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van T Veld BR, Hackeng WM, Luchini C, Brosens LAA, Dreijerink KMA. Clinical Relevance of ATRX/DAXX Gene Mutations and ALT in Functioning Pancreatic Neuroendocrine Tumors. Endocr Pathol 2025; 36:3. [PMID: 39954168 PMCID: PMC11829919 DOI: 10.1007/s12022-025-09848-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/30/2025] [Indexed: 02/17/2025]
Abstract
Functioning pancreatic neuroendocrine tumors (PanNETs) represent a subset of PanNETs that cause symptoms due to hormonal activity. Insulinoma is the most common functioning PanNET type. Mutations in the alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes result in genomic instability. ATRX/DAXX mutations and associated alternative lengthening of telomeres (ALT) are common in non-functioning PanNETs and associated with aggressive tumor behavior. Recent reports have shown that ATRX/DAXX mutations and ALT are also present in functioning PanNETs. In this review, we summarize the literature addressing ATRX/DAXX mutations and ALT in functioning PanNETs and discuss the clinical relevance with regard to distinguishing aggressive and indolent functioning tumors. ATRX/DAXX gene mutations and/or ALT have been reported in insulinoma, glucagonoma, gastrinoma, VIPoma and calcitoninoma. In insulinoma, the presence of ATRX/DAXX mutations and ALT are associated with aggressive behavior and could therefore be used as prognostic biomarkers. Although ATRX/DAXX mutation and ALT assessment may currently not be the standard of care in routine diagnostic pathology practice, the use of DAXX/ATRX immunohistochemistry at least can be encouraged not only for non-functioning but also for functioning PanNETs.
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Affiliation(s)
- Brenna R van T Veld
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Wenzel M Hackeng
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology and ARC-NET Applied Research on Cancer Center, University of Verona, Verona, Italy
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Koen M A Dreijerink
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
- Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
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Kenney LM, Hughes M. Surgical Management of Gastroenteropancreatic Neuroendocrine Tumors. Cancers (Basel) 2025; 17:377. [PMID: 39941746 PMCID: PMC11816225 DOI: 10.3390/cancers17030377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from enterochromaffin cells that can arise from the gastrointestinal (GI) tract and pancreas. Surgical management is the cornerstone of treatment, with the optimal approach tailored by tumor grade, size, location, and presence of metastasis. This review discusses the current strategies for the surgical management of NETs of the gastroenteropancreatic tract. METHODS A review of the available literature was conducted to evaluate surgical approaches to NETs. Consensus guidelines were incorporated to synthesize evidence-based recommendations. RESULTS For gastric NETs, surgical approach depends on Rindi Classification, WHO grade, and tumor size, with endoscopic approaches favored for smaller and low-grade lesions. Small bowel NETs can be multifocal and thus often require a surgical approach with careful evaluation of the entire intestine. Pancreatic NETs are categorized as functional or non-functional, with enucleation or formal resection strategies based on size, location, functional status, and risk of malignancy. Colorectal NETs are primarily treated with transanal localized or formal surgical resection, depending on lesion size and depth of invasion or presence of lymph node involvement. Appendiceal NETs are either treated with appendectomy or right hemicolectomy, depending on the size, location, and invasiveness of the lesions. For metastatic NETs, cytoreduction, liver transplantation, and targeted therapies offer symptom relief and possible survival benefits. CONCLUSIONS Surgical resection provides curative potential for localized NETs and symptom control in metastatic cases. Future research is essential to refine guidelines for intermediate-risk lesions and multifocal tumors, ensuring optimal outcomes for patients with gastroenteropancreatic NETs.
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Affiliation(s)
- Lisa M. Kenney
- Department of Surgery, Eastern Virginia Medical School, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, 825 Fairfax Avenue, Suite 610, Norfolk, VA 23507, USA;
| | - Marybeth Hughes
- Department of Surgery, Division of Surgical Oncology, Eastern Virginia Medical School, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, 825 Fairfax Avenue, Suite 610, Norfolk, VA 23507, USA
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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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Mukkala AN, Ray S, Bevacqua D, McGilvray I, Sapisochin G, Moulton CA, Gallinger S, Cleary SP, Shwaartz C, Wei AC, Reichman TW. Disease-free survival after pancreatectomy for pancreatic neuroendocrine tumors: A 17-year single-center experience of 223 patients. J Gastrointest Surg 2024; 28:1485-1492. [PMID: 38906319 DOI: 10.1016/j.gassur.2024.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 05/18/2024] [Accepted: 06/15/2024] [Indexed: 06/23/2024]
Abstract
BACKGROUND Metastasis or recurrence of pancreatic neuroendocrine tumors (pNETs) after pancreatectomy is an important source of postsurgical morbidity. This study aimed to define disease-free survival (DFS) in this population. METHODS Patients who underwent pancreatectomy for pNETs between January 2005 and January 2022 were included. Clinicopathologic and survival data were collected, and the primary endpoint was DFS. Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were performed. RESULTS Of the 223 patients, 144 (65%) distal/subtotal/partial pancreatectomies, 71 (32%) pancreaticoduodenectomies, 6 (3%) total pancreatectomies, and 2 (1%) enucleations were performed. Of the 223 patients, 45 (20%) experienced disease recurrence or metastasis after index pancreatectomy during the 17 years of the study. Nonfunctional pNETs (162 [73%]) were more common than hormonally functional subtypes. The 2- and 5-year DFSs were 82% and 76%, respectively. Kaplan-Meier analysis demonstrated that N1 node positive disease, size of ≥ 4 cm, lymphovascular invasion, perineural invasion, Ki-67 of ≥ 20%, and nonfunctional pNETs are significantly associated with a lower DFS (P < .05). Univariate Cox analysis identified the following predictors to be significantly associated with poorer DFS: larger tumor size (hazard ratio [HR], 1.16; 95% CI, 1.04-1.28), Ki-67 index of ≥ 20% (HR, 4.93; 95% CI, 2.00-11.44), perineural invasion (HR, 3.23; 95% CI, 1.40-7.89), open surgery (HR, 3.34; 95% CI, 1.03-1.33), node-positive disease (HR, 5.27; 95% CI, 2.28-13.26), and increased body mass index (HR, 1.10; 95% CI, 1.03-1.17) (P < .05). CONCLUSION Of note, 1 in 5 patients who underwent resection developed recurrence or metastasis after pancreatectomy. Prognostic predictors of DFS in pNETs could help optimize treatment and enhance follow-up protocols to improve quality and reduce morbidity.
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Affiliation(s)
- Avinash Naraiah Mukkala
- Institute of Medical Science, University of Toronto, Toronto, Canada; Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Canada; Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Samrat Ray
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada
| | | | - Ian McGilvray
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
| | - Gonzalo Sapisochin
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
| | - Carol-Anne Moulton
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
| | - Steven Gallinger
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
| | - Sean P Cleary
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
| | - Chaya Shwaartz
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
| | - Alice C Wei
- Weill Cornell School of Medicine, Cornell University, New York City, NY, United States; Memorial Sloan Kettering Cancer Center, New York City, NY, United States
| | - Trevor W Reichman
- Hepatobiliary and Pancreatic Surgical Oncology, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada.
