|
1
|
Massironi S, Gallo C, Coltro L, Dell'Anna G, Preatoni P, Danese S. Clinical and biological heterogeneity of Grade 2 digestive neuroendocrine neoplasms: prognostic significance of the 10% Ki-67 index cutoff and implications for treatment strategies. A longitudinal study. J Endocrinol Invest 2025:10.1007/s40618-025-02552-1. [PMID: 39969798 DOI: 10.1007/s40618-025-02552-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 02/10/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND Digestive neuroendocrine neoplasms (NENs) encompass a heterogeneous group of tumors with varying prognoses and clinical behaviors. Grade 2 (G2) tumors, defined by a Ki-67 index between 3% and 20%, are particularly challenging to manage due to their intermediate and variable biological behavior. Evidence suggests a distinct prognosis between G2 digestive NENs with a Ki-67 index < 10% and those with a Ki-67 index ≥ 10%. AIM To investigate the clinical and biological heterogeneity between Grade 1 (G1) and G2 digestive NENs, and within G2 tumors, with a focus on the prognostic significance of a 10% Ki-67 index cutoff. METHODS This study involved a combined retrospective and prospective analysis of patients with low-grade G1 and G2 digestive NENs managed at IRCCS San Gerardo Hospital in Monza, Italy, between January 2000 and May 2024. Data on patient demographics, tumor characteristics, treatment modalities, and survival outcomes were collected and potential differences were analyzed between G1, G2 with Ki-67 index < 10% and G2 with Ki-67 index ≥ 10%. RESULTS Out of a total of 113 enrolled patients, 69 (61%) had G1 tumors, and 44 (39%) had G2 tumors. Median tumor size at diagnosis was 19 mm (IQR: 12-25 mm), with primary lesions mainly localized in the pancreas (57% among G1 and 45% among G2). Most G1 tumors were diagnosed at stage I (29 patients, 42%), while the majority of G2 tumors were metastatic at diagnosis (24 patients, 54.5%). Patients with G1 tumors exhibited a slightly higher 5-year OS rate compared to G2 tumors (98.1% vs. 92.8% respectively, though not statistically significant), and a significantly longer median PFS (141 vs. 22 months, p = 0.0003). Within the G2 group, 31 patients (70%) had a Ki-67 index < 10%, while 13 (30%) had a Ki-67 index ≥ 10%, with comparable baseline characteristics. A Ki-67 index < 10% was associated with a significantly better median PFS (38 vs. 8 months for tumors with Ki-67 index ≥ 10% G2 tumors, p = 0.002). PFS after first-line medical therapy was significantly longer in patients with a Ki-67 index < 10%, compared to those with ≥ 10% (undefined vs. 16 months, p = 0.0085), as well as median post-surgical PFS (84 vs. 10.5 months, p < 0.0001). Multivariate analysis identified higher tumor grade, advanced stage at diagnosis, and absence of PRRT as independent predictors of worse outcomes. CONCLUSIONS The findings highlight the significant clinical heterogeneity within G2 digestive NENs. A Ki-67 index cutoff of 10% within G2 tumors may serve as a critical prognostic marker, with patients with a Ki-67 index < 10% exhibiting significantly better outcomes in terms of PFS. These results suggest that the Ki-67 index could play an essential role in guiding treatment strategies, emphasizing the need for personalized approaches in managing G2 digestive NENs.
Collapse
Affiliation(s)
- Sara Massironi
- Vita e Salute San Raffaele University, Milan, Italy.
- Gastroenterology Unit, Istituti Ospedalieri Bergamaschi, Zingonia (BG), Italy.
| | - Camilla Gallo
- Digestive and Interventional Endoscopy Unit, ASST GOM Niguarda, Milan, Italy
| | - Lorenzo Coltro
- Department of Medicine, Bicocca University of Milan, Milan, Italy
| | - Giuseppe Dell'Anna
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Paoletta Preatoni
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Silvio Danese
- Vita e Salute San Raffaele University, Milan, Italy
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| |
Collapse
|
|
2
|
Massironi S, Albertelli M, Hasballa I, Paravani P, Ferone D, Faggiano A, Danese S. "Cold" Somatostatin Analogs in Neuroendocrine Neoplasms: Decoding Mechanisms, Overcoming Resistance, and Shaping the Future of Therapy. Cells 2025; 14:245. [PMID: 39996718 PMCID: PMC11854070 DOI: 10.3390/cells14040245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 01/28/2025] [Accepted: 02/04/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) represent a heterogeneous group of tumors that pose significant therapeutic challenges due to their potential for progression, metastasis, and hormonal syndromes. Somatostatin analogs (SSAs) have emerged as a cornerstone in NEN treatment, offering both antisecretory and antiproliferative effects by targeting somatostatin receptors (SSTRs). Despite their proven efficacy, intrinsic and acquired resistance mechanisms, including receptor downregulation, tumor heterogeneity, and microenvironmental influences, limit their long-term effectiveness. Recent advances, including high-dose SSA regimens and novel formulations, have aimed to optimize their therapeutic utility and address these limitations. Body of the review. This review explores the cellular and molecular mechanisms underlying the antitumor effects of SSAs, including receptor-mediated signaling pathways, cell cycle arrest, apoptosis induction, and antiangiogenesis. The role of SSAs in combination therapies with mTOR inhibitors and peptide receptor radionuclide therapy (PRRT) is analyzed, emphasizing their synergistic potential. Key clinical trials, such as RADIANT-2, EVERLAR, and NETTER-1, support the efficacy of these approaches, demonstrating improved outcomes when SSAs are combined with targeted agents or radiolabeled therapies. Emerging strategies include high-dose SSA regimens, particularly in progressive cases with low Ki67 indices. Finally, novel formulations, including oral octreotide, paltusotine, and subcutaneous depot formulations like CAM2029, offer improved pharmacokinetics, bioavailability, and patient adherence. Ongoing clinical trials, including SORENTO, further evaluate their efficacy and safety profiles. CONCLUSIONS This paper provides a comprehensive analysis of the cellular and molecular mechanisms of SSAs. SSAs remain integral to the management of NENs, providing effective tumor stabilization and symptom control. However, resistance mechanisms and tumor heterogeneity necessitate innovative approaches, including high-dose regimens, combination strategies, and next-generation formulations. Future research should focus on refining these strategies to optimize patient outcomes, enhance long-term efficacy, and expand the therapeutic landscape for NENs.
Collapse
Affiliation(s)
- Sara Massironi
- Faculty of Medicine and Surgery, Vita e Salute San Raffaele University, Via Olgettina, 20132 Milan, Italy;
- Gastroenterology Unit, Istituti Ospedalieri Bergamaschi, 24046 Bergamo, Italy
| | - Manuela Albertelli
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy (I.H.); (D.F.)
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
| | - Iderina Hasballa
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy (I.H.); (D.F.)
| | - Piero Paravani
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sant’Andrea Hospital, Sapienza University, 00189 Rome, Italy; (P.P.); (A.F.)
| | - Diego Ferone
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy (I.H.); (D.F.)
| | - Antongiulio Faggiano
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sant’Andrea Hospital, Sapienza University, 00189 Rome, Italy; (P.P.); (A.F.)
| | - Silvio Danese
- Faculty of Medicine and Surgery, Vita e Salute San Raffaele University, Via Olgettina, 20132 Milan, Italy;
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy
| |
Collapse
|
|
3
|
Massironi S, Panzuto F, Zilli A, Rinzivillo M, Ciliberto A, Romano E, Danese S, Laviano A. Nutritional aspects in neuroendocrine neoplasms. bridging the gap between dietary interventions and cancer care strategies: a scoping review. J Endocrinol Invest 2025; 48:269-281. [PMID: 39395115 PMCID: PMC11785655 DOI: 10.1007/s40618-024-02462-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 08/26/2024] [Indexed: 10/14/2024]
Abstract
PURPOSE Neuroendocrine neoplasms (NENs) represent heterogeneous tumors arising from neuroendocrine cells in different organs. Despite growing interest in the nutritional aspects of NEN management, research in this area is limited. Aim of this review is to summarize the current state of knowledge, highlight research gaps, and underscore the significance of nutrition in the comprehensive care of NEN patients. METHODS We conducted an extensive bibliographic search focusing on studies (including retrospective and prospective studies, systematic reviews, case series, and guidelines) exploring the relationship between nutritional assessments, dietary interventions, micronutrient deficiencies, and their impact on NEN outcomes. RESULTS Significant gaps exist in current research, particularly in understanding the specific nutritional needs of NEN patients and how tailored nutritional interventions can improve clinical outcomes. Evidence suggests that a high-fat Western diet may promote the growth of NEN, while a Mediterranean diet may help lower insulin levels and strengthen the immune system, potentially preventing tumor development. The ketogenic diet and intermittent fasting may also have positive impacts. Addressing common micronutrient deficiencies, such as vitamin D and niacin, is crucial to mitigate disease progression. There's a crucial need for future studies to include a comprehensive nutritional assessment incorporating patient-reported outcomes, to fully capture the impact of nutritional strategies. CONCLUSION Nutritional management, an important but under-researched facet of NEN treatment, significantly improves patients' quality of life and survival. Integrating nutrition into personalized cancer care is essential, highlighting the role of nutritional strategies in optimizing patient outcomes.
Collapse
Affiliation(s)
- Sara Massironi
- Division of Gastroenterology Fondazione, IRCCS San Gerardo dei Tintori, Monza, Italia.
- Division of Gastroenterology, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy.
| | - Francesco Panzuto
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive Disease Unit, Sapienza University of Rome, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Maria Rinzivillo
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive Disease Unit, Sapienza University of Rome, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Ambra Ciliberto
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Elena Romano
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive Disease Unit, Sapienza University of Rome, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandro Laviano
- Department of Translational and Precision Medicine, Clinical Nutrition Unit, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| |
Collapse
|
|
4
|
Massironi S, Gervaso L, Fanizzi F, Preatoni P, Dell’Anna G, Fazio N, Danese S. Venous Thromboembolism in Patients with Neuroendocrine Neoplasms: A Systematic Review of Incidence, Types, and Clinical Outcomes. Cancers (Basel) 2025; 17:212. [PMID: 39857994 PMCID: PMC11763766 DOI: 10.3390/cancers17020212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/03/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with unique biological characteristics and complications, including thromboembolism. This systematic review evaluates the incidence, types, and clinical outcomes of venous thromboembolic events (VTEs) in NEN patients. Methods: A systematic search of PubMed, Scopus, and Embase was conducted to identify studies on TEs in NENs. Eligible studies included case reports, case series, and retrospective cohort studies reporting VTEs, including deep vein thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT). Data were extracted on tumor site, functionality, differentiation grade, and VTE type. Results: In total, 33 studies were included, comprising 26 case reports, 2 case series, and 5 retrospective cohort studies. VTE prevalence ranged from 7.5% to 33% across studies. The most common VTEs were DVT, PE, and portal vein thrombosis (PVT). A meta-analysis revealed a pooled VTE prevalence of 11.1% (95% CI: 9.07-13.53%). Pancreatic NENs exhibited the highest thrombotic burden, particularly in poorly differentiated and advanced-stage tumors. Functioning tumors, including glucagonomas and ACTH-secreting NENs, were strongly associated with VTEs, potentially related to their systemic effects on coagulation and inflammation. Conclusions: Venous thromboembolism is a significant complication in NEN patients, especially in advanced or poorly differentiated tumors. Early detection and targeted management are critical for improving outcomes. Further investigations are required to clarify the mechanisms underlying thromboembolism in NENs and to develop optimized prophylactic and therapeutic strategies tailored to this patient population.
Collapse
Affiliation(s)
- Sara Massironi
- Faculty of Medicine and Surgery Via Olgettina, Vita e Salute San Raffaele University, 56, 20132 Milan, Italy; (F.F.); (S.D.)
- Gastroenterology Unit, Istituti Ospedalieri Bergamaschi, 24046 Bergamo, Italy
| | - Lorenzo Gervaso
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Via Ripamonti, 435, 20141 Milan, Italy; (L.G.); (N.F.)
| | - Fabrizio Fanizzi
- Faculty of Medicine and Surgery Via Olgettina, Vita e Salute San Raffaele University, 56, 20132 Milan, Italy; (F.F.); (S.D.)
| | - Paoletta Preatoni
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Via Olgettina, 56, 20132 Milan, Italy; (P.P.); (G.D.)
| | - Giuseppe Dell’Anna
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Via Olgettina, 56, 20132 Milan, Italy; (P.P.); (G.D.)
