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Zhu L, Liu Y, Chen S, Yang G, Wang C. Extremely rare mucinous adenocarcinoma of the small bowel causing bilateral metastatic Kukenberg tumors of the ovaries: A case report. Medicine (Baltimore) 2024; 103:e40397. [PMID: 39496016 PMCID: PMC11537637 DOI: 10.1097/md.0000000000040397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 10/17/2024] [Indexed: 11/06/2024] Open
Abstract
RATIONALE Small bowel adenocarcinoma (SBA) is an extremely rare tumor that is not fully understood, SBA accounts for less than 5% of gastrointestinal cancers, Krukenberg tumors account for a lower proportion of all ovarian tumors, close to 2%. Stomach is the most common primary site of Krukenberg tumor. The phenomenon of bilateral ovarian Kukenberg tumor caused by implantation and metastasis of small bowel cancer is extremely rare, with few literature reports and limited clinical diagnosis and treatment data. We present a case of a 55-year-old woman with bilateral Kukenberg's tumor caused by small bowel cancer implantation and share our views on the diagnosis and treatment of this case. PATIENT CONCERNS A 55-year-old woman presented with vaginal bleeding and persistent lower abdominal pain after fatigue 10 days ago. Pelvic ultrasound at a local hospital revealed 2 solid masses in her pelvis, and she came to our hospital for further diagnosis and treatment. The results of colonofiberscope examination and histopathological examination confirmed intramucosal adenocarcinoma in the small intestine. DIAGNOSES The results of colonofiberscope examination and histopathological examination confirmed intramucosal adenocarcinoma in the small intestine. Contrast-enhanced computed tomography showed multiple cystic space-occupying lesions in the pelvic cavity, and the possibility of ovarian tumor was considered. INTERVENTIONS Radical treatment of right half colon cancer and pelvic mass resection were performed under general anesthesia. Combined with intraoperative and postoperative pathological examination, the diagnosis was mucinous adenocarcinoma of the small intestine stage IV (pT4N1M1). Bilateral ovarian metastasis, metastatic cancer (3/19): lymph nodes around the small intestine (3/12), lymph nodes around the colon (0/7). OUTCOMES He is currently receiving chemotherapy, the chemotherapy regimen is XELOX regimen. The specific drugs were oxaliplatin and capecitabine. LESSONS SBA is often difficult to diagnose due to few specific symptoms and is usually detected at stage IV. Bilateral ovarian Kukenberg tumor caused by small bowel cancer implantation metastases is extremely rare, and clinicians must be vigilant for women with fewer specific symptoms of gastrointestinal discomfort and conduct further diagnostic studies to avoid delayed diagnosis and treatment.
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Affiliation(s)
- Lichao Zhu
- Affiliated Hospital of North China University of Science and Technology, Gastrointestinal Oncology Treatment Center, Tangshan, Hebei, China
| | - Ye Liu
- Affiliated Hospital of North China University of Science and Technology, Breast Disease Treatment Center, Tangshan, Hebei, China
| | - Shuai Chen
- Affiliated Hospital of North China University of Science and Technology, Gastrointestinal Oncology Treatment Center, Tangshan, Hebei, China
| | - Guanghua Yang
- Affiliated Hospital of North China University of Science and Technology, Gastrointestinal Oncology Treatment Center, Tangshan, Hebei, China
| | - Changyou Wang
- Affiliated Hospital of North China University of Science and Technology, Gastrointestinal Oncology Treatment Center, Tangshan, Hebei, China
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Nakasone ES, Bustillos HC, Gui X, Konnick EQ, Sham JG, Cohen SA. Multidisciplinary Approach for the Management of Metastatic Poorly Differentiated Neuroendocrine Carcinoma of the Pancreas: A Case Report of an Exceptional Responder. Pancreas 2024; 53:e487-e491. [PMID: 38460151 DOI: 10.1097/mpa.0000000000002322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/11/2024]
Abstract
ABSTRACT Poorly differentiated pancreatic neuroendocrine carcinomas (pNECs) are rare, highly aggressive neoplasms. Frequently metastatic at diagnosis, prognosis is poor with median overall survival estimated to be less than 1 year. Although multidisciplinary management, including systemic medications and locoregional therapies aimed at reducing and preventing symptoms caused by mass effect, is the mainstay of treatment for patients with metastatic well-differentiated pancreatic neuroendocrine tumors, rapid progression, organ dysfunction, and poor performance status often preclude initiation of even single-modality palliative chemotherapy for patients with metastatic pNEC, limiting the use of and recommendation for multidisciplinary management.We describe the case of a 51-year-old male patient diagnosed with pNEC metastatic to liver and lymph nodes presenting with impending cholestatic liver failure for whom we were able to successfully initiate and dose-escalate cytotoxic chemotherapy with excellent radiographic response. After multidisciplinary review of his case, the patient underwent pancreaticoduodenectomy and hepatic wedge biopsies, with pathology demonstrating a pathologic complete response to chemotherapy in both the pancreas and liver. Surveillance scans at 2 years from initial diagnosis and 1 year from surgery remain without evidence of locoregional or distant recurrence, highlighting the importance and utility of multidisciplinary management in select cases.
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Affiliation(s)
| | - Hannah C Bustillos
- Clinical Pharmacy, University of Washington/Fred Hutchinson Cancer Center
| | - Xianyong Gui
- Departments of Laboratory Medicine and Pathology
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Jacques V, Dierickx L, Texier JS, Brillouet S, Courbon F, Guimbaud R, Vija L, Savagner F. Evaluation of a blood miRNA/mRNA signature to follow-up Lu-PRRT therapy for G1/G2 intestinal neuroendocrine tumors. Front Endocrinol (Lausanne) 2024; 15:1385079. [PMID: 38948517 PMCID: PMC11212830 DOI: 10.3389/fendo.2024.1385079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 05/21/2024] [Indexed: 07/02/2024] Open
Abstract
Background 177Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy. Methods Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT. Results Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year (p < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level (p < 0.05) for patients with progressive disease. Conclusion We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients.
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Affiliation(s)
- Virginie Jacques
- Biochemistry Laboratory, Federative Institute of Biology, Academic Hospital, Toulouse, France
- Inserm UMR1297, Institute of Cardiovascular and Metabolic Diseases, Toulouse, France
- Faculté de Santé, University Paul sabatier, Toulouse, France
| | - Lawrence Dierickx
- Nuclear Medicine Department, Regional Center of Cancer Care Oncopole Claudius Regaud, Toulouse, France
| | - Jean Sebastien Texier
- Nuclear Medicine Department, Regional Center of Cancer Care Oncopole Claudius Regaud, Toulouse, France
| | - Severine Brillouet
- Nuclear Medicine Department, Regional Center of Cancer Care Oncopole Claudius Regaud, Toulouse, France
| | - Frederic Courbon
- Faculté de Santé, University Paul sabatier, Toulouse, France
- Nuclear Medicine Department, Regional Center of Cancer Care Oncopole Claudius Regaud, Toulouse, France
| | - Rosine Guimbaud
- Faculté de Santé, University Paul sabatier, Toulouse, France
- Digestive Oncology Department, Academic Hospital, Toulouse, France
| | - Lavinia Vija
- Faculté de Santé, University Paul sabatier, Toulouse, France
- Nuclear Medicine Department, Regional Center of Cancer Care Oncopole Claudius Regaud, Toulouse, France
| | - Frederique Savagner
- Biochemistry Laboratory, Federative Institute of Biology, Academic Hospital, Toulouse, France
- Inserm UMR1297, Institute of Cardiovascular and Metabolic Diseases, Toulouse, France
- Faculté de Santé, University Paul sabatier, Toulouse, France
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Hinterleitner M, Pfeiffer R, Trautwein NF, Sipos B, Singer S, Nadalin S, Königsrainer A, Lauer UM, la Fougère C, Zender L, Hinterleitner C. Treatment modalities favoring outcome in well-differentiated neuroendocrine tumors G3. Front Endocrinol (Lausanne) 2024; 14:1285529. [PMID: 38260136 PMCID: PMC10800837 DOI: 10.3389/fendo.2023.1285529] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 12/06/2023] [Indexed: 01/24/2024] Open
Abstract
Introduction Neuroendocrine neoplasms (NEN) are a rare and heterogenous group of tumors arising from neuroendocrine cells in multiple organs. Neuroendocrine tumors (NET) G3 encompass a small subgroup accounting for less than 10% of all neuroendocrine neoplasms. In contrast to NET G1 and G2 as well as neuroendocrine carcinomas (NEC), in NET G3 data on treatment and patient outcomes are still limited. Especially in a metastasized tumor stage, the role of surgery, peptide receptor radionucleotide therapy (PRRT), and systemic chemotherapy is not clearly defined. Methods In this real-life cohort, we consecutively analyzed clinical outcome in NET G3 patients receiving different diagnostic and treatment. Results and discussion We found that even metastasized NET G3 patients undergoing surgery, or receiving radiation, somatostatin analogues (SSA), and PRRT showed a clear survival benefit. Interestingly, all treatment regimen were superior to classical chemotherapeutic agents. In addition, somatostatin receptor (SSTR) PET-CT, FDG PET-CT, and repetitive biopsies were shown to be useful diagnostic and prognostic tools in NET G3. Our study demonstrates that patients with highly proliferative NET G3 might benefit from less aggressive treatment modalities commonly used in low proliferative NEN.
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Affiliation(s)
- Martina Hinterleitner
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- German Research Foundation Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, Tuebingen, Germany
| | - Ruben Pfeiffer
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
| | - Nils F. Trautwein
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- Department of Nuclear Medicine and Clinical Molecular Imaging, University Hospital Tuebingen, Tuebingen, Germany
| | - Bence Sipos
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- German Research Foundation Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, Tuebingen, Germany
| | - Stephan Singer
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- Department of Pathology, University Hospital Tuebingen, Tuebingen, Germany
| | - Silvio Nadalin
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- Department of General and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
| | - Alfred Königsrainer
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- Department of General and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany
| | - Ulrich M. Lauer
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- German Research Foundation Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, Tuebingen, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Tuebingen, Germany
| | - Christian la Fougère
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- German Research Foundation Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, Tuebingen, Germany
- Department of Nuclear Medicine and Clinical Molecular Imaging, University Hospital Tuebingen, Tuebingen, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Tuebingen, Germany
| | - Lars Zender
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- German Research Foundation Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, Tuebingen, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Tuebingen, Germany
| | - Clemens Hinterleitner
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Tuebingen, Tuebingen, Germany
- German Research Foundation Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, Tuebingen, Germany
- Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, United States
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Pathak S, Starr JS, Halfdanarson T, Sonbol MB. Understanding the increasing incidence of neuroendocrine tumors. Expert Rev Endocrinol Metab 2023; 18:377-385. [PMID: 37466336 DOI: 10.1080/17446651.2023.2237593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/13/2023] [Indexed: 07/20/2023]
Abstract
INTRODUCTION Neuroendocrine tumors (NETs) are a diverse group of tumors with origins from different primary sites such as gastro-entero-pancreatic, lung and endocrine tissue. Worldwide, their incidence has increased in recent decades. Advances in imaging and better clinical awareness are traditionally attributed to this trend; however, other factors such as genetic and environmental contributors are appreciated as well. AREAS COVERED The purpose of this article is to review the worldwide epidemiologic trends in incidence of NET through the decades and discuss the various factors potentially contributing to the observed changes in incidence trends. EXPERT OPINION Overall, the incidence of NET has increased across the globe over the last few decades. Although multiple genetics and environmental factors have been proposed, the majority of this increase in incidence is secondary to earlier detection. Future studies will help in more accurate assessments and an improved understanding of disease incidence among patients with different grades and differentiation.
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Affiliation(s)
- Surabhi Pathak
- Attending Hematology-Oncology, King's Daughters Medical Center, Ashland, KY, USA
| | - Jason S Starr
- Division of Hematology- Oncology, Mayo Clinic Jacksonville Campus, Jacksonville, FL, USA
| | - Thorvardur Halfdanarson
- Division of Hematology- Oncology, Mayo Clinic, Mayo Clinic Cancer Center, Rochester, MN, USA
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Chen X, Zhou R, Li Y, Qu X, Qu YC, Li WZ, Ye YS, Liu LR, Zhu YJ, Zhang HB. Case report: A case of duodenal adenocarcinoma achieving significantly long survival treating with immune checkpoint inhibitors and chemotherapy without positive biomarkers. Front Immunol 2022; 13:1046513. [PMID: 36531985 PMCID: PMC9755197 DOI: 10.3389/fimmu.2022.1046513] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/22/2022] [Indexed: 12/04/2022] Open
Abstract
Small bowel adenocarcinoma (SBA), particularly duodenal adenocarcinoma (DA), is a rare gastrointestinal cancer with a dismal prognosis. Data on SBA treatments are limited, and the therapeutic strategy remains uncertain. Currently, chemotherapy is the most used treatment; however, it has a poor median progression-free survival (mPFS) of no more than five months in the second-line setting. We report a case with DA that responded well to the immune checkpoint inhibitor (ICI) tislelizumab plus irinotecan in the second-line treatment. To our knowledge, this is the first report of administering ICIs plus chemotherapy to SBA. Despite the absence of microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB), the patient with TP53/KRAS mutation achieved a significantly long PFS of 17 months, and the benefit is still ongoing. The mechanism of this remarkable efficacy might be associated with an increase in tumor immunogenicity after chemotherapy. The current study presents a promising effect of ICIs plus chemotherapy on SBA, affirming the need to investigate the clinical value of this combination in SBA and the underlying mechanism behind it.