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Huang J, Liu H, Yang D, Xu T, Wang J, Li J. Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading: A multicenter retrospective study. Chin Med J (Engl) 2024; 137:720-728. [PMID: 38384175 PMCID: PMC10950134 DOI: 10.1097/cm9.0000000000003029] [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: 10/17/2023] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND The incidence of well-differentiated gastric neuroendocrine tumors (G-NET) is increasing annually, and while they have a good prognosis and low mortality rate, their high recurrence rate makes treatment options controversial. This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET. METHODS We performed a multicenter, retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital, Yantai Yuhuangding Hospital, and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023. Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis. RESULTS After a median follow-up of 49 months, the overall recurrence rate among the 94 G-NET patients was 14% (13/94). The recurrence rates of endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), somatostatin analog (SSA) therapy, and surgery were 43% (6/14), 10% (5/49), 5% (1/22), and 11% (1/9), respectively. Post-treatment recurrence rates were significantly different ( P = 0.014) among four treatments (EMR, ESD, SSA, and surgery), and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group. From the second month onward, SSA therapy considerably reduced the gastrin levels from 1081.0 (571.5, 2472.8) pg/mL to 461.5 (255.3, 795.0) pg/mL ( Z = -3.521, P <0.001). Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied, only the pre-treatment gastrin level ( P = 0.018 and 0.005) and the type of treatment ( P = 0.014 and 0.017) were significantly associated with G-NET recurrence. CONCLUSIONS Individualized treatment strategies may reduce the risk of relapse after G-NET treatment. Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions, and it substantially decreases the incidence of post-treatment recurrence.
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Affiliation(s)
- Ju Huang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
- Key Laboratory of Gut Microbiota Translational Medicine Research, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Huimin Liu
- Department of Gastroenterology, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong 264000, China
| | - Dekun Yang
- Department of Gastroenterology, Beijing Zhong-Neng-Jian Hospital, Beijing 102401, China
| | - Tianming Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
- Key Laboratory of Gut Microbiota Translational Medicine Research, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Jing Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
- Key Laboratory of Gut Microbiota Translational Medicine Research, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
- Key Laboratory of Gut Microbiota Translational Medicine Research, Chinese Academy of Medical Sciences, Beijing 100730, China
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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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Surgical Outcomes and Prognostic Factors of G3 Pancreatic Neuroendocrine Carcinomas: A Consecutive Analysis Based on Previous Study Results. J Clin Med 2022; 11:jcm11113176. [PMID: 35683561 PMCID: PMC9181221 DOI: 10.3390/jcm11113176] [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: 04/06/2022] [Revised: 05/16/2022] [Accepted: 05/25/2022] [Indexed: 02/05/2023] Open
Abstract
In 2017, the World Health Organization (WHO) officially defined pancreatic neuroendocrine neoplasms into well-differentiated tumors, namely G1/G2/G3 pancreatic neuroendocrine tumors, and poorly differentiated carcinomas referring to G3 pancreatic neuroendocrine carcinomas (p-NECs). However, the surgical outcomes and prognostic factors of G3 p-NECs are still unclear. Methods: We retrospectively collected and analyzed the data of eligible patients with G3 p-NECs defined by the WHO 2017 grading classification. Results: We eventually identified 120 patients with G3 p-NECs, including 72 females and 48 males, with a median age of 53 y. The 3-year overall survival (OS) of G3 p-NECs by Kaplan−Meier method was 37.3%. The 3-year OS for functional G3 p-NECs was 57.4%, which was statistically longer than 23.0% of non-functional ones (p = 0.002). Patients with surgical resection presented a significantly better 3-year OS than those with palliative operation (43.3% vs. 13.1%; p < 0.001). The 3-year OS for Stage Ⅰ, Stage Ⅱ, Stage Ⅲ, and Stage Ⅳ was 87.1%, 56.5%, 12.9%, and not applicable, respectively (p < 0.001). We demonstrated in a Cox regression model that palliative operation (p = 0.013), vascular infiltration (p = 0.039), lymph node involvement (p = 0.024), and distant metastasis (p = 0.016) were independent predictors of poor outcome for patients with surgically treated G3 p-NECs. Conclusion: Our data in the present analysis indicated that patients with G3 p-NECs could significantly benefit from surgical resection. Meanwhile, vascular infiltration, lymph node involvement, and distant metastasis were independent predictors of poor outcome for these patients.
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Wang H, Ding D, Qin T, Zhang H, Liu J, Zhao J, Wu CH, Javed A, Wolfgang C, Guo S, Chen Q, Zhao W, Shi W, Zhu F, Guo X, Li X, Peng F, He R, Xu S, Jin J, Wu Y, Nuer A, Edil B, Tien YW, Jin G, Zheng L, He J, Liu J, Liu Y, Wang M, Qin R. Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors. HPB (Oxford) 2022; 24:681-690. [PMID: 34836754 DOI: 10.1016/j.hpb.2021.10.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/15/2021] [Accepted: 10/27/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. METHODS We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. RESULTS Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). CONCLUSION These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.
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Affiliation(s)
- Hebin Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ding Ding
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Tingting Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Jun Liu
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong 250000, China
| | - Junfang Zhao
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Chien-Hui Wu
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei 10002, Taiwan
| | - Ammar Javed
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Christopher Wolfgang
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Shiwei Guo
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai 200433, China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
| | - Weihong Zhao
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Wei Shi
- Department of Hepato-Pancreato-Biliary Surgery, Shandong Provincial Hospital, Shandong 250000, China
| | - Feng Zhu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xingjun Guo
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xu Li
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Feng Peng
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ruizhi He
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Simiao Xu
- Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jikuan Jin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Yi Wu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Abula Nuer
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Barish Edil
- Department of Surgery, University of Oklahoma, Oklahoma City, OK 73104, USA
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital No. 7 Chung-Shan South Rd, Taipei 10002, Taiwan
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai 200433, China
| | - Lei Zheng
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jin He
- Departments of Surgery and Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jianhua Liu
- Department of Hepato-Pancreato-Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
| | - Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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Nagel I, Herrmann K, Lahner H, Rischpler C, Weber F. Combined medical therapy, nuclear medicine therapy and other therapies in metastatic neuroendocrine tumor. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00156-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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Keihanian T, Othman M. Epidemiology, Pathogenesis, and Prognosis of Pancreatic Neuroendocrine Tumors. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:623-637. [DOI: 10.1007/978-3-030-41683-6_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Rossi RE, Elvevi A, Citterio D, Coppa J, Invernizzi P, Mazzaferro V, Massironi S. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J Gastroenterol 2021; 27:5890-5907. [PMID: 34629807 PMCID: PMC8475006 DOI: 10.3748/wjg.v27.i35.5890] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/29/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.
