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1
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Karimi A, Bogdani C, O'Dwyer E, Siolas D. Emerging innovations in theranostics for pancreatic neuroendocrine tumors. NPJ Precis Oncol 2025; 9:146. [PMID: 40389624 PMCID: PMC12089376 DOI: 10.1038/s41698-025-00938-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 05/06/2025] [Indexed: 05/21/2025] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) often overexpress somatostatin receptor type 2 (SSTR2), making them ideal targets for theranostics, which integrates molecular imaging with targeted radionuclide therapy. 177Lu-DOTATATE significantly extends progression-free survival (22.8 vs. 8.5 months) compared to octreotide LAR. Despite these advances, challenges remain, including treatment resistance and long-term toxicities. In this review, we explore advancements in specialized imaging techniques, rationale combination strategies, and exploring next-generation radiopharmaceuticals.
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Affiliation(s)
- Anita Karimi
- Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY, USA
| | - Christina Bogdani
- New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, NY, USA
| | - Elisabeth O'Dwyer
- Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Despina Siolas
- Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY, USA.
- Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
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2
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Lesmana CRA. Endoscopic loco-regional treatment in controlling pancreatic neuroendocrine tumors (PNETs) behavior: a case series and literature review. Clin J Gastroenterol 2024; 17:754-759. [PMID: 38536602 DOI: 10.1007/s12328-024-01959-2] [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: 11/01/2023] [Accepted: 03/16/2024] [Indexed: 07/29/2024]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are considered rare pancreatic neoplasms, and it is a challenging disease entity due to its indolent behavior and is difficult to manage. Diagnostic challenge is usually found in the imaging-based approach, such as transabdominal ultrasound, abdominal CT scan, and abdominal MRI. Surgery is still the main key player in controlling the disease. The main problems in clinical practice are the early detection of small PNETs lesion and non-functional PNET (NF-PNET) cases. Most cases usually come with large tumor size or metastatic disease. Endoscopic ultrasound (EUS) has been well-known as the most sensitive tool for early detection of pancreatic malignancy. It has now also been developed for managing pancreatic cancer, such as tumor ablation therapy. We presented four variety of PNETs cases (one patient with non-functioning PNETs and three patients with functioning PNETs) who have been successfully treated with EUS-guided radiofrequency ablation (RFA) with good control of tumor growth during follow-up. One patient with a large-size insulinoma could have the tumor controlled gradually after several EUS-RFA sessions. No adverse events or major complications were observed during and after the EUS-RFA procedure. EUS has been shown as a promising tool not only for more accurate diagnosis but also for tumor growth control. However, it would need further comparison studies between EUS and surgical approaches to make a better treatment strategy.
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Affiliation(s)
- Cosmas Rinaldi Adithya Lesmana
- Hepatobiliary Division, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jl. Diponegoro 71, Jakarta, 10430, Indonesia.
- Digestive Disease & GI Oncology Center, Medistra Hospital, Jakarta, Indonesia.
- Gastrointestinal Cancer Center, Mochtar Riyadi Comprehensive Cancer Center (MRCCC) Siloam Semanggi Hospital, Jakarta, Indonesia.
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Taherifard E, Bakhtiar M, Mahnoor M, Ahmed R, Cavalcante L, Zhang J, Saeed A. Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis. BMC Cancer 2024; 24:192. [PMID: 38347461 PMCID: PMC10860315 DOI: 10.1186/s12885-024-11926-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/27/2024] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET. METHODS Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs). RESULTS A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities. CONCLUSIONS In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).
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Affiliation(s)
- Erfan Taherifard
- Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Muhammad Bakhtiar
- Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mahnoor Mahnoor
- Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Rabeea Ahmed
- Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | | | - Janie Zhang
- Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- UPMC Hillman Cancer Center, Pittsburgh, PA, USA
| | - Anwaar Saeed
- Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
- UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
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Gorai PK, Bharti PS, Kumar S, Rajacharya GH, Bandyopadhyay S, Pal S, Dhingra R, Kumar R, Nikolajeff F, Kumar S, Rani N. C1QA and COMP: plasma-based biomarkers for early diagnosis of pancreatic neuroendocrine tumors. Sci Rep 2023; 13:21021. [PMID: 38030709 PMCID: PMC10686980 DOI: 10.1038/s41598-023-48323-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/24/2023] [Indexed: 12/01/2023] Open
Abstract
Pancreatic Neuroendocrine tumors (PanNET) are challenging to diagnose and often detected at advanced stages due to a lack of specific and sensitive biomarkers. This study utilized proteomics as a valuable approach for cancer biomarker discovery; therefore, mass spectrometry-based proteomic profiling was conducted on plasma samples from 12 subjects (3 controls; 5 Grade I, 4 Grade II PanNET patients) to identify potential proteins capable of effectively distinguishing PanNET from healthy controls. Data are available via ProteomeXchange with the identifier PXD045045. 13.2% of proteins were uniquely identified in PanNET, while 60% were commonly expressed in PanNET and controls. 17 proteins exhibiting significant differential expression between PanNET and controls were identified with downstream analysis. Further, 5 proteins (C1QA, COMP, HSP90B1, ITGA2B, and FN1) were selected by pathway analysis and were validated using Western blot analysis. Significant downregulation of C1QA (p = 0.001: within groups, 0.03: control vs. grade I, 0.0013: grade I vs. grade II) and COMP (p = 0.011: within groups, 0.019: control vs grade I) were observed in PanNET Grade I & II than in controls. Subsequently, ELISA on 38 samples revealed significant downregulation of C1QA and COMP with increasing disease severity. This study shows the potential of C1QA and COMP in the early detection of PanNET, highlighting their role in the search for early-stage (Grade-I and Grade-II) diagnostic markers and therapeutic targets for PanNET.
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Affiliation(s)
- Priya Kumari Gorai
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| | | | - Shashi Kumar
- Department of Metabolic Engineering, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Girish H Rajacharya
- Department of Metabolic Engineering, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | | | - Sujoy Pal
- Department of GI Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Renu Dhingra
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Fredrik Nikolajeff
- Department of Health Science, Lulea University of Technology, Luleå, Sweden
| | - Saroj Kumar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
- Department of Health Science, Lulea University of Technology, Luleå, Sweden.
| | - Neerja Rani
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
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Chen Y, Yamamoto T, Takahashi Y, Moro T, Tajima T, Sakaguchi Y, Sakata N, Yokoyama A, Hijioka S, Sada A, Tabata Y, Ohki R. Metabolic intervention by low carbohydrate diet suppresses the onset and progression of neuroendocrine tumors. Cell Death Dis 2023; 14:597. [PMID: 37679316 PMCID: PMC10484927 DOI: 10.1038/s41419-023-06123-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 08/22/2023] [Accepted: 08/29/2023] [Indexed: 09/09/2023]
Abstract
Insulin signaling often plays a role in the regulation of cancer, including tumor initiation, progression, and response to treatment. In addition, the insulin-regulated PI3K-Akt-mTOR pathway plays an important role in the regulation of islet cell proliferation, and this pathway is hyperactivated in human non-functional pancreatic neuroendocrine tumors (PanNETs). We, therefore, investigated the effect of a very low carbohydrate diet (ketogenic diet) on a mouse model that develops non-functional PanNETs to ask how reduced PI3K-Akt-mTOR signaling might affect the development and progression of non-functional PanNET. We found that this dietary intervention resulted in lower PI3K-Akt-mTOR signaling in islet cells and a significant reduction in PanNET formation and progression. We also found that this treatment had a significant effect on the suppression of pituitary NET development. Furthermore, we found that non-functional PanNET patients with lower blood glucose levels tend to have a better prognosis than patients with higher blood glucose levels. This preclinical study shows that a dietary intervention that results in lower serum insulin levels leads to lower insulin signals within the neuroendocrine cells and has a striking suppressive effect on the development and progression of both pancreatic and pituitary NETs.
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Affiliation(s)
- Yu Chen
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Tatsuki Yamamoto
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
- Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Yura Takahashi
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
- Tokyo College of Biotechnology, 1-3-14 Kitakoujiya, Ohta-ku, Tokyo, 144-0032, Japan
| | - Tomoka Moro
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
- Tokyo College of Biotechnology, 1-3-14 Kitakoujiya, Ohta-ku, Tokyo, 144-0032, Japan
| | - Tomoko Tajima
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yukiko Sakaguchi
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Naoaki Sakata
- Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Nanakuma 7-45-1, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Akihiko Yokoyama
- Tsuruoka Metabolomics Laboratory, National Cancer Center, Yamagata, 997-0052, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Akane Sada
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yuko Tabata
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
| | - Rieko Ohki
- Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.