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Affiliation(s)
- Xian Chen
- The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China,Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Rui Zhou
- The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yong Li
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Xin Qu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yan-chun Qu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Wen-zhu Li
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yong-song Ye
- Department of Image, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Li-rong Liu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
| | - Yan-juan Zhu
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hai-bo Zhang
- Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,*Correspondence: Hai-bo Zhang,
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El Bakouri A, El wassi A, Eddaoudi Y, Bouali M, EL Hattabi K, Bensardi F, Fadil A. Fortuitous discovery of an early neuroendocrine tumor during appendicular peritonitis. Ann Med Surg (Lond) 2022; 82:104735. [PMID: 36268349 PMCID: PMC9577830 DOI: 10.1016/j.amsu.2022.104735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/18/2022] [Accepted: 09/18/2022] [Indexed: 11/27/2022] Open
Abstract
Introduction Neuroendocrine tumors of the small bowel are rare but represent the most frequent histological type at this level; their incidence is increasing thanks to the evolution of diagnostic means.Intestinal NETs, developed at the expense of enterochromaffin cells of the embryological midgut, are frequently associated with mesenteric lymph node dissemination and distant metastasis (liver, peritoneum). Materials and methods We report a case of Incidental discovery of a small bowel neuroendocrinetumor during appendicular peritonitis in the department of Emergency visceral surgery P35 of the ibn rochd hospital in casablanca. Results Our patient Our patient was admitted to the emergency room for generalized abdominal pain with an appendicular symptomatology evolving five days before days the consultation with clinical examination: conscious patient stable on the hemodynamic and respiratory plan The examination noted generalized abdominal defense the hernial orifices were free The biological work-up revealed a hb 13 g/dL; hyperleukocytosis with predominantly PNN at 18,300 elements/mm3,CRP was elevated to 190, renal function was normal urea 5 mmol/L creatinemia 9 mg/l an abdominal ultrasound showed a 9 mm appenndix perforated at its tip with moderate peritoneal effusion.the patient were operated in the emergency room, approached by laparotomy with the exploration we found a swollen and inflamed appenndix perforated at the level of its tip with moderate peritoneal effusion with false membranes in all the peritoneal cavity with the presence of a polyp localized at 2 m from the duodenojejunal flexur .the patient benefited from a retrograde appendectomy with peritoneal cleansing and a resection of the polyp with 1cm on each side with a Grele-grele anastomosis with the examination of the anapathomopathologist: aspect compatible with a well differentiated neuroendocrine tumor of grade 2. Conclusion Digestive NETs are rare tumors, but their incidence has increased significantly in recent years. This is due to a better knowledge of these tumors, whose diagnosis is becoming easier with the advent of new morphological and biological techniques.The intestinal location is the most frequent. The digestive surgeon must therefore be familiar with its management. An update of knowledge and collaboration between surgeons, anatomopathologists, radiologists and oncologists are necessary, Whatever their location, these tumors are on the one hand capable of producing and secreting amines and on the other hand they are characterized by a common phenotype, expression of general endocrine markers (specific neuron enolase, chromogranin) or specific endocrine markers and expression of peptide receptors such as somastotatin receptors.These tumors are most often diagnosed incidentally during the workup of aspecific digestive disorders or during hormonal hypersecretion syndrome or rarely by a complication.
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Affiliation(s)
- Abdelilah El Bakouri
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
| | - anas El wassi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Yassine Eddaoudi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Mounir Bouali
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Khalid EL Hattabi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Fatimazahra Bensardi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Abdelaziz Fadil
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
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Fernández-Medina B, Vegas-Aguilar I, García-Almeida JM, Sevilla-García I, Hernández-García C, Tinahones-Madueño FJ. Morfo-functional nutritional status in patients with gastroenteropancreatic neuroendocrine tumors (GEPNET). ENDOCRINOL DIAB NUTR 2022; 69:466-475. [PMID: 35989228 DOI: 10.1016/j.endien.2022.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 09/18/2021] [Indexed: 06/15/2023]
Abstract
INTRODUCTION Patients with gastroenteropancreatic neuroendocrine tumors (GEPNET) can suffer from malnutrition. This is the first descriptive study of morfo-functional evaluation in GEPNET. OBJETIVES To describe a morfo-functional evaluation, and to compare with reference population available, and to correlate different nutritional parameters. Moreover, to compare nutritional evaluation in our study with another same location non-neuroendocrine tumors. MATERIALS AND METHODS A retrospective observational study, 50 patients with GEPNET, medium age 61 years. It was collected clinico-pathological characteristics and nutritional status was assessed by anthropometric, laboratory test, bioelectrical impedance analysis, phase angle, hand grip strength, and rectus femoris ultrasound for the assessment of muscle mass. We used SPSS statistics to describe and to analyze correlations of different variables. RESULTS Most frequent location of tumor was pancreas and small bowel, tumor grade 1 and advance stage. In morfo-functional evaluation highlighted: a low fat mass percentage (23,5 vs 34,4%), low muscle mass percentage (36,5 vs 41,2%) and low body mass cell percentage (40,4 vs 48,8%) compared with reference population available by sex and age. Standarized phase angle by sex and age result as positive (+0,851). There was no difference in hand grip strength compared with reference population. After a review of differents studies available, phase angle and hand grip strength of non neuroendocrine tumors in same location, could suggest a minor affection of nutritional state in our GEPNET sample. A positive correlation was observed between non classic methods of nutritional evaluation such as bioelectrical impedance analysis, hand grip strength and rectus femoris ultrasound. CONCLUSION Patients with gastroenteropancreatic neuroendocrine tumors (GEPNET) show a moderate affection of nutritional status in comparison to general population. Morphofunctional assessment provide us a precise knowledge about nutritional status.
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Affiliation(s)
- Beatriz Fernández-Medina
- Unidad de Gestión Clínica Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
| | - Isabel Vegas-Aguilar
- Unidad de Gestión Clínica Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - José Manuel García-Almeida
- Unidad de Gestión Clínica Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Isabel Sevilla-García
- Unidad de Gestión Clínica Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Carmen Hernández-García
- Unidad de Gestión Clínica Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain
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Fernández-Medina B, Vegas-Aguilar I, García-Almeida JM, Sevilla-García I, Hernández-García C, Tinahones-Madueño FJ. Valoración morfofuncional de la desnutrición en pacientes con tumores neuroendocrinos gastroenteropancreáticos (TNEGEP). ENDOCRINOL DIAB NUTR 2022. [DOI: 10.1016/j.endinu.2021.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Sonbol MB, Mazza GL, Mi L, Oliver T, Starr J, Gudmundsdottir H, Cleary SP, Hobday T, Halfdanarson TR. Survival and Incidence Patterns of Pancreatic Neuroendocrine Tumors Over the Last 2 Decades: A SEER Database Analysis. Oncologist 2022; 27:573-578. [PMID: 35348774 PMCID: PMC9255979 DOI: 10.1093/oncolo/oyac049] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/04/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (pNETs) are rare cancers with outcomes determined by multiple factors including grade, stage, and clinical presentation. In this study, we aimed to determine the prognosis of patients with pNETs using a large population-based database. MATERIALS AND METHODS In this population-based study, we identified patients with pNETs from the SEER 18 registry (2000-2016) using a combination of ICD-O-3 and histology codes. We calculated age-adjusted incidence rates using SEER*Stat 8.3.5. In addition, we analyzed overall survival (OS) using the Kaplan-Meier method, and investigated prognostic factors using a multivariable Cox proportional hazards model. RESULTS A total of 8944 pNETs patients were identified. Annual incidence rates increased from 0.27 to 1.00 per 100 000. This was largely explained by an increase in number of patients diagnosed with localized disease in more recent years (2012-2016). Median OS was 68 months (95% CI [64, 73]) and 5-year OS rates in localized, regional, and metastatic disease were 83%, 67%, and 28%, respectively. There was a significant improvement in OS for patients diagnosed between 2009 and 2016 (median OS 85 months) compared with those diagnosed between 2000 and 2008 (median OS 46 months) (HR 0.66; 95% CI [0.62, 0.70]). This improvement in OS was consistent across all stages. CONCLUSIONS AND RELEVANCE This study shows a steady increase pNETs incidence with notable stage migration to earlier stages in recent years. This increase in incidence is accompanied by a significant improvement in survival across different disease stages.
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Affiliation(s)
| | - Gina L Mazza
- Clinical Trials and Biostatistics, Mayo Clinic, Phoenix, AZ, USA
| | - Lanyu Mi
- Clinical Trials and Biostatistics, Mayo Clinic, Phoenix, AZ, USA
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11
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Smith D, Lepage C, Vicaut E, Dominguez S, Coriat R, Dubreuil O, Lecomte T, Baudin E, Venat Bouvet L, Samalin E, Santos A, Borie O, Bisot-Locard S, Goichot B, Lombard-Bohas C. Observational Study in a Real-World Setting of Targeted Therapy in the Systemic Treatment of Progressive Unresectable or Metastatic Well-Differentiated Pancreatic Neuroendocrine Tumors (pNETs) in France: OPALINE Study. Adv Ther 2022; 39:2731-2748. [PMID: 35419649 PMCID: PMC9123044 DOI: 10.1007/s12325-022-02103-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 02/22/2022] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Approval of sunitinib and everolimus for the treatment of progressive, unresectable or metastatic well-differentiated pancreatic neuroendocrine tumors (pNETs) was obtained in France in 2011 and 2012, respectively. OPALINE was set up as an observational study to evaluate the efficacy of sunitinib and everolimus compared to usual pNET treatments of chemotherapies and somatostatin analogues that had been previously recommended by the health authorities. METHODS The OPALINE study assessed the efficacy of everolimus and sunitinib in terms of survival, disease progression and tolerance. Patients (N = 144) were enrolled from May 2015 to September 2017, and their disease characteristics were analyzed from diagnosis to 2 years post-enrollment. RESULTS At inclusion most patients had comorbidities, and about 95% presented metastases. Patients received on average 3.2 lines of treatment from diagnosis to inclusion and two lines throughout the 2-year follow-up. Seventy-nine patients (59.0%) received at least one targeted therapy (TT) during their care path. For these patients, the overall survival (OS) was approximatively 176.5 months (95% CI: 97.2-not evaluable), with a 2-year survival rate estimated at 93.6% (SD 2.6%). Similar survival rates were observed whether the TTs were prescribed sooner or later in the treatment path. The main reasons for discontinuation of TTs were disease progression (54 patients) and adverse events (26 patients). Most patients receiving TTs did not change their dose during the follow-up reflecting the good treatment tolerability over time. No new safety alert was reported for everolimus and sunitinib during this study. CONCLUSION Given their good tolerance and positive impact on estimated OS, the two TTs have an important role to play in the care path of patients with pNETs. CLINICALTRIALS GOV NATIONAL CLINICAL TRIAL NUMBER NCT02264665.
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Affiliation(s)
- Denis Smith
- Oncologie digestive, Centre médico-chirurgical Magellan, Hôpital Universitaire de Bordeaux, Hôpital Haut-Lévèque, 33604 Pessac Cedex, France
| | - Côme Lepage
- Hépato-gastro-entérologie, Hôpital Universitaire Le Bocage, Dijon, France
| | - Eric Vicaut
- Unité de Recherche Clinique, Hôpital Lariboisière APHP, Paris, France
| | - Sophie Dominguez
- Hôpitaux Catholiques de Lille, Département d’Onco-hématologie, Université Catholique de Lille, Hôpital St Vincent de Paul, Lille, France
| | - Romain Coriat
- Unité de Gastro-entérologie, Hôpital Cochin, APHP Centre, Université de Paris, Paris, France
| | - Olivier Dubreuil
- Oncologie médicale, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France
| | - Thierry Lecomte
- Département d’ Hépato-gastro-entérologie et Oncologie digestive, CHRU de Tours, Tours, France
| | - Eric Baudin
- Institut Gustave Roussy, Service de Médecine Nucléaire, Villejuif, France
| | | | - Emmanuelle Samalin
- Département d’Oncologie médicale, Institut du Cancer de Montpellier (ICM), Université de Montpellier, Montpellier, France
| | | | | | | | - Bernard Goichot
- Département de Médecine interne, Hôpital Universitaire Hautepierre, Strasbourg, France
| | - Catherine Lombard-Bohas
- Service d’Oncologie Médicale Hôpital Edouard Herriot, GHC, Hospices Civils de Lyon, Lyon, France
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12
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Gelsomino F, Balsano R, De Lorenzo S, Garajová I. Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management. Curr Oncol 2022; 29:1223-1236. [PMID: 35200603 PMCID: PMC8870676 DOI: 10.3390/curroncol29020104] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/10/2022] [Accepted: 02/14/2022] [Indexed: 12/03/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy, with a rising incidence in recent decades, and accounts for roughly 40% of all cancers of the small bowel. The majority of SBAs arise in the duodenum and are associated with a dismal prognosis. Surgery remains the mainstay of treatment for localized disease, while systemic treatments parallel those used in colorectal cancer (CRC), both in the adjuvant and palliative setting. In fact, owing to the lack of prospective data supporting its optimal management, SBA has historically been treated in the same way as CRC. However, recent genetic and molecular data suggest a distinct profile from other gastrointestinal malignancies and support a more nuanced approach to its management. Herein, we briefly review the state-of-the-art in the clinical management of early-stage and advanced disease and recent discoveries of potentially actionable genetic alterations or pathways along with the most promising ongoing clinical trials, which will hopefully revolutionize the treatment landscape of this orphan disease in the foreseeable future.
