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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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Ito T, Ramos-Alvarez I, Jensen RT. Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B 12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients. Int J Mol Sci 2024; 25:7286. [PMID: 39000391 PMCID: PMC11242121 DOI: 10.3390/ijms25137286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | | | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA
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Ito T, Ramos-Alvarez I, Jensen RT. Successful Lifetime/Long-Term Medical Treatment of Acid Hypersecretion in Zollinger-Ellison Syndrome (ZES): Myth or Fact? Insights from an Analysis of Results of NIH Long-Term Prospective Studies of ZES. Cancers (Basel) 2023; 15:1377. [PMID: 36900170 PMCID: PMC10000208 DOI: 10.3390/cancers15051377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/09/2023] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Analysis of the efficacy/pharmacology of long-term/lifetime medical treatment of acid hypersecretion in a large cohort of ZES patients in a prospective study. This study includes the results from all 303 patients with established ZES who were prospectively followed and received acid antisecretory treatment with either H2Rs or PPIs, with antisecretory doses individually titrated by the results of regular gastric acid testing. The study includes patients treated for short-term periods (<5 yrs), patients treated long-term (>5 yrs), and patients with lifetime treatment (30%) followed for up to 48 years (mean 14 yrs). Long-term/lifelong acid antisecretory treatment with H2Rs/PPIs can be successfully carried out in all patients with both uncomplicated and complicated ZES (i.e., with MEN1/ZES, previous Billroth 2, severe GERD). This is only possible if drug doses are individually set by assessing acid secretory control to establish proven criteria, with regular reassessments and readjustments. Frequent dose changes both upward and downward are needed, as well as regulation of the dosing frequency, and there is a primary reliance on the use of PPIs. Prognostic factors predicting patients with PPI dose changes are identified, which need to be studied prospectively to develop a useful predictive algorithm that could be clinically useful for tailored long-term/lifetime therapy in these patients.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | | | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA
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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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Eom BW, Lee J, Lee IS, Son YG, Ryu KW, Kim SG, Kim HI, Kim YW, Kong SH, Kwon OK, Park JH, An JY, Kim CH, Suh BJ, Yoon HM, Son MW, Park JY, Park JM, Jeong SH, Yoo MW, Song GJ, Yang HK, Suh YS, Park KB, Ahn SH, Shin DW, Jee YS, Ahn HS, Lee S, Min JS, In H, Kim A, Hur H, Lee HJ. Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy. Cancer Res Treat 2021; 53:763-772. [PMID: 33421981 DOI: 10.20538/1682-0363-2021-2-233-238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 12/28/2020] [Indexed: 03/29/2025] Open
Abstract
PURPOSE Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. MATERIALS AND METHODS Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. RESULTS The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. CONCLUSION The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
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Affiliation(s)
- Bang Wool Eom
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Joongyub Lee
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - In Seob Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Gil Son
- Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, Korea
| | - Keun Won Ryu
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Sung Geun Kim
- Department of Surgery, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyoung-Il Kim
- Department of Surgery, Yonsei University Severance Hospital, Seoul, Korea
| | - Young-Woo Kim
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Seong-Ho Kong
- Department Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University of College of Medicine, Seoul, Korea
| | - Oh Kyoung Kwon
- Department of Surgery, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Ji-Ho Park
- Department of Surgery, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Ji Yeong An
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chang Hyun Kim
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Byoung-Jo Suh
- Department of Surgery, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Hong Man Yoon
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Myoung Won Son
- Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Ji Yeon Park
- Department of Surgery, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Jong-Min Park
- Department of Surgery, National Medical Center, Seoul, Korea
| | - Sang-Ho Jeong
- Department of Surgery, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Geum Jong Song
- Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Han-Kwang Yang
- Department Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University of College of Medicine, Seoul, Korea
| | - Yun-Suhk Suh
- Department Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University of College of Medicine, Seoul, Korea
| | - Ki Bum Park
- Department of Surgery, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Woo Shin
- Department of Surgery, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Ye Seob Jee
- Department of Surgery, Dankook University Hospital, Cheonan, Korea
| | - Hye-Seong Ahn
- Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Sol Lee
- Department of Surgery, Seoul Medical Center, Seoul, Korea
| | - Jae Seok Min
- Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea
| | - Haejin In
- Department of Surgery, Albert Einstein College of Medicine, New York, NY, USA
| | - Ahyoung Kim
- Department of Psychology, Ewha Womans University, Seoul, Korea
| | - Hoon Hur
- Department of Surgery, Ajou University Hospital, Suwon, Korea
| | - Hyuk-Joon Lee
- Department Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University of College of Medicine, Seoul, Korea
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Clauditz TS, Wallace MB, Lauwers GY. Inflammatory Disorders of the Stomach. GASTROINTESTINAL PATHOLOGY 2021:73-98. [DOI: 10.1002/9781119073048.ch4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Ma ZY, Gong YF, Zhuang HK, Zhou ZX, Huang SZ, Zou YP, Huang BW, Sun ZH, Zhang CZ, Tang YQ, Hou BH. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol 2020; 26:2305-2322. [PMID: 32476795 PMCID: PMC7243647 DOI: 10.3748/wjg.v26.i19.2305] [Citation(s) in RCA: 112] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/27/2020] [Accepted: 04/27/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.
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Affiliation(s)
- Zu-Yi Ma
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Yuan-Feng Gong
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Hong-Kai Zhuang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Zi-Xuan Zhou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Shan-Zhou Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yi-Ping Zou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Bo-Wen Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Zhong-Hai Sun
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Chuan-Zhao Zhang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yun-Qiang Tang
- Department of Hepatobiliary Surgery, the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Hua Hou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
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Cavalcanti E, Stasi E, Coletta S, Lorusso D, Rinaldi CM, Armentano R. Primary lymph node gastrinoma: a case report and review of the literature. World J Surg Oncol 2020; 18:80. [PMID: 32345299 PMCID: PMC7189517 DOI: 10.1186/s12957-020-01860-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 04/20/2020] [Indexed: 11/12/2022] Open
Abstract
Background Gastrinoma is a rare form of neuroendocrine neoplasm. The presence of a primary lymph node localization of gastrinoma is a much debated and controversial topic in the literature, as regards whether these cases represent metastatic disease from an as yet unidentified primary tumor, or the de novo occurrence of a gastrinoma in a lymph node. Case presentation We report the case of a 24-year-old male with intense epigastric pain treated at the beginning with high dose proton pump inhibitors. Further workup with CT and subsequent laparotomy revealed a single peripancreatic lymph node. Histological examination highlighted a well-differentiated neuroendocrine tumor. Conclusion This case underlines that the primitive lymph node gastrinoma is a distinct nosological entity with a precise location in the context of rare neuroendocrine tumors that should be considered when specific symptoms are associated with the identification of isolated lymph nodes, after excluding any possible primitive locations of neoplastic localization.