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Konstantinoff KS, Morani AC, Hope TA, Bhosale PR, Francis IR, Yano M, Iravani A, Trikalinos NA, Itani M. Pancreatic neuroendocrine tumors: tailoring imaging to specific clinical scenarios. Abdom Radiol (NY) 2023; 48:1843-1853. [PMID: 36737523 DOI: 10.1007/s00261-022-03737-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 02/05/2023]
Abstract
The clinical and imaging presentation of pancreatic neuroendocrine tumors (PanNETs) is variable and depends on tumor grade, stage, and functional status. This degree of variability combined with a multitude of treatment options and imaging modalities results in complexity when choosing the most appropriate imaging studies across various clinical scenarios. While various guidelines exist in the management and evaluation of PanNETs, there is an overall lack of consensus and detail regarding optimal imaging guidelines and protocols. This manuscript aims to fill gaps where current guidelines may lack specificity regarding the choice of the most appropriate imaging study in the diagnosis, treatment planning, monitoring, and surveillance of PanNETs under various clinical scenarios.
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Affiliation(s)
- Katerina S Konstantinoff
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, The University of California, San Francisco, 185 Berry Street Lobby 6, San Francisco, CA, 94107, USA
| | - Priya R Bhosale
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Isaac R Francis
- Department of Radiology, Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Hospital, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Amir Iravani
- Department of Radiology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Nikolaos A Trikalinos
- Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA.
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Sedhai S, Mohammed F, Sahtiya S, Sanaullah S, Pritwani P, Saleem F, Abere A, Ghaffari MAZ. Pancreatic Neuroendocrine Tumor (PNET) Presenting as a Pseudocyst: A Case Report. Cureus 2022; 14:e29617. [DOI: 10.7759/cureus.29617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2022] [Indexed: 11/05/2022] Open
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Buchholz M, Strotmann J, Majchrzak-Stiller B, Hahn S, Peters I, Horn J, Müller T, Höhn P, Uhl W, Braumann C. New Therapy Options for Neuroendocrine Carcinoma of the Pancreas—The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo. Cancers (Basel) 2022; 14:cancers14112685. [PMID: 35681665 PMCID: PMC9179328 DOI: 10.3390/cancers14112685] [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] [Received: 04/26/2022] [Revised: 05/20/2022] [Accepted: 05/25/2022] [Indexed: 11/22/2022] Open
Abstract
Simple Summary Neuroendocrine carcinoma of the pancreas is a highly aggressive form of neuroendocrine tumor associated with poor survival and increasing occurrence. GP-2250 is an emergent substance showing antineoplastic properties, especially in combination with Gemcitabine. This study was the first to evaluate the antineoplastic effects of GP-2250 on pancreatic neuroendocrine carcinoma. The combination of GP-2250 and Gemcitabine showed highly synergistic effects in a cell culture model, as well as in mice, without the development of secondary resistances. These findings form the basis for further clinical evaluation of a highly promising combination therapy. Abstract Neuroendocrine carcinoma of the pancreas (pNEC) is an aggressive form of neuroendocrine tumor characterized by a rising incidence without an increase in survival rates. GP-2250 is an oxathiazinane derivate possessing antineoplastic effects, especially in combination with Gemcitabine on the pancreatic adenocarcinoma. The cytotoxic effects of the monotherapy of GP-2250 (GP-2250mono) and Gemcitabine (Gemmono), as well as the combination therapy of both, were studied in vitro using an MTT-assay on the QGP-1 and BON-1 cell lines, along with in vivo studies on a murine xenograft model of QGP-1 and a patient-derived xenograft model (PDX) of Bo99. In vitro, Gemmono and GP-2250mono showed a dose-dependent cytotoxicity. The combination of GP-2250 and Gemcitabine exhibited highly synergistic effects. In vivo, the combination therapy obtained a partial response in QGP-1, while GP-2250mono and Gemmono showed progressive disease or stable disease, respectively. In Bo99 PDX, the combination therapy led to a partial response, while the monotherapy resulted in progressive disease. No development of secondary resistances was observed, as opposed to monotherapy. This study was the first to evaluate the effects of the emerging substance GP-2250 on pNEC. The substance showed synergism in combination with Gemcitabine. The combination therapy proved to be effective in vitro and in vivo, without the development of secondary resistances.
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Affiliation(s)
- Marie Buchholz
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
- Correspondence: ; Tel.: +49-234-509-6236
| | - Johanna Strotmann
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
| | - Britta Majchrzak-Stiller
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
| | - Stephan Hahn
- Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, 44780 Bochum, Germany;
| | - Ilka Peters
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
| | - Julian Horn
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
| | | | - Philipp Höhn
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
| | - Waldemar Uhl
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
| | - Chris Braumann
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (J.S.); (B.M.-S.); (I.P.); (J.H.); (P.H.); (W.U.); (C.B.)
- Department of General, Visceral and Vascular Surgery, Evangelische Kliniken Gelsenkirchen, Akademisches Lehrkrankenhaus der Universität Duisburg-Essen, 45879 Gelsenkirchen, Germany
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Arman T, Nelson PS. Endocrine and paracrine characteristics of neuroendocrine prostate cancer. Front Endocrinol (Lausanne) 2022; 13:1012005. [PMID: 36440195 PMCID: PMC9691667 DOI: 10.3389/fendo.2022.1012005] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/24/2022] [Indexed: 11/12/2022] Open
Abstract
Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.
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Affiliation(s)
- Tarana Arman
- Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Peter S. Nelson
- Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA, United States
- *Correspondence: Peter S. Nelson,
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10
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Salahshour F, Taslimi R, Moosavi NS, Yazdi NA, Esfandbod M. Pancreatic Neuroendocrine Tumor presenting as a diffuse pancreatic enlargement, case report and review of literature. J Radiol Case Rep 2021; 15:11-20. [PMID: 33717403 DOI: 10.3941/jrcr.v15i1.3822] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Pancreatic neuroendocrine tumors are rare neoplasms that comprise 1-2% of all pancreatic tumors. However, they are the second most common solid pancreatic neoplasms. They have a wide range of imaging appearances and they can show common to very rare imaging presentations. Most of the time they are solitary well-marginated enhancing solid mass arising in a certain aspect of the pancreas. We present a case report of a 41-year-old female who underwent clinical work-up for abdominal pain, loss of appetite and weight loss for the past year. Ultrasound, computed tomography, and magnetic resonance imaging show diffuse homogenous pancreatic enlargement without contour deformity or a focal mass. Lymphoma and autoimmune pancreatitis were suggested based on imaging findings but IGg4 level and other lab data were normal. Endoscopic ultrasonography confirmed the diffuse enlargement of the pancreas without peripheral structures involvement. The pathological results of multiple fine-needle aspiration biopsy from all parts of the enlarged pancreas revealed a low-grade neuroendocrine tumor.
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Affiliation(s)
- Faeze Salahshour
- Department of Radiology, Advanced diagnostic and interventional radiology research center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Liver Transplantation Research Center, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Reza Taslimi
- Department of Gastroenterology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Najme-Sadat Moosavi
- Department of Radiology, Advanced diagnostic and interventional radiology research center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Niloofar Ayoobi Yazdi
- Department of Radiology, Advanced diagnostic and interventional radiology research center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Liver Transplantation Research Center, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mohsen Esfandbod
- Department of Oncology and Hematology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
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11
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Cuthbertson DJ, Barriuso J, Lamarca A, Manoharan P, Westwood T, Jaffa M, Fenwick SW, Nuttall C, Lalloo F, Prachalias A, Pizanias M, Wieshmann H, McNamara MG, Hubner R, Srirajaskanthan R, Vivian G, Ramage J, Weickert MO, Pritchard DM, Vinjamuri S, Valle J, Yip VS. The Impact of 68Gallium DOTA PET/CT in Managing Patients With Sporadic and Familial Pancreatic Neuroendocrine Tumours. Front Endocrinol (Lausanne) 2021; 12:654975. [PMID: 34163434 PMCID: PMC8215358 DOI: 10.3389/fendo.2021.654975] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 05/11/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Pancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan localise and stage disease. This study aimed to evaluate the complementary role of 68Gallium (68Ga)-DOTA PET/CT in managing patients with panNETs. DESIGN A retrospective study conducted across three tertiary UK NET referral centres. METHODS Demographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a 68Ga-DOTA PET/CT scan for a suspected panNET. RESULTS We collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1 vs. 9.3% (n=163 vs. 17) alive vs. dead (3 data missing), 141 sporadic vs. 42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional vs. functional tumours comprised 73.2 vs. 21.3% (n=134 vs. 39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 224 68Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall, 68Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases. CONCLUSION 68Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease.