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Affiliation(s)
- Fabio Gelsomino
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, 41124 Modena, Italy
| | - Rita Balsano
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
| | | | - Ingrid Garajová
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
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13
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Coelho S, Costa C, Santos AP, Souteiro P, Oliveira J, Oliveira J, Azevedo I, Torres I, Bento MJ. Pancreatic neuroendocrine neoplasms: survival trend analysis of a comprehensive center. ENDOCRINE ONCOLOGY (BRISTOL, ENGLAND) 2022; 2:32-41. [PMID: 37435456 PMCID: PMC10259287 DOI: 10.1530/eo-22-0043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 04/20/2022] [Indexed: 07/13/2023]
Abstract
Objectives Therapeutic options for pancreatic neuroendocrine neoplasia (Pan-NEN) have increased over the last decade. We aim to understand the evolution of the prognosis of patients with diagnosis of Pan-NEN within a 12-year period, considering the implementation of new treatments. Methods This study is a retrospective cohort study of patients diagnosed with Pan-NENs between 2006 and 2017. Survival outcome estimates were calculated by Kaplan-Meier method. The impact of baseline clinicopathological characteristics on survival was explored with the use of Cox proportional hazard model. Results Of the 97 patients, 77 (79.9%) had well-differentiated neuroendocrine tumor (NET) according to WHO 2010 classification, and 52 (53.6%) had localized or locoregional disease. There were no differences between clinicopathological characteristics and survival outcomes when comparing patients diagnosed between 2006-2011 and 2012-2017. Neuroendocrine carcinoma - HR 2.76, 95% CI 1.17-6.55 - and stages III and IV at diagnosis were independent poor prognostic factors - HR 6.02, 95% CI 2.22-16.33 and HR 6.93, 95% CI 2.94-16.32, respectively. Conclusions The new therapeutic approaches did not induce better survival outcomes on Pan-NEN in recent years. This is possibly due to the indolent nature of NET grades 1 and 2, even metastatic, allowing patients to be submitted to new target therapies along their disease course.
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Affiliation(s)
- Sara Coelho
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Cláudia Costa
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Ana Paula Santos
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
- Research Center, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Pedro Souteiro
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Joana Oliveira
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Júlio Oliveira
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Isabel Azevedo
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Isabel Torres
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Maria José Bento
- Department of Epidemiology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
- School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
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Zhu J, Fu C, Zhang Y, Zhou X, Xiao W, Li Y. Observation Versus Resection for Small, Localized, and Nonfunctional Pancreatic Neuroendocrine Tumors: A Propensity Score Matching Study. Pancreas 2022; 51:56-62. [PMID: 35195596 DOI: 10.1097/mpa.0000000000001959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The best treatment modalities for small (1-2 cm), localized, and nonfunctional pancreatic neuroendocrine tumors remain controversial. Therefore, we aimed to evaluate whether surgical resection provides survival benefit over observation in those patients. METHODS From 1973 to 2015, all eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching (1:2) method was performed. The primary endpoints evaluated were overall survival (OS) and cancer-specific survival (CSS). RESULTS We identified 681 patients, of which 122 and 559 patients received observation and resection, respectively. Propensity score-matched patients who underwent surgery (n = 183) had significantly improved OS (P = 0.008) compared with matched patients who underwent observation (n = 106), but there was no difference in CSS (P = 0.310). On multivariate analysis, resection could improve OS but not CSS. Besides, poorly differentiated/undifferentiated tumor had a worse OS and CSS. Subgroup analysis showed that patients 60 years and older who underwent resection could achieve a longer OS and CSS. CONCLUSIONS This disease exhibits a very good prognosis. Patients undergoing resection were associated with comparable 5-year CSS but longer 5-year OS compared with those receiving observation. Elderly patients (≥60) may obtain benefit from surgery, whereas the treatment of younger patients should be individualized.
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Affiliation(s)
- Jisheng Zhu
- From the Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
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15
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Brugel M, Walter T, Goichot B, Smith D, Lepage C, Do Cao C, Hautefeuille V, Rebours V, Cadiot G, de Mestier L. Efficacy of treatments for VIPoma: A GTE multicentric series. Pancreatology 2021; 21:1531-1539. [PMID: 34404601 DOI: 10.1016/j.pan.2021.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/28/2021] [Accepted: 08/04/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma. OBJECTIVE Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma. METHODS We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received. RESULTS Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025). CONCLUSIONS Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.
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Affiliation(s)
- Mathias Brugel
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré Hospital and Reims-Champagne-Ardenne University, Reims, France.
| | - Thomas Walter
- Department of Digestive Oncology, ENETS Centre of Excellence, Hospices Civils de Lyon, Lyon, France
| | - Bernard Goichot
- Department of Internal Medicine, Endocrinology & Nutrition, Hôpital Hautepierre, Strasbourg University Hospital, France
| | - Denis Smith
- Department of Hepato-Gastroenterology and Digestive Oncology, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Côme Lepage
- Department of Hepato-Gastroenterology and Digestive Oncology, Dijon University Hospital, Dijon, France
| | - Christine Do Cao
- Department of Endocrinology, Hôpital Claude-Huriez, Lille University Hospital, Lille, France
| | - Vincent Hautefeuille
- Department of Hepato-Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Vinciane Rebours
- Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Hôpital Beaujon and Université de Paris Nord, Clichy, France
| | - Guillaume Cadiot
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré Hospital and Reims-Champagne-Ardenne University, Reims, France
| | - Louis de Mestier
- Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Hôpital Beaujon and Université de Paris Nord, Clichy, France
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16
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Raoul JL, Heymann MF, Dumont F, Morel A, Senellart H, Bertucci F. Case Report: Grade 2 Metastatic Pancreatic Neuroendocrine Tumor With Progression of One Metastasis After Pregnancy to Grade 3 Large-Cell Neuroendocrine Carcinoma: One Case Cured by Resection With Genomic Characterization of the Two Components. Front Oncol 2021; 11:646992. [PMID: 33954111 PMCID: PMC8092117 DOI: 10.3389/fonc.2021.646992] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 03/16/2021] [Indexed: 12/14/2022] Open
Abstract
Temporal and spatial tumor heterogeneity can be observed in pancreatic neuroendocrine tumor. We report the case of a young woman with long term stabilization of a G2 metastatic pancreatic NET that, after pregnancy, suddenly progressed into one single liver metastasis corresponding to a transformation into G3 large-cell neuroendocrine cancer. The patient underwent liver resection (the progressive and one dormant metastasis). With a 45 months follow-up the patient is without evolutive disease. Exome sequencing of the two metastases revealed completely different genomic signatures and gene alterations: the dormant metastasis was MSS without any gene alteration; the poorly differentiated tumor was MSI, with gain of many mutations including MEN1, BCL2, MLH1 and TP53 corresponding to a mutational signature 11. Could temozolomide play a role in this transformation?
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Affiliation(s)
- Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Saint-Herblain, France
| | | | - Frédéric Dumont
- Department of Surgery, Institut de Cancérologie de l'Ouest, Saint-Herblain, France
| | - Alain Morel
- Department of Oncopharmacology, Institut de Cancérologie de l'Ouest, Angers, France
| | - Hélène Senellart
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Saint-Herblain, France
| | - François Bertucci
- Predictive Oncology Laboratory, Department of Medical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France
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17
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Hashmi AA, Ali J, Yaqeen SR, Ahmed O, Asghar IA, Irfan M, Asif MG, Edhi MM, Hashmi S. Clinicopathological Features of Primary Neuroendocrine Tumors of Gastrointestinal/Pancreatobiliary Tract With Emphasis on High-Grade (Grade 3) Well-Differentiated Neuroendocrine Tumors. Cureus 2021; 13:e12640. [PMID: 33585126 PMCID: PMC7872883 DOI: 10.7759/cureus.12640] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Introduction The two broad subcategories of neuroendocrine neoplasms (NENs) are well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs), based on tumor architecture and cytology. Grade 3 WDNETs are a subset of WDNETs that not only are high grade by mitotic activity or proliferative index but exhibit a well-differentiated histology. In this study, we evaluated the clinicopathological features of primary neuroendocrine tumors of the gastrointestinal (GI)/pancreatobiliary tract with emphasis on high-grade WDNETs, as it is a newly defined entity. Methods We conducted a retrospective observational study, including a total number of 122 cases of primary GI and pancreatobiliary tract NENs. Slides and blocks of all cases were retrieved from the departmental archives. Immunohistochemical stains including Ki67 were applied to selected tissue blocks of all cases. Tumors were then evaluated for their histological differentiation and tumor grade. Results Our results showed that the mean age of patients was 46.8 ± 17.1 years. Majority of the NENs were GI tract origin (86.9%). The most common site of tumor in gastroenteropancreatic tract was the small bowel (31.1%), followed by the stomach (26.2%). Ninety five percent of the tumors were WDNETs, of which the most common grade was G2. The mean Ki67 index was 15.8 ± 23.8. Grade 3 WDNETs were noted to have an older mean age than grades 1 and 2 WDNETs. Ten out of 102 (9.8%) WDNETs of GI tract were grade 3, compared with four out of 14 (28.6%) of pancreatobiliary tract. Conclusion In this study, we found that high-grade (grade 3) WDNETs were more frequent in pancreatobiliary tract than GI tract. Moreover, high-grade WDNETs were associated with a higher mean age than low-grade (grade 1-2) WDNETs. It is extremely important to recognize this subset (high grade) of WDNETs and to distinguish it from PDNECs, as the latter are known to be associated with a worse overall survival. Despite high mitotic rate/proliferative index, high-grade WDNETs are characterized by organoid architecture and monomorphic cell population.
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Affiliation(s)
- Atif A Hashmi
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Javaria Ali
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | | | - Omer Ahmed
- Internal Medicine, Liaquat National Hospital and Medical College, Karachi, PAK
| | | | - Muhammad Irfan
- Statistics, Liaquat National Hospital and Medical College, Karachi, PAK
| | | | - Muhammad M Edhi
- Neuroscience/Neurosurgery, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, USA
| | - Shumaila Hashmi
- Pathology, Combined Military Hospital Multan Institute of Medical Sciences, Multan, PAK
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18
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Giraldi L, Vecchioni A, Carioli G, Bilotta M, La Rosa S, Imperatori A, Volante M, Brizzi MP, Inzani F, Petrone G, Schinzari G, Bianchi A, Margaritora S, Alfieri S, La Vecchia C, Boccia S, Rindi G. Risk factors for pancreas and lung neuroendocrine neoplasms: a case-control study. Endocrine 2021; 71:233-241. [PMID: 32869113 PMCID: PMC7835148 DOI: 10.1007/s12020-020-02464-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 08/19/2020] [Indexed: 01/13/2023]
Abstract
PURPOSE Neuroendocrine neoplasia (NEN) has been displaying an incremental trend along the last two decades. This phenomenon is poorly understood, and little information is available on risk factor for neuroendocrine neoplasia development. Aim of this work is to elucidate the role of potentially modifiable risk factors for pancreatic and pulmonary NEN. METHODS We conducted a case-control study on 184 patients with NEN (100 pancreas and 84 lung) and 248 controls. The structured questionnaire included 84 queries on socio-demographic, behavioral, dietary and clinical information. RESULTS Increased risk was associated with history of cancer ("other tumor", lung OR = 7.18; 95% CI: 2.55-20.20 and pancreas OR = 5.88; 95% CI: 2.43-14.22; "family history of tumor", lung OR = 2.66; 95% CI: 1.53-4.64 and pancreas OR = 1.94; 95% CI: 1.19-3.17; "family history of lung tumor", lung OR = 2.56; 95% CI: 1.05-6.24 and pancreas OR = 2.60; 95% CI: 1.13-5.95). Type 2 diabetes mellitus associated with an increased risk of pancreatic NEN (OR = 3.01; 95% CI: 1.15-7.89). CONCLUSIONS Besides site-specific risk factors, there is a significant link between neuroendocrine neoplasia and cancer in general, pointing to a shared cancer predisposition.
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Affiliation(s)
- Luca Giraldi
- Section of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Alessia Vecchioni
- Section of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Greta Carioli
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Mirna Bilotta
- Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Stefano La Rosa
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
- Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Andrea Imperatori
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Marco Volante
- Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Maria Pia Brizzi
- Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Frediano Inzani
- Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Gianluigi Petrone
- Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Giovanni Schinzari
- Department of Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Antonio Bianchi
- Department of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Stefano Margaritora
- Department of Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Sergio Alfieri
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Stefania Boccia
- Section of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia
- Section of Hygiene, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Guido Rindi
- Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia.
- Section of Anatomic Pathology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.
- Roma European NeuroEndocrine Tumor Society (ENETS) Center of Excellence, Roma, Italia.