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Affiliation(s)
- Elisabetta Cavalcanti
- National Institute of Gastroenterology "S. de Bellis", Research Hospital Castellana Grotte Bari, Via Turi 27, 70013 Castellana Grotte (Ba), Bari, Italy.
| | - Elisa Stasi
- National Institute of Gastroenterology "S. de Bellis", Research Hospital Castellana Grotte Bari, Via Turi 27, 70013 Castellana Grotte (Ba), Bari, Italy
| | - Sergio Coletta
- National Institute of Gastroenterology "S. de Bellis", Research Hospital Castellana Grotte Bari, Via Turi 27, 70013 Castellana Grotte (Ba), Bari, Italy
| | - Dionigi Lorusso
- National Institute of Gastroenterology "S. de Bellis", Research Hospital Castellana Grotte Bari, Via Turi 27, 70013 Castellana Grotte (Ba), Bari, Italy
| | - Caterina Mammone Rinaldi
- National Institute of Gastroenterology "S. de Bellis", Research Hospital Castellana Grotte Bari, Via Turi 27, 70013 Castellana Grotte (Ba), Bari, Italy
| | - Raffaele Armentano
- National Institute of Gastroenterology "S. de Bellis", Research Hospital Castellana Grotte Bari, Via Turi 27, 70013 Castellana Grotte (Ba), Bari, Italy
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9
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Gong S, Li Z, Liu XB, Wang X, Shen WW. Gastrinoma in multiple endocrine neoplasia type 1 after total pancreatectomy: A case report. Medicine (Baltimore) 2019; 98:e18275. [PMID: 31852099 PMCID: PMC6922403 DOI: 10.1097/md.0000000000018275] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
RATIONALE Surgery for patients with multiple endocrine neoplasia type 1(MEN-1) related gastrinoma remains controversial and total pancreatectomy (TP) has rarely been performed. We reported a case of patient with MEN-1 related gastrinoma treated by TP. PATIENT CONCERNS A 46-year-old female was admitted to our hospital due to abdominal distension and diarrhea for 2 years. The patient underwent pituitary tumor resection and kidney stone lithotripsy 10 years ago. DIAGNOSES Abdominal computed tomography showed single lesion in the duodenum and multiple lesions throughout the pancreas. The patient's gastrin level was significantly increased (1080 pg/ml). These findings in combination with the pituitary tumor history suggested the presence of gastrinoma associated with MEN-1 syndrome. INTERVENTION An exploratory laparotomy was performed. Intraoperative ultrasound confirmed the numerous tumors diffusely distributed throughout the pancreas and the patient eventually underwent TP. OUTCOMES Twelve months later, the patient was hospitalized again for anastomotic fistula and underwent a partial gastrectomy, small bowel resection and drainage of the abscess. One month later, she received gastrostomy and jejunostomy due to digestive tract fistula, and died a month later (14 months after TP). LESSONS There still might be the possibility of recurrence even after radical surgical resection of gastrinomas, and we suggest the need to measure the basal acid output and maintain regular anti-acid therapy in the long-term follow-up of patients with MEN-1 related gastrinoma.
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Affiliation(s)
- Shu Gong
- Department of Pancreatic Surgery
| | - Zhi Li
- Department of Pancreatic Surgery
| | | | - Xin Wang
- Department of Pancreatic Surgery
| | - Wen-Wu Shen
- Outpatient Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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10
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Hruban RH, Klimstra DS, Zamboni G, Klöppel G. A semicentennial of pancreatic pathology: the genetic revolution is here, but don't throw the baby out with the bath water! Hum Pathol 2019; 95:99-112. [PMID: 31521627 DOI: 10.1016/j.humpath.2019.08.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 08/28/2019] [Indexed: 12/19/2022]
Abstract
The last 50 years have witnessed an explosion in our understanding of the pathology of pancreatic diseases. Entities known to exist 50 years ago have been defined more precisely and are now better classified. New entities, previously not recognized, have been discovered and can now be treated. Importantly, new tools have been developed that have unraveled the fundamental biological drivers of a number of pancreatic diseases. Many of these same tools have also been applied clinically, supplementing the tried and true hematoxylin and eosin stained slide with a plethora of new, highly sensitive and specific tests that improve diagnostic accuracy and delineate best treatments. As exciting as these many advances are, our knowledge of pancreatic pathology remains incomplete, and there is much to be learned.
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Affiliation(s)
- Ralph H Hruban
- The Sol Goldman Pancreatic Cancer Research Center, Departments of Pathology and Oncology, the Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
| | - David S Klimstra
- The Department of Pathology, Memorial Sloan Kettering Cancer Center, NY, USA
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11
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Shao QQ, Zhao BB, Dong LB, Cao HT, Wang WB. Surgical management of Zollinger-Ellison syndrome: Classical considerations and current controversies. World J Gastroenterol 2019; 25:4673-4681. [PMID: 31528093 PMCID: PMC6718045 DOI: 10.3748/wjg.v25.i32.4673] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 04/29/2019] [Accepted: 05/03/2019] [Indexed: 02/06/2023] Open
Abstract
Zollinger-Ellison syndrome (ZES) is characterized by gastric acid hypersecretion causing severe recurrent acid-related peptic disease. Excessive secretion of gastrin can now be effectively controlled with powerful proton pump inhibitors, but surgical management to control gastrinoma itself remains controversial. Based on a thorough literature review, we design a surgical algorithm for ZES and list some significant consensus findings and recommendations: (1) For sporadic ZES, surgery should be routinely undertaken as early as possible not only for patients with a precisely localized diagnosis but also for those with negative imaging findings. The surgical approach for sporadic ZES depends on the lesion location (including the duodenum, pancreas, lymph nodes, hepatobiliary tract, stomach, and some extremely rare sites such as the ovaries, heart, omentum, and jejunum). Intraoperative liver exploration and lymphadenectomy should be routinely performed; (2) For multiple endocrine neoplasia type 1-related ZES (MEN1/ZES), surgery should not be performed routinely except for lesions > 2 cm. An attempt to perform radical resection (pancreaticoduodenectomy followed by lymphadenectomy) can be made. The ameliorating effect of parathyroid surgery should be considered, and parathyroidectomy should be performed first before any abdominal surgery for ZES; and (3) For hepatic metastatic disease, hepatic resection should be routinely performed. Currently, liver transplantation is still considered an investigational therapeutic approach for ZES. Well-designed prospective studies are desperately needed to further verify and modify the current considerations.
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Affiliation(s)
- Qian-Qian Shao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Bang-Bo Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Liang-Bo Dong
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Hong-Tao Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Wei-Bin Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
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12
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Rozenblum L, Mokrane FZ, Yeh R, Sinigaglia M, Besson F, Seban RD, Chougnet CN, Revel-Mouroz P, Zhao B, Otal P, Schwartz LH, Dercle L. The role of multimodal imaging in guiding resectability and cytoreduction in pancreatic neuroendocrine tumors: focus on PET and MRI. Abdom Radiol (NY) 2019; 44:2474-2493. [PMID: 30980115 DOI: 10.1007/s00261-019-01994-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms that secrete peptides and neuro-amines. pNETs can be sporadic or hereditary, syndromic or non-syndromic with different clinical presentations and prognoses. The role of medical imaging includes locating the tumor, assessing its extent, and evaluating the feasibility of curative surgery or cytoreduction. Pancreatic NETs have very distinctive phenotypes on CT, MRI, and PET. PET have been demonstrated to be very sensitive to detect either well-differentiated pNETs using 68Gallium somatostatin receptor (SSTR) radiotracers, or more aggressive undifferentiated pNETS using 18F-FDG. A comprehensive interpretation of multimodal imaging guides resectability and cytoreduction in pNETs. The imaging phenotype provides information on the differentiation and proliferation of pNETs, as well as the spatial and temporal heterogeneity of tumors with prognostic and therapeutic implications. This review provides a structured approach for standardized reading and reporting of medical imaging studies with a focus on PET and MR techniques. It explains which imaging approach should be used for different subtypes of pNET and what a radiologist should be looking for and reporting when interpreting these studies.