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Affiliation(s)
- Roberta Elisa Rossi
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Jorgelina Coppa
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20122, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
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Peltola E, Hannula P, Huhtala H, Metso S, Sand J, Laukkarinen J, Tiikkainen M, Sirén J, Soinio M, Nuutila P, Moilanen L, Laaksonen DE, Ebeling T, Arola J, Schalin-Jäntti C, Jaatinen P. Long-term morbidity and mortality in patients diagnosed with an insulinoma. Eur J Endocrinol 2021; 185:577-586. [PMID: 34374651 PMCID: PMC8784472 DOI: 10.1530/eje-21-0230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 08/06/2021] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN Retrospective cohort study. METHODS Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.
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Affiliation(s)
- Elina Peltola
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Division of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
- Correspondence should be addressed to E Peltola;
| | - Päivi Hannula
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Endocrinology, Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Saara Metso
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Endocrinology, Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Juhani Sand
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Johanna Laukkarinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | | | - Jukka Sirén
- Surgery, Abdominal Center, Helsinki University Hospital, Helsinki, Finland
- Surgery, Abdominal Center, University of Helsinki, Helsinki, Finland
| | - Minna Soinio
- Department of Endocrinology, Division of Medicine, Turku University Hospital, Turku, Finland
| | - Pirjo Nuutila
- Department of Endocrinology, Division of Medicine, Turku University Hospital, Turku, Finland
- Turku PET Centre, University of Turku, Turku, Finland
| | - Leena Moilanen
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | | | - Tapani Ebeling
- Faculty of Medicine, University of Oulu, Oulu, Finland
- Endocrinology, Department of Medicine, Oulu University Hospital, Oulu, Finland
| | - Johanna Arola
- Pathology, HUSLAB, Helsinki University Hospital, Helsinki, Finland
- Pathology, University of Helsinki, Helsinki, Finland
| | - Camilla Schalin-Jäntti
- Endocrinology, Abdominal Center
- Endocrinology, Abdominal Center, University of Helsinki, Helsinki, Finland
| | - Pia Jaatinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Division of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
- Endocrinology, Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
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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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14
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The role of radiotherapy for pancreatic malignancies: a population-based analysis of the SEER database. Clin Transl Oncol 2021; 24:76-83. [PMID: 34219204 PMCID: PMC8732853 DOI: 10.1007/s12094-021-02671-0] [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: 02/23/2021] [Accepted: 06/14/2021] [Indexed: 12/24/2022]
Abstract
Background To investigate the role of adjuvant radiotherapy in patients with pancreatic cancer. Methods and patients The patients with pancreatic cancer from 18 registered institutions in the Surveillance Epidemiology and End Results (SEER) database were retrospectively analyzed. The characteristics of patients who would benefit from adjuvant radiotherapy were screened, as well as whether neoadjuvant or adjuvant radiotherapy conferred to a better clinical outcome. Propensity score matching was used to control for confounding features. Results Thirty thousand two hundred and forty-nine patients were included in this study (21,295 vs 8954 in surgery and adjuvant radiotherapy group); 1150 patients were matched in two groups. The median survivals in the surgery (S) group and adjuvant radiotherapy (S + R) group were 24 and 21 months, respectively. The 1-, 3-, and 5-year overall survival (OS) rates in the S group and S + R group were 68%, 40%, 31%, and 75%, 30%, 20%, respectively (p < 0.001), and the median OS was 22 and 25 months in S and S + R group after PSM, the former 1-, 2-, 3-, and 5-year OS were 73%, 45%, 30%, and 19%, and the later were 81%, 52%, 37%, and 24% (p = 0.0015), respectively; stratified analysis showed patients whose carcinoma located at pancreatic head with II stage infiltrating duct carcinoma (22 vs 25, p = 0.0276), T4 adenocarcinoma (28 vs 33, p = 0.0022), N1 stage adenocarcinoma (20 vs 23, p = 0.0203), and patients with infiltrating duct carcinoma received regional resection (23 vs 25, p = 0.028) and number of resected lymph node were ≥ 4 (22 vs 25, p = 0.009) had better OS after additional radiotherapy than surgery alone. Patients with pancreatic body/tail carcinoma III stage adenocarcinoma (13 vs, p = 0.0503) and T4 adenocarcinoma (14 vs, p = 0.0869) had survival advantage within 24 months for additional radiotherapy. However, patients with T2 stage adenocarcinoma located in pancreatic body/tail had better OS in surgery group than that in R + S group. Conclusions Additional radiotherapy may contribute to improved prognosis for patients with pancreatic head II stage infiltrating duct carcinoma, III stage adenocarcinoma, T4 stage carcinoma, N1 stage adenocarcinoma, regional resection, or number of lymphadenectomy ≥ 4 in infiltrating duct carcinoma. A specific subgroup of patients with specific stage and histological type pancreatic cancer should be considered for additional radiotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s12094-021-02671-0.
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15
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Sánchez-Salazar SM, Torres-Alzate S, Muñoz-Cortés VM, Builes-Barrera CA, Gutiérrez-Montoya JI, Román-González A. VIPoma: a rare cause of diarrhea. A case report. REVISTA DE LA FACULTAD DE MEDICINA 2021. [DOI: 10.15446/revfacmed.v69n3.81603] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Introduction: Vasoactive intestinal peptide-secreting tumor (VIPoma) is a rare functional pancreatic neuroendocrine tumor (F-PNET) characterized by secretory diarrhea, hypokalemia, and hypochlorhydria. Its low incidence and high risk of malignancy pose a clinical challenge that requires a high degree of clinical suspicion.
Case presentation: A 61-year-old woman visited the emergency department of a tertiary care hospital in Medellín, Colombia, due to chronic diarrhea (7 months) that led to dehydration, renal failure, metabolic acidosis, and hypokalemia. As a result, a treatment based on loperamide, intravenous fluids and broad-spectrum antibiotics was started. In addition, chromogranin A levels of 477 ug/L (<100) were reported, while an abdominal MRI showed a 33x30mm mass in the head and uncinate process of the pancreas, so outpatient surgical management was decided. However, three days after discharge, and due to the persistence of clinical signs, the patient was admitted to another hospital (also a tertiary care hospital), where, given the high suspicion of VIPoma, and once the diarrhea was solved, the mass was removed (Whipple procedure) without any complication. Finally, the diagnosis was confirmed based on serum vasoactive intestinal peptide levels (930 pg/mL (RV<75)) and the pathology report (PNET tumor grade 2). Two years after the surgery, the patient was asymptomatic, and no residual lesions or metastases were evident in a control MRI.
Conclusion: Late diagnosis of VIPoma is associated with worsened quality of life, severe complications, and high prevalence of metastasis. Therefore, it should be suspected in patients with chronic secretory diarrhea that is not caused by an infection, since early diagnosis and timely treatment can contribute to achieving better survival rates in these patients.