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Affiliation(s)
- Daniel J. Cuthbertson
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
- Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
- *Correspondence: Daniel J. Cuthbertson,
| | - Jorge Barriuso
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Angela Lamarca
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Prakash Manoharan
- Department of Radiology and Nuclear Medicine, The Christie NHS Foundation Trust ENETS Centre of Excellence, Manchester, United Kingdom
| | - Thomas Westwood
- Department of Radiology and Nuclear Medicine, The Christie NHS Foundation Trust ENETS Centre of Excellence, Manchester, United Kingdom
| | - Matthew Jaffa
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Stephen W. Fenwick
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Christina Nuttall
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Fiona Lalloo
- Department of Clinical Genetics, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary’s Hospital, Manchester, United Kingdom
| | - Andreas Prachalias
- Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Michail Pizanias
- Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Hulya Wieshmann
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Mairead G. McNamara
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Richard Hubner
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Raj Srirajaskanthan
- Neuroendocrine Tumour Unit, KHP ENETS Centre of Excellence, Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Gillian Vivian
- Neuroendocrine Tumour Unit, KHP ENETS Centre of Excellence, Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - John Ramage
- Neuroendocrine Tumour Unit, KHP ENETS Centre of Excellence, Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Martin O. Weickert
- The Arden Neuroendocrine Centre, ENETS Centre of Excellence, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
| | - D Mark Pritchard
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
- Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Sobhan Vinjamuri
- Liverpool University Hospitals NHS Foundation Trust, ENETS Centre of Excellence, Liverpool, United Kingdom
| | - Juan Valle
- Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, United Kingdom
| | - Vincent S. Yip
- Barts and the London HPB Centre, Royal London Hospital, London, United Kingdom
- Department of Pancreatobiliary Surgery, Royal Liverpool University Hospital, Liverpool, United Kingdom
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12
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Pancreatic Neuroendocrine Tumor-Induced Hyperammonemic Encephalopathy in the Absence of Hepatic Involvement. ACG Case Rep J 2020; 7:e00425. [PMID: 32766367 PMCID: PMC7357707 DOI: 10.14309/crj.0000000000000425] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 05/08/2020] [Indexed: 11/17/2022] Open
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13
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Marincola Smith P, Baechle J, Solórzano CC, Tan M, Lopez-Aguiar AG, Dillhoff M, Beal E, Poultsides G, Cannon JGD, Rocha FG, Crown A, Cho C, Beems M, Winslow ER, Rendell VR, Krasnick BA, Fields RC, Maithel SK, Bailey CE, Idrees K. Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group. HPB (Oxford) 2020; 22:1042-1050. [PMID: 31806388 PMCID: PMC7263954 DOI: 10.1016/j.hpb.2019.10.2441] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 10/22/2019] [Accepted: 10/24/2019] [Indexed: 01/28/2023]
Abstract
BACKGROUND Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection. METHODS A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression. RESULTS Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia. CONCLUSION PRBC transfusion is associated with worse survival for patients undergoing PNET resection.
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Affiliation(s)
- Paula Marincola Smith
- Division of Surgical Oncology, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Carmen C Solórzano
- Division of Surgical Oncology, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Marcus Tan
- Division of Surgical Oncology, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Mary Dillhoff
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Eliza Beal
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - George Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - John G D Cannon
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Flavio G Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Angelena Crown
- Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Clifford Cho
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Emily R Winslow
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Victoria R Rendell
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Bradley A Krasnick
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Christina E Bailey
- Division of Surgical Oncology, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
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14
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Xu X, Honda K, Miura N, Hori S, Le Blanc S, Bergmann F, Gaida MM, Volkmar M, Schimmack S, Hackert T, Strobel O, Felix K. Actinin-4 splice variant - a complementary diagnostic and prognostic marker of pancreatic neuroendocrine neoplasms. J Cancer 2020; 11:2318-2328. [PMID: 32127958 PMCID: PMC7052930 DOI: 10.7150/jca.37503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 01/02/2020] [Indexed: 11/05/2022] Open
Abstract
Introduction: For pathological diagnosis of pancreatic neuroendocrine neoplasms (pNENs) the routinely used immunohistochemical markers are chromogranin A (CgA) and synaptophysin (Syn). Their ability as prognostic markers is not well established. A splice variant of actinin-4 (Actn-4sv) was recently found to be an excellent biomarker of neuroendocrine neoplasms of the lung. We aimed to investigate the expression of Actn-4sv in pNENs and evaluate its quality as a biomarker of pNENs. Methods: Paraffin-embedded and frozen tissues specimens from 122 pNENs were analyzed. Western blots were performed to prove and compare the relative amount of Actn-4sv expression in pNENs tissue homogenates. For comparison pancreatic ductal adenocarcinoma (PDAC) and normal pancreatic tissues were analyzed in parallel. Immunohistochemistry (IHC) of paraffin sections of pNENs for Actn-4sv were performed and compared to the classic neuroendocrine markers CgA and Syn. Correlations were calculated between the staining intensity and distribution of Actn-4sv and staging, grading and afflicted lymph nodes respectively. Results: Actn-4sv was expressed in 88.5% (108/122) of pNENs, but not in normal pancreatic tissues (0/14) or PDAC (0/14). Compared to CgA and Syn, Actn-4sv was not detectable in islet cells of the normal pancreas. Staining intensity of Actn-4sv on pNENs negatively correlated to the histological grading (Spearman r=-0.4990, p<0.0001) and staging (r = -0.2581, p = 0.0041) but no correlation to afflicted lymph nodes was found. A significantly better overall survival was observed for pNEN patients with higher expression of Actn-4sv (hazard ratio 2.7; log-rank test p= 0.0349). Conclusions: The expression of Actn-4sv may be an important prognostic factor for patients with pNENs. Its expression correlates with the grading and staging of the tumors.
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Affiliation(s)
- Xiaojun Xu
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Kazufumi Honda
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan
| | - Nami Miura
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan
| | - Shutaro Hori
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan
- Surgery Division, Eiju General Hospital, Taito-ku, Tokyo, Japan
| | - Solange Le Blanc
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Frank Bergmann
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Matthias M. Gaida
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
- Institute of Pathology, University Medical Center Mainz, Mainz, Germany
| | - Michael Volkmar
- Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Simon Schimmack
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Klaus Felix
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
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15
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Liu Y, Ye S, Zhu Y, He X, Pan J, Chen S, Ye B, Wang L. Impact of tumour size on metastasis and survival in patients with pancreatic neuroendocrine tumours (PNETs): A population based study. J Cancer 2019; 10:6349-6357. [PMID: 31772667 PMCID: PMC6856747 DOI: 10.7150/jca.27779] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 09/26/2019] [Indexed: 12/20/2022] Open
Abstract
Background: The relationship between tumour size and metastasis rate is poorly recognized in patients with pancreatic neuroendocrine tumours (PNETs). The impact of tumour size on prognosis was controversial in previous investigations. Methods: PNETs cases diagnosed from 1988 to 2013 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic features were retrospectively analyzed. Survival was calculated by the Kaplan-Meier method. Multivariable Cox regression models with hazard ratios (HRs) were constructed to analyze survival outcomes and risk factors. Cubic spline analysis was used to assess relationship between tumor size and probability of metastasis. Results: A total of 5424 patients were identified, 1226 (22.6%) with tumour size of 20mm or less. The probability of metastasis increased in a non-linear fashion with increasing tumour size. Univariate analysis showed that tumour size was significantly correlated with survival (P<0.001), no matter surgery was performed or not. However, subgroup analysis suggested this association to be linear for patients with localized and regional tumours (P<0.001), but stochastic in patients with distant stages (P=0.703). On multivariate analysis, tumour size was an indicator for metastasis (HR=1.010, 95%CI: 1.008-1.013, P<0.001) and size≤20mm was an independent prognostic factor for good survival. For tumours≤20mm, surgical treatment was associated with significantly improved survival (P<0.001). Conclusions: Tumour size affects the probability of metastasis. Its prognostic impact on survival is restricted to patients with localized and regional disease. For patients with tumour size ≤20mm, surgical treatment should be considered preferably.