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Affiliation(s)
- Laura Rozenblum
- Sorbonne Université, Service de Médecine Nucléaire, AP-HP, Hôpital La Pitié-Salpêtrière, 75013, Paris, France
| | - Fatima-Zohra Mokrane
- Radiology Department, Toulouse University Hospital, 1 Avenue du Professeur Jean Poulhes, 31059, Toulouse, France
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Randy Yeh
- Memorial Sloan Kettering Cancer Center, Molecular Imaging and Therapy Service, New York, NY, USA
| | - Mathieu Sinigaglia
- Department of Imaging and Nuclear Medicine, Institut Claudius Regaud - Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France
| | - Florent Besson
- Paris Sud University, Kremlin Bicêtre Hospital, Paris, France
| | - Romain-David Seban
- Department of Nuclear Medicine, Institut Curie-René Huguenin, Saint-Cloud, France
| | - Cecile N Chougnet
- Department of Endocrine Oncology, Hôpital Saint Louis, Paris, France
| | - Paul Revel-Mouroz
- Radiology Department, Toulouse University Hospital, 1 Avenue du Professeur Jean Poulhes, 31059, Toulouse, France
| | - Binsheng Zhao
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Philippe Otal
- Radiology Department, Toulouse University Hospital, 1 Avenue du Professeur Jean Poulhes, 31059, Toulouse, France
| | - Lawrence H Schwartz
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Laurent Dercle
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA.
- UMR 1015, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, 94805, France.
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13
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Management of Primary Lymph Nodal Gastrinoma With Liver Metastases Resulting in Zollinger-Ellison Syndrome. Clin Nucl Med 2019; 44:e36-e39. [PMID: 30394927 DOI: 10.1097/rlu.0000000000002368] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Primary lymph node gastrinoma has been defined as gastrin-producing tumor present in lymph nodes and predominantly found in well-defined anatomical region known as gastrinoma triangle. They are usually localized preoperatively with imaging, and their surgical resection results in long-term relief. The authors report a case of unresectable primary lymph nodal gastrinoma with liver metastases in a 14-year-old adolescent boy with proven histopathology detected on Ga-DOTANOC whole-body PET/CT scan followed by preoperative multiple Lu-DOTATATE cycles for cytoreduction. Subsequent surgical resection of residual mass resulted in complete response with a follow-up of around 4 years in this unusual case of Zollinger-Ellison syndrome.
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14
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Abstract
Our group observed the first case of synchronous gastric neuroendocrine tumor (NET) and duodenal gastrinoma with autoimmune chronic atrophic gastritis (CAG), in the absence of Helicobacter pylori infection. Demographic, clinical, endoscopic, and pathologic data were abstracted from the electronic medical record at Mount Sinai Hospital from 2013 to 2015. The patient's anonymity was carefully protected, and informed consent was obtained for publication of protected health information. A 53-year-old woman with hypertension presented to Mount Sinai Hospital in June 2013 for a second opinion for management of gastric and duodenal NETs. After evaluation by gastroenterology and surgery, repeat upper endoscopy with ultrasound and fine-needle aspiration revealed multiple diminutive type I gastric NETs and 2 duodenal NETs, against a background of autoimmune CAG, with biopsy pathology negative for H. pylori. She subsequently underwent a transduodenal resection of the duodenal NETs, confirming low-grade, gastrin-positive, stage T2 duodenal NET. On routine follow-up over the next 2 years, clinical, radiographic, and endoscopic surveillance revealed no recurrent or metastatic gastric or duodenal disease. This first report of synchronous duodenal gastrinoma and gastric NET in the setting of autoimmune CAG can broaden our understanding of gastric NET pathophysiology.
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15
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Dillhoff ME, Ellison EC. Zollinger-Ellison Syndrome. SHACKELFORD'S SURGERY OF THE ALIMENTARY TRACT, 2 VOLUME SET 2019:702-711. [DOI: 10.1016/b978-0-323-40232-3.00060-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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16
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Abstract
This article reviews the role of surgical and medical management in patients with Zollinger-Ellison syndrome (ZES) due to a gastrin-secreting neuroendocrine tumor (gastrinoma). It concentrates on the status at present but also briefly reviews the changes over time in treatment approaches. Generally, surgical and medical therapy are complementary today; however, in some cases, such as patients with ZES and multiple endocrine neoplasia type 1, the treatment approach remains controversial.
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Affiliation(s)
- Jeffrey A Norton
- Department of Surgery, Stanford University School of Medicine, 291 campus Drive, Stanford, CA 94305-5101, USA
| | - Deshka S Foster
- Department of Surgery, Stanford University School of Medicine, 291 campus Drive, Stanford, CA 94305-5101, USA
| | - Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, National Institutes of Health, Building 10, Room 9C-103, Bethesda, MD 20892-1804, USA.
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17
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Pipek LZ, Jardim YJ, de Mesquita GHA, Nii F, Medeiros KADA, Carvalho BJ, Martines DR, Iuamoto LR, Waisberg DR, D'Albuquerque LAC, Meyer A, Andraus W. Large primary hepatic gastrinoma in young patient treated with trisegmentectomy: A case report and review of the literature. World J Hepatol 2018; 10:517-522. [PMID: 30079138 PMCID: PMC6068851 DOI: 10.4254/wjh.v10.i7.517] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/25/2018] [Accepted: 05/30/2018] [Indexed: 02/06/2023] Open
Abstract
Primary hepatic gastrinoma is a rare disease, with fewer than 40 cases reported in the medical literature. Because it is located in an organ in which metastases are common, its diagnosis is difficult. We report a case of a 19 years old male patient with a history of gastric ulcers since the age of nine. Following gastric surgery, an antrectomy and a vagotomy, there was some alleviation of symptoms. Subsequently, the patient reported various intermittent episodes of diarrhea, diffuse abdominal pain, and vomiting. The patient underwent tomography, which revealed the presence of a hepatic mass measuring 19.5 cm × 12.5 cm × 17 cm. Primary hepatic gastrinoma was diagnosed based on laboratory examinations that indicated hypergastrinemia and a positron emission tomography/magnetic resonance study with somatostatin analogue that confirmed the liver as the primary site. After hepatic trisegmentectomy (II, III, IV, V, VIII), the patient's symptoms improved. The case is notable for the presence of a rare tumor with uncommon dimensions.
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Affiliation(s)
| | - Yuri Justi Jardim
- Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403, Brazil
| | | | - Fernanda Nii
- Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403, Brazil
| | | | | | | | | | - Daniel Reis Waisberg
- Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403, Brazil
| | | | - Alberto Meyer
- Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403, Brazil
| | - Wellington Andraus
- Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403, Brazil
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18
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Rossi RE, Rausa E, Cavalcoli F, Conte D, Massironi S. Duodenal neuroendocrine neoplasms: a still poorly recognized clinical entity. Scand J Gastroenterol 2018; 53:835-842. [PMID: 29726295 DOI: 10.1080/00365521.2018.1468479] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 04/16/2018] [Accepted: 04/16/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Duodenal neuroendocrine neoplasms (dNENs) are rare tumors, which usually show good prognosis. The optimal management of these tumors is still far from being clearly understood because of their rarity and the poor level of knowledge about their natural history. Herein, we have reviewed the literature on dNENs to collect and analyze the current data on epidemiology, diagnosis and management of these rare tumors. METHODS Bibliographical searches were performed in PubMed, using the following keywords: duodenal neuroendocrine neoplasm; duodenum; gastrinoma; diagnosis; therapy; guidelines. We searched for all relevant articles published over the last 15 years. Non-English language papers were excluded. RESULTS We reviewed the pertinent articles about dNENs. Upper gastrointestinal endoscopy with biopsy is the cornerstone of the dNENs diagnostic process. Endoscopic ultrasound with fine-needle aspiration/biopsy should be performed in order to locally stage the disease and in all cases of non-diagnostic endoscopy. Endoscopic or complete surgical removal of the primary lesion is the recommended treatment and is generally achievable for the majority of the patients. A less aggressive approach may be suggested for well-differentiated low-stage tumors. After NEN removal, patients should be closely followed-up especially during the first 3 years by endoscopic examination, imaging tests and CgA measurements. CONCLUSIONS The multi-disciplinary approach and the preservation of the quality of life of the patients play a key role in the therapeutic process for dNENs. Further studies are needed to better define standardized guidelines specific to dNENs, including optimal management approaches and follow-up intervals.