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Via Ripamonti, 435, 20141 Milan, Italy; (L.G.); (N.F.)
| | - Silvio Danese
- Faculty of Medicine and Surgery Via Olgettina, Vita e Salute San Raffaele University, 56, 20132 Milan, Italy; (F.F.); (S.D.)
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Via Olgettina, 56, 20132 Milan, Italy; (P.P.); (G.D.)
| |
Collapse
|
|
5
|
Maccauro M, Cuomo M, Bauckneht M, Bagnalasta M, Mazzaglia S, Scalorbi F, Argiroffi G, Kirienko M, Lorenzoni A, Aliberti G, Pusceddu S, Giuseppina C, Matteo GE, Seregni E, Chiesa C. The LUTADOSE trial: tumour dosimetry after the first administration predicts progression free survival in gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) patients treated with [ 177Lu]Lu-DOTATATE. Eur J Nucl Med Mol Imaging 2024; 52:291-304. [PMID: 39235614 DOI: 10.1007/s00259-024-06863-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 07/26/2024] [Indexed: 09/06/2024]
Abstract
PURPOSE In Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE of gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) a question remains open about the potential benefits of personalised dosimetry. This observational prospective study examines the association of individualized dosimetry with progression free survival (PFS) in G1-G2 GEP NETs patients following the standard [177Lu]Lu-DOTATATE therapeutic regimen. METHODS The analysis was conducted on 42 patients administered 4 times, and on 165 lesions. Dosimetry was performed after the first and the forth cycle, with two SPECT/CT scans at day 1 and 7 after administration. Global mean Tumour absorbed Dose of each patient (GTD) was calculated after cycle 1 and 4 as the sum of lesion doses weighted by lesion mass, normalized by the global tumour mass. Cumulative GTD_TOT was calculated as the mean between cycle 1 (GTD_1) and 4 (GTD_4) multiplied by 4. Patients were followed-up for median 32.8 (range 18-45.5) months, through blood tests and contrast enhanced CT (ceCT). This study assessed the correlation between global tumour dose (GTD) and PFS longer or shorter than 24 months. After a ROC analysis, we stratified patients according to the best cut-off value for two additional statistical analyses. At last a multivariate analysis was carried out for PFS > / < 24 months. RESULTS The median follow-up interval was 33 months, ranging from 18 to 45.5 months. The median PFS was 42 months. The progression free survival rate at 20 months was 90.5%. GTD_1 and GTD_TOT were statistically associated with PFS > / < 24 m (p = 0.026 and p = 0.03 respectively). The stratification of patients on GTD_1 lower or higher than the best cut-off value at 10.6 Gy provided significantly different median PFS of 21 months versus non reached, i.e. longer than 45.5 months (p = 0.004), with a hazard ratio of 8.6, (95% C.I.: [2 - 37]). Using GTD_TOT with the best cut-off at 43 Gy, the same PFS values were obtained as after cycle 1 (p = 0.035). At multivariate analysis, a decrease in GTD_1 and, with lower impact, a higher global tumour volume were significantly associated with PFS < 24 months. We calculated the Tumour Control Probability of obtaining PFS > 24 months as a function of GTD_1. DISCUSSION Several statistical analyses seem to confirm that simple tumour dosimetry with 2 SPECT/CT scans after the first administration allows to predict PFS values after 4 × 7.4 GBq administrations of 177Lu[Lu]-DOTATATE in G1-G2 GEP NETs. This result qualitatively confirms recent findings by a Belgian and a French study. However, dosimetric thresholds are different. This probably comes from different cohort baseline characteristics, since the median PFS in our study (42 m) was longer than in the other studies (28 m and 31 m). CONCLUSION Tumour dosimetry after the first administration of [177Lu]Lu-DOTATATE offers an important prognostic value in the clinical decision-making process, especially for the future as alternative emitters or administration schedule may become available.
Collapse
Affiliation(s)
- Marco Maccauro
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Mariarosaria Cuomo
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Matteo Bauckneht
- Nuclear Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Department of Health Sciences (DISSAL), University of Genova, Genoa, Italy
| | - Matteo Bagnalasta
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Stefania Mazzaglia
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Federica Scalorbi
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Giovanni Argiroffi
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Margarita Kirienko
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Alice Lorenzoni
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Gianluca Aliberti
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Sara Pusceddu
- Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | | | | | - Ettore Seregni
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Carlo Chiesa
- Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
| |
Collapse
|
|
6
|
Massironi S. Unraveling the Microbiome's Role in Neuroendocrine Neoplasms: A New Perspective. Neuroendocrinology 2024; 114:977-980. [PMID: 39406190 DOI: 10.1159/000541678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 09/26/2024] [Indexed: 11/12/2024]
Affiliation(s)
- Sara Massironi
- Department of Medicine and Surgery, University of Vita-Salute San Raffaele, Milan, Italy
| |
Collapse
|
|
7
|
Emengo PO, Kim MK, Divino CM. Second Primary Neuroendocrine Tumors: A Case Series. Pancreas 2024; 53:e467-e469. [PMID: 38728214 DOI: 10.1097/mpa.0000000000002348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/12/2024]
|
|
8
|
Manca G, Nonne G, Volterrani D. Intraoperative Radioguided Localization of an Occult Neuroendocrine Tumor of the Ileum. Clin Nucl Med 2024; 49:69-70. [PMID: 38048563 DOI: 10.1097/rlu.0000000000004971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/06/2023]
Abstract
ABSTRACT We report the intraoperative radioguided localization of an occult well-differentiated neuroendocrine tumor of the ileum in a patient with a known neuroendocrine lymphonodal metastasis in the mesentery. Preoperative imaging included CT, PET/CT with 68 Ga-DOTATOC, and SPECT/CT with 99m Tc-HYNICTOC. These scans revealed morphological and functional properties of the primary tumor localized in the ileum. The day after IV 99m Tc-HYNICTOC injection, the patient underwent surgery, and the target lesion was intraoperatively detected by a collimated handheld γ-probe. Postoperative pathology examination confirmed the target lesion to be a neuroendocrine tumor of the ileum.
Collapse
Affiliation(s)
- Gianpiero Manca
- From the Regional Center of Nuclear Medicine, University Hospital of Pisa, Pisa
| | | | | |
Collapse
|
|
9
|
Milewska-Kranc A, Ćwikła JB, Kolasinska-Ćwikła A. The Role of Receptor-Ligand Interaction in Somatostatin Signaling Pathways: Implications for Neuroendocrine Tumors. Cancers (Basel) 2023; 16:116. [PMID: 38201544 PMCID: PMC10778465 DOI: 10.3390/cancers16010116] [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: 11/28/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
Neuroendocrine tumors (NETs) arise from neuroendocrine cells and manifest in diverse organs. Key players in their regulation are somatostatin and its receptors (SSTR1-SSTR5). Understanding receptor-ligand interactions and signaling pathways is vital for elucidating their role in tumor development and therapeutic potential. This review highlights SSTR characteristics, localization, and expression in tissues, impacting physiological functions. Mechanisms of somatostatin and synthetic analogue binding to SSTRs, their selectivity, and their affinity were analyzed. Upon activation, somatostatin initiates intricate intracellular signaling, involving cAMP, PLC, and MAP kinases and influencing growth, differentiation, survival, and hormone secretion in NETs. This review explores SSTR expression in different tumor types, examining receptor activation effects on cancer cells. SSTRs' significance as therapeutic targets is discussed. Additionally, somatostatin and analogues' role in hormone secretion regulation, tumor growth, and survival is emphasized, presenting relevant therapeutic examples. In conclusion, this review advances the knowledge of receptor-ligand interactions and signaling pathways in somatostatin receptors, with potential for improved neuroendocrine tumor treatments.
Collapse
Affiliation(s)
| | - Jarosław B. Ćwikła
- School of Medicine, University of Warmia and Mazury, Aleja Warszawska 30, 10-082 Olsztyn, Poland
- Diagnostic Therapeutic Center–Gammed, Lelechowska 5, 02-351 Warsaw, Poland
| | | |
Collapse
|
|
10
|
Damaskos C, Dimitroulis D, Garmpi A, Antoniou EA, Kouraklis G, Psilopatis I, Mavri M, Diamantis E, Marinos G, Kyriakos G, Farmaki P, Patsouras A, Kontzoglou K, Garmpis N. Synchronous Insulinoma and Glucagonoma: A Review of the Literature. In Vivo 2023; 37:2402-2408. [PMID: 37905620 PMCID: PMC10621456 DOI: 10.21873/invivo.13345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/03/2023] [Accepted: 08/07/2023] [Indexed: 11/02/2023]
Abstract
BACKGROUND/AIM Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas. MATERIALS AND METHODS A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study. RESULTS A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021. CONCLUSION Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.
Collapse
Affiliation(s)
- Christos Damaskos
- Renal Transplantation Unit, Laiko General Hospital, Athens, Greece;
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Dimitroulis
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anna Garmpi
- First Department of Propedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Efstathios A Antoniou
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Department of General Surgery and HPB Surgery of Adults and Children, Hygeia Hospital, Athens, Greece
| | - Gregory Kouraklis
- Department of Surgery, Evgenideio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Iason Psilopatis
- Department of Gynecology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Maria Mavri
- Department of General Surgery and HPB Surgery of Adults and Children, Hygeia Hospital, Athens, Greece
| | - Evangelos Diamantis
- Academic Department of Internal Medicine - Endocrinology Unit, Agioi Anargyroi General Oncology Hospital of Kifisia, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Marinos
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Kyriakos
- Seccion de Endocrinologia y Nutrition, Hospital General Universitario Santa Lucia, Cartagena, Spain
| | - Paraskevi Farmaki
- First Department of Pediatrics, Agia Sofia Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Konstantinos Kontzoglou
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikolaos Garmpis
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Department of General Surgery and HPB Surgery of Adults and Children, Hygeia Hospital, Athens, Greece
| |
Collapse
|
|
11
|
Pokhrel A, Wu R, Wang JC. Review of Merkel cell carcinoma with solitary pancreatic metastases mimicking primary neuroendocrine tumor of the pancreas. Clin J Gastroenterol 2023; 16:641-662. [PMID: 37421584 DOI: 10.1007/s12328-023-01821-x] [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: 12/09/2022] [Accepted: 06/05/2023] [Indexed: 07/10/2023]
Abstract
OBJECTIVE/BACKGROUND Merkel cell carcinoma (MCC) but metastases to the pancreas are very rare. There are only a few cases of isolated metastases of MCC to the pancreas. Because of this rarity, it can be wrongly diagnosed as a neuroendocrine tumor of the pancreas(pNET), especially the poorly differentiated neuroendocrine carcinoma (PNEC) subtype, in which the treatment is vastly different than that of MCC with isolated metastases of the pancreas. METHODS An electronic search of the PubMed and google scholar databases was performed to obtain the literature on MCC with pancreatic metastases, using the following search terms: Merkel cell carcinoma, pancreas, and metastases. Results are limited to the following available article types: case reports and case series. We identified 45 cases of MCC with pancreatic metastases from the PubMed and Google Scholar database search and examined their potential relevance. Only 22 cases with isolated pancreatic metastases were taken for review including one case that we encountered. RESULTS The results from our review of cases of isolated pancreatic metastases of MCC were compared to the characteristics of the poorly differentiated pancreatic neuroendocrine tumor (PNEC). We found the following: (a) MCC with isolated pancreatic metastases occurred at an older age than PNEC and with male gender predominance (b) Most of the metastases occurred within 2 years of initial diagnosis of MCC (c) Resection of pancreatic mass was the first line treatment in case of resectable PNECs whereas resection of metastases was infrequently performed in MCC with pancreatic metastases.