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16
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Kriger AG, Berelavichus SV, Kaldarov AR, Gorin DS, Raevskaya MB, Kazennov VV, Zekster VY, Panteleev VI. Organ‐preserving procedures as an option for treatment of patients with pancreatic neuroendocrine tumours. SURGICAL PRACTICE 2021. [DOI: 10.1111/1744-1633.12473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Andrey G. Kriger
- Abdominal Surgery Department, Anesthesiology and Intensive Care Department A.V. Vishnevsky Centre of Surgery, Ministry of Health, Russia Moscow Russian Federation
| | - Stanislav V. Berelavichus
- Abdominal Surgery Department, Anesthesiology and Intensive Care Department A.V. Vishnevsky Centre of Surgery, Ministry of Health, Russia Moscow Russian Federation
| | - Ayrat R. Kaldarov
- Abdominal Surgery Department, Anesthesiology and Intensive Care Department A.V. Vishnevsky Centre of Surgery, Ministry of Health, Russia Moscow Russian Federation
| | - David S. Gorin
- Abdominal Surgery Department, Anesthesiology and Intensive Care Department A.V. Vishnevsky Centre of Surgery, Ministry of Health, Russia Moscow Russian Federation
| | - Marianna B. Raevskaya
- Abdominal Surgery Department, Anesthesiology and Intensive Care Department A.V. Vishnevsky Centre of Surgery, Ministry of Health, Russia Moscow Russian Federation
| | - Vladimir V. Kazennov
- Abdominal Surgery Department, Anesthesiology and Intensive Care Department A.V. Vishnevsky Centre of Surgery, Ministry of Health, Russia Moscow Russian Federation
| | - Vita Y. Zekster
- Therapy department I.M. Sechenov First Medical State University, Ministry of Health, Russia Moscow Russian Federation
| | - Vladimir I. Panteleev
- Abdominal Surgery Department, Anesthesiology and Intensive Care Department A.V. Vishnevsky Centre of Surgery, Ministry of Health, Russia Moscow Russian Federation
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17
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Sada A, Yamashita TS, Glasgow AE, Habermann EB, Thompson GB, Lyden ML, Dy BM, Halfdanarson TR, Vella A, McKenzie TJ. Comparison of benign and malignant insulinoma. Am J Surg 2020; 221:437-447. [PMID: 32873371 DOI: 10.1016/j.amjsurg.2020.08.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/21/2020] [Accepted: 08/05/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND How malignant insulinomas present relative to benign insulinomas is unknown. METHODS A single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used. RESULTS A total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01. CONCLUSIONS Larger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.
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Affiliation(s)
- Alaa Sada
- Department of Surgery, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA; Department of Health Services Research, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA
| | | | - Amy E Glasgow
- Department of Health Services Research, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA; Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, 200th 1st Street, Rochester MN, 55905, USA
| | - Elizabeth B Habermann
- Department of Health Services Research, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA; Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, 200th 1st Street, Rochester MN, 55905, USA
| | - Geoffrey B Thompson
- Department of Surgery, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA
| | - Melanie L Lyden
- Department of Surgery, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA
| | - Benzon M Dy
- Department of Surgery, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA
| | | | - Adrian Vella
- Division of Endocrinology, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA
| | - Travis J McKenzie
- Department of Surgery, Mayo Clinic, 200th 1st Street, Rochester MN, 55905, USA.
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18
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Shankar N, Linzay C, Rowe K. Vasoactive intestinal peptide-oma causing refractory diarrhea in a young woman. Proc (Bayl Univ Med Cent) 2020; 33:641-643. [PMID: 33100555 DOI: 10.1080/08998280.2020.1778963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Vasoactive intestinal peptide (VIP)-secreting neuroendocrine tumors are an exceptionally rare cause of chronic diarrhea. We describe a 36-year-old woman presenting with a 2-year history of severe diarrhea and electrolyte derangements ultimately diagnosed with VIPoma.
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Affiliation(s)
- Nagasri Shankar
- Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas
| | - Catherine Linzay
- Division of Gastroenterology, Baylor University Medical Center, Dallas, Texas
| | - Kyle Rowe
- Division of Gastroenterology, Baylor University Medical Center, Dallas, Texas
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19
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Hackeng WM, Schelhaas W, Morsink FHM, Heidsma CM, van Eeden S, Valk GD, Vriens MR, Heaphy CM, Nieveen van Dijkum EJM, Offerhaus GJA, Dreijerink KMA, Brosens LAA. Alternative Lengthening of Telomeres and Differential Expression of Endocrine Transcription Factors Distinguish Metastatic and Non-metastatic Insulinomas. Endocr Pathol 2020; 31:108-118. [PMID: 32103422 PMCID: PMC7250793 DOI: 10.1007/s12022-020-09611-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Insulin-producing pancreatic neuroendocrine tumors (PanNETs)/insulinomas are generally considered to be indolent tumors with an excellent prognosis after complete resection. However, some insulinomas have a poor prognosis due to relapses and metastatic disease. Recently, studies in non-functional PanNETs indicated that behavior can be stratified according to alpha- and beta-cell differentiation, as defined by expression of the transcription factors ARX and PDX1, respectively. It is unknown whether similar mechanisms play a role in insulinomas. Therefore, we determined ARX and PDX1 expression in a cohort of 35 sporadic primary insulinomas and two liver metastases of inoperable primary insulinomas. In addition, WHO grade and loss of ATRX or DAXX were determined by immunohistochemistry, and alternative lengthening of telomeres (ALT) and CDKN2A status by fluorescence in situ hybridization. These findings were correlated with tumor characteristics and clinical follow-up data. In total, five out of 37 insulinoma patients developed metastatic disease. Metastatic insulinomas were all larger than 3 cm, whereas the indolent insulinomas were smaller (p value < 0.05). All three primary insulinomas that metastasized showed ARX expression, 2/3 showed ALT, and 1/3 had a homozygous deletion of CDKN2A as opposed to absence of ARX expression, ALT, or CDKN2A deletions in the 32 non-metastatic cases. The two liver metastases also showed ARX expression and ALT (2/2). The presence of ARX expression, which is usually absent in beta-cells, and genetic alterations not seen in indolent insulinomas strongly suggest a distinct tumorigenic mechanism in malignant insulinomas, with similarities to non-functional PanNETs. These observations may inform future follow-up strategies after insulinoma surgery.