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Affiliation(s)
- Yangyang Liu
- Department of Gastroenterology, Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, Zhejiang Provine, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Shufang Ye
- Department of Gastroenterology, Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, Zhejiang Provine, China
| | - Yabi Zhu
- Department of Gastroenterology, Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, Zhejiang Provine, China
| | - Xingkang He
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China.,Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China Department of Gastroenterology, Zhejiang University Lishui Hospital
| | - Jie Pan
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China.,Department of Endocrinology and metabolism, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Shujie Chen
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China.,Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China Department of Gastroenterology, Zhejiang University Lishui Hospital
| | - Bin Ye
- Department of Gastroenterology, Lishui Municipal Central Hospital, Lishui, Zhejiang Province, China
| | - Liangjing Wang
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China.,Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
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16
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Hopper AD, Jalal M, Munir A. Recent advances in the diagnosis and management of pancreatic neuroendocrine tumours. Frontline Gastroenterol 2019; 10:269-274. [PMID: 31290854 PMCID: PMC6583562 DOI: 10.1136/flgastro-2018-101006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 09/12/2018] [Accepted: 09/14/2018] [Indexed: 02/06/2023] Open
Abstract
The incidence of pancreatic neuroendocrine tumours (PNET) is rising mainly due to the increased use of cross-sectional imaging. Although many PNETs are asymptomatic and non-functioning, the overall 5-year survival is still less than 50%. In this article, we review the advances in diagnosis, classification and staging of PNET that have evolved with the development of new cross-sectional imaging methods and biopsy techniques. With accurate classification, evidence-based, individualised prognostic outcomes and treatments are able to be given which are also discussed.
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Affiliation(s)
- Andrew D Hopper
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Mustafa Jalal
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Alia Munir
- Department of Endocrinology, Royal Hallamshire Hospital, Sheffield, UK
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17
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Akirov A, Larouche V, Alshehri S, Asa SL, Ezzat S. Treatment Options for Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2019; 11:E828. [PMID: 31207914 PMCID: PMC6628351 DOI: 10.3390/cancers11060828] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 06/06/2019] [Accepted: 06/12/2019] [Indexed: 12/12/2022] Open
Abstract
The management of pancreatic neuroendocrine tumors (PanNETs) involves classification into non-functional or functional PanNET, and as localized or metastatic PanNET. In addition, while most PanNETs are sporadic, these endocrine neoplasms can also be manifestations of genetic syndromes. All these factors may assist in forming a risk stratification system permitting a tailored management approach. Most PanNETs are classified as non-functional because they are not associated with clinical sequelae of hormone excess. They are characterized by non-specific symptoms, such as abdominal pain or weight loss, resulting from mass effect related to the pancreatic tumor or secondary to distant metastases. Accurate staging of the disease is essential for determining the appropriate approach to therapy. As cure is only potentially possible with surgical resection of the tumor, it is recommended to remove all localized and limited metastatic disease. However, many patients present with metastatic and/or advanced local disease. In such instances, the goal of therapy is to control tumor growth and/or decrease tumor burden, lengthen survival, and palliate local symptoms and those of hormone excess. This typically requires a multimodal approach, including surgery, liver-directed treatment, and systemic medical therapy.
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Affiliation(s)
- Amit Akirov
- Institute of Endocrinology, Beilinson Hospital, Petach Tikva 49100, Israel.
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
- Department of Endocrine Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 1Z5, Canada.
| | - Vincent Larouche
- Department of Endocrine Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 1Z5, Canada.
- Department of Medicine, Division of Endocrinology and Metabolism, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada.
| | - Sameerah Alshehri
- Department of Endocrine Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 1Z5, Canada.
| | - Sylvia L Asa
- Department of Pathology, University Health Network, University of Toronto, Toronto, ON M5S 1A1, Canada.
| | - Shereen Ezzat
- Department of Endocrine Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 1Z5, Canada.
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18
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Gill P, Kim E, Chua TC, Clifton-Bligh RJ, Nahm CB, Mittal A, Gill AJ, Samra JS. MiRNA-3653 Is a Potential Tissue Biomarker for Increased Metastatic Risk in Pancreatic Neuroendocrine Tumours. Endocr Pathol 2019; 30:128-133. [PMID: 30767148 DOI: 10.1007/s12022-019-9570-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Pancreatic neuroendocrine tumours (PNETs) are relatively uncommon, accounting for 1-2% of all pancreatic neoplasms. Tumour grade (based on the Ki67 proliferative index and mitotic rate) is associated with metastatic risk across large cohorts; however, predicting the behaviour of individual tumours can be difficult. Therefore, any tool which could further stratify metastatic risk may be clinically beneficial. We sought to investigate microRNA (miRNA) expression as a marker of metastatic disease in PNETs. Tumours from 37 patients, comprising 23 with locoregional disease (L) and 14 with distant metastases (DM), underwent miRNA profiling. In total 506 miRNAs were differentially expressed between the L and DM groups, with four miRNAs (miR-3653 upregulated, and miR-4417, miR-574-3p and miR-664b-3p downregulated) showing statistical significance. A database search demonstrated that miRNA-3653 was associated with ATRX abnormalities. Mean survival between the two groups was correlated with mean expression of miRNA-3653; however, this did not reach statistical significance (p = 0.204). Although this is a small study, we conclude that miRNA-3653 upregulation may be associated with an increased risk of metastatic disease in PNETS, perhaps through interaction with ATRX and the alternate lengthening of telomeres pathway.
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Affiliation(s)
- Preetjote Gill
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia
| | - Edward Kim
- Sydney Medical School, University of Sydney, Sydney, Australia
- Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia
| | - Terence C Chua
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia
| | - Roderick J Clifton-Bligh
- Sydney Medical School, University of Sydney, Sydney, Australia
- Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia
- Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, 2065, Australia
| | - Christopher B Nahm
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia
- Sydney Medical School, University of Sydney, Sydney, Australia
- Australian Pancreatic Centre, St Leonards, Sydney, Australia
| | - Anubhav Mittal
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia
- Sydney Medical School, University of Sydney, Sydney, Australia
- Australian Pancreatic Centre, St Leonards, Sydney, Australia
| | - Anthony J Gill
- Sydney Medical School, University of Sydney, Sydney, Australia.
- Australian Pancreatic Centre, St Leonards, Sydney, Australia.
- NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia.
- Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia.
| | - Jaswinder S Samra
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia.
- Sydney Medical School, University of Sydney, Sydney, Australia.
- Australian Pancreatic Centre, St Leonards, Sydney, Australia.
- Faculty of Medical and Health Sciences, Macquarie University, Sydney, Australia.
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19
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Abstract
OBJECTIVE The pathogenesis of pancreatic neuroendocrine tumors (PNETs) is still unclear. We propose Frabin as a new molecular alteration in PNETs. Frabin is a guanine nucleotide exchange factor playing a role in mediating actin cytoskeleton changes during cell migration, morphogenesis, polarization, and division. METHODS Patients with PNETs of different grades were assessed for Frabin expression using immunohistochemistry and tissue microarray. The tissue microarray included 12 grade 1 and 3 grade 2 PNETs and 14 grade 3 pancreatic neuroendocrine carcinomas (PECAs). Frabin immunostain was scored with Allred system. Statistical analysis used SAS and R software. Immunohistochemistry scores were correlated with tumor grade and stage. The Spearman correlation coefficient was calculated with P values. RESULTS Pancreatic neuroendocrine tumors were graded according to the World Health Organization 2017 guidelines. Frabin was expressed by 24 (82.7%) of the PNET/PECA studied. Only 5 (17.2%) of the 29 PNETs/PECA evaluated were Frabin negative. Frabin expression was cytoplasmic in all cases. We found a significant positive correlation (ρ = 0.47) between Frabin immunohistochemistry score and tumor grade (P = 0.01). No correlation was found between Frabin expression and tumor stage (P = 0.91). CONCLUSIONS We report Frabin overexpression as a novel molecular alteration occurring in PNETs/PECAs.
