatectomy (ODP) between October 2009 and June 2019 were retrospectively reviewed and compared. The median age of patients was 45 (33-61) years, and 14 (54%) patients were male. The median follow-up periods were 70 months for the LDP group and 46 months for the ODP group. The tumor diameter of the patients who underwent LDP for PNET was 18±9 mm compared with 37±25 mm for those who underwent ODP. The operation time, estimated blood loss, and complication were 290.2±115 vs. 337±131 min (P=0.338), 122±172 vs. 649±693 ml (P=0.019) and 31 vs. 54% (P=0.234), respectively. Pancreatic fistula developed in 8% of patients who underwent LDP compared with 31% who underwent ODP (P=0.131). Notably, the postoperative hospitalization period was significantly shorter in the LDP group (11±7 vs. 21±13 days; P=0.022). Tumor grade of 2017 World Health Organization classification (G1/G2/G3/NEC/unknown) was 9/2/0/0/2 for the LDP group compared with 5/5/0/3/0 for the ODP group. Furthermore, lymph node metastasis was detected in only 1 patient who underwent ODP, for whom the maximum tumor diameter was 70 mm and was classified as G2. In addition, 2 patients in the ODP group developed postoperative lung and liver metastases. LDP for PNETs of <2 cm in selected patients can be safely performed; however, the extent of lymph node dissection needs to be clarified.
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Affiliation(s)
- Hironori Shiozaki
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Yoshihiro Shirai
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Takashi Horiuchi
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Jungo Yasuda
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Kenei Furukawa
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Shinji Onda
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Takeshi Gocho
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Hiroaki Shiba
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
| | - Toru Ikegami
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
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Heidsma CM, Engelsman AF, van Dieren S, Stommel MWJ, de Hingh I, Vriens M, Hol L, Festen S, Mekenkamp L, Hoogwater FJH, Daams F, Klümpen HJ, Besselink MG, van Eijck CH, Nieveen van Dijkum EJ. Watchful waiting for small non-functional pancreatic neuroendocrine tumours: nationwide prospective cohort study (PANDORA). Br J Surg 2021; 108:888-891. [PMID: 33783475 PMCID: PMC10364894 DOI: 10.1093/bjs/znab088] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/21/2021] [Accepted: 02/15/2021] [Indexed: 12/12/2022]
Abstract
This prospective nationwide cohort study examined the feasibility of a watchful-waiting protocol for non-functional pancreatic neuroendocrine tumours (NF-pNET) of 2 cm or smaller. In total, 8 of 76 patients (11 per cent) with a NF-pNET no larger than 2 cm showed significant tumour progression (more than 0.5 cm/year) during 17 months of follow-up, of whom two opted for resection. No patient developed metastases. Quality of life was poorer than in the reference population. Watchful waiting seems a safe alternative to upfront surgery in patients with a NF-pNET no larger than 2 cm, although longer follow-up is necessary.
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Affiliation(s)
- C M Heidsma
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - A F Engelsman
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands
| | - S van Dieren
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - M W J Stommel
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - I de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - M Vriens
- Department of Surgery, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - L Hol
- Department of Gastroenterology and Metabolism, Maasstad Hospital, Rotterdam, the Netherlands
| | - S Festen
- Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
| | - L Mekenkamp
- Department of Medical Oncology, Medisch Spectrum Twente, Enschede, the Netherlands
| | - F J H Hoogwater
- Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands
| | - F Daams
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands
| | - H-J Klümpen
- Department of Medical Oncology, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - M G Besselink
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - C H van Eijck
- Department of Surgery, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - E J Nieveen van Dijkum
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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50
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Tsuchikawa T, Tanaka K, Nakanishi Y, Asano T, Noji T, Nakamura T, Okamura K, Shichinohe T, Hirano S. Clinical Impact of Organ-Preserving Surgery for Pancreatic Neuroendocrine Neoplasms: A Single-Center Experience. Pancreas 2021; 50:196-200. [PMID: 33565795 DOI: 10.1097/mpa.0000000000001739] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Organ-preserving surgery (OPS) has been accepted for pancreatic neuroendocrine neoplasms, particularly for the management of small tumors. This study aimed to analyze the surgical outcome following this treatment at our institute, focusing on the perioperative factors and postoperative locoregional recurrence. METHODS We analyzed 71 consecutive patients with no synchronous liver metastasis. These patients were classified into 1 of 2 groups: the standard operation group (SOG, 41 patients) with prophylactic regional lymph node dissection and the organ-preserving surgery group (OPG, 30 patients). We performed OPS based on size criteria (tumor size <1.5 cm in nonfunctional pancreatic neuroendocrine neoplasms and <2 cm in insulinoma with no evident bulky lymph node swelling on preoperative imaging). RESULTS The median follow-up periods were 37 months. The OPG included enucleation, partial resection, proximal parenchymal pancreatectomy, central pancreatectomy, spleen-preserving distal pancreatectomy, and Warshaw operation. The SOG included pancreatoduodenectomy and distal pancreatectomy, showing no statistically significant differences between the 2 groups in terms of operation time, hospitalization duration, and postoperative complications. Ten patients showed lymph node metastasis (25%) only in the SOG. There were no locoregional recurrent cases in the OPG. CONCLUSIONS In selected patients, OPS may be effective based on the appropriate tumor size criteria.
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Affiliation(s)
- Takahiro Tsuchikawa
- From the Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
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