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Hong L, Wang Y, Zhang T, Zhang C, Wang L, Wang L, Wang Z, Zhong J. Chromogranin A: A Valuable Serum Diagnostic Marker for Non-Insulinoma Neuroendocrine Tumors of the Pancreas in a Chinese Population. Med Sci Monit 2020; 26:e926635. [PMID: 33141811 PMCID: PMC7648406 DOI: 10.12659/msm.926635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background Pancreatic neuroendocrine tumors (P-NETs) are uncommon neoplasms, with few studies to date assessing serum biomarkers for the diagnosis of P-NETs. This study assessed the ability of serum chromogranin A (CgA) concentrations to distinguish P-NETs from other pancreatic lesions in a Chinese population and to determine the histological grades of P-NETs. Material/Methods This prospective study enrolled 165 patients, including 73 with proven P-NETs, 60 with malignant tumors of the pancreas, and 32 with benign lesions of the pancreas. Serum CgA concentrations were measured by ELISA. Results Serum CgA concentrations were significantly higher in patients with P-NET than in patients with other pancreatic malignancies and benign lesions (P<0.001), but did not differ significantly in the latter 2 groups (P=0.827). Serum CgA concentrations were significantly higher in patients with non-insulinoma P-NETs than in the other groups (P<0.001), but did not differ significantly in patients with insulinoma and patients with non-P-NETs (P=0.668). Receiver operating characteristic (ROC) curves revealed that a serum CgA concentration of 77.8 ng/ml could distinguish patients with non-insulinoma P-NETs from patients with non-P-NETs, with a sensitivity of 96.7%, a specificity of 76.1%, and an area under the ROC curve of 0.897. In patients with P-NETs, multifactor analysis showed that the non-insulinoma subtype and the presence of liver metastases were associated with elevated serum CgA (both p<0.001). Conclusions Serum CgA concentration may be a valuable diagnostic biomarker for non-insulinoma P-NETs. Elevated serum CgA is likely associated with liver metastases.
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Affiliation(s)
- Liwen Hong
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Yuan Wang
- Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China (mainland)
| | - Tianyu Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Chen Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Lei Wang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Liying Wang
- Department of Gastroenterology, Shangyu Hospital Affiliated to the Second Affiliated Hospital of Medical College of Zhejiang University, Shoaxing, Zhejiang, China (mainland)
| | - Zhengting Wang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Jie Zhong
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
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20
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Clinical Features and Long-Term Survival of Metastatic Hepatic Neuroendocrine Neoplasms Secondary to Gastroenteropancreatic Site: An Analysis by Applying the Grading Classification. JOURNAL OF ONCOLOGY 2020; 2020:6572398. [PMID: 33014053 PMCID: PMC7512090 DOI: 10.1155/2020/6572398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 08/11/2020] [Accepted: 08/28/2020] [Indexed: 02/05/2023]
Abstract
Method Data of patients who were surgically treated and clinicopathologically diagnosed as (MH)-NENs secondary to (GEP)-NENs at West China Hospital of Sichuan University from January 2006 to December 2018 were retrospectively collected and analyzed by the grading classification for (GEP)-NENs. Results We identified 150 patients with (MH)-NENs secondary to (GEP)-NENs, including 10 patients with G1 NETs, 26 with G2 NETs, 33 with G3 NETs, and 81 with G3 NECs. There were significant differences between patients with G1/G2/G3 NETs and those with G3 NECs, such as age at diagnosis (P=0.041), synchronous liver lesion (P=0.032), incidental diagnosis (P=0.014), tumor largest diameter (P=0.047), vascular invasion (P=0.017), and extrahepatic metastatic disease (P=0.029). The estimated 3-year overall survival for patients with G1 NETs, G2 NETs, G3 NETs, and G3 NECs was 100%, 79.4%, 49.5%, and 20.7%, respectively (P < 0.001). The survival of G1 NETs or G2 NETs was significantly better than that of G3 NETs (P=0.013, P=0.037, respectively) and G3 NECs (P=0.001, P < 0.001; respectively). Patients with G3 NECs present notably worse survival than those with G3 NETs (P=0.012), while survival comparison between G1 NETs and G2 NETs was not statistically different (P=0.131). The grading classification for (GEP)-NENs was an effective independent predictor of survival for (MH)-NENs secondary to (GEP)-NENs (hazard ratio: 4.234; 95% confidence intervals: 1.984–6.763; P=0.003). Conclusion Our demonstration revealed that the grading classification for (GEP)-NENs could well stratify (MH)-NENs secondary to (GEP)-NENs into prognostic groups and supported its wide use in clinical practice.
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21
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Impact of a Prior Nonpancreatic Malignancy on Survival Outcomes of Patients With Stage IV Pancreatic Neuroendocrine Tumor: A Population-Based and Propensity Score Matching Study. Pancreas 2020; 49:1090-1098. [PMID: 32833943 DOI: 10.1097/mpa.0000000000001630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE The aim of the study was to investigate the impact of a previous nonpancreatic malignancy on the survival outcomes in patients with a stage IV pancreatic neuroendocrine tumor (PanNET). METHODS The Surveillance, Epidemiology, and End Results database was reviewed, and patients diagnosed with a stage IV PanNET between 2004 and 2015 were selected. Patients were divided into 2 groups according to the presence or absence of a previous nonpancreatic malignancy. Clinicopathological characteristics and survival outcomes were compared. RESULTS A total of 1582 patients with stage IV PanNET were identified, of whom 116 (7.3%) had a prior malignancy. Prostate (33.62%), breast (17.24%), and gastrointestinal (12.07%) malignancies were the most common. Most prior malignancies (84.48%) were localized and regional. Patients with intervals of 36 months or less, 36 to 60 months, 60 to 120 months, and more than 120 months account for 25.86%, 14.66%, 31.03%, and 28.45% of all cases, respectively. Before and after propensity score matching, there was no significant difference detected regarding survival outcomes. CONCLUSIONS Stage IV PanNET patients with a history of a prior cancer had comparable survival outcomes with patients without such history. These patients could be candidates for clinical trials if otherwise appropriate, and aggressive and potentially curative therapies should be offered.
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22
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Muscogiuri G, Barrea L, Feola T, Gallo M, Messina E, Venneri MA, Faggiano A, Colao A. Pancreatic Neuroendocrine Neoplasms: Does Sex Matter? Trends Endocrinol Metab 2020; 31:631-641. [PMID: 32223919 DOI: 10.1016/j.tem.2020.02.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 02/19/2020] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
Genetic and molecular disparities between men and women have a role in the differing incidence, pathophysiology, clinical signs, and treatment outcome of several cancers. Sex differences in cancer incidence are attributed to regulation at the genetic/molecular level and to sex hormones that in turn modulate gene expression in various cancers. Sex differences in the incidence of cancer, its aggressiveness, and the disease prognosis have been reported for several types of cancer but little is known for pancreatic neuroendocrine neoplasms (PNENs). The aim of this Opinion article is to provide an overview of sex differences in PNENs in terms of epidemiology, pathophysiology, treatment responses, prognosis, and survival. This overview might allow better tailoring of the management of PNENs.
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Affiliation(s)
- Giovanna Muscogiuri
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy.
| | - Luigi Barrea
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy
| | - Tiziana Feola
- Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy
| | - Marco Gallo
- Department of Medical Sciences, Oncological Endocrinology Unit, University of Turin, Turin, Italy
| | - Erika Messina
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Mary Anna Venneri
- Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy
| | | | - Annamaria Colao
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy
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Megdanova-Chipeva VG, Lamarca A, Backen A, McNamara MG, Barriuso J, Sergieva S, Gocheva L, Mansoor W, Manoharan P, Valle JW. Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs). Cancers (Basel) 2020; 12:E1988. [PMID: 32708210 PMCID: PMC7409353 DOI: 10.3390/cancers12071988] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/19/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023] Open
Abstract
Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.
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Affiliation(s)
- Vera G. Megdanova-Chipeva
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Department of Radiotherapy and Medical Oncology, University Hospital “Queen Yoanna” ISUL, 1000 Sofia, Bulgaria;
- Department of Nuclear Medicine, Radiotherapy and Medical Oncology, Medical University—Sofia, 1000 Sofia, Bulgaria
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Alison Backen
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Mairéad G. McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Jorge Barriuso
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Sonia Sergieva
- Nuclear Medicine Department, SBALOZ, Sofia grad, 1000 Sofia, Bulgaria;
| | - Lilia Gocheva
- Department of Radiotherapy and Medical Oncology, University Hospital “Queen Yoanna” ISUL, 1000 Sofia, Bulgaria;
- Department of Nuclear Medicine, Radiotherapy and Medical Oncology, Medical University—Sofia, 1000 Sofia, Bulgaria
| | - Was Mansoor
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Prakash Manoharan
- Department of Radiology and Nuclear Medicine, The Christie NHS Foundation Trust, Manchester M204BX, UK;
| | - Juan W. Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
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24
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Lombard-Bohas C, Cao CD, Metges JP, Philippe Ruszniewski, Smith D, Guimbaud R, Lepage C, Ron Hollander, Goldstein G, Wolin E, Santos A, Baudin E. French patient-reported experience of diagnosis, management and burden of neuroendocrine tumors. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2020. [DOI: 10.2217/ije-2020-0013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background: There is a lack of knowledge regarding the experience of patients with neuroendocrine tumors (NET) in France. Materials & methods: A patient survey that captured information on diagnosis, disease impact/management and awareness was conducted. Data of respondents from France were analyzed and compared with US data as a reference. Results: Key topics included delays in diagnosis, negative impact on quality of life, patient access to NET medical experts and treatments, and information on NET and treatments. Significant differences were observed between France and the USA regarding NET diagnosis. Conclusion: This survey highlights the considerable burden experienced by patients in France with NET and differences in patient experience between France and the USA that may result from different healthcare and social systems.
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Affiliation(s)
| | - Christine Do Cao
- Centre Hospitalier Universitaire de Lille, Service Endocrinologie, Lille, France
| | - Jean-Philippe Metges
- Centre Hospitalier Régional Universitaire de Brest, Pôle Régional de Cancérologie, Brest, France
| | - Philippe Ruszniewski
- Université de Paris et Service de Pancréatologie, Hôpital Beaujon, Clichy, France
| | - Denis Smith
- Centre Hospitalier Universitaire de Bordeaux, Service d'Oncologie Médicale, Bordeaux, France
| | - Rosine Guimbaud
- Centre Hospitalier Universitaire de Toulouse, Service d'Oncologie Médicale, Toulouse, France
| | | | - Ron Hollander
- International Neuroendocrine Cancer Alliance (INCA), Newton, MA, USA
| | | | - Edward Wolin
- Center for Carcinoid and Neuroendocrine Tumors, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Eric Baudin
- Institute Gustave Roussy, Service de Médecine Nucléaire, Villejuif, France
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25
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Lepage C. Épidémiologie des tumeurs neuroendocrines intestinales. ONCOLOGIE 2020. [DOI: 10.3166/onco-2019-0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Les données disponibles concernant l’incidence et les facteurs pronostiques des tumeurs neuroendocrines (TNE) digestives sont souvent fragmentaires. Les TNE digestives sont rares et représentent environ 1 % des cancers digestifs. En France, l’incidence des TNE digestives malignes est estimée à 1,1/100 000 chez l’homme et à 0,9/100 000 chez la femme. L’incidence augmente au cours du temps. Du fait de leur longue survie, les TNE constituent, après le cancer colorectal, le cancer digestif dont la prévalence est la plus élevée. La plupart des TNE sont bien différenciées, les carcinomes neuroendocrines peu différenciés représentent moins de 20 % des TNE digestives. Parmi les TNE bien différenciées intestinales, les localisations les plus fréquentes sont l’intestin grêle et le colorectal. Plus de la moitié des TNE sont diagnostiquées au stade métastatique, principalement au niveau hépatique. Le degré de différenciation, le grade histologique, la localisation du primitif et le stade sont les principaux facteurs pronostiques. Les taux de survie relative à cinq ans étaient de 4,5 % pour les tumeurs peu différenciées versus plus de 55 % pour les TNE bien différenciées.
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26
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Hofland J, de Herder WW, Kann PH. Turning Up the Heat: Endoscopic Ablation of Pancreatic Neuroendocrine Neoplasms. J Clin Endocrinol Metab 2019; 104:5053-5055. [PMID: 31058975 DOI: 10.1210/jc.2019-00954] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 04/30/2019] [Indexed: 12/27/2022]
Affiliation(s)
- Johannes Hofland
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Cancer Institute, Erasmus Medical Center, GE Rotterdam, Netherlands
| | - Wouter W de Herder
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Cancer Institute, Erasmus Medical Center, GE Rotterdam, Netherlands
| | - Peter H Kann
- Centre for Endocrinology, Diabetology and Osteology, Phillipps University Marburg, Marburg, Germany
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27
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Panni RZ, Lopez-Aguiar AG, Liu J, Poultsides GA, Rocha FG, Hawkins WG, Strasberg SM, Trikalinos NA, Maithel S, Fields RC. Association of preoperative monocyte-to-lymphocyte and neutrophil-to-lymphocyte ratio with recurrence-free and overall survival after resection of pancreatic neuroendocrine tumors (US-NETSG). J Surg Oncol 2019; 120:632-638. [PMID: 31339198 DOI: 10.1002/jso.25629] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 06/25/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Preoperative systemic inflammatory response plays a crucial role in tumorigenesis, progression, and prognosis; and neutrophil, monocyte, and lymphocyte counts serve as important biomarkers. An altered monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and breast cancer. The aim of this study was to investigate the prognostic significance of MLR, NLR in patients with resectable PNETs. METHODS Patients undergoing surgery for PNETs between 2000 and 2016 were identified using a large, multi-center database. NLR and MLR were calculated and Contal and O'Quigley analysis was used to determine the optimal cutoff value. RESULTS A total of 620 patients were included in the analytic cohort. The prognostic implications of blood count parameters were evaluated in both univariate and multivariate analysis. The univariate analysis revealed that low MLR and NLR is associated with significantly improved overall survival (OS; P < .01) and recurrence-free survival (RFS; P < .01). On multivariate analysis, in addition to tumor size and grade, NLR was an independent predictor of improved OS and RFS. CONCLUSION In addition to established tumor-specific factors, preoperative NLR levels can serve as a valuable biomarker that can be used as a predictor of OS and RFS after resection of PNETs.