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20
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Bartolini I, Bencini L, Risaliti M, Ringressi MN, Moraldi L, Taddei A. Current Management of Pancreatic Neuroendocrine Tumors: From Demolitive Surgery to Observation. Gastroenterol Res Pract 2018; 2018:9647247. [PMID: 30140282 PMCID: PMC6081603 DOI: 10.1155/2018/9647247] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 05/29/2018] [Accepted: 07/04/2018] [Indexed: 02/07/2023] Open
Abstract
Incidental diagnosis of pancreatic neuroendocrine tumors (PanNETs) greatly increased in the last years. In particular, more frequent diagnosis of small PanNETs leads to many challenging clinical decisions. These tumors are mostly indolent, although a percentage (up to 39%) may reveal an aggressive behaviour despite the small size. Therefore, there is still no unanimity about the best management of tumor smaller than 2 cm. The risks of under/overtreatment should be carefully evaluated with the patient and balanced with the potential morbidities related to surgery. The importance of the Ki-67 index as a prognostic factor is still debated as well. Whenever technically feasible, parenchyma-sparing surgeries lead to the best chance of organ preservation. Lymphadenectomy seems to be another important prognostic issue and, according to recent findings, should be performed in noninsulinoma patients. In the case of enucleation of the lesion, a lymph nodal sampling should always be considered. The relatively recent introduction of minimally invasive techniques (robotic) is a valuable option to deal with these tumors. The current management of PanNETs is analysed throughout the many available published guidelines and evidences with the aim of helping clinicians in the difficult decision-making process.
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Affiliation(s)
- Ilenia Bartolini
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| | - Lapo Bencini
- Department of Oncology, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Matteo Risaliti
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| | - Maria Novella Ringressi
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| | - Luca Moraldi
- Department of Oncology, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy
| | - Antonio Taddei
- Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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21
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Abstract
Hypervascular pancreatic lesions/masses can arise due to a variety of causes, both benign and malignant, leading to a wide differential diagnosis. Accurate differentiation of these lesions into appropriate diagnoses can be challenging; however, this is important for directing clinical management. This manuscript provides a multimodality imaging review of hypervascular pancreatic lesion, with emphasis on an imaging-based algorithmic approach for differentiation of these lesions, which may serve as a decision support tool when encountering these uncommon lesions. Additionally, we stratify these lesions into three categories based on malignant potential, to help guide clinical management.
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22
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Whole-Body 68Ga-DOTANOC PET/MRI Versus 68Ga-DOTANOC PET/CT in Patients With Neuroendocrine Tumors: A Prospective Study in 28 Patients. Clin Nucl Med 2018; 42:669-674. [PMID: 28682844 PMCID: PMC5636054 DOI: 10.1097/rlu.0000000000001753] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE The aim of this study was to assess the diagnostic performance of simultaneous whole-body Ga-DOTANOC PET/MRI compared with Ga-DOTANOC PET/CT for detection of distant metastatic disease in patients with well-differentiated neuroendocrine tumors (NETs). METHODS Patients with histologically proven, well-differentiated NET (G1 or G2) were included in this prospective, institutional review board-approved study. Patients underwent Ga-DOTANOC PET/CT and subsequent Ga-DOTANOC PET/MRI after a single tracer injection on the same day for staging or restaging purposes. Images were evaluated for the presence of NET lesions by 2 rater teams, each consisting of a nuclear medicine physician and a radiologist, in an observer-blinded fashion. Overall agreement, accuracy, sensitivity, and specificity, relative to a composite reference standard (consensus review including follow-up data), were calculated. RESULTS Between July 2014 and June 2016, 28 patients were enrolled. Overall agreement and accuracy between the 2 rater teams were 91.7% (95% confidence interval [CI], 87.5%-95.9%) and 97% (95% CI, 94.4%-99.6%) for PET/MRI and 92.3% (95% CI, 88.3%-96.3%) and 94.6% (95% CI, 91.2%-98.1%) for PET/CT, respectively (P = 1.00).Overall, PET/MRI reached 89.8% sensitivity (95% CI, 77.8%-96.6%) and 100% specificity (95% CI, 97%-100%); PET/CT showed 81.6% sensitivity (95% CI, 68%-91.2%) and 100% specificity (95% CI, 97%-100%) for the detection of metastatic disease in NETs. CONCLUSIONS Whole-body Ga-DOTANOC PET/MRI appears to be comparable to Ga-DOTANOC PET/CT for lesion detection in patients with well-differentiated NETs.
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Wu Y, Tedesco L, Lucia K, Schlitter AM, Garcia JM, Esposito I, Auernhammer CJ, Theodoropoulou M, Arzt E, Renner U, Stalla GK. RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors. Oncotarget 2018; 7:57878-57893. [PMID: 27506944 PMCID: PMC5295397 DOI: 10.18632/oncotarget.11081] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 07/17/2016] [Indexed: 12/12/2022] Open
Abstract
The factors triggering pancreatic neuroendocrine tumor (PanNET) progression are largely unknown. Here we investigated the role and mechanisms of the sumoylation enhancing protein RSUME in PanNET tumorigenesis. Immunohistochemical studies showed that RSUME is strongly expressed in normal human pancreas, in particular in β-cells. RSUME expression is reduced in insulinomas and is nearly absent in other types of PanNETs suggesting a role in PanNET tumorigenesis. In human pancreatic neuroendocrine BON1 cells, RSUME stimulates hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A), which are key components of tumor neovascularisation. In contrast, RSUME suppresses nuclear factor-κB (NF-κB) and its target interleukin-8 (IL-8). Correspondingly, PanNET cells with RSUME knockdown showed decreased HIF-1α activity and increased NF-κB and IL-8 production leading to a moderate reduction of VEGF-A release as reduced HIF-1α/VEGF-A production is partly compensated by NF-κB/IL-8-induced VEGF-A. Notably, RSUME stabilizes the tumor suppressor PTEN, which is frequently lost in PanNETs and whose absence is associated with metastasis formation. In vivo orthotopic transplantation of PanNET cells with or without RSUME expression into nude mice showed that PanNETs without RSUME have reduced PTEN expression, grow faster and form multiple liver metastases. In sum, RSUME differentially regulates key components of PanNET formation suggesting that the observed loss of RSUME in advanced PanNETs is critically involved in PanNET tumorigenesis, particularly in metastasis formation.
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Affiliation(s)
- Yonghe Wu
- Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.,Current address: German Cancer Research Center, Heidelberg, Germany
| | - Lucas Tedesco
- Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina
| | - Kristin Lucia
- Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
| | - Anna M Schlitter
- Institute of Pathology, Technical University of Munich, Munich, Germany
| | - Jose Monteserin Garcia
- Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
| | - Irene Esposito
- Institute of Pathology, Technical University of Munich, Munich, Germany.,Current address: Institute of Pathology, University of Düsseldorf, Düsseldorf, Germany
| | - Christoph J Auernhammer
- Department of Internal Medicine II, University-Hospital Campus Grosshadern, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Marily Theodoropoulou
- Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
| | - Eduardo Arzt
- Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina.,Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Ulrich Renner
- Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
| | - Günter K Stalla
- Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
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24
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Fielitz K, Althoff K, De Preter K, Nonnekens J, Ohli J, Elges S, Hartmann W, Klöppel G, Knösel T, Schulte M, Klein-Hitpass L, Beisser D, Reis H, Eyking A, Cario E, Schulte JH, Schramm A, Schüller U. Characterization of pancreatic glucagon-producing tumors and pituitary gland tumors in transgenic mice overexpressing MYCN in hGFAP-positive cells. Oncotarget 2018; 7:74415-74426. [PMID: 27769070 PMCID: PMC5342675 DOI: 10.18632/oncotarget.12766] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Accepted: 10/13/2016] [Indexed: 01/28/2023] Open
Abstract
Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland. Pituitary tumors expressed chromogranin A and closely resembled human pituitary adenomas. Pancreatic tumors strongly produced and secreted glucagon, suggesting that they derived from glucagon- and GFAP-positive islet cells. Interestingly, 3 out of 9 human pancreatic neuroendocrine tumors expressed MYCN, supporting the similarity of the mouse tumors to the human system. Serial transplantations of mouse tumor cells into immunocompromised mice confirmed their fully transformed phenotype. MYCN-directed treatment by AuroraA- or Brd4-inhibitors resulted in significantly decreased cell proliferation in vitro and reduced tumor growth in vivo. In summary, we provide a novel mouse model for neuroendocrine tumors of the pancreas and pituitary gland that is dependent on MYCN expression and that may help to evaluate MYCN-directed therapies.