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Affiliation(s)
- Roberta Elisa Rossi
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
- b Department of Pathophysiology and Organ Transplant , Università degli Studi di Milano , Milan , Italy
| | - Emanuele Rausa
- c General and Emergency Surgery Department , ASST Trauma Center "Papa Giovanni XXIII" Hospital , Bergamo , Italy
| | - Federica Cavalcoli
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
- b Department of Pathophysiology and Organ Transplant , Università degli Studi di Milano , Milan , Italy
| | - Dario Conte
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
- b Department of Pathophysiology and Organ Transplant , Università degli Studi di Milano , Milan , Italy
| | - Sara Massironi
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
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19
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Guarnotta V, Martini C, Davì MV, Pizza G, Colao A, Faggiano A. The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma? Endocrine 2018; 60:15-27. [PMID: 29019150 DOI: 10.1007/s12020-017-1420-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 09/02/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE Analyze the role of somatostatin analogues (SSAs) in the treatment of sporadic and MEN1-related gastrinomas, trying to define whether recent trials have changed the landscape of gastrinoma therapy. METHODS We evaluate the rationale of SSA use in the treatment of gastrinomas, summarize the current literature concerning the effect of SSAs on the control of Zollinger-Ellison syndrome (ZES) and gastrinomas tumor progression and discuss their role in the most recent guidelines. RESULTS The medical treatment of gastrinoma and related ZES is aimed at controlling acid hypersecretion and tumor progression, in inoperable patients. The use of proton pump inhibitors (PPIs) to control the syndrome is a cornerstone in the ZES therapy. SSAs are not usually indicated for antisecretory purpose, because PPIs are considered the treatment of choice, due to their long lasting high efficacy and oral availability. The antiproliferative effect of SSAs has been established by two placebo-controlled trials that have clearly demonstrated a significant increase in progression free survival in patients affected by non-functioning well-differentiated advanced neuroendocrine tumors (NETs). The recent ENETS guidelines recommend the use of SSAs in advanced well differentiated NETs as antiproliferative agents. CONCLUSIONS The high sstr-expression in gastrinomas make them highly responsive to SSAs and support the use of such drugs to counteract the tumour growth in patients not amenable to surgical cure. Unfortunately, limited data, mainly case reports or small series, support the use of SSAs in advanced gastrinomas, therefore, it is difficult to quantify their ability to control tumour growth and disease progression.
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Affiliation(s)
- Valentina Guarnotta
- Biomedical Department of Internal and Specialist Medicine (DIBIMIS), Section of Endocrine-Metabolic Diseases, University of Palermo, Palermo, Italy
| | - Chiara Martini
- Clinica Medica 3^, Department of Medicine, DIMED, University of Padova, Padova, Italy.
| | - Maria Vittoria Davì
- Section of Endocrinology, Medicina Generale e Malattie Aterotrombotiche e Degenerative, Department of Medicine, University of Verona, Verona, Italy
| | - Genoveffa Pizza
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Annamaria Colao
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Antongiulio Faggiano
- Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy
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20
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Sporadic Gastroenteropancreatic Neuroendocrine Tumors. Updates Surg 2018. [DOI: 10.1007/978-88-470-3955-1_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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21
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Abstract
Peptide hormones represent a major class of hormones that are made from amino acids by specialized endocrine glands. The maturation of bioactive hormones take place in the rough endoplasmic reticulum and Golgi apparatus, where preprohormones are proteolytically cleaved into prohormones, and subsequently into mature peptide hormones. Once the bioactive hormones are released into the circulation, they interact with receptors located on the plasma membrane of target cells, and initiate intracellular signaling pathways to regulate physiological processes including energy metabolism, growth, stress, and reproduction. However, excessive amount of circulating peptide hormones often associates with the presence of tumors. Section 2 discusses 10 peptide hormones as tumor markers and their clinical application in aiding the diagnosis of tumors as well as monitoring the disease process.
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Affiliation(s)
- Qian Sun
- National Institutes of Health, Bethesda, MD, United States
| | - Zhen Zhao
- National Institutes of Health, Bethesda, MD, United States.
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22
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Chen Y, Deshpande V, Ferrone C, Blaszkowsky LS, Parangi S, Warshaw AL, Lillemoe KD, Fernandez-Del Castillo C. Primary lymph node gastrinoma: A single institution experience. Surgery 2017; 162:1088-1094. [PMID: 28705492 DOI: 10.1016/j.surg.2017.05.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 05/16/2017] [Accepted: 05/21/2017] [Indexed: 01/12/2023]
Abstract
BACKGROUND Gastrinomas are rare neuroendocrine tumors that ectopically secrete gastrin and classically originate within the duodenum or pancreas. The presence of primary lymph node gastrinoma is controversial. We report on a single institution's experience with gastrinoma, with focus on primary lymph node tumors. METHODS Patients who underwent operative resection of gastrinoma between 1992 and 2016 at a single institution were identified. A diagnosis of primary lymph node gastrinoma was defined as tumor confined to one or more resected peripancreatic lymph nodes, negative localization for any extra-nodal disease and normal gastrin postresection. RESULTS In the study, 39 consecutive patients underwent operative resection of gastrinoma. Mean age was 53 years and 49% were male. 93% of patients had successful preoperative localization. Furthermore, 19 patients (49%) underwent enucleation of their tumor and 14 (35.9%) a pancreatic resection. Overall 5- and 10-year survival for all patients was 80.8% and 60.7%, respectively. Primary lymph node gastrinoma was identified in 11 cases (28.2%). The presentation of primary lymph node and non-primary lymph node patients were similar. There was no significant difference in operation type, tumor size, or overall survival. At median follow-up of 59 months, patients with primary lymph node gastrinoma were less likely to have persistent or recurrent disease (9.1% vs 42.9%, P = .04). CONCLUSION This series supports the existence of primary lymph node gastrinomas, and indicates that as many as 1 in 4 patients with gastrinoma have this form of the disease. This entity should be considered when an isolated pathologic lymph node is identified, although thorough exploration is still recommended to exclude other occult disease.
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Affiliation(s)
- Yufei Chen
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Vikram Deshpande
- Department of Pathology, Massachusetts General Hospital, Boston, MA
| | - Cristina Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | | | - Sareh Parangi
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Andrew L Warshaw
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Boston, MA
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Abstract
Pancreatic neuroendocrine tumors (PNETs) are a rare, heterogeneous group of neoplasms infamous for their endocrinopathies. Up to 90% of PNETs, however, are nonfunctional and are frequently detected incidentally on axial imaging during the evaluation of vague abdominal symptoms. Surgery remains the mainstay of therapy for patients diagnosed with both functional and nonfunctional PNETs. However, the multifaceted nature of PNETs challenges treatment decision making. In general, resection is recommended for patients with acceptable perioperative risk and amenable lesions.
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Affiliation(s)
- Jason B Liu
- Department of Surgery, University of Chicago Hospitals, Chicago, IL, USA
| | - Marshall S Baker
- Department of Surgery, University of Chicago Hospitals, Chicago, IL, USA; Division of Surgical Oncology, Department of Surgery, NorthShore University Health System, Evanston, IL, USA.