Collapse
Affiliation(s)
- Akriti Pokhrel
- Department of Internal Medicine, Brookdale University Hospital Medical Center, Brooklyn, NY, USA
- Department of Hematology and Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Richard Wu
- Department of Pathology, Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA
- Department of Hematology and Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA
| | - Jen Chin Wang
- Department of Pathology, Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
- Department of Hematology and Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.
| |
Collapse
|
|
12
|
Lauritano D, Mastrangelo F, D’Ovidio C, Ronconi G, Caraffa A, Gallenga CE, Frydas I, Kritas SK, Trimarchi M, Carinci F, Conti P. Activation of Mast Cells by Neuropeptides: The Role of Pro-Inflammatory and Anti-Inflammatory Cytokines. Int J Mol Sci 2023; 24:ijms24054811. [PMID: 36902240 PMCID: PMC10002992 DOI: 10.3390/ijms24054811] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 02/24/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Mast cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in the scientific literature; it is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptide substance P (SP), corticotropin-releasing hormone (CRH), and neurotensin, and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.
Collapse
Affiliation(s)
- Dorina Lauritano
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Filiberto Mastrangelo
- Department of Clinical and Experimental Medicine, School of Dentistry, University of Foggia, 71100 Foggia, Italy
| | - Cristian D’Ovidio
- Section of Legal Medicine, Department of Medicine and Aging Sciences, G. d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
| | - Gianpaolo Ronconi
- Clinica dei Pazienti del Territorio, Fondazione Policlinico Gemelli, 00185 Rome, Italy
| | | | - Carla E. Gallenga
- Section of Ophthalmology, Department of Biomedical Sciences and Specialist Surgery, University of Ferrara, 44121 Ferrara, Italy
| | - Ilias Frydas
- Department of Parasitology, Aristotle University, 54124 Thessaloniki, Greece
| | - Spyros K. Kritas
- Department of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Macedonia, Greece
| | - Matteo Trimarchi
- Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milan, 20122 Milano, Italy
| | - Francesco Carinci
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Pio Conti
- Immunology Division, Postgraduate Medical School, University of Chieti, 66100 Chieti, Italy
- Correspondence:
| |
Collapse
|
|
13
|
Muttillo EM, Mazzarella G, Picardi B, Rossi S, Cinelli L, Diana M, Baiocchini A, Felli E, Pessaux P, Felli E, Muttillo IA. Treatment strategies for neuroendocrine liver metastases: a systematic review. HPB (Oxford) 2022; 24:1832-1843. [PMID: 35794053 DOI: 10.1016/j.hpb.2022.06.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 03/19/2022] [Accepted: 06/15/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of neuroendocrine liver metastases remains a topic of debate. The aim of this study was to make a systematic review of the current literature about the results of the different treatments of neuroendocrine liver metastases. METHODS A systematic review was conducted for English language publications from 1995 to 2021. Outcomes were analyzed according to survival, disease-free survival, and in the case of systemic therapies, progression-free survival. RESULTS 5509 patients were analyzed in the review. 67% of patients underwent surgery achieving 5 years overall survival despite only 30% percent without a recurrence. 60% of patients that had received a transplant reached 5 years survival with a low disease-free survival rate (20%). Five-year survival rate was 36.2% for patients undergoing loco-regional therapies. CONCLUSION Surgical resection is the best treatment when metastases are resectable, with the highest rate of survival, although liver transplantation shows good results for patients not eligible for surgery. Loco-regional therapies may be useful when surgical resection is contraindicated, or selectively used as a bridge to surgery or transplantation. Systemic therapies are indicated in patients for whom curative treatment cannot be obtained.
Collapse
Affiliation(s)
- Edoardo M Muttillo
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy; Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France
| | - Gennaro Mazzarella
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy
| | - Biagio Picardi
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy
| | - Stefano Rossi
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy
| | | | - Michele Diana
- Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France
| | | | - Eric Felli
- Hepatology, Department of Biomedical Research, Inselspital, University of Bern, Bern, Switzerland
| | - Patrick Pessaux
- Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France; HPB Unit, Digestive Surgery Department, Nouvel Hopital Civil, University of Strasbourg, Strasbourg, France
| | - Emanuele Felli
- Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France; Service Chirurgie Digestive et Transplantation Hépatique Hopital Trousseau CHU Tours, France
| | - Irnerio A Muttillo
- Department of General and Emergency Surgery, Ospedale San Filippo Neri, Rome, Italy.
| |
Collapse
|
|
14
|
Iabichino G, Di Leo M, Arena M, Rubis Passoni GG, Morandi E, Turpini F, Viaggi P, Luigiano C, De Luca L. Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:4943-4958. [PMID: 36160644 PMCID: PMC9494936 DOI: 10.3748/wjg.v28.i34.4943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 06/29/2022] [Accepted: 08/22/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors derived from the neuroendocrine cell system, which that have increased in incidence and prevalence in recent years. Despite improvements in radiological and metabolic imaging, endoscopy still plays a pivotal role in the number of GEP-NENs. Tumor detection, characterization, and staging are essential in management and treatment planning. Upper and lower gastrointestinal (GI) endoscopy is essential for correct localization of the primary tumor site of GI NENs. Endoscopic ultrasonography (EUS) has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors. Correct staging and histological diagnosis have important prognostic implications. Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall. Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.
Collapse
Affiliation(s)
| | - Milena Di Leo
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Monica Arena
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | | | | | - Francesca Turpini
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Paolo Viaggi
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Carmelo Luigiano
- Gastroenterology Section, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria 89124, Italy
| | - Luca De Luca
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| |
Collapse
|
|
15
|
Marinović S, Cigrovski Berković M, Zjačić-Rotkvić V, Kapitanović S. Analysis of polymorphisms in EGF, EGFR and HER2 genes in pancreatic neuroendocrine tumors (PNETs). Cancer Genet 2022; 266-267:44-50. [PMID: 35777127 DOI: 10.1016/j.cancergen.2022.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 05/31/2022] [Accepted: 06/14/2022] [Indexed: 11/18/2022]
Abstract
OBJECTIVES Pancreatic neuroendocrine tumors (NETs) are rare and account for about 7% of all cancers occurring in the pancreas. The epidermal growth factor family of receptors and their ligands play an important role in the growth and progression of tumors but their role in PNET development remains unknown. We hypothesized that functional single nucleotide polymorphisms (SNPs) in the EGF, EGFR, and HER2 genes might affect individual susceptibility to PNETs development and invasion like it was shown for various other tumors. METHODS We genotyped 68 patients with unresectable PNETs and 300 controls to evaluate the association between EGF, EGFR, and HER2 polymorphisms and susceptibility to PNETs and presence of metastases. RESULTS Genotype analysis of three SNPs EGF +61A/G (rs4444903), EGFR +1562 G/A (rs11543848), and HER2 +1963 A/G (rs1136201) showed that carriers of EGFR +1562 AG genotype and AA/AG EGF +61/HER2 +1963 genotype combination are at risk of developing PNET. Furthermore, EGFR +1562 AA genotype could be associated with the susceptibility to insulinoma development. CONCLUSIONS Our results suggest involvement of EGFR signaling pathway in etiology of PNET development.
Collapse
Affiliation(s)
| | - Maja Cigrovski Berković
- Department of Endocrinology, Diabetes, Metabolism and Clinical Pharmacology, University Hospital Dubrava, Zagreb, Croatia; Department of Endocrinology, Diabetes and Metabolism, University Clinical Hospital, Centre "Sestre milosrdnice", Zagreb, Croatia
| | - Vanja Zjačić-Rotkvić
- Department of Endocrinology, Diabetes and Metabolism, University Clinical Hospital, Centre "Sestre milosrdnice", Zagreb, Croatia
| | | |
Collapse
|
|
16
|
Shannon AB, Straker RJ, Fraker DL, Miura JT, Karakousis GC. Validated Risk-Score Model Predicting Lymph Node Metastases in Patients with Non-Functional Gastroenteropancreatic Neuroendocrine Tumors. J Am Coll Surg 2022; 234:900-909. [PMID: 35426404 DOI: 10.1097/xcs.0000000000000144] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The incidence of, and factors associated with, lymph node metastasis (LN+) in non-functional gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are not well characterized. METHODS Patients were identified from the 2010-2015 National Cancer Database who underwent surgical resection with lymphadenectomy for clinical stage I-III non-functional GEP NETs. Among a randomly selected training subset of 75% of the study population, variables associated with LN+ were identified using multivariable logistic regression analysis, and these variables were used to create a risk-score model for LN+, which was internally validated among the remaining 25% of the cohort. RESULTS Of 12,228 patients evaluated, 6,902 (56.4%) had LN+. Among the training set, variables associated with LN+ included age (70 years of age or older: odds ratio [OR] 1.12, 95% CI 1.00-1.24; ref: less than 70 years), tumor location (stomach: OR 3.72, 95% CI 2.94-4.71; small intestine: OR 19.60, 95% CI 17.31-22.19; ref: pancreas), tumor grade (moderately differentiated: OR 1.47, 95% CI 1.30-1.67; poorly differentiated/anaplastic: OR 1.53, 95% CI 1.21-1.95; ref: well-differentiated), tumor size (2-4 cm: OR 2.40, 95% CI 2.13-2.70; >4 cm: OR 5.25, 95% CI 4.47-6.17; ref: <2 cm), and lymphovascular invasion (OR 5.62, 95% CI 5.08-6.21; ref: no lymphovascular invasion). After internal validation, a risk-score model for LN+ using these variables was developed composed of low- (N = 2,779), intermediate- (N = 2,598), high- (N = 3,433), and very-high-risk (N = 3,418) groups; within each group the rate of LN+ was 8.7%, 48.6%, 64.9%, and 92.8%, respectively. CONCLUSIONS This developed risk-score model, including both patient and tumor variables, can be used to calculate the risk for LN metastases in patients with GEP NETs.
Collapse
Affiliation(s)
- Adrienne B Shannon
- From the Department of Surgery (Shannon, Straker), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Richard J Straker
- From the Department of Surgery (Shannon, Straker), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Douglas L Fraker
- Division of Endocrine and Oncologic Surgery, Department of Surgery (Fraker, Miura, Karakousis), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - John T Miura
- Division of Endocrine and Oncologic Surgery, Department of Surgery (Fraker, Miura, Karakousis), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Giorgos C Karakousis
- Division of Endocrine and Oncologic Surgery, Department of Surgery (Fraker, Miura, Karakousis), Hospital of the University of Pennsylvania, Philadelphia, PA
| |
Collapse
|
|
17
|
Kaliszewski K, Ludwig M, Greniuk M, Mikuła A, Zagórski K, Rudnicki J. Advances in the Diagnosis and Therapeutic Management of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs). Cancers (Basel) 2022; 14:2028. [PMID: 35454934 PMCID: PMC9030061 DOI: 10.3390/cancers14082028] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/10/2022] [Accepted: 04/14/2022] [Indexed: 02/07/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are an increasingly common cause of neoplastic diseases. One of the largest groups of NENs are neoplasms localized to the gastroenteropancreatic system, which are known as gastroenteropancreatic NENs (GEP-NENs). Because of nonspecific clinical symptoms, GEP-NEN patient diagnosis and, consequently, their treatment, might be difficult and delayed. This situation has forced researchers all over the world to continue progress in the diagnosis and treatment of patients with GEP-NENs. Our review is designed to present the latest reports on the laboratory diagnostic techniques, imaging tests and surgical and nonsurgical treatment strategies used for patients with these rare neoplasms. We paid particular attention to the nuclear approach, the use of which has been applied to GEP-NEN patient diagnosis, and to nonsurgical and radionuclide treatment strategies. Recent publications were reviewed in search of reports on new strategies for effective disease management. Attention was also paid to those studies still in progress, but with successful results. A total of 248 papers were analyzed, from which 141 papers most relevant to the aim of the study were selected. Using these papers, we highlight the progress in the development of diagnostic and treatment strategies for patients with GEP-NENs.