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Affiliation(s)
- Roheena Z Panni
- Division of HPB and GI Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Jingxia Liu
- Section of Oncologic Biostatistics, Division of Public Health, Washington University School of Medicine, St. Louis, Missouri
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, California
| | - Flavio G Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - William G Hawkins
- Division of HPB and GI Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Steven M Strasberg
- Division of HPB and GI Surgery, Washington University School of Medicine, St. Louis, Missouri
| | | | - Shishir Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Ryan C Fields
- Division of HPB and GI Surgery, Washington University School of Medicine, St. Louis, Missouri
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Mujica-Mota R, Varley-Campbell J, Tikhonova I, Cooper C, Griffin E, Haasova M, Peters J, Lucherini S, Talens-Bou J, Long L, Sherriff D, Napier M, Ramage J, Hoyle M. Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or metastatic neuroendocrine tumours with disease progression: a systematic review and cost-effectiveness analysis. Health Technol Assess 2019; 22:1-326. [PMID: 30209002 DOI: 10.3310/hta22490] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system. OBJECTIVES To estimate the clinical effectiveness of three interventions [everolimus (Afinitor®; Novartis International AG, Basel, Switzerland), lutetium-177 DOTATATE (177Lu-DOTATATE) (Lutathera®; Imaging Equipment Ltd, Radstock, UK) and sunitinib (Sutent®; Pfizer Inc., New York, NY, USA)] for treating unresectable or metastatic NETs with disease progression and establish the cost-effectiveness of these interventions. DATA SOURCES The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. REVIEW METHODS We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel® 2013 (Microsoft Corporation, Redmond, WA, USA) from the UK NHS and Personal Social Services perspective. This comprised three health states: (1) progression-free survival (PFS), (2) progressed disease and (3) death. RESULTS Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin®, Novartis) compared with 60 mg of octreotide, was excluded from the review, we nonetheless present the results of this trial, as it informs our estimate of the cost-effectiveness of 177Lu-DOTATATE. The pNETs trials consistently found that the interventions improved PFS and overall survival (OS) compared with BSC. Our indirect comparison found no significant difference in PFS between everolimus and sunitinib. Estimates of OS gain were confounded because of high rates of treatment switching. After adjustment, our indirect comparison suggested a lower, but non-significant, hazard of death for sunitinib compared with everolimus. In GI and lung NETs, everolimus significantly improved PFS compared with BSC and showed a non-significant trend towards improved OS compared with BSC. Adverse events were more commonly reported following treatment with targeted interventions than after treatment with BSC. In the base case for pNETs, assuming list prices, we estimated incremental cost-effectiveness ratios (ICERs) for everolimus compared with BSC of £45,493 per quality-adjusted life-year (QALY) and for sunitinib compared with BSC of £20,717 per QALY. These ICERs increased substantially without the adjustment for treatment switching. For GI and lung NETs, we estimated an ICER for everolimus compared with BSC of £44,557 per QALY. For GI (midgut) NETs, the ICERs were £199,233 per QALY for everolimus compared with BSC and £62,158 per QALY for a scenario analysis comparing 177Lu-DOTATATE with BSC. We judge that no treatment meets the National Institute for Health and Care Excellence's (NICE) end-of-life criteria, although we cannot rule out that sunitinib in the A6181111 trial does. LIMITATIONS A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials. CONCLUSIONS Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales. FUTURE WORK Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial. STUDY REGISTRATION This study is registered as PROSPERO CRD42016041303. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Ruben Mujica-Mota
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jo Varley-Campbell
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Irina Tikhonova
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Chris Cooper
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Ed Griffin
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Marcela Haasova
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jaime Peters
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Stefano Lucherini
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Juan Talens-Bou
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Linda Long
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - David Sherriff
- Plymouth Oncology Centre, Plymouth Hospitals NHS Trust, Plymouth, UK
| | - Mark Napier
- Exeter Oncology Centre, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK
| | - John Ramage
- Neuroendocrine Tumour Service, King's College Hospital NHS Foundation Trust, London, UK
| | - Martin Hoyle
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
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Li G, Tian ML, Bing YT, Tao LY, Wang HY, Jiang B, Yuan CH, Xiu DR. Clinicopathological features and prognosis factors for survival in elderly patients with pancreatic neuroendocrine tumor: A STROBE-compliant article. Medicine (Baltimore) 2019; 98:e14576. [PMID: 30882623 PMCID: PMC6426577 DOI: 10.1097/md.0000000000014576] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
To investigate the features and prognosis of the elderly patients with pancreatic neuroendocrine tumor (pNET).The patients diagnosed with pNETs between 2004 and 2014 were identified from the Surveillance Epidemiology and End Results database. The ethical approval was waived because the present study was analysis of the data from Surveillance Epidemiology and End Results database.A total of 4608 patients with "one primary only" histologically pNETs were confirmed and 653 were older than 75 years. Cancer-specific survival (CSS) and overall survival (OS) were examined. The elderly patients (≥75 years) have disadvantage in CSS and OS compared with younger cohort. Multivariate logistic regression revealed that the elderly patients have increased poorly differentiated composition, and decreased proportion of Black patients, receipt of surgery, married status, and number of removed lymph node. Multivariate Cox regression analysis demonstrated worse differentiation. Patients of T3-4 and M1 stage were associated with poor CSS, while patients of being female, tumor locating at pancreatic body/tail, receipt of surgery, and being married were associated with better CSS in the elderly patients. Meanwhile, patients with higher histological grade and M1 stage have poor OS, while patients with the characteristics of female, being married, tumor location at pancreatic body/tail and tumor surgery have better OS. Distant metastatic elderly patients underwent primary site surgery had better CSS and OS than the patients without surgery.The elderly patients have increased possibility of poorly differentiated tumor, and decreased proportion of Black patients, surgery of primary site, number of removed lymph node and married status. Worse differentiation and tumor metastasis were independent risk factors for both CSS and OS, while primary tumor located in body/tail of pancreas, female patients, surgery of tumor primary site, and being married were protective factors.
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Tai WM, Tan SH, Tan DMY, Loke KSH, Ng DCE, Yan SX, Hwang JSG, Lim KH, Loh LM, Kek PC, Goh BKP, Lee SY, Chung AYF, Ong SYK. Clinicopathologic Characteristics and Survival of Patients with Gastroenteropancreatic Neuroendocrine Neoplasm in a Multi-Ethnic Asian Institution. Neuroendocrinology 2019; 108:265-277. [PMID: 30399612 DOI: 10.1159/000495140] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Accepted: 11/06/2018] [Indexed: 11/19/2022]
Abstract
BACKGROUND Epidemiological evidence suggests there are differences in gastroenteropancreatic neuroendocrine neoplasm (GEPNEN) among population groups. We aimed to contribute to the current evidence by evaluating the clinicopathological characteristics of GEPNEN in a multi-ethnic Asian group. MATERIALS AND METHODS This was a retrospective chart review of patients diagnosed with GEPNEN at a tertiary medical institution at Singhealth Outram Campus, Singapore, between 1995 and 2015. RESULTS Two hundred ninety-five patients were included in the evaluation, comprising Chinese (74.6%), Malay (4.4%), Indian (9.5%) and other (11.5%) ethnic backgrounds. The median age at diagnosis was 59 years; 52.5% were males. Distribution of disease stage at diagnosis was: localised (42.4%), regional (15.3%) and distant (38.0%). The three most common primary tumour sites were located in the pancreas (38.6%), rectum (19.7%) and stomach (9.5%), which varied significantly with ethnic background and age at diagnosis. Malay patients were younger (median 42 years) at diagnosis than Chinese (60 years). Patients with an appendiceal neuroendocrine neoplasm (NEN) (48 years) were younger compared to oesophageal NEN (66 years). Disease stage correlated with primary tumour site and grade (p < 0.001). Median overall survival (OS) for all GEPNEN was 10.2 years. Age at diagnosis, disease stage and grading were prognostic factors of OS in multivariable analyses. CONCLUSION Our findings correspond with other studies that focus on GEPNEN incidences in Asian countries, with the pancreas, rectum and stomach being the most common primary tumour sites. Our findings suggest racial differences in primary tumour site and age at diagnosis. Further prospective population-based registries are required to understand these epidemiological differences.
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Affiliation(s)
- Wai Meng Tai
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore,
- Duke-NUS Graduate Medical School, Singapore, Singapore,
| | - Sze Huey Tan
- Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Damien Meng Yew Tan
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore, Singapore
- Department of General Surgery, Singapore General Hospital, Singapore, Singapore
| | - Kelvin Siu Hoong Loke
- Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore, Singapore
| | - David Chee Eng Ng
- Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore, Singapore
| | - Sean Xuexian Yan
- Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore, Singapore
| | | | - Kiat Hon Lim
- Department of Pathology, Singapore General Hospital, Singapore, Singapore
| | - Lih Ming Loh
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Peng Chin Kek
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Brian Kim Poh Goh
- Department of General Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Ser Yee Lee
- Department of General Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Alexander Yaw Fui Chung
- Department of General Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Simon Yew Kuang Ong
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
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Gudmundsdottir H, Möller PH, Jonasson JG, Björnsson ES. Gastroenteropancreatic neuroendocrine tumors in Iceland: a population-based study. Scand J Gastroenterol 2019; 54:69-75. [PMID: 30638086 DOI: 10.1080/00365521.2018.1553061] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To determine the incidence, distribution, and prognosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) over the last 30 years and analyze changes over time. METHODS All patients diagnosed with GEP-NETs in Iceland from 1985 to 2014 were identified through the Icelandic Cancer Registry and pathology laboratory records. Relevant clinical information was obtained from medical records. In order to assess trends, the study period was divided into two periods, 1985-1999 and 2000-2014. RESULTS A total of 364 patients with GEP-NETs were identified. Overall, 18 patients diagnosed at autopsy or with primary tumors of an unknown site were excluded, leaving 346 patients with 351 primary tumors for final analysis. The overall mean annual incidence 1985-2014 was 3.65/100,000, 3.39/100,000 during 1985-1999 and 3.85/100,000 during 2000-2014 (p = NS). The most common primary tumor site was the appendix (32%), followed by the jejunum/ileum (24%) and stomach (17%). In all, 18% of patients presented with distant metastases at the time of diagnosis, most noticeably patients with primary tumors of the colon (47%), pancreas (46%) and jejunum/ileum (39%). The most favorable 5-year survival was observed for tumors of the appendix (94%) and rectum (88%) and the least favorable for tumors of the pancreas (31%), colon (47%) and jejunum/ileum (66%). There were no statistically significant changes in incidence, staging or survival between the two time periods. CONCLUSIONS In this population-based study, the incidence of GEP-NETs has not changed significantly over the last decades. The incidence of metastatic disease has remained stable and overall prognosis has not improved in recent years.
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Affiliation(s)
- Hallbera Gudmundsdottir
- a Department of Internal Medicine, Division of Gastroenterology , Landspitali University Hospital , Reykjavik , Iceland
| | - Páll Helgi Möller
- b Department of Surgery, Division of Abdominal Surgery , Landspitali University Hospital , Reykjavik , Iceland.,c Faculty of Medicine , University of Iceland , Reykjavik , Iceland
| | - Jon Gunnlaugur Jonasson
- c Faculty of Medicine , University of Iceland , Reykjavik , Iceland.,d Department of Pathology , Landspitali University Hospital , Reykjavik , Iceland
| | - Einar S Björnsson
- a Department of Internal Medicine, Division of Gastroenterology , Landspitali University Hospital , Reykjavik , Iceland.,c Faculty of Medicine , University of Iceland , Reykjavik , Iceland
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Dima SO, Dumitrascu T, Pechianu C, Grigorie RT, Brasoveanu V, Sorop A, Lupescu I, Purnichescu-Purtan R, Croitoru A, Bacalbasa N, Tanase A, Tomescu DR, Herlea V, Popescu I. PROGNOSTIC FACTORS IN PATIENTS WITH SURGICAL RESECTION OF PANCREATIC NEUROENDOCRINE TUMOURS. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2018; 14:389-393. [PMID: 31149288 PMCID: PMC6525773 DOI: 10.4183/aeb.2018.389] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
CONTEXT Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. OBJECTIVE The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. SUBJECTS AND METHODS The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. RESULTS Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. CONCLUSIONS Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%.