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24
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Twerdahl EH, Costantino CL, Ferrone CR, Hodin RA. Primary Hepatic Gastrinoma. J Gastrointest Surg 2016; 20:662-3. [PMID: 26556475 DOI: 10.1007/s11605-015-3015-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 10/29/2015] [Indexed: 01/31/2023]
Affiliation(s)
- Eric H Twerdahl
- Division of General and Gastrointestinal Surgery, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA
| | - Christina L Costantino
- Division of General and Gastrointestinal Surgery, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA
| | - Cristina R Ferrone
- Division of General and Gastrointestinal Surgery, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA
| | - Richard A Hodin
- Division of General and Gastrointestinal Surgery, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
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25
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Anderson CW, Bennett JJ. Clinical Presentation and Diagnosis of Pancreatic Neuroendocrine Tumors. Surg Oncol Clin N Am 2016; 25:363-74. [PMID: 27013370 DOI: 10.1016/j.soc.2015.12.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Pancreatic neuroendocrine tumors are a rare group of neoplasms that arise from multipotent stem cells in the pancreatic ductal epithelium. Although they comprise only 1% to 2% of pancreatic neoplasms, their incidence is increasing. Most pancreatic neuroendocrine tumors are nonfunctioning, but they can secrete various hormones resulting in unique clinical syndromes. Clinicians must be aware of the diverse manifestations of this disease, as the key step to management of these rare tumors is to first suspect the diagnosis.
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Affiliation(s)
- Carinne W Anderson
- Department of Surgery, Helen F. Graham Cancer Center, 4701 Ogletown-Stanton Road, S-4000, Newark, DE 19713, USA.
| | - Joseph J Bennett
- Department of Surgery, Helen F. Graham Cancer Center, 4701 Ogletown-Stanton Road, S-4000, Newark, DE 19713, USA
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26
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Abstract
Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors with a range of clinical behavior. Some PNETs are associated with symptoms of hormone secretion, with increased systemic levels of insulin, gastrin, glucagon, or other hormones. More commonly, PNETs are nonfunctional, without hormone secretion. Surgical resection is the mainstay of therapy, particularly for localized disease. Surgical therapy must be tailored to tumor and clinical characteristics. Resection may be particularly indicated in the setting of hormone hypersecretion. Small, incidental PNETs are increasingly managed nonoperatively. Surgery may also be indicated in some instances of metastatic disease, if all metastatic foci may be removed.
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Affiliation(s)
- Thomas E Clancy
- Division of Surgical Oncology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
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27
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[Large gastric folds: Differential diagnosis]. Med Clin (Barc) 2015; 144:470-4. [PMID: 25577581 DOI: 10.1016/j.medcli.2014.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 11/20/2014] [Indexed: 11/23/2022]
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28
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Hall NC, Nichols SD, Povoski SP, James IAO, Wright CL, Harris R, Schmidt CR, Muscarella P, Latchana N, Martin EW, Ellison EC. Intraoperative Use of a Portable Large Field of View Gamma Camera and Handheld Gamma Detection Probe for Radioguided Localization and Prediction of Complete Surgical Resection of Gastrinoma: Proof of Concept. J Am Coll Surg 2015. [PMID: 26206636 DOI: 10.1016/j.jamcollsurg.2015.03.047] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Surgical management of Zollinger-Ellison syndrome (ZES) relies on localization and resection of all tumor foci. We describe the benefit of combined intraoperative use of a portable large field of view gamma camera (LFOVGC) and a handheld gamma detection probe (HGDP) for indium-111 ((111)In)-pentetreotide radioguided localization and confirmation of gastrinoma resection in ZES. STUDY DESIGN Five patients (6 cases) with (111)In-pentetreotide-avid ZES were evaluated. Patients were injected with (111)In-pentetreotide for diagnostic imaging the day before surgery. Intraoperatively, an HGDP and LFOVGC were used to localize (111)In-pentetreotide-avid lesions, guide resection, assess specimens for (111)In-pentetreotide activity, and to verify lack of abnormal post-resection surgical field activity. RESULTS Large field of view gamma camera imaging and HGDP-assisted detection were helpful for localization and guided resection of tumor and removal of (111)In-pentetreotide-avid tumor foci in all cases. In 3 of 5 patients (3 of 6 cases), these techniques led to detection and resection of additional tumor foci beyond those detected by standard surgical techniques. The (111)In-pentetreotide-positive or-negative specimens correlated with neuroendocrine tumors or benign pathology, respectively. In one patient with mild residual focal activity on post-resection portable LFOVGC imaging, thought to be artifact, had recurrence of disease in the same area 5 months after surgery. CONCLUSIONS Real-time LFOVGC imaging and HGDP use for surgical management of gastrinoma improve success of localizing and resecting all neuroendocrine tumor-positive tumor foci, providing instantaneous navigational feedback. This approach holds potential for improving long-term patient outcomes in patients with ZES.
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Affiliation(s)
- Nathan C Hall
- Department of Radiology, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH; Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA.
| | - Shawnn D Nichols
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH; Department of Surgery, San Antonio Military Medical Center, Fort Sam Houston, TX
| | - Stephen P Povoski
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Iyore A O James
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Chadwick L Wright
- Department of Radiology, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Randall Harris
- Division of Epidemiology, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Carl R Schmidt
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Peter Muscarella
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Nicholas Latchana
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Edward W Martin
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - E Christopher Ellison
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
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Doi R. Determinants of surgical resection for pancreatic neuroendocrine tumors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:610-7. [PMID: 25773163 DOI: 10.1002/jhbp.224] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 01/14/2015] [Indexed: 12/14/2022]
Abstract
Pancreatic neuroendocrine tumors (pNETs) include functioning and non-functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger-Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40-60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non-functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non-functioning pNETs should be operated on aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk-benefit ratio should be carefully weighted. Surgical liver resection is generally proposed in curative intent to all patients with operable metastases from G1 or G2 pNET. The benefits of surgical resection of liver metastases have been demonstrated in terms of overall survival and quality of life. Complete resection is associated with better long-term survival.
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Affiliation(s)
- Ryuichiro Doi
- Department of Surgery, Otsu Red Cross Hospital, 1-1-35 Nagara, Otsu, Shiga, 520-8511, Japan
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Grozinsky-Glasberg S, Mazeh H, Gross DJ. Clinical features of pancreatic neuroendocrine tumors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:578-85. [DOI: 10.1002/jhbp.226] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 01/14/2015] [Indexed: 12/18/2022]
Affiliation(s)
- Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Department of Medicine; Hadassah-Hebrew University Medical Center; P.O.B. 12000 Jerusalem 91120 Israel
| | - Haggi Mazeh
- Department of Surgery; Hadassah-Hebrew University Medical Center; Jerusalem Israel
| | - David J. Gross
- Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Department of Medicine; Hadassah-Hebrew University Medical Center; P.O.B. 12000 Jerusalem 91120 Israel
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Eyal A, Sueissa A, Braun E, Naffaa ME. From hypomagnesaemia to Zollinger-Ellison syndrome: an adverse effect of a proton pump inhibitor. BMJ Case Rep 2014; 2014:bcr-2014-205165. [PMID: 25274557 DOI: 10.1136/bcr-2014-205165] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
We describe the case of a 53-year-old man who presented with abdominal pain, diarrhoea and hypomagnesaemia. The hypomagnesaemia proved to be due to gastrointestinal loss as urinary fractional excretion was very low, suggesting non-renal loss. Common causes were discarded and the hypomagnesaemia was attributed to chronic use of the proton pump inhibitor, omeprazole. As such, omeprazole was discontinued and an H2 blocker was given. Several days later the patient presented with upper gastrointestinal bleeding. CT scan demonstrated marked enlargement of the duodenum and proximal jejunum, and abnormal thickening and enhancement of the bowel wall. Urgent oesophagogastroduodenoscopy revealed coffee-ground and bloody contents in the distal oesophagus and stomach, and numerous ulcers along the duodenum and jejunum. A positron emission tomography-CT scan using GA 68-DOTANOC demonstrated increased uptake in the gastroduodenum junction, suggesting a neuroendocrine tumour. Pancreaticoduodenectomy was performed and tumour cells stained positive for gastrin, confirming the tentative diagnosis of Zollinger-Ellison syndrome.