Collapse
Affiliation(s)
- Krzysztof Kaliszewski
- Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (M.L.); (M.G.); (A.M.); (K.Z.); (J.R.)
| | | | | | | | | | | |
Collapse
|
|
18
|
Patel KR, Nahar A, Elhassan YS, Shetty S, Smith S, Vickrage S, Kemp-Blake J, Palani R, Geh I, Venkataraman H, Shah T, Ayuk J. The effects of somatostatin analogues on glycaemia in the treatment of neuroendocrine tumours. J Neuroendocrinol 2022; 34:e13064. [PMID: 35078270 DOI: 10.1111/jne.13064] [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: 07/09/2021] [Revised: 11/10/2021] [Accepted: 11/15/2021] [Indexed: 11/30/2022]
Abstract
Long-acting somatostatin analogues (SSAs) are the most commonly used drugs in the management of neuroendocrine tumours (NETs) because of their ability to control symptoms and prolong survival. SSA use is associated with changes in glucose metabolism. However, the impacts on glycaemic control and body mass index (BMI) caused by SSAs in NETs are largely unknown. In the present study, we evaluated the effects of SSA treatment on BMI and glycated haemoglobin (HbA1c) in our cohort of patients with NETs. We also assessed changes in glycaemic control and BMI before and after SSA treatment. In addition, we assessed the incidence of new diabetes or whether there was worsening of glycaemic control for patients with pre-existing diabetes. The study comprised a retrospective study of 279 patients with NETs who were treated with SSAs between January 2014 and January 2019. Glycaemic control was assessed by measuring changes in Hba1c. A number needed to harm analysis was used to look at new cases of diabetes within the study population. Treatment with SSAs was associated with a mean increase in HbA1c of 3.35 ± 6.30 mmol mol-1 despite a mean decrease in BMI of -1.04 ± 2.79 kg m-2 . There were 19 new cases of type 2 diabetes mellitus (T2DM) in the population of 209 with a number needed to harm of 12.5. Of the 34 patients with pre-existing T2DM, five had worsening of their mean HbA1c. Treatment with SSAs for NETs is associated with an increase in HbA1c, despite a reduction in BMI and, importantly, a risk of developing T2DM with a number needed to harm of 12.5. This project was registered with the National Health Service Clinical Audit and Registries. It has a CARMS number - 17666.
Collapse
Affiliation(s)
- Kishen Rajan Patel
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Oncology Department, St Bartholomew's Hospital, Bart's Health NHS Foundation Trust, London, UK
| | - Ananda Nahar
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Yasir S Elhassan
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Shishir Shetty
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Stacey Smith
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Suzanne Vickrage
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Joanne Kemp-Blake
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Raghavendar Palani
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Ian Geh
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Hema Venkataraman
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Tahir Shah
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - John Ayuk
- Birmingham Neuroendocrine Tumour Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| |
Collapse
|
|
19
|
Haslerud T. SPECT/CT in Neuroendrocrine Tumours. CLINICAL APPLICATIONS OF SPECT-CT 2022:95-118. [DOI: 10.1007/978-3-030-65850-2_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
20
|
Naber MR, Ahmad S, Verrijn Stuart AA, Giles RH, Valk GD, van Leeuwaarde RS. Is There a Role for Biomarkers in Surveillance of Pancreatic Neuroendocrine Neoplasms in Von Hippel-Lindau Disease? J Endocr Soc 2021; 6:bvab191. [PMID: 35059546 PMCID: PMC8763608 DOI: 10.1210/jendso/bvab191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Indexed: 11/19/2022] Open
Abstract
Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of multi-organ neoplasms. Among the manifestations of VHL are pancreatic neuroendocrine neoplasms (panNENs). In order to detect these lesions in a timely manner, patients are enrolled in a surveillance program, in accordance with the several existing VHL guidelines. However, these guidelines remain unclear about the role of biomarkers in diagnosing panNENs, despite the benefits a biomarker may offer regarding early detection of new lesions, thereby possibly limiting radiation exposure, and improving quality of life. The aim is to determine which biomarkers might be available in VHL patients and to assess their clinical relevance in diagnosing panNENs in VHL patients. We searched the databases of PubMed/Medline, Embase, and Web of Science to identify relevant articles. Seven studies assessing the diagnostic or prognostic value of biomarkers were included. The results from these studies were conflicting. Since no evident association between VHL-related panNENs and biomarkers was established in studies with larger study populations, currently biomarkers do not play a significant role in early detection or follow-up for panNENs in VHL patients. The absence of evidence underscores the need for specific research to address this unmet need.
Collapse
Affiliation(s)
- Myrthe R Naber
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands
| | - Saya Ahmad
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands
| | - Annemarie A Verrijn Stuart
- Department of Paediatrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht 3584 EA, The Netherlands
| | - Rachel H Giles
- Dutch VHL Organization, Utrecht 3503 RD, The Netherlands
| | - Gerlof D Valk
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands
| | - Rachel S van Leeuwaarde
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands
| |
Collapse
|
|
21
|
Cockburn KC, Toumi Z, Mackie A, Julyan P. Radioguided Surgery for Gastroenteropancreatic Neuroendocrine Tumours: a Systematic Literature Review. J Gastrointest Surg 2021; 25:3244-3257. [PMID: 34506015 PMCID: PMC8654712 DOI: 10.1007/s11605-021-05115-w] [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: 02/26/2021] [Accepted: 08/07/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Radioguided surgery (RGS) for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has been suggested as a way to improve intraoperative lesion detection. This systematic literature review of reports of the use of RGS for GEP-NETs was performed to determine if there is a benefit. METHODS A literature search was conducted using Google Scholar and PubMed, and snowballing from any relevant literature. Full-text studies were included if they were published in the English language and reported outcomes of RGS on human subjects with GEP-NETs. Qualitative data synthesis was performed. RESULTS Twenty-six papers including a total of 209 patients were included. The tracers used were predominantly indium-111 pentetreotide, gallium-68 DOTA-peptides, and technetium-99m EDDA/HYNIC-peptides. Heterogeneous protocols make comparisons difficult, but most papers reported a benefit from the use of RGS in tumours in the gastrointestinal tract; utility in localisation of pancreatic tumours was less clear. Time between tracer administration and operation varied: from 16 h to 8 days with indium-111, 0-24 h with technetium-99m, and 19-193 min with gallium-68. Eight teams reported the thresholding technique used for discrimination-four used a ratio, four statistical methods, and one looked at the sensitivity and specificity of different cut-offs. Six teams performed follow-up of 24 patients (three pancreas, eight gastrinoma, 13 gastrointestinal tract) for between 3 months and 3 years. Two patients relapsed (one pancreas, one gastrinoma) between 6 and 12 months post-surgery. CONCLUSIONS RGS appears to aid in localisation of gastrointestinal NETs, but the benefit is more equivocal in pancreatic NETs. Further work into outcomes is warranted.
Collapse
Affiliation(s)
- Katrina Clair Cockburn
- Northern Medical Physics and Clinical Engineering, County Durham and Darlington NHS Foundation Trust, Hollyhurst Road, Darlington, DL3 6HX, UK.
| | - Zaher Toumi
- Department of General Surgery, County Durham and Darlington NHS Foundation Trust, Hollyhurst Road, Darlington, DL3 6HX, UK
| | - Alison Mackie
- Northern Medical Physics and Clinical Engineering, County Durham and Darlington NHS Foundation Trust, Hollyhurst Road, Darlington, DL3 6HX, UK
| | - Peter Julyan
- Department of Nuclear Medicine, The Christie Hospital NHS Foundation Trust, Manchester, UK
| |
Collapse
|
|
22
|
Splenic metastasis from neuroendocrine tumor of the stomach: A case report. Radiol Case Rep 2021; 16:3438-3441. [PMID: 34527118 PMCID: PMC8429624 DOI: 10.1016/j.radcr.2021.08.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/09/2021] [Accepted: 08/11/2021] [Indexed: 11/21/2022] Open
Abstract
Splenic metastasis is extremely rare, and neuroendocrine tumor of the stomach represents one of the rarest primary sources. The present study aimed to describe a rare case of an endocrine tumor of the stomach revealed by a splenic metastasis. We report a rare case of a 40 -year-old who presented a pain in her left hypochondriac, associated to sensation of heaviness. Abdominal ultrasound showed splenomegaly with a large lobulated hyperechoic mass associated to splenic vein thrombosis. A magnetic resonance imaging (MRI) confirming the splenomegaly, containing a large lobulated and heterogeneous mass occupying the almost totality of this organ and invading the venous system. The histological study of this splenic mass demonstrated to secondary splenic location of a grade 1 neuroendocrine tumor. As part of an investigation for a primary tumor, fibro scopy was performed and revealed an ulcerating-bourging fundic process with a histological study in favor of a grade 1 neuroendocrine tumor.
Collapse
|
|
23
|
Gao LP, Kong GX, Wang X, Ma HM, Ding FF, Li TD. Pancreatic neuroendocrine carcinoma in a pregnant woman: A case report and review of the literature. World J Clin Cases 2021; 9:4327-4335. [PMID: 34141797 PMCID: PMC8173422 DOI: 10.12998/wjcc.v9.i17.4327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/23/2021] [Accepted: 04/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Portal venous thromboembolism caused by malignant pancreatic neuroendocrine tumor metastasis, as the initial presentation of portal hypertension and upper gastrointestinal bleeding, is a rare entity. To our knowledge, there are no reports of this entity in pregnant women. We describe a case of pancreatic neuroendocrine carcinoma during pregnancy with hematemesis and hematochezia as the initial presentation and review the literature to analyze the demographic, clinical, and pathological features to provide a reference for clinical diagnosis and treatment.
CASE SUMMARY A 40-year-old woman presented with hematemesis and hematochezia at 26-wk gestation; she had no other remarkable medical history. The physical examination revealed normal vital signs, an anemic appearance, and lower abdominal distension. Abdominal color Doppler ultrasonography showed portal vein thrombosis, splenomegaly, intrauterine pregnancy, and intrauterine fetal death. Esophagogastroduodenoscopy revealed esophageal and gastric varicose veins and portal hypertensive gastropathy. Contrast-enhanced computed tomography demonstrated multiple emboli formation in the portal and splenic veins, multiple round shadows in the liver with a slightly lower density, portal vein broadening, varicose veins in the lower esophagus and gastric fundus, splenomegaly, bilateral pleural effusion, ascites and pelvic effusion, broadening of the common bile duct, and increased uterine volume. According to the results of Positron emission tomography-computed tomography and immunohistochemical staining, the final diagnoses were that the primary lesion was a pancreatic neuroendocrine tumor and that there were secondary intrahepatic metastases and venous cancer thrombogenesis.
CONCLUSION Upper gastrointestinal bleeding in a pregnant woman may be caused by portal hypertension due to a malignant pancreatic neuroendocrine tumor.
Collapse
Affiliation(s)
- Li-Ping Gao
- Department of Gastroenterology, The Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Gui-Xiang Kong
- Department of Gastroenterology, The Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Xiang Wang
- Department of Gastroenterology, The Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui-Min Ma
- Department of Gastroenterology, The Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Fei-Fei Ding
- Department of Gastroenterology, The Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Ting-Dong Li
- Department of Musculoskeletal Tumor, Gansu Provincial Cancer Hospital, Lanzhou 730000, Gansu Province, China
| |
Collapse
|
|
24
|
Bonilla Gonzalez C, Rusinque J, Uribe C, Carias A, Contreras ML. Pancreatic VIPoma as a Differential Diagnosis in Chronic Pediatric Diarrhea: A Case Report and Review of the Literature. J Med Cases 2021; 12:195-201. [PMID: 34434457 PMCID: PMC8383534 DOI: 10.14740/jmc3535] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 11/26/2020] [Indexed: 11/11/2022] Open
Abstract
Chronic diarrhea is a common chief complaint in the pediatric population with a wide range of diagnostic differentials; as such, whilst suspecting common causes, less prevalent conditions tend to be overlooked, such as neuroendocrine tumor pathologies. VIPomas are characterized by hypersecretion of the vasoactive intestinal peptide (VIP), causing watery diarrhea, hypokalemia, and achlorhydria. Nonetheless, its low incidence rate in children makes it an easily unnoticed pathology. Herein, we report a case of a 14-year-old female patient and a review of relevant literature. The patient complained of 7-month history of watery diarrhea, multiple emetic episodes, and relevant past medical history of multiple hospitalizations. Chronic diarrheal disease work-up studies, including a high VIP scintigram, showed a lesion suggestive of a VIPoma-type neuroendocrine pancreatic tumor. A distal pancreatectomy was performed with a complete resolution of the symptoms. When faced with a pediatric patient presenting with chronic secretory diarrhea and whose work-up studies rule out the most common pathologies, the possible presence of a neuroendocrine tumor as VIPoma should be considered.