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Affiliation(s)
- S O Dima
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
- Fundeni Clinical Institute - Center of Excellence in Translational Medicine - Bucharest, Romania
| | - T Dumitrascu
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
| | - C Pechianu
- Fundeni Clinical Institute - Center of Excellence in Translational Medicine - Bucharest, Romania
- Fundeni Clinical Institute - Department of Pathology - Bucharest, Romania
| | - R T Grigorie
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
| | - V Brasoveanu
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
| | - A Sorop
- Fundeni Clinical Institute - Center of Excellence in Translational Medicine - Bucharest, Romania
| | - I Lupescu
- Fundeni Clinical Institute - Department of Radiology and Medical Imaging - Bucharest, Romania
| | - R Purnichescu-Purtan
- Fundeni Clinical Institute - University Politehnica of Bucharest, Departament of Mathematical Methods and Models, Bucharest, Romania
| | - A Croitoru
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
- Fundeni Clinical Institute - "Titu Maiorescu" University - "Acad. Nicolae Cajal" Institute of Medical Scientific Research, Bucharest, Romania
| | - N Bacalbasa
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
- Fundeni Clinical Institute - Center of Excellence in Translational Medicine - Bucharest, Romania
| | - A Tanase
- Fundeni Clinical Institute - "Titu Maiorescu" University - "Acad. Nicolae Cajal" Institute of Medical Scientific Research, Bucharest, Romania
| | - D R Tomescu
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
| | - V Herlea
- Fundeni Clinical Institute - Department of Pathology - Bucharest, Romania
- Fundeni Clinical Institute - "Titu Maiorescu" University - "Acad. Nicolae Cajal" Institute of Medical Scientific Research, Bucharest, Romania
| | - I Popescu
- Fundeni Clinical Institute - Center of Digestive Diseases and Liver Transplantation - Bucharest, Romania
- Fundeni Clinical Institute - "Titu Maiorescu" University - "Acad. Nicolae Cajal" Institute of Medical Scientific Research, Bucharest, Romania
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Huang PY, Tsai KL, Liang CM, Tai WC, Rau KM, Wu KL, Huang CC, Chuah SK. Prognostic factors of patients with gastroenteropancreatic neuroendocrine neoplasms. Kaohsiung J Med Sci 2018; 34:650-656. [PMID: 30392572 DOI: 10.1016/j.kjms.2018.05.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 05/28/2018] [Accepted: 05/30/2018] [Indexed: 01/30/2023] Open
Abstract
There is an increasing trend in the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) worldwide. The aim of the present study was to identify the prognostic factors of patients with GEP-NENs. A cross-sectional, retrospective chart review study was conducted among patients with pathologically proven GEP-NENs between January 2003 and December 2016 at Kaohsiung Chung-Gung Memorial Hospital. A total of 97 patients who met the inclusion criteria were included (male/female = 56/41, age: 57.7 ± 15.4 years). The presentation, clinical characteristics, and disease outcomes were reviewed and analyzed. The most common primary site of the GEP-NENs was the rectum (49.5%), followed by the pancreas (17.5%), duodenum (11.3%), stomach (10.3%), colon (6.2%), and appendix (5.2%), and most GEP-NENs were hormonally nonfunctional (94.8%). There were 56 tumors classified as G1 neuroendocrine tumors (NETs), 9 as G2 NETs, and 14 as G3 neuroendocrine carcinoma (NEC). Metastasis was found in 15 patients (15%). Curative treatments, such as surgery or endoscopic resection, were performed in 83.5% of patients (n = 81). The mean overall survival duration was 107.2 ± 7.8 months. The estimated 3- and 5-year overall survival rates for all patients were 84% and 82%, respectively. Logistic regression analysis showed that large tumor size, non-rectal NENs, high histopathological grading, lymphatic metastases and distant metastases were associated with poor survival. This study suggested that the presence of lymphatic or distant metastases at diagnosis is an independent risk factor for poor prognosis in patients with GEP-NENs.
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Affiliation(s)
- Pao-Yuan Huang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kai-Lung Tsai
- Division of Colon and Rectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Ming Liang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wei-Chen Tai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kun-Ming Rau
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Keng-Liang Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Cheng Huang
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Abstract
Pancreatic neuroendocrine tumours (PNETs) might occur as a non-familial isolated endocrinopathy or as part of a complex hereditary syndrome, such as multiple endocrine neoplasia type 1 (MEN1). MEN1 is an autosomal dominant disorder characterized by the combined occurrence of PNETs with tumours of the parathyroids and anterior pituitary. Treatments for primary PNETs include surgery. Treatments for non-resectable PNETs and metastases include biotherapy (for example, somatostatin analogues, inhibitors of receptors and monoclonal antibodies), chemotherapy and radiological therapy. All these treatments are effective for PNETs in patients without MEN1; however, there is a scarcity of clinical trials reporting the efficacy of the same treatments of PNETs in patients with MEN1. Treatment of PNETs in patients with MEN1 is challenging owing to the concomitant development of other tumours, which might have metastasized. In recent years, preclinical studies have identified potential new therapeutic targets for treating MEN1-associated neuroendocrine tumours (including PNETs), and these include epigenetic modification, the β-catenin-wingless (WNT) pathway, Hedgehog signalling, somatostatin receptors and MEN1 gene replacement therapy. This Review discusses these advances.
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Affiliation(s)
- Morten Frost
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, OX3 7LJ. United Kingdom
- Endocrine Research Unit, University of Southern Denmark, Odense, 5000, Denmark
| | - Kate E Lines
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, OX3 7LJ. United Kingdom
| | - Rajesh V Thakker
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, OX3 7LJ. United Kingdom
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Walter T, Malka D, Hentic O, Lombard-Bohas C, Le Malicot K, Smith D, Ferru A, Assenat E, Cadiot G, Lievre A, Kurtz JE, Dahan L, Dubreuil O, Hautefeuille V, Lepere C, Gangloff A, Elhajbi F, Coriat R, Roquin G, Bouarioua N, Granger V, Scoazec JY, Lepage C. Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41-BEVANEC randomized phase II study. Dig Liver Dis 2018; 50:195-198. [PMID: 29258812 DOI: 10.1016/j.dld.2017.11.020] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 11/27/2017] [Accepted: 11/27/2017] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment. AIM PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC. MATERIALS AND METHODS The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy. RESULTS A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response. CONCLUSION The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.
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Affiliation(s)
- Thomas Walter
- Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
| | - David Malka
- Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France
| | - Olivia Hentic
- Gastroenterology-Pancreatology Department, Beaujon Hospital, PMAD, Clichy, France
| | - Catherine Lombard-Bohas
- Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | | | - Denis Smith
- Hepatogastroenterology and Digestive Oncology Department, Haut-Lévèque, University Hospital of Bordeaux, Pessac, France
| | - Aurélie Ferru
- Pôle régional de cancérologie, University Hospital of Poitiers, Poitiers, France
| | - Eric Assenat
- Medical Oncology Department, University Hospital St Eloi, Montpellier, France
| | - Guillaume Cadiot
- Department of Hepatogastroenterology and Digestive Oncology, Robert Debré Hospital, University Hospital of Reims, Reims, France
| | - Astrid Lievre
- Service des maladies de l'appareil digestif, University Hospital of Pontchaillou, Rennes, France
| | - Jean-Emmanuel Kurtz
- Oncology Department, Nouvel Hospital Civil, University Hospital of Strasbourg, Strasbourg, France
| | - Laetitia Dahan
- Digestive Oncology Department, University Hospital Timone, Marseille, France
| | - Olivier Dubreuil
- Hepatogastroenterology and Digestive Oncology Department, Pitié Salpêtrière Hospital, Paris, France
| | - Vincent Hautefeuille
- Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | | | - Alice Gangloff
- Gastroenterology Department, University Hospital of Rouen, Rouen, France
| | - Farid Elhajbi
- Oncology Department, Oscar Lambret Center, Lille, France
| | - Romain Coriat
- Gastroenterology Department, Cochin Hospital, Paris, France
| | - Guillaume Roquin
- Gastroenterology & Digestive Oncology, University Hospital of Angers, Angers, France
| | - Nadia Bouarioua
- Service de gastroentérologie et oncologie digestive, hôpital Nord, Saint Priest en Jarez, France
| | - Victoire Granger
- Hepatogastroenterology Department, Michallon Hospital, University Hospital of Grenoble, Grenoble, France
| | - Jean-Yves Scoazec
- Gustave Roussy Cancer Campus, Department of Surgical and Molecular Pathology, Villejuif Cedex, France; Université Paris Saclay, Université Paris Sud XI, Faculté de Médecine de Bicêtre, Le Kremlin-Bicêtre, France
| | - Côme Lepage
- Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Gastroenterology & Digestive Oncology, University Hospital Le Bocage, Dijon, France
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Lv Y, Huang C, Xu H, Han X, Zhang L, Mao W, Ji Y, Jin D, Lou W, Xu X. Clinicopathological Characteristics of the primary and metastatic Hepatic Neuroendocrine Tumors and the relevant Prognosis-Related Factors: A Retrospective Study of 81 Cases in a Single Chinese Center. J Cancer 2018; 9:479-487. [PMID: 29483952 PMCID: PMC5820914 DOI: 10.7150/jca.22157] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2017] [Accepted: 10/06/2017] [Indexed: 12/18/2022] Open
Abstract
Aims: We aim to describe the clinicopathological characteristics of hepatic neuroendocrine tumors (HNETs) and evaluate the relevant prognosis-related factors. Methods: The clinical data of 81 consecutive patients with primary or metastatic HNETs from March 2000 to July 2014 were retrospectively analyzed. Results: The mean (SD) age was 59.68 (11.64) years, 69.15% were men. The percentages of Grade G1, G2 and G3 tumors were 4.94%, 25.93% and 69.13%, respectively. Thirty-five cases were primary HNETs. Primary HNETs were more common in patients with larger tumors, lymph nodes invasions, tumor necrosis and portal vein tumor thrombus. The 1-, 3-, and 5-year overall survival rate were 88.89%, 32.10%, and 8.64%, separately. The relapse rate was 81.48% (66/81) and the mean (SD) relapse time was 18.79 (10.99) months. Reduced survival rate was associated with lymph node metastases (P=0.034), tumor necrosis (P=0.048), hard texture of tumor character (P=0.001), multifocality of tumor numbers (P=0.043), and the immunohistochemical expression of NSE (P=0.000) and Syn (P=0.037). Patients with metastatic HNETs were demonstrated with a more decreased period of Progression-free Survival (PFS) and Overall survival (OS) than their primary HNETs counterparts (P<0.05). Conclusion: Primary HNETs cohort patients were more common with aggressive clinical presentation. The hard texture of tumor character, multifocality of tumor numbers, and the immunohistochemical expression of NSE and Syn were independent predictive factors. Patients who were pathologically diagnosed as the primary HNETs seemed to achieve a long-term survival.
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Affiliation(s)
- Yang Lv
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Cheng Huang
- Department of Hepatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haizhou Xu
- Department of General Surgery, Nantong Second People's Hospital, Nantong, Jiangsu, China
| | - Xu Han
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lei Zhang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weilin Mao
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dayong Jin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xuefeng Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Manfredi S, Walter T, Baudin E, Coriat R, Ruszniewski P, Lecomte T, Laurenty AP, Goichot B, Rohmer V, Roquin G, Cojocarasu OZ, Lombard-Bohas C, Lepage C, Morcet J, Cadiot G. Management of gastric neuro-endocrine tumours in a large French national cohort (GTE). Endocrine 2017; 57:504-511. [PMID: 28664309 DOI: 10.1007/s12020-017-1355-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/13/2017] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Gastric neuro-endocrine tumours are rare. European guidelines for the management of neuro-endocrine tumours have been published in 2012. The aim of our survey was to study the management of gastric neuro-endocrine tumours registered in the national cohort. A prospective national cohort registers the Neuro-endocrine tumours in France since January 2003 (GTE network). We reviewed all the individual medical reports of gastric neuro-endocrine tumours in order to collect data on treatment. RESULTS One hundred and ninety seven gastric neuro-endocrine tumours diagnosed between 1964 and 2013 in 20 centres were registered. For 181 cases data were considered complete for our survey. Eighty four tumours were type 1 (46.4%); five types 2 (2.8%); 52 types 3 (28.7%) and 40 types 4 (22.1%). Types 1 and 2 were first endoscopically managed in 93 and 60% of cases, respectively, whereas surgery was first done in 45 and 42%, respectively, of types 3 and 4. Systemic treatment, chemotherapy and/or somatostatin analogue, was first administered exclusively for types 3 and 4. Near 3% of types 1 and 40% of types 2 received at a time somatostatin analogue treatment. Five-year survival rates were 98.3, 100, 63.2 and 31.8% for types 1, 2, 3 and 4, respectively. CONCLUSION The great majority of gastric neuro-endocrine tumours registered in this national cohort are treated in accordance with the current guidelines. The survival rates we reported must be interpreted with caution, because this cohort registered preferentially selected patients eligible for treatment. The registration of all the gastric neuro-endocrine tumours, in particular type 1 considered as benign and type 4 not eligible for specific anti-cancer treatment must be encouraged.