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Affiliation(s)
- Allon Eyal
- Department of Internal Medicine H, Rambam Health Care Campus, Haifa, Israel
| | - Alain Sueissa
- Gastroenterology Institute, Rambam Health Care Campus, Haifa, Israel
| | - Eyal Braun
- Infectious Diseases Unit and Internal Medicine H, Rambam Health Care Campus and the Rappaport's Faculty of Medicine, Technion, Haifa, Israel
| | - Mohammad Ebrahim Naffaa
- The B. Shine Rheumatology Unit and Internal Medicine H, Rambam Health Care Campus and the Rappaport's Faculty of Medicine, Technion, Haifa, Israel
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Grimaldi F, Fazio N, Attanasio R, Frasoldati A, Papini E, Angelini F, Baldelli R, Berretti D, Bianchetti S, Bizzarri G, Caputo M, Castello R, Cremonini N, Crescenzi A, Davì MV, D’Elia AV, Faggiano A, Pizzolitto S, Versari A, Zini M, Rindi G, Öberg K. Italian Association of Clinical Endocrinologists (AME) position statement: a stepwise clinical approach to the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. J Endocrinol Invest 2014; 37:875-909. [PMID: 25038902 PMCID: PMC4159596 DOI: 10.1007/s40618-014-0119-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 03/29/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Franco Grimaldi
- Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, P.le S.M. della Misericordia, 15-33100, Udine, Italy
| | - Nicola Fazio
- Unit of Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy
| | | | - Andrea Frasoldati
- Endocrinology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
| | - Enrico Papini
- Endocrinology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Francesco Angelini
- Oncology and Hematology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Roberto Baldelli
- Endocrinology Section, Regina Elena National Cancer Institute, Rome, Italy
| | - Debora Berretti
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy
| | - Sara Bianchetti
- Oncology and Hematology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Giancarlo Bizzarri
- Diagnostic Imaging Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Marco Caputo
- Dipartimento Servizi di Diagnosi e Cura, AUSL 22 Regione Veneto, Bussolengo, VR Italy
| | - Roberto Castello
- Medicina Interna ad indirizzo Endocrinologico, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Nadia Cremonini
- Endocrinology Unit, Maggiore and Bellaria Hospital, Bologna, Italy
| | - Anna Crescenzi
- Pathology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Maria Vittoria Davì
- Medicina Interna D, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Angela Valentina D’Elia
- Genetic Service, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy
| | - Antongiulio Faggiano
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Stefano Pizzolitto
- Pathology Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy
| | - Annibale Versari
- Nuclear Medicine Service, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
| | - Michele Zini
- Endocrinology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
| | - Guido Rindi
- Institute of Pathology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Kjell Öberg
- Department of Endocrine Oncology, University Hospital, Uppsala, Sweden
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Abstract
Metastatic neuroendocrine tumors of childhood are extremely rare, and as such present diagnostic and therapeutic challenges. Here, we report a case of gastrinoma with extensive hepatic metastases in a pediatric patient with Zollinger-Ellison Syndrome who underwent orthotopic liver transplant followed by cytotoxic chemotherapy, somatostatin analog therapy, and immune modulation.
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Abstract
Zollinger-Ellison syndrome (ZES) is an endocrinopathy characterized by gastrin-secreting tumors, responsible for causing the formation of multiple, refractory, and recurrent peptic ulcers in the distal duodenum and proximal jejunum. Two main variants have been described, sporadic and those found in association with parathyroid and pituitary tumors, a genetic disorder known as multiple endocrine neoplasia-1 (MEN-1). Biochemical serum evaluation for elevated gastrin, followed by radiological or nuclear localization of the primary lesion, is mandated for establishing diagnosis. The mainstays of treatment include management of hypersecretory state with medical suppression of gastric acid production and surgical resection of primary tumor for the prevention of malignant transformation and metastatic complications. Medical therapy with proton pump inhibitors has virtually eliminated the need for acid-reducing surgical procedures. Surgical approach to sporadic and MEN-1-associated ZES varies based on our understanding of the natural history of the condition and the probability of cure; however, resection to a negative microscopic margin is indicated in both cases. Postoperative surveillance involves measurement of gastrin level, followed by imaging if elevation is detected. Re-excision of recurrent or resection of metastatic disease is a subject of controversy; however, at the present time aggressive cytoreductive approach is favored.
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Affiliation(s)
- Irene Epelboym
- Department of Surgery, Columbia University Medical Center, New York, New York, USA; Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel
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Abstract
PURPOSE OF REVIEW To review the recent advances and current controversies in patients with Zollinger-Ellison syndrome (ZES). RECENT FINDINGS Recent advances in the management of ZES include: improved understanding of the pathogenesis of gastrinoma and pancreatic neuroendocrine tumors, new prognostic classification systems, new diagnostic algorithms, more sensitive localization studies, new treatment strategies including improved control of gastric acid secretion and role for surgery, and new approaches to patients with advanced disease. Controversies include: the best approach to a patient with hypergastrinemia suspected of possibly having ZES, the appropriate gastrin assay to use, the role of surgery in patients with ZES, especially those with multiple endocrine neoplasia type 1, and the precise order of therapeutic modalities in the treatment of patients with advanced disease. SUMMARY This review updates clinicians regarding important advances and controversies required to optimally diagnose and manage patients with ZES.
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Affiliation(s)
- Tetsuhide Ito
- aDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan bDigestive Diseases Branch, NIDDK, NIH, Bethesda, Maryland, USA
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Abstract
BACKGROUND Scant data exist on the normal range of serum gastrin in infants. In phase I and III trials of rabeprazole in gastroesophageal reflux disease, we studied serum gastrin levels in infants 1 to 11 months old, and assessed normal ranges and the effect of acid-suppressive drugs. METHODS Overall, 349 treatment-naïve or treatment-experienced (previously exposed to proton pump inhibitors and/or H2-receptor antagonists) infants with gastroesophageal reflux disease were screened for baseline serum gastrin. Repeat gastrin was monitored at early termination or end of study, allowing assessment of 1 to 8 week daily rabeprazole (5- or 10-mg) treatment on gastrin levels. RESULTS Median (5%-95% range) baseline gastrin was 118 ng/L (39-315) in the treatment-naïve group (n = 251), driven mostly by high levels (121.5 [48-326] ng/L) in the 1- to <4-month-old subgroup. Treatment-experienced infants (n = 98) had elevated baseline gastrin levels (152 [48-487] ng/L; P = 0.0011) with no clear difference between previously proton pump inhibitor-exposed and H2-receptor antagonist-exposed groups. At the end of study, mean (standard deviation) levels were unchanged from baseline in infants withdrawn from rabeprazole to placebo (124 [94] ng/L), but elevated from baseline in those continuing treatment with 5-mg (245 [151] ng/L) and 10-mg (332 [222] ng/L) rabeprazole during the study. CONCLUSIONS Gastrin levels in treatment-naïve infants were elevated through 8 months of age. Between 8 and 12 months of age, they declined so that the median level was within the upper limit of the normal adult range (<100 ng/L). Previous exposure to acid-suppressive medications and short-term exposure to rabeprazole significantly increased gastrin levels in infants younger than 1 year.