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Affiliation(s)
- Wenzel M Hackeng
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
| | - Willemien Schelhaas
- Department of Pathology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Folkert H M Morsink
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Charlotte M Heidsma
- Department of Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Susanne van Eeden
- Department of Pathology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Gerlof D Valk
- Department of Endocrinology and Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Menno R Vriens
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | | | - G Johan A Offerhaus
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Koen M A Dreijerink
- Department of Endocrinology and Internal Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
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20
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Lee L, Ito T, Jensen RT. Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies. Expert Rev Anticancer Ther 2019; 19:1029-1050. [PMID: 31738624 PMCID: PMC6923565 DOI: 10.1080/14737140.2019.1693893] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 11/13/2019] [Indexed: 02/06/2023]
Abstract
Introduction: Recent advances in diagnostic modalities and therapeutic agents have raised the importance of prognostic factors in predicting overall survival, as well as predictive factors for surgical outcomes, in tailoring therapeutic strategies of patients with pancreatic neuroendocrine neoplasms (panNENs).Areas covered: Numerous recent studies of panNEN patients report the prognostic values of a number of clinically related factors (clinical, laboratory, imaging, treatment-related factors), pathological factors (histological, classification, grading) and molecular factors on long-term survival. In addition, an increasing number of studies showed the usefulness of various factors, specifically biomarkers and molecular makers, in predicting recurrence and mortality related to surgical treatment. Recent findings (from the last 3 years) in each of these areas, as well as recent controversies, are reviewed.Expert commentary: The clinical importance of prognostic and predictive factors for panNENs is markedly increased for both overall outcome and post resection, as a result of recent advances in all aspects of the diagnosis, management and treatment of panNENs. Despite the proven prognostic utility of routinely used tumor grading/classification and staging systems, further studies are required to establish these novel prognostic factors to support their routine clinical use.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, 20892-1804, USA
- Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan
| | - Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, Fukuoka, 814-0001, Japan
| | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, 20892-1804, USA
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21
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Waters AM, Maizlin II, Russell RT, Dellinger M, Gow KW, Goldin A, Goldfarb M, Nuchtern JG, Langer M, Vasudevan SA, Doski JJ, Raval M, Beierle EA. Pancreatic islet cell tumors in adolescents and young adults. J Pediatr Surg 2019; 54:2103-2106. [PMID: 30954230 DOI: 10.1016/j.jpedsurg.2019.01.060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/26/2018] [Accepted: 01/09/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND Pancreatic islet cell tumors are rare in adolescents, and most studies published to date focus on older patients. We utilized a national database to describe the histology and clinical pattern of pancreatic islet cell tumors in adolescent and young adult (AYA) patients, and to compare AYAs to older adults. We hypothesized that AYAs with pancreatic islet cell tumors would have better overall survival. METHODS The National Cancer Data Base (NCDB, 1998-2012) was queried for AYA patients (15-39 years) with a pancreatic islet cell tumor diagnosis. Demographics, tumor characteristics, treatment modalities, and outcomes were abstracted and compared to adults (≥40 years). RESULTS 383 patients (56.4% female, 65% non-Hispanic Whites) were identified, with a median age of 27 (IQR 16-34) years. Islet cell carcinoma was the most common histology. Of patients with known stage of disease, 49% presented with early stage (I or II). Seventy percent of patients underwent surgical resection, including local excision 44%, Whipple procedure 37.5%, or total pancreatectomy 19%. Chemotherapy was utilized in 27% and radiotherapy in 7%. All-cause mortality was 36%. AYA patients underwent more extensive resections (p = 0.001) and had lower mortality rates (p < 0.001), with no differences in tumor stage or use of adjuvant therapies, when compared to adults. CONCLUSIONS AYA patients with pancreatic islet cell tumors had comparable utilization of adjuvant therapies but underwent more extensive resections and demonstrated a higher overall survival rate than adult counterparts. Further investigation into approaches to earlier diagnosis and tailoring of multimodality therapy of these neoplasms in the AYA population is needed. LEVELS OF EVIDENCE Prognostic Study, Level II - retrospective study.
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Affiliation(s)
- Alicia M Waters
- Department of Surgery, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL
| | - Ilan I Maizlin
- Department of Surgery, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL
| | - Robert T Russell
- Department of Surgery, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL
| | - Matthew Dellinger
- Division of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, Seattle, WA
| | - Kenneth W Gow
- Division of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, Seattle, WA
| | - Adam Goldin
- Division of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, Seattle, WA
| | - Melanie Goldfarb
- Department of Surgery, John Wayne Cancer Institute at Providence St. John's Health Center, Santa Monica, CA
| | - Jed G Nuchtern
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Monica Langer
- Department of Surgery, Maine Children's Cancer Program, Tufts University, Portland, ME
| | - Sanjeev A Vasudevan
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - John J Doski
- Department of Surgery, Methodist Children's Hospital of South Texas, University of Texas Health Science Center-San Antonio, San Antonio, TX
| | - Mehul Raval
- Division of Pediatric Surgery, Department of Surgery, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA
| | - Elizabeth A Beierle
- Department of Surgery, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL.
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22
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Abstract
Vasoactive intestinal peptide-secreting tumors (VIPomas) are a group of rare neuroendocrine tumors, which cause a typical syndrome of watery diarrhea. Most of these tumors are found in the pancreas and are usually detected at a later stage. Although curative resection is not possible in most of these tumors, both symptom and tumor control can be achieved by a multidimensional approach, to enable a long survival of most patients. There are no clear-cut guidelines for the management of VIPomas because of the rarity of this neoplasm and lack of prospective data. In this review, we discuss the available evidence on the clinical features and management of these rare tumors.
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Ma W, Wei M, Han Z, Tang Y, Pan Q, Zhang G, Ren J, Huan Y, Li N. The added value of intravoxel incoherent motion diffusion weighted imaging parameters in differentiating high-grade pancreatic neuroendocrine neoplasms from pancreatic ductal adenocarcinoma. Oncol Lett 2019; 18:5448-5458. [PMID: 31612053 PMCID: PMC6781772 DOI: 10.3892/ol.2019.10863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 08/16/2019] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to investigate the potential significance of intravoxel incoherent motion (IVIM)-diffusion weighted imaging (DWI) in differentiating high-grade pancreatic neuroendocrine neoplasms (pNENs) from pancreatic ductal adenocarcinoma (PDAC). A total of 50 patients, including 37 patients with PDAC and 13 patients with high-grade pNENs, underwent pancreatic multiple b-values DWI with 15 b-values including 0, 10, 20, 40, 60, 80, 100, 150, 200, 400, 800, 1,000, 1,200, 1,500 and 2,000 sec/mm2. Standard apparent diffusion coefficient (ADCstandard) and IVIM parameter [slow apparent diffusion coefficient (Dslow), fast apparent diffusion coefficient (Dfast), fraction of fast apparent diffusion coefficient (ƒ)] values of PDAC and pNENs were compared. P<0.05 was considered to indicate a statistically significant difference. Receiver operating characteristics analysis was performed in order to evaluate the diagnostic potential of IVIM parameters for differentiating high-grade pNENs from PDAC. Dslow of pNENs was significantly lower compared with that of PDAC (0.460 vs. 0.579×10−3 mm2/sec; P=0.001). Dfast of pNENs was significantly higher compared with that of PDAC (13.361 vs. 4.985×10−3 mm2/sec; P<0.001). Area under the curve of Dslow, Dfast and combined Dslow and Dfast was 0.793, 0.863 and 0.885 respectively. The specificity and sensitivity of Dslow≤0.472×10−3 mm2/sec were 97.3 and 53.9%, respectively, for differentiating high-grade pNENs from PDAC. The specificity and sensitivity of Dfast >9.58×10−3 mm2/sec were 91.9 and 69.2%, respectively, for differentiating high-grade pNENs from PDAC. When Dslow and Dfast were combined, the specificity and sensitivity for differentiating high-grade pNENs from PDAC were 76.9 and 100%, respectively. Taken together, these results indicated that the diffusion-associated parameter Dslow and the perfusion-associated parameter Dfast of IVIM-DWI may differentiate high-grade pNENs from PDAC with high diagnostic accuracy, and that IVIM-DWI may be a valuable biomarker in differentiating pancreatic neoplasms.