Collapse
Affiliation(s)
| | | | | | - Ailim Carias
- Pediatric Gastroenterology, University Hospital Fundacion Santa Fe de Bogota, Bogota, Columbia
| | - Maria Luisa Contreras
- Pediatric Critical Care, University Hospital Fundacion Santa Fe de Bogota, Bogota, Columbia
| |
Collapse
|
|
25
|
Cavalcoli F, Rossi RE, Massironi S. Circulating Biochemical Markers of Gastro-Entero-Pancreatic (GEP) Neuroendocrine Neoplasms (NENs). NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:55-74. [DOI: 10.1007/978-3-030-72830-4_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
26
|
Herman Mahečić D, Cigrovski Berković M, Zjačić-Rotkvić V, Čačev T, Kapitanović S, Ulamec M. Inflammation-related cytokines and their roles in gastroenteropancreatic neuroendocrine neoplasms. Bosn J Basic Med Sci 2020; 20:445-450. [PMID: 32156252 PMCID: PMC7664780 DOI: 10.17305/bjbms.2020.4471] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 01/21/2020] [Indexed: 12/13/2022] Open
Abstract
Proinflammatory counterworks are important at different stages of tumor development, particularly during invasion and metastasis. Immune cells and their signal molecules can influence all stages of tumor progression, as well as therapeutic intervention. Proinflammatory cytokines are known triggers of growth in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we explored the immunohistochemical expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), IL-2, and IL-6 in tissues from 43 GEP-NEN patients with tumors of gastric, duodenal, ileal, appendiceal, and colonic origin. The immunohistochemical expression of TNF-α was increased in tumor groups with high proliferation rates (Ki-67; p = 0.034), as well as in those with higher tumor grades (p = 0.05). Moreover, the immunohistochemical expression of TNF-α positively correlated with death outcomes (p = 0.016). Expression of IL-6, IL-1β, and IL-2 displayed similar immunohistochemical expression patterns regardless of Ki-67, although the expression between the ILs differed. Most GEP-NENs had high levels of IL-6 and lower levels of IL-1β and IL-2. Although further comprehensive studies are required for a complete understanding of activated mechanisms in proinflammatory protumoral microenvironment of GEP-NENs, TNF-α is a potential marker in the prognosis of those tumors.
Collapse
Affiliation(s)
- Davorka Herman Mahečić
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Centre Sestre milosrdnice, Zagreb, Croatia
| | - Maja Cigrovski Berković
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Centre Sestre milosrdnice, Zagreb, Croatia; Faculty of Kinesiology, University of Zagreb, Zagreb, Croatia
| | - Vanja Zjačić-Rotkvić
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Centre Sestre milosrdnice, Zagreb, Croatia
| | - Tamara Čačev
- Department of Molecular Medicine Rudjer Boskovic Institute, Zagreb, Croatia
| | - Sanja Kapitanović
- Department of Molecular Medicine Rudjer Boskovic Institute, Zagreb, Croatia
| | - Monika Ulamec
- Department of Pathology and Cytology Ljudevit Jurak, University Hospital Centre Sestre milosrdnice, Zagreb, Croatia; Pathology Department, School of Medicine, University of Zagreb, Zagreb, Croatia
| |
Collapse
|
|
27
|
Liu H, Xie R, Zhao Z, Xu D, Yang K, Ding M, Tan D, Liao W, Han X, Zhang J, Shen D, Yuan J, Xu Z, Fei J. An 11-year retrospective study: clinicopathological and survival analysis of gastro-entero-pancreatic neuroendocrine neoplasm. Medicine (Baltimore) 2020; 99:e21682. [PMID: 32872039 PMCID: PMC7437823 DOI: 10.1097/md.0000000000021682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
To investigate the clinicopathological characteristics and relevant prognostic factors of gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN), to improve our understanding of GEP-NEN.This was a retrospective analysis of 155 patients (average age 53.7 ± 13.6 years) pathologically diagnosed with GEP-NEN. We analyzed the clinicopathological characteristics, treatment, and prognostic factors of GEP-NEN.The most common primary site was the pancreas (41.9%), followed by the rectum, stomach and duodenum. Most cases were nonfunctional GEP-NENs (149/155) with nonspecific symptoms. TNM stage and histological grade were determined by the latest criteria. Surgical resection was the mainstay of treatment in 150 patients, and 22 patients received chemotherapy under different circumstances. A total of 130 patients were followed up for a median of 44 months, and 1-year and 3-year survival rates were 82.3% and 72.3%, respectively. According to univariate and multivariate analysis, incidental diagnosis, maximum tumor diameter, tumor stage, lymph node and distant metastasis, TNM stage, and histological grade were significantly correlated with overall survival, but histological grade was the only factor confirmed as an independent prognostic factor for long-term survival of GEP-NEN.GEP-NEN, with an increasing trend in incidence, occurred most frequently in the pancreas. Nonfunctional tumors with nonspecific symptoms comprised the majority of cases. The main treatment was surgical resection. Histological grade was confirmed as the only independent prognostic factor.
Collapse
Affiliation(s)
- Hua Liu
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine
| | - Rongli Xie
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
- Department of Surgery, Luwan Branch, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhifeng Zhao
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
| | - Dan Xu
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
| | - Kaige Yang
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
| | - Min Ding
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
| | - Dan Tan
- Department of Surgery, Luwan Branch, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenqiang Liao
- Department of Surgery, Luwan Branch, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xujie Han
- Department of Surgery, Luwan Branch, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Zhang
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
| | - Dongjie Shen
- Department of Surgery, Luwan Branch, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianmin Yuan
- Department of Surgery, Luwan Branch, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiwei Xu
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
| | - Jian Fei
- Department of General Surgery, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University, School of Medicine
| |
Collapse
|
|
28
|
Pancreatic Neuroendocrine Neoplasms and Gastrointestinal Stromal Tumors: A Single-Institution Experience of a Rare Association and Review of the Literature. Pancreas 2020; 49:918-923. [PMID: 32658075 DOI: 10.1097/mpa.0000000000001599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Pancreatic neuroendocrine neoplasms (pNENs) and gastrointestinal stromal tumors (GISTs) represent rare neoplasms. Nonsyndromic cases of pNENs associated with a synchronous GIST were evaluated, and a review of the literature was performed. METHODS We evaluated clinicopathologic features, postoperative outcome, and follow-up of patients operated on for nonsyndromic synchronous pNENs and GISTs in our unit (2003-2017). RESULTS Five (3.2%) of 156 patients with a pNEN had an associated GIST (3 male/2 female; average age, 67 years). They were diagnosed with a pNEN preoperatively and underwent pancreatic surgery. In 4 patients, GISTs were detected intraoperatively. Histology showed 3 G1 and 2 G2 pNENs. All GISTs were low risk (median size, 0.9 cm). Two patients were alive without disease 108 and 132 months after surgery. In the literature, 7 cases were described. They had low-risk GISTs, with a gastric location in 6 cases (median size, 2.85 cm). CONCLUSIONS Sporadic pNENs coexisting with a GIST have been demonstrated in 12 cases. This association is considered fortuitous, and its true incidence may be underestimated. Surgery should be performed on the GIST during the pancreatic surgery. The prognosis strictly depends on the pancreatic NENs.
Collapse
|
|
29
|
Warsinggih, Liliyanto, Prihantono, Ariani GDW, Faruk M. Colorectal neuroendocrine tumors: A case series. Int J Surg Case Rep 2020; 72:411-417. [PMID: 32563832 PMCID: PMC7306531 DOI: 10.1016/j.ijscr.2020.06.030] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/07/2020] [Accepted: 06/07/2020] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Neuroendocrine tumors (NET) of the colon and sigmoid colon are uncommon compared to colorectal adenocarcinoma. Few reports have been made of NET of the colon and sigmoid colon that presents with peritonitis and large bowel obstruction. CASE PRESENTATION Here, we report two cases of NET of the colon and sigmoid colon, which were diagnosed and treated at our institution. In our first case, a 66-year-old man with a history of abdominal distension was diagnosed with NET via histopathology of the sigmoid colon. The second case involved a 45-year-old woman with the chief complaints of abdominal distention and inability to defecate; specimen histopathology of the descending colon showed neuroendocrine carcinoma features. Clinical outcome was very poor in our patients: eight months after the resection, the second patient demonstrated a sign of metastasis on the liver. CONCLUSION An uncommon case of colon and sigmoid colon carcinoma with neuroendocrine and diagnostic difficulties precludes an exact description of the initial diagnostic criteria and management. Thus, our case series offers an overview of initial symptoms, radiological and histopathological features for early diagnosis, and proper management of NET.
Collapse
Affiliation(s)
- Warsinggih
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University Makassar, Indonesia.
| | - Liliyanto
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University Makassar, Indonesia.
| | - Prihantono
- Division of Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University Makassar, Indonesia.
| | - Gusti Deasy Wilda Ariani
- Department of Anatomic Pathology, Faculty of Medicine, Hasanuddin University Makassar, Indonesia.
| | - Muhammad Faruk
- Department of Surgery, Faculty of Medicine, Hasanuddin University Makassar, Indonesia.
| |
Collapse
|
|
30
|
Pediatric applications of Dotatate: early diagnostic and therapeutic experience. Pediatr Radiol 2020; 50:882-897. [PMID: 32495176 DOI: 10.1007/s00247-020-04688-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 03/17/2020] [Accepted: 04/22/2020] [Indexed: 12/12/2022]
Abstract
In recent years, new somatostatin receptor agents (SSTRs) have become available for diagnostic imaging and therapy in neuroendocrine tumors. The novel SSTR ligand DOTA-DPhel-Tyr3-octreotate (Dotatate) in particular can be linked with 68Gallium for diagnostic imaging purposes, and with the β-emitter 177Lutetium for radiotherapy in the setting of neuroendocrine tumors. Dotatate imaging offers distinct advantages in the evaluation of neuroendocrine tumors compared to standard techniques, including greater target-to-background ratio and lesion conspicuity, high sensitivity/specificity, improved spatial resolution with positron emission tomography (PET)/CT or PET/MR, and decreased radiation exposure. Although currently off-label in pediatrics, Dotatate theranostics in children are being explored, most notably in the setting of neuroblastoma and hereditary neuroendocrine syndromes. This article provides a multicenter case series of Dotatate imaging and therapy in pediatric patients in order to highlight the spectrum of potential clinical applications.
Collapse
|
|
31
|
Chiramel J, Almond R, Slagter A, Khan A, Wang X, Lim KHJ, Frizziero M, Chakrabarty B, Minicozzi A, Lamarca A, Mansoor W, Hubner RA, Valle JW, McNamara MG. Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours. World J Clin Oncol 2020; 11:205-216. [PMID: 32355642 PMCID: PMC7186236 DOI: 10.5306/wjco.v11.i4.205] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 04/05/2020] [Accepted: 04/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prognostic significance of lymph nodes (LNs) metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours (GEP NETs) undergoing curative resection is still debatable. Many studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy
AIM To evaluate the effect of lymph node (LN) status and yield on relapse-free survival (RFS) and overall survival (OS) in patients with resected GEP NETs.
METHODS Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed retrospectively. Grade 3 tumours (Ki67 > 20%) were excluded. Univariate Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS.
RESULTS A total of 217 patients were included in the study. The median age was 59 years (21-97 years) and 51% (n = 111) were male. Primary tumour sites were small bowel (42%), pancreas (25%), appendix (18%), rectum (7%), colon (3%), gastric (2%), others (2%). Median follow up times for all patients were 41 mo (95%CI: 36-51) and 71 mo (95%CI: 63–76) for RFS and OS respectively; 50 relapses and 35 deaths were reported. LNs were retrieved in 151 patients. Eight or more LNs were harvested in 106 patients and LN positivity reported in 114 patients. Three or more positive LNs were detected in 62 cases. The result of univariate analysis suggested perineural invasion (P = 0.0023), LN positivity (P = 0.033), LN retrieval of ≥ 8 (P = 0.047) and localisation (P = 0.0049) have a statistically significant association with shorter RFS, but there was no effect of LN ratio on RFS: P = 0.1 or OS: P = 0.75. Tumour necrosis (P = 0.021) and perineural invasion (P = 0.016) were the only two variables significantly associated with worse OS. In the final multivariable analysis, localisation (pancreas HR = 27.33, P = 0.006, small bowel HR = 32.44, P = 0.005), and retrieval of ≥ 8 LNs (HR = 2.7, P = 0.036) were independent prognostic factors for worse RFS.