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Biolato M, Alfieri S, Ianiro G, Pizzoferrato M, Gasbarrini G. Gastric non-secreting neuroendocrine tumor and hypochlorhydria-related hypergastrinemia: a case report. J Med Case Rep 2013; 7:53. [PMID: 23432909 PMCID: PMC3599386 DOI: 10.1186/1752-1947-7-53] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2012] [Accepted: 11/08/2012] [Indexed: 11/10/2022] Open
Abstract
Introduction Zollinger–Ellison syndrome is characterized by recurrent peptic ulcers and diarrhea that result from gastrin-secreting neuroendocrine tumors of the gastrointestinal tract; nevertheless, severe hypergastrinemia may also have alternative pathogenetic explanations. Case presentation A 61-year-old woman of Caucasian origin presented with a history of epigastric pain and early satiety, severe hypergastrinemia (approximately 2000 pg/mL) and a neuroendocrine polyp in the corpus of her stomach. Chronic atrophic gastritis and intestinal metaplasia was present, but she denied use of acid suppressant drugs and the results of tests for Helicobacter pylori as well as gastric parietal cell and intrinsic factor antibodies were negative. She underwent a radical gastric tangential resection. Six months later, serum gastrin was still elevated despite lack of recurrence of tumor. Conclusion The clinical picture was suggestive for a hypochlorhydria-related hypergastrinemia with subsequent development of a non-secreting carcinoid. We suggest a periodic endoscopic follow-up in patients with severe hypochlorhydria-related hypergastrinemia in order to earlier detect neuroendocrine polyps.
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Affiliation(s)
- Marco Biolato
- Fondazione Ricerca in Medicina ONLUS, Galleria Falcone e Borsellino 2, Bologna 40123, Italy.
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Giovinazzo F, Butturini G, Monsellato D, Malleo G, Marchegiani G, Bassi C. Lymph nodes metastasis and recurrences justify an aggressive treatment of gastrinoma. Updates Surg 2013; 65:19-24. [PMID: 23417896 DOI: 10.1007/s13304-013-0201-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Accepted: 01/30/2013] [Indexed: 01/26/2023]
Abstract
In the current study, short- and long-term outcomes after aggressive surgical treatment for gastrinoma were evaluated. From August 1990 to August 2009, 20 patients diagnosed with Zollinger Ellison syndrome were reviewed. Eleven pancreaticoduodenectomies, three total pancreatectomies, four lymph node dissections, four enucleations and two palliative procedures were performed. Four (27.8 %) patients had disease associated with MEN1 syndrome, 13 (72.2 %) had sporadic gastrinomas (SG) and 3 had disease of unknown primary origin. No in-hospital mortality was observed. After radical resection, lymph node metastasis was present in 82 % of the cases. Eight percent of patients who underwent radical resection developed recurrence compared with 100 % of those who underwent enucleoresection (p = 0.03). Average time to recurrence in patients with sporadic gastrinoma was 66.7 months (confidence interval (CI) 62.9-70.5) in those treated with enucloeresection compared to 181.1 months (CI 124.3-237.8) in the radical resection group (p = 0.007). One recurrence was observed in the MEN1 group. Based on post-operative mortality, recurrence and lymph node metastasis, our data suggest that patients with gastrinoma should undergo abdominal exploration with aggressive resection of the primary tumour and regional lymph nodes in place of conservative treatment.
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Trout AT, Dillman JR, Neef HC, Rabah R, Gadepalli S, Geiger JD. Case 189: Pediatric Ménétrier disease. Radiology 2013; 266:357-61. [PMID: 23264528 DOI: 10.1148/radiol.12111841] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Andrew T Trout
- Department of Radiology, Section of Pediatric Radiology, C.S. Mott Children's Hospital, University of Michigan Medical Center, Ann Arbor, Mich, USA
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Abstract
INTRODUCTION The role of pharmacotherapy in the management of patients with Zollinger-Ellison syndrome (ZES) is often equated with the medical management of acid hypersecretion. However, pharmacotherapy is also increasingly involved in the other management areas of these patients. AREAS COVERED This paper reviews the role of pharmacotherapy in all aspects of the management of patients with ZES. Newer aspects are emphasized. This includes the difficulty of diagnosing ZES in patients taking proton pump inhibitors. Also covered is the role of pharmacotherapy in controlling acid hypersecretion and other hormonal hypersecretory states these patients may develop, including hyperparathyroidism in patients with multiple endocrine neoplasia type 1 and ZES; tumor localization; and the treatment of advanced metastatic disease. The last includes chemotherapy, liver-directed therapies, biotherapy (somatostatin/interferon), peptide radio-receptor therapy and molecular-targeted therapies including the use of mTor inhibitors (everolimus) and tyrosine kinase inhibitors (sunitinib). EXPERT OPINION Pharmacotherapy is now involved in all aspects of the management of patients with ZES, with the result that ZES has progressed from being considered an entirely surgical disease initially to the present where medical treatment plays a major role in almost all aspects of the management of these patients.
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Affiliation(s)
- Tetsuhide Ito
- Kyushu University, Graduate School of Medical Sciences, Department of Medicine and Bioregulatory Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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Ito T, Cadiot G, Jensen RT. Diagnosis of Zollinger-Ellison syndrome: increasingly difficult. World J Gastroenterol 2012; 18:5495-5503. [PMID: 23112541 PMCID: PMC3482635 DOI: 10.3748/wjg.v18.i39.5495] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Revised: 08/03/2012] [Accepted: 09/12/2012] [Indexed: 02/06/2023] Open
Abstract
In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the perspective of clinical management.
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Naoe H, Iwasaki H, Kawasaki T, Ozaki T, Tsutsumi H, Okuda A, Konoe T, Nonaka K, Kaku E, Shono T, Yokomine K, Sakurai K, Iyama KI, Hirota M, Sasaki Y. Primary hepatic gastrinoma as an unusual manifestation of zollinger-ellison syndrome. Case Rep Gastroenterol 2012; 6:590-5. [PMID: 23271988 PMCID: PMC3529581 DOI: 10.1159/000343157] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
We report a rare case of primary hepatic gastrinoma. A 77-year-old woman exhibited continuous watery diarrhea for 8 months and weight loss. Bacterial cultures of the stools were negative and colonoscopy revealed no abnormalities. Esophagogastroduodenoscopy showed severe reflux esophagitis and multiple duodenal erosions. Computed tomography and magnetic resonance imaging detected two solid masses measuring <2 cm in diameter in the right lobe of the non-cirrhotic liver. Microscopically, the tumor was consistent with neuroendocrine tumor (grade 2) with abundant gastrin-immunoreactive cells. Endoscopic ultrasound detected no other alternative primary source of an endocrine tumor. The serum gastrin levels exceeded 40,000 pg/ml in the absence of H2 receptor antagonist and proton pump inhibitor administrations. Based on an arterial stimulation and venous sampling test, the patient was diagnosed as primary gastrinoma of the liver. Our findings demonstrated the presence of Zollinger-Ellison syndrome in a patient who was subsequently cured by surgical resection of the liver tumors.