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Affiliation(s)
- Wanling Ma
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Mengqi Wei
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Zhiwei Han
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Yongqiang Tang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Qi Pan
- Department of Radiology, Second Affiliated Hospital of Xi'an Medical Collage, Xi'an, Shaanxi 710038, P.R. China
| | - Guangwen Zhang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Jing Ren
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Yi Huan
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Na Li
- Department of Radiology, Ninth Hospital of Xi'an City, Xi'an, Shaanxi 710068, P.R. China
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Indications for resection and perioperative outcomes of surgery for pancreatic neuroendocrine neoplasms in Germany: an analysis of the prospective DGAV StuDoQ|Pancreas registry. Surg Today 2019; 49:1013-1021. [PMID: 31240463 DOI: 10.1007/s00595-019-01838-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 06/07/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE Pancreatic neuroendocrine neoplasms (pNENs) are rare, and their surgical management is complex. This study evaluated the current practice of pNEN surgery across Germany, including its adherence with guidelines and its perioperative outcomes. METHODS Patients who underwent surgery for pNENs (April 2013-June 2017) were retrieved from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery and retrospectively analyzed. RESULTS A total of 287 patients (53.7% male) with a mean age of 59.2 ± 14.2 years old underwent pancreatic resection for pNENs. Tumors were localized in the pancreatic head (40.4%), body (23%), or tail (36.6%). A total of 239 (83.3%) patients underwent formal resection with lymphadenectomy, 40 (14%) parenchyma-sparing resection, and 8 (2.8%) only exploration. Fifty (17.4%) patients underwent a minimally invasive approach. Among the 245 patients with complete pathological information, 42 (17.1%) had distant metastases, 78 (31.8%) had stage I tumors, 74 (30.2%) stage II, and 51 (20.8%) stage III. A total of 112 (45.7%) patients had G1 tumors, 101 (41.2%) G2, and 24 (9.8%) G3. Nodal involvement on imaging was an independent predictor of lymph node metastasis according to the multivariable analysis (odds ratio: 0.057; 95% confidence interval: 0.016-0.209; p < 0.01). R0 resection was reported in 240 (83.6%) patients. The 30- and 90-day mortality rates were 2.8% and 4.2%, respectively. CONCLUSION In Germany the rate of potential curative resection for pNEN is high. However, formal pancreatic resection seems to be overrepresented, while minimally invasive resection is underrepresented.
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Prognostic Validity of the American Joint Committee on Cancer Eighth Edition TNM Staging System for Surgically Treated and Well-Differentiated Pancreatic Neuroendocrine Tumors: A Comprehensive Analysis of 254 Consecutive Patients From a Large Chinese Institution. Pancreas 2019; 48:613-621. [PMID: 31091206 DOI: 10.1097/mpa.0000000000001305] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES We aimed to validate the novel American Joint Committee on Cancer (AJCC) eighth edition staging manual for well-differentiated (G1/G2) pancreatic neuroendocrine tumors (pNETs). METHODS Data of eligible patients were retrospectively collected, grouped, and analyzed by applying the new AJCC system. RESULTS According to the AJCC eighth staging manual for pNETs, 93, 66, 53, and 42 patients had stage I, II, III, and IV disease, respectively, with estimated 5-year overall survival (OS) rates of 96.9%, 92.8%, 48.4%, and 16.8% (P < 0.005), respectively. A total of 57, 28, 20, and 17 patients with G1 pNETs and 36, 38, 33, and 25 ones with G2 tumors were defined by the new AJCC system as having stage I, II, III, and IV disease, respectively. The estimated 5-year OS for stage I, II, III and IV disease was 100.0%, 97.1%, 52.5%, and 18.2%, respectively, for G1 pNETs (P < 0.005) and 94.2%, 90.3%, 38.7%, and 12.7%, respectively, for G2 tumors (P < 0.005). The novel AJCC classification, tumor grading, and radical resection were all prognostic predictors for OS in patients with pNETs. CONCLUSIONS The new AJCC eighth staging system for well-differentiated pNETs was prognostic and might be adopted in clinical practice.
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Feng T, Lv W, Yuan M, Shi Z, Zhong H, Ling S. Surgical resection of the primary tumor leads to prolonged survival in metastatic pancreatic neuroendocrine carcinoma. World J Surg Oncol 2019; 17:54. [PMID: 30898132 PMCID: PMC6429809 DOI: 10.1186/s12957-019-1597-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Accepted: 03/13/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Palliative resection of the primary tumor for metastatic pancreatic neuroendocrine carcinoma (pNEC) patients is not recommended because of the poor prognosis compared to that of patients with well-differentiated, lower grade tumors. However, the published data supporting this recommendation regarding pNEC are limited. In the present study, we assessed whether palliative primary tumor resection in stage IV pNEC patients affects survival and identified other factors that affect survival in these patients. METHODS We collected data from stage IV pNEC patients registered in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2014. Univariate and multivariate Cox regression analysis were used to compare overall survival (OS) and cancer-specific survival (CSS) of patients who did or did not undergo primary tumor resection. RESULTS We identified 350 patients with metastatic, poorly differentiated, and undifferentiated pNEC. A total of 14.3% (50/350) of patients underwent primary tumor resection. Multivariate Cox regression analysis showed that primary tumor resection provided a significant benefit for both OS and CSS in stage IV pNEC patients. Additionally, chemotherapy and the presence of the primary tumor in the pancreatic tail were independent positive prognostic factors for metastatic pNEC patients in the multivariate Cox regression analysis. CONCLUSIONS The present study suggests that chemotherapy, location of the primary tumor in the pancreatic tail, and, most importantly, surgical removal of the primary tumor are associated with prolonged survival in stage IV pNEC patients.