CONCLUSION An outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery. Removal of ≥ 8 LNs is associated with increased risk of relapse, which could be due to high rates of LN positivity at the time of surgery. Given that localisation had a significant association with RFS, a prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.
Collapse
Affiliation(s)
- Jaseela Chiramel
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
- Royal Free London NHS Foundation Trust, London NW3 2QG, United Kingdom
| | - Rose Almond
- Statistics Group, Digital Services, The Christie NHS Foundation Trust, Manchester, M20 4BX, United Kingdom
| | - Astrid Slagter
- Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam 1066 Cx, Netherlands
| | - Adeel Khan
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Xin Wang
- Statistics Group, Digital Services, The Christie NHS Foundation Trust, Manchester, M20 4BX, United Kingdom
| | - Kok Haw Jonathan Lim
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Melissa Frizziero
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Bipasha Chakrabarty
- Department of Pathology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Annamaria Minicozzi
- Department of Surgery, Barts Health NHS Trust, London EC1A 7BE, United Kingdom
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Wasat Mansoor
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Richard A Hubner
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, United Kingdom
| | - Juan William Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, United Kingdom
| | - Mairéad Geraldine McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, United Kingdom
| |
Collapse
|
|
32
|
Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome. JOURNAL OF ONCOLOGY 2020; 2020:8341426. [PMID: 32322270 PMCID: PMC7160731 DOI: 10.1155/2020/8341426] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 12/07/2019] [Accepted: 12/26/2019] [Indexed: 12/23/2022]
Abstract
Carcinoid syndrome (CS) develops in patients with hormone-producing neuroendocrine neoplasms (NENs) when hormones reach a significant level in the systemic circulation. The classical symptoms of carcinoid syndrome are flushing, diarrhoea, abdominal pain, and wheezing. Neuroendocrine neoplasms can produce multiple hormones: 5-hydroxytryptamine (serotonin) is the most well-known one, but histamine, catecholamines, and brady/tachykinins are also released. Serotonin overproduction can lead to symptoms and also stimulates fibrosis formation which can result in development of carcinoid syndrome-associated complications such as carcinoid heart disease (CaHD) and mesenteric fibrosis. Transforming growth factor beta (TGF-β) is one of the main factors in developing fibrosis, but platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF2), and connective tissue growth factor (CTGF or CCN2) are also related to fibrosis development. Treatment of CS focuses on reducing serotonin levels with somatostatin analogues (SSA's). Telotristat ethyl and peptide receptor radionuclide therapy (PRRT) have recently become available for patients with symptoms despite being established on SSA's. Screening for CaHD is advised, and early intervention prolongs survival. Mesenteric fibrosis is often present and associated with poorer survival, but the role for prophylactic surgery of this is unclear. Depression, anxiety, and cognitive impairment are frequently present symptoms in patients with CS but not always part of their care plan. The role of antidepressants, mainly SSRIs, is debatable, but recent retrospective studies show evidence for safe use in patients with CS. Carcinoid crisis is a life-threatening complication of CS which can appear spontaneously but mostly described during surgery, anaesthesia, chemotherapy, PRRT, and radiological procedures and may be prevented by octreotide administration.
Collapse
|
|
33
|
Lesén E, Granfeldt D, Berthon A, Dinet J, Houchard A, Myrenfors P, Björstad Å, Björholt I, Elf AK, Johanson V. Treatment Patterns and Survival among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumours in Sweden - a Population-based Register-linkage and Medical Chart Review Study. J Cancer 2019; 10:6876-6887. [PMID: 31839822 PMCID: PMC6909946 DOI: 10.7150/jca.32381] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 09/09/2019] [Indexed: 12/11/2022] Open
Abstract
Background: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are neoplasms derived from the endocrine system in the gastrointestinal tract and pancreas. Treatment options include surgery; pharmacological treatments like somatostatin analogues (SSA), interferon alpha, molecular targeted therapy and chemotherapy; and peptide receptor radionuclide therapy. The objective of this study was to describe treatment patterns and survival among patients with metastatic GEP-NET grade 1 or 2 in Sweden. Methods: Data was obtained via linkage of nationwide registers. Patients diagnosed with metastatic GEP-NET grade 1 or 2 in Sweden between 2005 and 2013 were included (n=811; National population). In addition, medical chart review was performed for the subpopulation diagnosed at Sahlgrenska University Hospital, Gothenburg (n=127; Regional population). Treatment patterns, including treatment sequences, and overall survival were assessed. Results: Most patients had small intestinal NET (76%). In the regional population, 72% had grade 1 tumours; 50% had functioning tumours. The two most common first-line treatments were surgery (57%) and SSA (25%). After first-line surgery, 46% received SSA, while 40% had no further treatment. After first-line SSA, 52% received surgery, while 27% had no further treatment. Overall median survival time from date of diagnosis was 7.0 years (95% CI 6.2-not reached). Among patients with distant metastases, pancreatic NET (vs. small intestinal NET) was associated with poorer survival (HR 1.9; 95% CI 1.1-3.3), as were liver metastases (HR 3.2; 95% CI 1.5-7.0). Conclusions: First-line surgery was typically followed by SSA or no further treatment. Among patients with distant metastases, pancreatic NET or liver metastases were associated with a poorer survival.
Collapse
Affiliation(s)
- Eva Lesén
- Former employee of PharmaLex, Gothenburg, Sweden
| | | | | | - Jérôme Dinet
- Former employee of Ipsen, Boulogne-Billancourt, France
| | | | | | | | | | - Anna-Karin Elf
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Viktor Johanson
- Former employee at Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| |
Collapse
|
|
34
|
Cavalcoli F, Pusceddu S, Zilli A, Tamagno G, Femia D, Prinzi N, Travers J, Consonni D, Ciafardini C, Conte D, Massironi S. Effects of low-dose aspirin on clinical outcome and disease progression in patients with gastroenteropancreatic neuroendocrine neoplasm. Scand J Gastroenterol 2019; 54:1111-1117. [PMID: 31454281 DOI: 10.1080/00365521.2019.1656773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Objective: The chemopreventive effect of aspirin (ASA) has been observed in the setting of colorectal cancer and other solid neoplasms. Recently, ASA has demonstrated a promising anti-proliferative effect on GEP-NENs in vitro. However, the direct anti-neoplastic impact of ASA on GEP-NEN clinical outcome is yet to be clarified. Materials and methods: All the GEP-NEN patients followed up in three European Centers from January 2005 to September 2016 were retrospectively enrolled. Patients taking ASA in doses of 75-100 mg daily for cardiovascular prevention for at least six months were evaluated. The possible association between ASA and disease grading, staging, primary site, OS and PFS were evaluated. Results: Two hundred fifty one patients were included (117 males, median age 63 years). Of these, 64 patients were prescribed with ASA. No clear impact on OS or PFS was observed in GEP-NEN patients taking ASA compared to those not taking it. ASA intake was related with the patients' older age. At Cox multivariate analysis, stage IV and Ki-67 resulted independent predictors for OS and PFS. In the setting of intestinal NENs, a suggestive, but not statistically significant, protective role of ASA on PFS was observed [HR 0.41 (95% CI: 0.13-1.29)]. Conclusions: Despite ASA showed promising anti-proliferative effects in vitro and a chemopreventive action in NENs has been reported, a clear impact of ASA on survival in NENs has not emerged from the present study. However, in the subgroup of patients with small-intestine NENs, ASA showed a trend toward a protective role.
Collapse
Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Sara Pusceddu
- Medical Oncology, Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Tumori Milano , Milan , Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Gianluca Tamagno
- Department of Endocrinology/Diabetes, Mater Misericordiae University Hospital , Dublin , Ireland
| | - Daniela Femia
- Medical Oncology, Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Tumori Milano , Milan , Italy
| | - Natalie Prinzi
- Medical Oncology, Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Tumori Milano , Milan , Italy
| | - John Travers
- Department of Endocrinology/Diabetes, Mater Misericordiae University Hospital , Dublin , Ireland
| | - Dario Consonni
- Epidemiology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
| | - Clorinda Ciafardini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| |
Collapse
|
|
35
|
A case report of three synchronous tumors in the same pancreatic specimen. Ann Med Surg (Lond) 2019; 44:79-82. [PMID: 31341616 PMCID: PMC6629607 DOI: 10.1016/j.amsu.2019.07.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 06/19/2019] [Accepted: 07/03/2019] [Indexed: 12/21/2022] Open
Abstract
It is known that Duodenal adenocarcinoma (DA) is a rare malignant solid tumor that cause occlusion symptoms with orthodox dysphagia when locally advanced. Pancreatic neuroendocrine tumors (PanNETs) account for about 2% of all pancreatic neoplasms. The combination of these two lesions, with the synchronous presence of ectopic pancreatic tissue (EPT) of the duodenum, has never been described in literature, to our knowledge. Here we report a case of combined DA, EPT and PanNET affecting a 71-year-old woman.
Simultaneous presence of Duodenal adenocarcinoma pancreatic neuroendocrine tumor ectopic pancreatic tissue of duodenum. Biochemical tests did not reveal abnormalities: CA 19-9 was normal, CEA was 153 U/L. Ultrasonography confirmed a nodule dislocating pancreas investigated with contrast-enhanced CT and esophagogastroduodenoscopy. The association between duodenal adenocarcinomas, PanNET and ectopic pancreatic tissue (EPT) of the duodenum is really rare.
Collapse
|
|
36
|
Briganti V, Cuccurullo V, Di Stasio GD, Mansi L. Gamma Emitters in Pancreatic Endocrine Tumors Imaging in the PET Era: Is there a Clinical Space for 99mTc-peptides? Curr Radiopharm 2019; 12:156-170. [DOI: 10.2174/1874471012666190301122524] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 06/15/2018] [Accepted: 10/19/2018] [Indexed: 12/18/2022]
Abstract
Background:
Pancreatic Neuroendocrine Tumors (PNETs) are rare neoplasms, sporadic or
familial, even being part of a syndrome. Their diagnosis is based on symptoms, hormonal disorders or
may be fortuitous. The role of Nuclear Medicine is important, mainly because of the possibility of a
theranostic strategy. This approach is allowed by the availability of biochemical agents, which may be
labeled with radionuclides suitable for diagnostic or therapeutic purposes, showing almost identical
pharmacokinetics. The major role for radiopharmaceuticals is connected with radiolabeled Somatostatin
Analogues (SSA), since somatostatin receptors are highly expressed on some of the neoplastic
cell types.
Discussion:
Nowadays, in the category of radiolabeled SSA, although 111In-pentetreotide, firstly
commercially proposed, is still used, the best choice for diagnosis is related to the so called DOTAPET
radiotracers labeled with 68-Gallium (Ga), such as 68Ga-DOTATATE, 68Ga-DOTANOC, and
68Ga-DOTATOC. More recently, labeling with 64-Copper (Cu) (64Cu-DOTATATE) has also been
proposed. In this review, we discuss the clinical interest of a SAA (Tektrotyd©) radiolabeled with
99mTc, a gamma emitter with better characteristics, with respect to 111Indium, radiolabeling Octreoscan
©. By comparing both pharmacokinetics and pharmacodynamics of Octreoscan©, Tektrotyd©
and PET DOTA-peptides, on the basis of literature data and of our own experience, we tried to highlight
these topics to stimulate further studies, individuating actual clinical indications for all of these
radiotracers.
Conclusion:
In our opinion, Tektrotyd© could already find its applicative dimension in the daily practice
of NETs, either pancreatic or not, at least in centers without a PET/CT or a 68Ga generator. Because
of wider availability, a lower cost, and a longer decay, compared with respect to peptides labeled
with 68Ga, it could be also proposed, in a theranostic context, for a dosimetry evaluation of patients
undergoing Peptide Receptor Radionuclide Therapy (PRRT), and for non-oncologic indications
of radiolabelled SSA. In this direction, and for a more rigorous cost/effective evaluation, more precisely
individuating its clinical role, further studies are needed.