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Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P, Scoazec JY, Salazar R, Sauvanet A, Kianmanesh R. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology 2012; 95:98-119. [PMID: 22261919 PMCID: PMC3701449 DOI: 10.1159/000335591] [Citation(s) in RCA: 369] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Zollinger-Ellison syndrome associated with a history of alcohol abuse: coincidence or consequence? Surgery 2012; 150:1129-35. [PMID: 22136832 DOI: 10.1016/j.surg.2011.09.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2011] [Accepted: 09/13/2011] [Indexed: 01/21/2023]
Abstract
BACKGROUND This 47-year observational study suggests that sporadic Zollinger-Ellison (Z-E) syndrome, particularly duodenal wall gastrinomas (DWG), is associated with a history of alcohol abuse. METHODS Thirty-nine consecutive Z-E patients were followed from 1962 through 2010. The drinking patterns of these patients were assessed and compared with 3,786 community controls. RESULTS Thirty-five patients had extrapancreatic gastrinomas (34 DWG and/or paraduodenal lymph nodes, 1 antral gastrinoma). Total gastrectomy was done in 24; 9 underwent less extensive operations to remove DWG, and 2 patients had no operations. There were no deaths from tumor progression. Four patients presented with pancreatic gastrinoma (PG) and liver metastasis, all died from tumor progression. Alcohol abuse (>50 g/d) was documented in 81% of patients with DWG and/or paraduodenal lymph nodes. The drinking patterns (drinks per day) of DWG patients were significantly different: DWG vs community control-abstainers, 3% vs 24%; 1-2 drinks, 16% vs 62%; 3-5 drinks, 29% vs 12%; and ≥ 6 drinks, 52% vs 2.5% (P < .01). CONCLUSION Alcohol abuse is strongly associated with and may be a risk factor for sporadic Z-E with extrapancreatic DWG. Liver metastases and tumor deaths were not observed in this subgroup, supporting the concept that DWG and PG are different tumor entities.
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Poitras P, Gingras MH, Rehfeld JF. The Zollinger-Ellison syndrome: dangers and consequences of interrupting antisecretory treatment. Clin Gastroenterol Hepatol 2012; 10:199-202. [PMID: 21871248 DOI: 10.1016/j.cgh.2011.08.012] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2011] [Revised: 08/11/2011] [Accepted: 08/18/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with Zollinger-Ellison syndrome (ZES) are treated by proton pump inhibitors (PPIs) to protect them from severe and potentially lethal peptic complications related to massive gastric acid hypersecretion. We report here on the dangerous consequences of interrupting PPI therapy. METHODS We describe 2 ZES patients in whom interruption of PPI treatment for diagnostic evaluation generated severe health complications. RESULTS Less than 48 hours after stopping PPIs, patient 1 developed multiple strictures of the esophagus caused by massive vomiting of gastric acid, and patient 2 presented with severe abdominal pain with intestinal microperforation from duodenal ulcers. Because of persistent gastrin stimulatory drive and because of the abolition of reflex protective defense mechanisms against gastric acid hypersecretion during PPI treatment, patients with ZES under PPI therapy are exposed to severe peptic complications when facing rebound acid secretion at the interruption of their antisecretory treatment. CONCLUSIONS PPI treatment interruption has dangerous consequences, and PPI therapy always should be maintained in patients known or suspected of ZES. Diagnostic evaluations should be performed under PPI protection.
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Affiliation(s)
- Pierre Poitras
- Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, Montréal, Québec, Canada.
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Nazir Z. Long-term follow-up of a child with primary lymph node gastrinoma and Zollinger-Ellison syndrome. J Pediatr Surg 2011; 46:969-72. [PMID: 21616263 DOI: 10.1016/j.jpedsurg.2011.02.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2010] [Revised: 02/04/2011] [Accepted: 02/04/2011] [Indexed: 12/19/2022]
Abstract
A 10-year-old child with Zollinger-Ellison syndrome and primary lymph node gastrinoma is reported to emphasize the difficulties encountered in management and the value of long-term follow-up. The gastrinoma was present in a lymph node close to the greater curvature of the stomach. Primary lymph node gastrinomas are relatively rare in children and, to the best of our knowledge, have not previously been reported at this location.
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Affiliation(s)
- Zafar Nazir
- Section of Pediatric Surgery, Department of surgery, The Aga Khan University Hospital, Karachi 74800, Pakistan.
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Chang FY, Liao KY, Wu L, Lin SP, Lai YT, Liu CS, Tsay SH, Wu TC. An uncommon cause of abdominal pain and diarrhea-gastrinoma in an adolescent. Eur J Pediatr 2010; 169:355-7. [PMID: 19565263 DOI: 10.1007/s00431-009-1013-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2009] [Accepted: 06/09/2009] [Indexed: 01/20/2023]
Abstract
Gastrinoma is a hormone-secreting tumor associated with the Zollinger-Ellison syndrome. It is quite rare among children, and it is also uncommon in locations other than the pancreas and the duodenum in the pediatric group. Here, we describe an adolescent male, presenting with recurrent secretory diarrhea and abdominal cramping pain, who had a solitary gastrinoma in the lesser sac, close to the stomach. The prognosis was good after complete resection.
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Affiliation(s)
- Fang-Yuan Chang
- Division of Gastroenterology, Children's Medical Center, Taipei Veterans General Hospital, 201 Shih-Pai Road Section 2, Taipei 11217, Taiwan
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Abstract
It is clear that a properly performed initial operation is the key to success in the management of a patient with ZES. However, reoperation is frequently a consideration in the management of patients with ZES because high rates of persistent and recurrent disease are manifest even with modern imaging and surgical approaches. In carefully selected patients, reoperation can result in durable biochemical cure and improved survival and should be considered. A thorough knowledge of the natural history of the sporadic form of ZES and ZES in the context of MEN-1, patterns of presentation, and sites of metastases are necessary to achieve the best outcome in patients with this unusual disease.
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Affiliation(s)
- Stephen R Grobmyer
- Division of Surgical Oncology, Department of Surgery, University of Florida, 1600 SW Archer Road, Room 6165, P.O. Box 100109, Gainesville, FL 32610, USA.
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Osefo N, Ito T, Jensen RT. Gastric acid hypersecretory states: recent insights and advances. Curr Gastroenterol Rep 2009; 11:433-441. [PMID: 19903418 PMCID: PMC2792981 DOI: 10.1007/s11894-009-0067-6] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Gastric acid hypersecretory states are characterized by basal hypersecretion of gastric acid and historically include disorders associated with hypergastrinemia, hyperhistaminemia, and those of unknown etiology. Although gastric acid secretion is infrequently measured, it is important to recognize the role of gastric hypersecretion in the symptoms of these disorders because they share several features of pathogenesis and treatment. In this article, recent important articles reporting insights into their diagnosis, pathogenesis, and treatment are reviewed. Particular attention is paid to Zollinger-Ellison syndrome, because it has the most extreme acid hypersecretion of this group of disorders and because numerous recent articles deal with various aspects of the diagnosis, molecular pathogenesis, and treatment of the gastrinoma itself or the acid hypersecretion. Two new hypersecretory disorders are reviewed: rebound acid hypersecretion after the use of proton pump inhibitors and acid hypersecretion with cysteamine treatment in children with cystinosis.
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Affiliation(s)
- Nauramy Osefo
- Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9C-103, Bethesda, MD 20892, USA
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Abstract
Refractory PUD is a diagnostic and therapeutic challenge. Optimal management of severe or refractory PUD requires a multidisciplinary team approach, using primary care providers, gastroenterologists, and general surgeons. Medical management has become the cornerstone of therapy. Identification and eradication of H pylori infection combined with acid reduction regimens can heal ulceration and also prevent recurrence. Severe, intractable or recurrent PUD and associated complications mandates a careful and methodical evaluation and management strategy to determine the potential etiologies and necessary treatment (medical or surgical) required.
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Affiliation(s)
- Lena Napolitano
- Department of Surgery, University of Michigan Health System, University of Michigan School of Medicine, Room 1C421, University Hospital, 1500 East Medical Drive, Ann Arbor, MI 48109-0033, USA.
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