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Affiliation(s)
- Tingting Feng
- Department of Abdominal Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Wangxia Lv
- Department of Abdominal Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Meiqin Yuan
- Department of Abdominal Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Zhong Shi
- Department of Abdominal Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Haijun Zhong
- Department of Abdominal Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Sunbin Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003 China
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27
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Brooks JC, Shavelle RM, Vavra-Musser KN. Life expectancy in pancreatic neuroendocrine cancer. Clin Res Hepatol Gastroenterol 2019; 43:88-97. [PMID: 30220478 DOI: 10.1016/j.clinre.2018.08.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 07/25/2018] [Accepted: 08/12/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The prognoses widely reported for pancreatic cancer reflect the very poor survival associated with the most common histological type, exocrine adenocarcinoma. We calculated life expectancies for patients with less common pancreatic neuroendocrine tumors (PNETs), and also for the subsets of these patients who survive 1 and 5 years post-diagnosis, all of which carry a significantly better prognosis. Results for 1- and 5-year PNET survivors appear not to have been previously reported, nor have life expectancies (average long-term survival times) been given. METHODS We identified 5287 cases of PNET in the SEER US national database, 1973-2013. The Kaplan-Meier estimator was used to compute empirical survival probabilities and median survival times for functioning (n = 279) and non-functioning PNET (n = 5008) cases. The Cox proportional hazards regression model was used to examine univariate associations of survival with covariates including patient age, sex, race, cancer stage, tumor grade, surgical treatment, and calendar year. A multivariate multiplicative hazard Poisson regression model estimated mortality rates for all combinations of the covariates. The rates were used to construct actuarial life tables, which gave life expectancies for male and female patients according to age, cancer stage, tumor grade, histology (functioning versus non-functioning), surgical treatment status, and time since diagnosis. These life expectancies were compared with age- and sex-specific figures from the US general population. RESULTS Life expectancy in PNET is lower than that of the US general population and varies significantly according to patient age, cancer stage, tumor grade, mode of treatment, and time since diagnosis. For example, it is near normal for persons aged 70 and older who undergo surgical resection of localized well-differentiated (i.e., grade I) tumors. By contrast, persons with metastatic high-grade tumors not amenable to surgery have life expectancies of only 1 to 4 years depending on patient age. Functioning PNETs were associated with somewhat lower mortality than non-functioning within the first few years after diagnosis, though no major differences were observed long-term. Positive factors for survival were younger age, localized stage, low tumor grade, and surgical treatment. Survival improved over the 1973-2013 study period: on average mortality rates fell by 1.2% per year after controlling for changes in the patient population. Life expectancy increased markedly with time since diagnosis: those surviving 1 and 5 years post-diagnosis had longer additional life expectancies. CONCLUSIONS Life expectancies of patients with PNETs may be markedly reduced from normal, but even in the worst cases their prognoses remain significantly better than that of patients with the more common pancreatic adenocarcinomas. In some very favorable cases, the life expectancy is near-normal, especially amongst 1- and 5-year survivors. This information can be used to counsel patients.
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Affiliation(s)
- Jordan C Brooks
- Life Expectancy Project, 1439 - 17th Avenue, San Francisco, CA 94122-3402, USA
| | - Robert M Shavelle
- Life Expectancy Project, 1439 - 17th Avenue, San Francisco, CA 94122-3402, USA.
| | - Kate N Vavra-Musser
- Life Expectancy Project, 1439 - 17th Avenue, San Francisco, CA 94122-3402, USA
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28
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Deguelte S, de Mestier L, Hentic O, Cros J, Lebtahi R, Hammel P, Kianmanesh R. Sporadic pancreatic neuroendocrine tumor: Surgery of the primary tumor. J Visc Surg 2018; 155:483-492. [PMID: 30448206 DOI: 10.1016/j.jviscsurg.2018.08.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The management of patients with sporadic pancreatic neuroendocrine tumors (PNET) is multi-disciplinary and often, multimodal. Surgery has a large part in treatment because it is the only potentially curative therapeutic modality if resection can be complete. The update reviews the operative indications and the different surgical techniques available (including parenchymal-sparing surgery) to treat the primary lesion according to patient status, preoperative work-up and whether the tumor is functioning or not. The place of observation for "small" non-functional sporadic PNET is also discussed.
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Affiliation(s)
- S Deguelte
- Service de chirurgie generale, digestive et endocrinienne, hôpital Robert-Debré, université de Reims Champagne-Ardenne, 51100 Reims, France
| | - L de Mestier
- Service de gastroenterologie-pancréatologie, hôpital Beaujon, université Denis Diderot, AP-HP Clichy, 92110 Paris 7, France
| | - O Hentic
- Service de gastroenterologie-pancréatologie, hôpital Beaujon, université Denis Diderot, AP-HP Clichy, 92110 Paris 7, France
| | - J Cros
- Service d'anatomie pathologique, hôpital Beaujon, université Denis Diderot, AP-HP, Clichy, 92110 Paris 7, France
| | - R Lebtahi
- Service of médecine nucléaire, hôpital Beaujon, université Denis Diderot, AP-HP, Clichy, 92110 Paris 7, France
| | - P Hammel
- Service de gastroenterologie-pancréatologie, hôpital Beaujon, université Denis Diderot, AP-HP Clichy, 92110 Paris 7, France
| | - R Kianmanesh
- Service de chirurgie generale, digestive et endocrinienne, hôpital Robert-Debré, université de Reims Champagne-Ardenne, 51100 Reims, France.
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29
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Labidi A, Hamdi S, Ben Othman A, Chelly B, Daghfous A, Fekih M. A rare cause of upper gastrointestinal bleeding: Primary gastrinoma of the lesser omentum. Presse Med 2018; 47:913-915. [PMID: 30361100 DOI: 10.1016/j.lpm.2018.08.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Revised: 05/17/2018] [Accepted: 08/29/2018] [Indexed: 12/23/2022] Open
Affiliation(s)
- Asma Labidi
- University of Tunis el Manar, La Rabta University Hospital of Tunis, Department of Gastroenetrology A, Tunis, Tunisia.
| | - Sarra Hamdi
- University of Tunis el Manar, La Rabta University Hospital of Tunis, Department of Gastroenetrology A, Tunis, Tunisia
| | - Aymen Ben Othman
- University of Sfax, Habib Bourguiba University Hospital, Department of Radiology, Tunis, Tunisia
| | - Beya Chelly
- University of Tunis el Manar, La Rabta University Hospital of Tunis, Department of Pathology, Tunis, Tunisia
| | - Amine Daghfous
- University of Tunis el Manar, La Rabta University Hospital of Tunis, Department of Digestive Surgery A, Tunis, Tunisia
| | - Monia Fekih
- University of Tunis el Manar, La Rabta University Hospital of Tunis, Department of Gastroenetrology A, Tunis, Tunisia
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30
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Matsumoto T, Okabe H, Yamashita YI, Yusa T, Itoyama R, Nakao Y, Yamao T, Umzaki N, Tsukamoto M, Kitano Y, Miyata T, Arima K, Nitta H, Hayashi H, Imai K, Chikamoto A, Baba H. Clinical role of fludeoxyglucose (18F) positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with pancreatic neuroendocrine tumors. Surg Today 2018; 49:21-26. [DOI: 10.1007/s00595-018-1703-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 07/10/2018] [Indexed: 12/26/2022]
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Goretzki PE, Mogl MT, Akca A, Pratschke J. Curative and palliative surgery in patients with neuroendocrine tumors of the gastro-entero-pancreatic (GEP) tract. Rev Endocr Metab Disord 2018; 19:169-178. [PMID: 30280290 DOI: 10.1007/s11154-018-9469-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The incidence of neuroendocrine tumors (NET) increases with age. Lately, the diagnosis of NET was mainly caused by early detection of small NET (<1 cm) in the rectum and stomach, which are depicted by chance during routine and prophylactic endoscopy. Also in patients with large and metastatic pancreatic and intestinal tumors thorough pathologic investigation with use of different immunohistologic markers discovers more neuroendocrine tumors with low differentiation grade (G2-G3) and more neuroendocrine carcinomas (NEC), nowadays, than in former times. While gastric and rectal NET are discovered as small (<1 cm in diameter) and mainly highly differentiated tumors, demonstrating lymph node metastases in less than 10% of the patients, the majority of pancreatic and small bowel NET have already metastasized at the time of diagnosis. This is of clinical importance, since tumor stage and differentiation grade not only influence prognosis but also surgical procedure and may define whether a combination of surgery with systemic biologic therapy, chemotherapy or local cytoreductive procedures may be used. The indication for surgery and the preferred surgical procedure will have to consider personal risk factors of each patient (i.e. general health, additional illnesses, etc.) and tumor specific factors (i.e. tumor stage, grade of differentiation, functional activity, mass and variety of loco regional as well as distant metastases etc.). Together they define, whether radical curative or only palliative surgery can be applied. Altogether surgery is the only cure for locally advanced NET and helps to increase quality of life and overall survival in many patients with metastatic neuroendocrine tumors. The question of cure versus palliative therapy sometimes only can be answered with time, however. Many different aspects and various questions concerning the indication and extent of surgery and the best therapeutic procedure are still unanswered. Therefore, a close multidisciplinary cooperation of colleagues involved in biochemical and localization diagnostics and those active in various treatment areas is warranted to search for the optimal strategy in each individual patient. How far genetic screening impacts survival remains to be seen. Since surgeons do have a central role in the treatment of NET patients, they have to understand the need for integration into such an interdisciplinary team.