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Affiliation(s)
- Sylvain Manfredi
- CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France.
| | - Thomas Walter
- Département d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, cedex 03, France
| | - Eric Baudin
- Gustave Roussy, Département d'Oncologie Endocrinienne, 94805, Villejuif cedex, France
| | - Romain Coriat
- Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, Paris Descartes University, Paris, France
| | | | - Thierry Lecomte
- CHRU de Tours, service d'Hépato-Gastroenterologie, CNRS, UMR 7292, GICC & Université Francois-Rabelais, Tours, France
| | | | - Bernard Goichot
- Department of Internal Medicine, Endocrinology and Nutrition, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
| | - Vincent Rohmer
- Service d'endocrinologie et maladies métaboliques, CHU d'Angers, 4 rue Larrey, 49100, Angers, France
| | | | | | - Catherine Lombard-Bohas
- Département d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, cedex 03, France
| | - Côme Lepage
- CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France
| | | | - Guillaume Cadiot
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France
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Functional and non-functional pancreatic neuroendocrine tumours: ENETS or AJCC TNM staging system? Oncotarget 2017; 8:82784-82795. [PMID: 29137302 PMCID: PMC5669928 DOI: 10.18632/oncotarget.20007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 06/12/2017] [Indexed: 02/05/2023] Open
Abstract
Background There are currently 2 Tumour-Node-Metastasis (TNM) staging systems for pancreatic neuroendocrine tumours (p-NETs) - European Neuroendocrine Tumour Society (ENETS) and American Joint Committee on Cancer (AJCC). P-NETs being heterogeneous, we investigated the prognostic value of the 2 systems in p-NETs, as a whole, and more interestingly in functional and non-functional sub-groups separately, with a view to ascertaining any potential clinical benefits of using one system over the other. Methods Data from patients with surgically resected p-NETs were retrospectively reviewed. Kaplan-Meier method and Cox Regression proportional hazards model were used to analyse overall survival (OS) and prognostic predictors respectively. Results In the whole group of 165 patients, both TNM systems successfully discriminated OS differences when comparing stages I and II with stages III and IV (P<0.05); ENETS stage III patients had a significantly better OS than those in stage IV (P=0.003). Patients with functional p-NETs in ENETS stage II showed a statistically better OS than those in stages III and IV (P<0.05). For non-functional tumours, the AJCC staging system could effectively discriminate between the OS differences of patients in stage I with stages III and IV, or stage II with III and IV (P<0.05). Along with surgical intent and World Health Organisation (WHO) 2010 grade, both ENETS and AJCC staging systems were effective predictors of OS for different function-status p-NETs. Conclusions The ENETS system might have potential advantages when applied to all p-NETs and to the functional sub-group, while the AJCC system might be clinically more practical for non-functional p-NETs.
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Valente R, Hayes AJ, Haugvik SP, Hedenström P, Siuka D, Korsæth E, Kämmerer D, Robinson SM, Maisonneuve P, Delle Fave G, Lindkvist B, Capurso G. Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms. Endocr Relat Cancer 2017; 24:405-414. [PMID: 28566532 DOI: 10.1530/erc-17-0040] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Accepted: 05/30/2017] [Indexed: 12/13/2022]
Abstract
Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case-control study was conducted to examine the association of selected environmental, family and medical exposure factors using a standardized questionnaire in face-to-face interviews. A ratio of 1:3 cases to controls were sex and age matched at each study site. Adjusted univariate and multivariate logistic regression analysis were performed for statistically significant factors. The following results were obtained: In 201 cases and 603 controls, non-recent onset diabetes (OR 2.09, CI 1.27-3.46) was associated with an increased occurrence of PNENs. The prevalence of non-recent onset diabetes was higher both in cases with metastatic disease (TNM stage III-IV) or advanced grade (G3) at the time of diagnosis. The use of metformin in combination with insulin was also associated with a more aggressive phenotype. Drinking coffee was more frequent in cases with localized disease at diagnosis. Our study concluded that non-recent onset diabetes was associated with an increased occurrence of PNENs and the combination of metformin and insulin was consistent with a more aggressive PNEN phenotype. In contrast to previous studies, smoking, alcohol and first-degree family history of cancer were not associated with PNEN occurrence.
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Affiliation(s)
- Roberto Valente
- Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Alastair J Hayes
- Department of General SurgeryRoyal Infirmary of Edinburgh, Edinburgh, UK
| | - Sven-Petter Haugvik
- Department of Hepato-Pancreato-Biliary SurgeryOslo University Hospital, Oslo, Norway
| | - Per Hedenström
- Unit of GastroenterologyDepartment of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Darko Siuka
- Department of GastroenterologyUniversity Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Emilie Korsæth
- Department of Hepato-Pancreato-Biliary SurgeryOslo University Hospital, Oslo, Norway
| | - Daniel Kämmerer
- Department of General and Visceral SurgeryZentralklinik Bad Berka, Bad Berka, Germany
| | - Stuart M Robinson
- Department of Hepatopancreatobiliary and Transplantation SurgeryThe Freeman Hospital, Newcastle upon Tyne, UK
| | - Patrick Maisonneuve
- Division of Epidemiology and BiostatisticsEuropean Institute of Oncology, Milan, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Bjorn Lindkvist
- Unit of GastroenterologyDepartment of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Gabriele Capurso
- Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Liu P, Zhang X, Shang Y, Lu L, Cao F, Sun M, Tang Z, Vollmar B, Gong P. Lymph node ratio, but not the total number of examined lymph nodes or lymph node metastasis, is a predictor of overall survival for pancreatic neuroendocrine neoplasms after surgical resection. Oncotarget 2017; 8:89245-89255. [PMID: 29179516 PMCID: PMC5687686 DOI: 10.18632/oncotarget.19184] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 06/28/2017] [Indexed: 12/13/2022] Open
Abstract
Aim To evaluate the prognostic significance of lymph node metastasis, extent of examined lymph nodes (ELNs) and lymph node ratio (LNR) for resected pancreatic neuroendocrine neoplasms (pNENs). Materials and Methods Surgically resected pNENs were assimilated from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier and Cox proportional hazard models were used to examine the prognostic effect of clinicopathological characteristics on overall survival; Harrell's concordance index was performed to assess the prognostic accuracy of all independent prognostic factors; and the Spearman's rank correlation was used to assess the correlation between LNR and other clinicopathological characteristics. Results Totally, 1,273 pathologically confirmed pNENs were included in our study. The extent of ELNs failed to show any survival benefit in entire cohort (ELNs ≤ 12 vs. ELNs > 12, P = 0.072) or pNENs without lymph node metastasis (ELNs ≤ 28 vs. ELNs > 28, P = 0.108). Lymph node metastasis and LNR > 0.40 were significantly (both P < 0.001) adverse prognostic factors of overall survival. However, only LNR > 0.40 was the independent predictor of survival after adjusted for other clinicopathological characteristics. Besides LNR, the age, gender, primary tumor site, grade and stage also were the independent predictors of overall survival; and this survival model had an acceptable predictive power (Harrell's concordance index, 0.731). Conclusions The current study suggested that the LNR, not the total number of ELNs and the lymph node metastasis, is an independent prognostic indicator of overall survival for pNENs after surgical resection.
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Affiliation(s)
- Peng Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China
| | - Xianbin Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.,Institute of Experimental Surgery, University of Rostock, Schillingallee 69a, Rostock, 18059, Germany
| | - Yuru Shang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China
| | - Lili Lu
- Department of Epidemiology, Dalian Medical University, Dalian, 116044, China
| | - Fei Cao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China
| | - Min Sun
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Zhaohui Tang
- Department of General Surgery, Xinhua Hospital Shanghai Jiaotong University, Shanghai, 200092, China
| | - Brigitte Vollmar
- Institute of Experimental Surgery, University of Rostock, Schillingallee 69a, Rostock, 18059, Germany
| | - Peng Gong
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.,Dalian Key Laboratory of Hepatobiliary Pancreatic Diseases Prevention and Treatment and Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, 116011, China
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Walter T, Tougeron D, Baudin E, Le Malicot K, Lecomte T, Malka D, Hentic O, Manfredi S, Bonnet I, Guimbaud R, Coriat R, Lepère C, Desauw C, Thirot-Bidault A, Dahan L, Roquin G, Aparicio T, Legoux JL, Lombard-Bohas C, Scoazec JY, Lepage C, Cadiot G. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort. Eur J Cancer 2017; 79:158-165. [PMID: 28501762 DOI: 10.1016/j.ejca.2017.04.009] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 04/05/2017] [Accepted: 04/06/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. PATIENTS AND METHODS All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. RESULTS 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). CONCLUSIONS We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.
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Affiliation(s)
- T Walter
- University Hospital, Lyon, France.
| | | | - E Baudin
- Gustave Roussy Institute, Villejuif, France
| | | | | | - D Malka
- Gustave Roussy Institute, Villejuif, France
| | - O Hentic
- Beaujon Hospital, Clichy, France
| | | | - I Bonnet
- Valenciennes Hospital, Valenciennes, France
| | | | - R Coriat
- Cochin Hospital, University Paris Descartes, Paris, France
| | - C Lepère
- Georges Pompidou European Hospital, University Paris-V, Paris, France
| | - C Desauw
- University Hospital, Lille, France
| | | | - L Dahan
- La Timone Hospital, Marseille, France
| | - G Roquin
- University Hospital, Angers, France
| | | | | | | | | | - C Lepage
- FFCD, Dijon, France; University Hospital, Dijon, France
| | - G Cadiot
- University Hospital, Reims, France
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Andriantsoa M, Hoibian S, Autret A, Gilabert M, Sarran A, Niccoli P, Raoul JL. An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value. PLoS One 2017; 12:e0177971. [PMID: 28562682 PMCID: PMC5451042 DOI: 10.1371/journal.pone.0177971] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 05/05/2017] [Indexed: 11/19/2022] Open
Abstract
Background In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). Patients and methods We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Results Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Conclusions Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.
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Affiliation(s)
- Maeva Andriantsoa
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Solene Hoibian
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Aurelie Autret
- Department of Biostatistics, Paoli-Calmettes Institute, Marseille, France
| | - Marine Gilabert
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Anthony Sarran
- Department of Medical Imaging, Paoli-Calmettes Institute, Marseille, France
| | - Patricia Niccoli
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
- Aix-Marseille University, Marseille, France
| | - Jean-Luc Raoul
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
- * E-mail:
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Montanier N, Joubert-Zakeyh J, Pétorin C, Montoriol PF, Maqdasy S, Kelly A. The prognostic influence of the proliferative discordance in metastatic pancreatic neuroendocrine carcinoma revealed by peptide receptor radionuclide therapy: Case report and review of literature. Medicine (Baltimore) 2017; 96:e6062. [PMID: 28178157 PMCID: PMC5313014 DOI: 10.1097/md.0000000000006062] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
RATIONALE Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors. DIAGNOSES AND INTERVENTIONS We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (Lu DOTATATE). OUTCOMES Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%-70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2. LESSONS This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy.
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Affiliation(s)
- Nathanaëlle Montanier
- CHU Clermont-Ferrand, Service d’endocrinologie, diabétologie et maladies métaboliques
| | | | - Caroline Pétorin
- CHU Clermont-Ferrand, Service de chirurgie et oncologie digestive
| | | | - Salwan Maqdasy
- CHU Clermont-Ferrand, Service d’endocrinologie, diabétologie et maladies métaboliques
- UMR CNRS 6293, INSERM U1103, Université Clermont-Auvergne, Génétique Reproduction et Développement, Aubiere
| | - Antony Kelly
- Centre de Lutte Contre le Cancer Jean Perrin, Service de Médecine nucléaire, Clermont-Ferrand, France
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Huguet I, Grossman AB, O'Toole D. Changes in the Epidemiology of Neuroendocrine Tumours. Neuroendocrinology 2017; 104:105-111. [PMID: 26505990 DOI: 10.1159/000441897] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Accepted: 10/15/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND The reviewing and assessment of epidemiological characteristics of neuroendocrine tumours (NETs) remains a challenge. Despite the fact that it is an uncommon family of neoplasms, several worldwide series have revealed an increasing incidence of this rare condition. However, the data are difficult to compare over time due to changes in classification. METHODS We compared the data related to incidence, prevalence, stage of the disease at diagnosis and survival reported in several series, focusing on the differences and trying to examine some of the probable reasons that may explain the variations in the results between studies. RESULTS AND CONCLUSIONS The incidence of NETs is increasing over time, and their incidental discovery due to improved and more frequent imaging does not seem to be enough to explain this rise. Significant differences can be found between geographic regions and races, suggesting that environmental or genetic factors may contribute to the clinical and biological behaviour of these tumours; increasing our knowledge of oncogenesis will be necessary to explain them. As with other rare diseases, creating specific databases and multidisciplinary working groups would improve the accuracy of the information gained.