Collapse
Affiliation(s)
- Vittorio Briganti
- Nuclear Medicine Unit - Azienda Ospedaliero Universitaria Careggi Firenze, Italy
| | - Vincenzo Cuccurullo
- Nuclear Medicine Unit, Department of Clinical and Experimental Medicine "F.Magrassi, A.Lanzara" – Università della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Giuseppe Danilo Di Stasio
- Nuclear Medicine Unit, Department of Clinical and Experimental Medicine "F.Magrassi, A.Lanzara" – Università della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Luigi Mansi
- Health and Development Section, Interuniversitary Research Center for Sustainable Development, Napoli-Roma, Italy
| |
Collapse
|
|
37
|
Mei S, Gibbs J, Economos K, Lee YC, Kanis MJ. Clinical comparison between neuroendocrine and endometrioid type carcinoma of the uterine corpus. J Gynecol Oncol 2019; 30:e58. [PMID: 31074241 PMCID: PMC6543113 DOI: 10.3802/jgo.2019.30.e58] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 12/28/2018] [Accepted: 01/24/2019] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE To compare the clinicopathologic features and survival outcomes of neuroendocrine tumor of the uterine corpus (NET-U) to endometrioid type endometrial carcinoma (EC). METHODS From 1993 to 2012, the Surveillance, Epidemiology and End Results cancer registry was queried for women diagnosed with EC or NET-U. Data regarding stage, grade, presence of extra-uterine disease, lymph node metastasis, receipt of adjuvant radiation, surgical intervention and overall survival (OS) was extracted. Chi-square tests, t-tests and Kaplan Meir curves were used for statistical analysis. RESULTS A total of 98,363 patients were identified: 98,245 with EC and 118 with NET-U. The mean age at diagnosis for EC was 61.7 years and 64.8 years for NET-U (p=0.01). NET-U cases were more likely to be poorly differentiated (97.0% vs. 15.6%; p≤0.01) and have nodal metastasis (56.4% vs. 11.1%; p≤0.01) when compared to EC. Presence of extrapelvic disease at the time of diagnosis was observed more frequently in NET-U compared to EC, 49.1% vs. 4.8%, respectively (odds ratio=18; 95% confidence interval=13.1-27.2; p≤0.01). Significant improvement in OS was observed in NET-U patient who received radiation (OS: 7.7 vs. 3.3 years; p≤0.01) or underwent surgical management (5.6 vs. 0.9 years; p≤0.01). The OS for EC was 14.4 vs. 4.6 years for NET-U (p≤0.01). CONCLUSION NET-U represents an aggressive form of uterine malignancy. When compared to EC, patients with NET-U present at more advanced stage, have more frequent extra-uterine disease and lower OS.
Collapse
Affiliation(s)
- Shirley Mei
- Division of Gynecologic Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA
| | - Jennifer Gibbs
- Division of Gynecologic Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
| | - Katherine Economos
- Division of Gynecologic Oncology, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY, USA
| | - Yi Chun Lee
- Division of Gynecologic Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA
| | - Margaux J Kanis
- Division of Gynecologic Oncology, SUNY Downstate Medical Center, Brooklyn, NY, USA
| |
Collapse
|
|
38
|
Local treatment of liver metastases by administration of 177Lu-octreotate via isolated hepatic perfusion - A preclinical simulation of a novel treatment strategy. Surg Oncol 2019; 29:148-156. [PMID: 31196481 DOI: 10.1016/j.suronc.2019.05.002] [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: 11/09/2018] [Revised: 04/17/2019] [Accepted: 05/10/2019] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Systemic 177Lu-octreotate treatment for metastatic neuroendocrine tumours is restricted by organs at risk. By administering 177Lu-octreotate during isolated hepatic perfusion (IHP), the uptake in organs at risk might be strongly reduced. The aim of this study was to investigate the feasibility to use the combination of IHP and radionuclide therapy. METHODS To simulate IHP, the liver of a pig was prepared for ex vivo perfusion. Blood containing 490 MBq 177Lu-octreotate was circulated through the liver for 60 min, after which the liver was rinsed. After IHP, the liver was examined by SPECT/CT. Lastly, an intraoperative gamma detector (IGD) was used to determine 177Lu activity concentration in the liver and results were compared with the activity concentration in corresponding liver biopsies. RESULTS Detector measurements over the liver during the IHP showed a fast increase with a maximum after approximately 10-15 min. After IHP, about 75% of the 177Lu in the liver could be washed out. The SPECT/CT images revealed a relatively inhomogeneous distribution. Nevertheless, the IGD values of 177Lu activity concentration showed acceptable agreement with the biopsy values. CONCLUSIONS Our results in pig show that it could be feasible to treat patients with liver metastases from NETs with 177Lu-octreotate via IHP 177. However, an inhomogeneous distribution of 177Lu-octreotate in normal liver tissue is expected, and in order to determine the activity concentration with satisfactory accuracy using an IGD, measurements need to be performed at several positions over the liver.
Collapse
|
|
39
|
Belotto M, Crouzillard BDNS, Araujo KDO, Peixoto RD. PANCREATIC NEUROENDOCRINE TUMORS: SURGICAL RESECTION. ACTA ACUST UNITED AC 2019; 32:e1428. [PMID: 30758476 PMCID: PMC6368164 DOI: 10.1590/0102-672020180001e1428] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 10/16/2018] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Pancreatic neuroendocrine tumors (pNET) correspond to about 3% of all tumors in pancreas and could be presented as a difficult diagnosis and management. OBJECTIVE To review the diagnosis and treatment of the pNET available in scientific literature. METHOD A bibliographic survey was performed by means of an online survey of MeSH terms in the Pubmed database. A total of 104 articles were published in the last 15 years, of which 23 were selected as the basis for the writing of this article. RESULTS pNET is an infrequent neoplasia and their incidence, in USA, is about 1:100.000 inhabitants/year. Thereabout 30% of them produce hormones presenting as a symptomatic disease and others 70% of the cases could be silent disease. Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) have similar sensitivy to detect pNET. They are very important when associated to nuclear medicine mainly Positron Emission Tomography (PET-CT) Gallium-68 to find primary tumor and its staging. The appropriate treatment should be chosen based on characteristics of the tumor, its staging and associated comorbidities. CONCLUSION The surgical resection is still the best treatment for patients with ressectable pancreatic NETs. However, the size, grade, tumor functionality, stage and association with multiple endocrine neoplasia type 1 (MEN-1) are important to define who will be eligible for surgical treatment. In general, tumors bigger than 2 cm are eligible for surgical treatment, except insulinomas whose surgical resection is recommended no matter the size.
Collapse
|
|
40
|
Lesén E, Granfeldt D, Houchard A, Berthon A, Dinet J, Gabriel S, Björstad Å, Björholt I, Elf AK, Johanson V. Cost-of-illness of metastatic gastroenteropancreatic neuroendocrine tumours in Sweden-A population-based register-linkage study. Eur J Cancer Care (Engl) 2019; 28:e12983. [PMID: 30652364 PMCID: PMC9285913 DOI: 10.1111/ecc.12983] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 12/03/2018] [Accepted: 12/03/2018] [Indexed: 12/12/2022]
Abstract
The objective was to estimate the cost‐of‐illness of grades 1 and 2 metastatic gastroenteropancreatic neuroendocrine tumours (GEP‐NETs) in Sweden in 2013 in a population‐based study including all patients diagnosed between 2005 and 2013. Data were obtained from national registers, and patients who utilised healthcare resources due to metastatic GEP‐NETs in 2013 were included. The study included 478 patients (mean age 64 [SD=11] years, 51% men). The majority (80%) had small intestinal NET, 10% had pancreatic NET, and 41% had carcinoid syndrome. The total cost‐of‐illness was €12,189,000 in 2013, of which direct costs constituted 77% and costs from production loss constituted 22%. The largest contributor to the direct medical costs was prescription drugs (54%; primarily somatostatin analogues [91% of the total drug cost]). Production loss due to sickness absence constituted 52% of the total costs of production loss. The total annual cost per patient was €25,500. By patient group, the cost was €24,800 (95% CI €21,600–€28,100) for patients with small intestinal NET, €37,300 (95% CI €23,300–€51,300) for those with pancreatic NET and €18,600 (95% CI €12,600–€24,500) for patients with other GEP‐NETs. To conclude, the total annual cost of grades 1 and 2 metastatic GEP‐NETs in Sweden was €25,500 per patient and year.
Collapse
Affiliation(s)
- Eva Lesén
- Nordic Health Economics, Gothenburg, Sweden
| | - Daniel Granfeldt
- PharmaLex Sweden, formerly Nordic Health Economics, Gothenburg, Sweden
| | | | | | | | | | - Åse Björstad
- PharmaLex Sweden, formerly Nordic Health Economics, Gothenburg, Sweden
| | - Ingela Björholt
- PharmaLex Sweden, formerly Nordic Health Economics, Gothenburg, Sweden
| | - Anna-Karin Elf
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Viktor Johanson
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| |
Collapse
|
|
41
|
Gupta N, Kankotia R, Sahakian A, Jayaram P, Shindel A, Dong E, Korc P, Eloubeidi M, Buxbaum J. Endoscopic Ultrasound Assessment of Pancreatic Duct Diameter Predicts Neuroendocrine Tumors and Other Pancreas Masses. Pancreas 2019; 48:66-69. [PMID: 30451795 DOI: 10.1097/mpa.0000000000001200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVES Distinguishing neuroendocrine tumors (NETs) and other pancreas lesions from adenocarcinomas via endoscopic ultrasound (EUS) requires additional tissue for special staining and processing. Our aim was to determine if main pancreatic duct (PD) diameter on EUS helps to differentiate NET and other unusual tumors from adenocarcinoma. METHODS We evaluated 30 consecutive patients diagnosed with NET or other pancreas lesions by EUS with 90 matched patients who were found to have adenocarcinoma. Dilated PD was defined as greater than 3 mm. Multivariate logistic regression was used to evaluate associations between lesion type and PD diameter. RESULTS Among the 30 patients with NET/other pancreas lesions, 21 had NETs, 7 had metastases, and 2 had lymphomas. A dilated PD was demonstrated in only 3.3% of pancreatic NET/other lesions but present in 88.9% of cases of primary adenocarcinoma (P < 0.01). In multivariate analysis, a normal PD diameter and absence of clinical symptoms strongly predicted the presence of pancreatic NET/other versus adenocarcinoma (P < 0.01). CONCLUSIONS The absence of PD dilation upstream of the lesion suggests NET or other lesions rather than adenocarcinoma. This finding should prompt endosonographers to obtain additional tissue at the time of EUS to send for special studies.
Collapse
Affiliation(s)
| | | | | | | | - Alex Shindel
- Division of Gastroenterology, Department of Medicine, Kaiser Permanente Los Angeles, Los Angeles
| | - Elizabeth Dong
- Division of Gastroenterology, Department of Medicine, Kaiser Permanente Los Angeles, Los Angeles
| | - Paul Korc
- Department of Medicine, Division of Gastroenterology, Hoag Hospital, Newport Beach, CA
| | - Mohamad Eloubeidi
- Department of Medicine, Division of Gastroenterology, Northeast Alabama Regional Medical Center, Anniston, AL
| | | |
Collapse
|
|
42
|
Yadav A, Gangwani G, Mishra N, Gupta A. Percutaneous Transhepatic Approach for Recanalization of Superior Mesenteric and Portal Vein in a Patient With Pancreatic Neuroendocrine Tumor Presenting With Bleeding Duodenal Varices: A Brief Case Report. J Clin Exp Hepatol 2018; 8:318-320. [PMID: 30302050 PMCID: PMC6175724 DOI: 10.1016/j.jceh.2018.03.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 03/22/2018] [Indexed: 12/12/2022] Open
Abstract
Occlusion of Portal Vein (PV) and Superior Mesenteric Vein (SMV) is a known effect of local infiltration by pancreatic or mesenteric neuroendocrine tumors. Venous occlusion leads to formation of collateral pathways to restore hepatopetal flow in main PV and these collateral pathways can be seen in the form of ectopic (duodenal or jejunal) varices. We present a case of bleeding duodenal varices secondary to SMV occlusion by a locally infiltrating pancreatic neuroendocrine tumor which was successfully treated by coil embolization of varices and SMV stenting of the occluded venous segment after failure of endoscopic glue injection. Various endovascular minimally invasive approaches have been described in literature for recanalization of SMV in such clinical scenarios which maybe challenging to treat for surgical methods. We recommend use of the retrograde transhepatic technique for recanalization of occluded SMV and embolization of associated varices as an alternate treatment option in such scenarios.