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Affiliation(s)
- Kathrin Fielitz
- Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Kristina Althoff
- Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Katleen De Preter
- Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium
| | - Julie Nonnekens
- Genetics and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Jasmin Ohli
- Center for Neuropathology, Ludwig-Maximilians University, Munich, Germany
| | - Sandra Elges
- Department of Pathology, University Hospital, Münster, Germany
| | | | - Günter Klöppel
- Department of Pathology, Technical University, Munich, Germany
| | - Thomas Knösel
- Department of Pathology, Ludwig-Maximilians University, Munich, Germany
| | - Marc Schulte
- Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Ludger Klein-Hitpass
- Cell Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Daniela Beisser
- Genome Informatics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Henning Reis
- Department of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Annette Eyking
- Division of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Elke Cario
- Division of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Johannes H Schulte
- Department of Pediatric Oncology and Hematology, Charité University Medicine, Berlin, Germany
| | - Alexander Schramm
- Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Ulrich Schüller
- Center for Neuropathology, Ludwig-Maximilians University, Munich, Germany.,Institute of Neuropathology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.,Research Institute Childrens Cancer Center, Hamburg, Germany.,Department of Pediatric Oncology and Hematology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany
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25
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Lee DW, Kim MK, Kim HG. Diagnosis of Pancreatic Neuroendocrine Tumors. Clin Endosc 2017; 50:537-545. [PMID: 29207856 PMCID: PMC5719919 DOI: 10.5946/ce.2017.131] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 10/15/2017] [Indexed: 12/11/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are relatively rare; however, the incidence has increased over the last few decades. They are classified as functional or non-functional tumors according to the presence of associated clinical symptoms. The majority are non-functional tumors. For classification and staging, the World Health Organization 2010 classification system is the most commonly accepted. Chromogranin A is the most sensitive marker but has insufficient specificity. In general, PNETs are hypervascular tumors, and multiphasic contrast-enhanced computed tomography is considered the first choice for imaging study. Multiphasic magnetic resonance imaging can detect PNETs smaller than 2 cm and small liver metastasis compared with other modalities. Somatostatin receptor scintigraphy is often used in cases where functional PNETs are suspected. Positron emission tomography (PET) scan with 18F-fluorodeoxyglucose cannot visualize PNETs, but PET with 68-Ga DOTATATE can. Endoscopic ultrasonography can characterize smaller PNETs using contrast and confirm histology through fine needle aspiration or biopsy. In this article, we review the characteristics of grading systems and diagnostic modalities commonly used for PNETs.
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Affiliation(s)
- Dong Wook Lee
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Michelle Kang Kim
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine, The Mount Sinai Medical Center, New York, NY, USA
| | - Ho Gak Kim
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
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26
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Saunders RN, Chung M. Locally Recurrent Well-Differentiated Nonfunctioning Pancreatic Neuroendocrine Tumor Requiring Re-excision Including Portal Vein Resection. J Gastrointest Cancer 2017; 50:324-327. [PMID: 28965184 DOI: 10.1007/s12029-017-0010-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Rachel N Saunders
- Spectrum Health/Michigan State University General Surgery Residency, 221 Michigan NE, Suite 402, Grand Rapids, MI, 49503, USA.
| | - Mathew Chung
- Spectrum Health Hospital, Surgical Oncology, Michigan State University College of Human Medicine, 221 Michigan NE, Suite 402, Grand Rapids, MI, 49503, USA
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27
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Yazici C, Boulay BR. Evolving role of the endoscopist in management of gastrointestinal neuroendocrine tumors. World J Gastroenterol 2017; 23:4847-4855. [PMID: 28785139 PMCID: PMC5526755 DOI: 10.3748/wjg.v23.i27.4847] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 05/05/2017] [Accepted: 06/12/2017] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are uncommon gastrointestinal neoplasms but have been increasingly recognized over the past few decades. Luminal NETs originate from the submucosa of the gastrointestinal tract and careful endoscopic exam is a key for accurate diagnosis. Despite their reputation as indolent tumors with a good prognosis, some NETs may have aggressive features with associated poor long-term survival. Management of NETs requires full understanding of tumor size, depth of invasion, local lymphadenopathy status, and location within the gastrointestinal tract. Staging with endoscopic ultrasound or cross-sectional imaging is important for determining whether endoscopic treatment is feasible. In general, small superficial NETs can be managed by endoscopic mucosal resection and endoscopic submucosal dissection (ESD). In contrast, NETs larger than 2 cm are almost universally treated with surgical resection with lymphadenectomy. For those tumors between 11-20 mm in size, careful evaluation can identify which NETs may be managed with endoscopic resection. The increasing adoption of ESD may improve the results of endoscopic resection for luminal NETs. However, enthusiasm for endoscopic resection must be tempered with respect for the more definitive curative results afforded by surgical treatment with more advanced lesions.
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28
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Finkelstein P, Sharma R, Picado O, Gadde R, Stuart H, Ripat C, Livingstone AS, Sleeman D, Merchant N, Yakoub D. Pancreatic Neuroendocrine Tumors (panNETs): Analysis of Overall Survival of Nonsurgical Management Versus Surgical Resection. J Gastrointest Surg 2017; 21:855-866. [PMID: 28255853 DOI: 10.1007/s11605-017-3365-6] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Accepted: 01/05/2017] [Indexed: 01/31/2023]
Abstract
BACKGROUND Outcomes of patients with pancreatic neuroendocrine tumors (panNETs) undergoing surgical or nonsurgical management and outcomes of enucleation versus standard resection were compared. METHODS MEDLINE, EMBASE, PubMed, Scopus, and Cochrane were queried (2000 to present). All studies comparing patients undergoing surgical versus nonsurgical treatments, or enucleation versus standard resection, were included. Pooled risk ratios and 95% CI for survival were calculated. RESULTS Eleven studies met criteria with 1491 resected and 1607 nonsurgically managed patients. Meta-analysis showed improved overall survival with resection at 1 year (risk ratio (RR) = 1.281, CI 1.064-1.542, p = 0.009), 3 years (RR = 1.837, CI 1.594-2.117, p < 0.001), and 5 years (RR = 2.103, CI 1.50-2.945, p < 0.001). OS of patients with resected nonfunctioning panNETs was improved at 3 years (RR = 1.847, CI 1.477-2.309, p < 0.001) and 5 years (RR = 1.767, CI 1.068-2.924, p = 0.027). OS was improved when panNETs ≤2 cm were resected at 3 years (RR = 1.695, CI 1.269-2.264, p < 0.001) and 5 years (RR = 2.210, CI 1.749-2.791, p < 0.001). Fifteen articles met criteria for enucleation versus standard resection (n = 1035; 620 were nonfunctioning). Enucleation had shorter operative time (weighted mean difference (WMD) = -95.6 min, 95% CI -131.4 to -59.8, p < 0.01), less operative blood loss (WMD = -172.6 ml, 95% CI -340 to -5.1, p = 0.04), but increased postoperative pancreatic fistula (POPF) (RR = 2.08, 95% CI 1.39-3.12, p < 0.01). CONCLUSION Surgical resection of panNETs, including small and nonfunctioning, appears to be associated with improved OS. Enucleation is associated with shorter operative time, less blood loss, but greater incidence of POPF. Prospective, randomized clinical trials are needed to confirm these results.
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Affiliation(s)
- Paige Finkelstein
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Rishika Sharma
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Omar Picado
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Rahul Gadde
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Heather Stuart
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Caroline Ripat
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Alan S Livingstone
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Danny Sleeman
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Nipun Merchant
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA
| | - Danny Yakoub
- Division of Surgical Oncology, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, CRB C232, Miami, FL, 33136, USA.