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Affiliation(s)
- Peter E Goretzki
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
- Leiter Arbeitsbereich endokrine Chirurgie, Chirurgische Klinik, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
| | - Martina T Mogl
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Aycan Akca
- Surgical Clinic 1, Lukaskrankenhaus Neuss, Preußenstrasse 84, 41456, Neuss, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany
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Li X, Gou S, Liu Z, Ye Z, Wang C. Assessment of the American Joint Commission on Cancer 8th Edition Staging System for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology, and End Results analysis. Cancer Med 2018; 7:626-634. [PMID: 29380547 PMCID: PMC5852336 DOI: 10.1002/cam4.1336] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 12/15/2017] [Accepted: 12/18/2017] [Indexed: 01/06/2023] Open
Abstract
Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2014). Overall survival was analyzed using Kaplan–Meier curves with the log‐rank test. The predictive accuracy of each staging system was assessed by the concordance index (c‐index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan–Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c‐index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection.
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Affiliation(s)
- Xiaogang Li
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital Of Hubei University of Arts and Science, Xiangyang, 441021, China
| | - Shanmiao Gou
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhiqiang Liu
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zeng Ye
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chunyou Wang
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger-Ellison Syndrome. Dig Dis Sci 2017; 62:2258-2265. [PMID: 28776139 DOI: 10.1007/s10620-017-4695-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 07/26/2017] [Indexed: 12/11/2022]
Abstract
Zollinger-Ellison syndrome (ZES) results from an ectopic gastrin-secreting tumor leading to peptic ulcer disease, reflux, and chronic diarrhea. While early recognition portends an excellent prognosis with >80% survival at 15 years, symptoms are often nonspecific making the diagnosis difficult to establish. Diagnosis involves a series of tests, including fasting gastrin, gastric pH, chromogranin A, and secretin stimulation. Performing these tests in the correct sequence and at the proper time is essential to avoid inaccurate results. Tumor localization is equally nuanced. Although providers have classically used 111indium-radiolabeled octreotide with somatostatin receptor scintigraphy to evaluate tumor size and metastases, recent studies have shown superior results with newer imaging modalities. In particular, 68gallium (68Ga)-labeled somatostatin radiotracers (i.e., 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE) used with positron emission tomography/computed tomography can provide excellent results. Endoscopic ultrasound is another useful modality, particularly in patients with ZES in the setting of multiple endocrine neoplasia type 1. This review aims to provide clinicians with an overview of ZES with a focus on both clinical presentation and the proper utilization of the various biochemical and imaging tests available.
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34
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Keutgen XM, Babic B, Nilubol N. Management of pancreatic neuroendocrine tumors. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2016. [DOI: 10.2217/ije-2016-0002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare tumors that have a better prognosis than their exocrine counterpart, but frequently present with advanced disease. Management of pNETs has evolved considerably over the past decade. Surgical resection remains the only potentially curative option for patients with pNETs. Patients who have locoregionally advanced and/or metastatic pNETs require additional treatments. These include liver-directed (transarterial (chemo)-embolization, selective intraarterial radio therapy) and systemic therapies (somatostatin analogs, targeted therapy such as tyrosine-kinase inhibitors and mammalian target of rapamycin inhibitor, peptide receptor radionuclide therapy and cytotoxic chemotherapy). The aim of this article is to review the current treatment options as well as potential future therapeutic perspectives for patients with pNETs.
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Affiliation(s)
- Xavier M Keutgen
- Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Bruna Babic
- Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Naris Nilubol
- Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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35
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Kandaswamy L, Raghavan R, Pappachan JM. Spontaneous hypoglycemia: diagnostic evaluation and management. Endocrine 2016; 53:47-57. [PMID: 26951054 DOI: 10.1007/s12020-016-0902-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2016] [Accepted: 02/15/2016] [Indexed: 02/07/2023]
Abstract
Spontaneous hypoglycemia is a puzzling clinical problem and an important reason for referral to endocrinologists. Several clinical conditions such as insulinomas, non-insulinoma pancreatogenous hypoglycemia syndrome, insulin autoimmune syndrome, postprandial hypoglycemia (reactive hypoglycemia), non-islet cell tumor hypoglycemia, primary adrenal insufficiency, hypopituitarism, and critical illness can be associated with spontaneous hypoglycemia. Rarely, in patients with mental health issues, factious hypoglycemia from extrinsic insulin use or ingestion of oral hypoglycemic agents can obfuscate the clinical picture for clinicians trying to identify an organic cause. In those presenting with Whipple's triad (symptoms ± signs of hypoglycemia, low plasma glucose, and resolution symptoms ± signs after hypoglycemia correction), a 72-h supervised fast test with measurement of plasma insulin, c-peptide, pro-insulin, and beta-hydroxybutyrate levels, coupled with plasma/urine sulphonylurea screen, forms the first step in diagnostic evaluation. A mixed meal test is preferable for those with predominantly postprandial symptoms. Additional non-invasive and/or invasive diagnostic evaluation is necessary if an organic hypoglycemic disorder is suspected. With the aid of a few brief clinical case scenarios, we discuss the diagnostic evaluation and management of spontaneous hypoglycemia through this comprehensive article.
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Affiliation(s)
- Leelavathy Kandaswamy
- Department of Endocrinology & Diabetes, New Cross Hospital, The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, WV10 0QP, UK
| | - Rajeev Raghavan
- Department of Endocrinology & Diabetes, New Cross Hospital, The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, WV10 0QP, UK
| | - Joseph M Pappachan
- Department of Endocrinology & Diabetes, New Cross Hospital, The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, WV10 0QP, UK.
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