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Affiliation(s)
- Isabel Huguet
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
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Faure M, Niccoli P, Autret A, Cavaglione G, Mineur L, Raoul JL. Systemic chemotherapy with FOLFOX in metastatic grade 1/2 neuroendocrine cancer. Mol Clin Oncol 2016; 6:44-48. [PMID: 28123727 PMCID: PMC5245060 DOI: 10.3892/mco.2016.1097] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 10/07/2016] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with various clinical presentations and evolution. NETs are often diagnosed at a late stage, when they are already metastatic. Treatment is currently based on traditional chemotherapies, such as streptozocin, with serious side effects. The favorable toxicity profile of the combination of 5-fluorouracil with oxaliplatin, together with its significant antitumor activity in several gastrointestinal malignancies, led to the evaluation of its efficacy and tolerability in patients with advanced grade 1/2 (G1/G2) NETs. The endpoints of the study were tumor response (according to the Response Evaluation Criteria in Solid Tumors 1.1), overall survival (OS), progression-free survival (PFS) and symptom improvement. From January, 2013 to January, 2015, during our Regional Multidisciplinary Tumor Board dedicated to NETs (RENATEN network), FOLFOX was recommended for the treatment of metastatic NETs as first-line therapy or after failure of other therapies. The inclusion criteria were metastatic, well-differentiated G1/G2 NETs, progressing within the last 3 months. Cases with previous antitumor therapy were allowed. The patients received modified FOLFOX-6 and were assessed every 3 months by computed tomography or magnetic resonance imaging examinations. A total of 31 patients were included. The median follow-up was 20 months [95% confidence interval (CI): 15-27]. Nine patients (29%) exhibited a partial response, and 13 (41%) achieved stable disease; the disease control rate was 70%. A total of 9 patients exhibited disease progression. The control rate was 78% for pancreatic and 65% for extrapancreatic NETs. The median OS was not reached; the 1- and 2-year OS rates were 89 and 70%, respectively (Fig. 1). No significant difference in OS was observed between the <5 and 5-20% Ki-67 subgroups (P=0.41) (Fig. 2A) or according to primary tumor location (P=0.71) (Fig. 2B). The median PFS was 14.1 months (95% CI: 9.3-24.1), with no significant difference in PFS between the Ki-67 subgroups (P=0.26) (Fig. 3A) or by primary tumor location (P=0.995) (Fig. 3B). The median time to treatment failure was 14.72 months (95% CI: 10.0-not estimable). No unusual toxicity or toxicity-related deaths were reported. Finally, 7 of 9 patients who achieved a partial response benefited from a break in treatment of ≥3 months. The median duration of this break was 9.2 months (range, 3-42 months). Of the 13 patients with stable disease, 12 may have also benefited from a chemotherapy break. The median break duration was 10 months (range, 0.5-26 months).
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Affiliation(s)
- Marjorie Faure
- Department of Medical Oncology, Paoli-Calmettes Institute, 13009 Marseille, France
| | - Patricia Niccoli
- Department of Medical Oncology, Paoli-Calmettes Institute, 13009 Marseille, France; Department of Endocrinology and Medical Oncology, La Timone Hospital, Faculty of Medicine, University of Mediterranée, 13005 Marseille, France
| | - Aurelie Autret
- Biostatistics Department, Paoli-Calmettes Institute, 13009 Marseille, France
| | - Gerard Cavaglione
- Medical Oncology Department, Antoine Lacassagne Cancer Center, 06100 Nice, France
| | - Laurent Mineur
- Medical Oncology Department, Sainte-Catherine Institute, 84000 Avignon, France
| | - Jean-Luc Raoul
- Department of Medical Oncology, Paoli-Calmettes Institute, 13009 Marseille, France
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Shen C, Chen H, Chen H, Yin Y, Han L, Chen J, Tang S, Yin X, Zhou Z, Zhang B, Chen Z. Surgical treatment and prognosis of gastric neuroendocrine neoplasms: a single-center experience. BMC Gastroenterol 2016; 16:111. [PMID: 27613657 PMCID: PMC5016962 DOI: 10.1186/s12876-016-0505-5] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Accepted: 07/29/2016] [Indexed: 02/05/2023] Open
Abstract
Background Gastric neuroendocrine neoplasms (G-NENs) are uncommon, and data on their management is limited. We here investigated the clinicopathological characteristics, surgical and survival outcomes in G-NENs among Chinese. Moreover, we will discuss their prognostic value. Methods From existing databases of the West China Hospital, we retrospectively identified 135 consecutive patients who were surgically treated and pathologically diagnosed as G-NENs from January 2009 to August 2015. Results This entire cohort comprised 98 males and 37 females, with a median age of 60 years. Twenty-five patients underwent endoscopic resection, while 110 patients underwent open/laparoscopic surgery. Thirty-nine patients had neuroendocrine tumor G1 (NET G1), seven patients had neuroendocrine tumor G2 (NET G2), 69 patients had neuroendocrine carcinoma G3 (NEC G3) and 20 patients had mixed adenoneuroendocrine carcinoma (MANEC). The median survival was not achieved for both NET G1 and NET G2 versus 19 months (range 3–48) for NEC G3 and 10.5 months (range 3–45) for MANEC. The 3-year survival rates for stage I, II, III, and IV were 91.1 %, 78.6 %, 51.1 % and 11.8 %, respectively (P < 0.001). As for the prognostic analysis, both surgical margin and the newly updated World Health Organization (WHO) classification were independent predictors of overall survival (OS). Conclusions G-NENs are a kind of rare tumors, and patients with NET G3 and MANEC have unfavorable prognosis even surgically treated. Moreover, surgical margin and the new 2010 WHO criteria are closely associated with OS for G-NENs.
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Affiliation(s)
- Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Huijiao Chen
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Haining Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Luyin Han
- Intensive Care Unit, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiaju Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Sumin Tang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Zongguang Zhou
- Institute of Digestive Surgery and State key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Zhixin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
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Abstract
Cutaneous flushing is a common presenting complaint in endocrine disorders. The pathophysiology of flushing involves changes in cutaneous blood flow triggered by multiple intrinsic factors that are either related to physiology or disease. Flushing can be divided into episodic or persistent causes. Episodic flushing is mediated by the release of endogenous vasoactive mediators or medications, while persistent flushing results in a fixed facial erythema with telangiectasia and cyanosis due to slow-flowing deoxygenated blood in large cutaneous blood vessels. The differential diagnosis of cutaneous flushing in neuroendocrine disorders is limited, yet encompasses a broad spectrum of benign and malignant entities, including carcinoid syndrome, pheochromocytoma, Cushing syndrome, medullary thyroid cancer, and pancreatic neuroendocrine tumors. In this review, we provide a concise and up-to-date discussion on the differential diagnosis and approach of flushing in neuroendocrinology.
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Affiliation(s)
- Fady Hannah-Shmouni
- Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
| | - Constantine A Stratakis
- Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA
| | - Christian A Koch
- Division of Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA.
- G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS, USA.
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48
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Coriat R, Walter T, Terris B, Couvelard A, Ruszniewski P. Gastroenteropancreatic Well-Differentiated Grade 3 Neuroendocrine Tumors: Review and Position Statement. Oncologist 2016; 21:1191-1199. [PMID: 27401895 DOI: 10.1634/theoncologist.2015-0476] [Citation(s) in RCA: 108] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 03/21/2016] [Indexed: 02/07/2023] Open
Abstract
: In 2010, the World Health Organization (WHO) classification of neuroendocrine neoplasms was reviewed and validated the crucial role of the proliferative rate. According to the WHO classification 2010, gastroenteropancreatic neuroendocrine neoplasms are classified as well-differentiated neuroendocrine tumors (NETs) of grade 1 or 2 in up to 84%, or poorly differentiated neuroendocrine carcinomas in 6%-8%. Neuroendocrine carcinomas are of grade G. Recently, a proportion of neuroendocrine tumors presenting a number of mitoses or a Ki-67 index higher than 20% and a well-differentiated morphology have been identified, calling for a new category, well-differentiated grade 3 NET (NET G-3). Studies that have reported the characteristics of neuroendocrine neoplasms have identified more well-differentiated NET G-3 than neuroendocrine carcinomas. The main localizations of NET G-3 are the pancreas, stomach, and colon. Treatment for NET G-3 is not standardized and is balanced between G-1/2 neuroendocrine tumor and neuroendocrine carcinoma treatments. In nonmetastatic neuroendocrine tumors, the European and American guidelines recommended a surgical resection for localized neuroendocrine neoplasm, irrespective of the tumor grading. In NET G-3, chemotherapy is the benchmark if the main treatment goal is reduction of the tumor mass, particularly if it would allow a secondary surgery. In the present work, we review the epidemiology and make recommendations for the management of NET G-3. IMPLICATIONS FOR PRACTICE Neuroendocrine tumors presenting a number of mitoses or a Ki-67 index higher than 20% and a well-differentiated morphology have been identified and named well-differentiated grade 3 neuroendocrine tumors (NET G-3). The main localizations of NET G-3 are the pancreas, stomach, and colon. The prognosis is worse than that for NET G-2. In nonmetastatic NET G-3, surgery appeared to be the first option. The chemotherapy regimen in pancreatic NET G-3 should be in line with that implemented in NET G-1/2 when the Ki-67 index is below 55% and should be in line with that implemented for neuroendocrine carcinoma when Ki-67 is above 55%.
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Affiliation(s)
- Romain Coriat
- Department of Gastroenterology, Cochin Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Thomas Walter
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Oncologie Digestive, Lyon Cedex 03, France Université Claude Bernard Lyon 1, Université de Lyon, , Lyon, France
| | - Benoît Terris
- Department of Pathology, Cochin Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Anne Couvelard
- Department of Pathology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Départements Hospitalo Universitaires, Paris, France Department of Gastroenterology and Pancreatology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Départements Hospitalo Universitaires, Clichy, France
| | - Philippe Ruszniewski
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France Department of Gastroenterology and Pancreatology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Départements Hospitalo Universitaires, Clichy, France
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49
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Raddaoui EM, Almadi MA, Aljebreen AM, Alsaif FA, AlShedoukhy AA, Al-Lehibi AH, Almohameed KA, Tsolakis AV, AlAbbadi MA, Almutrafi AR. Differential diagnosis between pancreatic neuroendocrine and solid pseudopapillary neoplasms on endoscopic ultrasound-guided fine-needle aspiration. An immunohistochemical study. Saudi Med J 2016; 37:744-749. [PMID: 27381533 PMCID: PMC5018637 DOI: 10.15537/smj.2016.7.14212] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 05/25/2016] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVES To evaluate the role of applying a limited panel of immunohistochemical stains on the cellblock preparation from samples obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the aim of differentiating solid pseudopapillary neoplasms (SPNs) from neuroendocrine tumors (NETs). METHODS We retrospectively retrieved all the EUS-FNAs of the pancreas that have a diagnosis of NET or SPN that were performed at 2 tertiary care hospitals in Riyadh, Kingdom of Saudi Arabia from May 2004 to December 2014. Diff-Quik, Papanicolaou, and Immunohistochemistry stains on cellblock preparations were performed. RESULTS Twenty cases were available (16 pancreatic neuroendocrine tumors (pNETs) and 4 SPNs). The pNETs were immunoreactive for synaptophysin, chromogranin A and CD56 while E-cadherin was diffusely to focally cytoplasmic positive. β-catenin was negative or showed focal cytoplasmic immunoreactivity. In comparison, SPNs were positive for vimentin, CD10, CD-56, focally positive for progesterone receptors and synaptophysin, and revealed nuclear immunostaining for β-catenin. They were negative for chromogranin A and E-cadherin. CONCLUSION Based on EUS-FNA samples, nuclear immunoreactivity for β-catenin with loss of membranous immunostaining for E-Cadherin can potentially facilitate differentiating SPNs from pNETs.
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Affiliation(s)
- Emad M Raddaoui
- Department of Pathology, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia. E-mail.
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50
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Guo LJ, Wang CH, Tang CW. Epidemiological features of gastroenteropancreatic neuroendocrine tumors in Chengdu city with a population of 14 million based on data from a single institution. Asia Pac J Clin Oncol 2016; 12:284-8. [PMID: 27170574 DOI: 10.1111/ajco.12498] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2016] [Indexed: 02/06/2023]
Abstract
AIM Recent studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in the United States as well as the European studies demonstrate an increasing GEP-NETs incidence. Most information on the epidemiology of neuroendocrine tumors comes from western countries. However, the epidemiological profile of GEP-NETs in West China is still unclear. The aim of study was to reflect the regional features of GEP-NETs in Chengdu city of West China based on data from a single institution. METHODS West China Hospital (WCH), the largest university hospital located in Chengdu (West China) with population of 14.04 million, has established a serial of databases in recent years. According to the data from Medical Records Section of WCH and Chengdu Health Bureau, the total patients per year in WCH covered about 25.6-28% patients of Chengdu city during the 5 years. Therefore, we have used GEP-NETs diagnosed in WCH from 2009 to 2013 to reflect the regional epidemiological profile of GEP-NETs. RESULTS GEP-NETs proportion in WCH increased 1.6-folds during past 5 years from 1.28/10(5) to 2.03/10(5) , P < 0.05. The average duration of symptom before diagnosis was 16.8 months. About 46.6% (115/248) of GEP-NETs were metastatic. Seventy-seven percent (190/248) of patients were over 40 years. Proportions of GEP-NETs from primary sites were rectum 30.6% (76/248), pancreas 23.4% (58/248), gastric 13.3% (33/248) and esophagus 11.3% (28/248). Proportions of insulinoma, vipoma and nonfunctional pancreatic neuroendocrine tumors (P-NETs) were 43.1% (25/58), 1.7% (1/58) and 55.2% (32/58) separately in the P-NETs. CONCLUSIONS There is a distinct epidemiologic profile between West China and western countries based on a single institution data. The delayed diagnosis reflects inadequate disease awareness of GEP-NETs and paucity of research funding.
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Affiliation(s)
- Lin-Jie Guo
- Department of Gastroenterology, West China Hospital of SiChuan University, ChengDu, SiChuan Province, China
| | - Chun-Hui Wang
- Department of Gastroenterology, West China Hospital of SiChuan University, ChengDu, SiChuan Province, China
| | - Cheng-Wei Tang
- Department of Gastroenterology, West China Hospital of SiChuan University, ChengDu, SiChuan Province, China
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