Collapse
Affiliation(s)
- Ajit Yadav
- Senior Consultant, Department of Interventional Radiology, Sir Gangaram Hospital, New Delhi, India
| | - Gaurav Gangwani
- Clinical Assistant, Department of Interventional Radiology, Sir Gangaram Hospital, New Delhi, India
| | - Nitin Mishra
- Fellow, Department of Interventional Radiology, Sir Gangaram Hospital, New Delhi, India
| | - Arun Gupta
- Chairperson, Department of Interventional Radiology, Sir Gangaram Hospital, New Delhi, India,Address for correspondence: Arun Gupta, Chairperson, Department of Interventional Radiology, Sir Gangaram Hospital, New Delhi 110060, India. Tel.: +91 9350335103.
| |
Collapse
|
|
43
|
Treatment Patterns and Clinical Outcomes in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors Treated in the Community Practice Setting in the United States. Pancreas 2018; 47:173-182. [PMID: 29206668 DOI: 10.1097/mpa.0000000000000955] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE This study was conducted to understand treatment patterns and clinical outcomes in metastatic gastroenteropancreatic neuroendocrine tumor patients treated in a large community oncology network. METHODS This retrospective study used the McKesson Specialty Health/US Oncology Network iKnowMed electronic health record database with supplemental chart review. Eligibility criteria included a metastatic neuroendocrine tumor diagnosis between January 1, 2008, and to December 31, 2012; at least 2 US Oncology Network visits; and age at least 18 years. Follow-up was through October 31, 2014. RESULTS Among the 229 patients identified, median age was 64.0 years, 52.4% were male, 69.4% were white, and 62.9% were overweight/obese. Primary tumor sites included small bowel (47.6%), pancreas (31.4%), and stomach/colorectum (21.0%). There were 16.2% under observation without treatment, 52.4% received only somatostatin analogs (SSAs), and 31.4% received chemotherapy/targeted therapy during treatment. In the first-line setting (n = 192), 77% received SSAs, 12% received chemotherapy, and 10.9% received targeted therapy. Fifty percent of patients receiving octreotide had a relative dose intensity of less than 85%, and 16.7% received above-label dose. Toxicities of SSAs included diarrhea (18.2%), abdominal pain (16.9%), and fatigue (13.5%). Median overall survival from diagnosis was 68.0 months (95% confidence interval, 57.1 to not reached). CONCLUSIONS Most metastatic gastroenteropancreatic neuroendocrine tumor patients received systemic treatment with SSAs. Patient treatment used an individualized dosing approach. Overall survival and toxicity were consistent with the published literature.
Collapse
|
|
44
|
Simultaneous Glucagon and Vasoactive Intestinal Peptide Producing Pancreatic Neuroendocrine Tumors in a Patient With Multiple Endocrine Neoplasia Type 1: A Case Report and Literature Review. Pancreas 2018; 47:e1-e2. [PMID: 29232343 DOI: 10.1097/mpa.0000000000000969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
|
|
45
|
Management of Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEPNETs): A Review. Clin Ther 2017; 39:2146-2157. [PMID: 29173655 DOI: 10.1016/j.clinthera.2017.10.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 10/05/2017] [Accepted: 10/05/2017] [Indexed: 12/31/2022]
Abstract
PURPOSE Neuroendocrine tumors (NETs) are heterogeneous tumors that arise from the neuroendocrine cells of the digestive tract and other organs, such as the lung, ovary, and thyroid glands. They can be well differentiated or poorly differentiated, and management of these tumors differs for each histologic subtype. We have performed a review of NETs and focused on management of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEPNETs) and carcinoid syndrome. METHODS A PubMed search was performed to obtain articles on the management of well-differentiated NETs. Using the key words neuroendocrine tumors, carcinoid, pNET, octreotide, somatostatin analogues, and radiolabeled therapy, we reviewed Phase II and III trials that were published over the past 30 years. We also reviewed guidelines from the European Neuroendocrine Tumor Society, North America Neuroendocrine Tumor Society, and National Comprehensive Cancer Network in our search. FINDINGS NETs are usually slow-growing tumors that remain asymptomatic for a long duration and can be either nonfunctioning or functioning. Surgical resection is recommended for locoregional disease, impending obstruction, symptom control, and advanced disease. Nonsurgical treatment options include somatostatin analogues (SSAs), multikinase inhibitors, targeted therapy, chemotherapy, and radiolabeled SSAs. Carcinoid syndrome is mainly treated with SSAs. IMPLICATIONS Although GEPNETs are slow-growing tumors, most patients are diagnosed with metastatic disease, and therefore it is important that the management of each patient be discussed in a multidisciplinary setting to optimize the treatment strategy. Patients should be considered for clinical trials and refractory cases referred to a specialty center.
Collapse
|
|
46
|
Cui Y, Li ZW, Li XT, Gao SY, Li Y, Li J, Zhu HC, Tang L, Cao K, Sun YS. Dynamic enhanced CT: is there a difference between liver metastases of gastroenteropancreatic neuroendocrine tumor and adenocarcinoma. Oncotarget 2017; 8:108146-108155. [PMID: 29296230 PMCID: PMC5746132 DOI: 10.18632/oncotarget.22554] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 06/18/2017] [Indexed: 12/26/2022] Open
Abstract
This study proposed to evaluate the feasibility of dynamic enhanced CT in differentiation of liver metastases of gastroenteropancreatic well-differentiated neuroendocrine tumors (GEP NETs) from GEP adenocarcinomas based on their characteristic features. CT images of 23 well-differentiated (G1 or G2) GEP NETs and 23 GEP adenocarcinomas patients with liver metastases were retrospectively reviewed. The distribution type, shape, intra-tumoral neovascularity, enhancement on hepatic artery phase, dynamic enhancement pattern and lymphadenopathy were subjective analyzed. Meanwhile, the size, number, CT value of tumor and adjacent normal liver parenchyma were measured and the metastasis-to-liver ratios were calculated objectively. Compared with GEP adenocarcinomas, the liver metastases of GEP NETs more frequently demonstrated a hyper enhancement on hepatic artery phase, washout dynamic enhancement pattern, absence of lymphadenopathy and higher metastasis-to-liver ratios on both hepatic artery phase and portal venous phase (P=0.017, P<0.001, P =0.038, P <0.001 and P =0.008, respectively). Logistic regression analysis showed that the dynamic enhancement pattern (P=0.012), and the metastasis-to-liver ratios on hepatic artery phase (P=0.009) were independent CT predictors for liver metastases of GEP NETs. The sensitivity and specificity of combing the two predictors in differentiation of liver metastases of GEP adenocarcinomas from GEP NET were 82.6% (19 of 23) and 91.3% (21 of 23), respectively. CT features are helpful in differentiating liver metastases of well-differentiated GEP NETs from that of GEP adenocarcinomas.
Collapse
Affiliation(s)
- Yong Cui
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhong-Wu Li
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiao-Ting Li
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Shun-Yu Gao
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ying Li
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jie Li
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Hui-Ci Zhu
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Lei Tang
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Kun Cao
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ying-Shi Sun
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| |
Collapse
|
|
47
|
Ayyagari R, Neary M, Li S, Rokito A, Yang H, Xie J, Benson AB. Comparing the Cost of Treatment with Octreotide Long-Acting Release versus Lanreotide in Patients with Metastatic Gastrointestinal Neuroendocrine Tumors. AMERICAN HEALTH & DRUG BENEFITS 2017; 10:408-415. [PMID: 29263774 PMCID: PMC5726060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 06/22/2017] [Indexed: 06/07/2023]
Abstract
BACKGROUND The 2 somatostatin analogs currently recommended by the National Comprehensive Cancer Network for the treatment of gastrointestinal (GI) neuroendocrine tumors (NETs) include octreotide long-acting release (Sandostatin LAR) for injectable suspension and lanreotide (Somatuline Depot) injection for subcutaneous use. OBJECTIVE To estimate the costs to payers associated with 30-mg octreotide LAR and 120-mg lanreotide treatment among patients with metastatic GI-NETs. METHODS The costs to payers associated with the 2 drugs were estimated by including the costs of each drug, drug administration, and adverse events. The unit drug costs for octreotide LAR and for lanreotide were obtained from ReadyPrice Wholesale Acquisition Cost; the doses were obtained from published studies. The adverse event rates were obtained from 2 phase 3 clinical trials, PROMID and CLARINET. Deterministic one-way sensitivity analyses were used to assess the impact of modifying assumptions and inputs on the results, including the 2017 Average Sales Price (ASP). All costs were estimated in 2016 US dollars, with a constant discount of 3%. RESULTS The costs to payers associated with the treatment of GI-NETs during 1-, 3-, and 5-year horizons were $74,566, $180,082, and $262,344, respectively, for octreotide LAR and $84,856, $205,562, and $299,667, respectively, for lanreotide. Thus, octreotide LAR was associated with lower costs by $10,290 (1 year), $25,480 (3 years), and $37,323 (5 years) compared with lanreotide. Over a 5-year horizon, the costs of adverse events and administration accounted for 0.72% of the total cost for octreotide LAR and 0.51% of the total cost for lanreotide. Sensitivity analyses confirmed that the main factor affecting the cost difference was the price of the drugs; analyses using the ASP yielded similar results. CONCLUSION For the management of metastatic GI-NETs, the cost to payers of treatment with 30-mg octreotide LAR is considerably lower than with 120-mg lanreotide over 1-, 3-, and 5-year horizons. In the presence of healthcare resource constraints, these findings may support decision-making when considering the care of patients with metastatic GI-NETs.
Collapse
Affiliation(s)
| | - Maureen Neary
- Director, Global Value & Access, Novartis Pharmaceuticals, East Hanover, NJ
| | - Shang Li
- Senior Analyst, Analysis Group, New York, NY
| | | | | | - Jipan Xie
- Vice President, Analysis Group, New York, NY
| | - Al B Benson
- Professor of Medicine, and Associate Director for Cooperative Groups, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
| |
Collapse
|
|
48
|
Improving quality of life in patients with pancreatic neuroendocrine tumor following peptide receptor radionuclide therapy assessed by EORTC QLQ-C30. Eur J Nucl Med Mol Imaging 2017; 45:38-46. [DOI: 10.1007/s00259-017-3816-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 08/22/2017] [Indexed: 01/01/2023]
|
|
49
|
Carrasco P, Zuazo-Gaztelu I, Casanovas O. Sprouting strategies and dead ends in anti-angiogenic targeting of NETs. J Mol Endocrinol 2017; 59:R77-R91. [PMID: 28469004 DOI: 10.1530/jme-17-0029] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 05/03/2017] [Indexed: 01/13/2023]
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that arise from cells of the neuroendocrine system. NETs are characterized by being highly vascularized tumors that produce large amounts of proangiogenic factors. Due to their complexity and heterogeneity, progress in the development of successful therapeutic approaches has been limited. For instance, standard chemotherapy-based therapies have proven to be poorly selective for tumor cells and toxic for normal tissues. Considering the urge to develop an efficient therapy to treat NET patients, vascular targeting has been proposed as a new approach to block tumor growth. This review provides an update of the mechanisms regulating different components of vessels and their contribution to tumor progression in order to develop new therapeutic drugs. Following the description of classical anti-angiogenic therapies that target VEGF pathway, new angiogenic targets such as PDGFs, EGFs, FGFs and semaphorins are further explored. Based on recent research in the field, the combination of therapies that target multiple and different components of vessel formation would be the best approach to specifically target NETs and inhibit tumor growth.
Collapse
Affiliation(s)
- Patricia Carrasco
- Tumor Angiogenesis GroupProCURE, Catalan Institute of Oncology - IDIBELL, Barcelona, Spain
| | - Iratxe Zuazo-Gaztelu
- Tumor Angiogenesis GroupProCURE, Catalan Institute of Oncology - IDIBELL, Barcelona, Spain
| | - Oriol Casanovas
- Tumor Angiogenesis GroupProCURE, Catalan Institute of Oncology - IDIBELL, Barcelona, Spain
| |
Collapse
|
|
50
|
Abstract
神经内分泌瘤是一类起源于神经内分泌细胞, 发病率低且具有分子和生物学行为异质性的肿瘤. 现报道一例右半结肠神经内分泌瘤G2伴多发淋巴结转移患者, 以期对临床工作者有所帮助.
Collapse
|