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29
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Stegehuis PL, Boogerd LSF, Inderson A, Veenendaal RA, van Gerven P, Bonsing BA, Sven Mieog J, Amelink A, Veselic M, Morreau H, van de Velde CJH, Lelieveldt BPF, Dijkstra J, Robinson DJ, Vahrmeijer AL. Toward optical guidance during endoscopic ultrasound-guided fine needle aspirations of pancreatic masses using single fiber reflectance spectroscopy: a feasibility study. JOURNAL OF BIOMEDICAL OPTICS 2017; 22:24001. [PMID: 28170030 DOI: 10.1117/1.jbo.22.2.024001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 01/12/2017] [Indexed: 05/04/2023]
Abstract
Endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) of pancreatic masses suffer from sample errors and low-negative predictive values. Fiber-optic spectroscopy in the visible to near-infrared wavelength spectrum can noninvasively extract physiological parameters from tissue and has the potential to guide the sampling process and reduce sample errors. We assessed the feasibility of single fiber (SF) reflectance spectroscopy measurements during EUS-FNA of pancreatic masses and its ability to distinguish benign from malignant pancreatic tissue. A single optical fiber was placed inside a 19-gauge biopsy needle during EUS-FNA and at least three reflectance measurements were taken prior to FNA. Spectroscopy measurements did not cause any related adverse events and prolonged procedure time with ? 5 ?? min . An accurate correlation between spectroscopy measurements and cytology could be made in nine patients (three benign and six malignant). The oxygen saturation and bilirubin concentration were significantly higher in benign tissue compared with malignant tissue (55% versus 21%, p = 0.038 ; 166 ?? ? mol / L versus 17 ?? ? mol / L , p = 0.039 , respectively). To conclude, incorporation of SF spectroscopy during EUS-FNA was feasible, safe, and relatively quick to perform. The optical properties of benign and malignant pancreatic tissue are different, implying that SF spectroscopy can potentially guide the FNA sampling.
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Affiliation(s)
- Paulien L Stegehuis
- Leiden University Medical Center, Department of Surgery, Leiden, The NetherlandsbLeiden University Medical Center, Department of Radiology, Leiden, The Netherlands
| | - Leonora S F Boogerd
- Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands
| | - Akin Inderson
- Leiden University Medical Center, Department of Gastroenterology and Hepatology, Leiden, The Netherlands
| | - Roeland A Veenendaal
- Leiden University Medical Center, Department of Gastroenterology and Hepatology, Leiden, The Netherlands
| | - P van Gerven
- Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands
| | - Bert A Bonsing
- Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands
| | - J Sven Mieog
- Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands
| | - Arjen Amelink
- Netherlands Organisation for Applied Scientific Research TNO, Department of Optics, Delft, The Netherlands
| | - Maud Veselic
- Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands
| | - Hans Morreau
- Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands
| | | | | | - Jouke Dijkstra
- Leiden University Medical Center, Department of Radiology, Leiden, The Netherlands
| | - Dominic J Robinson
- Center for Optical Diagnostics and Therapy, Department of Otolaryngology and Head and Neck Surgery, Erasmus MC, Rotterdam, The Netherlands
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30
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Campa D, Capurso G, Pastore M, Talar-Wojnarowska R, Milanetto AC, Landoni L, Maiello E, Lawlor RT, Malecka-Panas E, Funel N, Gazouli M, De Bonis A, Klüter H, Rinzivillo M, Delle Fave G, Hackert T, Landi S, Bugert P, Bambi F, Archibugi L, Scarpa A, Katzke V, Dervenis C, Liço V, Furlanello S, Strobel O, Tavano F, Basso D, Kaaks R, Pasquali C, Gentiluomo M, Rizzato C, Canzian F. Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors. Sci Rep 2016; 6:39565. [PMID: 28008994 PMCID: PMC5180167 DOI: 10.1038/srep39565] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 11/23/2016] [Indexed: 01/14/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (ORhom = 2.08, 95% CI 1.05-4.11, p = 0.035). This SNP is in linkage disequilibrium with another polymorphic variant associated with increased risk of several cancer types. In silico analysis suggested that the SNP could alter the sequence recognized by the Neuron-Restrictive Silencer Factor (NRSF), whose deregulation has been associated with the development of several tumors. The mechanistic link between the allele and the disease has not been completely clarified yet but the epidemiologic evidences that link the DNA region to increased cancer risk are convincing. In conclusion, our results suggest rs2518719 as a pleiotropic CDKN2A variant associated with the risk of developing PNETs.
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Affiliation(s)
- Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy
| | - Gabriele Capurso
- Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University of Rome, Rome, Italy
| | - Manuela Pastore
- Department of Biology, University of Pisa, Pisa, Italy
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Anna Caterina Milanetto
- Department of Surgery, Oncology and Gastroenterology (DISCOG), Pancreatic and Digestive Endocrine Surgery, University of Padova, Padova, Italy
| | - Luca Landoni
- Department of Surgery, University and Hospital Trust of Verona, Verona, Italy
| | - Evaristo Maiello
- Department of Oncology, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
| | - Rita T. Lawlor
- ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy
| | - Ewa Malecka-Panas
- Dept of Digestive Tract Diseases, Medical University of Lodz, Poland
| | - Niccola Funel
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, Medical School National and Kapodistrian University of Athens, Greece
| | - Antonio De Bonis
- Department of Surgery, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
| | - Harald Klüter
- Mannheim Institute of Transfusion Medicine and Immunology, Heidelberg University, Medical Faculty Mannheim, German Red Cross Blood Service Baden-Württemberg – Hessen, Mannheim, Germany
| | - Maria Rinzivillo
- Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University of Rome, Rome, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University of Rome, Rome, Italy
| | - Thilo Hackert
- Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Stefano Landi
- Department of Biology, University of Pisa, Pisa, Italy
| | - Peter Bugert
- Mannheim Institute of Transfusion Medicine and Immunology, Heidelberg University, Medical Faculty Mannheim, German Red Cross Blood Service Baden-Württemberg – Hessen, Mannheim, Germany
| | - Franco Bambi
- Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy
| | - Livia Archibugi
- Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University of Rome, Rome, Italy
| | - Aldo Scarpa
- ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christos Dervenis
- Department of Surgery, Konstantopouleion General Hospital Nea Ionia, Greece
| | - Valbona Liço
- Department of Surgery, Oncology and Gastroenterology (DISCOG), Pancreatic and Digestive Endocrine Surgery, University of Padova, Padova, Italy
| | - Sara Furlanello
- Department of Medicine (DIMED), Laboratory Medicine, University of Padova, Padova, Italy
| | - Oliver Strobel
- Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Francesca Tavano
- Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
| | - Daniela Basso
- Department of Medicine (DIMED), Laboratory Medicine, University of Padova, Padova, Italy
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Claudio Pasquali
- Department of Surgery, Oncology and Gastroenterology (DISCOG), Pancreatic and Digestive Endocrine Surgery, University of Padova, Padova, Italy
| | | | - Cosmeri Rizzato
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Jiang Y, Jin JB, Zhan Q, Deng XX, Shen BY. Impact and Clinical Predictors of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors. Chin Med J (Engl) 2016; 128:3335-44. [PMID: 26668149 PMCID: PMC4797510 DOI: 10.4103/0366-6999.171427] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background: The optimal surgical management of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) is still controversial. Here, we evaluated the impact of lymph node status on postoperative recurrence in patients with NF-PNET and the potential of preoperative variables for predicting lymph node metastasis (LNM). Methods: In this mono-institutional retrospective cohort study conducted in 100 consecutive patients who underwent NF-PNET resection between January 2004 and December 2014, we evaluated risk factors for survival using the Kaplan–Meier method and the Cox regression model. Predictors of LNM were evaluated using the logistic regression model, and the power of predictive models was evaluated using receiver operating characteristic curve analysis. Results: Five-year disease-free survival of resected NF-PNET was 64.1%. LNM was independently associated with postoperative recurrence (hazard ratio = 3.995, P = 0.003). Multivariate analysis revealed tumor grade as an independent factor associated with LNM (G2 vs. G1: odds ratio [OR] =6.287, P = 0.008; G3 vs. G1: OR = 12.407, P = 0.001). When tumor grade was excluded, radiological tumor diameter >2.5 cm (OR = 5.430, P = 0.013) and presence of symptoms (OR = 3.366, P = 0.039) were significantly associated with LNM. Compared to neoplasms with radiological diameter >2.5 cm (32.1%), tumors ≤2.5 cm had an obviously lower risk of LNM (7.7%), indicating the reliability of this parameter in predicting LNM (area under the curve, 0.693). Incidentally discovered NF-PNETs ≤2.5 cm were associated with a low-risk of LNM and excellent survival. Conclusions: LNM is significantly associated with postoperative recurrence. Radiological tumor diameter is a reliable predictor of LNM in NF-PNETs. Our results indicate that lymphadenectomy in small (≤2.5 cm) NF-PNETs is not routinely necessary.
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Affiliation(s)
| | | | | | | | - Bai-Yong Shen
- Department of General Surgery, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
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Wells SA. Progress in Endocrine Neoplasia. Clin Cancer Res 2016; 22:4981-4988. [PMID: 27742784 DOI: 10.1158/1078-0432.ccr-16-0384] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 08/24/2016] [Indexed: 01/17/2023]
Abstract
Most endocrine tumors are benign, and afflicted patients usually seek medical advice because of symptoms caused by too much, or too little, native hormone secretion or the impingement of their tumor on a vital structure. Malignant endocrine tumors represent a more serious problem, and patient cure often depends on early diagnosis and treatment. The recent development of novel molecular therapeutics holds great promise for the treatment of patients with locally advanced or metastatic endocrine cancer. In this CCR Focus, expert clinical investigators describe the molecular characteristics of various endocrine tumors and discuss the current status of diagnosis and treatment. Clin Cancer Res; 22(20); 4981-8. ©2016 AACR
See all articles in this CCR Focus section, "Endocrine Cancers Revising Paradigms".
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Affiliation(s)
- Samuel A Wells
- Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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Huang YQ. Current progress in diagnosis and therapy of neuroendocrine neoplasms of the digestive system. Shijie Huaren Xiaohua Zazhi 2016; 24:2625-2636. [DOI: 10.11569/wcjd.v24.i17.2625] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of heterogeneous, biologically diverse, rare malignancies originated from the peptidergic neurons and neuroendocrine cells. In recent years, the incidence of NENs has been increasing gradually. They typically arise in the pancreas and gastrointestinal tract. Chromogranin A (CgA) has long been used as an important broad-spectrum marker for the identification of NENs. The diagnosis is based on histopathology demonstrating neuroendocrine features such as positive staining for chromogranin A and specific hormones such as gastrin, proinsulin, vasoactive intestinal peptide (VIP) and glucagon. In addition, radiological modalities including computed tomography (CT), positron emission tomography and computed tomography (PET/CT), magnetic resonance imaging (MRI), ultrasound (US), endoscopic ultrasound (EUS), and somatostatin receptor scintigraphy (SRS) can help establish a diagnosis. Surgery is still one of the cornerstones in the management of NENs. This article reviews the current progress in the diagnosis and therapy of NENs of the digestive system, including the pathological features and clinical diagnostic modalities for primary esophageal, gastric, duodenal, small intestinal, appendiceal, colonic, rectal, hepatic, gallbladder, extrahepatic bile duct, and pancreatic NENs, according to a revised system of classification, nomenclature and grading of NENs proposed by the fourth edition of "World Health Organization (WHO) classification of tumours of the digestive system" in 2010, and consensus of diagnosis and treatment of gastroenteropancreatic NENs (GEP-NENs) proposed by the Chinese Society of Clinical Oncology (CSCO) in 2013.
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34
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Pancreatic Neuroendocrine Tumors: an Update. Indian J Surg 2015; 77:395-402. [PMID: 26722203 DOI: 10.1007/s12262-015-1360-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare and comprise only 1-2 % of all pancreatic neoplastic disease. Although the majority of these tumors are sporadic (90 %), pNETs can arise in the setting of several different hereditary genetic syndromes, most commonly multiple endocrine neoplasia type 1 (MEN1). The presentation of pNETs varies widely, with over 60 % having malignant distant disease at the time of initial diagnosis involving the liver or other distant sites. Functioning pNETs represent approximately 10 % of all pNETs, secrete a variety of peptide hormones, and are responsible for several clinical syndromes caused by profound hormonal derangement. Surgery remains the cornerstone of therapy and the only curative approach. It should be pursued for localized disease and for metastatic lesions amenable to resection. Multimodality therapies, including liver-directed therapies and medical therapy, are gaining increasing favor in the treatment of advanced pNETs. Their utility is multifold and spans from ameliorating symptoms of hormonal excess (functional pNETs) to controlling the local and systemic disease burden (non-functional pNETs). The recent introduction of target molecular therapy has promising results especially for the treatment of progressive well-differentiated G1/G2 tumor. In this review, we summarize the current knowledge and give an update on recent advancements made in the therapeutic strategies for pNETs.
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35
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Moriyama M, Matsumoto Y, Zhou Q, Yamana K, Ikeda Y, Ayukawa F, Abe E, Sato S, Takano K, Kaidu M, Aoyama H, Saijo Y. A case of pancreatic neuroendocrine tumors. Int Cancer Conf J 2015; 5:1-4. [PMID: 31149413 DOI: 10.1007/s13691-015-0230-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 06/20/2015] [Indexed: 11/30/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are an uncommon malignancy arising from the neuroendocrine cells of pancreas. Most cases of pNETs present with metastatic disease, but there are few reports in the literature describing pNETs metastasis to the lung and mediastinal lymph nodes [1]. Moreover, although a multimodal treatment including surgical resection and chemotherapy is acceptable for management of pNETs, advanced pNETs still remain a difficult therapeutic challenge [2, 3]. Radiotherapy or combined chemoradiotherapy has not been standard in the treatment of pNETs. An 80-year-old female was admitted to our hospital with cough and anorexia. She had been diagnosed and resected pNETs 8 years ago. Mass shadow was pointed out with chest X-ray, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed. Pathological examination revealed neuroendocrine tumors, so the lung mass was considered as metastasis of pNETs. Then, we discussed her treatment at Cancer Board, and radiotherapy was chosen. We hope this case suggests that radiotherapy will be one of the treatment options for metastatic pNETs.
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Affiliation(s)
- Masato Moriyama
- 1Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 Japan
| | - Yoshifumi Matsumoto
- 1Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 Japan
| | - Qiliang Zhou
- 1Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 Japan
| | - Kanako Yamana
- 2Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Yohei Ikeda
- 2Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Fumio Ayukawa
- 2Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Eisuke Abe
- 2Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Seijiro Sato
- 3Department of Thoracic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Kabuto Takano
- 4Department of Digestive Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Motoki Kaidu
- 2Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hidefumi Aoyama
- 2Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Yasuo Saijo
- 1Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 Japan
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Leal-Lopes C, Velloso FJ, Campopiano JC, Sogayar MC, Correa RG. Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies. J Diabetes Res 2015; 2015:284680. [PMID: 26347203 PMCID: PMC4544440 DOI: 10.1155/2015/284680] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Accepted: 07/09/2015] [Indexed: 12/12/2022] Open
Abstract
The pancreas plays a central role in metabolism, allowing ingested food to be converted and used as fuel by the cells throughout the body. On the other hand, the pancreas may be affected by devastating diseases, such as pancreatitis, pancreatic adenocarcinoma (PAC), and diabetes mellitus (DM), which generally results in a wide metabolic imbalance. The causes for the development and progression of these diseases are still controversial; therefore it is essential to better understand the underlying mechanisms which compromise the pancreatic homeostasis. The interest in the study of the commensal microbiome increased extensively in recent years, when many discoveries have illustrated its central role in both human physiology and maintenance of homeostasis. Further understanding of the involvement of the microbiome during the development of pathological conditions is critical for the improvement of new diagnostic and therapeutic approaches. In the present review, we discuss recent findings on the behavior and functions played by the microbiota in major pancreatic diseases and provide further insights into its potential roles in the maintenance of pancreatic steady-state activities.
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Affiliation(s)
- Camila Leal-Lopes
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Fernando J. Velloso
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Julia C. Campopiano
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Mari C. Sogayar
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Ricardo G. Correa
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
- *Ricardo G. Correa:
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